All Bat Notes

all bat notes
bat notes
term 01
anatomy
bat notes
term 01
Bones of Upper Limb
Clavicle
• Long bone – shaft, medial & lateral ends
• Side determination
- Lat. End – flat
Med. End – large, quadrilateral
- Med. 2/3 of shaft – convex forwards
Lat. 1/3 of shaft – concave forwards
- Inf. Surface – middle 1/3 – presence of a
longitudinal groove (subclavian groove)
- conoid tubercle and trapezoid ridge- for 2
parts of coracoclavicular ligament
• Special features
- Only long bone which lies horizontally
- Subcutaneous throughout
- 1st bone to start ossifying
- Only long bone which has a membranous ossification
- Only long bone which has 2 primary centers of
ossification
- Generally, has no medullary cavity
- The supraclavicular nerves crossing it can be rolled
against the bone
• Fracture
- Commonest site – junction between medial 2/3 & lat.
1/3 (weakest point) between costoclavicular and
coracoclavicular ligament
- Caused by falling on the out stretched hand
- Lat. Fragment – displaces downwards by the weight
of the upper limb
- Med. Fragment – displaces upwards by the action of
sternocleidomastoid
- Adductor muscles spasm – adduction of the arm
Scapula
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Triangular in shape, from 2nd to 7th rib level
Three Borders- Superior, medial, lateral
Three angles- Superior, inferior, lateral (glenoid fossa is present)
Three processes- acromion, coracoid, spinous(spine)
Two surfaces- Dorsal, costal
Clinical
- winging of the scapula - due to paralysis of the serratus

anterior (damage to long thoracic nerve)
- scaphoid scapula – medial border is concave
-
Suprascapular nerve and vessels
Navy under the bridge (superior transverse scapular ligament)
Army over the bridge
Humerus

The Humerus
Upper End Shaft Lower End
1) Head of humerus Rounded in the upper half and triangular Articular

in lower half
Directed medially backwards and Capitulum- head of the radius
upwards 3 borders- Anterior, Medial, Lateral
Trochlea- trochlear notch of ulnar
Forms about 1/3rd of sphere larger then 3 surfaces – Anterolateral
glenoid cavity Radial fossa, Coronoid fossa, Olecranon
Anteromedial fossa
2) Anatomical neck
Posterior Non-articular
3) Lesser tubercle (anterior aspect)
subscapularis attachment Deltoid tuberosity in anterolateral Medial epicondyle- related to ulnar nerve
surface behind runs downwards the and com. Fle. origin
4) Greater tubercle marked by three radial groove
impressions Lateral epicondyle
Nutrient foramen in anteromedial
Upper-supraspinatus surface
Posterior aspect bears radial groove

Middle- infraspinatus demarcating medial and lateral heads of
triceps
Lower -Teres minor
5) Intertubercular sulcus has medial and

lateral lips accommodates upper part of
biceps tendon
6)surgical neck- related to axillary nerve
Related nerves
- Surgical neck – Axillary nerve

- Radial groove – radial nerve
- Posterior to the medial epicondyle – Ulnar nerve
Common sites of FRACTURE
- Surgical neck – axillary nerve more prone to damage

- Shaft – radial nerve liable to injury
- Supracondylar region
- Elbow is unduly prominent. But 3 bony points are in usual equilateral triangle
- May cause damage to median nerve
- Volkmann’s ischaemic contracture
- Lower end of the proximal fragment, damages the brachial artery Ischaemia of
the forearm muscles fibrosis & contraction of long flexors & extensors
flexors are bulkier than extensors wrist – flexed
M/P – extend
I/P - flexed

Radius & Ulna
Clinical – Radius
• Commonly fractured 1” proximal to the

wrist
• Colles’ fracture
- More common
- Distal fragment dislocates backwards &
upwards
- Radial styloid process becomes
proximal to the ulnar styloid process
• Smith’s fracture
- Reverse of Colles’ fracture
• Subluxation of head of the radius
- Common in children
- Head is dislodged from the grip of
annular ligament (reason)
• Miner’s elbow / Student’s elbow
- Subcutaneous bursa over the olecranon
- Inflamed when exposed to repeated
trauma
- Olecranon bursitis
• Green stick fractures (common in children)
Clinical
• Paralysis of Serratus anterior causes ‘winging’ of the Scapula
- Medial border of scapula – unduly prominent
- Arm can’t be abducted beyond 90°
• Pec. Major testing
- Clavicular head - attempt to lift a heavy table
- fflex arm to a 90° against resistance
- sternocoastal head – try to depress a heavy table
- extend the flexed arm against resistance
press fists against each other

Muscles of Upper Limb
Muscles of shoulder
Muscle Origin Insertion Innervation Function

Trapezius Superior nuchal line, Superior edge of the Motor spinal Powerful elevator of the
external occipital crest of the spine of part of scapula during abduction
protuberance, medial the scapula, accessory of humerus above
margin of the ligamentum acromion, posterior nerve(XI),Sens horizontal: middle fibers
nuchae, spinous process border of lateral one ory(propriocep retract scapula: lower
of CVII to TXII and the third of clavicle tion)anterior fibers depress scapula
related supraspinous rami of C3 and
ligaments C4
Deltoid Inferior edge of the crest Deltoid tuberosity of Axillary Major abductor of
of the spine of the humerus nerve(C5,C6) arm(abducts arm beyond
scapula, lateral margin of initial 15 done by
the acromion, anterior supraspinatus):clavicular
border of lateral one third fibers assist in flexing the
of clavicle arm;posterior fibers assist
in extending the arm
Levator Transverse process of C1 Posterior surface of Branches Elevates the scapula
Scapulae and C2 vertebrae and medial border of directly from
posterior surface of scapula from anterior rami
transverse processes of superior angle to of C3 and C4
C3 and C4 vertebrae root of spine of the spinal nerves
scapula and by
branches(C5)
from dorsal
scapular nerve
Rhomboid Lower end of the Posterior surface of Dorsal Elevates and retracts the
minor ligamentum nuchae and medial border of scapular scapula
spinous process of C7 and scapula at the root nerve(C4,C5)
T1 vertebrae of the spine of the
scapula
Rhomboid Spinous process of T2-T5 Posterior surface of Dorsal Elevates and retracts the
major vertebrae and intervening medial border of scapular scapula
supraspinous ligaments scapula from the nerve(C4,C5)
root of the spine of
the scapula to the
inferior angle
Muscles of posterior scapular region

Supraspinatus Medial two thirds of the Most superior Suprascapular Rotator cuff muscle;
supraspinous fossa of the facet on the nerve(C5, C6) initiation of abduction of
scapula and the deep fascia greater tubercle arm to 15 at
that covers the muscle of the humerus glenohumeral joint
Infraspinatus Medial two thirds of the Middle facet on Suprascapular Rotator cuff muscle;
infraspinous fossa of the posterior nerve (C5, C6) Lateral rotation of arm at
scapula and the deep fascia surface of the the glenohumeral joint
that covers the muscle great tubercle
of the humerus
Teres minor Upper two thirds of a Inferior facet on Axillary nerve Rotator cuff muscle;
flattened strip of bone on the posterior (C5, C6) lateral rotation of arm at
the posterior surface of the surface of the the glenohumeral joint
scapula immediately greater tubercle
adjacent to the lateral of the humerus
border of the scapula
Teres major Elongate oval area on the Medial lip of Inferior Medial rotation and
posterior surface of the the subscapular extension of the arm at
inferior angle of the scapula intertubercular nerve (C5, the glenohumeral joint
sulcus on the C6,C7)
anterior surface
of the humerus
Long head of Infraglenoid tubercle on Common Radial nerve Extension of the forearm
triceps brachii scapula tendon of (C6, C7, C8) at the elbow joint;
insertion with accessory abductor and
medial and extensor of the arm at
lateral heads on the glenohumeral joint
the olecranon
process of ulna
Muscles of anterior wall

Pectoralis Clavicular head-anterior Lateral lip of Medial and lateral Flexion, adduction
major surface of medial half of intertubercular pectoral nerves; and medial rotation of
clavicle; sternocostal sulcus of clavicular arm at the
head-anterior surface of humerus head(C5,C6)sternocostal glenohumeral joint;
sternum; first seven head(C6,C7,C8,T1) clavicular head-flexion
costal cartilages: sternal of extended arm;
end of sixth rib; sternocostal head-
aponeurosis of external extension of flexed
oblique arm
Subclavius First rib at junction Groove on Nerve to subclavius Pulls tip of shoulder
between rib and costal inferior surface (C5,C6) down; pulls clavicle
cartilage of middle one medially to stabilize
third of clavicle sternoclavicular joint
Pectoralis Anterior surface and Coracoid Medial pectoral Pulls tip of shoulder
minor superior borders of ribs 3 process of nerve(C5,C6,C7,C8,T1) down; protracts
to 5;and from deep fascia scapula(medial scapula
overlying the related border and
intercostals space upper surface)

Muscles of medial wall of scapula

Serratus Lateral surface of upper 8 Costal surface Long Protraction and rotation of the
anterior ribs and deep fascia of medial thoracic scapula keeps medial border
overlying the related border of nerve(C5, and inferior angle of scapula
intercostals spaces scapula C6,C7) opposed to thoracic wall
Muscles of the lateral and posterior wall of the axilla

Subscapularis Medial two thirds of Lesser tubercle Upper and lower Rotator cuff muscle;
subscapular fossa of humerus subscapular medial rotation of the
nerves(C5,C6,C7) arm at the
glenohumeral joint
Teres major Elongate oval area on the Medial lip of Lower Medial rotation and
posterior surface of the intertubercular subscapular extension of the arm at
inferior angle of the scapula sulcus on the nerve(C5,C6,C7) the glenohumeral joint
anterior
surface of the
humerus
Latissimus Spinous processes of lower Floor of Thoracodorsal Adduction, medial
dorsi six thoracic vertebrae and intertubercular nerve(C6,C7,C8) rotation and extension
related interspinous sulcus of the arm at the
ligaments; via the glenohumeral joint
thoracolumbar fascia to the
spinous processes of the
lumbar vertebrae; related
interspinous ligaments, and
iliac crest; lower 3-4 ribs
Arm
Flexor Compartment

Coracobrachiali Apex of Linear roughening on Flexor of the arm at the
s coracoids mid shaft of humerus glenohumeral joint
process on medial side
Biceps brachii Long head- Radial tuberosity Musculocu-- Powerful flexor of the
supraglenoid taneous nerve forearm at the elbow
tubercle of joint the supinator of the
scapula; short forearm; accessory flexor
head-apex of of the arm at the
coracoids glenohumeral joint
process

Brachialis Anterior aspect Tuberosity of the Musculocutaneous Powerful flexor of the
of humerus ulna nerve (C5,C6) forearm at the elbow
(medial and small contribution joint
lateral surfaces) by the radial
and adjacent nerve(C7) to
intermuscular lateral part of
septae muscle
Extensor compartment

Triceps Long head-infraglenoid tubercle Olecranon Radial Extension of the forearm at the
brachii of scapula; medial head- nerve(C6, elbow joint; long head can also
posterior surface of humerus; C7,C8) extend and adduct the arm at
lateral head-posterior surface of the shoulder joint
humerus
Forearm
Flexor compartment
Superficial layer
Flexor Humeral head-medial Pisiform bone and then Ulnar nerve (C7, Flexes and adducts the
carpi epicondyle of via pisohamate and C8, T1) wrist joint
ulnaris humerus; ulnar head- pisometacarpal
olecranon and ligaments into the
posterior border of hamate and base of
ulna metacarpal v
Palmaris Medial epicondyle of Palmar aponeurosis of Median nerve Flexes wrist joint;
longus humerus hand because the palmar
aponeurosis anchors skin
of the hand, contraction
of the muscle resists
shearing forces when
gripping
Flexor Medial epicondyle of Base of metacarpals 2 Flexes and abducts the
carpi humerus and 3 wrist
radialis
Pronator Humeral head-medial Roughening on lateral Pronation
teres epicondyle and surface, midshaft ,of
adjacent supra- radius
epicondylar ridge;
ulnar head-medial
side of coronoid
process

Intermediate layer

Flexor Humero-ulnar head- Four tendons which Median Flexes proximal interphalangeal
digitorum medial epicondyle of attach to the palmar nerve joints of the index,middle,ring
superficialis humerus and adjacent surfaces of the (C8,T1) and little finger;can also flex
margin of coronoid middle phalanges of metacarpophalangeal joints of
process;radial head- the index,middle,ring the same fingers and the wrist
oblique line of radius and little finger joint
Deep layer

Flexor Anterior and medial Four tendons which Lateral half by Flexes distal interphalangeal
digitorum surfaces of ulna and attach to the palmar median joints f the indes,middle,ring
profundus anterior medial half surfaces of the distal nerve(anterior and little fingers;can also flex
of interosseous phalanges of the interousseous metacarpophalangeal joints
membrane index,middle,ring and nerve)medial of the same fingers and the
little finger half by ulnar wrist joint
nerve(C8,T1)
Floxor Anterior surface of Palmar surface of base Median Flexes interphalangeal joint
policis radius and radial of distal phalanx of nerve(anterior of the thumb;can also flex
longus half of interosseous thumb interosseous metacarpophalangeal joint of
membrane nerve) the thumb
Pronator Linear ridge on Distal anterior surface Pronation
qudratus distal anterior of radius
surface of ulna
Extensor compartment
Superficial layer
Bracioradialis Proximal part of Lateral surface of Radial Accessory flexor of elbow
lateral supra- distal end of nerve(C5,C6)before joint when forearm is
epicondylar ridge of radius division into midpronated
humerus and superficial and
adjacent deep branches
intermuscular septum
Extensor Distal part of lateral Dorsal surface of Radial Extends and abducts the
carpi radialis supra-epicondylar base of nerve(C6,C7)before wrist
longus ridge of humerus and metacarpal 2 division into
adjacent superficial and
intermuscular septum deep branches
Extensor Lateral epicondyle of Dorsal surface of Deep branch of Extends and abducts the
carpi radialis humerus and base of radial wrist
brevis adjacent metacarpals 2 nerve(C7,C8)before
intermuscular septum and 3 penetrating
supinator muscle

Extensor Lateral epicondyle of Four tendons Posterior Extends the
digitorum humerus and which insert via interosseous index,middle,rinf and little
adjacent extensor hoods nerve(C7,C8) fingers;can also extend the
intermuscular septum into the dorsal wrist
and deep fascia aspects of the
bases of the
middle and distal
phalanges of the
index,middle,ring
and little fingers
Extensor Lateral epicondyle of Extensor hood of Extends the little finger
digiti minimi humerus and the little finger
adjacent
intermuscular septum
together with
extensor digitorum
Extensor Lateral epicondyle of Tubercle on the Posterior Extends and adducts the
carpi ulnaris humerus and base of the interosseous wrist
posterior border of medial side of nerve(C7,C8)
ulna metacarpal 5
Anconeus Lateral epicondyle of Olecranon and Radial nerve Abduction of the ulna in
humerus proximal (C6,C7,C8) (via pronation;accessory
posterior surface branch to medial extensor of the elbow
of una head of triceps joint
brachii)
Deep layer
Muscle Insertion Innervation Function

Supinator Lateral surface of radius Posterior Supination
superior to the anterior interrosseous
oblique line nerve(C6,C7)
Abductor pollicis longus Lateral side of base of Abducts carpometacarpal jint
metacarpal 1 of thumb;accessory extensor
of the thumb
Extensor pollicis brevis Dorsal surface of base of Extends metacarpophalangeal
proximal phalanx of the joint of the thumb;can also
thumb extend the carpometacarpal
joint of the thumb
Extensor pollicis longus Dorsal surface of base of Extends interphalangeal joint
proximal phalanx of the of the thumb;can also extend
thumb carpometacarpal and
metacarpophalangeal joints of
the thumb
Extensor indicis Extensor hood of index Extends index finger
finger

Muscles testing of the upper limb
A. Muscles of pectoral girdle
1) Pectoralis Major- For the

clavicular head the arm is
abducted to 90 or more and the
patient pushes the arm forwards
against resistance. For the
sternocostal head the arm is
abducted to 60and then
adducted against resistance. The
contracting heads can be seen
and felt.
2) Trapezius- The shoulder is

shrugged against resistance and
the upper border of the muscle is
seen and felt.
3) Latissimus Dorsi- The arm is

abducted to a right angle and
then adducted, extended and
medially rotated against
resistance; the lateral part of the
muscle below the posterior
axillary fold can be seen and felt
contracting. The muscle can also
be felt to contract here when the
patient coughs.
4) Serratus Anterior- With the arm

flexed and the elbow extended
the outstretched hand is pushed
against a wall. Paralysis results in
‘winged scapula’, where the
vertebral border becomes
prominently raised off the
posterior chest wall.
B. Muscles of shoulder
1) Supraspinatus- The arm is abducted against resistance and the muscle

palpated (deep to trapezius) above the scapular spine.

2) Deltoid- The arm is abducted against resistance and the muscle is seen and
felt.
C. Anterior compartment of the arm
1) Biceps Brachii- With the forearm supinated the elbow is flexed against
resistance. The contracted muscle in the arm, and the tendon and
aponeurosis at the elbow are easily palpable.
D. Posterior compartment of the arm
1) Triceps- The flexed forearm is extended against resistance and the muscle
seen and felt.
E. Anterior compartment of the forearm
1) Pronator Teres- From the supine position the forearm is pronated against
resistance and the muscle palpated at the medial margin of the cubital fossa.
2) Flexor Carpi Radialis- The wrist is flexed and abducted against resistance and
the tendon is easily seen and felt.
3) Flexor Digitorum Superficialis- The fingers are flexed at the proximal

interphalangeal joints against resistance applied to the middle phalanges,
while the distal interphalangeal joints are kept extended.
4) Flexor Carpi Ulnaris- The wrist is flexed and adducted against resistance and
the tendon palpated.
F. Deep muscles of the forearm
1) Flexor Digitorum Profundus- With the fingers extended and the hand lying
supine on the table, the distal interphalangeal joints are flexed against
resistance with the middle phalanx held in extension.
2) Flexor Pollicis Longus- With the proximal phalanx of the thumb held steady,
the distal phalanx is flexed against resistance.
G. Posterior compartment of the forearm
1) Brachioradialis- With the forearm in the midprone position the elbow is flexed
against resistance; the muscle can be seen and felt.

Transverse section of the arm at the level of insertion of corocobrachialis
Transverse section of the forearm

Pectoral Region, Breast and Scapular region
Pectoral region
Muscle Origin Insertion Nerve supply Action
Pectoralis • Clavicle – ant. Surface Bicipital groove – Medial & lateral Adduction,
major medial part lateral lip pectoral nerves med.rotation &
• Manubrium (bilaminar tendon) flexion of shoulder
Sternum ant. joint
Upper 6 costal surface clavicular head-
Cartilage flexion of arm at
• External oblique shoulder
aponeurosis
Pectoralis 3,4,5 ribs Coracoid process Medial pectoral Protraction,
minor (Medial side) nerve depression and lateral
rotation of the
scapula
Serratus Upper 8 ribs Scapula medial Long thoracic Entire muscle
anterior border – entire nerve protracts scapula &
length holds it against ribs.
Rotates scapula
laterally
Muscle origin Insertion innervation Action

Deltoid Anterior border Deltoid tuberosity Axillary nerve • Abduction
(has a of lateral 1/3rd of • Flexion and medial
multipennate clavicle rotation- Anterior fibers
part) Acromion • Extension and lateral
Spine of scapula rotation of pos. fibers
Clinical
• Paralysis of Serratus anterior causes ‘winging’ of the Scapula
- Medial border of scapula – unduly prominent
- Arm can’t be abducted beyond 90°
• Pec. Major testing (Pec. Major is the only muscle of the upper limb to be supplied by all 5 segments
of brachial plexus)
- Clavicular head - attempt to lift a heavy table
- fflex arm to a 90° against resistance
- sternocoastal head – try to depress a heavy table
- extend the flexed arm against resistance
press fists against each other

Pectoral fascia- deep fascia
• Covers the pectoralis major muscle
• Passes septa into the muscle fasciculi
• Attaches superiorly - clavicle
Anteriorly – sternum
Inferolaterally – continuous with axillary fascia
Superolaterally – continuous with deltoid fascia
• Connected to clavipectoral fascia by septum passing deep
to deltopectoral groove
•
Clavipectoral fascia- deep fascia
• Lies deep to pectoral fascia
• Encloses subclavius & pectoralis minor
• Can be seen on the floor of deltopectoral triangle
• Superiorly attaches to the clavicle and inferiorly to the axillary fascia
• The part of this, below the pectoralis minor is called the suspensory ligament of axilla. It pulls the
floor of axilla upwards.
Pierced by, (CALL)
• Cephalic vein
• Acromiothoracic artery
• Lymphatics draining the posterior part of the breast to apical nodes
• Lateral pectoral nerve
Breast
• Modified apocrine sweat gland of compound tubuloalveolar type
• Rudimentary in males. Well developed in females
• Extent
2nd rib
Midaxillay line lateral border of

sternum
6th rib
- Lies within superficial fascia--------- EXCEPT – small

axillary tail of Spence which pierces the deep
fascia & lies in the axilla.
• Medial 2/3 – on Pectoralis major muscle

Lateral 1/3 – on Serratus anterior muscle
Small anterior part – over the aponeurosis of external oblique muscle

Retromammary space – loose areolar tissue layer separating
breast from pectoral fascia.
Blood Supply
Veins follow arteries
Arterial supply
1) Branches of axillary artery
I. Superior thoracic
II. Acromiothoracic
III. Lateral thoracic- Main
2) Branches of internal thoracic artery
3) Branches of posterior intercostal
arteries

Structure
Skin Parenchyma Stroma
• Covers the gland • Glandular tissue • Supporting framework
• Nipple • Secretes milk
- Level – 4th ICS jus medial to the • 15-20 lobes
midclavicular line • Components Fibrous Fatty
- Pierce by 15-20 lactiferous ducts -alveoli • Septa – • Main bulk
- Circular & longitudinal muscle fibres -lactiferous duct suspensory • Absent beneath
– can make stiff/flatten it -lactiferous sinus ligaments of nipple & areola
- Rich nerve supply cooper
- Few modified sweat & sebaceous • Anchor the
glands skin & gland to
• Areola pectoral fascia
- Pigmented circular area around the Piercing
nipple retromammary
- Rich in modified sebaceous glands space
During Pregnancy & • Alveolar epithelium
Lactation, become - Resting phase – cuboidal
Enlarged, modified. - Lactation – columnar
Tubercles of Montgomery
- Some sweat glands • Along the ducts –
- Accessory mammary glands myoepitheliocytes
• Smaller ducts- columnar
The skin of nipple & areola are devoid epithelium
of hair & no fat subjacent to it. • Larger ducts- stratified
squamous keratinized
Nerve supply
- Ant. & lat. Cutaneous branches of 4,5,6 intercostal nerves
- Nerves DO NOT control the secretion of milk. Controlled by hormone, Prolactin
LYMPHATIC DRAINAGE
Lymph nodes Lymphatic vessels
1. Axillary (75%) Anterior(Pectoral) Superficial Deep

(Lateral thoracic vessels) lymphatics lymphatics
Posterior - Skin except - Parenchyma of

(Subscapular vessels) nipple & areola nipple & areola
Axillary tail of breast
Lateral (medial to the
Axillary vein)
Apical Central (In the fat of axilla)

(Axillary vessels) receive lymph from ant,pot,lat. groups
Receive lymph from central and upper part of Breast

2. Internal mammary nodes (20%)
3. Posterior intercostal nodes (5%)
4. Other – Supraclavicular nodes

Cephalic (Deltopectoral)
Subdiaphragmatic & subperitoneal lymph plexus
Milk line – axilla to groin

By invagination of surface ectoderm
Developmental abnormalities
• Amastia
• Athelia
• Polymastia
• Polythelia
• Gynecomastia (XXY- Klinefelter)
Clinical
-Frequent site of carcinoma

-Incision – radially – to avoid cutting lactiferous ducts
-Dimpling / retraction (folding) of the skin – # infiltration of suspensory ligament- fibrous contraction
# Breast becomes fixed
-Retraction of nipple - infiltration of lactiferous ducts- fibrous contraction
-Peau d’ orange appearance - Obstruction of superficial lymph vessels Oedema
-Superficial lymphatics communicate across the mid line Cancer can spread from one breast
to another
-Communication of lymphatics * Spread to abdominal organs.

* secondaries in the pelvis.
Spread through veins

communication
Veins of breast vertebral venous plexus # vertebrae
# brain
Commonest nerves that can be damaged in complete mastectomy – long thoracic,

intercostobrachial, thoracodorasal

SCAPULAR REGION
Muscle Origin (Scapula) Insertion Nerve Supply Action
(Humerus)
Supraspinatus Supraspinous Greater tubercle Suprascapular • Initiate abduction (up

fossa – upper nerve to 15°)
impression • Steadies head of
Humerus
Infraspinatus Infraspinous Greater tubercle Suprascapular Lateral rotator of arm

fossa – middle nerve
impression
Teres Minor Upper 2/3 of Greater tubercle Axillary nerve
dorsal surface- – lower
lateral border impression
Subscapularis Subscapular Lesser tubercle Upper & lower •Medial rotator of arm
(Multipennate) fossa subscapular nerves •Adduction of arm
Teres major Lower 1/3 of Bicipital groove – Lower subscapular

dorsal surface- medial lip nerve
lateral border
CLINICALS
Intramuscular injections -- to lower part of the deltoid muscle (avoid injury to axillary nerve)
Muscle testing --- ask to abduct against resistance
INTERMUSCULAR SPACES
Quadrangular space
TERES MINOR # Axillary nerve
# Post. Circumflex humeral
vessels
TERES MAJOR (Surgical neck)
Upper triangular space

# Circumflex Scapular
vessel vvevessels
HUMERUS
(shaft)
M Lower triangular space L
# Radial nerve
# Profunda Brachii vessels
TRICEPS-LONG HEAD

Scapular movements
 Protraction- Serratus anterior
 Retraction- Rhomboids, Trapezius middle fibers
 Medial rotation- Weight of upper limb, Levator scapulae, Rhomboids
 Lateral rotation- Serratus anterior, Trapezius
 Elevation- Trapezius, Levator scapulae
 Depression- Weight of upper limb, Pec. Minor, Latissimus dorsi, Trapezius
Scapular Anastomosis
Around body of Scapula Over the Acromion process

Acromial branches of
- Suprascapular - thoracoacromial artery
branches of
- Deep branch of - Suprascapular artery
Thyrocervical trunk of
transverse cervical Subclavian A. - Posterior circumflex humeral
artery artery
-Circumflex scapular artery- branch of
subscapular A. of Axillary A.
Clinicals
These are anastomosis between -1st part of Subclavian artery
-3rd part of Axillary Artery
They provide a collateral circulation when distal part of subclavian A. or proximal part of Axillary A. is blocked
Important in coarctation of the Aorta

01. Regarding the mammary gland
a) Secretory cells do not develop until puberty.
b) Major lymph drainage is to the parasternal lypmph nodes.
c) Pectoral lymph nodes lie along the lateral thoracic artery.
d) The axillary tail lies along the superficial fascia and the skin.
e) Ducts are lined by stratified cuboidal epithelium.
f) Venous drainage is to the vertebral venous plexus.
g) The whole breast lies in the superficial fascia.
h) Most of the lymphatic drainage of the breast into the parasternal nodes.
i) Pectoral nodes lie along the subscapular artery.
j) During surgical removal of the breast the long thoracic nerve may get damaged.
k) Myoepitheliocytes are found around alveoli and ducts.
02. T/F regarding the breast

a) It is a compound tubuloalveolar gland.
b) The nipple has smooth muscles.
c) It receives its main blood supply from subscapular artery.
d) The axillary tail lies in relation to pectoral lymph nodes.
e) Gynaecomastia is seen in XYY.

Axilla
Definition
• Pyramidal shaped region situated between the upper part of arm and side of chest wall.
Boundaries
• Apex - truncated & bounded by,

Clavicle-upper border
Scapula-superior border
1st rib-outer border
- directed towards root of neck
- Also known as cervicoaxillary canal
• Base - directed downwards

- Skin, axillary fascia
• Anterior wall - Pec. Major

- clavipectoral fascia enclosing subclavius
and pec. Minor
• Pos. wall - Subscapularis

- Teres Major
- Lat. Dorsi
• Ant & post walls converge laterally.

• Lat. Wall - upper part of the shaft of the humerus
- coracobrachialis, short head of biceps
• Med. Wall - upper 4 ribs, their intercostals muscles
- Serratus ant.
Contents of the Axilla

• Axillary artery and its branches
• Axillary vein and its tributaries
• Infraclavicular part of the brachial plexus
• 5 groups of axillary lymph nodes and
associated lymphatics
Anterior group Lateral thoracic vein
Posterior group subscapular artery
Lateral group Axillary vein
Central group in the axillary fat
Apical group Axillary vein behind the clavicle
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Anterior, Posterior, lateral groups drain into the central group which in turn
drains into the apical group.
• Long thoracic and intercostobrachial (supplies skin of upper medial side of arm and axilla)
nerves
(These two nerves and thoracodorsal nerve can
Get damaged in surgeries of the axilla)
• Axillary fat and areolar tissue
Levels of axillary lymph nodes

• Level 1 – lateral to lower border of pec. minor
• Level 2 – behind pec. minor
• Level 3 – medial to upper border of pec. minor
Brachial plexus
• Plexus of nerves formed by the ant. Primary rami of the C 5 , C 6 , C7, C 8 , T 1 nerve
roots with contributions from the C 4 and T 2 nerve roots.
Roots – ant. Primary rami of C5 to T1

Trunks – upper, middle, lower
Divisions – ventral and dorsal divisions of each trunk
Cords – lateral, medial, posterior
Prefixed plexus -contribution by C 4 is large

- T₁ is reduced in size
-T 2 is often absent
post fixed plexus -contribution by T 1 is large
-T 2 is always present
-C 4 is absent
-C 5 is reduced in size
ROOTS between ant. & middle scaleni
TRUNKS Posterior triangle of neck
DIVISIONS behind middle 1/3 of clavicle
CORDS & BRANCHES axilla (within the axillary sheath so UL anesthesia)

Erb’s Duchenne Paralysis Klumpke’s Paralysis
Site Erb’s point – upper trunk – lower trunk
Cause Undue separation of head from - undue abduction of arm due

shoulders to- birth injury (breech delivery)
Due to –birth injury -clutching something after fall
fall on shoulder from a height
a anaesthesia
Nerve roots • C5, C6 • T1, C8
Muscles paralyzed Biceps,
Deltoid, • Intrinsic muscles of the
Brachialis, hand (T 1 )
Brachioradialis • ulnar flexors of wrist
and fingers (C 8 )
Supraspinatus,
Infraspinatus,
Supinator
Deformity Arm- adducted, medially rotated complete claw hand
Forearm- extended, pronated
Appearance Porters Tip Hand
Disability Lost movements, 1. Claw hand (unopposed

1. Abduction, lat. Rotation of action of long flexors &
arm extensors)
2. Flexion, supination of 2. Cutaneous anaesthesia-
forearm ulnar border of forearm
3. Biceps and supinator jerks and hand, lower medial
lost arm
4. Sensation lost of lower part 3. Horner’s syndrome- ptosis,
of deltoid & lateral side of miosis, anhidrosis,
arm & forearm enophthalmos

Injury to nerve to Serratus Ant. (Long thoracic nerve / Nerve of Bell)
Causes - sudden pressure on shoulder from above

- carrying heavy loads on shoulder
Deformity winging of scapula – inferior angle and medial

border of scapula are unduly prominent
Deformity -Pushing and punching actions absent, when trying

– winging of scapula
-Arm can’t be raised beyond 90° (overhead
abduction)
CUBITAL FOSSA
-Triangular, hollow space
-in front of elbow
Boundaries
- Laterally-medial border of brachioradialis

- Medially-lateral border of pronator teres
- Base-imaginary line joining 2 epicondyles
- Apex-downwards
- Roof-skin
• superficial fascia containing
median cubital vein, Lateral
cutaneous Nerve of forearm,
medial cutaneous nerve of
forearm
• Deep fascia
• Bicipital apponeurosis
-Floor-brachialis & supinator
Content (MBBS)
M to L-Median nerve N
-Brachial artery & its branches A
-Bicipital tendon T
-Superficial branch of radial nerve R

Brachial artery (divides at the level of the neck of the radius)
Radial artery ulnar artery
-Radial recurrent -anterior ulnar recurrent
-posterior ulnar recurrent
-common interosseous artery and branches
Clinicals
Medial cubital vein is chosen for intravenous injections
Brachial artery is used to record blood pressure
01. Regarding axillary region,

a) Divisions of the brachial plexus lie beneath the lateral 1/3 of the clavicle.
b) Damage to axillary nerve affects abduction.
c) Subclavian artery does not give any branches to scapular anastomoses.
d) All the lymph nodes which drain the mammary glands are palpable.
e) Apex of the axilla communicates with the posterior triangle of the neck.
02. In the axilla

a) Pectoral nodes lie along the subscapular artery.
b) Axillary fascia is a continuation of the prevertebral fascia.
c) Medial cord of the brachial plexus lies medial to the third part of the axillary artery.
d) Complete destruction of the brachial plexus will not affect sensation over the shoulder region.
e) Damage to axillary nerve results in the adduction of arm as seen in Erbs’ palsy.
03. Regarding the axilla

a) The pectoral lymph nodes are closely related to the lateral thoracic artery.
b) During surgical removal of the breast the long thoracic nerve may get damaged.
c) The intercostobrachial nerve is sensory to the floor of the axilla.
d) The axillary vein receives the brachial vein inferiorly.
04. Regarding the brachial plexus

a) Suprascapular nerves originate from the upper trunk.
b) Divisions lie behind the subclavius.
c) Posterior cord supplies the muscles of the posterior compartment.
d) The cords of the brachial plexus lie lateral to the first part of the axillary artery.
e) Lower trunk is likely to damage when the neck is suddenly turned to the other side.

Joints
Fibrous Cartilaginous Synovial
• Articular surfaces joined by

Synovial fluid
fibrous tissue
Joint capsule
• Limited movement
Synovial membrane (lines the
EG skull sutures, interosseus membrane
capsule, but does not cover articular
Primary Secondary surfaces)
Articular surface articular surface
Hyaline cartilage articular cartilage

articular
fibrocartilaginous disk
1) costochondral Normally placed midline

2)1st chondrosternal joint Eg:- Between the vertebrae,
1. Pubic symphysis
2. Manubriosternal
Synovial joints
Articular surfaces
• Plane- inter metatarsal

• Hinge- humero-ulnar, interphalangeal
• Pivot- atlanto-axial
• Bicondylar- knee, TM joint
• Ellipsoid- metacarpo-phalangeal
• Saddle- thumb carpo-metacarpal
• Ball and socket- shoulder
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Joints of Upper limb
Shoulder Joint / Glenohumeral Joint
• Type - Synovial , ball & socket, multiaxial
• Articular surfaces – Shallow, too small glenoid fossa ( deepened by glenoidal labrum )
Head of humerus ( 1/3 of a sphere) covered by hyaline cartilage
• Capsule – Collagen
Pain sensitive
Strong but lax (doesn’t strengthen the joint enough)
Attachment
Proximal – proximal margins of glenoidal labrum (margin of the glenoid fossa)
Distal – anatomical neck of humerus except inferiorly upto surgical neck
Superiorly allows the passage of biceps tendon
Supported by rotator cuff muscles SITS
• Synovial membrane – Lines the capsule

Not pain sensitive
Continued to surgical neck along with tendon of long head of biceps
Doesn’t cover articular surfaces
• Bursae – 1. Subacromial (Subdeltoid)
Situated Below-- coracoacromial arch & deltoid

Separates the supraspinatus tendon
Largest bursa in the body- Doesn’t communicate in normal conditions
2. Subscapular bursa- Communicates with joint cavity through an aperture between
superior and middle glenohumeral ligaments.
3. Infraspinatus bursa
• Ligaments Extracapsular
*Transverse humeral ligament
*Coracoacromial ligament
Middle
Intracapsular Superior
*Glenohumeral lig. Inferior

• Blood supply - Anterior & posterior circumflex humeral
-Suprascapular
-Subscapular
• Nerve supply - Axillary nerve , Musculocutaneous nerve, Suprascapular nerve
• Stability-
Muscular factors
1.Rotator cuff - Tendons of Supraspinatus, Infraspinatus, Subscapularis, Teres minor

blends with each other & joint capsule (doesn’t cover inferiorly)
2. Long heads of biceps and triceps- Only support inferiorly is tendon of long head of triceps
Ligamentous factors
3. coracoacromial arch- superiorly secondary socket for the head of the humerus
4. Glenoid labrum Deepning the glenoid cavity
• Bony stability is less.
• Movements -Abduction
*initiated by Supraspinatus (1st 15)
*up to 90 - Deltoid
*up to 180 - Serratus anterior & Trapezius
When abduction begins, Scapula rotates (Humerus : Scapula = 2 : 1 ) SITS also
p plays a role here by providing stability to head of humerus

Muscles acting on shoulder joint
Abductors - Supraspinatus, Deltoid (middle fibers), Serratus anterior Trapezius
Adductors -Lady between 2 Majors
Latissimus dorsi, Teres major, Pectoralis major
Flexors - Pectoralis major (clavicular), Deltoid (anterior fibers), Coracobrachialis,

Short head of biceps
Extensors - Deltoid (posterior fibers), Teres major, Latissimus dorsi, Pectoralis Major
(sternocostal fibers)
Medial rotators - Pectoralis major, Latissimus dorsi, Teres major, Deltoid (anterior fibers),
Subscapularis
Lateral rotation - Infraspinatus, Teres minor, Deltoid (posterior fibers)
Clinicals
Dislocation – inferiorly (usually occurs in abducted position)
Reduced by Kocher’s method
Axillary nerve can be damaged.
Deltoid is paralyzed loss of abduction
Sensory loss over batch area
Rounded contour is lost acromia become prominent
*Pain arch - 60 - 120
Subacromial bursitis???

Elbow Joint
• Type - Synovial, compound.
• 3 articulations.
1. humero-ulnar (hinge) – trochlea trochlear notch of ulna
2. humero-radial (ball & socket) – capitulum radial head
3. Superior radio-ulnar (pivot)- head of radius radial notch of ulna
• Capsule – round articular arrangement.

Lateral & medial epicondyles are extracapsular.
Thin and loose anteriorly and posteriorly.
Reinforced medially & laterally by medial & lateral collateral ligaments.
Lateral ligament expands to form annular ligament.
Annular ligament is attached to the anterior and posterior margins of radial notch of ulna.
• Blood supply – Anastomoses around the elbow joint.
• Nerve supply – Ulnar, Radial, Median, Musculocutaneous.
• Movements – Flexion – brachialis, biceps brachii, brachioradialis.

Extension – triceps brachi, anconeus.
• Carrying angle – Disappear in full flexion. (Normally 5 - 15away from the body.)
Clinicals
• Dislocation – posteriorly triangular relationship is lost and coranoid may fracture
• Subluxation - pulled elbow(radial head subluxate through the ligament)
• Minors elbow – bursitis over the olecranon process.
• Tennis elbow- pain and tenderness over lateral epicondyle…..
• Golfers elbow????(Medial epicondyle….)

Radioulnar Joint – Pivot
During pronation head of the radius rotates within the annular ligament.
Distal radius rotates in front and around the ulna.
Interrosseus membrane – downwards and medially from radius to ulnar
Superior aperture- posterior interosseous vessels
Inferior aperture- anterior interosseous vessels
Other than providing attachments for muscles and binding bones transmits forces from radius to
ulna.
Wrist Joint – Biaxial, synovial, ellipsoid
Between lower end of radius (+articular disc of inferior radioulnar joint),& scaphoid,
lunate, triquetral(SLT)
1st Carpo –Metacarpal Joint - Has a separated cavity (saddle)
Metacarpo- Phalangeal Joint – synovial ellipsoid variety
Interphalangeal Joint – Hinge

SUPINATION – Chiefly by biceps brachi
Supinator
PRONATION – Cheifly by pronator quadratus

Pronator teres
Supination more powerfull
AXIS OF BOTH – Between the two heads of ulnar & radius

Non-stationary due to non-fixed lower end of ulna
Acromio Clavicular Joint
• Type - Plane, Atypical synovial
• Between lateral end of clavicle & acromion process of scapular
• Articular facets are covered by fibrocartilage
• Has incomplete articular disc
• Coracoclavicular ligament(conoid and trapezoid parts)
• Stability of the joint is provided by coracoclavicular ligament. It transmits the weight of scapula to
clavicle.
Sternoclavicular Joint
• Type - Atypical Synovial, ball and socket
• Articular facets – covered by fibrocartilage
• Has complete articular disc
• Ligaments
1) Costoclavicular ligament
➢ Main stabilising factor
➢ It transmits the weight from clavicle to axial skeleton
2) Anterior and posterior sternoclavicular ligaments
3) Interclavicular ligament
01. The short (cuff) muscles of the shoulder joint
a. comprise subscapularis, supraspinatus, infraspinatus and teres major

b. provide the greatest stabilizing foresees at the shoulder joint
c. provide maximal support to the inferior aspect of the shoulder joint
d. are all attached to the greater tuberosity of the humerus
e. are all supplied by the branches of the posterior cord of the brachial plexus

02. The biceps muscles
a. is attached to the scapula
b. has an intra-articular tendon
c. is attached to the humerus
d. has an aponeurosis passing to the dorsal surface of the radius
e. is powerful pronator of the forearm
f. distal attachment is to radial tuberosity and by the bicipital aponeurosis to the deep facia of
the medial side of the forearm
03. The triceps muscle

a. is attached to the infraglenoid tubercle of the scapula
b. is attached to the boards of the radial groove of the humerus
c. is attached to the ulna olecranon
d. act mainly to the shoulder joint
e. is supplied by the median nerve
04. The anterior superficial group of forearm muscles

a. all arise from the anterior surface of the lateral epicondyle of humerus
b. includes pronator teres
c. all are supplied by the branches of the median nerve
d. may affect flexion of at the elbow
e. has attachment to the anterior surface of both the radius and the ulna
05. The supinator muscle

a. forms part of the flor od the cubital fossa
b. is attached to the medial epicondyle of the humerus
c. is attached to the proximal end of ulnar
d. is attached to the proximal end of the radius
e. is supplied by the ulane nerve
06. The interossei muscles

a. are 8 in total
b. all arise by two heads from adjacent metacarpal bones
c. all are attached distally to the base of the corresponding proximal phalanx and the dorsal
extensor expansion
d. may flex the metacarpophalangeal joints
e. may extend the middle and distal phalanges
f. these muscles are attached to the bodies of the metacarpal bones, the palmer by a single head
and dorsal by two heads, from adjacent sides of the metacarpal bones
07. The elbow joint

a. is lined by synovial membrane which is continus with that of the superior radio ulnar joint
b. is strengthened by radial colateral ligement
c. is strengthened by an ulnar colateral ligament
d. owes most of its stability to the close proximity of brachialis and triceps
e is supplied by posterior interossious nerve
d. the most important factors in stabilising the joint are the shape of the bones and strong
capsule
e. its is also supplied by the branches of radial , median, ulnar and musculocutaneous nerves

08. The proximal radio ulnar joint
a. is of condyloid variety
b. occers between the heads of the radius and the radial notch of the ulanr
c. is stabilized mainly by the surrounding capsular ligement of the elbow joint
d. owes its stability mainly to the annular ligament
e. is separated from the elbow joint by a fibrocartilaginous disc
09. The wrist joint

a. comprise the lower artcular surfaces of the radius and ulnar and the proximal row of carpal
bones
b. usually coomunicates with the distal radio-ulanr joint
c. owes its sability to the neighbouring tendons
d. is an ellipsoid joint
e. contributes the major degree of flexion at the wrist

Nerves – Upper Limb
Musculocutaneous Nerve
• Root values are C5, C6, C7 anterior primary rami.
• Main nerve of the front of the arm & cutaneous supply to lateral side of forearm.
• Originates from the lateral cord of the brachial plexus at the lower border of Pect Minor.
• In the axilla lies lateral to the 3rd part of the axillary artery & lateral root of median nerve.
• It supplies to the Coracobrachialis.
• Then pierces the Coracobrachialis and leave the axilla.
• Enter the anterior compartment of the arm, runs between Brachialis & Biceps brachi.
• Giives motor branches to Biceps brachi & Brachialis.
• At the level of the elbow, becomes superficial by piercing the deep fascia lateral to the tendon
of biceps and continues as the lateral cutaneous nerve of forearm.
• Gives articular branches to the elbow joint through the motor branch to brachialis.
Axillary Nerve
• Root values are C5, C6 anterior primary rami.
• Origin in axilla from posterior cord of brachial plexus, posterior to the axillary artery.
• Leaves axilla through the quadrangular space. (supply no structure within axilla)
• Below the capsule of shoulder joint.
• Gives articular branches to shoulder joint.
• Accompanied by posterior circumflex humeral vessels.
• Passes behind the surgical neck of humerus.
• Divides into anterior and posterior divisions.
 Anterior division – Winds around the surgical neck of humerus with posterior
circumflex humeral vessels.
Supplies Deltoid.
 Posterior division – Supplies Teres Minor.
Cutaneous supply to skin over lower half of deltoid via Upper lateral cutaneous nerve
of arm.

Clinical
Damaged in inferior dislocation of shoulder, Fracture of the surgical neck of the humerus &
Misplaced injection into deltoid.
 Paralysis of deltoid.
 Arm can’t be abducted beyond 15 degrees.
 Sensory loss over lower half of deltoid. (regimental badge sign)
 Greater tubercle becomes prominent. (atrophy of the deltoid) - flattened contour of
shoulder.
Median Nerve (labourer’s nerve)

• Root values are C5, C6, C7, C8, T1 anterior primary rami.
• Origin by the union of medial root from medial cord & lateral root from lateral cord in axilla
lateral to the axillary artery, where medial root crosses 3rd part of axillary artery from medial
to lateral and join with lateral root to form the median nerve.
• Nerve runs lateral to the 3rd part of the axillary artery.
• In the upper part of arm, runs lateral to the brachial artery.
• At the level of insertion of corachobrachialis, crosses brachial artery from lateral to medial
anteriorily.
• In the lower part of the arm, runs medial to brachial artery.
• Supplies Brachial artery.
• Gives a motor branch to Pronator teres before leaving the arm.
• Runs anterior to elbow joint supplying it with an articular branch.
• In the cubital fossa, runs medial to brachial artery. (RTAN)
• Gives motor branches to Flexor carpi radialis, Palmaris longus, Flexor digitorum superficialis.
• Passes between two heads of pronator teres. (here ulnar artery lies deep to the deep head of
pronator teres)
• Passes deep to the fibrous arch of flexor digitorum superficialis, on flexor digitorum
profundus.
• In the forearm gives Anterior interosseous branch supplying lateral half of Flexor digitorum
profundus, Flexor policis longus, Pronator quadratus.
• Continuation descends deep to flexor digitorum superficialis.
• At the lower border of forearm, gives Palmar cutaneous branch which goes superficial to
flexor retinaculum supplying lateral 2/3rd of palm.
• At wrist lies deep and lateral to the palmaris longus tendon.
• Enter the Carpal tunnel just deep to the flexor retinaculum.
• Lies medial to the muscles of thenar eminence.
• Gives off recurrent branch to thenar muscles. (Abductor pollicis brevis, Flexor pollicis brevis,
Opponens pollicis)
• Divide into medial and lateral branches.
• Gives Digital branches to 1st & 2nd lumbricals.
• Cutaneous supply to Palmar surface of lateral 3 ½ digits with their nail beds & distal dorsal
skin.

Clinical
If damage is above the elbow. (supracondylar fracture)
 Motor loss - 4 ½ flexors and 2 pronators of forearm - pointing index

finger while making fist due to unopposed action of extensors /
supinated forearm / ulna deviation of wrist.
 Thenar eminence muscles - wasting, mainly loss of abduction.
 1st and 2nd lumbricals paralysed.
 Gross movements of fingers are lost - labourer’s nerve.
Cutaneous loss-
 Lateral 2/3rd of palm.

 Palmar surface of lateral 3 ½ distal phalanges & their nail beds.
Vasomotor changes-
 Oedema
 Pigmentation of skin
 Friable nails
 Dryness of skin
Trophic changes –
 Flattening - lat. side forearm muscles.

- thenar eminence flattened.
- Ape like thumb – thumb adducted laterally rotated.
 Ulcers - lateral 3 ½ digits
 Commonly injured at wrist lies beneath Palmaris longus tendon
Carpal Tunnel Syndrome
 Caused by compression of median nerve within carpal tunnel.

 Causes - Dislocation of lunate.
- Bursitis of ulnar and radial bursae.
 Paralysis of thenar eminence leading to ape like hand.
 No cutaneous loss of lateral 2/3rd of palm but of palmar surface of lateral 3 ½ digits with
their nail beds is lost.
Clinical testing – median nerve
1) Unable to pick a pin with thumb & index finger. (Due to inability to oppose thumb)
2) Pen test for abductor pollicis brevis.
Lay the hand flat on a table, palm directed upwards. Patient is unable to touch a pen
held in front of the palm by a thumb.
3) Ape like hand. (adducted & lateraly rotated thumb)

4) Sensory loss.

Ulnar Nerve (Musician’s nerve)
• Root values are (C7), C8, T1 anterior primary rami.
• Originates from medial cord, medial to the 3rd part of the axillary artery.
• In the axilla, between the axillary vein and axillary artery on a deeper plane.
• In the arm, medial to brachial artery, runs downwards with it in its proximal part.
• Pierce the medial inter-muscular septum at the level of insertion of coracobrachialis.
• Passes into the posterior compartment with superior ulnar collateral artery.
• Passes behind the medial epicondyle (here it could be palpated, causes tingling sensations so
humerus is called funny bone)
• Enters forearm between two heads of flexor carpi ulnaris.
• Runs between flexor carpi ulnaris and flexor digitorum profundus medial to the ulnar artery
at lower two thirds of forearm.
• Supplies Flexor carpi ulnaris and medial ½ of Flexor digitorum profundus.
• Gives Palmar cutaneous branch for medial 1/3rd of palm and Dorsal cutaneous branch for
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medial of dorsum of hand.
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• At wrist lies between flexor carpi ulnaris and flexor digitorum superficialis.
• Passes superficial to the flexor retinaculum within guyon’s canal alongside the radial border
of the pisiform bone and medial to the ulnar artery.
• Divides into superficial and deep branches.
• Superficial branch palpated on hook of hamate, supplies Palmaris brevis and cutaneous
supply to ulnar 1 ½ fingers.
• Deep branch passes between the heads of origin of flexor digiti minimi and abductor digiti
minimi and through the origin of opponens digiti minimi.
• Passing down to the intrerossei, grooves the distal border of the hook of hamate and arches
in the palm within the concavity of the deep palmar arch.
• Gives motor branches to three hypothenar muscles, two lumbricals on ulnar side, interossei
and end by supplying Adductor pollicis.
Clinical
Damage at wrist
 Commonest.
 Produces Ulnar claw hand. (Claw hand - Hyperextension at m/p joints
due to paralysis of interossei &lumbricals, Flexion at I/p joints)
 Sensory loss – medial 1/3rd of palm & medial 1 ½ fingers including nail
beds.
 Vasomotor & trophic changes.
Cubital tunnel syndrome
 Ulnar nerve gets entrapped between two heads of FCU leading to

ulnar claw hand, loss of hypothenar eminence and muscle
paralysis.
Ulnar paradox
 If injured @elbow, clawing of fingers is less, because medial half of FDP is also paralysed.
 If injured @wrist, clawing is more, because intact FDP flexes digits more.
 Distal more clawing; Proximal less clawing.

Control fine movements of fingers - musician’s nerve.
Complete claw hand – both ulnar and median nerves get paralysed.
Dorsal guttering - wasting of interossei
Clinical Testing
1) Place the hand on a flat surface.

2) Place a paper between two fingers.
3) See how firmly it can be held.
Radial Nerve
• Root values are C5, C6, C7, C8, T1 anterior primary rami.
• Originate from the posterior cord posterior to the 3rd part of the axillary artery.
• In the axilla gives motor branches to long head & medial head of Triceps and Posterior
cutaneous nerve of arm.
• Passes through the lower traingular space along with the profunda brachi vessels.
• Enter the posterior compartment of arm.
• In the upper part of the arm, runs posterior to brachial artery.
• Then enters to the radial groove between medial and lateral head of triceps along with
profunda brachi vessels runs downwards medial to lateral.
• Gives motor branches to lateral & medial heads of Triceps brachi and Anconeus.
• Cutaneous branches Lower lateral cutaneous nerve of arm and Posterior cutaneous nerve of
forearm.
• At the level of insertion of coracobrachialis, pierces the lateral intermuscular septum with
anterior descending branch of profunda brachi artery and enter the anterior compartment of
arm.
• Descends on lower lateral front of arm deep in interval between brachialis on medial side and
brachioradialis and ECRL on lateral side to reach capitulum of humerus.
• Supplies Brachioradialis, lateral part of Brachialis, Extensor carpi radialis longus and articular
branches to elbow joint.
• Most laterally at cubital fossa. (RTAN)
• Divides into superficial and deep branches at the level of the lateral epicondyle.
• Superficial branch runs deep to brachioradialis (middle 1/3rd is accompanied by radial artery)
Winds around the radius deep to tendon of brachioradialis.
Enter the anatomical snuff box and divide into cutaneous branches supplying posterior aspect
of lateral 3 ½ digits except their nail beds and lateral 2/3rd of dorsum of hand.
• Deep branch gives branches to Extensor carpi radialis brevis, pass between the two heads of
supinator and winds around the radius and sprays out as the Posterior interosseous nerve
accompanying posterior interosseous artery.
Supply all muscles of posterior compartment of forearm except Anconeus, Brachioradialis
and Extensor carpi radialis longus.

Clinical
• In the axilla - Crutch palsy
• Saturday night palsy
• Fracture of the shaft of the humerus
• Damage to the radial nerve causes,
 Wrist drop
 No or weak extension of elbow
 Weak extension of wrist, MP and IP joints
 Sensory loss in the 1st dorsal web space
Damage to posterior interosseous nerve does not produce wrist drop. (ECRL is very
powerful which is supplied before division of radial nerve)
Long Thoracic Nerve

• Root values are C5, C6, C7.
• Origins at the roots of brachial plexus.
• Supply Serratus anterior.
• Damage results in winging of scapula.
Cutaneous
Innervation of
Upper Limb
Intercostobrachial
nerve
• This nerve is the lateral
cutaneous branch of the second
intercostal nerve.
• Emerges from the second
intercostal space anterior to the
long thoracic nerve and crosses the
axilla.
• Supplies the skin of the axilla
and over a variable extent on the
medial side of the upper arm, often
communicating with the medial
cutaneous nerve of the arm.
• It may be in contact with level
I lymph nodes and be at risk during
node excision.
• The thoracoepigastric vein
crosses the nerve vertically on its
posterior aspect and aids
identification.

Dermatomes of Upper Limb
Anterior view Posterior view
Myotomes of Upper Limb
C6, C7, C8
C7, C8

ARTERIAL SUPPLY OF THE UPPER LIMB
1) Axillary artery
• Continuation of Subclavian artery.
• Extends from outer border of 1st rib to lower border of Teres major.
• Continues as Brachial artery.
• Enclosed within axillary sheath with cords of brachial plexus.
2nd part

• 3 parts – divided by Pec. Minor – 1st part above, 2nd part behind and 3rd part below Pec. Minor
Branches
SALSAP
• 1st part -Superior Thoracic Artery
• 2nd part- Acromiothoracic Artery Acromial APCD

(Also thoracoacromial Artery) Pectoral
Clavicular
Deltoid
-Lateral Thoracic Artery
• 3rd part -Subscapular

 Circumflex scapular
 Continuation - thoracodorsal artery
-Anterior circumflex humeral Artery
 Ascending branch
-Posterior circumflex humeral artery
 Descending branch
Anteriorly Posteriorly Laterally Medially
1st part -skin -serratus ant. -lateral & pos. -Axillary vein
-superf. fascia -medial cord of cords of brachial
-deep fascia brachial plexus plexus
-pec major with medial
- clavipectoral pectoral nerve
fascia -1st intercostal sp.
2nd part -skin -post. Cord of -lateral cord of -Axillary vein
-superf. fascia brachial plexus brachial plexus -medial cord of
-deep fascia -subscapularis -coracobrachialis brachial plexus
-pec major -medial pectoral
-pec minor nerve
3rd part -skin -radial nerve -median nerve -Axillary vein

-superf. fascia -Axillary nerve -musculocut.n. -ulnar nerve
-deep fascia -subscapularis -coracobrachialis -medial cutane.
-pec major -tendons of lat nerves of arm &
-medial root of Dorsi & teres forearm
median nerve major

Scapular Anastomosis
Around body of Scapula Over the Acromion process

Acromial branches of
- Suprascapular - Thoracoacromial artery
Branches of
- Deep branch of - Suprascapular artery
Thyrocervical trunk of
transverse cervical - Posterior circumflex humeral artery
Subclavian A.
artery --
-Circumflex scapular artery- branch of
subscapular A. of Axillary A.
Clinicals
These are anastomosis between -1st part of Subclavian artery
-3rd part of Axillary Artery
They provide a collateral circulation when distal part of subclavian A. or proximal part of Axillary A. is blocked
Important in coarctation of the Aorta
2) Brachial Artery
• Continuations of the Axillary Artery.
• Extends from the lower border of Teres Major to front of the Elbow.
• In the proximal arm, lies on medial side.
• In the distal arm, it moves laterally to assume a position midway between lateral epicondyle and the
medial epicondyle of the humerus.
• It crosses anteriorly to the elbow joint, lies immediately medial to the tendon of biceps brachii muscle.
Relations of important structures to Brachial Artery
 Median Nerve -lies laterally in the upper part; Crosses in front of the of the artery from lateral to
medial side (at level of insertion of Coracobrachialis)
 Ulnar nerve -lies medially in the upper part
 Radial nerve -lies posteriorly in the upper part
 Basilic vein -lies medial to the upper part
Branches
-profunda Brachii artery -Superior Ulnar collateral artery
-Inferior ulnar collateral artery -Terminal branches – radial, ulnar (in cubital fossa)

3) Profunda Brachii Artery
• Arises just below Teres major.

• Accompanies radial nerve in lower triangular space and
radial groove.
• Pass along the radial groove on the posterior surface of the
humerus deep to the lateral head of triceps brachii.
Branches -Ascending branch

-Anterior descending branch (radial collateral)
-Posterior descending branch (middle collateral)
-(Nutrient branch to humerus)
4) Ulnar Artery
• Main artery of forearm.
• Starts at the level of neck of Radius.
• Oblique in upper 1/3 & vertical in lower 2/3.
• Runs on medial side of forearm with ulnar nerve (in lower
part) under flexor carpi ulnaris muscle upon flexor
digitorum profundus.
• Median nerve crosses superficially to ulnar artery
seperated by deep head of Pronator teres.
• Leaves forearm superficial to flexor retinaculum.
• Continues as superficial palmar arch in the hand.
Branches -Common interosseous branch (below radial tuberosity)

 Anterior interosseous
o Gives median artery
 Posterior interosseous
o Gives interosseous recurrent branch
-Anterior ulnar recurrent a.

-posterior ulnar recurrent a.
-Muscular branches
-palmar and dorsal carpal branches
-Deep palmar branch (completes deep palmar arch)
5) Radial Artery
• Main artery of hand.

• Starts at the level of neck of Radius.
• Lies laterally on muscles forming radial bed with radial nerve. (only in middle 1/3 of forearm)
• Medially related to brachioradialis in its whole length.
• Gives off a branch to assist in forming superficial palmar arch.
• Leave forearm by turning posteriorly then passes deep to the tendon of abductor pollicis longus and
extensor pollicis brevis to enter the anatomical snuffbox. (pulsation can be felt)
• Pierces the first dorsal interosseous muscle and adductor pollicis.
• Runs between 1st and 2nd metacarpals and goes on to form the deep palmar arch, with the deep branch
of ulnar artery.

Branches -radial recurrent artery
-muscular branches
-palmar carpal branch
-superficial palmar branch
-princeps pollicis A.
-radialis indicis a.
Elbow Anastamosis
Surface marking of arteries

Midpoint of clavicle
Axillary artery
Junction of Ant. 1/3 & posterior 2/3 of lateral wall of axilla
(At lower limit where pulsations are felt)
Brachial artery
Level of neck of radius
Medial to biceps tendon
Radial artery ulnar artery
Wrist – radius (ant. Border) laterally Junction – upper 1/3 & lower 2/3 of
Flexor carpi radialis tendon medially forearm medial border
(Radial pulse felt) Lateral to pisiform

Upper limb - venous drainage
Dorsal venous arch
Medial end
Basilic vein Lateral end
(Post axial) Cephalic vein
(preaxial)
-runs along medial side of arm & forearm -lies in the roof of anatomical snuff box
-Pierces deep fascia at the middle of arm -Lateral border of upper limb
-continues as axillary Vein at the lower -Most of the blood drains into basilic vein via
border of teres major median cubital vein
-Can be used for emergency venous cut
down at the deltopectoral groove.
-It pierces clavipectoral fascia and drains
into axillary vein
Median Cubital vein

-shunts blood from cephalic to basilic
 Cardiac catheterization
 Withdrawal of blood
 Suitable for intravenous injections- WHY?
1) Separated from brachial artery by bicipital aponeurosis
2) Perforator vein, piercing the aponeurosis fixes the MCV
Upper Limb- Lymphatic drainage

Two groups of one or two lymph nodes each.
 Infraclavicular group
• Lie along the cephalic vein in the upper part of the deltopectoral groove.
• Drain through the clavipectoral fascia into the apical axillary nodes.
• Receive afferents from the superficial tissues of the thumb and lateral side of forearm and arm.
 Supratrochlear group
• Lie in the subcutaneous fat just above the medial epicondyle.

• Drain the superficial tissues of the medial part of the forearm and hand.
• Afferent lymphatics running with the basilic vein and its tributaries.
• Efferent vessels pass to the lateral group of axillary nodes.

HAND
Bones of the hand
Carpal bones
• Arranged in two rows

proximal row- scaphoid, lunate, triquetral, pisiform
distal row- trapezium, trapezoid, capitate, hamate
Pisiform on the anterior surface of triquatrel where FCU is inserted
Scaphoid- tubercle (palpable)
Crest of trapezium
Hook of the hamate
Carpus is arched transversely, the palmer aspect being concave

The concavity is maintained by,
1) Shapes of Individual bones- broader posteriorly than anteriorly except lunate (Lunate is broader
posteriorly)
2) The tough flexor retinaculum passing from the scaphoid and the ridge of the trapezium laterally
to the pisiform and the hook of the hamate medially
3) Arrangement of metacarpals relative to carpal bones
She Looks Too Pretty

Try To Catch Her

• Fracture of Scaphoid
- Caused by falling on the palm with the hand abducted (
There the scaphoid lies directly facing the radius)
- May cause tenderness of anatomical snuff box (floor is
formed by scaphoid)
- 1/3 of cases – blood supply enters distally along waist
- If fracture is proximal to the waist
Avascular necrosis of proximal segment
Dislocation of Lunate carpal tunnel syndrome

- Carpal bones are broader posteriorly than anteriorly except Lunate
Therefore fall on the hand may dislocate carpal arch backwards from lunate (perilunate dislocation
of the carpus)
Dislocated carpus may then reduce spontaneously and tilt it over; its distal surface
facing forwards (dislocation of the lunate)
Increased pressure in the carpal tunnel

Leading to Carpal tunnel syndrome
CARPAL TUNNEL
• a fibro-osseous tunnel at the wrist

• formed by concavity of carpal bones - posteriorly
flexor retinaculum - anteriorly
Flexor Retinaculum
• A strong fibrous band, 2-3cm transversely and longitudinally
• Lies across the carpus at the proximal part of the hand
• Proximal limit- the level of the distal, dominant skin crease on the front of the wrist
• Attachments of the flexor retinaculum
- Laterally-tubercle of scaphoid & crest of trapezium
- Medially-hook of hamate & pisiform bone
• Surface marking of flexor retinaculum

Structures passing through the carpal tunnel
1. Median nerve lies most superficially within the canal

2. Flexor pollicis longus
3. Flexor digitorum profundus tendons
4. Flexor digitorum superficialis
5. Flexor carpi radialis (within a separate tunnel)
6. Radial bursa enclosing flexor pollicis tendon
7. Ulnar bursa enclosing long flexor tendons ( laterally opens,containing superficialis and profundus
tendons)
Structures superficial to the flexor retinaculum
1. Palmaris longus tendon

2. Ulnar artery & nerve(in guyons canal which is closed by the slender band of fascia called volar carpal
ligament)
3. Palmar cutaneous branch of median nerve and ulnar nerve
Clinicals
Carpal tunnel syndrome
Symptoms caused by compression of the median nerve within the carpal tunnel due to any lesion
deminishing the size of the compartment
- dislocation of the lunate
- arthritis
- odematous synovial sheaths
Dislocation of Lunate carpal tunnel syndrome

 Carpal bones are broader posteriorly than anteriorly except Lunate.
Therefore fall on the hand may dislocate carpal arch backwards from lunate
Increased pressure in the carpal tunnel
Carpal tunnel syndrome
• symptoms
1. Motor changes - ape like thumb deformity./ wasting of thenar eminence
loss of opposition
2. Sensory changes – loss of sensation in lateral 3 ½ digits

No sensory loss over thenar eminence
(because it is supplied by a branch of the median nerve which arises at the forearm)
3. Vasomotor changes - warm, reddish, dry & scaly

4. Trophic changes – nails get cracked with atrophy of pulp spaces

WRIST AND HAND
 Skin
• Thick
• Immobile
• Creased
 Superficial fascia
 Dense fibrous bands
 Bind skin to palmar aponeurosis
 Contains a subcutaneous muscle, Palmaris brevis
 Deep fascia
- wrist-flexor retinaculum
- palm-palmar aponeurosis
Palmar aponeurosis
• The deep fascia in the central region of the palm, reinforced by a superficial layer of longitudinal
fibres continuous with the tendon of the palmaris longus muscle and by deeper transverse fibres
• Triangular in shape
• Proximal apex blends with flexor retinaculum & continuous with the tendon of palmaris longus
• Distally divides into 4 strips; 1 for each finger
i. Distally divides into 2 layers
ii. Superficial layer – blends with skin
iii. Deep layer – 4 slips- blends with fibrous flexor sheaths
iv. No slip for thumb – more mobile( but plantar aponeurosis has)
• Fingers fibrous flexor sheaths (see grants pic)
Forms a blind fibrosseous tunnel – tendons of FDS and FDP
and synovial sheath lie there.

Clinical:
1) Dupuytren’s contracture
• Inflammation involving the ulnar side of palmar aponeurosis

• Thickening & contraction of aponeurosis
• Results- longitudinal thickening in the palm together with flexion of the metacarpophalangeal and
proximal interphalangeal joints- proximal and distal phalanges become flexed, can’t be straightened
• Distal interphalangeal joints- not involved
* Ring finger most commonly involved
2) Volkmann’s contracture
• Follows ischaemia and subsequent fibrosis and contraction of the long flexor and extensor muscles
of the forearm
• Deformities
1) Flexion at the wrist- since the flexors of the wrist are bulkier than the extensors,
their fibrous contraction is greater
2) Extension at the metacarpophalangeal joints- due to the contracture of the long
flexors inserted into the proximal phalanges
3) Flexion at the interphalangeal joints- due to the contracture of long flexors; inserted
into the distal and middle phalanges
Muscles of the Hand
 Extrinsic muscles
 Intrinsic muscles
Intrinsic muscles of hand- 20

•Muscles of thenar eminence- 3
1) opponens pollicis
2) flexor pollicis brevis
3) abductor pollicis brevis
• One adductor for thumb – Adductor pollicis
• Hypothenar muscles- 4
1) opponens digiti minimi
2) Flexor digiti minimi brevis
3) Opponens digiti minimi
4) Palmaris brevis
• 4 lumbricals
• 4 palmar interossei
• 4 dorsal interossei

Thenar muscles
Muscle Nerve Action
abductor median nerve (recurrent abduction of thumb C/M & M/P joints
pollicis branch) [acciossiated with medial rotation]
brevis
flexor superficial - median flexion of thumb
pollicis nerve deep head may be
brevis by ulnar nerve
opponens median nerve(recurrent opposition - thumb [flexion, medial rotation]

pollicis branch)
Hypothenar muscles
Muscle Nerve Action

opponens digiti ulnar nerve deep branch opposition with thumb,
minimi lat. Rotation
flexor digiti flexion of M/P joints
minimi brevis
abductor digiti abduction of M/P joints
minimi
- Other intrinsic muscles
Muscle Nerve Action

adductor ulnar nerve deep adduction of thumb
pollicis
palmaris ulnar nerve helps gripping [make
brevis superficial hypothenar more
prominant]
lumbrical 1,2 -median / 3,4 flexion of M/P joints,
origin from ulnar n. deep extention of I/P joints
the tendons
of FDP
dorsal ulnar nerve deep Inserion via Abduction of fingers
interossei extensor
expansion
palmar ulnar nerve deep Adduction of finger
interossei

Movements of the Thumb
1) Flexion at the metacarpophalangeal and interphalangeal joints- by flexor pollicis longus and
brevis
2) Extensiom at the metacarpophalangeal and interphalangeal joints- by extensor pollicis
longus and brevis
3) Palmar abduction ( abduction)- by abductor pollicus brevis ; thumb moves away from the
index finger in a plane at right angles to the palm
4) Radial abduction (extension)-by abductor pollicis longus and extensor pollicis brevis
5) Adduction- by adductor pollicis ; further transpalmar adduction is by flexor pollicis brevis
6) Opposition- a composite movement making the thumbnail lie parallel with the nail of the
opposed finger
Testing of Some Intrinsic Muscles
1) Pen test for abductor pollicis brevis- Lay the

hand flat on a table with the palm directed
upwards. The patient is unable to touch
2) Test for opponens pollicis – Request the

patient to touch the proximal phalanx of 2nd
to 5th digits with the tip of the thumb
3) The dorsal interossei are tested by asking the

subject to spread out the fingers against
resistance. As index finger is abducted one
feels 1st dorsal interosseous

4) The palmar interossei and
adductor pollicis are tested
by placing a piece of paper
between the fingers,
between thumb and index
finger and seeing how
firmly it can be held
Test for palmar interossei Testing adductor pollicis
5) Froment’s test or book test for adductor

pollicis muscle- When the patient is asked
to grasp a book firmly between the thumb
and the other fingers of both the hands,
the terminal phalanx of the thumb on the
paralyzed side becomes flexed at the
interphalangeal joint (by the flexor pollicis
longus which is supplied by the median
nerve)
6) The lumbricals and interossei are tested by asking the subject to flex the fingers at the
metacarpophalangeal joints against resistance

Dorsal digital/Extensor expansion
• Triangular aponeurosis, covering

dorsum of proximal phalanx and
metacarpophalangeal joint
• Base is proximal and the apex is
distal.
• Seperated from M/P joint by a
bursa
• Tendons of interossei and
lumbrical muscles attaches to
posterolateral corners
• Deep transverse metacarpal ligaments are attached to the corners
• Tendon of extensor digitorum occupy the central part
• Near the proximal IP joint, the extensor tendon divides in to a central slip and two collaterals
• Central slip is inserted on the dorsum of the base of the middle phalanx
• Two collaterals are inserted on the dorsum of the base of the distal phalanx
• Extensor expansion forms the dorsal part of the fibrous capsule of the MP and IP joints
• There is no extensor hood in thumb , but the extensor pollicis longus tendon recieves a fibrous
expansion from both abductor pollicis brevis and adductor pollicis
SEQ – Describe the arrangement of tendons of the middle finger. (70)
Synovial sheaths of flexor tendons
ULNAR BURSA RADIAL BURSA
1. Ulnar bursa (common flexor synovial sheath)
• is a common synovial sheath, enclosing the flexor tendons of fingers (FDS& FDP)
• pass deep to flexor retinaculum
• extent upwards -2”-3” into forearm
Downwards –upto middle of shafts of metacarpal bones into palm
Lower medial end- continuous with digital synovial sheath of the little finger
• Seems like tendons have invaginated the bursa laterally.
Clinical:
Infection of little finger infection of ulnar bursa forearm space of parona
Hour glass swelling

2. Radial bursa
• synovial sheath of flexor pollicis longus tendon
• Extent – Upwards – 2”-3” into forearm
Downwards – up to distal phalanx of thumb
3. Digital synovial sheath

• enclose flexor tendons in fingers
• line the fibrous flexor sheaths
• Digital synovial sheaths of index, middle & ring fingers are separate & independent
• Terminate proximally at the levels of the heads of the metacarpals
• Synovial sheath of the little finger continues proximally with the ulnar bursa and that of the
thumb with the radial bursa
SPACES OF THE HAND
• Palmar spaces Hypothenar space

Midpalmar space
Thenar space
• The forearm space of parona
• Pulp space
(01) Pulp spaces of the fingers
-in the tips of fingers

-subcutaneous fat arranged in tight compartments formed by fibrous septa
-septa pass from skin to periosteum of terminal phalanx
Cinical:
Whitlow
• infection of the pulp space rising pressure in space (not much space) severe pain
If neglected
Occlusion of vessels by pressure
Avascular necrosis of distal 4/5 th of terminal phalanx

(proximal 1/5 escapes because its artery doesn’t traverse the compact space which traversed by
fibrous septa)
• At each of the skin crease of the fingers,the skin is bound down to the underlying
flexor sheath so that the pulp over each phalanx is in a separate compartment cut off
from its neighbors. So usually infection doesn’t spread much. Infection may however track from one
space to another along the neurovascular digital bundles if the infection is not treated well.
02) Midpalmar space

Tenosynovitis of middle & ring fingers Web infection
(spread proximally
through lumbrical canal)
Midpalmar space infection

• Normal concavity of palm is obliterated
• Swelling extends to dorsal of the hand

(03) Thenar space
Thenar space infection (usually the infection in the web of thumb or untreated
infection in the pulp space of thumb or index finger)
Swelling of web of thumb & thenar region
(04) Forearm space of parona
• Rectangular
• Just above the wrist
• In front of pronator quadratus deep to long flexor tendons
• Extent
 Proximal- oblique origin of flexor digitorum superficialis
 Distal- Flexor retinaculum
• communicates with
- Midpalmar space
- Thenar space
• proximal part of ulnar & radial bursae protrudes into forearm space
Clinical:
Infections of Synovial sheaths (specially ulnar bursa)
Forearm space maybe infected
Pus points at margins of distal part of forearm,

swelling and pain
It may be drained by giving incision along the lateral
margin of the forearm
01)T/F
Ulnar bursa encloses all flexor tendons
Infections of little finger and thumb can spread
upto the forearm
Thick, creased skin in palmer surface increases
grasping ability of hand
02)T/F
• In whitlow distal 1/5th may get necrosed
• In infections of mid palmer spaces swelling can be seen in the dorsal surface
• Severe throbbing pain in pulp space infections is due to tight compartments formed by
subcutaneous fat
T/F in carpel tunnel syndrome

• Sensory loss over thenar eminence present
• The flexor retinaculum is cut to release pressure
• Guyon’s cannel transmit ulnar neurovasscular bundle

Blood supply of hand
Arterial Supply
• Supplied by ulnar & radial artery

• Radial artery is the main artery of the
hand
• Branches of these arteries
anastomose to form the deep &
superficial palmar arches
Superficial palmar arch
• Formed by direct continuation of ulnar artery

• Convexity towards fingers
• Most distal point- level of distal border of fully
extended thumb web
• Goes beyond flexor retinaculum
• Often not a complete arch
• Lateral side can be completed by one of superficial palmar branch

Branches of Radial artery radialis indicis
Princeps pollicis
Superficial
Deep to palmar Superficial
arch
- Palmaris brevis - Flexor digiti minimi
- Palmar - Flexor tendons of fingers
aponeurosis - Lumbricals
- Median nerve- digital branches
Branches - 4 common digital branches to medial 3 ½ fingers
Surface marking_ 1. Just lateral & distal to pisiform.

2. Hook of hamate.
3. on the distal border of the thenar eminence in line with the 2nd cleft

Deep palmar arch
Surface marking - 1.2cm Proximal to superficial
arch
• Formed by direct continuation of radial artery

• Goes between the 2 heads of the 1st dorsal
interossei and deep to the tendons of the abductor
pollicis longus, extensor pollicis longus & extensor
pollicis brevis and superficial to the lateral
ligament of the wrist joint
• Completed medially at base of 5th metacarpal
bone by deep palmar branch of ulnar artery
• Marked by a more or less horizontal line (4cm)
 Just distal to hook of hamate
 Immediately superficial to bases of metacarpal
bones
 Deep to long flexor tendons
• Slight convexity towards fingers
DEEP
PALMAR
Deep to Superficial to
ARCH
-Metacarpals-shafts-proximal parts
-adductor pollicis- oblique head -interossei
-long flexor tendons of fingers
-lumbricals
 Deep branch of ulnar nerve lies within the concavity of arch
Branches
1. 3 palmar metacarpal arteries – join with lateral 3 digital branches to form
common digital branches, each common digital branch divides into proper
digital branches & supply digits
2. 3 perforating digital arteries
3. recurrent branch
In the palm (deep to the oblique head of the adductor pollicis), the radial artery gives off
 Princeps pollicis artery-divides at the base of the proximal phalanx of the thumb into 2
branches for the palmar surface of the thumb
 Radialis indicis artery- descends between the 1st dorsal interosseous muscle and the
transverse head of the adductor pollicis to supply the lateral side of the index finger
Clinical
Allen’s test
• To test the patency of each ulnar & radial arteries, related to blood supply of the hand
Venous Drainage
• Mainly drainage by dorsal venous arch
• It lies on the dorsum of the hand
• Its afferents are
1. 3 dorsal metacarpal veins
2. Dorsal digital veins from thumb, little & index finger
• Medial side of dorsal venous arch is drained by basilic vein
• Lateral side is drained by cephalic vein
Joints of the Hand
• Wrist Joint – Synovial,
ellipsoid
• Between lower end of radius
(+articular disc of inferior
radioulnar joint),& scaphoid,
lunate, triquetral(SLT)
• 1st Carpo –Metacarpal Joint -
Has a separated cavity (saddle)
• Metacarpo- Phalangeal Joint –
synovial ellipsoid variety
• Interphalangeal Joint – Hinge
Cutaneous
Distribution of
Median, Radial and
Ulnar nerves

BONES - L.L.
HIP BONE
Side determination - acetabulum laterally

ilium- superiorly
obturator foramen - below acetabulum
 3 parts-
1. Ilium
 Iliac crest - from ant.sup.iliac spine to post.sup.iliac spine
(dimple-2nd sacral spine)
 3 borders - 1. Anterior ant.inf. iliac spine

2.posterior pos. inf. iliac spine, greater sciatic notch
3. medial
 3 surface - 1. gluteal surface anterior gluteal line

posterior gluteal line
inferior gluteal line
2.iliac fossa
3.sacropelvic surface
2. Pubis
 body - pubic crest, pubic tubercle,
-2ry cartilaginous pubic symphysis is formed
 superior ramus - pectineal line
 Inf. ramus - unites with ramus of ischium(ischiopubic ramus)
3. Ischium
 body - ischial tuberosity, ischial spine
 ramus
 Clinical  Inflammation of bursa over the ischial tuberosity due to
prolonged sitting (weaver’s bottom)
1 ©Repeat campaign 2015 A/L

 Acetabulum
- here ilium, pubis & ischium are joined to each other. (2/5th ,
1/5th , 2/5th)
• Obturator foramen covered with obturator membrane except at obturator groove.(pathway
for obturator vessels & nerve)
Anatomical position  pubic symphysis & ant. sup. iliac spine in same coronal plane
 Superior border of pubic symphysis, tip of the coccyx and ischial spine
in the same horizontal plane
Sex determination
Femur
• Nutrient artery (diaphyseal artery) - second perforating artery - branch of profunda

femoris

• Blood supply of head of the femur
- from 3 sources 1. vessels travelling up from the diaphysis( diaphyseal artery/
2nd perforating branch of prof. femoris)
2. retinacular arteries [ from the trochanteric anastomosis]
3. artery in the ligamentum teres capitis
[ negligible in adults, essential in children]
Clinicals
1. Fractures of the neck of the femur
2. Mid shaft fractures

• Considerable
shortening occurs.
• Due to longitudinal
contracture of
surrounding muscles.
3. Fracture of femur - distal

shaft
• damage to popliteal
artery
• Due to contracture of
gastrocnemius.

*** Bones that are prone to avascular necrosis.
1. Scaphoid
2. Head of Femur
3. Talus
4. Distal Phalanx
Patella
• Largest sesamoid bone of the body

• lies in the tendon of quadriceps tendon
• when set on a table it rests on the larger lateral surface
(side determination)
Clinical
 Has a natural tendency to dislocate laterally

(Patellar ligament vertical, but pull of quadriceps
is oblique)
• prevented by
1. Bony factors  prominent articular surface of the lateral
femoral condyle
2. Muscular factors  medial pull of the lower most
fibres of vastus medialis which insert almost horizontally
3. Ligamentous factors  tension of medial patella
retinaculum
Tibia

• Upper end of the shaft most common site for acute osteomyelitis.
(upper extremity of the tibial diaphysis is extracapsular; involvement of the knee joint
therefore only occurs in the late and neglected case.)
 Tibia-mostly fractured at - junction of upper 2/3 and lower 1/3

- poor blood supply Union is slow / non union
 commonest long bone to be fractured and to suffer compound injury. (Ellis)
 anteromedial surface- subcutaneous therefore a donor site for bone graft
Fibula
• Fibula is shorter than tibia.

• The fibula is subcutaneous for its terminal above the lateral malleolus, which
extends more distally than the stumpier medial malleolus of the tibia.
• Common peroneal nerve can be rolled against the neck of the fibula, where it is
commonly damaged (Foot drop)
• side determination - by the position of malleolar fossa behind triangular articular area
1.T/F
a).the common peroneal nerve turns around the medial surface of the neck of the fibula.
b).the shaft of the tibia unprotected posterolaterally
c).patella has a tendency to dislocate laterally
d).patella is developed in the tendon of quadratus femoris.
e).the posterior surface of patella contains a large medial surface.
2. T/F
a).subcapital fractures are known to cause avascular necrosis of femur head.
b).fractures of femoral shaft are accompanied by considerable shortening
c).upper end of tibia is a common site of acute osteomyelitis
d).a fracture of the trochanteric neck of femur leads to avascular necrosis.
e).acetabulum has both articular and non-articular fibres
3. What stabilizes patella,

a).intermediate fibres of vastus medialis
b).medial condyle of femur
c).lateral retinacular fibres
d).ligamentum patellae
e).medial retinacular fibres

Muscles - L.L.
Gluteal region
Muscle Nerve supply Action
01 Gluteus maximus Inf. gluteal nerve - chief extensor of thigh

-lat. Rotation of thigh
-abduction of thigh
-stabilises the knee through
iliotibial tract
02 Gluteus medius -abduction of thigh

-medial rotation of thigh
03 Gluteus minimus sup. Gluteal nerve -maintain balance of body when
opposite foot is off the ground
04 Tensor fasciae latae-------------------------------- extension of knee
05 Piriformis S1,S2- vental rami
06 Gamellus superior
nerve to obturator internus
07 Obturator internus
lateral rotation
08 Gamellus inferior
nerve to quadratus femoris
09 Quadratus femoris
10 Obturator externus obturator nerve - pos. division

Fascia lata
• Deep fascia of thigh
• Tough fibrous sheath
• Attachments
 Superiorly anterior – inguinal ligament
Lateral – iliac crest
Posterior (through gluteal fascia) – Sacrum, Coccyx, Sacrotuberous lig.
Medial – pubis. Pubic arch, Ischial tuberosity
 Inferiorly front & sides – subcutaneous bony prominences
Knee joint capsule
Posteriorly – becomes roof of popliteal fossa
Iliotibial tract
• Thigh – lateral side
• Thickened band of fascia lata
• Attachments
 Superiorly 2 slips superficial lamina iliac crest – tubercle
Deep lamina hip joint – capsule

 Inferiorly tibia – lateral condyle
• Importance
 Insertion of - Gluteus maximus
- Tensor fascia latae
 Stabilize knee (in extension & partial flexion)
• Leaning forward with slightly flexed knees tract is the main antigravity support
5. T/F
a).fascialata stabilizes the knee joint in the extended position
b).most parts of the gluteus maximusis attached to the gluteal tuberosity
c). gluteus maximus is supplied by inferior gluteal nerve
d).gluteus maximus has an origin from the sacrospinous ligament
e).tenser fasialata extends the knee.
Thigh - anterior compartment
• 4 muscles from other regions

01. iliacus 03. pectineus
Iliac region adductor compartment
02. Psoas major 04. adductorlongus
Muscle Origion Insertion Nerve supply Action
psoas major transverse process L2,L3 nerve

of all lumbar verte. root chief
& intervertebral disc lesser powerful
from T12- L5 trochanter flexor
of femur of
hip joint
iliacus iliac fossa femoral nerve
& Medial Rotator

 In fractures of femoral neck, psoas acts as a lateral rotator.
 If the fracture is intracapsular  partial lateral rotation
• 2 major muscles Sartorius, quadriceps femoris
Muscle Nerve supply Action
01 Sartorius -abduction,
-lateral rotation
of thigh
02 Quadriceps femoris
# rectus femoris -flexes of hip joint

femoral nerve - Extend Knee joint
# vastus lateralis
# vastus medialis strong extensor of hip joint

knee joint
# vastus intermedius
03 Articularis genu -pull the synovial membrane

upward during extension of the
knee
Thigh - Medial compartment
Muscle Nerve Action
01 Adductor longus obturator nerve- ant. Division
02Adductor brevis obturator nerve- pos. division - powerful addcutor of thigh

or ant. Division -help to flex the knee
03 Addcutor magnus
-- addcutor part obturator nerve -pos. division
--hamstring part sciatic nerve- tibial part exdends thigh
04 Gracilis obturator nerve -ant. Division -flexor thigh

-medial rotator
-weak addcutor
05 Pectineus femoral nerve

obturator nerve- ant. divdision
accessory obturator n.[ if present]

Back of thigh
Muscle Nerve Action
01 semitendinosus
medial rotators- leg
02 semimembranous sciatic nerve - tibial part
- chief flexor of knee
03 Bicep femoris -weak extensors of hip
--long head ---lateral rotater of leg
--short head sciatic nerve- common peroneal part
• Hamstrings are 01. Semitendinosus 02. semimembranosus

03. Biceps femoris- long head 04. Adductor magnus - hamstring part
• All hamstrings
- originate from ischial tuberosity
- inserted into leg bones (except adductor magnus)
- supplied by  sciatic nerve - tibial part
**Long head of the biceps femoris & semitendinosus have a common origin in medial facet of
ischial tuberosity
**semimembranosus originates from the lateral facet of ischial tuberosity
*pes anserinus
6. T/F
a).semimembranosus is inserted into posteromedial
surface of medial condyle of tibia.
b). reflected head of rectus femoris arises from a groove
immediately below the acetabulum.
c).semimembranosus is inserted posterior to gracilis &
Sartorius into the medial surface of tibia.
d).sciatic nerve innervates only the hamstring muscles
e).hamstring muscles all arise from the ischial
tuberosity
f).all hamstring muscles are inserted to the bones of the
leg
g) .all the hamstrings are innervated by tibial nerve.

Leg
Leg - anterior compartment

Muscle Muscle attachment nerve action
supply
Tibialis anterior -dorsiflexor of foot

- invertor
Extensor -dorsiflexor of foot

digitorum longus -extends distal
deep -phalanges of 4 toes
peroneal
nerve
Extensor -dorsiflexor of foot
hallucis longus -extends distal
phalanx of big toe
Peroneus tertius -dorsiflexor of foot

Clinical
1. Foot drop
Damage to common peroneal n.
Paralysis of ant. comp. muscles
Loss of dorsi flexion
Foot drop
 Can occur due to damage of

sciatic nerve as well
Leg - lateral compartment
Muscle Nerve Action
01 Peroneus longus Maintain lat. & trans. arches
superficial peroneal nerve -evertor of the foot

02 Peroneus Brevis
Peroneus longus -- Insertion
• passes deep to peroneal retinacula

• runs through the tunnel in cuboid
• inserts into lat. side of base of 1st metatarsal

Back of leg
Muscle Insertion Nerve Action

supply
superficial
01 Gastrocnimeus - 2 tendons
Tendonsfuse
fuse  Achilis flexor of the knee
achilis tendon
Tendon strong planter
02 Soleus -inserted to pos.surface
Inserted of
to post. Surface of tibial flexors
Calcaneous
calcaneus nerve
03 plantaris
---Soleus more powerful, postrural [ bottom gear]
---Gastrocnimeus faster acting [top gear]
deep
01 popliteus Tibia-- medial side of pos. asepect -Unlocus the knee joint
-flexes knee
-retracts & hence
protects lat. Meniscus
02 Flexor digitorum -lateral 4 toes distal phalages -flexion of lat. 4 toes

longus [plantar surface] tibial -planter flexion ankle
nerve
03 Flexor hallucis -big toe distal phalanx -flexion of big toe

-planter flexion ankle
04 Tibialis -navicular bone tuberosity -plantar flexion

posterior [gives slips to all tarsal bones -inversion
except talus & 2,3,4 metatasals]

Femoral Triangle
Definition - Triangular depression, on the front of upper 1/3 of the thigh immediately below inguinal
ligament
Boundaries -
Superior/base – Inguinal ligament
Lateral – Medial border of Sartorius
Medial – Medial border of Adductor Longus
Apex –Point where the medial & lateral boundaries
meet directed downwards
Continuous below with adductor canal
Floor – [Medial to Lateral]
Adductor Longus =>Pectineus => Psoas major
[tendon] =>Iliacus
Roof –
● Deep fascia [Fascia Lata] - Saphenous opening
with cribriform fascia
● Superficial fascia
- Upper part of Great saphenous vein
- Superficial inguinal nodes
- Genitofemoral nerve - femoral branch
- Ilioinguinal nerve - branches
- Femoral artery- 3 superficial branches &accompanying 3 superficial vein
(superficial circumflex iliac, superficial epigastric, superficial external pudendal)
● Skin
Contents - 01. Femoral artery and branches [midinguinal point to the apex -6 Branches-3 superficial and 3 deep
-superficial branches-superficial external pudendal
-superficial epigastric
-superficial circumflex iliac
-deep branches -profunda femoris
-deep external pudendal
-muscular branches]
02. Femoral vein and tributaries
[At base - medial to artery] Great saphenous vein
[At apex - post. to artery] Veins corresponding to branches of artery
(Receives greater saphenous vein, circumflex veins and corresponding branches of femoral artery)
03. Femoral sheath
04. Nerves
A) Femoral nerve (in the groove between iliacus & psoas muscles outside the femoral sheath)
B)Nerve to the pectineus (branch of femoral nerve)
C) Femoral branch of genitofemoral nerve
D) Lateral cutaneous nerve of the thigh
05. Deep inguinal lymph nodes
 Femoral artery lies in front of psoas major tendon
 Femoral vein lies in front of pectineus
 Femoral nerve lies in the groove between iliacus and psoas muscles
Femoral sheath
● Funnel shape sleeve of fascia
● It is asymmetrical
● Enclose upper 4cm of femoral vessels
 Prolongation of
o Fascia transversalis=>Ant. wall
o Illiacus fascia=>Pos. wall
 Inferiorly merges with adventitia of femoral vessels
Lateral Compartment Intermediate Compartment Medial Compartment

(arterial) (venous) (lymphatic/femoral canal)
Femoral branch of the
genitofemoral nerve
Femoral artery Femoral lymph node
Femoral vein
Lateral septum Medial Septum

 Femoral lymph node of Cloquet/ Rosenmuller in the medial compartment
Femoral Canal
-Medial compartment of femoral sheath
-Conical
-wide above at the base and narrow below
-Base is also known as Femoral ring
Boundaries Anteriorly - Inguinal lig.

Posteriorly - Pectineal ligament
Medially - Lacunar ligament
Laterally - septum separating from femoral vein
Closed by - Femoral septum [condensation of extraperitoneal tissue]
Contents - Deep Inguinal lymph nodes [of Cloquet/Rosenmuller]

Lymphatics (This Lymph node drains glans penis in males
and clitoris in female)
Areolar tissue
Functions ●dead space for expansion of the femoral vein
●lymphatic pathway from the lower limb to the external iliac nodes
Clinicals
Femoral Hernia
➢ Abdominal contents bulge out through femoral canal
➢ More common in female
• Wider pelvis
• Smaller size of femoral vessels
In strangulation, has to enlarge femoral ring => By incising lacunar ligament
• Normally => No Danger
• Abnormal(accessory) obturator artery => Alarming haemorrhage
Abnormal obturator artery
• Normal obturator artery is a branch of internal iliac artery
• Its pubic branch anastomoses with pubic branch of inferior epigastric artery.
(Abnormal ob.artery- when ob.artery is replaced by this branch from inferior epigastric artery)
Abnormal obturator artery
usually sometimes
Passes lateral to lies along the medial
femoral canal border of femoral ring
Differentiating inguinal hernia from femoral hernia??

Neck of the Femoral hernial sac protrudes below and lateral to the pubic tubercle and
neck of the inguinal hernial sack protrudes above and medial to the pubic tubercle.
Femoral hernia is never found in the newborn (not congenital)
Lump in the femoral triangle can be due to
# Skin& soft tissue --lipoma, sebaceous cyst, sarcoma
# Artery--- aneurysm of the femoral artery
# Vein--- varices of the great saphenous vein
# Nerve--- neuroma of femoral nerve / its branches
# Femoral canal--- femoral hernia
# Psoas fascia--- psoas abscess
# Lymph nodes--- Enlargement by any of the causes of lymphadenopathy
Stab wounds at apex of triangle
Cut all large vessels of lower limb
Because 01 Femoral artery
02 Femoral vein
03 Profunda femoris artery
04 Profunda femoris vein are arranged in an anteroposterior line.
Adductor Canal
[Hunter’s / Subsartorial canal]
Definition - Intermuscular space, triangular in cross section, on medial
side of middle 1/3 of thigh
Extent - From - Apex of femoral triangle above
To - Tendinous opening in adductor magnus below
Boundaries - Ant.lateral wall – Vastus medialis
Post.medialwall - Adductor longus[above]
- Adductor magnus [below]
Medial wall - Fibrous sheath joining ant. & pos. wall
Over lapped by Sartorius [Sub sartorial plexus --between
fibrous sheath & Sartorius, Formed by saphenous nerve,
medial cutaneous nerve of thigh Anterior division of
obturator nerve]
Contents=>01. Femoral artery & branches
o Muscular
o Descending genicular
Femoral artery leaves the adductor canal through
the opening in adductor magnus
At all levels in the thigh, the femoral artery lies
between saphenous nerve and femoral vein
02. Femoral vein => Upper - posterior to artery
Lower - lateral to artery
03. Saphenous nerve=>pierce roof to leave canal (Crosses anterior to femoral artery from lateral to medial side)
04. Obturator nerve =>Ant.& Pos. divisions
05.Nerve to vastus medialis
T/F
Saphenous nerve crosses femoral artery medial to lateral in the adductor canal
Popliteal fossa
Definition=> Diamond/Rhomboid shaped
depression behind the knee joint, lower
part of femur and upper part of tibia
Boundaries=>
Superomedial
* Semitendinosus
* Semimembranosus (supplemented
by Gracilis, Sarorius, Adductor
Magnus)
Superolateral
*Biceps femoris
Inferomedial
*Gastrocnemius medial head
Inferolateral
*Gastrocnemius lateral head
*Plantaris
Roof
Skin, superficial fascia
Contains
01. Short saphenous vein
02. Cutaneous nerves – 3
Medial cutaneous N. of thigh
Posterior cutaneous N. of thigh
Sural communicating N.
Floor
Above
01.Femur popliteal surface
02. Knee joint - capsule& oblique popliteal ligament below
03.Popliteal fascia covering popliteus
Contents
01. Popliteal artery &branches 05. Pos.cutaneous nerve of thigh
02. Popliteal vein & tributaries 06. Obturator nerve - genicular branch
03. Tibial nerve & branches [Sural N.] 07. Popliteal lymph nodes
04. Common peroneal nerve & branches 08. Fat
 Superficial to deep- N, V, A
 Medial to lateral- above- A, V, N
below- N, V, A
(popliteal vessels cross the tibial nerve anteriorly in the middle of fossa. Arrangement @ middle is N,V,A
behind forwards)
• Tibial nerve crosses fossa vertically downwards.
• Popliteal artery runs downwards and slightly laterally
• Common peroneal nerve crosses the fossa obliquely along the medial border of biceps femoris,
Regarding the contents of the popliteal fossa.
a) The Tibial nerve lies anterior to the popliteal vessels.
b) Lymph nodes of the fossa drain superficial tissues form the medial side of the foot.
c) The Sural nerve lies in a groove between the heads of gastrocnemius.
d) The common peroneal nerve can be palpated against the posterior surface of the lateral condyle of femur
immediately medial to the biceps tendon.
e) The roof is pierced by the small saphenous vein.
Joints of the lower limb
Hip joint
1) Type – synovial, multi axial, ball and socket
2) Articular surface- acetabulum & head of femur (2/3rd of a sphere)

- Acetabulum- horse shoe/crescent shaped articular surface
- covered by hyaline cartilage
- Deepened by acetabular labrum.
-Transverse acetabular ligament bridge the acetabular notch.
Gives origin to Ligamentum teres
3) Capsule – attachment :
proximal – margin of acetabulum, transverse acetabular ligament
Distal- ant- inter trochanteric line, base of 2 trochanters
Post.- neck of femur – 0.5 ” proximal to intertrochanteric crest
From the distal attachment fibers are reflected into the capsule as the retinacular fibers
Provide pathway for the blood supply of femur!
4) Synovial membrane- covers only non-articular surface. Lines the capsule.

Joint cavity communicates with a bursa lying deep to the tendon of iliopsoas.
(By synovium bulging out between Iliofemoral ligament and Ischiofemoral
ligament)
5) Ligaments-
* iliofemoral ligament (strongest, anteriorly)
Inverted “Y” shape, arise from anterior inferior iliac spine inserted to each end of
trochanteric line
*pubofemoral ligament (inferiorly)
Arise from ilio pubic junction
blend with capsule
*ischio femoral ligament(posteriorly)(weakest)
Arise from ischium inserted onto the greater trochanter
*round ligament (ligamentum teres)
Attached to the fovea capitis.

6) Relations -
ant: iliopsoas, pectineus, femoral artery, vein and

nerve.
Pos: obturator internus tendon, gemelli ,
quadratus femoris, gluteus maximus,
piriformis,sciatic nerve(injured in posterior
dislocation)
Sup: reflected head of rectus femoris , gluteus
minimus & medius.
Inf: obturator externus, adductors, hamstrings,
gracilis
Lat: tensor fasciae latae, gluteus min and medius
7) Movements- high stability and mobility
Flexors: iliacus, psoas, rectus fem, Sartorius, pectineus,
Extensors: gluteus maximus, hamstrings
Adductors: add. Longus, brevis and magnus, gracilis, pectineus
Abductors: gluteus medius, gluteus minimus, tensor fascia lata, sartorius
Medial lateral rotation: vertical axis passes through head of femur and condyle
Shaft doesn’t rotate around its own axis
Lat rotators: gluteus maximus, gemelli, obturators sup and inf, quadratus femoris, piriformis
Medial rotators: tensors fascia lata, gluteus medius and minimus
8) Blood supply :
* Through ligamentum teres of femur- from obturator artery
*retinacular arteries- from trochanteric anastomosis (main in adults)
* Nutrient artery of femur
9) Nerve supply (by the nerves that pass the joint)

*femoral
*obturator
*sciatic
*Nerve to quadrates femoris
*Superior gluteal nerve
10) Clinicals:
*dislocation-
# head of femur slips upwards onto the gluteal surface---lead to lurching gait (positive
Trendelenburg test)
 Usually dislocated backwards- which is produced by force applied along femoral shaft
when hip is flexed
leads to damage of sciatic nerve. Due to its close
relationship. (Foot drop)
 When hip is in adducted position- backward dislocation without acetabular fracture
 When hip is in abducted position- backward dislocation with fracture of posterior
acetabular lip
# safe area(eg for injections) --- upper outer quadrant of gluteal region

‹ 125°
#
*coxa vera -
*coxa valga- ›125° (angle in children: 150°)
*pain in the hip joint is referred to knee
*Congenital dislocation of the hip is more common than

any other joint. This occurs when the upper margin of the
acetabulum is developmentally deficient
*shenton’s line will be disturbed during

hip dislocation
Trendelenburg’s test-
positive when abductors of opposite side are paralyzed, dislocation, fracture of head of femur
1. T/F
a) Axis of gravity passes anterior to the hip joint.
b) Tensor fascia lata stabilizes the knee joint in the extended position
c) Acetabulum has both articular and non-articular surfaces
d) Trendelenburg test is positive when the normal side is raised
e) Capsule of the hip joint extends up to the trochanteric crest.
f) A fracture of the trochanteric neck of the femur leads to avascular necrosis
g) A disease of the hip joint may cause pain in the knee because of their common
nerve supply by the femoral nerve.
Knee joint
1) Type : complex synovial joint ( 2 condylar joints femur tibia)

(modified hinge joint) ( Saddle joint patella femur)
The joint cavity is divided into upper (flexion, extension) &
lower(rotation) compartments by the menisci.
2) Articular surface: main joint-

between femoral and tibial condyles
Patella joint-between patella and patellar surface of femur
(Fibula doesn’t contribute)
3) Capsule: attached littles beyond the margin of articular surface of tibia & femur. attached to
the sides of patella and anteriorly deficient and replaced by
patella
quadriceps femoris
ligament of patella
2 constant gaps- suprapatellar bursa, popliteal tendon
Attached to periphery of menisci

Capsule strengthened by - පැෙකො ISSO – patella retinacula, qudratus femoris,iliotibial tract,
sartorius, semimembranosus, oblique popliteal
ligament (this is an expansion of semimembranosus)
4) Synovial membrane:
lines the non-articular surface of the joint cavity
Cruciate ligaments are not covered,
covers deep surface of the infra patella fat pad (ala fold)
infrapatellar fat pad- deep to ligamentum patellae
5) Relations:
Ant- prepatellar, sub patellar infra patellar bursae and patellar plexus
Pos- muscle forming borders of popliteal fossa and contents of popliteal fossa
Medial- semi tendinosus, tendon of Sartorius and gracillis,great saphenous vein
with saphenous nerve
Laterally- biceps femoris, common peroneal nerve,tendon of origin of popliteus
6) Extracapsular ligaments – tibial collateral ligament – blends with capsule & medial menis.
fibular collateral ligament - separated from capsule and lat.
Meni. By popliteal tendon
Embraced by biceps tendon
7) Bursae: 12 bursae.
capsule communicates –
above supra patellar bursa

(between the lower femoral shaft and quadriceps)
posteriorly bursa under the

medial head of gastrocnemius
also communicate with bursa under the

semi membranous
8) Mobility :
flexion – hamstrings, Sartorius and gracillis popliteus, gastrocnemius, plantaris
Extension- quadriceps femori, tensor fascia lata
Medial rot.- popliteus
Lat rot.- piriformis, obturrator int, gemelli
Flexion and extension take place between the femoral condyle and the menisci
Rotation takes place between menisci and tibial condyle
Locking and unlocking mechanism
8) Stability – Locking of the knee joint – result of medial rotation of femur at
the last stage
Factors----- of extension
straighten the knee joint
Knee remains in full extension .ligaments are taut. No much
muscular effort against gravity.
Unlocking of the knee joint-lat rotation produced by popliteus

Menisci
• Crescent shaped (semilunar)

• Intra-capsular intra-synovial
• fibro-cartilaginous discs
• Thick peripherally and thin centrally
• Peripheral part is vascular.
• 2 ends attached to tibia
• 2 borders Outer border –Thick, convex , fixed to the capsule

Inner border – Thin, concave, free
• 2 surfaces upper surface

Concave
articulates with femur
lower surface
Flat
rest on tibial condyles
• Function:
• deepens articular surface of • Softens movements
tibial condyles • Proprioception
• Shock absorber • Divides joint cavity
• Increased mobility
Medial meniscus # semi circular

# peripherally adherent to tibial collateral ligament
#more prone to damage due to its more fixity.
Lateral meniscus # circular

# separated from the fibular collateral lig. By capsule & popliteal
tendon
# 2 meniscofemoral ligaments (join post. End to the femur)
#Poplitial tendon attached to it thus the mobility is controlled by

pulling backwords-less prone to injury
Cruciate Ligament
• Strong fibrous connection between femur and tibia
• Determines Antero- posterior stability
• Intra-capsular extra-synovial
Ant. Cruciate ligament

- Ant. part of inter condylar space pos. part of medial surface of lat condyle of femur
- runs upwards, backwards and laterally
- taut during extension
- prevents forward displacement of tibia on femur

Pos. Cruciate Ligament
- pos. part of inter condylar space ant. Part of lateral surface of medial condyle of
femur
- runs upwards forwards and medially
- taut during flexion
- prevents backward displacement of femur on tibia
7) Blood supply:
*From thigh- descending genicular branch of femoral,
popliteal and lateral circumflex femoral
* From leg- circumflex fibular artery
recurrent branch of ant. Tibial artery
9) Nerve supply:
* obturator *Femoral *Tibial *Common Peroneal
10)Stability
• Cruciate ligaments maintain anteroposterior stability
• Collateral ligaments maintain side to side stability
• Factors strengthening the capsule
• Iliotibial tract-plays an important role.
• Knee joint can work efficiently with a ligamentous damage
 Due to presence of powerful Quadriceps femoris muscle
Patella is stabilized by:

• Forward prominence of the lateral condyle of femur(the lateral edge of the patellar
articular surface is deeper than the medial edge)
• Tension exerted medially by the pull of the patellar ligament
• Lowest fibers of the Vastus medialis.
11) Clinicals: C1- Collateral ligaments- Taut in full extension Medial C.L- Damaged
so liable to injury in in violent abduction
this position Lateral C.L- Damaged in
violent adduction
C2- Cruciate ligaments- Anterior Cruciate- in hyperextension

Soft tissue Posterior Cruciate- in hyperflexion
injuries in knee
(3 Cs)  Both can be damaged in
violent adduction or
abduction
C3- Cartilages (Menisci)- Only damaged in Medial- In abduction

flexed position
Lateral- In adduction

• Medial menisci more vulnerable to damage than lateral
• Genu valgum(knock knee)
• Genu varum(bow knee)
2. T/F
a) (Patella)It has a tendency to dislocate laterally.
b) House maids’ knee involves prepatellar bursa.
c) Clergyman’s’ knee involves infrapatellar bursa.
d) (Patella)It is developed in the tendon of quadratus femoris.
e) (Patella)The posterior articular surface contains a large medial surface.
f) Foot baller is likely to injure his knee when his flexed knee twists while running.
g) Tendon of popliteus is intracapsular
Ankle joint
-A Hinge joint formed between mortise formed by two malleoli and between lower end of tibia and
body of talus.
01. Type ---uniaxial, hinge, synovial
02.Articular surface --- concavity convexity
# lower end of tibia # body of talus (trochlear surface,

comma, triangular)
# lateral malleolus
#medial malleolus [convex anteropost.
# tibiofibular ligament concave side to side]
03. capsule --- * thin anteriorly & post.

* strengthened on side by medial & lateral lig.
* attached to articular margin but anterioinferiorly to the neck of the talus &
posterosuperiorly to inf. Transverse tibiofib. Lig.
04. synovial membrane --- * line the capsule
05. ligaments --- * medial lig. (deltoid) & lateral lig.
1. superficial part --- Ant. talofibular lig.

tibio navicular Post. talofibular lig.
tibio calcaneal Calcaneo fibular lig.
posterior tibio talar
2. deep part--- ant. tibio talar
06. mobility --- only dorsiflexion, plantarflexion

invertion & evertion take place at subtalar and midtarsal joint not at ankle joint
Dorsiflexors-anterior & lateral compartment

Plantarflexors-Posterior compartment

07. stability --- unstable during plantarflexion
bony factor
* downward projection of malleoli on to the sides of the talus
* wedge shape of talus-being wider anteriorly
muscular factors
* tendon of long flexors & extensors
ligaments
* collateral ligaments
* inferior transverse tibiofibular lig. –bridges the gap between
the tibia and the fibula behind the talus.
08. blood supply --- peroneal artery

ant.tibial artery
post. tibial artery
09. nerve supply --- deep peroneal , tibial nerves
Clinical
01. pott’s fracture
02. Sprains of the ankle are almost always abduction sprains of subtalar joints. True sprains are
caused by forced plantarflexion
**Avascular necrosis of the Talus-Occur due to forced dorsiflexion causing fracture of the neck of
talus. If arteries to body of talus go through neck only as in some cases, the body will get avascular
necrosis.
3. T/F
a) Club foot is due to the shortening of plantar calcaneonavicular ligament.
b) A”bunion” is an inflamed adventitious bursa.
c) Dorsiflexion of the foot is limited than the plantarflexion.
d) Transverse arch is more prominent at the base of metatarsals.
e) Medial ligament of the ankle is attached to both calcaneus & cuboid.
f) Cuneonavicular joint cavity is continuous with that between the 2nd & 3rd
intermetatarsal joints.
g) Movements of the foot occurs around an axis that goes through the subtalar joint & the
head of the talus.
h) 2nd cuneiform is the shortest among the cuneiforms.
i) Subtalar joint is the only movable joint in the foot.
j) Calcaneocuboid cuboid articulation allows dorsomedial movement.
k) Talocalcaneonavicular joint complex is supported superiorly by the talonavicular
ligament.
l) Spring ligament aids in the maintenance of the medial arch of the foot.
m) Inversion and eversion both take place at ankle joint

Nerves of Lower Limb
Lumbar plexus (posterior abdominal wall)
Femoral nerve
Nerve of the extensor compartment of thigh
Root value - Posterior Divisions of Ant. Primary rami L2 , L3 , L4
Course
 Starts from the lumbar plexus
 Emerges at the lateral border of psoas major in abdomen then lies in the iliac fossa between psoas
and iliacus.
 Enters thigh by passing deep to inguinal ligament, at the lateral edge of the femoral sheath, which
seperates it from the femoral artery.(Lies behind illiacus fascia)
 Lies between illiacus and psoas tendons in the femoral triangle
 Not a content of the femoral sheath
 Divides into branches immediately (~4cm distal to the inguinal lig)
Branches
• Iliacus is supplied by the nerve in the abdomen.
• As it enters the femoral triangle, it gives off the branch to Pectineus, which passes behind the femoral
sheath to reach the muscle.
Femoral nerve supplying quadriceps femoris is tested by patellar jerk (L3, L4)
Femoral nerve
(Separated by
Anterior division lateral cicumflex artery) Posterior division

Anterior division Posterior division
Muscular • 2 nerves to Sartorious • Rectus femoris (usually double)
• Intermediate, medial, lateral
vasti
(medial – lat side of femoral
artery enter the adductor canal)
(lateral- with descending branch
of lat circumflex femoral)
Cutaneous • Intermediate cutaneous nerve • Saphenous nerve – leaves
(one of Sartorius) femoral triangle at its apex and
• medial cutaneous nerve enters the adductor canal then
run across the femoral artery.
leaves the canal between
Sartorius and gracillis)
Largest branch. Accompany
great saphenous nerve.
Hip joint (nerve to rectus femoris)
Articular Knee joint (nerves to all 3 vasti )
Obturator nerve
Nerve of the adductor compartment
Root values - Anterior Divisions of Ant. primary Rami of L2, L3, L4 nerves.
Course
− Emerges on the medial border of psoas major within the abdomen
− Crosses the pelvic brim
− Runs forwards on the lateral wall of pelvis
− Enters thigh by passing through the obturator canal
− Divides into anterior and posterior divisions in the obturator canal
− Articular branches to hip joint
Anterior Division
• Passes above and anterior to the obturator externus
• Then behind pectineus and adductor longus
• Over the ant. surface of adductor brevis
• After supplying gracilis, enters the subsartorial plexus ends by supplying femoral artery (supplies skin
over the medial side of thigh)
Posterior division
• Enters thigh, piercing obturator externus
• Passes vertically downwards on adductor magnus, deep to the other adductor muscles.
* Adductor brevis separates 2 divisions from each other.

Branches
Anterior Posterior
Muscular Pectineus Adductor magnus(adductor part)
Adductor longus Obturator externus
Gracillis
Adductor brevis Sometimes adductor brevis
Articular Hip joint Genicular(supplies knee joint
capsule and cruciate ligaments, it
passes along with the middle
genicular artery)
Clinical
• Both femoral and obturator nerves supply knee joint and hip joint. Pain in the knee can be referred to
hip joint
• Due to deep position, damage due to trauma is rare, but may be involved in obstetrics processes and
pelvic disease. (Ovarian tumour causes pain referred to medial side of thigh)
Subsartorial plexus
 Medial cutaneous nerve of thigh
 Saphenous nerve
 Obturator nerve- anterior division
Supplies the overlying fascia lata and an area of skin above the medial side of the knee.
Patellar plexus
 Lateral cutaneous nerve of thigh
 Intermediate cutaneous nerve of thigh
 Medial cutaneous nerve of thigh
 Saphenous nerve
Sciatic Nerve
 Nerve of the flexor compartment

 Thickest nerve in the body.
 Main Branch of sacral plexus
Root values - ventral divisions of anterior primary rami L4, L5, S1, S2 , S3 (tibial Part),
- dorsal divisions of anterior primary rami L4, L5, S1 , S2 (common peroneal part)
Surface Marking
Line arching laterally and downwards joining
the midpoint between the PSIS-ischial
tuberosity and the midpoint between greater
trochanter-ischial tuberosity.
Course
 In the pelvis
 Lies in front of piriformis
 Undercover of fascia
 In the gluteal region
 Enters through the greater sciatic foramen below piriformis (more laterally than the inferior
gluteal and pudendal nerves and vessels)
 Posteriorly related to the capsule of hip joint
 Passes vertically downwards on the posterior surface of Superior Gemellus, Obturator
Internus, Inferior Gemellus, Quadratus femoris.
Pass midway between the ischial tuberosity and greater trochanter. No branches given in this
region
Enters back of thigh at the lower border of gluteus maximus.
 Nerve to quadratus femoris is deep to the sciatic nerve.
 Superficially lies the posterior cutaneous nerve of thigh.
 In the thigh
 Lies under cover of the Gluteus Maximus, crossed posteriorly by the long head of Biceps
Femoris.
 Runs vertically downwards up to the superior angle of popliteal fossa on the posterior
surface of the adductor magnus, where it
 Terminates by dividing into tibial and common peroneal nerves above the knee. (variable
point)
Branches -Articular branch to hip joint

-muscular branches
Tibial part Common peroneal part

- Semitendinosus - Short head of biceps femoris
- Semimembranosus
Hamstrings
- long head of biceps femoris
- Ischial head of adductor magnus
Clinical
Sciatica
- Shooting pain over cutaneous distributions of sciatic nerve and its terminal branches
- Due to compression and irritation of nerve roots forming sciatic nerve (osteo arthritis, lumbar
disc prolapsed, spondiololisthesis
Foot drop
-Penetrating
wounds Loss of all
-Dislocation of Injury to movements Foot drop
the hip sciatic nerve below the (gravity)
-Fractures of knee
pelvis
Injury to sciatic nerve

• Sensory loss
o Whole of leg and foot
o except the area supplied by the saphenous nerve (branch of femoral nerve)
 Sciatic nerve is accompanied by a small artery (branch of inf. gluteal artery)
 In above knee amputation companion artery must be carefully isolated and ligated separately
-ligation of the nerve fibres with the artery causes severe pain in the stump.

Intramuscular injections
Gluteal region is a typical site for intramuscular injections. Sciatic nerve passes through this
region and it needs to be avoided. Safest place to inject is the upper outer region of the gluteal
region.
Sleeping foot
- Compression of sciatic nerve (Since sciatic nerve lies on femur between qudratus femoris and
adductor magnus)
- Unusual stretching after sitting for a long time
01. Sciatic nerve

a) Is formed by the ventral and dorsal divisions of sacral ventral rami
b) Emerges from the pelvis through the lesser sciatic foramen
c) It divides at a constant level
d) When the nerve is completely damaged plantar flexion is diminished
e) Is related to the upper lateral quadrant of gluteal region
Tibial Nerve
Nerve of the flexor compartment of the leg
Larger subdivision of sciatic nerve
Root values - ventral division of ventral rami L4 , L5 , S1 , S2, S 3
Course
− Descends vertically in the popliteal fossa
− Crosses popliteal vessels from lateral to medial side superficially
− Descends as the neurovascular bundle with post. tibial vessels (Post. Tibial artery first lies lateral to it,
but passes ant. To it and continues down on its medial side.
− Lies superficial to tibialis posterior and deep to flexor digitorum longus
− Passes deep to the middle of the flexor retinaculum and
− terminates by dividing into medial and lateral plantar nerves
Branches
Popliteal fossa Back of leg

Muscular Gastrocnemius Soleus
Soleus Flexor digitorum longus
Popliteus Flexor hallucis longus
Plantaris Tibialis posterior
Cutaneous Sural
articular 3 genicular branches- Ankle joint

sup. Med, middle, inf.
Med
Common peroneal nerve

Smaller terminal branch of sciatic nerve
Root values - Dorsal division of anterior primary rami L4, L5, S1, S2

Course
- Crosses the popliteal fossa from medial to lateral side along the medial border of biceps femoris
- Winds around neck of fibula
- Enter substance of the peroneus longus muscle and
- terminates by dividing into superficial and deep peroneal nerves
Branches
Cutaneous -lateral cutaneous nerve of calf
-Sural communicating nerve joins the sural nerve below the gastrocnemius heads
Articular - sup. Lat genicular

inf. Lat genicular
recurrent genicular
Clinical
• Commonest nerve to be damaged in the lower limb. (fracture of neck of fibula, compression of the
nerve by a plaster on the leg)
- Site- as it winds around the neck of the fibula
• Effects of injury (talipes equinovarus)
o Paralysis of dorsiflexors of the foot-------- foot drop (unopposed action of plantar flexors)
o Paralysis of evertors -------- inversion of the foot
Sensory loss
Back of leg
Lateral side of leg
Most of dorsum of foot
Deep peroneal nerve

Nerve of the anterior compartment of leg
(like posterior interosseus nerve of forearm)
Course
- Arises within PL, over the neck of the fibula at the bifurcation of the common peroneal nerve.
- Spirals around the neck of the fibula, under cover of peroneus longus muscle, pierces anterior
intermuscular septum then pierces fibres of the extensor digitorum longus and reaches the
interosseous membrane.
- Runs down lateral to the anterior tibial vessels
- Upper part lies between the EDL and Tibialis Anterior, in the middle lies between the Extensor
Hallucis Longus and Tibialis Anterior. (EHL crosses in front of the neurovascular bundle to lie on its
medial side)
- Ends by dividing into medial and lateral branches
Branches
Muscular -Tibialis Anterior (Muscles of the extensor compartment of leg)
-Extensor Hallucis longus
-Peroneus tertius
-Extensor digitorum brevis & longus
Cutaneous -dorsal digital nerves for the adjacent sides of the big toe and second toe
Articular - ankle joint

-Tarsal joints
-Tarsometatarsal joints
-Metatarsophalangeal joint of big toe

Superficial peroneal nerve
Smaller terminal branch of the common peroneal nerve, formed in the substance of PL.
 Descends in the lateral compartment of leg deep to peroneus longus.
 First lies between peroneus longus and peroneus brevis
 Then between peronei and extensor digitorum longus
 Pierces deep fascia in distal third of leg and descends to the dorsum of foot
Branches
Muscular -Peroneus longus

-Peroneus brevis
Cutaneous
- Anterolateral aspect of the lower leg.
- to most of the dorsum of foot
FOOT
Lateral plantar nerve & Medial plantar nerve
Terminal branches of tibial nerve
Begin deep to the flexor retinaculum
Medial plantar nerve Lateral plantar nerve

(=Median nerve in hand) (=Ulnar nerve in hand)
SUPPLY
4 muscles main trunk- 2 muscles (Runs between 1 &2)
1)Abductor hallucis 1) Abductor digiti minimi
2)Flexor digitorum brevis 2) Flexor digitorum accessorious
3) Flexor hallucis brevis
4) 1st lumbrical
Cutaneous branches
Nail beds of medial 3 ½ nail beds
superficial branch -3 muscles deep branch
1) flexor digiti minimi all other intrinsic muscles of sole
2) palmar interosseous
3) dorsal interosseous lateral most
MYOTOMES OF L.L.

CUTANEOUS SUPPLY
Clinical
Lateral cutaneous nerve is
sometimes compressed as it
passes through the inguinal
ligament, causing pain and
altered sensation in the lateral
side of the thigh (meralgia
paraesthetica)

ARTERIES OF LOWER LIMB
FEMORAL ARTERY
- chief artery of L.L

- continuation of external iliac artery
Surface marking
Thigh-slightly flexed, abducted & laterally rotated
Upper 2/3rd of the line joining Midinguinal point to adductor tubercle
Course
 Enters the thigh behind inguinal ligament (at midinguinal point)
 Lies in lateral compartment of the femoral sheath
 passes downwards & medially
- femoral triangle
- adductor canal (deep to
Sartorius)
 through adductor hiatus ( at junction of upper 2/3rd & lower 1/3rd of thigh)
 continuous as popliteal artery
Branches
In femoral triangle – 4 superficial –
1. Superficial epigastric
• emerges through the saphenous opening.
• runs towards the umbilicus.
2. Superficial circumflex iliac
• pierces the fascia lata
• to the anastomosis at the anterior superior iliac spine.
3. Deep external pudendal
• pierces the fascia lata
• behind the spermatic cord (round ligament)
• to supply the skin of the scrotum (labium majus).
4. Superficial external pudendal
• emerges from the saphenous opening
• in front of the spermatic cord (round ligament)
• to the penis and scrotum (labium majus).

2 deep-
1. profunda femoris
2. Muscular branches
In adductor canal -
1. Muscular
2. Descending genicular
Profunda femoris artery
 chief artery of the thigh

 largest branch of femoral artery which arises from the lateral side at apex of femoral triangle posterior to
femoral artery
 leave femoral triangle deep to adductor longus
descends 1st between – adductor longus &
adductor brevis
2nd between - adductor longus &
adductor magnus
Branches
 Medial circumflex femoral artery
pass posteriorly
• between psoas major & pectineus
• between obturator externus and adductor brevis
• between quadratus femoris and adductor magnus
and supplies adductor muscles
 Lateral circumflex femoral artery
runs laterally between ant. & pos. divisions of femoral Nerve
 4 perforating arteries
2nd branch = diaphysial artery

terminates as 4th perforating branch
• 1st perforating branch – above the adductor brevis
• 2nd perforating branch – through the adductor brevis
• 3rd and 4th perforating branches – below the adductor brevis
• Ascending and descending branches of these arteries form a vertical channel
• Upper end – to cruciate anastomoses
• Lower end – anastomoses with popliteal artery
Clinical:
- Compress femoral artery -at midinguinal point

- Against head of femur
- To control bleeding from distal L.L
- Femoral artery pulsations – at the mid inguinal point (against the head of femur/ psoas tendon)
- Femoral artery is superficial in the femoral triangle

- Easy exposure for ligature
- Cannulation

Trochanteric anastomosis
- In trochanteric fossa
- Communication between internal iliac A femoral A
- supplies the head of femur
Superior gluteal A. branch
Medial circumflex femoral A. Lateral circumflex femoral A.

Ascending branch Ascending branch
Inferior gluteal A
Cruciate anastomosis
- at the level of lesser trochanter

- Internal iliac A Femoral A
Inferior gluteal A
Medial circumflex femoral A Lateral circumflex femoral

Transverse branch Transverse branch
1st perforating A. of prof. femoris
OBTURATOR ARTERY
 Emerge through obturator foramen with the nerve
 divides into anterior and posterior branches that encircle the foramen.
 anastomose with each other and with the medial circumflex artery
 posterior branch - articular branch to hip joint
- enters the acetabular notch
- runs in the ligament of the head of the femur

POPLITEAL ARTERY
Course
 continuation of femoral artery
 begins at adductor hiatus (hands breadth above the knee joint)
 descends downwards & laterally
 terminates at the fibrous arch of soleus. (hands breadth below the knee
joint)
 deepest of the large neurovascular structures
 It enters the fossa medial to the sciatic nerve and lies medial to the
tibial nerve
 Then passes downwards and convex laterally to lie lateral to the tibial
nerve
 Below the fibrous arch in soleus as the posterior tibial artery – returns
medial side of the nerve
 At all levels the popliteal vein lies between the artery and the nerve.
 It passes under the fibrous arch in soleus and divides into
1. Anterior tibial arteries.
2. Posterior tibial arteries.
Branches –
- Muscular branches - 2 large sural nerves for heads of gastrocnemius
- Cutaneous
- 5 genicular branches
1. Medial superior genicular artery
2. Lateral superior genicular artery
3. Medial inferior genicular artery
4. Lateral inferior genicular artery
These four contribute to genicular anastomoses
5. Middle genicular artery
• pierce oblique popliteal ligament
• supply cruciate ligaments
• accompanied by
1. genicular branch of post division of Obturator Nerve
2. genicular branch of tibial nerve
Clinical:
-most prone to aneurysms
-used to record B.P in L.L
ANTERIOR TIBIAL ARTERY

- main artery of the anterior compartment of leg
- begins at the lower border of popliteus
- comes to anterior compartment through an opening of upper part of interosseus membrane (do not
pierce)
- continues to the dorsum of foot as dorsalis pedis artery

Course
o Accompanied by two venae comitantes on each side – Anterior Tibial Veins
o Runs vertically downwards on the interosseous membrane
o crosses the lower end of the tibia at the front of the ankle joint, midway between the 2 malleoli.
o deep peroneal nerve reaches from the lateral side, runs in front of it in middle of the leg,
returns its lateral side again below
Branches
1. Anterior recurrent Branch - genicular anastomoses
2. Posterior recurrent Branch - genicular anastomoses
3. Lateral malleolar branch
4. Medial malleolar branch
POSTERIOR TIBIAL ARTERY

o Begins at the lower border of popliteus
o Runs through fibrous soleal arch
o Deep to flexor retinaculum divides into
1. Lateral planter artery
2. Medial planter artery
Course
o runs down on tibialis posterior
o between flexor digitorum longus and flexor hallucis longus.
o Descends deep to soleus
o accompanied by a pair of venae comitantes
Branches
• Peroneal artery
- descends in a fibrous canal between flexor hallucis longus and tibialis posterior
- nutrient artery to fibula
- perforating branch pierces posterior intermuscular septum and supplies lateral compartment
- gives lateral calcanian branch may replace or supplement the dorsalis pedis artery.
• Nutrient artery – to tibia
• Circumflex fibular – laterally around the fibular neck to genicular anastomosis
• Muscular Branches – soleus, deep flexors
Anastomosis
* 4th perforating artery popliteal artery (upper muscular branch)
• Genicular anastomosis
around the patella and the femoral and tibial condyles
 Lateral superior genicular
 Lateral inferior genicular
Posterior Tibial Artery
 Medial inferior genicular
 Medial superior genicular
 Anterior tibial recurrent
Anterior Tibial Artery
 Posterior tibial recurrent
 Circumflex fibular→Posterior Tibial Artery
 Descending genicular→Femoral Artery
 Lateral circumflex femoral – descending branch
Anastomoses on the back of thigh

01. WOTF true regarding the arteries of the back of the leg
a) The popliteal artery divides into anterior & posterior tibial arteries at the distal border of popliteus.
b) The anterior tibial artery passes to the anterior compartment of the leg by piercing the interosseous membrane.
c) The posterior tibial artery is the main artery of the foot.
d) The main blood supply of both tibia & fibula is from posterior tibial artery.
e) The peroneal artery enters the peroneal compartment of the leg deep to flexor hallucis longus.
02. Regarding the blood vessels of the lower limb

a) Anterior tibial artery pierces the interosseous membrane.
b) Peroneal artery can be palpated at the medial malleolus.
c) Superficial veins drain into deep veins.
d) Venous drainage is mainly by the deep veins.
03. Regarding the arteries of the foot

a) Dorsalis pedis artery can be palpated at the foot in living.
b) Arcuate artery gives rise to the first metatarsal artery.
c) Medial /lateral plantar vessels are branches of the posterior tibial vessels.
d) Dorsal & plantar metatarsal arteries communicate with each other.
e) Plantar arch is produced by the medial plantar artery

Venous drainage of LL
3 types deep veins
Superficial veins
Perforating veins
Deep veins
• Ant. Tibial • Peroneal
• Post. Tibial
• Popliteal • Femoral
− Valves-more numerous
− Supported by surrounding powerful muscles
− Accompany major arteries
− More efficient
− Most of the venous return happens through the deep vein system.
Superficial veins
− Great (long) saphenous vein
− Small (short) saphenous vein
- Drains into deep veins via perforating veins
− Less valves
Great Saphenous vein

Longest vein in the body.
Course
− Starts by union of medial marginal vein &the medial end of dorsal venous
arch
− Runs upwards in front of medial malleolus (constant position)
− Crosses the lower third of the medial surface of the tibia obliquely along
with the saphenous nerve
− Along medial side of leg
− To Posteromedial aspect of knee (hand’s breadth behind the medial border
of the patella)
− Spirals forwards around the medial convexity of the thigh
− Ends by passing through the Cribriform Fascia covering the saphenous
opening. (About 4cm below and lateral to the pubic tubercle) Constant valve
is present here
− Receive 3 tributaries
1)Superficial circumflex iliac 2)Superficial epigastric 3)Superficial external pudendal
− Pierces cribriform fascia
After piercing
− Receives deep external pudendal
− Opens into femoral vein (constant valve) (saphenofemoral junction)
• 10 -15 valves
• Incompetence of valves is a cause of varicosity of the vein.
• Unusually thick wall
• Accompanied by saphenous nerve
 Thoracoepigastric vein - connects
o Lateral thoracic vein of axillary vein Obstruction of inferior vena cava
o Superficial epigastric vein

Small saphenous vein
Course
− Starts – drains the lateral side of the dorsal venous arch of the foot and lateral margin of the foot.
− Ascends behind the lateral malleolus, accompanied by the Sural nerve.
− Ascends in the subcutaneous fat along post. Aspect of leg up to midcalf level
− Pierces deep fascia (anywhere between midcalf to roof of the popliteal fossa)
− Drains into popliteal vein.
− It communicates by several channels with the great saphenous vein.
−
Perforating veins
Indirect direct
Through muscles 1) Hand’s breath above knee
Superficial veins deep veins
 Great saphenous vein femoral vein
2) Hands breath below knee
 Great saphenous vein post. Tibial v.
• valves – permit blood flow only 3) Hands breath above ankle
Superficial to deep  Medially- great saphenous post. Tibial v.
 Laterally- small saphenous peroneal v.
Factors helping venous drainage of lower limb

a) Veins are more muscular – more venous tone
b) Greater number of valves (deep veins> superficial)
perforators
Superficial veins deep veins
c) Muscular pump
d) Tight fascial sleeve - makes muscular compression more efficient.
e) Pulsations of arteries associated with deep veins
Clinicals
 Muscle pump
− Soleus (peripheral heart)
 Varicose veins & ulcers
− incompetence of
o valves of perforators or deep veins
o valves at termination of superficial veins
become high pressure leaks
high pressure transmitted to superficial veins
dilation & gradual degeneration of superficial veins
varicose veins & varicose ulcers

 Trendelenburg’s test (only for perforating & superficial veins)
Patient is made to lie down
Veins are emptied
Pressure applied to thumb to saphenofemoral junction
Patient is asked to stand up
Pressure released Pressure maintained for 1 min
Quick filling of varicose veins from above gradual filling of varices
INCOMPETENT SUPERFICIAL veins INCOMPETENT PERFORATORS
 Perthe’s test (only for deep veins)
Tourniquet tied around upper part of thigh

(tight enough to prevent reflux down the vein)
Patient is asked to walk quickly
If perforating & deep veins- NORMAL LOCKED perforating /deep veins
Varicose veins- SHRINK varicose veins- MORE DISTENDED
 Great saphenous vein in front of medial malleolus-

− Constant position for immediate blood transfusion
1. Regarding the venous drainage of the lower limb
a. Most of the blood return through the deep veins

b. Communicating veins do not possess valves
c. Main commmunications between the superficial & deep veins occurs at constant level
d. A valve is constantly seen at the termination of the great saphenous vein
e. Tendelenberg test is to assess the functioning of the valves of the deep veins
4. Small saphenous vein

a. Drains into femoral vein
b. Passes behind the lateral malleolus
c. Is accompanied by the sural nerve
d. Is formed in the sole of the foot
e. Runs through the roof of the popliteal fossa

LYMPH DRAINAGE - L.L.
01) Lymph nodes
Superficial Deep
• Superficial inguinal lymph nodes 1.Deep inguinal lymph nodes

About 10 nodes, T shaped eg:- lymph nodes of Cloquet/Rosenmuller
arrangement - afferents from
Proximal group – Just distal to * Superficial inguinal nodes
the inguinal ligament * Popliteal nodes
Distal group – Lies vertically * Glans penis / clitoris (→Cloquet)
along the terminal great * deep lymphatics – L.L.
saphenous vein. - efferent to
• Efferent – Pierce cribriform * external iliac nodes
fascia and terminate in deep
inguinal nods. 2. Popliteal lymph nodes
- near small saphenous vein termination
- afferents from
* territory of small saphenous vein
* leg – deep parts
Upper medial – Umbilicus and ant abd wall below it , * knee joint
External genitalia, lower anal canal and - efferent to
perineum, uterus. * deep inguinal nodes
Upper lateral – buttock, flanking back below the waist
Lower vertical – Superficial lymphatics of the lower limb 3. Anterior tibial lymph nodes

Foot
Bones of the foot
Comma shaped medial articular

surface
Fan shaped lateral

articular surface
• Talus has no muscle attachments.

• When it is fractured can undergo avascular necrosis
• side determination- (medial surface-comma shaped impression/lateral surface-fan
shaped)
Bony prominences of the foot

1. tuberosity of the navicular- stands out as a bony prominence in front of the
medial malleolus; it is the principal point of insertion of tibialis posterior.
2. base of the 5th metatarsal - easily felt on the lateral side of the foot and is the
site of insertion of peroneus brevis.
3. If the calcaneus carefully palpated→ the peroneal tubercle can be felt below
the tip of the lateral malleolus
4. Sustentaculum tali below the medial malleolus.
Peroneal tubercle and sustentaculum tali represent pulleys respectively for
peroneus longus and for flexor hallucis longus
Pott’s fracture
• Most usual ankle fracture.
• Tibia internally rotates with the foot rigidly held
01. spiral fracture of the lateral malleolus 1st degree
02. avulsion of the medial malleolus 2nd degree
03. posterior margin of the lower end of the tibia shears of against
the talus 3rd degree

Joints of the foot
• Subtalar joint (Talocalcaneal joint)- Multiaxial, synovial joint
Gliding & inversion eversion movements
associated with talo calcaneo navicular joint.
• Talo calcaneo navicular joint- Ball & socket synovial joint.

Talus, calcaneus, navicular
Inferiorly supported by spring ligament (plantar
calcaneonavicular ligament)
Inversioin and eversion take place
**Talonavicular & calcaneocuboid joints lie in one line and together called
“Transverse tarsal joint” here pronation and supination take place as hidden
movements for plantigrade contact (gripping)
• Cuboideonavicular joint- Fibrous joint. No movement (All other joints are synovial)
• Cuneonavicular joint-Continue with 2nd and 3rd intermetatarsal joints
• Calcaneocuboid joint-long and short plantar ligaments on its plantar surface
• Tarso metatarsal joints- Gliding and aid in pronation and supination. Synovial
• Metatarso phalangeal joints-Condyloid joints, Synovial
1st metatarsophalangeal joint is the site of hallux valgus. Oblique attachment
of tendons of flexor hallucis longus and flexor hallucis brevis increase the
deformity
• Inter pharyngeal joints- Hinge type
Long plantar ligament

Attached between plantar surface of the calcaneus and base of middle 3 metatarsals
It covers the short plantar ligament
It also covers the peroneus longus tendon
Short plantar ligament (plantar calcaneocuboid ligament)

Attached between plantar surface of the calcaneus and cuboid
Muscles of the foot
Dorsum of the foot
Muscles Nerve Action

Extensor digitorum brevis Deep peroneal nerve Extend the medial 4 toes
The tendon to the great toe is different from others and is named extensor hallucis brevis

Dorsum of the foot
Muscle Nerve Action
1st layer
01) Abductor hallucis -abduction of great toe

medial plantar
02) Flexor digitorum nerve -flexion of toe
brevis
03) Abductor digiti -abdution of little toe

Lateral planter nerve
minimi
main trunk
2nd layer
01) Flexor digitorum -tibial nerve ref.

longus
02) Flexor
Flexordigitorum
accessorius/ -lateral plantar nerve -straigthens the pull of long flexor
accessorius
Quadratus plantae main trunk tendons
03) Lumbaricals 4 1st -med. Plantar nerve -I/P joints -- extension

lat. 3- lat. Planter n.--deep bra.
04) Flexor hallucis tibial nerve ref.
3rd layer
01)Flexor hallucis brevis -medial plantar nerve -flexion of great toe
02) Adductor hallucis -lat. plantar nerve-deep branch -adduction-- great toe
03) Flexor digiti minimi lat. Plantar nerve-superf. Bran. -flexion of little toe
4th layer
01) Plantar interossei 3 -lat. Plantar nerve -adduction of toes

-most lat - superficial branch -PAD
-rest -deep branch
02) Dorsal interossei 4 -lat. Plantar nerve -abduction of toes

-most lat - superficial branch -DAB
-rest -deep branch
(See also tibialis post. and peroneus longus muscles)

Nerves of the foot
Lateral plantar nerve & Medial plantar nerve
• Terminal branches of tibial nerve

• Begin deep to the flexor retinaculum
• Lie between 1st and 2nd layers (Also the plantar arteries)
Medial plantar nerve (=Median nerve in hand)
SUPPLY-4 muscles
1)Abductor hallucis
2)Flexor digitorum brevis
3)Flexor hallucis brevis
4)1st lumbrical(unicipital)
Cutaneous-plantar surface of medial 3 ½ toes with their nail beds

Adjacent part of the sole
Lateral plantar nerve (=Ulnar nerve in hand)
Main trunk, superficial branch and deep branch supply all other muscles of the foot including
2nd ,3rd and 4th lumbricals(bicipital)
Deep branch lies within the concavity of plantar arch and ends by supplying adductor hallucis
Cutaneous-plantar surface of lateral 1 ½ toes

Adjacent part of the sole
OTHER CUTANEOUS NERVES OF THE FOOT
Saphenous nerve-Supply extends along the medial border of the foot as far as the level of
metatarsophalangeal joint of the great toe
Sural nerve-Supply extends along the lateral border of the foot up to the little toe
Medial calcanean branches of tibial nerve-Supply the heel
Superficial peroneal nerve-Supplies most of the dorsum of the foot (except medial and lateral
borders,1st toe cleft and nail beds)
Deep peroneal nerve-Supplies the 1st toe cleft

Arteries of the foot
LATERAL & MEDIAL PLANTER ARTERIES
• Runs between 1st & 2nd layers of the sole

• Lateral plantar artery forms planter arch between 3rd & 4th layer. Plantar arch is
anteriorly convex and lies on the bases of middle 3 metatarsal bones.
DORSALIS PEDIS ARTERY
Runs to the 1st intermetatarsal space and passes down in to the sole where it joins the
lateral plantar artery to complete the plantar arch.
Can be palpated between the tendons of extensor digitorum longus and extensor hallucis
longus.
Gives 3 branches,
Lateral tarsal artery
1st dorsal metatarsal artery
Arcuate artery (gives 2nd,3rd and 4th dorsal metatarsal arteries)
Arches of the Foot

medial longitudinal lateral transverse arch
arch longitudinal arch
Calcaneus Calcaneus
Talus Cuboid Metatarsals
Bones Navicular Lateral 2 Cuboid
3 Cuneiforms metatarsals Three cuneiforms
1st three metatarsals
Anterior – 1st three
Anterior – heads of
metatarsals (the
4th and 5th
phalanges do not take
metatarsals
part) Medial and lateral
Ends (Pillars)
arches
Posterior – medial
Posterior – Medial
tubercle of
tubercle of calcaneus
calcaneus
Superior surface of
Summit Body of Talus
calcaneus
Key Stone Talus Cuboid
Long plantar
Plantarcalcaneonavicular
ligament Dorsal interossei
ligament
Short plantar Transverse head of
Slip (Spring ligament)
ligament adductor hallucis
Long and short plantar
Short muscles of
ligaments
foot
Plantar aponeurosis
Plantar aponeurosis Abductor digiti
Flexor digitorum brevis minimi
Peroneus longus
Tie beam Flexor digitorum longus Flexor digitorum
Flexor hallucis longus longus
Flexor hallucis brevis Flexor digitorum
brevis
Tibialis anterior
Tibialis posterior Peroneus longus Peroneus longus
Suspension
Medial ligament of Peroneus brevis Peroneus brevis
ankle joint
Main stabilizing Peroneus longus
Muscles Ligaments
factor tendon
Function of the arches

• To distribute body weight
• Acts as a spring during running and walking
• Acts as a shock absorber in jumping
• Concavity protects the soft tissue of the sole
Clinical
Pes cavus-high arch

Pes planus-flat foot (more common)

Posture
Line of gravity
passes anterior to the
 atlanto-occipital joint
 knee joint
 ankle joint
 four vertebral curvatures
Except the hip joint – posterior to the hip joint.tendency to extend is

prevented by iliofemoral ligament
Postural/Anti gravity muscles:
*Erector Spinae
*Gluteus maximus
*Soleus
*Quadriceps femoris
Standing
• There are series of forward and backward movements

• During forward movement
• line of gravity moves forwards in front of hip joint
• prevented by Gluteus Maximus
• During backward movements
• line of gravity moves backwards
• knee joint tends to flex
• prevented by Quadriceps Femoris
Clinical: In wearing high heels the spine is pushed forward,knees excessively bent,soleus & gluteus
maximus in contraction,toes in extream flexion,forward tilting of pelvis,cervical extension,lumber
lordosis

Arches of the Foot
medial longitudinal arch Lateral longitudinal transverse arch

arch
Bones Calcaneus Calcaneus Metatarsals
Talus Cuboid Cuboid
Navicular Lateral 2 metatarsals Three cuneiforms
3 Cuneiforms
1st three metatarsals
Ends Anterior – 1st three Anterior – heads of 4th
metatarsals (the and 5th metatarsals
phalanges do not take
part) Posterior – medial
Posterior – Medial
Summit Body of Talus Superior surface of
calcaneus
Key Stone Talus Cuboid
Slip Plantarcalcaneonavicular Long plantar ligament Dorsal interossei
ligament Short plantar ligament Transverse head of
Short muscles of foot adductor hallucis
Tie beam Plantar aponeurosis Plantar aponeurosis Peroneus longus
Flexor digitorum brevis Abductor digiti minimi
Flexor digitorum longus Flexor digitorum
Flexor hallucis longus longus
Flexor hallucis brevis Flexor digitorum
brevis
Suspension Tibials anterior Peroneus longus Peroneus longus
Tibialis posterior Peroneus brevis Peronius brevis
Medial ligament of ankle
joint

Function of the arches
• To distribute body weight

• Acts as a spring during running and walking
• Acts as a shock absorber in jumping
• Concavity protects the soft tissue of the sole
1.Regarding the arches of the foot

a) Transverse arch is maintained by the peroneus longus tendon.
b) Plantar muscles play an active role in maintaining the arches even when the
arches are not subjected to stress.
c) Tibialis posterior tendon sends slip to talus.
d) Transverse arch is more prominent at the base of metatarsals.

Gait
• The gait cycle consists of one cycle of swing and stance by one limb.
Stance phase
o Begins with heel strike, when the heel strikes the ground and begins to assume the
body’s full weight
o Ends with push off, from the fore foot – a result of plantar flexion
o Occupy 60% of walking cycle
o Contains two periods
 double stance period -- when both feet are on the ground
 Single stance period – when one foot is on the ground
 In running there is no period of double stance
o After the heel strikes, the fore foot must be lowered to the ground via plantar
flexion
Swing phase
o Begins after push off, when the toes leave the ground
o Ends when the heel strikes the ground
o Plantar flexors (soleus, gastrocnemeus) contract to raise the heel
o The long flexors of the digits flex the toes – leads to toe off
o The Foot is raised off the ground by flexion of the hip and knee
o
As one foot is raised from the ground, pelvis of the unsupported side drops
This is corrected by the gluteus medius and minimus of the opposite side
When these muscles are paralyzed
In one side – lurching gait
Both sides – waddling gait
(+ve Trendelenburg test)
• Rising up
o Hip extension
o Knee extension
• Walking up stairs
o Extension of the hip & knee joint in the leading limb to pull up the trunk to the
Step above

1
VERTEBRAL COLUMN
33 vertebrae. 7 – Cervical , 12 – Thoracic , 5 – Lumbar , 5 – Sacral , 4 – Coccygeal
Flexibility of column 24 movable vertebrae

Vertebrae and many intervertebral joints close together
curvatures / sinous bends in the column
• 1ry curvatures - concave forward

thoracic curve & sacral curve
• 2ry curvature - convex forward

cervical curve ( 4-5 months ) - infant starts supporting it’s head
lumbar curve ( 12-18 months ) - Child assumes upright position
vertebra body pedicles

neural arch laminae
processes transverse processes - 2
spinous process
sup. articular processes - 2 & inf. articular processes - 2
• related ligaments -
01. Ant. longitudinal lig.
02. Pos.longitudinal lig.
03. ligamentum flavum
04. Interspinous lig.
05. Supraspinous lig.
06. Intertansverse lig.
07. Articular lig.
• Intervertebral joints -3
2 joints between articular processes (zygapophyseal) - plane synovial
joints between vertebral bodies - 2ry cartilaginous
o Intervertebral disc – thickest in lumbar
▪ outer—annulus fibrosus -collagen and fibrocartilage
▪ inner –nucleus pulposus –semiliquid gelatinous substance
 Repeat campaign 2015 A/L
2
Vertebra Body Vertebral foramen Transverse process Spine
Cervical presence of foramina transeversaria

sup.surface ●Larger than body, ●ant.root/tubercle ●short
●concave - ●triangular ●costotransverse bar ●bifid
Typical C3-C6 transversely ●pos.root/tubercle ●filled with
●lips - laterally ● foramen transversarium ligamentum nuchae
transmits vertebral
Inf.surface artery, venous plexus,
●saddle shaped sympathetic fibers
● C6 ant.tubercle-large
carotid tubercle
Atlas C1 ●no body, no spine, ring shaped

●median ant. tubercle→post. side oval facet for dens
Atypical
●median post. tubercle
●groove in sup.surface→vertebral artery
●sup. articular facet→concave atlanto occipital joint condyle
●inf. articular facet→flat atlantoaxial joint
Axis C2 ●dens from the superior surface of the body

●only posterior tubercle present
Vertebra ●thick long nearly horizontal spine, not bifid, ends in tubercle
prominens C7 ●only posterior tubercle present
Foramen transversarium doesn't transmit vertebral artery, only the vein
Thoracic costal facets on body and transverse processes

vertebrae
●heart shaped ●small, circular costal facets ●long
Typical T2-T8 ●Costal [demi] upper 6 lower 6 ●downward
facets: concave flat & backward
sup.-larger forward upward
inf.-smaller
laterally laterally
Atypical
T1 ●cervical type nearly horizontal
●sup. costal f.
complete
T9 ●inf. costal f.
missing

3
Vertebra Body Vertebral foramen Transverse process Spine
T10 ●sup. costal f.
complete
T11 ●sup. costal f. no facet

complete
T12 ●sup. costal f. ●3 tubercles horizontal

complete sup., inf., lateral
Lumbar * no costal facet or foramina transversaria

Vertebrae
●thin ,tapering
●large ●triangular ●postero-sup root→ quadrilateral plate
Typical L1-L4 ●kidney shape [medium] mamillary process
●postero-inf root→
accessory process
Atypical
L5 ●Transverse process attached to whole thickness of pedicle & also the body
●thick, short , pyramidal in shape.
●Distance between inf art processes equal or more than between sup art processes
●Spine- rounded at tip
Sacrum base ●sacral promontary - anteriorly

●sacral canal - triangular
●transverse process+costal elements - Ala
apex - oval facet for coccyx
Pelvic surface - concave

#4 transverse ridges
#4 sacral foramina
Dorsal surface - median sacral crest - spines

- sacral hiatus
- articular processes - sup. of S1 - free
- inf of S5 - sacral cornua
- 4 dorsal sacral foramina
- lateral sacral crest - transverse preocesses
- intermediate sacral crest - articular facets
Thoracic spines
T1, T2—horizontal
T3, T4—oblique
T5-T8—vertical
T9, T10—oblique
T11, T12 – horizontal

4
JOINTS OF THE NECK
• Lower 6 cervical vertebrae have joints similar to intervertebral discs

• Apex of ligamentum nuchae – 7th cervical spine
• Base of the ligamentum nuchae – external occipital crest
I. Atlanto – occipital joint

• Type : synovial joint of ellipsoid variety
• Articular surfaces : above - occipital condyles
below - superior articular facet of atlas
• Ligaments : Capsular ligament - thick posterolaterally, thin anteromedially
Anterior atlanto occipital membrane - from foramen magnum above to anterior
arch of atlas
Posterior atlanto occipital membrane - from foramen magnum above to
posterior arch of atlas
• Movements : flexion & extension around a transverse axis
Slight lateral flexion around anteroposterior axis
• Arterial supply : vertebral artery
• Nerve supply : first cervical nerve
II. Atlanto – axial joint

▪ Pair of lateral atlanto-axial joints between inferior facets of the atlas & superior facet of the
axis – PLANE JOINTS
▪ Median atlanto-axial joint between anterior arch of atlas, transverse ligament & dens –
PIVOT JOINT
• Ligaments : Capsular ligament , anterior longitudinal ligament , ligamentum flavum
• Movements : rotatory movements at all 3 joints
Transverse ligament
• a broad, strong band which arches across the atlantal ring behind the dens
• attached on each side to the medial surface of the lateral mass of the atlas
• in the median plane prolonged upwards to basiocciput and downwards to body of axis forming cruciform
ligament
• prevent dislocation of dens
Clinicals
• Death in execution is due to the rupture of the transverse ligament of dens, which then compress the
medulla oblongata & spinal cord
• Cervical spondylosis
• Due to the horizontal position of articular facets, dislocation occurs without fracture

5
Clinical
• 1/5 of height of vertebral column – Intervertebral disc
01. Disc prolapse [slip disc]
Trauma Degenerative disease Sudden stress
Rupture of annulus fibrosus in its weak posterolateral portion
protrusion of nucleus pulposus mostly posterolateral

[sometimes directly backwards, can compress all the nerves below the level. Ex: When cauda equina is compressed - paraplegia]
pressure on the nerve root
Irritation of the nerve root 01. pain 02 .muscle weakness

03. stiffness 04. paresthesia
** Affected nerve roots,
• most commonly - lower lumbar L4/L5, L5/S1 sciatic nerve is affected
• less commonly - lower cervical C5/C6, C6/C7
02. Spina bifida

• 2 halves of the neural arch fail to fuse. Causes spinal canal infection & ultimately, death.
** No any protrusion, but spina bifida is present spina bifida occluta
** spina bifida with,

• herniated meninges meningocele
• herniated meninges + spinal cord meningomyelocele
** posteriorly opened spinal cord myelocele
03. Spondylosis
• Degenerating changes with aging
• If causes spinal cord compressions back pain
04. Spondylolisthesis
• Inf. articular processes, spine & laminae of 5th lumbar vertebra separate from rest of body and
slip forward over the sacrum.(broken neck of scotty dog in Xray)

6
05. Abnormalities of curves

• Normal vertebral column is a straight line in A/P view.
I. Postural curvature
• Because of muscle abnormalities [ not due to abnormalities in vertebral column ]
II. Anterior- posterior curvature abnormalities
A. Kyphosis - Increased concavity anteriorly [thoracic]

[humpback/ hunchback]
• Due to erosion of ant. part of one or more vertebrae.
• Overall reduction of height
B. Lordosis - Increased convexity anteriorly [lumbar]
III. Lateral curvature abnormalities
C. Scoliosis - Accompanied by rotation of the vertebrae

• Asymmetric weakness of intrinsic back muscle Myopathic scoliosis
• Failure of half of vertebra to develop hemivertebra
• Difference in length of lower limbs [disappears when seated down]
• Habitual standing , sitting or improper position Habit scoliosis
[if entirely postural - disappears with max. flexion]
Lumbar Puncture
• Done to - obtain CSF

- inject local anesthetic drugs
• At the level of L4/L5 vertebra Highest point of iliac crest
(spinal cord finishes at lower border of L1)
• Structures pierced
- Skin
- Superficial fascia
- Supraspinous ligament
- Interspinous ligament
- Ligamentum flavum
- Dura mater , Arachnoid mater
Stability of the spine

3 column concept
Ant. column Middle column post. column
- body - body - facets

annulus fibrosus ant. annulus fibrosus pos. - everything posterior to
nucleus pulposus nucleus pulposus post. lon. lig.
- ant. lon. lig. - pos. lon. lig.
- fractures stable - unstable - unstable

Fertilization
• Male (sperm) and female (ovum) gametes fuse.
• Occurs at the ampullary region of the uterine tube
1. Deposition of sperms in the female genital tract

2. Movement of sperms to the isthmus of uterine tubes (self-propulsion by flagellum/tail,
muscular contraction of uterus)
3. Capacitation
o A modification of sperms increasing its motility and the capability to fertilize (Only
capacitated sperms can pass through corona radiata and undergo acrosome reaction)
o Epithelial interaction between sperm and mucosal surface of uterine tube – removal of
glycoprotein coat and seminal plasma proteins from the plasma membrane that overlies
the acrosome region of the sperm
o In uterine tube – lasts for 7 hours
4. Movement towards the ampulla – meet the ovum
5. Penetrate the corona radiata (Only the capacitated sperms)
6. Penetration of zona pellucida
a. Acrosome reaction
i. Induced by zona proteins (After binding to zona pellucida)
ii. Acrosin / Trypsin-like-enzymes (proteases) released – digestion of zona
pellucida
b. Cortical reaction
i. Release of lysosomal enzymes from cortical granules lining the plasma
membrane of the oocyte
ii. Induced by contact of head of sperm with oocyte surface
iii. Enzymes prevent further penetration of sperms and inactivate receptors on
zona surface by altering the composition of the zona pellucida [the changes of
the zona pellucida is called the – zona reaction]
iv. Prevents polyspermy
v. Oocyte membrane becomes impenetrable to other spermatozoa
vi. DID YOU KNOW – that there are receptor sites for sperms on the zona which
are species specific

i Fusion of oocyte and sperm cell membrane
a. Oocyte membrane and membrane that covers the posterior region the sperm head
b. Why?????
c. Both the contents of the head and tail of the sperm enter the oocyte leaving
behind the plasma membrane of the sperm.
ii Resumption of second meiotic division (which is arrested in meiosis II of metaphase)
a. Immediately after the entry of spermatozoon
b. Oocyte completes meiosis II
c. Divides into a definitive oocyte and a second polar body
i. Definitive oocyte
1. Contains the majority (almost all) of the cytoplasm of the ovum
2. 22+X chromosome in a vesicular nucleus – female pronucleus
ii. Second polar body
1. Hardly any cytoplasm
2. 22+X chromosomes
3. Functions in removing the sister chromatids of the secondary
oocyte – halving the amount of DNA
iii Metabolic Activation of oocyte
iv Fusion of male and female pronuclei
a. Paternal
i. The male pronucleus moves toward the female pronucleus ;)
ii. The nucleus of the sperm (now inside the ovum) swells – called the
male pronucleus
iii. The tail and mitochondria of the sperm degenerates
iv. DID YOU KNOW – that you cannot distinguish male and female
pronuclei by external appearance
b. Replication of DNA in each pronucleus
c. Chromosomes arrange in a spindle
d. Longitudinal splitting of DNA – sister chromatids move to opposite poles
e. Plasma cleavage resulting in two diploid daughter cells
10. Initiation of cleavage

RESULTS OF FERTILIZATION
• Restoration of the diploid number of chromosomes (zygote contains a new combination

of chromosomes different from both parents)
• Determination of chromosomal sex
• Initiation of cleavage (without fertilization oocyte degenerates 24 hrs after ovulation)
CLEAVAGE
• The two celled zygotes undergo a series of mitotic divisions

• BUT – Not as other cells- these cells do not GROW IN SIZE during their cell cycle
• Therefore, the total plasma content remains the same
• But the number of cells increase
• Therefore, the size of each cell reduces after each cleavage
• BUT – DNA replication occurs – Therefore amount of DNA increases – All cells are diploid
• These cells are called – BLASTOMERES
Due to
Cleavage
Increased Decreased Remain same

• Cell amount • Cell size • Amount of
• DNA amount plasma
2 cell
• Maximize their contact with other cells
• Form a compact ball of cells held by tight junctions- compaction
4 cell • ‘inner cells’ and ‘outer cells’ tend to function differently
• Called the morula

• Inner cells- inner cell mass
8 cell • Outer cells- outer cell mass
• Loosely arranged clump of cells

16 cell
Eventually
• The Inner cell mass become the –
Embryo Proper – Baby
• Outer cell mass – Trophoblast –
Placenta
WHAT IS THE STAGE OF THE EMBRYO

WHEN IT ENTERS THE UTERINE CAVITY?
– ‘Morula’
(Morula enter uterine cavity in 4th day)
BLASTOCYST FORMATION
• Fluid in the uterine cavity penetrates the zona pellucida
into the intercellular spaces of the inner cell mass.
• Intercellular spaces become confluent and forms a
single cavity – blastocele
• At this time, the embryo is called the – BLASTOCYST
BLASTOCYST
• Outer cell mass (trophoblast) flattens to form the epithelial wall of the blastocyst
• Inner cell mass (embryoblast) is concentrated to a pole of the blastocyst
• The fluid filled cavity between the aembryonic pole and the embryoblast is the blastocele
HATCHING
• The embryo getting out of the zona pellucida on the 5th day
IMPLANTATION
• On the sixth day
• Trophoblastic cells over the embryoblast pole penetrate into the uterine endometrium (mucosa)
• The endometrium is in the – SECRETORY PHASE
• SECRETORY PHASE
o Coiled uterine glands o Coiled
uterine arteries
o Glycogen granules found in cells
• Implantation occurs usually in the posterior (or anterior) wall of the uterus
(where it becomes embedded between the openings of the glands)

PLACENTA
Placenta – is the organ that facilitates material exchange between maternal and fetal compartments
So far learnt -
• Tertiary (& some secondary) anchoring villi are extending from the chorionic plate to the
cytotrophoblastic shell
• Uteroplacental circulation established
o Cytological process of erosion of maternal blood vessels – endovascular invasion

Cytotrophoblast cells undergo – epithelial to endothelial transition

Invade terminal ends of maternal spiral arteries

Create hybrid vessels (of maternal and fetal origin)

Connect the vessels to ‘lacunae’ / intervillous spaces

The hybrid vessels are large – sinusoids – low resistance
• Extraembryonic vascular system established
• Free villi extend from stem villi to intervillous spaces
o Develop as buds from stem villi
o Initial structure

Vascular mesoderm coverd by

Cytotrophoblast which inturn is covered by

Syncytiotrophoblst
o To reduce the resistance some (occur mainly in smaller villi)

Cytotrophoblastic cells disappear

Connective tissue disappear

Syncytium becomes thin – by shedding parts of syncytium as syncytial knots –
degenerate after entering maternal circulation
PLACENTA
• Disc shaped
1. Fetal Portion – Chorion frondosum
2. Maternal portion – Decidua basalis [ mostly the decidual plate]

EXTENT OF THE PLACENTA
• Fetal side – chorionic plate
• Maternal side – decidua basalis
• The placenta grows throughout the
pregnancy along with the uterus
• The increase in thickness of the placenta
is due to arborization of existing villi, not
by further penetration into maternal
tissue
Junctional zone of the placenta – The

intermingling zone of decidual and trophoblast
cells
Decidual septa project into intervillous spaces but do not reach the chorionic plate. Therefore the
placenta is divided into number of compartments called – cotyledons
BUT – connection is maintained between adjacent intervillous spaces. Why? – The decidual septa don’t reach
the chorionic plate
EXTERNAL APPEARANCE OF THE FULL-TERM PLACENTA

Maternal side
• Outermost thin layer of decidua basalis
• 15 – 20 cotyledons separated by grooves demarcating the decidual septa
Fetal side
• Innermost chorionic plate – smooth – no cotyledons
• Chorionic vessels converge towards the umbilical cord (the attachment of the umbilical cord is
usually eccentric)
CIRCULATION OF THE PLACENTA

• Maternal and fetal blood do not mix (occasionally few blood cells escape)
• Hemochorial placenta –(maternal blood in the intervillous spaces is separated from the fetal blood by a chorionic derivative)
• Materials can be exchanged with least resistance
• Placental exchange does not occur in large anchoring villi
• Why?
o Placental Membrane
1. The layers that separate the maternal and fetal blood
1. The endothelial lining of the fetal vessels
2. Connective tissue of the villus core
3. Cytotrophoblastic layer
4. Syncitium
• But exchange occurs in free villi and small anchoring villi
• Why?
o Placental Membrane
1. Endothelial lining of fetal vessels
2. Syncytium
• Microvilli are found in the maternal surface of the syncytium of free villi, increasing the surface
area and therefore the exchange rate
• Many substances pass through the placental membrane/ placental barrier freely.
TWINS
1. Dizygotic twins
2. Monozygotic twins
Dizygotic Twins
Fertilization of two ova by two different spermatozoa
• Genetically different zygotes
• Can be of same or different sex
• No more than the resemblance of brothers and sisters – fraternal
• Implant separately in the uterus
• Has separate placenta and all other fetal membranes for each embryo
• BUT if implanted close together, placentae, chorionic sacs can fuse
o Erythrocyte mosaicism?
Monozygotic twins
Develops from a single fertilized ovum
• Identical (morphologically, genetically, of the same sex)
Depending on the stage of separation monozygotic twin placentae and fetal membranes differ
Seperation at
• Two cell stage (Zygote divides to form two zygotes)
• Earliest separation
• Two zygotes
• Separate implantation
• Separate placentae
• Separate chorionic sacs

As in dizygotic twins the placentae and chorionic sacs can fuse if implanted
closeby
• Early blastocyst stage (separation occurs in the inner cell mass only)
• Common chorion
• Common placenta
• Separate amnions

• Bilaminar germ disc (before the appearance of the primitive streak)
• Common chorion
• Common placenta
• Common amniotic cavity
• After the appearance of primitive streak, node (partial splitting of primitive node, streak)
• Conjoined twins (craniopagus, pygopagus, thoracopagus)
• Common chorion
• Common placenta
• Common amniotic cavity

SECOND WEEK OF DEVELOPMENT – The week of twos
At the beginning – Blastocyst is partially embedded in the endometrial stroma. The embryonic pole of
the blastocyst is facing the endometrium.
TWO number ONE

The trophoblast over the embryoblast differentiates into the following by day 8.
1. Cytotrophoblast
a. The inner layer of trophoblast
b. Made out of cells
c. Cells divide (mitotic figures found)
2. Syncytiotrophoblast
a. Outer layer of the trophoblast
b. Multinucleated zone without distinct cell boundaries, therefore
called syncytium
c. Cells from cytotrophoblast migrate into syncytiotrophoblast, fuse
and lose their cell membranes
TWO number TWO

The embryoblast differentiates into two layers
1. Hypoblast layer
a. Adjacent the blastocyst cavity
b. Cuboidal cells - these form the exocoelomic cavity/primitive yolk sac/Heuser’s
membrane by migrating to the abembryonic pole
2. Epiblast layer
a. Amniotic cavity – between epiblast and amnioblasts
b. High columnar cells

TWO number THREE
Two cavities appear
1. Amniotic Cavity
a. A cavity named ‘AMNIOTIC CAVITY’ develops in the epiblast.
1. Cells towards the cytotrophoblast are called the – amnioblasts
2. Cells towards the hypoblast - Epiblast
Therefore, the amniotic cavity is surrounded by amnioblasts in one pole and epiblast layer in the
opposite pole
2. Primitive Yolk Sac/ Exocoelomic cavity

a. Cells from the hypoblast migrate and line the inner surface of the cytotrophoblast of the
abembryonic pole.
b. Thin/flattened cells
c. The lining is called the ‘exocoelomic membrane’ / Heuser’s membrane
The blastocyst is more deeply embedded in the endometrium and the penetration defect is closed by
a fibrin coagulum by day 9. Later the coagulum is replaced by endometrial surface epithelium.
Also, on day 9 syncytial vacuoles appear at embryonic pole, thus called lacunar stage of trophoblast.
Days 11 & 12
Uteroplacental circulation is established.
STATE OF THE ENDOMETRUIM [Decidua reaction]

• Odematous
• Highly vascular – spiral arteries – later the capillaries become congested and dilated - sinusoids
• Large tortuous glands which secrete glycogen and mucus
• Cells become polyhedral and loaded with glycogen & lipids
DEVELOPMENT OF THE TROPHOBLAST

Development in the embryonic pole is faster than that of the abembryonic pole.
Syncytiotrophoblast
1. Vacuoles develop -> vacuoles fuse -> form lacunae [lacunar stage of the trophoblast] - day 9
2. Penetrates deeper and erode endothelial lining of maternal sinusoids / capillaries
3. Maternal blood enters the lacunar system – [Uteroplacental circulation] - days 11 & 12

By the 13th day of development the uteroplacental circulation extends to the abembryonic pole as well. If the
implantation site of the endometrium is not healed properly, bleeding occurs and can be confused as normal
menstrual bleeding. – Leads to inaccuracy of the expected delivery date
Cytotrophoblast
1. Columns of cells develop into the syncytium. - day 13
2. Known as ‘Primary Villi’ (outer layer of syncytiotrophoblast surrounding core of cytotrophoblast)
DEVELOPMENT OF THE EXTRAEMBRYONIC MESODERM (days 11 & 12)

• Cells derived from the yolk sac occupy the space between the cytotrophoblast externally and
the amnion and the exoceolomic membrane/primitive yolk sac internally.
• Fine, loose connective tissue
• Called the ‘Extraembryonic mesoderm’
DEVELOPMENT OF THE EXTRAEMBRYONIC COELOM

• Cavities develop in the extraembryonic mesoderm
• The cavities coalesce
• Form a single cavity
• Called the ‘Extraembryonic coelom’/ chorionic cavity
Therefore, the extraembryonic coelom seperates the cytotrophoblast (lined internally by the
extraembryonic somatopleuric mesoderm) from the primitive yolksac and amniotic cavity. (lined
externally by the extraembryonic splanchnopleuric and somatopleuric mesoderms respectively)
BUT the germ disc is connected to the trophoblast by a ‘connecting stalk’ made of extraembryonic
mesoderm.
Therefore, the only place where the extraembryonic mesoderm traverses the chorionic
cavity/extraembryonic coelom is the ‘connecting stalk’ - later becomes the umbilical cord
Extraembryonic mesoderm lining the inside of the cytotrophoblast is called the – chorionic plate

EXTRAEMBRYONIC MESODERM
Lining;
• Cytotrophoblast + Amnion = Extraembryonic somatopleuric mesoderm
• Yolk sac = Extraembryonic splachnopleuric mesoderm
DEVLOPMENT OF THE SECONDARY / DEFINITIVE YOLK SAC

• Cells produced from the hypoblast migrate along the inside of the exocoelomic membrane and
form a new cavity within the primitive yolk sac by pinching off its portions.
• These portions are called - exocoelomic cysts
Therefore the exocoelomic cysts are found in the chorionic cavity / extraembryonic coelom
Secondary yolk sac is smaller than the primitive yolk sac.
Normal site of pregnancy: Posterior or anterior wall of the uterus
Sites of ectopic pregnancies: abdominal cavity, ovary, uterine tubes

THIRD WEEK OF DEVELOPMENT
Day 15: primitive streak appears. This establishes laterality (all 3 axes of embryo)
GASTRULATION
Process that establishes the three germ layers (ectoderm, mesoderm, and endoderm) of the embryo
Where are we? – Embryoblast – Two layered – Epiblast & Hypoblast

All three germ layers are derived from the cells of the epiblast
How?
• The ‘primitive streak’ appears on the surface of the epiblast
o A narrow groove with slightly bulging regions on either side
• The cephalic end of the streak is ‘primitive node’
o Slightly elevated area surrounding the ‘primitive pit’
Cells of the epiblast migrate toward the primitive streak -> Invaginate
(become flask shaped, detach and slip)
Invagination occurs from the primitive node and then proceeds along
the primitive streak.
The invaginated cells that
• Displaced the hypoblast become the endoderm (therefore
hypoblast cells do not contribute to the body of the foetus except
the part of the definitive yolk sac incorporated to the gut)
• Lie between epiblast and endoderm become the mesoderm
The remaining cells of the epiblast become the ectoderm
The mesoderm spreads laterally and fuses with the extraembryonic mesoderm
Therefore now,
• The ectoderm is in continuation with the amnioblasts
• The mesoderm is in continuation with the extraembryonic mesoderm (both splanchnopleuric and
somatopleuric)
• The endoderm is in continuation with the cells of the secondary yolk sac

MIDLINE STRUCTURES OF THE TRILAMINAR GERM DISC
Cranial to caudal in order
1. Oropharyngeal/ buccopharyngeal membrane
(ectodermal+endodermal)
2. Prechordal plate – (mesodermal)
3. Notochord- (mesodermal)
4. Primitive node – (ectodermal)
5. Primitive streak – (ectodermal)
6. Cloacal membrane (ectodermal+endodermal)
OROPHARYNGEAL MEMBRANE
• Tightly adherent ectoderm and endoderm
• Gives rise to the opening of the oral cavity
in the future
PRECHORDAL PLATE
• Derived from some of the cells that migrate
through the primitive node in the midline
• Induction of the forebrain development
• located between notochord and
oropharyngeal membrane
NOTOCHORD
• Represents the primitive skeletal structure
characteristic to the chordates
• Development of the Notochord
The caudal end of the primitive streak continually supplies new cells until the end of the fourth week. By this
time the germ layers are established and differentiation initiated in cephalic regions. Therefore the caudal
regions of the embryo are developmentally lagging in comparison to cephalic regions
Therefore most of the structures develop cephalocaudally
1. Prenotochordal cells invaginate through the primitive node,

move cranially in the midline towards the prechordal plate.
2. Become intercalated in the hypoblast
• Therefore at this moment the midline between the primitive node
and the prechordal plate is composed of two layers only – called
the notochordal plate
3. Cells of the notochordal plate proliferate and detach from the
endoderm
4. Form a solid cord of cells – definitive notochord
5. The formation of the notochord is cranial to caudal
The notochord then signals/induces formation of the neural
tube and axial skeleton. The nucleus pulposus of IV discs
is a remnant of it.

PRIMITIVE PIT
• At this stage of the embryo the primitive pit connects the amniotic cavity and the yolk sac through
the neurenteric canal.
• This canal is closed in eventual development
• Migratory gateway of epiblastic cells which form midline mesoderm and endoderm (and paraxial
mesoderm)
PRIMITIVE CHORD
• A shallow groove in the ectoderm.
• The migratory gateway of epiblast cells which form mesoderm and endoderm
CLOACAL MEMBRANE
• Tightly adherent ectodermal and endodermal cells that later form the anal membrane and the
urogenital membrane (separated by the urorectal septum).
• After the appearance of the cloacal membrane the posterior wall of the yolk sac forms a small
diverticulum which extends into the connecting stalk called – allantoenteric diverticulum /
allantois
GROWTH OF THE EMBRYONIC DISC

• The initial embryonic disc is round and flat
• Because the cells migrate through the streak forwards and laterally
o Expansion of the disc occurs mainly in the cephalic region
o Primitive streak remains more or less the same size
• Therefore the embryonic disc is elongated with a broad cephalic and a narrow caudal end
• By the fourth week the primitive streak disappears.
• Starts to disappear by day 21, finished by day 28
By day 20:
o neurulation begins
o primary villi become secondary villi
o allantois diverticulum forms
o mesoderm differentiates into paraxial, intermediate and lateral plate
o somites appear
DEVELOPMENT OF THE TROPHOBLAST

Primary villus – Cytotrophoblastic core
coverd by syncytium
Then Primary villus core penetrated by
mesodermal cells to form,
Secondary villus – Mesodermal core,

covered by cytotrophoblast and syncytium
Then differentiation of mesodermal cells
into blood vessels,
Tertiary villus/ definitive placental villi –

blood vessels covered by mesoderm,
cytotrophoblast and syncytiotrophoblast,
connect the intraembryonic and
uteroplacental circulations with the villi as
a barrier.
EXTRAEMBRYONIC CIRCULATION
o Blood and blood vessels are derived from the mesoderm
o Mesoderm in the core of secondary villi, chorionic plate, connecting stalk and intraembryonic
mesoderm are in continuity
o Therefore when blood vessels develop in each of the above sturctures, a connected
extraembryonic, and intraembryonic circulation is established
o Ie; capillaries in tertiary villi -> capillaries in the chorionic plate -> capillaries in the connecting stalk
-> intrarmbryonic capillaries
o The connecting stalk will develop into the umblical cord eventually
In the 4th week
o Cytotrophoblastic cells penetrate the syncitium until it meets the decidua basalis of the
endometrium.
o Neighboring villi are connected forming a thin outer cytotrophoblastic shell.
o These villi + cytotrophoblastic shell firmly attaches the chorionic sac to the endometrium.
o Villi that extend from the chorionic plate to decidua basalis – anchoring/stem villi
o Villi branching from the sides of stem villi – free villi

THE EMBRYONIC PERIOD (Organogenesis)
3rd to 8th weeks of development
The germ layers give rise to specific tissues and organs which leads to establishment of main organ systems.
Major features of the external body form can be recognized by the end of this period.
ECTODERM
Neurulation
Formation of the ‘neural tube’

Notochord and prechordal plate induces the overlying
ectoderm to thicken and form the – neural plate,
neuroectoderm
1. Lateral edges of the neural plate become elevated –
neural fold
2. Depressed mid region – neural groove
3. Neural folds approach each other in the midline and fuse – neural tube formed
• Fusion begins at the cervical region and proceed cranially and caudally
4. Cephalic and caudal ends communicate with the amniotic cavity by way of anterior (cranial), posterior
(caudal) neuropores respectively.
Neural tube begins to close on day 22. starts from 5th somite and proceeds cranially and caudally.
• Closure of cranial/anterior neuropore – 25th day
• Closure of caudal /posterior neuropore – 28th day
5. Closed tubular structure – represents the central nervous system
6. Cephalic portion widens and dilate – brain vesicles
7. Narrow caudal portion – spinal cord
Neural Crest Cells

Cells at the crest of the neural folds detach and leave the neuroectoderm and enter the underlying
mesoderm.
These cells become mesenchymal cells.
Therefore neural crest cells must undergo epithelial to mesenchymal
transition as it leaves the neural folds.
Mesenchyme refers to loosely organized embryonic connective
tissue regardless of origin
• Neural crest cells from the trunk region

o Dorsal pathway
Skin – melanocytes, hair follicles
o Ventral pathway
Sensory ganglia
Sympathetic neurons
Enteric nervous system
Schwann cells
Cells of adrenal medulla
• Neural crest cells from the cranial neural folds
o Craniofacial skeleton and connective tissue & meninges
o Endocardial cushions forming cornutruncal septum, etc.
Therefore it is common to find facial and cardiac abnormalities together
o Neurons of cranial ganglia
o Glial cells
o Melanocytes
o c-cells of the thyroid gland
o odontoblasts
• Following are derivatives of

the ectoderm.
CNS
PNS
Sensory epithelia
Epidermis, hairs, nails
Subcutaneous glands
Mammary glands
Pituitary gland
Enamel of teeth
MESODERM
The mesoderm beside the midline thickens and forms the paraxial mesoderm.
The most lateral mesoderm splits into two, giving rise to a cavity the intraembyronic cavity which becomes continuous with
the extraembryonic cavity.
The mesodermal layer continous with the extraembryonic somatopleuric mesoderm (covering the amniotic cavity) becomes
the parietal/somatic mesoderm.
The mesodermal layer continous with the extraembryonic splanchnopleuric mesoderm (covering the yolk sac) becomes the
splanchnic/visceral mesoderm.
The unsplit mesoderm connecting the lateral plate and paraxial mesoderms is called the intermediate mesoderm.
Paraxial mesoderm
Become organized into segments – somitomeres- mesodermal cells organized in concentric whorls . (in the 3rd
week)
Formation of somitomeres is cephalocaudal
From occipital region caudally somitomeres further organize into - somites at around 3 per day for 15 days
At the end of 5th week 42-44 somites are present
o 4 occipital (1st occipital disappear later) o 8 cervical
o 12 thoracic
o 5 lumbar
o 5 sacral
o 8 – 10 coccygeal (last 5 -7 disappear later)
The age of an embryo is determined by counting somites.

SOMITE DIFFERENTIATION
1. Presomite mesoderm – ball of mesoderm
2. Arrange into a donut shape by epithelization
3. Differentiation
a. Sclerotome – form the vertebrae and ribs
b. Dermatome – form the dermis of the back
c. Myotome – form segmental muscular component
Each somite and subsequently its derivatives, retain their segmental innervation, giving rise to specific
dermatomes and myotomes which are exclusively supplied by a specific spinal segment.
Each dermatome and myotome has its own segmental nerve component, and retains it no matter where the cells
ultimately migrate.
In addition to axial structures, The paraxial mesoderm gives rise to the muscles of the limbs.
For futher detail on somite differentiation read Langman’s, 11ed, p76
INTERMEDIATE MESODERM
Differentiate into urogenital structures (ie.
Gonads, internal genitalia, kidneys and
ureters) Cervical and upper thoracic – form
segments – nephrotomes
More caudally – unsegmented –
nephrogenic cord
LATERAL PLATE MESODERM
1. Parietal (somatic) mesoderm
o Lateral wall body folds
o Dermis of the skin of body wall and limbs
o Bones and connective tissue from the limbs
o Sternum
o Parietal layer of serous membranes lining body cavities (pleural, pericardial, peritoneal)
Sclerotome and myotome cells that migrate into this layer form costal cartilages and limb and body wall muscles respectivel
2. Visceral (splanchnic) mesoderm

o Wall of the gut tube (with the endoderm)
o Visceral layer of serous membranes lining body cavities (pleural, pericardial, peritoneal)
BLOOD AND BLOOD VESSELS

Of mesodermal origin (mesodermal cells -> hemangioblasts
->blood cells/vessels)
2 ways
1. Vasculogenesis – vessels arise from blood islands
2. Angiogenesis – sprouting from existing vessels
Vessel development start from the mesoderm surrounding

the yolk sac and spread into lateral plate mesoderm and
other regions
Hematopoetic Tissue Development (Blood cell forming
tissue)
First blood cells appear in the mesoderm surrounding wall
of yolk sac but lose its function eventually
The mesoderm surrounding the aorta colonize the liver and
form the definitive hematopoetic stem cells
After seven months of gestation these stem cells colonize
the bone marrow and form definitive blood forming tissue
(later the liver loses its hematopoetic function)
ENDODERM
Endoderm forms the ventral surface of the trilaminar germ disc, which is the roof of the yolk sac
Body Folding
Formation of a tubular body from a trilaminar germ disc
1. Cephalic folding
• Cephalic part of the germ disc (head fold) folding towards the middle of the disc
• The endodermal germ layer is incorporated into the body to form the foregut
2. Caudal folding
• Caudal part of the disc (tail fold) including the connecting stalk fold towards the middle
• Endodermal germ layer is incorporated into the body to form the hind gut
• The allantois initially incorporated to the connecting stalk develops a connection with the hind gut forming
the cloaca – (discussed later in system based embryology)
3. Lateral folding
• Lateral parts of the germ disc fold toward the anteroposterior midline(axis)
After folding the yolk sac is connected to the midgut by the vitelline duct
As a result of cephalocaudal and lateral body folding ventral

body wall of the embryo is closed except for the umbilical
region where,
1. Connecting stalk
2. Vitelline duct
3. Umbilical vessels are attached.
The vitelline duct is wide initially. But with further growth of the embryo it becomes narrower and longer.
1. The cephalic end of the foregut is closed by the oropharyngeal membrane

• Primitive oral cavity is derived from the ectoderm and is called
the stomodeum
• Pharynx is a part of the foregut (endodermal origin)
• The oropharyngeal membrane separate the stomodeum from
pharynx
• In the fourth week oropharyngeal membrane ruptures
establishing open connection between oral cavity and primitive
gut
2. Caudal end of the hindgut is closed by the cloacal membrane

• Lower part of the anal canal is developed from the ectoderm and is called the proctodeum
• The upper part of the anal canal is derived from the endoderm
• These two parts are separated by the cloacal membrane
• Cloacal membrane ruptures in the seventh week
In humans the yolk sac is vestigial (suspected to have a nutritive role in early development).
Therefore the endoderm basically forms the epithelial lining of the primitive gut tube, intraembryonic portion of allantois, an
vitelline duct.
All gut tube derivatives too are of endodermal origin.
1. Epithelial lining of the respiratory tract
2. Epithelial lining of urinary bladder and urethra
GENETICS
Human DNA
Nuclear DNA Mitochondrial DNA
3% coding 97% non-coding 37 genes
Microsatellite DNA Minisatellite DNA

• scattered throughout the genome • concentrated near telomeres &
centromeres
• Used to track inheritance of disease • used for DNA fingerprinting due to
alleles high variability
Mitochondrial genes
• The only organelles outside the nucleus that have their own DNA (extranuclear DNA)
• Circular rather than linear
• Double helix arranged as rings (2-10 rings)
• Unique sequences rather than repetitive
• Slightly different genetic code
• Exclusively transmitted to next generation by mothers through oocytes.
Chromosomal structure & function
Somatic chromosome complements consist of 46 chromosomes (23 pairs).

22 pairs are Autosomes.
23rd pair is a pair of sex chromosomes.
Male-46, XY Female-46, XX
Nucleosome: fundamental packaging unit made up of 8 histone proteins & DNA – In

metaphase chromatin is more condensed than in interphase
Chromatosome: the nucleosome plus the H1 histone occupying the linker region

Euchromatin: forms the main body active, high proportion of coding genes Lightly stains
Heterochromatin: genes are absent or inactive
Depending on the position of the centromere, chromosomes have short arms(p) / long arms(q)
o Metacentric –Centromere is in the middle (p=q), ex: - 1,3,16,19 and 20
o Submetacentric - Centromere is displaced from the centre (p< q), ex: - 6-12, X
o Acrocentric- centromere is at one end (p<< q), ex: - 13-15,21,22 & Y
Telomeres
• Are ends of chromatids

• specific telomeric proteins binds to this site forming a cap
Functions;
• prevent abnormal end to end fusion of chromosomes ensure complete replication of ends
• assist chromosome pairing in meiosis
• maintain stability/link chromosomes to the nuclear membrane during interphase and help
establish internal structure
• may be involved in aging process
Cytogenetics / chromosome cultures

• performed on rapidly dividing somatic cells from metaphase stage of mitosis
• prenatal / postnatal cells can be used
• to detect birth defects, cancer etc.
Chromosome analysis & classification ( at metaphase of division )
Commonly used cell: peripheral lymphocytes, fibroblasts, bone marrow cells, fetal cells
(amniocentesis, chorionic villi extraction), chordocentesis, fetoscopy
(Liver cells, Skin cells and Blood cells)

Karyotype: photographic representation of the entire chromosome complements
• G banding : uses the Trypsin and Giemsa

• high resolution banding to
Stain .To detect numerical defects
detect micro deletions.
• light band : active-lightly stained bands
• Detect structural defects
G-C rich
• dark bands : inactive, densely stained,
relatively inactive
Other staining methods- fluorescent dyes and examination under UV light
Mitosis (25)
• Process by which parent cell divides giving rise to two daughter
cells
• Which are genetically identical to the parent cell
• Each daughter cell receives the complete complement of 46
chromosomes
• Is an intermediate stage in cell cycle
• Has 4 phases
• Prophase
• Metaphase
• Anaphase
• Telophase
• Before cell entering the mitosis, each chromosome will
replicate its DNA
• During this replication process chromosomes are extremely
long & diffusely spread through the nucleus
• With the onset of mitosis chromosomes begin to coil, contract
& condense
• Marks beginning of prophase
• Each chromosome consists two parallel subunits, chromatids
• Joined to each other by centromere
• Throughout the phase chromosomes continue to condense,
shorten & thicken Metaphase
• Line up in the equatorial plane
• Each attached by microtubules
• Extending from centromere to centriole
• Form mitotic spindle Anaphase
• Division of centromere followed by migration of chromatids to
opposite poles of the spindle Telophase
• Chromosomes uncoil & lengthen
• Nuclear envelope reforms
• Cytoplasm divides giving rise to two genetically equal daughter
cells
• Each daughter cell receives half of doubled chromosome
material
• Maintains equal number of chromosomes as that of mother cell

MEIOSIS
PROPHASE I
1st meiotic division

Leptotene Zygotene Pachytene Oeplotene Oiakinesis
METAPHASE I
ANAPHASE I
TELOPHASE I
METAPHASE II
2nd meiotic division
ANAPHASE II
(• (• •) •)

MEIOSIS
• Before cell entering the meiosis, each chromosome will replicate its DNA
• Each chromosome resulting two sister chromatids
• In prophase l
• Chromosomes become visible as threads
• Homologous chromosomes pair
• Formation of synapsis
• Cross over of chromosomal material
• Further condensation of chromosomes
• Homologous pair begin to separate but held together at the point of cross over - chiasmata
• Metaphase l
• Homologous pair position on either side of equatorial plane
• Spindle formation
• Independent assortment
• Anaphase l
• Homologous chromosomes separate from each other & move to the opposite poles of the cell
• Telophase l
• Two haploid sets of chromosomes reach each pole & cytoplasm divide forming two new daughter cells
secondary oocyte & 1st polar body
• Enters meiosis ll following a brief interphase
• Arrest in metaphase ll
• Chromosomes attached to spindle at kinetochores
• Anaphase ll
• Centromeres separates allowing the chromatids to pull to opposite poles
• Telophase ll
• Chromosome begins to uncoil assuming the extended state characteristic of interphase
Additionally,
Meiosis Prophase 1:
 Leptotene -Chromosome visible as threads, chromatids unable to be distinguished
 Zygotene -homologues chromosomes pair along their lengths side by side. Synaptonemal complexes appear which
assist in synapsis and crossing over.
 Pachytene-Chromosomes condense further. Visible in fours(tetrads). Recombination through crossing over.
 Diplotene-Homologous chromosomes begin to separate but held together at chiasmata
 Diakinesis-Chromosome pairs attempt to separate & reach maximal condensation
The process of meiosis differs in males and females. In males this is a continuous process which begins in the
mature seminiferous tubules of adolescents. In females by birth the process is arrested in prophase 1 in a stage
called Dictyotene. After menarche with each ovulation meiosis 1 is completed and meiosis 2 begins. Meiosis 2
completes only following the entry of the spermatozoon into the egg.
Meiosis differs from Mitosis for the following reasons:
1. It occurs only in germ cells, whereas mitosis occurs in somatic cells.
2. It consists of two sequential cell divisions, whereas mitosis has only one.
3. Pairing of homologous chromosomes occurs, which is not seen in mitosis.
4. Recombination of homologous chromosomes takes place, which is not seen in mitosis.
5. There is a reduction in the number of chromosomes from 46 to 23, unlike in mitosis.
The genetic consequences of meiosis are:

1. It helps in the reduction of the number of chromosomes, and thereby assists gamete formation.
2. It helps in the segregation of alleles, thereby allowing only one of an original gene pair to be included
in each gamete.
3. It assists in the independent assortment of homologous chromosomes, so that each gamete contains a
mixture of paternal and maternal chromosomes.
4. By the process of crossing over, it ensures that each gamete carries genes inherited from both the father
and the mother.

Mutation
•
A heritable change in genetic material in less than 1% of the population
[More than 1% ----- polymorphism]
•
Occur in a coding or non-coding sequence
•
In somatic cell ---- cannot be transmitted
•
Gonadal tissue / gametes ---- transmitted to future generations
Mutations
Structural mutations Numerical mutations
Chromosomal Disorders
(ii) Polyploidy
Presence of more than 2 sets of chromosomes Ex: - triploids - 69, XXX
69, XXY
69, XYY
tetraploids
Imprinting is shown in triploidy [phenotypic expression varies

depending on whether the extra set of chromosomes are paternal
or maternal in origin]
maternal :- small fetus , placenta is not cystic
paternal :- large head, cardiac anomalies, cystic placenta
Triploidy (69 chromosomes) may result from a failure of meiosis in a germ cell or
dispermy. Tetraploidy (92 chromosomes) results from a failure of the first
cleavage division after fertilization.
(iii) Trisomy
• Presence of 3 copies of a single chromosome
• commonest cause is nondysjunction in meiosis I (80%)
• secondly in meiosis II (20%)
• in either sex (oogenesis 80% ,spermatogenesis 20%)
• in early mitotic division of the zygote , anaphase lag.
• Most triosomic embroyos are lost in early pregnancy. Usually only
trisomies 13,18 and 21 survive

Autosomal:
Down Syndrome (trisomy 21)
Karyotype:- [47,XY, +21 or 47,XX,+21]
96% - trisomy 21
4% - translocation to 13,14,15,21 or 22 - very
small percentage are mosaics
Can be diagnosed prenatally by ultrasound scan
My CHILD HAS a PROBLEM
C - congenital heart diseases H

– hypotonia,hypothyroidism I
- increased sandle gap
L - low set ears
D - duodenal atresia
H - hypertelorism,hirchsprung disease A - aplasia of middle
phalanx of 5th digit,alzeimer’s disease
S - simian crease,stubby hands
P - protruding tongue
R - respiratory infections
O - occiput flat
B - behavioural problems
L - low flat nasal bridge
E - epicanthic folds
M – mental retardation

Trisomy 13-Patau Syndrome
• Growth retardation
• Microcephaly with severe mental retardation
• Midline abnormalities (Scalp defects, Holoprosencephaly)
• Facial defects (Micrognathia, central/unilateral clefts)
• Eye defects (Hypotelorism, Micropthalmia, Anopthalmia or Cyclopia)
Trisomy 18-Edward Syndrome

• Growth deficiency
• Small faces
• Prominent occiput
• Sloping forehead
• Small malformed and low set ears
• Micrognathia
• Overlapping fingers
• Prominent heels
• Cardiac and renal malformations common
Sex chromosomes:
Klinefelter syndrome: - 47 XXY or 48XXXY or 49XXXXY
Adult phenotype is basically male though
Gynaecomastia, poor musculation eunuchoid habitus
feminine body hair distribution small genitalia
tall stature
long lower legs / forearm scoliosis/osteoporosis varicose veins and
ulcers
infertility due to azoospermia or subfertility due to oligospermia are evident.
Only 47XXY is accompanied with advanced maternal age [ intracytoplasmic sperm injection ICSI is done]
XYY syndrome
• Karyotype-[47, XYY]
• Affected males have a normal physical appearance
• Problems in motor coordination
• Above average stature
• Mildly impaired intelligence
• Aggressive behavior
Triple X Syndrome
• Karyotype-[47, XXX]
• Affected girls are physically normal
• Taller than average
• Arises form an error in meiosis 1
(iv) Monosomy- autosomal monosomies are lethal but monosomy for X is compatible with life.
Turners syndrome:- 45X
• phenotype basically female but streaky ovaries can be diagnosed prenatally
• neck webbing, cutis laxa, sheld shaped chest, coarctation of aorta, lymphodema of hands and feet,
short stature and cardiac murmur in childhood.
• Iry or IIry amenorrhoea, lack of IIry sexual characteristics
• oestrogen replacement therapy should be initiated at adolescence
• normal mentality.
• Adults may present with infertility
• Thyroiditis and kidney abnormalities may be present.

Random X inactivation/ Dosage compensation / lyanisation
• during late blastocyst stage
• in females either maternal / paternal X is permanently inactivated randomly in each cell
• forms a Barr body ---- seen in interphase
• areas crucial for development remain active
• in the extra-embryonic trophoblastic cells, the paternal X is preferentially inactivated.
• Hence every woman is a mosaic in expressing her X chromosomes.
4. Mosaicism
• presence of two or more cell lines with different karyotypes in a person
• caused by chromosomal nondisjunction during mitosis
• clinical feature depends on proportion of abnormality to normal cells
• The abnormal cell line may be confined to a particular tissue if the
aberration took place in the late embryonic or fetal development
• to multiple tissues if the changes took place in very early
development. Ex: 46, XX/47, XX, +21
Structural abnomalies
(i) deletion
leads to a loss of chromatin
terminal deletions
• Eg:- cri du chat syndrome :- deletion of tip of the short arm
of the chromosome[ 5p] malformed larynx [cat like cry].
• low birth weights and have failure to thrive.
• round faces, low set ears, profound learning disability,
Hypotelorism, epicanthic folds
micro deletions
• syndromes-Very small deletions often detected by high
resolution banding.
Imprinting is seen chromosomal 15q
paternal: Prader -Willi syndrome
maternal: Angelman syndrome
detected only by special high-resolution banding
Interstitial deletions
(ii) isochromosome
formed when a chromosome with two chromatids splits at right angles
to the normal length wise separation seen in normal division.
Chromosomes will have both short arms or both long
arms. Ex:- 20% of Turner Syndrome individuals
Down syndrome (long arm trisomy and short arm monosomy)
(ii) inversion
Chromosomes break at two points & the intervening broken segment turns 180 degrees to reverse
the order of chromatin.
If the break points are on the same arm - paracentric inversion
If it’s on either side of the centromere including it in the broken segment - pericentric
inversion. This leads to chromosomally unbalanced gametes.
(iii) translocation
exchange of chromosomal material between chromosomes 3 types:
• centric fusion or Robertsonian translocation
Fusion of whole arms of acrocentric chromosomes. Breakpoints are at or near the centromere.
Fused long arm chromosome survives while the fused short arm chromosome is lost.
No effect is produced as short arm of acrocentric contain genetically inert material or RNA genes.
(4% downs are of this type. commonest involving - long arms of chromosome 14 & 21 t(14q21q))

• Reciprocal
Breakage and then exchange of segments of chromosomes. Point of exchange may be anywhere along the
chromosome. No loss of chromosomal material.
Ex: Philadelphia chromosome – deleted chromosome 22 in which long arm has been translocated to the
long arm of chromosome 9. used to indicate prognosis of chronic myeloid leukemia (CML) & acute
lymphocytic leukemia.
The absence of the Ph chromosome in CML indicates bad prognosis.
• Insertional
Insertion of a deleted segment of a chromosome interstitially or inside another chromosome following
a break at that point
Insertion of a deleted segment of a chromosome interstitially or inside another chromosome following
a break at that point
(iv) Other anomalies

• Fragile X syndrome:
more frequent in males
tip of the long arm of X is fragile.
speech delay, mental retardation with moderate educational sub normality. triangular
face, prominent mandibles, macrochidism, closely set eyes, large ears. Females with
fragile x are mentally normal.
• Chromosome breakage syndrome: Due to errors in DNA repair & synthesis
Ex: Fanconi Anaemia, Ataxia Telangiectasia show multiple fragility.
Early development:
At the beginning of week 5 primordial germ cells migrate from endoderm cells of the yolk sac and infiltrate
primitive sex cords within mesodermal genital ridges which are products of coelomic epithelium.
Paired indifferent gonad is identical in males and females.
Bipotential Male external genitalia

External genitalia {After 8th week}
• Androgen receptors are coded by a gene on the X chromosome
1. Which of these are autosomal dominant disorders.

a) Huntington’s disease
b) Marfan syndrome
c) Occulocutaneous albinism
d) Achondroplasia
e) Duchenne muscular dystrophy
2. Regarding autosomal dominant inheritance
a) Every affected person has an affected parent.
b) Variable expressivity can be seen in marfan syndrome.
c) The heterogenous carriers may show clinical features.
d) Achondroplasias are usually caused by new mutations.
e) More males are affected than females.
f) Is transmitted through both males and females.
g) Reduced penetrance is seen.
h) There are more affected females than males.
i) Achondroplasia belongs to this category.
3. Regarding Down syndrome
a) Short stature is a common feature.
b) The disorder can be diagnosed prenatally.
c) Trisomy 21 is the commonest variety.
d) Carrier states can be detected in the translocation types.
e) AV canal defects are the commonest cardiac complication.
f) Karyotype may be 47, XX,+21.
g) Hypertonia is seen at birth.
h) Mental retardation is a common feature.
i) Complete atrioventricular canal defect is the commonest cardiac lesion in these
patients.
j) The commonest cause is non-disjunction in meiosis II in oogenesis.

Genetics –II Patterns of Inheritance.
Definitions (pg33 Basic Medical Genetics)
• Gene
• Locus
• Alleles
• Genotype
• Phenotype
• Homozygous
• Heterozygous
• Dominant
• Recessive
• Autosomal
• X or Y linked
Pedigree: - graphical representation of a family tree which show the biological

relationship of the index case.
Birth defects
Genetic Non-genetic
Single gene defects Chromosomal Mitochondrial Multifactorial (Gene +

environmental)
anomalies
Single gene defects
(Mendelian inheritance)
Autosomal dominant Autosomal recessive X-linked dominant X-linked recessive Y-linked
Autosomal dominant
•
Vertical Inheritance –Transmission of the trait
continues from generation without skipping.
•
2 sexes are affected equally.
•
Every affected child has an affected parent except for a
new mutation.
•
Affected heterozygous + normal homozygous = risk 50%

1. New mutation
e.g.:- achondroplasia osteogenesis imperfecta
• Isolated case
• Increased paternal age
2. Reduced penetrance
e.g.:-multiple neurofibromatosis, marfan syndrome, BRCA, retinoblastoma
• Expression of number of individuals who have the gene & show the trait.
• If the frequency is less than 100% reduced penetrance exists.
3. Variable expressivity
e.g.:-marfan syndrome, multiple neurofibromatosis
• Degree of expression of a trait.
• The individuals of a family may show mild to moderate to severe forms of the disease.
4. Variation in age onset
e.g.:-adult polycystic kidney disease
Huntington’s disease - clinical features manifest in the 3rd or 4th decades of life
5. Variation in severity dependent on sex. ‘Anticipation’
Eg:- Huntington’s disease-manifest earlier if the affected parent is the father
myotonic dystrophy- manifest earlier if the affected parent is the mother
6. Genetic heterogeneity
e.g.:-Retinitis pigmentosa – caused by both autosomal dominant and recessive inheritance
• similar clinical picture
• different mutations at same locus or different loci
7. Influence of non-genetic factors
diet→expression of familial hypercholesterolemia
barbiturates→precipitate porphyria
8. Variable severity
• All offspring will not have the entire severity of the
disease e.g.:-tuberous sclerosis
9. Phenocopy
It is an environmentally caused phenotype which resembles one produced by a mutant gene.
e.g: Warfarin induced embryonic defects resembling Conradis’ syndrome.
Clinical examples for autosomal dominant

1) Huntington’s disease- Adult onset disease. Associated with choreiform movements and progressive loss
of mental activity, mood disturbances.
o Gene-short arm of chromosome 4 (4p)
o Anticipation
o Triplet repeat expansion (CAG)
2) Marfan syndrome
• Long arm of chromosome 15 (15q)
• Shows variable expression
• Connective tissue disorder
• Abnormal body proportions, Kyphosis, Scoliosis, Arachnodactyly, Mitral and Aortic valve
defects, dissecting aneurisms, Lens dislocations.
3) Familial hypercholesterolemia
• Deletion of a gene producing LDL receptors
• Increased cholesterol levels
• Premature coronary artery disease
In autosomal dominance heterozygous normally survives. Homozygous do not survives. But
in hypercholesterolemia, homozygous also survives.
Autosomal Recessive
• Only manifest in homozygous genes.
• Horizontal inheritance.
• Both sexes affected.
• Normal parents, some normal offspring with affected
siblings among them.
• Parental consanguinity increases the incidence.
• Heterozygote male + heterozygote female. →25% risk
• Carriers –usually normal, exception-sickle cell anemia
• Certain racial groups →recessive genes at higher
frequency
• If the recessive genes are alleles, all the children of two
affected parents are affected.

Clinical example
1) Homocystinuria –Deficiency of cystathione beta synthase.
2) Cystic fibrosis- short arm of chromosome 7 (7p). Chronic respiratory infections and
malabsorption. Secretions of the gut and lungs are thick and sweat is thick with high NaCl.
3) Phenylketonuria –Severe mental retardation due to accumulation of phenylalanine in blood, tissues and
urine. Mutation in long arm of chromosome 12.
4) Sickle cell anemia
- Mutant β-globin polypeptide chains on chromosome 11
- Glutamate is replaced with valine at position 6 from the amino end
- Normal HbA/HbA
- Trait HbA/HbS
- Disease state HbS/HbS
5) Thalassemia
- Imbalance of synthesis of globin chains
- The excess accumulates in RBC, Insoluble precipitates are formed causing hemolysis
- Causes anaemia leading to hyperplasia of bone marrow.
- 2 types (α & β)
X- linked dominant
• Mutant gene is dominant and on the X chromosome.
• Males may be normal or affected and female heterozygotes
are more variably affected due to random inactivation of X
chromosomes.
• Affected males never transmit it directly to sons. But do
transmit to all the daughters.
• Heterozygous females transmit it to half their sons & their
daughters.
• More females than males; lethal in male.
• All daughters of an affected father are affected.
• E.g.: Vit.D resistant rickets.
Incontinentia Pigmenti
Rett syndrome
X- linked recessive
• Hemizygous affected males→ heterozygous carrier daughters
• More males than females
• Affected male-heterozygous mother except for a new mutation.
• Female heterozygote-random inactivation of X - wide spectrum of
clinical features.
• If the gene on the X is normal then the male is normal. There are no
carrier states in the male.
• Heterogeneity may be seen where the clinical features are
similar but inherited through different mechanisms
• X linked lethal conditions are those where affected males die before
birth.
• ZIg-zag inheritance
e.g.:- Classical hemophilia A
red-green colour blindness Ocular albinism
G6PD deficiency
Becker muscular dystrophy
Duchene muscular dystrophy
• Short arm of X (Xp21)
• Absence of dystrophin protein (maintain muscle Ca permeability)
• Progressive wasting and weakness of proximal muscles of all limbs ` accompanied with
hypertrophy of calf muscles
• Death in teens due to cardiac or respiratory failure
Fragile X syndrome-
• a chromosome aberration.
• fragile sites are at tips of long arms of the X chromosome.
• Commonest inherited mental retardation (more common in males)
• Megalotestis (macrochidism)
Y-linked
-Directly from father to son.
-No father to daughter transmission
-Hairy ears, webbed toes.
-Only males are affected.
Multifactorial Inheritance
Genes + environment → final outcome – occurrence of the disease depends on the environmental
conditions at which both the parents and offspring live.
Accounts for the majority of congenital malformations and responsible for many normal variations in
humans.
• Non-syndromal malformations
- ASD, tetralogy of Fallot, VSD, PDA.
- Anencephaly, meningocephalocele, spina bifida.
- Cleft lip with or without a cleft palate.
- Congenital hip dislocation.
- Diabetes mellitus
- Hypertension
- Pyloric stenosis which is more common in males
- Systemic lupus erythematosus which is more common in females
• The diseases tend to be familial
• Occurs more in one sex than the other
• The recurrence risk is the same for all the relatives who share the same proportion of genes.
• The recurrence risk reduces as the relationship becomes distant
• It’s more common among children of consanguineous parents
Mitochondrial Inheritance
Inheritance is matrilineal
- Only mothers transmit the condition to both sexes
Tissue rich in mitochondria are mostly affected
- Heart
- Striated muscle
- Kidney
- CNS
e.g.:- Leber’s hereditary optic neuropathy

Diabetes mellitus with sensorineural deafness
1. Following conditions are autosomal dominant

a) Familial hypercholesterolemia
b) Huntington’s disease
c) Phenylketonuria
d) Congenital polycystic kidney
e) Sickle cell anaemia
2. Which of the following conditions are caused by mutations in mitochondrial DNA?
a) Leber’s hereditary neuropathy

b) Diabetes mellitus with sensorineural deafness
c) Marfan syndrome
d) Fragile X syndrome
e) Duchenne muscular dystrophy

LYMPHOID TISSUE
Lymphocytes
 20-50% of WBC in circulation.
 Most of them are small lymphocytes & 3% large lymphocytes.
 Two types: T cells & B cells
T cells
T helper cells Cytotoxic T cells Suppresor T cells

[TH cells] [TC cells] [TS cells]
‘Help’ B cells, TC Kill virus infected Suppress immune

cells & cells & cancer responsiveness to
macrophages to cells self antigens.
perform their
function. Switch off immune
response.
B cells
 Formation & maturation in bone marrow.

 Synthesize immunoglobulins IgG,IgA,IgM,IgE & IgD. [GAMED]
 Once activated:
a) undergo mitosis.
b) Cells mature into plasma cells.
c) Few cells become memory B cells – [Respond quickly to subsequent encounter of
the antigen.]
THYMUS
 Location:- Upper anterior mediastinum and lower part of the neck.
 Origin :- From epithelial outgrowths of the ventral wings of the 3rd pharyngeal
pouches.
 Most active during childhood, undergoes slow involution with age.

 But secret hormones continuously
 Involution due to
a) Fatty infiltration
b) Lymphocyte depletion
1 2015 A/L Repeat Campaign

Structure:-
 Lobulated.
 Invested by loose collagenous capsule.
 Interlobular septae arise from the capsule.
 No afferent lymphatics.
 Outer cortex – deeply basophilic
 Inner medulla – eosinophilic
 Immature T lymphocytes enter thymus through Post capillary venules
 Thymic epithelium forms blood thymic barrier.
 Cortex
- T cells present.
- Mitotic figures present.
- Undergo further maturation as they move deeper.
(Cortex to medulla)
 Medulla
- Dominant feature – Epithelial component
- Hassall’s corpuscles present
 Hassall’s corpuscles
- lamellated.
- 1st appear in foetal life.
- Increase in number and size with age.
- Formed from keratinized epithelial cells.
 At the end of their journey through thymus mature T cells enter blood vessels and
lymphatics.
 Thymus secretes hormones throughout life.
 Thymus – cortex - Thymic nurse cells are present.

 Thymic hormones - various thymosin hormones.

LYMPH NODE
 Location :- Along course of lymphatic vessels.
Occur in groups where lymphatics converge to form larger trunks.
eg: neck, axillae, groins
Structure :-
 Bean shaped.
 Surrounded by collagenous capsule.
 Trabeculae extend from the capsule
 Afferent lymphatics pierce the capsule.
 Afferents drain in to subcapsular sinuses.
 Then through cortical and medullary sinuses.
 Lymph drains in to efferents at the hilum.
 Blood vessels also enter and leave at the hilum.
 Two zones : Outer cortex and central medulla
 Cortex
- Highly cellular/densely staining
- Densely packed with lymphocytes
- Lymphoid follicles are present in the superficial part
- Deep cortex / Para cortex is devoid of lymphoid follicles
- Cortical sinuses are found in the cortical cell mass
 Medulla
- Less cellular.
- Pale staining.
- Medullary cords are extensions of cortical cell mass.
- Medullary sinuses converge upon hilum.
 All the sinuses kept patent by a skeleton of reticulin fibres
 Blood supply
- High endothelial venules are the site of entry of
circulating lymphocytes in to the node
- HEV lined by tall cuboidal cells

 3 functional compartments are found within a node
a) Lymphatic sinuses
b) Blood vessels
c) Interstitial compartment
 Zones of immunological activity Main cell type

Sup. Cortex B lymphcytes
Para cortex T lymphocytes
Medulla Plasma cells
Sinuses Macrophages
 Final stages of maturation to form plasma cells occur in the medulla.
 Most of lymphocytes enter node via HEV(high endothelial valves).
 Rest by afferent lymphatics.
Lymphoid follicles
Primary follicles Secondary follicles
- unstimulated - has two zones: germinal center and

- consists entirely of the mantle zone
same cell type : - Germinal center: Actively dividing B
resting B cells cells
- Mantle zone: Resting B cells
- (Other cells in the germinal center:
- Follicular dendritic cells
- Tingible body macrophages)
MUCOSA ASSOCIATED LYMPHOID TISSUE (MALT)
Total mass of lymphoid tissue in GI, respiratory & genitourinary

tracts is collectively known as MALT.
Large non-encapsulated aggregations.

No afferent lymphatics but efferents.
Consist of both T & B

PALATINE TONSIL
Palatine + lingual + pharyngeal + tubal tonsils Waldeyer’s ring
 The luminal surface is covered by stratified squamous epithelium.

 It invaginates the tonsil forming tonsillar crypts.
 The base is separated from the underlying muscle by collagenous hemicapsule.
 Parenchyma contains lymphoid follicles.
 Efferent lymphatics pass to deep cervical chain.
 Mainly T lymphocytes. Small number of B lymphocytes.
GUT ASSOCIATED LYMPHOID TISSUE
 Organized lymphoid tissue is found in all parts of GI tract except in the stomach.
 Largest aggregates are Peyer’s patches of SI.
 Peyer’s patches are least numerous in duodenum & most prominent in terminal
ileum.
 Epithelium overlying is specialized for antigen uptake. Eg: M cells
 HEV present.

SPLEEN
Structure:-
 Surrounded by a thin fibroelastic outer capsule.
 Trabeculae extend into parenchyma.
 Macroscopically - white nodules in a red matrix
 White nodules represent white pulp.
 Red matrix represent red pulp.
 White pulp
- contains lymphoid aggregations.
- is of two types T cells & B cells.
- Small fraction (5-20%) of total mass.
- T cell areas surround central arteries forming periarteriolar
lymphoid sheath (mainly TH cells).
- B cells form follicles.
 Red pulp
- is vascular tissue.
- Consists of parenchyma with an interconnected network of
sinuses.
- Parenchyma is composed of macrophages of sheathed capillaries,
other macrophages & blood cells.
- vascular sinuses are lined by stave cells.
- Sinuses drain ultimately into portal vein.
 Splenic vasculature
- Splenic arterty branches repeatedly.
- Central arteries are surrounded by a cuff of lymphoid
tissue.(PALS)
- Central arteries give off penicilliary arteries at right angles.
- Penicilliary arteries terminate in 2-3 sheathed
capillaries.
- Sheathed capillaries are blind ending capillaries
surrounded by macrophages instead of endothelial
cells.

Summary
Thymus Lymphoid tissue Spleen MALT
Afferent lymphatics    
Efferent lymphatics    
Post capillary venules High endothelial Central arteries and _
venules branches
B follicles
White pulp - T & B Mainly T cells
Hassall’s corpuscles Primary Secondary Cells
Small number of B
Germinal center Mantle Red pulp - PALS cells
zone
Encapsulated Non capsulated

Epithelia
Epithelial type Adaptation Function Site where found
1.Simple squamous Flattened Passive transport Lunge(alveolar wall)

Irregular shaped (diffusion) Blood capillaries
2.Simple cuboidal Polygonal in shape Excretory Collecting tubules of kidney

Rounded nucleus Secretory Excretory ducts of salivary
Absorptive function gland & pancreas
3.Simple columnar Taller cells Absorption Small intestine

Polarity of the Secretory function Stomach
nucleus
Sometimes may be Secretory function Female reproductive system
ciliated
4.Pseudostratified Nuclei may be Mucociliary Respiratory tract

columnar ciliated disposed at different escalator
(Respiratory epi: ) levels, Ciliated
Found goblet cells
Nuclei confined to
the basal 2/3 of
epithelia
5.Stratified Basal layer cuboidal, Withstand abrasion Oral cavity

squamous surface layer Protection of drying Pharynx
flattened Oesophages
Dividing stem cells in Anal canal
basal layer Vagina
May have keratin skin
layer

6.Stratified cuboidal Thin cell layer Robust lining large excretory ducts
(2 or 3) eg:- Salivary glands
7.Transitional Surface cells are Great degree of only in urinary tract of

epithelium large & rounded stretch mammals
(urothelium) Basal cells roughly Withstand the
cuboidal toxicity of urine
Cilia are never present in true stratified epithelium.
Epithelia - glands
Exocrine glands
They maintain continuity with the epithelial surface (duct system)
Structure
Contains secretory component and duct system
Duct system – Unbranched (simple) Branched (compound)
Secretory component may be tubular or acinar
Both types of secretory component may also be coiled or branched
Any combination of duct system and secretory component can occur
Simple
1.Tubular 2. Coiled tubular 3. Branched 4. Acinar 5. Branched acinar
- colon , large - sweat glands - GIT , stomach -mucus secreting - sebaceous glands
intestine glands of
The penile urethra
Compound
1.Tubular 2. Acinar 3. Tubulo – acinar
- Brunner’s glands of - Pancreas - Submandibular
duodenum salivary glands
Secretary types
1.Merocrine 2.Apocrine 3.Holocrine
- Exocytosis -Membrane bound vesicle -Discharge of all secretery

-Most common way of -Breast, Sweat gland cells
secretion -Sebaceous glands

Connective tissue
Origin :- Mesoderm
Types :- Loose connective tissue
Dense connective tissue Bone & cartilage
Adipose tissue Cells of immune system
Composition :- 1. Cells
2. extracellular matrix
3. Blood vessels & lymphatics
1.Cell types :- Synthesize & maintain the ECM

I. Fibroblasts
- Commonest
-Produce precursors of ECM ( GAG, collagen, elastin )
-Active cells- large cell with cytoplasmic processes
-Inactive cells- small,spindle shaped
II. Myofibroblasts
- Contractile function, tissue repair after damage
III. Adipocytes
Lipoblasts Adipocytes
- Store energy
-Regulate fat uptake & release
White adipose tissue

- Adults 20-25% of TBW
- In the deep layer of the skin
- Energy store, thermal insulator, shock absorber
Brown adipose tissue
- Newborns
-Thermoregulation , unique uncoupling proteins
-Rich vascular network
IV. Defense cells

Macrophages – derived from monocytes, scavenger in tissue, 1st cell to make contact with antigen
Mast cells –derived from basophils,important in allergic eactions, secret histamine
IV. Chondrocytes & Osteocytes
2. Extracellular matrix ( ground substance + fibers )

Secreted by,
I. Fibroblast- most of CT
II. Chondrocytes- cartilage
III. Osteocytes- bone

Ground substance
- Transparent molecules
- Semi fluid gel
- Fibers are embedded
- Formed by GAGs
Fibers Collagen types
- Collagen & elastin I – Ligements,bones,tendons
II- Hyaline cartilage
Collagen – Type 1- fibrous supporting tissue
III- Bone marrow,lymphoid
Type 2- hyaline cartilage
tissue(supporting framework)
Type 3-(reticulin) supporting framework IV-Basement membrane
Elastin – stretching & elastic recoil
Basement membrane
Constituents- GAGs- heparin sulphate
Fibers- collagen type 4
Glycoproteins- fibronectin,laminin,entactin
Reticuloendothelial system
Function ;- 1. Phagocytose particular matters, microorganism, affected cells
2. Store iron & certain metabolic products
Structure ;- Diverse group of cells

Eg; In bone marrow, liver, spleen, lymph nodes, thymus
Supporting frame work of reticulin fibers
Reticular cells- similar to primitive mesenchymal cells
Long cytoplasmic processers
Phagocytic cells – similar to endothelial cells
Cell junctions
Tight junctions Adhering junctions Communication junctions
-Intestinal epithelium -In most tissues -Cardiac muscles
Excitable Tissue
Muscles (Contractile Tissue)
Single cell contractile units
 Myoepithelial cells - Secretory glands (salivary)
 Pericytes - Around blood vessels
 Myofibroblasts - Scar tissue
Skeletal muscles – “Voluntary” “ striated”

Sites :- 1. limbs
2. Tounge
3. Globe of the eye

Development Proliferation &
Differentiate Fusion
Mesenchymal cells Myoblasts Myotube
(mesoderm) ( long, mono Nucleus, (long , multi n.)
Precursors of mitochondria )
Histology
1. Extremely elongated
2. Unbranched
3. Cylindrical cells
4. Flatten , Peripheral nuc.
5. Cross striations
Functioning
Large motor nerves “motor unit”
(Fasciculation)
Contractile proteins *Ca2+ is most necessary ion of muscle contraction

- Cross striations
- Arranged in highly ordered Thin Filaments
1. Actin
2. Tropomyosin
3. Tropoin complex
Conducting system
 T system – Extension of sarcolemma in to the muscle to around muscle fibers
 Sarcoplasmic reticulum (SER) – Contains Ca2+
 T tubule + terminal cisternae – Triad (at the junction of the I & A bands )
Cardiac muscles
Histology Sarcomere
- Long cylindrical - mitochondria with closely packed cristae
- Branching fibers - glycogen granules
- Some striations - well developed sarcoplasmic reticulum
- 1 -2 central nuc. - T tubule system in Z line
- Intercalated discs
Junction between 2 cells
Conduction – spreads from cell to cell as a syncytium (mass of cell )

*Cardiac muscle tissue contains lot of spaces with capillaries
Smooth muscles
- Continuous contractions
- Contraction of whole muscle
- Spindle shaped cell

- Independence of neurological innervation
- Elongated spindle shape with tapered ends
- Central single nuc.
- No stiations
- Invaginations of plasma membrane “calveolae”
Contractile proteins
Actine (tropomyosin) & Myosin (only bind to actin ) in Criss-cross
Sites :- Walls of hollow viscera

Iris of the eye (rapid contractions )
Nerve Tissue
1.CNS 2. PNS
Nerve system
1.Somatic 2. Autonomic
Neurons
Structure
Cell body Processes Nucleus – large ,
Nucleus Axons Prominent
Perikaryon Dendrites
(Cytoplasm) Nissle bodies - RER
(darkly stained)
*Lack in axons
Types
Multipolar Bipolar Pseudo unipolar
neuron neuron neuron
eg:- Motor eg:- Recepto neurons eg:- primary sensory
smell, sight, balance nerve
Axons
Shawn cells - formed by Oligodendrocytes
- Supporting cells of PNS
- Bright pink cytoplasm in stains
Myalinated N. fibers Non Mylinated N. Fibers
Myelination – protection
Increase axon conduction velocity (soltatory conduction )
Synapses
Between 2 neurons -Axodendritic
-Axosomatic
-Axoaxonic
Between neuron & muscle – neuromuscular junction / Motor end plate

1. Peripheral nervous system
Contain afferent & efferent fibers of somatic or autonomic system. Structure:
- Nerve fibers form fascicles
- Surrounding layers of supporting tissue
- Rich blood supply
- Fibers follows a zig zag, longitudinal course (for stretching of the nerve)
- Supporting cells – shawn cells
Ganglia
- Aggregations of neuronal cell bodies located outside the CNS
- Cell bodies – surrounding satellite cells ( structural & metabolic support )
- Capsulated by supporting tissue
1. Spinal ganglia – Cell bodies of primary sensory nerves ( pseudo unipolar )
(somatic sensory ganglia)
2. Sympathetic ganglia –Multipolar cells – eccentrically located
-Widely spaced
3. Parasympathetic ganglia – Cell bodies of terminal efferent cells
-Cells – large N / dispressed Chromatin
-Basophilic cytoplasm
2. Central nervous system
Brain Spinal cord
Gray matter- Cell bodies White matter- Tracts of axons
Neuroglia (Non neural cells) – mechanical & metabolic support
1. Astrocytes - most numerous
- Star shaped, long branched processors
Function: - Mechanical support
Mediate exchange of materials between neurons & vascular system
Form part of blood-brain barrier
Repair of CNS tissue after damage
2. Oligodendrocytes – Responsible for myelination of axon
- Absent in Gray matter
3. Microglia – Small cells
- Nucleus—small, elongated / Cytoplasm- Scanty
Function:- Represent the monocyte- macrophage system
4. Ependyma- Make the specialized epithelium of ventricle & spinal cord
- Cuboidal cells
Choroid plexus – produce CSF

-Consist of mass of capillaries projecting into ventricles
Meninges
1. Dura mater – Dense fibroelastic layer, lined by flat cells
-Strongest layer
-Skull: - merges with the periosteam
2. Arachnoid mater – Cobweb like
- Pia + Arachnoid = Leptomeninges
(both found together)

3. Pia mater – Delicate, glia limitants
- formed of collagen, elastin, fibroblasts
Bone & Cartilage

Cartilage
Cells
1. Chondroblasts (in outer) 2.Chondrocytes
-Synthesize the matrix - former chondroblasts
-Immature cells, very active - mature cartilage cells
Function- Secrets ground substance & - initially located as clusters (2-4)
Fibrous materials - strapped in cartilageous matrix
Function- maintain the intergrity of
matrix
secrets ground substance & matrix
ECM
-Ground substance – Proteoglycans
-Fibers – Collagen & elastin
Perichondrium
- At the periphery of mature cartilage tissue
-Zone of condense tissue
-Collagen fibers & spindle shaped fibroblasts
Types
1. Hyaline Cartilage
2. Fibro Cartilage
3. Elastic Cartilage
1. Hyaline Cartilage
- Translucent, homogenous appearance
- small aggregations of chondrocytes
- Ground substance—collagen fibers (type 2)
Sites: - fetal skeleton
Nose, laryngs, trachea
Articular surfaces
Costal cartilage
*In articular surfaces of joints -> no perichondrium
2. Fibro Cartilage
-resistance to stretching
-collagen fibers in dense bundles
Sites: - Intervertebral discs
Pubic symphysis
Joint capsule
Ligaments

3. Elastic Cartilage
- equal to hayaline cartilage
- many branching elasting fibers
- gives flexibility
Sites: - External ear
External auditory canal
Epiglottis
Formation
- Mesenchymal cell
- Differentiate into Chondroblasts
- They divide & secrets ground substance & fibers
- Clusters of mature cells—chondrocytes
Nutrition
Most of cartilage devoid of blood vessels
Substance diffuse through ECM
In thick cartilage-- “cartilage canals” convey small vessels into cartilage mass
Bone
Cells
1. Osteoblasts 2.Osteocytes
-Synthesize osteoid - assist in nutrition of bone
-Mediate the mineralization - large, inactive osteoblasts
- inside the large lacunae
3. Osteoclasts
- important in constant turnover & refreshing of bone
- phagocytic cells
- large, multinucleated
Periosteum
- Condensed fibrous tissue
- Inner layer – contain oesteoprogeniter cells & osteoblasts
Sites : - outer shed of the bone
*Diaphysis
Types
1. Woven bone
-immature bone—foetal skeleton
-- fracture sites
-randomly arranged collagen fibers
2. Lamellar bone
Regular parallel bands of collagen sheets
I. Compact bone
 Osteon (haversian system)
 Contain neurovascular bundles

 Connect each other by Volkmann’s canals
 Lacunae contain osteoclasts
 Between adjacent lacunae & central canal  canaliculi
 Between haversian systems  interstitial system
II. Trabecular bone (medullary / spongy)
 Network of inter connecting structers
 Scanty lacunae containing osteocytes
Sites: - medullary cavity
Formation
1. Intra membranous ossification  membrane bone
Sites: - clavicle
Vault of skull
Mandible (most part)
Mesenchymal cells
Sheets of cells with good blood supply

Differentiation in to osteoblasts
Synthesize & secret osteoid matrix
Multiple ossification centres ( osteo progenitor cells osteoblasts )

Mineralization of osteoid
Oss: centers fuse
Bone is formed ( spongy like)
Woven bone lamellar bone
2. Enchondral ossification  cartilage bone

Sites: - long bones
vertebrae
pelvis
Mesenchymal cells
Sheets of cells with good blood supply

Cell differentiation – form a cartilage model ( solid hyaline cartilage)
Chondrocytes reabsorb the cartilage matrix and die
Cartilage matrix becomes calcified
Only a thin layer of matrix left
Empty spaces – infiltrated by B. vessels & mesenchymal cells
Periostium lays down
Mesenchymal cells become the osteoblasts. Osteoblasts synthesize & secret the osteoid
Formation of the 1ry ossification site (woven bone)
Growth of long bone
Epiphysis – areas of cartilage remains at the ends
Metaphysis – bone is laid down

Growth plate – between epiphyseal cartilage & diaphysis
 Growth in length of the bone
 Epiphyseal end- proliferation of cartilage
 Diaphyseal end – bone formation
 Less stratified cell columns
Bone growth
Shaft woven bone
-Cartilage layer of non-lamellar bone formed – primary osteons
-Erosion & deposition of concentric lamellae of bone – secondary osteons (Haversian
system)
Remolding of bone
Osteoclastic & osteoblastic activity
Old osteons remove deposition of new, shaft diameter increase
-occurs throughout life

-due to mechanical stress
Repair of bone
Blood clot highly vascular collagenous tissue hyaline cartilage
Newly formed primary bone secondary bone

biochemistry
bat notes
term 01
Functions of the cell
1) Prokaryotic vs Eukaryotic cell
Prokaryotic Eukaryotic
• High S/V ratio • Low S/V ratio
• Unicellular • Uni or multicellular
• Single membrane surrounded by • Lipid bilayer membrane with
rigid cell wall. proteins.
Membrane-phospholipid
Cell wall-heteropolysaccharides
• No membrane bound organelles • Contains membrane bound
organelles
• No well-defined nucleus, no • Nucleus well-defined.
nucleolus Nucleolus with rich in RNA
• Circular DNA, plasmids present • DNA linear. No plasmids
• Ribosomes are 70S with 50S and • Ribosomes are 80S with 60S and
30S subunits 40S subunits
• Reproduce by binary fission • Divide by mitosis
• Cytoskeleton absent • Cytoskeleton present
Lysosomes - Contains hydrolytic enzymes for intracellular digestion.

Peroxisomes - β oxidation of excess fatty acids.
- Removal of H2O2. Catalase converts to H2O and O2.
- Participate in synthesis of cholesterol, bile acids.
- Breakdown of excess purine nucleotides to uric acid.
- Synthesis of lipids used to make myelin.
- Detoxify toxic molecules.

Mitochondria - Aerobic respiration and ATP production.
- Certain heme synthesis reactions, urea cycle.
- β oxidation of fatty acids.
RER - Synthesis of membrane lipids and secretory proteins
SER - Synthesis of lipids and steroids
- Detoxification of drugs and chemicals
Golgi - Receive, modify, sorts and package of proteins(secretory)
- Creation of lysosomes.
Cell membrane - Permeable to water, carbon dioxide, and oxygen
- Acts as a gate for different substances / semipermeable
- Forms vesicles and participate in exocytosis and
endocytosis.
Importance of cell specialization  division of labor.

Mechanisms of intercellular communication;
1) Direct communication – gap junctions
2) Paracrine communication
3) Endocrine communication
4) Synaptic communication

pH and Buffers
𝐩𝐩𝐩𝐩 = − 𝐥𝐥𝐥𝐥𝐥𝐥 𝟏𝟏𝟏𝟏 [𝐇𝐇 + ] (where [H+] is in moles/dm3 or moles/litre)
Unit change in pH changes [H+] by ten-fold (e.g. when pH increases by 1, [H+] decreases by 10 times)
Biological systems (e.g. enzymes) are extremely sensitive to changes in pH.
pH < 7.2 → acidosis pH > 7.6 → alkalosis
Conjugate Acid-Base Pair: A proton donor and its corresponding proton acceptor
Dissociation of Weak Acids and the Henderson-Hasselbach Equation

HA ⇌ H + + A− Drug absorption – an application of the
Acid dissociation constant = K a Henderson-Hasselbach equation:
[𝐻𝐻+ ][𝐴𝐴− ] • Weak acids (e.g. aspirin, pK a ≈ 3.5) are in
𝐾𝐾𝑎𝑎 = the unionized form in the stomach (due
[𝐻𝐻𝐻𝐻]
(Higher the K a , better the dissociation of the to its highly acidic pH)
acid) • Unionized form of a drug (i.e. HA) is
𝐾𝐾𝑎𝑎 [𝐻𝐻𝐻𝐻] more soluble in phospholipid bilayer
[𝐻𝐻+ ] = • Therefore will cross the cell membranes
[𝐴𝐴− ]
[𝐻𝐻𝐻𝐻] more rapidly and move into blood
− log10 [𝐻𝐻+ ] = − log10 𝐾𝐾𝑎𝑎 − log10 − • In the blood, at physiological pH, they
[𝐴𝐴 ]
[𝐀𝐀− ] are in the ionized form (i.e. A–) and does
𝐩𝐩𝐩𝐩 = 𝐩𝐩𝐊𝐊 𝐚𝐚 + 𝐥𝐥𝐥𝐥𝐥𝐥 𝟏𝟏𝟏𝟏 not flow back into the stomach
[𝐇𝐇𝐇𝐇]
The pK a of any acid is equal to the pH
when [A-] = [HA]
Buffers
• Substances that resist pH changes
• Combinations of H+ donors and H+ acceptors (weak acids or weak bases)
• Mixture of weak acid/base and its conjugate base/acid
• Buffers work by accepting H+ when they are in excess and donating H+ to the solution when
they are depleted
• Buffering capacity depends on the type of buffer and the molarity of the solution
• Optimum activity of buffer occurs when pH = pK a (i.e. when [A-] = [HA])
• Maximum buffering capacity in the pH range (pKa ± 1)
• Conjugate acid-base pairs act as buffer when pH = pK a
Buffering systems in the body: (controlled by lungs/kidney)
In plasma: H2 CO3 ⇌ H+ + CO2− 3
In RBCs: HHb ⇌ H + + Hb (Hb = deoxygenated haemoglobin)
In body cells: protein ∙ H ⇌ H + + protein
In urine: NH+ +
4 ⇌ H + NH3
H2 PO− +
4 ⇌ H + HPO4
2−
H2 CO3 ⇌ H+ + CO2− 3
pH & BUFFERS
1. T/F
a) Weak acid has a higher pKa.
b) Weak acid & its salt act as a buffer.
c) Buffering capacity is not affected by its molarity.
d) Ten fold decrease in H+ concentration leads to increase pH from 6 to7.
e) HCO 3 - /H 2 CO 3 is the main buffer in urine.
a) T
b) T
c) F – increases with increase in molarity
d) F
e) T
2. T/F
a) pH is –log [H+].
b) If pH is 3, [OH-] = 10-3 moles per liter.
c) Buffering range is determined by the pKa of the weak acid.
d) Buffering capacity of buffer depends upon concentration of buffer.
e) pH of normal blood is 7.4
a) T
b) F – pOH = 14-3 = 11, so [OH-] = 10-11 moles per liter.
c) T
d) T
e) T – normal range is 7.35-7.45
3.T/F
a) Methyl red is useful in pH 1-10 range.
b) When added 1ml of 0.1M HCl to 10ml of 0.5m phosphate buffer pH will not change from the
original pH.
c) When pH = pKa of a weak acid 50% is ionized.
d) Ionic product of water is the equilibrium constant.
e) H 2 PO 4 - can act as both a base and an acid.
a) F – pH range of colour change is 4.8-6.0
b) F – minute change
c) T
d) T
e) T
4. T/F
a) Buffering capacity decreases with increasing molarity.
b) At pH= pKa salt concentration is equal to acid concentration.
c) Acetate/acetic acid (pKa=3.6) is effective as a buffer in the cytosol.
d) Buffering capacity of the buffer does not depend on the concentration of the buffer.
e) Buffering capacity depends on the pK of the buffer acid or base.
f) Buffering capacity depends on the molarity of the buffer.
a) F – increase
b) T
c) F – cytosol pH around 7.2
d) F
e) T
f) T
(1) ©2015 A/L Repeat Campaign D – Glucose (Dextrose) Dextrans Inulin
- biologically active -polysaccharide bacterial origin Polymer of fructose furanose.
- parenteral source of calories -branched polymer of D- Measure GFR by Inulin clearance
Isomer Epimer Anomer water glucopyranose. test.
Same molecular Different configuration Different stereoisomers 5% dextrose drip -Plasma volume expander.
Formula but around 1 specific ‘C’ except after cyclization aldehyde/ketone C- As a substitute for plasma
-Fed intravenously -Used to treat hypovolemia
different structure Carbonyl C called anomeric C -IV injections of - Improve microcirculation
Eg:glucose,fructose, eg:D-glu & D-gal - C-4 OH - Treatment of iron deficiency
mannose,galactose D-glu & D-mann - C-2 25%/50% dextrose (iron-dextran complex)
(C6H12O6) mann & gal - not epimers
OH β anomer - used to restore blood glucose concentration Glycoproteins
α anomer in the treatment of acute Used in blood group analysis.
ISOMERISM symptomatic hypoglycemia
Enantiomer - mirror images. differ in configuration at every chiral center -reviving unconscious patients who have
Eg: D & L forms consumed too much alcohol
D form is more abundant MEDICAL IMPORTANCE
CARBOHYDRATES
*(CH2O) n * Energy – 4 kcal/g
CLASSIFICATION
Simple Complex
Mono. Di. Oligo. Poly.
-Cannot hydrolyze - Can be hydrolyzed. (>10 mono.)
-reducing sugars (except sucrose) -3-10 mono.
-reducing sugars -contains glycosidic bond -eg: Raffinose, Stachyose
(Benedict’s Test) components of cell membrane and Homo Hetero
-cyclization(become stable) Maltose (from hydrolysis of starch) human milk (1 type of monomer) (Dif. types of
-sugars prefer cyclic structures Glu+Glu monomers)
to linear structures α-1-4 glycosidic Glycosidic Bond
6 member ring- pyranoses Sucrose 1)No.: Designate Unbranched
Branched
Eg: glu & gal Glu+fru C atom that Cellulose
forms the bond. Glycogen Conjugated Pure
5 member ring –furanoses α-1-2 glycosidic • Group of plant
2) α / β: Bond up • Animal polysaccharide
Eg: fructose Eg:1) Sugar Phosphates- Glucose-6-phosphate for glucose storage polysaccharides
-derivatives or down • Unbranched
2) Sugar alcohols – sorbitol • Highly branched – rapid • GAGs
3) Sugar acids – glucuronic acid 3)Type breakdown (more • β-1-4 glucosidic type of with with • Pectin
-Digestible branched than glycosidic bond Proteins Lipids • Gums
No. of C Aldoses Ketoses Lactose amylopectin) not hydrolysed in humans
Eg: Lactose -
3 Triose Glyceraldehydes DHA Glu+ gal • α-1-4 & α-1-6 glycosidic
β-1-4
4 Tetrose Erythrose erythrulose β-1-4 glycosidic bond
galactosidic type Amylose
5 Pentose Ribose ribulose -galactosidic type Amylopectin • proteoglycans • glycolipid
of glycosidic • 20% in starch
6 Hexose Glucose fructose • α-1-4 & α-1-6 glycosidic • α-1-4 glycosidic • glycoproteins
bond
nnose bonds bond
Oligo,mono & disaccharides; Polysaccharides
-Indigestible
• Difficult to digest. • Blue-black colour
• forms crystals Eg:cellulose β-1-4 • Most abundant in with iodine
N glycosidic(nucleotides) glucosidic type of starch • Easy to digest.
• readily soluble in water O glycosidic (sugar) glycosidic bond
• sweet taste Starch
(2) ©2015 A/L Repeat Campaign
Heteropolysaccharides
Conjugated Lipids Glycolipid
(eg :glycoglycerolipids,
Pure Glycophosphotidylinositol,
Simplest ones
(Pectin, Gums, GAG)
-Galactosyl ceramide Glycospingolipids(major glycolipid
-Glucosyl ceramide In animal)
Glycosaminoglycans (GAGs)
*Most abundant heteropolysaccharides in body
functions- receptor molecules,
*Long, unbranched Cell to cell interactions, provide
*Composed of repeating disaccharide units –acid sugar(uronic acid eg:D-glucuronic Proteins energy, blood group antigens
L-Iduronic) *Bacterial cell wall-peptidoglycan
--amino sugar(N-acetyl glucosamine/ N-acetyl galactosamine)
*Negatively charged – due to SO42-, COO-
Proteoglycans (Protein content-low) glycoprotein(Carbo.content-low)
*(-)charge Attract cations Sucks in water Enable ECM to withstand - GAG covalently bound to core
. and creates pressure compressive forces Protein Functions
*Contain sulphate group (except hyaluronic acid.) -In CT, ECM, surface of many cell Predominant sugars -structural molecules eg. ECM
*Rigidity and Low compressibility
types. -glucose, galactose, -lubricants/protective agents eg. mucin
-secreted proteases & Mannose, fucose, -transport molecules
Hyaluronic acid
antiproteases GalNAc, GlcNAc, -immunologic molecule eg. immunoglobulin
• Synovial fluid(shock absorber, lubricator), ECM of loose connective tissue
• Vitreous humor of eye, embryo, umbilical cord -polypeptide growth factors NANA -hormones eg. TSH, chorionic gonadotrophin
• Not covalently bound to protein, forms noncovalently linked complexes -cell surface proteoglycans -Nearly all proteins on -enzymes
with proteoglycans to form proteoglycan aggregates in ECM.
-aggregating proteoglycans the outer surface -cell attachments/recognition eg.
• Degradation by hyaluronidase.
-heperan sulfate in glomerular -abundant in plasma hormone receptor
Keratan sulphate basement membrane. -cell surface antigenicity
• For corneal transparency, bone, cartilage
• Aggregate with chondroitin sulphate N-inked
• Galactose instead of acidic sugar O-linked
• Most heterogenous of GAGs. Ex functions Ex functions of carbohydrate moiety
-Glycophorin -recognition -cell surface -resist proteolysis
Chondroitin sulphate
• Cartilage, bone, heart valves, certain neurons (maintain their shape)
-mucin -interaction Receptors -solubility
• Most abundant GAG in ECM -Notch -enzyme regulation -ECM protein -correct folding
-thrombospondin -plasma protein (except albumin) -recognition marker in molecular
Dermatan sulphate: -factor VII, IX -luminal lysosomal interactions & cell targeting
• Skin, blood vessels, cornea, heart valves. -plasminogen
• Binds LDL
Protein
activator -intra cellular organellar
Heparin & Heparan sulphate: proteins
• Heparan sulphate - Basement membrane of kidney-determine charge selectiveness, component of cell surface
receptors.
• Heparin - anti coagulant in blood
• Heparans - less sulphate groups than heparins.
(3) ©2015 A/L Repeat Campaign
Diseases Lysosomal disease

Glucosidases do not degrade CHO part of
• Diabetes mellitus proteoglycan
• GAGs – mucopolysaccharidosis • CHO accumulates
• Hyaluronic acid, Chondroitin sulphate – Osteoarthritis • Oligosaccharides in urine
Glycoprotein Proteoglycan
1)Length of CHO chain relatively shorter. 1) Relatively longer
2)CHO do not have serial repeats 2) Gags present ∴have repeating
3)CHO chain often branched disaccharides
4)CHO may /may not be negatively charged 3) Unbranched
5)Less CHO 4) Negatively charged
5) More CHO
Tests Dextrin – Intermediate of starch hydrolysis

1) Benedict’s test – Test for reducing sugars Dextrose – Similar to glucose
Result – Brick red precipitate - Use 5% dextrose drip
2) Barfoed test – Specific for monosaccharides
Result – Red precipitate Dextran – Polysaccharides of bacterial origin
3) Iodine Test – For starch - use as a plasma substitute
Result – Blue black color
LIPIDS
• Major stored form of energy

• Enzyme cofactors
• In bio membranes
• Electron carriers Eg; Co Q
• Emulsifying agents
• Hormones/ signaling molecules
Building blocks of lipids

Lipid = Fatty acid + Alcohol/ amino alcohol
E.g. = Palmitic + glycerol sphingosine

CH2-OH H
CH3-R-COOH + CH-OH or R-C-CH2OH
CH2-OH NH3
Fatty acids
• Transported bound to albumin
Saturated Unsaturated
• No = /≡ bonds • Has 1 / many = /≡ bonds

• Abundant in animals • Monounsaturated (only 1 = bond) - Palmitoleic & Oleic (Olive)
Eg. - palmitic (palm) • Polyunsaturated (more than 1 = / ≡ bond)
- stearic Eg; - Linoleic (sunflower /olive/gingerly)
Strong interactions -α-Linolenic
between FA chains - Lauric (coconut)
- Arachidonic
(except palmitic and stearic all other examples given for FAs on lec. are unsaturated )
• Weak attractions between FA chains, chain length, and presence, number, position and
confirmation of double bonds affect the melting point. (length of tail melting point )
• Most naturally occurring unsaturated fatty acids have cis double bonds.
• Trans double bonds increase the melting point of unsaturated fatty acids.
Eg; Margarine
Elaidic acid (natural trans unsaturated)
Fatty acid saturation/ unsaturation indication method Position of double bond

(from last carbon)
16:0  saturated ω carbon = last carbon
16:1ω9 first carbon with double bond
(counting from the end) e.g. –C-C-C=C-C=C-COOH in this example it is a ω-3 FA
123 4
No. of double bonds ω carbon doesn’t change in metabolism so can trace.
No. of carbons e.g. Arachidonic ω-6
Linoleic ω-6 sounds same but different No.
αLinolenic ω-3
• αLinolenic & Linoleic acids are essential fatty acids.

Eicosanoids (Derived from Arachidonic acid/Eicosapentenoic acid)
Prostaglandins Thromboxanes Leukotrienes
• Mediate pain • Blood clotting • Attract WBC
sensitivity, fever, • Constriction of arteries • Involved in
inflammation n • Has 6 membered ring/ inflammatory diseases
swelling cyclopentane ring • Has 3 conjugated = n
• Has cyclopentane ring interrupted with an one more
oxygen atom unconjugated
• No ring structures
Eicosanoids precursor intermediate precursor

Linoleic Arachidonic (20 C) COX 1/COX 2 Prostacyclin
Acid phospholipase A2
COX 1/COX 2
Prostaglandin
lipoxygenase COX 1/COX 2
SAID
inhibits Inhibition in
(cortisol) asthma Thromboxane
treatment Leukotrienes
NSAIDS,
Aspirin,
inhibits
Types of Lipids
Storage lipids Membrane (complex lipids)  all amphipathic

↓
TAG
Sphingolipids Glycerophospholipids Steroids
Cholesterol
Sphingophospholipids Glycosphingolipids
TAG
• Storage lipids
• Neutral fat
• Hydrophobic
• Not components of bio membranes
• High energy molecule
• Anhydrous
• C1 & C3 of glycerol is not identical. Enzyme specific.

CH2−O-CO-R1 Typically, saturated
|
CH -O-CO-R2 Typically, unsaturated
|
CH2-O-CO-R3 Can be either
Presence of unsaturated FAs reduce melting T of lipids

Phospholipids - polar, ionic
- form micelles, bilayers, liposomes oral delivery of certain dietary n
Emulsion – non-polar lipid in an aqueous medium nutritional supplementary drugs /
stabilized by emulsifying agents gene transfer
Phosphoglycerides
Eg; 1. Lecithin/ Phosphatidyl Choline
Alcohol is choline
G
FA Nervous transmission
L
Y ; Dipalmitoyl Lecithin
C Major constituent of lung surfactants
FA 2.Cardiolipin (Diphosphatidylglycerol)
E
R Only in mitochondria
O PHOSPHORIC ACID ALCOHOL 3.Phosphatidylinositol (IP3 & DAG)
L Alcohol is inositol
Precursor of second messengers
Ceramide (Sphingosine + fatty acid)
HYDROCARBON
S
BRANCH
P
H
I
N
G FA
O
S
I
OH
N
E
Phosphosphingolipids
S HYDROCARBON
P BRANCH
H Eg; Sphingomyeline
I In all cell membranes
N Important structural
G component in myeline sheath
O FA
S
I
N PHOSPHORIC ACID ALCOHOL
E

Glycosphingolipids (Ceramide structure + one or more sugars)
1) Cerebrosides
S HYDROCARBON
P BRANCH
- Galactosylceramide in brain
H
I - Glucosylceramide in extra neural
N tissue
G
FA
O
S
I
N MONOSACCHARIDE
E
2) Gangliosides (derived from glucosylceramide)
S HYDROCARBON
P BRANCH
H - Receptors
I
N
G
FA
O
S
I
N OLIGOSACCHARIDES
E
Cholesterol
• Animal origin, not in plants or bacteria
- steroid hormones Eg; Cortisol, Aldosterone, Testosterone, Estradiol, Progesterone
- bile acids
- vitamin D
• Weakly amphipathic
• Flat rigid structure
• 4 fused rings with OH, 2CH3, Aliphatic side chain at C17
• Maintains the fluidity of cell membrane
Cholesteryl ester
CHOLESTEROLE FA
• Hydrophobic

Proteins
• Most abundant macromolecule in human body.
• Proteins hydrolysis Amino acids
Amino Acids
• All amino acids are α amino acids.

• But proline is not α amino acid, it’s animino acid.
Hydrophobic – Glycine, Alanine, Valine, Leucine, Isoleucine, Phenylalanine, Tryptophan,

Methionine, Proline
R group Polar uncharged – Serine, Threonine, Tyrosine, Asparagine, Glutamine, Cysteine
Acidic – Aspartic acid, Glutamic acid

Polar
Basic – Histidine, Lysine, Arginine
• S containing AA – Methionine (Essential), Cysteine (Non-essential)
• BCAA – Valine, Leucine, Isoleucine
AA are charged in nature.
Isoelectric pH (pI)
• pH at which zwitter ion predominates with equal but very small amounts of cationic & anionic forms.
• At pI - no net charge
- not move in an electric field
- solubility is least
Ninhydrin reaction
T
AA + ninihydrin Bluish purple but Pro & OH-Pro yellow
Peptide Bond
• Rigid
• Planar
• Trans configuration
• Partially double bond
• Uncharged but polar
Non-enzymatic hydrolysis requires strong acid (6M HCl) or bases at high temperature.
Biologically impotent peptides
1. Glutathione (antioxidant, AA transporter)

- Glutamine, Cysteine, Glycine
- 2GSH (reduced) GS – SG (oxidized)
2. Insulin
Structure
1. Primary 2. Secondary 3. Tertiary 4. Quaternary
Found in all proteins Found only in some

 Primary
• Nature & sequence of a.a in polypeptide chains that a protein is comprised of.
• Each protein has a unique primary structure
• Proteins have a common backbone, different R group sequence
• 3D arrangement depends in this
 Secondary
• Structure that arises as a result of interactions between backbone groups that are close to one another in
proteins
α Helix β pleated sheet
I. Intra chain H bonds inter chain or different segments H bonds

(CO of one AA to NH of AA 4 of same chain
residues ahead)
II. H bonds parallel to imaginary perpendicular to the axis
Axis
III. Disrupt α helix favored by
Pro OH-Pro AAs having small R groups –
Charged R groups Gly Ala Ser
Destabilize α helix
Glu, Asp
His, Lys, Arg
Trp, Val, Ile
IV. Found in α keratin in both fibrous & globular proteins
Myoglobin
Hemoglobin
v. Spiral, Extensible, cannot be extended further
right handed, 3.6AA per turn
• Other secondary structure

β bend- Pro -Gly at the bend
Non repetitive Structures-Loops and Coils
Super secondary structures
 Tertiary
Structure due to interactions of R groups in protein with
- Aqueous environment
- Other R groups far apart
Such as
- H bonds
-Hydrophobic interaction
-Ionic
- Disulphide linkages
When proteins fold
Non polar in polar, charged out
Proline kinks proteins
Proteins
Fibrous Globular
- Structural -Functional
- Insoluble -Compact, tight packing in core
- Long half-life -Secondary, Tertiary(& quaternary) structure
- Secondary structure Hb, myoglobin, lysozyme, ribonuclease
α keratin, collagen, elastin
Myoglobin
• Haem protein - heart & skeletal muscles
• O 2 storing
• Single polypeptide chain & single haem unit
• Eight α helical segments.
• Haem unit stabilized by ‘His’ & hydrophobic interactions
• Globular functional protein
 Quaternary
In functional molecule
• 2 or more polypeptide chains
Individual polypeptide chain Protomeres

Monomers
Sub units
Quarternery structure: Characteristic manner in which individual polypeptide chains held together
by non-convalent
• H bonds
• ionic linkage
• Hydrophobic interactions
One type of subunit : homo multimer

Several diff. subunits :hetero multimer
example: Hb α 2 β2 - tetramer
Domains
• Distinct 3-dimensional structural units of a polypeptide chain which may have separate functions.
• Often encoded by different exons
• A chain with a domain folds independently of others
• Core of domain is composed of super secondary structures(motifs).
Protein folding
• Governed mainly by interactions between side chains
• Not all proteins fold spontaneously as they are synthesized
• Usually supported by action of molecular chaperons 1. Specialized proteins
(Heat Shock Proteins) 2. Facilitate correct folding pathway
3. Reversible interact with partially
or improperly folded polypeptides
• Complex trial and error process
Protein misfolding - usually degraded
• Spontaneously
• Mutation of a particular gene
• Other stimuli
Prion diseases Amyloidosis
• Natural non-infectious form - apparently normal protein undergo
is α helical found in human brain cells abnormal proteolytic cleavage
• Infectious β pleated sheet - Form long fibrillar assemblies of β pleated sheets
Act as a template (Amyloids)aggregates spontaneously which are toxic
and converts naturally deposits in tissue
occurring non-infectious - degenerative disease
prion protein ∝ helical structure ex : Alzheimer’s disease – deposited in brain
to β pleated sheets
• insoluble aggregates of fibrils
ex : Creutzfeldt Jakob disease in human
Mad cow disease in cattle
Properties of Proteins
1. Charged nature
Mainly from charged R groups and to a lesser extent COOH or NH2,
can exist as cations, anions or zwitter ions, depending on pH
IpH depend on nature of R groups
At IpH least solubility and osmotic pressure
Alkaline medium negative ions react with Zn2+/Ba2+deproteinising body fluid
Acidic medium  positive ions  react with complex ions precipitate

ex : sulphosalicylic test
2. Buffering action
pH = pK  buffering is maximum
Imidazole of His important in buffering action of Hb (Globin is rich in His, pka = 7)
3. MW is very high 5000-5X106 , not dialysible, can separated by ultra centrifugation
4. Solubility
Most need small amount of salt to solubilization
Ex: globulins in plasma
5. Denaturation Denaturants
II, III, IVry structures altered Heat
Iry structure unchanged Organic solvents
1) Loss of biological activity Mechanical mixing
2)Solubility decreased Strong acids/bases
ex : heat coagulation test Detergents
3) Digestibility increased Heavy metal ions
4) Irreversible Urea 8M
Plasma protein Serum protein

-Fibrinogen present no fibrinogen
-Most have pI < 7 (negatively charged
in physiological pH)
70-80g/L
-Albumin main
-Globulins
Functions
• Control of fluid distribution • Transport (albumin, others) • Haemostasis(enzymatic activity)
• Defense - Immunoglobulins (γ globulins)
- acute phase proteins
Proteins Simple
Conjugated = apoprotein + non protein
Electrophoresis
Separation of proteins  based on charge & MW
pH of medium charge of protein
<pI positive
>pI negative
Proteins migrate to anode or cathode when a electric field applied
Carried out in
Constant pH 8.6 barbiturate buffer
Constant temp. & DC voltage
Plasma proteins move towards anode (+) pH > pI negative charged
Rate of movement ∝ 1. magnitude of -ve charge

2. Shape
3. Charged: size ratio
Apply electric current for given period of time and stain paper or gel for protein in normal serum
Electrophoretic pattern of normal serum

albumin
γ β
α2 α1
Abnormal patterns
• Cirrhosis - albumin↓, γ globulin ↑
• nephrotic syndrome- albumin↓ γ globulin↓ ∝2 macroglobulin↑
• paraproteinaemia
eg: multiple myeloma albumin ↓ , sharp ↑ of γ globulin band
Normal plasma including fibrinogen peak between β and γ
Nephrotic syndrome
Albumin lost in urine β α2 α1
albumin
γ
Multiple myeloma – cancer of plasma cells (B cells)

A single γ globulin in very large excess
γ
albumin
β α2 α1
Liver disease
Albumin, α, β globulin synthesis
Comparative in γ
γ β α2 α1 albumin
Electrophoresis can also be used to separate different Hb s , plasma lipoproteins
HbA HbS HbC
+ - cathode
• Sickle cell- HbS , HbC

• β globin chain 6th AA
Normal Hb – Glutamine
HbS - Valine
HbC - Lysine
Collagen
• High amount in supporting structures
• Most abundant protein 25% of proteins in mammals
• Rigid insoluble
• Several types depend on structural role
Unusual amino acid composition
33% Glycine – enables easy packing
25% Proline/Hydroxy proline
Also contain Lysine , Hydroxy lysine
• low aromatic amino acids
• gly-X-Y - repeating sequence
• X = proline or other Y= OH-pro , OH-lys or other
• Pro α chain forms a left handed kinked helix with 3 AA per turn
• Triple helical structure with 3α chains (not α helixes) interwined in right handed manner to form pro-collagen.
Opposing twist give added strength
• type 1 is the most
• Types- type 1-skin, bone,tendon,blood vessels Type3-blood vessels foetal skin
Type2-cartilage, intervertebral disc Type4-Basement membrane
Synthesis of collagen
• genes for pro ∝1/pro ∝2 are transcribed in to mRNA
• mRNA translated in to pre-pro ∝ polypeptide chains and extruded into RER lumen
• removal of signal sequence
-Hydroxylation
• proline prolyl hydroxylase hydroxyl proline
• lysine lysyl hydroxylase hydroxyl lysine
Vit C (Vit C deficiency Scurvy)
-glycosylation
• lysine by glucose & galactose
-3 pro ∝ chains assemble→ triple helicle structure
-inter & intra chain disulfide bonds formed at C terminal and N terminal extensions which have no helical structure
-Secretion
-removal of C & N terminal ends
-triple helicle structures arranged with ¼ length displacement
-cross linking between slide chains,mainly by Lys
• denaturation→ converted in to gelatin
• Degradation- collagen molecules are highly stable. Degrade during connective tissue remodeling by
collagenases producing amino acids.
• OH Pro not reused and excreted in Urine so reflects collagen turnover
Collagen diseases
Caused by defects in colagen synthesis or structure.
1. Vit C defi.-Defective Hydydroxylation
Scurvy – increased fragility of blood vessels, delayed wound healing, gum decay,
2. Ehlers Danlos syndrome-Defects in collagen processing enzymes.(Lysyl hydroxylase or procollagen
peptidase) Type 1 and Type 2
Or mutation in collagen genes – alteration of AA sequence & those degraded.
3. Osteogenesis Imperfecta-Mutations in genes for pro ∝1 or pro∝2 genes of Type 1 collagen. Gly replaced by
AA with bulky R groups.
Brittle bones, twisted spine
THE CYTOSKELETON
 It is a 3 dimensional meshwork of protein filaments that extend throughout
the cytoplasm.
• Dynamic • Highly • Adaptable
organized
Made of proteins- 3 types
- Microfilaments
- Intermediate filaments
- Microtubules
Microfilaments /Actin filaments:-

− Thinnest (7 nm) − Dynamic
− Helical polymer structure
− Has Polarity − Flexible
+ end / barbed end
 G actin self-assemble into F actin Higher order
organization
F actin
(Filamentous)
G actin
(Globular)
- end / pointed end
− Reversible Polymerization at both ends of Actin Filaments. Faster at (+)

end.
Accessory proteins regulate polymerization / depoln
− Even at steady state, there is polymerization & depolymerization at both
ends. - A dynamic equilibrium exists.
Functions
 Mechanical strength
 Maintains cell shape
 Cell Motility
-Pseudopodia – actin reorganizes/ weakens to form a pseudopodia
-Cell streaming – cytoplasm cycles over a carpet of actin filaments
within the cell. Myosin also contributes
 Cell division - cytokinesis (Division of cytoplasm by forming Cleavage
furrow )
 Contractile structures (with Myosin)
 Involvement in cell adhesion- Tight junctions , Adherent junctions
 Any process which involves a change in the shape of the cell needs
microfilaments.

Ex: -
 platelet aggregation, phagocytosis, development of embryo, immune
response, cell crawling, , angiogenesis, extension of neurons , muscle
contraction , cell division
 RBC Cytoskeleton has no Microtubules or intermediate filaments. Structural

support. Biconcave Shape
Hereditary Spherocytosis
Defective Cytoskeleton (Ankyrin, Spectrin )
Production of Sphere shaped RBCs.
Leads to breakdown of RBCs. Haemolysis in spleen.
Duchenne’s muscular dystrophy (DMD)/Becker’s muscular dystrophy (BMD):-

Dystrophin require for anchoring muscle cells
Absence or the expression of abnormal Dystrophin leads to DMD
Microtubules:-
− Hollow tube like structures 25nm
− Composed of tubulin dimer (αβ subunit ) Requires GTP
− Show polarity. Dynamic.
− Reversible polymerization. Faster at (+) end
− (-) end anchored at the centrosome
− Growth and shrinkage depend on cellular signals
− Slow growth, rapid shrinkage
Functions:-
• Structural support of cilia / flagella
• Forms mitotic spindle (moves chromosomes during mitosis)
• Determines position of organelles
• Provide “tracks” for movement of organelles / vesicles (Dynein, Kinesin )
• Polarize cells. Ex : cell division, T-cells(positioning of Golgi apparatus)
• Centrioles

 Microtubules provide “tracks” for movement of organelles / vesicles
Motor proteins • Transport is driven by motor proteins
motor proteins are proteins that use energy to do mechanical work
A
Eg: Kinesin – towards the + end away from the centrosome
dynein – towards the – end
• Motor proteins interact with & move along microtubules
Microtubules • Energy dependent process
*Cilia & flagella:-

(9+2) microtubule structure
Responsible for cellular movements (unicellular) or move fluid over a surface
Associated with Dynein (motor protein)
Dynein cause bending of cross linked micro tubules resulting in flagella
movement
cilia
Non motile/Primary- Acts

Motile
as a sensory antenna to
-lungs
cells
-respiratory tract
-kidney
-middle ear
-eye - photoreceptors
Clinical -cancer treatment by targeting microtubules

Drugs bind with Microtubules and stabilize them. Mitotic Spindles cannot
form.
• Taxol- binds & stabilizes microtubules
Drug Name Target component Effect Clinical application

Vinblastine Microtubules Prevents Chemotherapy
polymerization
Colchicine Microtubules Prevents Used to treat gout
polymerization
Paclitaxel(Taxol) Microtubules Stabilizes Chemotherapy
microtubules and
prevents mitosis

Intermediate filaments:-
− Apolar.
− More stable. Not involved in movement
− Different subunits
− 8 tetramers twisted into a rope-like filament
− Various globular protein subunits are incorporated into IF filaments
− Heterogeneous group of proteins
− Assembly & disassembly is controlled by phosphorylation.
Functions
• Maintains cell shape (specialized for tension bearing)
• Anchorage of nucleus and other organelles
• Formation of nuclear laminar
• Involvement in cell adhesion- Desmosomes (cell-cell),
Hemidesmosomes(cell-BM)
Type Proteins Site of expression

I and II Keratins epithelial cells
III Vimentins
Eg: Vimentin Variety of cell types
(fibroblasts,WBC, Smooth muscle
cells)
Eg: Desmin muscle cells
IV Neurofilaments mature neurones
V Nuclear Lamins nuclear lamina of all cells
VI Nestin Stem cells of the CNS
Disorders
Keratin- Epidermolysis bullosa simplex.
− Skin blistering in response to mild mechanical trauma in skin and mucous
membranes
− Defective keratins in basal layer of epidermis due to mutation in certain
keratin genes.
− Lysis of cells in Basal Layer of Epidermis
Neurofilaments – Parkinson’s disease

Amyotrophic lateral sclerosis
tooth disease
*Microvilli – Microfilaments anchored to a network of Intermediate filaments

Overall Functions
1. Structural support
 acts as scaffolding (stabilize cell shape)
 provides shape to sub-structures of cells
 anchorage for cells / organelles
2. Movement
 movement of whole cells
 provides “tracks” for movement of cellular components
 cell division
3. Regulation
 organizers structures and activities of the cell
 regulation of cytoskeleton dynamics
1. T/F
a) Cytoskeleton is present in prokaryotes.
b) Microtubules are important in moving the organelles in cytosol.
c) Cytoskeletal proteins are found in prokaryotes.
d) Continuous assembly and deassembly of micro tubules is seen at pH 7.6 than
at pH 6 in mammalian erythrocytes.
e) Actin is a major cytoskeletal protein involved in muscle contraction.
F,T,F,F,T
f) Synthesis of cytoskeletal proteins in platelets is induced by activation.
g) Most cytoskeletal proteins are encoded by multigene family.
h) Microfilaments are arranged in fibres and networks by various crosslinking
proteins.
i) Microtubule production is inhibited in cell division.
j) Keratin is an example of intermediate filaments.
T,T,T,F,T
k) Axonal transport is an example of intracellular transport based on
microfilaments.
l) Microtubules have distinct (+) & (-) ends.
m) Microtubules are present in mitotic spindle
n) Cytokinasis requires the contraction of actin filaments
o) In nerve cells microtubules are continuously assembled and dissembled
p) Continuous assembly and dissembly of microtubules is seen in mammalian
erythrocytes
F(microtubules),T,T,T,T,F
2. True or False?
a) Intermediate filaments are formed by polymerization of tubulin dimmers.
b) Tubulin polymerization inhibitors are potential anti cancer drugs.
c) Disintegation of nuclear envelope during mitosis is initiated by the
phosphorylation of nuclear lamins.
d) Defective microtubule structure in flagella causes infertility.
e) Actin filament network undergoes re-organization during phagocytosis.
F(microtubules),T,T,T,T

Extra Cellular Matrix
• Acellular material around cells (ground substance + protein network)

• Dynamic
• Filled with complex network of macromolecules secreted by cells
• Degradation controlled by proteases
• Highly organized , complex structure
• Proportion and composition of ECM varies between tissues. (Reflects functional role)
Key Functions: -
 Anchorage for cells
 Structural support for tissues
 barrier functions for segregates tissues from one another
 Lubrication of joints
 Regulates cell migration and intercellular communication
Composition of ECM
1.Polysaccharide GAGs (often found as Proteoglycans) – ground substance
Structural proteins (fibrous proteins)

2. Protein -Collagen, Elastin, Fibrin
adhesive proteins
- Fibronectin, Laminin, Fibrillin
3. Water
Glycosaminoglycans
• Long unbranched polymer
• Have repeating disaccharide units
Coo- Coo- Coo-
Amino Uronic Amino Uronic Amino

sugar sugar Uronic
acid acid sugar acid
SO4- SO4- SO4-
• Negatively charged
• Forms hydrated gel
• Often form proteoglycans (except Hyaluronic acid)
Proteoglycans
GAGs linked to core protein = Proteoglycan
 Expanded structure (due to repulsion of negative charges)
Aggrecan- cartilage
Syndecan- cell surface
Na+
High negative charge Ex -Chondroitin sulphate: Cartilage, tendons,
Na+
bone
Dermatan sulphate: Skin, blood vessels
Hydrophilic Osmotically Heparin: Mast Cells, Liver
active
Heparan sulphate: Cell Surface
Keratan sulphate: Cartilage, Cornea
H2O H2O
Matrix Hyaluronic acid
• Non sulphated
H2O H2O • Doesn’t attach to
proteins covalently.
• Found in vitreous
Swell (Hydrated) humor, lips, cartilage,
synovial fluid
 When compressed, -Lubrication
the water 'squeezed out'. Molecules ‘slip' past each other due to -Shock absorber
repulsion -Selective barriers
 when compression released, -Masks pain
returns to original hydrated volume.
Mucopolysaccharidoses (Lysosomal Storage Disease)

Lysosomes degrade proteoglycans
Proteases-protein component Acid Hydrolases / Glycosidase - GAG
Deficiency of glycosidase
Leads to accumulation of partially degraded GAGs in tissues --------- urine
Fibrous proteins
Collagen Types
o I - Major collagen in wide variety of tissues
Collagen :- (Bone, ligaments, tendons, skin, …)
 Rich in Pro & Lys o III, V, VI -Found in most tissues (frequently with type I)
 Contain OH-Pro & OH-Lys o II , IX , X , XI – Hyaline Cartilage
o IV – Basement Membranes (non fibrillar )
 Low in aromatic AA
o VII - Anchoring structures at juncs b-n epithelium &
 Glycosylated mesenchyme
Types :- I, II, III, V -fibrillar
IV - network like (BM)
VI, IX – fibril associated

 Bone Matrix
 Type of mineralized ECM embedded with
 Ehler-DanlosSyndrome
bone cells, blood vessels and nerves. -Defects in collagen processing enzymes and mutations in
ECM↑ Cells ↓ collagen genes.
-Abnormally stretchy skin.
Protein ↑ (type I collagen)  Osteogenesis Imperfecta
Polysaccharide ↓
-Defect in synthesis of collagen. Often type I collagen.
 Mineralization gives mechanical strength
& rigidity. (Hydroxyapatite) -Defective ∝ chains. Inadequate bone mineralization
-Brittle bones
Elastin :-
 Rich in Pro & Gly little OH-Pro
 hydrophobic Emphysema due to α 1 –antitripsin deficiency
 Non-glycosylated − Neutrophils secrete elastase
 Permit deformability and passive recoil
− Elastase breaksdown Elastin in lung tissue
− α 1 –antitripsin inhibits Elastase
− Smoking – oxidize Methionine of active site of Antitripsin
Marphan’ s syndrome
-Mutations in fibrillin gene − Leading to Emphysema (Chronic obstructive pulmonary
-Elongated bones in fingers & arms disease)
Adhesive proteins
Fibronectin Laminin
(In Basal Laminar)
(widespread)
Attach cells to ECM
 Maintain tissue / organ structure

 Cell - ECM communication
 Cell migration
Epidermolysis Bullosa
Type Defect Lysis region
EB Simplex Keratins (cytoskeletal protein) Epidermis
Junctional EB Laminin Dermal-epidermal junction
Dystrophic EB Collagen type VII Dermis

 Cartilage
 Semi rigid connective tissue
 Though and yet flexible
 ECM
− Proteoglycan aggregates (chondroitin sulphate, keratan sulphate)
− Collagen (type II) , Elastin
Hyaline Cartilage in joint - Cushions bones at joints

o Protects bones by preventing rubbing
o Helps movements allowing bones to glide over each other
o Near-frictionless articulation at joints
Synovial fluid in joints - Prevents cartilage from grinding against each other
(High amount of hyaluronic acid) Allows diffusion of nutrients to cartilage
Osteoarthritis
• Proteoglycans autoantigens
• Destruction of the cartilage
• Replacement by bones
Synovial fluid &Osteoarthritis
• Reduction in Synovial fluid volume (Reduction of
Hyaluronic acid in synovial fluid)
• Loss of elasticity & fluidity
• Affects shock absorbing power of the joint
• Prone to injury
Fibrosis
Excessive collagen production- over expression of collagen gene
Decreased activity of removing enzymes- decreased ECM degradation
Cancer
ECM barrier to cancer metastasis
Invation requires cell adhesion, migration and protease activity
Development of Atherosclerotic plaque
DS binds plasma LDL / Atherosclerotic lesion ----------- arterial smooth muscle cell proliferation

Functions of ECM
− Wound healing
− Mechanical support for cells & tissues
− Integrate cells into tissues. Provides framework for cell adhesion.
− Binds tissues to each other
− Influences cell shape and movement. Influences Growth, Proliferation and migration of
cells.
− Influences cell development and differentiation. (Embryogenesis)
− Serving as a medium for exchange
− Aiding in defense and protection
− Coordinates cellular functions through signaling with cellular adhesion receptors
− Reservoir for extra cellular signaling molecules
− Regulation of filtration (kidney glomerulus)
− Regulation of blood clotting (damage to blood vessels-----exposure of ECM---interaction of
platelets with ECM)
− Scaffolding for tissue renewal
− ECM binds many growth factors and hormones
 Migratory cells bind to ECM via - Focal adhesions

 Stationary cells bind to ECM via - Hemidesmosomes

1. T/F
a) Proteoglycan is the major macromolecule in the ground substance.
b) Adhesive proteins in ECM contain many functional domains.
c) Mucopolysaccharidosis is a defect in the synthesis of proteoglycan.
d) Chondroitin sulphate & keratin sulphate are major components of cartilage matrix.
e) Basal lamina contains type IV collagen.
T,T,F(degradation),T,T
f) Integral proteoglycans binds cell membrane to the ECM.

g) Basement membrane in the lung alveoli acts as a highly selective filter.
h) During remodeling bone matrix is deposited on cartilage matrix.
i) N-acetylated galactose amine is present in glycosaminoglycans.
j) Hyaluronic acid is unique in structure amongst glycosaminoglycans in that it is not sulphated.
T,T,F,T,T
k) Mucopolysaccharidoses lead to accumulation of glycosaminoglycans in the cell.

l) Mucopolysaccharidosis is a defect in the synthesis of proteoglycans.
T,F(degradation)
2. True or False?
a) ECM regulates the transport of nutrients.
b) Mutations in fibrillin gene result in marfan syndrome.
c) Chondroitin sulphate is a polymer made up of repeating disaccharide units.
d) Over expression of ECM results in hepatic fibrosis.
e) Collagen fibers give elasticity to tissues.
f) Hyaluronic acid is a lubricator in synovial joints.
T,T,T,T,F,T

BIO MEMBRANES
Structure
Lipid bilayer
Components proteins
Carbohydrates covalently linked to proteins (glycoproteins)
Lipids (glycolipids)
Only in outer leaflet.
Structure is described in Fluid mosaic model by Singer and Nicolson.

Membrane function depends on Lipid ratio.
Protein
Lipids Choline phospholipids (PC,SM)

Glycerophospholipids
Amino phospholipids (PE,PS)
Types Sphingolipids
Cholesterol
Hydrophilic head→ exposed to water

Hydrophobic tails→ in interior
Lipids are amphipathic
Unsaturated tail → sis double bond→ forms kinks
When mixed with
water Saturated tail
Micelles/emulsions Lipid bilayers Liposomes→ can be made from solutions of

pure phospholipids.
Enzymes
Used in DNA to target
delivery of Anticancer tissues.
drugs
Membrane proteins.
 Determine most of the specific function of membranes.
Peripheral proteins → not embedded (loosely bound to the surface of
proteins)
Two classes
Integral proteins →penetrate the hydrophobic core of the bilayer
→ transmembrane proteins. (completely spanning the
membrane)
 Protein asymmetry → functional difference.

Functions of membrane proteins
o Transporter
outside
o Enzyme binding site
o Cell surface receptor
o Cell surface identity marker
o Cell adhesion inside
o Attachment to cytoskeleton
PROPERTIES OF BIOMEMBRANES
• Asymmetry • Dynamic • Selectively

• Fluidity • Self-sealing permeable
• Flexibility
1. Asymmetry
Transverse Asymmetry Lateral Asymmetry
Asymmetry between inner & outer Regional Heterogeneities
Leaflets of bilayer Some proteins are localized in
different parts of the cell
Carbohydrates mainly
in outer leaflet
Phosphatidylserine (PS)
Anionic-Gives negative charge to cytoplasmic side
of the membrane.
Cofactor for membrane bound enzymes
Eg: Protein kinase c, Na˖/K˖ ATPase
2.Fluidity
Temperature→ fluidity is mentioned over a wide range.
Depends on
Membrane composition
Types of phospholipids Amount of cholesterol

1.Saturation Fluidity Buffer
 Unsaturated – high fluidity
2.Chain length
 Briefly explain the role of cholesterol in maintaining the fluidity of the bio membranes.
o The steroid cholesterol is wedged between phospholipid molecules in plasma
membrane

o At warm temperatures it controls the movement of phospholipids and reduces
fluidity
o At cool temperatures it maintains fluidity by preventing tight packing
3.Flexibility
Permits shape change without loss of integrity
4.Dynamic
movement in lipid bilayer
1. Lateral diffusion → fast

2. rotation → very fast
3. Transverse diffusion (flip flop) → slow → need flippase to make it fast.
Membrane transport.
Simple diffusion → small uncharged molecules.
Passive transport
Substrates move down the Facilitated diffusion →
concentration gradient
Transporters Ion channels (Very selective)
Eg: erythrocyte glucose transporter channel mediated Non-gated

-GLUT 1
Gate
{Ligand , Voltage, Mechanical}
Passive mediated transport (facilitated diffusion)

o Transporters bind to substrate through weak non-covalent bonds and binding induces
conformational change
o Faster than simple diffusion
o Show saturation kinetics
o Susceptible to competitive inhibition (like enzymes)
o Chemical and stereo chemical specificity for
transported molecules
Eg glucose transporters (GLUT1,2…..)

Passive mediated transport –protein channels
o Highly selective for

specific molecules
o Very fast
o Cannot be saturated
Eg – gated channels
open and close in
response to stimulus
 Gap junctions – Transport ions
connects the cytoplasms of two cells by 2 CONNEXONS
A connexon is made by 6 connexin proteins
 Aquaporins- Transport water (too narrow for ion transportation)

Tetrameric transmembrane protein
Categories of assisted transport

Uniport—transport single solute
Symport
o Two different solutes to be transported

o Gradient of one substrate drive uphill transport of co-substance
Eg – glucose –Na+ symport
Antiport
o Exchange one solute for another

Eg - Na+ - H+ exchanger
Symport and antiport are secondary

active transport methods

Active transport
o requires energy as it is against concentration gradient

o two types
1. primary active eg - Na+ / K+ ATPase, H+ / K+ ATPase
2. secondary active
Na+ / K+ ATPase
o Moves 3 Na+ out and 2K+ in for each ATP hydrolyzed
o Required to maintain osmotic balance and cell volume
Cell contain high concentration of solutes
This create large osmotic gradient which pulls water in
Counteracted by opposite osmotic gradient due to high concentration of inorganic
ions
o Careful use as a therapeutic benefit for
heart patients
Eg Digitalis inhibits this pump
Explain the molecular mechanism of

acidification of the stomach lumen by parietal
cells in the gastric lining
Secondary active transport
As concentration of glucose is higher inside the

cells compared to the intestine, Glucose needed
to be pumped into cells against the concentration
gradient.
Energy required for this comes from the

electrochemical gradient maintained by Na+ / K+
ATPase.
Na+ within intestinal cell < lumen So SGLT (Sodium
glucose symporter) which is located at the apical
membrane of intestinal cells pumps glucose in to cells against its concentration gradient while
taking Na+ down its concentration gradient.
Bulk transport – energy requiring
o two types
1. endocytosis
2. exocytosis

Endocytosis
o plasma membrane envelope
particulate matter and liquids
1. Phagocytosis (cellular eating)

Ingest solid particles
2. Pinocytosis (cellular Drinking)

Ingest liquid and matter dissolved in liquid
3. Receptor mediated endocytosis, specific molecules are taken in
Exocytosis
o Form vesicles that transport to the membrane
o Vesicles fuse with the membrane releasing substance out
MCQ
1. Myelin sheath of certain neurons is primarily composed of lipids.
2. Inner mitochondria consist of more proteins.
3. Animals during Hibernization synthesize more unsaturated FA to core with low body
temperature.
4. Permeability of a gap junction can be regulated.
5. Tight Junctions prevent leaking.
6. Ionophores are mobile proteins.
7. Multidrug resistance associated protein helps in detoxification of foreign substances.
8. Simple diffusion does not show saturation kinetics.
9. When albumin is dissolved on 0.9% NaCl solution, it is isotonic to the human plasma.
10. The sugar moieties of surface glycoprotein influence the folding of proteins.
11. Membrane proteins act as cell surface identity markers.

NUCLEIC ACIDS & DNA PACKAGING
Nucleic acids
DNA (Deoxyribonucleic acid)
Two major types
RNA (Ribonucleic acid)
Components of nucleic acids

• Pentose (C5) Sugar
• Nitrogenous Base
 Purines ( bicyclic)
 Adenine (A)
 Guanine (G)
• Pyrimidines ( monocyclic)
 Cytosine (C)
 Thymine (T) - only in DNA
 Uracil (U) - only in RNA
• Phosphate group
 Nucleoside=Pentose sugar + Nitrogenous Base (N-linked ß Glycosidic bond)

Eg :- Adenosine, Guanosine, Cytidine, Thymidine, Uridine
 Nucleotide=Nucleoside + Phosphate group (one or more)
Eg :- Deoxyadenosine triphosphate-dATP
Adenosine triphosphate-ATP
FEATURES OF THE POLYNUCLETIDE CHAIN

• Backbone – repeating sugar phosphate groups
 (-)vely charged
• Bases directed away from backbone.
• Two distinct ends
 5’ OH end (phosphate group)
 3’ OH end (free hydroxyl group)
Results in Polarity
STRUCTURE OF DNA (Watson & Crick Model)

• Two polynucleotide chains coiled around a common axis
• Double helical
• Antiparallel
5’ 3’
3’ 5’
• Complementary(not identical)
• Right handed coiling
 10 bp/turn, 20oA diameter
• Sugar phosphate backbone outside
 Hydrophilic
 Polar sugar molecules
 Negatively charged phosphate groups
 Poly anionic backbone
• Bases inside
 Hydrophobic
 Plane of basses perpendicular to the axis of backbone
Base pairing in the double helix;
• A=T & G= C
• A+G= T+C (number of purines=number of pyrimidines)
• Complementary base pairing sequence of basses in a single chain will automatically determine the sequence of
the other chain.
Stability
• Base stacking interactions • H-bonds between bases
• Ionic interactions
• When viewed from outside 2 groves can be observed – due to base pair stacking and phosphate sugar
(Important for binding of drugs & proteins) backbone twisting
• Additional DNA strand can form a triple stranded DNA at the groove
 Strong acid & high temp. - completely hydrolyzed
 pH 3-4 : apurinic nucleic acids
 High pH has a small effect on DNA structure, but can change the tautomeric state of the bases which can
result in instability & denaturation
RNA is unstable at higher pH as 2’OH group in RNA hydrolyses
Denaturation?
H bonding of the duplex DNA can be broken and the two strands can be separated by increasing the temperature,
increasing the pH, specific enzymes.
Denaturation is a reversible process.
Melting temperature (Tm)?

The temperature where half the duplex DNA is unwound is called melting temperature
Why does a genome containing a higher percentage of GC bases have a higher melting temp?
There are three hydrogen bonds between G & C but only two between A & T. DNA that contains high concentration of
GC bases denatures at a higher temperature than AT rich DNA.
Renaturation?
Process where the denatured complementary strands of DNA forms the duplex DNA.
Slow cooling of denatured DNA allows renaturation.
Hybridization?
Denatured DNA when cooled in the presence of exogenous DNA, strand association occurs to form a duplex hybrid.
Depends on
 Favorable temperature of the solution
 Salt-ion concentration
Even if two sequences do not match perfectly they can be hybridized. – Used in disease diagnosis
RNA (Ribonucleic acid)

• Chemically similar to DNA, but linear & single stranded
• Shows 5’ to 3’ polarity
• Have modified bases ( specially in t RNA)
E.g. Methylated
Acetylated
Deaminated
• Some have secondary structures
E.g. Hair pin (stem-loop) structure → intra-molecular base pairing
Types of RNA
• Coding mRNA
• Non-coding tRNA rRNA –major
sn-RNA, sc-RNA - involved in RNA Splicing, protein trafficking etc.
• Viral genomes contain DNA or RNA with single stranded or double stranded.
DNA PACKAGING
Supercoiling of DNA
• Bending ,twisting of the DNA helix(coil)
• DNA in cells is always negatively supercoiled-important in replication, transcription
How DNA is supercoiled

Underwind Relaxed DNA Overwind
Removal of turns in the DNA helix Addition of turns to the DNA helix
Structural Strain
Released by
SUPERCOILING
(-ve) supercoils (+ve) supercoils

Topoisomerases
Increase or decrease the extent of DNA supercoiling by,
 Cleaving DNA (nuclease activity)
 Rotating DNA strands
 Rejoining DNA strands (ligase activity)
Important in DNA packaging, replication, transcription & DNA repair.
Topoisomerase I Topoisomerase II
1. Cleaves one DNA strand 1. Cleaves both DNA strands
2. No energy Required 2. Energy Required
3. Present in both prokaryotes and Eukaryotes 3. Present in both prokaryotes and Eukaryotes
4. Prokaryotes: Relaxes (-ve) supercoils only 4. DNA gyrase (bacterial)- introduce (-ve) supercoils
Eukaryotes: can work on both (-ve) and (+ve) Remove (+ve) supercoils
supercoils • Eukaryotic topo 2 cannot introduce supercoils. It
can only relax them.
5. Linear daughter chromatids are separated by Type II
topoisomerases following replication.
• DNA Gyrase
Responsible for maintaining (-)ve supercoiling of bacterial chromosomes.
Inhibited by: Novobiocin –blocks ATP binding do not inhibit eukaryotic
Nalidixic acid- blocks the breakage and rejoining mechanism topoisomerases
• Doxorubicin, etoposide – eukaryotic topo 2 inhibitor. Used as chemotherapeutic agents.

DNA packaging in eukaryotes
DNA + Proteins Chromatin
1 : 2
Euchromatin Heterochromatin
Poorly stained Darkly stained
Loosely packed Densely packed
Transcriptionally active Transcriptionally inactive
DNA Binding Proteins
Histones Non-Histone proteins

4 major types Not involved in packaging
H1,H2A,H2B,H3,H4 Eg:- topoisomerases ,gene regulatory proteins
Rich in lysine & arginine Highly species/ organ specific
(+ve) charge
Nucleosomal histones H1 histones

H2A,H2B,H3,H4 Less conserved
Help fold DNA into nucleosomes Help pack nucleosomes to higher order structure
Form ‘’Histone core’’ Histone H1 binds to linker DNA; act as ‘hinge’
Most highly conserved
Nucleosomes - Unit of packaging

“Beads on a string appearance”
30nm fibre - H1 binds to linker DNA & ‘pulls’

the nucleosomes together.
Looped domains
Chromosomes
• Packaging alter in replication & transcription

 To make DNA sequences accessible,
DNA has to separate from the histones.
 Histones undergo reversible covalent modifications
By; Histone acetyltransferases
Histone methyltransferases
Protein kinases
E.g. Selected lysine side chains – acetylated
Selected serine side chains – phosphorylated
These modifications regulate transcription, DNA repair, apoptosis.
Histone acetylation/deacetylation
• In bacteria
 “Nucleoid” is the packaging structure
 Don’t have Histone proteins.
 Have several types of chromatin proteins;
e.g. HU proteins (Histone like proteins)

Vitamins
➢ Vitamins are unrelated organic compounds that cannot be synthesized in adequate amounts by
humans. Therefore, must be supplied by diet.
• Organic compounds
• Essential to human health
• Involved in fundamental functions of body
• Some are not dietary essential
o Eg: Vitamin D
o Niacin containing coenzymes are derived from tryptophan
• Micronutrients
• Absence is usually manifested as deficiency diseases
Water soluble Fat soluble

Readily excreted in urine (after exceeding the Not readily excreted in urine
renal threshold)
Not stored except vitamin B12 Stored in liver and adipose tissue
Toxicity is rare (except vitamin B6) Excess amounts of vitamin A and D are toxic
Deficiency can occur quickly Deficiencies are rare
Absorbed and transported in chylomicrons with
dietary fat
Most vitamins are precursors of coenzymes Only vitamin K has coenzyme function
2015 A/L Repeat Campaign

WATER SOLUBLE VITAMINS
1. Folic acid (pteroyl glutamate)

a. Structure
Pteridine-PABA-glutamate
(-)
Sulphonamide is a competitive inhibitor
b. Active form – tetrahydrofolate (THF)

DHF reductase
Dietary folate (DHF) THF
(-)
Methotrexate is a competitive inhibitor
c. Function
Donors transfer one C segment intermediates in the synthesis of
• Amino acids
• Purines
• Thymidine monophosphate
N10 formyl THF purine synthesis
N5,N10 Methylene
THF THF
TMP synthesis
N5 Methyl THF Homocystein B12 Methionine
d. Deficiency
i. Macrocytic megaloblastic anaemia
Synthesis of TMP → DNA → Cell division
ii. Neural tube defects eg: spina bifida, anencephaly (common among pregnant
women and alcoholics)
2. Vitamin B12 (cobalamin)
a. Structure – contains cobalt
b. Active form
i. Methyl cobalamin (methionine production)
ii. Deoxy adenosyl cobalamin (succinyl CoA production)
c. Function
i. Methylation
Cobalamin Methyl cobalamin
Homocysteine Methionine synthase Methionine
N5 methyl THF THF

ii. Isomerization
Methyl malonyl CoA Vitamin B12 Succinyl CoA
d. Bioavailability
e. Only from microorganisms, not present in plants and animals.
f. Absorption, transportation and storage
B12 in diet is released in acidic environment
Free B12 Bind Intrinsic factor B12+IF Absorption Mucosal cells of ileum
Binding protein
In blood
Stored in liver B12+B12 binding protein
Released to bile and efficiently restored.
g. Deficiency
i. Reasons
• Decreased intake (take several years to develop)
• Impaired absorption (more quicker)
• Reduced secretion of gastric acid
• Reduced secretion of IF (autoimmune destruction of
parietal cells
ii. Pernicious anaemia
• Folate trap
Homocysteine Methyl cobalamin THF
Methionine Cobalamin N5 Methyl THF
▪ N5 methyl THF can’t be translated into other active forms of

THF regeneration
▪ The only reaction, occurs when vit B12 is present
▪ If vit B12 is deficient, THF will accumulate in methyl form
▪ Thus, other forms, needed for purine and TMP production will
be reduced. Cell division impaired, anaemic conditions occur.
▪
Folic acid can partially reverse the haematological abnormalities of B12 deficiency, and therefore can mask the B12
deficiency. So treatment initiated with both folic acid and B12 until the cause of the anaemia is diagnosed
3. Vitamin C (Ascorbic acid)

a. Active form – Ascorbic acid
b. Functions
i. Cofactor for reactions requiring reduced metal ions
Eg: Cu containing hydroxylases (Cu2+ Cu+)
Hydroxylation of Proline and Lysine in collagen synthesis
ii. Non-enzymatic reducing agent, can readily donate electrons to,

1. Reactive free radicals

2. Other biological anti-oxidants
iii. Decreases lipid peroxidation
iv. In Iron absorption, reduction of Fe3+ to Fe2+ by vit C
v. Carnitine biosynthesis
vi. Degradation of tyrosine
vii. Bile acid formation
c. Deficiency
i. Microcytic anaemia (due to decreased absorption of dietary iron)
ii. Scurvy (due to deficiency in hydroxylation of collagen)
4. Vitamin B1 (Thiamine)
a. Active form - Thiamine pyrophosphate (TPP)
b. Functions
i. coenzyme in energy metabolism
ii. oxidative decarboxylation reactions
Eg: Pyruvate Pyruvate Dehydrogenase Acetyl CoA + CO2
TPP
α keto glutarate α keto glutarate dehydrogenase Succinyl CoA + CO2

TPP
iii. Transketolase reactions in HMP
c. Deficiency
i. Decreased production of ATP, increase in plasma lactate and pyruvate
ii. Beri beri
5. Vitamin B2 (Riboflavin)
a. Active form
i. Flavin mono nucleotide (FMN)
ii. Flavin adenine dinucleotide (FAD)
b. Functions
i. Reduced substrate Oxidized substrate
FAD/FMN FADH2/FMNH2
ii. Temporarily hold electrons

iii. Serve as cofactors to flavoenzyme
6. Vitamin B3 (Niacin)
a. Active forms
i. Nicotinamide adenine dinucleotide (NAD)
ii. Nicotinamide adenine dinucleotide phosphate (NADP)
b. Functions
i. Serves as coenzymes in redox reactions

NAD+/NADP+ + H+ NADH/NADPH
Reduced substrate Oxidized substrate
Eg: coenzyme for lactate dehydrogenase and malate dehydrogenase

ii. Source of ADP ribose in DNA repair mechanism
c. Deficiency – Pellagra
7. Vitamin B5 (Pantothenic Acid)

a. Active form - Coenzyme A
b. Function - transferring acyl groups, thiol group carries acyl component
CoA, Succynyl CoA

Fatty Acyl CoA, Acetyl CoA
Metabolized into two
Main cofactors
Acyl carrier protein (ACP)
8. Vitamin B6 (Pyridoxine)
a. Active form - pyridoxal phosphate (PLP)
Pyridoxamine phosphate
b. Function -
i. Catalyzes reaction involving amino acids
Reaction Type Ex.
• Transaminase OAA + Glu AST Asp + αKG

• Deamination Glu Glu Dehydrogenase αKG + NH3
• Decarboxylation Histidine Histamine + CO2
ii. Glycogen metabolism

Glycogen phosphorylase
iii. Important in steroid hormone reactions
9. Vitamin Biotin
• Vitamin Biotin required by human is produced by intestinal bacteria
Function -as a co-enzyme in carboxylation reactions, carrier of active CO2

Carboxylation reactions
Substrate product
−
carboxylase-biotin-COO
E.g. pyruvate pyruvate carboxylase oxaloacetate
Acetyl CoA carboxylase

Fat Soluble Vitamins
(1) Vitamin A (retinoids)

Structure
Retinol
Retinal
Retinoic Acid
Visual Cycle
all trans retinol


11 - cis retinol all trans
retinal

11-cis retinal
 opsin
Rhodopsin
➢ Retinol → Retinal → β-carotene (conversion of β-carotene to retinal is inefficient)

Active Form - Retinoic Acid and 11 - cis retinal

Absorption, Transportation and storing
trans retinol
β carotene(plant) retinal Retinyl
palmitate
Diet
retinyl esterase(animal) retinol Chylomicron remnants

Fatty Acyl CoA
CoA Chylomicrones
fatty acids
Retinyl esters plasma
Retinol
Intestinal cell Binding
Proteins
(RBP)
Retinol

Retinoic Acid RBP Vitamin A deficiency results in night blindness RBP

RAR(Retinoic Acid Receptors)
 Keratin of most
gene activation all trans
epithelial tissues
 Retinol
mRNA all trans
 retinal
specific proteins all trans
 retinyl esterase
cellular differentiation light
opsin Rhodopsin
11- cis retinol
Function
opsin 11 cis retinal
dim light - rods
• Vision → Visual Cycle
colour - cones
• Growth and maturation
• Reproduction → spermatogenesis
→ fetal resorption prevention (making placenta)
• Maintenance of epithelial cells (integrity)
• and mucus secretion (glycoprotein synthesis)
• against anaemia - promotes red cell proliferation, better utilization of iron
• involved in immune response

Deficiency → To prevent Retinol and carotenoid precursor are used as dietary supplement
Night blindness is the earliest sign
Toxicity → excessive intake → hypervitaminosis A
(2) Vitamin D
A group of sterols in human body is produced from 7 - Dehydrocholesterol.
Active form – calcitriol 1,25 - dihydrocholecalciferol
cholecalciferol 25 hydroxylase 25 - hydroxycholecalciferol 1-hydroxylase 1,25 - dihydroxy

cholecalciferol
Regulation of hydroxylation of Vitamin D

Functions as a hormone
➢ Main function - Ca absorption and homeostasis
Deficiency
• Nutritional rickets and osteomalacia
• Renal osteodystrophy
• Hyperphosphatemia and hypocalcemia
•
Toxicity
• enhanced calcium absorption and bone resorption → hypercalcemia
(3) Vitamin E (Tocopherol)
Active Form - D α tocopherol
Functions
• First line of defence against membrane phospholipid peroxidation (lipid peroxidation is

a chain reaction. DANGEROUS! Vitamin E is a chain breaking, free radical trapping
antioxidant)
Antioxidants
• Vitamin E - effective in high PO2
• β carotene - effective in low PO2
Toxicity and Deficiency both low.
(4) Vitamin K (Phylloquinone)
Active form
• Phylloquinone, menaquinone, menadione
Functions
1. Post translational modification of proteins
• Coenzyme in the gamma carboxylation of glutamic residues in clotting factors and
calcium binding proteins.

ENZYMES
• Biocatalysts.
• Most enzymes are proteins. But certain RNAs also act as enzymes called, “Ribozymes”.
• Show remarkable selectivity towards their substrates - enzyme specificity.
• Enzyme specificity.
-Catalyze one or few reactions.
-Act on one type of bond and one type of linkage.
-Optical specificity (stereo specificity) -Act on either D or L forms.
• Lowers the activation energy.
• Unit: - μ moles of substrate converted per minute at a given pH and T
• Enzyme activation
• Pepsinogen H+ Pepsin + peptide
• Mg2+ activates Enolase; 2-phosphoglycerate Enolase PEP + H2O
• Isoenzymes
Different molecular forms of enzymes that catalyze the same reaction. Different
primary structures  Different kinetic properties.
Can be separated by electrophoresis.
Creatine kinase
Isoenzyme Subunits Major source
CK1 BB brain
CK2 MB heart
CK3 MM Skeletal muscle, heart
COFACTORS
1. Organic molecule cofactors/ Coenzymes. – lightly bound eg:- NAD+
2. Prosthetic group. _ tightly or covalently bound eg:- pyridoxal phosphate
3. Inorganic metal ions – part of the catalytic site or may bind the substrate to the
enzyme. eg: - Cu2+, Mn2+
Michaelis constant - Km
- Reflects the affinity of the enzyme towards the substrate.
- Km is numerically equal to the substrate concentration at which the reaction
velocity (Vo) is equal to ½Vmax.
- Km is inversely proportionate to affinity of the enzyme. (High Km → low affinity)
- Km doesn’t vary with concentration of enzyme, but with temperature, pH and structure
of the substrate
Km = Rate constant of breakdown of [E][S] complex / Rate constant of formation
of [E][S] complex
Glucokinase – High Km , act at high concentration.
Present only in the liver.
Hexokinase- Low Km , act at low glucose concentration. present in extra
hepatic tissue and in fetal liver.

Vmax. – maximum capacity of the enzyme to catalyze the reaction.
Vmax[S]
V0 – The initial velocity of the reaction is taken as its velocity. V 0 = K +[S]
m
Factors that affect enzyme catalyzed reactions

1. The substrate concentration.
- V0 increases with the substrate concentration, as it become higher V0 become constant.
V0
[S]
2. Enzyme concentration.
- Rate of the reaction increases with the enzyme concentration.
V0
[E]
3. pH of the reaction medium.

- For each enzyme there is a effective pH, increasing or lowering
It would decrease the V0.
Eg:- Pepsin 1.5-2.5, Trypsin 8-9
Trypsin Papain
Pepsin
V0
2 4 6 8 10 pH
4.Effects of the temperature.
0oC <--------------------------37 oC -------------------------------> 70 oC
rate is close to zero optimal temperature completely destroyed
% activity
20 40 60
Temperature 0C
5. Effect of electrolytes.

ENZYME INHIBITION
Any substance that can diminish the velocity of an enzyme catalyzed
reaction is called, “an inhibitor”.
Enzyme inhibition
Reversible Irreversible Suicide inhibition

- Competitive
- Non- c o m p e t i t i v e
- Uncompetitive
Competitive inhibition
• Inhibitor competes with the substrate for the active site.
• Inhibitor similar in structure to substrate.
• Inhibition can be removed by increasing [S].
E+S ↔ ES ↔ E + P *Km ↑
+ *Vmax no change
I
↕
EI
Eg:- Inhibition of succinate dehydrogenase by malonate.

E + Succinate  E-Succinate E + Fumarate
(True substrate)
E + Malonate  E-Malonate  No product

(Competitive inhibitor)
Practical usages
 Use of Sulphanilamide as an antibiotic.
-Is a structural analog of PABA (Para Amino Benzoic Acid)
-Para amino benzoic acid [PABA] is a component of folate.
-Certain bacteria need PABA to synthesize folic acid.
-Sulphanilamide acts as a competitive inhibitor in folic acid synthesis and therefore interfere
with bacterial cell division.
-humans do not synthesize folic acid but takes it from diet.
-So in bacterial infections, sulphanilamide drugs would be harmful only to bacteria.

 Use of Neostigmine.
- Is a structural analogue of acetylcholine.
- Therefore, a competitive inhibitor of acetylcholine esterase.
Ach choline + acetate
Ach esterase
-During surgery,
Curare is administrated.
Competes with Ach. and blocks receptors.
Muscle relaxation.
-After surgery,
To remove curare from receptors
High [Ach] required.
Neostigmine administered.
Neostigmine competes with Ach for acetylcholinesterase.
↑ [Ach] and displace the curare
 Disulfiram
NAD+ NADH
Ethanol Acetaldehyde
Alcohol D.H
NAD+ NADH
Acetaldehyde acetate
Aldehyde D.H
-Disulfiram inhibits Ald. D.H.

-[Acetaldehyde]↑
-This produce symptoms of nausea and headache.
-Then discourage the consumption of alcohol due to the bad side effects.
Nonc ompetitive inhibition

• Inhibitor binds to the enzyme but not to the active site.
• Inhibitor not similar in structure to substrate.
E+S ↔ ES ↔ E + P
+ +
I I
↕ ↕ **Km No change
EI Km ↑ ESI Km↓ ** Vmax ↓
Eg:-
• MAO inhibitors (Proadifen) - non-competitively inhibits drug metabolizing enzyme cyt.
P450. So prolong action of hypnotic agent hexobarbitol. - ↑ half-life of hexobarbitol.
• Heavy metal ions inhibit enzymes by reacting with SH groups. Hg2+ Pb2+, Ag+

Uncompetitive inhibition.
In uncompetitive inhibition the inhibitor bind with the enzyme substrate
complex.
E + S ↔ ES ↔ E + P
+
I
↕ ** Km↓
ESI ** Vmax ↓
Eg:- Inhibition of intestinal ALP by L-Phenylalanine.
Irreversible inhibition.
• No structural similarity.
• Bind covalently with enzymes and inactivate them.
1. DFP(Diisopropylfluorophosphate)
• Called nerve gas
• Forms covalent bond with -OH group of serine in the active site.
• DFP inhibits many enzymes
• Mostly affects acetyl cholinesterase.
• Inhibits Acetylcholinesterase accumulation of Ach. Muscle
paralysis suffocation.
• Same principle in organophosphate insecticides.
2. Use of irreversible inhibitors as drugs – Aspirin
Inhibit COX
Suicide Inhibitors.
• Special group of irreversible inhibitors.
• Bind to active site of an enzyme, undergo some catalytic steps, form a reactive
compound that covalently bind with the active site and inhibits the enzyme.
E + I ↔ EI → EI2
Play a central role in rational drug design.
Specific for a particular enzyme.
Therefore, very effective and have few side effects.
Eg:-1. Allopurinol
Adenosine Guanine
↓ ↓
Hypoxanthine Xanthine Uric acid
Xanthine oxidase Xanthine oxidase
Allopurinol Alloxanthine / Oxypurinol

Xanthine oxidase
Alloxanthine is tightly bound to the active site and cannot be removed.

Enzyme looses its activity.
So, by inhibiting xanthine oxidase, formation of uric acid is inhibited.
So accumulating hypoxanthine & xanthine can be excreated easily.
2. 5’ fluorouracil
 Using Ethanol in Methanol poisoning. (not competitive inhibition)
-Methanol + NAD+ Alcohol
Formaldehyde+ NADH + H+
Dehydrogenase
-Formaldehyde - very toxic to nervous system specially to optic nerve.

-Enzyme is highly affinitive to ethanol than to methanol.
-So ethanol is consumed & methanol excreted via urine, breath and by
sweating.
-Methanol is removed via gastric lavage and hemodialysis
-Bicarbonate therapy for acidosis
Acidosis
 Ethylene Glycol (antifreeze in radiators)
Ethylene Glycol Glyco-aldehyde Glycolic acid Glyoxylic acid Oxalic acid
 α1 protease inhibitors
present in blood and plasma. Inactivates proteinase enzymes released from
phagocytic cells.
Proteinase inhibitors + proteinase enzymes non-dissociable stable complex
Control -blood coagulation
-Dissolution of blood clots
-Activation of complements cascade
Eg: α1 protease inhibitor (α1 anti-trypsin) inhibit proteinases with serine in active
site (elastase, trypsin, chymotrypsin)
Genetic deficiency of α1 protease inhibitor pulmonary emphysema
Proteinases and their inhibitors play major role in metastasis of cancer
Regulatory enzymes
Allosteric enzymes induction & reduction (synthesis) reversibly covalent modification

# Allosteric enzymes Vm
Have allosteric site and a catalytic site. V0 vs [S] give a
sigmoid curve.
Do not follow Michaelis Menton kinetics. So they have Vm/2
apparent Michaelis constant Km0.5 / Km’ =[S] at the ½ Vmax
Regulation is brought about by non-covalent changes.
0.5 Km

Allosteric Modulators
(+) modulators (-) modulators

Km ↓ Km ↑
Or Or
Vmax ↑ Vmax ↓
Binding modulators to the allosteric site lead to change in

conformation of the active site as above.
Allosteric activation Allosteric inhibition Eg:-

Acetyl CoA carboxylase Eg:- HMG CoA reductase
By Citrate. By cholesterol. (feedback inhibition)
Homotrophic allosteric activation.

In some allosteric enzymes, the substrate itself acts as an activator.
Reversible covalent modifications.

This can occur by covalent attachment of phosphate groups.
These enzymes exist either in high activity or low activity states depending
upon phosphorylation.
Eg:- Glycogen phosphorylase is active in the phosphorylated form while
glycogen synthase is active in the dephosphorylated form.
Clinical Applications of enzymes.

• Enzyme activity in body fluids (serum and urine) in diagnosis and
prognosis.
• As analytical reagents in measurement of non-enzyme substance
(Drugs, Proteins).
• As therapeutic reagents.
Enzymes in plasma.
1. Constituent enzymes.
- Plasma specific enzymes.
- Functional enzymes.
- Present in high concentrations.
e.g. Thrombin
Plasmin
Lipoprotein Lipase
2. Non-constituent enzymes.
- Non-plasma enzymes
- No functional role.
- Generally present in low concentration.
- Present in blood due to leakage from tissues.
a) Increased cell permeability.
b) Increased cell death.
c) Increased cell turnover (neoplastic)
d) Increased synthesis (γ GT in response to alcohol)
e) Obstruction to rout of secretion(ALP in cholestasis)
- Present in urine - amylase is secreted in urine
- Present in bile - ALP
- Increase in non-constituent enzymes in serum indicates tissue damage or
change in metabolism.
- May not indicate disease.
Eg:- Transient hyperphosphatasemia in infancy - ALP levels in serum are 20×normal.
In children 2-38 months old.
- Metabolism in most tissues is similar.
- Specific enzymes are selected to indicate certain tissues.
Enzymes as therapeutic agents
 Glutamine + Aspartate Asparagine + Glutamate

ATP ADP
Asparagine is incorporated into proteins
Helps in cell growth
In Leukemia, Asparaginase is given
Asparaginase
Asparagine Aspartate
Reduce malignant cell growth.
 Fibrolytic enzymes
Streptokinase / Tissue-type plasminogen activator (tPA)
Convert Plasminogen to plasmin
Fibrin clot is dissolved by plasmin

BIOENERGETICS, OXIDATIVE PHOSPHORYLATION AND ELECTRON
TRANSPORT CHAIN
There are two major sources of high energy phosphate for formation of ATP synthesis:
Substrate Level Phosphorylation Oxidative Phosphorylation
Substrate-P (or Pi) + ADP → Product + ATP Electrons stored in the form of reduced coenzymes
(NADH & FADH2)
Examples: These electrons are passed to oxygen, through a highly
1. In Glycolysis - cytosol organised chain of proteins and coenzymes called
Phosphoglycerokinase Electron Transport Chain (ETC).
1,3-bisphosphoglycerate → 3-bisphosphoglycerate A proton gradient is established across the inner
2. In TCA Cycle - mitochondria mitochondrial membrane - cristae
Succinate thiokinase It is the energy that drives ATP synthesis.
Succinyl CoA + Pi → Succinate + ATP (erythrocytes do not have mitochondria to generate
ATP by ETC)
Standard free energy change (ΔG) for aerobic respiration is negative. The standard free energy change for
phosphorylation of ATP is positive. The energy released in respiration (in ETC) is coupled to
phosphorylation of ATP.
Aerobic respiration uses an ETC to break the fall of the electrons to oxygen into several energy–releasing
steps. (If electrons were transferred directly to oxygen, a large proportion of the energy would be lost.)
Mitochondria
• Mitochondria Outer Membrane: (channels by proton porin)  permeable to most ions and small
molecules.
• Mitochondria Inner Membrane Impermeable to most

- Need specialized carriers/ transport systems
- Highly convoluted (increase surface area)
- Rich in proteins (involved in Oxidative Phosphorylation)
• Inter membranous Space

• Mitochondria Matrix
Electron Transport Chain

o Coupling reactions with a common intermediate.
o Coupling concept is provided by dehydrogenation reactions.
o The ETC is a multi-compartmental system with four large proteins – Complex I, II, III, IV – and two
mobile carriers present in cristae – Coenzyme Q and Cytochrome C – which contains electron carriers.
 Complex I – NADH dehydrogenase (NADH CoQ oxidoreductase)

 Complex II – Succinate dehydrogenase
 Complex III – Cytochrome bc1
 Complex IV – Cytochrome c oxidase (Cytochrome a+a3) – only electron carrier with coordination
site that reacts directly with O2.
 Electron Carriers in ETC:
• NAD+/NADH
• FAD+/FADH2
• FMN/FMNH2
• Coenzyme Q
• Cytochrome C
Coenzyme Q (CoQ or ubiquinone) - located in the lipid core of the membrane and very hydrophobic.
- the only non-protein electron carrier – quinone derivative (lipid)
Cytochrome C - a small water-soluble mobile protein.
- shuttles electrons from complex III to IV.
o Cytochromes use the ability of metal atoms to accept and release electrons.
o Iron is most commonly used.
o Copper and iron (as haem) are used in the Complex IV – Cytochrome c oxidase.
Pathways from which electrons are donated to Coenzyme Q:

• NADH (Complex I)
• Succinate (via succinate dehydrogenase – Complex II)
• Fatty acyl CoA (in β-oxidation, the electrons in the FADH2 are donated here)
• Glycerol 3-phosphate (the FADH2 produced in the glycerol phosphate shuttle – see below)
 The energy released by electrons (as they move down the ETC) is used to pump H+ ions (protons) from
the matrix to the intermembrane space of the mitochondria. Only complex I, III and IV pump H+ this
way. Complex II does not.
 Oxygen (O2 molecule) is the final electron acceptor. O2 accepts the electrons to form H2O, catalysed by
complex IV (cytochrome c oxidase).
(Transport of a pair of electrons from NADH to O2 through ETC releases 52.58kcal)
ATP synthase (Complex V)

 Synthesizes ATP using the energy of proton gradient
 2 domains
o F0 – spans inner mitochondrial membrane
o F1 – protrudes into the mitochondrial matrix
 F0 rotation causes conformational changes in β subunit of F1.
 These changes allow,
o Binding of ADP + Pi
o Phosphorylation of ADP  ATP Flow of 3H+
o Release of ATP
 Oligomycin binds to F0  Close protein channel.
 pH and electrical gradients cannot be dissipated in the presence of this drug, electron transport
stops because of the difficulty of pumping anymore protons against the steep gradient.

Chemiosmotic Theory of ATP Production/ Mitchell hypothesis
A proton concentration gradient formed as a result of electron transfer serves as the energy reservoir for
driving ATP formation.
Electrons release energy as they flow down the ETC

↓
This energy is used to pump H ions (protons) from the matrix to the intermembrane space (by complex I,
+
III and IV only – NOT complex II) This pump is vectorial (specific direction)
↓
This creates an electro-chemical gradient and a pH gradient (due to H+ concentration difference)
↓
+ charge outer membrane ↓ lower pH outside
↓
ATP synthase (Complex V) on the inner membrane provides a way for the H+ to flow back into the matrix
down the gradient
↓
This releases energy (stored in the electro-chemical and pH gradients)
↓
This causes a conformational change in ATP synthase which uses the energy released to produce ATP
(Flow of three H+ ions through ATP synthase complex causes a conformational change which causes ATP
synthase to synthesise ATP using ADP and Pi – this is oxidative phosphorylation)
NADH results in more net H+ movement than FADH2 because complex I pumps protons but complex II
does not.
One NADH → 3 ATP
One FADH2 → 2 ATP
Transporters on the Inner Membrane

• Once ATP is formed, the ATP is transported out of the matrix, in exchange for ADP, by adenine
nucleotide translocase (an antiport).
• Phosphate (as H2PO4-) is brought to the matrix by phosphate translocase which is a symport that
transports H2PO4- and H+ ions into the matrix through the inner membrane.
• Together, adenine nucleotide translocase and phosphate translocase provide substrates and
remove the product of ATP synthase.(multisubunit enzyme)
(See Lippincott’s Figure 6.13)
Uncoupling
• Normally, ETC and oxidative phosphorylation are tightly coupled for ATP synthesis
• Certain substances can uncouple the ETC from oxidative phosphorylation
• This causes the collapse of the electro-chemical H+ gradient
• The energy stored in the gradient is dissipated as heat
• This leads to Non-shivering thermogenesis.

Natural uncouplers
Natural uncoupling protein ‘thermogenin’ (UCP1) is found in brown adipose tissue in the newborn. Brown
adipose tissue contains many mitochondria and helps maintain body temperature. Thermogenin (UCP1) is
an important factor in heat production and in lipid turnover. [Brown fat containing natural uncouplers is
also important in animals – e.g. adapting to the cold & during hibernation]
Synthetic uncouplers
Synthetic uncouplers such as 2,4-DNP and FCCP are hydrophobic and contain a dissociable proton (i.e. they
are hydrophobic weak acids). In their uncharged form, they can pass into the mitochondrial matrix and
release H+ in the matrix – dissipating the H+ gradient.
Drugs such as aspirin (and other salycilates) which are weak acids at high doses can act as uncouplers.
Inhibitors/Uncouplers/Drugs Affecting ETC and Oxidative

Phosphorylation
Name Function Site of Action
Rotenone, Amytal Electron transport inhibitor Complex I
Antimycin A Electron transport inhibitor Complex III
CN-, CO, Azide Electron transport inhibitor Complex IV
2,4-DNP, FCCP Uncoupling agents Act as transmembrane H+ carriers
Oligomycin Inhibits ATP synthase ATP synthase
Atractyloside Inhibits ATP/ADP translocase (adenine ATP/ADP translocase (adenine
nucleotide translocase) nucleotide translocase)

Shuttles for NADH
NADH made in the cytosol (in glycolysis) cannot move into the matrix of the mitochondria.
Two mechanisms are present in cells to shuttle the cytosolic NADH to the mitochondrial matrix:
1. Glycerol phosphate shuttle (in muscle, brain)
2. Malate/Aspartate shuttle (in liver, heart)
Glycerol Phosphate Shuttle Malate/Aspartate Shuttle
Synthesize 2 ATPs for each cytosolic NADH Yields 3 ATPs for each cytosolic NADH oxidized.
oxidized
Cyanide Poisoning
CN- binds with the Fe3+ of haem in complex IV (cytochrome c oxidase)
↓
This prevents binding of O2 to complex IV (cytochrome c oxidase), where O2 is the final electron acceptor
↓
CN- causes a rapid and extensive inhibition of ETC
↓
So aerobic respiration stops, no ATP synthesis by ETC
↓
Leads to anaerobic metabolism and concomitant lactic acidosis and cell death

Antidotes to Cyanide Poisoning
1. Administration of nitrite (as sodium nitrite)
nitrite
oxyhaemoglobin (Fe2+ ) �⎯⎯⎯� methaemoglobin(Fe3+ )
Cyanide preferentially binds with Fe3+ of metHb (producing cyanomethaemoglobin) as compared

to Fe3+ of complex IV (cytochrome C oxidase).
So administering nitrite restores inhibition of complex IV (cytochrome c oxidase).
2. Administration of thiosulphate
This converts the cyanide to non-toxic thiocyanate
CN- + S2O32- → CNS-
Inherited Defects in ETC and Oxidative Phosphorylation

Inherited diseases of mitochondrion respiratory chain can cause lactic acidosis. Fatal infantile
mitochondrial myopathy and renal dysfunction involves in severe deficiency/absence of most
oxidoreductases of the respiratory chain.
Also, absence of ATP/ADP translocase can cause lactic acidosis. WHY?
- 13/90 polypeptides needed for Oxidative phosphorylation are coded by mit.DNA and
synthesized in the mitochondria (>rate for mutation)
- Alterations in mitochondrial DNA  Defects in Oxidative Phosphorylation
- Remainder coded by nuclear DNA, synthesized in the cytosol
- Tissues with greatest ATP requirement (CNS, skeletal muscles, liver etc.) are affected by
defects in Oxidative phosphorylation.
Mitochondria and Apoptosis
 Apoptosis (programmed cell death)

 Initiated through the intrinsic pathway by formation of pores in the outer mitochondrial
membrane.
 These pores allow cytochrome C to leave the intermembranous space and enter cytosol.
 Cytochrome C activates proteolytic enzymes  cause cleavage of key proteins  cell apoptosis.

physiology
bat notes
term 01
HOMEOSTASIS
Homeostasis
Maintaining the conditions of the internal environment relatively constant.
Internal Environment
In a multicellular organism, it is the interstitial fluid or tissue fluid.
What should be kept constant?

• Volume
• Osmolality
• Temperature
• Chemical composition
All the systems of the body help to maintain the homeostasis.

Eg: Supply of nutrients & waste products – Respiratory sys, GI sys
Protection of the body – Immune sys, Skin & surface membranes
There are various physiological arrangements which serve to restore the normal state once it is
disturbed.
Eg: Plasma [H+]
Buffers Respiration Renal mechanisms
Plasma [H+]
There are various Control Systems to make this happen. They maintain a variable at a particular set
point.
-Gets inputs from set point & feedback

from the sensor.
Set point
-Detects the error
-Output to effector.
Controller
Inputs Set point- Output
Feedback Feedback
signals =error
Sensor Effector
-Continuous -Receives output of the

monitoring of the controller
variable -Applies necessary correction
-Detects disturbance
-Sends feedback to Response
controller
Controlled
variable
Correction
1 Disturbance(s) ©2015 A/L Repeat Campaign

Negative feedback mechanisms Positive feedback mechanisms
Keeps a physiological level of a substance Accelerates a process which has already started
constant to reach an end point
Effects are negative to initiating stimulus Effects are positive to initiating stimulus
Vomiting, Childbirth, Blood clotting, Nerve
impulse transmission
Effectiveness of a control system
Measured by GAIN 𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶

𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺 =
𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸
Not 100% effective.
If the gain is higher, system is better.
Variable Set Disturbance Hypothetical Actual Correction Error Gain

point change change
Systolic BP 120 Blood loss 60 100 100-60=40 120- 40/20=2
mmHg 100=20
Temperature 37 cold 17 36.5 36.5- 37- 18.5/0.5=
C 17=18.5 36.5=0.5 37
1. T/F regarding homeostasis

a) Disturbances in variables are detected by sensor.
b) Controller is responsible for calculating the error.
c) In negative feedback it facilitates the initial stimulus.
d) Efficient systems have a higher gain.
2. T/F regarding physiologic regulatory system

a) They are negative feedback systems.
b) The essential inputs of the controller are the set point and current value of the variable.
c) If the set point changes with time of the system is called a “servo mechanisms”.
3. Regarding a physiological regulatory system

a) Error is calculated by the controller
b) Efficient systems have a higher correction / error ratio
4. A 25-year-old person was admitted to the hospital after a road traffic accident. He has lost blood.
His systolic pressure was 90mmHg at the time of admission (normal systolic point is 120mmHg).
Deviation of blood pressure from the set point would,
A) Be due to decreased volume in the intra vascular compartment
B) Larger in the absence of a regulatory system
C) Be detected by the sensors in the circulatory system
D) Blood pressure can be normal by positive feedback
E) Can be normal 100% by negative feedback

Fluid and electrolyte balance
Body fluid and compartments
Total Body Water (TBW)

60% of Body weight(BW)
ECF ICF
1/3 of TBW or 20% of BW 2/3 of TBW or 40% of BW
Plasma Interstital Transce

Fluid/ Tissue llular
5% of
BW Fluid Fluid-
(1/4 of 15% of BW negligi
ECF)
(3/4 of ECF) ble
Transcellular fluid belongs to ECF & includes CSF, secretions in gut, fluids in joints and eye
Blood-8% of the BW
*Calculate approximate values for a 70 kg young adult male. (1kg=1L)
Factors affecting TBW
1) Age - age TBW

(Infants – 70%, Young adults – 60%, Old – 50%)
2) Gender - F – 50% < M – 60% (low percentage of fat)
3) Fat content - Fat TBW
Water Balance
Water gain = water output

3L/day = 3L/day
Over hydration - gain > loss

• Parenteral administration
• Polydipsia
• Renal failure - dysfunction in output.

Dehydration - gain < loss
• Vomiting
• Diarrhea
• Polyuria
• Vascular bleeding
Dehydration
• Hypertonic Eg: – sweating, diabetes insipidus
• Hypotonic Eg: – adrenaline insufficiency, diuretic over use, vomiting, diarrhea
• Isotonic
Infants & children more prone to dehydration
 TBW : infants (70%) > adult (60%)
 ECF/ ICF : Infants & Children > adults
 ECF volume : Infants & Children < adults
 Possibility of H 2 O loss : ECF > ICF
 Dehydration develops
1) More rapidly
2) Frequently more severe in children than adults
Distribution of electrolytes
ICF ECF
Major Cation (+) K+ Na+
Major anion (-) PO 4 3- Cl-

Prot -
Proteins - [ICF]>>[plasma]> [interstitial fluid]
Measurement of electrolytes
SI unit - mmol/L
Traditional unit- mEq/L

Serum Intracellular
Na+ 135-145 mmol/L 15 mmol/L
K+ 3.5-5 mmol/L 150 mmol/L
Dilution principle
Known amount of
1. A known amount of substances (x) introduced to substance injected (x)
the concerned body of fluid compartment & Volume (v)
allowed to equilibrate.
2. After equilibrium is reached concentration in the
sample is measured (C) volume of body fluid
compartment (V) is calculated Body fluid
sample compartment
𝑥𝑥
𝑉𝑉 =
𝐶𝐶
Characteristics of the substances used
1. non-toxic
2. easily measured
3. distribution limited to the compartment
4. mix evenly throughout the compartment
5. not changed or lost in time taken for equilibrium to reach or amount changed or lost is known
6. compartment should be accessible for sample collection
7. must not have an effect on its own on body fluid distribution.
Measurement of volumes of body fluid compartments
 TBW - D 2 O, T 2 O, aminopyrine
 ICF - not measured, TBW - ECF
 ECF - radioactive inulin (most accurate)
Mannitol
Sucrose
Radioactive Cl- / Br-
 Plasma - dyes which bind to plasma proteins
Serum albumin labeled with radioactive iodine
100
 TBV -
100−𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻
× 𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝 𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣
 Interstitial fluid - ECF - plasma
1. In a normal healthy adult

a) the ratio ECF/ ICF is less than one
b) interstitial fluid has a higher osmotic pressure than plasma
c) the quantity of total body water is directly proportional to the fat content of the body
d) increase Na+ loss causes a reduction in ECF
e) the percentage of total body water is higher in children

2. In health the proportion of the water in the body is higher
a) in infants than in adults
b) in young adults than in the old
c) in thin people than in fat people
d) in women than in men
e) than in edematous person
Movement of substances across biological barriers
Mechanism
Solvent
Drag
Diffusion
• Facilitated Filtration
• Simple
Mechanisms
Active
transport
Osmosis
Exocytosis and
endocytosis
Examples
1. Diffusion
Simple Gases O 2, CO 2
Lipid soluble substances
Facilitated glucose
2. Active transport
Іry Na+ /K+ ATPase
IIry Na+/glucose (SGLT), Na+ / bile salt
co-transporters
3. Filtration Glomerular filtration
4. Osmosis
5. Exocytosis Nerve impulse transmission
6. Endocytosis Phagocytosis, Pinocytosis
7. solvent drag Transport of nutrients
RBCs in blood

1) Diffusion
 The process by which
-a gas or
-a substance in solution
-expands
-because of the continuous random movements of particles
-to fill all of the available volume
 Net flux of
-solute particles
-from areas of high
To areas of low concentrations
Factors affecting diffusion
1. Fick’s Law of diffusion

Tendency to diffuse α A × Concentration gradient
(magnitude)
2. Electrical charge of the ion
3. Distance
Time taken to reach α (diffusion distance) 2
Equilibrium
4. Donnan effect
5. membrane permeability
i. thickness of membrane (d)
ii. lipid solubility
iii. no. of protein channels per unit area
iv. Temperature
v. Molecular weight of substance
Types of diffusion
a. Simple Diffusion
b. Facilitated Diffusion

c. Non ionic diffusion
HA HA H+ + A-
H+ X
A- X
Net movement of undissociated substance (in GIT & kidney)
Donnan effect
Presence of a non-diffusible ion

-on one side of a membrane
-affects the
-distribution of
-diffusible ion
-across that membrane
In a predictable manner.
Effects of Donnan’s phenomenon

1. Rupture of cells
Normal cell volume & pressure depends on Na+ - K+ ATPase
2. inside of cell membrane is (-) charged
3. (plasma proteins) ion movement across the capillary wall
2) Active transport uphill movement

Energy required
Іry Active IIry Active

Energy Source ATP (directly) Derived from
concentration gradients
by Iry Active transport
Eg:- Na+-K + ATPase pump Na+ /glucose transporter

2ry active transport
• Symport Eg: – SGLT 1 (driving ion Na+ : driven Glu)
• Antiport Eg: – Na+ - H+ antiporter
3) Exocytosis & endocytosis

 Exocytosis
Energy dependent
Ca+ dependent process (in nerves)
 Endocytosis
Energy dependent
Reverse of exocytosis
Types –
1. phagocytosis
Polymorphonuclear leukocytes engulf bacteria, dead tissue
2. pinocytosis
“cell drinking” - engulf substances in solution
4) Filtration
Movement of fluid due to difference in pressure on two sides
Amount of fluid filtered depends on
1. pressure difference on either side (∆P)

2. membrane permeability
3. surface area of membrane
Ex: - Across capillary wall. (But across cell membrane no filtration)
5) Osmosis
Diffusion of solvent from a region of low solute [conc.]/ low osmotic pressure to a region of high
solute [conc.]/ high osmotic pressure across a semi permeable membrane.
Occurs from low osmotic pressure to high osmotic pressure

Osmotic pressure (OP)
Pressure necessary to be applied to a solution to prevent the inward flow of solvent across a
semipermeable membrane by osmosis
Depends on no. of dissolved particles
Osmole = amount of solute that dissociates in solution to form 1 mole
Glucose 1 mol/L =1osmol / L
NaCl 1mol/L = 2 osmol/L
Osmolarity - no. of osmoles per litre of solution

Osmolality - no. of osmoles per kilogram of solvent
Plasma osmolality - 290 mOsm/kg

Measured by - freezing point depression (By osmometer)
Calculated by -
Osmolarity 2 [ Na + ] + 0.055[Glucose] + 0.36[BUN]
(mOsm/L) = mEq/L (mg/dL) (mg/dL)
BUN- Blood Urea Nitrogen
Osmolarity measured is higher than calculated value

Why??
Osmolarity must have been increased due to a substance other than Na+, glucose, BUN like ethanol,
mannitol or poisons.
Tonicity
Osmolality of a solution relative to plasma
Isotonic - same as plasma
{0.9% Saline, 5% Dextrose, king coconut water}
Hypertonic - greater than plasma
Hypotonic - lesser than plasma
1. The osmolality of a solution

a) is the number of osmoles per kg of solvent
b) is independent of the volume of the solutes
c) varies with temperature
d) containing 180 g of glucose per kg of distilled water is about the same as that of normal human
plasma
e) containing 58.5 g of NaCl in 500 g of distilled water is one osmole
2. Assuming complete dissociation into Na+ & Cl- a solution of 5.85 g NaCl in litre of water
a) will have an osmolality of 0.1 osmole
b) will contain 0.1 mole of Na+ per litre
c) would be more concentrated than ECF
d) would have higher H+ concentration than ECF
e) will cause hemolysis of a normal red cells added to the solution in a few seconds
Interstitial fluid formation
Diffusion through the capillary membrane
1. Lipid soluble - diffuse directly

2. Water soluble - through the capillary pores (Na+, Cl-, Glu)
3. Protein & large substances - Transcytosis
This suggests capillary walls acts like semi permeable membranes. Impermeable to colloids.
So COP develops. COP due to plasma colloids is called the oncotic pressure.
Factors contributing to the formation of interstitial fluid
 Starling forces –Filtration (depends on hydrostatic pressure gradient)

−Osmosis (depends on colloid osmotic pressure gradient)
 Capillary permeability
 Available surface area
Hydrostatic pressure - Pressure exerted by fluid (eg:- blood in the capillary)

Colloid osmotic pressure - Pressure exerted by colloidal substances (eg: - mainly albumin)
Net Pressure = ↓( 37 – 1) – 25 mmHg ↑(1-17) + 25 mmHg

↓ 11 mmHg ↑9 mmHg
∆P = ↓(11-9) mmHg
= ↓ 2 mmHg
Balance carried by lymphatics

Odema
Abnormal accumulation of fluid in interstitial spaces.
Odema
Generalized Localized
1. ↑ venous pressure 1. ↑ venous pressure in local obstruction
In right heart failure -Late pregnancy (IVC)
↑ R atrial pressure.
2. lymphatic obstruction (lymphoedema)
2. hypoalbuminemia -cancers
+ protein malnutrition -filariasis
+liver disease
+nephrotic syndrome 3. ↑ capillary permeability
+Hypoproteinemia -insect bites
-Inflammation & allergy
-Substance P, histamine, kinins
Odema first seen in most dependent parts of the body.

Ex- Ankle odema.
Oedema causes weight gain.
Oedema (except lymphedema) leads to pit formation.
1. Ankle oedema is known to be caused by

a) Nephrotic syndrome
b) Severe protein energy malnutrition
c) Chronic renal failure
d) Deep vein thrombosis in legs
e) Systemic hypertension in the absence of heart failure
2. Capillary filtration
a) decrease if interstitial oncotic pressure increases
b) is normally smaller in magnitude than capillary reabsorption
c) is the main mechanism of cerebro-spinal fluid formation
d) will decrease if the capillary hydrostatic pressure decreases
e) is increase in protein malnutrition

Hormones & Receptors
• Chemical transmitters
• Showa ductless secretion in to blood/ Interstitial fluid
• Act on target organs distant or nearby
• Has specific receptors
• Regulate cellular activities in multiply places simultaneously
• Maintains homeostasis
Types of hormone activity

 Endocrine – Thyroid hormone, Growth hormone
 Paracrine – Estrogen, Testosterone, All GIT hormones
 Neuroendocrine – Oxytocin, Vasopressin
 Autocrine – Interleukins, Lymphokines
Hormones
Polypeptide Steroid Amines-Derivatives of tyrosine
Most hormones in the body Gonadal hormones Thyroid, adrenal medullary

Anterior & Posterior pituitary Adrenocortical hormones hormones
Hormones, Insulin, Glucagon
PTH
Synthesis
RER Golgi Packed to From cholesterol Derivatives of tyrosine
vesicles Exocytosis By SER
Storage
As prohormone in the Are not stored Thyroid-Bound to thyroglobulin in
secretory granules follicles
Catecholamine-in the secretory
granules
Secretion
Exocytosis diffuse through the Thyroid- first pinocytosis then
(Ca2+/cAMP dependent) membrane diffuse through membrane
Catecholamine-Exocytosis
Transport
Dissolved in plasma Bound to plasma protein Thyroid - Bound to plasma
(Biologically active) (Biologically inactive, TBG (biologically inactive)
Only free form is active) Catecholamine - Dissolved in
plasma (Biologically active)
Bound Free (Hormonal effects)

Receptor & Activating system
-Receptor-on cell surface -Receptor-Inside the nucleus or Thyroid-same as steroid

In the cytoplasm hormone (inside the nucleus)
-Activating system-activation of -activating system-regulatory action Catecholamine-same as peptide
membrane associated effectors on gene transcription hormones
system
eg: cAMP system, Ca2+
G-Protein linked receptors
• Hormone bound to extracellular domain of the

receptor
• Conformational change in the receptor
• G protein coupled to intracellular domain
become active
• GDP exchanged for GTP
• α subunit dissociate
• Activate adenylyl cyclase
• ATP -> cAMP – Activation of protein kinases
• Physiological effects
Hormones bound to plasma proteins are –

1. Not diffused easily
2. Biologically inactive
3. Don’t engage in feedback controls
4. Serve as stores
5. Slow to clear from plasma. Why??
Inactivation / Clearance
1. Metabolic destruction by the tissues
2. Binding with the tissues
3. Excretion by liver (Bile) or kidney (urine)
Rate of disappearance of hormone from the plasma

Metabolic clearance rate =
Concentration of the hormones
Regulation of hormone activity

• By feedback control (positive & negative)
• By regulation of the receptors
• By substrate
Hormone receptor regulation

• Down regulation - when hormone level increases, number of receptors on the cell surface decreases by
1. Receptor molecules are inactivated/ destroyed
2. Intracellular protein signaling molecules are inactivated
3. Internalization of the receptors
4. Reduced production of the receptors
• Up regulation - when hormone level decreases number of active receptors increases.
Other factors that affect hormone secretion

• Higher centers of brain (e.g. – Stress hormones)
• Time of day (Cortisol)
• Sleep
• Starved or fed status (Insulin, Glucagon)
Rhythms of hormone secretion

• Ultradian rhythm
• Circadian rhythm
• Infradian rhythm
Ultradian rhythm –
Episodic/ pulsatile secretion in repeated cycles within 24 hrs. e.g. – Growth hormone
Circadian rhythm –
Secretion following day & night cycles (responding primarily to light & darkness) e.g. – Cortisol, melatonin
Infradian rhythm –
Periods longer than 24 hr cycles. E.g. – FSH, LH, Estrogen

Measurement of hormones –
• Radioimmunoassay
• Enzyme linked immunosorbent assay
1. Regarding hormone receptors,

a) Receptors have a unique structure to discriminate between many similar messengers.
b) Androgens act on intracellular receptors.
c) Regulate cell function by regulating gene expression.
d) Increase in circulating hormone levels causes a decrease in receptive receptors.
e) Cell surface hormone-receptor complexes are active membrane associated effector system.
2. Peptide hormones,
a) Are lipid soluble
b) Bind to receptors on cell membrane
c) Cause phosphorylation of proteins in the cell
d) Alter transcription of genes
e) Activate G-protein bound receptors
3. Regarding Radioimmunoassay
a) Specificity is good but the sensitivity is poor
b) Antibodies can be used as binding proteins
c) Binding of radiolabelled and non-radiolabelled antigen onto the antibodies is proportional to
their relative concentration
d) Bound and free form ratio plotted against concentration of standard solution provides a linear
graph
e) Enzymes cannot be used as labels
Physiology of Blood
Composition of Blood
Plasma (55%)
Buffy Coat (WBC and Platelets)(1%)
Red Blood Cells(44%)
(Packed Cell Volume/Haematocrit)
Measurement of Haematocrit- Macrohaematocrit method, Microhaematocrit method
• Total Circulating Blood Volume - 8% of body weight

• Total Plasma Volume - 5% of Body weight
Composition of Plasma
• Water - 90%
• Proteins - 8%
albumin
globulin (α,β,γ)
fibrinogen
• Inorganic Ions - 1% (Na+, K+, HCO3-, Cl-, Mg+, Ca+)
• Others - 1% (Hormones, gases, waste products)
Functions of Plasma Proteins

1) Binding and Career Proteins (albumin - hormones, fatty acids )
2) Osmotic Regulators (albumin)
3) Buffering action of Blood(15% of buffering action of blood)
4) Producing the viscosity of blood (with RBC)
5) Immunity (γ globulin )
6) Blood coagulation/clotting factors
7) Anti-coagulation
8) Inflammatory responses
• SERUM is the plasma without
• Clotting factors
• Has a higher Serotonin content- Due to breakdown of platelets during clotting
(fluid left behind after a clot is formed)
Haemopoesis ( formation of blood cells)

First few weeks → yolk sac
6 week-6 months→ liver, spleen
5-9 months bone marrow (medullary haemopoesis)
Long bones Membranous bones

Eg: femur, humerus Eg: sternum, ribs,
1 ↓ vertebrae, pelvis, cranium © 2015 A/L Repeat Campaign
Stop at 30 years ↓
Continuous
Extra medullary hematopoiesis occurs when bone marrow becomes destroyed / fibrosed-liver and
spleen can resume.
In the bone marrow

Pluripotent Haemopoietic stem cell (PHSC) (Multipotent uncommitted stem cell)
IL-1, GM-CSF, IL-6, G-CSF, IL-3, SCF
Committed stem cell (Progenitor cell)
Erythroid Megakaryocyte progenitor CFUGM CFUEO CFUBaso

progenitors (CFUM) GM-CSF  GM-CSF, IL-5  IL-4, IL-3
(CFUE )  GM-CSF, Thrombopoietin Eosinophil Basophil
GM-CSF, Megakaryocyte
Erythropoietin 
Red cells Platelets
CFUM CFUG
 M-CSF  G-CSF
Monocyte Neutrophil
Growth factor actions
1. cell proliferation
2. differentiation
3. suppression of apoptosis
4. maturation
5. functional activation
-sources of growth factors-
• Mature RBC - Biconcave disc shaped - High surface area: Volume ratio

Less
basophilic
Normoblast Reticulocyte Mature RBC

Nuclear DNA Yes No No
RNA in cytoplasm Yes Yes No
In marrow Yes Yes Yes
In blood No Yes Yes
• No Nucleus
• Life span-120 days
• Higher concentration in males than females - sex hormones affect the rate of haemopoiesis
• Contains Hemoglobin
Functions of RBC
• Transport of O2 and CO2

• Buffering action by Hb and proteins
• Contains CA enzyme
Functions of RBC membrane

• Maintain the shape of the cell
• Helps in the transportation of essential cellular ions and gases
• supporting system for surface antigens

Reticulocytosis (normal <1% of RBC)
Reticulocyte count is more than 2 % :
1. To compensate for hemolysis

2. Following treatment for deficiency anemia
Requirements for normal erythropoiesis
1) Erythropoietin- Specific growth factor (85%-kidney, 15%- liver) = glycoprotein

2) Iron for Hb synthesis
3) Vit B12 & Folic acid (for DNA synthesis)
4) B6, A, C, E, Riboflavin(B2)
5) Trace metals- Zn, Cu, Co
6) Hormones - androgens & thyroxine
Erythropoietin
Glycoprotein Hormone, having following functions
1) Proliferation of Progenitor cells committed to erythropoiesis

2) Differentiation of stem cells committed to erythropoiesis
3) Suppresion of apoptosis - maintain cells of erythroid series
4) Release of reticulocytes to the circulation
5) Promoting Transferrin receptor synthesis
6) Hb synthesis
Kidney and liver has O2 sensors, when there is hypoxia, erythropoietin synthesis is stimulated.
Hemoglobin
HbA (adult ) = 2α 2β HbF (fetal) = 2α 2γ
Glycated haemoglobin = HbAIC (increased in patients with Diabetes mellitus. )
Hb + 402 oxygenation Hb (O2)4 oxyhaemoglobin
RBC Abnormalities
• Due to a defect in the membrane - Hereditary spherocytosis

• Due to a defect in hemoglobin production - Thalassemia , sickle cell disease
• Due to the deficiency of enzyme G6PD-Haemolysis
Red cell destruction
Intravascular hemolysis- Hb is released into the plasma
Extravascular hemolysis => Reticulo-endothelial system ( Tissue macrophage system)

Bilirubin Metabolism
RBC Hb Hb
Haem Globin
Porphyrin Fe2+ A.A

Biliverdin
CIRCULATION Bilirubin
Bilirubin + Albumin
**Pre hepatic
UPTAKE
Bilirubin+ 2UDPGA **Hepatocellular
Conjug Glucuronyl Transferase

i
Bilirubin Diglucruonide[BDG] EHC
Excreted in Bile
EXCRETION
BDG Urobilinogen
**Posthepatic
Stercobilin Faecal excretion
(Jaundice GIT)
Anaemia
Reduction in concentration Of Hb below accepted normal range (which depends on sex, age, ethnic
group, altitude)
Features - Tachycardia, palpitations, heart murmur, dyspnoea, pallor
Causes of Anaemia
↓ Production
↑ Loss ↑ Destruction
*nutritional deficiency
Haemorrhages Eg: hemolytic
anaemia *↓ bone marrow erythroid cells
*renal disease
Examples of anaemia
1) Blood loss anaemia - normocytic/normochromic

2) Microcytic hypochromic - Fe2+ deficiency , Thalassemia
3) Aplastic anaemia - defects at bone marrow level (less production)
4) Macrocytic megaloblastic anaemia- Vit B12 / folic acid deficiency
5) Hemolytic anaemia - defects in RBC membrane
6) Sickle cell anaemia - due to abnormal type of Hb
7) Normocytic normochromic Anaemia - renal disease, leukemia, Aplastic anemia
MCV = Mean corpuscular volume = Average volume of a RBC = 76- 96 fL
Microcyte < 76 normocyte Macrocyte>96 (Values not needed )
MCH = Average amount of Hb in RBC 27-33 pg
MCHC = amount of Hb in a dL of RBC 32-36 g/dL Hypochromic<25 g/dL
RBC being Hyperchromic is impossible since RBCs normally carry the maximum amount of Hb they can carry
Polycythemia (erythrocytosis)
Primary Secondary
pathological Physiological
-cancer ↑ erythropoiesis
*polycythemia rubra vera Hypoxic
Renal disease
Fe deficiency anaemia Thalassemia
MCV, MCH Reduced Reduced
Serum iron Reduced Normal
Serum ferritin Reduced Normal
Total iron binding capacity (TIBC) Raised Normal
Blood groups
Agglutinogens (Antigens) : complex oligosaccharide substances found only on RBC membrane
Agglutinins: antibodies against Agglutinogens , present in plasma after birth
Phenotype Agglutinogens Agglutinins genotype

( on RBC ) (in plasma) A antigen H antigen + N acetyl galactosamine
A
A Anti-B AA,AO B antigen H antigen + Galactose
B
B Anti-A BB,BO
O antigen H antigen
AB
A,B None AB
Bombay blood group do not have H antigen in
O their RBC, have both anti A and anti B
None Anti-A ,Anti-B OO
antibodies in blood.
Rh system
Antigens present only on RBC
C , D , E - three types of antigens, D is most antigenic
• Unlike ABO antibodies Anti D antibodies do not develop without exposure of D- RBC to D+ RBC by transfusion or
pregnancy
• Cross matching Donor RBC + Recipients plasma

Complications of blood transfusion
1. Incompatibility reactions
Antigens on Donor RBC + Antibodies in recipients plasma
RBC Agglutination
Clumps
IV Hemolysis
May block blood
Release Hb
Jaundice vessels
Renal failure
2. Fever, allergic reaction, circulatory overload, Iron overload, Air embolism, diseases (ex:- malaria, AIDS)
Hemolytic disease of newborn
Rh+ incompatibility
↓
When mother Rh-, first baby Rh+
↓
Fetal blood can leak into maternal circulation at the time of the delivery
↓
Mother is sensitized
↓
Formation of Anti D antibodies in mother’s circulation
↓
These antibodies can cross the placenta in subsequent pregnancies
↓
Hemolysis of fetal RBCs
↓
Hemolytic disease of the new born (erythroblastosis fetalis)
• At first IgM antibodies which are pentamers are formed, they cannot cross placenta
• Secondly IgG antibodies which are dimeric are formed, so they can cross the placenta in subsequent
pregnancies
• Rhogam is administered within 72 hours after delivery, it consist of synthetic anti D antibodies, prevent
sensitization of mother to D antigen
Complications
o Death,
o severe anaemia
o jaundice
o oedema(hydrops fetalis)
o Kernicterus = destruction of neuronal cells due to deposition of bilirubin (as fetal blood brain barrier is
still underdeveloped and may be permeable to certain substances

White Blood Cells
Neutrophils
• Highly Motile • Granules containing powerful digestive
• Phagocytic enzymes
• Multi lobed nucleus
Action of Neutrophils
• Chemotaxis -Attracting to infected areas
• Adhesion - Adhering to vessel walls
• Diapedesis - Squeezing through the spaces in endothelial lining
• Opsonization - Coating of material to be phagocytosed, is done by antibodies
• Phagocytosis - Ingestion of bacteria by endocytosis
• Degranulation -Releasing of granular contents
• Production of toxic oxygen metabolites
First line of defense against bacterial infections
NADPH + H+ + 2 O2 Cl- , Br- , H2O2
NADPH
Oxidase Myeloperoxidase
NADP+ 2H+ Free

oxygen radicals {2 O°−
2 } HOCl , HOBr
Superoxide
Dismutase
H 2O 2 + O 2
Neutrophils secrete
• Metalloprotinases Facilitate the movements of other
• Elastase neutrophils by digesting collagen in the ECM
• Defensins - Antimicrobial peptide
• Thrombaxanes - Vasoconstriction
• Leukotrines - Increases vascular permeability and attraction of other
neutrophils
• Prostaglandins - Inflammatory mediator
• PAF - platelet aggregation
• Lactoferrin -Binds to iron required for bacterial growth
•
Eosinophils Basophils Monocytes Lymphocytes
• Chronic • Receptors for IgE • Largest WBC • Smallest WBC
hypersensitivity • Immediate type of • Tissue macrophages • In Viral infections ↑
reaction Hypersensitivity (after 72 hours in • T&B
• Allergies ↑ • Release histamine, circulation) • Secretory T
• Parasitic Infections ↑ heparin when • Activated by lymphokines lymphocytes
• Abundant in mucosa activated by • Antigen presenting cells
• Actively Motile Histamine releasing • destruction of cell debris
• Release factor • Secrete IL, TNF and clot
Inflammatory agents promoting factors
WBC in order of abundance in health- Neutrophils>Lymphocytes>Monocytes>Eosinophils>Basophils
• WBC count, Differential count, Absolute count
• leucopenia, leukocytosis, –Decrease, increase in no. of WBC
• leukemia- increase in no. of abnormal WBC in blood
• Pancytopenia, - Decrease of RBC,WBC and platelet count
• Bicytopenia- decrease in any two of above
Ability to resist almost all
Immunity types of organisms or toxins
that tend to damage tissues
and organs
Acquired
Innate
1. Phagocytosis- WBC, tissue

macrophage Humoral Cell mediated
2. Acid & enzymes in GIT • Antibody mediated • Involves T lymphocytes,
3. Skin • Involves B antigen presenting cells
4. Blood- lysozyme ,basic polypeptides lymphocytes, plasma and MHC (major
Complement complex cells and antibodies histocompatibility
Natural killer lymphocytes complex) molecules
5. Sneezing, coughing reflex
Innate immunity Acquired immunity

Non specific Specific to antigen
First response Second response
Immediate Delayed
Cell structure is not modified (no memory) Memory acquired, so ability to produce
accelerated response to the second infection
Persist for a long time
Immune tolerance – deactivation of lymphocyte
precursors that react to self-antigens
Clonal section – stimulate division of effector
cells that respond to particular antigen
Complement system
• Plasma proteins
• Bridge between innate and acquired immune systems
• 3 pathways to activate
o Classic pathway – activated by immune complexes
o Mannose binding lectin pathway – triggered when lectin binds to mannose groups in
bacteria
o Alternative pathway – triggered by contact with virus, bacteria, fungi and tumor cells
Acquired immunity pathway

MHC (major histocompatibility complex)
• Glycoproteins
• Present on the surface of the cells
o MHC I – All nucleated cells
o MHC II – Macrophages, dendritic cells and natural killer cells
Antigen (pathogen)
Invaded by macrophages, dendritic cells, natural killer cells and other nucleated cells
Polypeptide products of antigens are digested and coupled to MHC
MHC I APC (antigen presenting cell) MHC II APC
Present it to CD8 of cytotoxic T cells Present it to CD4 of T helper cells
Secrete cytokines
that activate other lymphocytes
Suppressor T cells
Memory T cells
Cytotoxic T cells
Directly destroy the B cell
cells containing the
Memory B cells Plasma cells
antigen (virus, fungi,
tubercle bacillus) by Important in Produce antibodies
initiating apoptosis secondary infection
(programmed cell
Antibodies
death)
Agglutination Complement system

activation (classic
Precipitation pathway)
Neutralization of protein toxin
Lysis by enzymes
Functions of Complements
• Opsonization and facilitate phagocytosis (acts over bacteria to make them tasty)
• Chemotaxis (attract neutrophils to infected areas)
• Lyses of the cells (destruction of the cells)
• Activation of B lymphocytes
Immunoglobulin
• Ig G = Monomer; complement activation, can cross placenta
• Ig A = localized protection in external secretion , Monomer/Dimer/Trimer
• Ig M = Complement activation, can't cross placenta, Pentamer
• Ig D = Antigen recognition by B cells, Monomer
• Ig E = Binds to basophiles & mast cells, Monomer
Active Immunity - Person's own body develops either antibodies or activated T cells in
response to invasion of the body by a foreign antigen
Passive Immunity - By infusing antibodies, activated T cells or both, obtained from the blood
of someone else or from some other animal that has been actively
immunized against the antigen
Immune Tolerance - process by which the immune system does not attack an antigen.
Auto Immunity - the failure of an organism in recognizing its own constituent parts as self, which,
allows an immune response against its own cells and tissues.
Primary Immune response : Slow, Lower level, shorter duration, IgM Main type
Secondary Immune Response : Rapid, Potent, Longer duration, IgG main type
Electron dense Platelet

Platelets granules Membrane
Ca, ADP, ATPm Binding sites for

• Small Granulated bodies collagen,
Serotonin(5- HT)
• No Nuclei fibrinogen VWF,
• 2-4 µm in diameter ADP
Cytoplasm
• Life span 7-10 days α Granules
• 60-75% in circulation, others in spleen Lysosomes-hydrolytic
enzymes PDGF
• 150-400 x 109 per liter Peroxisome -catalase β thromboglobulin,
Actin , myosin heparin antagonist
thrombosthenin fibrinogen clotting factors
VWF
 Thrombocytopenia - Decrease in platelet count above normal eg: HIV AIDS, dengue
 Thrombocytosis - Increase in platelet count above normal eg: splenectomy, bone marrow cancer
Von WILLEBRAND Factor (VWF)
• Forms adhesive bridges between endothelial cells and platelets as well as in between platelets
• Extends the half-life of factor VIII (factor VIII regulation)
Haemostasis
 A balance between procoagulants and anti-coagulants
Injury to a vessel
Anticoagulants
Bleeding
Breakdown the clot once the
damage is repaired
procoagulants
Prevent intravascular
Formation of clot
coagulation or Thrombus
formation (thrombosis)
Stop bleeding

Vessel injury
Vasoconstriction Exposure of collagen Tissue

thromboplastin
Vascular response
Clotting response
Platelet response
(Formation of a
(Formation of a definitive clot)
temporary clot)
Vascular response
Obliteration of lumen of the damaged blood vessel Stop bleeding
• Nervous reflexes - pain

• Local humoral factors - 5 HT, thromboxane A2
• Local myogenic contractions of blood vessel
Platelet Response Vessel injury
Collagen & endothelial

cells exposed
VWF needed
Platelet adhesion
Intraplatelet Ca2+ ↑
-Change shape
Platelet Activation -Put out pseudopodia
Discharge granular
Platelet release
contents
reaction
Neutrophils
Monocytes PAF, ADP, Thromboxane A2
Platelets
Platelet aggregation
Platelet Plug
• Aspirin is a non-selective irreversible inhibitor of Cyclooxygenase enzyme.
Clotting response
Loose aggregation of platelets Definitive clot

in the temporary plug
Clotting response
01. Formation of activated factor X (Xa) Intrinsic &
Extrinsic pathways
[Rate limiting step in the clotting process]
02. Conversion of Prothrombin to Thrombin
03. Conversion of Fibrinogen To Fibrin [ fundamental reaction in the clotting of blood ]

Intrinsic pathway
Exposure of blood to collagen fibers underlying endothelium – in vivo

[Exposure of blood to electronegatively charged water wettable surface e.g. glass – in vitro]
(High molecular weight Kininogen)
(Platelet Phospholipids)
Extrinsic Pathway
Xa
Common Pathway
Prothrombin (IIa)
(II)
Once blood clot has formed, (Ia)

clot retraction occurs (I)
expelling most of the fluid
(serum) in it.
Formation of fibrous tissue - if the clot is too small OR Dissolution of the clot - if the clot is too large
Anti-clotting mechanisms
In order to prevent clotting inside the blood vessels and to break down any clots formed
1. Endothelial surface factors

- Smoothness of endothelium
- Glycocalyx layer- repels clotting factors and platelets
- Thrombomodulin-thrombin binding protein
Thrombomodulin-thrombin complex
Protein C Activated protein C

- Thrombomodulin-thrombin complex isn’t present in the cerebral microcirculation
2. Antithrombin III (circulating protease inhibitor)

Antithrombin III Binds to thrombin
This binding is facilitated by Heparin.
Heparin-Antithrombin III complex inhibits Factors IXa, Xa, XIa, XIIa
3. Tissue Factor pathway inhibitor

4. Interaction between TXA2 & Prostacyclin
5. Fibrinolytic system (Plasminogen System)
Plasminogen plasmin
t-PA, u-PA

Streptokinase -bacterial enzyme -fibrinolytic
Fibrinolytic agents
Streptokinase & Human recombinant t-PA are used in treatment of myocardial infarction
Streptokinase cannot cross blood brain barrier, so recombinant t-PA is given in stroke medication
Anti-coagulants
A. In vivo
1. Heparin -Facilitates the action of antithrombin ш
2. Coumarin derivatives -dicoumarol, warfarin
Inhibit the action of Vitamin K , vitamin K is necessary for the production of Factors II
(Prothrombin), VII, IX and X, protein C and protein S
Glutamic acid residues γ-Carboxy-glutamic acid residues

Cofactor – Vit K
B. In Vitro
1. Heparin
2. Oxalate - E.g.-Na Oxalate, K Oxalate
From insoluble salts with Ca2+
3. Citrates -E.g.- Na Citrate ACD CPD

4. EDTA - Chelating agent- bind Ca 2+
Abnormalities of hemostasis
1. Vessel wall abnormalities

2. Platelet disorders - platelet number & quality
3. VIII deficiency - Hemophilia A(classic hemophilia)
4. IX deficiency -Hemophilia B(Christmas disease)
5. Congenital deficiency of VWF
6. Liver disease - production of clotting factors is decreased
Clearance of plasminogen activator is reduced
7. Bile duct obstruction - Vit K absorption is reduced

8. Excess of clot formation & excessive activation of the fibrinolytic system- DIC (Disseminated
intravascular congestion) – in infections, extensive tissue injury
9. Renal failure
Test for Haemostasis
1. Bleeding time test - for vascular response & platelet response

2. Platelet count
3. Hess Test - for vascular integrity (capillary integrity)
4. Prothrombin time test - For extrinsic pathway and common pathway of clotting
5. Whole blood clotting time test- for intrinsic pathway and common pathway of clotting
6. Activated Partial Thromboplastin Time Test(APTT) -For Intrinsic+common pathway of clotting

GIT
1.0) Mouth
1.1) Saliva - Composition
A. Water
Lingual lipase # FA + 1,2 DAG #glands of the tongue
B. Enzyme # Active in stomach
# can digest up to 30% of dietary TAG
Salivary α amylase (optimal pH 6.7) #salivary glands
Function stops in the stomach
C. Mucin – lubricates food, protect oral mucosa

D. Immunological factors - IgA --- defense against bacteria and virus
Lysozyme --- destroy bacterial cell wall
Lactoferrin --- bind Fe (bacteriostatic)
Proline rich proteins --- Bind toxic tannins
Protect enamel
Salivary glands
E. Blood group antigens (only ABO)
Parotid 20%
Gland to gland
Submandibular 70%
F. Inorganic ions Vary from
Sublingual 5%
Rest/active period
*1500ml per day

1.2) Salivary secretion
When active Parotid
Active Rest
K+, HCO3- NaCl, H2O is highest
Never become Rate ↑ Rate ↓
Tonicity ↑ Tonicity ↓
Iso/hypertonic Iso. Hypo.
NaCl ↑ NaCl ↓
K+ ↓ K+ ↑
pH ↓ pH ↑
**Aldosterone increases K+ and decreases Na+ in
1.3) Control of salivary secretion
Conditional
• Sight, smell & thought of food.
Reflex • Food in mouth
Secretion
• Vagal afferents from gastric end of
Neural control esophagus
Sympathetic Parasympathetic
(VII, IX cranial nerves)
vasoconstriction Vasodilatation
↓ amount ↑ amount
↑ organic ↓ organic

1.4) Problems related to impaired salivary secretion
(1) Dry mouth

(2) Difficulty in swallowing
(3) Bad smell (Halitosis)
(4) Dental caries
(5) Speech difficulty
2.0) Oesophagus
Two sphincters
1. upper - less functionally important (normally closed by continuous contraction)
2. lower – tonically active, made of
Prevent regurgitation (heart burn, strictures) 1.Oesophageal smooth muscles
2.Crural fibers of the diaphragm
Tone -↑ Ach, ↓ NO, VIP
3.Oblique part of stomach
Clinically impaired in,

• GERD
• NG tube insertion
• Achalasia – LES is always tight
2.1) Swallowing
• Is a reflex
Stimulus Food in the mouth 3 phases

1.oral
Receptors Pharyngeal receptors 2.pharyngeal
3.oesophageal
Afferents Vth, IXth, Xth cranial nerves
Centre NTS/ NA
Efferents Vth, VIIth,IXth,Xth, XIIth cranial nerves.
Effectors Pharyngeal muscles, tongue.
Effect Swallowing
Act of swallowing
Voluntary collection of food on the tongue and pushing then back on the pharynx
Involuntary contraction of pharyngeal muscles, pushes food in to oesophagus
Inhibition of respiration and glottis closure
Relaxation of UES
Peristalsis
Relaxation of LES
Food in the stomach

2.2) Peristalsis
• A reflex which is initiated when gut wall is stretched by the contents of the lumen.
• Occurs in all parts of GI tract.
• Independent of extrinsic innervation but can be regulated.
• Peristalsis does not stop if a part of gut is removed and resutured in its original
In front of,
position, but will stop if it is reversed and resutured.
Stimulus 6. Relax smooth muscles ahead
,
Behind, 1. Local stretch due to the pressure of a food bolus of the bolus
9. Contraction of smooth
muscles behind the bolus
5. Activate neurons to .
release NO, VIP
8. Activates neurons to release

substance P and Acetylcholine
4. Cholinergic neurons passing in
an anterograde direction
7. Cholinergic neuron 2. Release serotonin
in retrograde direction
3. Activates sensory neuron which activate the

myenteric plexus
10. This results in the bolus to move in oral to caudal direction.
3.0) Stomach
Functions
• Storage of food
HCl: - Parietal cells
• Digestive function Pepsinogen: - chief cells
Gastric lipase: - chief cells
Mixing
Gastric mucosal barrier

• Protective function HCl
Histamine: - ECL cells
• Controlled release of food into duodenum

• Production of Intrinsic Factor: - Parietal cells
Hormones (Motilin/Glucagon)
• Absorptive Ethanol / water

3.1) Gastric secretion Pepsinogen 1→in high [HCl]
Gastric secretions – 2.5 L per day
HCl
Chief cells Pepsinogen 1 & 2 Pepsin
Proteins and Small peptides
large peptides
Gastric lipase
TAG FA + Glycerol
Parietal cells Intrinsic factor (a glycoprotein)

Intrinsic factor + cyanocobalamin (vitamin B12) (binding occurs at SI)
Ileal receptors
Absorbed by endocytosis
HCL Aids protein digestion

Makes the necessary pH for the action of pepsin to start protein
digestion
Kills ingested bacteria
Stimulate the flow of bile & pancreatic juice
3.2) Mechanism of secretion
Postprandial Alkaline Tide

Increase HCl secreted after a meal
Increase HCO3- absorbed to blood
Alkaline urine
On stimulation tubovesicular structure with H+/K+ ATPase molecules in the walls move to apical membrane
and fuse with it.
Increase surface area to H+/K+ exchange

3.3) Regulation of HCl secretion Stimulated by
1. Cephalic –
• Food in mouth, sight/ smell/ thought of food
Inhibited by
• Stimulation of hypothalamus/ frontal cortex
• Emotional responses – anger/hostility increase
 Fear/ depression decrease
• 1/3 – ½ of acid secretion in response to a normal meal in
this phase
• Due to vagal outflow →causes ↑ of
M3 receptors
Ach and GRP
 Activation of one receptor type

potentiates the response of another for H2 receptors Gastrin
stimulation synergistic action Receptors CCK-B
2. Gastric – a local reflex arc
Stimulus: -
- Stretch
Gastrin↑ - Products of digestion Receptors in stomach wall
- Amino acids & ↑pH
Meissner’s plexus From vagus

(Intrinsic innervation) (Extrinsic innervation)
Parietal cells
Acid secretion
3. Intestinal
Neural effects Gastric acid and pepsin
Fats, carbohydrates and Hormonal effects (somatostatin,GIP,VIP) secretion
acids in duodenum
Gastric motility
Others - Stimulants
Hypoglycemia – acts via brain and vagal afferents
Alcohol – acts directly on the mucosa
Caffeine – Stimulate CCK / gastrin
Mucus
• Forms a flexible gel coating the mucosa • Secretion stimulated by prostaglandins
• Made up of glycoproteins(mucins) • Function – “Gastric mucosal barrier”
• Secreted by neck and surface mucosal cells

3.4) Gastric mucosal barrier
A. Surface mucous layer -fast turnover of cells
-thick B. Mucous cells C. Trefoil peptides
-Trapped HCO3- -surface membrane -acid resistant
- finger like -tight junctions
channels for HCl between cells
#Disrupted by
-ethanol NSAIDS Inhibits cyclooxygenase
-Vinegar
Prostaglandin secretion is inhibited
-Bile salts
-NSAIDS-e.g.-Aspirin
Mucus secretion↓ Acid secretion ↑
-Helicobacter pylori infections
3.5) Gastric motility & emptying
1. Food enters the stomach

2. Fundus & upper part of body relaxes (receptive relaxation)
-vagally mediated
-trigger by movement of pharynx and oesophagus
3. Peristalsis in the lower part
-Controlled by BER
-sweeps towards pylorus
4. Mixing & grinding of food
5. Gastric emptying
-Antrum, pylorus, upper part of the duodenum function as one unit
-contraction of pylorus persists slightly longer than that of duodenum, preventing regurgitation
Clinical implications
Gastric by-pass surgery
 Effects: -
o Hyperinsulinemia and consequent hypoglycemia
o Diarrhoea
o Inability to digest protein
o Transient hypovolemia
o Inadequate food intake
o Malabsorption of nutrients
4.0) Liver
4.1) Functions
1. Carbohydrate, protein and Lipid metabolism
2. Inactivation of substances (toxins, ammonia, steroids and other hormones)
3. Storage (blood, vitamins A, D, B12, iron)
4. Synthesis of Plasma proteins (clotting factors, binding proteins, albumin)
5. Immunity (Kupffer cells)
6. Formation and secretion of Bile
4.2) Liver Enzymes Within hepatocytes

• Cytochrome P450 – metabolize many
substances
• ALT / AST: - ↑ in hepatocellular damage
Within cells lining the bile ducts

• ALP: - ↑ in bile duct obstruction
• γ-glutamyl transferase: - ↑ in bile duct obstruction
Induction of hepatic metabolic enzymes
4.3) Bile
Synthesized in the liver and concentrated and acidified in the gall bladder
Composition- water, inorganic salts, bile salts and pigments, Cholesterol, Fatty acids, Lecithin, fat,
ALP mainly HC03 −
Functions – Emulsification, assisting in lipid absorption
Cholesterol and ALP excreted in bile.
4.4) Bilirubin Metabolism
RBC Hb Hb
Haem Globin
Porphyrin Fe2+
Biliverdin
Biliverdin reductase
CIRCULATION Bilirubin
Bilirubin + Albumin
**Pre hepatic
UPTAKE
Bilirubin+ 2UDPGA **Hepatocellular
CONJU.
Glucuronyl Transferase
Bilirubin Diglucuronide [BDG]
EXCRETION
Rate limiting step EHC
Excreted in Bile **Post hepatic
BDG Urobilinogen
Faecal excretion

Unconjugated bilirubin (Indirect) Conjugated bilirubin (Direct)
Poor water solubility More water soluble
Not excreted in urine Excreted in Urine
High lipid affinity Low lipid affinity
High albumin binding Low albumin binding
4.5) JAUNDICE(Icterus)
When total plasma bilirubin (free and conjugated bilirubin) level is greater than 2mg/dL or 34µmol/L it is
known as Jaundice.
Yellowish tint to the body tissues (skin, sclera, deep tissues)
Classification of Jaundice
Prehepatic Hepatocellular Post-hepatic
excess production of bilirubin • decreased uptake of bilirubin extrahepatic bile duct obstruction
into hepatic cells
• disturbed intracellular protein
binding or conjugation
• disturbed secretion of
conjugated bilirubin into bile
canaliculi.
• intrahepatic bile duct
obstruction
unconjugated bilirubin conjugated or unconjugated conjugated bilirubin
bilirubin
hemolytic anemia cirrhosis bile duct obstruction (cholestasis)
4.6) Bile Salts

• Synthesis and Circulation
Cholesterol HEPATOCYTE
↓
Iry bile acids (0.2 g/d)
↓conj: with glycine and taurine
Glychocholic/Taurocholic acid
↓ Na/K
Bile salts (3.5 g/d)
↓ At the terminal ileum 90% - 95% reabsorbed by

Excreted in bile Na+ - bile salt cotransporter via enterohepatic
circulation
Secondary bile salts are produced by action of bacteria on Iry bile salts in the colon.
4.7) Functions of Gall Bladder

1. Reservoir for bile
2. Concentration of bile
3. Acidification of bile
4. Release of stored bile-mediated by CCK

4.8) Regulation of Biliary Secretion
1. Hormones- Secretin -↑production of HCO3- rich watery bile
CCK - causes contraction of gall bladder
2. Autonomic Nerves- Vagal stimulation-↑production of bile
3. Bile salts *most important physiological stimulus
Choleretics - Substances that increase secretion of bile
-Vagus nerve stimulation
-Secretin
-Bile salts
Cholagogues – Substances that cause gall bladder contraction
-CCK
- Ach
4.9) Gall stones

1. Pigmented stone
2. Causes: -
• Due to increased hemolysis increased bile pigments
• Disturbance of cholesterol: FA: lecithin
5.0) Pancreas
5.1) Pancreatic juice
• ↑ Duodenal pH to 6-7
• Secreted by exocrine pancreas (compound alveolar gland)
• Composition - Na, K, Ca, Mg, HCO3, Cl, SO4, HPO4, proteins
• Enzymes- Proteins (Trypsin, Chymotrypsin, Elastase, Carboxypeptidase A & B)
Fat- (Colipase, Pancreatic lipase, Cholesterol ester hydrolase)
Starch - (pancreatic α amylase)
Nucleic acid - (Ribonuclease, Deoxyribonuclease)
Phospholipids - (Phospholipase A2)
Protein in lumen
⊕
Pro enzyme Enzyme

Trypsin inhibitor
Trypsinogen Enteropeptidase Trypsin ○-

Chymotrypsinogen Chymotrypsin
Proelastase Elastase
Procarboxypeptidase Carboxypeptidase
Procolipase Colipase
Prophospholipase A2 Phospholipase A2
5.2) Pancreatic secretion regulation
Watery secretion of alkaline juice,

Secretin Pancreatic duct cells cAMP↑
↑in HCO3, ↓ in Enzymes
Hormonal
CCK Acinar Cells Phospholipase C Juice rich in enzymes
Vagus Ach
9 Neural © 2015 A/L Repeat Campaign

6.0) Small Intestine
• Adaptations for absorption
1. ↑ Surface area – valvular connivantes, villi, microvilli

2. ↑ Contact time of products of digestion – segmentation contraction, tonic contraction
• Intestinal secretion
Isotonic fluid
3L/d p, H=7.8-8
Enzyme ↑ stimulated by hormones e.g.: - VIP
Contents – water & mineral salts, digestive enzymes, mucus
Digestion done in lumen, brush border, intracytoplasmic

Enzymes • Enteropeptidase
• Amino/Carboxy/Di peptidase
• Maltase/Lactase/Sucrase
• Α-dextrinase/Nuclease
6.1) Carbohydrate absorption
Luminal Enterocyte Basolateral
3Na+
2Na +
SGLT 1 & 2 2K+
Glucose
GLUT 2
Glucose
Fructose GLUT 5
Pentose
Simple Diffusion
6.2) Amino acid absorption
• ↑absorption in duodenum and jejunum
• Na+/AA Co transporter
AA
• Na+ independent transport
• H+/di or tri peptide co transport (hydrolysis release AA in muscle cells)
• Clinical implications
• Congenital transport system Hartnup’s disease: - neutral AA Absorption
defects Cystinuria: - Basic AA impaired
• Infants IgA in colostrum

• Food allergy absorb small quantities of proteins / small peptides

6.3) Fat absorption
Finally emulsified in SI
(Detergent action of bile salts, lecithin, monoglycerides)
Bile salt concentration
Spontaneously aggregate in to micelles
Take up lipids
Move down concentration gradient to unstirred layer of brush border
Lipids diffuse out of micelles
Enter Enterocyte
FA > 10 - 12 C & Re-esterified Tri Glycerides Chylomicrons

Cholesterol
Fat & cholesterol
Lacteals
FA < 10 - 12 C
Actively transported in to capillaries Lymph
Free fatty acids
Long Chain Fatty Acids Mostly absorbed in upper S.I
• Steatorrhea Fatty
Bulky
Clay coloured
Stools Pale
Foul smelling
Greasy
Hard to flush
Lipase deficiency Chronic liver ↓ Alkaline secretion from

disease pancreas
Acidity
Fat ↑ Gastric Acid
Bile duct
Malabsorption
obstruction
Defective reabsorption of
bile salts in distal ileum
Pancreatic disease

Fat soluble A, D, E, K (“kade”)
Vitamins Mostly absorbed in upper SI
Others - Na dependent
Water Soluble B12,
Na independent Terminal ileum
Folate
Fe2+
Gastric acid and ascorbic acid
Fe3+ Fe2+
Fe2+ via DMT1 in duodenum
Ca2+
30 – 80 % active transported facilitated by Vit. D
Water – mainly (98%) in small intestine.
Small Intestine Colon

Absorption of
Upper Middle Lower
Sugars ++ +++ ++ 0
AA ++ +++ ++ 0
LCFA +++ ++ + 0
Bile salts + + +++ −
Vitamin B12 0 + +++ 0
Other vitamins +++ ++ 0 0
Na +
+++ ++ +++ +++
K+ + + + secrete
6.4) Protective function
Mucus
Solitary
Protection Lymph
Aggregated (Payer’s patches)
Defensins Paneth cells
Fat mal
absorption Fat malabsorption
Vit B12 Protein

deficiency deficiency
Resection Resection
or disease Vit A, D, E, K or disease
of ileum of upper SI Vit A, D, E, K
Diarrhea Ca2+
Ca2+ PT
PT

6.5) Motility of Small Intestine
• MMC
• Peristaltic waves
• Segmentation contraction
o Ring like contractions which appear at regular intervals, which are replaced by another set of
contractions in the segments between the previous contractions
• Tonic contraction
o Relatively prolonged contractions that in effect isolate one segment from another
7.0) Large Intestine

7.1) Functions K+, HCO31-
1. Absorption of water (1 – 2 L) and electrolytes
Na+, Cl-, H2O
2. Formation and excretion of faeces
Water 75% Solids 25% Cellulose Bacteria (30%) Desquamated mucosal cells/mucus
Non-dietary in origin (unaffected by diet & starvation)
3. Microbial activity LI colonized in early life.

Effects of intestinal bacteria But sterile at birth
Harmful effects to Host (Pathogen) Beneficial effects to host No effect to host (commensals)
(Symbiont)
1. Utilization of nutritionally important 1. Synthesis of useful 1. Deconjugation of bile

substances. substances. pigments
Ex: Vit B12 Ex: Vit. K / B complex
Folic acid, SCFA
2. Cause UTI/ septicaemia 2. Anti-inflammatory effects 2. Odour
By E. coli Ex: probiotics
3. Synthesis of potentially toxic amines. 3. Digestion of cellulose in 3. Production of some gases in

Ex: Histamine, Tyramine herbivores flatus
4. Conversion of AA NH3
• Harmful in liver disease
• Associated with hepatic
encephalopathy
Vit B12 ↓ Macrocytic anaemia

Vit ADEK ↓
Overgrowth of bacteria
Steatorrhoea Ca2+↓
E.g. blind 100p Unconjugated
syndrome PT ↑
bile salts Irritates
Colon Diarrhea

• Gastroileal reflex
Food leaving stomach Relaxation of caecum Passage of chyme through ileocaecal valve
• Ileocaecal valve
Usually closed. Opens when ileal pressure ↑ & closes when colonic pressure ↑
7.2) Movements of colon
• Peristalsis • Segmentation contraction

• Mass action contraction
o Only in colon. Simultaneous contraction of smooth muscle over a large confluent area.
8.0) Defecation
Spinal reflex which can be modified voluntarily.
In infants no voluntary control
Resting
• rectum empty
• External anal sphincter in a state of tonic contraction
• Internal anal sphincter tone - ↑ by sympathetic stimulation
↓ by parasympathetic stimulation
Distension of rectum with faeces
Increased rectal pressure (18mmHg)
Reflex relaxation of internal anal sphincter
Reflex contraction of external anal sphincter
Urge to defecate
Inappropriate Appropriate
Urge temporarily subsided External sphincter voluntarily open
Sphincter tone becomes normal Ab. Contraction + diaphragm
Voluntary defecation Intra-abdominal pressure increased

Straining Rectal pressure up to 55mmHg
Contracts abdominal muscles Evacuation
Increased intra ab. Pressure

Gastrocolic Reflex
Pelvic floor lowered
Distension of stomach with food
Puborectalis relaxed ↓
Decreased anorectal angle Contraction of rectum (due to gastrin on colon, not neural)
↓
Relaxation of ext. sphincter Desire to defecate
Defecation
Constipation
• ↓ Water
• ↓ Fiber  70% of undigested food → 72 hours
• ↓ Colon motility  100% recovery → 1 week
• ↑ Ca2+
• ↑ Sympathetic action
• ↓ Parasympathetic action
• Intestinal obstruction
9.0) Motility of GIT
Peristalsis Oesophagus to rectum A reflex response to stretch

BER All part of the GIT except Spontaneous rhythmic fluctuations in RMP
oesophagus and proximal of GIT smooth muscles
part of the stomach
MMC Stomach to distal ileum Cycles of motor activity during fasting
period
Segmentation Small intestine Ring like contractions appear at regular
contraction Large intestine intervals, then disappear and replaced by an
another between previous two
Tonic contractions Small intestine Prolonged contraction of isolated segments
at a time
Mass action Large intestine Simultaneous contraction of smooth muscles
contraction over a large confluent area
10.0) Vomiting
3 phases Vomiting reflex
1) Nausea – hypersalivation/ pallor/ Salivation and sensation of nausea

sweating
2) Retching – strong involuntary effort
Reverse peristalsis
to vomit
3) Vomiting – expulsion of gastric (Upper part of SI to stomach)
contents through mouth
Glottis closure
Breath held in mid inspiration
Contraction of abdominal muscles. (Increase intra-abdominal pressure)
Relaxation of LES & then UES
Reverse peristalsis
Ejecting gastric content

Stimulation of vomiting
11.0) GI regulatory mechanisms

Hormonal act in paracrine fashion, also enters blood stream
Regulation
Extrinsic
Neural
Intrinsic (enteric nervous system)
CNS Sympathetic Enteric nervous system

/parasym.
GI function
Intestinal smooth muscles
Sympathetic post ganglionic fibers End on blood vessels (vasoconstriction)

(Noradrenergic neurons)
Cholinergic neurons
(Inhibit release of Ach)

Result in - constriction of sphincters
Reduced activity of smooth muscles
Parasympathetic pre-ganglionic fibers end on cholinergic nerve cells in

(Post ganglionic parasympathetic system)
Result in - relaxation of sphincters
Increased activity of smooth muscle
Intrinsic innervation
Myenteric/ Auerbach’s Submucous/ Meissner’s

plexus plexus
Circular and longitudinal Glandular epithelium

smooth muscle Intestinal endocrine cell
Submucosal blood vessels
Primarily motor Primarily secretomotor

Hormonal regulation
Gastrin family Gastrin
CCK
Secretin family Secretin
VIP
GIP
Others
Hormone Produced Increased by Action Decreased by
by
Gastrin G cells in Luminal • ↑Acid secretion Luminal
gastric Peptides, AA. • ↑ Pepsin secretion Acid
antral cells distension • ↑ Insulin after protein meal Somatostatin
Neural • ↑ Motility
↑ Vagal discharge via • Growth of stomach/ SI/ LI/ Blood borne
GRP Mucosa Calcitonin
Blood borne Glucagon
↑ [Ca2+] Secretin family
epinephrine
CCK- PZ I cells in • Inhibit gastric emptying, When chime moves down
upper SI • GB contraction from upper SI
• Pancreatic juice rich in

(CCK) FA > 10 C atoms in enzymes
duodenum • trophic action on pancreas
• augments action of
(PZ) Contact of products of secretion
digestion (peptides,
aa) with intestinal
mucosa

Secretin S cells in Products of protein • ↓Gastric acid secretion
mucosa of digestion • ↑Secretion of HCO-3 by
upper SI Acid bathing mucosa biliary tract and pancreas
of SI • ↑ Secretion of watery
pancreatic juice
• Augments action of CCK to
produce digestive enzymes
• Contraction of pyloric
sphincter
(CCK augments action • ↑ Insulin
of Secretin)
GIP K cells Glucose and fats in ↑ Insulin secretion

duodenal/ duodenum ↓ acid secretion
jejuna
Mucosa
VIP • marked stimulation of
(rem. secretion of electrolytes
VIPoma) and water
• relaxation of intestinal
smooth muscles (including
sphincters)
• dilation of blood vessels
• ↓ gastric acid secretion
(A) Volume of secretions of GI tract per day

o Salivary glands 1500ml
o Stomach 2500ml
o Bile 500ml
o Pancreas 1500ml
o Intestine 1000ml
(B) Hormones in GI tract

Hormone Action
(1) Motilin Contraction of intestinal smooth muscles.
(Stomach/SI/colon)
(2) Ghrelin (stomach) Central control of food intake
(3) Somatostatin ↓ secretion of gastrin, VIP, GIP, secretin and motilin
(Pancreas/GI mucosa)
(4) Peptide YY(Jejunum) Inhibits food intake ↓ acid secretion & motility
(C) Chemical digestion in GI tract
Site Enzyme Action

Mouth Lingual lipase (act in stomach) TG → FA + DAG
Salivary α-amylase Starch → α dextrins + maltose
Stomach Pepsinogen
HCl Proteins + Large peptides → small peptides
Pepsin
Gastric lipase TAG → FA + monoglycerides

Exocrine pancreas Trypsin Proteins + PP → Small PP
Chymotrypsin Proteins + PP → Small PP + AA
Carboxypeptidase Proteins + PP → Dipeptide + AA
Pancreatic α-amylase Starch → α dextrins + maltose
Pancreatic lipase TAG → FA + monoglycerides
Ribonuclease RNA → ribonucleotides
Deoxyribonuclease DNA → Deoxyribonucleotides
Phospholipase A2 Phospholipids → FA + lysophospholipids
Intestinal Mucosa Enteropeptidase Trypsinogen → Trypsin
Aminopeptidase Polypeptides → Dipeptide + AA
Carboxypeptidase PP → DP + AA
Dipeptidase DP → AA
Amylase Starch → maltose
Sucrase Sucrose →Glucose + Fructose
Maltase Maltose → Glucose
Lactase Lactose → Glucose + Galactose
Nucleotidase Nucleotide → Nucleoside + PO43−
Nucleoside → Nitrogenous bases + pentose
sugar
01. T/F regarding swallowing

a) Occurs without voluntary control.
b) Reflexly initiated.
c) May occur simultaneously with respiration.
d) LES relaxes upon swallowing.
e) Possible when the mouth is open.
02. T/F regarding peristalsis

a) It occurs independent of the extrinsic innervations of the GI tract.
b) The movement is generally in an oral to caudal direction.
c) NO is known to mediate the relaxation in front of a bolus of food.
d) Gastric peristalsis begins in the fundus of the stomach upon entry of food.
e) The basal electric rhythm (BER) coordinates peristalsis.
03. Regarding gastric acid secretion by parietal cells

a) H+ ions are pumped out of apical membrane via facilitated diffusion.
b) Acetylcholine stimulates nicotinic receptors on parietal cells.
c) Gastrin causes an increase in intracellular Ca2+ ions.
d) Gastrin secretion is increased by stimulating M2 receptors.
e) Gastrin is produced by cells in the small intestine.
04. Gastric emptying is stimulated by

a) Hyperosmolality in the duodenum
b) CCK
c) Distension of duodenum
d) Excitation
e) Vagotomy
05. Regarding gastric motility

a) BER coordinates peristalsis in the stomach.
b) Segmentation contractions are formed in the small intestine.
c) Peristalsis can be altered by extrinsic innervations.
d) Mass action contractions move chime from ileum to caecum.
e) Segmentation contractions allow the intestines to be cleared.
06. Choleretics are

a) Gastrin
b) CCK
c) Secretin
d) Bile salts
e) Alkaline phosphate
07. Serum direct bilirubin normal, serum indirect bilirubin increased. What may be the cause for this?
a) Chronic pancreatic disease
b) Obstruction of the bile canaliculi
c) Excessive haemolysis
d) Resection of terminal ileum
e) Increased gastric acid secretion
08. T/F regarding protein digestion & absorption.

a) Gastric secretion of HCl facilitates protein digestion in the stomach.
b) The action of small intestine is maximal in the upper small intestine.
c) Endopeptidase activates pepsinogen into pepsin.
d) Amino acid absorption is maximum in the ileum.
e) Protein absorption declines with age.
09. Steatorrhea is caused by

a) Pancreatic lipase deficiency.
b) Impaired production of intrinsic factor.
c) Resection of the ileum.
d) Obstruction of common bile duct.
e) Gastrectomy.
10. Which of the following hormones are correctly matched with their function?
a) GIP - Increasing insulin secretion
b) Secretin - gallbladder contraction
c) CCK - Increase secretion of pancreatic juice rich in enzymes.
d) Gastrin - Induces tropic changes in gastric mucosa.
e) VIP - Increases water absorption in the small intestine.

Excitable tissues
Functional components of a neurone

• A receptor zone – Dendrites or the cell body
• Cell body
• Generator of propagated impulse – Initial segment or the 1st node of Ranvier
• Pathway to transmit the impulse - axon
• Nerve endings to release the neurotransmitters – axon terminal
Glial cells
Microglia – Derived from macrophages
Macroglia
1. Oligodendrocytes – Forms myelin sheath in CNS
2. Schwann cells – forms myelin sheath in PNS
3. Astrocytes
Macroglia secrete nerve growth factors.
Multiple sclerosis – Myelin destruction in CNS

Guillain barre syndrome – Myelin destruction in PNS
Resting Membrane potential

• Membrane potential is the electrical potential energy difference between the inside and outside of a cell
• Resting membrane potential (RMP) is the membrane potential when not transmitting an impulse
• In neurons it’s value is usually -70 mV (inside the cell membrane compared to outside)
• The bulk solution inside and outside is electrically neutral
• The potential difference exists only across the cell membrane
• Main determinant of RMP is the movement of K+ through K+ leak channels
• Therefore, changes in extracellular [K+] have major effects on RMP
• Negativity inside is maintained by Na+/K+ ATPase pump
Ion concentrations when R.M.P
– An electrogenic pump
is -70 mV
– Inhibited by Ouabain and Digitalis
• At rest the membrane is impermeable to proteins Extra cellular Intra cellular
• Due to leak channels, the membrane is Na+ - 150 Na+ - 15
– Slightly permeable to Na+ K+ - 5.5 K+ - 150
– Highly permeable to K +
Cl- - 125 Cl- - 9
– Freely permeable to Cl -
• K+ diffuses “out” of the cell along it’s concentration gradient

• Na+ diffuses “in” to the cell along it’s concentration gradient
• If ion leakage across the membrane continues unopposed, it would proceed until concentration
gradients are balanced by the electrical gradient
• But, Na+/K+ ATPase pumps 3Na+ out & brings 2K+ in per turn
• This maintains the concentration gradients of K+ and Na+
• Therefore, the membrane potential is maintained at RMP

Electrical reposnses of nerve to a
stimuli
Propagated action Local, non-propagated

potential potential
Receptor potenial
End plate potential
Synaptic potential
• Changes in membrane potential that

reach the threshold level can be propagate along a nerve fibre
• Threshold is usually 15 to 20 mV above RMP (about -55 mV)
Action Potential
• Is generated in response to a stimulus
• Is a rapidly spreading changes in membrane potential
• Membrane needs to be depolarized to the firing level (-55mV) for its generation
• Self-propagating
• Nerve impulses are transmitted as action potentials.
Site of Generation of action potentials

• In spinal motor nerve  Initial segment
•
•
•
•
• In cutaneous sensory nerve  First node of Ranvier.
RMP Depolarization  Repolarization  HyperpolarizationRMP

RRP ARP-Absolute Refractory Period
←---ARP------→←---→
RRP-Relative Refractory Period
Depolarization
Hyperpolarization
-55
Ionic basis of an Action Potential

Depolarization
• Stimulus generates a graded potential in the nerve fibre
• Some voltage gated Na+ channels open.
• Na+ INFLUX
• Membrane potential rises to threshold level. (-55mV)
• More voltage gated Na+ channels open
• Rapid influx of Na+ makes the membrane potential more positive.
• Membrane potential overshoots zero potential.
• This is a positive feedback cycle
Repolarization
• Resistance for Na+ influx increases as membrane potential becomes more positive reversing the
electrical gradient for Na+.
• Voltage gated Na+ channels close 1/104 s after they open.
• Na+ INFLUX stops.
• When MP rises from -70mV to 0mV, voltage gated K+ channels open.
– They are slow to open and slow to close.
• Opening of K+ channels coincide with the closure of Na+ channels.
• Resulting K+ EFFLUX makes the membrane potential negative again.
Hyperpolarization
• K+ efflux lasts longer than needed to restore membrane potential to RMP.
• Therefore, the membrane is hyperpolarized.
• When K+ channels close, K+ EFFLUX stops.
• Membrane stops becoming more negative.
• RMP is restored. But large amount of Na+ remain within the cell & large amount of K+ has escaped out.
• Na+ / K+ ATPase corrects the ionic distribution.

Effects of ion concentration
ECF Increased Decreased
Na + RMP unchanged
RMP unchanged
Action potential (AP)amplitude
Amplitude decreased
increased
K+ RMP decreased (RMP closer to
RMP increased
threshold potential)
Ca2+ Excitability↓ (more Excitability↑ (less
depolarization required to depolarization required to
generate an action potential) generate an action potential)
How do changes in Ca2+ concentration affect the excitability?

________________________________________________
________________________________________________
________________________________________________
________________________________________________
All or None Principle

• Once the threshold potential is reached, a full-sized action potential is created.
• Further increase in intensity of the stimulus does not produce any changes in the amplitude of the AP.
• Subthreshold stimuli fail to produce an AP.
• Threshold &supra-threshold stimuli produce APs of constant amplitude.
Refractory Period of the membrane
Absolute Relative
• Time period from reaching the • Time period from the last 2/3 of
firing level to the first 1/3 of repolarization to the begining of
repolarizaiton after-depolarization
• Does not respond to any stimuli • Only suprathreshold stimuli can
evoke an AP
1. In a nerve cell
a) K+ efflux contributes to repolarization.
b) Initial rapid depolarization is due to opening of Na+ channels.
c) High Na+ concentration in ECF increases the magnitude of action potential.
d) Conductance of fibre type A is faster than type C.
e) Slightly higher cation concentration in the interstitial space affects the RMP of the cell.
2. Regarding myelinated nerve fibres,

a) A local response can be evoked by a subthreshold stimulus
b) Is refractory to stimuli during the spike potential
c) Spike potential has a refractory period
d) Is susceptible to conduction block by hypoxia
e) Susceptible to damage in hypoxia

Strength Duration Curve
• Strength-duration curves are drawn to test the nerve
function
• Graph is drawn with the duration of stimulus against
the strength of the stimulus
A - Rheobase – minimum strength to elicit response

B - Chronaxie – Duration of stimuli at twice rheobasic strength.
• Longer the time of application of the stimulus Smaller the required minimum strength of the stimulus
• Shorter the time of application of the stimulus Greater the required minimum strength of the stimulus
• Very slowly increasing current  No AP
o Slow opening of voltage gated Na+ channels and slow opening of voltage gated K+ channels
coincide. Na+ influx is balanced by K+ efflux.
Action Potential Propagation
• Active, self-propagating process

• Impulses move with constant magnitude (mV) (amplitude) & constant velocity (ms-1).
• Spreads away from a stimulus.
• An action potential creates a “current sink” (an area to which current, i.e. “positive” charges flow)
• Positive charges move in to the current sink, depolarizing the adjacent membrane to firing level.
• Therefore, action potentials are generated in the adjacent membrane.
• These too act as current sinks and the process repeats.
• Actions potentials are thus generated sequentially further and further away from the point of
application of the stimulus.
• APs that reaches a synapse from the wrong side (along a dendrite) dies out because synapses permit
conduction in one direction only.
Propagation along unmyelinated nerve fibre Propagation along myelinated nerve fibre
(Simple Conduction) (Saltatory Conduction)

Local Potentials
1. Receptor potential
2. End plate potential
3. Synaptic potential
3. Synaptic Potential
• Temporary, partial depolarization of post

EPSP synaptic membrane, due to
• Closure of K+ channels
(Excitatory Post • Opening of Na+ channels/Ca2+ channels
Synaptic Potential) • Acetylcholine, Glutamate produce EPSPs in
post synaptic membrane
• Hyperpolarization of post synaptic

membrane, due to
• Opening of Cl- channels
IPSP (Inhibitory Post • Opening of K+ channels
Synaptic Potential) • Closure of Na+ channels
• Closure of Ca2+ channels
• GABA & glycine produces IPSPs in
postsynaptic membrane
Nerve fibre types
1. Erlanger & Gasser classification

2. Numerical classification of sensory nerves
3. Relative susceptibility of A, B, C fibres to conduction block by various agents

Most Least
Susceptibility To: Susceptible Intermediate Susceptible
Hypoxia B A C
Pressure A B C
Local anesthetics C B A
Clinical relevance
• Demyelination – Conduction velocity is decreased
• Axonopathy – Reduction of amplitude. Later the velocity also reduced.
• Injury to nerves – PNS likely to regenerate, CNS mostly degenerated.
• Local anaesthesia – Block only the C fibres
Neutrophins
Nerve growth factor (NGF)
• Necessary for the growth & maintenance of sympathetic and other sensory neurons
• Reduce apoptosis of neurons
• Produced in structures innervated by them. Eg: muscles. In the CNS, produced by astrocytes
• Transported retrogradely to the nerve cell body
Synapse
Impulses transmitted from nerve cell to other cells
at synapses
Permit conduction of impulses in one direction only
Transmission in most synapses are chemical but in
few electrical

Junction between 2 excitable
cells • Voltage gated Ca2+ channels are found in the
active zone.
• When an AP reaches an axonal terminal, Ca2+
Nerve - Nerve diffuses in.
Nerve - Muscle
- Axodendritic • Triggers exocytosis of neurotransmitters into
the synaptic cleft.
- Axoaxonal
• Synaptic delay is usually 0.5 ms.
- Axosomatic • Synaptic transmission of Ach??
Events at synapses
1. Summation
Summation of
synaptic potentials
Spatial Temporal
Many presynaptic terminals are Successive discharges from a
stimulated at the same time. single presynaptic terminal, if
they occur rapidly enough, can
The depolarization induced at
add to one-another and
several points on the neuron
summate
spread to trigger zone before
decaying out and the potentials
summate to elicit an AP
2. Convergence 3. Divergence
e.g.: - Preganglionic & post ganglionic neurons in ANS
4. Inhibition
a. Presynaptic b. Postsynaptic
Inhibitory interneuron-GABA
Reduce transmitter release from the

excitatory neuron by,
Inhibitory interneuron-
1. Opening of K+ channels->K+ efflux
2. Increase in Cl- conductance GABA, Glycine etc.
Decrease the size of the AP reaching
the nerve ending
8 Reduce Ca2+ influx ©2015 A/L Repeat Campaign
Reduce neurotransmitter release
5. Facilitation
6. Negative feedback inhibition
Renshaw cell
Motor neuron
Tetanus (medical condition) – Tetanus toxin blocks the release of “inhibitory” neurotransmitters (glycine and
GABA) from presynaptic cells resulting in a marked increase in motor neuron activity in the CNS causing spastic
paralysis
Botulism – Botulinum toxin blocks acetylcholine release into the NMJ causing flaccid paralysis
Synaptic Plasticity
Changes in the function of synapses due to past experience
Basis of learning and memory
1. T/F
a) Decrease in ECF [K+] hyperpolarize the nerve axons
b) Chronaxie is a time measurement
c) Rheobase the minimum strength of a stimulus to initiate an action potential
d) A slight increase in extra cellular Na+ is enough to depolarize the membrane
e) Increased extra cellular Ca2+ increases the excitability of the nerve membrane
2. In a myelinated nerve fibre

a) Action potentials are mostly generated in axon hillock
b) Synaptic potentials are integrated in receptor zone
c) Node of Ranvier is rich in voltage gated Na+ channels
d) Conduction velocity progressively increases along the length
e) Local pressure around nerve fibres inhibit conduction of impulses
3. Factors that affect the velocity of conduction in nerves include

a) Diameter of the nerve.
b) Myelination of the nerve.
c) Compression of the nerve fibre.
d) Length of the nerve fibre.
e) Local anaesthetic infiltrated around the nerve.
4. Saltatory conduction
a) Occurs only in myelinated fibers.
b) Does not depend on depolarization of the nerve cell membrane.
c) Velocity decreases as the temperature increases.
e) Transmits impulses with a velocity proportionate to fiber diameter.
d) Produces a great voltage change in the membrane than in non-salutatory conduction.

Neuromuscular transmission
• Impulse arrives at the terminal bouton.

• Opening of voltage gated Ca2+ channels, permeability to Ca2+ is increased, Ca2+ influx.
• Triggers exocytosis of Acetylcholine (Ach) vesicles
• Ach. binds with muscle type nicotinic Ach. Receptors in the motor end plate (M.E.P)
• Opens a gate within the channel, equally permeable to Na+ and K+.
• Increased Na+ and K+ conductance & Na+ influx greater than K+ efflux as electrochemical gradient is ↑ for Na+
• Depolarization
• End plate potential - local graded potential
• Acts as a current sink
• Depolarizing adjacent muscle fibre (Rapid Na+ channels are not present in motor end plate)
• Firing level  action potential spreads in both directions into T tubules
• Initiates muscle contraction
(Removal of Ach. from the synaptic cleft is by Ach esterase)

Neostigmine is a competitive inhibitor of Ach. esterase.
Acetylcholine receptors
1. Muscarinic (M1-5)
• G-protein coupled receptor • Blocked by atropine
2. Nicotinic – NMJ and synapses

• NMJ and synapses both blocked by alpha bungarotoxin (found in snake venom)
• NMJ type blocked by curare and Synapses type blocked by hexamethonium
• ligand gated ion channel
Events at motor end plate at rest
• At rest continuous release of Ach occurs from the nerve terminal, this produces minute changes in polarity
of the MEP. These changes in voltage are called Miniature end-plate potentials.
• Important for the integrity of the muscle. Otherwise muscle wasting occurs.

Skeletal muscle
• Contractile unit of muscle fibre – sarcomere
• Heads of Myosin have Actin binding sites and ATP hydrolyzing sites
Troponin
• C – binds Ca2+
• T – binds to tropomyosin
• I – Inhibits actin-myosin interaction
Thin filament
• In contraction Z lines move closer. ‘A’ bands remain constant. All others get shorter.
• Functional unit of muscle – motor unit (=single motor neuron and all the muscle fibres innervated by it)
All the muscle fibers in one motor unit is innervated by one motor neuron.
Contraction of the skeletal muscles
• Discharge of motor neuron
• Release of acetylcholine at motor end plate
• Binding of acetylcholine to muscle type nicotinic cholinergic receptors
• Increased Na+ & K+ conduction at motor end plate
• Generation of end plate potential (local non-propagated)
• Generation of action potential in muscle fiber
• Inward spread of depolarization along T tubules
• Depolarization leads to conformational change in voltage sensitive dihydropyridine receptors opens
ryanodine Ca 2+ channels of terminal cistern- release of Ca2+ into cytoplasm
• Binding of Ca2+ to troponin C
• Conformational change exposes myosin binding sites of actin.
• Myosin binds to the newly uncovered binding sites on the thin filament (cross bridge formation)
• Upon formation of cross bridge ADP is released.
• This causes a conformational change in myosin head that moves the thin filament relative to the thick
filament, causing the “power stroke”.
• This will pull the Z-lines towards each other, thus shortening the sarcomere and the I-band.
• ATP quickly binds to free site on myosin, allowing it to release from actin and return to the weak binding
state.

• ATP is then hydrolyzed and the energy released is used to move into the "cocked back" conformation (“re-
cocking” of myosin head) completing the cycle.
• Steps mentioned above repeat as long as ATP is available and Ca2+ level remains elevated.
• Many myosin heads cycle at or near the same time, and they cycle repeatedly, producing gross muscle
contraction.
Relaxation
• Ca2+ pumped in to SR by Ca2+ - Mg2+ ATPase pump (this pump needs ATP, therefore ATP dependent
process)
• Release of Ca2+ from troponin C
• Interaction between actin-myosin stops
If Ca2+ transport into reticulum is inhibited, relaxation does not occur, resulting in sustained contraction called
contracture.
Terminal cistern
Dihydropyridine
Before receptor
2+
Ca
Ca2+
and Ryanodine Ca2 +
2+
Ca
channel
after
Ca2+ Mg 2+
depolarization Ca2
ATPase
Skeletal muscles - Rapid excitation and contraction coupling
Electrical response
Mechanical response-
Starts 2ms after the onset of depolarization
before repolarization is complete

Isotonic contraction Isometric contraction
Work = negative or positive Work = 0
Has a change in the fiber length No change in fiber length
Muscle twitch – a single action potential causes a brief contraction followed by relaxation
Summation of Contraction
a) Tetanus- when there are repeated stimulations with a high frequency, individual responses fuse into a single
contraction.
Twitch Summation Unfused incomplete tetanus Tetanus
b) Treppe (Staircase phenomenon) – Maximal stimuli given at a frequency just below the tetanizing frequency
Increase in tension develop in each twitch. After few contractions uniform tension per contraction is
developed (due to progressive increase in Ca2+ in the sarcoplasm)
Tension
Time
Length tension relationship Length of the

muscle at which
Resting length of muscle the active tension
fiber is maximal
In isometric contraction,
Tension α cross linkages between actin & myosin

Muscle fiber types
Type 1 Type 2
Other names Slow, oxidative, red Fast, glycolytic, white
Ca pumping at SR
+
Moderate High
Capillary content High Low
Myoglobin content High Low
Contraction Slow, posture maintaining Fast, skilled movements
Diameter Moderate High
Muscle atrophy
Fibrillation – Fine irregular contractions of individual fibres, cannot be seen by
Denervation
naked eye but observed by electromyography
Denervation hypersensitivity – due to increased sensitivity to circulating ACh
1. Regarding skeletal muscles

a) Tension that can be produced during contraction is maximal at resting length.
b) In treppe uniform strength per contraction can be produced.
c) Actin & myosin filaments shorten when muscle contracts.
d) Become more excitable as its RMP falls.
e) During isometric contraction length is constant.
2. In the neuromuscular junction of skeletal muscle,
a) Neurexin facilitates the close proximity of the pre & pro synaptic membrane
b) Exocytosis of Ca2+ is a passive process
c) Analogues of acetylcholine blocks the receptors of the synapse
d) Acetylcholine esterase is needed to terminate transmission of impulses
3. Skeletal muscle
a) Tone is due to voluntary contraction
b) Muscle fibres shorten when running
c) Is tetanized with rapid repeated stimulation
d) Doesn’t generate heat at rest
e) Fibres in short muscles of hand, myosin ATPase action is high
Cardiac muscle
0- Rapid depolarization
1- Initial rapid repolarization
2- Plateau phase
3- Late rapid repolarization
4- Basal level
Contraction starts 2msec after

onset of depolarization

This electrical response of cardiac muscle fibers prevents summation of the contractions.
Ionic fluxes
• Initial rapid depolarization and overshoot- Opening of Voltage gated Na+ channels
• Initial rapid repolarization - Closure of Na+ channels, opening of one type of K+ channels
•
Plateau – Slower prolonged opening of Ca2+ channels, Ca2+ influx
• Late repolarization - closure of Ca2+ channels and K+ efflux
Excitation contraction coupling
Method of Ca2+ influx – Initially Ca2+ enter through DHPR.

Triggers Ca2+ induced Ca2+ release by RyR receptors from SR.
Q- At the neuromuscular junction of skeletal muscle
a) Several motor fibers end on one motor end plate.
b) Atropine blocks transmission.
c) Release of Ach is facilitated by Mg ions.
d) Ach increases the permeability of the post synaptic

membrane for Ca2+. e) RMP is less at the post synaptic
membrane than elsewhere of the sarcolemma
Smooth muscle
• Lacks visible cross striations as actin and myosin
filaments are not arranged in regular arrays. Ionic fluxes
• Troponin is absent
• Binding of Ach muscarinic receptor
• Poorly developed sarcoplasmic reticulum • Increased influx of Ca2+ into cells
• Few mitochondria from ECF through voltage gated Ca2+
• Depends mostly on glycolysis channels
• Activation of calmodulin dependent
myosin light chain kinase
• Phosphorylation of myosin
• Binding of myosin to actin and
increased myosin ATPase activity
• Contraction
• Dephosphorylation of myosin by
various phosphatases
• Relaxation or sustained contraction
due to latch bride mechanism
E.g.: - vascular smooth muscles

Smooth muscles have no constant RMP. Very slow excitation contraction coupling(200ms) compared to skeletal &
cardiac muscles(10ms). Ca2+ release is mostly from the ECF.
Vericosites - Dilated areas of nerve fibers innervating smooth muscles that release neurotransmitters.
Latch bridge mechanism
Dephosphorylated myosin cross-bridges remain attached to actin for some time after the cytoplasmic Ca2+
concentration falls. This produces sustained contraction with little expenditure of energy.
Important in vascular smooth muscle.
Types
1. Visceral smooth muscle/ Single unit smooth muscles
• Large sheets
• Low resistance bridges {gap junctions) between cells
• Functions in a syncytial fashion
• Contracts when stretched, stretch causes decline in membrane potential, increase in frequency of
spikes, general increase in tone.
• E.g.- walls of hollow viscera
2. Multi-unit smooth muscle
• Individual units
• No interconnecting bridges
• Functional similarities to skeletal muscles
• E.g. – iris of eye
Action of catecholamine and acetylcholine on smooth muscle (Reverse happen in some smooth muscles.)
Catecholamine Acetylcholine
Membrane potential become more negative Membrane potential become less negative
Spikes decrease in frequency Spikes more frequent
Muscle relaxes Muscle tone increases
α action – increased Ca2+ efflux from cells By phospholipase C and IP3, increase intracellular
β action – via cAMP increased intracellular binding of Ca2+ concentration
Ca2+
Smooth muscles also can undergo summation of contractions.

Myasthenia gravis – Autoimmune disorder that destroys muscle type nicotinic Ach receptors. What
happen????
Lambert-Eaton syndrome – Autoimmune disease. Patients develop antibodies against voltage gated Ca2+
channels in the nerve endings. What happen???

SKELETAL MUSCLE CARDIAC MUSCLE SMOOTH MUSCLE
Innervated by myelinated ANS and pace maker cells ANS
nerves
No absolute refractory period Long absolute refractory
in contraction period
Can be tetanized Can’t be tetanized Not tetanized but prolonged
contraction by latch-bridge
mechanism
Have a fixed RMP = -90mV Have a fixed RMP = -90mV Unstable membrane potential
(average about -50mV)
Metabolism is aerobic, can be Metabolism is aerobic Mostly by glycolysis
anaerobic
Rapid excitation-contraction Slow excitation – contraction Very slow excitation –
coupling coupling contraction coupling (200 ms
after onset of spike)
Ca2+ influx intracellular Initially from ECF and then extracellular
intracellular Ca2+
cAMP increases force of cAMP relaxes smooth muscles
contraction
1. T/F
a) Visceral smooth muscle – well developed sarcoplasmic reticulum
b) Multi-unit smooth muscle – low resistance junctions
c) Cardiac muscle – high myoglobin content
d) Type I (slow) skeletal muscle – high oxidative capacity
e) Type II (fast) skeletal muscle – high number of Ca2+ channels

Autonomic Nervous System
Regulates most of the involuntary activities of the body

Visceral afferents with endocrine system maintain body homeostasis
General Organization (reflex arc)

Cell bodies of peripheral & visceral
afferents are in dorsal root ganglia
OsmoR & cranial nerve ganglia (follow the
ChemoR same pathway as somatic afferents) Central
BaroR integrating
Receptor
Pain and
Afferents modulating
Temperatur
area (Spinal
Cord)
Effector
Postganglionic Preganglionic neuron
• Cell bodies are outside • Cell bodies are in intermediolateral

CNS –ganglia grey column of the spinal cord and
• Unmyelinated C fibers the cranial nuclei
• Myelinated B fibers
Two neurons between CNS & effector system unlike somatic

nervous system
ANS
SYMPATHETIC NS PARASYMPATHETIC NS ENTERIC NS
Sympathetic Nervous System
Myelinated type B Unmyelinated type C

fibers fibers
Receptors – alpha, beta
Transmitter – Noradrenaline, adrenaline
Nicotinic Ach Ach in few
receptors
Parasympathetic Nervous System
Myelinated type B Unmyelinated type C

fibers fibers
Receptors – Muscarinic
Transmitter - Acetylcholine

ANS
Sympathteic (Throcolumbar Parasympathetic
Outflow) (Craniosacral Outflow)
• Mostly generalized effects • Most responses are specific
• 1st thoracic to 3rd/4th lumbar spinal nerves • To Head - cranial nerves III, VII, IX To
• To head arise in superior, middle and stellate ganglion Thorax and upper abdomen - Cranial nerve
& travel with blood vessels X, To sacral region S2-S4 spinal nerves
• Parts of uterus and male genital tract from collateral
ganglia
• Short preganglionic and long postganglionic fibres • Long preganglionic and short
postganglionic fibres
• Ganglion in sympathetic chain and superior, middle & • Near the viscera/ inside the viscera
stellate ganglion
• Some pre ganglionic fibers pass through sympathetic
chain and end on post ganglionic neurons located in
collateral ganglia (close to visera)
• some pregaglionic neurons terminate directly on the
effector organ,the adrenal gland
• Pre ganglionic synaptic transmitter-ACH • Pre ganglionic synaptic transmitter-ACH
• Post ganglionic synaptic transmitter • Post ganglionic synaptic transmitter

• Acetylcholine - blood vessels in skeletal muscles, • Acetylcholine
uterus, sweat glands, pilomotor muscle
• Noradrenaline - except above
• Receptors
• Receptors
• Ach - muscarinic
• Ach - muscarinic
• α - α1 , α2
• β - β1 , β2
ACETYLCOLINE NOADRENALINE
• No systemic circulation • Noradrenaline, adrenaline, dopamine found

in plasma
• Effects are localized and short term • Spread further than ACH more prolonged &
diffuse action
• Receptors • Receptors
Nicotinic Alpha receptors-α1, α2
muscarinic Beta receptors-β1, β2

RECEPTORS
Cholinergic receptors Adrenoreceptors

(all are GPCR)
Nicotinic (ion gated channels) Muscarinic (GPCR)- α1

Blocked by atropine
α2
NN-Autonomic ganglia M1
Blocked by hexamethonium M2-HEART β1
M3-SMOOTH MUSCLES & GLANDS
M4 β2
NM-NMJ (Blocked by curare) M5
β3
Most of the organs are supplied by both divisions of The ANS but few organs are supplied only by one
division of ANS
Exclusively by sympathetic-blood vessels, sweat glands, pilomotor muscles
Exclusively by parasympathetic-lacrimal glands, ciliary muscles, sublingual glands
 The axons of some of the

postganglionic neurons leave the
chain ganglia and reenter the spinal
nerves via the grey rami
communications
 Other post ganglionic fibers leave
the chain ganglia to reenter the
thoracic cavity terminate in visceral
organ
Parasympathetic action
Acetylcholine - Muscarinic receptor
01. Decrease heart rate
02. Bronchoconstriction and increase
mucous secretion
03. Increase motility and secretion and decrease sphincter tone in GIT
04. Increase gastric acid secretion (M3)
Sympathetic action
Norepinephrine α1 1. Vasoconstriction.
2. Inhibit mucous secretion in respiratory tract.
Epinephrine β1 1. Increase heart rate.
2. Increase myocardial contractility
β2 1. Bronchodilation
2. Increase mucous secretion in respiratory tract.
3. Vasodilation in liver and skeletal muscles.
Effect of Sympathetic stimulation
1.GIT a) Decrease motility
b) Decrease secretions
c) Increase sphincter tone
2.Eyes a) Pupillary dilation
b) Relaxation of ciliary muscle (far vision)
Sympathetic cholinergic system

1. Generalized sweating.
2. vasodilation in skeletal muscles.
Propranolol inhibits β1 and β2 receptors
Problem Component of ANS Treatment

activated
Anxiety Sympathetic β blocker (propranolol)
Salivation Parasympathetic Ach Receptor blocker
Atropine
To cause pupillary dilation Sympathetic (oppose Ach Receptor blocker
parasympathetic) (Atropine)
High blood pressure sympathetic α blocker (Prazosin)
-vasoconstriction β blocker (atenolol)
-↓cardiac output
Narrowing of airways Reduced sympathetic β stimulant
(Bronchoconstriction) (salbutamol)
• Sometimes referred to as mini brain

• Situated with in the walls of digestive tract (esophagus to anus)
• Comprised of 2 organized neural plexuses
1. Myenteric plexus
• Situated between longitudinal & circular muscle layers of GIT
• Control the motility of GIT
2. Submucosal plexus
• Located between circular & luminal mucosa
• Regulate the blood flow & epithelial cell functions
Although the enteric NS can function autonomously, normal digestive function often requires
communication between the CNS & the enteric NS

bat notes
term 02
anatomy
bat notes
term 02
THORAX
Thoracic cage
Borders
• Anterior-sternum
• Posterior-12 thoracic vertebrae &
intervening intervertebral discs
• On each side- 12 ribs with their
costal cartilages+ intercostal muscles
Shape
• Adult
Transverse section - kidney shape
Transverse diameter> antero-posterior diameter
Ribs - oblique ribs
Thoracic & abdominal respiration
• Infant
Transverse section – circular
Transverse diameter< antero-posterior diameter
Ribs - horizontal ribs
Purely abdominal respiration
Superior Thoracic Aperture

• Anterior- upper border of manubrium sterni
• Posterior- superior surface of body of 1st
thoracic vertebra (T1)
• On each side- 1st rib & cartilage
Inclined at an angle of 45 degrees
*Suprapleural membrane= ”Sibson’s fascia”

• Triangular
• Separates thorax from the neck
• Attachments
o apex-tip of the transverse process of C7
o Base-inner border of the 1st rib & cartilage
Inferior Thoracic Aperture

• Anterior-infrasternal angle
• Posterior-inferior surface of body of T12
• On each side-costal margin
*Diaphragm separates thorax from abdomen.

Bones of thorax
A) Ribs
12 pairs of ribs
1-7 True ribs 8-12 False ribs

Vertebrosternal
Vertebrochondral Vertebral(floating ribs)

8-10 11-12
Atypical -1, 2, 10, 11, 12
Typical -3-9
Longest -7th rib
Most angular -9th rib
Typical rib
• Anterior end
− concave depression
− attach with costal
cartilages
• Posterior end
Head – 2 facets & a crest in between
• Upper facet – body of the higher vertebra
• Crest – intra articular ligament
• Lower facet – body of the numerically corresponding vertebra
Neck – 2 surfaces
• Anterior – smooth related to costal pleura
• Posterior – rough inferior costotransverse ligament
• Superior border or crest superior costotransverse ligament
Tubercle – at the junction of the neck & shaft

2 parts
• Medial articular – costotransverse joint with the transverse process
• Lateral non-articular – lateral costotransverse ligament
Shaft
• Convex outwards
• Bent & twisted at the angle (weakest point)
• Has two surfaces
− Inner surface – covered by pleura
- Grooved inferiorly (subcostal groove)
Contains from superior to inferiorly
V- Posterior intercostal Vein
A- Posterior intercostal Artery
N- Intercostal Nerve
− Outer surface – rough up to the angle
Attachment of Erector spinae

Atypical ribs
1st rib
• Shortest, broadest, most curved, flattest
• Shaft has no twist
• Flattened from above downwards
• Upper surface – 2 shallow grooves for the subclavian artery and vein.
− Separated by scalene tubercle near the inner border
• Lower surface – no subcostal groove
Relations of the 1st rib
− Superior surface
• In between insertion of scalenus anterior to
the scalene tubercle
− Subclavian vein - anteriorly
− Subclavian artery & the lowest trunk of
the brachial plexus - posteriorly
− Medially
• Apex of the lung & cervical pleura
• Suprapleural membrane is attached
− Neck
From Medial to Lateral
S – Sympathetic trunk
V – 1st posterior intercostal Vein
A – Superior intercostal Artery
N – T1 Nerve (Larger portion of T1 nerve to form inferior trunk of brachial plexus)
2nd rib 10th rib 11th rib 12th rib

Much less curved Only 1 articular Short
than 1st rib Twice facet on the No tubercles, No neck
as long as 1st rib head Only 1 facet on the head
Tapering ends
11th have a slight angle a 12th have neither
shallow subcostal groove
CLINICALS
• Rib fractures
Children – rare - Chest wall is highly elastic
Adult – common
By Direct or indirect violence

Indirect weakest point (at the angle) but, upper 2 ribs – protected by the clavicle
Lower 2 ribs – floating, are least commonly fractured

• Cervical rib
Attached– C7 transverse process
− Articulates with 1st rib or if short the free distal extremity attached to the 1st
rib by a fibrous band
− Can be unilateral or bilateral
Pressure on
1) Lowest trunk of brachial plexus (T1) -
Parasthesia along the ulnar border of forearm -
Wasting of intrinsic muscles of the hand
2) Subclavian artery (less likely due to Thickness

of the wall)
-Vascular changes -Gangrene
3) Subclavian vein - Oedema
• Thoracic inlet syndrome

-cervical rib
-Variation of the insertion of scalenus
anterior -above structures compressed
1. Lowest trunk of brachial plexus (T1)
2. Subclavian artery
3. Subclavian vein
• Coarctation of the aorta

• Constriction of aorta beyond the origin of left subclavian artery
• If collaterals open up,
− Posterior intercostal arteries enlarged -notching of ribs
− thyrocervical trunk,internal thoracic artery are also enlarged
B) COSTAL CARTILAGES
• Hyaline cartilage
• In old age – progressive ossification
− Add resilience to the thoracic cage - Protects sternum & ribs
C) STERNUM
3 parts- manubrium, body, xiphoid process
Clavicle
1st costal cartilage
2nd costal cartilage
Manubriosternal joint

• Manubrium − opposite to T3/T4
• Body – opposite to T5 - T8
4 sternebrae - fused between puberty & 25 years Lateral border – notched
Articulate with part of 2nd, 3rd- 7th costal cartilages
Lower end – primary cartilaginous xiphisternal joint
• Xiphoid - Cartilage
May ossify at adult life
Overlies the Epigastric fossa
*bone marrow – manubriosternal puncture
JOINTS OF THE THORAX

1) Manubriosternal joint – secondary cartilaginous
2) Costovertebral
Articular surfaces – 1. head of the rib
2. Body of the vertebra above & numerically corresponding
vertebra
Ligaments – 1. capsular
2. Intra-articular
3. Triradiate
3) Costotransverse joint - synovial

Articular surfaces – 1. medial part of tubercle of rib
2.Transverse process of numerically corresponding vertebra
Ligaments
1. capsular
2. Superior, Inferior, lateral costotransverse
• superior – crest on the neck of the rib

Transverse process of the vertebra
above
• inferior – posterior surface of the neck of the rib
Transverse process of the
corresponding vertebra
• lateral – lateral part of the tubercle of the rib
tip of the transverse process of the
corresponding vertebra
4) Costochondral – primary cartilaginous

Immovable
5) Chondrosternal – 1st primary cartilaginous
2nd-7th - synovial
6) Interchondral - 5th-9th – synovial (among hyaline cartilages of those ribs)
Between 9 & 10 - fibrous

RESPIRATORY MOVEMENTS
Vertical diameter
Contraction of the diaphragm (losing its convexity)
Transverse diameter
• Mainly ribs 7-10 (partly 2-6)
• Bucket handle movement
 Replacement of a shorter rib with a longer rib
 Axis of rotation- costovertebral joints
− Chondrosternal joints
Antero-posterior diameter
• Mainly ribs 2-6 (partly 7-10)
• Pump handle movement
 Forward movement of manubrio-sternum
 Axis of rotation – costovertebral joints
-Costotransverse joints
Muscles
Quiet inspiration – diaphragm
External intercostals muscles
Quiet expiration – passive
Forced inspiration – scalene muscles

Sternocleidomastoid
Pectoralis major
Pectoralis minor
Levator scapulae
Trapezius

Rhomboidus
Serratus anterior
Serratus posterior superior
Forced expiration –Lattisimus dorsi

Anterior abdominal wall muscles
Internal & innermost intercostals
Serratus posterior inferior
IMPORTANT SURFACE LANDMARKS OF THORAX

1. Superior angle of scapula – T2
2. Suprasternal notch or jugular notch (T2/T3) trachea is palpable in this notch
3. Spine of the scapula – T3
4. Sternal angle of Louis
(T4/T5) 2nd costal cartilage
Ascending aorta ends
Descending aorta begins
Arch of the aorta begins & ends Trachea
divides into 2 principal bronchi
Azygos vein arches over right lung root & drains into SVC
5. Inferior angle of scapula – T8
6. Xiphisternal joint – T9
7. Longest part of the costal margin – 10th rib
8. Sternum – T5/T8
Overlies heart
9. C7 – vertebral prominence, 1st palpable
10. All thoracic spines in the posterior midline
11. Nipple – in a male – 4th intercostals space, 10cm from the midsternal
line Female – it varies
12. Apex beat
Left 5th intercostal space 9cm from the midline
Just below & medial to nipple

THE WALLS OF THORAX
Intercostals spaces
• Intercostals muscles
3 layers – external intercostals
Internal intercostals
Innermost intercostals
Muscle Fibre direction Origin Insertion Extent Nerve supply Action

External Forwards Lower Outer lip of From the Elevate
Downwards border of the upper b tubercle to the the ribs
Medially the rib order of the Costochondral during
above the rib below Junction inspiration
space
Internal Backwards Floor of the Inner lip of Lateral border
Downwards costal the upper of the sternum Intercostals
groove of border of to the angle of nerves
the rib the rib the rib depress
above below the ribs in
Innermost Backwards Middle 2/4 Inner lip of forced
Downwards of the ridge upper expiration
above border of -
costal the rib
groove below
Intercostal nerves
• Intercostal nerves – anterior primary rami of T1-T11 spinal nerves, after the dorsal primary rami has
been given
• Subcostal nerve – anterior primary rami of T12
• Typical intercostal nerve – T3-T6
− Branches – lateral cutaneus, anterior cutaneus, and collateral muscular

CLINICALS
Pus from the vertebral column tends to track around the thorax along the course of the neurovascular
bundle,
• Dorsal primary ramus
• 2 cutaneus branches
Intercostal arteries
Each intercostal space contains
• 1 posterior intercostal artery
• 2 anterior intercostal arteries
 posterior intercostal artery (gives a collateral branch)

• 11 in number
- 1, 2 – superior intercostal artery, branch of the costocervical trunk
- 3-11 – descending thoracic aorta
 anterior intercostal artery
• 9 intercostal spaces anteriorly
- 2 in each space
- 1-6 – internal thoracic artery
- 7-9 – musculophrenic artery (branch of internal thoracic)
Intercostal veins
Anterior intercostal veins
- Upper 6 spaces internal thoracic vein
- Lower 3 spaces musculophrenic vein
Posterior intercostal veins Right side Left side

1st Right brachiocephalic Left brachiocephalic
Join to form the right superior Join to form the left superior
intercostal vein intercostal vein
2-4th Azygos vein Left brachiocephalic vein

5-8th Azygos vein Accessory hemiazygos vein
9-11th Azygos vein Hemiazygos vein
Posterior intercostal veins communicate with vertebral venous plexus

Lymphatic drainage
Anterior aspect Posterior aspect
Internal mammary nodes Posterior intercostal nodes

(along internal thoracic artery)
Tracheobronchial nodes
Lower 4 spaces upper spaces
Brachiocephalic nodes
Cisterna chili Right Left
Bronchomediastinal trunk right lymphatic duct thoracic duct
Right Left
Subclavian trunk Thoracic duct
Neurovascular bundle
From above downwards - V A N
Between: internal intercostal & innermost intercostal muscle layers (neurovascular plane)
Lying in the subcostal groove
• intercostal nerve block – upper border of the space/ just below the rib
INTERNAL THORACIC ARTERY

st
• branch of the 1 part of the subclavian artery opposite the thyrocervical trunk
• at the 6th space divide in to –superior epigastric
musculophrenic
Branches
i. anterior intercostal arteries for upper 6 spaces
ii. pericardiophrenic
iii. perforating branches
iv. superior epigastric artery
v. musculophrenic artery
AZYGOS VEIN

• drains the thoracic wall & upper lumbar region
• forms an important channel connecting SVC & IVC
• lies anterior to the vertebral column to the right of the thoracic duct& aorta
Formation
• Formed by right subcostal vein, ascending lumbar vein
• Drains right superior intercostal vein (2-4 posterior intercostal veins)
• 5-11 right posterior intercostal veins
• Hemiazygos, accessory hemiazygos – T8 level
CLINICALS
SVC obstruction – azygos vein transmits blood from the upper half of the body to unobstructed part of
the SVC or to the IVC.
Thoracoepigastric vein (Superficial vein formed by anastomoses between lateral thoracic vein of
axillary vein and superficial epigastric vein of greater saphenous vein) opens up.
HEMIAZYGOS VEIN
• Formed by the left ascending lumbar & left subcostal
• 9-11 left posterior intercostal veins
ACCESSORY HEMIAZYGOS VEIN

• 5-8 left posterior intercostal veins
THORACIC SYMPATHETIC TRUNK

• Descending from the cervical chain It crosses
- Neck of the 1st rib
- Heads of the 2nd-10th ribs
- Bodies of 11th & 12th thoracic vertebrae
- Passes behind the medial arcuate ligament of diaphragm
st
• 1 thoracic ganglion + inferior cervical ganglion = stellate ganglion
• Post ganglionic fibres T1-T5 heart, great vessels, oesophagus

• Splanchnic nerves formed by T5-T12 preganglionic fibers Supply to abdominal
viscera via -coeliac
-Inferior mesenteric
-Superior mesenteric
-Renal plexus
 Greater splanchnic (T5-T10)
 Lesser splanchnic (T10-T11)
 Least splanchnic (T12)
DIAPHRAGM
- dome shaped fibromuscular septum
- partition between the thorax & abdomen
- chief muscle of respiration
- 2 parts : peripheral muscular
Central tendon (aponeurosis)

Muscular fibers (origin)
- Sternal – 2 small slips from the back of the xiphisternum
- Costal – inner aspect of lower 6 ribs & costal cartilages
- Vertebral/ lumbar – from the crura & arcuate ligaments
Right crus: anterolateral aspect of bodies of upper 3 lumbar vertebrae & intervening inter-vertebral discs
Left crus: corresponding parts of upper 2 lumbar vertebrae
Median arcuate ligament: medial margins of 2 cruratendinous arch in front of the Aorta
Medial arcuate ligament: thickening of psoas fascia

Medially- side of body of L1
Laterally- transverse process of L1
Lateral arcuate ligament: thickening of fascia covering quadratus lumborum medially- transverse
process of L1
Laterally- 12th rib
Central tendon (insertion)
- Trefoil shaped
- Partially fused with pericardium
*right dome of the diaphragm is higher than the left dome (due to liver)
Nerve supply
Entire motor supply: phrenic nerves (C3, C4, C5)
Sensory: central- phrenic
Peripheral (including crura) - lower 6
intercostal nerves
CLINICAL
*paradoxical movements *referred pain
Position
- Highest in supine position
- Lowest while sitting
- Intermediate while standing
OPENINGS OF THE DIAPHRAGM
Large
1. aortic- T12 (osseoaponeurotic)
- abdominal aorta
- azygos vein
- thoracic duct
2. oesophageal – T10 (muscular)
- oesophagus
- 2 vagi
- Oesophageal branches of left gastric artery
3. venacaval - T8 (central tendon)
- IVC
- Branches of the right phrenic nerve

CLINICALS
Diaphragmatic hernia
Congenital hernia – unusual to occur
1. Anteriorly – through foramen of morgagni (retrosternal); between xiphoid & costal margin
2. Posteriorly – through the foramen of bochdalek (pleuroperitonial canals) - posterolateral hernia
3. through a deficiency of the whole central tendon (central hernia)
4. congenitaly large oesophageal hiatus
Acquired hernia - common

- traumatic
- hiatal – sliding hernia
- upper stomach and lower esophagus slide upwards
- competence of cardia disturbed
- gastro-esophageal reflux take place
-rolling hernia
- gastro-esophageal junction remain constant
- fundus rolls up
- no gastro-esophageal reflux
Irritation of diaphragm can cause referred pain in the shoulder tip (via root values C3, C4 and C5)

Mediastinum
**Space between the two pleural cavities situated at the center of the thorax.
Boundaries of mediastinum.
• Anterior – Sternum
• Posterior – 12 thoracic vertebrae
• Superior – Superior thoracic aperture
• Inferior – Inferior thoracic aperture
• On each side - mediastinal pleurae
Divisions
Imaginary plane through sternal angle of Louis
& lower border of T4 divides
mediastinum into
Mediastinum
Superior Inferior
Anterior Middle Posterior
 What is the anatomical significance of the plane through sternal angle?
Superior mediastinum
Boundaries
• anterior - manubrium sterni
• posterior- upper 4 thoracic vertebrae
• superior- superior thoracic aperture
• inferior- imaginary plane through sternal angle and lower border of T4
• on each side- mediastinal pleura
Contents:
1. Trachea, oesophgus, thymus, thoracic duct
2. Nerves - Vagi, phrenic,left recurrent laryngeal, cardiac nerves
3. Veins - Left & right brachiocephalic, SVC, left superior intercostal veins
4. Arteries - Left common carotid, left subclavian, brachiocephalic artery & arch of aorta
5. Muscles - Sternothyroid, sternohyoid
6. Lymph nodes – paratracheal, brachiocephalic, tracheobronchial

CLINICALS
Superior mediastinal syndrome
Cause: enlargement of mediastinal lymph nodes, aortic aneurysm, bronchogenic carcinoma

Compression of mediastinal structures results in:
• Oesophagus– dysphagia (difficulty in swallowing)

• Trachea – dyspnea (difficulty in breathing)
• Phrenic nerves – paralysis of diaphragm (paralyzed diaphragm is raised, paradoxical movements),
shoulder tip pain (C4 – pain referred from diaphragmatic peritoneum)
• Left recurrent laryngeal nerve – hoarseness of voice
• SVC – dilatation of neck & facial veins *thoracoepigastric vein
• Stellate ganglion (sympathetic trunk) – Horner’s syndrome
• Vertebral bodies – erosion
• Intercostal nerves - intercostal neuralgia
Mediastinitis
• Little loose connective tissue
• Lots of dead space – expand veins,more on the right side
• Easy spread of infection
• Large surface area
• Toxins get absorbed
• Attachment of prevertebral fascia to T4 – infections spread from the neck to the sup
mediastium
• Attachment of pretracheal fascia with arch of aorta – neck infections spread to sup
mediastinum & through it to posterior mediastinum

Inferior mediastinum
Anterior Mediastinum Middle Mediastinum Posterior Mediastinum
Boundaries • anterior – Body of • anterior – sternum & • anterior - pericardium,
sternum Sternopericardial ligaments bifurcation of trachea,
• posterior – Pericardium • posterior - oesophagus, pulmonary vessels, posterior
• superior – imaginary thoracic duct, descending part of upper surface of
plane thoracic aorta, azygos vein diaphragm
• inferior – Diaphragm • On each side – mediastinal • posterior– lower 8 thoracic
• On each side – pleura vertebrae
mediastinal pleura • On each side – mediastinal
pleura
Contents • Thymus • Heart & pericardium • Esophagus, Thoracic duct
• Areolar tissue • Ascending aorta, pulmonary • Descending thoracic aorta &
• Lymph nodes trunk, 2 pulmonary arteries branches
&lymphatics • Phrenic, deep cardiac plexuses • Azygos, hemiazygos&
• Sternopericardial • Tracheobronchial nodes accessory hemiazygos veins
ligaments • Bifurcation of trachea, • Vagi, splanchnic nerves
• Mediastinal branches principal bronchi • Posteriormediastinal lymph
of internal thoracic • SVC, azygos vein (terminal nodes along aorta
artery part), pulmonary veins

Great vessels
SVC
1. Internal jugular vein + subclavian vein = Brachiocephalic (behind the sternoclavicular joint)
2. Right + left brachiocephalic vein = SVC (behind the sternal end of the right fist costal cartilage)
3. Pierces pericardium – second right costal cartilage
4. Opens in to upper part of RA – third right costal cartilage
*no valves
Tributaries:
• Azygos - second right costal cartilage
Before SVC enters pericardium
• Mediastinal, pericardial veins
CLINICALS
Obstruction of SVC
Above azygos opening – through azygos
Below azygos opening – through IVC
Aorta
1. Ascending aorta
• Lower border of 3rd costal cartilage
• Forwards, upwards to the right
• Ends at sternal angle(upper border of 2nd right costal cartilage)
Branches: right & left coronary arteries
Relations:
o Anterior
• Sternum
• Left lung & pleura
• Infundibulum
• Root of pulmonary trunk
• Right auricle
o posterior
• Transverse sinus
• Left atrium
• Right pulmonary artery
• Right principal bronchus
o To the right – SVC, right atrium
o To the left – pulmonary trunk, left atrium

2. Arch of aorta
∗ Begins at upper border of right 2ndsternochondral joint
∗ Upwards, backwards to the left across the bifurcation of trachea
∗ Downwards behind left bronchus
∗ Arches over root of left lung
∗ Ends at the sternal angle
Relations: anteriorly
to the left
• Left phrenic nerve, cardiac nerves, vagus
• Left superior intercostals vein
• Left lung & pleura
• Remains of thymus
posteriorly to the right

• Trachea with deep cardiac plexus & tracheobronchial lymph nodes
• Oesophagus
• Left recurrent laryngeal nerve
• Vertebral column
• Thoracic duct
Superiorly
• 3 branches of aorta-brachiocephalic, left common carotid, left subclavian
• All of these crossed by the left brachiocephalic vein close to origin
Inferiorly
• Bifurcation of pulmonary trunk
• Left bronchus
• Ligamentum arteriosum with superior cardiac plexus on it

3. Descending thoracic aorta
∗ Begins on the left side of the lower border of T4
∗ Descends with an inclination to right
∗ Terminates at lower border of T12
Relations:
• anterior – root of left lung
pericardium & heart
oesophagus in the lower
part diaphragm
• posterior – vertebral column
hemiazygos veins, accessory hemiazygos vein
• Right – oesophagus in the upper
part Azygos vein
Thoracic duct
Right lung &
pleura
• Left – left lung & pleura
Branches
O 9 posterior intercostals
arteries
o Subcostal artery
o 2 left bronchial
arteries
o Oesophageal
branches
o Pericardial branches
o Mediastinal branches
o Superior phrenic arteries
CLINICALS
∗ Aortic aneurysm
∗ Ductus arteriosus, ligamentum arteriosum, patent ductus arteriosus
∗ Coarctation of aorta
• Pre ductal– patent ductus arteriosus
• Post ductal – collateral circulation between branches of subclavian & descending thoracic aorta
a. anastomoses between anterior & posterior intercostals – notching of ribs
b. anastomoses between inferior epigastric & internal thoracic arteries
c. Scapula anastomoses – pulsating scapula
RADIOGRAPHY
• the diaphragm is higher on the Dome of right side (due to the liver)
• mediastinal shadow – heart & great vessels
Right border – right brachiocephalic vein
SVC
Right atrium
IVC
Left border – aortic knuckles (arch of the aorta)
Pulmonary trunk
Left auricle
Left ventricle
Inferior border – centrally merge with diaphragm
Either side forms cardiophrenic angles
Oesophagus
∗ 25cm long muscular tube
∗ Begins – C6 – lower border of the cricoid cartilage
∗ Traverses the superior & posterior mediastina
∗ Curvatures-2 side to side curvatures ( to the left)
-anteroposterior curvature corresponding to the curvature of cervicothoracic spine
∗ Pierces the diaphragm – T10
∗ Ends at the cardiac orifice of the stomach (T11)
Constrictions:
• at the beginning (cricopharyngeal sphincter) – 15cm (6’’) from upper incisor teeth
(narrowest-commencement)
• Crossed by aortic arch – 22.5 cm (9’’)
• Crossed by left bronchus – 27.5cm (11’’)
• Pierces diaphragm – 37.5cm (15’’)
Relations:
Cervical
• Anterior – trachea, thyroid gland
• Posterior – C6, C7, prevertebral fascia
• On each side – common carotid arteries
 Recurrent laryngeal nerves
 Left subclavian artery
 Terminal part of thoracic duct
Thoracic
 Anterior – trachea, left bronchus  Posterior– vertebral column
• Pericardium with left atrium • Thoracic duct
• Diaphragm • Azygos vein &its tributaries
• Right pulmonary artery • Right posterior intercostal arteries
• Near the diaphragm - thoracic aorta
 To the right – right lung & pleura

− Azygos vein
− Right vagus
 To the left – in the superior mediastinum,
• Left subclavian artery
• Aortic arch
• Thoracic duct
• Left pleura & lung
-In the posterior mediastinum
• Descending thoracic aorta
• The left lung & pleura
Abdominal
• Passes through an opening in the right crus of the diaphragm
• Behind it, lies the left crus
• Comes to lie in the oesophageal groove on posterior surface of left lobe of liver
• Covered by peritoneum anteriorly & left
Blood supply
Arterial supply:
• Cervical – inferior thyroid arteries
• Thoracic – oesophageal branches of aorta
• Abdominal – oesophageal branches of left gastric artery
Venous drainage:
• cervical – inf. thyroid vein/brachiocephalic veins
• Thoracic – azygos vein
• Abdominal – partly azygos partly left gastric
Lymphatic drainage:
perioesophageal lymphatic plexus
• Cervical – deep cervical nodes supraclavicular
• Thoracic – post. mediastinal nodes
• Abdominal – left gastric nodes
Nerve supply:
• Parasympathetic - below the root of the lung vagi form a plexus on it
• Sympathetic – middle cervical & thoracic ganglia
CLINICALS
• Barium swallow
•
3 indentations – aortic arch, left bronchus, Left atrium
•
Oesophageal varices in portal hypertension
•
Left atrial enlargement – mitral stenosis
• Achalasia cardia – lower esophageal sphincter fails to open up during swallowing
• Dysphagia -difficulty in swallowing (can be caused by mediastinal syndrome)
Thoracic duct
• 45cm long
• Beaded appearance - presence of valves
• Continuation of cisterna chyli
• Ascends through the aortic opening of the diaphragm (T12)
• Runs through posterior mediastinum
• Crosses from right to left (T5)
• Arches laterally – C7 transverse process
• Descends over – left subclavian artery
• Drains – commencement of left brachiocephalic vein (confluence of internal jugular and subclavian veins)
• Drains the whole lymphatic field below the diaphragm & left half of the body above it
• Right side – right subclavian + jugular trunks = right lymphatic duct
Together with mediastinal trunk drains into the origin of right brachiocephalic vein
At the aortic opening; A T A
(R) (L)
Azygos Aorta
Heart & Pericardium
Pericardium
**Fibroserous sac which encloses heart and the roots of great vessels
Pericardium
Fibrous pericardium Serous pericardium

Apex fuses with adventitia of great vessels
Parietal layer
Base blends with central tendon. Visceral layer
Fused with fibrous (E
(Epicardium)
pericardium
Adherent to heart
(except along cardiac grooves)
Nerve supply → Phrenic nerve autonomic nerves

Pain sensitivity → sensitive Insensitive
Blood supply → 1) Internal thoracic Artery coronary vessels

2) Musculophrenic Artery
3) Descending aorta
Embryological origin→ pleuropericardial membrane mesothelium of septum

transversum
•
Parietal and visceral (epicardium) layers of pericardium
•
Continuous at the root of great vessels
•
Encloses pericardial cavity → a potential space

Sinuses of pericardium
 Serous pericardium forms an arterial tube
around ascending aorta and pulmonary trunk.
&
 A venous tube around vena cavae and
pulmonary veins.
Transverse sinus
 Horizontal gap
 Lies between arterial and venous tubes
 Bounded,
o Anteriorly → arterial tube
o Posteriorly → superior vena cava
o Inferiorly → left atrium
Oblique sinus
 Bounded,
O Anteriorly – left atrium
O Posteriorly – parietal pericardium
o On right & left-reflections of the pericardium
.
 A recess between left atrium and parietal
pericardium
Clinical
Pericardial effusion→collection of fluid in the pericardial
cavity
• Drained by puncturing -
o Left 5th or 6thintercostals space just lateral to sternum
o Left xiphicostal space
o Needle directed upward, backward and to the left
• Structures pierced by,

 skin
 superficial fascia
 deep fascia
 external intercostal muscle
 Internal intercostals
 innermost intercostals
 Fibrous pericardium
 parietal layer of serous pericardium
Pericarditis inflammatory condition of the pericardium.

Heart
Position → behind the body of the

sternum,
In the middle mediastinum,
In front of the T5 – T8
vertebral bodies,
2/3 of the heart- to the left

of the midline
External features
a) Apex → entirely by left ventricle

Left 5th intercostal space, 9 cm lateral to midline
Just medial to midclavicular line
Pulsation can be left (apex beat)
b) Surfaces→
• Anterior / sternocostal surface
mainly right ventricle & right
atrium (left ventricle, left auricle)
• Posterior/base left atrium
(mainly) & small part of right
atrium
• Inferior/ diaphragmatic right 1/3
of right ventricle, left 2/3 of left
ventricle, on central tendon of
diaphragm
• Left surface mainly left
ventricle, Upper end by left
auricle
c) Borders
• Right → right atrium only
• Left → left ventricle, partly by left auricle
Grooves
• Atrioventricular/ coronary sulcus→ separate atria and ventricle

• Interventricular sulcus →Anterior -separate apex from rest of inferior border
Posterior- situated in inferior surface
• Interatrial groove faintly visible posteriorly, anteriorly hidden by aorta &
pulmonary trunk

Surface marking
1) 2nd left costal cartilage

2) 3rd right costal cartilage 0.5 inch from sternal angle
3) th
6 right costal cartilage
4) 5th left intercostal space 3.5 inches(9cm) from midline
Chambers of Heart
Right Atrium
Right upper chamber
External features
• Sulcus terminalis→ groove from SVC to IVC along the right border
(Produced by internal muscular ridge- Crista terminalis)
• Upper part of the sulcus contains SA node
• Right atrioventricular groove → separates right atrium from right ventricle
• Right auricle → prolonged upper end
Openings to the right atrium

• SVC • Coronary sinus • Venae cordis minimi
• IVC • Anterior cardiac veins
Smooth post. Part Rough ant. Part Interatrial septum
Derived from right horn of sinus venosus Derived from primitive atrial Derived from septum
chamber primum& septum secundum
Contains muscular ridges Fossa ovalis present in the
Openings arising from crista terminalis lower part
 SVC-upper end (musculi pectinati) Limbus fossa ovalis
 IVC-lower end Forms posterolateral wall of
 Coronary sinus- between the IVC and Right the right atrium
atrioventricular orifice
 Venae cordis minimi through small
foramina

Right ventricle
2 parts interior (separated by infundibuloventricular crest)
o In flowing part rough
shows trabeculae carneae/ muscular ridges (proximal part of bulbus cordis)
o out flowing part (infundibulum) smooth (mid portion of bulbus cordis)
2 orifices
• right atrioventricular orifice/tricuspid valve
• pulmonary orifice/semilunar valve
Papillary muscle→3 muscles: Anterior, Posterior, Septal
• Attached to cusps of tricuspid valve via cordae tendinae
• Moderator band contains right branch of AV bundle
(septomarginal trabecula)
-Cavity of the right ventricle is cresentic in shape
Left atrium
• Posterior surface forms the anterior wall of the
oblique sinus
• Greater part of interior is smooth walled
• Fossa lunata on the septal wall
• Two pairs of pulmonary veins open on each side
of posterior wall
• Musculi pectinati are present only in auricle
Left ventricle
2 parts interior
• Upper smooth part →aortic vestibule gives
origin to ascending aorta
• Derived from mid part of bulbus cordis
• Lower rough part with trabaculae carneae derived
from primitive ventricle
• Contains 2 well developed papillary muscles
(anterior & posterior)
• 2 orifices Left atrioventricular orifice/bicuspid (mitral) valve
Aortic orifice/semilunar valve
• Interventricular septum upper part is thin & membranous
Lower part is thick and muscular
Valves of the heart
uus 1) Atrioventricular valves

• Fibrous ring to which the cusps are attached
• Cusps → Smooth atrial surface, Rough ventricular surface
• Rough margins to which cordae tendineae are attached
• Papillary muscles attached to the cusps
• Blood vessels only in fibrous ring
a) Tricuspid valve - between right atrium and right ventricle
b) Bicuspid valve -between left atrium and left ventricle

2) Semilunar valves
• 3 semilunar cusps, No cordae tendinae attached
• Nodule in the free margin & lunule extends upto the base of the cusp
• Opposite cusps vessel walls are slightly dilated to form sinuses
a) Aortic valve between left ventricle and ascending aorta
b) Pulmonary valve between right ventricle and pulmonary trunk
-Valves prevent back flow of blood

-Cordae tendinae prevent eversion of cusps
-Normal heart sounds are produced by closure of heart valves
Auscultation
Valve Auscultatory area
Pulmonary Second left intercostals space near the sternum
Aortic Second right intercostal space near the sternum
Mitral Cardiac apex- left 5th intercostal space at mid clavicular line
Tricuspid Just to the left of the lower part of the sternum near the 5th intercostal space
Conducting system
*Composed of specialized cardiac muscle fibres
SA node
 Pace maker of the heart , Horse shoe shaped
 Situated at the atrio-caval junction in the upper part of
the sulcus terminalis
 Supplied by right coronary artery (60%)
AV node
 Situated lower posterior part of interatrial septum
 Just above the opening of coronary sinus
AV bundle of His only muscular connection
between atrial and ventricular musculatures
Right branch A large part enters moderator band
Left branch
Purkinje fibres form a subendocardial plexus, pale fibres striated only at margins
Due to defects or damages to this system cardiac arrhythmias
Coronary circulation

Arterial supply
• Heart is supplied by right and left coronary arteries.
Right coronary artery
Arises from anterior coronary sinus ascending aorta. SA nodal artery
Emerges between pulmonary trunk and right auricle. Right atrial
Infundibular branches
It runs in the right anterior coronary sulcus/right anterior atrioventricular groove.
Winds around the inferior border of the heart right marginal artery
Enters diaphragmatic surface. AV nodal artery
posterior interventricular(IV) artery
runs in the posterior IV groove.
Terminates by anastomosing with the terminal part of the left coronary artery.
• Distribution –
o Right atrium
o Right ventricle except a small area near the anterior IV groove.
o Left ventricle near posterior ventricular groove.
o Posterior 1/3 of the intervent. Septum.
o Whole conducting system except a part of left bundle branch.
Left coronary artery

Arises from the left posterior coronary sinus of ascending aorta.
Emerges between the pulmonary trunk and the left auricle. Left atrial artery
After a short course (sometimes) Diagonal artery
circumflex artery anterior IV artery.
Runs in the left anterior coronary sulcus Runs in the anterior IV sulcus
Winds around the left border of the heart and Anastomose with the post. inter. Artery at the
gives off the left marginal artery. apex.
Runs in the left posterior coronary sulcus Gives off several ventricular branches. Largest
branch is called ‘Diagonal artery’
Ends by anastomosing with terminal branches of right. Coro. Artery
• Distribution –
o Left atrium
o Left ventricle except for a small area near posterior IV groove.
o Right ventricle – small area near anterior IV groove
o A part of the bundle branch of the AV node.
o Anterior 2/3 of IV septum.

Veins of the heart
A) Coronary sinus→ largest vein
Situated In left posterior coronary sulcus
Opens into posterior wall of R/atrium
It receives;
Accompanies
Great cardiac vein - first anterior interventricular artery then left coronary artery
Middle cardiac vein - posterior interventricular artery
 Small cardiac vein right coronary artery

(Right marginal vein may drain into this)
Posterior vein of left ventricle
 Right marginal vein marginal artery of right coronary artery
 Oblique vein of left atrium derived from left common cardinal vein
B) Anterior cardiac veins directly to right atrium

C) Venae cordis minimi numerous small veins (more in right side)
Present in all four chambers which open
directly into the cardiac cavity
Clinicals
Cardiac pain
*Ischaemic pain- Angina Pectoris
*Incomplete obstruction of a coronary artery, Spasm occurs
*Pain sensations from the heart carried by sympathetic
fibres which relayed on T1 -T5of spinal cord
*Sensations from the medial side of the arm, forearm
upper part of front of the chest carried by somatic
fibres which is relayed on T2 –T5
*Pain is referred to those areas
*Coronary bypass is done using
 Great saphenous vein OR
 Internal thoracic artery
Nerve supply of heart

• Parasympathetic – via vagus - Cardioinhibitory
• Sympathetic – from upper 2 to 5 thoracic segments of spinal cord - Cardioacceleratory, Dilate coronary arteries
• Both parasympathetic and sympathetic nerves form superficial and deep cardiac plexuses.
• Superficial plexus - Below arch of aorta, in front of right pulmonary artery
• Deep plexus - In front of bifurcation of trachea, behind arch of aorta

Pleura and Lung
Pleura
 Serous membrane lined by single layered mesothelium.
 2 layers Parietal
Visceral
 2 layers are continuous with each other around the hilum of the lung.
 In between a potential space - the pleural cavity
01. Pulmonary/Visceral Pleura

 Firmly adherent to the lung
 Covers the surfaces & fissures of lungs except along the pulmonary ligament & hilum
of the lung
 Pain insensitive – autonomic supply (T2-T5sympathetic, vagus parasympathetic)
 Supplied by – bronchial arteries
 Drained by – Bronchial veins
 Lymphatic drainage - bronchopulmonary lymph nodes
02. Parietal Pleura

1. cervical
2. costal
3. mediastinal
4. diaphragmatic

• Pain sensitive Intercostal and phrenic nerves
• Blood Supply Intercostal, Internal thoracic & musculophrenic arteries
• Drained by Azygos & internal thoracic veins
• Lymphatics Intercostal nodes
Internal mammary nodes
Posterior mediastinal nodes
Diaphragmatic nodes
Recesses of pleura
1. Costomediasinal recess
 Between costal & mediastinal pleurae

 obvious in regions of cardiac notch of the
left lung
 Filled by anterior margins of the lungs
even during quiet breathing
2. Costodiaphragmatic Recess
 vertically 5 cm
 extends from 8-10 ribs along the
midaxillary line
 between costal & diaphragmatic pleura
Pulmonary Ligament
 Parietal Pleura extend downwards beyond the
root
 Provide a dead space for pulmonary veins and
lung roots
*Root of lung-structures that connect lung to
mediastinum
*Hilum-site where structures enter & leave the lung

Costomediastinal recess
Surface markings of the lung
(8th rib)
(10th rib) (12th rib)
Cervical Pleura
 curved line
 over the medial 1/3 of the clavicle
 2.5cm above the junction between medial 1/3 & middle 1/3 of the clavicle
 5 cm above the 1st rib
Anterior margin
 from the sternoclavicular joint
 downwards & medially to the midpoint of sternal angle
 Right side - vertically downwards to the midpoint of xiphisternal joint (6th costal
cartilage)
 Left side – same course up to the level of the 4th costal cartilage
arches laterally
descends along the lateral border of the sternum up to the 6th c.c.
Inferior margin
 laterally downwards
 crosses the 8th rib -midclavicular line
10th rib -midaxillary line
12th rib -lateral border of erector spinae
Posterior margin
 2cm lateral to the T12 and C7 spine
**Pleura descends below the costal margin

@ 3 places
 right xiphicostal angle
 right and left costo vertebral angles below the 12th rib

Clinicals
 Paracentesis thoracis
Safety triangle
Mid axillary line
Anterior axillary fold
Superior Border of the 5th rib
Posteriorly 7th intercostal space

8th intercostal space in the mid axillary line
Structures pierced
a. Skin
b. Superficial fascia
c. Serratus anterior
d. External intercostals
e. Internal intercostals
f. Innermost intercostals
g. Endothoracic fascia
h. Parietal pleura
**needle should be inserted close to the upper border of the rib or lower part of the space
 Pleurisy – inflammation of pleura

 Pneumothorax – air in the pleural cavity
 Haemothorax – blood in the pleural cavity
 Hydropneumothorax – both fluid & air in the pleural cavity
 Empyema – pus in the pleura cavity

Lungs
 Apex – blunt
 Base – rests on the diaphragm
 Anterior border – thin
 Posterior border – ill defined
 Inferior border
 Costal & mediastinal surfaces
Surface Markings
Anterior view
Lung
• Apex
- a line convex upwards rising 2.5cm above the junction between medial 1/3 & middle
1/3 of the clavicle
• anterior border
- sternoclavicular joint
- midpoint of the sternal angle
- Right lung - just above the xiphisternal joint
- Left lung - upto 4th cc, curves laterally & forms the cardiac notch, reaches the 6th cc

• Lower border
Crosses
- mid clavicular line @ the 6th rib
- mid axillary line @the 8th rib
- lateral border of the erector spinae
ends 2cm lateral to the 10th thoracic spine
• Posterior border
- 2cm lateral to the midline from T10 –C7
Posterior view
Fissures
Oblique Fissure
** 2cm lateral to the T3 spine

** 5th rib in the mid axillary line
** 6th cc 3 inches (7.5cm) from mid line
OR
* Full abduction of the shoulder
* Oblique fissure corresponds to the position of the medial border of the scapula
Transverse Fissure (horizontal)
* Line drawn horizontally along the 4th cc

*meet the oblique fissure on the 5th rib

Root of the lung
From before backwards-
• Superior pulmonary vein

• Pulmonary Artery
• Bronchus
From above downwards-
Right Left
• Eparterial bronchus Pulmonary artery
• Pulmonary Artery bronchus
• Hyparterial bronchus inferior pulmonary vein
• Inferior pulmonary Vein
Relations of the root
Anterior-
- Phrenic nerve
- Pericardio phrenic vessels on both sides
- Anterior Pulmonary plexuses
*on the right - svc, right atrium
Posterior-
- Vagus nerve
- Posterior Pulmonary plexus both sides
* Left side - descending thoracic aorta

Superior-
On the right - Terminal part of the azygos vein
On the left - arch of aorta
Inferior-
Pulmonary ligament
Relations of the mediastinal surface

Right Left
• right atrium and auricle left ventricle, auricle, infundibulum
• right ventricle Pulmonary trunk
• SVC ,IVC Arch of aorta, Descending thoracic aorta
• Azygos vein Left brachiocephalic vein
• Oesophagus,Trachea Thoracic duct , Oesophagus
• Right vagus & phrenic Left recurrent laryngeal nerve, Left vagus and phrenic

Arterial Supply  Bronchial arteries
R-1 artery, 3rd post. Intercostal
L-2 arteries, descending aorta
Venous drainage2 bronchial veins on each side

R-azygos vein
L-left superior Intercostal vein
Greater part-pulmonary veins
Lymphatic drainage
Superficial lymphatics(Sub pleural) Deep lymphatics
Pulmonary nodes
Broncho pulmonary nodes
Inferior & superior tracheobronchial nodes (bifurcation of the trachea)
Paratracheal nodes
R & L broncho mediastinal trunks
Directly to the brachiocephalic veins

Indirectly via thoracic or right lymphatic duct
Nerve supply
Parasympathetic- vagus anterior & posterior pulmonary plexuses

Sympathetic - T2-T5 situated in front and behind the lung root

Bronchial Tree
Trachea (C6-T4)
Lower border of T4
Primary/principal bronchi
Secondary/lobar bronchi
One for each lung lobe
2 for Left and 3 for Right
Tertiary / segmental bronchi -

10 for each side, one for each segment
Divide repeatedly
Terminal bronchioles
Respiratory bronchioles
Alveolar ducts
Atria
Air saccules
Alveoli
Bronchi
Right principal bronchus

-wider
-shorter
-more in line with trachea (more vertical) than left
-2.5cm long
-angle with tracheal bifurcation - 25°
-infections are common in right side (right lower lobe apical segment)
-before entering the lung gives superior lobar bronchus
-superiorly - right - terminal part of the azygos vein

Left principal bronchus
-nearly 5cm
-downwards and outwards below the arch of aorta
-pulmonary artery anteriorly and above
-oesophagus posteriorly
-narrower, longer, more oblique
-angle with tracheal bifurcation - 45°
Bronchopulmonary segments
Definition - a segment of lung supplied by a single segmental (IIIry) bronchus
Features
• 10 in each lung
• independent respiratory unit(surgical, functional, structural)
• each segment has its own separate artery
• veins lie in the intersegmental planes, can isolate a particular segment along the veins
• bronchopulmonary segment is not a bronchovascular segment(as it doesn’t have its
own vein)
Clinicals
 Bronchoscopy
 Widening and distortion of the angle between the primary bronchi
-carina
-carcinoma of tracheobronchial lymph nodes around the bifurcation of the trachea
Trachea

 10-15cm long
 Commencement - lower border of cricoid cartilage (C6)
 bifurcation- lower border of T4(sternal angle)
 in a living subject-varies during respiration--T6-deep inspiration & T4-expiration
 felt in the jugular notch **displacement
 blood supply –inferior thyroid arteries

- left brachiocephalic veins
 lymphatics -pretracheal and paratracheal nodes
 nerve supply-sympathetic-middle cervical ganglion

-parasympathtic-vagus
 radiology-translucent as it contains air
 tracheostomy :
 tracheal tug :
Relations
Cervical
Anterior
• Isthmus of thyroid gland
• inf. Thyroid veins
• sternothyroid
• sternohyoid
Posterior
• Oesophgus
• Recurrent laryngeal nerve
Laterally
• Lobes of the Thyroid gland
• Common carotid artery {carotid sheath & its contents}

Thoracic
Anterior
• Brachiocephalic artery
• Left carotid artery
• Left brachiocephalic vein
• Thymus
Posterior
• Oesophagus
• Recurrent laryngeal nerve
To the left
• Arch of aorta
• Left common carotid artery
• Left subclavian artery
• Left lung and pleura
To the right
• Right vagus
• Azygos vein
• Right lung and pleura
Histology
Layers of the RT
• Respiratory epithelium Respiratory mucosa
• Underlying lamina propria
• Smooth muscle layer
• Submucosa
• Cartilage
• Adventitia
Nasal cavity
• Nasal mucosa – Epithelium - pseudostratified ciliated columnar
Lamina Propria - Serous and mucous glands
Thin walled blood vessels
MALT
**olfactory mucosa
Larynx
• False vocal cords - respiratory epi thelium
• True vocal cords - non keratinized stratified squamous epithelium
Skeletal muscle
Trachea
• Mucosa – epthelium- pseudostratified columnar ciliated
lamina propria-blood vessels

• submucosa- seromucinous glands
• cartilage -anteriorly-hyaline cartilage (c shaped)

posteriorly- trachealis muscle
• adventitia - elastic
Cross section through trachea
Primary bronchus
• -goblet cells become fewer in lower respiratory tract
• -columnar epithelium becomes less tall in lower respiratory tract
• -between the lamina propria and submucosa-a smooth muscle layer
• -interconnected plates of hyaline cartilage rather than distinct rings
Tertiary bronchi
• -irregular cartilage plates
• -prominent smooth muscle layer
Bronchiole
• -no cartilage
• -no submucosal glands
• -terminal ,respiratory bronchioles-no goblet cells,only clara cells

Cross section through a bronchiole
Terminal bronchiole
• -columnar epithelium
• -no goblet cells
• -no cilia
Respiratory bronchiole
• -cuboidal epithelium
Alveolus
Wall-components
1. Lining epithelium
• type 1 pneumocytes - large squamous
• type 2 pneumocytes - surfactant secretion-small
2. Supporting tissue
3. Capillaries
Alveolar capillary membrane (Air blood barrier)

• -alveolar epithelium composed of type 1 pneumocytes
• -fused basement membrane
• -capillary endothelium

Functions of respiratory system
1. Air conduction
• Non collapsing/patencycartilages
• Flexibilitydiscontinuous cartilages
• Adjust diametersmooth muscles
2. Air conditioning
• Humidifyserous cells
• Cleaninggoblet cells & cillia
• Warmingcountercurrent mechanisms
01. Regarding the pleura

a) Inferior border of the pleura crosses the 6th rib in the midclavicular line.
b) Costodiaphragmatic recess extends from 8th to 10th rib.
c) Central part of the diaphragmatic pleura is pain sensitive.
d) Pulmonary pleura drains into bronchopulmonary lymph nodes.
e) Paracentesis thoracis is done in the 6th intercostals space in the midaxillary line.
02. Right lung

a) Has two lobes.
b) Apex rises above middle 1/3 of the clavicle 2.5 cm above.
c) Mediastinal surface is related to the thoracic duct.
d) Pulmonary vein drains right lung.
e) Bronchopulmonary segments are supplied by IIry bronchi.
03. In the bronchial wall

a) The epithelium is pseudostrtified columnar ciliated.
b) Goblet cells are absent.
c) Seromucous glands are abundant.
d) Smooth muscle layer is prominent.
e) Cartilage framework is limited to irregular plates

ABDOMEN
Surface Anatomy
• T9 – Xiphoid
• L1 – Transpyloric plane{passes through tips of 9th costal cartilage(bears a distinctive step) anteriorly
and Lower border of L1 posteriorly)}
*Lies halfway btw the suprasternal notch & the top of the pubis /a hand’s breadth below the xiphoid
*transpyloric plane passes through,
1. Pylorus of stomach 5. Termination of spinal cord
2. Hila of the kidneys 6. Duodenojejunal flexure
3. Fundus of gallbladder 7. Origin of superior mesenteric artery
4. Neck of pancreas 8. Tip of 9th costal cartilage
9. Splenic vein → portal vein
Mnemonic-
Please - pylorus
Feed – fundus of gall bladder
Him – hilum of the kidney
Some – origin of superior mesenteric artery
Love – lower end of spinal cord
• L3 – Subcostal plane( inferior margin of 10 rib)

1.Origin of Inferior Mesenteric artery
• L4 – Plane of highest point of iliac crest (supracristal plane)

1.Bifurcation of aorta
2.Lumbar puncture
• L3-L4 (Inter vertebral disc) 9

1.Umbilicus
 L5-Transtubercular plane(passes through tubercles of iliac crest)
Liver(Points)
1. Tip of right 10th rib in mid axillary line
2. Left 5th intercostal space in mid clavicular line
3. Right 5th intercostal space in mid axillary line
*Not palpable in normal subject
Spleen(Points) – Left side

1. Axis – 10th rib directed downwards forwards and laterally
2. Upper border – upper border of 9th rib
3. Lower border – lower border of 11th rib
4. Medial end – 2 inch from midline
5. Lateral end – Mid axillary line
*Must be enlarged 3 times than normal to be palpated
Fundus of Gallbladder (Right side)

1. Tip of 9th costal cartilage
(at the intersection of9th costal cartilage & lateral border of rectus abdominis)
Kidney
Two horizontal lines
1. Level of upper border of T12
2. Level of center of L3
Hilum-on the transpyloric plane 4 finger breadths from the midline
*This plane passes through the upper part of the hilus of the right kidney, & through the lower part of
the left kidney
*Right kidney is 1inch lower than the left
*Left kidney is nearer to the median plane
Anterior Abdominal wall
Mid clavicular line
Transpyloric plane
Transtubercular plane
Layers of the wall

a. Skin
b. Superficial fascia
c. Muscles - External Oblique, Internal Oblique, Transversus abdominis
d. Fascia Transversalis
e. Extra peritoneal fat
f. Parietal peritoneum
-Superficial fascia
2 layers below Umbilicus Camper’s Fascia/ superficial fatty layer
Penis – Devoid of fat
Scrotum – Replaced by Dartos muscle
Scarpa’s fascia/ deep membranous layer
Scarpa’s fascia
Goes to corona of penis Over scrotum Over perineum Goes over the inguinal
(junction between neck and ligament and blends with
shaft of the penis fascia lata (holden’s line)
Dartos fascia Colles’ fascia
Buck’s fascia
• Abdomen has no deep fascia**
Line of attachment of membranous layer
o Holden’s line-a horizontal line extending laterally from pubic tubercle where membranous layer
is firmly attached to the deep fascia of the thigh
**Importance of this line- when the urethra is injured in the perineum, it prevents extravasated
urine from descending into the thigh beyond this line
o Pubic tubercle
o Body of pubis & margins of the pubic arch
o The posterior border of the perineal membrane
( Chaurasia-fig 16.8)
 RECTUS SHEATH
▪Definition – Aponeurotic sheath covering the rectus abdominis muscle
▪2 walls - Anterior wall- continues throughout
Adherent to the rectus muscle at tendinous intersections
- Posterior wall - free
Above costal margin – ant wall: external oblique
Post wall: deficient (muscle rests on 5, 6, 7 Costal Cartilages )
Between costal margin - ant wall: ext. oblique, ant. Layer of int. oblique
& arcuate line post wall: transverses abdominis, post. Layer of int. oblique
(arcuate line=halfway between umbilicus and pubic symphysis)
Below arcuate line – ant wall: aponeurosis of all 3 muscles
Post wall: deficient, muscle rests on fascia transversalis
9Contents- muscles- rectus abdominis & pyramidalis

Superior & inferior epigastric vessels
Lower five intercostal nerves and subcostal nerves
Splitting of internal oblique aponeurosis along the lateral border of rectus sheath forms the semilunar line.
**Two rectus sheaths fuse in the midline to form the linea alba
**Functions: increases the efficiency of the muscle, gives strength to the ant. abd. wall

Blood supply
Flanks – intercostal, lumbar, subcostal arteries
Ventral structures – Superior epigastric- internal thoracic
Inferior epigastric – external iliac
Venous drainage
Above umbilicus – Lateral thoracic vein, Internal thoracic vein
Below umbilicus – Great saphenous vein
In obstruction, superficial abdominal veins are dilated & provide a collateral circulation.
In vena caval obs: Thoracoepigastric veins open up, connecting the great saphenous vein &with the axillary
vein
Inferior vena caval obstruction – blood flow upwards watershed barrier broken
Superior vena caval obstruction- blood flow downwards
Few para-umbilical veins accompany ligamentum teres. In portal vein obs: dilated veins cause caput medusae at
the umbilicus
▬ Lymph drainage
Above umbilicus – Axillary nodes
Below umbilicus – Superficial inguinal nodes
 Water-shed line – lymph and venous blood flow upwards above the plane of umbilicus &
downwards below the plane
- Innervation -lower 5 intercostal and subcostal(between internal oblique & transverse

abdominis) T7- xiphoid process, T10- umbilicus level
- Iliohypogastric L1
- Ilioingunal L1
- Subcostal and iliohypogastric supply the gluteal region as well
Anterolateral abdominal muscles
External oblique Internal oblique Transversus abdominis

Fiber Downward, forward, Upward, forward, medially Horizontal
direction medially
Nerve Lower 6 thoracic nerves Lower 6 thoracic & L1 Lower 6 thoracic nerves &
supply L1
-between the anterior superior iliac spine & the pubic tubercle the external oblique
aponeurosis folds on itself to form the inguinal ligament
-internal oblique muscle arises from its lateral 2/3 -
transversus abdominis arises from its lateral 1/3
-Conjoint tendon : fused lowest aponeurotic fibers of the internal oblique & transversus abd.
muscles. Is attached to the pubic crest

INGUINAL CANAL
▪Definition – Oblique musculo-aponeurotic passage in lower anterior abdominal wall Just above the medial
half of inguinal ligament, extending from deep ring to superficial ring(4cm)
▪Rings - Superficial inguinal ring
*Is a triangular gap in the external oblique aponeurosis, above the pubic crest
- Deep inguinal ring
*Is an opening in the fascia transversalis, situated ½ inch above the mid inguinal point and
immediately lateral to the stem of the inferior epigastric artery
▪Walls – Anterior wall
Whole extent – skin, superficial fascia, external oblique aponeurosis
Lateral 1/3 – Internal oblique muscle fibers
Posterior wall
Whole extent – Fascia transversalis, extraperitoneal tissue, parietal peritoneum
Medial 2/3 – Conjoint tendon, at the medial end by the reflected part of the
inguinal lig.
Lateral 1/3 -interfoveolar ligament
Roof
Arching fibers of internal oblique &transversus abdominis(arching infront of the
cord laterally to behind the cord medially)
Floor
Grooved upper surface of Inguinal ligament
Medial end by Lacunar ligament
▪Contents – Male
1. Spermatic cord(male reproductive system)
• three layers of fascia – the external spermatic, from the external oblique aponeurosis; the
cremasteric, from the internal oblique aponeurosis (containing muscle fibres termed the
cremaster muscle); the internal spermatic, from the transversalis fascia;
• three arteries – the testicular (from the aorta); the cremasteri (from the inferior epigastric
artery); the artery of the vas (from the inferior vesical artery);
• three veins – the pampiniform plexus of veins (draining the right testis into the inferior vena cava
and the left into the left renal vein), and the cremasteric vein and vein of the vas, which
accompany their corresponding arteries;
• three nerves – the nerve to the cremaster (from the genitofemoral nerve); sympathetic fibres
from the T10 and T11 spinal segments; the ilioinguinal nerve (strictly, on and not in the cord);
• three other structures – the vas deferens; lymphatics of the testis, which pass to the para-aortic
lymph nodes; and, pathologically present as the third structure, a patent processus vaginalis in
patients with an indirect inguinal hernia!
2. Ilioinguinal nerve (don’t enter through the deep ring, enters the canal through the interval
between external & internal oblique muscles & passes out through the superficial ring) supplying
inguinal region,upper part of thigh, anterior third of scrotum,root of penis

Female
1. Round ligament of uterus 2. Ilioinguinal nerve
MECHANISM OF INGUINAL CANAL

• Obliquity of the inguinal canal
• Sup. ring guarded from behind by conjoint tendon& by reflected part of ing. ligament
• Deep ring guarded from in front by i muscle fibers of transverse abdominis
▪Clinical – Hernia-> abnormal protrusion of abdominal contents through any of its walls
▫Hasselbach’s triangle
Boundaries
A-inguinal ligament
B B-inferior epigastric artery
C C-lateral border of rectus abdominis
Deep inguinal ring
medial lateral
A
Surface marking of inferior epigastric artery
0.5in just above the femoral pulse (midinguinal point=halfway between pubic symphysis and
anterior superior iliac spine)
Indirect inguinal hernia Direct inguinal hernia

• Passes through the deep inguinal ring • Passes through the posterior wall of inguinal
• Passes lateral to the inferior epigastric artery canal, occurs through Hasselbach triangle
• Can descend in to the scrotum • Passes medial to the inferior epigastric artery
• Corrected by digital pressure • Mainly in adults
Coverings • Uncommon
• Cant be corrected by digital pressure
• Coverings
Skin, external spermatic fascia, conjoint tendon,
Skin, external spermatic fascia, cremasteric fascia, fascia transversalis, extra peritoneal tissue,
internal spermatic fascia, extra peritoneal tissue, bowel bowel
Inguinal hernia – neck of the sac lies above & medial
to pubic tubercle
Femoral hernia – neck of the sac lies below & lateral
to pubic tubercle
Reffered pain from gut-derived structures,

Pain of foregut- T8 – epigastric area
Pain of midgut- T10 – periumbilical area
Pain of hindgut- T12 – suprapubic area
Abdominal incisions
• Mcburney’s incision – for appendisectomy
(Iliohypogastric and ilioinguinal nerves should be
preserved)
• Kocher’s incision
• Midline incision
• Paramedian incision
Peritoneum
• Peritoneum is a serous membrane which lines the abdominal cavity.
• 2 Layers – Parietal
Visceral
• Various folds or reflections of the peritoneum connect viscera to abdominal wall or to one
another.
Some are properly called folds, others are called mesentery, omentum or ligament.
Peritoneal folds of anterior abdominal wall

Falciform ligament - connects liver to anterior abdominal wall & diaphragm, sickle shaped
Ligamentum teres - from umbilicus to the inferior margin of Falciform lig. (remnant of
left umbilical vein)(left is left)
Median umbilical fold - containing median umbilical lig. (remnant of urachus),from apex
of bladder to umbilicus
Medial umbilical fold - containing medial umbilical lig. (remnant of umbilical artery)
Lateral umbilical fold - containing inferior epigastric vessels

(only up to arcuate line)
Median umbilical fold
Arcuate line Medial umbilical fold
Lateral umbilical fold

 Ligaments
Left triangular lig. – formed from the left leaf of the Falciform lig.
Superior layer of coronary lig. – formed from the right leaf of the Falciform lig.
Right triangular lig. – formed where the superior & inferior layers of the Coronary lig. meet.
Ligament Extend Contents

4.Gastrosplenic Greater curvature of the stomach Short gastric vessels
to Hilum of spleen L. Gastro-epiploic vessels
5. Lienorenal Hilum of spleen Tail of pancreas

to anterior surface of kidney Splenic vessels
Pancreaticosplenic lymph nodes
1.
6. Phrenicocolic ligament – From left colic flexure (Splenic flexure) to Diaphragm.

Separates left paracolic gutter from Lienorenal space & spleen
7. Gastrophrenic ligament

Mesentery
Contents Attachment of root
 
Jejunal & ileal branches of Begins at duodenojejunal flexure
1. Mesentery
proper superior mesenteric vessels. Ends at right sacroiliac joint

Autonomic nerve plexuses 
Crosses =>
[Mesentery of
 rd
Small intestine]  Lymph nodes & lymphatics 3 part of duodenum
 Fat  Abdominal aorta
 IVC
 Right Psoas Major
 Right ureter

2. Mesoappendix  Appendicular vessels From - Posterior surface of the mesentery of the
terminal ileum

To - Tip of the appendix
 
3. Transverse Middle colic vessels Anterior surface of neck &

Mesocolon Lymph nodes anterior border of body of pancreas
 
Lymphatics Crosses 2nd part of duodenum

ANS
4. Sigmoid 
Sigmoid & superior rectal vessels 
Inverted V shape
Mesocolon 
ANS 
Apex - at bifurcation of common iliac vessels on
pelvic brim at left sacroiliac jnt.

Medial limb - slopes down to front of S3 (rectum
begins here)

Lateral limb - along pelvic brim
Omentum
Contents Attachment
1. Greater omentum 
R & L gastro epiploic vessels 
Double layer of peritoneum folded on itself to form four

Fat layers

Lymph nodes & lymphatics 
Anterior two layers descend from greater curvature

Curves back on itself & ascends

Blend with – peritoneum on anterior surface of transverse
colon & transverse mesocolon
 Bile duct
 Hepatic artery
 Portal vein

2. Lesser omentum  Right gastric vessels Superior - liver (inverted L shaped attachment to porta

Hepatogastric lig.  Left gastric vessels hepatis & Ligamentum venosum)


Hepatoduodenal lig.  Lymph nodes Inferior - lesser curvature of stomach, 1st part of duodenum
 Gastric nerves

Peritoneal cavity
• divided – Greater sac
Lesser sac (omental bursa)
• 2 sacs communicates via epiploic foramen
• Male - totally enclosed,9

Female - perforated by openings of uterine tubes
1. Lesser sac (left sub hepatic space)
Anterior wall - Caudate lobe

Lesser omentum
Posterior surface of Stomach
Anterior two layers of greater omentum
Posterior wall - Posterior two layers of greater omentum

Anterior surface of transverse colon & transverse mesocolon
Peritoneum covering the stomach bed
Left border - Gastrosplenic ligament

Lienorenal ligament
2. Greater sac - Rest of the space among the serous coated organs


Epiploic foramen - a slit at the right border of lesser sac though which it communicate with greater sac
Boundaries Anterior – Right free margin of lesser omentum
Containing – Common bile duct (R)
Hepatic artery proper (L)
Portal vein (P)
Posterior – IVC , T12 vertebra, right suprarenal gland.
Inferior – 1st part of duodenum
Superior – Caudate process of liver

Peritoneal compartments
1. Right sub-phrenic space (closed above by – superior layer of coronary lig.)
2. Left sub-phrenic space (closed above by – left triangular lig.)
3. Right sub-hepatic space(closed above by – inferior layer of coronary lig. & right triangular lig.)
4. Right para colic gutter (lateral to ascending colon)
5. Left para colic gutter (lateral to descending colon)

9Recto-vesical pouch – a peritoneal pouch between rectum & bladder in males

Recto-uterine pouch (pouch of Douglas) - a peritoneal pouch between rectum & uterus in females -most dependent part
of the peritoneal cavity.
-pus which are collected here can be drained through the rectum or pos. fornix of the vagina

Vesico-uterine pouch - a peritoneal pouch between uterus & bladder in females

Hepato-renal / Morrison’s pouch/ Right sub-hepatic -

Behind the right lobe of liver & in front of
right kidney.

On the left – it communicate with lesser sac
via epiploic foramen

Inferiorly – continuous with right paracolic
gutter

When lying down - the most dependent part
9 of the peritoneal cavity
**So area where intra peritoneal fluid tends
to accumulate


Clinical
Peritonitis – Inflammation of peritoneum o Caused
by =>
Ascites – Fluid in peritoneal cavity
▪Fluid Collects in the Lesser sac => Fluid may passes through epiploic foramen 9to
hepatorenal pouch
1. By Posterior Gastric ulcer 2. By Pancreatitis - Pancreatic pseudocyst

Fluid Collects in the Hepatorenal pouch of Douglas =>Subphrenic abscess (Commonest site)

Most dependant part in the supine postion
9By spread of infection from GB, Appendix
▪Treatment =>

Paracentesis – Removal of fluid in abdomen by puncturing the abdominal wall

Posterior Colpotomy – Drain pus from the Hepatorenal pouch of Douglas through
Rectum or Posterior fornix of the vagina

Pneumoperitoneum
 – Air in peritoneal cavity

Haemoperitoneum9 – Blood in peritoneum
o Inflammation of Parietal Peritoneum => localized severe pain & tenderness
o Delay the onset of peritonitis =>

By Greater omentum – limits the spread of infection by sealing off the site.
2. Laparoscopy – Examine the peritoneal cavity under direct vision

o Instrument used =>Laparoscope
o Opening up abdominal cavity (Small incisions to insert Laparoscope) =>Laparotomy
3. Peritoneal dialysis – is done in renal failure
4. Internal Hernia –
o Through epiploic foramen into the lesser sac (Strangulated)
Surgically approached through the greater omentum =>
Epiploic foramen cannot be enlarged because there are important structures
o In between Paraduodenal recesses =>related to Inf. Mesenteric V.
5. Palpation of abdominal viscera– When the patient is in supine position & hip, knee are flexed.

Gastro-intestinal tract
1. Stomach
External features
• Two orifices 1.cardiac orifice- Lies behind the left 7th costal cartilage(T11).
Has a physiological sphincter.(Not anatomical)
2.pyloric orifice-Lies at the level of transpyloric plane(L1).
Its position is indicated by,
o A circular groove produced by underlying pyloric sphincter
• The prepyloric vein/ vein of mayo lying in front
• Anatomical , physiological sphincter
• J shaped muscular bag
• In epigastric , umbilical and left hypochondrial region
• Widest and most distensible part of GI tract
Fundus-filled with air
Parts of the stomach Cardiac part Body
Pyloric part Pyloric antrum

Pyloric canal
▪Relations –
-Peritoneal,
Ventral mesogastrium(dorsal part)- lesser omentum
Dorsal mesogastrium 1.along the greater curvature-greater ometum
2. near the fundus- gastrosplenic ligament
3. near the cardiac end-gastrophrenic ligament
-Visceral,
Anterior - Anterior abdominal wall
Left costal margin
Diaphragm
Left lobe of liver
1 ©2015 A/LRepeat Campaign

- Posterior/Stomach bed
Pancreas
Transverse colon
Left kidney
Left suprarenal gland
Spleen
Splenic artery
▫Are separated by the lesser sac
- Superior – left dome of diaphragm
- Inferior – coils of intestine
Functions
• Storage of food
• Mechanical grinding and digestion
• Prevent reflux
• Prevent digestion and damage of its wall
• Controlled release of food at pylorus
• Absorption (H2O,Ethanol)
• Intrinsic factor
Nerve supply –
Sympathetic greater splanchnic nerves
Parasympathetic ant & post vagal trunks
Anterior vagal trunk

• Gives off
Hepatic branch
Gastric branches-fundus,body
Anterior nerve of Latarjet-pyloric antrum,sphincter
Posterior vagal trunk
• Gives off
Celiac branch(bulk)
Gastric branches-fundus,body
Posterior nerve of Latarjet-pyloric antrum(Not to sphincter)
Anterior & posterior vagi give secretary & motor supply

Gastric divisions of both vagi reach stomach at cardia
Then descend along lesser curvature in the lesser omentum
Terminal part of this nerve innervates pylorus –nerve of latarjet
Complete vagotomy
Selective vagotomy
Highly selective vagotomy
-divide branches which supply acid secreting body of stomach
-preserving nerve of latarjet
-function of pylorus remain intact
Anterior gastric nerve fibers of left vagus(mainly)

Posterior gastric nerve fibers of right vagus(mainly)
▪Clinical – a. posterior ulceration of stomach, damaging the pancreas & splenic artery
(common in lesser curvature) because rugae are longitudinal (gastric canal)
b. gastric carcinoma- commoner along greater curvature
c. “signal nodes” – left supraclavicular node is enlarged (troisier’s sign)
d. pyloric stenosis- causes vomiting after meals
1. Regarding stomach
a. Prepyloric vein marks the pyloric sphincter
b. Cardiac orifice lies deep to the left seventh costal cartilage
c. Part of lesser sac lies within gastrocolic ligament
d. Left supraclavicular nodes enlarges in gastric carcinoma
e. Lymph from upper part of greater curvature drains into pancreaticosplenic nodes
O2. The stomach

a) Is supplied in part by arteries arising from the splenic artery
b) Is supplied by arteries which each arise from branches of the coeliac trunk
c) Has a venous drainage passing equally to the portal and systemic venous systems
d) Is lined by columnar and squamous epithelium
e) Is totally covered by serosa (peritoneum)
2)Duodenum - C shaped loop around head of pancreas
secondarily retroperitoneal except duodenal cap.
1st part – L1 level (2 inch)
2nd part – to the right of L2 (3 inch)
3rd part – crosses in front of L3 (4 inch)
4th part – to the left of L2 (1 inch)
▪Relations
Parts of Anterior Posterior Medial Superior Inferior

duodenum
Superior(1st Peritoneum Portal vein Neck of gall bladder Neck of
part) Gall bladder Gastroduadenal pancreas
Quadrate lobe artery
Bile duct
IVC
Descending(2n Transverse colon Hilum of right Head of
d
part) Transverse kidney pancreas
mesocolon Renal vessels Pancreatic
Coils of SI Ureter duct
Fundus of gall Aorta Bile duct
bladder Right ureter
Horizontal(3rd Superior Right psoas major Head &uncinate process
part) mesenteric IVC of pancreas
vessels Aorta Superior mesenteric
Coils of SI Right ureter vessels
Root of mesentry Gonadal vessels
th
Ascending(4 Beginning of root Left psoas major Head of Body of pancreas
part) of mesentery Left margin of pancreas
Coils of jejunum aorta

• Two papillae – Major – hepatopancreatic ampulla ( ampulla of vater). 8-10cm distal to pylorus
Minor – accessory pancreatic duct opens. 2cm above the major papilla
• Duodenal cap- Seen after a barium meal, 1st part of duodenum is seen
as a shadow .
Reason: absence of circular folds (intraperitoneal)-no plicae circularis
Form lower most boundary of epiploic foramen of Winslow.
▪Clinical – a. peptic ulcer – common site – 1st part
b. obstruction
▫Annular pancreas
▫pressure by the superior mesenteric artery
▫contraction of suspensory ligament of duodenum
c. Ulceration of gall stones into duodenum & obstruct the lower ileum-gall stone ileus
d.Posterior duodenal ulcer
▫damage the gastroduodenal artery & pancreas
o MCQ – shortest, widest, most fixed part of SI
• Suspensory ligament of Treitz

-between DJ junction and right crus of diaphragm
-marks DJ junction
1. Duodenum
a) Is almost completely covered by peritoneum
b) Lies behind the portal vein
c) Lies anterior to the hilum of the right kidney
d) Is crossed anteriorly by the superior mesenteric vessels
3.Jejunum & Ileum
Jejunum Ileum
1.Wall Thicker & more vascular Thinner & less vascular
2.Lumen Wider &often empty Narrow & often loaded
3.mesentery • Less fat • More fat
• Windows present • No windows
• 1/2 arcades(few) • 3/5 arcades(numerous)
• Vasa recta long & few • Vasa recta short & numerous
4.Plicae Large & closely placed Small & sparse

circularis
5.Villi Large, thick & more Short, thin & few
6.Payers Absent Present
patches
7. solitary fewer More

lymph follicles
8.Location Upper left part of abdomen Lower right part
9.length 2/5 3/5
4. Large Intestine
▪Caecum
▪Ascending colon
▪Transverse colon
▪Descending
colon
▪Sigmoid colon
▪Appendix
●Caecum – intraperitoneal,in right iliac fossa
▪large blind sac

▪form commencement of large
intestine
▪width is greater than length
▪Distensible
▪appendix opens in to posteromedial wall, 2cm below ileocaecal valve
Relations
Anterior – Coils of intestine

Anterior abdominal wall
Posterior -▪ Muscle – right psoas &Iliacus
▪ Nerves – Genitofemoral
Femoral (in iliopsoas groove)
Lateral cutaneous nerve of thigh
▪Vessels – Right gonadal
External iliac
1. The caecum
a) Is completely invested in peritoneum
b) Possesses a longitudinal muscle coat but no taeniae coli
c) Lies on the right psoas muscle
d) Has an ileocaecal orifice opening inferiorly
e) Lies adjacent to the right femoral nerve

• Colon,ceacum - taniae coli
• Colon - appendices epiploicae
●Appendix (opens into posteromedial wall of caecum)

▪vermiform blind ended tube ,situated in right iliac fossa, larger in children & base is fixed
▪Position - Retrocaecal – 65%
Pelvic – 30%
Retro ileal
▪Base - Mcburney’s point (gridiron incision)
Junction between lat 1/3 & med 2/3rd of line joining the umbilicus & the right
anterior superior iliac spine
▪Taeniae coli meet at the base
▪Blood supply – Lower division of ileocolic artery
Appendicular artery
Pass behind terminal ileum & enters mesoappendix
Runs 1st in free margin of mesoappendix and then along the appendicular wall.
▫It is an end artery
▪ Clinical - ▪Inflammation - Appendicitis

Pain initially referred to umbilicus (T10)
Later when parietal peritoneum irritates – pain in right iliac fossa
▪Thrombosis of appendicular artery course gangrene Mcburney’s

point- site of maximum tenderness in appendicitis
Inflamed pelvic appendix Inflamed retrocaecal appendix

• Lies on obturator internus, • Lies between caecum & right psoas
More pain when seated(medially More pain when standing(extended
rotated thigh) thigh)
Appendix of ,
• Children – larger
• Adults – obliterated
• So appendicitis more in middle aged ones.
1. The appendix
a) Arises from the inferior aspect of the caecum
b) Has a mesentery
c) Is commonly absent
d) Usually lies retrocaecally
e) Is clothed in peritoneum

Colon
Feature Small intestine Large intestine

1.Caliber Smaller Larger
2. Sacculation Absent Present
3. Taeniae coli Absent Present
4.Transverse mucosal folds Permanent Obliterated when longitudinal
muscle coat relaxes
5.Appendices epiploicae Absent Present
6.Fixity Greatly mobile Greater part fixed
7.Villi Present Absent
8.Common infection Intestinal worms E.hystolytica
Typhoid Dysenteric organisms
Tuberculosis Carcinoma
9.Effects of infection Diarrhoea Dysentery
10. X ray identification 1.Complete transverse lines across Incomplete septa projecting into
bowel shadow due to transverse gas shadow due to sacculation
folds of plicaecircularis
2.shadow – centrally Periphery

Blood Supply of GIT
Supplied by ,
1. Coeliac Trunk – derivatives of foregut
2. Superior Mesenteric Artery - derivatives of midgut
3. Inferior Mesenteric Artery - derivatives of hindgut
Coeliac Trunk (T12)

– between crura of diaphragm just below median arcuate ligament @the upper border of pancreas
divided in to,
Cystic artery
Left gastric artery

 Runs towards the oesophageal opening
 Gives off oesophageal branches
 Runs along lesser curvature
 Anastomose with right gastric artery
Splenic artery
Coeliac Trunk
• Tortuous
• Runs behind upper pancreatic border
• Gives off posterior gastric artery
• Runs towards the hilum of left kidney
• Runs in splenorenal ligament
left gastroepiploic atery 6 short gastric arteries

• anastomose with right
gastroepiploic artery
1
©2015 A/L Repeat Campaign
Right Gastric Artery
Common Hepatic
Gastroduodenal artery
• Pass behind the 1st part of the
duodenum
Right gastro epiploic artery Superior pancreaticoduodenal

• Enters the greater artery
omentum • Anastomose with
inferior pancreatico
duodenal artery
Anterior Posterior
Hepatic artery proper Left
(runs upwards between 2

layers of lesser omentum)
Right Cystic Artery
Clinicals
Foregut - Posterior gastric ulcer or cancer may erode the pancreas giving pain referd to back.
Ulceration into splenic artery (direct posterior relation to stomach) may cause torrential hemorrhage.
posterior duodenal ulcer can erode gastroduodenal artery resulting a severe hemorrhage.
Midgut - Acute infection in appendix may result in thrombosis of appendicular artery, which is an end
artery thus leading to gangrene of appendix.
Hindgut – Hemorrhoids in the anal canal.
2
Superior Mesenteric Artery (L1)
Inferior pancreatico duodenal artery
• Anastomoses with superior
pancreatico duodenal artey
Left branch
Anastomose with a branch
of left colic artery at splenic
flexure
Middle colic artery

(descends in the transverse
mesocolon)
Superior mesenteric artery
• Runs downwards behind Right branch
splenic vein and body of Anastomose with
pancreas with superior ascending branch of right
mesenteric vein on right Jejunal and Ileal branches colic artery at hepatic
• Lies anterior to left renal (from main trunk, to the left) flexure
vein, uncinate process of (runs in the mesentry proper)
pancreas and 3rd part of
duodenum Ascending branch
Anostomose with right
branch of middle colic
artery
Right colic artery
(runs to the right across right psoas
major, gonadal vessels, ureter and
Ileal branch genito-femoral nerve and Descending branch
Anastomose with terminal quadratus lumborum) Anatomose with superior
branch of superior branch of ileocolic artery
mesenteric artery
Ileocolic artery
Superior branch
Inferior branch Anastomose with right colic
artery
Appendicular artery
Anterior caecal artery Posterior caecal artery
• End artery
• 1st runs in the free margin of
the mesoappendix, then
3
©2015close to appendicular
A/L Repeat Campaignwall
Ascending branch
• Cross left psoas, gonadal
Inferior mesenteric artery (L3) vessels, ureter, genitofemoral
nerve, quadratus lumborum
• Crossed anteriorly by inferior
Left colic artery mesenteric vein
Descending branch
• Anastomoses with highest
Sigmoid arteries (2-4) sigmoid artery
• Runs in the sigmoid
mesocolon
At the apex of Ʌ (inverted V)

attachment of sigmoid colon,
bifurcation of left common iliac
vessels over sacro iliac joint;
Inferior mesenteric artery
Continues as Superior rectal artery
• Inferior border of 3rd part
of duodenum
Left branch
Superior rectal artery

• Descend in the medial limb
of sigmoid colon reach
rectum at S3 level
Right branch
Clinicals
• Anastomostic branches near inner margin colon forms marginal artery of Drummond.
• Avascular window lies between middle colic and left colic arteries around the splenic flexure where
surgeons use to enter the lesser sac.
4
Venous Drainage of GIT Paraumbilical vein
Right Branch Left Branch Ligamentum venosum
Ligamentum Teres
Portal Vein
• Runs in the free
Right Gastric Vein margin of the lesser Left Gastric vein
omentum short Gastric
Behind the neck of Splenic vein

the Pancreas
Prepyloric vein of mayo
( not accompany an
artery) Left Gastroepiploic vein
Superior
Pancreaticoduodenal vein Passes behind the lower border of the body
of the pancreas in front of left renal vein and
joins splenic vein
Crosees the third
part of the
duodenum and
uncinate process
Left colic vein Sigmoid veins
of pancreas.
Right Gastroepiploic vein

Inferior Mesenteric vein
Middle Colic vein
Superior mesenteric vein Superior Rectal vein
Right colic vein
Jejunal and Ileal Ileocolic vein

tributaries
5
6
Liver
Surface marking
2. Left 5th intercostal space in mid clavicular line
*Not palpable in normal subject
Tuber Omentale
Papillary Process
Caudate Process

Peritoneal Attachments –
o Liver is enclosed in peritoneum (Ventral mesogatrium), Except at the bare area
Ventral part
i. Falciform lig. – Attached to liver & anterior abdominal wall
o Inferior margin – Ligamentum teres hepatis (Remnant of L. Umbilical V.)
ii. Right & left triangular ligaments
iii. Coronary ligament – Superior & Inferior layers
Dorsal part

Lesser omentum – arise from inverted ‘L’ attachment
o Vertical limb - Ligamentumvenosum (Remnant of DuctusVenosus)
o Horizontal limb - margins of portahepatis

Lobes – Right & Left

Anatomical Division
Diaphragmatic surface – Falciform lig.
Visceral surface – Fissure for Ligamentum Venosum + Fissure for Ligamentum Teres
o Right Lobe

Caudate lobe
-Between groove for IVC & Fissure for Ligamentum venosum
-Caudate process – Inferior to the right, connecting to the right
lobe
- Papillary process – Inferior to the left

Quadrate lobe
-Between GB fossa & Fissure for Ligamentum Teres

Porta hepatis
-Arrangement (from anterior to
posterior )
V – Portal V.
A – Hepatic A.
D – Common Hepatic Duct
o Left Lobe

Tuber Omentale (omental tuberosity) – near the fissure for Ligamentum venosum, right to gastric
impression
Functional Division
 According to distribution of Bile duct, Hepatic artery, Portal vein. Oblique plane through
the GB Fossa & IVC groove (Middle hepatic V. lies)
 Caudate lobe is supplied by both arteries, both portal veins, both
hepatic ducts, but it has independent venous drainage
 Stability – Ligaments, Hepatic veins, Ab. Muscle tone
Relations-5 Surfaces
Anterior Surface
●Diaphragm
●Pleura
●Anterior Abdominal Wall
●Xiphoid Process
Posterior Surface-Right Lobe

(Bare Area – Area that grows in to the Septum Transversum)
●Diaphragm ●IVC+
Hepatic V.
●Suprarenal Impression - R. Suprarenal Gland
Left Lobe
●Oesophageal Impression- Oesophagus
●2 Crura ●Aortic
Opening ●Celiac
Trunk
Inferior Surface (visceral surface)

Right Lobe
●Gall Bladder
●Colic Impression - Hepatic Flexure
●R. Kidney - Renal Impression
Left Lobe
●Gastric Impression -Stomach
●Fissure For LigmentumTeres
Quadrate Lobe
●Pylorus Of Stomach
●Duodenal Impression -1st Part of Duodenum
Superior Surface ●Right & Left Domes Of Diaphragm
Right Surface - ●Upper 1/3-Lung, Pleura, Diaphragm

(In Mid Axillary line) ●Middle 1/3-, Diaphragm
●Lower 1/3-Diaphragm
Blood supply Right hepatic artery cystic artery

1. Hepatic artery proper
Left hepatic artery
Right
2. Portal vein
Left
Left In the plane

3. Hepatic veins IVC
Middle
between
functional 2 lobes
Right
4
 [Small accessory hepatic veins drains directly to the IVC]

Clinical
1. Liver biopsy - Needle passes through right 8th intercostal space
2. Cirrhosis – Liver Fibrosis, causes Caput medusae
3. Malignant growths – Tumors
o Can send an embolus to destroy tumors (contain end-arteries)
o Secondary tumors – from colon cancers
4. Hepatomegaly – Liver enlargement
5. Pringle Manoeuvre – Liver bleeding stopped by = compressing right free margin of lesser omentum
6. Liver resection & transplantation

Important Facts
o Can regrow
o Occupies R.Hypochondrium, Epigasrium, L.Hypochondrium
Under the Costal margin
Normally not palpated in the infrasternal angle
Due to - tone of the recti muscles & the softness of the liver

EXTRA HEPATIC BILIARY SYSTEM

Apparatus consists of –
i. Right & left hepatic ducts
ii. Common hepatic duct
iii. Gall bladder
iv. Cystic duct
v. Bile duct

Calot’s triangle –
i. Cystic duct
ii. common hepatic duct
iii. inferior surface of liver
 Cystic artery and cystic lymph nodes can

be located here.
i. Gall bladder
 Pear shaped.
 Lying in gall bladder fossa
 On visceral surface of right lobe of liver,adjacent to quadrate lobe.
 Volume:- 30-50 ml
 Relations
Neck – Superior – Attached to liver, by areolar tissue
Inferior - 1st part of duodenum
Body – Anterior –Adherent to liver, not covered by peritoneum

Posterior – Transverse colon,1st & 2nd parts of duodenum
Inferior – Covered by peritoneum
Fundus – Anterior – Anterior abdominal wall = 9th costal cartilage tip (transpyloric plane)
Posterior – Transverse colon
▪Clinical
1. It has a Dual blood supply from:
-Cystic artery( cystic veins do not accompany the cystic artery) Venous drainage is via multiple
veins in gall bladder bed to Liver
-From liverbed So gangrene is rare.
2.Gall Stones
 In gall bladder-Cholelithiasis
Spasmodic pain occurs
Murphy’s sign – Pain felt when pressing at 9th costal cartilage tip in
 Hartmann’s pouch. (Gall stones lodge here)
Posteromedial wall of the neck is dilated

3.Inflamation of gall bladder
Refered pain -in the lower border of the scapula via
Sympathetics
- Stomach via vagal fibers
-Shoulder tip via phrenic
4. Courvoisier’s Law
• Extrinsic obstruction (Carcinoma of head of the pancreas) – Dilation of GB
• Intrinsic obstruction (Stones) – Fibrosis, no dilation of GB
2. Bile duct
( commences approximately 2.5 cm above the duodenum )
▪Diameter-6mm (not more than 8mm)
▪Relations
▫Supraduodenal part
(Lie in free
edge of lesser
omentum)
- Anterior-
liver
-Posterior-portal vein, epiploic foramen( more posteriorly IVC)
-Left-hepatic artery
▫Retro duodenal part(most accessible part of surgery)
-Anterior-1st part of
duodenum
-Posterior- IVC
-Left -Gastroduodenal
artery ▫Infraduodenal part
-Anterior-head of
pancreas
(neoplasm of duct may
obstruct here)
-Posterior-IVC,Left renal
vein
• Join main pancreatic duct of wirsung at angle of 600 degrees,to form Ampulla of Vater guarded by sphincter
of Oddi.
• Open to postero medial wall of middle of second part of duodenum.

• 8-10 cm from pylorus.
 Small bile ducts from liver enter to the GB bed.

Pancreas
Surface marking
The transpyloric plane defines the level of the neck of the pancreas which overlies the vertebral Column.From
this land mark head passes downward & to the right, the body & tail pass upward
&to the left

Ducts – Main Pancreatic duct of Wirsung– Begins at the tail =>lies near posterior suface
Joins with bile duct =>Hepatopancreatic ampulla of Vater =>Major duodenal papilla
Accessory Pancreatic duct of Santorini – Begins at the uncinate process => Minor D. P.

Relations –
Head – Anterior –●Gastroduadenal artery

● Transverse colon+transverse mesocolon
In C shaped ● Loops of small intestine
concavity of Posterior – ● IVC
duodenum ●Right renal vessels+left renal
vessels
●Right crus of diaphragm
● Bile duct
Inferior - • Third part of duodenum
Uncinate process- Anterior- superior mesenteric artery
Posterior- Aorta
Neck - Anterior – ●Pylorus( lies on the transpyloric plane )
●Peritoneum of lesser sac
(L1)Transpyloric
Posterior – ● Termination of superior mesenteric vein
plane
●Beginning of portal vein
Body - Anterior – ● Lesser sac & stomach

Posterior – Slops upwards and to the left renal
Inferior mesenteric vein
vein,aorta,L. crus,L.Psoas to the hilum joins the splenic vein over
of kidney. left psoas in front of renal
-Splenic vein plastered to post. Surface vein and behind pancreas.
Inferior – ●Duodenojejunal flexure
●Splenic flexure
Superior – Splenic artery runs along the superior boarder.
iv. Tail = Lies in - the lienorenal .lig.

Contact with – Visceral surface of the Spleen
Blood supply
• Mainly from splenic artery.

• Head- superior and inferior pancreatico duodenal arteries.
• Venous drainage – accompany arteries.
• Splenic vein
• Head Superior pancreatico duodenal veins portal vein
Inferior pancreatico duodenal veins Superior mesenteric vein
Lymph drainage
Colic
Head Neck Pancreaticosplenic nodes
Superior mesenteric

Clinical – 1.Carcinoma of head of the pancreas - may cause obstruction of the bile duct 2.Pancreatitis – fluid collect in
the lesser sac = Pseudocyst(or by posterior gastric ulcerations)
Spleen
Surface anatomy
(Points) – Left side

1. Axis – 10th rib directed downwards forwards and laterally
5. Lateral end – Mid axillary line
*Must be enlarged 3 times than normal to be palpated

Important Facts
1) 1 X 3 X 5 inches
7 ounces
Lies deep to the left 9th to 11th ribs
2) Lies obliquely along long axis of the
10th rib
3) Impressions on visceral surface
i. Gastric – Fundus of
Stomach
ii. Renal – L. Kidney
iii. Colic – Splenic Flexure
Pancreatic – Tail of
pancreas
7 ©2015 A/L Repeat
Campaign
Ligament Extend Contents
1.Gastrosplenic Greater curvature of the stomach to Short gastric vessels
Hilum of spleen L. Gastro-epiploic vessels
2. Linorenal Hilum of spleen to Tail of pancreas

anterior surface of left kidney Splenic vessels
Pancreaticosplenic lymph nodes
Forms the left lateral extremity of the lesser sac


Clinical –
1. Thin tense capsule - Commonest intra abdominal structure to rupture
2. Normal spleen is not palpable
Splenomegaly- Spleen enlarge along the axis of the 10th rib =>Right iliac fossa
Notch on its anterior border felt under the left costal margin
3. Splenectomy – Tail of the pancreas & contents of the lig. should be preserved Only
one segment can be removed, due to segmental blood supply
Can be cut into small pieces & implanted within the greater omentum
4. Splenic puncture – through 8th or 9th intercostal space in midaxillary line, using L. Puncture needle
5. Splenic Infarction – since splenic A. are end-arteries, can be obstructed
Referred Pain
Referred pain is a term used to describe the phenomenon of pain perceived at a site adjacent to or at a distance
from the site of an injury's origin.
1. Biliary tract – stretch of GB or CBD

• Epigastrium& R. hypochondrium => T7 to T9
• R. shoulder tip => C4 via R. phrenic N.
• Inferior angle of R. Scapula
2. Spleen – Splenic Infarction
•Epigastrium => T7
•L. Shoulder tip (Kehr’s sign) => C4 via L. phrenic N.
3. Appendix - appendicitis
•Umbilical region – 1st felt => T10
•Right iliac fossa - increased inflammation =>Inflamed appendix touches the parietal peritoneum
4. Pancreas - Pancreatitis
•Epigastrium => T6 to T10
•Posterior paravertebral region =>inflamed soft tissues of retro-peritoneum
5. Kidney
• Lumbar region of back
• External genitalia of Anterior abdominal wall
=>T12 to L1 via sympathetic fibers
6. Ureter
• Renal colic – severe pain due to a ureteric stone
• Pain starts in the loin & radiates down the groin, the scrotum or labium majus & the inner thigh [Pain
is referred to the cutaneous areas innervated by segments, mainly T11 & L2 which also supply
the ureter]
7. Uterus .
• corresponding dermatomes =>T10-L1 via sympathetic fibers
8. Ovary.
• loin& groin =>T10-T11 via Aortic plexus

Superficial Lymphatic Drainage – Thoracic and Abdominal wall
Some may drain to

Axillary lymph nodes parasternal and inferior
deep cervical lymph
Ant – pectoral nodes.
Post - scapular
Upper half of trunk above

the umbilicus
Watershed line Umbilical level
Lower half of trunk below

the umbilicus
Superficial inguinal lymph nodes

Anterior- medial
group
Superficial
inguinal lymph
Lateral & Lateral nodes
posterior - group
(flank too)
Parasternal
Deep lymphatic of the thoracic wall nodes
Intercostal nodes

Deep Lymphatics – Thorax
1. Esophagus
2. Pericardium
(Left) Thoracic duct
Intercostal Right Lymphatic duct
Posterior mediastinal
Bronchomediastinal
lymph trunk Diaphragmatic Liver
Cysterna chyli through
bare area
Paratracheal Brachiocephalic Parasternal
1. Thyroid Lymphatics
2. Thymus around
3. Pericardium and heart sternum
Tracheobronchial
Deep Superficial
Lungs
(pulmonary) (sub-pleural)

Lymphatic Drainage – Abdomen
Thoracic
duct
Cysterna chyli
Supra-renal Duodenum
kidney Para-aortic Coeliac

Cecum &
appendix
ureter
Common
iliac Jejunum &
Superior Ileum
Mesenteric
External iliac Internal iliac

Colon
Inferior
Mesenteric
Deep inguinal
lymph nodes
1st group 2nd group 3rd group
• Adjacent to peritoneum • Intermediate nodes • Pre-aortic nodes

• Mural nodes (along main blood (at origin of coeliac, superior
• Paracolic nodes vessels) mesenteric, inferior mesenteric arteries

Deep Lymphatics – Abdominal Viscera
Liver Bare
(except bare + area
area)
Nodes in posterior
Hepatic Gall
mediastinum
nodes bladder
Sub Pyloric Cystic

nodes nodes
Coeliac
nodes Up Uncinate
Pancreas To the left
Head process
of neck Down
Pancreaticosplenic
Spleen Hilar nodes nodes
Superior mesenteric nodes

Right gastric nodes Left gastric nodes
Left gastro-epiploic
nodes
Right gastro-epiploic
nodes Clinicals
In gastric carcinoma, left supra clavicular nodes
may rarely become palpably involved (troisier’s
sign) presumably by spread along thoracic duct

POSTERIOR ABDOMINAL WALL
• Made up of 3 bony & 4 muscular structures
• Bones- Bodies of lumbar vertebrae
Sacrum
Wings of ilium
(11th &12th ribs)
• Muscles - Diaphragm
Quadratus lumborum
Psoas major & minor
Iliacus
Psoas major
• Origin - transverse process of all lumbar vertebrae
Side of the bodies (T12-L5 )
Intervening discs (T12-L5 )
• Insertion - lesser trochanter of femur
• Action – flexion of the hip joint
 roots of lumbar plexus lies within the substance of the muscle.
 Genitofemoral nerve - front of psoas
 Femoral, Iliohypogastric, ilioinguinal, lateral femoral cutaneous nerves,Femoral nerve
- lateral border
 Obturator & lumbosacral trunk - medial border
• Nerve supply - first 3 lumbar nerves
 Psoas fascia - invests the surface of psoas major

- Attached to vertebral bodies, fibrous arches & transverse processes
- Thickening ,curving from body of L1 - medial arcuate ligament
Clinical
 Psoas abscess
− enclosed in sheath
− pus from tubercular infection may tract down through the sheath in to the thigh
− soft swelling in the femoral triangle
Iliacus
• Origin - Upper 2/3 of iliac fossa,Anterior sacroiliac and iliolumbar ligament.
• Insertion - lesser trochanter of femur along with the psoas tendon
• Nerve supply - femoral nerve (L2-L4)
 Iliac fascia - covers iliacus muscle

Attached to the margins of the muscle & to the inguinal ligament
Quadratus lumborum
• Origin - transverse process of vertebra LV, the iliolumbar ligament, and the adjoining
part of the iliac crest
• Insertion - attach superiorly to the transverse processes of the first four lumbar
vertebrae and the inferior border of rib XII.
• Nerve supply - anterior rami of T12 and L1 to L4 spinal nerves.

Thoraco lumbar fascia
 enclose deep muscles of the back
 3 layers, enclose 2 muscle compartments as anterior & posterior
− anterior layer → forms lateral arcuate ligament only the lumbar region
− middle layer
− posterior layer → extends above, to the lower part of the neck and below the dorsal
surface of the sacrum
 Anterior muscle compartment - quadratus lumborum

 posterior muscle compartment - erector spinae
Abdominal aorta

-
Enters the abdomen behind the median arcuate ligament Behind peritonium slightly
inclining to left.
Inferior phrenic arteries Supra renal branches

(slights upwards over th crus of the diaphrgm)
T12 Coeliac trunk Left

(Behind posterior wall
of lesser sac)
Supra renal arteries
Right
(Behind IVC)
Crossed by the splenic vein and
body of pancreas
L1 Left
Superior mesenteric artery
• Short
• Crosses left crus & psoas behind
left renal vein
• Covered by tail of pancreas &
splenic vessels
L2 Renal arteries
(At right angle)
Right
• Long
Crossed by left renal vein
• Crosses right crus & psoas
behind IVC & right renal vein
Crossed by uncinate process
Crossed by 3rd part of duodenum

Testicular artery – enters deep
inguinal ring, runs in
Gonadal arteries the spermatic cord
Ovarian artery – enters the
suspensory ligament
L3 Inferior mesenteric artery
Lumbar arteries 4
(Leave the aorta opposite the
bodies of L1-L4)
Divide in to common iliac arteries

L4 (Pass in front of sacroiliac joint, ureter Median sacral artery-Posteriorly arises
lies in front)
Porto systemic anastomosis
Site Systemic vein Portal vein In portal

hypertension
Lower end of Oesophageal branches of the Oesophageal Hematemesis
oesophagus azygos system branches of left (vomiting of blood)
gastric vein
Anal canal Inferior rectal branch- Superior rectal Hemorrhoids
internal iliac vein branch- inferior
mesenteric vein
Around Veins of abdominal wall Portal branches of the Caput medusae
umbilicus liver
Bare area of Veins of diaphragm Portal branches of
liver liver
Posterior Renal,lumbar & phrenic veins Portal tributaries in
abdominal mesenteric &
wall mesocolon
Portal vein
• Formed by superior mesenteric + splenic vein
• Behind the neck of the pancreas
• Relations
 Infraduodenal part
Anteriorly – neck of pancreas
Posteriorly – IVC
 Retroduodenal part
Ant. - 1st part of duodenum
Common bile duct
pancreas
Gastroduodenal artery
Post. – IVC
 Supraduodenal part - between the 2 layers of the free edge of lesser omentum
Ant . – hepatic artery
Bile duct
Post. - Epiploic foramen
• Tributaries
− Splenic vein
− Superior mesenteric vein
− Left gastric vein
− Right gastric vein
− Superior pancreatico duodenal vein
− Periumbilical vein
− Cystic vein
• Branches
Right – shorter & wider
Receive cystic vein
Left - longer & narrower
Receive paraumbilical vein
Ligamentum teres
Ligamentum venosum

Inferior Vena Cava
Right common iliac vein Left common iliac vein
Iliolumbar vein
Median sacral vein
Lateral sacral vein
Inferior Vena Cava (L5) -runs right to midline
3rd & 4th lumbar veins

(1st & 2nd lumbar veins join ascending
lumbar vein
2 Right gonadal veins 2 venae

commitantes unite on psoas
Right gonadal vein
2 left gonadal veins unite on psoas

Left renal vein
Left gonadal vein
(3 times long as right, crosses
aorta)
Left suprarenal vein
Right renal vein
Right supra renal

vein
Inferior phrenic veins

Below liver
Left hepatic vein Middle hepatic Right hepatic vein

vein
T8 (Pierce the central tendon of the diaphragm)
Drain to the right atrium

Sympathetic trunk (lumbar part)
• Ganglionated chain situated on either side of lumbar vertebrae.

• Continuous with thoracic part of sympathetic trunk deep to medial arcuate ligament.
• Runs vertically downwards along medial margin of psoas major and across lumbar
vessels.
• On the right side it is overlapped by inferior vena cava and on left side by the aortic
lymph nodes.
• Chain ends by becoming continuous with the sacral part behind common iliac
vessels.
• Lumbar ganglia are usually 4.
• White rami communicantes from first 2 lumbar nerves, join the trunk and relay in
lumbar and sacral ganglia.
• Gray rami communicantes from lumbar ganglia accompany the lumbar arteries,
around the sides of the vertebral bodies, medial to the fibrous arches to join the
anterior rami of lumbar nerves, for distribution to the body wall and lower limb,
through the branches of lumbar plexus.
Autonomic plexuses
• Coeliac Situated anterior to the aorta

• Superior mesenteric containing sympathetic and
• Inferior mesenteric parasympathetic which supplies
• Superior hypogastric abdominal viscera.
 Fibers pass downwards into pelvis from superior hypogastric plexus as the
hypogastric nerves to form the inferior hypogastric plexus with pelvic splanchnic
nerves.
Somatic nerves
Lumbar plexus
Formed by anterior rami of upper 4 lumbar nerves.
• L1 - iliohypogastric & ilioinguinal
− Skin over the inguinal region & front of the scrotum
− Motor supply for the internal oblique & transversus abdominis
• L1,L2 - genitofemoral
Genital branch - Sensory to tunica vaginalis & spermatic fascia
Motor to cremaster muscle
Femoral branch – supplies an area of skin below the middle of the inguinal ligament
• L2,L3 (posterior division) - lateral femoral cutaneous
− Wholly sensory to the iliac fascia & peritoneum of the iliac fossa &
− To the lateral side of the thigh down to the knee.
• L2,L3,L4 (posterior division) - femoral
• L2,L3,L4 (anterior division) - obturator

KIDNEY
Location
 Retroperitoneal – in the paravertebral gutters
 Long Axis – Parallel with the lateral border of the Psoas major
 Vertically – (Approximately) From Upper border of T12 Body of L3 vertebra
 Hilum – directed anteromedially
Left hilum
Transpyloric plane
Right hilum
 Side differences –
o R. kidney little lower => Liver Superiorly located
o R. kidney little away from the mid-line => IVC Medially located
o R. kidney lies anterior to 12th rib, while L. kidney lies anterior to 11th & 12th ribs
Relations
- Posterior – similar to both kidneys
 Diaphragm & quadratus lumborum muscles
 Behind the diaphragm – costodiaphragmatic recess
 Medially overlaps (hilum) – Psoas major
 Laterally overlaps – Transversus abdominis
 Upper pole – Medial &lateral arcuate ligaments
 Emerging beneath the lateral arcuate ligament – Subcostal vein, artery and
nerve
 Emerging from the lateral border of psoas major – Iliohypogastric & ilioinguinal nerves
- Anterior Right Left

Superior R. Suprarenal gland L. Suprarenal gland
Liver Stomach & Spleen
Peritoneum of hepatorenal Peritoneum of lesser sac medially
pouch (greater sac) Peritoneum of greater sac laterally
Middle 2nd part of Duodenum Body of the pancreas
Splenic A. & V.
Lateral Hepatic flexure Splenic flexure of colon
Inferior Beginning of Descending colon
Medial Small intestine Jejunum
1
Medial
Above the hilum - Suprarenal glands
Below the hilum - Ureter
Lateral
Right kidney Left kidney
Right lobe of the Liver Spleen
Hepatic flexure of the colon Descending colon
Relations of the hilum (Ant to Pos - VAP)

Renal vein (V)
Renal artery (A)
Renal pelvis (P)
Coverings (inside to outside)

1. Fibrous/true capsule - easily stripped off in normal
2. Perinephric fat (fatty capsule) - fills up extra space in renal sinus
3. Renal fascia/false capsule –

Condensation of the Areolar tissue between parietal peritoneum & posterior abdominal wall
2 Layers – Anterior & Posterior
Superiorly
Enclose Suprarenal gland – A fascial septum forms a separate compartment for it
Then fuse with each other
Inferiorly
Two layers remain separately
Enclose ureters (fading into extraperitoneal tissue around them)
Laterally
2 layers fuse
Continues with Fascia transversalis
Medially
Anterior layer-fuse with aorta & IVC
Posterior layer-fuse with fascia covering Psoas & Quadratus lumborum
Forms a septum
4. Paranephric fat
Variable amount of fat lying outside the renal fascia
Fills up the paravertebral gutter, forming a cushion for the kidney
▪ Structure
Renal pyramids – Conical masses in the medulla
Apices of the pyramids form the Renal Papillae which indent into Minor calyces
Cortical Arches – Form the caps over the pyramids
Renal columns – Dip in between the pyramids
A lobe of the kidney – Each pyramid along with the overlying cortical arch
Renal sinus – Space extending into kidney from the Hilum, Containing
 Renal artery – branches
 Renal vein – tributaries
 Renal pelvis ( Major calyces Minor calyces Papillae)
Hilum – A deep vertical slip on the medial aspect of the kidneys extending to the Renal sinus
Level – L1 lower border [Transpyloric plane]
Renal V,A,P and Lymphatics and Nerves travel through this
2
 Blood supply
Supply each vascular segment
Venous drainage Arterial supply [END ARTERIES]
But their corresponding veins
i t ith h th
RENAL
SEGMENTAL A.
LOBAR A. One for each pyramid
INTERLOBAR
Arches over pyramid bases
ARCUATE At right angles to interlobar A
At corticomedullary junction
INTERLOBULAR
s
AFFERENT ARTERIOLES Ascends in cortex radially
At right angles to Arcuate A
GLOMERULUS [END ARTERIES]
EFFERENT ARTERIOLES
PERITUBULAR CAPILLARIES
• Renal arteries leave the abdominal aorta at right angles to it at L2 level

• They lie behind the pancreas and renal veins
Posterior division Posterior segment
• Renal artery
Apical segment
Upper segment
Anterior division
Middle segment
Lower segments
Lymphatic Drainage
Into para aortic nodes- L2 level
Nerve Supply
• Sympathetic – from T12 to L1
• Pain may be referred to back and lumbar region which may radiate to anterior abdominal wall and down to
the external genitalia
3
▪ Clinical
1. Kidney exposure
Skin
Superficial fascia
Posterior layer of TLF [Thoraco-Lumbar fascia] with
Latissimus dorsi
Erector spinae
Middle layer of TLF
Quadratus lumborum
Anterior layer of TLF
• Costodiaphragmatic recess –
 an important posterior relation
 Risk of entering it during lumbar approach to kidney
2. Renal angle – Angle between 12th rib-lower border & Erector spinae-outer border
▪ Enlarged kidney – Lower pole Bimanually palpated, on deep inspiration
3. Perinephric Abscess – Blood from ruptured kidney or pus
▪ Can’t cross to opposite side – prevented by the fascial septem
▪ Can descend in to the pelvis – along the covering of ureter
4. In Renal Failure –
o Kidney Transplantation – In recipient’s pelvis
o Peritoneal Dialysis or Haemodialysis
5. Polycystic kidney – Leads to hypertension
o In children => Autosomal Recessive – Form from collecting ducts
o In Adults => Autosomal Dominant – Form from all segments of the nephron
Ureter
 Throughout extraperitoneally
 25cm
Constrictions
1. Pelvi-ureteric junction
2. Pelvic brim
3. Passage through bladder wall
(narrowest at all)
▪ Course
1) Abdominal part
• Begins within renal sinus=renal pelvis
• Renal pelvis lies along medial border of kidney behind it
• At lower pole it becomes ureter proper
• Lies on Psoas major, underneath the peritoneum
• Crosses in front of the genitofemoral nerve
• It descends in front of tips of transverse processes of L2-L5
Crossed By [Anteriorly]
Right Both Sides Left
3rd part of Duodenum Gonadal vessels Left colic
Right colic Genitofemoral N. [Posteriorly]
Ileocolic
Root of the mesentery of small intestine
2) Pelvic part
• Passes anterior to the bifurcation of the common Iliac A.
o At pelvic brim + In front of Sacroiliac jnt. + Level of lumbosacral disk
o Left side – In the Intersigmoid recess [Under the apex of Sigmoid mesocolon]
• Goes along the curvature of greater sciatic notch & anterior to Internal Iliac A.
• Reaches ischial spine & turns forwards & medially
MALE FEMALE
Crossed By - [Superiorly from Lateral to Medial]
Ductus deferens Uterine artery
Lies - [Superior to]
Seminal vesicles Lateral fornix of vagina
3) Intravesical part
• Enters the bladder at an acute angle
• Obliquity of the course produces a sphincteric function
4) Nerve supply
- Sympathetic => T10 to L1 Parasympathetic => S2 to S4
5) Blood Supply
• Segmental blood supply
• Upper end – ureteric branch of renal artery
• Middle – abdominal aorta, gonadal, common iliac, internal iliac
• Lower end – superior and inferior vesical, uterine artery
Clinical
1. Ureteric Stones [Calculus]
- Lodge in constricted sites of ureter
- Renal [Ureteric] Colic => Due to spasm of the ureter
Severe pain – radiates from Loin to Groin,Referred toTestis
- In X-rays =>
 Postero-Anterior View - Ureteric stones – At the tip of transverse processes of lumbar vertebra
 Lateral view - Ureteric + Kidney stones – On the body of vertebra GB stones – Anterior to the body of
vertebra
Supra renal gland

• Lies antero superiorly to each kidney
• Lies within its own compartment formed by renal fascia
• Shape –
 Right – pyramidal
 Left - crescentic
Two parts
- Cortex -- mesodermal origin
- Medulla -- neural crest origin
 Right supra renal gland apex related to bare area of liver
5
 Blood supply
o Arterial supply
 Superior suprarenal artery – from inferior phrenic artery
 Middle suprarenal artery – abdominal aorta
 Inferior suprarenal artery- renal artery
o Venous drainage
 Right suprarenal vein – to IVC
 Left suprarenal vein – right renal vein
 Lymph Drainage
To para aortic lymph nodes
 Nerve Supply
Preganglionic sympathetic fibers from splanchnic nerves via coeliac plexus
Urinary system –Histology

 Glands with highly modified secretory unites and highly specialized ducts
Renal corpuscles - Afferent arteriole

Intervening space/ mesangium
Bowman’s capsule
Part of tubules Type of epithelium Special features
PCT Simple cuboidal Microvilli (brush border)
Extensive basolateral interdigitation
Plentiful mitochondria
Pars recta of proximal tubule Simple cuboidal Microvilli (brush border)
(thick descending limb) No basolateral interdigitation
Thin descending/ascending Simple squamous No basolateral interdigitation or microvilli
limbs Mitochondria scanty
Thick ascending limb Simple cuboidal Microvilli absent
DCT Simple cuboidal Extensive basolateral interdigitation
Mitochondria plentiful
Collecting tubule Simple cuboidal Principal cells
Intercalated cells
Collecting tubule cells
Cortical collecting ducts Simple columnar Principal cells
Intercalated cells
Medullary collecting ducts Simple columnar Mainly principal
DIFFERENCES BETWEEN PCT AND DCT

PCT DCT
Lumen- not clear Open and clear
Cells size- larger than DCT cells Smaller than the PCT cells
Nuclei- less in cross section More in cross section
Brush border- present due to micro villi Absent
URETER
4 Layers
1. Transitional epithelium – Withstand to toxic substance & stress in the lumen
[Urothelium]
2. Lamina propria – Collagen
3. Muscular layer – Inner Longitudinal
Outer Circular
Outermost Longitudinal [In lower 1/3rd ONLY]
4. Adventitia – Loose collagen [Contain Blood vessels, Lymphatics, Nerves]
• Bladder is histologically similar to the structure of lower 1/3rd of the Ureter
6
PELVIS
1. Bony Pelvis formed by 4 bones united by 4 joints
• 2 hip bones anteriorly by pubic symphysis (2ry cartilaginous joint)
• Sacrum & coccyx by sacrococcygeal joint
• Sacrum & 2 hip bones each side by 2 sacroiliac joints
2. Bony pelvis is divided into true pelvis & false pelvis by,
Pelvic brim (pubic crest, pectinate line of pubis, arcuate line of ilium, ala & promontory of sacrum)
Pectineal line of pubis
3. The plane of the pelvic brim is oblique, lying at 600 with the horizontal plane (the vagina lies in the same plane)
4. Pelvic floor slopes downwards and faces forwards (so that the anterior superior iliac spine (ASIS) and the upper
border of the pubic symphysis lies in the same coronal plane)
True pelvis ASIS

Superior
aperture
Pelvis False pelvis Head of Ischial spine
the femur
Inferior Perineum
aperture
Upper border of
pubic symphysis Apex of Tip of the
greater coccyx
Boundaries of true pelvis trochanter
1. Upper border of pubic symphysis
2. Pubic crest
Pelvic 3. Pubic tubercle
4. Pectineal line
inlet
5. Arcuate line
6. Sacral promontory
1. Lower border of pubic symphysis

Pelvic 2. Ischio pubic rami
outlet 3. Ischial tuberosity
4. Sacrotuberous ligament
5. Coccyx
Stability
Joint Bony factors Ligamentous factors
1.Lumbosacral Widely spaced inferior Strong iliolumbar ligament (prevents forward
Articular disc is very thick; articular processes of L5 movement of sacroiliac joint)
thickest anteriorly • From – transverses process of L5 to iliac crest
Lumbo sacral ligament
• From – transverse process of L5 to ala
2. Sacroiliac joint Interlocking articular Thick & strong interosseous ligament
Anterior, interosseous, surfaces Vertebro pelvic ligaments (Iliolumbar, sacrotuberous,
posterior sacroiliac ligaments sacrospinous ligaments)

Sex differences
• Due to easier passage of fetal head in labour
• female bones are more slender than male bones
Male Female
1.Pelvic inlet Heart shaped Oval shaped
2.Sub pubic angle Acute (angle between index & middle Wide (angle between thumb & index
finger/gothic arch) finger/roman arch)
3.Pelvic canal Long & tapered (long segment of a short Short, with almost parallel sides (short segment
cone) of a long cone)
4.Pelvic outlet Comparatively small Large
5.Ischial tuberosities Inturned Everted
6.Sacrum Long & narrow with little concavity Short & wide, curving forward in lower part
Identify the sex from a X –ray by the shadow of the penis
Obstetrical Pelvic measurements
1. transverse diameter of the outlet- distance between the ischial tuberosities along a plane of the anus
2. anteroposterior outlet diameter-distance from the pubis to the sacrococcygeal joint.
3. diagonal conjugate—from the lower border of the pubic symphysis to the promontory of the sacrum.
Clinical
Caudal anaesthesia
The sacral hiatus, between the last piece of sacrum and coccyx - entered by a needle which pierces skin, fascia
and the tough posterior sacrococcygeal ligament to enter the sacral canal.
Pelvic fascia
• Parietal pelvic fascia on the pelvic surface on Obturator Internus with periosteum at the upper margin of the
muscle.
• The sacral anterior primary rami emerging from the anterior sacral foramina lie behind the Piriformis fascia.
• Internal iliac vessels, are in front of the fascia over the Piriformis; but large (presacral) lateral sacral veins lie
initially behind this fascia as they emerge from the anterior sacral foramina.

Pelvic muscles
Piriformis
• origin – front of the middle 3 pieces of its own
half of the sacrum
• sacral plexus and sacral nerves lie on the muscle
• pelvic surface of the muscle and sacral plexus are
covered by pelvic fascia.
Obturator Internus
• origin – from the whole Obturator membrane and from the bony margins of the foramen
• leaves the pelvis through the lesser sciatic foramen; a bursa separates the body ridge from the tendon at the
lesser sciatic foramen
Postanal plate/anococcygeal ligament/median fibrous raphe

• Layered musculotendinous structure between the anal canal and the caudal part of the vertebral column, on
which the terminal rectum sits.
Pelvic diaphragm
Levator ani
• Nerve supply from the S4 sacral nerve & inferior rectal nerve
• Arises from the posterior aspect of the body of the pubic bone, the fascia of the side wall of the pelvis
(covering obturator internus/white line) and the spine of the ischium.
• Contain 2 parts
1. Pubococcygeus
 Levator prostate/Sphincter vaginae
o Anterior fibres
o form a sling around the prostate/vagina
o In both sexes, fibres also attach to the perineal body
 Puborectalis
o Middle fibres
o inserting into the perineal body to form a sling around the rectum and also insert into
deep part of the longitudinal muscle coat of the anal sphincter at the anorectal ring
 Pubococcygeus proper
o Posterior fibres
o attached to the sides of the coccyx and to the median fibrous raphe, which stretches
between the apex of the coccyx and the anorectal junction.
2. Iliococcygeus
o posterior half of the white line & ischial spine
Coccygeus (3. Ischiococcygeus part of pelvic diaphragm)

• Nerve supply from S4 & S5 sacral nerves
• Arises from ischial spine & sacrospinous ligament and insert to the side of the coccyx and the lowest piece of
the sacrum.
Actions
1. Acts as the principal support of the pelvic floor
2. Has a sphincter action on the rectum and vagina
3. Assists in increasing intra-abdominal pressure during defaecation, micturition and parturition.

Superior vesicle
• Umbilical artery (medial umbilical artery)
Pelvic vessels • Adjacent ureter, vas deferens
Obturator
• Periosteum of back of pelvis
• Accessory/abnormal obturator artery can arise
from the inferior epigastric artery*
Uterine
• Uterus, cervix, uterine tube
Anterior
Uterine
division
Vaginal
• Upper part of vagina
Inferior vesical
• Trigone, lower bladder, vas deferens
Internal iliac Middle rectal (frequently absent)
Internal pudendal
• Leaves the pelvis through the greater sciatic foramen below the piriformis
• Anal region, external genitalia
Inferior gluteal
• Leaves the pelvis through the greater sciatic foramen
below the piriformis
Anterior (lateral)
• Psoas, Quadratus lumborum
Lumber branch (5th
lumbar segmental
artery) Posterior
• Erector spinae
iliolumbar Spinal branch
Iliac branch
• Iliac fossa, iliacus, iliac
bone
Posterior Anastomosis
Lateral sacral around ASIS
division
• Piriformis
Spinal branches
Superior gluteal
• Leaves the pelvis through the greater sciatic
foramen above the piriformis
Bladder
• Pelvic organ; as the bladder fills, it
domes into the abdominal cavity.
• Trigone of the bladder
o Least mobile part of the bladder
o Mucous layer tightly adhered
• Blood supply; mainly by superior and
inferior vesical arteries. Veins do not
follow the arteries; instead forms the
vesicoprostatic plexus in the groove
between the bladder and prostate,
which drain into internal iliac vein.
• Lymph drainage is mainly into external iliac nodes.
• Nerve supply;
o Sympathetic (vasomotor & inhibitory to Detrusor muscle) – superior and inferior hypogastric plexus
(L1,L2)
o Parasympathetic (motor and sensory) – Pelvic splanchnic nerves
Relations
• Empty bladder is tetra hedral in shape.
• Has an apex, base, neck, superior surface and 2 inferolateral surfaces.
o Apex lies anteriorly in the Retropubic space (of Retzius)
o Base lies posteriorly
o Superior surface is covered by the peritoneum (distending bladder strips the peritoneum from
behind rectus abdominis, leaving transversalis fascia on the back of the muscle)
o Neck
 In the male; lies against the upper surface or the base of the prostate
 In the female; lies above the urethra in the connective tissue of the anterior abdominal wall
1. Anteriorly - the pubic symphysis.

2. Superiorly - the bladder is covered by peritoneum with coils of small intestine and sigmoid colon lying against it.
In the female; the body of the uterus flops against its posterosuperior aspect
3. Posteriorly - in the male; the rectum, the termination of the vas deferens and the seminal vesicles
in the female; the vagina and the supravaginal part of the cervix (with no peritoneum intervening)
4. Laterally - the levator ani and obturator internus
Supports of the bladder

1) Lateral true ligament
True ligaments 2) Lateral puboprostatic ligament
(condensation 3) Medial puboprostatic ligament
of pelvic fascia) 4) Urachus
5) Posterior ligament
Ligaments
False ligaments 1) Median umbilical fold
(condensation 2) Medial umbilical fold
of peritoneum) 3) Lateral false ligament

Perineum
Diamond shaped region positioned inferior to the pelvic diaphragm between thighs at lower
end of the trunk
Inferior boder of pubic symphysis
Urethral opening Urogenital Hiatus
Ischiopubic ramus
Vaginal opening Urogenital triangle
Ischial tuberosity
Anal aperture
Sacrotuberous ligament,
covered by inferior border
Anal triangle of gluteus maximus
Perineum boundaries: - Peripheral – Pelvic outlet

Roof – Pelvic diaphragm
Lateral walls – Pelvic cavity walls below the origin of levator ani
Anterior point – inferior border of pubic symphysis

Posterior point – tip of the coccyx
Lateral points – anterior of ischial tuberosity
Lateral borders – Anterior – ischiopubic rami
Posterior – sacrotuberous ligament
Anal tringle Urogenital triangle

• Anal canal • External genitalia
• Ischioanal fossae
Cutaneous supply
1. Inferior rectal nerve 1. Ilioinguinal nerve (L1) - anterior third of the scrotum
2. Perineal branch of S4 (labium majus)
3. Twigs from coccygeal plexus 2. Dorsal nerve of penis (clitoris) (S2) – branch of
pudendal nerve
3. Posterior 2/3rd of scrotum
a. Medially – scrotal branches of the perineal
branches of pudendal neve
b. Laterally – perineal branches of the posterior
cutaneous nerve of thigh

Anal triangle
Ischio-anal fossa (Ischio-rectal fossa)
wedge shaped space filled with fat either side of anal canal Below the pelvic diaphragm.
• Base- skin over the anal triangle of perineum

• medial wall – external anal sphincter and levator ani
• lateral wall- Obturator Internus and its fascia below the attachment of levator ani
muscle and ischial tuberosity
• Apex- medial and lateral wall meeting
• Base
 Anterior- posterior border of perineal membrane
 posterior- Sacro tuberous ligament overlapped by lower border of gluteus
maximus
Anterior recesses of Ischioanal fossa
Arrangement of fat lobules Lies above the perineal membrane as far as the
upper part - large lobules perineal surface of body of the pubis
lower part -small lobules
(adjacent to skin)
Clinical
1. Abscesses can be ruptured internally or externally into the anal canal or to the surface of perineum –
anorectal fistula.
2. Ischiorectal fossa acts as a cushion giving support to rectum & anal canal.
3. Anteriorly infection of one space can't communicate across the mid line, but posteriorly communicate
through horse shoe shaped path
Pudendal canal
connective tissue tunnel on the lower lateral wall of the ischioanal fossa
splitting of the obturator fascia (fascia

posterior border of the
lesser sciatic foramen lunata ) above the falciform process
perineal membrane.
Contents – 1. Pudendal nerve 2. internal Pudendal vessels
arches convexity upwards through ischioanal fossa towards anal canal
inferior rectal branch

Perineal body (Central Tendon of Perineum)
midline fibromuscular mass attached to the posterior border of perineal membrane

between anal canal and Vagina / bulb of the penis
Attachments: -
• external anal sphincter
• pubovaginalis / puboprostaticus of levator Ani.
• Bulbospongiosus
• Superficial transverse perineal muscle
• deep transverse perineal muscle
action: -
stabilizing influence for pelvic and perineal structures
Weakness causes prolapse of the vagina and uterus.
Urogenital Region
Superior fascia of urogenital diaphragm
Deep perineal space (pouch)
Deep transverse perineal muscles

Urogenital diaphragm Sphincter urethrae
+
Membranous part of urethra
pudendal vessels
Inferior fascia of urogenital diaphragm
Perineal Membrane
Anteriorly – anterior free border

• Base of penis and penile musculature are fixed
• transverse perineal ligament
• When upright standing horizontal
Laterally attached to
• Membrane is pierced by urethra ducts of
• ischio pubic ramus
bulbourethral glands, Nerves and vessels
Posteriorly attached to
• centrally perineal body
Pubic arcuate ligament
deep dorsal vein of penis Vasicoprostatic venous plexus
Transverse perineal ligament

Deep perineal space
Boundaries Male Female
Superficial Perineal membrane Same
Deep Superior fascial layer of urogenital diaphragm Same
Laterally Ischiopubic rami Same
Posteriorly Closed by fusion of superior & inferior fascia Same
of urogenital diaphragm
Anteriorly Closed by fusion of superior & inferior fascia Same
of urogenital diaphragm
contents ●membranous Urethra ●Urethra, vagina
●Deep perineal muscles ●Same
●Bulbourethral glands ●no glands
●Nerves( branches of pudendal nerve) ●Same
Superficial perineal space

Boundaries Male Female
Superficial Colles fascia Same
Deep Perineal membrane Same
Laterally Ischiopubic rami Same
Posteriorly Closed by fusion of the colles fascia Same
& the perineal membrane
Anteriorly Continuous with spaces of scrotum, Continuous with spaces of clitoris,
penis, anterior abdominal wall anterior abdominal wall
contents ●Root of penis with urethra ●Clitoris, urethra & vagina
●Superficial perineal muscles ●Same
●No glands ●Greater vestibular glands
●Nerves (branches of perineal bran ●Same
ch of pudendal nerve)
Superficial perineal fascia of Colles

Continuation of the Scarpa’s fascia of anterior abdomen wall
attached → ischiopubic rami and post margin of the perineal membrane
• encloses superficial perineal space
bulbous scrotal expansion cylindrical penile expansion
attached round the corona of the glans penis

Pudendal nerve Branches –
Pudendal nerve 1. Inferior rectal nerve
2. Perineal nerve
Origin -anterior primary rami of S2,3,4
3. Dorsal nerve of penis or clitoris
Course –
o 3 parts- pelvic region, gluteal region, ischiorectal
fossa
3
o leave pelvis through greater sciatic foramen
below piriformis
o to enter gluteal region 2
o crosses dorsum of ischial spine
o relations in gluteal region - PIN
o through the lesser sciatic foramen enter into
pudendal canal 1
o travels along lateral wall of ischiorectal fossa
o accompanied by internal pudendal vessels
Clinical
Pudendal nerve block Inferior rectal nerve
Needle passes through
vaginal wall to ischial
spine guided by finger
OR
Just medial to ischial
tuberosities

Internal Pudendal Artery
In the pudendal canal
Inferior Rectal artery

Enters the deep perineal pouch and
runs along the ischiopubic ramus.
Pierce the perineal membrane

at the posterior angle.
Perineal Artery Artery to the bulb

Corpus spongiosus
Anterior Anastomose at
Transverse Posterior
margin of
scrotal artery Glans penis
perineal artery perineal
membrane
Deep artery of the penis Dorsal artery of the penis
Enter the crus Between crus and pubic

symphysis to pierce
suspensory ligament
Helicine arteries
Skin, fascia of penis
Supply cavernous
 Inferior Rectal Artery-

At the pudendal canal arches over in the ischiorectal fossae.

Rectum and Anal canal
Rectum
• Continuation of sigmoid colon at the level of S3

• from the rectosigmoid junction to the Anorectal junction
• 12cm long
• In front of lower 3 pieces of sacrum and coccyx
• No taenia coli, sacculations, appendicises epiploicae
• Lower part is dilated to form the rectal ampulla
• Direction of the rectum
 Downwards & backwards Downwards
Downwards & forwards
• Shows lateral and antero-posterior curvatures
• 3 lateral curvatures which are convex to,
1. Right
2. Left Due to mucosal folds
3. Right
• 2 Antero-posterior curvatures
1. Sacral flexure – due to concavity of sacrum and coccyx.
2. Perineal flexure – due to backward bend at the anorectal junction.
Relations
Peritoneal relations
upper 1/3rd front and side
middle 1/3rd only the front
lower 1/3rd below the level of peritoneum
visceral relations
Posterior – [female, male similar]
o Waldeyer’s fascia
o Sacrum, coccyx
o Median sacral, superior rectal vessels
o Sympathetic trunk
Anterior – [Male]
Denonvilliers fascia
Upper 2/3 – rectovesical pouch
Lower 1/3 – base of bladder
Ductus deferens
Seminal vesicles
Anterior - [Female]
Denonvilliers fascia
Upper 2/3 – rectouterine pouch
Lower 1/3 – lower part of vagina
Supports
1. Pelvic floor by levator ani
2. Waldeyer fascia
• Condensation of pelvic fascia behind the rectum.
• Attaches the lower part of the rectal ampulla to
the sacrum.
• Encloses superior rectal vessels and lymphatics
3. Lateral ligaments of rectum
4. Rectovaginal fascia of Denonvilliers
5. Perineal body

Anal Canal
• Terminal part of the GI tract.
• Below the level of the pelvic diaphragm.
• Lies in the anal triangle of the perineum between the right and left Ischioanal fossae.
• Length 4cm
• From anorectal junction to anus.
• Anorectal junction is marked by the forward convexity of the perineal flexure.
Relations
 Anteriorly-
• In both sexes Perineal body
• In males Membranous urethra & bulb of the penis
• In females Lower end of vagina
 Posteriorly-
• Anococcygeal ligament
• Tip of the coccyx
 Laterally-
• Ischioanal fossae
 All around-
• Sphincter muscles
Upper 2/3 Lower 1/3

Origin Hind gut-Endoderm proctodeum
Epithelium Columnar Stratified squamous
Folds Anal columns No anal columns
-vertical mucosal folds
Anal valves
-at lower ends of columns
Nerve supply Hypogastric plexus/autonomic Inferior rectal nerve
nerves Pain sensitive
Sensitive to stretch
Arterial supply Superior rectal artery Inferior rectal artery
Inferior rectal vein to
Venous drainage Superior rectal vein to inferior internal
mesenteric vein pudendal vein
(portal system)
Lymph drainage Pararectal nades Superficial inguinal nodes

Musculature of the Anal canal
1. External anal sphincter

a. Voluntary
b. 3 parts –
1. Subcutaneous
2. Superficial
3. Deep
c. extend throughout the anal canal (surrounds
the whole length of the anal canal)
d. nerve supply – Perineal branch of S4
2. Internal anal sphincter
a. extends from upper end of
anal canal to white line of
Hilton
b. Formed by the thickened
muscular coat of this part of
gut.
c. Surrounds the upper ¾ of the
anal canal.
d. Involountary
Anorectal ring
muscular ring formed by puborectalis, deep
external sphincter & internal sphincter
main support of rectum.
Blood supply of the rectum and anal canal
-Arterial supply
• Superior rectal artery
-Divide into right and left branches opposite S3
-Runs on each sides of rectum
-Pierce the muscular coat and runs in the anal columns upto anal valves
-Form looped anastomoses
• Middle rectal artery
• Inferior rectal artery
Portal vein
-Venous drainage
Splenic vein
 Major site for
portosystemic
anastomoses Superior rectal Inferior
vein mesenteric vein
Internal rectal External rectal Middle rectal

venous plexus venous plexus vein
Inferior rectal
vein
Internal iliac Internal

vein pudendal vein

Clinicals
Haemorrhoids
Haemorrhoids (piles) are dilatations of the superior rectal veins.
• 1st degree-contained within the anal canal
• 2nd degree- prolapse on defaecation
• 3rd degree- remain prolapsed through the anal orifice
Internal piles External piles

Saccular dilatations of
internal rectal Dilatation of external rectal
venous plexuses venous plexuses
Inside the anal sphincter Outside

Above pectinate line Below pectinate line
Painless Painful
Do not bleed on straining at
Bleed profusely stool.
Primary piles occur in 3,7,
11 O’ clock positions of anal
wall when viewed in the
lithotomy position.
Per rectal examination

Finger directed towards umbilicus
normal
• both sexes — the anorectal ring, coccyx and sacrum,ischiorectal fossae, ischial spines
• male—prostate, rarely the healthy seminal vesicles
• female—perineal body, cervix, the ovaries.
Abnormalities which can be detected
• within the lumen—faecal impaction, foreign bodies
• in the wall—rectal growths, strictures, granulomata
• outside the rectal wall — pelvic bony tumours, abnormalities of the prostate or
seminal vesicle, distended bladder, uterine or ovarian enlargement,collections of fluid
or neoplastic masses in the pouch of Douglas.
HEMORRHOIDS CAN’T BE DETECTED UNLESS THEY ARE THROMBOSED
Anal fissure
Caused by the rupture of one of the anal valves by passage
of dry hard stool.
Anal fistula
Fistula is an abnormal epithelialized track connecting two
cavities or one cavity with the exterior.
Anorectal abscess tend to track in various directions and
may open medially into the anal sinus, laterally into the
ischioanal fossa, inferiorly at the surface and superiorly
into the rectum.

01. The rectum
a. is related posteriorly to the 3rd, 4th and 5th sacral nerves
b. has a lining of stratified squamous epithelium
c. has a venous drainage into the superior mesenteric vein
d. sends lymph vessels to the superficial inguinal nodes
e. is a straight structure
02. The rectum

a. begins infront of the 1st sacral vertebra
b. has no mesentery
c. forms the posterior wall of a peritoneal pouch
d. in the male is related anteriorly to the seminal vesicles and prostate
e. is related anteriorly to the cervix
03. The anal canal

a. possesses an internal sphincter of voluntary muscles
b. possesses an external sphincter supplied by parasympathetic nerves
c. is adjacent to the ischiorectal fossa
d. has a lymph drainage to both the nodes around the common iliac vein and to the
superficial inguinal nodes
e. is lined by both columnar and squamous epithelium

Male reproductive system
External genitalia Internal genitalia
▪ Scrotum ▪ Epididymis
▪ Testis ▪ Ductus deferens
▪ Penis ▪ seminal vesicle
▪ Prostate
▪ Ejaculatory ducts
External genitalia
1. Scrotum: - layers
• Skin
• Superficial fascia /Dartos muscle
• External spermatic fascia- from external oblique muscle
• Cremasteric fascia-from internal oblique
• Internal spermatic fascia-from fascia transversalis
Clinical
Scrotum is supplied by widely separated dermatomes (L1 & S3)
So whole scrotum is difficult to anesthetize
2. Testis
Coverings: - Covered by the layers of the scrotum and in addition by;
• Tunica vaginalis (parietal & visceral layers)
• Tunica albuginea
• Tunica vasculosa
• Tunica Vaginalis – represents the lower persistent portion of the processus vaginalis. It’s a partial visceral
layer with a cavity in between. Covers the whole testis except for its posterior border.
• Tunica Albuginea- Dense white fibrous coat
• Tunica Vasculosa- Innermost vascular coat of the testis.
The glandular part of the testis consists of lobules which contains seminiferous tubules. seminiferous
tubules join to form the rete testis which gives rise to the efferent ductules which emerge from the
testis to enter the epididymis.
Supplied by the testicular artery and venous drainage by the pampiniform plexus of veins
Clinical
1. Referred pain: - loin
2. Varicocele: - dilation of veins in pampiniform plexus
mostly left side. Why??
• Left testicular vein drains in to left renal vein at right angle
• Tumour of the left kidney can invade left renal vein & block the drainage of left testicular vein
• Left renal vein put into spasm by adrenalin rich blood by suprarenal vein
• Pressure of the superior mesenteric artery
3. Undescended testis fails to descend into scrotum
• May rest anywhere along its course to scrotum Intra abdominally
• Inguinal canal
• External ring
• Malignancies are more prone to occur in undescended testis
4. Ectopic testis
• Testis remain in a site other than its normal course
• Abdomen
• Perineum
• Upper thigh
• Femoral canal
• Penis
• The testis is fully developed. Usually accompanied by indirect inguinal hernia

5. Hydrocele
• Condition where fluid accumulates in the processus vaginalis of peritoneum
3. Penis
Made up of
• A root (attached portion)
• Body (Free portion)
▪ Root
Made up of 3 masses of erectile tissue:
• two crura – covered by ischiocavernosus muscle
• bulb - covered by bulbospongiosus muscle. the deep surface is pierced by the urethra.
▪ Body
Composed of three elongated masses of erectile tissue
• Right and left corpora cavernosa- Forward continuation of the crura. They terminate
under the cover of the glans penis.
• Corpus spongiosum- this is the forward continuation of the bulb of the penis. Its terminal part
enlarges to form the glans penis. Traversed by the urethra throughout the whole length.

Supports of penis
Fundiform ligament Suspensory ligament of penis

(Continuation of linea alba) (Formed by scarpa’s fascia & attached to the pubic symphysis)

Male urethra
▪20cm long
▪3 parts
1. Prostatic urethra [3cm]
Posterior wall contains
o Urethral crest
o Colliculus seminalis (verumontanum) – prostatic utricle opens here
o Prostatic sinus- openings of prostatic glands
2. Membranous urethra [2cm]

Surrounded by external urethral sphincter
3. Penile urethra [15cm]

Dilated at commencement- Intrabulbar fossa
Within glans penis – Navicular fossa
Clinical
1. Catheterization – catheter should be introduced into the urethra beak downwards???
Roof of navicular fossa bears a mucosal fold called lacuna magna. It directed forwards with can
catch the tip of catheter.
2. Urethral rupture- In damage to spongy part of urethra urine does not extravasate into
a) Thigh
b) Ischiorectal fossa
Urine passes into
a) Scrotum
b) Penis
c) Lower part of abdomen
Because the attachment of membranous layer of superficial fascia.
• Holden’s line (just below the inguinal ligament, Scarpa’s fascia joins to the inguinal ligament,
prevents urine going into thigh)
• Pubic tubercle
• Body of pubis
• Pubic arch
• Posterior border of perineal membrane
Membranous layer of abdomen continuous in to the perineum as the Colles fascia

Internal genitalia
1. Epididymis
• Organ made of a highly coiled tube
• Three parts
o Head
o Body
o Tail(inferiorly)
• Lies on lateral part of posterior border of testis
• Supplied by branches of the testicular artery
2. Ductus deferens
 45cm long thick-walled muscular tube.
 Originate from tail of epididymis
 Ascends along posterior border of testis medial to epididymis
 Enters the spermatic cord.
 Traverses the inguinal canal within spermatic cord
 At deep inguinal ring winds around inferior epigastric artery
 Along its course in the pelvic wall it is crossed by the obturator vein, artery, nerve and
obliterated umbilical artery and the ureter
 Crosses the ureter and approaches its opposite from the other side.
 Turn medially to base of bladder
 Medial to seminal vesicles and dilate to form ampulla
 Ampulla is joined by duct of seminal vesicle to form the ejaculatory duct and
 Open in to the prostatic urethra at the verumontanum on either side of utricle
3. Spermatic cord
▪ Coverings (out to inwards)
External spermatic fascia - Derived from the external oblique aponeurosis. Acquired as the
cord passes through the superficial inguinal ring.
Cremasteric fascia – derived from internal oblique and transverse abdominis muscles.
Acquired as the spermatic cord passes through the inguinal canal.
Internal spermatic fascia - derived from transversalis fascia. Acquired as the
cord passes through the deep inguinal ring.
▪ Contents
• 3 arteries
• Testicular artery - from abdominal aorta
• Cremasteric artery - from inferior epigastric. Supplies the cremesteric muscle.
• Artery of vas - from inferior vesical
• 3 veins
• Pampiniform plexus – drain as testicular vein, Right side to IVC
Left side to left renal vein
• Cremasteric vein
• Vein of ductus deferens
• 3 nerves
• Genital branch of genitofemoral supplies cremasteric muscle
• Sympathetic T 10,11
• Ilioinguinal nerve – not inside the cord but on the cord
• 3 other structures
• Ductus deferens
• Lymphatics
• Patent processes vaginalis (pathological)
4. Seminal vesicles
• Lies on each side extra peritoneally at the bladder base, between the bladder and the
rectum at termination of ductus deferens.
5. Prostate gland
• Pyramidal shape fibromuscular gland
• Apex lies inferiorly
• Five lobed
• The prostatic urethra emerges just in front of the apex. Base directed upwards and fused
with the neck of the bladder.
• Relations
• Superiorly- neck of bladder
• Inferior – apex rests on urogenital diapharagm
• Anterior – pubic symphysis separated by retropubic fat
Prostatic venous plexus
Puboprastatic ligment
• Posterior – Rectum (Separated by Denon Villiers fascia)
• Lateral – Levator ani
• Capsules
• TRUE capsule :- condensation of peripheral part of gland
• FALSE capsule :- endopelvic fascia
o Prostatic venous plexus lies between two capsules
• Zones
Peripheral zone - 70% of glandular tissue. Located behind the central zone.
Central Zone – 20% glandular tissue. Forms the base of the gland. Surrounds the ejaculatory ducts.
Transistional zone - 5% of glandular tissue. Lies around the distal part of the pre-prostetic urethra.
• Blood supply:
Supplied by the artery to the ductus deferens.
Venous drainage is to the venous plexus situated between the false and the true capsules.
▪ Clinical
1. pathological capsule
benign prostatic hypertrophy
normal peripheral part of the gland become compressed into the capsule.
2. Prostatic venous plexus has valve-less communications with vertebral venous plexus
Carcinoma of prostate may spread to pelvic bones, vertebrae & to skull
● deep dorsal vein of penis also drains in to the prostatic venous plexus
3. Denon Villiers fascia

in excising rectum, the plane passes through this without damaging prostate &
urethra act as a barrier of spreading carcinoma of prostate into the rectum
4. Prostectomy
both true & false capsules are left with venous plexus
5. Prostetic cancer
o Occurs mainly in the peripheral zone.
o The cancer may spread to the vertebral column through the vertebral venous plexus due to
the valve-less communications between the prostatic venous plexus and the internal
vertebral venous plexus.
6. Benign prostatic hyperplasia

Occurs due to enlargement of the transitional zone. Causes obstruction of the prostatic urethra
and inability of passing urine. Trans-urethral resection of the prostate is performed

Female reproductive system
1. Uterus
▪ Peritoneal attachments
1. Anterior ligament or uterovesical fold
2. Posterior ligament or rectovaginal fold
3. Two broad ligaments
Mesovarium-ovary to posterior layer
Mesosalpinx - part between ovarian ligament & uterine tube
Mesometrium- part below ovarian ligament
4. Suspensory ligament of ovary
▪Supports of the uterus
Primary Secondary
Broad ligament
Fibromuscular muscular Uterovesical fold
Rectovginal fold
1. Uterine axis 1. Pelvic diaphragm
2. pubocervical ligament 2. Perineal body
Cervix to pubis 3. Distal urethral sphincter mechanism
3. Uterosacral ligament
Cervix to sacrum
4. Round ligament of uterus
5. Transverse cervical ligament
Cervix to lateral pelvic wall
 angle of anteversion Is kept by round ligament & uterosacral ligament

 sphincter vaginae of pubococcygeus is partially inserted into perineal body
so it supports as well as forms a sphincter.

▪ Relations
Ant - Body :- uterovesical pouch
Cervix :- directly to bladder
Pos - Body,cervix,posterior fornix :- pouch of Douglas containing intestinal loops
Lat - Uterine tubes, Broad ligament with its contents
▪ Site of implantation posterior wall of fundus
Ureter runs forwards slightly above the lateral fornix of vagina and is 2cm lateral to
supravaginal part of cervix
Uterine artery crosses ureter superiorly at right angles from lateral to medial

▪ Clinical
- In hysterectomy ureter can be divided in the process of clamping uterine artery
- The only site where an ureteric stone can be palpated is where the ureter relates to
supravaginal cervix
2. Ovaries
▪Situated in ovarian fossa of lateral pelvic wall
▪relations
Boundaries of ovarian fossa Ant – obliterated umbilical artery, external iliac vessels
Pos - Internal iliac vessels, ureter Obturator nerve lies laterally
Peritoneal relations
• Mesovarium – attaches anterior border of ovary to broad ligament
• Suspensory ligament of ovary – from ovary to lateral pelvic wall
• Ligament of ovary – lower pole of ovary to lateral angle of uterus
3. Uterine tubes
- form a connection between abdominal & uterine cavities
Infundibulum – mouth is fimbriated
Ampulla – widest
Isthmus
Intrauterine/ Interstitial part – narrowest
- clinical
Blockage of uterine tubes – commonest cause for female sterility
Rubins test
Hysterosalpingography
4. Vagina
▪ cervix projects into anterior wall of vagina forming a gutter
▪ gutter divides into anterior ,posterior , lateral fornices.
▪ ant fornix is shallow
▪ ant wall of vagina > pos wall

▪Relations
Ant 1. Base of bladder
2. Urethra embedded in anterior wall
Pos (above downwards)
1. Pouch of Douglas(in upper ¼ )
2. Rectum
3. Anal canal(in lower ¼)
Lat 1. Levator ani
2. Transverse cervical ligament
▪ per vaginal examination
1. Anterior & posterior relations are palpable
2. Ureteric stones
3. Ovary, uterine tubes, side of pelvis is felt laterally
4. Collection of fluid, prolapsed uterine tubes, ovaries & distended bowel in pouch of Douglas
5. External Genitalia
1. Regarding the vagina

a) Anterior wall is related to the base of the bladder.
b) Lymph from upper part drains into the internal iliac nodes.
c) Internal surface is lined by pseudostratified columnar epithelium
d) has no glands in lamina propria
e) posterior fornix is shallow
2. Cervix of the uterus

a) Triangular in shape.
b) Directly overlies the superior surface of the bladder without in between peritoneum.
c) Uterine arteries are laterally related.
d) Supported by transverse ligament.
e) Supplied by the vaginal artery.

Body cavities
Lateral plate mesoderm is involved in forming body cavity. Parietal
(somatic)
Solid mesoderm clefts appear in the clefts coalesce
lateral plate mesoderm & split the solid layer
into 2 visceral
(splanchnic)
• space created between the two layers of lateral plate mesoderm constitutes the primitive
body cavity
Cephalocaudal & lateral folding
Incooparation of yolk sac cavity into the intraembryonic cavity
endoderm layer folds ventrally and closes
Forms the GUT tube
Lateral body wall folds meet in the midline and fuse to close the ventral body wall

Clinicals
Ventral body wall defects

1- Cleft sternum – thoracic region
2- Omphalocoele
3- Gastrochisis – abdominal region
4- Bladder or cloacal exstrophy – pelvic region
Cleft sternum
Ventral body wall defect.
Two lateral mesodermal bars fuse to form the sternum If failed Cleft sternum
In some  ectopia cordis (heart protrudes through sternal cleft)
Sometimes defect involves both the thorax and abdomen
Cantrell pentalogy
1- Cleft sternum
2- Ectopia cordis
3- Omphalocele
4- Diaphragmatic hernia
5- Congenital heart defects (VSD, TOF)
Development of diaphragm
Diaphragm is derived from 4 components.
• Septum transversum
Is a thick plate of mesoderm occupying the space between the thoracic cavity and the stalk of
the yolk sac.
- It is developed at cervical segments.
- And during cephalocaudal folding it descends to thoracic level.
- By dragging its nerve supply from C3, C4, C5, spinal segments (phrenic nerve).
- And forms the central tendon of the diaphragm.
• Pleuroperitoneal membranes
Closes the foetal communication between pleural and peritoneal cavities. Form a part of the
diaphragm
• Dorsal mesentery of the oesophagus forms the crura of the diaphragm.
• Foetal body wall forms the peripheral muscular rim.

Clinicals
Congenital diaphragmatic hernia - pleuroperitoneal membranes fail to close the
space completely
Respiratory System
Out growth from the ventral wall of the foregut Lung bud (respiratory diverticulum)
At first the lung bud communicates with the foregut
2 longitudinal ridges appear

fuse
Tracheooesophageal septum formed
The oesphagus is separated posteriorly & trachea anteriorly
Clinicals
• Oesophageal atresia with or without tracheoesophageal fistula

- upper portion of the esophagus ending in a blind pouch and the lower
segment forming a fistula with the trachea
- Isolated esophageal atresia and H-type TEF without esophageal atresia
TEF associated other defects
Vertebral abnormalities
Anal atresia
Cardiac defects
Tracheo-esophageal fistula
Esophageal atresia
Renal abnormalities
Limb defects

Tracheo-esophageal fistula
• Respiratory diverticulum formed by ventral wall of the foregut.
• 2 longitudinal ridges appear
• They fused in the midline
• And forms trachea anteriorly and oesophagus posteriorly.
• Posterior deviation of this septum or
• Mechanical pulling of foregut anteriorly
• Resulting tracheo-oesophageal fistula and
• Oesophageal atresia.
• Upper oesophagus ends in a blind pouch
• Lower oesophagus connects to trachea above bifurcation.
• Prevent normal passage of amniotic fluid.
• Causes accumulation of amniotic fluid.
• Resulting polyhydramnion.
-
Trachea, bronchi and lungs

Lung bud gives 2 lateral out pouches [bronchial buds]
Bronchial buds enlarges
form right and left main bronchi
3 2
Secondary bronchi
Divides in adichotomous fashion
Tertiary bronchi forming bronchopulmonary segments
• mesoderm, which covers the outside of the lung visceral pleura

• somatic mesoderm layer, covering the body wall from the inside
parietal pleura
• space between the parietal and visceral pleura - pleural cavity

Development of the CVS
Vascular system develops in the middle of the 3rd week before the folding of the embryo
as it is no longer able to satisfy its nutritional requirement by diffusion.
Development of heart involves,

• Cardiac Tube formation
• Cardiac looping
• Septum formation
• Positioning of heart tube
Development of vessels
• Arterial Aortic arch, Umbilical vessels, vitelline
• Venous  Cardinal system, umbilical, vitelline
1) Cardiac Tube formation
• Heart, all blood vessels and all blood cells originate from mesoderm.
• Cardiac progenitor cells which are in the splanchnic layer of the lateral plate
mesoderm forms cardiac myoblasts.
• Also, blood islands (blood islands - The innermost cells of these blood islands
are hematopoietic cells that give
rise to the blood cell lines. The
outermost cells give rise to the
endothelial cell layer of blood
vessels) which appear in the
mesoderm
• Blood islands unite and forms a horseshoe shaped endothelial lined tube
(Endocardial Tube) that is surrounded by cardiac
myoblasts.
• Endocardial tube- Primary heart tube
Heart initially formed as two parallel tubes on
either side of embryo, anterior to the
Oropharyngeal membrane
• As a result of growth of the brain and
cephalic folding of the embryo the cardiogenic
field is brought ventrally thoracic region
• As a result of the lateral folding of the
embryo the two parallel tubes merge and forms
the Heart tube
• Primary heart tube has a dorsal mesentery
but not ventral.
• Disappearance of the middle section of the dorsal mesentery forms the
transverse pericardial sinus.
Expansions appear in the cardiac loop throughout its length.

Dorsal mesocardium
↓
Epicardium
↓
Coronary arteries
From venous end they are:

1. Sinus venosus 2. Primitive atrium 3. Primitive ventricle
4. Bulbus Cordis Proximal ⅓ - (Trabeculated part of right ventricle)
Middle ⅓ - [Conus cordis] (Outflow tract of both ventricles)
Distal ⅓ - [Truncus Arteriosus] (Roots of ascending aorta and
pulmonary trunk)

2) Cardiac looping
Day 23-28
• Cephalic portion bends ventrally, caudally & to the right
• Caudal portion shifts dorsally, cranially & to the left
This bending due to cell shape change in Cardiac loop

Externally, junction between the Bulbus cordis & Primitive ventricle →
Bulboventricular junction → Primitive interventricular foramen
Primitive ventricle and the primitive atrium → Atrioventricular canal
3) Septal formation
Two methods.
1. By 2 actively growing tissue mass that approach each other or single mass
approaching the other end until they fuse. These tissue masses are called
Endocardial cushions.
2. By merging of 2 expanding portions of the wall of the heart (never completely

separates 2 cavities)
Does not involve endocardial cushions.

Atrial Septal formation (End of 4th week)
Septum primum Appears as a sickle shaped fold on the roof of common
atrium towards the endocardial cushions
↓
Ostium Primum Opening between the free margin of Septum primum &
Endocardial cushions
↓
Closes Ostium primum by fusion of septum primum with Inferior and Superior
Endocardial cushions
↓
At the same time cell death occurs in the upper part of the Septum Primum
↓
Forms the Ostium Secondum
↓
Septum Secondum appears from the common atrium, right to the Septum primum
↓
The septum secondum overlaps the
ostium secondum
↓
The opening left by septum secondum -
Foramen Ovale
↓
The upper part of septum primum
disappears
The rest of septum primum act as the
valve of foramen ovale
↓
At birth Left atrial pressure increases as
the lung circulation begins  foramen
ovale closes  becomes Fossa ovale
Septum formation in the atrioventricular canal
Primitive atrium and primitive ventricle are separated by the formation of endocardial
cushions that form AV septum.
Endocardial cushions appear in the atrioventricular canal as superior, inferior and two
lateral.
They approach each other and fuse forming the left and the right atrioventricular
orifices.

AV Valves
Each AV orifice Is surrounded by local
proliferations of mesenchymal tissue
and flow of blood hollows them out
and the AV valves are formed
Septum formation in the ventricles

Ventricular septum
1. Muscular portion
2. Membranous portion
Muscular portion
The ventricles expand  Medial walls merge 
Forms the muscular Interventricular septum
Membranous portion
• The two ventricles are connected by
interventricular foramen which is above
muscular portion of the ventricular septum
• The interventricular foramen is closed by
fusion of inferior endocardial cushion with
muscular part of interventricular septum
• Conus septum also helps
Septum formation of Truncus arteriosus

2 Swellings/truncus cushions appear in the Truncus arteriosus (Supported by the
Neural crest cells)
• Right superior truncal swelling grows towards left.
• Left inferior truncal swelling grows towards right.
• They twist around each other and then fuse to form aorticopulmonary septum.
• It separates truncus arteriosus into aortic channel and pulmonary channel.
2 swellings appear in the Conus cordis (Supported by the Neural crest cells)
1. R: dorsal
Unite each other → Unite with the Truncus septum →
Conotruncal septum → 2 Outflow tracts for two ventricles and
roots of aortic and pulmonary arteries
2. L: ventral
Neural crest cells migrate through the 3, 4, 6 Pharyngeal arches. They are important in
craniofacial development.
Therefore, heart defects and craniofacial abnormalities are associated.

Semilunar valves
Appear on truncus swelling when the partition is completed

↓
Swellings hollow out and produce semilunar valves
↓
Neural crest cells have a contribution
Conducting System
SA node – Initial pacemaker lies in the caudal part of the left cardiac tube.
Then in the sinus venosus and finally in the right atrium as the sinus venosus
in incorporated in to the R atrium.
AV nod and bundle of His – derived from 1. Cells in the left wall of the sinus venosus.
2. Cells from the atrioventricular canal.
4) Vascular development
1.Vasculogenesis – coalescence of angioblasts. (dorsal aorta and cardinal veins)

2.Angiogenesis – Vessels develop from existing vessels.
Arterial System
Aortic arches:
• Supply the pharyngeal arches.
• Arise from the aortic sac (distal part of the truncus arteriosus.
• 6 pairs appear.
• 5th arch either never forms or forms incompletely.
• Terminates in the Right and Left dorsal Aortae.
• R and L dorsal aortae are fused caudally to form a single vessel.
1st arch – Maxillary artery

2nd arch – Hyoid & Stapedial arteries
3rd arch – Common carotid & 1st part of Internal Carotid
4th arch – Right – R: subclavian artery, Proximal part (Distal part →R: Dorsal aorta)
Left - Part of the Aortic arch between L: Common carotid & L: Subclavian
6th arch – Right- R: Pulmonary artery (Distal part regresses & Looses connection with the Dorsal aorta) **
- Left - L: Pulmonary artery & Ductus Arteriosus
Both Recurrent Laryngeal nerves hooks around the 6th Aortic arch. With further
development, 5th arch and distal part of right 6th arch disappear.
So;
R: side → ** Hooks around the 4th arch
L: side → Due to the Persistence of the Ductus arteriosus as Ligamentum arteriosum, it
has to remain winding round the 6th arch

Vitelline arteries - Forms the 3 arteries of the GUT (celiac, Superior and inferior
mesenteric arteries)
Umbilical arteries – Earlier arises from the dorsal aorta
Later from the common iliac arteries
Distal part →(obliterated) Medial umbilical ligament

Proximal part → Internal iliac artery & Superior vesical artery
Development of Venous System

Sinus Venosus
• It receives venous blood from R & L sinus horns.
Vitelline Vein = Omphalomesenteric vein

Sup: Mesenteric Vein

• After left to right shunting most of left sinus horn disappears and the right horn
enlarges greatly. All that is left of this sinus horn is
Oblique vein of the L: atrium
Coronary sinus
• At the sinoatrial orifice (Opening of the sinus venosus to right atrium, R: & L:
venous valves are present.
• The only remaining part, Inferior part of the R: venous valve →→ Valve of IVC,
Valve of Coronary sinus
• The right sinus horn expands and is absorbed into right atrium →→ Sinus venarum
• Crista terminalis divides the trabeculated part & Sinus venarum of the right atrium
• In the left atrium Initially → 1 Pulmonary vein → The pulmonary vein and its
branches are incorporated to the L: atrium → 4 Pulmonary veins
So smooth walled part of the L: atrium → from Pulmonary veins
Vitelline veins → Plexus around the Duodenum → Portal vein and the liver sinusoids
Proximal part of the R vitelline vein forms the hepatic part of the Inferior vena cava
Umbilical veins –Right completely regresses

Proximal part of the L umbilical vein regresses
Distal part of the left vein connects the placenta to the liver
Before birth it bypasses the live sinusoids through the ductus venosus
Cardinal Veins
Both posterior cardinal veins

disappear entirely
The formation of the vena cava
system is characterized by the
appearance of anastomoses
between left and right in such a
manner that the blood from the
left is channeled to the right.
As the cardinal system develops

additional to the anterior and
posterior cardinal veins –
subcardinal, supracardinal,
sacrocardinal etc. appear.
Inferior vena cava

Has, Hepatic - Formed by the R vitelline vein
Renal - Formed by the R subcardinal vein
Sacrocardinal - Formed by the R sacrocardinal vein

Circulation before and after birth
Before Birth:
Blood from placenta- 80% saturated with O2
Returns to the fetus via the umbilical vein
Short circuit the Liver by the Ductus Venosus (But a small amount enters
the liver and Mixes with blood of Portal vein)
And enters the IVC (Here it Mixes with deoxygenated blood from LLs)
RA (Mixes with SVC)
Foramen ovale (@ the Opposite side of the Opening, by the Valve of IVC)
LA (Mixing with Pulmonary veins)
LV
Ascending aorta (Coronary & Common carotid arteries receive well
oxygenated blood)
Receives blood from Ductus arteriosus (Mixes with blood from the RV –
As lungs are collapsed, Blood flow in lungs are negligible)

Descending aorta
2 Umbilical arteries
Placenta
Changes at Birth
1. Closure of umbilical arteries  medial umbilical ligament
2. Closure of umbilical vein  ligamentum teres hepatis
3. Closure of ductus venosus  ligamentum venosum
4. Closure of ductus arteriosus  ligamentum arteriosum
• Functionally closed  just after birth (Muscular contraction)
• Anatomical closure  1-3 months
5. Closure of foramen ovale
• Up to 1-year closure is reversible
• Lungs are functioning → Pulmonary venous return ↑ → LA
Pressure ↑
Clinicals
Atrial septal defects (ASD)
Females: Males= 1:2
Can be due to
1-Ostium secondum defect –
Excessive cell death (Enlarged ostium secondum). Too short septum secondum
2-Complete absence of atrial septum
3-Ostium primum defects

VSD – Ventricular Septal Defects
• Most common cardiac congenital defect • Usually involves the membranous portion
• Often associated with abnormalities in partitioning of the conotruncal septum.
Dextrocardia
• Cardiac looping to left instead of right. • Related to the laterality establishment.
• Associated with - situs inversus (complete reversal of all organs)
- reversal of some organs.
Tetralogy of Fallot
Due to an unequal division of the conus
1. Pulmonary infundibular stenosis 3. VSD
2. Hypertrophy of the right ventricle 4. Overriding Aorta
Persistent truncus arteriosus
• The conotruncal ridges fail to fuse. • VSD is always present.
Transposition of great vessels

• Conotruncal septum follows is normal spiral course.
• Aorta from the  right ventricle
• Pulmonary artery from the  left ventricle
• Some times VSD is present
• Usually there is opened ductus arteriosus
 Neural crest cells contribute to the formation of conotruncal septum. Conotruncal
septal defects are accompanied by craniofacial defects.
Valvular defects
• valvular stenosis • valvular atresia
Coarctation of aorta
• Defect in tunica media.
• Leads to proliferation of tunica intima.
Constriction of aorta beyond the origin of left subclavian artery.
Preductal Post ductal
Constriction above the Constriction below the entrance of
entrance of ductus ductus arteriosus
arteriosus ↓
↓ Ligamentum arteriosum
Patent ductus arteriosus more common
Collateral circulation between
proximal and distal parts of the aorta
(intercostal and internal thoracic
arteries)
Collateral circulations
1. Subclavian artery  internal thoracic artery  anterior intercostal artery 
posterior intercostal artery  descending thoracic aorta.
2. Subclavian artery  axillary artery  scapular anastomosis posterior intercostal
artery  descending thoracic aorta
3. Subclavian artery  internal thoracic artery  superior epigastric artery  inferior
epigastric artery  external iliac artery
Intercostal arteries get dilated and torturous  erode lower surface of the ribs
(notching of ribs)
Right arm pressure increases & lower limb pressure decreases  radio-femoral delay

1
Embryology – Digestive System

Portion of endoderm lined yolk sac cavity => Primitive gut
• Pharyngeal gut – From Buccopharyngeal membrane to tracheo-bronchial diverticulum
Important for the development of head and neck
Forms pharynx and related glands
• Foregut – Up to liver bud
• Midgut – Up to junction between right 2/3rd & left 1/3rd of the transverse colon
• Hindgut – Up to cloacal membrane
MESENTERY
1. Ventral Mesogastrium – Derived from the Septum Transversum
Foregut (only) => divided by the liver
Ventral part – Falciform, Coronary, Triangular lig.
Dorsal part – Lesser omentum
2. Dorsal Mesogastrium – Divided by the spleen
Ventral part – Gastrosplenic lig.
Dorsal part – Lienorenal lig.
Duodenum => Dorsal mesoduodenum
Midgut => Mesentery proper
Hindgut => Dorsal mesocolon
FOREGUT
• Derivatives – Lung, Liver, Gall bladder & Pancreas
• Supplied by – Celiac artery
1. Oesophagus
Tracheo-oesophageal septum separates – Dorsal oesophagus from the ventral trachea
At first it is short.It elongates with the descent of heart and lungs.
Surrounding splanchnic mesoderm forms the muscular coating Lamina Propria,Mucosa,Submucosa and
Adventitia
Abnormalities
I. Oesophageal atresia and/or Tracheo-oesophageal fistula
Due to - Posterior deviation of tracheo-oesophageal septum
Dorsal wall of foregut pushed anteriorly
II. Oesophageal stenosis (usually in lower 1/3rd) – Failure to Recanalize
2. Stomach
At fourth week begins as a fusiform dilation in foregut.
Rotations
I. 900 Clock wise in longitudinal axis
- Left side become anterior =>
Left vagal fibers – Anterior vagal trunk
- Right side become posterior =>
Right vagal fibers – Posterior vagal trunk
II. In antero posterior axis
- Pylorus => to right & upwards
- Cardia => to left & downwards
© Repeat campaign 2015 A/L

2
Rotation of stomach causes changes in mesogastrium.

1.Around Longitudinal axis
Pulls dorsal mesogastrium to the left.
Formation of vacuoles and fusion of them Lesser Sac
2.Around Antero –Posterior axis

Bulging down of dorsal mesogastrium as Greater Omentum
Growth Difference
Posterior wall > Anterior wall
- Greater curvature => to the left
- Lesser curvature => to the right
• Spleen (mesodermal origin) grows in the left leaf of dorsal mesogasrium with the rotation of stomach
around longitudinal axis,dorsal mesogastrium rotates to left.Meso gastrium between spleen and dorsal
midline of the body fuses with the peritoneum over the posterior abdominal wall and disappears.
3. Duodenum
Formed by – both foregut & midgut (Therefore blood supply by both coeliac and superior mesenteric
arteries)
- Due to rotation of the stomach, becomes ‘C’ shaped & rotates to the right.
- Right surface of the dorsal mesoduodenum press against the posterior abdominal wall and disappears.
- Become retroperitoneal [secondarily]
- Duodenal cap – intraperitoneal
- Solidification => recanalization
4. Liver & Gall bladder
- Liver bud appears as an outgrowth of endodermal epithelium, at the distal end of foregut (3rd to 4th week)
- Hepatic cells of the liver bud proliferate & penetrate septum transversum
- Mesoderm of septum transversum forms haematopoetic cells, kupfer cells, connective tissue
- Invasion by liver cells into the septum transversum forms
Lesser omentum – between liver & foregut
Falciform, coronary, triangular lig. – between liver & body wall
- Cranial surface of the liver remains in contact with the original septum transversum & forms the bare area
of the liver
- Connection between the liver bud & the foregut form the bile duct
-Bile duct moves dorsally due to rotation of duodenum
- Ventral out growth from the bile duct gives rise to the gall bladder & cystic duct

3
Functions of liver in fetal life

1.Haematopoiesis- not after birth 2.Production of bile – from 12th week
5. Pancreas
- 2 buds originate from the endodermal lining of the duodenum

I. Dorsal pancreatic bud – in the dorsal mesentery
II. Ventral pancreatic bud – close to the bile duct
- Ventral pancreatic bud moves dorsally, in a manner similar to shifting of entrance of bile duct
- Finally comes to lie immediately below & behind the dorsal bud
- Parenchyma of the buds fuse

I. Ventral bud => Uncinate process & inferior part of head
II. Dorsal bud => remaining part
- Duct systems fuse
I. Main pancreatic duct =>
- Distal part of the dorsal pancreatic duct + entire ventral pancreatic duct
- Opens into the major duodenal papilla
II. Accessory pancreatic duct =>
- Proximal part of the dorsal pancreatic duct
- Opens into the minor duodenal papilla
Exocrine pancreas – Dorsal and ventral pancreatic buds

Islaets of Langerhan - Migrating neural crest cells
Abnormalities
I. Annular pancreas
- Ventral pancreatic bud usually consists of right & left parts which fuse & rotates around the
duodenum
- If they fail to fuse, left part migrates in the opposite direction
- But the right part goes in the normal direction
- Duodenum surrounded by the pancreatic tissue => Obstruction

4
II. Accessory pancreatic tissue

Frequently found in => Mucosa of the stomach
Meckel’s diverticulum
MIDGUT
• Supplied by – superior mesenteric artery
• Elongation of the gut & mesentery proper => Primary intestinal loop
• At the apex, communicates with the yalk sac by way of the vitelline duct
Cephalic limb – Distal part of duodenum ,jejunum,part of ileum

Caudal Limb – Lower part of ileum,cecum,appendix,ascending colon,proximal 2/3 rd of transeverse colon
Elongation of Loop
Jejunum and Ileum – coil formation
Large Intestine – Does not coil
Physiological herniation –
- Intestinal loops bulge out through the umbilicus => Physiological umbilical herniation
Rotation
When viewed from the front -
Counterclockwise around an axis formed by the superior mesenteric artery
I. While herniating - 900 [6th wk]
II. While retracting - 1800 [10th wk]
Retraction
-During 10th week due to decreased growth of liver and adequate expansion of abdominal cavity
- Herniated intestinal loops return to the abdominal cavity
- Cecal bud => Conical dilation of the primary intestinal loop
Last part of the gut to reenter the abdominal cavity
Then lies below the right lobe of the liver, which descends into the right iliac fossa
Distal end of the cecal bud => Appendix
• Mesentery of ascending & descending colon press against posterior abdominal wall =>
to become retroperitoneal
Abnormalities
Mesentery defects
I. Mobile cecum – Persistence of mesentery of ascending colon, without fusing

5
Body wall defects

II. Omphalocele – Herniation of abdominal viscera, through an enlarged umbilical ring [eg- liver]
Due to failure of retraction from physiological herniation
Associated with cardiac anomalies,neural tube defects and chromosomal abnormalities
III. Gastroschisis – Protrusion of abdominal contents through body wall directly in to amnionic cavity
Lateral to umbilicus,Viscera are not covered by peritoneum or amnion.
Due to abnormal closure of bodywall around connecting stalk
Not associated with chromosomal abnormalities.
Vitelline duct defects
IV. Meckel’s diverticulum - Persistence of a small part of vitelline duct
Found in antimesenteric border of ileum, 2ft proximal to ileocecal valve
V. Vitelline cyst – Both ends of duct become fibrous, middle portion become a cyst
VI. Vitelline fistula – Duct remains patent over entire length
Gut Rotation abnormalities

VII. Incomplete Rotation
VIII. Reverse rotation
HINDGUT
Derivatives – Distal 1/3 rd of tranverse colon , descending colon, Sigmoid colon. Rectum,Anal
canal(upper part)
(Endoderm of Hindgut also forms internal lining of bladder and urethra)
• Supplied by – Inferior mesenteric artery
• Terminal part of hindgut enters the posterior part of cloaca.
• Alantois enters the anterior part of cloaca.
• Urorectal septum(a layer of mesoderm)separates Anterior Allantois & Posterior hindgut, those which enter
the cloaca .Grows caudally with the caudal folding of embryo.Tip of urorectal septum comes close to cloacal
membrane.
• Cloacal membrane ruptures
o Anterior opening – for the urogenital sinus
o Posterior anal opening – for the hindgut
In between urorectal septum forms perineal body.
• Anal canal
-Upper 2/3 rd – From endorderm of hindgut.Supplied by Superior rectal artery.(branch of inferior
mesenteric)
- Lower 1/3 rd – From ectoderm around proctodeum.Supplies by inferior rectal artery(branch of internal
pudendal)
Junction is delineated by pectinate line just below anal columns(Epithelium => Columnar to Stratified Squamous)

6
Abnormalities
I. Imperforated anus – Failure to breakdown of anal membrane
II. Congenital megacolon(Hirschsprung Disease)– Dilation of colon due to absence of parasympathetic
ganglia in the bowel wall.Defect in neural crest cell migration.
III. Rectourethral/Rectovaginal fistula
- When the urorectal septum does not extend far enough caudally
- When the cloaca is too small, causing the opening of the hindgut to shift anteriorly
IV. Rectoanal atresia

Development of Urogenital System
Urogenital system
Develops from the
• Upper parts - …………………………………………………………………………….
• Lower parts - …………………………………………………………………………….
Intermediate mesoderm  urogenital ridges
Urinary system
Kidney system
• Three slightly overlapping kidney systems formed In cranial to caudal sequence
 Pronephros
 Mesonephros
 Metanephros
1. Pronephros 2. Mesonephros
Appear at the beginning of the 4th week and completely
Appear during the regression of the pronephros (4th week)
regress at the end of the 4th week
In cervical region In thoracic & upper lumbar
Non functional Functional in intrauterine life
No duct system Duct system – mesonephric duct
Completely disappears – Not associated to form any Important to produce genital organs. Not associated to form the
urogenital structure definitive kidney
Mesonephros and the mesonephric duct
3. Metanephros (In 5th week)

• Form the definitive kidney.

Duct System
• Collecting system - formed by ureteric bud

o Ureteric bud – an outgrowth of mesonephric duct close to the entrance of cloaca
o It forms;
 Collecting tubules
 Major and minor calices
 Renal pelvis
 ureter
• Excretory system - formed by metanephric mesoderm

o Newly formed collecting tubule is covered at its distal end by a Metanephric tissue cap
o Cells of the tissue cap form Renal vesicles; which in turn give rise to “S” shaped tubules
o Capillaries grow into the pocket at one end of the “S” and differentiate into glomeruli.
o glomeruli + renal tubules = Nephron (excretory units)
o Renal tubules give rise to;
 PCT
 Loop of Henle
 DCT
o Nephrons are formed until birth (after birth nephrons grow without increasing in number). And the
urine production takes place in early gestation
Position of the Kidney

• Initially lie in the pelvic region; later ascend to the abdomen
• In pelvis, receive arterial supply from pelvic branch of the aorta
• In the ascent, receive arterial supply from the corresponding higher levels of aorta.
• Lower vessels usually degenerate but, some may remain. (seq – accessory renal arteries)

Clinicals
• Congenital polycystic kidney disease –(Autosomal recessive) – cysts form from collecting ducts
o Kidney- very large. Renal failure occurs in childhood
• Adult polycystic kidney disease- (Autosomal dominant) – Cysts form from all segments of the nephrone
o Usually renal failure occurs in adulthood
• Duplication of ureter – early splitting of ureteric bud (partial or complete)
• One ureter may be ectopic. In such cases it may open into,
o Vagina
o Urethra
o Vestibule
• Abnormal locations of kidneys
o Pelvic kidney - Remain in the pelvis close to the common iliac artery.
o Horseshoe kidney - Lower poles fuse due to fusion of two metanephric masses in the midline. So
ascent is blocked by inferior mesenteric artery . Ureters pass anterior to the isthmus.
Development of Bladder and Urethra

• Cloaca is divided into Urogenital sinus (anteriorly) and anal canal (posteriorly) by the Urorectal septum
• Urogenital sinus
o Upper part - Urinary bladder
Allantois (continuous with the upper part of the urogenital sinus) Urachus
median Umbilical ligament
o Pelvic part prostatic urethra & membranous urethra
o Definitive urogenital sinus ( phallic part) associate to form external genitalia/penile urethra

• Trigone of bladder – formed by the absorption of mesonephric duct into bladder
• Urethra
o Epithelium is formed by the endoderm
o Smooth muscles – by the splanchnic mesoderm
o In males; epithelium of the prostatic urethra proliferate to form the Prostatic gland
o In females; cranial part of Urethra give rise to urethral and para-urethral glands
Clinicals
• Urachal fistula-persistence of the lumen of the intraembryonic portion of the allantois
• Urachal cyst –cystic dilation in a local area of the persistent part of allantois
• Urachal Sinus-lumen in the upper part persist
• Exstrophy of bladder – ventral body wall defect.
o Epispadias is a constant feature
o Opening extends along the dorsal aspect of the penis through the bladder to the umbilicus
• Exstrophy of cloaca – more severe ventral body wall defect
o Exstropy of the bladder, spinal defects, imperforate anus, omphalocoele may associate.

Genital system
Gonads
• Gonads appear initially as Genital/Gonadal ridges
(formed by the intermediate mesoderm + coelomic
epithelium)
• Germ cells reaches the ridges on 6th week (they have a
inductive influence on the development of gonads)
(Indifferent gonads – shortly before & during the
arrival of germ cells)
• Shortly before and during arrival of primordial germ
cells, the epithelium of the genital ridge proliferates,
and epithelial cells penetrate the underlying mesenchyme to form a
number of irregularly shaped cords, the Primitive Sex cords.
• Gonads acquire male or female morphological changes after 7th week
Testis
• The germ cells which reach the gonadal ridges contain XY
chromosomes.
• Under the influence of the Y chromosome  primitive sex cords 
medullary cords
o Cords proliferate towards the hilum  Rete testis (network
of cell strands)
o Surface epithelium  Tunica albuginea
• Seminiferous tubules – testis cords which acquire a lumen during
puberty
• Rete testis – network of cell strands formed at the hilum by breakage of cords
• Efferent ductules – remaining parts of the excretory tubules of the mesonephric mesoderm
• Vas deferens ejaculatory duct and epididymis-
formed by Wolffian duct
• Appendix epididymis –vestigial cranial portion
of the Mesonephric duct
• Seminal vesicles – outbudding of the
mesonephric duct
• Appendix testis – vestigial small cranial portion
of the paramesonephric duct in males
• Utriculus prostaticus – homologous to female
vagina in males
Ovary
• The germ cells which reach the gonadal ridges contain XX
chromosomes.
• Due to the absence of Y chromosome  primitive sex
cords  cortical cords (surface epithelium)
• Cortical cords  split into isolated cell clusters 
surround germ cells
o Germ cells  oogonia
o Epithelial cells surround the oogonia  follicular cells

Genital ducts
1. Mesonephric duct (Wolffian duct) - Duct system of Mesonephros
2. Paramesonephric duct (Mullerian duct)
o Connects the peritoneal cavity with cloaca
o Crosses the mesonephric duct (lateral to medial)
 Genital ducts in males (mainly - mesonephric duct)
o Mesonephric duct - Efferent ductules , Epididymis , Vas deferens , Seminal vesicles , Ejaculatory duct ,
Appendix epididymis
o Paramesonephric duct – Appendix testis, Prostatic utricle
 Genital ducts in Females (mainly - paramesonephric duct)
o Paramesonephric duct
 Cranial, vertical part + Horizontal part = Uterine tubes
 Caudal vertical part - uterine canal
o Mesonephric duct - epoophoron , paroophoron , (Gartner’s cyst)
Vagina
• Fornix + upper part –uterine canal (paramesonephric duct)
• Lower part –urogenital sinus (sinovaginal bulb vaginal plate)
Clinicals – Defects of vagina and uterus
External genitalia
• Indifferent stage
o Cloacal folds – Slightly elevated
folds around the cloacal membrane
o Genital tubercle – Fused cranial
part of cloacal folds
• In 6 week –
th
Urogenital membrane
Cloacal membrane
Anal membrane
Urethral folds
Cloacal folds
Anal folds
• Genital swellings- Pair of elevations on each side of urethral folds
External genitalia in the Male

• Genital tubercle  Rapidly elongate  forms phallus  Glans penis
• Urethral folds fuse  penile urethra
• Tip of the glans penis penetrates inwards  External urethral meatus
• Genital swellings  scrotal swellings  Scrotum
Clinicals
Hypospadias – Fusion of the urethral folds is incomplete
o Abnormal openings of the urethra occur along the inferior (ventral) aspect of the penis
(near the glans, shaft or base of penis)
Epispadias – (rare) A ventral body wall defect
o Urethral meatus is found on the dorsum of the penis
o Associated with exstrophy of bladder
External genitalia in the Female
• Genital tubercle  Clitoris
• Urethral swellings  Labia minora
• Genital swellings  Labia majora
• Urethral groove  Vestibule
Decent of the testis

• Testis develops inside the abdominal cavity; Later it descents into scrotum
• Urogenital mesentery attached to posterior abdominal wall degenerates
• Caudal end of the testis is attached to the gubernaculum, which terminates in the inguinal region
• Later testis begins to develop towards the inguinal region, while gubernaculum grows towards the scrotal
floor
• Therefore the extra abdominal course of the gubernaculum produces the intra-abdominal migration
• regression of the gubernaculum completes the descent
• Processes vaginalis follows the course of the gubernaculum; remaining part forms the parietal & visceral
layers of tunica vaginalis
• 3th month - reach the iliac fossa

• 4th – 8th months - rest at deep ring
• 7th month - traverses the inguinal canal
• 8th month - superficial inguinal ring
• 9th month - reach scrotum

Histology of CVS
Myocardium
Cardiac muscle fibres

Central nuclei

Cross striations

branched

intercalated discs

cylindrical
Arteries
 Elastic arteries
e.g.- aorta, common carotid, subclavian, brachiocephalic
1) Tunica intima
• Endothelium- squamous epithelium
• Subendothelial tissue- Myointimal cells
with increasing age - accumulate lipid→Intima progressively thickens→Atherosclerosis
2) Tunica media
- Elastic
- Broad
3) Tunica adventitia
- vasa vasorum
 Muscular arteries
e.g. - femoral artery
tunica intima →internal elastic lamina→tunica media→external elastic lamina
(Less prominent, more variable)
 Small muscular arteries - No external elastic lamina
 Arterioles - No internal elastic lamina
Capillaries
Continuous (endothelium) Fenestrated (endothelium)

- In most of the tissue * small intestines
*kidney
*endocrine gland
with a diaphragm without a diaphragm discontinuous

basement membrane
e.g. - glomerulus e.g. -sinusoids
Pericytes → embrace the capillary endothelium, Contractile
Veins
−
3 layers
−
Elastic & collagen tissue less prominent
 Large muscular veins - vena cava
− Vasa vasorum in adventitia
− Longitudinaly arranged smooth muscle fibres

Histology of RS
Layers of the respiratory tract
− Respiratory epithelium-pseudostratified columnar ciliated epithelium
-Mucociliary escalator
− Lamina propria-underlying connective tissue
− Smooth muscle layer - more prominent in lower airways
-Regulate airway diameter
− Submucosa
− Cartilage - amount decrease from trachea downwards
− Adventitia
Regional differences
epithelium Lamina propria Smooth muscles submucosa cartilage adventitia
1. Nasal Pseudostratified − Serous, mucous glands
cavity columnar ciliated − Thin walled blood vessels
− MALT  
− Venous plexuses (for
humidification)
2. Larynx
− False vocal Pseudostratified Serous
cords columnar ciliated mucous
glands
− True vocal Keratinized stratified present
cords squamous
3. Trachea Tall pseudostratified Mixed C shaped elastin↑
columnar ciliated seromucous (patency
Neuro endocrine cells gland without
collapsing)
4. Main Progressive ↓ in More elastin Discontinuous Fewer glands Flat, few
bronchus goblet cells & tallness layer intercalated
of epithelial cells plates
5. IIIry Few goblet cells Prominent MALT present Irregular few
bronchus Arranged Fused with cartilage
spirally adventitia plates
6. Bronchioles − Ciliated columnar Thick layer No Merge
D<1mm epithelium submucous with lung
glands  parenchy
− No goblet cells
− Clara cells present ma
7. Terminal Simple ciliated Less folded than thick Submucous
bronchioles columnar bronchioles glands
Simple ciliated 
cuboidal
− Goblet cells absent
8. Respiratory − Ciliated cuboidal
bronchioles epithelium
  
− Clara cells
− Goblet cells
Alveoli Surface epithelium

− Alveolar lining cells
− type I pneumocytes large squamous cells, form gas
diffusion border Alveolar septum Supporting tissue
− type II pneumocytes (60%) - small, secrete surfactant
− Alveolar macrophages - phagocytic action
 Lymph capillaries are not found in alveolar wall. But Central area of
present in walls of respiratory bronchioles and above. alveolar capillaries
Pleura
1. Outer mesothelium - flattened cuboidal cells with surface microvilli
2. Basement membrane
3. Connective tissue
4. Visceral pleura - contains fibrous septa, lymph vessels, blood vessels

GIT - Histology
Functional layers of the GI tract
1. Mucosa epithelium
Lamina propria
Muscualris mucosa
2. Submucosa supportive tissue collagenous fibres
Blood vessels, lymphatics
3. Muscularis propria smooth muscle (Inner circular and outer longitudinal (oblique layer present innermost in
stomach)
4 Serosa loose supportive tissue, lined by mesothelium
 Meissner’s plexus- in submucosa
 Myenteric plexus/ Auerbach’s plexus – between 2 muscle layers of muscularis propria
Parts of GIT
Type of epithelium Cell types in epithelium Distinctive features
tract
Esophagus Stratified squamous squamous Lamina propria contain scattered
epithelium lymphoid aggregates
Submucosa –seromucous glands
Muscularis propria-
Upper1/3- skeletal muscle
Middle1/3- both
Lower 1/3- smooth muscle
Stomach-body glandular Surface mucosal cells No lymphoid aggregates
and fundus Neck muscle Mitotic figures can see after
Parietal cell damage to mucosa -gastritis
Fried egg appearance
Chief/peptic cells
Endocrine cells
Stem cells
Fundus/body pylorus
Glands- straight tubular Glands- Branched coiled
Occupies ¼ of thickness of gastric mucosa Occupies half the thickness of the mucosa
duodenum Glandular Enterocytes Submucosa
epithelium with villi Goblet cells . Brunner glands -
and crypts of Paneth cells coiled branched tubular
Lieberkühn Defensive function
Base of crypts - Plicae circularis -
Neuroendocrine cells Submucosa and mucosal folds
Stem cells
Jejunum and Glandular with villi Enterocytes with micro Plicae circularis
ileum and crypts of villi
Lieberkühn Goblet cells
Paneth cells
Colon and glandular Goblet cells Straight tubular glands in
rectum Absorptive cells muscosa
Taeniae coli
appendix glandular Goblet cells Prominent lymphoid tissue
Tall columnar cells
anus Stratified squamous Squamous cells Columns of Morgagni
 Villi longest in duodenum, Shortest in ileum

 Lymphoid – most important in the ileum (payer’s patches)
 Goblet cells – number high distally
 Plicae circularis – absent in proximal duodenum & distal ileum
More prominent in jejunum & proximal ileum
Junctions of GI tract
1 gstro-oesophageal junction – 3 Ileocaecal junction -
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2 gastroduodenal junction - 4 rectoanal junction -

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Liver
 Structural unit of liver – hepatic lobule
-Hexagonal boundary
-Hepatic lobule contains
• Sinusoids intervening between cords
• Cords of hepatocytes
• Central vein
Portal triad -arteriole of hepatic artery
-Terminal branch of portal vein
-Bile ductules
• Lymphatics
• Sinusoids are lined by discontinuous,
fenestrated endothelium
• and separate from hepatocytes by
narrow space - space of tissue
Sinusoidal lining cells types –
• endothelial cells
• Kupffer cells
• Stellate cells – storage vitamin A
 Zone 1- receive most oxygenated blood

 Zone 2
 Zone 3- receive least oxygenated blood
Gall bladder
• Small amount of smooth muscles in the wall
• Mucosa –
o epithelium - simple columnar
o Folds-honeycomb appearance in the body
o Spiral valve of Heister in the neck
o No goblet cells
• Muscle layer – longitudinal, transverse, oblique
• Submucosa contains mucous glands
Pancreas
• Exocrine component- secretory acini and duct system
• Endocrine component –islets of Langerhans
• β-cells-insulin • α-cells-glucagon • δ-cells-somatostatin
• Acinar cells –> intercalated ducts –> interlobar ducts –> interlobular duct (small cuboidal-stratified cuboidal)

Urinary system - Histology
Kidney
Nephron
• Functional unit of kidney
• Nephron is made up of a renal
corpuscle and the renal tubules
• Bowman’s capsule and the glomerulus
make the renal corpuscle
• Glomerulus is a capillary network.
• Lined by an endothelial cell layer which
is fenestrated and luminal surface is
negatively charged.
• Glomerular basement membrane is
thick.
• Bowman’s capsule is cup shaped.
• Lined by flattened squamous epithelial
cells.
• Visceral layer of the capsule is a
podocyte layer.
• There are primary and secondary
processes and filtration slits.
• This layer invests the capillary loops
exposed to the bowman’s space.

• Capillary endothelial layer,
basement membrane and
the podocyte layer make
the glomerular filtration
membrane.
• Intervening space between
the bowman’s capsule and
the glomerulus is the
mesengium.
• Consist of mesengial cells.
• Parts of the tubule system
are proximal convoluted
tubules, thick descending
limb, thin descending limb,
thin ascending limb, thick
ascending limb, distal
convoluted tubule and the
collecting tubule.
• Proximal convoluted
tubule, distal convoluted
tubule, collecting tubule
and the thick part of the
loop of henle are lined by
simple cuboidal epithelial
cells.
• Epithelial cells of PCT have
microvilli/ Brush border
• Thin part of the loop of
henle is lined by the simple
squamous epithelium.
• Cell in PCT are taller than
DCT.
• But more numerous in DCT
than PCT.
• Lumen is clear in DCT and the lumen in narrow in the PCT.
• Juxtaglomerular apparatus Specialization of glomerular afferent arteriole and distal convoluted tubule of the
same nephron.
• Three components
o Macula densa of distal convoluted tubule
o Juxtaglomerular cells of afferent arteriole.
o Extraglomerular mesengial cells/ Lacis cells

Part of tubules Type of epithelium Special features
PCT Simple cuboidal Microvilli (brush border)
Plentiful mitochondria
Pars recta of proximal tubule Simple cuboidal Microvilli (brush border)
(thick descending limb) No basolateral interdigitation
Thin descending/ascending Simple squamous No basolateral interdigitation or
limbs microvilli
Mitochondria scanty
DCT Simple cuboidal Microvilli absent
Thick ascending limb Simple cuboidal Extensive basolateral interdigitation
Mitochondria plentiful
Collecting tubule Simple cuboidal Principal cells
Intercalated cells
Collecting tubule cells
Cortical collecting ducts Simple columnar Principal cells
Intercalated cells
Medullary collecting ducts Simple columnar Mainly principal
DIFFERENCES BETWEEN PCT AND DCT

PCT DCT
Lumen Not clear Open and clear
Cell size Larger than DCT cells Smaller than the PCT cells
Nuclei Less in cross section More in cross section
Brush border Present due to micro villi Absent
URETER
• 4 Layers
1.Transitional epithelium –Urothelium
Withstand to toxic substance & stress in the
lumen
Allow stretching during passage of urine
Tight junctions prevent leakage of urine
2. Lamina propria – Collagen

3. Muscular layer – Inner Longitudinal In upper 2/3rd
Outer Circular
Outermost Longitudinal [In lower 1/3rd ONLY]
4. Adventitia – Loose collagen [Contain Blood vessels, Lymphatics, Nerves]

Urinary Bladder
• Bladder is histologically similar to the structure of lower 1/3rd of the Ureter
• So muscle layers are arranged as inner longitudinal, outer circular and outermost longitudinal. All together these
smooth muscle layers are known as Detrusor muscle
• Epithelium is thrown in to folds in relaxed state
Urethra
• Male urethra is lined by stratified or pseudo stratified columnar epithelium (Except prostatic urethra which is
lined by transitional epithelium)
• External urethral meatus is lined by Stratified squamous epithelium (This become continuous with epithelium of
glans)

Male Reproductive System
Testis-Male Gonad
• Tunica vaginalis
-Double layer of mesothelium (parietal and visceral)
-Mesothelial cells secrete serous fluid
-Collection of fluid within tunica vaginalis Hydrocele
• Tunica albugenia(capsule)
-Dense fibrous tissue with fibroblast and myofibroblast
• Deepest layer(Tunica vasculosa)
-Loose connective tissue
-Blood vessels
-Lymphatics
• Capsule forms septa Lobules
Seminiferous tubules
• Tubules within testicular lobules
• Tightly packed, highly convoluted
• Each lobule has 1-4 seminiferous
lobules
• Production of spermatozoa
• Tubules lining cells(stratified)
-germ cells
-non germ cells: sertoli
cells(support and nourish
spermatozoa)
• Between tubules(interstitial space)
-Leydig cells
-Very vascular
• Seminiferous tubules converge
upon the mediastinum testis
which consist of plexus of
channels known as Rete testis

Rete Testis
• Surrounded by highly vascular collagenous supporting tissue containing myoid cells.
• The rete testis is lined by a single layer of cuboidal epithelial cells with surface microvilli and a
single cilium.
• Myoid cell contraction helps to mix the spermatozoa and move them towards the epididymis.
• The lining epithelium reabsorbs protein and potassium from the seminal fluid.
Ductulus efferens
• The rete testis drains into the head of the epididymis via some 15-20 convoluted ducts, the
ductuli efferentes.
• The ductuli are lined by a single layer of epithelial cells,
-tall columnar and ciliated
- short and non-ciliated
• Ciliary action in the ductuli propels the still non-motile spermatozoa towards the epididymis.
• A thin band of circularly arranged smooth muscle surrounds each ductulus and aids propulsion
of the spermatozoa towards the epididymis
Epididymis
• The epididymis is a long extremely convoluted duct extending down the posterior aspect of the
testis to the lower pole where it becomes the ductus deferens.
• The epididymis consists of a head at the upper pole of the testis, a body lying along the posterior
margin and a tail at the lower pole of the testis.
• The major function of the epididymis is the accumulation, storage and maturation of
spermatozoa in the epididymis, the spermatozoa develop motility.
• The epididymis is a tube of smooth muscle lined by a pseudostratified epithelium.
• Proximally, the smooth muscle exhibits slow rhythmic contractility which gently moves
spermatozoa towards the ductus deferens.
• Distally, the smooth muscle is richly innervated by the sympathetic nervous system which
produces intense contractions of the lower part of the epididymis during ejaculation.
• The epithelial lining of the epididymis exhibits a gradual transition from a tall pseudostratified
columnar form in the head, to a shorter pseudostratified form at the tail.

Ductus deferens
• The ductus (or vas) deferens, conducts
spermatozoa from the epididymis to the
urethra
• It is a thick-walled muscular tube
consisting of inner and outer longitudinal
layers and a thick intermediate circular
layer.
• Like the distal part of the epididymis, the
ductus deferens is innervated by the
sympathetic nervous system, producing
strong peristaltic contractions to expel
its contents into the urethra during
ejaculation.
• The ductus deferens is lined by a
pseudostratified columnar epithelium.
• The dilated distal portion of each ductus
deferens, known as the ampulla, receives
a short duct draining the seminal vesicle,
thus forming the short ejaculatory duct;
the ejaculatory ducts from each side
converge to join the urethra as it passes
through the prostate gland
Seminal vesicle
• Each seminal vesicle is a complex
glandular diverticulum of the associated
ductus deferens.
• Between them the seminal vesicles
secrete up to 85% of the total volume of seminal fluid, most of the rest being secreted by the prostate gland.
• The epithelial lining is usually of a pseudostratified tall columnar type.
• The prominent muscular wall is arranged into inner circular and outer longitudinal layers and is supplied by
the sympathetic nervous system; during ejaculation, muscle contraction forces secretions from the seminal
vesicles into the urethra via the ampullae

Prostate gland
• The prostate consists of branched tubulo-acinar

glands embedded in a fibromuscular stroma.
• There is a partial capsule enclosing the
posterior and lateral aspects of the prostate
but the anterior and apical surfaces are
bounded by the anterior fibromuscular stroma,
a part of the gland consisting, as the name
implies, only of collagenous stroma and muscle
fibres.
• The transition zone surrounds the proximal prostatic

urethra and comprises about 5% of the glandular
tissue.
• The central zone (20%) surrounds the ejaculatory
ducts.
• The peripheral zone makes up the bulk of the gland
(approximately 70%).
• The anterior fibromuscular stroma contains no
glandular tissue and lies anteriorly.

Female Reproductive System
Function :- reproduction
endocrine function
Ovaries
-flattened
-ovoid structures
-paired
-no anatomical distinct covering
-outer epithelial covering (germinal epithelium),
continuation of peritoneum
Lined by cuboidal /columnar cells
Inside body of the ovary

1 superficial cortex
2 deep cortex Ovary
3 medulla – blood vessels – helicine arteries
Hilus cells
(A) follicles
early in life until menarche
oogonia – migrates to ovarian cortex – mitosis (2n)

some enlarge and attain the potential for maturation, becoming primary
oocytes
commence 1st stage of meiosis
Primary oocyte
With a surrounding layer of flatten cells
- primordial follicle
- meiosis arrested at diplotene of meiosis 1
- at birth approximately 500,000
Follicular Maturation
Primordial follicle small follicle in periphery
Single layer of follicular cells
Primary folliclecells get multiplied and converted in the cuboidal cells

(granulosa cells)
Zona pellucida-a proteoglycan and glycoprotein coat
between oocyte and follicular cells
Zona granulosa
Oocyte enlarges

Secondary follicle Antrum formation
Theca interna and theca externa formation
Graffian follicle  Large follicular antrum

Zona granulosa forms a layer of even thickness
Oocyte surrounded by corona radiata
 Degeneration can occur at any time (atresia)
And become –atretic follicles
When these follicles become enlarged without maturation form ovarian cysts (Normally not malignant)
Remaining parts of the follicle –become corpus luteum after ovulation
If fertilization does not occur becomes corpus albicans .

(inactive fibrous mass)
If fertilization occurs corpus luteum of Pregnancy (Has blood Surrounding cell layers)
Primordial follicle
Primary follicle
Secondary follicle Graafian follicle

Corpus Luteum Corpus Albicans
Basic structure of genital tract

- wall of smooth muscle
- inner mucosal lining
- outer layer of supportive tissue
Fallopian tube
3 types of cells line the mucosa
- Ciliated tall (showing irregular cell margin)
-non-ciliated secretory cells (prominent in ampulla)
-intercalated cells
Non-ciliated cells secrete substances to take ova forward with the aid of cilia
Uterus
Basic organization (1) endothelium / decidua (pregnancy)
Epithelium lining pseudostratified columnar ciliated cells
Form numerous simple tubular glands supported by endometrial stroma
Histological layers
1. Stratum compactum
2. Stratum spongiosum functional layers are shed off during menstrual phase
3. Stratum basalis No shedding during menstrual cycle
Changes occur in the endometrium during menstrual cycle

Proliferative phase Secretory phase Menstrual phase
-glands-initially simples tubular, straight, sparse Coiled tubular glands Functional layers shed
But proliferation is started Tall columnar cells off due to the absence
Lined by long columnar cells of implantation
-gradually stroma become thicker, very cellular Stroma reaches to the
maximum thickness
-Blood vessels less
-Mitotic figures can be seen
-Endometrial surface epithelial cells acquire • Glycogen vacuoles(basal)

microvilli, cilia, cell organelle • Saw tooth appearance
In cross section of glands
When taking endometrial curettings/biopsies the first day of last menstrual cycle is very important
Uterine cervix Endocervix –lined by simple columnar epithelium

Ectocervix – lined stratified squamous epithelium

Endocervical canal
Lined by tall columnar mucous secreting cells
Leucocytes are more between junction of endocervix and ectocervix
Cervical cytology
Cervical smear /pap test
Vagina
(1) Epithelium – stratified squamous, non-keratinized
Superficial cells of epithelium form glycogen
anaerobic
Glycogen respiration lactic acid (inhibit growth of microorganisms)
(2) Lamina propria -no glands

(3) smooth muscle layer
(4) Adventitia

biochemistry
bat notes
term 02
Hormones
• What is a hormone?
Chemical messenger produced in the body that interact with receptors of the
target tissue to cause a change in function of that tissue.
Characteristics of hormones
1. Secreted in very small amounts.
2. Transport – blood / other body fluids
3. Have a relatively long-lasting effect on distant target cells.
4. Target cells have specific receptors.
5. Regulating cell reactions by affecting gene expression.
6. Have no effects on the cells that produce them?
Endocrine system
• A system of ductless glands that secrete hormones.
Endocrine system
Purely endocrine organs Endocrine cells in other organs

Pituitary gland Pancreas
• Acts along with the nervous system to coordinate body functions.
Endocrine system Nervous system
Hormones Electrical signals
Slower High-speed
Longer acting Short lasting
Via blood/other body fluids Along neurons
Hormone signaling pathways
• Types of chemical signals

1. Autocrine signals - act on the cell that synthesized them
2. Paracrine cells - acts on nearby cells
3. Neural signals - released by one neuron & acts on the adjacent neurons
(Neurotransmitters)
4. Endocrine signals - travel via blood stream
5. Neuroendocrine signals - secreted from a neuron
Travel via blood stream
6. Pheromone signals - released to the environment
Acts on another individual
• Types of hormone signaling pathways
1. Endocrine pathway – through the blood stream
2. Neuroendocrine pathway – ex: hypothalamus control over the adrenal medullae to
produce epinephrine/norepinephrine
3. Paracrine pathway – insulin secretion by beta cells affect secretion of glucagon
secretion by alpha cells
• Normally these are regulated by negative feedback mechanism.
Hypothalamus and pituitary
• Most dominant portion of the entire endocrine system. Hypothalamus – boss
• Hypothalamus regulates hormone secretion via
1. Endocrine pathway Pituitary – manager
2. Neuroendocrine pathway
• Hypothalamus controls hormone release of the anterior pituitary Other endocrine organs - workers
There are two types of hormones.
1. Releasing hormones (6)-
TRH (Thyroid releasing hormones)
CRH (Corticotrophin releasing hormone)
GnRH (Gonadotropin releasing hormone)
PRF (Prolactin releasing factor)
GHRH (Growth hormone releasing hormone)
MSH-RH (Melanocyte stimulating hormone – releasing hormone)
2. Inhibiting hormones (2)-
PIF (Prolactin Inhibiting Factor)
GHIH (Growth hormone inhibiting hormone)
Anterior pituitary control
T3
Skin Thyroid
MSH TSH* T4
Mammary PRL Anterior pituitary ACTH* Adrenal

Gland cortex
GH FSH*/LH* corticosteroids
Bones aldosterone
Muscles cortisol
Adipose tissue Ovary Testis
Estrogen androgen *tropic

Mechanisms of hormone release
1. Hormonal – stimulation received from other hormones
2. Neural – stimulation by nerves
3. Humoral – in response to changing levels of ions or nutrients in blood
Functions of hormones
• Growth & development Primary sex determination is NOT
• Energy production determined by hormones.
• Reproduction
• Environmental challenges
• Homeostasis – maintaining constant internal environment

How hormones coordinate the activities of the cells
• Hormonal effects on the body are complex.
One hormone → multiple actions
Multiple hormones → one function
• Example for a multi hormonal process – maintenance of blood glucose
Insulin Glucagon Epinephrine
Structure of hormones
Synthesis of amine hormones Tyrosine
Catecholamine Tyrosine hydroxylase*
Tyrosine
Derivatives Thyroid DOPA
hormones
Amino acid
Derivatives
Tryptophan
Derivatives
Dopamine feedback inhibition
Noradrenaline Catecolamines
Short polypeptides
Peptide Small proteins

Hormones Hormones
Adrenaline
Glycoproteins
Eicosanoids
Lipid
Derivatives Steroid
hormones
a) Catecholamines in the adrenal medulla

• Dopamine is a very important neurotransmitter in the brain.
• But Dopamine cannot cross the Blood/Brain Barrier.
• So the brain has to make its own catecholamine.
Parkinson’s disease (local deficiency of dopamine synthesis)
• Due to lack of tyrosine hydroxylase
• Treatment – DOPA (readily cross the BBB)
b) Biosynthesis of thyroid hormones
• Two types – T3 & T4
• Precursor (of both T3 and T4) – thyroglobulin
• Thyroglobulin has tyrosine residues
Step 1:- Oxidation of iodine in plasma Hypothalamus
I2 + H2O2 Peroxidase
I2 ↓TRH
Step 2:- Iodination of tyrosine (of thyroglobulin) Anterior pituitary
↓TSH
I2 + Tyrosine portion of thyroglobulin
Thyroid
(Monoiodotyrosine) MIT DIT (diiodotyrosine) Negative feedback
Step 3:- Coupling of MIT AND DIT Inadequate Iodine adequate Iodine
MIT + DIT ↓ ↓
Low T3 and T4 T3 and T4
T3* T3 (inactive) ↓
OR Low negative feedback
↓
Step 3:- coupling of DIT and DIT Excess TSH
DIT + DIT → T4 ↓ Iodine deficiency
Thyroid
• When the thyroid gland is stimulated via ↓
TSH, T3 and T4 are secreted to the blood
Abnormal growth
stream.
• They bind to plasma carrier proteins. (Goiter)
Adrenal cortex
Biosynthesis of steroid hormones
a) Adrenal cortex hormones
• Mediated by the increase of Adrenocorticosteroid/ Androgens
• cAMP Corticosteroid
• Ca+2
• Inositol-triphosphate, in response to
hormonal stimulus. Mineralcorticoid glucocorticoid
b) Sex hormones in gonads •Aldosteron •cortisol
Main precursor – cholesterol
c) calcitriol
Actions of Calcitriol
Calcitriol
Intestine KIDNEY Bone
Increased absorption of Ca+2 and phosphate Increased release of Ca+2 and phosphate to the ECF

Receptors
• Protein
• There are 3 types of receptors.
o Membrane bound
o Cytoplasmic
o Nuclear
• These are categorized by their solubility.
Hydrophilic Ex:- catecholamines
 Membrane bound receptors
Hydrophobic Ex:- thyroid and steroid hormones

 Cytoplasmic receptor
 Nuclear receptors
• Fits / tightly binds with the active site of the hormone
• Convert the signal to a response.
• Highly specific for a particular protein.
• Tissues have their own pattern of distribution of receptors.
• The number of receptors in a cell is not constant.
o Up regulation-
 Increased gene expression
o Down regulation
 Inactivation
 Separation of the receptor from the surface
 Destruction within lysosomes
 Decreased production/repair
Hormone signal transduction
• The series of events and components that takes part in transmitting hormonal signal to
the interior of cells
Hormone (first messenger)
↓
Membrane / cytosolic receptor
↓
Signal initiator → initiation
↓
Signal mediator – second messenger → amplification
↓
Target molecule
↓
Action
• Each of the above steps are more powerfully activated.
• So a very low concentration of hormones brings out a huge effect.
Classification of receptors according to their mechanism of hormone signal transduction

• Ion channel linked receptors – open / close Ca+2 channels
• G protein linked receptors – regulate cellular actions via G proteins
o Adenyl cyclase receptors o Phospholipase C
• Enzyme linked receptors
o Outside – hormone binding site
o Inside – catalytic domain site

Intracellular receptors
o Cytoplasmic receptors Hormone binds to the receptor
o Nuclear receptors ↓
Opening of Ca+2 channels
Ca+2 channel linked receptors ↓
Ca+2 influx
G protein linked receptors ↓
• Exist in two states Increased cytoplasmic Ca+2 levels
o Active state bound to GTP ↓
o Inactive state bound to GDP Biochemical effect
• Work with many receptors
• Can both
o Stimulate
o Inhibit hormone signals
• When GTP is hydrolyzed to GDP, stimulation is stopped
G protein mediated transduction activating adenylate cyclase (second messenger – cAMP).

Ex: - Epinephrine binding to its β adrenergic receptor.
Hormone binds to the receptor
↓
Conformational change transferred to the cytoplasmic domain
↓
Interaction of the receptor with G protein in the cytoplasmic surface of the membrane
G protein has 3 domains; α, β and γ. α subunit has GDP bound to it.
↓
The binding of the G protein to the receptor causes the replacement of GDP by GTP
↓
α subunit dissociate from the others.
↓
α subunit bind to adenylate cyclase
↓
Activation of adenylate cyclase
↓
ATP is converted to cAMP→ cAMP activates protein kinases (phosphorylation)
↓
Inherent GTPase activity in the α subunit
↓
GTP hydrolyzes to GDP
↓
α subunit re-associate with the other two subunits

Transduction via G protein activating phospholipase C (Second messengers – IP3 and DAG)
Ex:- Epinephrine binds its α adrenergic receptor
Hormone binds to the receptor
↓
Conformational change transferred to the cytoplasmic domain
↓
Interaction of the receptor with G protein in the cytoplasmic surface of the membrane
G protein has 3 domains; α, β and γ. α subunit has GTP bound to it.
↓
GTP hydrolyzes to GDP
↓
α subunit dissociate from the others.
↓
α subunit bind to phospholipase C
↓
Activation of phospholipase C
↓
Phosphatidylinositol bisphosphate hydrolyze into Diacylglycerol (DAG) and inositol triphosphate (IP3)
↓
IP3 release stored Ca+2 from ER
DAG opens Ca+2 ion channels and increase Ca+2 influx
↓
Increased Ca+2 levels inside the cell
↓
Calmodulin binds with Ca+2
↓
Activation of enzymes
Therefore, epinephrine can act through two second messenger systems.
1. Alpha adrenergic receptor system
2. Beta adrenergic receptor system
Transduction via phosphodiesterase (inhibition)
Hormones bind to receptor
↓
G protein activation
↓
↓
Activation of phosphodiesterase
↓
cAMP is hydrolyzed to AMP
↓
Inhibition of enzymes
Clinically important G protein linked receptors
α→ α1 and α2
Adrenergic receptors
β→ β1 and β2
Adrenaline – excite both α and β receptors
Noradrenaline – excite mainly α (β to a lesser extent)
• Many antihypertensive drugs are β blockers. They block the binding site of
catecholamines to β receptors.
Enzyme linked receptor action
• The binding of a hormone to the receptor directly activate its inherent enzyme activity.
Ex:- insulin receptor is a kinase by itself
• The insulin receptor has 2 α chains on the outside of the membrane and 2 β
transmembrane chains.
• The transmembrane β chains have tyrosine residues on the cytosolic surface.
• When insulin binds the tyrosine, residues get phosphorylated. This is called
autophosphorylation.
• Autophosphorylation activate the kinase activity of the receptor.
• Then the cytosolic target proteins are activated to bring about the effect of insulin.
Intracellular receptors – steroid hormones

• Steroid receptors are of two types
o Type 1 – cytosolic
o Type 2 – nuclear
• Cytosolic receptors have heat shock protein (hsp) associated with the inactive receptor.
• Nuclear receptors don’t have hsp.
 Steroid hormone crosses the cell membrane

↓
Interaction with the cytoplasmic receptor
↓ Or directly bind
Dissociation of the hsp with nuclear
↓ receptors
The complex is transported into the nucleus
↓
Formation of dimers
↓
The complexes bind to HRE (hormone response element) of the enhancer region
↓
Activation of gene transcription
↓
Protein synthesis
↓
Cellular response
 Thyroid hormone diffuses across the cell membrane
Hormone binds to mitochondrial receptors Hormone binds to nuclear receptor

↓ ↓
Increased ATP production Complex bind to DNA
↓ ↓
Cellular response Gene activation
↓
Cellular response

GLYCOLYSIS
Importance
• Provides energy and metabolic intermediates.
• Provides ATP directly by substrate level phosphorylation
Emergency energy supply in hypoxia - does not need O2
Myocardial infarction.
Strenuous exercise in skeletal muscle
Tumor cells
Major energy supply of RBC (lack of mitochondria)
• Provides NADH which provides ATP by ETC – oxidative phosphorylation
• Provides intermediates for other metabolic pathways
• Aerobic – glucose to pyruvate
Anaerobic – glucose to lactate
Transporters of glucose
Occurs in cytosol - Glucose is polar – can’t cross membranes – need transporters (tissue specific)
Passive transporters ( Na+ independent Facilitated diffusion) - along conc. Gradient
GLUT transporters – exist in 2 conformation states

• GLUT 1 -RBC, Endothelial (BBB), Fetal tissues Low Km , High affinity( take up even when
blood levels are low)
• GLUT 2 -Renal medulla, Liver, Pancreatic β cells High capacity, low affinity, High Km , DUAL
(glucose sensing for insulin secretion) ROLE: transport glucose in both directions
• GLUT 3 -Neurons, Placenta, testis High affinity, high capacity
• GLUT 4 -Adipose tissue, Striated muscle Insulin dependent (diabetes)

(cardiac, skeletal) stored in intracellular vesicles
GLUT 5 – fructose transporter
Active transporters(Na+ Dependent ) – against conc, gradient

Na+-Glucose cotransporter (luminal side)
Eg: SGLT 1 – Duodenum
SGLT 2 - Kidney tubules
Na-K-ATPase pump (basal side) – establishes electrochemical gradient
Regulation of Glycolysis
3 regulatory steps (Irreversible reactions)

• Hexokinase or Glucokinase (HK/ GK)
• Phosphofructokinase 1 ( PFK 1 ) RATE LIMITING / COMMITTED STEP
• Pyruvate kinase( PK)

(6C) Glucose
ATP Glucokinase/ hexokinase

G6P -
Glucose-6- Phosphate
F-2,6-BP +
AMP +
Fructose-6-phosphate
Phosphofructo-kinase 1
ATP
COMMITTED STEP
ATP –
Citrate -
Fructose-1,6-bisphosphate (6C)
( 3C) DHAP Glyceraldehyde-3-phosphate (3C)
2 NADH
Glyceraldehyde-3-
Phosphate dehydrogenase
2(1,3-bisphosphoglycerate)
2 ATP
2(3-phosphoglycerate)
2 ( 2-phosphoglycerate)
Enolase
F-1,6-BP + 2 ( PEP)
Pyruvate kinase
ATP - 2 ATP
2 ( Pyruvate)

1.phosphorylation of glucose ( commits glucose for further metabolism in the cell, by trapping glucose)
Hexokinase/glucokinase
Glucose Glucose – 6-P
Glucokinase –liver and pancreatic beta cells

Hexokinase – all tissues ( Inc. liver )
• Hexokinase – Low Km [high affinity]

 efficient phosphorylation of glucose at low concentration
 broad substrate specificity( catalyzes phosphorylation of other monosachcharides as well)
 inhibited by high G6P
 Glucokinase high Km(low affinity)

 high Vmax
 NOT inhibited by G6P
 Efficient phosphorylation in the liver while glucose concentration is high in the portal vein
 prevents excess glucose entering the systemic circulation
 In the pancreas determines the glucose threshold for insulin secretion(glucose sensing )
 Mutations in GK- Maturity onset diabetes of the young people type 2 ( MODY 2 )

2. Phosphorylation of Fructose-6-P by Phosphofructokinase 1 ( rate limiting and committed
step in glycolysis)
AMP
F-2,6-BP – most potent activator
PFK 2 +
PFK 1
F-6-P F-1,6- BP
-
ATP
Citrate
PFK 2 – Phosphofructokinase 2 / FBP 2 – fructose- 2,6-bis phosphatase
(PFK 2 / FBP 2) is a bifunctional enzyme – covalently modified

When phosphorylated – PFK 2 inactive / FBP 2 active
When dephosphorylated – PFK 2 active / FBP 2 inactive
PFK 2
F-6-P F-2,6- BP
FBP 2
Adenylate
cyclase
Glucagon cAMP Active protein kinase A phosphorylates the
Bifunctional enzyme
In Fed state high insulin/glucagon ratio low cAMP dephosphorylaton
Activates PFK 1 Formation of F-2,6- BP
Fructose-2,6-bisphosphate is an inhibitor of gluconeogenesis enzyme fructose-1,6-bisphosphatase. Therefore

reciprocal regulation of glycolysis and gluconeogenesis.
3. Formation of pyruvate by pyruvate kinase
Pyruvate kinase
PEP Pyruvate
+ Feed forward regulation
F-1,6-BP
When blood glucose level is low, HEPATIC pyruvate kinase is phosphorylated (via cAMP) and thereby
inactivated inhibiting glycolysis and driving gluconeogenesis .

Pyruvate kinase Deficiency
RBCs entirely depend on glycolysis for ATP production as they lack mitochondria . In the deficiency of
the enzyme ATP production by glycolysis is reduced. Premature lysis of RBCs occurs due to inability of
maintaining ion pumps in the cell membrane. Hemolytic anemia results.( prickle cells, jaundice and
splenomegaly)
Energy Production in Glycolysis

For 1 glucose molecule
2 ATP –consumed
4 ATP –produced by substrate level phosphorylation
Net production – 2 ATP and 2 NADH( directed to ETC)
Fate of pyruvate
Pyruvate
Aerobic Anaerobic
Acetyl CoA Lactate / NAD+

(cytosol)
TCA
Cycle (mitochondria)
CO2 /H2O/ATP/
NADH/FADH
Effect of insulin and glucagon

Regular consumption of carbohydrates and administration of insulin  increase synthesis of regulatory enzymes
In DM, due to reduced insulin levels  decrease synthesis of regulatory enzymes
Clinically important facts
Lactic Acidosis
• In glycolysis 2 NADH are formed using NAD+

• There is only a limited amount of NAD+ in a cell. So NADH should be re oxidized and NAD+ should be
regenerated.
• This is normally achieved by transporting NADH in to the mitochondria and oxidizing into NAD+ via
electron transport chain.
• When this process is impaired, NAD+ is regenerated by converting pyruvate into lactate.
• Accumulation of lactate (lactic acidosis) will lead to;
1.Reduction of pH→ Accumulation of water →Loss of membrane integrity →Leakage of cellular
proteins →Death of cell (MI)

2.Neurological disturbances
Causes:
Inhibition of ETC
 Hypoxia
 Inherited diseases of mitochondria
 Absence of ATP/ADP translocase
 Inhibitors and uncouplers of ETC
 CN- poisoning
Impaired activity of PDH

Accumulation of pyruvate → Excesive lactate production→lactic acidosis
Eg:
• Mercuric and Arsenic poisoning (Heavy Metals) - binds to SH (thiol) groups of lipoic acid
which is a coenzyme of PDH
• Alcoholism – poor nutrition & impaired absorption of thiamin
→thiamin deficiency ( TPP is a coenzyme for PDH)
• Inherited PDH deficiency
Treatment- give a ketogenic diet (rich in lipids and low in carbohydrates)
Alcoholism (refer gluconeogenesis)
Haemolytic anaemia -Deficiency of aldolase and pyruvate kinase
Conversion of Glyceraldehyde-3-P to 1,3-BPG catalyzed by

glyceraldehyde-3-P dehydrogenase is the first oxidation reduction
reaction in glycolysis. It produces 2 NADH per glucose
molecule.Arsenate ( a structural analog of phosphate) does not inhibit
the pathway but can prevent the net ATP and NADH production by
competing with phosphate for Glyceraldehyde-3-P dehydrogenase
forming a complex that spontaneously hydrolyzes to 3PG without
forming NADH.
Fluoride ions in the presence of phosphite ions inhibit the glycolysis enzyme Enolase by forming a
fluorophosphate complex with Mg which is the co-factor of the enzyme. Blood collection tubes for glucose
estimation contain NaF to inhibit glycolysis and prevent further utilization of glucose. Water containing fluoride
reduces lactate production by mouth bacteria, decreasing dental caries.
Role of 2,3-BPG in RBCs- made from 1,3-bisphosphoglycerate in response to chronic hypoxia.(high altitudes
,etc) Binds with beta chain of hemoglobin and reduces its affinity for oxygen. More oxygen is released in the
tissues.

TCA Cycle
Needs aerobic conditions (O 2 )- (to regenerate NAD and FAD via ETC)
Occurs in mitochondrial matrix. ( but not a part of TCA cycle )
So a specific transporter helps pyruvate to cross the inner mitochondrial membrane
Pyruvate +CoA + NAD + PDH Acetyl CoA + NADH + H+ + CO 2
PDH is a multi enzyme (multiple copies of three enzymes) complex in the mitochondrial matrix - cAMP
insensitive
COENZYMES
CoA vitamin B5
FAD vitamin B2
Lipoic acid
NAD vitamin B3
TPP vitamin B1
( mnemonic – CFL Nethi Torch )
Regulation of PDH complex

PDH P
(inactive)
ADP
PDH
PDH kinase Phosphatase
ATP
PDH
NAD+ (active) NADH + H+
Pyruvate Acetyl CoA
CoA CO 2
Activators of PDH kinase - NADH/NAD+ , ATP/ADP , Acetyl CoA/CoA
Inhibitors - Pyruvate,Ca²⁺(skeletal muscles)
Activators of PDH phosphatase – Insulin(only in adipose tissue), Ca²⁺, Mg²⁺
© Repeat Campaign 2015 A/L

PDH kinase and phosphatase  cAMP insensitive
End product inhibition of PDH

Acetyl CoA
NADH
PDH activity affected in
• Dietary deficiency of thiamine

• Inherited PDH deficiency
• The presence of agents that oxidize or complex with thiol (S-H) groups (such as heavy metals, arsenite )
– inhibit PDH
Energy produced by PDH

For one molecule of glucose
2* NADH 2*3 = 6 ATP
Energy produced by TCA cycle

For one molecule of Acetyl CoA entering TCA cycle
1 FADH2 1*2 ATP = 2 ATP
3 NADH 3*3 ATP = 9 ATP
Substrate level phosphorylation =1 GTP
12 ATP
Aconitase

Regulation of TCA cycle
Control step
Citrate synthase
OAA+ Acetyl CoA Citrate
ATP
LCFA CoA
Rate limiting step

Isocitrate DH
Α ketoglutarate +NADH +CO 2
isocitrate
ATP ADP
NADH Ca2+
PDH and αKGDH
 Structurally similar
o 3 distinct enzymes
o Coenzymes are similar
o αKGDH is not subjected to regulation by phosphorylation & dephosphorylation.
 αKGDH is inhibited by
Succinyl CoA, NADH
ATP, GTP (high energy)
Arsenite
• Activated by Ca2+
Succinate dehydrogenase
Embedded in inner MT membrane(complex II in ETC)
Inhibited by OAA, Malonate
Aconitase
Inhibited by fluoroacetate (use as pesticide)
Citrate Isocitrate
Steps which are important

• NADH formation
1) Isocitrate Isocitrate DH αKG
NAD+ NADH + H+
2) αKG α KGDH Succinyl CoA
NAD + NADH + H+

3) Malate Malate DH OAA
NAD+ NADH + H+
• Substrate level phosphorylation
Succinyl CoA succinate thiokinase succinate
GDP GTP
• FADH 2 formation
Succinate succinateDH Fumarate
FAD+ FADH 2
In TCA Cycle:
For one glucose molecule;
→ 4 CO2
→ 6 NADH
→ 2 GTP
→ 2 FADH2
Summary:
At the end of the TCA Cycle, for
one glucose molecule:
→ 6 CO2
• 2 from PDH
• 4 from TCA cycle
→ 10 NADH
• 2 from glycolysis
• 2 from PDH
• 6 from TCA cycle
→ 2 FADH2 (from TCA cycle)
→ 4 ATP (from glycolysis)
→ 2 GTP (from TCA cycle)

HEXOSE MONOPHOSPHATE PATHWAY(HMP) / PPP
• Important source of 1) NADPH
♦ For reductive biosynthesis
♦ Counter free radical damage
2)Ribulose-5-phosphate
♦ Rapidly dividing cells to make DNA & RNA
• Occurs in cytosol.
• No ATP is directly consumed or produced in the cycle.
• 2 parts- 1. Irreversible oxidative reactions 2. Reversible non-oxidative reactions.
Irreversible Oxidative Reaction…-active in liver, adipose tissue, adrenal cortex, RBC, lactating mammary glands
Glucose 6 phosphate
dehydrogenase
Glucose-6-P 6-phosphogluconolactone 6-phosphogluconate
NADP+ NADPH NADP+
CO2
6-phosphogluconate
dehydrogenase
• Important in cells with high demand of NADPH.
Eg: -RBC -to keep glutathione reduced. NADPH
-Liver –adipose tissue
-Mammary gland- for fatty acid bio synthesis.
- Testis, ovaries, placenta, adrenal cortex –steroid hormone synthesis Ribulose-5-P
• Glucose-6-Phosphate dehydrogenase is the regulatory enzyme. (G6PD)
• High NADPH/NADP+ ratio inhibits the enzyme.
• Insulin enhances gene expression of the enzyme.
Reversible non-oxidative reaction….
Catalyzes inter conversion of 3,4,5,6 & 7 carbon sugars.
Ribulose-5-phosphate
Transaldolase &
Transketolase reactions
Ribose-5-P
Glyceraldehyde-3-P + Fructose-6-P
Nucleotide synthesis
Glycolysis
In the cell, phases of HMP taking place is altered according to demand.
1. Cells, needed only NADPH (E.g.: RBC)
Glucose Glucose-6-PRibose-5-P--------- glyceraldehyde-3-P + fructose-6-P
NADPH Glycolysis for energy
2. Cells that only need Ribose-5-P

- When NADPH is abundant in a cell, high [NADPH] completely inhibits Glucose-6-P dehydrogenase.
- Raw materials for reversible phase taken from glycolysis produce ribose-5-P.
Glyceraldehyde-3-P Ribulose-5-P Ribose - 5- P
Fructose-6-P
NADPH
Ratios of reduced/oxidized forms in cytosol of hepatocytes favor:
- Reductive biosynthesis for NADPH NADPH:NADP+ = 10:1
- Oxidative role for NAD+ NADH:NAD+ = 1: 1000
Functions of NADPH
Detoxification
a) Maintains the stability of the cell membrane. (esp. RBC)
Metabolic reactions formation of free radicals. E.g.: peroxides, superoxides…..
• Attack lipid bilayer and cause lipid peroxidation. → Cell membrane breakdown (hemolysis)
H2O2 is reduced by glutathione. NADPH reduces Oxidized glutathione into its reduced form.
G-Glutamate
C-Cysteine
G-Glycine
G6PD deficiency – hemolytic anemia

-X linked
- G6PD → main regulatory enzyme in HMP.
- Production of NADPH in RBC is entirely dependent on HMP. Occurs in all cells of body but most sever at RBC
- In G6PD deficiency, no NADPH→ Can’t reduce oxidized glutathione→Can’t maintain stability of RBC membrane
→ Hemolysis.
- Commonly manifests when exposed to oxidative stress
Oxidant drugs e.g.: antimalarial (primaquine), herbicides, antibiotics, antipyretics
Favism (fava beans)
Infection (from oxidants produced during inflammation)
Ionizing radiation

b) Destruction of bacteria by WBC – Phagocytosis O2 independent mechanism
O2 dependent mechanism
- Respiratory burst
- Reactive Oxygen
species O2-, H2O2, OCl-,
OH-
c) Cytochrome P450 mono oxygenase pathway.

- involved in biosynthesis of steroid hormones, bile acids.
- detoxify foreign compounds.
Reductive biosynthesis
Fatty acid biosynthesis
Fatty acid chain elongation
Cholesterol biosynthesis
Neurotransmitter synthesis
Nucleotide synthesis
NO synthesis
NADPH NO synthase NADP+
Arginine Citrulline
O2 NO
Functions of NO
 Relax smooth muscle
 Prevent platelet aggregation
 Act as a neurotransmitter in brain
 Mediate tumoricidal & Bactericidal action in macrophages
Q. Explain the importance of pentose phosphate pathway

in testis.
- Cholesterol is a precursor for testosterone synthesis.
- NADPH is the co-enzyme used here for reduction.
- Ribose-5-P for nucleotide synthesis.
- NADPH is used to synthesis fructose (the main energy
source of spermatozoa) via sorbitol pathway.
- NADPH has an antioxidant defence.

Sorbitol Pathway
Reduction of monosaccharides to polyol by Aldose reductase –an alternative mechanism for metabolizing
sugars (E.g.- lens, retina, liver, kidney, ovaries, seminal vesicles, Schwann cells)
glucose
Aldose reductase NADPH Elevated Sorbitol
Sorbitol Glucose
Sorbitol can’t pass efficiently through
Sorbitol dehydrogenase NAD+ membranes.
Due to osmotic effect water comes in & cells swell
NADH
fructose
Causing cataracts etc.
Fructose & Galactose entry to cells is not insulin dependent
Fructose metabolism
Essential fructosuria Hereditary fructose
intolerance (HFI)
Fructokinase aldolase B
Fructose fructose-1-P glyceraldehyde
DHEA
Galactose metabolism
Galactosemia, galactoseuria Classic

Autosomal recessive galactosemia
galactokinase
galactose galactose-1-P UDP glucose
ATP ADP galactose-1-P uridyltransferase
UDP galactose glucose-1-P
UDP glucose glucose-6-P
Lactose synthesis
Lactose synthase – (UDP: galactose: glucose galactosyl transferase)
Normal tissues Lactating mammary gland

UDP galactose + N acetyl-D-glucosamine in the presence of lactalbumin
β-D-galactosyltransferase UDP galactose + glucose
N-acetyllactosamine + UDP
Lactose + UDP
(lactalbumin synthesis is
stimulated by prolactine –
a peptide hormone)

GLYCOGEN METABOLISM
Glycogen
• Major carbohydrate storage in animals
• Highly branched,homopolysachcharide(one reducing end-more non reducing ends)
• Stored in liver (5%) and muscle (0.7%) as large particles containing enzymes
(Total amount of glycogen is higher in skeletal muscles because more mass.)
• Also in brain – single most conc. carbohydrate store in brain
• Main storage site is liver
Why more branches?

 For efficient glycogen synthesis. (More free
non-reducing endings-glycogen synthase)
 To maximize the rate at which glucose can
be released to meet high energy demand-
(glycogen phosphorylase-attack non-
reducing ends)
 To store the most amount of glucose in the
least amount of space.
Advantages
 Than glucose
Insoluble  low osmotic activity no influx of water into cell
 Than FAs
Can provide energy under anaerobic conditions by glycolysis
(FAs can’t net produce glucose)
 Formation of glu-1-PO 4 3- →no ATP is needed to channel glucose into glycolysis
Importance
• Liver glycogen:- Maintain blood glucose level between meals- lasts 24h in fasting
• Muscle glycogen:- Provide energy for muscle to perform strenuous exercise (aerobic &
anaerobic)
 Muscle glycogen is not affected by short period of fasting
GLYCOGEN SYNTHESIS
 Glycogen synthase is the key regulatory enzyme
• Glucose activation
Glucose Glucose-1-P
UDP-Glucose pyrophosphorylase
Glucose-1-P + UTP UDP-Glucose + PP i
(activated form)
 PPi + H2O  2Pi
 Therefore all reactions producing PPi are shifted to right & almost
irreversible

• Initiation of glycogen synthesis
Glycogen synthase needs a primer to initiate synthesis.
 Protein called glycogenin (Autocatalytic activity- glucose transferase)-has Tyrosine
 Glycogen fragment
• Chain elongation
Glycogen synthase
(Glycogen) n + UDP-Glucose (Glycogen) n+1 + UDP
Glucose is added to non-reducing ends.- α-1→4-glycosidic bonds
ATP + UDP UTP + ADP
So, for each α added 1 ATP is consumed
• Branching
Branching enzyme cuts a string of glycogen (8-10 glycosyl units) from the growing end and grafts
onto the 6th C atom of a glucose residue in the chain. –α-1→6-glycosidic bonds
Further elongation by glycogen synthase

GLYCOGEN BREAKDOWN
Not the reversal of synthesis. Has separate set of enzymes
Glycogen phosphorylase is the key regulatory enzyme
Glycogen(n) + P i Glucose-1-P + Glycogen(n-1)
• Breaking of α-1-4 bonds at non reducing ends to release Glucose-1-P

By glycogen phosphorylase – needs vit B 6 (pyridoxal phosphate) as coenzyme
 Vit B6 is required to mobilize glucose from glycogen
Phosphoglucomutase
Glucose-1-P Glucose-6-P
Liver Muscle
Glucose 6-phosphatase
Used for muscle contraction via

Lysosomal degradation of Glycogen. Glucose Glycolysis as phosphorylated
 Glycogen granules are engulfed by
Glucose cannot leave
lysosomes and degraded
 Important in neonates the cell
 Function unknown in adults but defects Blood
cause diseases
Eg: Type II – Pompe disease

REGULATION OF GLYCOGEN METABOLISM
Glycogen metabolism is regulated by regulating glycogen

phosphorylase and glycogen synthase.
Hormonal regulation
Synthesis increases in :
Well-fed state (liver) By insulin
Resting state after a meal(muscle)
• Actions of insulin (after a meal)

 Stimulates glucose uptake via GLUT 4
 Promotes glucose use by activating glycogen
synthase – by dephosphorylation
 Decreases glycogenolysis by inhibiting
glycogen phosphorylase – by
dephosphorylation
Breakdown increase in :
Fasting state (liver)  glucagon, epinephrine
Exercise state (muscle)  epinephrine, (NOT
glucagon)
 Muscle is not responsive to glucagon

 Both hormones use G protein dependent signal transduction
pathway
 Both affect the first reaction(glycogen phosphorylase)

Glycogen Metabolism
Liver Muscle
Insulin Glucagon Epinephrine Epinephrine Insulin Ca2+ AMP
Covalent Modification Allosteric Regulation
 Glycogen phosphorylase in both liver and muscle has product inhibition

o In liver, glycogen phosphorylase inhibited by glucose-6-phosphate and
glucose
o But in muscles only by Glucose-6-phosphate

LIVER MUSCLE
Glycogen acts as a glucose reserve. Glycogen acts as an energy reserve.
Maintains blood glucose level – buffers glucose Provide ATP for muscle action.
End product is glucose. End product is Glucose-6-phosphate.
Glucose-6-phosphatase enzyme is present. Glucose-6-phosphatase enzyme is absent.
Hormonally regulated by glucagon, insulin, Insulin, epinephrine. (no glucagon influences.)
epinephrine.
Receptors: insulin, glucagon, adrenergic (α,β) Insulin, β adrenergic.
2 messengers:
nd
2nd messengers:
cAMP, Ca2+, IP 3 , DAG cAMP, Ca2+
Ca2+ doesn’t stimulate glycogen phosphorylase Ca2+ released from sER during muscle contraction
activates phosphorylase kinase without
phosphorylation(partially active)→activates
glycogen phosphorylase
AMP has no role in regulating glycogen AMP directly activates glycogen phosphorylase
phosphorylase without phosphorylation.
Glucose allosterically inhibits glycogen Glucose has no action in regulation of glycogen
phosphorylase. phosphorylase.
Glycogen stores: Glycogen stores:
Increased- during well-fed state. Increased- during resting state
Depleted- during fasting. Depleted-during muscle contraction.
Glycogen storage diseases.

VON GIERKE DISEASE POMPE DISEASE McARDLE DISEASE
(type 1 glycogen storage
disease)
Due to inborn lack of Due to lack of α-1,4- Loss of glycogen
glucose-6-phosphatase glucosidase phosphorylase in muscles
CAUSE
Glucose-6-P can’t be Accumulation of glycogen Occasional vacuoles are

converted into glucose, in lysosomes. filed with glycogen.
leads to hypoglycemia.
RESULT
Hepatomegaly, fasting Massive cardiomegaly, Temporary weakness,

hypoglycemia, fatty liver, excessive glycogen cramping after exercise.
renomegaly, hyper lactic concentration. Abnormal
SYMPTOMS
academia, hyperlipidemia, vacuoles in lysosomes.

hyperuricemia

FATTY ACID BIOSYNTHESIS
Tissues- liver sub cellular location - cytoplasm
Lactating mammary glands
Adipose tissue (lesser extent)
Substrates - Acetyl CoA

ATP Amino acid degradation
NADPH
CO2
Dietary CHO glucose glycolysis Acetyl CoA Fatty acids oxidation

HMP
Malic enzyme NADPH lipogenesis
ATP
The main regulatory step

1st step = committed step = irreversible = regulation point
Acetyl CoA Malonyl CoA

(Initial Acetyl CoA carboxylase
Substrate) CO2, Biotin, ATP

Regulation mechanisms short term Allosteric
Covalent modification
Long term gene expression
Acetyl CoA Carboxylase gene

+
CHO
Long -
Term Fat
Regulation +
Insulin Transcription
Citrate L.C.F.A
_
+
Acetyl CoA Acetyl CoA carboxylase
Allosteric carboxylase [ dimer ]
Regulation [Polymer] inactive
Active
Covalent Modification
Regulation of acetyl coA carboxylase by phosphorylation and dephosphorylation
Insulin
+
protein phosphatase
Acetyl coA Acetyl coA carboxylase

carboxylase -P
Inactive Active
AMP dependent
ADP ATP
protein kinase (AMPK)
Glucagon + AMP
AMPK
Epinephrine Kinase
Fatty acid synthase
 Multi functional
 7 enzyme functions
 Cytosolic
 Contains Vit.B5 ---- Acyl carrier protein
Primary end product is palmitate

Fatty acid synthesis process
 Major7 steps for one cycle.

 Repetition of cycle of reactions producing palmitate as the primary end product.
 For the initial step Acetyl CoA is utilized but for further elongation 2C donor is Malonyl CoA.
Elongation
Further elongation
 Primary end product (Palmitate) In SER and mitochondria
Separate enzymic processes
 Brain also has this capacity (Very long chain FA)
Desaturation
 In SER  Add cis bond

 Require NADH & oxygen
 Mammals cannot synthesize double bonds from C10 to ω end but mammals require
poly unsaturated fatty acids
Role of L.C.F.A
citrate
+
Acetyl CoA [dimer] Acetyl CoA [ polymer ]
L.C.F.A
AMPKK AMPK Acetyl CoA
_
(active) (active) carboxylase (inactive)
Transcription of of Acetyl CoA carboxylase gene

_
PDH
Role of citrate
--- Transport Acetyl CoA

--- Produce NADPH Via Malic enzyme
--- Regulates Acetyl CoA carboxylase

TAG synthesis
• Synthesis in liver& adipose tissue

• No storage in liver
• Made in to VLDL for transport
• Glycerol 3-phosphate is the initial acceptor of fatty acids
• Only liver has glycerol kinase. So in Adipose tissue, glycerol-3-phosphate is supplied only by
glycolysis.
Synthesis of Glycerol phosphate

Liver
Can synthesize glycerol 3 phosphate from glycolysis and by glycerol kinase activity
Adipose tissue
Glycerol kinase is absent in adipose tissue
Synthesis of TAG molecule from Glycerol Phosphate
• FA should be activated by attaching it to coA by Fatty Acyl coA synthatase

• Addition of 2FAs from fatty acyl coA by Acyl transferase
• Removal of phosphate by phosphatase
• Addition of 3rd FA by Acyl transferase
Importance of glycolysis in adipose tissue and Liver in TAG synthesis
Liver
insulin
Glycerol 3pDH
DHAP Glycerol – 3 -P
NADH NAD+
Glycerol kinase
insulin HS-Lipase(inactive)
glycerol (+) (+)glucagon
cAMP Ephinephrine
ACTH
(+) HS - Lipase –P (active)
Glu Glu Glycerol-3-phosphate DG + FA FA

(+) TG
LpL MG + FA FA
VLDL FA FA Fatty acyl CoA
Glycerol FA FA
CM
Glycerol

Cholesterol Biosynthesis
• Tissue -- mainly in liver & intestine

• Site – cytosol
• Substrates – Acetyl CoA using NADPH
• Regulating enzyme – 3 hydroxy-3 methyl-glutaryl CoA reductase enzyme or HMG CoA

reductase
• Two forms of HMG CoA synthase isoenzyme
• Cytosolic -- cholesterol biosynthesis
• Mitochondrial matrix – ketone bodies synthesis
Acetyl CoA [C2]
HMG CoA (β - hydroxy β Methyl Glutaryl CoA)

NADPH
HMG CoA Reductase (Rate limiting)
NADP +
Mevalonate [C6 ] Cholesterol
Cholesterol biosynthesis regulation

SREBP
Binds DNA at SRE SREBP
Regulation of Proteolytic cleavage
HMG coA reductase Transcription SREBP-ER

_
P Protein
kinase(AMPK) Translation HMG CoA Inhibition by drugs
+ AMP _
HMG CoA HMG CoA Reductase structural Simavastatin
Reductase Active analogues Lovastatin
(Inactive) Mevalonate of HMG CoA Mevastatin
Competitive inhibition
Phosphoprotein Cholesterol
Phosphatase +
Proteolysis Cholesterol, oxidized forms of
ubiquitination Cholesterol, mevalonate
Low concentration
HMG CoA Reductase
Long term regulation  Insulin and thyroxine favours up regulation of gene expression
 Glucagon down regulates.

TRIGLYCERIDES AND FATTY ACID CATABOLISM
• TAG storage in adipocytes

As globules in muscles (lesser amount)
• TAG is broken down to free fatty acids and glycerol by Hormone sensitive lipase in
adipose tissue
• HSL removes a FA from C1 and/or C3 of TAG and additional lipases remove the
remainder.
Hormonal regulation of TAG degradation in adipose tissue
Adrenaline glucagon
and ACTH
Hormone Receptor
Adenyl cyclase
ATP cAMP
Protein kinase Protein kinase

(inactive) (Active)
P
TAG
ATP ADP
HSL Inactive HSL Active
High level of
insulin and glucose Free FA
Protein
phosphatase
pi H2O
• Glycerol is delivered to liver for glycolysis or gluconeogenesis

• Free fatty acids are bound to albumin and delivered to tissues
FA Oxidation
• Occurs in the mitochondrial matrix
• Products – Acetyl CoA, NADH, FADH2
• The products of oxidation will further be oxidized through the electron transport chain in the
mitochondria, to form ATP
1st step – Activation Step

Fatty Acyl CoA Synthatase
(thiokinase)
R—COO- R—CO—S—CoA
Fatty Acid Fatty Acyl CoA
CoA—SH
ATP AMP + PPi

` PPi + H2O  2 Pi
• Easily reversible
• ATP dependent
• Short and Medium Chain Fatty Acids (SCFA & MCFA)- can cross the inner mitochondrial
membrane directly - activation occurs inside mitochondria
• Long Chain Fatty Acids – cannot cross inner membrane – activation occurs at outer
mitochondrial membrane (ER/peroxisome)
2nd Step – Transporting to mitochondria

• Long Chain Fatty Acyl CoA are transported into the mitochondria through Carnitine Acyl-
Transferase System.
• Outer membrane has – Carnitine Acyl Transferase-1 (CAT-1)/ Carnitine Palmitoyl

Transferase- 1 (CPT-1) enzyme
• This transfers the fatty acid part from CoA to Carnitine, forming Acyl Carnitine
• Malonyl-CoA inhibits CAT-1 (product of FA biosynthesis)
• Hence prevents the degradation of newly formed palmitate/ FA.
• This is the regulation point of β – oxidation by regulating entry of Long Chain Fatty Acids into
mitochondria.(rate limiting step)

• In muscles, though they do not synthesize FAs, has mitochondrial isoform of ACC to regulate
β - oxidation
• Inner membrane has Carnitine Acyl Transferase-2 (CAT-2) enzyme
• It transfers the Fatty acid part again to CoA, forming Fatty Acyl CoA and releasing Carnitine
• Carnitine-Acyl Carnitine Translocase – inner mitochondrial membrane antiport
• This sends Acyl Carnitine into the mitochondrial matrix, taking free Carnitine out of it.
 Sources of Carnitine
o Primarily in meat
o Synthesized from AAs  Lysine & methionine  Liver & Kidney
Carnitine deficiency
1. Primary Carnitine Deficiency
a. Congenital deficiency in components of CAT system – genetic mutations
b. Decreased renal tubular reabsorption
Defect in the membrane transporter
c. Poor uptake of Carnitine by cells
2. Secondary Carnitine Deficiency

a. Liver disease – decreased synthesis
b. Malnutrition/Strict vegetarian diets (main source of Carnitine is meat)
c. Increased requirement for Carnitine in pregnancy, severe infections, trauma, burns
d. Patients undergoing haemodialysis
e. Organic acidurias - inhibit renal tubular reabsorption of carnitine
3rd step - β -Oxidation
• A cyclic process [ one cycle  4 reactions]

• Occurs inside the mitochondrial matrix
• Each Cycle produces one acetyl CoA and a Fatty acyl
CoA with 2 carbons reduced.
• Also each cycle produces 1 NADH and 1 FADH2 
they enter e-transport chain to yield ATP
• The Acyl CoA dehydrogenases vary according to the
no. of carbons in the Acyl CoA (very long
chain/medium chain/short chain Acyl CoA
Dehydrogenase)
• Acetyl CoA can
o Enter TCA and form ATP
o Be used as a substrate for Amino Acid biosynthesis
But CANNOT be used as a substrate for
gluconeogenesis
Palmitoyl CoA + 7CoA + 7FAD + 7NAD + 7H2O
8Acetyl CoA + 7FADH2 + 7NADH + 7H+
7FADH2 + 7 NADH 131 ATP But 2 ATP for

activation step
∴ 129 ATP

β oxidation of odd number C FAs.
• Initial steps are same until final 3C are reached. (Propionyl CoA)
• Propionyl CoA is metabolized into succinyl CoA
Peroxisomes can β oxidize VLCFA forming acetyl CoA and H2O2
Effect of oxygen supply & energy status on β – oxidation
• β – oxidation only produces the reducing equivalents NADH and FADH2. But ATP is made in the
e-transport chain.
• Oxygen is necessary for the electron transport chain
• When oxygen is deficient  e-transport chain inhibited  Accumulation of NADH and FADH2
 inhibit β – oxidation
• When energy status is high  ATP will accumulate  ADP low
e – transport chain inhibited  NADH & FADH2 high  inhibit β – oxidation
• When energy status is low  ADP is high  e – transport chain activated
 NADH & FADH2 low  NAD+ & FAD high  stimulate β – oxidation
• Low Insulin/Glucagon ratio will stimulate β- oxidation
Low Insulin / Glucagon ratio
Acetyl CoA carboxylase inhibited (FA synthesis inhibited)
Low malonyl CoA (it is an intermediate in FA synthesis)
Activate carnitine shuttle
More fatty acyl CoA enter mitochondria
Increased β – oxidation
Facilitate ATP production for use in gluconeogenesis under fasting conditions
KETOGENESIS
• Ketone bodies are small, water soluble, transportable forms of acetyl units
• 3 substances : - β - hydroxybutyrate
Functional forms
Acetoacetate
Acetone – volatile, non-metabolized and released in breath.
• Produced in liver mitochondria
• When FA oxidation rate is high (insulin/glucagon ratio is low)
• In response to prolonged starvation, uncontrolled diabetes and severe exercise
• Markedly reduces the breakdown of muscle protein during starvation.
• If produced in large amounts  acetoacetate and β - hydroxybutyrate are acidic  lowers
body pH ketoacidosis
• Why produce ketone bodies

o Can be lysed to form acetyl CoA, which produces ATP through entering the TCA cycle
o Heart muscle and renal cortex use acetoacetate in preference to glucose
o Brain utilizes ketone bodies when glucose is deficient
o As it is water soluble, it is easily transported via blood
• Under conditions for ketogenesis,
o Acetyl CoA is produced in excess
o Acetyl CoA  Inhibition of PDH
 Activation of Pyruvate Carboxylase
o OAA produces  Gluconeogenesis
o Acetyl CoA amount exceeds the oxidative capacity of liver  Ketogenesis
Formation of ketone bodies
3- hydroxybutyrate
HMGcoA synthase
(Regulatory step) HMGcoA lyase
2AcetytlcoA AcetoacytylcoA HMGcoA Acetoacetate
+acetyl coA Mitochondrial
matrix +acetylcoA
CO2
Acetone
Utilization of Ketone bodies
β - hydroxybutyrate
dehydrogenase
β - hydroxybutyrate Acetoacetate Succinyl CoA
NAD+ NADH + H+
Acetoacetate – Succinyl CoA transferase
Succinate
Acetoacetyl CoA
2 Acetyl CoA
TCA
Liver lacks and enzyme to metabolize Acetoacetate. Hence do not utilize but export to other tissues.

Lipid Transport
Plasma lipids
Cholesterol esters (36%) Phospholipids (30%)
Triacylglycerol (16%) Cholesterol (14%)
Free fatty acids (4%) – metabolically most active
Lipid transport
Majority
FFA + albumin Lipoprotein

Why?
• Lipids are water insoluble.
• Only SCFA are soluble in aqueous medium of blood plasma
• Therefore, cannot be transported in the free state.
Lipoproteins
Spherical particles
Contents : TAG, CE, PL, Cholesterol, Proteins
Lipids
Proteins
Hydrophobic Hydrophilic (Polar)

TAG, CE PL, Cholesterol
(Core) (Surface)
Classes of LP
CM highest % of TG lowest % of proteins
VLDL high % of TG
LDL high % of CE
HDL highest % of proteins & PL
Lipoprotein separation
Ultracentrifugation – by density Electrophoresis - by size
Density CM
Origin
CM
VLDL LDL (β lipoprotein)
LDL protein content & density
HDL Mobility VLDL (pre β
lipoprotein)
-+ Phospholipids
Apoprotein
HDL
(α lipoprotein)

CM – Transport exogenous TG synthesized in intestine, to peripheral tissues (adipose,
skeletal & Cardiac). Formation fluctuates with load of TG absorbed. Give turbidity after
a fatty meal, rapidly catabolized and cleaved from circulation (1-2 hrs)
C I II III, B48,E,AI, AII
VLDL- Transport endogenous TG synthesized in liver to extra hepatic tissue.

CI II III, B100, E, A
Less affected by dietary TG. Precursor for LDL
LDL- Forward transport of cholesterol produced in plasma during intra vascular metabolism
of VLDL.
B100
HDL- Reverse transport of cholesterol produced in liver and intestine.

A1, AII, CI CIII, D, E
Functions of Apoliporotein (Apoprotein)

• Solubilizing and transport of hydrophobic lipids.
• Structural components of lipoprotein
• Co-factors and recognition sites for LP metabolism.
Functions of major Apolipoproteins

Apo LP LP Function
AI HDL Structural protein. Activates LCAT (PCAT). Interacts with
ABC AI transporter.
AII HDL Structural protein
B48 CM Structural protein required for synthesis and secretion of

CM remnants CM.
B100 VLDL , LDL, IDL Structural protein required for synthesis and secretion of
VLDL
Recognition and binding of LDL to LDL receptors.
CII CM, VLDL, HDL Activates LPL.
Apo E CM, VLDL & Triggers clearance of remnants of VLDL (IDL) & CM
remnants remnants. Is recognized by remnant receptors.
CM Metabolism
• Nascent CM synthesized in the intestines contain Apo B 48.
• It receives Apo C2 and E from HDL in the blood plasma.
• Apo C2 activates LPL
• LPL degrades TAGs in the CM and FFAs are released to peripheral tissues
• C2 is returned to HDL & CM remnants binds to Apo E to receptors on the
liver.

VLDL Metabolism
• VLDLs are secreted directly in to the blood by the liver as nascent VLDL.
• Nacsent VLDL contain Apo B100.
• They obtain Apo C2 & E from HDL in the blood plasma.
• Apo C2 activates LPL
• LPL hydrolyzes TAG into FFA & glycerols.
• Remnants of VLDLs, (IDL) now take part in the formation of LDLs.
• VLDL remnants return the Apo C & E to HDL but retain Apo B100
Lipoprotein lipase
• Insulin induces synthesis and transfer of LPL to the luminal surface of
capillaries
• LPL has different Km values depending on the tissue.
• Ex: Km in heart muscle cells < Km in adipose tissue
• So adipose tissue only take up TAG when there is excessive amount.
• LPL activated by Apo C

LDL metabolism
LDLs are produced in the intravascular metabolism of VLDLs.
• Some TAG are transferred from VLDL to HDL in exchange of some CEs from HDL
to VLDL by cholesteryl ester transfer protein.
• This modifies circulating VLDLs to LDLs.
Uptake of LDLs
• Uptake of LDL by tissue is mediated through specific cellular LDL receptors.
It’s a negatively charged glycoprotein.
• LDL binding domain of the receptor is in the N terminal end. ( rich in Glu,
Asp) (-)
• Cytosolic domain controls interaction with clathrin coated pits & participates
in endocytosis.
• Uptake is controlled by intra cellular free cholesterol concentration.
• Adrenals, gonads, etc has more LDL receptors.
DEFECTIVE UPTAKE →LDL accumulates in plasma → hypercholesterolemia

• Decrease LDL uptake due to receptor defects
-reduced membrane LDL receptors
-decreased synthesis
-defects in transport to cell surface
-defective binding to LDL
-defective internalization

• Familial defective apoprotein B-100

FORMATION OF ATHEROSCLEROTIC PLAQUE
• In response to endothelial injury caused by oxidized LDL, monocytes enter
subendothelium and transform into macrophages.
• These macrophages consume excess oxidized lipoproteins (LDL).
• Due to unregulated excess uptake of oxidized LDL they become foam cells.
• Then they migrate from media to intima of the smooth muscle cells of blood vessels.
• These foam cells accumulate releasing growth factors and cytokines that produce
collagen and take up lipids which participate in the formation of atherosclerotic
plaque.

HDL functions
• Produced in liver & intestine. Apo C& E synthesized in liver- transferred to intestinal form in
plasma
• Acts as a repository of Apo C & E required for CM & VLDL metabolism
• Uptake of unesterified cholesterol
• Esterifies Chol & transfer to other LPs
• Reverse transport of Chol ( from tissues to liver)
HDL metabolism
1. Nascent HDL are disc shaped particles that contain PL and Apoproteins A,C and E.
2. They rapidly accumulate cholesterol via ATP binding cassette transporter-1
(ABC-A1) .
3. Cholesterol is esterified within HDL by LCAT/PCAT ( lecithin cholesterol acyl transferase)
4. LCAT is activated by Apo AI.
5. As the nascent HDL accumulates CE, it 1st becomes a relatively CE-poor HDL3 and eventually
CE-rich HDL2.
6. CEs are transferred to VLDLs via cholesterol ester transfer protein( CETP).
7. Liver contains a receptor for HDL2.

Protein Metabolism
• Amino acids that undergo modifications in proteins
Proline 3, 4 hydroxyl proline
Glutamic acid y carboxy glutamic acid
Cysteine Cystine
• Some amino acids are not found in proteins
Ornithine, Citrulline, Epinephrine, Homocysteine
Glutathione
• Tripeptide
• Y glutamyl cysteinyl glycine
• Widely distributed cytosolic antioxidant
• Protect cells from oxidative damage
• Takes part in amino acid transport in kidney tubules
• Insulin - 2polypeptide chains (A and B)
- 1 interchain s-s bridge (A chain)
- 2 interchain s-s bridges
Protein turnover
• Constant degradation and synthesis of body proteins
• Daily protein turnover 500g -- 1-2% of body weight
• In healthy adults
 the total amount of protein is constant
 the rate of synthesis equals the rate of catabolism
 400g broken down daily
 400g synthesized daily
 100g of amino acids catabolised
 100g of dietary amino acids maintain amino acid pool
 Total amino acid pool 500g per day.
Body
Proteins
Synthesis of Dietary
non-essential Proteins
A.A
AA
Pool
Catabolism of Synthesis of
A.A other N
containing
compounds
Body
Proteins

• Proteins are subjected to environmental influences and are damaged,
e.g.: - Reactive Oxygen species
• The capacity to repair this damage is limited, therefore all proteins are degraded and re-
synthesized as a form of quality control
• Functions of protein turn over-
 Synthesis or degradation of proteins depending on demand.
 Degradation of unnecessary and defective proteins.
Amino acid pool
 50% of total amino acid pool in skeletal muscle.
 Only a small percentage is in plasma.
 All amino acids are found but glu, ala predominate.
• Rate of turnover is expressed as half life (t 1/2)
• Half life – time required to reduce concentration of a given protein by 50% of initial value.
 Functional proteins- short half-life (e.g.: - enzymes, plasma proteins)
 Structural proteins- long half-life (e.g.: - muscle proteins, collagen)
 Key regulatory proteins are rapidly degraded.
e.g.: -HMG CoA Reductase, Tyrosine transaminase, Tryptophan oxygenase
 Some regulatory enzymes have long half-lives.
e.g.: - LDH, Aldolase
Clinical
Dietary Protein AA pool Redistribution to Degradation HB level Reduce

Reduce reduce meet essential
of HB resulting anaemia
needs
 Anemia is more tolerant than other protein deficiency.
Degradation of Proteins
1. Lysosomal pathway — for exogenous proteins
e.g.: - cathepsins
 Act in acidic medium.
 Digest proteins engulfed by phagocytosis.
 ATP independent.
2. Cytosolic pathway – for mainly endogenous proteins.
(a) Ca 2+ activated - calpains
(b) ATP dependant - proteosomes
Chemical signals for degradation

1. Ubiquitination
2. Oxidation of amino acid residues
3. PEST sequence
4. N terminal amino acid residues

Ubiquitination
• Ubiquitin is a small heat stable highly conserved
protein.
• Present in all eukaryotes.
• Binding with ubiquitin targets a protein for
degradation via the proteasomes.
• Degradation depend on N terminal AA.
• Ubiquitin is recycled.
Oxidation of amino acid residues

• Lys and Arg in proteins can be oxidized
• Cellular ageing
PEST sequence
• Repeated sequences of pro, Glu, Ser, Thr, are
known as pest sequences
• Usually half life less than 2 hours
N terminal amino acid

• Proteins with and amino terminal of Phe, leu,
Tyr, Trp, Lys, Arg
• Have short metabolic half life
Nitrogen balance
• The amount of nitrogen retained in the body
(Balance = Intake-Output)
States of balance
a) Zero N balance (equilibrium)

In a healthy adult intake and output of N are
equal.
b) Positive N balance
Intake > output
• Pregnancy
• Growth
• Wound healing
c) Negative N balance
Intake <output
• Starvation
• Trauma (protein malnutrition, diet low in
essential amino acids)
• Wasting

Amino acid metabolism
Transamination
α keto acid 1 glutamate

aminotransferase/transaminases
α amino acid α ketoglutarate
• Freely reversible reactions

• Glutamate / αKG obligate pair
• Occur in mitochondria and cytosol
• Vitamin B6 – Pyridoxal Phosphate required for transaminations
• Thr & Lys do NOT take part in transamination reactions
E.g.: alanine transaminase (ALT)
Pyruvate glutamate
ALT
Alanine αKG
Aspartate transaminase (AST)
OAA glutamate
AST
Asp αKG
 Ala tr. And Asp tr. Important in diagnosis of liver and heart damage.
Oxidative Deamination
Glutamate DH
NAD(P)+ NAD(P)H + H+
Glu αKG
NH4+
• Mitochondrial enzyme
• Found in high amounts in liver and kidney
• Reversible reaction
• Both NAD+ /NADP+/NADH +H+ can be used
• Allosteric enzyme
• α-amino groups can be removed at a high rate.
NAD(P)+ NAD(P)H + H+
Glu αKG
Glutamate DH
(+) (-) NH4+
Low ADP ATP High energy state

Energy state GDP, some aa GTP, NAD
• αKG is used for energy production via the TCA cycle
amino αKG NH4+ NADH + H+

acid
Glutamate
aminotransferase dehydrogenase
α keto
acid Glu NAD+
 α keto acids are metabolized and can be used to replenish the TCA cycle.

• Ketogenic amino acids
 Amino acids that only yield acetyl CoA can’t be used for gluconeogenesis
 Used for ketogenesis
 Lys, Leu
• Ketogenic and Gluconeogenic amino acids
 Amino acids that yield both Acetyl CoA and TCA cycle intermediates
 Trp, Tyr, Phe, Ile
• Gluconeogenic/Glucogenic amino acids
 Yields TCA cycle intermediates
 Can be used for gluconeogenesis
 Ala, Asp, Asn, Cys, Glu, Gln, Gly, Pro, Ser, Arg, His, Met, Thr, Val
Production of Ammonia
α keto acid α Amino acid

Transamination
Glu GDH α KG
Other nitrogenous compounds
Purines & Pyrimidines

CO2
NH4+
Bacterial urease in GIT
Gln Glu Urea
Glutaminase
AMP IMP
AMP deaminase
AMP Deamination
 Adenosine is a coronary vasodilator.
Toxicity of NH3
Particularly toxic to CNS – cross blood brain barrier

1) Depletion of α KG
GDH
α KG Glutamate
NH4+ NADH NAD+
- High NH4+ levels convert α KG to glutamate

- Therefore [α KG] is reduced
- TCA cycle activity reduced
- ATP production impaired
2) Inhibition of glutaminase
NH3
Glutamine Glutaminase Glutamate
- NH4+ inhibits glutaminase

- Therefore [glutamate] [Glutamine]
- Glutamate is a neurotransmitter Low neurotransmitter levels
- Glutamate is required for GABA synthesis synaptic transmission impaired
- Gln is osmotically active
- Accumulation leads to brain oedema.
3) Neuronal membrane dysfunction

- NH4+ increase permeability of K+ and Cl-
- NH4+ increase 6 Phosphofructokinase activity ↑glycolysis ↑H+
4)  [NH4+]  transport of Trp
 Trp  [serotonin] and [quinolinic acid]
Anorexia, pain insensitivity, insomnia
Transport of NH3
Because of its toxicity NH3 is transported in blood as Gln.
High solubility
+
H3N +H N
3
Gln uncharged- can cross

membranes
High N content
NH2
Glutamine synthetase reaction
Glutamine synthetase
NH4 + Glutamate Glutamine
ATP ADP
Glutamine (Gln)
• Major method of detoxifying NH3 in brain.

• Also produced in liver, kidney and muscle.
• Hydrolyzed in kidney to liberate NH3.
In metabolic acidosis
In metabolic alkalosis

Urea Cycle
• Mitochondria and cytosol
• Occurs in liver
• 3 ATP used
• 1 N derived from free NH3. Other N from Asp.
• C from CO2
• Arginase is present only in liver
• Dietary ornithine is required for continues activity of urea cycle, but not dietary Aspartate.
CARBAMOYL
PHOSPHATE
SYNTHETASE I
ARGININOSUCCINIC ACID
SYNTHETASE

Regulation of the Urea Cycle
Allosteric enzymes – CPS-1 (Present in mitochondria)
Mg2+
2ATP 2ADP + 2Pi
CO2 +NH3 Carbomyl phosphate
CPS 1
(+)
N- acetyl
Glutamate +Acetyl Co A
Glutamate NAG synthesis
(+)
Arginine
In the well-fed state:
• Glycolysis   Acetyl Co A
• A.A. uptake   Arginine & Glutamate
• Arginase activity & [ornithine] by dietary arginine
Therefore activity of Urea Cycle
In the fasting state:

• β oxidation of fatty acids    Acetyl Co A
•  Degradation of proteins   Arginine, Glutamate & Acetyl CoA
Again activity of urea cycle
Long term regulation

• A long-term high protein diet and prolonged starvation induces synthesis of urea cycle
enzymes
Defects in Urea Cycle
1) CPS 1 deficiency  treated with Arg

2) OTC deficiency
- Carbomyl phosphate & NH3
- CPS II activity
- [Orotic acid] – Orotic aciduria
- In the cytosol, CP+Asp Orotate Uridine
- Often mental retardation and death.
3) N-Acetyl glutamate (NAG) synthase deficiency

- Treated with carbomyl glutamate – An analogue of NAG

AMINO ACID METABOLISM
Metabolism in different tissues
Liver
- Metabolism of all amino acids except Branched Chain Amino Acids (Val, Leu, Ile)
- Production of non essential amino acids
- Urea synthesis – presence of arginase
- Plasma protein synthesis
- Liver amino acid catabolising enzymes with high Km
- Only excess a.a. are metabolized
- Liver t-RNA charging enzymes low Km
- Ensures a.a. for hepatic protein synthesis
Skeletal muscle
- Uptake of amino acids for protein synthesis
- Metabolize Ala, Asp, Glu, BCAA
- Major site for amino acid pool
- Release of amino acids during starvation-mainly alanine and glutamine(during
starvation Acetyl Co A↑ from FA oxidation.→Inhibit PDH→↑Pyruvate→Alanine
from Transamination)
Small intestine mucosa

- Metabolize dietary – Glu, Gln, Asp, Asn
- Nucleotide synthesis - rapid cell division
- Glutamine obtained from liver and muscle used for nucleotide synthesis.
Kidney
- Major site of production of Ser
- Uptake of Gln  NH4+ production for acid base regulation
Brain
- Uptake of Branched Chain Amino Acids (Val, Leu, Ile)
- Val as an energy source

҉ Degradation of Branched chain amino acids (BCAA)
Leucine, valine, isoleucine
i. Transamination
ii. Oxidative decarboxylation (branched chain keto acid dehydrogenase – TPP, NAD,
FAD, lipoic acid, CoA )
iii. Dehydrogenation
Leucine Valine Isoleucine
Acetoacetyl CoA Propionyl CoA Acetyl CoA
Succinyl CoA
҉ Metabolism of Cystein and Methionine

- Methionine is an essential amino acid
- Cystein is a non essential amino acid and that can be synthesized from
methionine
o Sulphur from methionine
o C skeleton from serine
Methionine
Cobalamin N5- Methyl THF
Homocystein Methyl THF

Cystathionine
Cobalamin (B12)
β synthase Vitamin B6
Cystathionine Homocystein is a toxic intermediate

-Produce free radicals O°, O°°
Cystathionine
Vitamin B6
γ lyase
Homocystein is removed via 2 pathways
Cystein -Conversion to Methionine synthase
-Conversion to Cystein
Glutathione

• Deficiency of enzymes that convert Homocystein to Cystein
Eg:- cystathione β synthase, Cystathione γ lyase
- hypermethionemia
- hyperhomocystenemia
- homocysteinurea
- Skeletal abnormalities, Mental retardation, Ectopia Lentis
- Susceptibility to thromboembolism
• Deficiency of vitamins required for the conversion to methionine

Vit. B12, Folate
-hyperhomocystenemia
-homocystenemia
Metabolism of Homocystein involve Folate, Vit B12,Vit B6 and Riboflavin
҉ Glutathione (gamma glutamylcysteinylglycine)
- Reductant ( maintain stability of RBC membrane )

- Conjugate with drugs to make them water soluble
- Transport of amino acids across membranes
- Synthesis of leukotrienes
- Cofactor for enzyme reactions
- Rearrangement of disulfide bonds
҉ γ Glutamyl transferase
- Present in all tissues (kidneys↑)

- Serum enzyme primarily by hepatobiliary system
- γ GT increased in
o post or intrahepatic hepatobiliary obstruction
o pancreatic cancers
o Alcohol induced liver damage
o Prostate carcinoma
o Drugs – phenobarbitol, phenytoin
҉ Creatine phosphate
- Energy is obtained by hydrolysis of ATP
- But ATP/ADP affect activity of many enzymes
- So ATP cannot be stored in high concentration
- So energy is stored as phosphocreatine for rapid muscle activity
- Creatine phosphate is broken down to creatinine & excreted in urine
- Creatinine production depends on muscle mass
Creatine Kinase
Cr PCr
ATP ADP
Increased Protein Intake
- Urinary urea increases
- Creatinine remains constant
- NH4+ increase because high protein diet gives acidic urine
- Uric acid increase specially with animal protein
Renal failure
- GFR decreases
- Plasma creatinine increase
- Plasma urea increase
Acidosis
- More N diverted to Gln in liver
- Kidney – Gln is hydrolysed to Glu by Glutaminase
Treatment of Leukemia with Asparaginase enzyme
Asparagine Asparaginase Aspartate
• This reduce Asparagine available for Leukemic cells since they cannot
systhesise it by their own like animal cells
• Cause death of leukemic cells
҉ Serotonin
- a neurotransmitter in brain
- involved in mood, sleep, appetite, temperature regulation
• serotonin is produced from tryptophan
• when a protein meal is taken, all amino acids are available in blood ; traffic jam
occurs in amino acid transport system so tryptophan the bulkiest amino acid is
taken up very slowly, serotonine production is low, so protein meals cause alertness
• when a carbohydrate rich meal is taken, insulin secretion is increased, will lower the
amino acid concentration in blood, so tryptophan easily enters brain cells, so
carbohydrates will induce sleep
҉ NO production
• From the enzyme NO synthase utilizing Arginine

• 3 major isoenzymes-2 cNOS, 1iNOS
eNOS Endothelial cells Ca2+ and

cNOS Calmodulin
nNOS Neurones
dependent
iNOS Macrophage and neutrophils – Ca2+ independent

• Physiological functions - relaxation of smooth muscle
- inhibition of platelet aggregation
- neurotransmisssin
- cytotoxicity
• Reduced NO production
- hypertension
- impotence
- suseptsbility to infection
- arthrogenesis
• Increased NO production
- septic shock
- inflammatory diseases
- neurotransmission
- cytotoxicity
҉ Alkaptonuria
- Deficiency of homogentisate oxidase ( enzyme of degradation pathway of
tyrosine & phenyl alanine )
- Excretion of homogentsic acid
- Autosomal recessive
• Blackening of urine on standing ( homogentisic acid is oxidized to
benzoquinone acetate, it is then polymerized to black colored alkaptone
bodies )
-chronosis  deposition of alkaptone bodies in interevertebral discs,

cartilages
- Ferric Chloride test positive

- Benedict’s rest strongly positive

҉ Phenylketonurea
Phenylacetate
Phenylpyruvate Phenyllactate
Phenylalanine
Phenylalanine
Hydroxylase
Tissue proteins
Tryosine melanin
Catecholamies
Fumarate
Acetoacetate
• Autosomal recessive
• ↑[Phe] tissues,plasma,urine
• ↑Phenyl lactate, Phenyl acetate, Phenylpyruvate
• Cause-mental retardation
-failure to talk and walk
-seizers hyperactivity tremor
-microcephaly
-failure to grow
-hypopigmentation because high [Phe] competitively inhibit hydroxylation of Tryosine by
tryosinase
Treatment
- [Phe] ↓ diet
- Tyrosine supplied in diet
Maternal PKU
- PKU mother [Phe]↑

- Cause microcephaly, mental retardation, congenital heart abnormalities in foetus
Laboratory diagnosis
1. Blood phenylalanine
2. Guthrie test
3. Ferric chloride test – blue green colour

Gluconeogenesis
• All pathways responsible for converting non carbohydrate precursors to glucose or

glycogen
• During prolonged fasting,
- No glucose from diet →hepatic glycogen stores are depleted
- But glucose is essential for RBC(sole),nervous tissue, brain (main), testes,
kidney medulla, embryonic tissue
- Gluconeogenesis is the only source of blood glucose
- During an overnight fast→90% in liver & 10% in kidney
- During prolonged fasting →40% in kidney (substrate- Gln)
Importance of gluconeogenesis
1) Maintains glucose levels within a narrow range in blood
2) Maintains level of intermediates of TCA cycle (in skeletal muscles) even when fatty
acids are the main source of acetyl CoA in tissues
3) Clears lactate produced by muscle and erythrocytes
Lactate  Pyruvate  OAA  PEP  Glucose (Cori cycle)
4) Clears glycerol produced by adipose tissue
Glycerol  Glycerol phosphate  DHAP
Glucogenic substrates
1) Lactate: The Cori cycle- from exercising skeletal muscle, mitochondria less cells (RBC)
2) Amino acids: Except leucine & lysine all other A.A are glucogenic. eg:glucose- alanine
cycle
Alanine, Glutamine are the major sources of Glucose during fasting
Amino Acid  α KG  OAA
3) Glycerol: glucagon→activates HS lipase→hydrolyses TG in Adipocytes→ glycerol & Fatty

acids
• Glycerol → transports to liver → forms DHAP (gly. Kinase is not present
in adipocytes)
• Fatty Acid → Acetyl Co A → no net production of glucose (not
glucogenic)
• Odd chain F.A → propionyl Co A → glucogenic
Gluconeogenesis,
- occurs in cytosol and mitochondria
- highly energy consuming process (4 ATP, 2GTP, 2NADH required)
- ATP → FA oxidation (mostly)
- NADH → FA oxidation, lactate → pyruvate, malate → OAA
- Not Merely the reverse of glycolysis. Common Intermediates are there
- Bypass the irreversible glycolytic steps

Glycolysis Gluconeogenesis
Hexokinase Glucose 6 Phosphatase
PFK1 FBP 1
Pyruvate Kinase Pyruvate Carboxylase and PEP Carboxykinase
Locations of Enzymes : All cytosolic except,

1) Glucose 6 Phosphatase (ER)
2) Pyruvate Carboxylase (MT)
3) PEP Carboxykinase (Cytosol and/or MT)
Glucose
Glucose 6 phosphatase*
Glucose 6 phosphate
Fructose 6 phosphate
Fructose 1,6 bisphosphatase*
Fructose 1-6 bisphosphate
Glyceraldehyde 3 phosphate DHAP
2NAD+ Glycerol 3PDH

+
2NADH+ H
Glycerol-3-P
2 ( 1,3 bisphosphoglycerate ) Glycerol

Kinase
2ADP
2ATP
Glycerol
2 ( 3-Phosphoglycerate)
TAG
2 ( 2-Phosphoglycerate)
2(Phosphoenol pyruvate) FA β oxidation

PEP
CK*
2OAA
Gluconeogenic
Pyruvate Carboxylase* + CO2 + Biotin
Amino acids
Ex.: Ala, Gly, Cys 2 Pyruvate LDH Lactate

Sources of pyruvate
1) From lactate ( transported into MT ) Glucose
2) Transamination of alanine ( within MT )
Gluconeogenesis
OAA
REGULATORY STEPS Pyruvate
Carboxylase (+)
Pyruvate
1) Pyruvate  OAA PDH (-)
Acetyl CoA
• Pyruvate Carboxylase (mitochondria)
• Use ATP TCA
• Biotin- prosthetic group FA Oxidation
• Activated by acetyl Co A Energy
Importance- gluconeogenesis, replenish OAA for TCA cycle in muscle
OAA cannot cross the mitochondrial membrane
- OAA- malate shuttle or OAA- Asp shuttle

Inner mit. membrane
MC Cytosol
PC
Pyruvate OAA
NADH+H+
MDH
Alanine
Malate Malate OAA

NAD+
MDH
NAD+ NADH+H+
2) OAA  PEP
• PEP Carboxykinase
• In both Cytosol and Mitochondria
• If substrate Alanine, Cytosolic PEP CK
• If substrate Lactate, Mitochondrial PEP CK (NADH already produced)
• Use GTP

3) Conversion of fructose 1,6 BP to F6P
F6P
+ F26BP - F26BP
+ AMP - AMP
- ATP PFK1 F1,6BPase + citrate
- Citrate + ATP
- H+ F1,6BP
4) Dephosphorylation of G6P
G6P Glucose
G6Pase
• Liberate free glucose
• Primarily a function of liver to buffer blood glucose level (liver, kidney)
• G6Pase is absent in brain and muscle
• G6Pase is present in ER lumen
• Genetic defects in either G6Pase or T1 (G6P transporter) lead to increase in
glycogen synthesis  glycogen storage disease (Von Gierke’s disease)
Severe fasting hypoglycemia
Regulation
*Glycolysis and Gluconeogenesis – Reciprocally Regulated to prevent a futile
cycle
1. Substrate availability ( Ala, glycerol, lactate)

2. Energy state
↑ATP / AMP
- PK inhibited. PEP guided to form glucose Gluconeogenesis Stimulated
- PFK 1 is inhibited
- F 1,6 Bisphosphatase activated
↓ATP/AMP
- PK activated
- PFK 1 activated Gluconeogenesis Inhibited
- F-1,6- bisphosphatase inhibited
ADP
-Pyruvate Carboxylase and PEP Carboxykinase inhibited

3. Allosteric regulation Acetyl CoA activates PC
AMP& F-2,6 BP inhibit fructose-1,6-bisphosphatase
Citrate & ATP activates Fructose 1,6 Bisphosphatase
4. Covalent Modification Glucogen, - Phosphorylate Pyruvate Kinase and inactivates it

-Phosphorylate PFK 2 and inactivate it. So F 2,6
Bisphosphate level is reduced.
5. Induction & repression
• Glucagon induces
- F 1,6 BPase
- PEPCK
- G6phosphatase
• Glucagon represses
- GK
- PFK 1
- PK
Glucagon stimulates gluconeogenesis in 3 mechanisms

Short term regulation
1) Allosteric regulation
Lowers F2,6BP level so activates F1,6BP and inhibits PFK
2) Covalent modification
Elevation of Cyclic AMP  increase cyclic AMP dependent PK activity  PK
phosphorylated  PK is inactivated
Long term regulation
3) Induction of enzyme synthesis
Increase transcription of PEP Carboxykinase gene  ↑ availability of this enzyme’s
activity.
Alcohol intoxication
Alcohol DH AldehydeDH
CH3CH2OH CH3CHO CH3COO-
NAD+ NADH NAD+ NADH

• ↑NADH/NAD+
• Pyruvate+ NADH +H+ NAD+ +Lactate
• OAA +NADH +H+ NAD+ + Malate

• DHAP + NADH Glycerol 3 Phosphate + NAD+
• Pyruvate & OAA and DHAP for gluconeogenesis decrease
• Hypoglycemia
• NADH accumulates. Prevents Lactate Pyruvate. Lactic acidosis. Uric acid excretion
• NADH Fatty Liver
• Cytosolic NADH is transported to mitochondria via malate-Asp shuttle
• It is necessary for OAA transportation from mitochondria to cytosol
• Limits availability of malate & OAA for gluconeogenesis
*Ethanol Metabolism – 2nd pathway : MEOS

Oxidize NADPH to NADP+. Oxygen free radicles. Glutathione regeneration reduced.

METABOLIC INTEGRATION & FEED FAST CYCLE
• Major intermediates of metabolic integration
AA
(degradati TCA Cycle
on)
KB FA
(ketolysis) synthesis
Acetyl
co-A
FA (beta KB
oxidatio) synthesis
Pyruvate Cholesterol
(PDH) synthesis
Lactate Alanine
(LDH)
OAA (PC)
Glycolysis
Pyruvate
Acetyl
coA
(PDH)
AA
degradat- Glucose
ion (Glucon-
Lactate
(LDH) ogenesi)

Aerobic
Glycolysis
Ethanol
Oxidation
ETC
NADH
Beta
Oxidation
Pyruvate
to lactate
PDH
Reaction TCA Cycle
Regulation Of Metabolic Pathways
Short Term Regulation Long Term Regulation

a)Induction and repression of
a) Substrate availability
enzyme synthesis
b) Allosteric regulation
c) Covalent modification

Feed Fast Cycle
1) FED/ABSORPTIVE STATE (just after meal)
• High plasma levels of glucose, amino acids, TAG (chylomicrons)
• Stimulation of pancreatic islet cells →secrete insulin
• ↑ Insulin/glucagon = 10:1
• ↑Synthesis of glycogen, TAG & protein to replenish fuel stores - anabolic period
• All tissues – use glucose
LIVER (nutrient distributing center)
 Portal blood is rich in absorbed nutrients and insulin secreted from pancreas.
 In well fed state, liver uses glucose
Carbohydrate
• ↑ Supply of glucose to liver via portal vein.
• ↑ Glucose uptake by hepatocytes via GLUT-2
 insulin independent
 Km high
 uptakes only when blood glucose level is high
• ↑Glucose 6 Phosphate (Glucokinase activity)
Activation of glycogen synthase

Glycogenesis 1)Allosteric activation by G6P
2)Dephosphorylation by insulin
G6P
G6PD ACTIVATED
HMP Pathway
NADP/NADPH
LCFA
Glucose 6 phosphate
FA Synthesis
Glycolysis
(Insulin/glucagon high, Acetyl coA
hepatic PK activated)
TCA Cycle
Inactivation of PC,
Gluconeogenesis PEPCK, F 1,6 Bpase,
G6Pase

Fat
• Liver is the primary tissue for de novo synthesis of fatty acids.
• Fat is not stored in liver.
• A) Increased FA synthesis Activation of ACC
• By dephosphorylation
• Allosteric activator - citrate
↑metabolism of
dietary glucose
and AA ↑ Acetyl CoA
↑ FA synthesis
↑ HMP ↑ NADPH
B) Increased TAG synthesis
Hydrolysis of TAG component of

chylomicron remnant
FA
De novo synthesis
TAG Utilized by muscle
VLDL
and adipose tissue
Glycolysis Glycerol 3 Phosphate
Proteins
• Amino acids high in portal blood – alanine, lactate, citrulline, proline
• Metabolism of all amino acids except Branched Chain Amino Acids (Val, Leu, Ile)
• Liver AA catabolizing enzymes with high Km
• Therefore, only excess AA are catabolized
• Liver t-RNA charging enzymes low Km
• Ensures metabolism of AA for hepatic protein synthesis
• A)↑ Protein synthesis
Only a transient increase in synthesis of hepatic proteins resulting in replacement of
any proteins that may have been degraded during fasting period.
B) ↑AA degradation (excess)
o More AAs are present than the amount that the liver can use in the synthesis of
proteins
o Excess is not stored but either released to blood or deaminated.
Resulting C skeletons
NH3 Group - ↑Urea synthesis
AA deamination C Skeleton - Degraded to Pyruvate, Acetyl CoA & TCA

cycle intermediates – used for FA synthesis

ADIPOSE TISSUE (energy storage depot)
Carbohydrate
• ↑glucose uptake - Insulin dependent GLUT-4

• ↑ glycolysis → ↑ glycerol 3 phosphate (utilized for TAG synthesis)
• ↑HMP → ↑ NADPH
Fat
• ↑ Synthesis of FA (not a major source of FA Synthesis)
Chylomicron Lipoprotein lipase
VLDL FA
↑ TAG synthesis
• ↑ Glycolysis → ↑Glycerol 3 phosphate
• ↓degradation of TAG,
↑Insulin/Glucagon →inactivation of HSL
RESTING SKELETAL MUSCLE

Carbohydrate
• Skeletal muscle is unique in being able to respond to substantial changes in the demand for
ATP that accompanies muscle contraction.
• ↑ glucose uptake by GLUT-4
• ↑ glycolysis - to provide energy needs.
• ↑ glycogen synthesis (Particularly if glycogen stores have been depleted as a result of
exercise.)
Lipids
• FAs are released from VLDL & Chylomicrons – lipoprotein lipase
• However fatty acids are of IIry importance as a fuel for muscle during well fed state in
which glucose is Iry energy source.
Amino acids
• ↑ Protein synthesis
• ↑uptake of branched chain AAs (principle site for degradation of the BCAA)
BRAIN
Carbohydrate
• Brain uses glucose exclusively as a fuel (GLUT 1)
• No significant stores of glycogen.
• Therefore completely dependent on the availability of blood glucose.
Lipids
• No significant stores of TAG.
• Oxidation of FAs provides little contribution to energy production (protein bound FA cannot
cross BBB)

INTESTINES
• Assembly of dietary TAG to Chylomicrons lymphatic blood
• Metabolize amino acids (Aspartate, Asparagine, Glutamate, Glutamine)
2) FASTING STATE
• ↓ glucose, AAs & TAG plasma levels.
• ↓ insulin/glucagon
• Degradation of TAG, glycogen & proteins.
Two priorities: -
1. Need to maintain adequate plasma levels of glucose to sustain energy by metabolism of
brain, RBC & other glucose requiring tissues.
2. Need to mobilize FAs from adipose tissue & the synthesis & releasing of ketone bodies from
the liver to supply energy to all other tissues.
LIVER
Carbohydrate
• Primary role- maintenance of blood glucose level by
 Glycogen degradation
 Gluconeogenesis
• ↑ glycogen degradation
• Glycogen phosphorylase – activated
• (↑ glucagon and epinephrine levels→ phosphorylates glycogen phosphorylase)
• Glycogen is nearly exhausted after 10-18 hours of fasting
• Hepatic glycogenolysis is a transient response to early fasting
• ↑ gluconeogenesis-
• Substrate
 Proteins → Gluconeogenic AA
 TAG → Glycerol
 Muscle → Lactate
• Glucagon
Induction of Phosphorylate hepatic

PEPCK synthesis Phosphorylate pyruvate kinase (inactive)
PFK2 (inactive)
F-2,6-BP
FBP-1 inhibition PFK 1 actively inhibited
Gluconeogenesi Glycolysis
pyruvate carboxylase PDH
In adipose tissue, FA oxidation→ acetyl CoA

Lipids
• ↑ glucagon/insulin ratio - Phosphorylates Hormone sensitive lipase (active form)

1. ↑ FA oxidation
↓ Malonyl CoA (inactivation of ACC by phosphorylation)
CAT-1 activated (carnitine shuttle)
NADH FADH2 Acetyl co A (facilitate PC)
Energy via ETC Gluconeogenesis
2. ↑ ketone body production

↑FA oxidation → ↑ acetyl CoA (exceeds liver’s oxidative capacity of the TCA cycle)
• What is the importance of making ketone bodies?
I. Small water-soluble molecules
II. Energy source for most tissues including brain during high plasma concentration
III. Reduce gluconeogenesis from AA carbon skeleton preserving essential proteins
Liver cannot utilize ketone bodies - liver lacks thiophorase, an enzyme needed for its
degradation
ADIPOSE TISSUE
Carbohydrate
• ↓glucose uptake & metabolism
• ↓ glycerol-3-phosphate
• ↓ acetyl CoA
Lipids
A) ↑ Degration of TAG - Activation of HSL
B) ↑ Release of FA - Transported to various tissues
↑ Glycerol → glycerol phosphate → gluconeogenesis (liver)
C) ↓ Uptake of FA - inhibition of LPL
RESTING SKELETAL MUSCLE

Carbohydrate
• ↓ Uptake
Lipids
• During first two weeks muscles use FAs
FAs ← adipose
Ketone bodies ← liver
• After about 3 weeks
↓ use of ketone bodies
& oxidizes FAs almost exclusively
So ↑ ketone body concentration in plasma

Proteins
• During the first few days, there is some breakdown of protein→ AAs → gluconeogenesis
Mostly Alanine & Glutamine
Catabolism of branched chain AAs
• By several weeks rate of proteolysis decreases
• After several weeks of starvation, when ketone bodies also reduce, proteolysis begins
BRAIN
Carbohydrate
1. Exclusively uses glucose
2. After 2 or 3 weeks  Ketone bodies becomes the Iry fuel
KIDNEY
Carbohydrate
Late fasting 50% of gluconeogenesis occurs in kidney
Glutaminase
BCAA breakdown (Muscle)→ glutamine α-KG + NH3
& GDH
Substrate for Compensates the acidosis

gluconeogenesis accompanied by
ketogenesis.

Diabetes Mellitus
Diabetes
Diabetes Mellitus Diabetes Insipidus
Diabetes Mellitus
• Metabolic disorder of multiple aetiology.

• Characterized by chronic hyperglycaemia due to relative or absolute deficiency of
insulin.
• “Starvation among plenty”
• Due to defects in insulin release, action or both.
Functions of insulin in cells.

1) Effects of carbohydrate metabolism
Acts on liver, muscles and adipose
Muscle – Increase glycogen synthesis
Increase GLUT 4 transporters thereby increase glucose uptake
Liver – Increase glycogen synthesis
Inhibit gluconeogenesis and glycogenolysis
Adipose – Increase GLUT 4 transporters thereby increase glucose uptake
2) Effects on lipid metabolism
Decrease TAG degradation

- By inactivating hormone sensitive lipase by dephosphorylation
Increase uptake of FAs from VLDLs and chylomicrons
- By increasing the activity of lipoprotein lipase
- Increase TAG synthesis from the FAs taken in
2 types: -
a) Type 1 diabetes
b) Type 2 diabetes

Type 1 Diabetes Mellitus (IDDM)
• Complete absence of insulin production.
• Due to destruction of β cells in Islets of Langerhan resulting from autoimmune
reactions within the body.
• Leads to deficiency of insulin
• Blood insulin levels do not increase in response to glucose
Metabolic changes in uncontrolled type 1 DM
1. Hyperglycaemia
Deficiency of Insulin Decreased activity of GLUT 4 Reduced uptake of glucose

transporters in adipose tissue and in the peripheries
skeletal muscles
Hyperglycaemia
Accelerated hepatic gluconeogenesis

using amino acids obtained from
peripheral tissues
2. Hypertriacylglycerolemia
Increased lipolysis in adipocytes Increased transport of Fatty Acids

Starved state within cells
and mobilization of Fatty Acids to liver
Excess Fatty Acids converted to

TAG and transported in blood as
VLDL
Decreased synthesis and activity Reduced degradation of

of lipoprotein lipase Hypertriacylglycerolemia
VLDL and chylomicrons

3. Ketoacidosis
β oxidation of Fatty acids and

Increased mobilization of production of ketone bodies Ketoacidosis
fatty acids to the liver (acetoacetate and 3-hydroxybutyrate)
Type 2 Diabetes Mellitus

• Result of insulin resistance in peripheral tissue coupled with insufficient
production of insulin by dysfunctional β cells. (Partial insulin deficiency with
insulin resistance.)
Insulin resistance
• Decreased ability of the target tissues (liver, adipose and muscles) to respond
to normal circulating concentrations of insulin.
• Caused by weight gain and obesity.
• Insulin resistance itself does not cause type 2 DM. Initially with insulin
resistance, insulin secretion by β cells increase causing hyperinsulinemia.
• However, with time β cells dysfunction and insulin secretion decreases leading
to type 2 DM.
Metabolic changes in type 2 Diabetes Mellitus
1. Hyperglycaemia
Deficiency of insulin Decreased activity of GLUT 4 Reduced uptake of glucose

and insulin resistance transporters in adipose tissue and in the peripheries
skeletal muscles
Hyperglycaemia
Accelerated hepatic gluconeogenesis

using amino acids obtained from
peripheral tissues

2. Hypertriacylglycerolemia
Starved state within cells Increased lipolysis in adipocytes Increased transport of Fatty Acids
and production of Fatty Acids to liver
Excess Fatty Acids converted to

TAG and transported in blood as
VLDL
Decreased synthesis and activity Reduced degradation of Hypertriacylglycerolemia

of lipoprotein lipase lipoproteins
*Ketosis is usually
minimal/absent because of presence of insulin even with insulin resistance restrains
hepatic ketogenesis.
Glucose homeostasis
 The body naturally tightly regulates blood glucose levels as a part of metabolic
homeostasis.
Phases of glucose homeostasis
Phase Duration Origin of glucose Tissues using Major fuels

glucose of brain
1 Well-fed state Exogenous All Glucose
All except liver,
Glycogenolysis,
After 6-12 hrs of muscle and adipose
2 Hepatic Glucose
fasting tissue at diminished
Gluconeogenesis
rates
All except liver,
muscle and adipose
Hepatic
tissue at rates
3 After 20 hrs of fasting Gluconeogenesis, Glucose
intermediate
Glycogen
between phase 2
and 4
Brain, RBC, renal Glucose
After several days of Gluconeogenesis
4 medulla, small Ketone
fasting (Hepatic, Renal)
amount by muscles bodies
Brain at a diminished Ketone
After prolong
Gluconeogenesis rate, RBC, renal bodies
5 starvation (after 2-3
(Hepatic, Renal) medulla Glucose
weeks)

Enzymes active in phosphorylated form
 Glycogen phosphorylase
 Fructose 2,6 BP
 HSL
• In the glucogenic state of the liver, when glucagon/insulin is high, action of

glucagon
• converts them to the phosphorylated form and activates them.
• In lipogenic state, glucagon/insulin is low and these enzymes are inactivated.
• Other enzymes are activated in lipogenic state. e.g. PFK2, glycogen synthase,
ACC
• These enzymes are activated by dephosphorylation.
Metabolic profiles of various tissues
Liver as fuel provider for other tissues

• Glucose provider - Glycogenolysis < gluconeogenesis
• Fatty acid provider - Excess fuel converted to triacylglycerol then to VLDLs
Provide fatty acids to other tissues or for storage in
adipose tissue
• Ketone body provider - Soluble form of fatty acid fuel
Produced when blood glucose level is low
Metabolic Profile
Liver
• Fuel(s)- Major fuel fatty acids
• Fuel use(s)- Biosynthesis of glucose, fatty acids, glycogen, triacylglycerol,
cholesterol,
bile salts, proteins, urea
• Main metabolic pathways - Metabolic hub.
 Carbohydrate - incoming- glycolysis, glycogenesis
 Lipogenesis
 ETC
 Citric acid cycle
 Low blood glucose – glycogenolysis, gluconeogenesis
 Lipid- incoming- fatty acid oxidation, citric acid cycle, ETS, Cholesterol
synthesis, Ketone body synthesis

Skeletal muscle
• Fuel(s)
Resting muscle- fatty acids
Highly active muscle
Initially – glycogen
During intense exercise – G-6-P lactate
When glycogen stores are depleted – free FAs provided from increased
mobilization of TAGs from adipose tissue
• Fuel use(s) – contraction, active transport (ca2+)
• Main metabolic pathways
– Resting muscle(aerobic) - fatty acid oxidation, citric acid cycle, ETC
- Highly active muscle (anaerobic) - glycogenolysis, glycolysis.
Adipose tissue
• Fuel(s) – major fuels – glucose, fatty acids
• Fuel use(s) – biosynthesis of triacylglycerol, fatty acids synthesis (high blood
glucose)
• Main metabolic pathways – glycolysis, fatty acid oxidation, citric acid cycle,
ETC, triacylglycerol synthesis, lipolysis.
Brain
• Fuel(s) – glucose is prime fuel. Uses 120g per day
• Fuel use(s) – active transport, (Na+, k+), biosynthesis
• Glucose uptake – transporter of half-saturated at 1.6 mM
Normal blood glucose level ~ 5 mM (90% mg)
Hexokinase saturated at 0.5 mM
Hypoglycemic danger level 2.2 mM (40% mg)
• Main metabolic pathways – totally aerobic metabolism; glycolysis, citric acid
cycle, electron transport chain
Heart Muscle
• Fuel(s) – main fuel fatty
• Fuel use(s) – contraction, active transport (Ca2+)
• Main metabolic pathways – totally aerobic metabolism, fatty acid oxidation,
citric acid cycle, ETC
Kidney
• Fuel(s) – major fuels glucose, fatty acids
• Fuel use(s) – active transport, biosynthesis(glucose)
• Main metabolic pathways –
Normal conditions - glycolysis, fatty acid oxidation, citric acid
cycle, ETC
During starvation - gluconeogenesis

Fed state - Liver
Fed state – Skeletal Muscle Fed state –Adipose tissue

Fasting state
CORI CYCLE
Type 1 Diabetes Mellitus
• Hyperglycaemia
• Hypertriacylglycerolmia
• episodes of severe ketosis
Type 2 Diabetes
Mellitus
• Hyperglycaemia
• Hypertriacylglycerolmia
physiology
bat notes
term 02
CARDIOVASCULAR SYSTEM
Electrical properties of the heart
Heart muscle
Contractile tissue Excitatory / conducting tissue
Pacemakers Latent pacemakers
Pacemaker tissue/cells
• Rhythmically discharging cells

• Show prepotentials/pacemaker potentials
Membrane potential declines to firing

Level after each impulse
Triggers the next impulse
 IK brings repolarization (K+ reflux)

 When IK decreases (K+ efflux
decreases)
 A channel permeable to both Na+
and K+ is activated – Called the ‘h’
channel (funny
Na+ channel)
 h channel (Ih) – Forms 1st part of the
prepotential
 Transient Ca2+ channels (ICa2+ T )
open & complete the prepotential
 L channel opening produces the
rapid depolarization (ICa2+ L)

No contribution from Na+ for rapid
depolarization
Other features
1. RMP varies from-50 to -60 mv

2. Prepotentials are only prominent in SA & AV nodes
3. Latent pacemakers (other portions of conducting system) discharge only when SA & AV nodes are depressed
or blocked
4. Atrial & ventricular muscle cells discharge spontaneously only when injured or abnormal.

Effect of ANS
Parasympathetic Sympathetic
Membrane hyperpolarized Slope of prepotential is
& Slope of prepotential is increased
decreased
Ach Noradrenalin
↓ ↓
M2 muscarinic R
β1 R
cAMP in the cell ↓ ↓

↓ ↓ cAMP in the cell ↑
G Slows the opening of ↓
Open K+ channels Ca2+ channels Facilitates opening of
↓ ↓ Ca2+L channels
Stimulate K+ Decrease firing rate ↓
conductance ICa2+ ↑
↓ ↓
Counters IK decay Membrane hyperpolarized Speeds up depolarization
(Slows the depolarizing
effect of Ih)
Other factors
Rate of discharge of SA & other nodal tissue
Increased
Decreased
- Temp. ↑ (tachycardia in fever)
- Drugs
- Drugs - Digitalis(+ve inotrope)
(Depresses nodal tissue &exerts
vagal effects)
Mainly to AV node

Heart rate control
Sympathetic Parasympathetic (Vagus)

Resting (Noradrenergic) (Cholinergic)
(-)45
(+)5
Resting, recumbent,
Young adult SA NODE
Intrinsic
discharge rate • Temperature
100 –110 / min. Local factors • pH
Rate= 70/min High • Circulating substances
cholinesterase
Heart rate - variation
Wide variation—rate of 80-90 seen in healthy persons

Muscular training reduces the rate (Trained athletes- rate 50-60)
Age: at birth-----130/min -decreases till adolescence. Increases slightly with old age
Physiological Pathological
Increase during muscular exercise Fever ( 10 beats / 1 deg F )
emotional excitement Haemorrhage
high environmental Hyperthyroidism
temperature
during digestion (mild
increase)
Decrease sleep (55 – 60) Hypothyroidism
In trained athletes Increased ICP
Conducting system of the heart
Tissue Location Rate of discharge Conduction Rate Importance

SA node Junction of SVC & R 70 /min 0.05 Referred to as the
atrium “Pacemaker” of the
heart
AV node Right posterior inter 60 /min 0.05 Responsible for the
atrial septum AV nodal delay
Bundle of His IV 50 /min 1 Sole connection
septum(subendocardial between atrial &
tissue) ventricular syncytia
2 branches
Purkinje fibres Ventricular 40 /min 4
myocardium

Spread of cardiac excitation
SA node
Atrial Atrial myocardium
depolarization
0.1 S Internodal pathways(rapid) Reasons?
↓Symp.stimulation
AV
AV node
nodal
Advantage – give
(0.1S) time for atria to
delay
↑Parasymp. contract
↓Symp.
Bundle of His
* Maximum = 230 impulses

Purkinje fibres Conduction min
0.08 - 0.1 S
of AV node
Ventricular myocardium
 Spread of cardiac excitation is from endocardial to epicardial direction (Easy to remember - ‘n’ before ‘p’)
 Depolarization moves from left to right of the interventricular septum.
 The last portions of the heart to become depolarized are
1. Posterobasal portion of the left ventricle
2. Pulmonary conus
3. Uppermost part of the septum
Contractile tissue

Phase
0 - Initial rapid depolarization Opening of voltage gated Na+ channels
1 - Initial rapid repolarization Closure of voltage gated Na+ channels &opening of

one type of K+ channels (also Cl- influx)
2 - Plateau phase Slower but prolonged opening of voltage gated Ca2+
Channels
3 - Final repolarization Closure of voltage gated Ca2+ channels and efflux

Of K+ ions through K+ channels
4 - RMP (-90 mv) Slow delayed efflux of K+ channels
 Depolarization (2ms) is followed by a prolonged plateau (200ms)

 Mechanical response starts 2 msec after the onset of depolarization and lasts 1.5 times longer than the action
potential.
 Cell is refractive to excitation during contraction (during Phase 0 – 2 and half of Phase 3) - Prevents tetany
Electrocardiogram (ECG)
 Body fluids are good conductors – Changes in potential that measure the algebraic sum of action
potentials can be recorded
 Record of these changes are known as an electrocardiogram
ECG wave patterns and their genesis +ve

 The electrocardiogram is a recording of electrical activity of the heart.
 Depolarization moving towards the active electrode is recorded as a positive deflection.
−ve
 Depolarization moving away from the active electrode is recorded as a negative deflection.
ECG leads
 Record the electrical potential differences between electrodes placed on the body.
Standard 12 lead ECG
Chest leads(unipolar) Limb leads

V1, V2, V3, V4, V5, V6
Standard limb Augmented limb leads

Leads (bipolar) (Unipolar)
I, II, III aVR, aVL, aVF

- Unipolar leads (Chest)
 Measure heart’s electrical activity in the antero-posterior plane
 Unipolar chest leads do not require any augmentation unlike bipolar leads (since they are placed close to the
heart)
 6 chest leads are used
1. V1 - Placed in 4th intercostal space just right to the sternum
2. V2 - Placed in 4th intercostal space just left to the sternum
3. V3 - Placed between V2 and V4
4. V4 - Placed in 5th intercostal space along the midclavicular line
5. V5 - Placed in anterior axillary line 5th intercostal space
6. V6 - Placed in mid axillary line 5th intercostal space
- Unipolar leads (Limb)

 Measure electrical activity of the heart in coronal plane
 Augmented leads (aVR, aVL and aVF) increase the size of the potential by 50% without any change in the
configuration
• aVR – Augmented right arm lead
• aVL – Augmented left arm lead
• aVF – Augmented left foot lead
Relating ECG leads to heart chambers
View of heart Leads
Inferior II, III, aVF
Lateral I, aVL, V5, V6
Anterior V3, V4
Septal V1, V2
- Bipolar leads/ Standard limb leads

 Measure electrical activity of the heart in the coronal plane
 Consists on a single positive and a negative electrode
 Location of lead doesn’t depend on location of leads on arm and leg
(NOTE: Leads are placed on RA and LA avoiding thick muscle and on the left lateral calf muscle)
 When placed, these leads form an equilateral triangle – Einthoven’s triangle with heart in centre
 3 bipolar leads are used
1. Lead I – Right arm/Left arm
2. Lead II – Right arm/Left leg
3. Lead III – Left arm/ Left leg

(−) (+)
LI
(+) (+)
LIII LII
The ECG pattern obtained from the above leads is as follows ECG Paper
 ECG waves are recorded on special graph

paper with 1mm2 grid-like boxes
 Horizontal – duration
 Vertical – wave amplitude
Horizontal
 Paper speed usually 25 mm/s
 each 1mm (small square) = 0.04s (40ms)
 Each 5mm (large square) = 0.2 s (200ms)
Vertical
 10mm (10 small squares) = 1mV
1mV
0.2 s 0.04s
• P wave – atrial depolarization

• QRS interval –
- Reflects ventricular depolarization
- From beginning of Q to end of S wave (When Q is absent, measured from R/R’ to S)
- Normal duration 0.04 – 0.1 S
 Important → In QRS complex waves represent septal, ventricular and last part of depolarization is different
from lead to lead (But; 1st (+)ve deflection is always a ‘R’ wave)
• T wave – Ventricular repolarization (from bottom to top)

• U wave – May be present due to slow repolarization of papillary muscles

- PR interval - Atrio ventricular conduction,
- From beginning of ‘P’ wave to beginning of QRS
- atrial depolarization +AV nodal delay (0.12-0.20s)
- QT interval - Ventricular action potential

- From beginning of ‘QRS’ to Beginning of ‘T’
- Ventricular depolarization + Ventricular repolarization
- ST segment – From end of ‘QRS’ to beginning of ‘T’ Ventricular repolarization (NOTE: In myocardial infarction
electrical activity is seen here, known as ST segment elevation)
Normal rhythm of heart – 60-100 bpm

electrical impulses are initiated in the SA node and conducted to the AV node,
then the Bundle of His, bundle branches and the Purkinje fibres
Heart rate is increased - >100 bpm

RR intervals are constant and regular and all wave forms are present
Occurs during exercise, fever, emotional periods and sometimes medical conditions
Heart rate is decreased - <60 bpm

RR intervals are constant and regular and all waveforms are present
Occurs during sleep and is seen in athletes
Also cause by β blockers and Ca2+ channel blockers
RR intervals change according to a pattern which typically follows the respiratory rate
which has become irregular
RR interval decreases when patient inhales and increases when he exhales
Efficiency of heart as a pump

• Substantial AV nodal delay.
• Sustained action potential maintaining contraction until the entire myocardium has had time to depolarize
and contract.
• Absence of tetany.
• Coordinated contraction of ventricular cells. Depolarization through cardiac muscle rapid with ventricular cells
contracting nearly simultaneously.
• Ventricular contraction begins at the apex & progress upwards: squeezes blood towards exit.

Cardiac cycle
Series of events
that occurs
during a single
heart beat
.
Mechanical events of the cardiac cycle
1) late diastole
2) atrial systole VD VS
3) ventricular systole
AD AS AD
a. isovolumetric ventricular contraction
b. ventricular ejection (0.8 – 1s)
4) early diastole → a) Protodiastole
b) Isovolumetric contraction
c) Rapid ventricular filling
Late diastole
 Atrio-ventricular valves opened; aortic & pulmonary valves are closed

 Blood flows into the heart through SVC, IVC & pulmonary veins; filling atria and ventricles.
 The rate of filling ↓ when ventricles become distended
(Specially when HR ↓)
 cusps of AV valves drift towards closing position
 70% filling occurs
 Pressure remains low
Atrial systole
 Coincides with late ventricular diastole
 About 30% of ventricular filling occurs
 Atrial musculature contacts & propels additional blood to ventricles
 Orifices of SVC, IVC & pulmonary veins narrows
But some regurgitation occurs

Ventricular systole
At the start AV valves close.
Isovolumetric contraction (0.05 s) Ventricular ejection
 AV & semilunar valves closed  Ventricular pressure exceeds aortic &

 Ventricular muscle initially shortens Pulmonary arterial pressure
relatively little(Volume remains more or  Semilunar valves open & ejection begins
less same)  Rapid at first ; slows down later
 But IV pressure ↑ sharply (myocardium  The IV pressure rise to a maximum
presses the blood of the ventricle)  (LVP =120, RVP = 25) & declines
 This lasts until the pressure of L& R somewhat before the ventricular systole
ventricles exceed the pressure of Aorta ends
(80 mmHg) & pulmonary Artery (10  (the pressure in aorta can exceed that of
mmHg) left ventricle but for a short period the
 AV valves bulge towards atria ( ↑ atrial momentum keeps the blood moving)
pressure) but they remain closed  AV valves pulled down (atrial Pressure↓)
 Amount of blood ejected → 70 - 90 ml
Early diastole (rest)
1) protodiastole (0.04 s)
 Ventricular muscle is fully contracted
 Already falling ventricular pressure drops more rapidly
 It ends when the momentum of ejected blood is overcome and
 Aortic & pulmonary valves closed.
2) Isovolumetric relaxation
 Both AV & semilunar valves are closed
 Ventricular Pressure continues to drop rapidly
 Atria in diastole are filling and atrial pressure increases
 Ends when ventricular pressure falls below atrial pressure & AV valves open; permitting ventricles to
fill
3) Rapid ventricular filling
 Once AV valves open. Blood accumulated in atria fill rapidly into ventricles
 Rate ↓ as ventricles filled
• End diastolic volume – Final volume in each ventricle at the end of diastole just before the systole. (130ml)
• Stroke volume – Amount of blood ejected by each ventricle in each heartbeat. In a resting supine man of
average size, (it is 70 - 90ml)
• End systolic volume – Amount of blood left in each ventricle at the end of ventricular systole.
 d→a – ventricular filling

 a→b – isovolumetric contraction
 b→c – ventricular ejection
 c→d – isovolumetric relaxation

Timing of events in cardiac cycle
Similar in 2 sides but take place at different times(asynchronous)

• RA systole precedes LA systole (Because electrical activity of RA finishes before LA, as SA & AV nodes are in RA)
• L ventricular systole precedes right ventricular systole
(Because in RV impulses have to travel through moderate band to purkinje; but not in LV)
• R Ventricular ejection begins before L Ventricular ejection, in other words pulmonary valve opens before aortic valve
[ pulmonary arterial pressure (10 mmHg) < aortic pressure (80mmHg)]
• Aortic valve closes before pulmonary valve (in inspiration)- Reduced impedance of pulmonary vasculature and
increased venous return
(Resistance of pulmonary vascular tree becomes lower in inspiration)
• Pulmonary & aortic valves close almost at the same time during expiration.
• But during inspiration physiological splitting of 2nd heart sound occurs due to asynchronous closure of semilunar
valves.
When measured over a period of time, outputs of 2 ventricles are equal
Length of Systole and Diastole

Systole is more fixed than diastole
Diastole is more affected when heart rate is increased.
• Compromised filling (70% of ventricular filling occurs in rapid inflow and diastasis phases of diastole)
• Marked decrease of blood to subendocardial portions of left ventricle
• It is during diastole that the heart muscle rests.
• Increased vulnerability of left ventricle (sub endocardial) to ischaemia.
Heart sounds
Name Character Reason Timing Specialities
S1 Low pitched- slightly Vibrations set up by At the start of Loud in tachycardia

prolonged closure of mitral ventricular systole (poor filling)
(Lub) valve
)
S2 Shorter - high pitched Vibrations set up by End of ventricular Loud when diastole
(Dub) closure of aortic & systole P. is elevated in
( pulmonary valves aorta
S3 near the end of the rapid filling phase of the ventricle

(Sometimes normal-healthy young people)
S4 due to ventricular filling (when atrial pressure is high or when there is ventricular hypertrophy)
Abnormal – immediately before S1
Murmur
• Abnormal sound within heart
• When the velocity of blood surpasses the critical velocity, flow becomes turbulent and creates sound
Type of Murmur Timing

Mitral stenosis Diastole
Mitral regurgitation Systole → Pan systolic
Aortic stenosis Systole → Ejection systolic
Aortic regurgitation Diastole

• Systolic murmur seen in anaemia. (As a result of low viscosity of blood & associated rapid flow)
(NOTE- Systole and diastole of the cardiac cycle are named regarding to ventricles)
Bruits – abnormal sounds in blood vessels

E.g. 1. Aneurysmal dilatation of one of the large arteries
2. An arteriovenous fistula
3. Patent ductus arteriosus
Pulse
Characteristics of pulse
• Rate
• Rhythm
• Character – feeling of pulse (eg :- thready in shock)
• Volume – normal / high / low (eg:- strong pulse during exercise ↑SV)
• Presence or absence of femoral pulse in relation to radial pulse (e.g. Post ductal coarctation)
• Vessel wall [e.g. Adults – vessel wall is calcified, so pulse is strong
Children – vessel wall is elastic, so pulse is weak]
Arterial pulse
• Blood forced into aorta during systole sets up a pressure wave that travels around arteries
• This pressure wave expands arterial wall which is palpable as pulse
Venous pulse
• Seen, not felt
JVP
 Measurement
Right internal jugular vein
Patient at 450 and head turned slightly to the left
Vertical distance between angle of Louise& highest level of jugular vein pulsation
Add 5cm (since R. atrium is 5cm below the angle)

Central Venous Pressure (CVP) – pressure in the SVC near the right atrium (= R. atrial P)
• Important determinant of Preload
normal CVP=8 cm H2O (6mmHg during expiration, 2mmHg during inspiration)
The changes in right atrial pulse pressure are transmitted to the great veins producing 3 characteristic waves
Diastole Ventricular Diastole

Systole
Name Timing Reason
a wave Atrial systole Regurgitation of blood through
narrowed orifice
c wave Isovolumetric ventricular Bulging of tricuspid valve into R
contraction atrium
v wave Diastole (before tricuspid valve Rise in atrial pressure
opens)
Three descents and reasons for them.

X1 descent- right atrium relaxes
X2 descent-tricuspid valves move downwards due to papillary muscle contraction
Y descent –filling of left ventricle after tricuspid valve opens
Special.......
 Chronotropy → Heart rate
 Inotropy → Force of contraction
 Dromotropy → Transmission in cardiac conductive tissue
Cardiac output
Cardiac output (CO) = SV × HR
The volume of blood The volume of blood No of beats per unit

pumped by each pumped by each time
ventricle per unit time. ventricle per beat in a ~72 / min
5.5 l/minute (from resting, supine man of
each ventricle) average size.
~70 ml
Stroke Volume
Preload Afterload Myocardial contractility
The degree to which Resistance against which The intrinsic ability of heart
Myocardium is stretched blood is expelled muscle to generate force and to contract
Before it contracts at a given degree of stretch
(α EDV) (α TPR)
Factors affecting EDV
Venous Return Ventricular filling time Ventricular filling pressure Ventricular compliance
Depends on Depends on Depends on ↓ compliance by;
1. Total blood Heart Rate 1. Blood volume 1. Ventricular wall stiffness

Volume ↓in tachycardia 2. Atrial contraction 2. Pericardial thickening
2. Venous tone ↑in bradycardia (constructive pericarditis)
3. Thoracic pump 3. Pericardial collection of
4. Muscle pump fluid (pericardial effusion)
Increased resistance in (1) Hypertension

Arterial tree (2) Obstruction of LV outflow tract (aortic stenosis)
Factors affecting (3) Vasoconstriction
Afterload Anaphylaxis
Decreased resistance in (1) Hypotension • Severe allergic condition
Arterial tree (2) Vasodilation • ↓ BP due to histamine
• Treat with adrenaline
Frank starling law of heart
• Force of contraction α initial muscle fibre length
• SV α EDV
SV
EDV

Changes in contractility • Sympathetic β1 adrenergic stimulation + activation
• Catacholamines of adenylyl cyclase cAMP
SV
• Inotrophic agents (Dopamine)
• Digitalis (Na+/K+ ATPase inhibitor)
Increased contractility
• Xanthines – (Caffeine, theophylline) – Inhibit breakdown of cAMP
• Force frequency relationship
decreased contractility
• Parasympathetic
• Hypoxia , hypercapnia
• Acidosis
• Pharmacological agents (barbiturates, quinidine, procainamide)
• Loss of myocardium
EDV • (Intrinsic depression) Heart failure
Downregulation of β1 receptor
Impaired Ca2+ release from SR
Ejection fraction = SV 60-65%

EDV
Cardiac index = CO
Surface area of the body
Measuring CO
1) direct Fick method
CO = O2consumption (ml/min)
Theoretical Amount of O2 in − Amount of O2 in
arterial blood (ml/L) venous blood (ml/L)
2) Indicator Dilution method

3) Doppler combined with echo-cardiography → - non-invasive
Practical 4) Electromagnetic flow meter on aorta - ventricular function, velocity &
Volume of flow can be assessed
Factors affecting CO
Increase Decrease No change
Exercise Standing/sitting from Sleep

Environmental temp. (High) lying position Moderate changes in
Eating Arrhythmias environmental temp.
Epinephrine Heart disease
Emotions (Anxiety, Excitement)
Pregnancy
Oxygen consumption by heart
• Heart muscle is supplied by coronary arteries

• When O2 consumption increases, an organ may; 1. ↑ O2 extraction from arteries
2. ↑ its blood supply
• But heart muscles can only ↑ its blood supply because it extracts almost maximum O2
from arteries.
O2 consumption by heart determined primarily by
Intramyocardial tension Contractile state Heart rate

↑ EDV → ↑ R → ↑ T to → ↑ O2 ↑ number & strength of contraction
maintain P consumption
Stroke work / Ventricular work = SV x MAP Cardiac work = CO x MAP
• Stroke work of LV is higher than RV (Because LV has to pump blood against a higher pressure in aorta)
• ↑ in stroke work due to an ↑ in MAP causes a greater O2consumption than ↑ in preload.
• An ↑ in afterload causes greater O2consumption than an ↑ in preload.
∴ Angina pectoris is more common in aortic stenosis than aortic regurgitation.
Dynamics of blood and Lymph Flow
Structural features of circulation
2 major cell types
Endothelium Vascular smooth muscle (VSM)

Respond to * Flow changes * contains K+, Ca2+, Cl− channels
* Stretch * Determines vascular tone
* Circulatory substances * Has different and opposite effects in response
* Inflammatory mediators to high and low levels of cytosolic Ca2+
Secrete Growth regulators

Vasoactive substances e.g. 1. Influx of Ca2+ via voltage gated Ca2 channels
• Endothelium is an endocrine organ produce diffuse ↑ in cytosolic Ca2+ & contraction

(because it is active & has a regulatory function)
2. Release of Ca2+ via Ryanodine 
Produce Ca2+ sparks with resultant K+ efflux
3. Closure of voltage gated Ca2 channels
Cause relaxation
Arteries and arterioles
• Elastic tissue % aorta > large arteries > small arteries > arterioles
• Smooth muscle % aorta < large arteries < small arteries < arterioles
• Muscle is innervated by Noradrenergic fibres
(But in some instances, by cholinergic fibres)
• Arterioles are the major site of resistance to blood flow
(As R α 1/r4 ; small change in calibre causes large change in TPR)

Capillaries
• Surrounded on upstream side by ‘precapillary sphincters’

Not innervated
Can respond to local stimulating substances
• Diameter → - Just sufficient to permit RBC to squeeze through in a single file
- Large in venular end than arteriolar end.
Lymphatics
Following features differ a lymphatic from a capillary
1. No fenestrations in endothelium
2. Very little if any basal laminar under endothelium
3. Junctions between endothelial cells are open
4. No tight intracellular connections
5. Contain valves
Venules & Veins

1. Wall is thin and easily distended
2. Relatively little SM
(But considerable venoconstriction is
produced by noradrenergic nerves & vasoconstrictors)
3. Variations in venous tone are important in circulatory adjustment
4. Contain valves (Except in; small veins, great veins, & veins in brain)
Biophysical considerations of circulatory physiology
Flow
Q = MAP - MVP
Flow = Effective Perfusion Pressure (P) R
(Q) Resistance (R)
P = MAP − MVP
Streamline Flow * When the vessel is obstructed flow
Parallel to long axis beyond that become turbulent.
Laminar Occurs in layers * Turbulent flow produces a noise
Flow Layer close to the wall doesn’t flow due to vibration.
Centremost layer has highest velocity * Results in bruits and murmurs
Flow is silent * This is being used as the principle of
Occurs in normal blood vessels auscultation method of BP measurement
Re – Reynolds number * Higher the Re, higher the turbulence

v – velocity
Re = vDρ
D – diameter
η ρ – density
η – viscosity
Resistance

Poiseuille – Hagen Formula
Q=P → Q= πr4P
R = 8ηl
R
πr4 8ηl
• Resistance to blood flow → Vascular hindrance

Radius (R α 1/r4)
Determined by
Viscosity (R α η )
Determined largely upon haematocrit

Viscosity
Conditions ↑ η Conditions ↓ η
Polycythemia Anaemia
↓ Temperature Pregnancy
↓ Flow rate
↓ Plasma volume
↑ Plasma proteins
Hereditary spherocytosis
Shear stress
• Shear stress → force created on the endothelium parallel to the long axis of vessel
Shear stress = viscosity x shear rate

(γ) (η) (dy/dr)
Average velocity
Q = AV Aα1/V ∴ V → - Higher in aorta

- Declines steadily in small vessels
Flow area of average - lowest in capillaries
conduit velocity
Application of Bernoulli’s theory in circulation
• During standing MAP is 100mmHg in proximal aorta and 180mmHg in foot

• Yet blood flows from heart to foot
• Explanation: proximal aortic blood has 90 mmHg more gravitational potential energy so total energy of
aortic blood is 190 mmHg.

Critical closing pressure (CCP)
• Tissue surrounds the vessel exerts a pressure on them.
• When intraluminal pressure < tissue pressure ; vessel collapse
• At this time as the intraluminal pressure is not ‘0’ no blood flows from vessel
• The pressure at which flow ceases is called the CCP
Law of La-place
• Tension (T) α Transmural pressure (P) ∴ T = Pr
T α Radius (r) w
T α 1/wall thickness (w)
• T α r usage :- Tension becomes low from arteries to capillaries

In dilated heart → r ↑ → T ↑ to produce given P
Resistance vs capacitance vessels

Resistance Capacitance
• Principle site of peripheral resistance Have large capacity to accommodate extra

• Only 1 % of extra circulatory fluid will volume of blood
Be distributed e.g. 1. Veins (50% of blood)
e.g. 1. Small arteries & arterioles 2. Low pressure system
2. High pressure system
Arterial Pressure
Flow through systemic circulation = CO
Q = MAP − CVP CO = MAP − CVP * CVP is close to ∴ MAP = CO x TPR

TPR TPR atmospheric pressure ∼ 0

Systolic Pressure :- Peak pressure in aorta and other large arteries during cardiac cycle
Depends on CO
∼ 120 mmHg
Diastolic Pressure :- Minimum pressure in aorta and other arteries during cardiac cycle
Depends on TPR
∼ 70 mmHg
∴ recorded as SBP/DBP = 120 mmHg
70
Measurement of arterial blood pressure (Korotkoff sounds)
Snapping sound onset marks SYSTOLIC phase I
Becomes soft murmur (bruit) phase II
Sounds louder clearer phase III
Muffling of sounds phase IV
Sounds disappear phase V
Factors affecting arterial BP

1. Gravity 6. Sleep Pulse pressure (PP) = SBP – DBP
2. Emotions 7. Posture
3. Aging 8. Exercise
Mean pressure (MP) = DBP + 1/3 PP
4. Gender 9. Body size
5. Digestion
Venous Pressure
• In head → Sub atmospheric in Dural sinuses (important to know in neurosurgery)

• In neck → close to ‘0’
• Venules → 12 – 18 mmHg
• Great veins outside thorax → 5.5 mmHg
• Great veins at entrance to RA (CVP) → 4.6 mmHg (fluctuate with respiration & heart beat)
above
• Peripheral veins →
RA
Below
Thoracic Pump
Venous Pressure is affected by Muscle pump
Variations in RA pressure
Shunt
• Communication that deviate from the normal circulatory circuit

• Cardiac shunts → between chambers of heart
• Extracardiac shunts → Between systemic & pulmonary circulations
• Clinical consequences will depend on whether the shunt is ;
1. Physiological → e.g. venae cordis minimi
Draining of bronchial veins to pulmonary veins
2. Pathological → e.g. ASD
3. Direction of the flow

Circulation Through Special Regions
2) Cerebral blood flow

• 750-900 ml per min
• Gray matter - high O2 demand
• Both large and small arteries contribute to vascular resistance
• Perfusion pressure P= PA-PV(depend on ICP & CVP whichever is high)
Depends on
1. CPP - MAP, ICP
2. Viscosity
3. Vessel diameter- Auto Regulation
Neural factors
Metabolic factors – CO2, Acidosis, Hypoxia

 Neural regulation is not clear
Coronary circulation
• 250ml/min (5% of CO)
• Supplies myocardium (no supply from blood within chambers)
• Myocardium
–High O2 consumption and high O2 extraction (70-80%)
–Requires regular uninterrupted coronary blood flow to function
• Left & right coronary arteries are end arteries.
• If need to increase O2 supply - blood supply is increased. (Flow is coupled
to O2 demand)
• Considerable autoregulation present
Coronary flow to
• Left ventricle – mostly in diastole
• Other chambers – throughout cardiac cycle

 Effect of autonomic nerve system
o SNS alpha 1 adrenoceptors - vasoconstriction
o Metabolites (mainly adenosine) - vasodilation
o SNS activity – Transient vasoconstriction followed by vasodilation.
(Metabolites from increased mechanical & metabolic activity of the heart
due to β1 adrenoceptor stim. cause vasodilation)
 Most important single factor determining the coronary blood flow

is the requirement of the heart for oxygen. Metabolic regulation of
coronary vascular resistance is major determinant

Systolic compression
• Left ventricular wall- Generate a large force
during contraction within myocardium.
• Due to intra myocardial forces, pressure inside
becomes greater(121mmHg) than aortic
pressure(120mmHg). So coronary
vessels get collapsed increasing the coronary
vascular resistance.
• In systole, blood supply is interrupted to the area
close to the cavity (sub endocardium). Blood flows
only during diastole. (But more superficial areas
of the L ventricle gets blood supply throughout the
cardiac cycle.)
• When HR is increased diastole becomes shorter.
reduced blood supply to sub endocardium of the L
ventricle.
• More prone to IHD
• But pressure difference between aorta & R ventricle
or atria is greater during systole. (Aortic P ) So
coronary flow to these regions is not much reduced
during systole.
• Anterior interventricular artery- more prone to
atherosclerosis
3) Splanchnic circulation
• 30% of cardiac output
• Reservoir function (Important in moderate arterial blood loss)
• Active hyperemia caused by food ingestion
High responsiveness to vasoconstrictors
Reciprocal blood flow between liver and other organs
Portal vein 75% hepatic artery 25%
4) Cutaneous circulation
Varies with the temperature of the body
Only vasoconstrictors no dilators (By
sympathetic)
Dilation is done by reduction of vasoconstrictor
tone and bradykinin

Reactive hyperemia seen on skin
Reduction in core temperature of body
Sensed by posterior hypothalamus
Reduced skin blood flow (by low resistance AV anastomoses)
Reduce heat loss
Special fetures of cutanous circulation

 Reactive hypermia
 White reaction
 Triple response - Reddening
- Swelling
- Flare
Applied CVS
Hypertension
 Sustained elevation of blood pressure above 140/90 mmHg

 BP determined by Cardiac output & Peripheral
resistance
 Hypertension usually caused by increased peripheral
resistance
Causes –
 essential hypertension – multi factorial
 Renal disease – increased secretion of renin
 Hormonal over activity – aldosterone, glucocorticoids,
 catecholamine, GH
 Coarctation of aorta
 Drugs – oral contraceptives, cocaine
 Pregnancy induced hypertension
 Increased blood viscosity – polycythemia
 Baroreceptor resetting at a higher BP in chronic HT

Hypertension – principles of management
Vasodilators
Ca2+ channel blockers
Angiotensin Converting Enzyme Inhibitors (ACEI)
Angiotensin II Receptor Blockers (ARB)
α blockers
Drugs decreasing heart rate
β blockers
Diuretics (drugs reducing blood volume by increasing urine output)
Others----
IHD
 Inadequate blood supply to heart muscle to satisfy oxygen requirements
• Mechanical obstruction -atheroma
Thrombosis
• Non mechanical destruction- anaemia
Hypotension
• Increased demand for O2 by the myocardium
Angina unstable angina Myocardial Infarction
Effects of IHD – ECG Abnormalities (ST segment elevation)

Release of enzymes and proteins from damaged cells (troponin T & I)
Heart failure
Arrhythmias
Management
• Vasodilatation - nitrates
• Fibrinolytics- streptokinase
• Antiplatelet therapy-aspirin
• Anti thrombotics- heparin
• Reducing myocardial O2 demand-β blockers
• Reducing cholesterol deposition-statins
• Increasing O2 supply
• Reperfusion - fibrinolytic , angioplastin , bypass grafting
• Pain relief- Morphine
Heart failure
Inability of the heart to maintain a sufficient cardiac output to meet tissue needs
Types
Acute or chronic
LV (commonly), RV or both ventricles
Systolic or diastolic
High-output or low-output

Management –
• ↓preload and afterload
• Decrease venous congestion-diuretics, venodilators, aldosterone antagonist
• Decrease peripheral resistance-ACE inhibitors, Angiotensin receptor blockers
• Improving contractility-Digitalis, ACEI
• Improving symptoms
• Reducing mortality- beta blockers
Shock
 Definition: Inadequate tissue perfusion with a relative or absolute inadequacy in cardiac
output
Classification
Hypovolaemic
Haemorrhage, trauma, severe diarrhoea
Cardiogenic
Myocardial infarction, heart failure, arrhythmia
Obstructive
Tension pneumothorax, cardiac tamponade, pulmonary embolism
Distributive
Neurogenic shock (major brain or spinal injury)
Anaphylaxis (triggered by allergens)
Septic shock
Cardiac tamponade - fluid collects between myocardium and pericardium. pressure within the
pericardium prevents heart chambers from expanding fully.it reduces the preload.
Pulmonary embolism – blockage of a main artery of the lung or one of its branches
Neurogenic- due to disruption of autonomic pathways in spinal cord. lack of sympathetic supply
for arterioles causes hypotension. Unopposed vagal action causes bradycardia
Anaphyalactic shock- triggered by allergens
Septic shock- due to an infection
Ex>> Haemorrhagic shock

•Blood volume is reduced.
• So the venous return to the right atrium is reduced .It causes reduced preload and
stroke volume resulting in reduced cardiac output .It results in decrease in blood
pressure.
• Low blood volume causes reduction of discharge rate and stimulation of volume
receptors on atrial wall at the opening of the SVC, IVC and pulmonary vessels .low blood
pressure causes reduction of discharge rate and stimulation of carotid sinus and aortic
arch baro receptors.
• This reduces the neural discharge of buffer nerves to the nucleus tractus solitarius which

in turn causes the stimulation of the vaso motor centre and inhibition of the cardiac
inhibitory centre resulting in an overall sympathetic stimulation and reduction of
parasympathetic activity.
• Sympathetic stimulation via norepinephrine on α1 receptors constricts arterioles in the
circulation which increases the arterial pressure and thus the perfusion pressure of vital
organs which helps maintain perfusion.
• Furthermore, sympathetic stimulation also causes constriction of veins displacing blood
towards the heart, thus increasing venous return. Decreased vagal activity increases
heart rate. Also sympathetic stimulation via both norepinephrine and epinephrine on β1
receptors increases heart rate and contractility of heart muscle. Both these factors
increase cardiac output and hence blood supply to vital organs.
• Increased heart rate causes rapid but thready pulse because the blood volume is
reduced.
• Another part of the mechanism to maintain perfusion to vital organs is autoregulation.
This is the dilation of vessels in brain and heart due to local metabolites which maintains
a normal blood flow despite the reduction in volume.
• Sympathetic stimulation causes increased secretion of catecholamines from adrenal
medulla and sympathetic nerve endings secretes catecholamine. These act on
juxtaglomerular cells.
• In addition, a decrease in the stimulation of intra renal baro receptors would cause renin
to be secreted by juxta glomerular cells which converts Angiotensinogen to Angiotensin
I which is in turn converted to Angiotensin II by ACE which is produced by the
endothelium of pulmonary vessels.
• Angiotensin II causes the secretion of aldosterone and ADH which increase renal Na+
reabsorption from tubules and water reabsorption from collecting ducts respectively.
•Angiotensin II constricts renal afferent and efferent arterioles; efferent arterioles are
constricted more.and angiotensin II causes constriction of mesangial cells.In both these
ways it will reduce UFR resulting in oliguria and thus increasing blood volume in turn
increases the blood pressure to supply vital organs.
• In addition Angiotensin II and ADH can act as a vaso constrictor and cause an increase in
venous return.
• Haemorrhage causes decreased blood flow through aortic and carotid body chemo
receptors resulting stagnant hypoxia which stimulate the peripheral chemoreceptors.
• And also due to the blood loss amount of RBC is reduced.resulting anemia causes
inadequate tissue perfusion.so the cells generate energy from anaerobic glycolysis.lactic
acid is produced.lactic acid reduce blood pH and stimulate pheripheral chemoreceptors.
• The impulses from these via afferent nerves modulate the respiratory centre to increase
discharge in the efferent nerves supplying respiratory muscles which would increase
respiratory rate and depth resulting in adequate O2 supply to vital organs.
• In addition the release of epinephrine as a stress reaction in shock could be having the
same effects of a sympathetic stimulation.
●It is in the wake of these physiological adaptations inside the body that you would see a rapid
thready pulse, increased respiratory rate, oliguria and cold clammy hands in a person with
shock.

CVS regulation
Regulation – 1. Long term - RAAM
2. Short term
1) Local Mechanisms (SEQ)
2) Systemic mechanisms
Local regulatory mechanisms
1. Auto regulation
2. Vasoactive metabolites
3.Substances secreted by endothelium
Auto Regulation
Capacity of tissues to control their own blood supply.

• Partly as an intrinsic contractile response of smooth muscle to stretch (myogenic
theory)
• Partly as accumulation of vasodilator metabolites in active tissues. (Metabolic
theory)
• Localized vasoconstriction
Injured arteries and arterioles constrict strongly (Due to serotonin)
Cold causes vasoconstriction (MCQ)
Places where autoregulation takes place – Kidney,Brain,Skeletal muscles,Liver
,Myocardium,Mysentry etc.
Myogenic Theory Metabolic Theory
Increase Blood Flow Decrease flow
Dilation of arterioles Increase accumulation of Vasodilatory metabolites
Smooth muscles of Dilation of arteriole

tunica media are stretched
Muscle contraction Increase flow
Constriction of arteriole
Decrease flow

2) Localized vasodilation by vasoactive metabolites
Increase in Decreased in
PO2 PCO2
T pH
K+
Lactate (Mainly in skeletal Muscles)
Histamine (Increases vascular Permeability)
Aenosine (only in cardiac muscle)
 In generalized/ systemic hypercapnia vasodilation takes place only in Brain and Skin.
3) Substances secreted by endothelium (MCQ)

Dilators- NO, Prostaglanin
Constrictors -Endothelin (most potent vasoconstrion)
Endothelins
Most potent vasoconstrictor identified Family of ET (ET-1, ET-2, ET-3)
Release stimulated by
? Stretching of blood vessels
Thrombin
Epinephrine

Functions
Constricts vascular smooth muscle (veins & arteries)
Positive chrono/inotropic effects on heart
Increases plasma ANP, renin, aldosterone, catecholamin
Systemic Regulatory Mechanisms

1) Hormonal regulation
Vasodilators
VIP
Kinins
Natriuretic hormones
ANP, BNP found in blood
CNP not found in blood (MCQ)
ANP
• Increases when atria are stretched and central venous P is increased.
• Natriuresis (Excretion of sodium and water in urine) (MCQ)
• Vasodilation
BNP- secreted when ventricles are stretched
- Also from brain
Vasoconstrictors
Epinephrine, Norepinephrine, Vasopressin, Angiotensin II, Thromboxane A2
Receptor Place Function Neurotransmitter

α1 Blood Vasoconstriction Norepinephrine
Vessels
𝛽𝛽1 Heart Increase HR & Norepinephrine
myocardial Epinephrine
contractility
β2 Skeletal Vasodilation Epinephrine
Muscles Bronchodilation
Bronchi
Liver

Blood Pressure (BP)
CO TPR Sympathetic
(No parasympathetic)
SV HR Circulatory substances Diameter

Sympathetic Viscosity
Parasympathetic Elasticity
Temperature
pH
Preload → EDV Venous Return ← TBV, Posture

Venous tone
Thoracic Pump
Muscle pump
Filling time ← HR
Filling pressure ← Atrial contraction
Blood volume
Ventricular compliance ← Stiffness

High intrapericardial pressure
Afterload ← BP
TPR (Total peripheral resistance)
Size of ventricle
Viscosity
SV • Sympathetic
• Digitalis
Myocardial contractility → • Xanthines
• Positive inotropes
• Parasympathetic
• Hypoxia
• Hypercapnia
Frank Starling Law
• barbiturates, quinidine, procainamide
• Heart failure
EDV

2) Neural Regulation
• Stretch of walls of heart and blood vessels

Stimulus • Both pulse pressure and mean arterial pressure
• Blood volume
Receptor Barorecepto
Afferent Buffer Nerve
Centers IN Medulla
Sympathetic and parasympathetic fibers to heart and

Efferent
sympathetic fibers to blood vessels, adrenal medulla , JGA
Effector
Buffer nerve – Both vagus and glossopharyngeal nerves together known as buffer nerve. Vagus nerve
carries impulses from aortic sinus . glossopharyngeal nerve carries impulses from carotid sinus.

Hypercapnia
Hypoxia Chemoreceptors (cardiac, aortic)
Pain emotions, sexual excitement
HR
Stretching of lungs
TPR
Sympathetic RVLM
Adrenal From cortex via hypothalamus
Medulla
GABA (−)
Myocardial CVLM
Contractility
Glutamate (+)
Glutamate (+)
NTS Nucleus Dorsal Parasympathetic
Glutamate ambiguus Vagal
(+) Nucleus
HR Myocardial
Buffer nerve contractility
Baroreceptors
High pressure (Arterial) Low pressure (cardiopulmonary)
* aortic arch * R and L atria

* carotid sinus * Entrance of SVC, IVC, pulmonary veins
Pulmonary circulation
RVLM – Rostral ventrolateral medulla

CVLM – Caudal ventrolateral medulla
NTS – Nucleus of Tractus Solitarius
VMA – Vasomotor Area (presently this VMA is known as RVLM)

Cushing reflex
Raised intracranial pressure Impairs blood supply vasomotor area Stimulates

vasomotor center directly Increases sympathetic discharge Increases systemic B
Restores blood supply to VMA and stimulates baroreceptors Inhibits VMA
Bradycardia
Valsalva Manuever
To check baroreceptors MCQ

Occurs during coughing, defecation, heavy coughing
Take a deep breath → exhale against closed glottis → blood pressure goes up (due to
the compression of aorta at onset) → Venous return decreases (due to compression
of great veins) → CO decreases → blood pressure decreases → baroreceptor
discharge decreases → parasymp inactivate, symp activate → HR increases,
Contractility increases, CO increase, vasoconstriction → BP increase with tachycardia
→ exhale → venous return come to normal → blood pressure increases →
baroreceptor discharge increases → symp. inactivates parasymp. Activates→ HR
decreases, contractility decreases → still vessels compressed → Hypertension with
bradycardia.

Respiratory Physiology
Functions of the RS
1. Main function is gas exchange to supply tissues with O 2 and remove CO 2 .
2. Defence 3. Metabolic & Endocrine
Humidify air and control its temperature Manufacture surfactant (DPPC)

Epithelium secretes IgA, collectins, Pulmonary circulation contributes to
defensins, Proteases, peptides and Fibrinolytic system
reactive O & N species.
Prevent foreign matter from entering Pulmonary endothelium has ACE,
alveoli (hairs, mucous membrane and Therefore converts AT-I to AT-II and
curvature with Waldeyer’s ring) Inactivates bradykinin
Reflex bronchial constriction & coughing
Mucociliary escalator
Pulmonary alveolar macrophages/ PAM

(phagocytosis, antigen processing)
External/ Pulmonary respiration Internal/ cellular respiration

Occurs at respiratory membrane in alveoli, Occurs at cellular level where O 2 is consumed, CO 2 is
exchange Produced and gases are exchanged with ECF then with
Gas between blood and air blood across the endothelium
Gas exchange organ = lungs
Respiratory System Structural = respiratory muscles, chest wall
Pumping CNS
mechanism
Regulatory Nerves = motor & sensory
(phrenics, vagus etc)
The collective activity of all above results in the main function of gas exchange to supply O 2 and remove
CO 2 . This task of delivering gases between atmosphere and cells is staged into the following processes.
1. 2. 3. 4.
VENTILATION GAS EXCHANGE GAS TRANSPORT REGULATION

VENTILATION
It is the process by which air is transferred between the lungs and the atmosphere, so that O 2 and CO 2 can
be exchanged in alveoli.
Mechanism Airways & Compliance & Alveolar

of Breathing Airflow Surface Tension
Lung Volumes, Capacities & Alveolar Ventilation Equation & Work of

Lung Function Tests Breathing
Mechanism of Breathing
The movement of air between the lungs & atmosphere depends on;
1. Total pressure gradient (mass movement)
2. Partial pressure gradient of individual gases
• Lung & chest wall are elastic (elasticity-resistance to deformation) and are held together by the
adhering parietal & visceral pleura
• Recoil forces of the lung & chest wall pull in opposite directions
• At rest these forces just balance each other.
• Negative P in the intrapleural space (Intra-pleural pressure)
• Lymphatic channels are more abundant in the lungs than any other organ (WHY?). They absorb excess
fluid and maintain a slight suction.
• Therefore at rest there is a slight IPP= - 2.5 mmHg (relative to atmospheric pressure)
Lungs expand & contract in 2 ways

1. Upward & downward movement of the diaphragm (this is sufficient for normal quiet breathing) –
almost entirely this method accounts for75% of the change in ITP. (Vertical diameter)
2. Elevation & depression of ribs by pump handle and bucket handle movements. (Transverse &
anteroposterior diameters)
Inspiration
• Active process
• Contraction of inspiratory muscles increase thoracic
volume
• Main muscle of inspiration – diaphragm
• Other/ accessory muscles – external intercostals,
sternocleidomastoid, scaleni, serratus anterior
• Chest wall expands, lung begins to expand because
visceral pleura is in contact with parietal pleura,
expansion of lungs lead to increased elastic recoil
• Intrapulmonary volume increases
• Negative IPP transmitted to alveoli (-6 mmHg)
• Intrapulmonary pressure drops
• Air flows into lungs

Expiration Strong inspiration
• IPP more negative, up to - 30mmHg
• Passive process during rest. • Accessory muscles become more active-
• Inspiratory muscles stop contracting sternocleidomastoid, scaleni, serratus
• Thorax & lung come back to their original anterior
positions because the lung & chest wall are
elastic (passive process) Forced expiration
• Intrathoracic volume decreases. • Active process (cough & sneeze, exercise,
• Alveolar pressure becomes positive relative to voluntary hyperventilation)
the atmosphere • Contraction of expiratory muscles –int.
• Air flows out until the pressure equalize intercostals & anterior abdominal
• Negative intrapleural pressure returns to • IPP can be positive
previous value (-2.5 mmHg) but does not
become positive. * If the lungs lose their elasticity, the lungs do not
pull the chest wall inwards and therefore the
chest expands to spring out and takes a BARREL
SHAPE CHEST
Airways & Airflow
• Nose
Upper
• Pharynx Airways
• Larynx
• Trachea
• RL main bronchi Lower
• Lobar bronchi Airways
• Segmental bronchi
• Terminal bronchioles
Anatomical dead space (150 mL)
• Respiratory bronchioles
Gas
• Alveolar ducts
Exchange
area
• Alveoli

These 3 together is called an acinus
Collectively form most of the lung volume (2.5 – 3 L at rest)
Air flows by bulk flow up to the terminal bronchioles, thereafter the volume / total cross area greatly
increases causing velocity of air to rapidly decrease.
Therefore there is a high chance of unfiltered inhaled dust particles depositing in the respiratory zone
Blood Supply of Lungs
Lungs have a dual blood supply:

• Pulmonary circulation (to respiratory zone)
• Bronchial circulation (to conducting zone & pleura. Physiological shunts occur between bronchial veins
and pulmonary veins)
Dilatation Constriction
Inspiration Expiration
Circadian rhythm (max 6 pm) Circadian rhythm (max 6 am)

Factors Affecting Airflow (Resistance & Compliance)
1. Resistance ”Pressure difference required for a unit air flow (R = ΔP/Flow Rate)”
Depends on:
• Pressure gradient between the mouth and alveoli (determines the volume of air coming in)
• Caliber of the airways
o Tone of bronchial smooth muscle (affected by ANS, circulating agents and PO 2 & PCO 2 )
o Patent bronchi
o Lung volume How??
• Density & viscosity of the inhaled gas (O 2 mixed with He is given in hospitals)
• Large bronchi  Medium size bronchioles  Increase resistance
Medium size bronchi  Small bronchioles  Decrease resistance
1
Airway resistance ∝
𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑
Bronchoconstriction is precipitated by Dilators

1. Cool air 1. VIP – Relaxes smooth muscles
2. Exercise 2. Salbutamol – β2 agonist
3. Irritants 3. Atrophine – Parasympathetic antagonist
4. Inflammatory agents (bacteria, virus,
Draw the graph for vital capacity against time in an
allergens)
asthma patient and comment on the ratio FEV1/VC
5. Cytokines
6. Adenosine
7. Leukotrines
8. Histamines
9. Substance P
10. Epinephrine/ Norepinephrine
What happens in Asthma?
The diameter of airways is decreased by

• Increased smooth muscle tone
• Oedema & inflammation of submucosal layer
• Obstruction of the lumen by excess secretions
Is asthma an obstructive or restrictive lung disease?
How to overcome airway resistance?
1. Dilate airways – bronchodilators. Ex: Salbutamol (β2 receptor agonist)
2. Reduce density of gas – He & O2 mixtures
3. Increase the pressure gradient – Mechanical ventilators & accessory muscles of inspiration

Compliance & Alveolar Surface Tension
2. Compliance/Stretchability/Distensibility
“Change in lung volume per unit change in transpulmonary pressure (ΔV/ΔP)” 200 mL/cm H 2 O
Depends on:
• Lung volume
• Surface tension
• Structural properties
The P-V curves are different for inspiration &

expiration. “Hysteresis”.
1
𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶 𝛼𝛼
𝐿𝐿𝐿𝐿𝐿𝐿𝐿𝐿 𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉
High Compliance Low Compliance

Greater change in V per unit change in P Smaller change in V per unit change in P
Expiration is difficult Inspiration is difficult
Lungs are expanded Lungs are stiff
Causes: Causes:
Old age, Emphysema, Reduced elastin content Lung fibrosis, pulmonary oedema, atelectasis
Draw the graph for vital capacity against time in a lung

fibrosis patient and comment on the ratio FEV1/VC

Alveolar Surface Tension
“Surface tension is the force acting across an imaginary line 1cm long on the surface of a liquid”
This occurs due to the intrinsic property of a liquid to assume the minimum surface: volume ratio (the
attractive forces between liquid molecules is greater than their attraction to other surrounding molecules.
2𝑇𝑇
𝐿𝐿𝐿𝐿𝐿𝐿𝐿𝐿𝐿𝐿𝐿𝐿𝑒𝑒 ′ 𝑠𝑠 𝐿𝐿𝐿𝐿𝐿𝐿 ∶ 𝑃𝑃 = 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡 𝛂𝛂 𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒 𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟
𝑅𝑅
Surfactant
• A lipid surface tension lowering agent present in the fluid lining the alveoli
• Secreted by type II alveolar epithelial cells
• Rapid rate of turnover
• Recycled by type II pneumocytes & pulmonary alveolar macrophages (PAMs)
• DPPC (dipalmitoylphosphatidylcholine) + lipids + proteins
• Formed 32 / 34 weeks in fetal life.
• Maturation of surfactant at this time is by
• glucocorticoid hormones
• Smoking decreases surfactant
How does surfactant ↓ ST?

• DPPC molecules are hydrophobic at one end and hydrophilic at the other.
• Align on surface
• Inter molecular repulsive forces oppose normal attractive forces between liquid molecules on the
surface
Functions & Advantages of Surfactant (Explain how each is achieved by surfactant)
1. Increases compliance
2. Decreases the work of expansion
3. Increases alveolar stability – Prevent smaller alveoli from collapsing and large alveoli from bursting
4. Prevents atelectasis. *Infant respiratory distress syndrome
5. Keeps the alveoli dry – ST forces suck fluid in to the alveoli.
Write the relationship of DPPC to ST What is the function of type I alveolar epithelial
cells?
Which cell type is more numerous?
Which cells occupy a greater surface area of the

alveoli?

Work of Breathing
Work done by respiratory muscles.
 To move inelastic tissue  7%

 To move elastic tissues in lung and chest wall  65%
 To move air through respiratory passage  28%
Work = Pressure × Volume
In asthma the resistance work is greatly increased.

In Emphysema elastic work is increased.
Lung Volumes, Capacities & Lung Function Tests
Volumes are measured. Capacities are additions of volumes.

Measurement Typical Definition
value (mL)
TV 500 The volume of air inspired or expired with each normal breath
IRV 3000 The maximum extra volume of air that can be inspired over and
above the normal TV when the person inspires with full force
ERV 1200 The maximum extra volume of air that can be expired by forceful
expiration after the end of a normal tidal expiration
RV 1200 The volume of air remaining in the lungs after the most forceful
expiration
VC or FVC 4700 The maximum amount of air that can be expelled IRV+TV+ERV
after first filling the lungs to their maximum extent
and then expiring to the maximum extent
IC 3500 The amount of air that can be inspired, beginning TV+IRV
at the normal expiratory level and distending the
lungs to the maximum amount
FRC (relaxation 2400 The amount of air that remains in the lungs at the ERV+RV
volume) end of normal expiration
TLC 5900 The maximum volume to which the lungs can be VC+RV
expanded with the greatest possible effort
RV, FRC, TLC – cannot be measured by spirometry WHY?

Measured by He/N 2 dilution method & Total body plethysmography
FEV 1 – Fraction of FVC expelled during first second of forced expiration (Normally 75% of VC)
Respiratory minute volume = RR × TV
Lung Function Tests
Normal
Obstructive
Restrictive
Obstructive Restrictive
Caused by airway obstruction Caused by stiff lungs
FEV 1 decreases FEV 1 decreases
VC unchanged VC decreases
FEV 1 /VC ratio less than 75% FEV 1 /VC ratio normal or higher than
75%
Ex: Asthma, COPD Ex: Lung Fibrosis
Maximum/ Peak Expiratory Flow
• Peak flow is the volume of air that can be expired in a unit time in a maximum expiratory effort.
• This ranges from 400 – 750 L/min
• Measured by a Peak flow meter
• Peak flow is reduced in
o Restrictive diseases
 Fibrotic diseases (Tuberculosis, Lung fibrosis, Silicosis)
 Abnormal chest walls (Kyphosis, Scoliosis)
o Obstructive diseases
 Asthma
 Emphysema
Alveolar Ventilation Equation
Dead Space
The volume of gas, which occupies that region of the respiratory system, which does not take part in gas
exchange.
• Anatomic dead space (150 mL)

o The volume of all the airways proximal to the respiratory bronchioles
o Increases in deep breathing. WHY?
o Depends on the body size and posture
• Physiologic dead space

o The total volume of air that it not equilibrating with blood (wasted ventilation), simply, the
volume of alveoli, which are ventilated but not perfused.
o Un-perfused alveoli
o In diseases, un-perfused and over-ventilated alveoli increases.
Calculation of Ventilation
To increase ventilation, increasing
TV is better than increasing RR.
Tidal volume = Anatomic dead space + alveolar compartment Because of the dead space, rapid
= 150 mL + 350 mL shallow breathing produces much
= 500 mL less alveolar ventilation than slow
deep breathing at the same
Respiratory rate = 15 cycles/min (12 – 20) respiratory minute volume.
Total ventilation/ = TV × RR
RMV = 500 mL × 15 min-1
= 7500 mL/min (RMV) VA – Alveolar ventilation. Volume of air
that reach the alveoli.
Alveolar ventilation equation
V A = (TV – DSV) × RR Tidal volume
= (500-150) × 15 Respiratory rate VA
= 5250 mL/min Dead space

GAS EXCHANGE
Partial pressure Oxygen Diffusion Pulmonary Ventilation – Perfusion
Cascade Circulation Relationships
Partial Pressure
o Pressure exerted in any one gas in a mixture of

gases.
o Dissolved gases also exert partial pressure
o Partial pressure of a dissolved gas in the liquid is
proportional to its concentration
o Net diffusion between alveolar air and pulmonary
blood depends on difference of partial pressures
Oxygen Cascade
PA – Alveolar partial pressure

Pa – Arterial partial pressure
Gas exchange occurs at blood gas interface – Made of alveolar & capillary walls + fused basement
membrane/ Alveolar capillary membrane/ Respiratory membrane
Factors effecting the rate of diffusion across the membrane (V/t)

• Thickness of the membrane (T)
• Surface area of the membrane (A)
• Pressure difference of the gas across the membrane (P 1 -P 2 )
• Diffusion coefficient (D) – Depend on solubility (sol) & square root of the gas’s molecular weight (MW)
𝐕𝐕 𝐀𝐀
∝ × 𝐃𝐃 × (𝐏𝐏𝟏𝟏 − 𝐏𝐏𝟐𝟐 )
𝐭𝐭 𝐓𝐓
𝐬𝐬𝐬𝐬𝐬𝐬
𝐃𝐃 ∝
√𝐌𝐌𝐌𝐌
In emphysema surface area decreases as alveoli coalesce

Diffusion Capacity (DL)
“Volume of gas that will diffuse through the respiratory membrane each minute for a partial pressure
difference of 1 mmHg”
It is a measure of the ability of the lung to transfer gas across the respiratory membrane. (High surface
area, adequate perfusion with haemoglobin)
Diffusion capacity depends on

- Surface area
- Capillary blood flow
- Haemoglobin available
Diffusion capacity is measured using DL CO method

Inhale a gas mixture with 0.3% CO.
Hold breath foe 10s.
CO diluted by gas already present and also taken up by Hb.
Exhale 1st to wash out the dead space
Next exhaled alveolar sample collected.
CO concentration measured.
DLCO = VCO / Alveolar-Arterial pressure difference of CO
* Arterial pressure is taken as Zero.
Should make corrections for Hb concentration and lung volume.
• Diffusing capacity increased in – exercise (because of capillary dilation and distension)

• Diffusing capacity decreased in – emphysema, lung fibrosis, lung lobe resection, anaemia
• Diffusing capacity CO 2 >>O 2 → CO 2 retention is rarely a problem in patients with lung fibrosis
• O 2 diffusing capacity reduction severe
Diffusion and Perfusion limitations
• N 2 O is perfusion limited. WHY?
• CO is diffusion limited. WHY?
• O 2 is perfusion limited. WHY?

Why does O2 transfer become diffusion limited
during severe exercise?
Why is it not so for mild exercise?
Pulmonary Circulation
2 main supplies
o Bronchial arteries – oxygenated blood from aorta, supply nutrients to the pulmonary tree.
o Pulmonary arteries – deoxygenated blood from r. ventricle for gas exchange.
After exchange, oxygenated blood is carried to the heart by pulmonary veins. There it is mixed with
deoxygenated blood draining the lungs. Thus a physiological shunt is seen here.
Differences from systemic circulation

• Much less smooth muscle
• Walls thinner
• Larger diameters
• Large numerous capillaries
• Multiple anastomoses
Shunts
Deoxygenated blood entering the arterial side of the circulation without undergoing gas exchange within
ventilated regions of the lung for oxygenation.
Hypoxaemia caused by shunts
Right to left Left to right
can never be abolished by
Bronchial veins → Pulmonary veins ASD
breathing 100% O2 because
Coronary veins → Left atrium shunted blood is never
Under ventilated but perfused alveoli ventilated. But PaO2 slightly
increases with 100% O2.
Physiological Pathological
shunts
When enlarged to cause pathological

conditions, ‘pathological shunts’

Pressures in the Pulmonary System
Mean pressure = 15 mmHg

• Alveolar Pulmonary Exposed to pressure of
vessels capillaries alveoli. Compressed if
alveolar pressure is increased
• Extra Pulmonary Pulled open by radial traction
alveolar vessels arteries & veins of surrounding lung tissue
Pulmonary Vascular Resistance – PVR
 Very low
 1/10 of systemic vascular resistance
 Due to absence of muscular arterioles.
 Compatible with distributing blood in a thin film over a vast area.
 When pressure within the system rises, PVR become smaller by;
o Recruitment – previously closed capillaries open
o Distension – vessels increase in caliber
 Serotonin, histamine, norepinephrine increase PVR
 Acetylcholine decreases PVR
Effect of Lung Volume on PVR
Inspiration PVR↓
 Extra alveolar vessels are opened by radial traction from
surrounding lung tissue.
Pulmonary Reservoir
 Due to distensibility
 Lying down position –
Blood volume ↑ vital capacity ↓
Uneven Ventilation
Upright
• Lower regions ventilated better than upper
zones.
Supine
• Apical ventilation = basal ventilation.
• Lowermost (posterior) > Uppermost (anterior)
 Dependent lung is best ventilated

Effect of Gravity on Regional Blood Flow
Bases are better perfused than the apex in the upright position
(Blood flow is greater in the most dependent part) Lowermost parts of the
lungs are well perfused
Zone 1: Upper-most part than uppermost parts.
 Pulmonary capillary pressure is very low
 Alveolar pressure at the apices cause capillary collapse at apices
 Therefore ventilated but un-perfused. More “Alveolar dead space”
Zone 2: Middle part
 Pulmonary capillary pressure overcomes alveolar pressure
 Flow rate depends on the difference of PA and Pa
 Perfusion occurs to a limited extent, only during systole
 Therefore not a dead space
Zone 3: Lower part
 Pulmonary venous pressure is also high
 Therefore PA is overcome easily
 Flow rate depends on Pa – Pv
 More “Shunting”
Ventilation Perfusion Relationships
• Diffusion of gases is not enough to achieve the best gas exchange; there must be a matching
between ventilation (V) and perfusion (Q).
• This matching is expressed as a ration V/Q
• Ideal alveoli must have V/Q = 1
• However, in reality V/Q = 0.8
The V/Q Scatter Spectrum of Alveoli
Shunts Dead space

Variation of V & Q Along the Lung Intra-pleural pressure more negative
Larger alveoli (Compliance low)
Lower intravascular pressure
Less blood flow
Less ventilation
L/min
But V/Q is high
Q
So low O2 extraction
Dead spaces are high
V
Bottom Top
Intra-pleural pressure less negative
Smaller alveoli (Compliance high)
Higher intravascular pressure
Better blood flow
Better ventilation
But V/Q is low
So O2 Extraction is high
Shunts are high
State the sizes of alveoli & state of perfusion at the lung apex and base. Explain why there is
a difference. Based on your answer, what factor is the main reason for this variation?
Which part of this lung is susceptible to tuberculosis?
Draw a graph showing the variation of V, Q & V/Q from the dependent part to non-
dependent part of a lung

• V/Q abnormalities
o Do not commonly lead to CO 2 retention, if ventilation can be increased.
o Hypoxemia cannot be eliminated by increasing ventilation
• Different behavior of the 2 gases result from the different shapes of their dissociation curves.
• V/Q mismatch is an important & common cause of hypoxemia. It can also cause hypercapnia BUT it
does not manifest! WHY?
• V/Q ratio increase in emphysema decrease in fibrosis.
Autonomic supply – (sympathetic - ↓blood flow)

Active
- O2
Local factors (Hypoxic vasoconstriction)
- CO 2 (→ pH↓ → vasoconstriction)
- NO
Systemic factors (eg- systemic hypoxia → constrict arterioles, P↑)

Regulation
Of Blood Flow
Gravity
Passive The main controllers under normal conditions

Cardiac output
• PVR
• Distribution of
flow
Hypoxic pulmonary vasoconstriction – HPV

o Occurs when PAO 2 is reduced. NOT PaO 2
o Doesn’t depend on CNS High altitude → PVR ↑
o Due to decreased production of NO (EDRF) At birth → PVR ↓
o Contraction of smooth muscle in vessels
o Directs blood away from the under ventilated regions.
Water Balance of Lungs

Inward directed pressure gradient of -15 mmHg
Numerous lymphatic channels
Keeps alveoli dry
25 10

Gas Transport
O 2 Transport
O 2 delivery system = CVS + RS

O 2 delivery to a particular tissue depends on
• Amount of O 2 entering the lungs
• Adequate gas exchange
• Blood flow to the tissues (degree of constriction of the vascular bed, Cardiac Output)
• Capacity of blood to carry O 2
Dissolved O2 follows Henry’s Law

Transported in 2 ways
o Bound to Hb 97%
𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴 𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑 𝛼𝛼 𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃 𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝
o Dissolved 3%
Name 3 types of Hb found in human

Amount of O 2 in blood depends on
• Hb – Amount
Affinity for O 2
• Dissolved O 2
O 2 & Hb
• Hb has Globin (2α + 2β), Fe2+, Porphyrin

• Each Fe2+ binds reversibly to 1 O 2 molecule
• Oxygenation – Iron remains Fe2+
• Hb 4 O 8
1st O 2 molecule is bound
DeoxyHb (less affinity) Relaxed configuration – R
Tense configuration – T Affinity greatly increased
Saturation = % of O 2 binding sites which have O 2 attached.

At 100% saturation, in vivo bound O 2 is less than in vitro
Reason – minor structural differences of Hb & small amounts of inactive Hb derivatives
Systemic arterial blood - Why 97%, not 100% O 2 saturation?
Physiological shunts
1. Pulmonary veins (pulmonary capillaries bypassed by bronchial veins)
2. Thebesian veins?
3. Poor V/Q matching
1. O 2 capacity – Maximum amount of O 2 that can be combined with Hb

(1.39 mL/g in vitro, 1.34 mL/ g in vivo)
1.39mL/g ×15 g/100 mL = 20.8 mL/100 mL
2. O 2 saturation
𝑂𝑂2 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 𝑤𝑤𝑤𝑤𝑤𝑤ℎ 𝐻𝐻𝐻𝐻 Arterial blood = 97%
× 100% Venous blood = 75 %
𝑂𝑂2 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐

O 2 – Hb Dissociation Curve • Shape- sigmoid (due to tense-relax
configuration)
• Steep lower part
o At low PaO2, low affinity of
Hb to bind with O2
o O2 unloading is maximum for
small change in PaO2
o Capillary PO2 > Tissue PO2,
therefore diffusion is high
• Flat upper part
o At high PaO2, high affinity of
Hb to bind with O2
o Even if PAO2 is less, O2
loading is not affected
o Saturation % changes very
little
o PAO2 > PaO2, therefore
diffusion is high
P50 = the PO2 at which Hb is 50% saturated

with O2.
Left shift – P 50 decrease Right shift – P 50 increase

↓ 2,3 BPG ↑ 2,3 BPG
↓ temperature ↑ temperature
↑pH ↓pH Exercise
↓Pco 2 ↑Pco 2
Fetal Hb
HbF affinity for O2 ↑ than HbA.
∴Mother to baby O2 movement is
facilitated.
Reason: γ chains in HbF have poor
affinity for 2,3, BPG than in β chains
in HbA.

2,3 - BPG in RBC
↑ ↓
Thyroid hormones, androgens, Acidosis - pH ↓ → 2,3, BPG ↓
growth hormones
Exercise
Anemia
Chronic hypoxia
In exercise, temp↑,pH ↓,P5o ↑ 2,3 BPG↑

How does CO cause a left shift of Hb – O2
curve?
CO 2 Transport
Solubility of CO 2 in blood is about 20 times that of O 2
Mainly 3 ways. - In
o RBC
o Plasma
1. Dissolved - 7%
2. Carbamino compounds - 23% - bound to amino groups of Hb, plasma proteins
3. Hydration – HCO 3 - - 70%
Haldane effect
•Occurs at lung level

•Deoxy Hb
o binds more H+ than HbO 2 Plasma
o forms carbamino compounds more readily RBC
than HbO 2 CO2 CO2+ H2O
∴Binding of O 2 to Hb ↓affinity for CO 2 . Carbonic

anhydrase
Bohr effect H2CO3
• Occur at tissue level H+ HHb

Band 3 HCO3-
• Rise in Pco 2 causes rise in H+ (AE1)
• ↓ in O 2 affinity of Hb when ↓ pH Cl- Hb
• Deoxy Hb binds H + more actively than HbO 2 HbO2
• Curve shift to the right.
O2 O2
• P 50 ↑ , thus affinity decreases

Chloride Shift
• 70% of HCO 3 - formed in RBC enters the plasma in exchange for Cl-.
• By Anion Exchanger 1 (AE1/ Band 3)
• Cl- of RBC in venous blood >>> arterial blood
• For each CO2 molecule added to a RBC −−−→ ↑of 1 osmotically active particle in the RBC
• HCO 3 - or
• Cl-
RBC takes up water → increase in size Small amount of arterial

blood return via lymphatics
Haematocrit of venous blood 3% greater than arterial blood
In the lungs, Cl- moves out of the lungs →RBC shrinks
Lungs
RBC
CO2 CO2+ H2O
Carbonic
anhydrase
H2CO3
H+ HHb
Band 3 HCO3-
(AE1)
Cl- Hb
HbO2
O2 O2

RS REGULATION
Neural
Chemical Regulation Non-chemical

Negative feedback
mechanism
Central controller Descending tracts,
Buffer nerves – IX, X motor neurons
Medulla, pons,
other areas of the
brain
Sensors Effectors
Chemoreceptors – Respiratory muscles
• Central  Reciprocal innervation-
• Peripheral PaCO2 excite agonists, inhibit
PaO2 antagonists
H+
Response
Change ventilation
Rate & depth
Chemical (via chemoreceptors)
Central-medullary Peripheral
Carotid Bodies-X Buffer nerves
Monitor [H+] in CSF and brain ECF Aortic bodies-IX
Stimulated by –
↑ PaCO2, ↑ H+ in CSF and ECF • Has a rich blood supply for a unit
mass.
• H+ in blood cannot pass through BBB • ∴respond to changes in dissolved
• CO2 diffuses O2, CO2 and pH
CO2 + H2O ↔H2CO3↔ H+ +HCO3- • Not stimulated in
o Anaemia (PaO2 is normal)
o CO poisoning
Receptors for H+ • Receptors stimulated
o pH↓ Discharge rate ↑
• Main stimulation PaCO2 o PCO2↑(above 40mmHg) ↓
• When PaCO2 ↑ cerebral vasodilatation o PO2 ↓ (below 60mmHg) Respiratory
o Vascular stasis centre
• More CO2 diffuses to CSF and brain ECF
o CN- poisoning ↓
• Stimulate respiration
o K+ Infusion ↑ Ventilation
o Exercise
o Nicotine & Lobeline

Mechanism of peripheral
chemoreceptors
Type I cells of these receptors have O2

sensitive K+ channels.
Its conductance is reduced proportional

to the degree of hypoxaemia.
So when the PaO2 drops K+ efflux

reduces and the cell get depolarized.
This triggers influx of Ca2+ producing
an action potential.
Neurotransmitter dopamine released
Neural Stretch receptors/

irritant receptors
airways, lungs
Voluntary Autonomic
Inspiration
Cortex Medullary respiratory center Vagal afferents

Pre-Botzinger complex
Pacemaker cells Inhibitory effect
Override the activity of Damaged:-depth ↑

medulla within limits Rhythmic
discharge  Pneumotaxic centre -
(RAMP action pons
Potential)  Groups of neurons active
during inspiration,
expiration
 Role in switching
• Phrenic nerve- between inspiration &
diaphragm expiration
• other motor nerves to Damaged:-tidal volume↑, rate ↓
other respiratory
muscles
• glossopharyngeal Apneutic centre
nerve-tongue-air way • In the pons
resistance • Maintains inspiration
• If damaged inspiratory
gasps occur
*Impulses from proprioceptors of joints can increase the ventilation.
*Baroreceptors inhibit respiration. (little effect)

 Response to changes in acid base status
 Metabolic acidosis – chief site of action – peripheral chemoreceptors

Pronounced respiratory stimulation → PCO 2 ↓
Diabetic ketoacidosis – Kussmaul’s breathing
• Metabolic alkalosis – ventilation depressed. PCO 2 ↑
Most important factor in controlling ventilation under normal conditions is PaCO 2

*Reduction in PaO 2 increase the sensitivity of peripheral chemoreceptors to PaCO 2
 Response to hypoxia
PO 2 must fall below 60mmHg for a marked response
Hb less saturated
PaO2 ↓ Hb
↑ Ventilation
HHb
Buffering of
↓ PCO2 H+
[H+] ↓ in plasma
Respiration inhibited
Hypoxemia should be severe enough to overcome above inhibitions.
o Sensitive to ↑ plasma [K+]

o ↑ discharge in - hypoxic hypoxia
- vascular stasis
- cyanide poisoning
Other sensors & non chemical control

 airway and lung receptors
 proprioceptors
 Baroreceptors
 afferents from pons, hypothalamus, limbic system

Voluntary Hyperventilation
Changes is RS, CNS, CVS and skin.
Increased rate and depth of ventilation
RS Changes
 PaO 2↑ PaCO 2 ↓ ,
 Periodic breathing - apnoea →few shallow breaths → apnoea →
 CO 2 + H 2 O ↔H 2 CO 3 ↔H++ HCO3-
CNS Changes
When CO2 is washed out, H+↓
Minus charges in proteins exposes
Binds with plasma Ca+ and precipitate.
Plasma [Ca+] ↓
Excitability of nerve fibres ↑
Synaptic transmission ↓
Net effect is ↑ excitability → Chvostek’s sign-on face
→ Trousseau’s sign - carpopedal spasms
 Hypocapnia  Cerebral vasoconstriction-paresthesia, dizziness, light headedness
CVS Changes
• HR - ↑
• BP - ↑
Before During Hyperventilation After 5 min

HR 75 80 70
BP (mmHg) 130/70 135/86 125/75
Skin changes
 Hypocapnia  Cutaneous vasoconstriction-cold extremities

High altitude
Total barometric P↓. But, composition - constant

Acclimatization – variety of compensatory mechanisms
Initial changes Delayed changes

1. Involuntary hyperventilation to hypoxemia
stimulation. Initial increase in ventilation is small Active transport of H+ into CSF / lactic acidosis in brain →
due to respiratory alkalosis ↑ventilatory response to hypoxia
2. Respiratory alkalosis
3. Increased 2,3 –DPG in RBC Erythropoietin ↑ → RBC ↑ → polycythemia
2,3 –net effect on HB-O2 Dissociation curve.
 Increase P50 Tissue changes
 Right Shift  mitochondria ↑
 cytochrome oxidase ↑
 myoglobin ↑
Natives at high altitudes-barrel chested, polycythemia
At 3000m above the sea level PAO2 is about 60mmHg. And there is enough hypoxic stimulation of chemoreceptors
under normal breathing to cause hyperventilation.
Raptures in deep
↑ barometric P
P on the body rises
Pushes N2 into blood
N2 is very lipid soluble (nervous system, bone marrow, fat)
If ascent rapid, PN2 ↓ abruptly, N2 ‘boils’ out of tissues→air bubbles → bends and chokes
N2 narcosis is seen

Hypoxia
O2 deficiency at tissue level
Anaemic hypoxia
Hypoxia PaO2 normal
Hb ↓
O2 content of arterial blood is
low
Hypoxic Stagnant / Ischaemic Histotoxic hypoxia
hypoxia hypoxia O2 delivery normal Respiratory symptoms not
↓PaO2 O2 delivery inadequate Tissue O2 utilization severe at rest unless Hb is
Normal PaO2, Hb impaired very low
Impaired circulation (Dissolved O2 is normal →
• Local Eg- CN- poisoning Chemoreceptors not
• Generalized Inhibit cytochrome stimulated)
oxidase
CO poisoning
1. ↓ in total barometric P Irreversible
↓ in O2 % in air −−−−−−−−→ COHb
Cherry red
Cannot take up O2
Depression of respiratory controller Curve of remaining Hb → left
2. Pump
failure Neuropathies which affect respiratory motor neurons
(Ventilatory Muscle fatigue
failure)
Mechanical defects in the chest wall
• V/Q imbalance – most common cause

3. Lung o Shunt  Lung collapse
failure o Dead space  Pulmonary embolism
• Defects in diffusion
o Pulmonary edema
o Lung fibrosis
4. Conduction block  eg: Asthma
Effects – Hypoxemia Compensatory - increased ventilation

-increased CO
-polycythemia as erythropoietin ↑
Non compensatory -cellular changes-2,3 BPG ↑
Cyanosis -other
Dusky, bluish discoloration of tissues due to
increase of deoxygenated Hb concentration
(above 5g/dL)
Depends on;
-total Hb level in blood(polycythemia)
-degree of saturation
-state of capillary circulation
Central peripheral
e.g.: - VSD e.g.: - impaired local circulation
Conjunctiva nail beds
tongue

Cyanosis more prominent in polycythemia
Cyanosis - not seen –
 CO poisoning / CN- poisoning – cherry red
 Histotoxic hypoxia
Difficult to see in –
 Anaemia
 Dark skinned people
In methhemoglobinemia (higher than normal level of methhemoglobin - metHb, [Fe3+] rather than [Fe2+]) in the
blood) discolouration is seen. Caused by nitrite, thiosulphate like drugs.
Effects of hypoxia on brain

Sudden severe drop in PIO2 → death
Less sever changes →
Impaired judgment, drowsiness, dulled pain sensibility, excitability, disorientation, headache, vomiting, tachycardia,
hypertension
Management of hypoxia
Hypoxic hypoxia – O2 therapy very valuable except in R→L shunts
Anaemic, stagnant, histotoxic hypoxia – O2 of limited value. Primary cause should be treated
O2 therapy in chronically hypercapnic patients – dangerous. WHY??

O2 – can be toxic, if given in high concentration for a long duration
Hypercapnia
Depression of CNS, confusion, diminished sensorium, coma, respiratory depression, death
Severe acidosis
Hypocapnia
Constriction of cerebral vessels
Respiratory alkalosis
Hypocalcaemia
Pneumothorax - the presence of air or gas in the pleural cavity
Peak Expiratory Flow Meter (PEFM)
Used to monitor the progress of obstructive lung diseases. Ex: Asthma

Unit: l/min
Normal rate: 400l/min (varies with age, gender, height and ethnicity)
Method
1. Should hold the peak flow meter horizontally.
2. Do not block the indicator with your fingers.
3. Mouth piece and lips should be sealed.
4. Inhale deeply then blow as fast as possible.
5. Do this three times and take the highest reading as the result.

1
Renal Physiology
Excretory
Urea,
creatinine
Regulatory Metabolic
Fluid, Functions of Kidney
Gluconeogenesis
electrolyte, pH
Endocrine
renin,
erythropoietin,
25(OH)D3
Urine Formation
• Site – Nephron (functional unit)
• 3 steps
Mesangial cells
1. glomerular filtration
Contractile – Play a role in regulating
2. tubular reabsorption
glomerular filtration.
3. tubular secretion
Contraction by –Angiotensin II, Vasopressin,

1) Glomerular Filtration Endothelin
I. Filtration Membrane
Relaxation by – ANP, PGE2
Afferent arteriole
Efferent arteriole
Capillary
endothelium
Mesangial
cells
Basal lamina
Epithelium of
capsule Podocytes
Filtration slit
II. Filtrate
• Isotonic to plasma
• Contain plasma except – plasma proteins/ fat/ blood cells/protein bound calcium ion
III. GFR
• The amount of plasma ultrafiltrate formed by two kidneys per minute
Repeat Campaign 2014 A/L

Determinant-Effect on GFR
Net filtration pressure 2
• 125 ml/min in a healthy adult male - Hydrostatic pressures

• Depends on - Osmotic pressures
 Age – with age ↓ Glomerular ultrafiltration coefficient -Kf
 Gender – (F) < (M)
- Surface area of filtration
 Body surface area – with body surface area ↓
- Permeability of membrane
- Mesangial cells regulate this
Glomerular filtration
Filtration
Glomerular colloid
Glomerular
osmotic pressure
hydrostatic
pressure (20)
pressure (45)
Bowmann’s capsule
Bowmann’s capsule
hydrostatic
colloid osmotic
pressure (10)
pressure (0)
Capillary length
Why glomerular capillary oncotic pressure is higher than plasma??
𝐺𝐺𝐺𝐺𝐺𝐺
𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹 𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹 = = 0.16 − 0.20
𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅 𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃 𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹
Renal blood flow
255 of the cardiac output

High blood flow for a gram of tissue
RBF & RPF measured using the Fick principle.
Significant autoregulation can be seen – Renal vascular resistant varies with blood pressure.
Keep RBF and GFR constant
Renal Blood Flow/ GFR
(mL/min)
Arterial pressure
(mmHg)

3
Renal clearance –
The volume of plasma that is completely cleared or removed of substance by the kidneys in unit time.
Renal Clearance
Complete
Zero Partial
Eg:- PAH (para amino hippuric
Eg:- glucose acid) Eg:- creatinine
All substances filtered is Almost completely removed in a By filtration & tubular secretion
completely absorbed single circulation, by filtration and Inuline
tubular secretion
Only by filtration.
• Clearance of inulin – no tubular reabsorption or secretion

o CInulin = GFR
• Inulin is the standard substance used to measure GFR but in clinical practice creatinine is used.
Advantages Disadvantages
Inulin • Free filtered • Not an endogenous substance
• Neither reabsorbed nor • Have to administered
secreted intravenously
• Not metabolized in the kidney • Need to keep arterial plasma
• Not toxic level of inulin constant
Creatinine • Endogenous substance • Secreted by tubules
• Daily production – constant • UCr V high
• Plasma level – constant • Inaccurate at low levels
• Clearance of creatinine easy to • PCr – high
measure • Need accurate UFR
measurement
Measuring GFR
The amount of a substance ‘y’ filtered = amount excreted in urine.
Plasma[y] ml/min × Plasma volume filtered ml/min = Urine[y] ml/min × Urine volume excreted ml/min
GFR = Volume of plasma cleared of substance ‘y’ by the kidneys per minute
GFR = Uy mg/ml × V ml/min Uy – Urine concentration of ‘y’

Py mg/ml Py – Plasma concentration of ‘y’
V – Urine volume

4
q
• CCr < Serum creatinine level
Serum creatinine (μmol/L)
• No linear relationship
• Indicator of renal function
• Not much change in CCr seen until unit
renal function decreases up to 50-60%.
• Based on Scr, GFR can be estimated.
CCr (mL/min)
0 60
• Creatinine clearance over-estimates GFR by 10-20% (due to the secretion)
Good measure of GFR
• Serum Urea
• influenced by many factors. not constant.
• 95% of urea excretion is by the kidneys.
Calculate Renal Blood Flow – By Fick principle
ERPF = Amount of substance excreted in urine/min

Renal arterial – Venous concentration of substance
• PAH completely removed by the kidney. So venous concentration approximately = 0

• Plasma flow to kidney = Effective renal plasma flow
• Renal extraction ratio of PAH = 90 %
EPRF
• Actual renal plasma flow = × 100 mL/min
90
𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴 𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴
• 𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅 𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏 𝑓𝑓𝑓𝑓𝑓𝑓𝑓𝑓 = × 100 𝑚𝑚𝑚𝑚/𝑚𝑚𝑚𝑚𝑚𝑚 = × 100𝑚𝑚𝑚𝑚/𝑚𝑚𝑚𝑚𝑚𝑚
1−ℎ𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎 55
• Renal Blood Flow = 1200 ml/min ≈ 25% of cardiac output
• Extraction ratio of PAH = Arterial concentration – venous concentration

Arterial concentration
Features of a substance that can be used to measure RPF

 Excreted by the kidney
 Renal arterial and venous levels of that substance can be measured
 Not stored
 Not metabolized
 Not produced
 Should not affect the renal blood flow

5
Physiological control of
GFR & RBF
Autoregulation Reflex activation of

Hormones
Sympathetic N.S.
t
1. Autoregulation
• Intrinsic renal mechanism
• Change of arterial pressure between 90-220 mmHg → Renal vascular resistance varies →Keeps
RBF and GFR relatively constant
• When pressure is high →Constriction of AA as a response to stretch and dilatation of arterioles
by NO
• At low perfusion pressure, angiotensin II → constrict EA
A. Tubuloglomerular feedback
Rate of flow through the ascending limb of Loop of Henle & 1st part of distal tubule increases→
sensed by macula densa → AA constrict → GFR decreases
B. Myogenic contractions of vessels to stretch
Due to stretch, Ca2+ moves to muscle cells from ECF.
C. Glomerulotubular balance
GFR increases → reabsorption of solutes increases →reabsorption of water increases in PCT →
% of the solute reabsorbed is held constant.
2. Reflex activation of Sympathetic nervous system

Symp  renal vasoconstriction  reduced RBF & GFR (Indirectly by RAAM)
3. Hormones and other factors

Norepinephrine Reduce GRF NO Increase GFR and renal
Epinephrine and Dopamine plasma flow
Angiotensin II Renal plasma Ach
Endothelin flow Prostaglandin
Exercise

6
(H) norepinephrine/ epinephrine – released from adrenal medulla

(A) endothelin – released by damaged vascular endothelial cells of kidney
(H/A) angiotensin II – constricts EA>AA
When BP/volume ↓ GFR ↓

RBF ↓
Angiotensin II ↑
• Help prevent decrease in PGC (pressure in glomerular capillaries) and GFR
• ↓ RBF by EA constriction causes ↓flow through peritubular capillaries which in turn ↑ reabsorption
of Na+ and H2O
Tubular Function
Reabsorption
Secretion
• Na+
• PAH
• Glucose
• Urea
• H2O
• Uric acid
• Most solutes
• Creatinine
• NH4+, H+, K+
• Drugs
• Solutes are reabsorbed via transcellular and paracellular pathways.

• Paracellular pathway is the major pathway for reabsorption of water.
• Most absorption occurs in PCT.
GLUCOSE
Glucose reabsorbed most in early portion of PCT.
Reabsorbed by IIry active transport.
In a healthy adult, all of glucose in glomerular filtrate is reabsorbed
So, renal clearance of glucose is zero in a healthy person.
Upto TmG,
Amount reabsorbed α amount filtered α PG × GFR (PG =Glucose concentration in plasma)
Basolateral
Luminal membrane
membrane PCT cell
3 Na+
ATP
2 K+ Glucose
SGLT 2
Glucose SGLT 2 Na+ (down electrochemical
(Facilitated gradient)
diffusion
Interstitial fluid Tubular lumen

7
 TmG is 375 mg/min in men & 300mg/min in Women.

 When PG exceeds TmG, as in uncontrolled Diabetes Mellitus, the amount of glucose in urine rises
proportional to the rise in plasma concentration.
 The renal threshold for glucose is the plasma level at which the glucose 1st appears in urine.
 It is about 200 mg/dL of arterial plasma & 180 mg/dL of venous level.
 Actual renal threshold is less than predicted.
 Because - all nephrons don’t have same TmG
- some nephrons excrete glucose before others reached their TmG
Na+
99% reabsorbed
7% cotransporter
Na+/ Cl-
ENaC channels - Na+

3%
Aldosterone
Bind with receptors of P cells
Na+,K+/2Cl-
→ Increase ENaC synthesis
60% mainly at PCT Cotransporter
and insertion →Increased
1. Na+ /H+ exchanger 30%
Na+/K+ exchange → Increase
2. Na+/glu CT
Na+ reabsorption & K+
3. Na+/AA CT
excretion
4. Na+/Lactate CT
K+
Freely filtered in glomeruli.
Mostly reabsorbed in PCT
Secreted in DCT & CD

• Faster flow in tubules cause more secretion
• Amount approximately equal to the intake
• Decreased when K+ reaching the DCT is less
Reabsorbed in DCT in exchange for H+ Via H+/K+ ATPase

The ability to eliminate unwanted K+ is less dependent on GFR than urea and creatinine

8
Urea
Required to maintain the medullary hyper osmolality

Reabsorption is increased by vasopressin
Urea reabsorption increases after a high protein diet as urea excretion increases.
Tubular secretion
More excretion make substance less dependent on GFR

PCT is the main site except for K+
Penicillin, Urea, Uric acid etc.
Control blood pH
Overview
PCT
• Na+, water, HCO3-, Cl-, K+, Ca2+, K+, Uric acid (later secreted), Urea reabsorbed.
• H+ secreted
• Fluid remain isotonic
LOH
• Descending limb – Water Reabsorbed
• Ascending limb – Na+, K+, Cl-
• At the end fluid become hypotonic
DCT
• Early part – Na+ by Na+/Cl- Cotransporters
• Late part – Na+ by ENaC Reabsorbed
• Water
• K+, H+ secreted
CD
• Na+, Water (ADH dependant) Reabsorbed.
• K+/H+ Secreted
H2O
PCT – passively along osmotic gradient 65%-70% reabsorbed.

Aquaporin 1(not sensitive to ADH), simple diffusion
LOH-thin descending limb of LOH → 15% reabsorbed

Thick ascending limb of LOH → not permeable
DCT-5% (with solutes) (early part)
CD- predominantly Na+ independent.

Depends on ADH (vasopressin) → Bind with V2 receptors of P cells → insert aquaporin 2 channels→
↑ Permeability of CD to H2O

9
Hypotonic
Cortex
Isotonic
Medulla Hypertonic interstitium
If no ADH
• Only 2% of filtrate is reabsorbed.
• 13% of filtrate is excreted.
Diabetes insipidus
ADH deficiency (Central DI)
CD fails to respond to ADH (Nephrogenic DI)-unresponsive v2 receptors,non-functional water
channels
Formation of Concentrated urine depends on two factors

1. ADH
2. Hyperosmolarity of medullary interstitium
Humans have the concentrating ability of urine according to the needs of the body.
This is maintained by counter current mechanism.
Counter current mechanism

Inflow runs, parallel, counter, in close proximity to outflow.
Depends on
• Maintenance of a Gradient of increasing osmolality alone the medullary pyramids
Produced by Maintained by
(1) Counter current multiplier (2) counter current exchanger
Counter current multiplier

1. Active process (Active transport of Na+/Cl- out of thick ascending LOH)
2. High permeability of thick descending LOH to H2O
3. Inflow of tubular fluid from PCT/out flow into the DCT

10
Produce a gradient of hyperosmolarity in medullary interstitium
↓ Gradient of Osmolality
Counter current exchanger
• Solutes recirculate in medulla while water get absorbed to the vasa recta.
• This maintain the medullary hyperosmolality
• Vasa recta do not create the medullary hyperosmolarity, but they do prevent it from being dissipated.

11
Isotonic
Hypotonic
Isotonic
Cortex
Isotonic
Medulla
Hypertonic (If ADH is

available)
Hypertonic
Kidney maintain the osmolality of body fluid approximately 290mosm/kg

Osmolality of urine varies in a vast range according to the body water need. (30-1400 mosm/kg)
Tubulo-Glomerular feedback – Relate this to regulation of renin secretion when learned
Increased flow through the ascending limb of LOH cause decreased GFR in the same nephrone.
Maintain the consistency of load delivered to DCT.
Define, Anuria
Mechanism
Increased Na+ reabsorption via Na+,K+/2Cl- co[transporter Oligouria
Na+ and Cl- in DCT sensed by macula densa
Increased Na+,K+ ATPase activity
Polyuria
More adenosine formed by ATP hydrolysis
Act on receptors of macula densa cells
Nocturia
Release of Ca2+
Cause afferent arteriolar constriction
Decrease GFR and RPF Enuresis

12
Urea Circulation
 Thick loop of Henle, DCT & cortical CD are relatively impermeable to urea.
 Permeability of medullary CDs to urea is increased by ADH.
 Recirculation of urea contributes to hyperosmotic medullary interstitium.
Regulation of renal functions
Renin-Angiotensin-Aldosterone mechanism
Renin is a glycoprotein
Secreted by juxtaglomerular cells in the juxtaglomerular apparatus
Converts angiotensin to angiotensin I
Lead to formation of Angiotensin II from angiotensin I by ACE
ACE found in vascular endothelium
Specially lungs
Factors effecting the renin secretion
Increased Na+ and Cl- reabsorption

Increased sympathetic activity via
via macula densa
renal nerves
Increased afferent arteriolar
Catecholamine
pressure
Angiotensin II
Vasopressin
Decrease in plasma K+ level
Intra renal baroreceptor mechanism – Renin is secreted when the blood pressure falls.
Stimulate aldosterone Stimulate vasopressin secretion

secretion
Stimulate thrust Vesoconstriction
Angiotensin II
Constrict glomerular PCT direct – Na+

vessels reabsorption
Increase sympathetic nerve

Mesangial cell contraction
activity
13
Mesangial cell contraction – Reduce GRF

Constrict glomerular vessels – Angiotensin II constrict both Reduce the renal
afferent and efferent arterioles. But the efferent arteriole plasma flow
is constricted comparatively more.
Explain how Angiotensin II reduce the GFR, but increase the filtration fraction.
Natriuretic peptides
ANP, BNP and CNP
Actions –
• Dilate arterioles Decrease RPF and GFR
• Relax mesangial cells
• Inhibit Na+ reabsorption
• Increase capillary permeability
• Decrease blood pressure
Regulation of ECF osmolality and volume
ECF osmolality – 280-296 mosm/kg (285 normal)

NaCl is the main contributor for the ECF osmolality.
ECF osmolality is regulated mainly by changing the blood volume.
Thrust
Aldosterone is not involved in
Two main mechanisms
regulating the osmolality
Vasopressin secretion
Thrust and vasopressin secretion
Both occur concurrently
Receptors
• Osmoreceptors – In hypothalamus
• Baroreceptors – In blood vessels
Vasopressin
Cause vasoconstriction.
Increase water reabsorption. How??

14
Regulation of vasopressin secretion
Increase in plasma osmotic pressure

Reduction in plasma volume Decrease in plasma osmotic
Pain, Emotions pressure
Stress, exercise, standing Increase in ECF volume
Nausea, vomiting Alcohol
Angiotensin II
Stimulation for vasopressin secretion
Pain nausea Stress Angiotensin II
Hypothalamic osmoreceptors CVLM

Hypothalamus
NTS
Low pressure baroreceptors

Vasopressin
Increased plasma osmolality
Decreased blood
volume
Decreased plasma osmolality and

increased plasma volume

15
Stimulation of thrust
Plasma hypertonicity Hypovolemia
Osmoreceptors in Baroreceptors
hypothalamus Angiotensin II
Hypothalamus
Dryness in Drinking
pharyngeal mucosa
Thrust
Increase blood volume

Decrease plasma osmolality
What stimulate vasopressin secretion in an acute haemorrhage??
Explain the autoregulation of GFR combining the effect of renin and tubulo-glomerular feedback
Explain the responses of kidney to hypovolemia and hypotension.
Maintaining GFR
Decreased urine output
Increased renin release

16
Diuresis
Increased urine output
WATER DIURESIS OSMOTIC DIURESIS

CAUSE Drinking large amounts of hypotonic Administration of filtered but
fluids unabsorbed osmotically active
particles (mannitol etc.)
Infusion of large amounts of NaCl,
urea
In diabetes mellitus
WATER REABSORPTION AT PCT Normal decreased→due to↑osmotically
active particles
ADH SECRETION Inhibited Maximum
o By act of drinking But less effect
o Due to↓plasma osmolality
URINE OSMOLALITY Reduced(hypotonic) isotonic
URINE FLOW increased Increased + ↑excretion of Na⁺and
other electrolytes
GFR Normal/Increased Decreased
Plasma osmolality Decreased *if pathological Increased *if pathological
Water Diuresis –
Begins 15 mins. After drinking water (40 mins maximum)
Small decrease in vasopressin secretion even before water is absorbed from the gut.
• Ethanol → inhibit vasopressin secretion
• Antagonists of V2 receptors → inhibit action of vasopressin on CD
Osmotic Diuresis –
Increase in urine volume due to presence of large quantities of unabsorbed solutes in the renal tubules
 In diabetes mellitus filtered glucose is not completely reabsorbed. Remaining glucose cause osmotic diuresis
leading to polyuria and polydipsia
Process-
1.↑concentration of osmotically active particles in PCT lumen hold water in the tubules, not allowing
reabsorption
2.↑water volume in lumen→↓[Na⁺] concentration in spite of high Na⁺ amount→ limiting concentration
gradient reached (at DCT) →Na⁺ reabsorption down the concentration gradient prevented→↑Na⁺ reducing
further water reabsorption
3.↓[Na⁺] →↓Na⁺ reabsorption by Na⁺K⁺2Cl⁻ co transporter→↓medullary hypertonicity→↓water
reabsorption
4.maximum ADH secretion but less influence due to osmotically active particles in lumen

17
Explain presence of polydipsia in a patient with uncontrolled diabetes mellitus.??
Class of Diuretic Mechanism of Action Tubular Site of

Action
Osmotic diuretics (mannitol, Inhibit water and solute reabsorption by Mainly proximal
sucrose, glucose) increasing osmolality of tubular fluid tubules
Loop diuretics (furosemide, Inhibit Na+-K+-Cl- co-transport in luminal Thick ascending
bumetanide) membrane loop of Henle
Thiazide diuretics Inhibit Na+-Cl- co-transport in luminal membrane Early distal
(hydrochlorothiazide, tubules
chlorthalidone)
Carbonic anhydrase inhibitors Inhibit H+ secretion and HCO3- reabsorption, Proximal tubules
(acetazolamide) which reduces Na+ reabsorption
Aldosterone antagonists Inhibit action of aldosterone on tubular receptor, Collecting
(spironolactone) decrease Na+ reabsorption, and decrease K+ tubules
secretion
Sodium channel blockers Block entry of Na+ into Na+ channels of luminal Collecting
(amiloride) membrane, decrease Na+ reabsorption, and tubules
decrease K+ secretion
• Aldosterone antagonists and Sodium channel blockers are K+ sparing natriuretics.

18
Renal contribution towards H+ Homeostasis
Plasma [H+] = 40 nmol/dl

Very high amount of H+ added to the circulation daily.
Fate of H+ in the body

• 1st line of buffering – Plasma & intracellular
• 2nd line of defence – Removal of volatile acids as CO2 from lungs
• 3rd line of defence – removal of non-volatile acids by kidney
Kidney regulate ECF [H+] by

• Secreting acids
• Reclaiming filtered HCO3-
• Regenerating HCO3-
Urine pH may vary from 4.5 - 8
Mechanisms of H+ secretion
1. Na+/H+ exchange – PCT, Thick ascending limb of LOH and early DCT
2. ATP-driven proton pump – Intercalated cells in late DCT and CD (Increased by aldosterone)
3. H+/K+ ATPase – In DCT and CD
Main buffers in urine that buffer the secreted acid –

• HCO3- - Mainly in PCT
• NH3/NH4+ - In PCT, DCT and CD
• Phosphate – In DCT and CD
HCO3- buffer
Rapidly remove H+ from urine. But no excretion of H+ in urine.
Prevent decrease in pH of filtrate
For each HCO3- absorbed from filtrate one HCO3- added to blood – “Reclaiming HCO3- “
NH3 buffer
Buffer about 50% of the acid excreted.
Buffering action increase in chronic acidosis.
Only method of passing acids over the normal level. Generates new HCO3-.
For each NH4+ or
Phosphate buffer phosphate execrated,
Buffer about 50% of the acid excreted. one HCO3- added to
Mostly in DCT and CD as the concentration increases. the blood
Excreted as titratable acidity.

19
Metabolism of proteins
↓
Non-volatile acids
H+ secretion HCO-3
PCT 85% PCT

Thick limb of the LOH
DCT, CD
No H+ secretion or HCO3- reabsorption happen at the level of LOH
H+ secretion at the level of PCT
• H+ secretion coupled with Na+ reabsorption IIry active transport

• For each H+ added one Na+ and HCO3- added to the blood.
• Most of the HCO3- (over 80%) absorbed by this process.
• Secreted H+ buffered by
HCO3- buffer system
NH3 buffer system

20
H+ secretion at the level of late DCT & CD
H+ secretion
• independent of Na+ reabsorption
• secreted by ATPase driven proton pump – I cells of CD
• Iry active transport
• Aldosterone increases its activity.
• In acidosis many tubulo-vesicular structures inserted to the apical membrane to increase H+ secretion.
• limiting pH is achieved. (4.5pH)
• for each H+ secreted HCO3- enters the interstitial fluid
• Secreted H+ buffered by
o phosphate buffer in the filtrate
o NH3 made in the cells
NH3 buffer in DCT & CD

• mainly in I cell
• amino acid metabolism  Glutamine ( in liver )
• Glutamine glutamate + NH4+
Glutaminase
• Glutamate ∝-KG + NH4+

Glutamate DH
NH4+ NH3 + H+
∝-KG + 2 H+ 2HCO3-
 NH3 lipid soluble  diffuse across cell membranes
 chronic acidosis  ↑ NH3 buffer system activity

21
Interstitial fluid I cell Lumen
Na+ Na+A-
NH3 NH3 +
H+ + NH3
ATP
↓
NH4+A-
• ↑ NH4+ excretion in urine in acidosis

• HCO3- buffer system mainly important at the level of PCT
• Prevent reaching the limiting pH
• Phosphate buffer system important at the level of DCT & CD reaches the limiting pH = 4.5
Most of the acid is execrated in PCT.

- But only little × 4 increase in urine [H+]
- Lower limit pH 6.7 WHY??
Only 5% of the acid secreted in DCT
- But × 900 increase in [H+]
- Lower pH limit 4.5
Factors increasing / decreasing H+ secretion & HCO3- reabsorption
Increase Decrease
• PCO2 ↑
• H+ ↑ , HCO3- ↓
• ECF volume ↓ Opposite
• angiotensin II ↑
• aldosterone ↑
• Hypokalaemia

EXERCISE PHYSIOLOGY
Muscle Fiber Types
Fast Twitch Slow twitch

Larger diameter Smaller diameter
Phosphogen & anaerobic systems Aerobic system more active
more active
For extreme amounts of power for For endurance eg: Soleus
sec-mins eg: gastrocnemius
 Fast twitch to slow twitch fibre proportions differ in individuals.

Marathoners – Fast twitch < Slow twitch
Sprinters - Fast twitch > Slow twitch
Weight lifters - Fast twitch > Slow twitch
Average male - Fast twitch > Slow twitch
Integrated CVS & RS mechanisms operate to supply

O2 & nutrients and remove CO2, metabolites & heat.
CVS in exercise
Types of contraction
# Isometric contraction(iso=same, metric=measurements/length) – no

appreciable muscle shortening; no work done
.(eg: Weight lifter trying to lift a weight but not being able to lift it ,a
person trying to push a heavy load but not moving it)
# Isotonic contraction(same muscle tone/tension) - contraction against a

constant load; work done.(climbing a staircase, slow running )

Systemic circulatory changes
Isometric Isotonic
A prompt
increase in HR
a result of psychic stimuli on medulla oblongata. [due to a decrease in vagal tone (mainly) +
increase in sympathetic activity]
Increased total peripheral resistance due to Net fall in PR due to vasodilation in

compression of vessels(increased intra muscles(initially neural , then local vasodilation
muscular pressure due to sustained due to accumulation of metabolites)
contraction)
Decreased or zero muscle BF (>70% of max Increased muscle blood flow
muscle tension)
Low increase in venous return(lack of muscle Marked increase in venous return
pump)
Stroke volume relatively unchanged(due to very Marked increase in stroke volume
less increase of venous return )
CO increased (CO=HR*SV; HR has ) CO markedly increased(both HR ,SV )
Sharp increase in systolic & diastolic pressure Moderate increase in systolic
(increased CO and PR) pressure.(increased CO)
Diastolic pressure decreased/unchanged(due
to the fall in PR)
Exercise Sympathetic
Accounts mostly for
Discharge(psychic)
in CO
Contractility (of heart) HR(270%)

Max HR decreases
with age
(Max HR=200-age)
(Frank- Starling)
EDV SV(50%) Cardiac
Output
Increase due to,
- Muscle pump
Venous return - Thoracic pump
(Not the main cause - Mobilization from viscera
of CO) - Noradrenergic
venoconstriction(shunting
blood from reservoirs
:skin,GUT)
- Increased pressure
transmitted from dilated
arterioles to veins.

 Trained athletes have lower heart rates, greater end-diastolic
volumes,greater ventricular capacity, greater cardiac mass and greater
stroke volumes at rest than untrained people.(since both generate equal
CO at rest)
 Therefore they can achieve a given increase in Cardiac Output by further

increases in Stroke volume without increasing their HR as much as an
untrained individual does.
 After exercise BP may fall transiently due to vasodilation by accumulated

metabolites.
RS in exercise
Changes occur in:

 O2 consumption(cellular respiration)
 Pulmonary ventilation
 Diffusing capacity External/pulmonary respiration
O2 consumption:
O2 Consumption
VO2 max
Exercise intensity
VO2 max : Rate of oxygen usage under maximal aerobic metabolism.

VO2max:the maximum amount of O2consumed by a unit weight of muscle per unit
time.
VO2 max=COmax (ml per minute)* Max O2 extraction(ml per unit weight of
muscle)

Above the exercise intensity corresponding to VO2 max oxygen consumption
levels off.
Rate of utilization of E stores > Rate of aerobic resynthesis of E stores
Therefore anaerobic metabolism begins Lactate is produced

O2 debt incurred
Pulmonary Ventilation: The respiratory rate does

not reach basal level until
O2 debt is repaid
Gradual increase due to

o increased body T,
o increased plasma K+
o increased sensitivity of
the neurons controlling
Abrupt increase due to psychic
the response to CO2
stimuli + impulses from
(oxygen may also play a
proprioceptors in muscles, tendons &
role)
joints
 During moderate exercise Arterial pH, pCO2 & pO2 remain constant.
 When exercise becomes more vigorous buffering of lactic acid liberates

more CO2 this further increases ventilation.
 Increases in ventilation(CO2 washout) & CO2 production remain

proportionate. So, alveolar and arterial CO2 change relatively little –
isocapnic buffering
 Further accumulation of lactic acid (stimulates Carotid body)causes

increased ventilation which outstrips CO2 production. Thus alveolar &
arterial pCO2 fall.
 The decline in arterial pCO2 provides respiratory compensation for the

metabolic acidosis caused by lactic acid.
 Moderate exercise: depth of breathing increase
 Strenuous exercise: depth and rate of breathing increase

Respiratory rate does not reach basal levels until O2 debt
is repaid!
# The stimulus for respiration is elevated arterial H+

concentration due to lactic acidemia.
# During repayment
- O2 concentration in muscle myoglobin rises.
- ATP & phosphorylcreatine resynthesized.
- Lactic acid removed. (80% converted to glycogen &
20% oxidized to CO2 & H2O)
Diffusing capacity:
( rate at which O2 diffuses from alveoli to blood)
 PO2 in pulmonary capillaries fall from 40 to 25mmHg.

(increased alveolar-capillary gradient)
 Pulmonary blood flow increases(recruitment of under-perfused alveoli)
(increased surface area)
CO2 excretion also increase from 200ml to 8000ml

Changes in muscle
 Muscle blood flow
 O2 extraction
Muscle blood flow:

 When muscle contracts vessels are compressed ( > 70% of
max tension – blood flow is completely stopped)
 Between contractions blood flow is increased.

 Rise in blood flow at the onset of exercise neurally mediated
( sym. Vasodilator system )
 Once exercise has started local mechanisms maintain high blood
flow.
- Fall in tissue PO2
- Increase in tissue PCO2
- Accumulation of K+ & other
vasodilators
- Rise in temperature
 Dilation of arterioles and precapillary sphincters increases number of
open capillaries.
Distance between blood and cells reduced.
(the distance O2 & metabolic products must diffuse
reduced)
Increased cross sectional area leads to a fall in

velocity of blood flow.
 Fluid transudation into interstitial spaces is increased.

- Capillary pressure rises until it increases oncotic pressure
throughout the length of the capillaries.
- Osmotically active metabolites accumulate in the interstitium.
- Therefore the lymph flow is increased limiting the accumulation of
interstitial fluid.
- Increase in muscle diameter due to accumulated interstitial fluid

O2 extraction
 More O2 used by muscles muscle PO2 falls O2 gradient from blood
to muscle increased
More O2 removed Blood pO2 drops More O2 diffuses

from Hb from blood
 Mean distance from blood to cells is decreased, therefore facilitates

movement of O2.
 High T/ high 2,3BPG & acidosis (due to accumulation of CO2) shift the
O2-Hb dissociation curve to right. Reduces affinity of Hb for O2
 Ergo increased CO2 and a decreased O2 level is maintained around an

active muscle
Changes in temperature during exercise
Muscle work (eff:20-25%)

 Nutrient energy
Heat (75-80%)
When body T Hypothalamus centres controlling heat dissipation

activated.
- Sweat secretion –vaporization causes heat loss
- Cutaneous vasodilation (due to inhibition of
vasoconstrictor tone + locally acting vasodilators)
- Ventilation – heat loss in expired air
- Heat loss by radiation
I
Changes in muscles with training N
C
R
- Myofibrils E
A
- Mitochondrial Ez S
- Glycogen stores E
- Stored triglycerides
- Metabolic systems (aerobic + anaerobic)

Male & Female athletes…….
 Maximal force of contraction almost similar.
 But muscle bulk is lesser in females
 Other values for females are 2/3- 3/4 of thoses of males.
(CO,ventilation)
 Due to testosterone.
Ageing & Exercise……..

 Sedentary(disuse) muscle atrophy
 Decrease of max breathing capacity
 Max CO & HR decrease
 But muscle training results 100% increase in muscle strength.
How is energy provided for exercise
Primarily our muscles use ATP as its source of energy

ATP has 2 high energy (7300cal) bonds and one low energy bond but only the 2
high energy bonds are utilized .(????? not sure)
Adenosine----PO4-----PO4----PO4
To generate ATP we use different substrates at different levels of physical

activity.
In resting state we use fatty acids as our primary substrate for ATP
generation.
As soon as we start exercising we initially use the available ATP in the muscle
(stored as Phosphocreatine)
Phosphocreatine Creatine+PO43-
(only enough for 3 seconds of maximal muscle power)
As we have run out of ATP we have to generate ATP ; so now we use Glucose,
Gycogen (stored in the Muscle), Fatty acids ,Amino acids to generate ATP

Acid Base Balance
[H+] normal range= 37-45 nmol/l Daily production rate >12500 mEq /L
Arterial blood 7.4 (7.38-7.42) no significant effect between 7.35-7.45

Venous blood /Interstitial fluid 7.35(venous blood CO2 > arterial blood CO2)
Limiting pH of urine-4.5
Intracellular pH 6.8
If pH more than normal alkalaemia. If pH lower than normal acidaemia
ECF survival range 6.8-7.7
Defence mechanisms
1. Buffer systems in body fluid ( Act immediately)
2. Respiratory system ( within minutes)
3. Renal system (hours, days) – Most effective
1.) Buffer systems

act immediately
• Body `s 1st line of defence.
• Cannot remove or add H+ by themselves.
• Only keep H+ ions tied up temporary.
• Replace a strong acid or base with a weak acid or base respectively.
I. HCO-3 III NH3
II. Phosphate IV Proteins
Buffer systems in the body
A] plasma-
• Bicarbonate buffer
• Protein buffer:HPr→H⁺ + Pr⁻
B] RBC *phosphate buffer important at renal tubules.
• Protein
• Deoxyhaemoglobin:HHb→H⁺ + Hb⁻
C] Tissue fluid
• Bicarbonate buffer
D] Intracellular fluid
• Protein
• Phosphate buffer:H₂PO₄→H⁺ + H PO₄⁻
HCO₃⁻ buffer system-

Largest quantity When a strong base is added
When a strong acid is added H2CO3 + OH- HCO-3 + H2O

Weak base [HCO₃⁻] replaces strong base
H+ +HCO-3 H2CO3 H2O + CO2 H₂CO₃ ↓ so more CO₂ and H₂O forms H₂CO₃
CO₂ is formed CO2 level↓
CO2 stimulates respiration Depresses respiration
CO2 eliminated CO2 level ↑

Non-bicarbonate buffer systems
1.Phosphate buffer system
• Important at the DCT and CD of the renal tubules
• Major intracellular buffer
2.Proteins
• Including Hb
• Work in blood and ICF
• Carboxyl group gives H+
• Amino group buffers H+
3.Ammonia
• Renal buffer ONLY
2.) Respiratory system

• 2nd line of defence
• Controls ECF [CO2] – Remove volatile acids
• Not 100% effective[effectiveness-50%-75%]
↑H+ in ECF ↓ H+ in ECF

↓ ↓
↑ Stimulation of chemoreceptors ↓Stimulation of chemoreceptors&
↓ the respiratory centre
↑ Stimulation of respiratory centre ↓
↓ Depression of respiration
↑ Respiratory rate & depth ↓
↓ DecreaseCO2 eliminated
CO2 eliminated ↓
↓ ↑ Pco2
↓Pco2 ↓
↓ ↑ H+
↓H+
3.) Renal Contribution

• Most powerful regulatory system
• Excrete acidic or alkaline urine
• Remove non-volatile acids
• Buffer systems and RS keep [H+] from changing too m
until the kidneys takeover
 H+ in ECF  H+ in ECF
H+ Secretion HCO-3  HCO-3 H+ HCO-3  HCO-3

reabsorption production & Secretion reabsorption excretion
NH3
production
Production of acidic Production of alkaline

urine urine

Arterial Blood Gas Report Analysis
pH
<7.4 >7.4
↓ ↓
Acidaemia Alkalaemia
HCO-3 < 24meq/L Pa co 2>40mmHg HCO-3>24meq/L Pa co 2 <40mmHg
Metabolic Respiratory Metabolic Respiratory

acidaemia acidaemia alkalaemia alkalaemia
Respiratory Metabolic Respiratory Metabolic

Compensation Compensation Compensation Compensation
Pa co 2 <40mmHg HCO-3>24meq/L Pa co 2 >40mmHg HCO-3< 24meq/L
• Compensation is not perfect

• Respiratory acidosis Respiratory Metabolic acidosis Metabolic alkalosis
alkalosis
Primary ↑Pᴄᴏ₂ ↓Pᴄᴏ₂ ↓plasma H₂CO₃ ↑plasma H₂CO₃
cause
reasons Any respiratory disorder 01. Voluntary 01. Kidney fails to 01. Diuretics (due to ↑H+ loss; part
producing ↑H₂CO₃ hyperventilation excrete normally of loss of K+ and H+ by loop &
VA=RR(TV-DS) 02. High formed acids thiazide diuretics results from
01. Fibrosis, oedema, stiff altitudes 02. ↑Metabolic acid activation of RAAM that occurs
lung [↓ TV] formation (keto because of ↓blood volume and
02. Pump defects acidosis from arterial pressure)
(denervation of respiratory diabetes mellitus or 02.↑aldosterone→↑Na+
muscles) [↓ TV] lactic acidosis etc) reabsorption→
03. Depression of the 03. ↑Loss of HCO3- ↑Secretion→↑HCO3- reabsorption
respiratory centre [↓ RR] [diarrhoea] 03. increase ingestion of alkaline
04. airway obstruction 04. Ingestion of drugs
metabolic acids 04. Vomiting of gastric contents
compensation ↑HCO₃⁻ in plasma ↑HCO₃⁻ ↑ventilation ↓ventilation
excretion
How to ↓pH ↑pH ↓pH ↑pH
identify? ↑Pᴄᴏ₂ ↓Pᴄᴏ₂ ↓HCO₃⁻ ↑HCO₃⁻
↑HCO₃⁻ due to partial ↓HCO₃⁻ due to ↓Pᴄᴏ₂ due to ↑Pᴄᴏ₂ due to respiratory
renal compensation partial renal respiratory compensation
compensation compensation
Question
The following observations were made in a 45-year-old man
RR=40min
Arterial blood gas analysis report
Ph=7.2(normal range 7.35-7.45
Pᴄᴏ₂=28mmHg (normal range 38-40mmHg)
HCO₃⁻=12mmol/L (normal range 24-26mmol/L)
Explain the above findings
 Write the observations
 Decision
 Compensation
• Respiratory rate is higher than normal
• pH is reduced
• pᴄᴏ₂is reduced
• HCO₃⁻ is reduced
• Actions is due to reduced HCO₃⁻
• So, this person is having metabolic acidosis
• Acidosis stimulate the peripheral chemoreceptors
• They stimulate the respiratory center in the medulla
• Via the buffer nerves
• Increasing the respiratory rate
• Which decreases pᴄᴏ₂
• pHʹαHCO₃⁻/pᴄᴏ₂
• so, there is partial respiratory compensation
•
Q) Briefly state the acid base balance of the following patients
01. pH = 7.0 [7.34 - 7.44] 02. pH= 7.5 [7.34 - 7.44]
HCO3-= 18meq/L [24meq/L] HCO3-= 38meq/L [24meq/L]
PCO2 = 24mmHg [40 mmHg] PCO2 = 44mmHg [40mmHg]
Q) .1 What is the acid base disorder? (20) [normal ranges; pH→7.35-7.45, PCO2→38-40mmHg, HCO3-→24-26mmHg]
2 Explain the compensatory mechanisms which are involved in H+ regulation in this patient (80)
01. A 45-year-old man has the following ABG report. He is suffering from uncontrolled diabetes mellitus. His
capillary blood glucose is 490 mg/dL and urine ketone bodies are positive.
pH = 7.1 - HCO3 = 14 mmol/L - primary PCO2 = 30 mmHg
02. A 24-year-old woman has taken an overdose of opioid analgesics. Her respiratory rate is 8/min ABG shows
pH = 7.2 HCO3 = 28 mmol/L PCO2 = 49 mmHg
03. A 13-year-old child comes to the hospital with severe vomiting. He has eaten egg rolls from the school canteen
the day before. ABG shows
pH = 7.5 HCO3 = 32 mmHg PCO2 = 45 mmHg
04. A 21-year-old medical student has developed an attack of acute severe asthma. ABG shows
pH = 7.48 HCO3 = 16 mmHg PCO2 = 25 mmHg PO2 = 60 mmHg
05. A 35-year-old woman has the following ABG report. She has ingested a large dose of aspirin.
pH = 7.3 HCO3 = 20 mmol/L PCO2 = 30 mmHg

bat notes
term 03
anatomy
bat notes
term 03
SKULL
• Skull is the skeleton of the head. Skull also includes the mandible
Brain case (calvaria) Facial skeleton

• Paired • Paired
1. Parietal 2.Temporal 1. Maxilla 2. Zygomatic 3. Nasal 4.Lacrimal 5.Palatine
• Unpaired 6.Inferior nasal concha
1. Frontal 2. Occipital 3. Sphenoid 4. Ethmoid
• Unpaired
1. Mandible 2. Vomer
SKULL JOINTS
1. Fibrous joints – immovable
2. Few primary cartilaginous joints
3. Pair of synovial joints – temporomandibular joints
• Sutures start ossifying from INSIDE between 30 – 40 years

• Sutures complete ossification on the outside at about 50 years
EXTERIOR OF THE SKULL
1. Superior view (normaverticalis)

Clinicals
Fontanelle: sites of growth of skull – permits growth
Anterior fontanelle: Lies between four bones. Two
parietal bones bound it behind, the two halves of the
frontal bone lie in front.
Overlies the superior sagittal dural venous sinus.
Closed by 18 months bregma
Posterior fontanelle: Lies between apex of squamous part

of occipital bone & posterior edges of the two parietal
bones.
Closed by 3 months lambda
Sphenoidal & mastoid: Smaller fontanelles at lateral

sides; sphenoidal more anteriorly & mastoid posteriorly
During vaginal delivery, helps to reduce the size of the

skull.
Coronal suture: between frontal & parietal bones

• Sagittal suture: between the parietal bones
• Lambdoid suture: between occipital & 2 parietal bones
• Metopic suture: between 2 frontal bones
• Vertex: highest point of sagittal suture
• Bregma: coronal & sagittal sutures meet – anterior fontanelle in the fetal skull, closed by 18 months
• Lambda: sagittal &lambdoid sutures meet – posterior fontanelle in fetal skull, closed by 3rd month
• Parietal eminence- most prominent part of the parietal bone – commonly fractured
• Parietal foramina – transmits emissary veins in front of the lambda
• Temporal lines begin from zygomatic process of frontal bone and then divide into superior & inferior lines over
parietal bone. Superior line lost over posterior part.

2. Posterior view
(normaoccipitalis)
• External occipital protuberance – junction of head & neck, most prominent point – INION
• Superior nuchal line – junction of head & neck – pass from the protuberance
• Highest nuchal line – begin from upper part of the protuberance
• Occipital point – above inion farthest from glabella
• Occasionally interparietal bone present
Lateral view
(temporal view)
• Zygomatic arch – temporal process of zygomatic bone + zygomatic process of temporal bone
• Jugular point – anterior end of zygomatic arch
• PTERION: point where frontal, parietal, temporal, sphenoid bones meet
- Deeply lies middle meningeal vein, anterior of middle meningeal artery & stem of the lateral sulcus of the
brain (7.17 C) grants
- 4cm above zygoma, 2.5cm behind frontozygomatic suture

3. Norma basalis
*attachments
 Pharyngeal tubercle : raphe of superior constrictor
 Medial pterygoid: pharyngobasilar fascia, superior constrictor, pterygomandibular raphe
 Lateral pterygoid plate: lateral pterygoid and medial pterygoid
 Foramen magnum: anterior , posterior atlanto-occipital membrane, alar ligament
 External occipital protuberance: ligamentum nuchae
*relations: spine of sphenoid medial – chorda tympani
Lateral –auriculotemporal
: foramen spinosum posterolateral to foramen ovale
4. Norma frontalis
• Nerves come out,

which have the same
names as their
foramina.

Structures passing through foramina
Anterior view
Supra-orbital foramen – supra-orbital nerve and vessels
Infra-orbital foramen – infra-orbital nerve and vessels
Mental foramen – mental nerve and vessels
Lateral view
Zygomaticofacial foramen – Zygomaticofacial nerve
Superior view
Parietal foramen – emissary veins
Inferior view
Incisive foramen – nasopalatine nerve, greater palatine vessels
Greater palatine foramen – greater palatine nerve
Lesser palatine foramen – lesser palatine nerve
Pterygoid canal – pterygoid nerve and vessels
Foramen ovale – Mandibular nerve
Accessory meningeal artery
Lesser petrosal nerve
Emissary vein
Foramen spinosum – middle meningeal artery, meningeal branch of mandibular nerve
Foramen lacerum – filled with cartilage
Foramen magnum – continuation of brain and spinal cord, vertebral arteries and nerve plexus
Anterior spinal artery
Posterior spinal arteries
Roots of accessory nerve
Meninges
Carotid canal – internal carotid artery and nerve plexus
Condylar canal – emissary veins
Hypoglossal canal – hypoglossal nerve (XII) and vessels
Jugular foramen – Internal jugular vein
Glossopharyngeal nerve (IX)
Inferior petrosal sinus
Vagus nerve (XII)
Accessory nerve (XI)
Stylomastoid foramen – Facial nerve (VII)
INTERNAL FORAMINA
Anterior cranial fossa

Foramen cecum – emissary veins to nasal cavity
Olfactory foramen in cribriform plate – olfactory nerve (I)
Middle cranial fossa

Optic canal – Optic nerve (I)
Ophthalmic artery
Superior orbital fissure – Oculomotor nerve (III)
Trochlear nerve (IV)
Ophthalmic division of trigeminal nerve (V1)
Abducent nerve (VI)
Ophthalmic veins
Foramen rotundum – Maxillary division of trigeminal nerve (V2)
Foramen spinosum – middle meningeal artery
Hiatus for greater petrosal nerve – greater petrosal nerve
Hiatus for lesser petrosal nerve – lesser petrosal nerve
Posterior cranial fossa

Foramen magnum – End of brain stem/beginning of spinal cord, vertebral arteries, spinal roots of accessory nerve,
meninges
Internal acoustic meatus – Facial nerve (VII)
Vestibular-cochlear nerve (VIII)
Hypoglossal canal – Hypoglossal nerve (XII)
Meningeal branch of ascending pharyngeal artery
Condylar canal – Emissary vein

5. Interior of skull
Cranial fossa
fossa Boundaries features
Anterior Anteriorly & Frontal Bone Foramen caecum
cranial On the sides Cribriform plate
Fossa Posteriorly -- Posterior border of lesser wing of
Sphenoid, ant. clinoid process ,
Anterior margin of sulcus chiasmaticus
Middle cranial Anteriorly—posterior boundary of ant.cranial fossa Foramen spinosum

Fossa Posteriorly—sup.border of petrous temporal bone & Foramen ovale
Dorsum sellae of sphenoid Hiatus for greater petrosal
Laterally—greater wing of sphenoid, anteroinferior nerve
angle of parietal bone, squamous temporal Hiatus for lesser petrosal
bone. nerve
Posterior Anteriorly—post.boundary of middle crn.fossa Internal acoustic meatus
cranial Posteriorly—squamous part of occipital bone Jugular foramen
Fossa Laterally—mastoid part of temporal &mastoid angle of Hypoglossal canal
parietal Foramen magnum
Clinicals
Anterior cranial fossa fracture:
⋅ bleeding or CSF leakage through nose
⋅ Black eye
Middle cranial fossa fracture: -
commonly fractured
⋅ Bleeding & leakage of CSF through ear
⋅ Bleeding through nose & mouth
⋅ Vertigo
⋅ Damage to the VII & VIII nerves
Posterior fossa fracture: Bruise extends over mastoid region to sternocleidomastoid
Cranial fossa contents

Anterior
Frontal lobe
Olfactory nerves
Anterior ethmoidal artery and nerve
Sphenoparietal sinus(along the edge of lesser wing of
sphenoid)
Middle
Pituitary
Optic chiasma
Cavernous sinus
III to VI cranial nerves
Trigeminal ganglion
Internal carotid artery and ophthalmic artery
Middle and accessory meningeal vessels
Greater and lesser petrosal nerves
Temporal lobes
Posterior communicating artery
Posterior
Cerebellum
Pons
V to XII cranial nerves
Spinal root of accessory nerve
Vertebral arteries
Basilar artery

*principles governing fractures of skull
I. Prevented by: elasticity, rounded shape, muscles
II. Passes through lines of resistance
III. Bas more fragile
IV. Inner table more brittle
V. Common sites : parietal area, middle fossa
VI. Commonly fractured facial bones: nasal bone, mandible

Meninges
1. Pia mater
Closely invests brain and spinal cord
Contains blood vessels.
No structure in between brain tissue and pia
2. Arachnoid mater
Delicate impermeable membrane
Deep to inner layer of dura
From the inner surface, thin processes or trabeculae extend downwards, crossing the subarachnoid space and
continuous with pia mater.
Subdural space – between dura and arachnoid
Vessels penetrate the space
Arachnoid villi – arachnoid herniate into venous sinuses through dura
CSF enters venous sinuses
More numerous in superior sagittal sinus
Subarachnoid space – between pia and arachnoid
Traversed by trabeculae running from arachnoid to pia
3. Dura mater
Dense
Inner (meningeal) and outer (endosteal) layers
Inner layer – prolonged into vertebral canal as the dura of spinal cord
Outer layer – periosteum of the bone
Not prolonged into vertebral canal
2 layers fuse except where the 2 layers are separated by venous sinuses
Folds of dura project into the cranial cavity as – tentorium cerebelli, falx cerebri, falx cerebelli.

MANDIBLE
• Horizontal U-shaped body anteriorly
• Vertical ramus posteriorly is quadrangular in shape
• Body arbitrarily divided into base of mandible inferiorly and superior alveolar part
• The alveolar part contains teeth and is reabsorbed when teeth are
removed
• Mental protuberance on anterior surface where the two sides meet
marked by a midline swelling in the base
• Slightly pronounced bumps on either side of the protuberance are
mental tubercles
• Laterally a mental foramen is visible halfway between upper border of
the alveolar part and the lower border of base
• Behind the foramen is an oblique line passing in front of ramus to the
body of mandible
• Superior part of the ramus extends as a condylar and a coronoid
process
• Condylar process for articulation with temporal bone (temporo-
mandibular joint)
• Coronoid process is the point of attachment for temporalis muscle
• Ramus join the body to form the angle
• Pterygoid fovea, a shallow depression on neck of mandible for
attachment of lateral pterygoid muscle
• Medial surface of ramus of mandible is the lateral wall of infratemporal
fossa
• Mandibular foramen opens up the mandibular canal carrying inferior alveolar nerves and vessels
• Immediately anterosuperior to the mandibular foramen is a triangular elevation, lingula for attachment of
sphenomandibular ligament
• Mylohyoid groove runs antero-inferiorly from the foramen carrying nerve to mylohyoid
• Medial to mylohyoid groove is a roughened area for attachment of medial pterygoid muscle
• Body composed of left and right parts fused each other in midline at mandibular symphysis
• 2 halves fuse at symphysis menti at 2 years
• Posterior to mandibular symphysis is superior and inferior mental spines, they are muscle attachment of tongue muscles
and to connect to hyoid bone
• Above the anterior 1/3rd of mylohyoid line is sublingual fossa while below posterior 2/3rd is submandibular fossa
• Between last molar tooth and mylohyoid line is a shallow groove for lingual nerve
Children Adult Old age

Angle of jaw > 1400 0 0
110 -120 > 1400
Mental foramen lower border middle alveolar border
Temporomandibular joint
• Atypical synovial joint
• Articular surfaces covered by fibrocartilage
• Joint is completely divided by a fibrous articular disc
• Extra-capsular ligaments
1. Lateral ligament - diagonally backward from the margin of the articular tubercle to the neck of
8mandible
2. Sphenomandibular ligament – from the spine of sphenoid bone at the base of the skull to the lingula on
the medial side of the ramus of the mandible
3. Stylomandibular ligament – passes from styloid process of temporal bone to the posterior margin and
angle of mandible

Venous sinuses
• Lie between the inner meningeal and outer endosteal layers of dura mater – except inferior sagittal &
straight sinuses (between inner layers)
• Receives all the blood from the Brain,
Meninges,
Bones of skull
• Communicates with veins outside the skull via emissary veins
• Lined interiorly by endothelium
• Do not contain valves
1. Superior sagittal sinus
Commence just above the foramen cecum

Ends turns at the internal occipital protuberance, generally to the right and becomes transverse sinus
Course lies between the two layers of the falx cerebri along the convexity of its attached margin
Drains from superior cerebral veins
 Upper and posterior parts
 Lateral and medial parts of both hemispheres
 Does not drain frontal pole of hemispheres.
Drains into Right transverse sinus

• 3/4 lakes of blood project laterally from it.
• Into these lakes, arachnoid granulations project to return CSF into blood.

2. Inferior sagittal sinus
Commence little distance above the crista galli

Ends as the straight sinus at the attachment of falx cerebri and tentorium cerebelli
Course along the free margin of falx cerebri
Drains from lower parts of medial surface of each hemisphere
Drains into straight sinus
3. Straight sinus
Commence continuation of inferior sagittal sinus with receiving the great cerebral vein of Galen
Ends turning into the transverse sinus generally to the left at the internal occipital protuberance
Course slopes down steeply in the attachment of the falx cerebri into the tentorium cerebelli
Drains from inferior sagittal sinus, great cerebral vein, adjacent occipital lobes, upper surface of cerebellum
Drains into left transverse sinus

4. Transverse sinus
Commence at the internal occipital protuberance
Ends as the sigmoid sinus
Course runs laterally from the internal occipital protuberance,

Horizontally forwards, grooving the occipital bone and the mastoid angle of the parietal bone.
Drains from Right sup sagittal sinus Left inf sagittal sinus
Nearby surfaces of cerebral and cerebellar hemispheres
• One sinus is larger – which receives the sup sagittal sinus (right)
• Communicate with each other at confluence of sinuses
5. Sigmoid Sinus
Commence as the termination of transverse sinus

Ends expands into the superior jugular bulb of the internal jugular vein
Course Deeply grooving the inner surface of the mastoid part of the petrous bone
Curves downwards and forwards to the post margin of the jugular foramen through which it passes
Drains from transverse sinus at superior end - sup petrosal sinus
Inferior end – occipital sinus
Cerebellar veins
Veins from mastoid air cells
Drains into internal jugular vein
• Mastoid emissary vein sigmoid sinus with post auricular vein (mastoid foramen)
• Emissary vein through post condylar foramen sigmoid sinus with suboccipital plexus of veins
6. Occipital sinus
Commence confluence of sinuses (the commencement of the transverse sinus)

Ends inferior ends of the sigmoid sinuses
Course runs downwards towards the foramen magnum as a single trunk and becomes a pair of sinuses and
runs around the margins of the foramen magnum
Drains from receives tributaries from cerebellum and medulla and drains choroid plexus of the 4th ventricle
Drains into sigmoid sinuses
• Communicates with the internal vertebral plexus (veins outside the spinal dura) at the foramen magnum
7. Basilar plexus
• On the clivus
• Connects the two inferior petrosal sinuses
• Drains from the lower part of medulla and pons
• No veins accompany the vertebral and basilar arteries
• Vertebral vein itself commences outside the skull below the occipital bone.
8. Cavernous sinus
Commence medial end of the superior orbital fissure (apex of the orbit)
Ends apex of the petrous bone
Course alongside the body of the sphenoid bone in the middle cranial fossa

Relations
• Outside the sinus
a. Superiorly – Optic tract
Internal carotid artery
Anterior perforated substance
b. Inferiorly – Foramen lacerum
Junction of body and greater wing of sphenoid
c. Medially – Pituitary gland
Sphenoidal air sinus
d. Laterally – Temporal lobe with uncus
e. Anteriorly – Superior orbital fissure
Apex of orbit
f. Posteriorly – Apex of petrous temporal bone
Crus cerebri of midbrain
• In the lateral wall of sinus (from above downwards)

-Oculomotor nerve (divides in to superior and inferior divisions in the anterior part of sinus)
-Trochlear nerve
-Ophthalmic nerve (divides in to lacrimal, frontal and nasociliary nerves in the anterior part)
-Maxillary nerve
-Trigeminal ganglion
• Passing through the center of sinus
-Internal carotid artery + venous and sympathetic plexuses around it
-Abducent nerve (inferolateral to internal carotid artery)
• Structures in the center and lateral wall of sinus are separated from blood by the endothelial lining.
Tributaries – a. From orbit – Superior ophthalmic vein

Inferior ophthalmic vein
Central vein of retina
b. From brain – Superficial middle cerebral vein
Inferior cerebral veins
c. From meninges – Sphenoparietal sinus
Frontal trunk of middle meningeal vein
Communications (valve-less)
• Transverse sinus (through superior petrosal sinus)

• Internal jugular vein (through inferior petrosal sinus and plexus around internal carotid)
• Pterygoid plexus of veins (through emissary veins)
• Facial vein (through superior ophthalmic vein)
• Cavernous sinus of opposite side (through anterior and posterior intercavernous sinuses
and basilar plexus of veins)

Clinical
• Thrombosis of cavernous sinus

- Caused by sepsis in dangerous area of face, nasal cavities, paranasal air sinuses
- Nervous symptoms – Severe pain in eye and forehead (ophthalmic nerve)
Paralysis of ocular muscles (3rd, 4th and 6th cranial nerves)
- Venous symptoms – Oedema of eyelids, cornea, root of nose
Exophthalmos
• Pulsating exophthalmos
- In head injury, a communication between cavernous sinus and internal carotid artery may
occur.
- Eyeball protrudes and pulsates with each heartbeat.
Extradural hemorrhage
• Fractures of the side of the skull may rupture the middle meningeal artery (especially the frontal
branch)
• Hematoma between the bone of the skull and the dura
• In x-rays, it has a lens shaped whitish area as it is attached to the sutures.
Subdural hemorrhage
• Venous blood escapes into the (potential) space between the dura and arachnoid
• Venous blood is involved (so it is slower to develop and less severe)
• In x-rays, they are shown in a crescent shape (falx cerebri)
Subarachnoid hemorrhage
• Rupture of arteries that lie within the space, such as aneurysms of arterial circle at the base of
brain.
• Causes blood to contaminate CSF
Appear in whitish (accumulation of blood in fissure)
• Blood accumulates along fissures

SCALP, TEMPLE & FACE
Scalp
 Extent
• supraorbital margin, superior temporal line, superior nuchal line, external occipital protuberance
 5 layers
• S - Skin
• C - Connective tissue
• A – Aponeurosis
(epicranial/deep fascia)
• L - Loose connective tissue
• P - Pericranium
 Skin
• Thick (thickest in occipital
region)
• High concentration of sebaceous glands
 Connective tissue (superficial fascia)

• dense in the center
 Aponeurosis
• Epicranial aponeurosis is movable on
Pericranium
• on each side attached to superior temporal
line – blends with temporoparietal fascia
• Occipitofrontalis
 Occipitalis arises from the highest
nuchal line, lateral 2/3 of superior
nuchal line
 Occipital muscle bellies are separated
across the midline by the aponeurosis
 Occipitalis is innervated by posterior
auricular branch of facial nerve
 Frontalis arises from the front of the aponeurosis/skin of forehead and is inserted to the upper part of
orbicularis oculi and overlying skin of the eye brow. (frontalis part has no attachment to the skull)
 Frontalis muscle bellies are partially united in the midline and innervated by temporal branch of facial nerve
 Loose connective tissue

• extends anteriorly to eyelid because- no bony attachment to frontalis, posteriorly to highest and superior nuchal
line & on each side to superior temporal lines
 Pericranium
• Loosely attached to surface of the bones but adherent to the sutures

 Blood Supply
• External carotid – occipital, posterior auricular, superficial temporal
• Internal carotid – supraorbital and supratrochlear (via ophthalmic artery)
• There is an external and internal carotid anastomosis around the vertex.
• Veins receive diploic veins from vault bones and emissary veins from intra cranial sinuses.
 Superficial temporal vein retromandibular vein
 Posterior auricular vein external jugular vein
 Occipital vein vertebral vein
 Supratrochlear & supraorbital veins angular vein facial vein
 Lymph drainage
• Anterior – pre auricular
• Posterior – mastoid
• Ultimately drain into deep cervical chain
• No lymph nodes within the scalp.
 Nerve supply
• Occipital region – greater occipital & 3rd occipital nerves
• Skin behind the ear – lesser occipital
• Temple – auriculotemporal & zygomaticotemporal
• Forehead & front of head – supratrochlear & supraorbital
 Clinicals
• Common site for sebaceous cysts – abundant sebaceous glands
• Rich blood supply – wounds bleed profusely because the dense superficial fascia prevents the vessels
from retracting (arterial walls are attached to fibrous septa); therefore can be arrested by pressing
against the bone.
• Loose areolar tissue is the danger area of the scalp because emissary veins open here
• Blood in loose connective tissue extends to eye lids causing black eye
• Collection of fluid deep to pericranium – cephaloheamatoma; take the shape of the bone concerned
because, pericranium is attached to the sutures.

Face
 Extends from adolescence position of hairline to base of mandible & auricles

 Forehead common both to face & scalp
• Skin – very vascular(wounds heal rapidly)
• rich in sebaceous & sweat glands
• Lax
• Boils in nose & ear causes pain because of fixity of skin to cartilage
• Superficial fascia
 facial muscle inserted into skin – injuries tend to gape
 Fat absent in eyelids but well developed in cheeks
• Deep fascia – absent but present over parotid gland & buccinator muscle
 Facial muscles (muscles of facial expression)
Orbicularis oculi
• 2 parts
 palpebral part (close eye lids gently)
 Orbital part (both parts – close eye lids forcibly)
• Nerve supply – temporal & zygomatic branches of facial nerve
Orbicularis oris
• Bulk is formed by buccinator
• Nerve supply – buccal and marginal mandibular branches of facial nerve
Buccinator
• Origin – alveolar processes of maxilla & mandible, pterygomaxillary ligament, pterygomandibular raphe
• Insertion – orbicularis oris (fibres from the raphe dicussate; maxillary & mandibular fibres donot dicussate)
• Nerve supply – buccal branch of facial nerve
• Action – prevent distention of cheeks when intraoral pressure rises
• Pierced by the parotid duct opposite the 3rd upper molar teeth.

Lymph drainage
• Submental (chin, tip of tongue)
• Submandibular
• Preauricular/parotid nodes (forehead, temple, orbital contents, cheek)
• Ultimately drains into deep cervical nodes
 Blood Supply
Facial course of Facial Artery

• Grooves the posterior part of
submandibular gland.
• Winds around the base of mandible,
• Pierces deep fascia at anteroinferior
angle of masseter – can be palpated
• Tortuous course – room for facial
expressions
• Lying on buccinator, deep to the dilator
muscles of the mouth,
• Passes upwards to lateral part of mouth
• Reaches medial part of eye
• Ends up supplying lacrimal sac
• Anastomose with dorsal nasal branch of
ophthalmic artery
• Branches; inferior labial, superior labial
(anastomose with the corresponding
artery of opposite side) & lateral nasal

Transverse Facial Artery
• Branch of superficial temporal artery.
• Emerges from within the parotid gland behind the neck of mandible
• Runs over the masseter accompanied by the upper buccal nerve between
the parotid duct & zygomatic arch
Venous drainage
• Entirely superficial
• Forehead – supraorbital & supratrochlear veins unite at medial canthus to
form the angular vein
• Angular vein – continues as facial vein (straight)
• Facial vein – just below the lower border of mandible pierces the deep fascia and joins retromandibular
vein;
 Anterior branch internal jugular
 Posterior branch external jugular
 CLINICALS
• Facial vein communications

 Supra orbital vein superior ophthalmic vein
 Deep facial vein pterygoid plexus
 hence the cavernous sinus is connected to the facial vein
 infections in the face can cause thrombosis of cavernous sinus
• When the buccal nerve is damaged- food accumulates in the vestibule

• Bell’s palsy (LMN lesion in Facial Nerve)
• Black eye: blood in loose areolar tissue seeps into the eyelids
• Subdural & extradural hemorrhages
• Dangerous area of the face – area lying between angular and deep fascial veins
 Parotid Gland
• largest salivary gland
• Serous gland.
• situated below the external acoustic meatus
• between the ramus of the mandible & sternocleidomastoid
• gland overlaps these structures
• anteriorly it overlaps the masseter
Parotid capsule
• deep cervical fascia splits to form the capsule
• superficial lamina thick & adherent
• attached to zygomatic arch
• deep lamina thin & attached to styloid process & angle of mandible
• part of the deep lamina forms stylomandibular ligament which separates the gland from the submandibular
gland
• thickened anteroinferiorly
Surface marking
1. upper border of the head of the mandible
2. center of the masseter muscle
3. posteroinferior to the angle of the mandible
4. upper part of the anterior border of the mastoid process

Relations
 pyramid shaped: base, superficial surface, anteromedial & posteromedial surfaces
• Apex
a) Overlaps posterior belly of digastric
b) Cervical branch of facial nerve & 2 divisions of retromandibular vein
• Base
a) Cartilaginous part of external
acoustic meatus
b) Posterior part of TM joint
c) Superficial temporal vessels
d) Auriculotemporal nerve
• Superficial surface
a) Skin
b) Parotid fascia
c) Lymph nodes
d) Anterior branch of great auricular
nerve
• Anteromedial surface
a) Grooved by ramus of mandible
b) Masseter
c) Lateral part of TM joint
d) Medial pterygoid
e) Emerging branches of facial nerve
• Posteromedial surface
a) External carotid artery enters
through this surface
b) Mastoid process
c) Styloid process & structures
related to it
Structures within the gland

1) External carotid artery, maxillary artery, superficial temporal
artery , transverse facial artery
2) Retromandibular vein formed by union of superficial
temporal& maxillary vein
3) Facial nerve
4) Parotid lymph nodes
Parotid duct (of Stensen)

 from the anterior surface runs forward on the masseter
 surface marking; lower border of the tragus to point between
ala of nose & red margin of lip (midpoint of philtrum)
• Relations
 Superior: accessory parotid gland
Upper buccal nerve
Transverse facial artery
 Inferior: lower buccal branch
• At the anterior border of masseter turns medially & pierce the

Buccal fat pad, Buccopharyngeal fascia and Buccinator
• & opens above the crown of the 2nd upper molar tooth

Blood supply
• Arterial supply - external carotid artery
• Venous drainage – Retromandibular vein
Nerve supply:
 Secretomotor (reach the gland by hitch-hiking along the auriculotemporal nerve)
Inferior salivatory ganglion Glosopharyngeal nerve Tympanic branch Tympanic plexus
Auriculotemporal nerve Otic ganglion Lesser petrosal nerve
 Sympathetic plexus  Sensory

• Vasomotor from the plexus around • Parotid gland – Auriculotemporal nerve
external carotid artery • Parotid fascia – Greater auricular nerve
Lymphatic drainage
• Parotid nodes upper deep cervical nodes
CLINICALS
 Parotid swellings are painful due to the unyielding nature of fascia
 Can be infected by infections spread from mouth
 Horizontal incisions
 Facial nerve divides the gland into superficial & deep parts
 Parotid tumor painless – malignant changes are indicated by pain
 Facial Nerve
• Extra-cranial course
 Crosses the lateral side of the styloid process after emerging through stylomastoid foramen
 Enters the posteromedial surface of the parotid gland
 Crosses the retromandibular & external carotid artery
 Behind the neck of mandible divides into terminal branches
• Branches & distribution

A. Within Facial Canal:
a) Greater petrosal nerve
b) Nerve to stapedius
• Arises opposite pyramid of middle ear
• Causes hyperacusis if paralysed
c) Chorda tympani
• Vertical part of facial nerve, arises 6mm above the Stylomastoid Foramen
• Closely related to tympanic membrane
• Leaves middle ear through petrotympanic fissure
• Medial to the spine of sphenoid
• Joins the lingual nerve
• Carries,
1. Preganglionic secretomotor fibers to submandibular & sublingual glands
2. Taste fibres from tongue

B. Exit from Stylomastoid Foramen
a) Posterior auricular:
1. auricularis posterior
2. occipitalis
3. Intrinsic muscles on the back of the auricle
b) Digastric
c) Stylohyoid
C. Terminal branches
a) Temporal
1. auricularis anterior & superior
2. Intrinsic muscles on lateral side of ear
3. Frontalis
4. Orbicularis oculi
5. Corrugator supercili
b) Zygomatic
1. orbicularis oculi
c) Buccal
1. Orbicularis oris
2. Bucciator
3. Muscles of nostrils & upper lip
d) Marginal mandibular
1. Platysma
2. Muscles of lower lip & chin
e) Cervical
1. platysma

Orbit & Eye
Orbit
Orbital Skeleton
 Orbital margin
• Above – frontal bone
• Lateral – frontal & zygomatic
• Inferior – zygomatic & maxilla
• Medial – maxilla & frontal
 Walls
• Roof – orbital plate of frontal bone & lesser wing of sphenoid
• Lateral – zygomatic & greater wing of sphenoid
• Floor – orbital plate of maxilla, zygomatic, palatine bone
• Medial – anterior lacrimal crest on frontal process of maxilla, posterior lacrimal crest on lacrimal, orbital plate
of ethmoid, body of sphenoid
 Clinicals
1. In blow out fracture, orbital floor or medial wall may be damaged.
2. Fracture of floor causes herniation of orbital fat into maxillary sinus
3. Entrapment of an extra-ocular muscle causing diplopia
4. Injury to infra-orbital nerve
 Openings
• Supra orbital notch - supraorbital nerve & vessels
• Infraorbital groove - infraorbital nerve & vessels
• Nasolacrimal canal - nasolacrimal duct
• Inferior orbital fissure - maxillary & zygomatic nerves, branch of inferior ophthalmic vein, sympathetics
(gap between lateral wall and floor)
• Superior orbital fissure - L,F,T,S,O,N,I,A
(gap between lateral wall and roof)
• Optic canal - optic nerve & ophthalmic artery

Orbital Fascia
• Periosteum of orbital skeleton
• Continuous with dura & sheath for optic nerve
• Orbitalis - sympathetic supply
• Orbital septum- extension of orbital fascia
• Holds the fibrous pulley of tendon of superior oblique
• Lacrimal fascia
Eye lids
• Covered in front with loose skin and behind with
conjunctiva.
• Eye lids meets at medial and lateral canthi.
• Fibrous framework is orbital septum, thickened at the
margins of lids to form tarsal plates.
• Upper & lower eye lids
• Layers (from superficial to deep)
1. Skin
2. Loose connective tissue
3. Orbicularis oculi
4. Tarsal plates
5. Tarsal glands
6. Conjunctiva
• Eye lashes arise along mucocutaneous junction
• Immediately behind lashes – openings of meibomian
glands/Tarsal glands
• Tarsal glands
o large sebaceous glands
o secretions help to see the palpebral fissure when eyelids are closed.
o Forms a thin layer over the exposed surface of the open eye
 Clinicals
• Meibomian cysts – distention of the meibomian glands due to the blockage
Conjunctiva
• Delicate mucous membrane lining the inner surface of lids
• Attached to sclera at the margins of cornea.
• Reflected to inner surfaces of eye lids.
o Over the eye lids – thicker and highly vascular
o Over the sclera – thinner
o Over the cornea – reduced to a single layer
• Superior conjunctival fornix receives opening of lacrimal glands
Conjunctival fornix – line of reflection from lid to the sclera
Orbital septum
 Attached to margins of orbit forming palpebral fissure between eye lids.
 Above and below the fissure form superior and inferior Tarsal plates.
 At the medial end – medial palpebral ligament
 At the lateral end – lateral palpebral ligament
 Levator palpebral superioris is attached to superior tarsal plate.
 Tarsal/meibomian glands embedded within tarsal plates

Lacrimal apparatus
• Concerned with secretion & drainage of tear fluid
• Components-lacrimal gland & ducts, lacrimal canaliculi, lacrimal sac ,nasolacrimal duct
Lacrimal gland
• A serous gland situated in the lacrimal fossa
(in the upper lateral part of the orbit)
• J shaped
• Indented by the tendon of levator palpebrae
superioris
• Has orbital part & palpebral part
• Orbital part - large & deeper
• Palpebral part - smaller & superficial
• 8-12 small ducts drain the gland
• Ducts open into superior Conjunctival fornix
• secretions spread over the surface of the eye
• lacrimal canaliculi drain tears to the lacrimal
sac via lacrimal papillae
• Lacrimal sac lies in lacrimal groove formed by
the maxilla and lacrimal bone.
• Nasolacrimal duct begins at lower end of
lacrimal sac
• Naso-lacrimal duct opens into inferior Meatus
of nose.
• Small accessory lacrimal glands are found in the conjunctival fornices
• Supplied by lacrimal branch of ophthalmic artery& lacrimal nerve
secretomotor fibres from superior salivary nucleus which travel in greater petrosal nerve
pterygopalatine ganglion
zygomatic branch of maxillary nerve
Lacrimal nerve
Extra-occular muscles • Superior rectus

Muscles of the eye • Inferior rectus
Intra-occular muscles • Medial rectus
• Lateral rectus
• Superior oblique
• Inferior oblique

Extra-occular muscles
Muscle Origin course insertion Innervations
Annular tendon
Lateral rectus -
(tendinous ring around To the sclera, anterior to
abducent (LR6)
4 recti the optic canal and the the equator of the
Other recti –
medial part of the eyeball
Occulomotor (CN3)
superior orbital fissure)
Tendon runs through
Sclera behind
Body of sphenoid pulley in trochlear
Equator. Below Trochlear (CN4)
Superior oblique (just above the fossa. Then
superior, (SO4)
tendinous ring) down, back,left below
& lateral recti
superior. rectus
Maxilla, lateral to Up, back, left, below Sclera behind equator,
Inferior oblique lacrimal groove Inferior rectus, deep between superior and Occulomotor (CN3)
(medial side of orbit) to lateral rectus lateral rectus
Levator palpebrae Lesser wing of Anterior Surface of

superior tarsus, skin of
Superioris Sphenoid Occulomotor (CN3)
eyelid, Upper margin of
(apex of the orbit)
superior tarsus

Movements
• Superior rectus elevation, adduction, medial rotation
• Inferior rectus depression, adduction, lateral rotation
• Medial rectus adduction
• Lateral rectus abduction
 superior rectus (turns up and in)+inferior oblique(up and out) = vertical upward movement
 inferior rectus(down and in) + superior oblique(down and out) = vertical downward movement
 Superior rectus + superior oblique = intortion
 Inferior rectus + inferior oblique = extortion
Nerves of the orbit

1. Optic nerve
2. Occulomotor nerve with ciliary ganglion
3. Trochlear nerve
4. Branches of maxillary and ophthalmic divisions of trigeminal nerve
5. Abducent nerve
6. Sympathetic nerves
 II – optic nerve
• Nerve of sight
• Made up of axons of ganglionic layer of retina
• Passes through optic canal to enter the middle cranial fossa
• Enclosed in 3 meningeal sheaths
• Relations:
1. Ciliary ganglion is between optic nerve & lateral rectus
2. Pierced by central artery of retina, inferomedially
3. Crossed inferiorly by the nerve to medial rectus
4. Crossed superiorly by ophthalmic artery, nasociliary nerve & superior ophthalmic vein

 III – Occulomotor nerve
• Arise medial to the cerebral peduncle
• Passes forwards between superior cerebellar & posterior cerebellar artery
• Runs lateral to posterior communicating artery
• Pierces dura & runs in lateral wall of cavernous sinus
• Divides into superior & inferior branches & enters superior orbital fissure
• Superior division runs above optic nerve and supply superior rectus and levator palpebre muscles.
• It carries sympathetic fibres from internal carotid plexus to smooth muscle part of levator palpebre muscle.
• Inferior division passes below optic nerve and supply medial, inferior rectus and inferior oblique.
• Gives off parasympathetic root to Cilliary ganglion.
Ciliary ganglion
• Lies at the apex of the orbit just lateral to optic nerve bet nerve and lateral rectus.
• Has 3 roots.
• Motor root – from nerve to inferior oblique (inferior branch of occulomotor)
• They are Preganglionic parasympathetic fibres from Edinger Westphal nucleus
• Supplies sphincter pupillae & ciliary muscle
• Sensory root – branches of nasociliary nerve; supply eye but not conjunctiva.
• Sympathetic root – from internal carotid plexus; vaso-constrictor fibres to vessels of eye.
• Branches – short ciliary nerves which contain fibres from all 3 roots.
• Supplies blood vessels & dilator pupillae
 IV – trochlear nerve
• Arise dorsally from inferior colliculus
• Passes between superior cerebellar & posterior cerebellar arteries
• Runs forwards in lateral wall of cavernous sinus
• Enters superior orbital fissure
• supply superior oblique (SO4)
 VI – abducent nerve
• Arises from between pons & medulla
• Passes forwards to enter cavernous sinus
• Lies inferolaterally to internal carotid artery
• Enters superior orbital fissure
• Supply Lateral rectus (LR6)

Trigeminal nerve
Ophthalmic division
Lacrimal Frontal Nasociliary

• Passes on upper surface of
• Joined by branch of • crosses above optic nerve
levator palpebrae superioris
zygomatico-temporal • Divides into supra-orbital and from lateral to medial
nerve containing supra-trochlear branches • ends by dividing in to
parasympathetic fibres to • Supra-trochlear anterior ethmoidal and
lacrimal gland  Conjunctiva infra-trochlear nerves
 upper eyelid
• Supplies conjunctiva and  skin over the root of nose • branches
upper eye lid - To ciliary ganglion
• Supra-orbital - Long ciliary nerves
 Conjunctiva - Posterior ethmoidal
 central part of upper eyelid
 frontal air sinus
 skin over the forehead and
scalp up to vertex.
Zygomatic
Maxillary division
Infra-orbital
Vessels of the orbit
 Ophthalmic artery
• Branch of internal carotid artery
• Runs through optic canal inferolaterally to optic nerve within its Dural sheath.
• In orbit the artery pierces the dura mater & crosses above the optic nerve from lateral to medial along with
nasociliary nerve anterior to it.
• Terminates by dividing into supratrochlear & dorsal nasal branches
• Branches
 Central artery of retina - supply optic nerve and retina (Posterior ciliary capillaries supply the choroid coat of
eye, they also supply outer layers of retina but there is no anastomosis bet central artery and them)
 Lacrimal artery
 from main trunk (branches accompany all the branches of nasocilliary, lacrimal and frontal nerves)
i. Ciliary branches
ii. Supraorbital & supratrochlear
iii. Anterior & posterior ethmoidal
iv. Medial palpebral branches
v. Dorsal nasal
• Establish connections between external and internal carotid systems.

 Ophthalmic veins
Superior ophthalmic vein
• Commences above the med palpebral ligament
• Passes back above optic nerve
• Drain to cavernous sinus via superior orbital fissure
• Communicate with angular vein at its commencement.
Inferior ophthalmic veins

• Drains to pterygoid plexus via inferior orbital fissure or to cavernous sinus via superior orbital fissure
Eye
 Bulbar fascia (Tenon’s Capsule)
• Facial sheath of the eye
• Attached anteriorly to sclera just behind limbus
• Extends from optic nerve to limbus
• Pierced by extra-ocular muscles and ciliary vessels and nerves.
• Reflected back around those muscles forming ligaments
• Medial Check ligament - from medial rectus to lacrimal bone
• Lateral Check ligament - from lateral rectus to zygomatic bone.
• Sleeve of inferior rectus blends with check ligaments and form - Suspensory ligament (of Lockwood)
 Eye ball
• Formed by segments of 2 spheres of different size – sclera-corneal junction
• Anterior – transparent 1/6th – cornea
• Posterior – opaque 5/6th – sclera
• Optic nerve enters 3mm nasal to posterior pole

 3 coats
1. Fibrous coat
• anteriorly transparent cornea & posteriorly opaque sclera – sclerocorneal junction
Sclera
• is tough
• outer surface is covered by Tenon’s capsule
• deep part of limbus contains canal of Schlemm
 maintains shape of eyeball
 receives insertion of extraocular muscles
 posteriorly pierced by optic nerve
 dura sheath continues
Cornea
• avascular
• layers
 Epithelium
 Basement membrane
 Connective tissue
 Descemet membrane
 Endothelium
• Cornea is supplied by
 Short ciliary nerves
 Long ciliary nerves
2. Vascular coat
• consists of choroid, ciliary body and iris
Choroid
• thin
• pigmented
• highly vascular
• pierced by optic nerve
• lines the inner surface of the sclera
• anteriorly connected to iris by ciliary body
Ciliary Body
• ciliary ring & ciliary process continuous with iris and choroid
• suspensory ligament (zonular fibres)
• ciliary muscle changes convexity of lens (accommodation)
Iris
• 4 layers
i. anterior mesothelial lining
ii. connective tissue with pigment cells (few melanin granules)
iii. smooth muscle
iv. posterior pigmental cell layer (packed with melanin granules)
3. Neural coat
Retina
• outer pigmented
• Inner neural
• Continuous with optic nerve
• anterior pole is called ora serrata
• posterior pole is called macula lutea
macula lutea fovea centralis 3mm nasally Blind spot
Optic disc
(site of central vision) (only cones) (no rods or cones)
Central artery
Temporal Temporal
Upper Lower
Nasal Nasal
• no blood vessels over macula lutea

• maximum visual acuity is in fovea centralis (fovea centralis is the thinnest part of the retina)
• Outer Receptor Layer
 The rods and cones, synapse with bipolar cells
 bipolar cells synapse with ganglion cells.
 Horizontal cells connect photoreceptor cells to the other photoreceptor cells in the outer plexiform layer.
 Amacrine cells connect ganglion cells to one another in the inner plexiform layer via processes of varying
length and patterns.
Lens
• Biconvex obliteration of iridocorneal angle
• Enveloped by lens capsule; an elastic membrane
• between vitreous body & aqueous humor impaired reabsorption
• more curved posteriorly
• Anterior surface is kept flattened by the tension of suspensory ligament increased intra-occular tension
Aqueous Humor GLUCOMA

• filtered plasma
• secreted into posterior chamber from vessels of iris & ciliary body
• reabsorbed through canal of Schlemm
Vitreous Humor
• thin transparent gel within hyaloid membrane
• pierced by lymph filled hyaloid canal
• occupies the posterior 4/5th of the eye ball
Clinicals
 Oculomotor nerve para lysis
• Ptosis – paralysis of levator palpebre superioris
• When the lid manually lifted up, eye is looking down and out - unopposed action of lateral rectus and superior
oblique
• Diplopia (double vision)
• When looking out diplopia disappears - lateral rectus intact
• Pupil is dilated and doesn’t react to direct light reflex or accommodation - interruption of parasympathetic fibres
• Consensual light reflex of opposite eye works.
 Abducens nerve paralysis
• Can’t look outwards - paralysis of lateral rectus
• diplopia
 Trochlear nerve paralysis
• Can’t look downwards - superior oblique paralysis (patient complain of diplopia when reading or difficulty in
going downstairs
• Extortion effect due to inferior oblique (to compensate extortion, patient tilts the head towards the opposite
shoulder)

TEMPORAL AND INFRATEMPORAL REGIONS
Temporal Fossa
 Boundaries
1. Superiorly – temporal lines
2. Inferiorly – zygomatic arch
3. Roof – temporalis fascia(deep temporal fascia)
4. Floor – side of skull including Pterion
5. Anterior wall – zygomatic processes of frontal bone, zygomatic bone , maxilla
 Contents
1. temporalis muscle
2. Deep temporal arteries
3. Deep temporal branches of mandibular nerve
4. Middle temporal artery – a branch of superficial temporal artery
Muscle Origin Insertion Innervation Action

Temporalis Floor of temporal Coronoid process Mandibular nerve Elevation and
fossa of Mandible – anterior division retraction of
Masseter Lower border of Ramus of the mandible
Zygomatic Arch Mandible

Infratemporal Fossa
 Walls of Infratemporal Fossa
• Medial – lateral pterygoid plate, tensor palatini , superior constrictor muscle
• Lateral – ramus and coronoid process of mandible
• Anterior – posterior surface of maxilla
• Posterior – styloid process, carotid sheath
• Roof – greater wing of sphenoid , squamous temporal bone
 Communications of Infratemporal Fossa
Fissure/Foramen Communicates with Structures going through

1. Inferior Orbital Fissure Orbit Infraorbital Artery
2. Pterygomaxillary Fissure Pterygopalatine Fossa Maxillary Artery
3. Petrotympanic Fissure Middle Ear Chorda Tympani
Anterior Tympanic Artery
4. Foramen Ovale Middle Cranial Fossa Mandibular Nerve
Accessory Meningeal Artery
Lesser Petrosal Nerve
Emissary Veins
Nervus Spinosus
5. Foramen Spinosum Middle Cranial Fossa Middle Meningeal Artery
Nervus Spinosus
6. Mandibular Foramen Mandibular Canal Inferior alveolar vessels and nerves
7. Foramina in posterior surface of Posterior superior alveolar artery
maxilla and nerve

 Muscles of infratemporal fossa
Muscle Origin Insertion Innervation Action

1. Medial Superficial head Medial aspect of angle Main trunk • Protrusion
pterygoid tuberosity of maxilla , pyramidal of mandible of • Elevation
process of palatine bone Mandibular • Deviation to
nerve opposite side
Deep head
medial side of lateral pterygoid
plate
2. Lateral Upper head • Neck of mandible Anterior • Depression
pterygoid roof of infratemporal fossa • Articular disc of the division of • Protraction
temporomandibular Mandibular • Deviation to
Lower head joint nerve oppsite side
lateral side of lateral pterygoid • Pterygoid fovea on • Pulls articular
plate the front of the disc forwards
neck of the
mandible
 Maxillary artery
• Larger terminal branch of
external carotid.
• Enters infratemporal fossa
by passing forwards between
the neck of mandible and
sphenomandibular ligament.
• Above – auriculotemporal
nerve N
• Below – maxillary vein A
• Runs forwards deep to the V
lower head head of lateral
pterygoid and then between
the 2 heads.
• Enters pterygopalatine fossa.
• Then enters infraorbital
canal through inferior orbital fissure and continues as the infraorbital artery.

• 3 parts- Sphenomandibular ligament
 1st part – before lateral pterygoid muscle
5 branches • arises from the spine of
 2nd part – on the lateral pterygoid muscle
each sphenoid and inserts into the
 3rd part – beyond the lateral pterygoid muscle
lingula and inferior margin of
mandibular foramen.
1st part
• It runs deep to
auriculotemporal nerve,
maxillary artery & vein
2nd part • It is pierced by mylohyoid
Inferior alveolar artery nerve, which is accompanied
by mylohyoid vessels.
Middle meningeal artery
3rd part
pterygoid
Accessory meningeal artery Infraorbital artery
Masseteric
Deep auricular artery Sphenopalatine
2 Deep temporal • main supply to nasal cavity
Anterior tympanic artery
Buccal Posterior superior alveolar
Greater palatine
 Pterygoid plexus
• Lie around and within the lateral pterygoid muscle Pharyngeal
• Plexus is valved, and acts as a peripheral heart
• Receives inferior ophthalmic vein, deep facial vein Artery of Pterygoid Canal
• Drains into Short Maxillary Vein
• Connect with cavernous sinus via emissary veins through Foramen Ovale and Foramen Lacerum
 Mandibular Division of the

Trigeminal Nerve
• Enters fossa through
foramen ovale.
• Lies between upper
head of lateral pterygoid
and tensor palatine.
• Otic ganglion lies
between upper head of
lateral pterygoid and
tensor palatine muscles.
• Otic ganglion lies on
deep surface of the
nerve.
• After a short course
divides into a small
anterior division and a
large posterior division.

Main trunk
Tensor Vali Palatine

Meningeal branch
(nervus spinosus) Nerve to Medial Pterygoid
supplies dura
Anterior Posterior
division division
Auriculotemporal nerve
• Forms a loop around the middle meningeal artery
deep temporal branches
Motor Masseteric Inferior alveolar nerve

• before entering the mandibular
Nerve to Lateral Pterygoid foramen, gives off the nerve to
mylohyoid.
Buccal nerve - sensory
Nerve to mylohyoid
Lingual nerve • Pierces Sphenomandibular
Ligament
Mental nerve • supplies mylohyoid and
anterior belly of digastric.
Chorda tympani nerve

• emerges from the Petrotympanic Fissure
• joins lingual nerve at an acute angle
• supplies taste sensation to anterior 2/3 of the tongue
• carries parasympathetic fibres to Submandibular Ganglion.
 Pterygopalatine fossa
• Narrow space communicating with infratemporal fossa through
pterygomaxillary fissure.
• Boundaries
 Anterior wall – posterior surface of maxilla
 Posterior wall – sphenoid bone
 Medial wall – perpendicular plate of palatine bone
 Roof – body of sphenoid
 Floor – articulation of pyramidal process of palatine bone with
lateral pterygoid plate.
• Contents
 maxillary vessels (3rd part – 5 branches)
 Maxillary nerve
 Pterygopalatine ganglion & fat
 Maxillary nerve enters fossa through Foramen Rotundum and runs through inferior orbital fissure into
Infraorbital Canal as Infraorbital Nerve.
 Branches
o Zygomatic nerve
o Zygomaticofacial
o Zygomaticotemporal
o Posterior Superior
Alveolar Nerve
• Foramina which opens into

pterygopaltine fossa
1. Foramen rotundum
2. Pterygoid canal
3. Palatovaginal canal
4. Inferior orbital fissure
5. Pterygomaxillary fissure
6. Sphenopalatine foramen
7. Palatine canal
 Temporomandibular Joint
• Atypical synovial joint.

• Articular surfaces
 Head of mandible
 Mandibular fossa of the squamous part of temporal bone
 Covered by fibrocartilage. No hyaline cartilage.
 Joint cavity is separated into 2 compartments as upper and lower by a fobrocartilaginous disc.
 The periphery of the articular disc is attached to the capsule.
 Articualr disc is anteroposteriorly concavoconvex (to fit the articular eminence and fossa)
 Inferior surface is concave.

• Joint capsule
 Mandible – Anteriorly to the Neck of mandible; Posteriorly Lower down in the neck
 Skull – Anteriorly, Just in front of the articular eminence.
 Posteriorly – to the Squamotympanic fissure
 Medially and laterally – Articular margins.
• Synovial membrane lines the capsule.

• Ligaments
 Lateral ligament - Zygomatic arch to neck of mandible
 Sphenomandibular ligament – From spine of sphenoid to lingula of mandible
• Stability
 Most stable when teeth in occlusion.
 Forward displacement is more common.
• Movements
1. Depression and elevation
a. Lower compartment – hinge movement
b. Upper compartment – gliding movement
c. Axis – horizontal
2. Side to side movements – Medial and lateral pterygoids of the same side contract together.
3. Protraction – All 4 pterygoids contract.
Retraction – Elastic recoil (Temporalis, Masseter)
Depression – digastric, mylohyoid, geniohyoid
Elevation – masseter, medial pterygoid, temporalis
• Nerve Supply
 Auriculotemporal Nerve
 Nerve to Masseter
 Middle meningeal artery

• Branch of 1st part of maxillary artery (in Infratemporal Fossa)
• Enters Middle Cranial Fossa through Foramen Spinosum
• Runs forwards and laterally grooving the squamous temporal bone following an extradural course
• Ends by dividing into frontal (anterior) and parietal (posterior) branches
• Frontal branch crosses the Pterion and is closely related to motor area of cerebral cortex
• Predominantly a periosteal artery supplying bone and red marrow in diploe (gives small branches to dura
mater)
• Relations
 In infratemporal fossa
o Deep to lateral pterygoid muscle
o Superficial to sphenomandibular ligament
o Passes through a loop formed by 2 roots of auricotemporal nerve
 In middle cranial fossa – Middle meningeal veins are closer to the bone than artery
• Branches – ganglionic, petrosal, superior tympanic, temporal, anastomotic

THE SUPERFICIAL NECK
SURFACE MARKING
• Notch of thyroid cartilage

• Hyoid bone – C3
• Cricothyroid ligament (important cricothyroid puncture)
• Isthmus of thyroid gland – 2-4 tracheal rings (sometimes palpable)
• Lower border of Cricoid cartilage - C6
Also at the lower border of the cricoid cartilage (C6) lies the,
1. junction of larynx with trachea
2. junction of pharynx with oesophagus
3. inferior thyroid artery enters & middle thyroid vein leaves the thyroid gland
4. vertebral artery enters foramen transversarium of C6 vertebra
5. superior belly of omohyoid crosses carotid sheath
6. middle cervical sympathetic ganglion
7. carotid artery can be compressed against anterior tubercle of the transverse process (carotid tubercle) of 6th
cervical vertebra
• carotid sheath – join the following points

i. a point midway between tip of mastoid process & angle of the jaw
ii. sternoclavicular joint
• bifurcation of common carotid artery – upper border of thyroid cartilage
Cutaneous innervation
• C2, C3, C4
• anterolateral part – anterior primary rami through
 lesser occipital
 great auricular
 Transverse cervical
 supraclavicular
• posterior part – posterior primary rami
*C1 – no cutaneous innervation
C4 – through supraclavicular nerves supply pectoral region
SUPERFICIAL FASCIA
− platysma
− cervical branch of facial nerve
− lymph nodes & vessels.
− external jugular vein
• deep to platysma
• posterior auricular + posterior division of
retromandibular vein
External jugular vein

• begins within lower part of parotid gland
• crosses the sternocleidomastoid obliquely
• pierces the anteroinferior angle of the roof of the posterior triangle
• opens into subclavian vein
• used to assess venous pressure * air embolism when cut

Clinical:
Division of the external Jugular vein in the supraclavicular space may cause air embolism and death because the cut
ends of the vein are prevented from retraction and closure by the fascia, attached firmly to the vein.
− anterior jugular vein

• begins in submental region
• Descends in the superficial fascia
• Above the sternum it pierces the investing
layer of deep fascia
• Enters suprasternal space
• Connected to opposite vein by jugular
venous arch
• Turns laterally and runs deep to
sternocleidomastoid just above the
clavicle
• Ends in the external jugular vein.
DEEP CERVICAL FASCIA

The deep fascia of the neck is condensed to
form the following parts:
1. investing layer
• surrounds the neck like a collar
• Forms the roof of anterior & posterior
triangle.
• attachments
− superiorly – external occipital
protuberance,
Superior nuchal line
Mastoid
Lower border of mandible
 between angle of mandible &
mastoid process, the fascia splits to
enclose the parotid gland
 superficial lamina is thick – attached to zygomatic arch
 deep lamina is thin – attached to styloid process, mandible,
tympanic plate
o deep lamina forms stylomandibular ligament – separates parotid & submandibular glands
o pierced by external carotid artery
− inferiorly – spine of scapula
Acromion process Clavicle Manubrium
− posteriorly – ligamentum nuchae Spine of C7
− anteriorly – hyoid bone
• encloses 2 muscles, salivary gland, 2 spaces
sternocleidomastoid Parotid Suprasternal

trapezius supraclavicular
• forms pulleys for digastric & omohyoid
Suprasternal space of Burns
• jugular venous arch and
the anastomotic arch
between them
• sternal heads of
sternocleidomastoid
• lymph node
• interclavicular ligament
supraclavicular space
• external jugular vein
• supraclavicular nerves
• lymphatics
2. pretracheal layer
• forms the false capsule
of thyroid gland
• The posterior layer of
the Thyroid capsule is thick. On either side it makes the suspensory ligament of Berry which is attached to the cricoid.
• attachments
− superiorly – hyoid bone
Oblique line of thyroid cartilage Cricoid cartilage
− inferiorly – encloses inferior thyroid veins
Passes behind brachiocephalic veins & blend with arch of aorta
− laterally – fuses with carotid sheath
Clinical:
Thyroid gland and all thyroid swellings move with deglutition because the thyroid is attached to
cartilage of the larynx by the suspensory ligament of Berry.
3. prevertebral layer
• in front of prevertebral muscles
• forms floor of posterior triangle
• attachments
− superiorly – base of skull
− inferiorly – anterior longitudinal ligament & body of T4
− anteriorly – separated from pharynx & buccopharyngeal fascia by retropharyneal space (areolar tissue)
anterior surfaces of transverse processes and bodies of vertebrae C1 – C3
− Laterally – thins out deep to trapezius
• cervical & brachial plexuses lie behind the fascia
• forms the axillary sheath – does not contain axillary vein
− Posteriorly – ligamentum nuchae
4. carotid sheath
• condensation of fibroareolar tissue around vessels of neck
• Attachments
− Superiorly – base of the skull
− Inferiorly – adventitia of the arch of the aorta
• anteriorly embedded in the carotid sheath lies the ansa cervicalis
• posteriorly between the carotid sheath and the prevertebral fascia lies the sympathetic chain
• fuses with above mentioned layers of deep fascia
5. buccopharyngeal layer
covers superior constrictor externally & extends on to the superficial surface of buccinator.
6. pharyngobasilar layer
Thick between upper border of superior constrictor & base of skull
Clinicals
− parotid swellings are painful due to the unyielding nature of parotid fascia
− while excising submandibular gland external carotid artery should be secured
− thyroid gland & all swellings move with deglutition due to fascial attachments
− pus due to tuberculosis of vertebrae may pass forward forming a chronic retropharyngeal abscess in the
median plane
o it may extend laterally through axillary sheath; it may descend as far as superior
mediastinum
o pus collected from neck infections infront of prevertebral fascia will extend in a
paramedian position as far as the posterior mediastinum
neck infections in front of pretracheal fascia may extend into the anterior mediastinum
Muscles of the Neck

Sternocleidomastoid Suprahyoid Infrahyoid (strap muscles)
STERNOCLEIDOMASTOID MUSCLE
• origin
- sternal head – (tendinous) manubrium sterni
- clavicular head – (musculotendinous) medial 1/3rd of superior surface of clavicle *deep to the interval between the 2
heads lie the internal jugular vein
• insertion
- mastoid process
- lateral half of superior nuchal line
• nerve supply
motor – spinal accessory nerve proprioceptive – ventral rami of C2
• blood supply
occipital artery (2 branches), superior thyroid & suprascapular arteries
• actions
contraction of 1 muscle – 1. Turns chin to opposite side
2. Tilts head towards shoulder
contraction of both muscles – 1. Draw head forwards
2. Flex neck against resistance
3. Forced inspiration
• relations
 superficial
 skin
 superficial fascia
 platysma
 external jugular vein
 superficial layer of investing fascia
 lymph nodes
 parotid gland
 great auricular, transverse cutaneous, medial supraclavicular
nerves
(The muscle is crossed superficially form above downwards by the great auricular nerve, external jugular vein and the
transverse cervical nerve)

 deep
• bones & joints – mastoid process, sternoclavicular joint
• carotid sheath
• muscles – sternohyoid, sternothyroid, omohyoid, 3 scaleni. Levator scapulae, longissimus capitis,
posterior belly of digastric
• arteries – common, internal & external carotids, arteries to muscles, occipital, subclavian,
suprascapular, transverse cervical
• veins – internal jugular, anterior jugular, facial & lingual
• nerves – X, XI, cervical plexus, upper part of brachial plexus, phrenic, ansa cervicalis
• lymph nodes deep cervical.
CLINICALS
− most common cause for swelling in the posterior triangle is due to – enlargement of supraclavicular lymph nodes
− left supraclavicular nodes – signal nodes (malignancies in stomach & testis)
− wry neck – head bend to 1 side & chin points to other side: spasm of muscles supplied by spinal accessory nerve
Muscle Innervation Action

Suprahyoid muscles
1. Digastric Posterior belly – Facial nerve
Anterior belly – Nerve to mylohyoid
2. Stylohyoid Facial nerve
3. Mylohyoid Own nerve from inferior alveolar
4. Geniohyoid Branch from hypoglossal nerve
Infrahyoid muscles
1. Sternohyoid Ansa cervicalis
2. Omohyoid Superior belly – superior root of
ansa cervicalis
All depressors of larynx
Inferior belly – ansa cervicalis
3. Thyrohyoid Branch from hypoglossal nerve
4. Sternothyroid Ansa cervicalis
Triangles of the neck
Posterior triangle Anterior triangle

• Submental triangle
• Digastric/ Submandibular triangle
• Muscular triangle
• Carotid triangle
POSTERIOR TRIANGLE OF NECK
It’s a space on the side of the neck situated behind the sternocleidomastoid muscle
Boundaries
o anteriorly – posterior border of sternocleidomastoid
o posteriorly – anterior border of trapezius
o base – middle 1/3rd of clavicle
o apex – superior nuchal line where the 2 muscles meet
o roof – investing layer of deep cervical fascia
o floor – prevertebral layer of deep cervical fascia covering splenius capitis, levator scapulae, scalenus medius
 Divisions – divided by inferior belly of omohyoid into larger upper part (occipital triangle) & smaller lower
part (subclavian triangle)
ANTERIOR TRIANGLE OF NECK
Boundaries
− medially – anterior medial plane
− laterally –anterior border of the sternocleidomastoid
− superiorly – base of mandible & a line joining the angle of mandible to mastoid process

submental lymph nodes
submental on each side - anterior belly of digastric formation of anterior jugular vein
triangle base – body of hyoid bone apex – chin
floor – mylohyoid muscle
The triangle crosses the midline
Submandibular salivary gland and lymph nodes
digastric Anteroinferiorly-anterior belly of digastrics Facial, submental and mylohyoid vessels
triangle Posteroinferiorly-posterior belly of digastrics Hypoglossal and mylohyoid nerves
Base-the lower border of the mandible and
line joining the angle of mandible to mastoid
process
Roof – skin, superficial fascia, deep fascia
Floor – anteriorly – mylohyoid: posteriorly –
hyoglossus
• Arteries
carotid Antero-superiorly – posterior belly of Common, internal & external carotid
triangle digastric Carotid sinus & body
Antero-inferiorly – superior belly of All branches of external carotid except posterior auricular
omohyoid • Veins
Posteriorly – sternocleidomastoid Internal jugular
Roof – skin, superficial fascia, deep fascia Common facial
Floor – thyrohyoid, hyoglossus, middle & Lingual
inferior constrictors Pharyngeal
• Nerves
Vagus
Superior laryngeal
Spinal accessory
Hypoglossal
Sympathetic chain
• Carotid sheath
• Lymph nodes
Anteriorly – median plane
Muscular
Postero-superiorly – superior belly of omohyoid The Infra hyoid strap muscles
triangle
Postero-inferiorly – sternocleidomastoid
Clinicals
Common anterior midline swellings of the neck are

o Enlarged submental lymph nodes
o Sublingual dermoids
o Thyroglossal cyst
o Subhyoid bursitis
o Goiter
o Carcinoma of the larynx
o Enlarged supra sternal lymph nodes

Cervical plexus
Formed by ventral rami of upper cervical nerves. (C1 gives no cutaneous branches)
Branches:
Superficial branches-
1. Lesser Occipital (C2)
2. Great auricular (C2, C3)
3. Transverse cutaneous nerve of the neck (C2, C3)
4. Supraclavicular (C3, C4)
Deep branches –
Muscular branches to:
1. Rectus capitis anterior (C1)
2. Rectus capitis lateralis (C1, C2)
3. Longus capitis (C1-C3)
4. Lower root of Ansa cervicalis
Communication branches:
1. Grey rami from the superior cervical ganglion to C1-C4 nerves.
2. Branch from C1 joins the hypoglossal nerve
3. Branch from C2 to sternocleidomastoid & branches from C3 & C4 to the Trapezius
communicate with accessory nerve.
Ansa Cervicalis
− This is a thin nerve loop that lies embedded in the anterior wall of carotid sheath over the lower part of larynx.
− It supplies the infrahyoid muscles.
− Formed by a superior and inferior root.
− Superior root is the continuation of the descending branch of the hypoglossal nerve derived from C1.
− Inferior root derived from C2, C3. This root winds around the internal jugular vein and continues anteroinferiorly to join
the superior root in front of the common carotid artery.
Distribution:
− superior root to the superior belly of omohyoid
− Ansa cervicalis to the sternohyoid, the sternothyroid and the inferior belly of omohyoid
− Thyrohyoid and geniohyoid are supplied by separate branches from the first cervical nerve through the hypoglossal
nerve.

1) Cervical fascia splits
a) and embraces the infrahyoid muscles
b) and partially encloses submandibular salivary gland
c) inferiorly enclosing jugular venous arch
d) posteriorly around the scapula
e) to enclose sternocleidomastoid muscle
2) Prevertebral fascia
a) encloses the thyroid gland
b) extends laterally into the upper limb as the axillary sheath
c) has the cervical sympathetic chain embedded in it
d) blends inferiorly with anterior longitudinal ligament infront of body of C6 vertebra
e) splits around the hyoid bone
3) Carotid sheath
a) is attached superiorly to the base of the skull
b) fuses with the pericardium inferiorly
c) lies deep to the prevertebral fascia
d) encloses the jugular vein and vagus nerves
e) encloses the external carotid artery
4) Posterior triangle of the neck

a) is floored by the prevertebral fascia
b) is bordered posteriorly by the rhomboideus major muscle
c) has the spine of the scapula as its inferior border
d) is bordered anteriorly by the sternocleidomastoid muscle
e) is crossed by the internal jugular vein

Lymph drainage of the neck
Horizontally arranged nodes –
At the junction between head and neck there is a circular arrangement of lymph nodes.
Drain superficial tissues
Submental nodes – submental triangle
of head & neck
Submandibular nodes – digastric triangle
Preauricular(parotid) nodes – within/deep/superficial to parotid gland
Mastoid nodes – on the mastoid process
Occipital nodes – apex of posterior triangle of the neck
Mandibular and buccal nodes
Vertically arranged nodes –
Superficial cervical nodes – along external jugular vein Drain trachea

Anterior cervical nodes – along anterior jugular vein. larynx
Deep to investing deep fascia of front of neck - infrahyoid nodes – on thyrohyoid membrane esophagus
Prelaryngeal nodes – on cricothyroid membrane thyroid
Pretracheal nodes – on trachea part of pharynx
Paratracheal nodes – either side of trachea and esophagus
Retropharyngeal nodes – behind the pharynx – back of nose, pharynx, auditory tube
All lymph from horizontal and vertical groups drain in to deep cervical nodes.
Deep cervical nodes

Vertical group along the internal jugular vein.
Within or outside the carotid sheath.
All the structures in the head and neck pass ultimately to this group directly or indirectly.
Efferents form jugular trunk.
Left trunk thoracic duct

Right trunk right lymphatic duct

DEEP NECK
Root Of The Neck (Thoracic Outlet)
• Is bounded by the
1. T1 vertebra
2. 1st pair of ribs & costal cartilages
3. Manubrium of the sternum
• It’s the junction of structures and tissue spaces passing to and

from the neck thorax and upper limb. An arbitrary area above the apex of the lungs.
• Structures pass through it between the apices of the lungs.
• The key to the root of the neck is the Scalenus Anterior & its relations.
 Scalenus Anterior
• Origin – Anterior tubercles of the transvers processes of typical vertebrae (C3-C6)
• Insertion – Scalene tubercle & adjacent ridge on 1st rib
• Nerve supply – Anterior rami of C4-C6
Anterior relations
• The Phrenic Nerve,
 passes vertically down across the obliquity of the muscle. (plastered to the prevertebral fascia).
 The nerve leaves the medial border of the muscle low down.
 Crosses in front of the Subclavian Artery and its internal thoracic branch, behind the Subclavian Vein.
 Lying on the supra pleural membrane it passes medial to the apex of the lung, in front of the Vagus Nerve,
to enter the superior mediastinum.
• The Ascending Cervical Artery,

 a branch of the inferior thyroid artery of the thyrocervical trunk, runs up medial to the phrenic nerve. (on
the prevertebral fascia)
• Transverse Cervical & Suprascapular,

 In front of the prevertebral fascia, these arteries lie between the scalenus anterior and the carotid sheath
(internal jugular vein).
• The Vagus Nerve

 (in the carotid sheath) passes down in front of the subclavian artery, on the right side giving off its
recurrent laryngeal branch. It hooks around the artery and passes upwards.
 The vagus nerve inclines posteriorly and runs on the medial surface of the apex of the lung to enter the
superior mediastinum.
• The Internal Jugular Vein

 is surrounded by the inferior deep cervical lymph nodes.
• The Subclavian Vein

 lies in a groove on the 1st rib; in a lower level than the Scalenus Anterior.
 It runs below the clavicle and subclavius, and joins the internal jugular vein at the medial border of scalenus
anterior.
 The thoracic duct (left) and the right lymph duct (right) enter the angle of confluence of the two veins.

Medial relations
• Pyramidal Space,
 The medial edge of scalenus anterior muscle makes a pyramidal space/ ∆ with the lateral border of the lower
part of longus colli.
 There’s no fascial roof across the pyramidal space between the muscles.
o Base - is formed by the subclavian artery lying on the suprapleural membrane.
o Apex - is the Carotid (Chassaignac's) Tubercle on the transverse process of C6 vertebra. (Common carotid
artery can be compressed against it.)
 The common carotid artery, medial to the internal jugular vein, lies deep to sternocleidomastoid immediately
in front of the pyramidal space.
 The space contains the stellate ganglion & vertebral artery and vein(s).
 The inferior thyroid artery arches medially in a bold curve whose upper convexity lies in from of the apex of
the pyramidal space (C6 level).
 At a lower level, and further forward, the Thoracic Duct (or right lymphatic duct) makes a similar convexity
as it arches over the lung apex and subclavian artery enter the confluence of the subclavian and internal
jugular veins.
• The 1st Part Of The Subclavian Artery,

 is medial to the muscle. It arches over the suprapleural membrane and impresses a groove upon the apex of
the lung.
• The Vertebral Vein,

 emerges from the foramen in Transverse Process of C7 & runs forwards in front of vertebral & subclavian
arteries to empty into the brachiocephalic vein.
Posterior relations
• 2nd part of the Subclavian artery.
• Cervical pleura covered by supra pleural membrane.
• Scalenus Medius
• Anterior rami of lower cervical & 1st thoracic nerves.
Lateral relations
• 3rd part of the Subclavian artery.
• Trunks of the brachial plexus.
Cervical pleura:
• Covers the apex of the lung.
• It rises into the root of the neck.
• The pleural dome is strengthened on its outer surface by the supra pleural membrane (Sibson’s Fascia) so that
the root of the neck is not puffed up and down during respiration.

Pressure on
Existence of a cervical rib
Subclavian artery
Thoracic inlet/outlet syndrome
Elevation of 1st rib by scalenus anterior & lowest root of
brachial plexus
 Contents of the root of the neck

1. Glands - Thyroid & Parathyroid
2. Arteries - Subclavian & Carotid
3. Veins - Subclavian, Internal jugular & Brachiocephalic
4. Nerves - IX, X, XI, XII, Sympathetic chain, Cervical plexus
5. Lymph nodes & Thoracic duct
6. Viscera - Trachea & Oesophagus
7. Scalene muscles (Anterior , Middle & Posterior)
1) Glands
Thyroid Gland
Introduction
• Butterfly shaped/ shield like endocrine gland.
• The gland has 2 conical lobes each joined by an isthmus in its lower part.
• An inconstant pyramidal lobe may project upwards form the isthmus.
Extent & Location

• In the lower part of the front & side of the neck.
• Gland lies against C5, C6, C7 & T1 vertebrae / each lobe extend from the middle of the side of the thyroid
cartilage to the 4th & 5th tracheal rings.
• Isthmus overlies 2nd to 4th tracheal rings.
Capsules & ligaments
• Has 2 capsules.
• True capsule – derived from peripheral condensation of the connective tissue.
• False capsule – derived from the pretracheal fascia which encloses it.
• Dense capillary plexus present deep to the true capsule.
• Inner surface of the gland connected to the Cricoid Cartilage by thickened pretracheal fascial layer -
Suspensory ligament (of Berry) to which the recurrant laryngeal nerve is closely associated.
Arterial supply
1. Superior Thyroid Artery
 The 1st anterior branch of external carotid artery
 Close relation to external laryngeal nerve away from gland.
 At the upper pole divides into anterior and posterior branches.
2. Inferior Thyroid Artery –

 A branch of thyrocervical trunk
 Passes behind the carotid sheath & in front of the vertebral vessels.
 Close relation to recurrent laryngeal nerve near the gland.
 Divides into branches before piercing false capsule.
3. Additional supply
 Thyroidea ima artery (brachiocephalic or arch of aorta)
 Oesophageal and tracheal branches.
• Superior thyroid artery reaches the upper pole of the gland and (anastomosis with the opposite artery
along the upper border of the isthmus).
• Inferior thyroid artery reaches the lower pole.
Venous drainage
• Superior thyroid vein emerges from the upper pole of the gland drains into internal jugular vein.
• Middle thyroid vein also drain into internal jugular vein.
• Inferior thyroid vein emerges from the lower border of the isthmus, to be eventually drained into the left
brachiocephalic vein.
• Dense capillary plexus present deep to the true capsule.

Lymphatic drainage
• Lymph from the upper part of the gland drains into upper deep cervical lymph nodes.
Nerve supply
• Sympathetic fibres are mainly derived from the middle cervical ganglia / cervical sympathetic trunk.
Relations
• Superficially/Anterolateral
 skin, superficial fascia and investing deep fascia
 strap muscle of the neck (sternohyoid, sternothyroid, superior belly of omohyoid) overlapped by
sternocleidomastoid.
 Anterior jugular vein courses over the isthmus.
• Medially
 On the deep aspect lie the larynx (Cricothyroid) and trachea, pharynx (Inferior constrictor)and
oesophagus
 Recurrent laryngeal nerve coursing on the tracheoesophageal groove is closely related to the inferior
thyroid artery.
 External laryngeal nerve is closely related to the superior thyroid artery.
• Behind/Posterolaterally
 the carotid sheath (common carotid artery) lies on either side.
Clinical Anatomy
1. Swellings (goiter) move with deglutition (gland is adhered to the trachea)
2. Flex head when palpating
3. Cancer recurrent laryngeal nerve damage hoarseness of voice.
4. In thyroidectomy Superior thyroid ligated near gland to save the external laryngeal nerve. Inferior thyroid
ligated away from gland to spare the recurrent laryngeal nerve
Parathyroid gland
• 2 pairs Superior and inferior.(1 pair on each lateral lobe).
• Lies on the posterior surface of the thyroid gland, within the false capsule
• Size of split pea
• Lie close to anastomosis between superior & inferior thyroid arteries.
• Superior parathyroid more constant in position
• Inferior parathyroid inconsistent position
 Within capsule
 Outside capsule
 Within substance of lobe Within thymus (due to the same embroyological origin )
 Behind trachea
 Behind great vessels
• Blood supply – mainly from Inferior Thyroid Artery (both inferior & superior glands)
• Easily subject to subscapular haematoma formation on handling

2) Arteries
Subclavian Artery
• Left subclavian arises from arch of aorta.
(Immediately behind commencement of Left
common carotid.)
• It ascends laterally, against the mediastinal surface of
left lung & pleura, with the trachea & oesophagus
medially, to lie behind sternoclavicular joint.
• Right subclavian artery arises behind right
sternoclavicular joint from the brachiocephalic trunk.
• It is divided by the scalenus anterior into 3 parts.
Relations
1st part 2nd part 3rd part

Anterior • Sternocleidomastoid • Scalenus anterior • External jugular vein
• Strap muscles
• Phrenic nerve
• Vagus nerve
• Vertebral vein
• Carotid sheath
• Thoracic duct (left side)
Posterior • Right recurrent • Scalenus medius • Scalenus medius

laryngeal nerve (right • Anterior rami of lower • lower trunk of brachial
side) cervical & 1st thoracic plexus
nerves
Inferior • 1st rib
Branches (Mnemonic: VIT C D)
1st PART 1. Vertebral Artery

• Arises from the upper convexity of the artery.
• Passes up to disappear at the apex of the pyramidal space into the foramen
of the transverse process of C6.
• Ascends through transverse foramina of C6 to C1.
• Turns posteriorly and medially over posterior arch of atlas to enter cranial cavity at
foramen magnum (pierces dura).
• Runs anteromedially to ascend over the medulla oblongata.
• Two arteries join at pons to form the basilar artery.
• Branches
1. Anterior & Posterior spinal A.
2. Posterior inferior cerebellar A.
2. Internal thoracic artery

• Arises from the lower surface of the artery.
• Passes downwards over the lung apex.
• Crossed usually anteriorly by the phrenic nerve.
3. Thyrocervical Trunk (Lateral To The Vertebral Artery)

1. Transverse cervical (Deep & Superficial)
2. Suprascapular
3. Inferior thyroid

2nd PART
3rd PART
Costocervical trunk Axillary artery
• Passes back across the suprapleural membrane
towards the neck of the 1st rib & divides into. Dorsal scapular
1. Superior/Supreme intercostal (Descending) – into • Runs laterally through the brachial
the thorax. plexus in front of scalenus medius &
2. Deep cervical (Ascending) – Passes backwards then deep to the levator scapulae to
between the transverse process of C7 & the neck take part in the scapular
of the 1st rib and then ascends. anastomosis.
Common Carotid Artery

• Enclosed in carotid sheath medial to the internal jugular vein with the vagus nerve intervening.
• Terminates at the neck by dividing into External & Internal carotids at the level of the upper border of the
thyroid cartilage/ Upper border of C4.
• At the termination point, shows a slight dilatation – Carotid sinus
Relations
Anterolateral Posterior Medial Lateral

• Sternocleidomastoid • Transverse process of • Larynx • Internal jugular
• Sternohyoid lower 4 cervical vertebrae • Pharynx vein
• Sternothyroid • Prevertebral muscles • Trachea • Vagus nerve
• Superior belly of • Sympathetic trunk • Oesophagus
Omohyoid • Inferior Thyroid artery • Thyroid
• Superior thyroid vein Vertebral artery • Recurrent laryngeal nerve
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1. Internal carotid artery

• One of the two terminal branches of the Common
Carotid Artery.
• Begins at the upper border of thyroid cartilage (C4)
• Supplies the brain, eyes, forehead and part of nose
• Ascend within the Carotid Sheath
• First lies lateral to the external carotid at its origin,
but soon passes up posteriorly to a medial & deeper
level.
• Passes into the cranial cavity through Carotid Canal in
petrous part of temporal bone.
• Course of the artery is divided into 4 parts.
 Cervical part, in the neck
 Petrous part , within the petrous temporal bone.
 Cavernous part, within the cavernous sinus
 Cerebral part, related to the base of the brain.
• No branches of the internal carotid artery in the neck.

2. External carotid artery
• Supplies the neck, face, scalp, tongue,
maxilla
• Terminates in substance of parotid
gland behind neck of mandible by
dividing into maxillary & superficial
temporal branches.
• Emerges from undercover of
sternocleidomastoid where pulsations
can be felt
• First it is medial to internal carotid
but then comes to lie lateral to it
(generally lying more anteriorly)
Branches (Mnemonic * :p)
1) Superior Thyroid
2) Ascending Pharyngeal
3) Lingual
4) Facial
5) Occipital
6) Posterior Auricular
7) Maxillary
8) Superficial Temporal
3) Veins
1. Subclavian Vein
• Continuation of the axillary vein at
the outer border of 1st rib. Joins
internal jugular vein to form
brachiocephalic vein.
• Receives External jugular vein.
• Receives the thoracic duct (left) or
right lymphatic duct (right) at its
confluence with the internal jugular
vein.
• Relations
 Anterior - Clavicle
 Posterior - Subclavian artery,
Scalenus anterior & Phrenic nerve
 Inferior - Upper surface of 1st rib
• Tributaries are:
 External Jugular vein
 Dorsal scapular vein
2. Internal Jugular Vein

• Direct continuation of the Sigmoid Sinus.
• Drains the brain, face & neck.
• Leaves skull through Jugular Foramen (Posterior Compartment) and descends through neck in carotid
sheath.
• Joins Subclavian to form Brachiocephalic Vein
• Related to deep cervical nodes.

• Has 2 dilatations; Superior &
Inferior bulbs
• Between the two heads of the
sternocleidomastoid JVP
• Tributaries:
 Inferior Petrosal Sinus – 1st
tributary
 Common facial vein
 Lingual vein
 Pharyngeal veins
 Superior thyroid vein
 Middle thyroid vein
3. Brachiocephalic vein
• The left is longer than the right.
• Formed behind the Sternoclavicular
Joint
 Right – Vertical
 Left – Oblique
• The two unite at lower border of right 1st coastal cartilage to form SVC
• Tributaries
 Branches of 1st part of subclavian artery
 1st posterior intercostal vein
Clinical Anatomy
1. Cardiac failure - Internal jugular vein dilated.
2. Closely associated lymph nodes means that the vein should also be resected in removing malignancy.
4) Nerves
1. Phrenic nerve
• Origin - C3,C4 (main), C5
• Mixed nerve
 The sole motor supply of diaphragm.
 Sensory to Central Tendon of Diaphragm, Pleura, Pericardium & part of Peritoneum.
• Formed at lateral border of scalenus anterior at the level of upper border of Thyroid Cartilage.
• Runs vertically downwards on Scalenus Anterior from lateral to medial.
• Leaves scalenus anterior & runs downwards on cervical pleura & enters thorax behind 1st costal cartilage.
• Descends anterior to the lung root & then on the surface of the pericardium.
• In the left side, the nerve leaves the medial margin of the Scalenus Anterior at a higher level and crosses in
front of the first part of the Subclavian Artery.

Root
Bridge
NOSE & PARANASAL SINUSES
Nose
Consists of external nose and nasal cavity Dorsum
External nose − bony & cartilage framework
Bones
• 2 nasal bones
• frontal process of maxilla Tip
Cartilages
• lateral cartilages
Base
• major alar cartilages
• minor alar cartilages
• Ala→solely of fatty tissue at its free lower border
Nasal cavity − Anterior nares to posterior choanae

Communicate with nasopharynx
divided by medial nasal septum (medial wall)
Medial wall
• perpendicular plate of ethmoid bone
• vomer bone
• septal cartilage
Lateral wall
• frontal process of maxilla (mainly)
• perpendicular plate of the palatine bone
• medial pterygoid plate
• ethmoid labyrinth
• inferior conchae
• nasal bone
• lacrimal bone
Conchae and Meatus

Conchae
− curved bony projections directed downwards and
medially
1. Superior conchae Projections from
2. Middle conchae ethmoid bone
3. Inferior conchae – independent bone
Meatus
− Passages beneath the
overhanging conchae
− Paranasal sinuses
open into meatus
1. Superior meatus→ posterior ethmoidal air cells
2. Middle meatus→ ● Ethmoidal bulla middle ethmoidal air cells
• hiatus semilunaris (A deep semicircular sulcus below bulla)→Frontal sinus (anteriorly)
Anterior ethmoidal air cells (middle)
Maxillary air sinus (posteriorly)
3. Inferior meatus→ nasolacrimal duct
 Spheno-ethmoidal recess (just above the superior conchae) → sphenoidal air cells

* Roof
− horizontal – made by cribriform plate
− anteriorly – frontal bone
− posteriorly – sphenoid bone
* Floor
Hard palate = Palatine process of maxilla + horizontal plate of palatine bone
Soft palate
Mucous membrane
• Olfactory epithelium - thin
− confined to superior conchae and adjacent upper part of septum
• Respiratory epithelium - thick (mucous secretions)
Blood supply & nerve supply

Nerve supply

Blood supply
Little’s area
♦ Anterior inferior part of the septum
♦ Has rich arterial supply
♦ Anastomoses between
− Superior labial branch of facial artery
− Greater palatine artery
− Branch of sphenopalatine artery
Forms the Kisselbach’s plexus
♦ A common site for nosebleed
(epistaxis)
Paranasal sinuses
• air containing sacs lined by ciliated
epithelium
• function of the sinuses →resonators to the voice; reduce the weight of the skull
• at birth→maxillary, sphenoid present but rudimentary
• all become fully formed only in adolescence
1. Frontal sinus
• related to anterior cranial fossa and orbit
• only sinus not present at birth
• sizes vary greatly, one or both occasionally absent
Clinicals
1. closely related to frontal lobe infections may result in frontal lobe abscess
2. C.S.F rhinorrhea contralateral due to inter communication
-trickling of CSF through nostrils
-due to tearing of meningeal layers → subarachnoid space communicates with nasal cavity
(due to fracture of anterior cranial fossa involving frontal sinus)
2. Maxillary sinus (largest)
1. pyramidal shaped, within the body of the maxilla
2. opening is inefficient, superiorly placed drains the apex
3. infraorbital nerve in the groove bulges down into the roof
4. Floor separated from upper premolar, molar teeth by only a thin layer of bone. Dental roots project into
the sinus
5. Floor corresponds to the level of alveolus (not to the floor of nasal cavity)
Clinicals
1. symptoms in carcinoma of maxillary sinus
1) Medial – epistaxis, obstruction of nares
epiphorea (blocked nasolacrimal duct)
2) Orbit - diplopia + exophthalmos
infraorbital nerve facial pain, anesthesia of skin over the maxilla
3) Floor - bulging of palatal roof
4) Lateral - swelling of face
5) Posterior - palatine nerves referred pain to teeth of upper jaw
2. Infections of the maxillary sinus
 From nasal cavity
 From caries of upper molar teeth
3. Ethmoidal sinus
• Numerous, small, intercommunicating spaces (8-10)
• Lie within the labyrinth of ethmoid bone
• Divided in to anterior, middle and posterior groups
Clinicals
• related to frontal lobe - frontal lobe abscess
• C.S.F rhinorrhea
4. Sphenoid sinus
• Either side of midline, in body of sphenoid
• Drain above superior conchae (spheno-ethmoidal recess)
Clinicals
In pituitary tumor, Pituitary gland may be excised through fibre-optic trans-nasal trans-sphenoidal approach
(endoscopically)

ORAL CAVITY
PALATE
Separates the oral cavity from the nasal cavity
1.Hard palate:
Palatine plate of maxilla
Horizontal plate of palatine bone
2.Soft palate:
Divide naso & oro pharynx
Anterior surface marked by median
raphe uvula at posterior edge
* Muscles
• tensor veli palatini (tenses soft palate) Framework by the aponeurosis
• levator palatine (elevation)
• palatoglossus
• palatopharyngeus inserted to the aponeurosis
• muscular uvulae
Nerve supply - Motor
All palatine muscles→X, XI

Passavant’s ridge
excepttensor vali palatine by V Some fibres of plalatopharyngeus, Closes
pharyngeal isthmus with soft palate
if paralyzed nasal regurgitation during swallowing.
impaired voice
flat palatal arch

TONGUE
Muscles
External Internal
• genioglossus (protudes tongue) ● Vertical
• hyoglossus (depresses tongue) ● inferior longitudinal
•styloglossus(pulls upward & backwards) ● transverse
•palatoglossus (pulls upwards &backwards) ● superior longitudinal
(thus narrows oropharyngeal isthmus)
* Under aspect median frenulum linguae

either side of the frenulum deep lingual veins
* Main blood supply: lingual artery
* Lymph drainage
• tip bilaterally submental nodes
• remaining anterior 2/3 unilateral submandibular
• posterior 1/3 bilateral jugulo-omohyoid

* Nerve supply
General Taste
Anterior 2/3 Lingual(V) chorda tympani(VII)
Posterior 1/3(also the palate) IX IX
Posterior most X X
Motor supply: XII(hypoglossal nerve)
exceptpalatoglossus→cranial root of accessory nerve
Openings of salivary glands

• Parotid duct→ opposite crown of 2nd molar tooth
• Submandibular ducts→ on either side of the base of frenulum of tongue
• Sublingual ducts→ sublingual fold

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PHARYNX
Introduction
 Fibromuscular tube
 Anteriorly incomplete
 Acts as a common entrance for RS & GIT PHARYNX
Base of the skull=>Nasopharynx =>Soft palate=> Oropharynx=>Tip of Epiglottis => Laryngopharynx=>Esophagus
[Pharyngeal isthmus][C6]
Extent
Superiorly => Base of the skull –Medial pterygoid plate
Pharyngotympanic tube
Petrous temporal
Basal part of Occiptal
Inferiorly => Esophagus
Anteriorly => From above downwards – Posterior nasal apertures [Choanae]
Oropharyngeal isthmus
Laryngeal inlet
Posteriorly =>Verebral column
Pharyngeal wall
From inside to outside

• Mucosa
• Submucosa
• Pharyngobasilar fascia: Thickest in upper part
From pharyngeal raphe posteriorly
Deficient below superior constrictor
• Muscular coat:Outer circular - 3 constrictors
Inner longitudinal
Pharyngeal plexus of veins & nerves
• Buccopharyngeal fascia: extend forward across pterygomandibular raphe to cover Buccinators

Muscles
3 pairs of Constrictors =>Constrict the pharyngeal cavity
From => Posterior Opening of => Nose + Mouth+ Larynx
Superior – Pterygoid Hamulus + Pterygomandibular raphe

Middle – Stylohyoid lig. + Lesser & greater horns of hyoid
Inferior – Oblique line of thyroid =>Thyropharyngeus
Cricoid => Cricopharyngeus
Gap between 2 parts => Killian’s Dehiscence
To=>Pharyngeal Raphe [From pharyngeal tubercle to C6]

 Covers the above muscle by the below
3 pairs of Longitudinal =>Elevate the pharyngeal wall

From=> Styloid process - Stylopharyngeus
Palate - Palatopharyngeus
Auditory tube - Salphingopharyngeus
To => Inner aspect of constrictor

 Repeat campaign 2014 A/L
Gaps among constrictors
Above superior constrictor- Auditory tube + Levator palatini + Ascending palatine A.
Closed by Pharyngobasillar fascia
Bw Sup & Mid constrictors - Stylopharyngeus + CN9
Bw Mid &Inf constrictors - Internal laryngeal N. + Sup laryngeal Vessels
Piercing Thyrohyoid membrane
Below Inf constrictor - Recurrent laryngeal N. + Inf. Laryngeal Vessels
1. Nasopharynx
 base of the skull to upper surface of soft palate

 Contents
o pharyngeal tonsil- at the junction of roof and post. wall
Pathological enlargement – Adenoids - prominent in children, when chronically inflammed, mouth
breathing & cause deafness an
o Opening of auditory tube just behind the inferior nasal concha
 Posterior lip of the opening elevated [Tubal elevation] – contains tubal tonsil
 Posterior to the tubal elevation - Pharyngeal recess – related to internal carotid.
 Salpingopharyngeal fold descends downwards from tubal elevation – Overlies Salpingopharyngeus muscle
2. Oropharynx
 from lower surface of soft palate to upper border of epiglottis.
 Anterior boundary - Palatoglossal arch + Sulcus terminalis
 Contents
o Palatine Tonsils
In the lateral wall=>Tonsillar fossa
- between Palatoglossal arch – OverliesPalatoglossus &
Palatopharyngeal arch – Overlies Palatopharyngeus
- Floor[Bed]i.=Tonsillar hemicapsule
=> Condensation of pharyngobasilar fascia
ii. Loose Areolar tissue
iii. Superior constrictor
b/w capsule and sup. constrictor – paratonsillar vein – bleeding after tonsillectomy
- Posteriorly = Carotid sheath
- Contain=>lymphoid tissue covered by squamous epithelium
Pitted by crypts
Bears a deep intratonsillar cleft [2nd pharyngeal pouch]
o- Blood supply=>Tonsillar branch of facial artery, twigs from lingual, ascending palatine,
ascending pharyngeal arteries
Veins drain into pharyngeal plexus and a constant vein - paratonsillar vein
- Lymph drainage => to Jugulodigastric nodes - piercing the superior constrictor, in tonsillitis,
most commonly undergo pathalogical enlargement
 When holding liquid in the oral cavity =>Oropharyngeal isthmus is closed by

 Depression of the soft palate Lingual Tonsils
 Elevation of the back of the tongue In the mucosa covering the posterior 1/3 of the
 Movement toward the midline of the palatoglossal and tongue
palatopharyngeal folds
3. Laryngopharynx
fro upper border of epiglottis to cricoid cartilage(c6)

 Valleculae => Mucosal pouches on each side of
the midline bw the base of the tongue
 Piriform fossae => Mucosal recess, anterolaterally on either side
- bw aryepiglottic fold & Lamina of the thyroid c.
- Internal laryngeal nerve lies beneath the mucosa
- ingested
2 sharp foreign bodies may lodge (eg: fish bones) © 2015 A/L Repeat Campaign
Nerve supply
From Pharyngeal Plexus =>Chiefly lying on middle constrictor
I.Pharyngeal branch of Vagus with cranial accessory nerve fibres

II.Pharyngeal branch of glossopharyngeal
III.Pharyngeal branch of superior cervical sympathetic ganglion
 Motor
All musclesby =>CN10 - Vagus
Except Stylopharyngeus by =>CN9
 Sensory
Nasopharynx – V2
Oropharynx – CN 9
Laryngopharynx – CN 10
Deglutition - Occurs in 3 stages
1st stage = Voluntary from oral cavity in to Oropharynx

I. Tongue pushes bolus into posterior part of oral cavity
II. Oropharyngeal isthmus is closed by Soft Palate => helps to form the Bolus
III. Hyoid moves upwards & forwards – by Suprahyoid muscles
IV. Posterior tongue elevated – by Styloglossus
V. Palatoglossal arches approximated – by Palatoglossus =>push the bolus to oropharynx
2nd stage= Involuntary from oropharynx to laryngopharynx

I. Nasopharyngeal isthmus closed by soft palate & Palatopharyngeal sphinchter
II. Laryngeal inlet closed
III. Larynx & pharynx elevated
IV. Epiglottis closes
3rd stage= Involuntary from laryngopharynx to oesophagus

By inferior constrictor of pharynx
Clinicals
1) Pharyngeal Pouch [Diverticula] - Killans dehiscence

Due to neuromuscular incoordination in the 2 parts of Inferior Constrictors
If Cricopharyngeus [by recurrent pharyngeal] fail to relax,
When Thyropharyngeus [by pharyngeal plexus] contracts
=> Food bolus is pushed backwards and produces a diverticulum
Backward extension is prevented by the Prevertebral fascia
=> Project to one side of the pharynx [usually more exposed left]
With further enlargement
=> Pouch pushes the esophagus aside & lies in line with pharynx
Resulting
Food passes to the pouch => Dysphagia
Spillage of the pouch contents into the larynx => Respiratory
infections & Lung abscess
2) In Palatine tonsillitis
Referred pain in the ear
Tonsillectomy
- Lymphoid tissue is removed with the capsule
- Paratonsillar V. may be damaged
- Structures preserved
Superior constrictor => as it is separated from the capsule by loose areolar tissue
Internal Carotid A. =>as it lies within Carotid sheath covered by fatty tissue
3) Quinsy - suppuration in the peritonsillar tissue secondary to tonsillitis
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THE SUBMANDIBULAR REGION
• Area between mandible & hyoid bone including floor of mouth & root of the tongue
• includes the suprahyoid muscles (digastric, stylohyoid, mylohyoid, geniohyoid) , submandibular & sublingual
gland & submandibular ganglion
SUBMANDIBULAR SALIVARY GLAND

• Large salivary gland; not the largest
• Anterior part of the digastric triangle
• J shaped, indented by the posterior border of the mylohyoid
• Large superficial part, smaller deep part
* Superficial part
 Situated in the digastric triangle
 Enclosed between 2 layers of deep cervical fascia
Relations
 Inferior surface is covered by
- Skin
- Platysma
- Cervical branch of facial nerve
•
- Deep fascia
- Facial vein
- Submandibular lymph nodes
 lateral surface
- Submandibular fossa
- Insertion of medial pterygoid
- Facial artery
 Medial surface
- Lies against the mylohyoid muscle.
- Behind it hyoglossus, lingual nerve, hypoglossal nerve
* deep part
• Lies deep to mylohyoid
• Superficial to hyoglossus & styloglossus
• Continuous with superficial part round the
• posterior border of mylohyoid Anteriorly
extends up to posterior end of sublingual
gland
*Submandibular duct
 Emerges from anterior end of deep part
 Runs forward on hyoglossus between hypoglossal & lingual nerves
 Lingual nerve crosses at anterior border of hyoglossus
 Lingual nerve double crosses at the duct. 1. medial to lateral 2.lateral to medial
 Opens lateral to the base of the frenulum of the tongue
* Blood supply
- facial artery
- drains to common facial / lingual vein
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* Lymph drainage - To submandibular lymph node © 2015 A/L Repeat Campaign
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* Innervation
Secretomotor
Superior salivatory nucleus
Sensory root of facial nerve
Geniculate ganglion
Facial nerve
Chorda tympani nerve
Lingual nerve
Submandibular ganglion
Relay
Post ganglionic fibers
Submandibular gland and sublingual gland
Clinical
- In excision of submandibular gland incision is carried out 2.5 cm below the base of the mandible to preserve
marginal mandibular nerve
- Injury to spine of sphenoid may impair secretions from salivary glands
- Bi manual method.
SUBLINGUAL SALIVARY GLAND

 Beneath the mucosa of the floor of the mouth
 Medial to the sublingual fossa of mandible
 Ducts open on the floor of mouth
 Blood supply – lingual, submental artery
SUBMANDIBULAR GANGLION
 Parasympathetic peripheral ganglion
 Relay station for secretomotor fibers to submandibular &
sublingual salivary gland
 Topographically related to lingual nerve
 Functionally related to chorda tympani nerve
 Lies on hyoglossus muscle
 Sensory fibers reach the ganglion through lingual nerve
1. The hyoglossus muscle

a) Lies lateral to the styloglossus.
b) Has a different nerve supply from palatoglossus.
c) Has the hypoglossal nerve on its lateral surface.
d) Has the submandibular duct on its medial surface.
e) Has the submandibular gland wrapped around its posterior border.
2. The submandibular gland

Repeat campaign 2014 A/L
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a) Like the sublingual receives, its parasympathetic innervation from the facial nerve.
b) Is grooved superiorly by the loop of the lingual artery.
c) Overlies the glossopharyngeal nerve.
d) Is a mixed salivary gland.
e) Develops from 2nd pharyngeal arch mesoderm.
3. The submandibular duct

a) Lies deep to mylohyoid.
b) Opens at the base of the frenulum.
c) Passes deep to the lingual nerve.
d) Passes superficial to the lingual nerve.
e) Receives all the sublingual gland secretion.
4. The pharynx
a) Extend from the base of the skull to the 4th cervical vertebra.
b) Is supported superiorly by the pharyngobasilar fascia.
c) Is related posteriorly to the prevertebral fascia.
d) Is related anteriorly to the pretracheal fascia.
e) Has a muscular attachment to the pterygomandibular raphe.
5. The middle constrictor muscle

a) Lies medial to the superior constrictor.
b) Is attached anteriorly to the stylomandibular ligament.
c) Is attached ed anteriorly to the stylohyoid ligament.
d) Has the superior laryngeal artery between it and the inferior constrictor.
e) Is innervated by the glossopharyngeal nerve.
6. The interior of the pharynx

a) Is ridged by the salpingopharyngeus muscle.
b) Receives a sensory innervation from the accessory nerve.
c) Has the palatine tonsil in the lateral wall.
d) Receives a sensory innervation from the mandibular nerve.
e) Has an anterior extension on each side of the larynx known as the vallecula.
7. The palatine tonsil

a) Lies on the middle constrictor muscle.
b) Is a posterior relation of the palatopharyngeal muscle.
c) Has its lymph drainage to the submandibular nodes.
d) Has a sensory innervation from the vagus.
e) Is a derivative of the 1st pharyngeal arch.
8. The 2nd stage ( pharyngeal stage ) of swallowing is

a) Voluntary.
b) Initiated through the glossopharyngeal nerve.
c) Partly effected through the hypoglossal nerve.
d) Partly effected through the maxillary nerve.
e) Partly effected through the recurrent laryngeal nerve.

LARYNX
 Extent
• In the anterior midline of neck, from root of tongue
to trachea.
• In adult male C3 – C6
 Constitution
• Cartilage
 Paired- Arytenoid, Corniculate, Cuneiform
 Unpaired- Thyroid, Cricoid, Epiglottic.
• Ligaments
• Membranes
 Cartilages
Thyroid
• Right & left laminae
• Anterior borders fuse at laryngeal prominence
anteriorly
• Superior horn connected hyoid bone by
thyrohyoid membrane
• Oblique line muscles
Cricoid
• Signet-ring shaped
• Only complete cartilaginous ring in the whole
air passage
Epiglottis
• Placed in anterior wall of laryngopharynx
• Aryepiglottic fold
• Hyoepigottic ligament
• Glossoepiglottic fold
Corniculate
• Lie in posterior parts of aryepiglottic fold
Cuneiform
• Lie in aryepiglottic fold, anteriorly to
corniculate
Arytenoid
• Pyramidal shaped
• Apex articulates with corniculate cartilages
• Prolonged anteriorly to form vocal process &
laterally to form muscular process
Histology
• Thyroid, hyoid & arytenoids (basal part) –
hyaline
• Others – elastic

 Ligaments/Membranes
Extrinsic membranes/ligaments
• Thyrohyoid membrane
 Has an aperture for,
o Superior laryngeal artery
o Superior laryngeal vein
o Internal laryngeal branch of superior
laryngeal nerve
 Form the lateral wall of piriform recess
• Hyoepiglottic ligament
• Cricotracheal ligament
Intrinsic membranes/ligaments
• Quadrangular membrane
 Thin fibro elastic membrane
 Between arytenoid cartilage & epiglottis
 Lower border is a free margin, thickened to
form the Vestibular ligament (false vocal
cords)
• Cricothyroid ligament/membrane
 Mainly elastic tissue
 Anteriorly in the midline, thick band called
Median Cricothyroid ligament
 Free upper margin forms the Vocal Ligament
(True vocal cords) inserting to the vocal
process of arytenoid cartilage
 Cavity of Larynx
• extends up to lower border of cricoid cartilage

• inlet is bounded anteriorly by epiglottis, posteriorly by
inter arytenoids folds & the sides by aryepiglottic fold
• vestibular fold superiorly (opening - “rima vestibuli”)
• vocal fold inferiorly (opening – “rima glottidis”)
 Mucous membrane
• anterior surface & upper half of posterior surface of
epiglottis, the upper part of epiglottic folds & vocal
folds – stratified squamous
• others – ciliated columnar
• mucous glands absent over vocal folds
 Above vocal fold
1. superior laryngeal artery
2. superior thyroid vein
3. internal laryngeal nerve ( sensory )
4. Antero-superior (deep cervical) lymph drainage

 Below vocal fold
1. inferior laryngeal artery
2. inferior laryngeal vein
3. recurrent laryngeal nerve0 ( sensory )
4. Postero-inferior (deep cervical) lymph drainage
 Muscles
Muscles Nerves Action

External
Cricothyroid Tensor of vocal cords
laryngeal
Posterior cricoarytenoid Abduct vocal cords

Lateral cricoarytenoid Adduct vocal cords
Transverse arytenoids Adduct vocal cords
Oblique arytenoids Recurrent Adducts vocal cords
Aryepiglottic laryngeal Close laryngeal inlet
Thyroarytenoid Relax vocal cords
Vocalis Tense vocal cords
Thyroepiglotticus Open inlet
Clinicals
1. Bilateral complete damage to Recurrent Laryngeal Nerves
• Vocal cords in cadavaric position
• Phonation lost
• Breathing difficult
2. Bilateral partial damage of Recurrent Laryngeal Nerves

• Vocal folds completely adducted
• Breathing lost (Outer fibres supply abductors)

Ear
External ear
3 parts Middle ear
Inner ear
External ear
• Comprises of auricle/pinna and the external
acoustic meatus
− Auricle-mostly cartilaginous with skin closely
applied
− External acoustic meatus-
i. S shaped canal
ii. Conduct sound waves from the concha to tympanic
membrane
iii. Medial 2/3 is bony and lateral 1/3 is cartilaginous
iv. Bony part – narrower, formed by tympanic plate of
temporal bone and the squamous temporal bone,
lined by thin skin firmly adherent to the periosteum
v. Cartilaginous part – Lined by skin containing hair,
sebaceous glands and wax glands (modified sweat
glands - ceruminous)
vi. Nervous supply –
anterior ½ by auriculotemporal nerve
Posterior ½ by auricular branch of vagus nerve
**external acoustic meatus is straightened for introduction of an
otoscope by pulling the auricle upwards, backwards and
slightly laterally
Tympanic membrane
• Separates external acoustic meatus from middle ear
• Oval shaped, faces downwards, forwards and laterally
• Placed obliquely at an angle of 55 with the floor of the meatus
• Has outer and inner surfaces
• Thickened circumferentially which is attached to the tympanic sulcus of the temporal bone and
superiorly attached to the tympanic notch where the sulcus is deficient
• Outer surface – concave, lined by skin
• Inner surface – convex, provide attachment to the handle of the malleus
• Point of maximum convexity – umbo, lies at the tip of the handle of the malleus
• Greater part of the membrane tightly stretched – pars tensa
• Loose part between the two malleolar folds, thin and lax – pars flaccida
• Pars flaccida – crossed internally by chorda tympani and more likely to rupture than pars tensa

•
Nerve supply
Outer surface – anteroinferior part – auriculotemporal nerve

Posterosuperior part – auricular branch of vagus with a communicating
branch of facial nerve
Inner surface – tympanic branch of glossopharyngeal nerve through tympanic plexus
Middle ear/tympanic cavity

• Narrow, air filled space located in the petrous temporal bone
• Cube shaped with six walls
• Roof/tegmental wall – formed by tegmen tympani, separates middle ear from middle cranial
fossa and temporal lobe of the brain
• Floor/jugular wall – formed by a part of temporal bone, separates middle ear from the superior
bulb of the internal jugular vein
• Anterior/carotid wall – superior part has the opening of the canal for tensor tympani muscle
Middle part has the opening for the auditory tube
Inferior part -formed by a thin plate of bone which forms the posterior
wall of carotid canal, separates middle ear from internal
carotid artery.
• Posterior/mastoid wall –
 has an opening through which middle ear communicate with mastoid/tympanic
antrum and mastoid air cells,
 posterior canaliculus for chorda tymapni through which the nerve enter middle
ear
 has an opening for passage of the tendon of stapedius muscle.
• Lateral/membranous wall –
i. Separates middle ear from external acoustic meatus
ii. Formed mainly by tympanic membrane and partly by squamous temporal bone
iii. Petrotympanic fissure lodge anterior process of malleus and transmit tympanic branch
of maxillary artery
iv. Contain anterior canaliculus for chorda tympani nerve

• Medial/labyrinthine wall –
i. Separates middle ear from internal ear
ii. Presents – promontory : formed by first turn of cochlea, fenestra cochleae(round window),
fenestra vestibule(oval window), prominence of facial canal.
Ossicles of the middle ear
01. Malleus –
 Largest
 Most laterally placed
 Rounded head articulates posteriorly with body of incus
 Neck lies against pars flaccida
 Handle attached to upper half of tympanic membrane
 Anterior and lateral processes present, lateral processes form
malleolar folds
02. Incus –
 Anvil shaped
 body present – articulate with melleus
 two processes
 short process – attach to posterior wall of middle ear
 long process - articulates with head of stapes.

03. Stapes –
 Stirrup shaped
 small and most medially placed
 head articulates with incus
 neck provide attachment to tendon of
stapedius posteriorly
 footplate is oval shaped and fits in to fenestra vestibuli.
Muscles of middle ear

01. Tensor tympani – lies in a bony canal
above auditory tube,
Origin - walls of the canal
Insertion – handle of malleus,
Nerve supply - mandibular nerve.
02. Stapedius – Lies in a bony canal,
Origin - walls of the canal
Insertion - posterior surface of neck
of stapes
Nerve supply- facial nerve
 Both serve to damp high frequency
vibrations
Epitympanic recess
• Lateral wall of the middle ear cavity is formed by the tympanic membrane mainly and a part above it
is formed by the squamous temporal bone.
• The part of the middle ear cavity above tympanic membrane is known as epitympanic recess.
• It contains head of malleus and incus.
Mastoid Antrum
• In petrous temporal bone
• Connected to the epitympanic recess by narrow aditus
• Communicate with mastoid air cells and posteriorly related to sigmoid sinus and cerebellum
CLINICAL ANATOMY
Otitis media (middle ear infection)
• Throat infections commonly spread through auditory tube to the middle ear and cause otitis
media.
• Pus from the middle ear can take one of the following courses.
01. May discharge into external ear following rupture of tympanic membrane.
02. May erode the roof and spread upwards causing meningitis and brain abscess.
03. May erode the floor and spread downwards causing thrombosis of sigmoid sinus and internal
jugular vein.
04. May spread backwards causing mastoid abscess.

Tympanic nervous plexus
• Lies over the promontory.

• Formed by, tympanic branch of glossopharyngeal nerve + superior and inferior caroticotympanic
nerves which arise from the sympathetic plexus around the internal carotid artery.
• Supply mucous membrane of the middle ear.
Inner ear
• Lies in the petrous temporal bone.
• Consist of bony labyrinth within which there is the
membranous labyrinth.
• Membranous labyrinth is filled with endolymph
and is separated from the bony labyrinth by
perilymph.
• Bony labyrinth – consist of 3 parts.
a. Cochlea(anteriorly)
b. vestibule (in the middle)
c. semicircular canals(posteriorly)
• Membranous labyrinth –
i. Epithelium is specialized to form receptors for
sound (organ of corti), receptors for static
balance(maculae), receptors for kinetic
balance(cristae)
ii. Contains 3 parts
a. organ of corti(anteriorly)
b. maculae (within vestibule)
c. cristae(posteriorly)
• Blood supply – Mainly from labyrinthine branch of basilar artery and partly from stylomastoid
branch of posterior auricular artery.

Auditory tube/Eustachian tube
• Trumpet shaped channel connecting middle ear cavity with nasopharynx thus ensuring equal air
pressures on both sides of tympanic membrane.
• Usually closed. Opens during swallowing, yawning and sneezing.
• Is about 4cm long, directed downwards, forwards and medially.
• Divided into bony and cartilaginous parts.
Bony part –
i. Forms posterior 1/3 of the tube, 12mm long.
ii. Lie in petrous temporal bone near tympanic plate.
iii. Lateral end open on the anterior wall of middle ear and the medial end is narrow and jagged.
iv. Relations – superior : canal for tensor tympani, medial : carotid canal, lateral : chorda tympani ,
auriculotemporal nerve, spine of sphenoid and temporomandibular joint.
Cartilaginous part –
i. Forms anteromedial 2/3 of the tube and 25mm long
ii. Lies in sulcus tubae (a groove between greater wing of sphenoid and apex of petrous temporal)
iii. Made up of a triangular plate of cartilage which forms the superior and medial walls. Lateral wall
and floor are completed by a fibrous membrane.
• Blood supply – Arterial supply by ascending pharyngeal artery, middle meningeal artery and
artery of pterygoid canal.
Veins drain into pharyngeal and pterygoid plexuses of veins.
• Nerve supply –
− at the ostium : by pharyngeal branch of
− cartilaginous part: by nervus spinosus
branch of mandibular nerve,
− bony part: by tympanic plexus.

Clinicals
Dental causes( impacted wisdom tooth, caries, tooth abscess)
Temporomandibular joint
Lesions of anterior 2/3 of the tongue Mandibular nerve
lesions
Great auricular
nerve and facial EAR ACHE Vagus nerve Pharyngeal and
nerve laryngeal lesions
Glossopharyngeal nerve
Cervical spine lesions, other Tongue –

neck lesionspand geniculate posterior1/3 lesions
herpes.
Tonsillar lesions Nasopharynx lesions

NEUROANATOMY
Spinal Cord
• Extent
o Fetus – occupies the entire length of the vertebral canal
o at birth – upper border of L3
o Adult – lower border of L1
• Nearly cylindrical in shape & approximately circular in cross section
• Diameter varies in different levels
• Two enlargements – cervical (C3-T2) and lumbar (L1-S3) (where the brachial and lumbar plexus starts)
• Surrounded by 3 meninges
o Dura mater
o Arachnoid mater
o Pia mater
• End of the spinal cord is cone shaped – conus medullaris
• Dura matter ends at S2
• Filum terminale (Prolongation of pia mater) pierces the dura at S2 and ends at its attachments to the dorsum of coccyx
• As the spinal cord is shorter than the vertebral column, lower spinal nerves have a long downward course –cauda equina
• Spinal cord is a segmented structure
Spinal segments
- Area of spinal cord that gives origin to single spinal nerve
-Spinal nerve arises from spinal cord by number of rootlets
- Spinal cord is shorter than vertebral canal so spinal segments do not align with vertebral segments
Vertebral level Spinal level
Cervical +1
T1 – T6 +2
T7 – T9 +3
T10 L1/L2
T11 L3/L4
T12 L5
L1 Sacral/Coccygeal
Spinal meninges
- 3 Coverings
1. Dura mater
 Dense, strong, outermost, fibrous membrane
 Inferiorly extends upto S2 vertebral level
 Extends along spinal nerves
 Attaches to epineurium of nerve
2. Arachnoid mater
 Delicate and impermeable
 Extends along spinal nerves
 Subarachnoid space extends along spinal nerves upto intervertebral foramen
 Ends on filum terminale at S2 level
3. Pia mater
 Vascular membrane
 Extends laterally to form tooth like extensions which attach to inner
surface of dura mater-“Ligamenta denticulata”  22 pairs, hold spinal
cord in position.

Spinal nerves
• 31 paired spinal nerves
Dorsal root – afferent nerve fibers
Ventral root – efferent nerve fibers
• Dorsal / ventral rootlets cross the sub arachnoid space and unite to form mixed nerve as coming through Intervertebral foramina
• Dorsal root bears dorsal root ganglia
• C1- C7 nerves run superior to corresponding vertebrae
• C8 runs between C7 and T1 vertebrae
• Other nerves run inferior to vertebrae of same number
• C1 nerve has only motor fibers
• S5 and Coccygeal nerve have only sensory fibers
Clinicals-
 Lumbar Puncture
• To obtain CSF
• Spinal cord ends at lower border of L1
• Subarachnoid space extends to the lower border of S2
• Below 1 lumbar vertebrae can be used to do a lumbar puncture. Usually done between 4th / 5th
st
• Flexed position – open the space between adjoining laminae

• Structures that are pierced,
o Skin
o Superficial fascia
o Supraspinous ligament
o Interspinous ligament
o Ligamentum flavum
o Areolar tissue with the internal vertebral venous plexus
o Dura mater
o Arachnoid mater sub arachnoid space
Blood supply
Longitudinal and segmental vessels
3 longitudinal arteries  Arise from vertebral artery
o One anterior spinal artery – anterior 2/3 of spinal cord
- runs in the anterior median fissure
o 2 posterior spinal arteries – posterior 1/3 of spinal cord
Segmental arteries
o Lower cervical
o Lower thoracic
o Upper lumbar
o The great anterior segmental artery of Adamkiewicz - Large, arise from aorta unilaterally
- Major source of supply to lower 2/3
o Posterior intercostal arteries
 Plexus in pia mater supplies peripheral parts of anterior and lateral white columns.
Venous drainage
• Internal and external venous plexuses
• Have connections
Internal structure
• Outer white matter, inner gray matter
• Amount of gray matter α amount of muscles that innovate, skin, viscera
• Larger in cervical and lumbar
• The absolute amount of white matter is greater in cervical levels
• Decrease progressively at lower levels because descending fibers shed as they descend and ascending fibers
accumulate as they ascend.

Spinal gray matter
• Dorsal gray horn / ventral gray horn
• Gray communicants connect dorsal – ventral horns
• H shaped - “butterfly” shaped
• Dorsal horn – termination of primary afferent fibers
• Ventral horn –alpha efferent and gamma efferent nerves
• A small intermediate lateral horn is present at the thoracic and
lumbar levels
Dorsal gray horn

• The dorsal horn is a major receptive zone of primary afferent fibers
• 4 nerve cell groups
o Substantia gelatinosa
o Nucleus proprius
o Nucleus dorsalis (Clarke’s column)
o Visceral afferent nucleus
Lateral gray horn

• First thoracic to 2nd / 3rd lumbar segments
• Preganglionic sympathetic fibers
• Similar group of cells found in 2nd , 3rd ,4th sacral segments for parasympathetic fibers
Ventral gray horn

• Most nerves are large and multipolar
• Alpha efferent – innervates skeletal muscles
• Gamma efferent – innervates intrafusal muscle fibers of neuromuscular spindles
• 3 nerve cell groups
o Medial o Central o Lateral
Cell group Position in gray matter Extend Action
Substantia gelatinosa Apex of dorsal column Throughout of Pain, temperature, touch, pressure
Nucleus proprius Anterior to s.gelatinosa its length Proprioception, vibration
DORSAL
Base of dorsal root, Proprioception from neuromuscular

Nucleus dorsalis C8-L3/L4
medially spindles
Visceral afferent Base of dorsal root, Visceral afferents
T1-L3
nucleus laterally
Sympathetic Lateral gray column T1-L3/L2 Preganglionic sympathetic
Lat
Parasympathetic Lateral gray column S2, S3, S4 Preganglionic parasympathetic

Medial part of ventral Most of Skeletal muscles of trunk
Medial
column segments
Central Phrenic Central part of ventral C3-C5 Diaphragm
VENTRAL
Accessory column C1-C5/6 Trapezius, sternocleidomastoid

lumbosacral L2-S1 Unknown
Lateral part of ventral Cervical and Skeletal muscles of upper and lower
lateral
column lumbar segments limb

Spinal White matter
• Surrounds the central gray matter
• Contains nerve fibers, neuroglia, blood vessels
• Most nerve fibers arranged longitudinally
• Arranged in 3 large masses either side of spinal cord - dorsal, lateral and ventral columns
• Fibers of common function, common origin, destination are grouped as ascending and descending tracts within columns
• Narrow dorsal and ventral white commissure run between two halves of the spinal cord
• Fibers may vary in caliber, size, myelinated, non-myelinated
• Significant overlap between adjacent tracts occur
• Ascending tracts –
o Afferent fibers
o Dorsal root
o Carry afferent to supra spinal levels
• Descending tracts –
o Long fibers
o Descends from supra spinal levels to synapse with spinal nerves
• Intersegmental tracts –
o Short ascending and descending tracts that originate and end within the spinal cord
 Tract – Group of fibers in CNS that have common origin, course and termination
 Nucleus – Group of nerve cells that have common cellular features and giving rise to fibers that have common
path, termination and function
 Decussation – Fibers from right cross to left side and fibers from left cross to right
 Ipsilateral – Fibers that enter spinal cord pass on the same side
 Contralateral – Those who cross to opposite side
Ascending tracts
 Dorsal column
o Fasciculus gracilis - Tract of Goll
o Fasciculus cuneatus – Tract of Burdach
 Lateral column
o Lateral spinothalamic
o Anterior and posterior spinocerebellar
o Spino reticular
 Ventral column
o Anterior spinothalamic
o Spinotectal
o Spino-olivary
Lateral spinothalamic tract

First order neuron
o Pain and temperature sensation
o Free nerve endings as receptors
o Aδ fibers – fast conducting; sharp pain
o c fibers – slow conducting; prolonged, burning pain
o Enter the spinal cord through dorsal root
o Cell bodies – dorsal root ganglion
o Terminated by synapsing with the cells in the dorsal gray column, substantia gelatinosa
Second order neuron

o 2nd order neurons cross obliquely to the opposite side in the anterior gray and white commissure
o Within one spinal segment
o Ascend up to thalamus
o Somatotopic organization can be seen - fibers crossing at any level join the deep aspect of those that already crossed
o Tracts are segmentally laminated

o In medulla oblongata spinothalamic tract lies near the lateral surface and between the
inferior olivary nucleus and spinal nucleus of trigeminal
o Then it is accompanied by anterior spinothalamic tract and spinotectal tract to form
spinal leminiscus
o In the mid brain it lies in the tegmentum lateral to medial leminiscus
o Fibers of the lateral spinothalamic tract end by synapsing with the third order neurons
In the ventral posterolateral (VPL) nucleus of the thalamus
In the thalamus
• Crude pain and temperature sensation
• Localization is poor and dull
• Emotional reaction initiated
Third order neuron

o Passes from thalamus to post central gyrus of cerebral cortex
o Fibers pass through the posterior limb of internal capsule and the corona radiata
o Interpretation of sensory information at the level of consciousness
o The contralateral half of the body is represented as inverted
Anterior spinothalamic tract

First order neuron
• Enter the spinal cord through dorsal root
• Terminated by synapsing with the cells in the dorsal gray column,
substantia gelatinosa
Second order neuron
• 2nd order neurons cross very obliquely (across several segments) to the
opposite side in the anterior gray and white commissure
• Then it is accompanied by lateral spinothalamic tract and spinotectal tract
to form spinal leminiscus
• Synapse - ventral posterolateral (VPL) nucleus of the thalamus
Third order neuron
• Passes from thalamus to post central gyrus of cerebral cortex
• Through the posterior limb of internal capsule and the corona radiata
• Interpretation of sensory information (touch and pressure) at the level of
consciousness
• The contralateral half of the body is represented as inverted
Dorsal columns
Has 2 large ascending tracts
o Fasciculus gracilis
o Fasciculus cuneatus
Discriminative touch, proprioception and vibration sensation
High portion of myelinated fibers
First order neurons

• Dorsal root ganglion and passes directly to the dorsal white
column of the same side
• Many fibers ascend upward as fasciculus gracilis and fasciculus cuneatus
• fasciculus gracilis – throughout the length of spinal cord and fibers from
sacral to lower 6 thoracic spinal nerves
• fasciculus cuneatus – starts from 6 thoracic spinal nerve and fibers from
upper 6 thoracic and cervical spinal nerves
• fibers ascend in the same side
• arranged in a somato topical manner
• lower fibers are more medially and upper fibers are more laterally
• 1st order neurons terminate by synapsing with nucleus gracilis and
nucleus cuneatus of medulla oblongata

Second order neuron
• Internal arcuate fibers cross anteromedially around the central gray matter and cross the median plane
• decussate with the corresponding fibers of the opposite side – the sensory decussation
• fibers then ascend as a simple single compact bundle – the medial lemniscus, throughout the medulla, pons and mid brain
• synapse with 3rd order neurons in the ventral posterolateral nucleus in the VPL nucleus of the thalamus
Third order neuron

• Leave the thalamus and pass through the posterior limb of the internal capsule and corona radiata
• To the somatosensory area in the post central gyrus of cerebral cortex
• The contra lateral half of the body is represented inversely
Other ascending pathways

1. Anterior/posterior spinocerebellar tract
• First order neuron – Receives unconscious proprioception
- Posterior root fibers pass to Clarke’s column
• Second order neuron
- Ascend on the same side upto medulla as Posterior spinocerebellar tract
- Enter cerebellum via inferior cerebellar peduncle
- majority cross to the opposite side and ascend as Anterior spinocerebellar tract
- Enter cerebellum through superior cerebellar peduncle
- Fibers cross back within cerebellum
2. Spino tectal tract – Cross to opposite side
- Afferent information for visual reflexes and bringing about movements
of eye and head towards the source of stimulation
3. Spino reticular tract – Uncrossed tract
-Afferent pathway for reticular formation, important in influencing level of consciousness
4. Spino olivary tract – Cross midline
- Enter cerebellum through inferior cerebellar peduncle
Tract Lateral spinothalamic Anterior spinothalamic Fasciculus gracilis/ Fasciculus cuneatus

1st order neuron Dorsal root ganglion
2nd order neuron Substantia gelatinosa Nucleus gracilis & Nucleus cuneatus
Point of decussation Cross obliquely within Cross obliquely across spinal Medulla (sensory decussation)
same spinal segment segments
Leminiscus Ant + Lat spinothalamic + spinotectal =spinal leminiscus Medial leminiscus
3rd order neuron VPL nucleus of thalamus
3rd order neuron
Posterior central gyrus
termination
action Pain and temperature Touch and pressure 2-point discrimination, vibration,
proprioception

Descending Tracts
General arrangement
First order neuron (UMN) – Has cell body in the cerebral cortex. Axon descends to spinal cord.
Second order neuron – Internuncial neuron situated in anterior gray column.
Third order neuron(LMN) - In anterior gray column. Innervates skeletal muscles.
- Originate primarily in the cerebral cortex and numerous sites within the brain stem
- Control of the movements, muscle tone, posture, modulation of spinal reflexes
 Lateral column
o Lateral corticospinal tract
o Rubrospinal tract
 Ventral column
o Anterior corticospinal tract
o Vestibulospinal tract
o Tectospinal tract
o Reticulospinal tract
o Olivospinal tract
Corticospinal tract (pyramidal tract)

Corticospinal fibers facilitate α motor neurons
• Responsible for rapid skilled movements
• Arise as axons of neurons of the cerebral cortex
• About one-third of the fibers originate from the primary
motor cortex (area 4), one-third originate from the
secondary motor cortex (area 6), and one-third originate
from the parietal lobe (areas 3, 1, and 2)
• Descend down – corona radiata, posterior limb of internal
capsule, ventral part of the midbrain in the cerebral
peduncle (middle 3/5)
• As they continue through the pons the are separated from
its ventral surface by transversely running pontocerebellar fibers
• In medulla they form a discrete bundle, the pyramids,
longitudinal elevation on the ventral surface of medulla
• Just superior to the spino-medullary junction 90% of the
fibers in the pyramids cross the median plane – motor decussation
• Continue caudally as lateral corticospinal tract
• 10% of uncrossed fibers descend as anterior corticospinal
tracts
• Somatotopic organization –cervical fibers medially; sacral
fibers laterally
• As it descends progressively diminish in size
• Terminate in the anterior gray column of all the spinal cord
segments
• Most corticospinal fibers synapse with internuncial neurons, which, in turn, synapse with α motor neurons
and some γ motor neurons
• Only the largest corticospinal fibers synapse directly with the motor neurons.
Other descending pathways

o Reticulospinal tract
o Rubrospinal tract
o Descending autonomic fibers
o Vestibulospinal tract
o Tectospinal tract

Clinical
UMN lesion
Pyramidal tracts Extrapyramidal tracts

• When skin of the sole scratched • Spastic paralysis
(Loss of inhibition)
Babinski sign present • No muscle atrophy
(normal - plantar flexion of big toe) (LMN intact)→
• Corticospinal tract lesion • Exaggerated deep muscle reflexes & clonus
- Dorsiflexion due to the influence of other descending tracts (Loss of inhibition)
- Loss of performance of voluntary fine skilled movements
- Superficial abdominal reflexes absent • Clasp knife reaction
- Cremasteric reflex absent
Lower motor neuron lesion

 Flaccid paralysis
 Muscle atrophy
 Loss of reflexes
 Muscular fasciculation
Types of paralysis
 Hemiplegia- paralysis of one side of the body
 Monoplegia- paralysis of one limb
 Diplegia- paralysis of 2 corresponding limbs
 Paraplegia- paralysis of both legs
 Quadriplegia- paralysis of all 4 limbs
Spinal shock syndrome

• Clinical condition following acute severe damage to the spinal cord
• All the cord functions below
• level of the lesions become depressed /lost
o Sensory impairment o Flaccid paralysis
Syndrome Cause At the level of the lesion Below the level of the lesion
Sensory Motor Sensory Motor
Complete cord Bullet hole All gone bilaterally LMN type lesion All gone Bilaterally UMN type lesion
transaction Stab wound -post. Grey column -Ant. Gray column (pain & temp- from the level -descending tracts
Touch& pressure- 2/3 segments below) -asc. tracts
Brown Sequard Fracture dislocation Ipsilateral band of LMN type lesion Pain & temp-contralateral from the level UMN type lesion
syndrome Bullet cutaneous loss Ipsilateral Touch & pressure –contralateral 2/3 segments Ipsilateral
Stab wound below
Proprioception / 2point discrimination/ vibration –
ipsilateral from the level
Anterior cord Fracture dislocation UMN lesion bilateral Pain temp. touch & press. UMN type lesion
syndrome Injury to ant spinal (ant grey column) Bilateral -Ant corticospinal
artery Ant/lateral spinothalamic -Extrapyramidal tracts
Proprio/2point discrimination preserved
Central cord Hyperextension of Bilateral loss of pain temperature, Bilateral spastic paralysis with
syndrome the cervical region light touch and pressure characteristic sacral sparing,
of spinal cord because of lamination
Syringomyelia Development LMN weakness spasms in the Loss of pain and temp. –bilateral Bilateral spastic paralysis with positive
abnormality in the small muscles of hand -crossing fibres damaged Babinski reflex
formation of central -ant grey column Vibration and proprioception normal • Horner’s syndrome
canal Descending autonomic fibres
Poliomyelitis Viral infection of the LMN type paralysis, mostly in
neurons of the ant. lower limb, respiration is
Grey column affected due to paralysis of
intercostal muscles and
diaphragm

Brain stem
It consists of 3 parts
• Medulla oblongata
• pons
• mid brain
• In the posterior cranial fossa of the skull
• Pathway for ascending & descending tracts
• Reflex center (CVS, RS) Are located in the brainstem
• Cranial nerve nuclei
Cranial nerve nuclei

Mid CN 3
brain CN 4 Mesencephalic
Pons CN 6
CN 7 Motor
CN 5
Main sensory
Medulla CN 8
CN 9
Spinal nucleus
CN 10 (NA, NTS, DNV)
CN 11
CN 12

Medulla oblongata
Gross appearance
• Connects superiorly with the pons and inferiorly spinal cord
• Conical in shape , its broad extremity being directed superiorly
• In the upper part of medulla the central canal expands as cavity of the 4th ventricle
• Each side of the anterior median fissure is the pyramid
• The pyramids taper inferiorly at the level of motor decussation (decussation of the pyramids)
• Posterolateral to pyramids – olives
• Posterior to olives – inferior cerebellar peduncle
• The roots of the glossopharyngeal and vagus nerves and the cranial roots of accessory nerve
• The posterior surface of the superior half of the medulla forms the lower part of the floor of the fourth
ventricle
• On each side of posterior median sulcus, there is an elongated swelling – the gracilis tubercle, and lateral to
that is cuneate tubercle

Internal structure
Internal structure of the medulla oblongata is considered at 4 transverse levels
1. Level of decussation of pyramids
2. Level of sensory decussation (level of decussation of lemnisci)
3. Level of the olive
4. Just inferior to pons
Level of decussation of pyramids
• Decussation of pyramids – cortico spinal tract

• The decussation displace the central canal dorsally
• The fasciculus gracilis and fasciculus cuneatus continue to ascend superiorly posterior to the central gray matter
• Substantia gelatinosa –spinal nucleus of trigeminal nerve
Level of sensory decussation
• Dorsal columns decussate at this level

• Anteriorly to the central gray matter and posterior to pyramids
• Lemnisci have been formed from the internal arcuate fibers
• Which have emerge from the anterior aspect of the nucleus gracilis and nucleus cuneatus
• The anterior and lateral spinothalamic tracts and spinotectal tracts unite and form spinal lemniscus
Levels of olives
• Section pass through the inferior part of 4th ventricle
• The amount of gray matter is increased at this level
• Olivary nuclei complex
• Nuclei of vestibulocochlear, glossopharyngeal, vagus, accessory, and hypoglossal nerves and the arcuate
nuclei
Olivary nuclei complex

• Largest nucleus – inferior olivary nucleus
• Smaller dorsal and medial accessory olivary nuclei also are present
• Afferent fibers to inferior olivary nucleus from spinal cord ( spino-olivary tract ) and from the cerebrum and
cerebral cortex
• Inferior olivary nucleus send fibers to cerebellum through inferior cerebellar peduncle
• Function – associated with voluntary muscle movements
Vestibulocochlear nuclei
• 4 vestibular nuclei
o Medial vestibular nucleus
o Inferior vestibular nucleus
o Lateral vestibular nucleus
o Superior vestibular nucleus
• 2 cochlear nuclei
o Anterior cochlear nucleus
o Posterior cochlear nucleus
Nucleus ambiguus
• The nucleus ambiguus consists of large motor neurons
• Situated deep within the reticular formation
• Motor nucleus of glossopharyngeal, vagus and cranial part of the accessory nerve
• Distributed to voluntary muscles
Central gray matter

• Central gray matter lies beneath the floor of the 4th ventricle at this level
• From medial to lateral
o Hypoglossal nucleus
o Dorsal nucleus of vagus
o Nucleus of tractus solitarius
o Medial and inferior vestibular nuclei
• Anteriorly - pyramids
• Medial leminiscus formes a flattened tract on each side of the midline posterior to the pyramids
• Medial longitudinal fasciculus situated on each side of midline posterior to the medial lemniscus
• It’s a small tract of nerve fibers with ascending and descending fibers
• It connects 3, 4, 6, 8 cranial nerves
• The inferior cerebellar peduncle is situated posterolaterally
• Spinal tract of trigeminal nerve/nucleus are situated anteromedial aspect of inferior cerebellar peduncle
• Reticular formation is consists of a diffused mixture of nerve fibers and small group of nerve cells
• It is deeply placed posterior to the olivary nucleus
• The glossopharyngeal, vagus and cranial part of accessory nerves can be seen running forward and laterally
through the reticular formation
• The nerves emerge between the olives and inferior cerebellar peduncle
• The hypoglossal nerve also run anteriorly and laterally through the reticular formation and emerge between
pyramids and the olives
Level of just inferior to the pons

• No major changes
• The lateral vestibular nucleus has replaced the inferior vestibular nucleus
• Cochlear nuclei are visible on the anterior and posterior surface of the inferior cerebellar peduncle
Pons
Gross appearance
• Connects the medulla oblongata and midbrain
• Anterior to cerebrum
• Pons – “bridge” that connect right and left hemispheres
• The anterior surface is convex from side to side
• Shows many transverse fibers that converge on each side to form the middle cerebral peduncle
• Shallow groove in mid line – basilar groove , basilar artery lodge there
• Trigeminal nerve emerge from the anterolateral surface of pons
• In the groove between medulla and pons there emerge abducent, facial and vestibulocochlear nerves
• Posterior surface is covered from cerebellum
• It forms the upper half of the floor of the fourth ventricle and is triangular in shape
• The posterior surface is limited laterally by the superior cerebellar peduncles and is divided into symmetrical
halves by a median sulcus

Internal structure
• Pons is commonly divided in to
1. Tegmentum – posteriorly
2. Basal part – anteriorly
• Internal structure of the pons is considered at 2 transverse levels
1. Transverse section through the caudal part, passing through the facial colliculus
2. Transverse section through the cranial part, passing through the trigeminal nuclei
Transverse section through the caudal part, passing through the facial colliculus
• Medial leminiscus rotates as it passes from medulla to pons to the most anterior part of the tegmentum with
its long axis running transversely
• The medial lemniscus is accompanied by spinal and lateral lemnisci
• Laterally and posteriorly to the medial lemniscus is the facial nucleus
• Medial and posterior to the facial nucleus is the abducent nucleus
• Fibers of the facial nerve wind around the abducent nucleus and produce facial colliculus
• The medial longitudinal fasciculus is situated beneath the floor of the fourth ventricle on either side of the
midline
• The medial vestibular nucleus is situated lateral to the abducent nucleus
• The posterior and anterior cochlear nuclei are also found at this level
• The trapezoid body is made up of fibers derived from the cochlear nuclei and the nuclei of the trapezoid body
• The corticopontine fibers of the crus cerebri of the midbrain terminate in the pontine nuclei, which are small
masses of nerve cells situated in the basilar part of the pons
• The axons of these cells give origin to the transverse fibers of the pons , forms the main pathway linking the
cerebral cortex to the cerebellum
Transverse section through the cranial part, passing through the trigeminal nuclei
• Similar to the caudal part

• Contains the motor and main sensory nucleus of the trigeminal nerve
• The motor nucleus of the trigeminal nerve is situated beneath the lateral part of the fourth ventricle within the reticular
formation
• The principal sensory nucleus of the trigeminal nerve is situated on the lateral side of the motor nucleus
• The superior cerebellar peduncle is situated posterolateral to the motor nucleus of the trigeminal nerve
• It is joined by the anterior spinocerebellar tract
• The trapezoid body and the medial lemniscus are situated in the same position as they were in the previous section
• The lateral and spinal lemnisci lie at the lateral extremity of the medial lemniscus
Midbrain
Gross appearance
• Connect the pons and the cerebellum with the forebrain
• The midbrain is traversed by a narrow channel, the cerebral aqueduct
• On the posterior surface are four colliculi, rounded eminences that are divided into superior and inferior pairs
by a vertical and a transverse groove
o Superior colliculus - centers for visual reflexes
o Inferior colliculus - lower auditory centers
• The trochlear nerves emerge from the posterior surface of midbrain, below the inferior colliculi
• The superior brachium passes from the superior colliculus to the lateral geniculate body and the optic tract
• The inferior brachium connects the inferior colliculus to the medial geniculate body
• Interpeduncular fossa, the deep depression in the midline

• It is bounded on either side by the crus cerebri
• Many small blood vessels perforate the floor of the interpeduncular fossa - the posterior perforated
substance
• The oculomotor nerve emerges from a groove on the medial side of the crus cerebri
Internal structure
• Midbrain comprise 2 lateral halves – cerebral peduncles
• Midbrain is divided in to 3 parts
1. Crus cerebri
2. Tegmentum
3. Tectum
• Crus cerebri is the most anterior
• Tegmentum is posterior to crus cerebri and it is divided by a pigmented band of gray matter, substantia nigra
• Narrow cavity of the midbrain is the cerebral aqueduct which connect the 3rd and 4th ventricles
• Tectum is posterior to cerebral aqueduct
• Internal structure of the pons is considered at 2 transverse levels
1. Transverse section at the level of inferior colliculus
2. Transverse section at the level of superior colliculus
Transverse section at the level of inferior colliculus
• Consisting of a large nucleus of gray matter

• Inferior colliculus receives many of the terminal fibers of the lateral lemniscus
• The pathway then continues through the inferior brachium to the medial geniculate body
• The trochlear nucleus is situated in the central gray matter close to the median plane just posterior to the
medial longitudinal fasciculus
• Fibers of the trochlear nucleus pass laterally and posteriorly around the central gray matter and leave the
midbrain just below the inferior colliculi.
• The mesencephalic nuclei of the trigeminal nerve are lateral to the cerebral aqueduct
• The decussation of the superior cerebellar peduncles occupies the central part of the tegmentum
• The medial lemniscus ascends posterior to the substantia nigra
• The spinal and trigeminal lemnisci are situated lateral to the medial lemniscus and the lateral lemniscus is
posterior to the trigeminal lemniscus.
• The crus cerebri contains important descending tracts and is separated from the tegmentum by the
substantia nigra
• The corticospinal and corticobulbar fibers occupy the middle 2/3 of the crus.
• The frontopontine fibers occupy the medial part of the crus
• The temporopontine fibers occupy the lateral part of the crus
Transverse section at the level of superior colliculus

• Superior colliculus forms part of the visual reflexes. It is connected to the lateral geniculate body by the superior
brachium.
• It receives afferent fibers from the optic nerve, the visual cortex, and the spinotectal tract
• The oculomotor nucleus is situated in the central gray matter close to the median plane, just posterior to the
medial longitudinal fasciculus
• The fibers of the oculomotor nucleus pass anteriorly through the red nucleus to emerge on the medial side of
the crus cerebri in the interpeduncular fossa.
• The medial, spinal, and trigeminal lemnisci form a curved band posterior to the substantia nigra
• But the lateral lemniscus does not extend superiorly to this level
• The red nucleus is a rounded mass of gray matter situated between cerebral aqueduct and substantia nigra
• Afferent fibers reach the red nucleus from
o The cerebral cortex through the corticospinal fibers
o The cerebellum through the superior cerebellar peduncle
o The lentiform nucleus, subthalamic and hypothalamic nuclei, substantia nigra, and spinal cord
• Efferent fibers leave the red nucleus and pass to
• The spinal cord through the rubrospinal tract (as this tract descends, it decussates)
o The reticular formation through the rubroreticular tract
o The thalamus
o The substantia nigra
• Descending tract arrangement in the crus is same as the inferior colliculus level
o The corticospinal and corticobulbar fibers - middle 2/3
o The frontopontine fibers - medial part of the crus
o The temporopontine fibers - lateral part of the crus
Lemnisci
• anterior spinothalamic
Spinal lemniscus • lateral spinothalamic
• spinotectal → VPL nucleus (thalamus)
• nucleus cuneatus
Medial lemniscus • nucleus gracilis
Trigeminal lemniscus • sensory nuclei of CN 5 →VPM nucleus (thalamus)
Lateral lemniscus • superior olivary & trapezoid body →medial geniculate body
Note
Medial longitudinal fasciculus→ connect CN 3, 4, 6, 8
Applied neuroanatomy
Brainstem lesions
• ipsilateral cranial nerve damage
• contralateral hemiparesis
• contralateral sensory loss in the body
Brainstem lesions
Medulla oblongata Pons Mid brain
• Vascular disorders • Pontine hemorrhage • Vascular disorders

- Medial medullary syndrome • Tumors of pons - Weber syndrome
- Lateral medullary syndrome • Infections of pons - Benedikt’s syndrome
• Raised pressure • Trauma to midbrain

- Downward herniation of the • Blockage of cerebral
medulla and cerebellar aqueduct
tonsils through the foramen
magnum

Medulla oblongata
• Vascular disorders
Blood supply
• Posterior inferior cerebellar artery (from vertebral artery)
• Medullary artery (from vertebral artery)
• Anterior inferior cerebellar artery (from basilar artery)
Lateral medullary syndrome

Cause: Thrombosis in PICA or vertebral artery
1. Analgesia &thermoanesthesia on ipsilateral face Spinal nucleus of trigeminal (CN 5)
2. Vertigo, nausea, vomiting, nystagmus Vestibular nuclei (CN 8)
3. Dysphagia & dysarthria Paralysis of ipsilateral palatal & laryngeal muscles
(Nucleus Ambiguus) (CN 9,10,11)
4. Loss of pain & temperature (contralateral body) Spinal lemniscus (spinothalamic tracts)
5. `Ipsilateral Horner’s syndrome Descending sympathetic fibers
6. Ipsilateral cerebellar signs(ataxia) Inferior cerebellar peduncle
Medial medullary syndrome

Cause: thrombosis of medullary branch of vertebral artery
1. Contralateral hemiparesis Pyramidal tract
2. Contralateral loss of proprioception & 2point discrimination Medial leminiscus
3. Ipsilateral tongue paralysis (deviate to paralyzed side when protruded) Hypoglossal nerve

Pons
Tumor of pons
1. Weakness of jaw muscles Motor nucleus of trigeminal nerve (CN5)
2. Weakness of ipsilateral facial muscles Facial nerve (CN 7)
3. Paresis of lateral rectus Abducent nucleus (CN 6)
4. Nystagmus, vertigo Vestibular nuclei (CN 8)
5. Impairment of hearing Cochlear nuclei (CN 8)
6. Contralateral hemiparesis, quadriparesis Pyramidal tracts
7. Anesthesia to light touch in face(pain & Main sensory nucleus of CN 5 (spinal nucleus intact)
temperature preserved)
8. Contralateral sensory defects in trunk Medial & spinal lemnisci
9. Ipsilateral cerebellar signs Cerebellar peduncle/corticopontocerebellar fibers
Pontine hemorrhage
The pons is supplied by the basilar artery and the anterior, inferior, and superior cerebellar arteries
1. facial paralysis on the side of thelesion facial nerve nucleus

2. paralysis of the limbs on the opposite side corticospinal fibers as they pass through the pons
unilateral
3. paralysis of conjugate ocular deviation the abducent nerve nucleus and the medial
longitudinal fasciculus
1. the pupils may be “pinpoint” ocular sympathetic fibers
2. bilateral paralysis of the face and the limbs corticospinal fibers and facial nerve nucleus
Bilate
3. poikilothermic (body temperature varies severe damage to the pons has cut off
l
with the environment) the body from the heat-regulating centers in the hypothalamus
Midbrain
Vascular lesions of midbrain
Weber syndrome
• Cause: Occlusion of a branch of a posterior cerebral artery
• There is ipsilateral ophthalmoplegia – damaged medal
longitudinal fasciculus
• Contralateral paralysis of the lower part of the face, the
tongue, and the arm and leg
• The eyeball is deviated laterally
• There is drooping (ptosis) of the upper lid and the pupil is
dilated and fixed to light and accommodation.
Benedikt’ssyndrome
• Similar to Weber syndrome
• But the necrosis involves the medial lemniscus and red
nucleus
• Contralateral hemianesthesia and involuntary movements
of the limbs ofthe opposite side

1.Explain the term decussation. (10)
Describe the motor & sensory decussations in the medulla. (60)
State briefly the changes in sensory & motor functions in lesions above and below each decussation. (30)
(AL2002 main)
2. Sixty-year-old hypertensive female patient complains of imbalance& difficulty in speaking. She also complains
of nausea & vertigo. On examination she was found to have right sided palatal paralysis, loss of pain &
temperature sensation over the right side of the face. There were also positive cerebellar signs on the right side.
a) Where is the most possible site of the lesion?
b) What is the most possible cause?
c) Explain the above signs & symptoms
d) What other clinical features would you expect to find in this patient?
3. Draw & label a cross section at the trigeminal level of the pons to show the position of the ascending &
descending tracts (50 marks)
Give the commencement & the termination of these tracts (50 marks)
4. Draw a labeled diagram of the transverse section through the pons at the level of the facial nucleus (40)
On what anatomical basis would you differentiate between UMN lesion& LMN lesion of the facial nerve (20)
5. Draw & label a diagram of the midbrain at the level of inferior colliculus (30)
Describe the trochlear nerve from its origin to its termination (70)
T/F
1. Facial colliculus is formed by facial nucleus.
2. Facial nerve curves over the 6th cranial nerve to form facial colliculus.
3. Spinal lemnisci are most posterior in the lower part of the mid brain.
4. Trochlear nerve leaves the brainstem on its dorsal aspect.
5. Hypoglossal nerve leaves the brainstem between olives & inferior cerebellar peduncles.

CEREBELLUM
− Consists of two hemispheres and a vermis.

− 3 peduncles
− Superior – midbrain with cerebellum
− Middle – pons with cerebellum
− Inferior – medulla oblongata with
cerebellum
− 3 lobes
− Anterior
− Middle / posterior (largest)
− Flocculonodular
− 3 fissures
− Primary - separates anterior and middle
lobes
− Uvulonodular - separates middle and
flocculonodular lobes
− Horizontal - no importance
Outer cortex (gray matter)
− Cerebellum consists of Inner white matter
Intracerebellar nuclei
Outer cortex
• Larger sheets with folds → arbor vitae appearance

− Structural layers of cortex: (My Poor Granny from
superficial to deep)
− Molecular cell layer – outer stellate, inner basket cells
− purkinje cell layer – purkinje cells, Golgi type 1 neurons
− granular cell layer – granular cells, Golgi cells
− Functional areas of cortex:
− Vermis (vestibulo-cerebellum) - axial movements
− intermediate zone (spino-cerebellum) - distal limb
movements
− lateral zone (cortico-cerebellum) - planning sequential
movements
Internal white matter
− Afferent fibres → via inferior and middle cerebellar

peduncles
− Intrinsic fibres
− Efferent fibres → via superior and inferior cerebellar
peduncles

Intracerebellar nuclei:
− Dentate, emboliform, globose, fastigial

(Dental Embolies Grow Fast from
lateral to medial)
− Cerebellar outflows from fastigial
nucleus run through inferior peduncle,
while ouflows from other nuclei run
through superior peduncle)
Cerebellar cortical mechanism

− Cortex receives 2 main types of afferent
inputs
1. Climbing fibres (olivocerebellar tract)
2. Mossy fibres (all other afferents)
− They are excitatory to purkinje cells
− Inhibitory cells: Stellate, Basket, Golgi cells
Cerebellar afferent fibres

Brain stem, spinal cord, cerebrum→mossy fibres→granular cells→parellal fibres→purkinje cells
Inferior olivary nucleus→climbing fibres→purkinje cells
• From cerebrum
− Corticopontocerebellar pathway (middle peduncle)
− Cerebroolivocerebellar pathway (inferior peduncle)
− Cerebroreticulocerebellar (middle, inferior
peduncles)
• From spinal cord
− Anterior spinocerebellar tract (superior peduncle)
− Posterior spinocerebellar tract (inferior peduncle)
− Cuneocerebellar tract (inferior peduncle)
• Vestibular afferents

Cerebellar efferent fibres
• Entire output via purkinje cells
• Purkinje cells→deep cerebellar nuclei→efferent
fibers from deep nuclei→brain stem→spinal cord,
cerebrum
− Globose-emboliform-rubral pathway (superior
peduncle)
− Dentothalamic pathway (superior peduncle)
− Fastigial vestibular pathway (inferior peduncle)
− Fastigial reticular pathway (inferior peduncle)
Blood supply of cerebellum
• Basilar artery
• Superior cerebellar artery
• Anterior inferior cerebellar artery
• Posterior inferior cerebellar artery
Functions of cerebellum
Cerebellum has no direct neuronal connections with the lower motor neurons, but exerts its influence
indirectly through the cerebral cortex and brainstem.
 Coordination of precise movements (cerebellum survey as a comparator)
How?
1. By continuously comparing the output of the motor area of cerebral cortex with the proprioceptive
information received from the site of muscle action.
2. Bringing about necessary adjustment by influencing the activity of the lower motor neurons.
 Control tone and posture
 Control of equilibrium
 Control of voluntary movements

CLINICALS
Signs & symptoms are limited to the same side of the body.
1. Hypotonia
2. Postural changes & alterations of gait
3. Ataxia- disturbance of voluntary movement.
-Decomposition of movement.
(Muscle groups fail to work harmoniously)
-Past pointing with gross corrections.
4. Dysdiadochokinasia-inability to perform alternating movements regularly and rapidly
5. Disturbance of reflexes
-pendular knee jerk
6. Disturbance of ocular movements
Nystagmus-rhythmical oscillation of eyes
7. Disorder of speech-Dysarthria(slurred speech)

THE CEREBRUM
Diencephalon – central core
• Divided into 2 parts Telencephalon – cerebral hemispheres
• The largest part of the brain, Situated in the anterior and middle cranial fossae
• Developed from the forebrain
• Each hemisphere has a covering of gray matter, the cortex and internal masses of gray matter, the basal nuclei, and
a lateral ventricle
Cerebrum
Diencephalon the third ventricle and the structures that Telencephalon

form its boundaries - Cortex (Gray matter)
- 3rd ventricle - Internal white matter
- the thalamus - Basal ganglia
- subthalamus - Lateral ventricle
- epithalamus
- hypothalamus
Diencephalon
• Extent – from interventricular foramen of Monroe to commencement of cerebral aqueduct.
• Inferior surface – anterior to posterior – optic chiasma, infundibulum with tubercinereum, mammillary
bodies
• Superior wall – roof of 3rd ventricle
• Lateral wall – internal capsule
• Medial wall – thalamus, hypothalamus (lateral wall of 3rd ventricle)

Thalamus
• on either side of 3rd ventricle
• Relays all sensations except olfactory
• Important in crude sensation (for detailed localization & interpretation→cerebral cortex) – pain &
temperature
• Below – hypothalamic sulcus
Relations
● Anterior - Interventricular foramen of Monroe
● Posterior - Forms pulvinar which overhangs superior colliculus
telachoroidea, fornix
choroid plexus of lateral ventricle
● Superior -
body of the caudate nucleus (thalamus forms a part of the floor of the body of lateral
ventricle)
Hypothalamus
● Inferior - tegmentum of mid brain
3rd ventricle
● Medial - interthalamic connection (gray matter)
internal capsule
● Lateral - lentiform nucleus
● Poster superiorly - Epithalamus (pineal gland + 2 habenular nuclei)

Important thalamic nuclei
Ventral posterior nucleus
Ventral posterolateral Ventral posteromedial

Relays spinal & medial lemnisci Relays trigeminal & taste
(sensations from the body) (sensations from face)
lateral geniculate body (LGB) -relays vision (optic tract)

medial geniculate body (MGB) - relays hearing (lateral lemniscus → inferior colliculus)
3rd ventricle
• Slit like cleft between 2 thalami
• Anterior wall – lamina terminalis with anterior commissure
• Posterior wall – opening of cerebral aqueduct,
posterior commissure
pineal recess
habenular commissure
• Roof – ependymal + telachoroidea,
Choroid plexus of 3rd ventricle,
More above - fornix & corpus callosum
• Floor – optic chiasma,
tubercinerium
infundibulum
mammillary bodies
cerebral peduncles
tegmentum
• Lateral wall – thalamus
hypothalamus
• Communicate,
o Anteriorly – lateral ventricle (via interventricular foramen)
o Posteriorly – 4th ventricle (via cerebral aqueduct)
Regarding the thalamus
a) Has the body of the fornix on its superior aspect.

b) Is separated from the lentiform nucleus by the external capsule.
c) Has bands of gray matter connecting the thalami of both sides.
d) Has the medial lemniscus ending in its VPL.
e) Has the anterior pole forming the posterior boundary of the interventricular foramen.

Hypothalamus
• Controls autonomic nervous system
• Controls endocrine system (via the pituitary gland)
• Maintains body homeostasis, emotion & behavior
• Controls body temperature, hunger, thirst,
fatigue, sleep, and circadian cycles, sexual
behavior
Relations
● Anterior - optic chiasma
lamina terminalis
anterior commissure
● Posterior - tegmentum of the mid brain
● Superior - thalamus
● Inferior - optic chiasma
tuber cinereum & infundibulum
mammillary bodies
● Medial - 3rd ventricle
Hypothalamo - hypophyseal tract
• Supraoptic nucleus - Vasopressin
• Paraventricular nucleus - oxytocin
Clinical syndromes of hypothalamus
• Carried by axons to the pituitary
• Obesity/wasting
Hypophyseal portal system • Sexual disorders
• Carries releasing & release inhibitory hormones to the pituitary • Sleep disorders
(GnRH, GHRH, GHIH)
• Hyperthermia/hypothermia
• Formed by the superior hypophyseal artery of the internal carotid
• Diabetes insipidus
Epithalamus
• consists of the habenular nuclei and the pineal gland
Subthalamus
• Lies inferior to the thalamus
• Superior to the tegmentum of the mid brain

Sulci
Gyri
Telencephalon
Parietal
Cerebral cortex
• thin layer of gray matter Fronta
• The largest part of the brain
Temporal Occipital
• Two hemispheres are
separated by a deep midline
sagittal fissure, the
longitudinal cerebral fissure.
• In the depths of the fissure,
the corpus callosum connects
the hemispheres.
• The surface of each cerebral
hemisphere is thrown into
folds or gyri, which are
separated from each other by
sulci or fissures
• Each hemisphere is divided in
to lobes which are named
according to the cranial
bones under which they lie.
o Frontal
o Parietal
o Temporal
o Occipital

Important cortical areas
• Frontal lobe
o Precentral area
• Primary motor area (4) -
carry out the individual
movements of different
parts of the body
• Premotor area, secondary
motor area - store
programs of motor activity
assembled as the result of
past experience
o Frontal eye field - control
voluntary scanning
movements of the eye and
is independent of visual
stimuli
o Motor speech area of Broca
- formation of words by its
connections with the
adjacent primary motor
areas
o Prefrontal cortex - the
makeup of the individual's
personality
• Parietal lobe
o Primary somatic sensory
cortex (SI)
o Secondary somesthetic area
(SII)
o Somesthetic association
area–stereognosis
• Occipital lobe
o Primary visual area (17) -
afferent from LGB
o Secondary visual area (18) -
relate the visual information
received by the primary visual area to past visual experiences, thus enabling the individual to recognize and
appreciate what he or she is seeing
o Occipital eye field - reflex and associated with movements of the eye when it is following an object
• Temporal lobe
o Primary auditory area (41, 42)
o Secondary auditory area (22) – interpretation of sounds and for the association of the auditory input with other
sensory information
o Sensory speech area of Wernicke - permits the understanding of the written and spoken language and
enables a person to read a sentence, understand it, and say it out loud.

BASAL GANGLIA
• Collection of grey matter in cerebral hemisphere.
• Control voluntary movements by influencing the cortex (no direct control on descending pathways)
• Set posture before a movement
1. Caudate nucleus
Separated almost entirely by the internal capsule
2. Lentiform nucleus
I. Globus pallidus
II. Putamen
3. Amygdaloid nucleus
4. Claustrum
Lentiform nucleus
Corpus Striatum
Caudate nucleus
Caudate nucleus
 C shaped
 Closely related to lateral ventricle
 Lateral to thalamus
 Laterally internal capsule
Lentiform nucleus
 wedge shaped
 Medially – internal capsule –
seperates it from caudate nucleus
and thalamus
 Laterally – external capsule –
seperates it from claustrum
Diseases of basal ganglia
Huntington’s disease - Chorea

(involuntary jerky movements)
Parkinson’s disease
1. Resting tremor (pill rolling tremor)
2. Lead pipe rigidity (cogwheel, plastic)
3. Bradykinesia (slurred speech,
expressionless face, can’t initiate
movements)
4. Postural instability (Shuffling gait)

Internal white matter
1. Commissural fibers - between 2 hemispheres
 corpus callosum
 anterior & posterior commissures
 fornix
 habenular commissure
2. Association fibers - various cortical regions of the same hemisphere
3. Projection fibers - afferents & efferent from brainstem to cortex
 Internal capsule
 corona radiata
 optic radiation
Commissural fibers
1. Corpus callosum- At the
bottom of the longitudinal
cerebral fissure
2. Anterior commissure-
Rostrum (continuous with
the lamina terminalis)
3. Posterior commissure
4. Hippocampal
commissure - Genu, body,
splenium
5. Fornix – from
hippocampus to
mammillary bodies

Internal capsule
• Compact band of fibers
• Separates the caudate
nucleus and the thalamus
from the putamen and the
globuspallidus
• Contains both ascending and
descending fibers
• In a transverse section the
internal capsule is V-shaped
• The bend in the V is the genu
• The anterior limb is between
the head of the caudate
nucleus and the lenticular
nucleus
• The posterior limb is
between the thalamus and
lenticular nucleus
• The retrolenticular part
contains fibers from the
optic system, coming from
the lateral geniculate
nucleus of the thalamus.
More posteriorly, this
becomes the optic radiation
• The sublenticular part

contains fibers connecting
with the temporal lobe.
These include the auditory
radiations
• The anterior limb of the
internal capsule contains:
o Frontopontine fibers
project from frontal
cortex to pons
o Thalamocortical fibers connect the thalamus to the frontal lobes
• The genu contains corticobulbar fibers, which run between the cortex and the brainstem.
• The posterior limb of the internal capsule contains
1) corticospinal fibers
2) sensory fibers (including the medial lemniscus and the anterolateral system) from the body
Blood supply
1. Middle cerebral artery- medial & lateral striate central branches
2. Anterior cerebral artery- central branches
3. anterior choroidal artery
• Anterior limb: middle cerebral artery (superior half) & anterior cerebral artery (inferior half)
• Genu: middle cerebral artery
• Posterior limb: middle cerebral artery (superior half) & anterior choroidal artery of the internal carotid artery
(inferior half)
Lesions
• Cause: high blood pressure
• Even a small lesion causes severe damage
• contralateral hemiparesis or hemiplegia
1. Regarding the thalamus
a) Has the body of the fornix on its superior aspect.
b) I s separated from the lentiform nucleus by the external capsule.
c) Has bands of gray matter connecting the thalami of both sides.
d) Has the medial leminiscus ending in its VPL.
e) Has the anterior pole forming the posterior boundary of the interventricular foramen.
2. Regarding the cerebrum,

a) Motor area for speech is supplied by the central branch of the middle cerebral artery.
b) The lower limb areas extend to the medial surface.
c) The fibres of the cortical tract lie in the genu and the posterior limb of the internal capsule.
d) Fibres in the optic radiation pass to both parietal and temporal lobes.
3. Regarding the basal ganglia

a) The lentiform nucleus joins the head of the caudate nucleus.
b) The head of the caudate nucleus lies in the floor of the anterior horn of the lateral ventricle.
c) The internal capsule lies between the caudate and lentiform nuclei.
d) In damage to the basal ganglia there is paralysis of the muscles of the opposite side of the body.
e) Dopamine is the chief neurotransmitter.
4. The thalamus
a. Is limited anteriorly by the interventricular foramen
b. Overlies the midbrain anteriorly
c. Lies in the floor of the body of the lateral ventricle
d. Forms the medial relation of the anterior limb of the internal capsule
e. Is related medially to the third ventricle
5. The globus pallidus

a. Forms the lateral part of the lateral ventricle
b. Send afferent fibers to the venteroanterior nucleus of the thalamus
c. Lies adjacent to the internal capsule
d. Receive its main afferent fibers from the claustrum
e) Is separated from the insula by the claustrum
6. The internal capsule

a) Lies lateral to caudate nucleus
b) Carries somatosensory fibers in the posterior limb
c) Carries fibers from the ventroanterior nucleus in the posterior limb
d) Carries pyramidal tract fibers in the posterior limb
e) Carries visual radiation
7. The caudate nucleus c) Forms the superior relation of the anterior perforated substance
a) Lies on the convexity of the lateral ventricle d) Send most of its efferent fibers in the striaterminalis
b) Forms part of the corpus striatum e) Has a narrow tail
8. Regarding the basal ganglia

a) The lentiform nucleus joins the head of the caudate nucleus.
b) The head of the caudate nucleus lies in the floor of the anterior horn of the lateral ventricle.
c) The internal capsule lies between the caudate and lentiform nuclei.
d) In damage to the basal ganglia there is paralysis of the muscles of the opposite side of the body.
e) Dopamine is the chief neurotransmitter.
9. Components of the basal nuclei include

A) Caudate Nucleus
B) Lentiform Nucleus
C) Red Nucleus
D) Amygdaloid Nucleus
E) Claustrum
The autonomic nervous system controls the internal environment of the body
Controlled by higher centers
Anterior – parasympathetic
1. Hypothalamus Posterior – sympathetic
2. Lower brainstem Vasopressor
Vasodilator
Cardio accelerator
Cardio deaccelerator
Respiratory center
3. Cerebral cortex
Through hypothalamus
Limbic system
Autonomic Ganglia Autonomic Plexuses Enteric Nervous System
Autonomic ganglia
Basic structure
Preganglionic neuron Postganglionic neuron

Myelinated Ganglion Non-myelinated
Relatively slow conducting B fibers Relatively slower conducting C fibers
One preganglionic axon→synapse→several post ganglionic neurons

Visceral receptors→chemoreceptors, baroreceptors, osmoreceptors, pain receptors
Sympathetic nervous system

Outflow(preganglionic) → thoracolumbar outflow
Lateral grey column (horns) T1 - L2 (L3)
Preganglionic nerve fiber leave through anterior nerve root
Pass via white ramus communicantes to paravertebral ganglia of sympathetic trunk
Sympathetic ganglion – preganglionic fibers synapse with post ganglionic neuron
Lies lateral to vertebral column as a chain

1. They synapse with a postganglionic neuron in the
ganglion. The postganglionic nonmyelinated axons
leave the ganglion and pass to the spinal nerves as
gray rami communicantes (the gray rami are gray
because the nerve fibers are devoid of myelin).
They are distributed in branches of the spinal nerves
to smooth muscle in the blood vessel walls, sweat
glands, and arrector muscles of the hairs of the skin.
2. They travel superiorly in the sympathetic trunk to
synapse in ganglia in the cervical region. Many of the
preganglionic fibers entering the lower part of the
sympathetic trunk from the lower thoracic and upper
two lumbar segments of the spinal cord travel
inferiorly to synapse in ganglia in the lower lumbar
and sacral regions.
3. They may pass through the ganglia of the sympathetic trunk without synapsing. These myelinated
fibers leave the sympathetic trunk as
I. greater splanchnic (5-9 II. lesser splanchnic (9-11 III. least splanchnic
thoracic ganglions) thoracic ganglions) nerves (12th thoracic
It descends and pierces the crus It descends with the greater ganglion)
of the diaphragm to synapse with splanchnic nerve and pierces the The least splanchnic nerve (when
the ganglia of the diaphragm to join with the ganglia present) pierces the diaphragm,
i. celiac plexus in the lower part of the celiac and synapses with the ganglia of
ii. renal plexus plexus. the renal plexus
iii. suprarenal medulla.

Sympathetic trunk – ● in the Neck - anterior to transverse processes of cervical vertebrae
● Thorax – anterior to the heads of the ribs or on the sides of the vertebral bodies
● Abdomen – anterolateral to the sides of the bodies of the lumbar vertebrae
● Pelvis – anterior to the sacrum
Ganglion impar
Afferent →Without synapsing in ganglion via white rami communicantes → Posterior root ganglion
(myelinated)
afferent component of local reflex arc Central axons
Ascend to higher centres
Supra-renal medulla
A few preganglionic fibers, traveling in the greater splanchnic nerve, end directly on the cells of the
suprarenal medulla. These medullary cells, which may be regarded as modified sympathetic excitor
neurons, are responsible for the secretion of epinephrine and norepinephrine.
CERVICAL SYMPATHETIC TRUNK
• The sympathetic chain continues upwards from thorax by crossing the neck of the first rib
• Then ascends embedded in the posterior wall of the carotid sheath to the base of the skull
• No white rami communicans from cervical part of sympathetic chain
• Preganglionic fibres origin from lateral grey horn of T1-T4 & ascend to the cervical ganglia.
• 3 ganglia –Superior, Middle, Inferior
Superior cervical ganglion (fusion of C1-C4 ganglia)
• Largest
• Lies opposite C2 and C3 vertebrae
• Sends grey rami communicantes to C1-4 spinal nerves
Middle cervical ganglion (fusion of C5-C6 ganglia)

• Lies level with C6 vertebra
• Sends grey rami to C5 and 6 nerves

Inferior ganglion (fusion of C7-C8 ganglia)
• Lies level with C7 Tucked behind the vertebral artery
• Frequently fuses with the first thoracic ganglion to form stellate ganglion at the
neck of the first rib.
• Grey rami pass from it to C7 and 8 nerves
Superior Cervical Ganglion
Internal carotid plexus External carotid plexus
Ciliary Ganglion Pterygopalatine Otic Ganglion Submandibular

ganglion Ganglion
Dilator pupillae Lacrimal gland Parotid gland Submandibular &
Sublingual gland
Parasympathetic nervous system

Outflow – brainstem parasympathetic nuclei
Craniosacral outflow
Pelvic splanchnic nerves (S2, S3, S4)
Parasympathetic ganglia – lies close to the viscera

• Cranial outflow
1. Ciliary
2. Pterygopalatine
3. Submandibular
4. Otic
• Sacral outflow
• Pelvic splanchnic nerves synapse in ganglia of hypogastric
plexuses
Afferent – cell bodies sensory ganglia of cranial serves
(myelinated) posterior root ganglia of sacrospinal nerves
SYMPATHETIC PARASYMPATHETIC
Action Prepares body for emergency Conserves & restores energy
Outflow T1 - L2(3) Cranial nerves III, VII, IX, & X;
S2,3 & 4
Preganglionic fibres Myelinated B Myelinated B
Ganglia Paravertebral (sympathetic trunks), Small ganglia close to viscera
prevertebral (ex: celiac, superior (eg: otic, ciliary) or ganglion cells
mesenteric, inferior mesenteric) in plexuses
(eg: cardiac, pulmonary)
Neurotransmitter within ganglia Acetylcholine Acetylcholine
Postganglionic fibres Long non-myelinated C Short non-myelinated C
Characteristic activity Wide spread due to many post-ganglionic Discrete action with few post
fibres & liberation of epinephrine & ganglionic fibres
norepinephrine from supra renal medulla.
Neurotransmitter at postganglionic Norepinephrine at most endings & Acetylcholine at all endings
endings acetylcholine at few endings (sweat glands)
Higher control Hypothalamus Hypothalamus

Autonomic plexuses
Large collections of sympathetic and parasympathetic efferent nerve fibers and their
associated ganglia, together with visceral afferent fibers, form autonomic nerve plexuses.
Thorax
1. Cardiac plexus
Sympathetic – cardiac nerves, fibers from upper thoracic ganglia
2. Pulmonary plexus
Parasympathetic – vagal fibers
3. Esophageal plexus
Abdomen
1. Coeliac plexus Sympathetic – Greater, lesser, least splanchnic nerves, upper two
2. Superior mesenteric plexus lumbar splanchnic nerves
3. Inferior mesenteric plexus Parasympathetic – vagal fibers (coeliac branch of posterior gastric
nerve)
4. Superior hypogastric plexus Sympathetic – lower two lumbar splanchnic

Parasympathetic – pelvic splanchnic nerves
Pelvis
1. Inferior hypogastric plexus
The postganglionic fibers arise from the peripheral plexuses and are distributed to the
smooth muscle and glands of the viscera.

Two parasympathetic plexuses of nerve cells and fibers extend continuously along and
around the length of the gastrointestinal tract from the esophagus to the anal canal.
Submucous/Meissner plexus between mucous membrane and control of the glands of the
circular muscle layer mucous membrane
Myenteric/Auerbach plexus between circular and longitudinal controls muscle and

muscle layers movements of the gut wall

CLINICALS
1. Horner’s syndrome
1. Partial ptosis – slight drooping of the eyelid –partial paralysis of levator palpebrae
2. Miosis – constriction of the pupil –due to unopposed parasympathetic innervation via CNIII
3. Anhydrosis –loss of sweating –sudomotor denervation
4. Enophthalmos – retraction of the eyeball
Due to interruption of the sympathetic nerve supply to the head and neck.
Causes
- Lesion in the brain stem or cervical part of the spinal cord- damage to the descending tracts from
hypothalamus (Reticulospinal tract)
-Lesion of the preganglionic fibre from the T1 spinal segment

Multiple sclerosis, syringomyelia, Compression from a cervical rib, Klumpke’s paralysis
-damage to the postganglionic fibres from the superior cervical ganglion
2. Argyll Robertson pupil

– Does not contracts in response to the light
– Contracts in accommodation
– Because lesion of the fibres from the pretectal nucleus to the Edinger Westphal nuclei due to mostly
neurosyphilis
3. Frey’s syndrome
– Nerves will supply the sweat glands instead of the salivary tissue (sweating at the time of salivation)
– Nerves will supply the lacrimal gland instead of submandibular and sublingual (tearing with salivation)
called crocodile tears
4. Hirschsprung’s disease
– Aganglionic segment in the colon
– No peristalsis
– Proximal colon distended
5. Vagotomy
– Delayed gastric emptying
– Diarrhoea
The autonomic nervous system:

a. Supplies the glands, smooth muscles & cardiac muscle.
b. Rises from the special visceral column of the spinal cord.
c. Has peripheral ganglia near the walls of the organ it supplies.
d. Prepares the body for fight & flight.
e. Has no distribution to the lower limbs.
2. The sympathetic nervous system:

a. Has myelinated postganglionic fibers passing from the sympathetic trunk to the spinal nerves.
b. Has trunks extending from the base of the skull to the coccyx.
c. Has usually only 5 ganglia in the sympathetic trunk.
d. Fibers passing to the head & neck leave the spinal cord in the 5th-8th cervical spinal nerves.
e. Sends preganglionic fibers to the cortex of the suprarenal gland.

Cranial Nerves
• 12 pairs
• For head & neck (vagus-also thorax & abdomen)
sensory motor Mixed
I III V
II IV VII
VIII VI IX
XI X
XII
Nerve sensory motor parasympathetic Opening in the skull

I Olfactory smell - - Cribriform plate
II Optic vision - - Optic canal
III Occulomotor - Eye muscles – MR, Ciliary body Superior orbital fissure
SR, IR, IO, levator Constrictor pupillae
palpebrae superioris
IV Trochlear - Superior oblique - ““

(LR6SO4)
V Trigeminal Face Muscles of - V1 – superior orbital fissure
Scalp mastication
Cornea Mylohyoid V2 – foramen rotundum
Paranasal sinuses Anterior belly of
Nasal cavity digastric V3 – foramen ovale
Anterior 2/3 of tongue Tensor palatine
Oral cavity tensor tympani
VI Abducent - Lateral rectus - Superior orbital fissure
(LR6SO4)
VII Facial Anterior 2/3 of tongue Stapedius Submandibular Internal acoustic meatus
Mouth floor taste Muscles of facial Sublingual Facial canal
Palate expression Lacrimal Stylomastoid foramen
Posterior belly of Nasal and palatine
digastric glands
Stylohyoid
Scalp muscles
VIII Vestibulocochlear Inner ear - - Internal acoustic meatus
IX Glossopharyngeal Posterior 1/3rd of the tongue stylopharyngeus Parotid gland Jugular foramen
Carotid sinus
Carotid body
X Vagus viscera viscera Blood vessels Jugular foramen
viscera
XI Accessory - Jugular foramen
~Cranial Muscles of larynx,
pharynx, soft palate
~Spinal Trapezius,
sternocleidomastoid
XII Hypoglossal - Tongue muscles - Hypoglossal canal

Cranial nerve
Motor part Sensory part
Alar plates – sensory root

Basal plate – motor root
Therefore motor roots and nuclei are medial to the sensory root and nuclei
Motor part arrangement

Axons whose cell bodies are in the brainstem.
Cell bodies (LMN) = motor nucleus
Motor nucleus receives impulses from cerebral cortex via corticonuclear tracts.
Corticonuclear tract
Pyramidal cells (precentral gyrus) corona radiata genu of the internal capsule CN nucleus
Bilateral connections are present for all the motor nuclei except,
1. Part of the facial nucleus that supply the muscles of the lower part of the face
2. Part of the hypoglossal nerve that supply the genioglossus muscle
Therefore, unilateral corticonuclear lesions will not produce symptoms except in the above nerves.
Sensory part arrangement

First order neuron -Axons whose cells are outside the brain
Cell bodies are situated in the ganglion on the nerve trunks (= posterior root ganglion of spinal nerves)
or in the sensory organ- nose, eye, ear
Second order neuron – Cells and axons of the cranial nerve nucleus
Axons cross the midline and synapse with the thalamus/nuclei of termination/another sensory nuclei
Third order neuron – Terminates in the cerebral cortex

CN 1 - OLFACTORY NERVE
Central processes of olfactory hair cells in the olfactory mucosa pass through the cribriform
plate to synapse with mitral cells in olfactory bulb.
Axons of mitral cells pass as olfactory tract to uncus (1ry olfactory cortex)
Fibres do NOT relay in thalamus
Bilateral anosmia – due to fracture of anterior cranial fossa associated with CSF rhinorrhoea.
CN 2 - OPTIC NERVE
• Fibers=axons of the ganglionic cells
• Leave the eye at the optic disc (medial to the center- blind spot)
• Fibers are myelinated. BUT from oligodendrocytes (comparable to CNS- a tract not a nerve)
• Optic chiasma→ fibers of the nasal half of the retina decussate

• Optic chiasma is situated at the junction of anterior wall and floor of the 3rd ventricle
• Posterolateral angles of optic chiasma are continuous with optic tracts.
• Most of the fibers terminate by synapsing in Lateral Geniculate Body (LGB)
o Directed via optic radiation to the visual cortex (area 17)
• Fibers related to light reflex leave the optic tract →join pretectal nucleus in the superior
colliculus of the mid brain

CN 3 - OCULOMOTOR NERVE
Nuclei
Main motor nucleus - anterior part of the grey matter surrounding cerebral aqueduct
-at the level of superior colliculus
Edinger-Westphal nucleus (parasympathetic) - posterior to main motor nucleus
- Connect with pretectal nuclei of both sides
Connections
→ Corticonuclear fibers from both hemispheres
→Via medial longitudinal fasciculus connect with CN 4, 6, 8
→Visual cortex
Course
Intraneural
Through red nucleus
Anterior surface of mid brain
Intracranial
Inter peduncular fossa
B/w superior cerebellar & posterior cerebral arteries
Middle cranial fossa
Lateral wall of the cavernous sinus (above CN 4)
Divides into superior & inferior divisions
Orbit- through middle part of the superior orbital fissure (SONIA)
Posterior communicating artery
Distribution
• Motor –superior division (+symp) 1. superior rectus
2.levator palpebrae superioris
Superior cervical ganglion → Postganglionic sympathetic fibres → Internal carotid cavernous plexus →
Superior division of occulomotor nerve → Smooth muscle part of the LPS
-inferior division 1.medial rectus

2.Inferior rectus
3.Inferior oblique (gives off the branch to ciliary ganglion)
• Parasympathetic (ciliary ganglion→ short ciliary nerves) 1. ciliary muscle
2. constrictor pupillae of iris
Clinical
Total paralysis in CN 3
Ptosis Levator palpebrae superioris
Lateral squint Paralysis- medial rectus
Unopposed action of lat rectus
Dilatation of pupil Paralysis-constrictor papillae
Loss of accommodation Paralysis-ciliary muscle
Slight proptosis(forward projection of eye) Loss of integrity of muscle cone
Diplopia(double vision)

Trochlear nerve(CN 4)
• Most slender CN
• Only CN to leave the posterior surface of the brain stem
Nuclei- Trochlear nucleus
• Anterior part of the grey matter around cerebral aqueduct
• At the level of the inferior colliculus
Connections → Corticonuclear fibers from both hemispheres
→medial longitudinal fasciculus
→visual cortex
Course
Intraneural
1. Posteriorly around grey matter
Intracranial
1. Dorsal aspect of the mid brain
2. Decussate (attached to superior medullary velum)
3. Ventrally around the superior cerebellar & cerebral peduncles
4. Between superior cerebellar & posterior cerebral arteries
5. Lateral wall of the cavernous sinus (b/w CN3 & CN51)
6. Crosses over CN 3
Extracranial
1. Orbit through lateral part of the superior orbital fissure (LFT)
Distribution -Superior oblique muscle( turns eye downwards & laterally)
Clinical
Diplopia on looking downwards
Extortion effect

Abducent nerve (CN 6)
Nucleus
• Floor of the 4th ventricle
• Beneath facial colliculus - pons
Connections → Corticonuclear fibers from both hemispheres
→ medial longitudinal fasciculus
Course
Intraneural
1. Pass anteriorly through the pons
2. Leave it through the groove b/w pons & medulla (above pyramids)
Intracranial
1. Longest intracranial course
2. Cisterna pontis
3. Sharp bend over the superior surface of the petrous temporal bone
4. Through cavernous sinus (inferolateral to internal carotid artery)
Extracranial
1. Orbit →middle part of the superior orbital fissure (inferolateral to CN 3 & nasociliary) (SONIA)
2. Enter the occular surface of the lateral rectus muscle
Clinical
Complete paralysis
1. Medial (convergent) squint
2. Diplopia
False localizing sign in raised intra cranial pressure
Due to
1. long course
2. Sharp bend over petrous temporal bone
-Downward shift of brainstem due to raised intracranial pressure

Visual reflex
Direct & consensual light reflex
If a light is shown in to an eye pupils of both eyes constrict
● Same eye- direct
● Opposite eye- consensual
1. Optic nerve
2. Optic chiasma
3. Optic tract
4. Pretectal nucleus
5. Edinger-Westphal nucleus of both sides
6. CN 3
7. Ciliary ganglion
8. Short ciliary nerves
9. Constrictor pupillae muscle
Accommodation reflex
When eyes are directed from a distant to near objects
1. Medial recti contract -Occular axis converge
2. Ciliary muscle contract -Lens thickens & refractive power increases
-direct light waves to the thickest central part of the lens
3.Pupils constrict 1. Optic nerve
2. Optic chiasma
3. Optic tract
4. Lateral geniculate body
5. Optic radiation
6. Visual cortex
7. Eye field of the frontal cortex
● CN 3 nucleus →medial recti
● Edinger-Westphal nucleus of both sides
CN 3
Ciliary ganglion
Short cilliary nerves
Constrictor pupillae & ciliary muscle
Corneal reflex
Light touching of cornea results in blinking of the eye (V1→MLF→VII)

The 3rd cranial nerve
a) Is related to the 4th and the 6th in the cavernous sinus.

b) Closely related to the posterior communicating artery.
c) Supplies the lateral rectus muscle
d) Leaves the brain stem through the interpeduncular fossa
e) Enters the inferior rectus muscle on its ocular aspect
Trochlear nerve
a) Leaves the brainstem on its dorsal aspect

b) Is exclusively a motor nerve
c) Pass between the superior cerebellar & posterior cerebellar arteries
d) crosses over the CN 3 in the anterior part of the cavernous sinus
e) Is important in light leflex
Regarding optic nerve
a) when damaged to optic chiasma bitemporal hemianopia results

b) is covered by dura upto eyeball
c) cannot regenerate after destruction
d) is connected to the CN 3 via pretectal nucleus
e) is connected to CN 3,4,,8 via the medial longitudinal fasciculus
Regarding abducent nerve
a) winds over the superior border of the petrous temporal bone

b) gives rise to false localizing sign
c) when damaged lateral squint results
d) lies inferomedial to the internal carotid artery in the cavernous sinus
e) travels on the superior border of the lateral rectus muscle

FACIAL NERVE CN-7
• Nerve of the 2nd branchial arch.

• Both motor & sensory, facial colliculus level
Components-
•SVE - muscles of face & scalp
Stapedius, posterior belly of digastric & stylohyoid
•SVA - taste from anterior 2/3 of tongue
•GVE - submandibular & sublingual salivary glands.
•GVE - lacrimal gland
nuclei-
3. Main motor
lacrimatory
2. Parasympathetic in pons
sup. Salivatory
3. Sensory - NTS
Main motor
–lower part of the pons (at the level of facial colliculus)
•Part of nucleus that controls the muscles of lower half of the face receive corticonuclear fibres only
from contralateral cerebral hemisphere.
•Upper part from both cerebral hemispheres.
Lesion at A – No paralysis
Lesion at B – paralysis of lower part of the

contralateral face
Lesion at C – paralysis of ipsilateral face
Parasympathetic--
same level
-fibers from hypothalamus
Sensory-
Taste- anterior 2/3 of tongue
Floor of mouth
Palate
• Taste sensation travels through axons of cells situated in geniculate ganglion. (1st order)
• Central processes synapse on cell bodies of NTS.
• Efferents (2nd order neurons) from NTS cross the medial plane and ascend to VPM nucleus to
thalamus.
• From the thalamus fibers (3rd order neurons) pass through internal capsule, corona radiata
to taste area of cortex.
NTS VPM of
Lingual Chorda Facial thalamus
nerve tympani nerve
Tongue Geniculate cortex
Course- ganglion
Intracranial-
-Consists of motor & sensory root
-motor fibers travel posteriorly around the medial side of the abducent nucleus. (facial colliculus)
-sensory root + parasympathetic root→Nervus intermedius
Emerges through CP angle
Secretomotor to sublingual
Laterally in the post. Cranial fossa & submandibular gland,
gustatory to ant.2/3 of
In internal acoustic meatus (IAM) with 8th nerve tongue.
Secretomotor to
Bottom of the IAM-sensory & motor roots fuse
Lacrimal gland
Enters the facial canal
To submandibular ganglion
Pterygopalatine Directed laterally above the vestibule joined by lingual nerve
ganglion
Sharp bend
Through petrotympanic fissure
Greater petrosal Geniculate ganglion to infratemporal fossa
Runs above the promontory

Middle ear
Bend gradually
Vertically downwards medial to aditus

Chorda tympani
Nerve to stapedius Stylomastoid foramen (6mm above stylomastoid
foramen)
Posterior auricular, occipitalis
Nerve to stylohyoid
Muscular branch
Nerve to posterior belly of digastric
Crosses styloid process laterally
Enters the posteromedial surface of parotid gland
Crosses external carotid artery & retromandibular vein superficially
Temporofacial Cervicofacial
Temporal Zygomatic Buccal Buccal Marginal mandibular Cervical
Orbicularis oculi orbicularis oris platysma

CLINICAL NOTES
SYMPTOM SITE OF LESION
Internal strabismus Pons
Hearing loss IAM
Loss of lacrimation Facial canal, before geniculate ganglion
Hyperacusis Facial canal, before giving nerve to stapedius
Loss of taste in ant.2/3 of tongue + lack of salivation Facial canal, before giving chorda tympani
Paralysis of muscles of facial expression Extracranial
TRIGEMINAL NERVE CN-5
• Largest cranial nerve
• Both motor & sensory
• 4 nuclei
main sensory
spinal
mesencephalic
 Motor- only for mandibular division
 Main sensory-
-posterior part of pons
-lateral to the motor nucleus
-continues with spinal nucleus
touch & pressure
 Spinal-
-continues -superiorly with main sensory nucleus
-inferiorly with substantia gelatinosa of the spinal cord
-extent: whole length of medulla oblongata and inferiorly to the C2 segment of spinal cord
-pain & temperature
 Mesencephalic—
midbrain –proprioception from
1)Muscles of mastication
2) Facial muscles
3) Extraocular muscles
These fibres bypass trigeminal nucleus (They are dendrites of unipolar cells)
Motor-
-pons,medial to main sensory nucleus
-Supply:- muscles of mastication
-anterior belly of Digastric
-mylohyoid
-tensor velipalatini & tensor tympani
Course-
Leaves the anterior aspect of the pons as a small motor root & a large sensory root
Pass forward out of the posterior cranial fossa
Upper surface of the apex of the petrous temporal bone
In the middle cranial fossa
Sensory root expands to form a trigeminal ganglion in meckel’s cave

(a pouch of dura mater)
Ophthalmic maxillary mandibular

Ophthalmic
Trigeminal ganglion
Lateral wall of cavernous sinus,inferior to Trochlear nerve & superior to maxillary nerve
Lacrimal frontal nasocilliary
Lateral part of superior lateral part of SOF middle part of SOF

orbital fissure(SOF) between 2 divisions
parasym. sensory of occulomotor nerve
zygomatico lacrimal gland supratrochlear supraorbital sensory root to

Temporal cilliary ganglion
Upper eye lid frontal air sinus long cilliary nerves -

upper eye lid sensory-cornea,iris -
skin up to vertex sym-dilator papillae
post.ethmoidal
infratrochlear ant.ethmoidal
Maxillary
Lateral wall of cavernous sinus most inferiorly
foramen rotundam
pterygopalatine fossa zygomaticofacial
post.sup.alveolar zygomatic IOF
zygomaticotemporal
inf. orbital fissure(IOF)
infraorbital nerve ant.sup.alveolar
infraorbital foramen
face
sensory root to
greater palatine pharyngeal branches orbital branches

lesser palatine nasal branches
greater palatine palatovaginal canal inferior orbital
fissure
canal lesser palatine sphenopalatine foramen
canal
hard palate nasopharynx orbit
lateral wall of nose soft palate lateral wall & septum of nose
Mandibular
Nerve of 1st branchial arch.
Motor & sensory roots pass through foramen ovale
Fuse to form main trunk which lies in infratemporal fossa on the tensor veli palatini,
Sensory to deep to lateral pterygoid
buccinator Meningeal (nervous spinosus) medial pterygoid
(only sensory branch)
nerve to medial pterygoid Tensor veli
Buccal
otic ganglion palatine &
Tensor tympani
masseteric
ANTERIOR (mainly motor) Otic POSTERIOR (mainly sensory) Inf.alveolar

ganglion
Deep
temporal Lateral Auriculo
temporal Lingual Chorda
Pterygoid Mandibular
branch tympani foramen
TMJ temporalis
2 roots Superficial to
hyoglossus,deep
Mental
Encircle MM to myelohyoid
nerve
artery
winds around the Nerve to Mylohyoid

Sensory to parotid submandibular (only motor branch)
pinna, Ext. duct
AcousticMeatus
& tympanic Secretomotor
membrane Myelohyoid &
& sensory
Sensory& post.belly of
gustatory to digastric
ant.2/3 of
tongue,
Secretomotor to
the sublingual &
submandibular
glands
Trigeminal Ganglion
Motor root (small & medial) and sensory root(large & lateral) emerge from pons
Present in meckel’s cave
Contains axons from main sensory and spinal nuclei
Motor root lies below it
Three nerves arise from the ganglion
V1 & V2- sensory only
V3- mixed (both sensory and motor)
CLINICALS
Clinical testing-Sensory div. by using a cotton & pin
Very little overlap of dermatomes
Motor div. –by asking the patient to clench his teeth & feeling for the contracting masseter.
& asking the patient to move the jaw from side to side
TRIGEMINAL NEURALGIA
Severe stabbing pain of unknown cause involving mainly of V2 & V3
Sensory root is divided preserving fibres of the ophthalmic div. to avoid damage to the cornea.
Lingual nerve can be damaged in extracting the malplaced wisdom tooth as the nerve lies in
contact with the medial surface of the 3rd molar tooth.
VESTIBULOCOCHLEAR NERVE CN-8
Emerges from CP angle
VESTIBULAR
SSA- from utricle,saccule & semicirucular canals- Balance
Nerve fibres-central processes of nerve cells located in the vestibular ganglion.
Enter through CP angle lateral to 7th nerve
ICP Vestibular nuclei(sup,inf,lat,med) - medulla
MLF
Cerebellum nuclei of 3,4,6 cranial nerves cortex
COCHLEAR
SSA-organ of Corti –hearing
Nerve fibres-central processes of nerve cells in the spiral ganglion
CP angle
Cochlear nuclei-in medulla,on the surface of ICP
Trapezoid body sup. olivary nucleus
Inferior colliculus + medial geniculate body
Internal capsule-acoustic radiation
Auditory cortex( areas 41,42)

(Sup.temporal gyrus)
Glossopharyngeal nerve (CN IX)
Nuclei
1. Nucleus ambiguus- motor to stylopharyngeus muscle

2. Inferior salivatory nucleus- parasympathetic supply to parotid gland via otic ganglion
3. Nucleus of Tractus Solitarius- taste from post. 1/3 of the tongue, carotid sinus afferents
Course
Leave medulla -between the olives & inferior cerebellar peduncle
Parotid gland
Anterior part of the jugular foramen otic ganglion
Superior ganglion (no branches) tympanic plexus (middle ear,

auditory tube, mastoid antrum & air cells)
Inferior ganglion tympanic branch tympanic canaliculus
Between the internal jugular vein & the internal carotid artery carotid branch (carotid sinus)
Deep to the styloid process & muscles attached to it
Turn forward →winds around the stylopharyngeus supplies stylopharyngeus
Between internal & external carotid arteries pharyngeal branches pharyngeal plexus
Pass deep to hyoglossus (sensory to mucous membrane of the pharynx)
submandibular region tonsillar branch tonsil, soft palate
Lingual branch taste & general sensation

for posterior 1/3 of the
tongue & circumvallate
papillae
Tympanic nerve→ tympanic canaliculus→ tympanic plexus on the promontory of the mid
brain→lesser petrosal nerve→ penetrate the tegmen tympani→ middle cranial fossa→ foramen
ovale→ otic ganglion→ auriculotemporal nerve→ parotid gland
Clinicals
Clinical testing
1. gag reflex→ on tickling the posterior wall of the pharynx there is reflex contraction of
pharyngeal muscles
2. testing the taste sensibility of the posterior 1/3 of the tongue
Vagus nerve (CN X)
Nuclei
Nucleus ambiguus- motor to pharynx & larynx
Dorsal nucleus of vagus- parasympathetic
Nucleus of tractus solitaries- taste
Course
• Between olives & inferior cerebellar peduncles
• Through the middle part of the jugular foramen
anterior to C.N 11
• Joined by the cranial part of accessory
1. Meningeal branch (post cranial fossa)
• Superior ganglion 2. Auricular branch (root of auricle,
• Inferior ganglion posterior ½ of external meatus &
tympanic memb.)
1. Pharyngeal branch (muscles of
• Descend within the carotid sheath pharynx & soft palate except
(between & posterior to the internal jugular vein & tensor veli palatini)
internal/common carotid arteries) 2. Carotid branch (carotid sinus)
• At the root of the neck 3. Superior laryngeal nerve
right→cross 1st part of the subclavian left (cricothyroid: ex laryngeal,
→b/w common carotid & subclavian mucosa up to vocal folds: int
laryngeal)
1. Recurrent laryngeal (muscles of
larynx, mucosa up to vocal folds,
inferior constrictor, trachea)
2. Cardiac branches
Clinical
Nerve damage
Paralysis of palatine muscles (uvula pulled to normal side)
Dysphagia
Nasal regurgitation of swallowed fluids
Cadaveric position of vocal cords
Hoarseness of voice
Irritation of auricular branch→ear cough

Stimulation of auricular branch→↑appetite
Herpes zoster →skin of auricle→ communication
with geniculate ganglion of CN 7
Accessory nerve (CN XI)
Cranial & spinal roots
Cranial root distributed via vagus (vago accessory complex)
Nuclei
1. Nucleus ambiguus
2. Spinal nucleus (lateral part of the anterior grey column-C1-C5)
Cranial root
• B/w olives & inf cerebellar peduncle (posterolateral sulcus)
• Unite with the spinal root
• Middle part of the jugular foramen
• Separate from the spinal root
• Fuse with vagus below inf ganglion
• Distributed through its branches to palate, pharynx, larynx
Spinal root
• B/w ventral & dorsal roots of spinal cord up to C5
• Enters the cranium through foramen magnum
• Unite with the cranial root
• Middle part of the jugular foramen
• Separate from the cranial root
• Descend b/w internal jugular vein & internal carotid artery
• Deep to styloid process
• Deep to sternocleidomastoid
• Pierce the posterior border of it near its middle
• Enter the posterior triangle
• Pass deep to ant border of trapezius 5cm above clavicle
• Supply → sternocleidomastoid & trapezius
Clinical
Ask the patient to shrug the shoulders against resistance
Ask the patient to turn the chin to opposite side against resistance
Nerve damage→torticollis/ wry neck

Hypoglossal nerve (CN XII)
Supplies the muscles of the tongue
Nuclei
Hypoglossal nucleus (floor of the 4th ventricle) – Medulla
Part of the nucleus supplying the genioglossus receives fibres ONLY from the Contralateral cortex.
Course
Intraneural
1. Lateral to medial longitudinal fasciculus & medial lemniscus & pyramids
2. Medial to olives
3. Anterolateral sulcus
4. Leave the skull through hypoglossal canal (anterior condylar canal)
Extracranial
1. Lies deep to internal jugular vein
2. Then b/w internal jugular vein & internal carotid artery
3. Crosses the vagus laterally deep to parotid & styloid process
4. At the lower border of the posterior belly of the digastric hooks around the occipital artery
5. Crosses the external & internal carotid arteries & the loop of the lingual artery
6. Pass deep to the posterior belly of digastric
7. Enter the submandibular region
8. On hyoglossus & genioglossus deep to submandibular gland& mylohyoid
9. Supply the all the tongue muscles except palatoglossus (supplied by the vago accessory
complex)
10. Spinal nerve C1 joins & form the descendens hypoglossi→ supply strap muscles (thyrohyoid
& geniohyoid supplied directly by C1 via CN 12)
Clinicals :
• Nerve lesion - Tongue deviates to the side which is paralyzed
PERIPHERAL PARASYMPATHETIC GANGLIA
1. CILIARY GANGLION
Location: - Near the apex of the orbit. Between the optic nerve & the tendon of the lateral rectus
Parsympathetic root Sensory root Sympathetic root

EdingerWestphal Trigeminal nerve Sup. cervical
nucleus ganglion
Oculomotor nerve
Opthalmic div. Post ganglionic
fibres
Inferior division
Nasocilliary nerve Internal carotid plexus

( Opthalmic Artery)
Nerve to Inf.
Oblique
Cilliary
Ganglion
Short cilliary
nerves
Dilator pupillae&
Sphincter blood vessels
pupillae& eyeball (vasomotor)
Cilliaris

2. OTIC GANGLION
∗ Topographically related to mandibular nerve * only ganglia with four roots

∗ Functional component of glossopharyngeal nerve
∗Location:-Infratemporal fossa, just below the foramen ovale,medial to the mandibular nerve, lateral to the
Tensor veli palatini.
Parasympathetic root
Inferior Salivatory
nucleus
Sensory root & Motor root Sympathetic root

Glossopharyngeal
nerve Trigeminal nerve Superior cervical ganglion
Tympanic Branch Trigeminal Postganglionic fibres

ganglion
Tympanic plexus
Mandibular nerve External carotid plexus (middle meningeal artery)
Lesser petrosal
nerve
Auriculotemporal
nerve Nerve to Medial
Pterygoid
(Middle Cranial
cavity) Tensor
velipalatini&
Tensor tympani
Parotid gland

3. PTERYGOPALATINE GANGLION
● Largest peripheral parasympathetic ganglia
● Topographically related to maxillary nerve
● Functional component of Facial nerve (Greater petrosal nerve)
● Location :- Pterygopalatine fossa,
Just below the maxillary nerve,
In front of pterygoid canal,
Lateral to the sphenopalatine foramen.
Lacrimatory nucleus Parasympathetic root
NervusIntermedius
Maxillary nerve Nasal branches
{ Medial posterior superior
Facial nerve nasal nerves ( largest one
Sensory roots called nasopalatine nerve ) and
Lateral posterior superior
nasal nerves }
Geniculate ganglion
Greater petrosal nerve PTERYGOPALATINE

GANGLION Orbital branches
Nerve of
pterygoid canal Pharyngeal branches
Deep petrosal nerve

Greater & Lesser palatine
Zygomatic nerve nerves
Internal carotid plexus
Postganglionic fibres Zygomaticotemporal

nerve
Superior cervical
ganglion Lacrimal nerve Lacrimal gland
Sympathetic root

4. SUBMANDIBULAR GANGLION
● Topographically related to Lingual nerve
● Functional component of Facial nerve (Chorda tympani branch)
● Location :- Lies on the Hyoglossus muscle,
Just above the deep part of the submandibular
gland, suspended from the lingual nerve.
Parasympatheticroot Sensory root Sublingual gland

Superior salivatory Trigeminal nerve
nucleus Sympathetic root
Sup. cervical ganglion

Trigeminal ganglion
Nervusintermedius
Mandibular nerve Post ganglionic fibres
Chorda tympani
Lingual nerve
External carotid plexus
(Facial artery)
Petrotympanic fissure
Submandibular gland

MCQ
The Pterygopalatine ganglion;
a) Supplies the sphincter pupillae muscle through its zygomatico temporal fibres
b) Supplies secretomotorfibres for the lacrimal gland
c) Gives passage to sympathetic fibres
d) Distributes secretomotorfibres to the glands of the nose, palate and nasopharynx
e) Receive fibres from the maxillary nerve
The submandibular ganglion
a) Distributes secretomotorfibres to the sublingual gland

b) Distributes fibres from the lesser petrosal nerve to the submandibular ganaglion
c) Gives passage to the taste fibres from the circumvallate papillae
d) Is situated medial to the hyoglossus muscle
e) Is closely related to the mandibular nerve

Blood Supply of the CNS
 Supplied by the
 2 internal carotid arteries
 2 vertebral arteries
• These 4 arteries unite to form the Circle of

Willis.
• Lies in the interpenduncular cistern
• At the base of the brain
• Around the Optic Chiasma and the infundibulum
of Pituitary
 Internal Carotid Artery

• Arises from the common carotid artery
• Common carotid artery bifurcates into the
internal and external carotid arteries
• at level of the Fourth Cervical Vertebra (at the
upper border of the thyroid cartilage)
• Internal carotid artery has 4 main parts
1. Cervical part
2. Petrous part
3. Cavernous part
4. Cerebral part
• The 1st 3 parts give no branches.

Cerebral part of the Internal Carotid Artery
Anterior Cerebral Artery

• Anastomoses with the opposite artery by Anterior Communicating artery
• Supplies;
 Medial surface of the cerebral cortex upto parieto-occipital sulcus
 Strip of cortex on adjoining lateral surface.
 Leg area of pre central gyrus.
 Anterior limb of the internal capsule
• Runs medially superior to the optic nerve

• Enters the longitudinal fissure
• Connects with the opposite artery by the Anterior Communicating Artery
Ophthalmic Artery
Middle Cerebral Artery
• Largest branch
• Supplies;
Internal Carotid  Entire lateral surface of hemisphere
(except the part supplied by anterior
cerebral artery)
 All the parts of the Internal capsule
 Lentiform and Caudate nuclei
Anterior Choroidal Artery

• Passes posteriorly close to the optic tract
Posterior Communicating Artery
• Enters the inferior horn of the lateral ventricle
• Runs above the
• ends in choroidal plexus
occulomotor nerve
• Supplies;
 the posterior limb of the internal capsule
 Crus cerebri
 Lateral geniculate body
 Optic tract
 Vertebral Artery
• Vertebral arteries are major arteries of the neck
• branch of 1st part of the subclavian artery
• Ascends through foramen transversarium of upper 6 cervical vertebrae (not through C7)
• Enters the skull through Foramen Magnum
• Pierces dura and arachnoid maters to enter the sub arachnoid space
• 2 vertebral arteries join upto form the Basilar Artery at the lower border of Pons.

Posterior Inferior Cerebellar Artery (PICA)
Basilar Artery • Largest branch of the Vertebral artery
• Supplies;
 Medulla
 Cerebellum
Anterior Spinal Artery

• Arises as 2 arteries; then unite and
form one Anterior Spinal Artery
Vertebral Artery • Descends on the anterior aspect of
Medulla Oblongata and Spinal Cord
along the Anterior Median Fissure
embedded in the Pia Mater
• Supplies anterior 2/3 of the Spinal
Cord
2 Posterior Spinal Arteries

• Descend on the posterior surface close
to the posterior roots of the Spinal Cord
• Supplies posterior 1/3 of the Spinal Cord
 Basilar Artery
• Ascend in a groove on the anterior surface of the Pons
Posterior Cerebral Artery Communicates with

• Supplies; Posterior Cerebral
 Occipital Lobe artery to form the
 Visual Cortex Circle of Willis
Superior Cerebellar Artery
• Supplies;
 Pons
 cerebellum
Pontine Arteries
• Supplies;
Basilar Artery  Pons
Labyrinthine Artery
• Accompany Facial & Vestibulo-Cochlear
nerves to Internal Acoustic Meatus
• Supplies;
 Inner ear
Anterior Inferior Cerebellar Artery (AICA)

• Supplies;
 Cerebellum
Vertebral  Pons
arteries  Upper medulla

 Circle of Willis
Medulla Pons
 Vertebral artery  Basilar artery
 Ant. and post. spinal arteries  Anterior inferior cerebellar
 Posterior inferior cerebellar artery artery
 Basilar artery  Superior cerebellar artery
Cerebellum
Mid brain  Anterior inferior cerebellar
 Basilar artery Circle of Willis artery
 Superior cerebellar artery (Regions supplied)  Posterior inferior cerebellar
 Posterior cerebral artery artery
 Superior cerebellar artery
Thalamus Corpus Striatum & Internal Capsule

 Basilar artery  Mainly Middle Cerebral Artery
 Posterior communicating artery  Also by Anterior Cerebral Artery
 posterior cerebral artery

 Blood supply of the Spinal Cord
• Posterior spinal arteries – Posterior 1/3
• Anterior spinal artery – Anterior 2/3
• This blood supply is reinforced by;
1. Segmental spinal arteries (Anterior and Posterior Radicular Arteries)
2. Feeder arteries (Eg : Great anterior medullary artery of Adamkiewicz)
 Uni lateral.
 In majority, enter the spinal cord in the left side
 Arises in lower thoracic or upper lumbar region from aorta.
Clinicals
• No anastomoses after circle of Willis.
• More capillaries can be seen in grey matter (metabolic activity of cell bodies are high)
• Anterior cerebral artery occlusion – Contralateral Hemiparesis & hemi-sensory loss involving leg & foot.
• Middle cerebral artery occlusion – Contralateral Hemiparesis & hemi-sensory loss involving face & arm (+
Aphasia if left-sided lesion)
• Posterior cerebral artery occlusion – Contralateral Homonymous Hemianopia with macula sparing due to
collateral supply from middle cerebral artery.
• Occlusion of the posterior inferior cerebellar artery (PICA) or vertebral artery causes Lateral Medullary
Syndrome (of Wallenberg)
• Occlusion of the medullary branch of vertebral artery (or anterior spinal artery) causes Medial Medullary
Syndrome
 Affect the Hypoglossal nerve, Medullary Pyramids and Medial Lemniscus
• Occlusion of a branch of the posterior cerebral artery that supplies the midbrain causes Weber syndrome
 Ipsilateral occulomotor nerve palsy
 Contralateral hemiparesis

01. In lesions of the right posterior inferior cerebellar artery is
a. Loss of pain and temperature on the same side
b. Paralysis of facial muscles on the opposite side
c. Deviations of the protruding tongue the same side
d. Dysphagia
e. Hypotonia
02. Posterior inferior cerebellar artery thrombosis give rise to

a. Hoarseness of voice
b. Hypotonia
c. Loss of pain and temperature sensation on the opposite half of the face
d. Loss of pain and temperature sensation on the opposite lower limb
e. Loss of cough reflex
03. Left posterior inferior cerebellar artery syndrome causes

a. Left sided incoordination in the upper limbs
b. Paralysis of muscles of the upper right extremity
c. No taste sensation in the anterior 2/3 of the tongue
d. Deafness in the right year
e. Difficulty in swallowing
04. Regarding medial medullary syndrome

a. Condition may be caused by thrombosis of the posterior inferior cerebellar artery
b. Nucleus ambiguus of the same side may be affected
c. There may be analgesia on the same side of the face
d. There may be thermoanesthesia on the same side of the face
e. There may be nausea
05. Features of basilar artery occlusion includes

a. Monoplegia
b. Contralateral cerebellar signs
c. Quadriplegia
d. Hypopyrexia
e. Contralateral cranial nerve palsies
06. Features of posterior inferior cerebellar artery occlusions include

a. Contralateral Horner’s syndrome
b. Ipsilateral analgesia
c. Contralateral ataxia
d. Dissociated analgesia
e. Ipsilateral analgesia in the face

VENTRICULAR SYSTEM
• Four CSF filled cavities located within the brain
• Lined throughout with ependyma
• Derived from the cavity of neural tube
• Consists of 2 lateral ventricles, 3rd ventricle, cerebral aqueduct and 4th ventricle
Lateral ventricle
• Largest of the ventricles
• One is present in each cerebral hemisphere
• C shaped cavity
• Divided into
• Body – extends to parietal lobe
• anterior horn – extends to frontal lobe
• posterior horn – extends to occipital lobe
• inferior horn – extends to temporal lobe
• Two lateral ventricles and third ventricle
communicate with each other through
interventricular foramen

3rd ventricle
• Slit like cleft between the 2 thalami
• The interthalamic adhesion runs through the ventricle
• Communicate with the lateral ventricles anteriorly by the interventricular foramen (of Monroe)
• Communicate with the 4th ventricle posteriorly by the cerebral aqueduct of Silvius
Cerebral aqueduct
• Narrow channel which connects the 3rd ventricle with the 4th ventricle
• No choroidal plexus
4th ventricle
• Diamond shaped
• Situated anterior to the cerebellum
• Posterior to the pons and the superior half of the medulla oblongata
• Roof – cerebellum
• Floor – medulla oblongata
• Walls – cerebellar peduncles
• Posterior wall is pierced by a large medial aperture – foramen of magendie
Laterally – foramen of Luschka
• Communicate with subarachnoid space
CEREBRO-SPINAL FLUID (CSF)

FORMATION
• From choroid plexus of the
ventricles
• Which is a vascular fold composed
of pia mater covered with
ependymal cells lining the
ventricular cavity
• CSF is actively secreted
• Production is not pressure
dependent
• Continuous even if the reabsorption
is obstructed
ABSORPTION
• By arachnoid villi (arachnoid granulations)
• They are projected in to the Dural venous sinuses, especially Superior Sagittal Sinus (SSS)
• Grouped together to form Arachnoid granulations
• Which is diverticulum of the subarachnoid space that pierces the dura mater
• Covered by endothelium of the venous sinuses.
• Absorbed when, CSF fluid pressure in sub-arachnoid space > Venous pressure in sinuses
• Villi act as valves
BLOOD BRAIN BARRIER

• Tight junctions between adjacent endothelial cells in the blood capillaries
• Assisted by a thick basal lamina and enveloping foot processes of surrounding astrocytes
• Blood-CSF barrier – Barrier similar to the BBB exist in choroid plexus.
CLINICAL NOTES
1. Papilledema
• Intracranial subarachnoid spaces extend forward around the optic nerve
• High CSF pressure compress the retinal wall → bulging forward of the optic disk causes edema of
the disk
2. Hydrocephalus - abnormal increase in the volume of CSF within the skull
• Communicating hydrocephalus – due to obstruction of interventricular foramen or cerebral
aqueduct by tumors
• Non-communicating hydrocephalus – due to increased formation or decreased absorption of CSF
The third ventricle

a. communicate with the 4th ventricle through the interventricular foramen
b. is related superiorly to the transverse fissure
c. is bounded anteriorly by the lamina terminalis
d. is recessed in to the mamillary body
e. is related to the posterior perforated substance

Embryology – Head and Neck
Mesenchyme Structure
Paraxial mesoderm Brain floor, small portion of occipital bone, all voluntary craniofacial
muscles
Lateral plate mesoderm Laryngeal cartilage (aratynoid, cricoids)
Neural crest cells Hyoids, skeletal structures in face, Temporal bone, V VII XI X nerves
Ectodermal placodes Sensory ganglions of V, VII, IX, X
Pharyngeal Arches endoderm
• Core – mesoderm and neural crest cells

• Internal lining – endoderm
• External lining – ectoderm
• Artery – aortic arch Artery
Cartilage Ectoderm
• Nerve – cranial nerve Nerve
• Internal depressions –pouches
• External depressions –clefts
• Appear in the 4th- 5th weeks
Derivatives of the pharyngeal arches and their innervations
Pharyngeal arch Nerve Muscles Skeleton

Premaxilla, maxilla, zygomatic
Muscles of mastication
bone, part of the temporal bone,
(temporal, masseter, medial &
V (Trigerminal) Meckel’s cartilage, mandible,
lateral pterygoids)
1-Mandibular Mandibular & malleus, incus, anterior ligament
Mylohyoid, anterior belly of
Maxillary divisions of malleus, sphenomandibular
digastric, tensor palatines,
ligament
tensor tympani
Muscles of Facial Expressions

(Buccinator, auricularis,
Stapes, styloid process, stylohyoid
frontalis, platysma,obicularis
2-Hyoid ligament, lesser horn and upper
VII - facial occuli)
portion of body of hyoid bone
Posterior belly of digastric,
stylohyoid, stapedius.
Greater horn and lower portion of

3 IX -glossopharyngeal Stylopharyngeus
body of hyoid bone
X-vagus
• Superior laryngeal Cricothyroid, levator palatine,
branch (4th arch) constrictors of pharynx Laryngeal cartilages (thyroid,
4-6 cricoids, arytenoids, corniculate,
• Recurrent cuneiform)
laryngeal nerve Intrinsic muscles of larynx
(6th arch)

Pharyngeal pouches – 5 pouches in between 6 arches
Pharyngeal pouch Derivative

Tympanic (middle ear) cavity
1
Auditory (Eustachian) tube
Palatine tonsil
2
Tonsilar fossa
Inferior parathyroid gland
3
Thymus
4 Superior parathyroid gland
Ultimobronchial body
5
(Parafollicular [c] cells of the thyroid gland)
Pharangeal clefts
1st External auditory meatus

2,3,4 Cervical sinus (normally obliterated)

Clinical
Birth defects
1) Ectopic thymic and parathyroid tissue
• Accessory glands remain in the migration pathway
• May found in the neck
• Inferior parathyroids may found at the bifurcation of the common carotid artery
2) Branchial fistula
External
• 2nd arch fails to fuse with epicardial ridge
• 2,3,4th clefts open to the surface
• Anterior to the sternocleidomastoid
• Provides drainage for lateral cervical cyst
Internal
• Cervical sinus connected to the pharynx via a canal
• Due to rupture between the 2nd pharyngeal pouch & cleft
3) Cervical cysts
• Remnants of cervical sinus
• Found anywhere along ant. border of SCM, frequently just below the angle of jaw
• Become evident in child head
Tongue
Structure in embryo Arch Nerve Structure in adult

Lateral lingual Sensory – cranial V3
1 Body of the tongue anterior 2/3
swellings Taste – cranial VII
Tuberculum impar 1 Overgrown by lateral lingual swellings

2 Overgrown by 3rd arch
Copula 3 Cranial IX Posterior 1/3 of tongue
4 Cranial X Posterior most part of the tongue root
Tongue musculature
Occipital myoblasts - Cranial XII
(Except palatoglossus)

Clinical
Ankylogossia (tongue tie)
• Normal –tongue become free from floor by cell degeneration except frenulum.
• Abnormal – cell degeneration doesn’t occur.
Thyroid Gland
• Epithelial outgrowth from floor of the tongue - Foreman cecum (between tuberculum impar and
copula)
• Connected to the tongue by thyroglossal duct
• Descends in front of pharyngeal gut in midline
• Descend in front of hyoid bone, thyroid & cricoid cartilages
• Positioned in front of trachea in 7th week - with an isthmus & two lobes
• Ultimobranchial body (5th pouch) – incorporated into the gland – give rise to C cells
• Starts function at the end of 3rd month
o Follicular cells  thyroxine & triiodothyronine
o Parafollicular cells( C cells)  Calcitonin
Clinical
• Thyroglossal Cyst
o Always in the midline
o Cystic remnant of thyroglossal duct
o 50% under hyoid bone
• Thyroglossal fistula
o Thyroglossal cyst connected to the outside by canal
o May be present at birth
• Aberrant thyroid tissue
o Remnants of tissue along the migratory pathway
Development Of Face
Facial prominences formed by
• Neural crest cells
• 1st pair of pharyngeal arches
At the end of the 4th week
• Lateral to stomodium – Maxillary prominence
• Superiorly – Frontonasal prominence
• Inferiorly – Mandibular prominence – appear and grow
5th week
• Nasal placodes appear on both sides of frontonasal prominence
• Medial nasal and lateral nasal prominences are formed in each side

6th-7th weeks
• Maxillary prominence grow & push medial nasal prominences toward midline
• Medial nasal prominences fuse
Structures contributing to formation of the face
Prominence Structure formed

Frontonasal Forehead, bridge of nose and medial and lateral
nasal prominences
Maxillary Cheeks, lateral portion of upper lip
Medial nasal Philtrum of upper lip, crest and tip of nose
Lateral nasal Alae of nose
Mandibular Lower lip
Nasolacrimal groove
• Between maxillary & lateral nasal prominence
• Floor forms a solid epithelial cord
• By canalization forms nasolacrimal duct with lacrimal sac

Development of palate
Primary palate
o Formed by intermaxillary segment
Secondary palate
o Formed by palatine shelves of maxillary bones
Intermaxillary segment
Formed by two merged medial nasal prominences
3 parts
o Labial – philtrum of upper lip
o Upper jaw – Upper 4 incisor
o Palatal – triangular primary palate
Palatine shelves
• Two shelf like outgrowths
• Forms main part of palate
• At 6th week directed obliquely by sides of the tongue
• Later ascends and fuse with each other and nasal septum
• Anteriorly fuse with primary palate
• Incisive foramen is the landmark between primary and secondary palates

Clinical
1.Facial clefts
• Two types- anterior and posterior cleft deformities
• Incisive foramen is the landmark
Anterior Posterior
Lateral cleft lip Secondary cleft lip
Cleft upper jaw Cleft uvula
Primary cleft palate
Intermaxillary segment fail to fuse with Palatine shelves fail to fuse with each other
maxillary processes or palatine shelves
2.Oblique facial clefts

• Nasolacrimal ducts exposed to surface
• Maxillary prominences fail to fuse with lateral nasal prominences
3.Median cleft lip
• Incomplete merging of two medial nasal prominence in midline
Nasal cavities
• 6th week – nasal pits deepen
• Oronasal membrane which separates it from nasal cavity disappears
• Primitive choanae formed
• Secondary palate develops
• Definitive choanae formed
MCQ
1. In the development of the face
a. Mandibular process is derived from the second pharyngeal arch
b. Maxillary process is developed from the first pharyngeal arch
c. Nasolacrimal canal develops along the line of fusion of the frontonasal and maxillary
processes
d. Part of the upper jaw bearing the incisor teeth develops from the frontonasal
process
e. Forehead is formed from the maxillary processes
2. Regarding the pharyngeal and branchial arches
a. Cartilage of the first arch is called Reichet’s cartilage
b. Mesoderm of the 2nd arch gives rise to muscle supplied by the maxillary division of
the third cranial nerve
c. Palatine tonsils are derived from the endoderm of the second pharyngeal pouch
d. Branchial cyst form the persistence of the epicardial ridge
e. Only blood vessels remaining from the 5th aortic arch on the right side is the
proximal part of the subclavian artery

3. In the development of the pharyngeal arches
a. Nerve of the 4th arch is the superior laryngeal
b. External acoustic meatus is derived from the 2nd pharyngeal cleft
c. Sphenomandibular ligament is a remnant of the 2nd pharyngeal arch cartilage
d. Greater and lesser horns of the hyoid bone have the same origin
e. Larynx is derived from cartilage of the 4th and 6th arches
4. First pharyngeal arch
a. Gives rise to the malleus and the incus
b. Is innervated by the trigeminal nerve
c. Gives rise to the palatine tonsil
d. Gives rise to the muscles of facial expressions
e. Gives rise to the external auditory meatus
5. Following structures are derived from the 2nd pharyngeal arch
a. Posterior third of the tongue
b. Incus and stapes
c. Maxillary artery
d. Stylohyoid ligament
e. Stylohyoid muscle
Answers
1-FTFTF
2-FFTFF
3-TFFFT
4-TTFFT
5-FFFTT

SKIN - HISTOLOGY
1. Epidermis
2. Dermis
3. Hypodermis (subcutis)
Epidermis
• Ectodermal origin
• Thickness – variations: eyelid – thick, palms and soles – thin
• Stratified squamous keratinized epithelium
• Avascular, no nerves
Epidermis
Layers cell types
• Stratum basale • Keratinocytes
• Stratum spinosum • Melanocytes
• Stratum granulosum • Langerhan cells
• Stratum corneum • Merkel cells
• Stratum basale – basement membrane dermal epidermal junction
Epidermal cell reneval – mitotic figures
• Stratum spinosum – cytokeratin
Desmosomal bridges used to diagnose epithelial tumours
• Stratum granulosum – cytokeratin aggregate + keratohyalin = keratin
• Stratum corneum – by keratin
Dermal epidermal junction

• Epidermal ridges
• Dermal papillae
Dermis
Mesodermal origin
• Horizontally arranged collagen and elastin fibers
• Blood vessels
• Sensory nerve endings, sensory organs
Papillary dermis – outer, thinner, Meissner corpuscles
Reticular dermis – deeper, loose CT
Hypodermis
subcutaneous layer, loose CT, adipose tissue
Skin appendages
Hair Sebaceous gland Sweat glands
Modified keratinized 1. Branched acinar Eccrine – present in most part of the body
structure 2. Holocrine secretion
Hair follicle, hair bulb, hair 3. In relation to hair follicle or Apocrine – present in axillae, genital organs
shaft independent of hair follicle
− Arrector Pilli muscle

Breast
• Modified apocrine sweat gland
• Compound tubulo-acinar gland
Endocrine system - Histology

1. Thyroid gland
• Fibrous capsule
• Fibrous septae, rich supply of blood vessels, nerves, lymphatics
• Fenestrated capillaries
• Septae divide gland into lobules
• Lobules contain thyroid follicles
• Thyroid follicle
 Functional unit, spheroidal structure
 Follicular cells rest on a basement membrane
 Store inactive T3/T4 (colloid)
• Follicular cells
 Secrete T3/T4
 Stored within follicles in inactive form
• Parafollicular cells
 Secrete calcitonin
 Scattered among follicular cells
• Colloid – fills the interior of thyroid follicle
Active follicle Inactive follicle

 Small  Large
 Cells tall columnar/cuboidal  Cells flattened
2. Hypothalamus 3. Pituitary gland (hypophysis) 4. Parathyroid gland

Neurosecretory cells Anterior pituitary Within thyroid capsule
Glial cells (supporting – Fenestrated capillaries – facilitate hormone passage – Rich vascular network
cells) Cell types Principal cells, oxyphil cells
Blood vessels – somatotrophs, lactotrophs, thyrotrophs, gonadotrophs
Posterior pituitary
– Neurosecretory activity
– Dilated end of axons – herring bodies
5. Adrenal gland
• Cortex – mesoderm
• Medulla – neural crest cells
• Cortex – zona glomerulosa, zona fasciculata, zona reticularis
• Medulla – secretory cells

Do you know ???
Important surface marking
• Axillary artery becomes the brachial artery – lower border of teres major
• Brachial artery divides – neck of the radius
• Brachial pulse – medial to biceps tendon, infront of the elbow
• Radial artery at wrist – between the flexor carpi radialis tendon & radial styloid
• Superficial palmar arch – levelwith distal border of outstretched thumb
• Deep palmar arch – 1cm proximal to superficial palmar arch
• Flexor retinaculum – two finger breath distal to the distal dominant skin crease on the front of wrist
• Metacarpophalangeal joints – at the level of distal palmar crease
• Median nerve at wrist – between tendons of flexor digitorum superficialis to middle finger &flexor carpi radialis
• Femoral pulse – midinguinal point

• Femoral artery – upper 2/3 of a line between midinguinal point to adductor hiatus
(when thigh is flexed, abducted & laterally rotated)
• Popliteal artery – divides in to anterior & posterior tibial branches at the lower border of the popliteus muscle
• Posterior tibial artery pulse – behind the medial malleolus, 2.5cm infront of the medial border of the tendo
calcaneus
• Dorsalispedis artery pulse – lateral to extensor hallucis longus tendon on the navicular& intermediate
cuniform bones
• Great saphenous vein – anterior to medial malleolus, hand breath behind the medial border of the patella
• Saphenous opening – 4cm lateral & below the pubic tubercle
• Small saphenous vein – posterior to lateral malleolus
• Perforators – hands breath above & below the knee, hands breath above the ankle
• Adductor canal – middle 1/3 of a line between midinguinal point to adductor hiatus
• Femoral nerve – finger breath lateral to midinguinal point
• Sciatic nerve – mid point between ischial tuberosity & greater trochanter
• Deep peroneal nerve – mid point between two malleoli anterior to ankle joint
• Intercostals neurovascular bundle – upper border of intercostals space/lower border of the rib
• Internal thoracic artery divides into terminal branches – 6th intercostals space
• Lung apex –2.5cm above the medial 1/3 of the clavicle
• Commencement of the brachiocephalic vein – behind the sternoclavicular joint
• Commencement of the SVC – behind the 1st right costal cartilage
• SVC pierces the pericardium – behind the 2nd right costal cartilage
• SVC enters the right atrium – behind the 3rd right costal cartilage
• Apex of the heart – left intercostal space in the midclavicular line
• SA node – top of the sulcus terminalis, below the opening of SVC
• Anterior division of the middle meningeal artery – pterion, posterior to coronal suture
• C3 – Hyoid bone
• C4 – bifurcation of the common carotid artery (upper border/notch of the thyroid cartilage)
• C6 – carotid tubercle, common carotid artery compress, cricoid cartilage, middle cervical ganglion,
larynx trachea, pharynx eosophagus, inferior thyroid artery
• C7 – vertebra prominence
• T2/T3 – suprasternal notch
• T4/T5 – Bifurcation of trachea & pulmonary trunk, opening of azygos into SVC (sternal angle)
• T5 – Thoracic duct crosses from right to left
• T8 – IVC, right phrenic pierces diaphragm
• T9 – Xiphoid
• T10 – esophagus, both vagi pierces diaphragm
• T12 – aorta, thoracic duct pierces diaphragm, origin of celiac trunk, upper pole of the kidney

• L1 – Transpyloric plane (passes through tips of 9th costal cartilage anteriorly and Lower border of L1 posteriorly)
1. Pylorus of stomach 5. Termination of spinal cord
2. Hila of the kidneys 6. Duodenojejunal flexure
3. Fundus of gallbladder 7. Origin of superior mesenteric artery
4. Neck of pancreas
• L3 – Subcostal plane( inferior margin of 10 rib)
1. Origin of Inferior Mesenteric artery 2. Lower pole of the kidney
• L3-L4 (Inter vertebral disc)
1. Umbilicus
• L4 – supracristal plane (Plane of highest point of iliac crest)
1. Bifurcation of aorta 2.Lumbar puncture
• L5 – Transtubercular plane (passes through tubercles of iliac crest)
1. commencementof IVC 2. Bifurcation of the common iliac artery
• S2 –dura mater terminates (posterior superior iliac spine - dimple)
• S3 – rectum begins, termination of the medial limb of sigmoid mesocolon
• Deep inguinal ring – 0.5 inches above the midpoint of the inguinal ligament
• Superficial inguinal ring – medial to pubic tubercle
• Liver(Points)
3. Left 5th intercostal space in mid clavicular line (Not palpable in normal subject)
• Spleen(Points)–Left side
1. Axis – 10th rib
5. Lateral end – Mid axillary line (Must be enlarged 3 times than normal to be palpated)
• Fundus of Gallbladder (Right side)
1. Tip of the right 9th costal cartilage
• Kidney(left)
1.1 inches from
Level of upper border of T12
Level of center of L1
3 inches from midline
• Base of the appendix – McBurney’s point (junction between medial 2/3 & lateral 1/3 of a line from umbilicus to ASIS)
Surface marking of lung & pleura
Erector spinae lateral
border
6th rib
8th rib
10th rib
8th rib 10th rib 12th rib

Stomach,liver,pancreas
Regionsof the Abdomen

Right Epigastric Left Spleen,left kidney,pancreas,stomach
Liver,gallbladder,right kidney
hypochondric hypochondric
Liver,gallbladder,ascending
colon,right kidney Descending colon,left kidney
Right lumbar Umbilical Right lumbar
Cecum,appendix Descending & sigmoid colon

Right iliac Hypogastric Left iliac
fossa fossa
Duodenum,jejunem,ilium
Sigmoid colon,urinary bladder
Referred pain
• Stomach – Epigastric area (T6-T7), back pain between two scapulae
• Gallbladder – R. hypochondric area, inferior angle of scapula, shoulder region(phrenic nerve)
• Appendix – umbilicus McBurney’s point(highest tenderness)
• Ureter & kidney – loin to groin (T11-L2)
• Spleen – left hypochondric area
Nerve supply of pharynx, larynx& tongue
 Tongue
• Except palatoglossus, all the muscles of the tongue are supplied by Hypoglossal nerve.
• Palatoglossus is supplied by pharyngeal plexus of Vagus
• Anterior 2/3
o General sensation – lingual nerve of mandibular nerve
o Taste – chorda tympani facial nerve
• Posterior 1/3
o General sensation & taste – glossopharyngeal nerve
 Larynx
• Except cricothyroid, all the muscles of the larynx are supplied by Recurrent laryngeal nerve.
• Cricothyroid is supplied by external laryngeal nerve
• Above the vocal cords sensory supply – internal laryngeal nerve
• Below the vocal cords sensory supply – Recurrent laryngeal nerve.
 Pharynx
• Except stylopharyngeus all the muscles of the pharynx are supplied by vagal branches.
• Stylopharyngeus is supplied by Glossopharyngeal nerve
• Sensory supply
o Nasopharynx – maxillary nerve
o Oropharynx – glossopharyngeal nerve
o Laryngopharynx – vagus nerve
 Stylohyoid is supplied by Facial nerve.

Myotomes
Upper limb
Flexion, abduction, lateral rotation (outward) - C5

Arm
Extension, adduction, medial rotation (inward) - C6, C7, C8
Flexion – C5, C6 supination – C6

Forearm Forearm
Extension – C6, C7 pronation – C7, C8
Flexion – C7 Flexion, extension – C7, C8

Hand Fingers
Extension – C6 Abduction, adduction – T1
Lower limb
Abduction, lateral rotation – L1, L2, L3, L4

Thigh
Adduction, medial rotation – L5, S1
Flexion – L2, L3
Thigh
Extension – L4, L5
Extension – L3, L4
Leg
Flexion – L5, S1
Dorsiflexion, inversion –L4, L5

Foot
Plantarflexion, eversion – S1, S2
Dorsiflexion – L5, S1
Toes
Plantarflexion – S1, S2
Dermatomes
 See Grants for dermatomes & cutaneous nerve.
 Remember,
• There is no dermatome for C1
• C6 dermatome overlies posterior surface of forearm & arm.
• There is no T1 dermatome on thorax
• T4 dermatome overlies nipples.
• T10 dermatome overlies umbilicus.
• L1 dermatome overlies inguinal area
• S2 dermatome overlies posterior surface of leg & thigh.

Secretomotor pathways Nerve Roots
Submandibular gland Axillary nerve – C5, C6
Musculocutaneous nerve – C5, C6, C7
Superior salivatory nucleus Median nerve – C6, C7, C8, T1
↓ Radial nerve – C5, C6, C7, C8, T1
Nervus intermedius Ulnar nerve – (C7), C8, T1
↓ Long thoracic nerve – C5, C6, C7
Facial nerve
↓ Femoral nerve – L2, L3, L4 (posterior divisions)
Chorda tympani Obturator nerve - L2, L3, L4 (anterior divisions)
↓ Sciatic nerve – L4, L5, S1, S2, S3
Joins lingual nerve of mandibular nerve Tibial nerve - L4, L5, S1, S2, S3 (anterior divisions)
↓ Common peroneal nerve - L4, L5, S1, S2( posterior
Submandibular ganglion (relay) divisions)
↓ Pudendal nerve – S2, S3, S4
Postgangionic fibres Ilioinguinal, iliohypogastric nerve – L1
↓ Lateral cutaneous nerve of thigh – L2, L3
Submandibular & sublingual glands
Phrenic nerve – C3, C4, C5
Parotid gland Pelvic splanchnic nerve – S2, S3, S4 (parasympathetic)
Inferior salivatory nucleus

↓
Glossopharyngeal nerve
↓
Tympanic branch
↓
Tympanic plexus
↓
↓
Otic ganglion (relay)
↓
Postganglionic fibres
↓
Joins auriculotemporal nerve
↓
Parotid gland

biochemistry
bat notes
term 03
Purine & Pyrimidine Metabolism
 Purines
01. De Novo Synthesis – base can`t synthesize separately always built upon a PRPP
02. Catabolism-no breakage in purine ring just a conversion
03. Salvage Pathway
 Pyrimidine
01. De Novo Synthesis- primary base orotate is synthesized separately & attach to a PRPP
02. Catabolism-ring is broken
03. Salvage pathway (few pyrimidines-bases in treating orotic aciduria)
Purines
01. Adenine
02. Guanine
∗ Double ringed structures

∗ Cannot be opened in human cell
∗ Purine ring primarily constructed in liver
De Novo Synthesis
4 major steps
1. PRPP synthesis
2. amidotransferase reaction
3. IMP synthesis
4. conversion to AMP, GMP
HMP→ Ribose -5-phosphate

ATP ↙ + Pi
Mg+2
AMP PRPP synthase (x linked)
↖ - AMP, GMP (end product
inhibition)
5-Phsophoribosyl-1-pyrophsophate (PRPP)
↙ + PRPP
Glutamine Glutamine-PRPP amidotransferase
Committed step Mg+2
↖ - AMP, GMP
Glutamate
IMP
5-Phsophoribosylamine
∗ Normal [PRPP] is much less than km value of amidotranferase reaction.

∗ So reaction rate is proportional to [PRPP]
∗ Amidotransferase is subjected to end product inhibition by AMP, GMP, and IMP by converting active dimer
to inactive monomer.
Dimer (active) monomer (inactive)
AMP, GMP, IMP

5-Phsophoribosylamine
Glycine, Glutamine, Aspartate
(10 steps) 2 N10 formyl tetrahydro folate,
CO2, 3 ATP
GTP IMP NAD
Pi + GDP IMP NADH

AS synthase Dehydrogenase
Adenylosuccinate [AS] Xanthosine mono P [XMP]
ATP
ADP
AMP GMP
dADP ADP GDP dGDP

Ribonucleoside Ribonucleoside reductase
reductase
ATP GTP
∗ IMP is a precursor of adenine and guanine containing nucleotides

∗ ATP is needed for conversion IMP to GMP, GTP is needed for convert IMP to AMP.
∗ Ribonucleoside reductase converts ribonucleoside diP to deoxyribonucleoside diP. This enzyme is
o inhibited by dATP(important in adenosine deaminase deficiency)
o activated by ATP
∗ Both AMP and GMP inhibit de-novo synthesis of purine (inhibit amidotransferase step)
Salvage pathway of purine synthesis

• Uses catabolic products of nucleic acids (purine bases) to resynthesize nucleotide monophosphate.
• Requires less energy than de-novo pathway.
Adenine + PRPP APRT AMP + PP1
Guanine + PRPP HGPRT GMP + PP1
Hypoxanthine + PRPP HGPRT IMP + PP1
[APRT = Adenine phsophoribosyl transferase]

[HGPRT= Hypoxanthine - guanine phsophoribosyl transferase]
Purine Catabolism
Nucleotide → nucleoside → base → xanthene → uric acid
∗ Dietary nucleic acids → intestine mucosal cells
∗ Denovo synthesized nucleic acids → primarily degraded in liver
o Salvaged by peripheral tissues

AMP AMP deaminase IMP GMP
adenosine Inosine guanosine

adenosine deaminase
Hypoxanthine Guanine
Xanthine oxidase Xanthine
[-] Xanthine oxidase

[-]
Uric acid
Allopurinol
[Purine analog]
Clinicals
Dihydrofolate synthase Dihydrofolate reductase

♦PABA folic acid Tetrahydrofolate
Sulphonamide DHF Methotrexate THF
[Antibiotic] [Anticancer]
Sulphonamide is a structural analogue of PABA [para amino benzoic acid]

• So, it binds with and competitively inhibits dihydrofolate synthase & inhibits folic acid
synthesis in microorganism.
• Folic Acid is required to from THF which is in from need in purine synthesis
• Humans do not synthesize folic acid, but obtain it from diet.
• Sulphonamides can be used as an antibiotic without affecting Humans.
Methotrexate Is a structural analogue for folic acid

• Methotrexate competitively inhibits Dihydrofolate reductase.
• Dihyrofolate reductase is needed for synthesis of THF which is needed in purine synthesis.
• Leukemia consists of rapidly dividing white blood cells.
• Rapidly dividing cells have high demand of purines for DNA replication
• Decreases in purines have more effect on cells with high demand **
• Methotrexate is used as a drug for leukaemia
** Any drug that blocks nucleotide synthesis will regulate neoplastic cells
IMP dehydrogenases
♦ IMP Xanthosine monophosphate GMP
Mycophenolic acid – reversible uncompetitive inhibitor of IMP dehydrogenase.

• T, B cell division is impaired
• Used to prevent graft rejections
PRPP amidotransferase
♦ PRPP Phosphoribosyl amine
Glutamine Glutamate

• These two are glutamine antagonists
Mercaptopurine
• The reaction cannot go ahead without glutamine
Azaserine (diazo acetyl – L – serine
• So purine synthesis is blocked at PRPP.
• PRPP accumulates
Gout (Hyperuricemia)
Accumulation of urate crystals in synovial fluid lead to arthritis (sp. In cooler areas like distal joints)
1ry hyperuricemia
• 5-PRPP amido tranferase not sensitive to feedback inhibition
by nucleotides
• Abnormal PRPP synthetase → no allosteric inhibition →
↑PRPP production
• Deficiency of salvage enzymes → ↑PRPP production & ↓ purines → ↑ Purine production

Inhibit feedback inhibition → ↑PRPP
Eg: Lesch nyhan syndrome[X linked recessive] ↑ Purine breakdown
Due to HGPRT deficiency
Neurological features (self-mutilations, involuntary movements) ↑ Production of uric acid
Hyperuricemia, urate crystals in joints, urate crystals in kidney
• Glucose 6 phosphatase deficiency → ↑Glucose 6 phosphate →

↑ HMP pathway → ↑Ribose 5 phosphate → ↑PRPP
(Von-Gierk disease)
2ry hyperuricemia
• Rapidly growing malignant tissues, leukemia or lymphomas
• ↑ Tissue breakdown after treatment of malignant tumors

↑ Purine ↑ Purine breakdown
• ↑ Tissue damage due to trauma & catabolism in starvation
↑ Production of uric acid
• ↑ increase consumption of purine nucleotides
• Defects in excretion
o Due to kidney disease
o lactic acidosis-compete for same transporter to secrete
o thiazide diuretics reduce secretion of uric acid
Treatments for gout:

• Allopurinol – suicide inhibitor of xanthine oxidase
• Uricosuric drugs eg: probencid - ↓ reabsorption of uric acid
• Reduce alcohols & dietary purine intake (meat, sea food)
• Colchicine - anti-inflammatory agent
Adenosine deaminase deficiency - SCID (severe combined immune deficiency syndrome)

o ↑ Adenosine, AMP and dATP level
o dATP inhibit ribonucleotide reductase
o ↓ deoxyribonucleotide levels
o DNA synthesis interrupted
o ↓T cell B cell growth
o SCID - without treatment die @ age 2
o Bone marrow replacement , enzyme replacement done
Pyrimidines
01. Thymine
02. Cytosine
03. Uracil (only in RNA)
** Single ringed structures
** can be opened in human cell
Easily opened and degraded to soluble β-alanine and β-aminoisobutyrate
De Novo Synthesis
2 ATP + Glutamine + HCO3 -

Key regulatory step in ↙ + PRPP, ATP
Carbamoyl P synthetase ΙΙ (in cytosol)
mammals ↖ - UTP, UDP
2 ATP + Glutamate + P1
Carbamoyl Phosphate
CAD
Aspartate Aspartate transcarbomoylase ↙ + ATP (multifunctional
Polypeptide)
↖ - CTP
Carbamoyl aspartate
Orotate
 Mammalian CPS-2 is inhibited by UTP & activated by PRPP.

 Prokaryotic aspartate transcarbomoylase is inhibited by CTP and activated by ATP
Orotate
Orotate phsophoribosyl transferase
PRPP
Two domains of one enzyme- UMP synthase
OMP Deficiency anaemia & increased
excretion of orotate in urine
CO2
OMP decarboxylase - UMP, CMP
UMP
Orotic aciduria
• Absence of orotate phosphoribosyl transferase or OMP decarboxylase or both
• Retarded growth , anemia
• Can also occure due to Ornitine transcarbomylase deficiency, allopurinol-compete with OPT
• give uridine , cytidine as treatment
• then they Converted to UTP,CTP by salvage pathway & inhibit pyrimidine synthesis process

UMP NADPH +H+
UDP Reductive Thioredoxin Thioredoxin reductase

Ribonucleotide
UTP reductase Oxidized Thioredoxin NADP +
CTP synthatase dUDP

(add amino grp frm glutamine)
CTP
dUMP
Methylene H4 folate
Thymidylate [-] 5-FdUMP

Synthase [permanently bind to enzyme]
dihydrofolate
dTMP 5 florouracil
NADPH +H+ [Thymine analogue- suicide inhibitor]
Dihydrofolate
reductase
NADP +
[-] Methotrexate
tetrahydrofolate
Association of HMP pathway in nucleotide synthesis
HMP pathway
NADPH Ribose -5- P
Pyrimidine synthesis purine synthesis
Pyrimidine Catabolism
Easily opened and degraded to soluble β-alanine and β-aminoisobutyrate

Cytosine Thymine
Uracil Dihydrothymine
Dyhydro Uracil β-Aminoisobutyrate
β-Alanine

HEME BIOSYNTHESIS
Important haemproteins
• hemoglobin
• cytochromes ( heam + protein )
• chlorophyll (Mg containing porphyrin)
Heam
Protoporphyrin Fe2+
( Porphyrin)
Porphyrins
Cyclic compounds Coloured Bind with metal ion
Pyrrole rings (4)
Fe2+
Methylene bridges
-CH3
Side chains
CH2CH2COO-
Porphyrinogens
E.g. uroporphyrinogen, coproporphyrinogen
• Porphyrin precursors / intermediates of heme synthesis

• Colourless
• Unstable  auto oxidize to porphyrins
Haem
• Haem is the Most common porphyrin in human.
o In Erythroid - Haemoglobin
o In Nonerythroid – Myoglobin, Cytochromes, Catalase, Tryptophan pyrrolase

Heme biosynthesis
• Occurs in most cells (not in RBC)
In Liver (e.g. cytochrome p450 )
Bone marrow (haemoglobin) (85%)
• 1 and last 3 reactions take place in Mitochondria. Other reactions occur in cytosol.
st
• All C & N atoms of the porphyrin molecule are provided by Glycine (non-essential AA) &
Succinyl Co A (Intermediate in TCA, Origin from acetate)
Pyridoxal phosphate (PLP)

(Vit B6) serves as coenzyme
Hemin (Fe3+) for ALA Synthase .
(-)
Oxidize
ALAS 1
Heme (Fe )2+
Succinyl CoA
+ ALA
Glycine (δ - aminolevulinic
acid)
ALAS 2
Zn containing enzyme
2ALA
ALA Dehydratase
ALA Porphobilinogen (PBG)
anemia Pb2+ poisoning
Protoporphyrinogen IX
Protoporphyrin IX
Via Transferrin Fe2+ Spontaniously / Enhanced by Frerrochelatase
Pb2+ poisoning
Heme
Formation of haem anaemia
Regulation
• In the liver – Rate is variable, responds to

alterations in cellular haem pool
• In erythroids – Rate is constant, matched
to the rate of Globin synthesis

ALA synthase
This reaction is the committed and rate-controlling step in hepatic porphyrin ( heam)
biosynthesis.
Regulation of Haem synthesis in the Liver
1. Haem / Haemin control

• Feed back Allosteric inhibitor
• Decrease ALAS1 enzyme synthesis (controls transcription, translation, translocation)
(Repression derepression)
- Decrease transcription at gene level
- Decrease stability of mRNA, therefore decreases translation
- Decrease transport of enzyme from cytosol to mitochondria
Done by ATP I. ALAS I only unfolded form can cross

dependent II. N terminal signal sequence, cleaved by
chaperon III. To active refolding by oligomeric folding protein.
proteins Metal Proteins
2. Glucose – repression
3. Substrate availability – Fe2+
4. Drugs – derepression
5. Other (Certain steroids)
Effect of drugs on ALA synthase activity
Some drugs are detoxified/metabolised by Cyt. P450 in liver (Microsomal monooxygenase system)
synthasis of Cyt. P450
consumption of haem
[Haem] in liver cells
Derepression of ALAS 1
Synthasis of ALAS 1

Effect of Pb2+
Inhibits,
1. ALA dehydratase - Impairs PBG formation, Elevated porphyrin levels in RBC,
Elevated ALA & coproporphyrin in urine
2. Ferrochelatase – Decreases Haem formation, Causes sideroblastic anaemia
Regulation of erythroid heam biosynthesis
Bone marrow ALAS II
- not induced by drugs
- no feedback inhibition by haem
So, erythroid heam bio-synthesis depend on,
1. erythropoietin – stimulates synthesis of ALAS II
2. availability of intracellular iron
3. (Availability of globin)
Porphyrias
• Heterogeneous group of rare inborn errors of metabolism
• Due to defect in 7 enzymes (2nd step – 8th step)
• Accumulation and increase excretion of metabolic intermediates; Porphyrins
• Chemicals and drugs can predispose the disease
Mutations in various genes
Abnormalities of enzymes of haem synthesis
Accumulation of ALA & Accumulation of

PBG and/or decrease in porphyrinogens in skin
haem in cells and body and tissues
Neuropsychiatric signs and symptoms Spontaneous oxidation or

porphyrinogens to porphyrins
Photosensitivity
(Skin itches, blisters..)
Porphyrias can be classified into hepatic and erythropoietic, and subdivided into acute and non-acute.
Acute – Accumulation of ALA & PBG
Neurological, psychiatric & acute GI disturbances
Non-acute – Increased ALAS & defect in uroporphyrinogen carboxylase
Specific uro & coproporphyrins accumulate
Urinary uroporphyrin excretion increase (Urine turns red on standing)
Nutritional and environmental factors precipitate symptoms
• Low carbohydrate diet
• Drugs /alcohol/ smoking
Managing
1. Avoid Cyt. P450 inducing dugs
2. Carbohydrate diet??
3. Administration of hematin-
4. Administration of β carotin to detoxify free radicals ( to ↓ photosensivity)
 Cancer phototherapy (additional)

• Tumors take up more porphyrins
• Hematoporphyria are administrated to patient
• Tumor is exposed to argan laser
• Cytotoxic effects to cells
HAEM CATABOLISM
• Occurs in microsomal haem oxygenase system in reticuloendothelial cells of liver, spleen and bone
marrow.
Hemoglobin
Heme Globin
Heme oxyganase
NADPH+H+, O2
A.A
recycled Fe2+ NADP +
A.A pool
Biliverdin (green)
• Lipophilic.
Biliverdin reductase
• Slightly soluble in plasma
Bilirubin (red orange) • Non covalently bonds to
albumin for transport
• Can’t be filtered by
glomerulus(kidney).
Albumin- bilirubin(in blood)
Albumin
Liver cell ligandin
UPTAKE
Bilirubin + 2UDP glucuronic acid
Bilirubin UDP glucuronyl

transferase
Bilirubin diglucuronide
• Distrupt H
(Conjugated )
bonds-
solubility ATP
Urobilinogen
Enterohepatic Bilirubin diglucuronide

circulation
Bacterial oxidation
Urobilinogen in blood Urobilinogen

Intestine
Kidney
Stercobilin
Urobilin (urine)
Stools

Two binding sites in albumin for bilirubin,
High affinity – 25mg bilirubin
Low affinity – excess, loosely binds and easily detached
Uptake by liver – Not rate limiting, Facilitated transport
Conjugation - Drug inducible ( Phenobarbital)
Secretion by liver – Rate limiting, active transport, drug inducible ( Phenobarbital)
Secretion of Bilirubin diglucuronide into bile canaliculi is the rate limiting step.
Clinicals
1. Jaundice (Icterus)
• Definition – Yellowish discoloration of skin, sclera and nail beds due to increased levels of
conjugated or unconjugated bilirubin or both in blood.
• Clinically detectable when serum bilirubin > 2-2.5 mg/dl
Types of jaundice
Pre-hepatic (before uptake)
Jaundice Hepatocellular (Uptake to secretion)
Post-hepatic (from bile canaliculi to small intestine)
A. Prehepatic jaundice (Hemolytic jaundice)

Can be seen in sickle cell anemia, G-6-PDH deficiency, pyruvate kinase deficiency, in malaria
treatment.
• RBC lysis at high rate bilirubin production>conjugation.

• Unconjugated bilirubin level increases.
• Heme breakdown conjugation bile secretion urobilinogen
Therefore high levels of urobilinogen in urine-dark colour urine.
• ALT, AST, ALP levels normal. ( why?..........)
B. Hepatocellular jaundice :
Due to liver damage (cirrhosis/ hepatitis)
• Uptake
• Conjugation  unconjugated bilirubin in blood
• Impaired secretion  pale stools(low stercobilin) and low urobilinogen
 regurgitation of conjugated bilirubin in blood
Dark urine
• Enterohepatic circulation of urobilinogen  more enter into blood  filtered into the urine
• Plasma AST, ALT levels due to liver damage but no increase in ALP.
C. Post-hepatic jaundice (Obstructive jaundice)

Retention and regurgitation of bile due to bile duct obstruction (extrahepatic cholestasis).
• Conjugated biirubin in blood  tea colour urine

• Unconjugated bilirubin normal. Why??..........................................................
• No urobilinogen pale, clay coloured stools
• ALP in plasma
• AST and ALT level normal
Prolonged obstruction can lead to liver damage leading to increase in unconjugated bilirubin in blood.
2. Displacement of bilirubin from albumin by drugs – Salicylates, Sulfonamides

(permiting bilirubin to enter the CNS)
3. UDP glucuronide transferase deficiency

Bilirubin - Uridine glucuronyl transferase ( UGT) activity can be induced by drugs  eg: phenoibarbital
4. Jaundice in new born

Due to
i. Activity of hepatic glucoronyl transferase is low at birth (Immature hepatic system)
ii. Conversion of HbF  HbA
So catabolism is increased. Unconjugated bilirubin ↑
5. Haemolytic disease of the newborn (HDN)

- Feto-maternal incompatibility for red cell antigens (ABO/ Rh)
- Maternal antibodies against fetal RBC antigens

- Transfer from mother to fetus through placenta
-Destroy fetal RBCs
Severe jaundice
BBB is immature  bilirubin can pass through

 deposits in basal ganglia
 kernicterus - Toxic encephalopathy
• Treated with blue florescent light. Converts bilirubin to more polar compound (more water
soluble). Can be extracted with bile without conjugation.
• Administration of phenobarbital
• Exchange transfusion in severe cases
6. Congenital disorders
• Deficiency of bilirubin glucuronyl transferase - Crigler-Najjar I & II, Gilbert syndrome
• Deficiency in transport protein – Dublin Johnson syndrome
Tests for bilirubin

1. Vandenberg test bilirubin in plasma.
• Conjugated bilirubin level  direct test.
• Unconjugated bilirubin level  indirect test.(by measuring total bilirubin level)
2. Ehrlich’s test bilirubin in urine

Ehrlich’s diazo reagent +bilirubin  reddish purple

Mineral Metabolism
“Trace Elements” – Inorganic metals which occur in biological fluids at a very low concentration (less than
1μg/g of wet weight). Most essential, others may be required.
Deficiency common for Iron, Iodine, Fluorine.

Deficiency identified for Manganese, Chromium, Cobalt, Molybdenum, Zinc, Selenium, Copper
Deficiency of trace elements may occur due to: BUT, trace elements may be toxic,
• Inadequate intake • If taken excessively
 Due to malnutrition (→ “food • If taken in the wrong chemical form
faddism”) (e.g. Cr3+ is the normal active form while
 Due to malabsorption Cr6+ is toxic)
 Due to alcoholism
• Low bio-availability
• Depending on rate of excretion
• Antagonistic interactions
• Increased loss
→ As a consequence of disease
→ As a consequence of therapy (e.g. dialysis,
total parenteral nutrition/TPN)
Iron
 Dietary sources : Meat, fish ,poultry, dark green leafy vegetables, pulses
Deficiency Functions Symptoms/Consequences of
(Requirement- 15mg/day) Deficiency
• Inadequate intake Active form: Fe 2+
• Compromised development in
 Malnutrition Component of: young children (iron enzymes
 food faddism • Hb & myoglobin in neurotransmitter systems →
 malabsorption • Cytochromes affect motor & cognitive
• Low bio-availability • Haem enzymes development)
• Antagonistic interactions (peroxidises) • Impairs work performance &
2+ 2+
(Ca and Zn compete • Non-haem enzymes exercise capacity
2+
with Fe during (NADH dehydrogenase,  ↓Cytochromes→
absorption) phenylalanine hydroxylase) ↓Oxidation reactions in
→ Due to disease • Iron-Sulphur clusters muscles→ ↓Energy
→ Due to therapy production
 ↓Hb→ ↓O2 transport
1. Risk groups ; infants,pre-schoolers ,adolescent females, pregnant females
2. Body prioritizes the use of iron in deficiencies
Mild deficiency progresses Anaemia
Iron is never found in free form (Fe2+) in cells because Fe2+ can generate oxygen free radicals.
Always converted to Fe3+ and bound to proteins:
 During transport – bound to apotransferrin (to form transferrin)

 During storage – bound to apoferritin (to form ferritin)

Iron Absorption
HT = Haem Transporter, DMT1 = Divalent Metal Transporter 1,

Hp = Hephaestin, FP = Ferroportin, TF = Transferrin
NOTE: There is no specialised route for excretion of iron. Iron absorption is controlled
so that the amount absorbed is just sufficient to replace losses.
Regulation of absorption at intestines:

1) Dietary Regulator (Recently consumed iron-ferritin in intestinal cells affects absorption)
2) Stores regulator (total body iron affects levels of apical transporter) in deficiency Fe absorption
increases 2 – 3
3) Erythropoietic regulator (erythropoiesis requirements change iron absorption irrespective of
current iron levels → a soluble signal from bone marrow to intestine)
Iron Transport & Uptake by Tissues

Transported bound to apotransferrin (apotransferrin + Fe2+ = transferrin)
Transferrin binds to Transferrin receptors (TfRs) on cells
Iron taken into cells is stored in ferritin and haemosiderin
Old RBCs → Phagocytosed by macrophages → Haemoglobin in RBCs

↓ Haem oxygenase
Biliverdin + Fe2+
↓
Released to blood via ferroportin

Regulation of iron absorption and uptake by tissues:
Whole body iron status is regulated through a combination of :

• Hepcidin and ferroprotein mediated iron released from hepatocytes , enterocytes and macrophages
• Regulation of iron absorption at gut level
1) Iron deficiency and hypoxia stimulate:

↑Expression of DMT-1, Ferric reductase, Ferroportin → ↑Increased iron absorption & uptake
2) Cellular iron status is regulated at cellular level through reciprocal regulation of transferrin receptors
and ferritin expression
Translation of mRNA coding for ferritin and transferrin receptors (TfRs) is reciprocally
regulated.
When intracellular iron level is high, ↑ferritin ↓TfR
When intracellular iron level is low, ↓ferritin ↑TfR
Discussed in detail under “Regulation of Gene Expression” lesson
3) Systemic iron levels controlled by hepcidin

Hepcidin – Protein produced by liver and secreted to blood
Hepcidin binds to ferroportin and triggers its internalization & degradation
Hepcidin inhibits:
 Transfer of iron to blood by intestinal cells
 Release of iron by macrophages
Hepcidin production is regulated by:
 Iron availability (in deficiency, ↓ hepcidin release)
 Erythropoiesis
 Inflammation/Chronic diseases (↑ hepcidin release) – “anaemia of inflammation”

Assessment of Iron Status
• Hb & peripheral blood film
• Erythrocyte protoporphyrin (ZincPP measured)
• Serum Iron (SI)
Transferrin-bound iron
[NOTE: Only 1/3 of transferrin’s binding sites are used]
• Total Iron Binding Capacity (TIBC)
Total capacity of serum transferrin to bind iron
𝑆𝑆𝑆𝑆
• Percentage of Transferrin Saturation (TS) = × 100%
𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇
• Serum ferritin indicates amount of stored iron.
Iron overload
1. Excessive absorption→Hereditary haemochromatosis
2. Excessive intake
3. Transfusional haemosiderosis – multiple blood transfusions
4. Inappropriate administration of iron
Calcium
• Minearl present in largest amount in the body.
 99% in bones and teeth.
 <10g found in soft tissue and ECF (part in ionized form)
Increased absorption Decreased absorption

• Vit. D adequacy • Vit.D deficiency
• Increased mucosal mass • Decreased mucosal mass
• Ca deficiency • Decreased gastric acid
• Phosphate deficiency • Menopause
• Pregnancy • Old age
• Lactataion • Rapid intestinal transit time
• Mucosal permeability
Absorption
• Intestine most rapid in duodenum ( pH <7 )
• 2 mechanisms,
 Active transcellular absorption
Duodenum and proximal jejunum, at low luminal Ca conc. , controlled by Vit.D through the
protein calbindin.
 Passive paracellular absorption ( between cells)
At high luminal Ca conc. and is bidirectional.
1. Entry across brush border – by Ca transporter 1(CaT1)
2. Intracellular diffusion – calbindin
3. Extrusion – CaATPase
Effects of Hormones
Parathyroid Hormone 1,25-dihydroxycholecalciferol
Calcitonin
(PTH) (Calcitriol)
Increase plasma Ca • In intestine: • ↓ Plasma Ca2+ level
• In bone: ↑ Ca2+ absorption (By: minor effect
↑ Ca2+ mobilisation from ↑ calbindin, [By ↓ Ca2+ mobilisation
bone (↑ osteoclastic ↑ membrane transporters) from bones]
resorption)
• In bone:
• In kidney: ↑ Ca2+ mobilisation from
↑ Ca2+ reabsorption bone (in presence of PTH)
↓ Ca2+ excretion
↓ PO43- reabsorption • In kidney:
↑ Calcitriol production ↑ Ca2+ reabsorption
(↑ 1-hydroxylase activity) ↓ Ca2+ excretion

Functions
1) Structural – Supporting material in bones and teeth
2) Neuromuscular – control of excitability
- release of neurotransmitters
- initiation of muscle contraction
3) Signalling – 2nd messenger
4) Enzymic – co enzyme for clotting factors
Cellular proteins binding or activated by Calcium

1) Calmodulin – modulator/regulator of several protein kinases
2) Troponin C – modulator of muscle contraction
3) Protein kinase C – protein kinase
4) Calbindin – Ca storage
Ca transport in plasma
Non diffusible (protein bound) (40%)
Total Ca
Free ionic Ca physiolo. Active (50%)
Diffusible (60%)
Complexed [with citrate, Phosphate] (10%)
Associated disorders
Hypocalcaemia Hypercalcaemia
• With low PTH • Hyperparathyroidism-high serum Ca2+,

Hypoparathyroidism Ca excretion & renal calculi can occur
• Malignant diseases
• With high PTH • Excessive vit D and Ca intake
Deficient intake/absorption of vit D or Ca
Inadequate exposure to sunlight
Disordered vit. D metabolism
CRF failure to form 1,25 dihydroxyD3
Measurement of plasma Ca
• Only ionized Ca is phys. active & its concentration maintained by homeostatic mechanisms
• Total Ca commonly measured
• Changes in plasma albumin affect total Ca independently of ionized Ca
-measure Alb & correct
• Venous stasis during blood sampling common cause of hyperalbuminaemia & hypercalcaemia
Avoid use of tourniquet
Iodine
Importance: As a component of thyroid hormones
Active form: I- (iodide ion)
Sources: Iodised salt, sea foods, drinking water
Rapidly absorbed in small intestine and transported in plasma loosely attached to proteins
Nearly 1/3rd taken up by thyroid gland (by Na+/I- symporter), remainder excreted in urine
 Thiocyanate & perchlorate: Inhibit the Na+/I- symporter in thyroid follicle cells
 Propyl thiouracil, carbimazole, methimazole: Inhibit iodination & coupling

Movement of Iodine between Compartments
 T4 – most abundant form synthesized in the thyroid gland.

 Most T3 is derived by deiodination of T4 in peripheral tissues.
 T3 – more active but less amount
Thyroid hormone synthesis

1) Follicular cells synthesise enzymes and thyroglobulin for colloid.
2) I- is co transported into cell with Na+ ( Na-I symporter) and then into colloid.
3) Oxidation of iodine.
4) Iodination of tyrosine portion of the thyroglobulin.
5) Coupling of MIT & DIT/DIT & DIT to form T3/T4
6) Product is taken back into cells.
7) Intracellular enzymes separate T3 & T4 from proteins.
8) Free T3 & T4 enter circulation.
Regulation of Thyroid hormone

Transport of thyroid hormones in plasma:
• 99% protein-bound → Mainly Thyroxine Binding Globulin (TBG) and a smaller amount bound to
prealbumin & albumin also
• Only the free (unbound) form is physiologically active
Free T4 concentration is 2 to 3 times higher than free T3 concentration
• Bound hormone acts as a reservoir which helps maintain free T3 and T4 levels in plasma
Actions of Thyroid Hormones

• Promote normal differentiation & growth. Essential for normal foetal & neonatal development.
• Overall effect is to speed up metabolic reactions and BMR:
 ↑ Oxidative phosphorylation
 ↑ Carbohydrate metabolism
 ↑ Lipid metabolism
• Increase sensitivity of cardiovascular and nervous systems to catecholamines
Tests of Thyroid Function

 Free T4 (fT4) and free T3 (fT3) → methodological problems if binding proteins grossly altered
(plasma total T3 and T4 affected by binding proteins)
 TSH
 TRH test – TSH measured before and after IV administration of TRH
 Thyroid antibodies – Thyroperoxidase antibodies, thyroglobulin antibodies
 Thyroid imaging
 Uptake tests
Iodine Deficiency → ↓Thyroid hormone production → ↑TSH (due to less negative feedback)
↑TSH → ↑Blood flow to thyroid, stimulates follicular cells, ↑colloid production
Iodine deficiency will produce hypothyroidism and then it will lead to goitre. Goitre is not always iodine
deficiency.(Selenium deficiency)
Disorders of Thyroid Function:

 Hypothyroidism – Due to iodine deficiency, Hashimoto’s thyroiditis, Congenital thyroiditis, Idiopathic,
Secondary
 Hypertyroidism – Grave’s disease, Toxic multinodular goitre, Solitary toxic adenoma, Exogenous iodine
containing drugs

Mineral Functions Deficiency/Special Notes
 Zinc Zn-dependant enzymes in all major Primary Deficiency:
pathways (e.g. carbonic anhydrase, ALP, Inadequate intake2+or low bio-availability (due to
glutamate dehydrogenase) fibre, phytate, Ca )
Iron:Zinc ratio > 3:1
Required for gene expression, growth & Inherited defects (acrodermatitis enteropathica)
development (e.g. interaction of
hormone-receptor or vitamin-receptor Secondary Deficiency:
complexes with DNA) Malabsorption, prolonged total parenteral nutrition
Hypercatabolic states (burns, injuries)
Maintain integrity of cell/organelle Alcoholism
membranes Sickle cell anaemia
Immuno-stimulant (esp. cell-mediated Manifestations are different in different age groups
immunity)
Antioxidant
Vit. A and alcohol metabolism
Central role in normal progress of
gestation, parturition, foetal development
 Selenium Component of glutathione reductase & Deficiency causes hypothyroid cretinism
Functional thyroxine deiodinase
form: Reduced requirement for Vit. E Linked to chronic degenerative and inflammatory
selenocysteine Protects against toxic doses of Cd/Hg diseases such as cancer, rheumatoid arthritis,
ischemic heart diseases
Selenium and iodine deficiency linked
Se def. can be a factor to goiter.
 Fluoride Fluoride is a bone seeker Only traces required. Excess is harmful. Excessive
Drinking intake causes mottling & discolouration of teeth.
water 1-2ppm Protects against dental caries, especially Very large intakes cause irregular deposition in
in children. Acts by remineralising early axial skeleton, secondary involvement of nervous
carious lesions, increasing resistance of system – crippling fluorosis
enamel to acid, inhibiting growth of
acid-forming bacteria in dental plaque Deflouridation can be done by distilling water
Protects against osteoporosis in older
adults (esp. women)
Cobalt Component of Vit. B12, so required for
methionine metabolism & regeneration
of THF
 Chromium Active form is Cr3+ - as an organic
complex
Insulin-receptor interaction, glucose
factor (GTF), role in glucose & lipid
metabolism
 Copper Connective tissue metabolism (collagen
elastin cross linking)
Bone development
Haemoglobin synthesis
Ferroxidase (ceruloplasmin)
Free radical scavenging (superoxide
dismutase)
Catecholamine, melanin synthetic
enzymes
Molybdenum Xanthine oxidase
Manganese Oxidative phosphorylation
Fatty acid, mucopolysaccharide and
cholesterol metabolism

Medical diagnostics
Clinical lab tests are important in,
• Diagnosis of diseases
• Determination of its severity
• Assess patient response for specific treatment
Types of samples: -
• Blood, serum, plasma • CSF
• Urine, Faeces • Other body fluids and tissues
Phlebotomy: - Drawing blood from a vessel for laboratory analysis
Preparation of Blood Sample
Whole blood Plasma Serum

 Must be analyzed  Serum = plasma – clotting factors
within limited time
Haemolysis high high

Over time
Bilirubin lipid
Increase K+ release Hb
Cell lysis continuation of Ca2+, PO43−, due to rupture icteric lipemic
cellular metabolic SGOT, LDH, of RBC
processes Acid phosphate
Changes the
concentration of Pink to red yellow turbid/milky
some analytes Glycolysis
Ex: (K+, PO43−,

LDH increase in [glucose] [lactate] Serum colour changes
blood sample) Reduces increases
 Contents of electrolytes, enzymes and hormones are similar in plasma and serum
Common biochemical tests
1. Testing for glycaemic levels (diabetes mellitus)

• Fasting plasma glucose • 2h plasma glucose (OGTT) • HbA1C

2. Cardiac biomarkers
• Cardiac troponin T & I • Myoglobin
• CK2 / CK MB • Heart Fatty acid binding protein
• Lactate Dehydrogenase (LDH) • Natriuretic peptides (BNP)
3. Lipid Profile
• Total cholesterol • LDL cholesterol
• HDL cholesterol • Serum triglyceride
4. Renal Profile – serum creatinine
5. Urine testing – microalbuminuria
(1) Testing for glycaemic level – diabetes mellitus

WHO criteria for diagnosis of diabetes mellitus
If, fasting plasma glucose (FPG) ≥ 126 mg/dl OR presence of
2h plasma glucose (OGTT) ≥ 200 mg/dl diabetes mellitus
If, FPG < 126mg/dl Impaired glucose tolerance (IGT)

OGTT → 140 – 200 mg/dl
If, FPG → 110 – 125 mg/dl AND Impaired fasting glucose (IFG)
OGTT < 140 mg/d
• ADA (American Diabetic Association) criteria for diagnosis of DM

HbA1C ≥ 6.5%
FPG ≥ 126 mg/dl
OGTT ≥ 200 mg/dl Same as WHO criteria
Random plasma glucose ≥ 200 mg/dl in a patient with hyperglycaemic crisis.
• Presence of one or more from above criteria confirms presence of DM.
 Oral Glucose Tolerance Test (OGTT)

• Not recommended for routine diagnosis of type I or type 2 diabetes
• OGTT is recommended when FPG is in IFG range (110 – 125 mg/dl)
3 days unrestricted carbohydrate diet
Overnight fast
Oral ingestion of 75g glucose, in 250 – 300ml of water, over 5 min.
Check blood samples, 2h after glucose load
 HbA1C Test / Glycated haemoglobin

Average amount of HbA1C reflects the mean blood glucose concentration over the previous 6 – 8 weeks.
(directly proportional)
Glucose can attach to many proteins via non-enzymatic process (post translational modification)
1. Reversible reaction
2. Followed by Amadori rearrangement to form irreversible ketoamine

Misleading results
Low RBC turnover Rapid RBC turnover
Disproportionate number of Greater younger red cells

Older cells in circulation in circulation
Falsely high values Falsely low values

Ex: iron / vitamin B12 /Folate Ex: haemolysis
deficiency anaemia haemoglobinopathies
(2) Cardiac biomarkers

• Are myocardial proteins
• Characteristic rise and fall pattern
• Differ in, location within myocyte
Release after damage (depends on location and molecular weight)
Clearance from the serum
Troponins
• Biochemical gold standard for the diagnosis of
acute myocardial infarction
• Proteins in thin filament of myofibril
-TnT and TnI have specific cardiac isoforms.

-cTnI (cardiac troponin I) is specific for heart
-cTnT released in small amounts by skeletal muscles, but
clinical assays do not detect skeletal TnT.
-TnC is similar to cardiac and skeletal muscle / not cardiac
specific
-cTnT, cTnI released early peak early at 12 – 24 hours and remain elevated for 7 – 10
-Fewer false positive results in skeletal muscle injury
-Discriminates myocardial injury when CK MB is minimally increased

Creatine Kinase (CK)
CK2 / CK MB – specific to myocardium

CK 1 / CK BB – in brain tissue
CK 3 / CK MM – in skeletal and heart
muscle
After MI,
CK MB - rises within 3 – 8 hours
Peaks in 10 – 24h, returns to
normal in 48 – 72 h
Lactate dehydrogenase (LDH)

Cytosolic enzyme / in all tissues
After MI, LDH activity increases 5-fold
LDH 1 > LDH 2 (LDH 1 – in heart muscle
LDH 2 – mainly in serum)
(3) Lipid Profile

9 – 12h fasting, before test
Blood collection,
For serum – without anticoagulant
For plasma – with EDTA
LDLC = TC – HDLC – TG/5 (c – cholesterol)
(4) Renal Profile
Creatinine clearance = (140 – age)* mass(kg)* (0.85 if female)
Over estimates GFR 72 * serum creatinine (mg/dl)
(5) Urine testing
Microalbuminuria
• Excretion of 30 – 300g of albumin / 24h
• Strongly predictive of death of CVS disease
• During the phase of microalbuminuria,
 GFR starts to decline
 Retinopathy, peripheral vascular disease and neuropathy
 Increasing blood pressure
 Lipid abnormalities develop

DNA REPLICATION
DNA –only molecule that can duplicate itself
DNA Replication is,
• Semi conservative - new strand built on parent strand, so each DNA molecule consists of one old
(parental) strand and one new (daughter) strand.
(Advantage – Replication errors can be repaired)
• Bi-directional – The two replication forks move in opposite directions.
• Semi-discontinuous
Machinery for DNA replication
Enzymes Other proteins

-DNA polymerases, Primase, DNA ligases, - Single stranded binding proteins (SSB),
-Helicase, Topoisomerases - Brace and clamp proteins (Beta subunits of pol
III)
DNA Polymerases
Uses DNA as a template to synthesize new DNA by catalyzing chain growth (phosphodiester bonds) in 5´ to
3´ direction.
This requires,
• A template
• A primer with a free 3´ OH
• Deoxynucleotides in the form of triP (PP released in reaction)
• DNA polymerase has nuclease activity too.
1. 3´ to 5´ exonuclease activity - Proofreading activity ( Removing wrong nucleotides added)
2. 5´ to 3´ exonuclease activity – Removes nucleotides from 5´ end. This is used in removal of RNA
primer and DNA repair.
**** Only DNA Pol I has 5´ to 3´ exonuclease activity.

Activity Pol I Pol II Pol III
Polymerization 5´ to 3´ Yes Yes Yes
3´ to 5´ exonuclease activity Yes Yes Yes
5´ to 3´ exonuclease activity Yes No No
Primase
• DNA polymerases require a free 3 OH group.

• Primase is a RNA polymerase that synthesize a short sequence of RNA in a template dependant
manner known as the primer.
Helicase
• DNA polymerases cannot use double stranded DNA as template.

• Helicase unwind duplex DNA providing single stranded DNA to act as a template.
• Require ATP.
Topoisomerases
• Separation of DNA strands causes topological strain on the rest of the DNA strand.
• Topoisomerases relieve this strain.
DNA ligase
• Seals nicks (gaps) between DNA fragments by catalyzing formation of 3´ to 5´phosphodiester

bonds in an ATP dependant reaction.
Replication occurs in 3 stages.
1. Initiation
2. Elongation
3. Termination
Replication in E.coli is well characterized.

Initiation
Occurs at a single specific site called ‘origin of replication’ (oriC). It is a highly conserved AT rich
sequences.
1. DnaA (Initiation factor) binds and induces melting of DNA strands.

2. DnaB (Helicase) binds and begins further unwinding of DNA strands.
3. SSB binds and stabilize ss DNA
4. Primase binds and synthesizes RNA primer.
5. Topoisomerases relieve topological strain.
6. DNA pol III binds and begins to add dNTPs to the primer.
Elongation
DNA pol III,
• Reads the template from 3´ to 5´ end.

• Synthesize new DNA strand in 5´ to 3´ end. (Polymerase activity)
• Has proofreading activity. (3´ to 5´ exonuclease activity)
• Synthesizes DNA from both strands simultaneously.
• High processivity / high fidelity
Two DNA strands grow in opposite directions.
Leading strand
 Continuous synthesis
 Chain elongation in the same direction as replication fork movement.
Lagging strand
 Synthesized in the opposite direction to the fork movement.

 Discontinuous synthesis.
 Synthesized short fragments – Okazaki fragments.
 Each okazaki fragment has its own RNA primer.
DNA pol I,
• 5´ to 3´ exonuclease activity – Digest RNA primer.

• 5´ to 3´ polymerase activity – extends strand up to adjacent okazaki fragment and replaces
RNA primer with DNA.
• 3´ to 5´ exonuclease activity – proofreading
DNA Ligase joins adjacent okazaki fragments.
Termination
• Replication forks from bi-directional replication run into each other and terminates Or
• One fork STOP and WAIT for the other.
Eukaryotic DNA replication
• Slow compared to prokaryotes.(1/10 0f rate of bacterial DNA synthesis)

• Multiple origins of replication.
• Atleast 5 DNA polymerases identified.
 Pol α – Synthesis of DNA primer (DNA portion), No proofreading
 Pol β – Base excision repair
 Pol γ – Replication of mtDNA
 Pol δ – Synthesis of leading and lagging strands, proofreading activity
 Pol ε – DNA repair, proofreading activity
Overcoming the end replication problem
• In the lagging strand, synthesis at the 5’ end cannot be completely done because the primer
cannot be laid down at the very end of the chromosome.
• Therefore each time cell divides, a small part of the 5’ end will be lost from the chromosome
end, making the chromosome shorter.
• This end replication problem is overcome by addition of G+T neucleotides at the 3’end of
parental strand
• These added sequences are known as “Telomeres” which are special DNA sequences found at
the ends of eukaryotic chromosomes. They are essential for genome stability.
• Telomeres are several thousand bases of tandem repeats. The G T rich region at the end of one
strand extends as a single stranded G rich overhang (G tail) and fold back on itself.
• Addition of the bases at the 3´ end is done by the “Telomerase”
Telomerase:
 Ribonucleoprotein complex
 Has a RNA template
 Has Reverse Transcriptase activity.
 Has other proteins for binding of DNA.
Telomerase recognize the G rich single stranded 3´ end of the parent strand and elongates it by copying
its RNA template. It contains both template and enzyme activity.
• Telomerase maintains appropriate length of telomere.

• Telomerase activity is absent in most somatic cells, therefore telomere length gradually
decreases with aging due to repeated cell division.
• Loss of telomeres lead to chromosomal instability and cell senescence.
• Telomerase activity is found in tissues associated with reproduction and abnormal (cancer)
cells.
• Telomerases make cancer cells immortal and is a potential drug target.
Retroviruses
• RNA genome containing viruses

• Synthesize DNA using RNA by Reverse Transcriptase activity
• Reverse Transcriptase enzyme has no proof reading activity
Higher error during replication
Faster rate of evolution

DNA TRANSCRIPTION
• Central dogma
Transcription Translation
DNA RNA Proteins
Nucleus Cytosol
RNA
Informational RNA - Translated

• mRNA
Structural/Functional RNA - Not translated
• rRNA - An integral component of ribosome
• tRNA – Involve in translation
• snRNA – Involve in RNA splicing
• scRNA – Involve in protein trafficking
Transcription
The synthesis of RNA molecules using DNA strands as templates so that the genetic information is transferred from DNA
to RNA.
 Promoter - The nucleotide sequence, upstream of agene, that acts as a signal for RNA Polymerase binding
 Exons - coding DNA segments of eukaryotic genes
 Introns -non-coding DNA segments of eukaryotic genes
 The enzyme responsible for the RNA synthesis is DNA dependent RNA polymerase.
RNA polymerase 100% processive.
Prokaryotic RNA polymerase
Multiple sub unit protein

Coenzyme – Has 4 subunits → 2α, 1β and 1β’
Cannot recognize the promoter region
Holoenzyme – Core enzyme + σ factor → can recognize the promoter region
Termination factor – Termination of transcription needs termination factors
Sub unit Role
α Determines the DNA to be transcribed

β Catalyzes polymerization
β’ Binds and open DNA template
σ Recognizes promoter for synthesis initiation
σ–sigma factor
• Act as initiation factor
• Stabilize specific binding to promotor of DNA
• σ–sigma factor release after initiation and rebind to other core enzymes.

Functions
1. Searches for initiation site

2. Selects correct NTP for base pairing for initiation & elongation
3. Detects terminal signals
4. Interacts with activator or repressor proteins
• But no error correcting ability (error rate very low 10-4- 10-5) & needs no primer to initiate
• Eukaryotic RNA Polymerases - 3 types
Enzyme Transcription
• RNA polymerase I rRNA
RNA Polymerase II mRNA, some SnRNAs
RNA Polymerase III tRNA, SnRNA, ScRNA
3 steps of DNA transcription
1. Initiation
2. Elongation
3. Termination
Transcription – A Brief Overview
Transcription starts with RNA polymerase binding to the promoter

(When the gene is on, transcription factors help RNA polymerase
bind to the promoter.)
↓
Once it binds, RNA polymerase unwinds a small section of the DNA &
uses it as a template
↓
The complementary RNA copy is made from 5’ end to 3’ end
↓
DNA-RNA base pairing occurs in the open complex bubble
(When the bubble is moved, supercoils are generated.
It is relieved by topoisomerases)
↓
Recognize the termination sequence
↓
Termination
Bubble moves forwards by unwinding in front & rewinding behind the DNA strand. DNA
– RNA base pairing CG GC TA AU
 Transcription unit – extends from the promoter to the terminator region

 Primary transcript – mRNA coming straight off the DNA template

Transcription begins with binding of RNA polymerase holoenzyme to the promoter region on the DNA.
Eg; In prokaryotes -prinbow box , -35 sequence

In eukaryotes – TATA or Hogness box, CAAT box, GC rich regions
Transcription elements (Regulatory elements)

-regulates efficiency & frequency of transcription
-located upstream, downstream or within genes
-can be very close to or thousands of base pairs away from a gene
Transcription elements
 Enhancers ( increase transcription rate)
 Silencers ( decrease transcription rate )
Termination of prokaryotic transcription
Rho- independent(direct) Rho- dependent(indirect)

• mRNA transcript has a termination • mRNA transcript has a termination
sequence sequence
• Hair pin(stem) loop structure is formed • Stem loop structure is formed

• Long tail of Uracil is transcribed • No poly uracil tail.
• Tail (hairpin loop) acts as a signal to • The ATP dependent RNA – DNA helicase
release RNA polymerase activity of rho, separates the RNA –DNA
hybrid helix
No clear evidence for a discrete termination in eukaryotes.

Differences between prokaryotic transcription and eukaryotic transcription
Prokaryotes Eukaryotes
• Transcription & Translation occurs • Transcription in the Nucleus

simultaneously • Translation in the cytosol
• One type of RNA polymerase • 3 types of RNA polymerase
• Polycistronic–mRNA codes for more • Monocistronic - mRNA codes only for
than one gene one gene
• Most part of DNA is accessible to • Only small amounts are accessible
transcription
• m RNA doesn’t show post • All mRNA, tRNA, rRNA undergo
transcriptional modification post transcriptional modification
• Eukaryotic transcription more complex.

• Need transcriptional factors for initiation of eukaryotic transcription.
Inhibitors of Transcription
INHIBITOR EFFECT
• Rifampicin (on prokaryotes) • Inhibit transcription by binding to RNA
polymerase (prevent chain extension beyond
8 nucleotides)
• Block initiation
• Actinomycin D (on both prokaryotes and • Intercalate between DNA base pairs.
eukaryotes) • Stop movement of RNA polymerase.
• RNA elongation inhibitor.
• Both prokaryotes & eukaryotes
• α amanitin (on eukaryotes) • Eukaryotic RNA polymerase II inhibitor
Post transcriptional modifications of eukaryotes → occur in the nucleus
1. mRNA
Modification Function
1) Addition of the 7-methyl guanosine cap at the • Prevent nucleases from destroying the
5’ position (5’capping) transcript
• Occur at the beginning of transcription • Ribosome recognition
• Enzyme-Guanylyl transferase • Transfer of the transcript to the cytoplasm
2) Adding the poly A tail to the 3’ position • Stability
• At the end of transcription • Transfer of RNA to the cytoplasm
• Enzyme- Poly A polymerase
3) Splicing – Removal of Introns & joining • Make exon intron boundaries recognizable by
together of exons. SNURP
• Important in translation

2.tRNA
• Remove introns
• 3’ end is cut off and replaces by a CCA sequence
• Removal of the leader sequence
• Some base modifications
3.rRNA
Large pre-RNA in to 3 mature rRNA
(endonuclease & exonuclease cleavages,
base modifications, removal of introns)
Prokaryotic post transcriptional modifications
Primary transcript is processed into mature rRNA & tRNA
• Endonuclease & exonuclease cleavages

• Base modifications
Similarities between DNA transcription & replication
• Occur in the 5’ to 3’ direction

• Use DNA strands as templates
• Catalyzed by polymerases
• Substrate is nucleoside triphosphate
• Phosphodiester bonds are formed in both cases.
Differences between replication and transcription
Replication Transcription
Template Both strands Single strand
Substrate dNTP NTP
Primer Yes No
Enzyme DNA Polymerase RN Polymerase
Product dsDNA ssRNA
Base Pairs A-T, G-C A-U, T-A, G-C
Differences between DNA polymerase and RNA polymerase
DNA polymerase RNA polymerase

Involved in DNA replication and repair Involved in transcription
Requires a primer Needs no primer to initiate.
Have proofreading activity No proof reading activity

TRANSLATION
The central dogma of life
transcription translation
DNA mRNA protein
Flow of information from DNA to RNA to protein.
THE GENE
• Genetic code-information in the cell is stored in the form of linear sequence of nucleotides in DNA
• The code has 4 different letters- A,C,G & T (4 bases)
• The code is composed of triplet codes/codons. eg - AGC, CTC, TGG
• Each codon codes for one amino acid.
• There are 64 different codons. ( 𝟒𝟒𝟑𝟑 = 𝟔𝟔𝟔𝟔 )
• But only 61 of them code for amino acids.(rest of them are stop codons) (61 codons  20 AAs)
• A series of codons in DNA that coding for a protein is a GENE.
Characteristics of the genetic code

• Unambiguous (specific) - The code occurs as codons. Each codon code for only one amino acid.
• Degenerate - But an amino acid may have more than one codon. eg;- Ala - 4 codons
• Non-overlapping - Code is read,
1. From a fixed starting point. (AUG) 5’ to 3’
2. 3 bases at a time
3. No punctuation
• Universal (almost) - The code is almost the same for all the living organisms.
Why “almost”? Because there are minor variations

1. The amino acid for start codon (AUG)
 In eukaryotes- Met  In prokaryotes- fMet
2. Variations in mitochondrial genome, chloroplast & some ciliated protozoa.
 Human UAG – stop
 Mitochondrial UAG – Trp.
Translation
Converting the coded message in the mRNA into the amino acid sequence of the protein
Translation requires –
• mRNA
• tRNA
• ribosomes
• initiation factors (proteins)
• AAs
• Aminoacyl tRNA synthetase
• Energy (Both ATP & GTP)

tRNA
• Large number of modified bases.

• brings the correct AA from cytoplasm to ribosome
• cloverleaf structure(because of unusual bases folds into three dimensional
shape)
• has duel specificity-translate language of nucleic acid to language of proteins
(Adaptor molecule/ bilingual translation molecule)
• 3’ end carries the amino acid.
• base pairing is antiparallel & complementary.(3rd base of codon pair with 1st
base of anticodon)
• bases read always 5’ to 3’ direction
• wobble hypothesis
pairing of 3rd base in codon with 1st base of anticodon
not strictly by Watson-Crick rule. (3rd base of codon = Wobble base)
Genetic Code  61 codons  Coding for 20 amino acids
All 61 codons do not have individual tRNA to pair.
• Therefore more than one tRNA can bring one amino acid
eg;- anticodon- (3’) XYU (5’) codon -(5’) YXA (3’) or (5’) YXG(3’)
So the 1st base of the anticodon determines the number of codons read by a given tRNA.
 Formation of amino acyl tRNA = Charging of AAs

Occurs in cytosol
Catalyzed by Aminoacyl tRNA synthetase – In addition to their synthetic activity
It has a 3’-5’ proof reading activity to ensure that the correct amino acid is bound to the tRNA.
TtRNA
AA + ATP Aminoacyl AMP Aminoacyl tRNA
+ +
1st step PPi AMP
2 nd step
If wrong amino acyl AMP is bound to If wrong amino acid is bound to

the enzyme,it is hydrolyzed to tRNA,The ester linkage of
amino acid and AMP amino acyl tRNA is hydrolyzed.
Ribosome  composed of ribosomal protein (ribonucleoprotein) + ribosomal RNA
eukaryotic- 80𝑆𝑆 → 40𝑆𝑆 + 60𝑆𝑆
prokaryotic- 𝟕𝟕𝟕𝟕𝟕𝟕 → 𝟑𝟑𝟑𝟑𝟑𝟑 + 𝟓𝟓𝟓𝟓𝟓𝟓
 Ribosome has 2 subunits,

 Small  mRNA binding site
 Large  A site (Aminoacyl tRNA binding site)
 P site (Peptidyl tRNA binding site)
 E site (tRNA exit site)

Prokaryotic DNA translation.
Three steps: - initiation → elongation → termination

Recruitment of aminoacyl tRNA
Peptide bond formation
Translocation
Initiation – Ribosome binds to mRNA and 1st AA, attach to its tRNA
• 2 subunits of ribosome separate

• 30S subunit joins mRNA near 5’ end, the P site opposite the initiation codon. (Shine-Delgano sequence
just upstream of AUG in prokaryotic mRNA help in positioning)
• fMet-tRNA binds to AUG forming 30S initiation complex
• 50S subunit binds to 30S initiation complex forming 70S initiation complex.
Elongation (From N terminal to C terminal) – Ribosomes add 1 AA at a time to carboxylic end of growing
polypeptide chain, GTP required.
• Ribosome translocates by 3 bases after peptide bond formed.

• New charged tRNA aligns in the A site
• Peptide bond between amino acids in A and P sites is formed by peptidyl-transferase.
• Ribosome translocates by three more bases.
• The uncharged tRNA in the P site is moved to the E site.
 Translocation: translocation of the new peptidyl t-RNA with its mRNA codon in the A site into the free
P site occurs. Now the A site is free for another cycle of Aminoacyl tRNA codon recognition and
elongation. Each translocation event moves mRNA one codon length through the ribosomes.
Termination – The ribosome release the mRNA and the polypeptide
• Requires specific protein factors identified as releasing

factors.
RFs in E. coli and eRFs in eukaryotes.
• Signals for termination  3 termination codes, UAG,

UAA and UGA. Same in both prokaryotes and
eukaryotes.
• Nonsense codon = termination codon of mRNA
appears in the A site.
• Recognize as a terminal signal by eukaryotic releasing
factor which cause the release of the newly
synthesized protein from ribosomal complex releasing
requires GTP.
• Polyribosome/ Polysome- several ribosomes attached
to one mRNA. Can be free in cytosol or attached to
ER (RER)

Prokaryotes eukaryotes
70s ribosomes 80s ribosome
Prokaryotic mRNA is polycistronic. Eukaryotic mRNA is monocistronic.
Initiator Met-tRNAi or Met-tRNAf carries formyl- Initiating tRNA carries methionine
methionine
Prokaryotic mRNA has specific purine rich shine No specific purine-rich sequence.40s subunit binds
Dalgano sequence on the mRNA. to 5’ cap region and scan for the first AUG
fewer translation factors Many translation factors
Elongation GTP driven translocation Similar to prokaryotes but specific elongation
factors
Termination two release factors are present Termination in eukaryotes is carried out by a single
released factor eRF 1
Antibiotics that inhibit ribosomal protein synthesis

Drug subunit Target organism effect
Streptomycin 30S Prokaryotes Stop initiation & misread mRNA
Aurintricarbocylic 30S Prokaryotes & Inhibit formation of initiation complex
acid 40S Eukaryotes
Tetracycline 30S Prokaryotes & Stop aminoacyl tRNA binding, so elongation
Eukaryotes is inhibited
Chloramphenicol 50S Prokaryotes Inhibit peptidyl transferase activity of 50s
subunit
Colicin E3 30S Prokaryotes Interfere with function of small subunit.
Erythromycin 50S prokaryotes Inhibit translocation
Puromycin 50S prokaryotes & Structural analogue of aminoacyl-tRNA
60S eukaryotes incorporated at c-terminal & stop
elongation, causes premature chain
termination
Cycloheximide 60S eukaryotes Inhibit peptidyl transferase, activity of 60s
subunit laboratory tool in blocking protein
synthesis.
Effect of diphtheria toxin on protein synthesis
Produced by Corynebacterium diphtheriae, a bacterium
a. The toxin bind to one fragment enter the EF2 is required for the Stop protein synthesis
b. receptors on cell &inactivate GTP driven & kills the cell.
elongation factor 2 translocation of
c. mucosal cell surface
(EF2) It is equivalent to ribosome along mRNA.
d. & is proteolytically prokaryotic EF-G
cleaved.
Act as an enzyme & small amount is sufficient for a great damage.

QUESTIONS
1. Explain the role of amino acyl tRNA synthetases in protein synthesis. (50)
• AA are activated by linkage to proper tRNA carrier before translation.
• This occurs in the cytosol and known as amino acylation or charging
• This is done by amino acyl tRNA synthetases
• Enzyme is specific for each AA & corresponding tRNA (2nd genetic code)
• One AA can bind to many tRNAs, same enzyme recognize all of them so
• there are minimum 20 tRNA synthetases
• Specific nucleotides on tRNA s are involved in this recognition.
• Charging of tRNA occurs in two steps
• 1. Activation of AA – AA binds to enzyme with ATP
• 2. Transfer of aminoacyl group to tRNA – Correct t-RNA binds to the binding site of enzyme
• This enzyme also has a proof reading activity.
• When wrong AA is attached the mistake can be corrected at 2 stages.
2. Explain the role of tRNA in the accurate reading of the nucleotide. (40)
• tRNA has dual specificity

• It carries AA to site of protein synthesis by forming amino acyl tRNA
• tRNA has large number of modified bases
• because of the unusual bases, it folds into 3-dimensional shape, which forms an tRNA binding site
• tRNA can recognize the codon in mRNA
• Because it has modified, unusual bases if folds into 3-dimensional shape, which forms an anticodon
site.
3. Explain the biochemical basis for the use of erythromycin as an antibacterial agent. (50)
• Erythromycin interfere with elongation process of prokaryotic translation process, thus inhibited
protein synthesis
• 70s ribosomes which have 30s & 50s subunits are involved in prokaryotic protein syn.
• 50s subunit act as peptidyl transferase which catalyze breakdown of ester bond between AA &
tRNA, which are on P site.
• Then AA transferred to A site.
• & forms a peptide bind with the AA there.
• Ribosome moves to next codon in direction on mRNA. Il is called translocation.
• Now A site is empty & can bind a new amino-acyl tRNA.
• Erythromycin binds with 50s subunit & inhibits translocation.
• From this point mRNA is not read & protein syn. is stopped.

Post translational modification of proteins
What are they?
• Removal of part of translational sequence or covalent addition of one or more
chemical groups required for protein activity after translation is initiated.
• This is also a key mechanism to increase proteomic diversity.
• PTMs are found in both Prokaryotic & Eukaryotic.
• PTM can be a single or a combination of events.
• PTMs can be reversible or irreversible.
Native proteins –inactive

Undergo post-translational
modifications
Active protein
When are they done?

• Shortly after translation is completed;
gives; - proper protein folding
- Stability
directs the nascent protein to distinct cellular compartments (e.g. nucleus, membrane)
• After folding and localization are completed;

To; - activate or inactivate catalytic activity.
- influence the biological activity.
- target a protein for degradation.
 Chaperones:- proteins in the cell which assist the covalent folding or unfolding
They guide folding of proteins present in cytosol, lumen of RER, mitochondria, etc.
Chaperones promote the assembly of protein complexes from subunits.
And prevent the aggregation of unfolded proteins.
 Heat shock proteins: - A set of proteins induced by a brief exposure of cells to

Elevated temperature (420C).
Many molecular chaperones are HSPs.
The heat shock causes many proteins to unfold or misfold and the HSPs are induced
to help refold these proteins correctly.
HSPs bind to exposed hydrophobic regions of proteins to achieve Proper folding.
ATP required for action.
e.g. -hsp 70 in cytosol
-hsp 60
-BiP (binding proteins) → in lumen of RER
-Mitochondrial hsp (mhsp 60 &mhsp 70)

Types of post translational modifications
1. Trimming – proteolytic cleavage

• Proproteins – synthesized as inactive precursors (e.g. pancreatic enzymes,
enzymes involved in clotting)
• Preproteins – proteins that contains a signal peptide.
• Preproproteins – proproteins having a signal peptide destined for secretion
and proteolytic cleavage prior to activation.
E.g.
a) Insulin Removal of signal peptide (Preproinsulin Proinsulin)
Removal of the C peptide (Proinsulin Insulin)
b) Collagen Removal of signal peptide (Prepro α chains Pro α chains)

Extracellular cleavage of N & C terminal propeptides
(Procollagen Tropocollagen)
c) Trypsinogen Trypsin (active enzyme)

(Proenzyme) Removal of a hexapeptide
d) Pepsinogen Pepsin (active)

Removal of 44 AAs from amino terminal
2. Covalent attachments
a) Hydroxylation
e.g. In collagen synthesis; hydroxylation of selected proline and lysine
residues of proα chains.
Prolyl hydroxylase
Proline Hydroxy proline
Vit C= Ascorbic acid
Lysyl hydroxylase
Lysine Hydroxy Lysine
Vit.C = Ascorbic acid
(Note – ClinicalVit.C deficiency leads to scurvy)
b) Glycosylation
Functions of glycosylation;
• Aids in proper protein folding
• Provide protection against proteases (e.g. lysosomal membrane
proteins)
• Employed for signaling
• Targeting of proteins
E.g.
• In collagen synthesis glycosylation of selected hydroxylysine residues by
glucose or galactose.
• Glycosylation of Hb 
- Non-enzymic addition of a sugar residue to amino groups of protein.
-97% of Hb are HbA (α2β2). Different types of glycation products are formed
from the HbA, depending on the carbohydrate moiety.

-Carbohydrate moieties attached to amino terminal of the Valine in beta chain.
-HbA1C; Glycated by glucose. Glycosylation of HbA1C depends on prevailing
glucose concentration in blood. Once a HB molecule is glycated, it remain in
the RBC for the rest of its life span (120 days). Useful to check long term
glycemic control.
[HbA1C] α Average blood glucose concentration over the previous 3
months.
• Glycosylation of serum albumin [Fructosamine] α Average blood glucose

concentration over the
previous 1-2 weeks
Useful to check midterm glycemic control
Albumin-NH2 + Glucose → Glycosylamine

↓rearrangement
Fructosamine
• Generally not tested. But together with HbA1C it will give a better estimation.
c) Phosphorylation
E.g.
• Selected serine side chains of Histone proteins are phosphorylated  DNA packaging
is altered.
• Glycogen synthase Glycogen synthase
(Active) (Inactive)
d) γ – carboxylation ; Clotting factors II, VII, IX, X

E.g.
Carboxylase
Glutamic residue γ – carboxy glutamic residue
O2, CO2,Vit.K
3) Formation of disulphide bonds between cystine residues

E.g.
• Insulin – 2 interchain S-S bonds
1 intrachain S-S bonds
• Oxytocin – 1 intrachain S-S bond

• Vasopressin (ADH) – 1 intrachain S-S bond

Important:-
Post Translational Modifications of Insulin
• N-terminal signal peptide direct preproinsulin into secretory pathway

• Signal peptide cleaved off in the ER, leaving proinsulin.
• Proinsulin falls into specific tertiary structure to form correct disulphide bonds in
secretory granules of β cells.
• Elevated blood glucose trigger insulin secretion.
• Proinsulin converted into active insulin by proteolytic cleavage of the connecting peptide C.
4) Ubiquitination; Addition of ubiquitin to a protein.

This can affect proteins in many ways,
• Signal for degradation via proteasomes
• Alter the cellular location of protein
• Affect their activity and promote or prevent interactions
5) Others
S-Nitrosylation
NO is a chemical messenger. It reacts with free cysteine residues to form
S-nitro thiols (SNOs).
S-Nitrosylation is a critical PTM used by cells to; -stabilize proteins
-regulate gene expression
-provide NO donors
Methylation – Different methylases modify specific proteins including

Ribosomal proteins.
Acylation– Includes acetylation, formylation, other acyl groups.

Helps to stabilize proteins. (~80% eukaryotic cytosolic proteins are
acetylated at their N-termini.

Lysosomal targeting of enzymes
• Lysosomal enzymes are synthesized in RER and modified in the golgi apparatus.
• A carbohydrate moiety, mannose-6-phosphate label (man 6-PO4) is tagged to direct
these hydrolytic enzymes to lysosomes.
• Man 6-PO4 is bound by a specific glycosyltransferase or phosphotransferase.
• Man 6-PO4 acts as a Targeting signal that is identified by receptor that target the protein
into lysosomes.
I- cell disease
Defective phosphotransferase in the Golgi→ cannot add PO43-to the mannose residue.
Enzymes are not targeted to direct it to lysosome but excreted outside the cell.
Lysosomes cannot function without enzymes.
Partly digested materials (oligosaccharides, lipids, GAGs, etc.) accumulated within lysosomes.
Lysosomes accumulate partly digested materials that manifest as Inclusion bodies.
Causes disease called ‘’I cell disease’’ or ‘’inclusion cells’’.
 Defective lysosomal enzymes are found in high concentrations in the blood and urine.
(lysosomal enzymes are normally found only within lysosomes.)
Signal hypothesis
• This explains how proteins destined for secretion are synthesized.
• Free ribosomes in the cytosol are directed to the ER by the presence of a signal peptide
in the protein being synthesized.
 Signal peptide; ~18-36 AAs near the N-terminal of the chain
absent in the mature protein
direct the ribosome to ER
• ER membrane bound ribosomes make 3 classes of proteins;

1. Secretary proteins – expel from cells
2. Lysosomal proteins
3. Proteins spanning the plasma membrane
Protein synthesis in ER
 ER synthesize proteins which are to be exported out of the cell( Eg: Insulin, Collagen )
 Signal hypothesis  Explains how proteins destined for secretion, are synthesized
 Signal sequence,
• Free ribosomes in the cytosol are directed to the ER by the presence of a
signal peptide in the protein being synthesized.
• Absent in the mature protein.

Steps involved in secretory protein synthesis
• mRNA attached to the free ribosome makes the signal peptide.

• Signal Recognition Particle (SRP) in the cytosol recognizes the signal peptide and
binds to it.
• The elongation of the peptide is arrested.
• The ribosome diffuses to the ER and the SRP binds to the SRP binding protein
(docking protein).
• The signal peptide opens special channels in the ER (by a complex mechanism).
• When the SRP is released the protein synthesis starts again.
• The signal peptide is cleaved by a signal peptidase in the lumen side of the ER.
Protein folding
 BiP (hsp) helps to fold protein correctly.
ATP
Open state confirmation, BiP-ATP
BiP
weakly binds to target protein
hsp 40;
helps to hydrolyze ATP to ADP
conformational changes that causes BiP-ADP
BiP to clamp tightly to hydrophobic
region of the protein
This process is repeated over and over until protein is folded into its final form.

Damage tolerance
• Repair double strand breaks caused by high energy radiation and oxygen free radicals
End-joining repair (mutagenic) Recombination repair
repair proteins bind to ends of the double stranded break • Damage not repaired
• DNA polymerase uses DNA sequence in other
nucleases remove few bases from the ends
strands to complete replication
ends joined by ligase
Two daughter molecules, one complete, other with a gap
• Few bases lost, if wrong ends are joined,
Crossing over/strand exchange
mutations can happen
Resulting gap in sister chromatid filled by polymerase
Diseases due to defects in DNA repair pathways
• Mismatch repair defects – caused by loss of function mutations in genes

HNPCC (hereditary non-polyposis colorectal cancer) – Autosomal dominant, multigenic
• Nucleotide excision repair pathway defects – Xeroderma pigmentosum
↑Skin cancers
• Recombination repair defects – defects in homologous recombination
Eg: defects in BRCA1, BRCA2 which are tumor suppressor genes
Predisposed to breast and ovarian cancers
• End joining repair defects – predisposition to cancers and immuno-deficiency syndrome
© 2015 A/L Repeat Campaign

Mutations
Stable changes in nucleotide sequence
Gross mutations Fine scale mutations
• Observed cytogenetically • Involve less than 100 base pairs

• Include deletions, duplications, inversions and • Often point mutations
translocations
Silent Substitutions Deletion Insertions

Nucleotide change 1. Transversion
Purine Pyrimidine Frame shift mutations
Number of AA change
2. Transitions
• Change in the reading frame
But no phenotypic change Purine Purine
• Out of frame translocation
Pyrimidine Pyrimidine
Mostly occur in wobble of all downstream codons
base • Causing different AA
sequences
Eg: α thalassemia, β thalassemia

Missense Nonsense
Base pair substitutions Net change result in stop codon Triplet expansion
Eg: β globin gene – Eg: truncated proteins Increasing the number of triplets in sequence
substitution of Valine in 6th
place with Glutamate Premature termination of translocation Eg: fragile X syndrome, Huntingdon’s disease
of proteins
Causing change of cell Huntingdon’s disease – accumulation of
shape − Cystic fibrosis protein aggregates, neuro degenerative
− Duchenne muscular dystrophy disease
-sickle cell anaemia
− Β thalassemia

Modification of bases
• Deamination:
Endogenous DNA damage Base damage
cytosine  uracil
• Tautomerization: G (enol) pairs with T
C (imino) pairs with A
Replication errors Loss of bases
• Depurination
Recombination Due to a defect in
• During replication, DNA polymerase
errors DNA polymerase
will incorporate a random base
Unequal opposite the apeurinic site
crossover Base pair Replication slippage
mismatch • Insertions Heat induced hydrolysis of B-N
• Deletions glycosidic bond
Repeat regions are • Base missing, making a gap
Alkylation more prone.
Eg: Reaction of S- Byproducts of metabolism:
adenosyl methionine H202, oxygen radicals, hydroxyl
with DNA radicals
Induced/ Exogenous DNA Damage
1. CHEMICAL MUTAGENS 2. RADIATIONS
1. Naturally in foods 4. Alkylating agents Pyrimidine
eg; aflatoxin Alkylate N or O atoms of UV dimers IONIZING
2. Food preservatives bases T
Eg: methylbromide, Cannot Free radicals
Nitrites T T
ethylene oxide, nitrogen penetrate • α, β, γ
mustard (nerve gas) beyond the • x rays
HNO2 outer layer of No safe threshold
Deaminating agent skin Penetrates the whole body, affects both
Adenine  hypozanthine
somatic & germ cells
Guanine  xanthine 5. Benzopyrene
Cytosine  uracil Polycyclic aromatic Indirect
CH3cytosine  thymine hydrocarbons from coal, Direct
3. Intercalating agents cigars By radiolysis of water -DNA strand cleavage (one/both)
Proflavin/ EtBr/ acridine orange -Damage or loss of base
DNA adducts H2O  O° + OH° -Cross-linking of DNA to itself or
Planar/ aromatic molecules
inserted between base pairs proteins.
Bulky lesions Cell death
stretching DNA duplex © 2015 A/L Repeat Campaign
Inserts extra base during
replication Substituions/deletions
Double stranded
breaks
DNA damage types
Single stranded breaks Response
DNA-DNA
Cross links DNA-prot Activation of checkpoints
Dimers
Apurinic sites
Apyrimidic sites
Base alterations, REPAIR OR CELL DEATH
hydroxylations
-Reduce potential mutations
for acceptable levels
Damage Reversal -several systems
-specific for different types
Ligation of single Photoreactivation

stranded breaks Not found in humans DNA damage tolerance
-simple breaks -by photolyase
rapidly repaired by enzyme
ligase -breaks covalent
Recombinational Mutagenic
-damages caused by bond of dimers in
repair repair
xrays & peroxidases presence of light
-Bloom syndrome
when ligase is
deficient
DAMAGE REMOVAL
1. Base excision repair 3. Mismatch repair
Recognize damage
-Recognizes which base to
excise
Removing damage by
-follows replication fork
excising part of one strand
2. Nucleotide excision repair -Repairs mismatched bases
(endonuclease)
-final spellcheck
Carried by multi-protein
-Conserved through
DNA pol fills the gap using complex
evolution
complimentary strand Damaged DNA
recognition Mut proteins identify &
Ligate to restore bind mismatched
continuity Incision followed by methylated parental
(ligase seals nick) excision (removes strand on GATC sequence
oligonucleotides)
Eg: Uracil N-glycosylase Exonuclease cleaves
NH3 DNA pol makes new daughter strand in region
Cytosine uracil DNA of mismatch
Removed by above
enzyme, leaving apeurinic DNA ligase seals nick DNA pol fills the gap
site Eg: TT dimers
-methylated Adducts Ligase seals the nick
-deaminated Aflatoxins
-abasic sites Cisplatin Multiprotein complexes
-oxidized bases 99.9.% efficiency
Regulation of Gene Expression
Definitions
1. Gene Expression –
Information in genes is turned into gene products (RNA or proteins) through biological
processes, transcription and translation
2. Constitutively expressed genes –

Genes that are actively transcribed (and translated) at essentially all developmental stages,
in virtually all cells
Housekeeping genes –
Constitutive genes that are transcribed at a relatively constant level. These gene products
are needed for maintenance of the cell.
3. Facultative genes –
Genes that are expressed only when needed compared to constitutive genes.
4. Inducible/Repressible genes –
Genes whose transcription and translation increases/decreases in response to an
inducing/repressing signal. Induction/Repression is due to environmental change or position
of the cell cycle.
Regulation
Spatial
Temporal
Tissue
Time bound specific
according to the
different stages in
life
Prokaryotes
Gene expression at Transcription
initiation
Operons- Functional unit of DNA

consisting clusters of genes under
one promoter.
1 ©Repeat Campaign 2015 A/L

Eukaryotic Gene Regulation
Condensed DNA
1. Chromatin level
Decondensed DNA
2. Transcriptional control**
Primary transcript
3. Post-transcriptional control
4. Nuclear
Transport Control
5. mRNA
Degradation
6. Translation initiation Control
Control Inactive
mRNA mRNA
7. Post translational
Modification
Protein Mature Protein
8. Protein Transport
1. Chromatin Level
Epigenetic [Do not change the DNA sequence]-Heritable
o Euchromatin – Relaxed form of chromatin – Actively transcribed genes-Easily accessed
by RNA pol.
o Heterochromatin – Highly condensed form of chromatin – Inactive transcriptionally
• Constitutively heterochromatin-No genes EG: centromeres & telomeres
• Facultative heterochromatin –inactive in some cells for some period
a) Histone modification – Histones are positively charged. DNA negatively charged.

Therefore, tight binding.
When Lysine residues of histones are acetylated , positive charge reduces. Less
affinity to DNA. So, loosens chromatin structure promoting initiation of transcription.
Unacetylated 30 nm fibre HAT Acetylated free nucleosomes

(Inactive) HDAC (Active)
HAT – Histone Acetyl Transferase
DHAC – Histone Deacetylase
 This can also be done by phosphorylation.

b) DNA methylation – When methylated genes become inactive.
Seen in GC-rich regions (CpG islands)
Converts cytosine to 5-methylcytosine causing a silenced gene
 Housekeeping genes – Unmethylated,
 Tissue specific genes – Methylated
2. Transcriptional Control @ the point

of initiation of transcription
Cis acting sequences Trans acting proteins
Promoters Enhancers
- upstream Silencers Transcription Factors Co-Activators
- proximal Basal TFs
- For all genes Bind to an enhancer
control element Distal control element act on
& stimulate gene
- Strength of more than one promoter
Specific TFs expression.
the promoter - for high level of
Regulatory DNA sequences transcription for 2 domains
that increase/ decrease specific genes
transcription of genes in DNA binding domain
vicinity Embryology for
- 15 – 20 bp development of Transcription factor
upstream/downstream/ switches binding domain
within the gene
↑100 folds
Receptors of lipid soluble hormones are specific transcription factors. The hormones bind to
intracellular receptors before binding to enhancers → hormone response elements.
E.g. - steroid hormones, thyroid hormones, retinoic acid, calcitriol

1. Activator proteins bind to
response elements in
enhancer (3 binding sites)
2. Bending proteins bring
bound activators close to
the promoter, transcription
factors and mediator
proteins.
3. Activators bind to
mediator proteins and
transcriptional factors which
forms an initiation complex
on promoter where RNA
polymerase bind.
3. Post transcriptional modifications
I. Alternative splicing/twisting
• Different mRNA molecules are produced form same primary transcript.
• Differently spliced  differently expressed in tissue specific manner
E.g. Calcitonin and calcitonin gene-related peptide in thyroid gland and neuronal cells
ɑ Tropomyosin in smooth muscles and skeletal muscles.
A gene is transcribed. The primary mRNA is spliced in different ways in different tissues
resulting in different mRNAs. When translated these give biologically different proteins.

II. mRNA editing
In intestines apoB gene undergoes deamination converting CAA
sequence to UAA which is a stop codon. This causes the producing
of truncated protein apoB-48. In liver this editing doesn’t occur
thus only produces apoB-100.
III. RNA Stability

The time duration and mRNA remain in cytosol influence protein
production.
E.g. – Regulation of cellular Fe status.
Iron
- IRE-BP (Cell)
IRE – Iron Responsive Element
Low High
IRE-BP binds to IRE IRE-BP binds to iron Fe2+ Fe2+ Fe2+
Transferrin receptor mRNA IRE
5` 3` 5` 3`
Coding Coding
Stabilize mRNA Increased mRNA

degradation
TfR Synthesis TfR Synthesis
Apoferritin mRNA
Fe2+ Fe2+ Fe2+
IRE
5` 3` 5` 3`
Coding Coding
Prevent the use of mRNA mRNA can be used
Apoferritin synthesis Apoferritin production

RNA interference
Gene silencing by short non-coding RNAs (micro RNAs- miRNA) which are derived from long
double stranded RNAs. They bind to complementary sequences and silence it.
• Important in development regulation
4. Post translational modifications
Initiation of translation – inhibiting cif2 by phosphorylation in eukaryotes thus inhibiting

initiation.
Protein degradation – ubiquitination
Diseases
1. Epigenetic modifications in response to cellular environments during important stages

of foetal development lead to obesity and diabetes in later life.
Eg: Mothers with DM.
2. Genomic imprinting,
Methylation of one allele in gene is silenced in a parent origin specific manner.
Eg: Prader Willi syndrome.
Angelman syndrome

DNA BASED TECHNOLOGY
(BASIC DNA-BASED TECHNIQUES IN MOLECULAR MEDICINE)
Some basic concepts: These concepts are used for:

 Recombinant DNA  DNA Cloning
 Restriction Enzymes  DNA Libraries
 DNA Ligation  DNA Fingerprinting (DNA Typing/DNA
 Hybridization Profiling)
 Agarose Gel Electrophoresis
 Southern Blotting
 DNA Sequencing
 Polymerase Chain Reaction (PCR)
Definitions:
 Recombinant DNA – Creation of a new combination of DNA not found naturally
 DNA Cloning – making genetically identical copies of DNA/genes using a cellular process
Restriction Enzymes
• Isolated from bacteria
• Recognize specific DNA sequences (palindromes)
• Does not cleave RNA, only dsDNA
• Cleave at specific sites, within/close to recognition sequence.
• Cleave both strands at a specific site – Endonuclease activity
• produce Blunt Ends (EcoRI/TAQI) or Sticky Ends (HaeIII)
Blunt ends Sticky ends

5’
CCGG3’ 5’
CC3’ 5’
GG3’ 5’
GAATTC3’ G
5’ 3’ AATTC3’
5’
3’GGCC 5’ 3’GG5’ 3’CC5’ 3’CTTAAG5’ 3’CTTAA5’ 3’G5’
Do not easily form H bonds easily form H bonds
DNA Ligation
• Joins DNA fragments of compatible termini via phosphodiester bonds
• Enzyme – DNA Ligase
DNA Cloning (Biological cloning)

Above techniques are used in DNA Cloning.
1. Obtain DNA fragments
• Cleave DNA (Restriction Enzyme digestion)
• Reverse transcribe mRNA (by Reverse Transcriptase)
2. Insert into Cloning Vector — Plasmid/ Bacteriophages (see below)
• By DNA Ligase
3. Introduce into host cell — Transformation/Transfection
• Bacteria or Yeast cells in culture
4. Screen for Transforments/Recombinants
• Transformant – Host cells which have taken up plasmid vector
• Recombinant – Host cells which have taken up recombinant plasmid
5. Amplification of DNA of interest as the host cell multiplies

Cloning Vector
•Transports foreign DNA into host cells
•Used to amplify a DNA fragments
→ Plasmids
→ Bacteriophages (virus)
Properties of a Cloning Vector
• Self replicating — contain an origin of replication
• Small — can incorporate large portions of foreign DNA
• High copy number — exist in large numbers within the cell
• Multiple cloning site — Polylinker
→ Restriction enzyme cleavage sites
→ Polylinker is a DNA fragment with many such sites
• Selection markers — Antibiotic resistance genes
→ Enables the identification of transformed bacteria
• Contain universal primer binding sites and strong/inducible promoters
Applications of DNA Cloning

• Production of recombinant proteins
→ human insulin (see below)
→ clotting factor VIII
→ human growth hormone
→ tissue plasminogen activator
• Production of recombinant Vaccines (e.g. Hepatitis B- Hep B surface antigen produced in yeast)
• Gene therapy (SCID – Severe Combined Immunodeficiency Disease)
• Diagnostics – species specific DNA probe based diagnosis of disease (e.g. Dengue, Tuberculosis,
Filariasis)
• Enhanced nutrition – e.g. Golden rice (increased Vit. A content by incorporating β-carotene gene)
• Edible vaccines(e.g. Hepatitis B, Diarrhoea, Measles)
• Medical research( Transgenic mice)
Production of recombinant human insulin:

Reverse Insertion Cloning Transformation
Isolate Transcriptase cDNA Bacteria/
Vector Culture
mRNA (Plasmid) Yeast
Extraction and
Purification of Insulin protein

DNA Libraries
 DNA Library / Genomic Library
Collection of DNA Clones (transformed bacteria) that together represents the entire genome of an
organism
Genomic Restriction DNA Insertion Cloning Transformation Bacterial
DNA Endonuclease Fragments Vector Host
 cDNA Library
Collection of DNA clones (transformed bacteria) that represents the expressed genes in an organism
Reverse cDNA Insertion Cloning Transformation Bacterial
mRNA
Transcriptase Fragments Vector Host
cDNA libraries,
• Are smaller than a genomic library
• May vary according to
 Particular tissue
 Particular developmental stage
 Particular conditions (e.g. disease states)
• Can be used to synthesize eukaryotic proteins as cDNA has no intervening sequences (i.e. no
introns, only the expressed exons)
Library Screening – Finding the gene of interest in a DNA Library. Can use the following techniques:
→ Extraction of plasmid DNA
→ Hybridization
→ Restriction enzyme digestion followed by Agarose gel electrophoresis
→ Southern blotting
→ DNA sequencing
Denaturation
Separating DNA in to single strands by heat and alkali.
Annealing
Forming double stranded DNA using single strands.
Renaturation
Annealing
Hybridization
Renaturation
Annealing of DNA of same origin
Hybridization
Hybridization is the annealing of DNA (nucleic acids) from different origins. The sequences of the strands
do not need to be 100% complementary (as long as they are similar enough, hybridization can occur).
Used for identification of complementary or homologous molecules
Types – DNA to DNA DNA to RNA RNA to RNA
1. Using a hybridization probe — a radio-labelled nucleic acid fragment

2. Forms a base paired stable hybrid (Probe is hybridized to immobilized DNA forming a double
stranded DNA)
3. Autoradiography—radiation from the radio-labelled probe is detected using an X-ray film
Factors affecting hybridization
• Temperature
• Salt concentration
• Denaturing agents (urea, formamide)
• High molecular weight polymers (dextran sulphate)
• Shear forces
Gel Electrophoresis
• Electrophoresis in polyacrylamide or agarose gel
• Separation according to size of fragment
• DNA negatively charged – moves to positive electrode
• Smaller fragments – higher mobility
• Results can be visualized by ethidium bromide stain
→ Fluoresces pink under UV light when bound to DNA
→ Only used if a small number of fragments present
Southern Blotting
• The transfer of DNA from agarose gel to a nitrocellulose or nylon membrane
• Used to locate and identify genes on DNA fragments
• Can be used with large number of fragments because only specific fragments are visualized
1. After gel electrophoresis DNA fragments are denatured to give ssDNA

2. ssDNA fragments are blotted to nitrocellulose paper
DNA binds permanently to the membrane (DNA fragments are immobilized on the membrane)
An exact copy of the pattern on the gel is obtained
3. Target fragments are visualized by hybridization with radio-labelled probes
4. Excess probes are washed out and obtain an auto-radiograph
DNA Sequencing
• Sanger’s method – use dideoxynucleotides
• Used to identify the nucleotide sequence in a DNA fragment
Steps involved
1. Denaturation of dsDNA
2. Annealing ssDNA with a primer
3. Extension by a DNA polymerase and 4 types of deoxynucleotides
4. Termination due to ddNTP
• ddNTP lacks a 3’-OH, therefore chain elongation stops
• 4 different types of dideoxynucleotides are added to 4 different samples
5. So bands with same terminal nucleotide can be separated and the sequence can be read
• Agarose gel electrophoresis
• Autoradiography

PCR – Polymerase Chain Reaction
Amplification of specific DNA fragments in vitro (i.e. a cell-free DNA amplification system)
Requirements:
• Template DNA
• DNA primers (×2) – specify target DNA fragment
• DNA polymerase – Thermostable DNA polymerase (e.g. Taq polymerase)
• Deoxynucleotide triphosphates (dATP, dGTP, dCTP, dTTP)
• Buffer
The reaction takes place in three repetitive steps that are automated
Step 1: Denaturation at 94°C (1 min)
Step 2: Annealing at 54°C (45 sec)
The forward and reverse primers anneal to the specific DNA sequence
Step 3: Extension at 72°C (2 min)
The Taq polymerase synthesizes the DNA fragments.
Important features of PCR:

• Highly sensitive and very fast, while being technically easy to operate
Just 30 cycles of the 3 steps can amplify the selected target DNA fragment 109 times!
• The polymerase used must be able to stand repetitive heating and cooling cycles → Hence the need
for thermostable DNA polymerases such as Taq polymerase
• For PCR, it is not necessary to know the target DNA sequence (the sequence which will be amplified),
BUT it is required to know the base sequence of the flanking sequences (the sequences on either side
of the target sequence to which the primers bind) – since proper primers must be chosen
• Only small fragments are amplified
Applications of PCR:
1. Genetic disease diagnosis
2. Detection of infectious diseases – Dengue, Malaria, Tuberculosis
(Using primers specific to pathogen’s DNA)
3. DNA fingerprinting (DNA typing/ DNA profiling)
DNA Fingerprinting
Determination of an individual’s unique collection of DNA fragments (restriction fragments)
• No two people, except identical twins, have the exact same DNA sequence
• Most of the human genome (≈99.9%) is similar from one person to the next
• BUT, there are small regions (≈0.1%) which are highly variable – “Polymorphic Regions”
• If we focus on such regions, although only a limited portion of DNA of a person is analyzed in this
procedure, those segments are proven to be statistically unique to identify that person
• Has applications in:
→ Forensics (criminal investigations)
→ Paternity testing
→ Diagnosis of presence/carriers of genetic diseases
REMINDER: Two main types of variations:-

1. Variation in single nucleotide bases scattered along the chromosomes → Single Nucleotide
Polymorphisms (SNPs)
2. Variations in copy number of tandem repeats → Variable Number of Tandem Repeats (VNTRs) &
Simple Sequence Repeats/Simple Tandem Repeats (SSRs/STRs)
DNA fingerprinting is based on three main methods:

1. RFLP (Restriction Fragment Length Polymorphism)
2. RAPD (Random Amplified Polymorphic DNA)
3. AFLP (Amplified Fragment Length Polymorphism)
RFLP (Restriction Fragment Length Polymorphism)

The variability of the size of fragments obtained from the same restriction enzyme digestion
Digest DNA with restriction enzymes
↓
Gel electrophoresis
(Separate DNA fragments by size)
↓
Southern blotting
(Obtain ssDNA copy in nitrocellulose)
↓
Hybridize with a radio-labelled probe
Wash the blot to remove excess probes
↓
Autoradiography
(Expose to X-ray film and develop)
Specific examples are given later on in this note (see below).
RAPD (Random Amplified Polymorphic DNA)

The variability of the size of the PCR products obtained with the same random primers
(Use of PCR on the genomic DNA with an arbitrary oligonucleotide primer results in amplification of
several discreet DNA products)
RAPD technique is not used that much. Instead, we use the AFLP technique given below.

AFLP (Amplified Fragment Length Polymorphism)
AFLP uses a combination of features of RFLP and RAPD for the amplification of a set of fragments
using selective primers.
 Since PCR is efficient at amplifying only small fragments, AFLP is usually used for analysing
SSRs/STRs. AFLP is not used for analysing VNTRs.
Example for use of AFLP for analysing SSRs/STRs to identify two people:
A B Rohini
CACACACACA
A B Rohan
CACACACACACACACACACAC
• A and B are the primers for PCR – by using 2 primers the selected region can be specifically
amplified (microsatellite marker – PCR primers designed from unique flanking DNA)
• PCR products differ in length, depending on the number of repeat units (copy number)
• Since the PCR product is a single amplified segment, the use of Southern blotting and hybridization
is not needed
Rohini (-) (+)
Rohan
Examples for use of RFLP technique:

1. In analysis of SNPs
Features of SNPs:
• A single base pair is changed
• Leads to creation or removal of a restriction endonuclease site
Examples:
• In sickle cell anaemia → single base pair substitutions in β-globin gene removes an existing site
• DMD (deletions in dystrophin gene)
• Cancers (various mutations)
Consider the restriction fragments:

1)
Normal
2)
Carrier
3)
Diseased

Using a radio-labelled probe that binds to sequence in the larger fragment in a normal person, after
gel electrophoresis:
1 2 3
2. In analysis of VNTRs
• Select restriction sites on either side of VNTR sequences
• As the repeat number changes, the size of the restriction fragment change
• Probes can be homologous with repeat unit, or with the unique sequence adjacent to the repeat
units
3. In Paternity Testing
• Paternity testing using RFLP uses analysis of VNTRs of the child, mother and the suspected fathers
• The corresponding alleles of a child come from the father and the mother
• When comparing the patterns of RFLP, each line in the child’s analysis should correspond to a line
of the father or to a line of the mother
In a normal family: In a paternity case:
Mother Child Child Child Father Mother Child F1 F2

1 2 3
Possible
fathers

Cell Cycle
Cell cycle; - Composed of orderly sequence of biochemical events.
- Directional
- Leads to the production of two daughter cells containing chromosomes that identical to parental cells.
 Eukaryotic cell cycle take place in a highly coordinated fashion. It consists of several phases & gaps.
• S phase – DNA synthesis
• M phase – Mitosis
• Two gaps (G1 & G2) separate the two processes.
• G0 (gap 0) – The cells that are not subjected to cell division after maturity, reside in this resting state.
 Frequency of cell division varies depending on the cell type.
• Embryo < 20 minutes
• Skin cells – divide frequently throughout the life. (12-24 cycle)
• Liver cells – retain ability to divide, but keep it in reserve. Divide once every year or two.
• Mature nerve cells & muscle cells- do not divide at all after maturity. Permanently in G0
Initiation of cell cycle

• Should receive positive signals.
• Molecular signals present on cytoplasm;
- Polypeptide hormones
- Growth factors (e.g. PDGFs)
- Cytokines - interleukins
Cell cycle control proteins

• Cyclin dependent kinases (CDKs)
• Cyclins
• Cyclin-dependent kinase inhibitors (CKIs) – (inhibit CDK activity)
• Ubiquitin ligases
The cell-cycle control system is based on 2 key families of protein
Cyclin-dependent Cyclins;
protein kinases (CDK); - the regulatory subunits
- catalytic subunits of CDK
Association of these 2 subunits is

necessary for the phosphorylation of proteins
to regulate cell cycle
 Cyclin dependent kinases (CDKs)

• Serine /Threonine kinases.
• Activation /inhibition of these kinases regulate the progression of the cell cycle
• CDK modulate the metabolic activities of the cell at precisely timed intervals
to produce orderly cell division
 Cyclins
• Serves as regulatory subunits of CDKs. It binds and activates its specific CDK.
• Important in cell cycle control & that depends on their concentration. Concentrations fluctuate with
the phases of the cycle, due to changes in synthesis & degradation.
• Cyclin-CDK complex phosphorylates other proteins to control cell activities.
 Activity of a cyclin-CDK complex is changed during cell cycle by;

• Differential synthesis of CDKs & cyclins→ The levels of kinases present are constant. Levels of cyclin
proteins fluctuate cyclically. So activity of one cyclin-CDK complex
is proportional to corresponding cyclin concentration.
• Specific degradation of cyclin by ubiquitination.
Check points (cell cycle control systems)
• Sense problems that may occur during DNA synthesis & chromosomal segregation.
• Minimize the occurrence of mistakes in cell cycle events.
• Ensures that;
- chromosomes are intact
- each stages of the cell cycle is completed before the following stage is initiated.
• If conditions fail, cell cannot move onto next phase.
e.g. G1 checkpoint - external factors
G2 checkpoint - chromosomes have replicated, DNA damage
M checkpoint - chromatids attached to spindle
DNA damage/cell cycle abnormalities/hypoxia
Mdm2-p53 p53
Cell cycle arrest Apoptosis (cell death)

↓
DNA repair
↓
Cell cycle events

Cancer
Cancer usually arises from the mutation of a normal gene.
Mutated genes that cause cancer → oncogenes
Causes of cancer
Exogenous carcinogens Endogenous carcinogens

• Chemicals – Nickel,
• Chronic inflammation
Nitrosamines (smoked &
pickled foods) • Metabolic intermediates (free
• Physical – UV, X rays, etc. radical intermediates)
• Biological – Viruses, (DNA & • Alterations of DNA replication &
retroviruses, HPV, Hepatitis B) repair
Molecular basis of cancer

• Cancer involves uncontrolled cell division.
• Growth regulation is lost.
• Caused by;
- Mutations in genes during cell division
- External agents
- Random events resulting in altered proteins
Some traits of Cancer cells

1. Independent of GROW signals from other cells - e.g. Ras
2. Ignores STOP signal - defective damage control, so problems are not corrected.
3. No cell suicide (apoptosis)
4. No limit to cell divisions - Cancer cells express telomeres to prevent shortening of chromosomes.
5. Angiogenesis; formation of new blood vessels;
Steps in angiogenesis;
• Cancer cells secrete angiogenic factors – VEGF (Vascular Endothelial Growth Factor)
• VEGF stimulate endothelial cells to grow, divide and proliferate.
• Bind to receptors on endothelial tissue
• Endothelial cells become activated
• Release enzymes metalloproteinase enzyme
• Plasminogen system is activated
• Break down basal lamina
• Cells migrate through basal lamina into surrounding tissue
• Express integrins to attach to new locations
• Divide and develop into a mature blood vessel network
6. Metastasis
Ability to move to other tissues.
benign: do not move from tumor site.
malignant: invasive cells, can travel in blood & lymph system.
Steps in metastasis;
• tumor cell secrete plasminogen activator
• convert serum plasminogen to active protease plasmin
• plasmin digests basal lamina
• allows cells to migrate through basal lamina
• invade surrounding host tissue
• penetrate lymphatic or blood capillaries
• release cells or clumps of cells into circulation
• arrest in capillary beds in distant tissue
• penetrate the vessel wall and enter tissue

 Normal cells obey the following.
• Dependence on growth factors.
o Cell and tissue specific signals.
o Loss of these signals leads to apoptosis
• Anchorage dependent proliferation.
o Requires interaction of trans-membrane proteins (integrins) with components of the ECM
• Contact inhibition
o Contact with the cells inhibits cell proliferation and movement.
• Limited proliferation capacity
o Normal somatic cells have a limited number of divisions they can do. (telomeres wear out etc.)
 Loss of telomeres which occurs normally during DNA replication limits the number of cell
divisions. Telomerase is abundant in stem and germ line cells but not in somatic cells. The length
of the telomere is a measure of replicative capacity.
Normal tissues
Rate of new cell growth = Old cell death rate
Modifications leading to cancer
Genomic non genomic
Epigenetic Genetic
Occur outside the coding Inside the coding
sequence sequence
eg. Promoter/ enhancer
silencing
Mutations of DNA
Viral infection chromosomal gene point mutation

translocation amplification
 Proteins that lead to cancer when mutated;

1. Growth factors and other signaling molecules
2. Receptors for growth factors or other signaling molecules.
3. Signal transduction proteins
4. Transcription factors
5. Pro – or anti –apoptotic proteins
6. Cell –cycle control proteins
7. DNA repair proteins
8. Cell adhesion molecules
• Certain viral proteins can activate signal receptors
 Alterations that lead to the unregulated cell growth;
1. Gaining an unlimited proliferation capacity.
2. Loss of contact inhibition.
3. Loss of anchorage dependent growth.
4. Failure to respond to substances that signal to stop proliferation.
5. Self-generation of factors that promote growth.
6. Evasion of apoptosis.
7. Motility and invasiveness.
8. Facilitated angiogenesis.
 These mutations lead to production of abnormal proteins, which lead to uncontrolled and random cell
growth and division, which lead to tumor growth or cancer.

 Genes that could mutate to cause cancer are divided into 2 groups
1. Proto-oncogene
(Normal genes contributing to cell proliferation & survival)
Proto-oncogene oncogene (genetically dominant)

• Proto oncogene become oncogene by a gain of function mutation.
• Results in increased action of the gene.
• Oncogenes act dominantly, so even if only one gene of the pair is mutated, it can cause cancer.
E.g. RAS gene.

• An Intracellular signal transduction protein
• Normally remain bound to GDP
• Activated by growth factors to bind to GTP
• Once protein is mutated, it remains bound to GTP and stimulate cell division without the ligand binding to
the receptor.
RAS activated by gene amplification
point mutation
chromosomal translocation
 Proto-oncogene converted to oncogene by;

1) Point mutation making an overactive protein – eg: proto-oncogene receptor proteins
2) Amplification- resulting in many copies of same gene in the genome. Lead to overproduction of the
protein.
3) Chromosomal translocation where gene comes under a stronger promoter/ enhancer leading to
excess protein production
4) Chromosomal translocation where 2 genes fuse to make a hyperactive protein
5) Recombination of a retroviral and host gene
e.g. Effects of a Retrovirus – eg: c-myc gene
• Insertion of viral DNA changes host DNA to make oncogenes by promoter or enhancer insertion
• Viral proteins can activate host receptors for growth factors
• Host genes can be truncated to code for a hyperactive gene
• Long terminal repeats can act as promoters or enhancers, cause over expression
of a normal gene
2. Tumor Suppressor genes
• Normal function- inhibit cell proliferation when necessary. Regulates the cell cycle.
e.g. P53 gene, Rb gene
• Mutated gene acts recessively
• So both gene copies should be defective for the action to be lost.
• Absence/inhibition of inhibitor uncontrolled cell proliferation
Classes of tumor suppresser genes

• Genes that control cell divisions
• Genes that repair DNA
• Cell suicide genes
• Genes for cell adhesion molecules
Tumor suppressor genes

• RB  encodes a protein that interact with transcription.
factors & indirectly control gene expression & cell division process
• APC  Regular (suppress) Cell growth
• DNA Repair genes  BRCA 1
• P53  can halt cell division, induce abnormal cells to apoptosis, DNA repair

 Role of p53 protein as a tumor suppressor.
• P53 exists in a normal cell at low concentrations
• During stress conditions it accumulates and the concentration increases
• Protein kinases and acetyltransferases are activated
• Results in stabilization and activation of p53 within nucleus
• Phosphorylated or acetylated p53 interacts with DNA at p53 response elements
• Induce transcription of genes involved in DNA repair
• Arrests cell cycle till repair is complete
• Once complete p53 is degraded and cell cycle restarts
• If damage is extensive, cell apoptosis is started
 If p53 is Inactive, a damaged or mutated cell will continue to proliferate instead of starting to
apoptosis.
 Function of retinoblastoma protein

• Retinoblastoma protein exists in phosphorylated and dephosphorylated states
• Its normally in Dephosphorylated form
• Which attaches to E2F transcription factor and inhibits it.
• When cell is stimulated by a growth factor
• Signal is carried from receptor to nucleus via intra cellular signaling pathway
• G1 phase Cyclin-CDK complex is activated
• G1 CDK kinase phosphorylates Rb protein
• Which prevents it from attaching to E2F transcription factor
• Inhibition of E2F is removed
• E2F activates transcription of genes needed to enter S phase
• Once needed proteins are made cell moves into S phase
 If RB is inactive or constantly phosphorylated, E2F will be always active and cell will enter S phase
without any regulation. Lead to uncontrolled cell division.
Cancers caused by epigenetic changes
 Some cancers are caused by epigenetic changes. This refers to heritable changes in gene expression that
occur without alteration in DNA sequence.
2 mechanisms
DNA methylation covalent modifications of histones
 Changes in methylation pattern;

o Hypermethylation can silence nearby tumor suppressor genes
(E.g. Hypermethylation of CpG islands in the promoter region of tumor suppressor genes is a major
event in the origin of many cancers)
o Hypomethylation can permit activation of silenced proto-oncogenes
 Epigenetic mediated gene regulation is affected by several factors.

• base analogs
• radiation
• smoke
• stress
• hormones
• other agents ( such as nickel arsenic cadmium)
• reactive oxygen species.
 Cancer can be treated by halting cell division.

Microtubules targeted drugs,
• Taxol-binds and stabilizes microtubules
• Colchicine
• Vinblastine bind to the tubulin subunits prevent polymerization
• Vincristine
• Nocodazole
THE HUMAN GENOME
1 base pair(bp)Single A=T or G≡C pairing Types of sequences in the human
1000bp=1kb 1000kb=1Mb genome
3,.1 billion basesBut, only<25,000 genes • Exons (protein coding

sequencesvery little (less
(Gene density of human genome is VERY LOW) than 2%)
Arrangement of genes • Introns (non-coding, but
within gene)24%
 Gene dense areas G,C richlight bands • Repeat sequences A lot
 Gene poor areasA,T richdark bands (50%)
 Genes are concentrated in random areas • Others24.5%
with vast expanses of non-coding DNA
 CG repeating sequences (CpG islands) occur
Near gene rich areas. Form barrier between
genes & junk DNA
REPEAT SEQUENCES
• Repeat sequences differ in their,

o Position in the genome
o Sequence
o Size
o Number of copies
o Presence or absence of coding regions
Interspersed Tandem
Repeats Repeats
Transposable Minisatellites Micro-

Others Satellites
Elements satellites
Satellites Mini satellites Micro satellites

Highly repetitive
Very large array Moderately Repetitive
(100 Mbp )
In heterochromatic Large array Small array
regions near (30 kbp ) (200 bp)
Centromeres , Found in Found in
Telomeres euchromatic regions euchromatic
Transposable elements (Transposons)
-Derived from parasitic DNA
VNTR STR or SSR

-Propagate by replicating & inserting a new copy. (jumping elements)
Tandemly repeated sequences show exceptional variability among individuals in terms of copy
number. (used to study polymorphisms)
Variations in the Human Genome
-99.9% of the sequences is similar among individuals. 0.1% may vary.
Mutation-differences in DNA sequence in an individual that are rare, may be unique to the individual
or family line, occur in coding/ regulatory region. (<1% in population)
Polymorphism-differences in DNA sequences found in 1% or greater in the population. Has a higher

frequency than mutations. (mainly in non-coding regions)
Two types of variations.
1. SNPSingle Nucleotide Polymorphism-variation in single

nucleotide bases scattered along the chromosomes
Variations in copy number of 2. VNTRVariable Number of Tandem Repeats-
tandem repeats SSR/STRSimple Sequence Repeats/Simple Tandem Repeats
Importance of SNPs
• Genetic markers for disease
• Development of personalized drugs
• Mapping migration of population
• Information about evolution
• Gene therapy

Drugs, Toxins & Inhibitors
Drug/Toxin/Inhibitor Action
Dextran  As a plasma volume expander – to treat hypovolaemia
 In the treatment of iron deficiency anaemia (to solubilise iron)
Aspirin (NSAIDs)  Irreversibly inhibits cyclooxygenase
Snake Venom  Contain phospholipase A2
 Catalyzes the hydrolysis of fatty acid of glycerophospholipids (e.g.
lecithin) forming lysolecithin which acts as a detergent.
 Dissolves the RBC membrane (causes haemolysis)
Valinomycin  Mobile iron carrier (ionophore)
 Transports K+ down its electrochemical gradient
 Used as an antibiotic
Digitalis  Inhibit Na+/K+ pump, causes high levels of Na+ inside the cell
 High intracellular Na+ levels decreases activity of Na+ / Ca2+ exchanger
(which normally transports Ca2+ out in exchange for bringing Na+ in)
 Causes increased intracellular Ca2+, Stimulate muscle contraction
 Used in the treatment of congestive heart failure
Omeprazole  Inhibits the H+/K+ ATPase pump
 (Prodrug and a weak base which gets activated in acid)
 Used for gastric ulcers
Colchicine  Tubulin polymerization inhibitor
 Anti cancer drug
Disopropyl fluorophosphates  Forms a covalent bond with OH group of serine in the catalytic site of
(DFP)/ Organophosphate acetylcholine esterase and irreversibly inhibits it
insecticides  Inhibits breakdown of acetylcholine
 Accumulation of acetylcholine causes overstimulation of muscles
causing muscle fatigue finally leading to paralysis
 Death due to respiratory failure (when respiratory muscles are
paralysed)
Neostigmine  Competitive inhibitor of acetylcholine esterase
 Used at the end of a surgery to remove the effects of curare like drugs
 Also used in the treatment of Myasthenia Gravis
Sulfonamide (Sulphanilamide)  Structural analogue of PABA
 Competitive inhibitor of folic acid synthesis in bacteria

Disulfiram  Inhibit aldehyde dehydrogenase
 Accumulation of acetaldehyde
 Acetaldehyde causes nausea & headache symptoms after taking
alcohol
 Discourage the consumption of alcohol due to the bad side effects
Allopurinol  Suicide inhibitor of xanthine oxidase
 Used in the treatment of gout and hyperuricaemia
Asparaginase  Cells require asparagine to synthesis proteins
 Normal cells can produce their own asparagines but leukaemic cells
cannot (leukaemic cells have to obtain asparagine from blood)
 Asparaginase converts asparagine to aspartate
 Low asparagine level reduces malignant cell growth
Streptokinase (from bacteria)  Converts plasminogen to plasmin
 Plasmin dissolves fibrin clot
 Used in treatment of MI
Fluoride  Inhibit enolase enzyme therefore inhibit glycolysis
 Used for blood glucose estimation (mixing fluoride inhibits glycolysis in
red blood cells so glucose in the sample won’t be used up by the cells
during transport/storage of the blood sample)
Rotenone, Amytal  Inhibit complex I (NADH dehydrogenase)
 But does not inhibit ETC (because CoQ can get electrons from complex
ll)
Antimycin A  Inhibit complex III & ETC
CN‐/ CO/Azide  Inhibit complex IV (cytochrome c oxidase) & ETC
Nitrite, Thiosulphate  Used as antidotes in CN‐ poisoning
 Nitrite converts Hb to MetHb, CN‐ preferentially binds to Fe3+ of
MetHb
 Thiosulphate converts CN‐ to non‐toxic CNS‐
2,4‐DNP, FCCP [Also, Aspirin and  Uncoupling agents, dissipate the proton gradient (energy lost as heat)
Salicylates at high doses]  Uncouples oxidative phosphorylation from ETC
(Hydrophobic weak acids)
Oligomycin  Inhibits ATP synthase
Atractyloside  Inhibit ATP/ADP translocase (adenine nucleotide translocase)
 Can cause lactic acidosis
Statin drugs (e.g. lovastatin,  Structural analogues of HMG CoA
simvastatin)  Competitive inhibitors of HMG CoA reductase
 Inhibits cholesterol synthesis (so decreases plasma cholesterol levels)

Lead  Inhibit ALA dehydratase & ferrochelatase
 Cause acquired porphyrias
Azaserine /DON  Glutamine antagonist
 Inhibit glutamine:PRPP amidotransferase
Methotrexate  Folate analogue
 Inhibit both bacterial and eukaryotic dihydrofolate reductase
 Used as an anticancer drug
Mercaptopurine  An antipurine
 Inhibit glutamine:PRPP amidotransferase
5 –fluorouracil  Thymine analogue
 Converted to 5‐FdUMP in the body
 Inhibit thymidylate synthase (suicide inhibition)
 Used as an anti cancer drug
Acycloguanosine/Acyclovir  Purine analogue
 Used in the treatment of herpes virus
Azidothymidine(AZT)/  A pyrimidine analogue
Zidovudine(ZDV)  Used in the treatment of HIV
 Inhibit reverse transcriptase so HIV cannot convert its RNA to cDNA
Nalidixic acid/Ciprofloxacin  Inhibit DNA gyrase (found in E. coli) but do not inhibit eukaryotic
topoisomerase
 Used as antibiotics
Camptothecin  Inhibit topoisomerase I
 Used as chemotherapeutic agents
Doxorubicin/Etoposide  Eukaryotic topoisomerase II inhibitors
 Used as chemotherapeutic agents
Rifampicin/Rifampin  Bind to β subunit of RNA polymerase
 Block initiation of RNA chain (prevent RNA synthesis)
Actinomycin D/ Dactinomycin  Intercalates between DNA base pair
 Stop movement of RNA polymerase
 Act on both prokaryotes & eukaryotes
 Found in some cancer drugs
‐ amanitin  Eukaryotic RNA polymerase II inhibitor
 Found in poisonous mushrooms

Streptomycin  Binds to 30s subunit
 Stop initiation of translation & misread mRNA
Tetracycline  Interact with 30s subunit
 Stop aminoacyl tRNA binding
Chloramphenicol  Effect on 50s subunit
 Inhibit peptidyl transferase action
Erythromycin  Bind irreversibly to 50s
 Inhibit translocation of ribosome
 Acts as an antibiotic
Puromycin  Effect on both 50s & 60s
 Structural analogue of aminoacyl‐tRNA
 Stop elongation in both prokaryotes and eukaryotes
Diphtheria toxin  Inactivate EF‐2,which is required for the GTP driven translocation of
ribosome along mRNA
 Stop protein synthesis & kills the cells
Nitrites/Nitrous acid  Deaminating agent, found in food preservatives
Benzopyrene  Polycyclic aromatic hydrocarbon
 Forms DNA adducts
 Cause bulky lesions
 Ultimately can cause substitutions/deletions and chromosomal
rearrangements
Aflatoxin  Carcinogenic agent – responsible for liver cancer
(Associated with mutations of p53 gene by adduct formation)

physiology
bat notes
term 03
REPRODUCTION
Sex determination (Testis or Ovaries) - By SRY region of Y chromosome.
• SRY is a DNA-binding regulatory protein.
• It initiates transcription of other downstream genes required for testicular development. Eg. MIS gene
Sexual differentiation (male or female phenotype) - Hormonal.

Genetic Sex: Male – XY Female – XX
Gonadal Sex: Male – Testes Female – Ovaries
Genital Sex (Phenotype): Male – Penis, Scrotum Female – Vulva
SEXUAL DIFFERENTIATION
5α Reducatse type 2
(From 8th -
13th week)
• Sex chromatin (Barr body) – inactive, condensed X chromosome(s) seen in

the nucleus
• Hormonal treatment of the mother has no effect on gonadal differentiation as opposed to ductal and
genital differentiation.
• Bipotential stages of the embryo:
o Bipotential gonads – up to the 6th week of gestation

o Bipotential genital ducts – up to the 7th week of gestation
o Bipotential external genitalia - up to the 8th week of gestation
• At the 13th week development of genitalia is complete

• Both DHT and testosterone bind with the same receptors
• After puberty plasma MIS level is equal in both male and female. (2mg/dL)
ABERRANT SEXUAL DIFFERENTIATION
Genetic Hormonal
Transposition of parts to Male pseudohermaphroditism (XY,Testis

other chromosomes + Female external genitalia)
•Deletion of SRY - XY female (MIS is present)
•Translocation of SRY to X
chromosome or an •Defective embryonic testes
autosome - XX male •Enzyme defect in androgen synthesis
pathway
•protein mutation (StAR protien)
•cholesterol desmolase
•17 α hydroxylase, 17,20 lyase
Chromosomal abnormality (Non-
•5 α reductase type 2 deficiency (Penis at
disjunction) 12 syndrome)
• Turners Syndrome - XO •DHT not formed
•streaky ovaries •At birth: testes, female genitalia
•female external genitalia •At puberty: penile enlargement due to
•lack of secondary sexual increased testosterone secretion.
development •Often request sex change
• Kleinefelters Syndrome - XXY

•Testis - seminiferous tubule •Androgen resistence
dysgenesis
•Mutation in androgen receptor gene -
•Male external genitalia complete loss of receptor function
•Defective spermatogenesis + (Testicular feminization syndrome)
azoospermia *mcq •Testes,Female external genitalia
•Presence of MIS - Female internal genitalia
• True Hermaphroditism - XX, not properly formed.
XY mosaicism (Nondisjunction •Blind ending vagina
in mitosis) •Breast development
•both ovaries and testes •Primary amenorrhoea
•ambiguous external genitalia •Defects in post receptor events
Female pseudohermaphroditism
(XX,Ovaries + Male external genitalia)
•Exposure of fetus to androgens during 8th
to 13th weeks of gestation
•Congenital virilizing adrenal hyperplasia
•Androgen treatment to mothers
•Androgen secreting tumors in fetus
•Synthetic pathway defects
Pseudo hermaphroditism – Individuals have gonads (genetic constitution) of one sex and the genitals of the other

Androgen Synthetic Pathway
Cholesterol 17α hydroxylase 17,20 lyase
Cholesterol
desmolase
Pregnanolone 17-OH Pregnanolone DHEA
3β HSD
Progesterone 17-OH Progesterone Androstenedione
21β HSD
11 – deoxy 11 – deoxy cortisol Testosterone
Corticosterone
11β HSD
Corticosterone Cortisol Oestrogens
PUBERTY
• Puberty is the period when endocrine and gametogenic functions of the gonads have first developed to
the point where reproduction is possible.
• Age of onset
o Girls: 8 – 13 years
o Boys: 9 – 14 years

BOTH SEXES
1. Increased physical growth
 Increased GH pulse amplitude
 Increased Insulin like Growth Factor (IGF)
 Increased Thyroid activity (not important for pubertal growth but for infancy)
 Effects of androgens and oestrogen
 Female androgens- from adrenal glands.
Androgens - Protein anabolic
Oestrogens – fusion of epiphysis (in both sexes)
• Peak height velocity; Peak of Growth Spurt
o Girls: 12 years
o Boys: 14 years
2. Appearance of Secondary sexual characteristics
Boys Girls
• Axillary and Pubic hair • Axillary and Pubic hair
• Growth and enlargement of internal • Growth and enlargement of internal
and external genitalia and external genitalia
• Increased facial + body hair • Breast development
• Decreased scalp hair (hair line goes • Subcutaneous fat deposition
above) • Menarche
• Increased muscle mass
• Low pitched voice
3. Behavioural and emotional changes

 Libido (attraction to opposite sex)
 Aggressiveness in boys
 Concerned about appearance
 Withdrawn/ Apprehension / Emotional instability
4. Adrenarche
 Increase in adrenal androgens without a simultaneous increase in ACTH.
 Due to increased activity of enzymes in androgen producing pathway
 Principal adrenal androgen – DHEA (Dehydroepiandrosterone)
 Promotes physical growth, axillary and pubic hair growth, sebaceous gland development, body
odour and acne.
GIRLS -Order-
Breast budding (Thelarche)
1. Thelarche
Pubic hair begins (Pubarche)
 Development of breast followed by development of pubic and axillary hair
 Ovarian oestrogen stimulates growth of lactiferous ducts Peak height spurt
 Progesterone – Alveolar lobule development
Menarche
2. Menarche Pubic hair adult

 First menstrual bleeding
 Often anovulatory. Next 1-2 years can be anovulatory Breast adult
 Irregular cycles follow. Takes about 1 year for regularity of cycles.
 Due to maturation of H-P-O axis
BOYS
-Order-
1. Nocturnal Emissions
 Emission of seminal fluid during sleep (wet dreams) Genital development begins
 LH pulse first appear during nocturnal sleep ↓
2. Spermarche (1st ejaculation) Pubic hair begins
↓
Peak height spurt
Factors affecting age of menarche
↓
Genitalia adult
1. Nutrition – Well-nourished  early
↓
Undernourished  delayed Pubic hair adult
“Critical body fat” (~ 17% of body weight) - leptin secreted by adipocytes
2. Constitutional - some families, ethnic groups…. early or late
3. Secular trend – age of menarche decreased over the years, due to increased nutritional status.
Endocrine changes seen in puberty
• Pulsatile secretion of GnRH brings on puberty (Hypothalamo-pituitary-gonadal axis)

• GnRH (hence LH) pulse first appears in nocturnal sleep and later spreads to daytime awake periods
• GnRH pulse FSH, LH pulse Maturation of gonads
Control of the onset of puberty
Reduced sensitivity of the Gonadostat

Reduced intrinsic CNS inhibition
Extremely low levels of sex hormones in pre-
Could be that, some gene products stimulate
pubertal years keep the Hypothalamus and
GnRH secretion
Pituitary inhibited
Inhibition of those genes during prepubertal period
At puberty: Sensitivity of the gonadostat ↓
GnRH, LH, FSH levels ↑
Gonads stimulate to increase activity.
• Removal of gonads from birth to puberty causes only a slight increase in gonadotrophin secretion.
Precocious puberty
• Early development of secondary sexual characteristics with or without gametogenesis
True-precocious Pseudo-precocious
- H-P-G axis is immature
- Maturation of H-P-G axis
- GnRH, FSH, LH levels are low
- GnRH, FSH, LH increased
- No gametogenesis
- True gametogenesis
- Excess oestrogen in girls and Androgens
- Early, but normal pubertal pattern of
in boys
pituitary gonadotrophin secretion.
Causes
Causes
- Androgen/Oestrogen secreting tumours
- Idiopathic
In adrenals or gonads
- CNS lesions
• Only true precocious will have fertility.

Delayed puberty
Boys Girls
- No genital growth by 20 years - No menarche by 17 years (primary
amenorrhoea)
Causes Causes
- Klinefelter Syndrome - Turner’s Syndrome
- Anorexia Nervosa
Male Reproductive System

Blood Testis Barrier
o Formed by tight junctions between Sertoli cells
o Allows Testosterone (steroids) to enter seminiferous tubules
o Allows maturing germ cells to pass through and move to the lumen, without disrupting the barrier
o Won’t let sperms leak into blood
o Protects germ cells from blood-borne noxious agents
o Establish an osmotic gradient that facilitate movement of fluid into tubular lumen.
o Prevents antigenic products of germ cell division and maturation, from entering the circulation
and generating an autoimmune response
• Hormone secreting Cells in the Testis
Leydig cells Sertoli Cells Cannot synthesise
Synthesize synthesize testosterone, but
*Testosterone *Inhibin contains
*Estrogen *Estrogen aromatase.
*MIS
Effects of Testosterone (ABP)*Androgen Binding Protein Converts
• Male secondary characteristics Helps in nourishment of germ cells androgens to
Formation of blood-testis barrier. oestrogen
• Protein anabolic effect
• Growth promoting effect
• Maintain spermatogenesis (along with FSH)
• ↑ Sebum & acne
• Development of male internal genitalia
• Hypothalamus Pituitary (LH) regulation
Spermatogenesis
Spermatogenesis [Spermatogonia  spermatid] Spermiogenesis

- Androgen independent [spermatid sperm (morphological changes)]
- in deep folds of the cytoplasm of the Sertoli cells
- Androgen (hence LH) and FSH dependant
Begins during Puberty
Requires - FSH
Testosterone (LH indirectly)
Locally produced oestrogen
Low Temperature 34°c
Takes about 74days.
Further Maturation of Sperms
Acquire motility within epididymis.
Capacitation - Functional changes which make sperms able to fertilize.

Occurs in isthmus of uterine tubes
 Increase motility
 Preparation for acrosome reaction
Acrosome Reaction
Breakdown of acrosome and release of enzymes- proteases
Proteolytic enzymes help in penetrating zona pellucida
Acrosomal reaction can occur in many sperms. But only one acrosome reacted sperm fuses with the oocyte.
Seminal Fluid
Testicular products Products of accessory glands

Sperms Fluid Eg- Seminal vesicles (60% of seminal volume)
Prostate
“Fertile” Seminal Fluid
Sperm count - 60-100million/ml Chemical disrupters of Reproductive
Volume - 2.5 to 3.5 ml/ ejaculate function
pH – 7.35-7.5
Sperm motility - >40% actively motile • Alcohol
Sperm morphology - <20% abnormal • Smoking
Liquefication time - 5 to 30 mins • Narcotics
Azoospermia – absence of sperms • pesticides/ Weedicides
Oligospermia – count <20 million
Asthenospermia – active motility <40%
Neuroendocrine regulation of male reproductive system
Hypothalamus
GnRH
stimulation
negative feedback
Anterior pituitary
LH FSH Male gonadotrophin secretion is
noncyclical
Leydig cells Sertoli cells

In both sexes main regulator of FSH is
inhibin
Testosterone Inhibin B
Estrogen Estrogen
Steroid Free Bound to albumin Bound to SHBG
Testosterone ##
Estradiol ##(mainly)
Female Reproductive System

Menstruation
Periodic vaginal bleeding with shedding of uterine mucosa, from menarche to menopause which is absent during
pregnancy & sometimes during lactation.
• Avg - 3 to 5 days [normal - 1 to 8 days]
- 30 ml [normal – 0 to 80 ml]
28days (range 21 to 35 days)  < 21d short cycle

>35 d long cycle
Development of
Recruitment of dominant follicle Formation & maintenance
follicles(1-5 d) Rest – become atretic of corpus luteum
1 6 14 25 28
Dominant follicle Ovulation Corpus luteum
regression begins
Follicular (proliferative) phase – more variable Luteal (secretory) phase – less variable
Cyclical changes in reproductive organs
Ovarian Changes
Follicular phase Luteal phase

Recruitment of follicles Formation & maintenance of the corpus luteum
Emergence of dominant follicle Synthesis of estrogen, progesterone, inhibin
Synthesis of estrogen & inhibition

Pattern of secretion of reproductive hormones during the normal menstrual cycle

Oogenesis
•2 million at birth --> 50% are atretic follicles

- 400 used for ovulation (300 000 at puberty)
- rest - undergo atresia at various stages of development
Primodial •primary oocyte (arrested in prophase of meiosis I)
follicles •Basement membrane
•1 layer of granulosa cells
•primary oocyte (Formed at puberty)

Primary •zona pellucida
follicles •additional layers of granulosa cells
•primary oocyte
Secondary •granulosa cells
(Pre-Antral) •theca cells (interna + externa)
follicles
•primary oocyte - eccentrically placed

•granulosa cells
•theca cells Many for
Antral
•antrum formation each cycle
follicle
•produces oestrogen
•secondary oocyte (meiosis I- completed, meiosis II begun) 1 for each cycle

•granulosa cells - for final maturation
•theca cells
Dominant - may be selected by
follicle •antrum
•becomes the Graffian follicle ability of follicle to
secrete oestrogen
•oocyte arrested in metaphase of meiosis II

•caused by pre-ovulatory LH surge.
•weakening of follicular wall, rupture
Ovulation
•release of ovum & follicular fluid
Corpus •when graffian follicle ruptures, it fills with blood.

haemorrha •fat cells get accumulated
gicus
•granulosa lutein cells

- secretes oestrogen, progesterone and inhibin
Corpus •theca lutein cells
Luteum - secretes androgens and progesterone
Corpus •regressed corpus luteum

Albicans

Uterine Cycle/Changes
Menstruation
Proliferative phase
•due to regression of Corpus
Luteum (5th - 14th day)
•endometrium - becomes thinner •rapid increase in
•spasm & degeneration of walls of thickness. (proliferation)
arteries --> ischemia and necrosis •Straight uterine glands
of superficial layers --> spotty lengthen
haemorrhages --> confluence --> •Maintained by estrogen
menstrual flow Secretory phase
•highly vascularised
•stroma oedematous
•coiled glands
•spiraling of the arteries
increased
Length of the secretory •secretes clear fluid
•changes in cell adhesion
phase is more constant than molecules etc
the length of the proliferative •later --> Prolactin
phase. production
•Maintained by estrogen
& progesterone
Stratum Functionale – Superficial 2/3rd Stratum Basale – Deep 1/3rd

Long, coiled, spiral arteries Short, straight, basilar arteries
Shed. Not shed.
Uterine cervix does not undergo cyclical desquamation

Basal body temperature rises 1-2 days after ovulation
Cervical mucus
Follicular phase Mid cycle Luteal phase

Volume Highest
Viscosity Lowest
Stretchability Highest
Ferning begins Well developed Disappears
Vaginal Epithelium changes
Oestrogen – Epithelium is cornified. (fern pattern)
Progesterone – Thick mucus secreted

Epithelium proliferates and becomes
infiltrated with leukocytes.

12
Anovular menstruation
Follicle development fails to reach no ovulation & corpus

ovulatory maturity luteum is not formed
Estrogen synthesized
endometrium develops absence of progesterone
Follicular atresia
Estrogen endometrium breaks
Oestrogen Synthesis
LH FSH
cholesterol Antrum
cholesterol androstenedione
aromatase
androstenedione
estradiol estrone estrone estradiol
Circulation
theca interna cells granulosa cells
Neuro-endocrine regulation of the Menstrual Cycle
Hypothalamus Stimulate
GnRH Negative
Follicular
feedback
Ant. pituitary
LH FSH
Ovarian follicles
Oestrogen Inhibin
Hypothalamus Positive
Mid Cycle
GnRH feedback
Ant pituitary
LH and FSH
Dominant follicle
Oestrogen++  Repeat campaign 2015 A/L

13
GnRH
Luteal phase
Ant pituitary
LH stimulate progesterone LH and FSH
production. FSH and LH both
stimulate Oestrogen
production.
Corpus Luteum
Oestrogen Inhibin
Progesterone
Detection of ovulation
Menstrual history – regularity, Dysmenorrhoea (pain in menstruation),
Mid cycle pain(indicate the ovulation)
During second half of cycle – Serum hormones (progesterone day 21 to 24)
Changes in cervical mucus (watery change to viscid)
Rise in BBT (1-2 days after ovulation)
Secretory endometrium
Visualization by ultrasound and laparoscopy (corpus luteum or Graafian follicle)
Oestrogens Progesterone
IIry sexual characteristics Thermogenic
Regulation of hypothalamus and pituitary Regulation of hypothalamus
Reproductive
Proliferation of endometrium and pituitary
Myometrium - ↑contractile proteins, excitability, Gap Jun. Breast-lobular, alveolar growth
Effects
Breast – duct growth & fat deposition Endometrium-secretory
Cervical mucus – thin & watery changes
Oviduct motility
Growth of ovarian follicles & reproductive organs Myometrium- ↓frequency and
intensity of uterine contractions
Na+ and water retention ↑Sebum/acne
Prevents osteoporosis cervical mucus thick & viscid
Non- Lipid metabolism – LDL ↓ HDL ↑
Reproductive Glucose tolerance ↓
Effects Mitogen activity – tumour formation (oppose most of the actions
Bone epiphyseal closure (in both sexes) of oestrogen)
Menopause
Last menstrual period (45-55 yrs)
Identified retrospectively. After menopause main product of oestrogen is Estrone
Climacteric: Period during which reproductive function diminish
Q. Why FSH, LH found in the urine of women after menopause in considerable amounts?
Transitional period (4th decade) -

↓Reduction in gonadotrophin ↓Estradiol ↑FSH (Progesterone and LH no
Responsive follicles Inhibin significant change)

14
After menopause -
↓Absent gonadotrophin ↓Estradiol ↑ FSH, LH (Excreted in urine)
responsive follicles Inhibin
Progesterone
Oestrogen synthesis after menopause

• Adipose tissue, Liver, Brain, Hair, Muscle
Adrenal cortex, Ovarian stroma
Androstenedione Estrone (major product)
Testosterone Estradiol
Estrogen deficiency
• Hot flushes
• Atrophy of breast & reproductive tract
• Reduced vaginal acidity (reduced glycogen in cells – prone to infections)
• Dyspareunia (pain during sexual intercourse)
• Prone to IHD. Why?
• Behavioural & emotional changes
• Osteoporosis
Hot flashes(flushes)
• Set point of the central thermostat lowered
• Heat dissipating mechanisms are activated
• Wave of heat passing over the chest & spreading to neck, face, upper arms followed by
sweating
• Marked vasodilatation followed by vasoconstriction
• Oestrogen therapy brings relief
Fertilization & Implantation
Millions of sperms deposited in vagina
Chemoattraction by substances secreted by ovum
Penetration of corona radiata
Sperm head adheres to zona pellucida
Acrosomal reaction and penetration of zona pellucida
One sperm fuse with ovum membrane, nucleus released, fusion of nuclei
Sperms move up due to their own motility and due to propulsion by uterus and oviducts.
Sperms fertile up to 72 hours in female genital tract
Ovum fertilizable up to 24 hours after ovulation
15
Implantation
• Usually, upper posterior part of uterine cavity.
• Endometrium → decidua
• Blastocyst lies in a cavity of endometrial glands.
• Maternal vessels eroded by trophoblast; blood extravasates around blastocyst
Corpus luteum of pregnancy

• Starts enlarging after fertilization in response to HCG secreted by placenta.
• Secretes oestrogen, progesterone, relaxin.
• After 6wk function declines, taken over by placenta.
Placenta
 Exchange of O2, CO2, nutrients, waste products

 Hormone production (hCG, hPL, Oestrogen, Progesterone)- almost all the body hormones
 Barrier function
 Placental circulation: no direct mixing of maternal and foetal blood occurs.
Oestrogen synthesis during pregnancy 37th week of gestation is called the Term
Source - Corpus luteum of pregnancy-2/3months
Feto placental unit
Main type-estriol
Functions- Enlargement of uterus, genitalia
Enlargement & ductal proliferation of breast
Relaxation of pelvic ligaments
Placenta Fetal adrenal
Cholesterol
Pregnenolone DHEAS 16OHDHEAS
progesterone Cortisol, Corticosterone Urinary estriol excretion by

mother is an index of the state
of the foetus.
Estradiol DHEAS
Estriol 16OHDHEAS
Progesterone synthesis during pregnancy

Sources - Corpus luteum -2/3months
Placenta
Functions-Development of decidual cells
Prevents uterine contraction
Nutrition and cleavage of the early embryo
Prepares breasts for lactation

16
Endocrine changes during pregnancy
hCS
hCG: - (glycoprotein)
• Secreted by the syncytiotrophoblast (also; fetal liver n kidney)
• Primarily luteinizing effect. (prevent degeneration of CL)
Acts on the same receptors as LH.
• Present in blood  6 days after conception/fertilization Basis of
present in urine  14 days after conception/fertilization pregnancy test
• Peak-10th week
Human Chorionic Somatomammotropin(hCS) / hPL

• Secreted by syncytiotrophoblast
• Lactogenic
• Structure similar to GH
• progressive increase throughout the pregnancy
• Maternal Lipolysis ↑ & glucose utilization↓ Glucose for the fetus.
• Pregnancy induced diabetes mellitus.
• K+, Ca2+, Na+ retention
• Amount secreted is proportionate to size of the placenta.
low hCS  placental insufficiency.
Relaxin
Secreted by
 Corpus luteum  Uterus
 Placenta
Actions
 Relaxes pubic symphysis & other pelvic joints
 Softens and dilates uterine cervix
 Inhibits uterine contraction
o hCG and relaxin – peak in first trimester
o oestrogen, progesterone, hCS – peak at term

17
Amniotic fluid
o 300-800 ml term
o Similar to ECF. Contains waste products, foetal cells
o Allows free movement, diffusion of external trauma, provides constant environment
o Amniocentesis for pre-natal diagnosis
Diagnosis of pregnancy
Clinical: Amenorrhoea Foetal heart sounds
Uterine enlargement Breast, skin changes
Nausea, vomiting Frequency of micturition
Investigations: Biological, immunological assays Ultrasound scanning
Period of gestation-280days
conception
1st 2nd 3rd trimesters
12 28 40 weeks
Last regular menstrual period
Changes in other systems during pregnancy
General -
o Weight gain
o Increased BMR (5-25%)
Uterus
o Decidual reaction-endometrial changes during pregnancy
o Hypertrophy& hyperplasia
o ↑vascularity
o Changes in connective tissue and contractile proteins
Cervix, Vagina, Vulva

o Cervix softens, ↑vascularity and secretions
Skin
o Linear nigra
o Striae gravidarum
Breast
o Enlarge to almost double size

o Dilated veins become visible
o Nipples, areola enlarge & get pigmented
Blood & cardiovascular system

o Blood volume↑↑with haemodilution Physiological anaemia
o Plasma volume (40-50%) RBC mass (20-30%)
o Relatively hypercoagulable (prevent excess bleeding at delivery)
o Albumin, globulin & fibrinogen ↑ESR↑
o HR, SV Cardiac output↑
o ↓Diastolic blood pressure. Lowest in 2nd trimester and then rises to non-pregnant level. Why?
o No change in pulmonary BP
18
o Ankle oedema due to

 venous stasis (reduction in venous tone compression of pelvic veins by uterus)
 Fluid retention (about 5L)
 Decreased colloid osmotic pressure
Urinary tract
o ↑RBF, GFR (↓serum creatinine, urea)
o ↓Tubular reabsorption – renal glycosuria
o ↑ frequency of micturition
o ↑renal size, hydronephrosis, hydroureter
Respiratory system
o ↑minute ventilation & respiratory rate.
o ↑IRV, Tidal volume
o ↓RV, FRC (Uterus exert pressure on diaphragm; more thoracic muscles used)
o ↑oxygen consumption
o ↓arterial / alveolar PCO2
Gastro-intestinal system
o Nausea, vomiting (morning sickness, hyperemesis gravidarum)
o Alteration of appetite
o Tone, motility, ↓gastric emptying time prolonged
o Constipation
o Gastro-oesophageal reflux- heart burn in pregnancy (↓ sphincter tone)
Locomotor system - Softening of ligaments and joints
Metabolic changes
o ↑Fat mobilization and tendency of ↑ketoacidosis
Parturition
Changes during the last 2 to 3 weeks of pregnancy culminating in child birth
Final maturation Ripening and

of fetal organs Activation of myometrial
softening of the
contractile apparatus
(lung, liver etc) cervix
Oestrogen
 Increase gap junctions between myometrial cells (function as syncytium)
 ↑prostaglandin synthesis
 Increase uterine contraction by ↑ contractile proteins
 Increase no. of oxytocin receptors
Prostaglandins
 Ripening of cervix
 Myometrial contractions (↑Ca ions for actin myosin interactions)
Ripening - Events happening in the cervix during parturition
 dilate
 Softens

19
Increase in oxytocin receptors distension of uterus

Oestrogen
Oxytocin
Endometrium
Myometrium Prostaglandin synthesis

Positive
feedback Uterine contraction
mechanism
Dilation of cervix &Distension of vagina
Nerve endings stretched
Neural impulses to hypothalamus
Oxytocin release
 In early labour, maternal plasma concentration of oxytocin, is not elevated from the pre-
labour value. There is only a marked rise in receptors.
Labour
Painful uterine contractions aided by voluntary contractions of, maternal abdominal muscles for
expulsion of uterine contents
Beginning of painful uterine contractions
Full cervical dilation
birth of baby
Delivery of placenta
Puerperium
Changes in pregnancy revert approximately to the non-pregnant state during the 6 weeks from
child birth
Lactation is established.
Systems come to non-pregnant levels
Lactation
 During puberty
Oestrogen Progesterone
Developments of ducts development of lobules & alveoli
 During pregnancy
• [Oestrogen]&[ progesterone] are high
20
• Prolactin levels increase steadily in term  Full lobulo-alveolar development of breast

• Milk secretion is inhibited by oestrogens.
 Ejection of milk
• Expulsion of placenta initiates lactation.
Prolactin – Regulation of Secretion

Hypothalamus
↓ Suckling
Dopamine Pregnancy
↓(-) Sleep
L – Dopa Stress
(+) Pituitary
Apomorphine Exercise
↓(+) Nipple stimulation
Bromocriptine
Prolactin Sexual intercourse in women
Hypothyroidism (TRH)
Phenothiazine
VIP and other polypeptides
Suckling
Sensory nerve endings in nipples stimulated
Hypothalamus
Oxytocin ↓Dopamine
Contraction of myoepithelial cells ↑ Prolactin
Milk ejection/ let down ↑Milk production
(↑mRNA of milk proteins-
Lactalbumin, casein
↑mRNA of UDP-galactosyl transferase
Oestrogen – prevents lactation
↓ binding of PRL to receptors
↓ milk volume
Progesterone – prevents initiation
No effect once established
Prolactin
From anterior pituitary
Secretion inhibited/regulated by dopamine (prolactin inhibiting hormone)
A peptide, structurally similar to GH & hCS.
Receptors resemble GH receptors
1) Inhibits GnRH secretion and action of it on pituitary
2) Antagonizes the gonadotrophins' actions in ovary
So, women who nurse regularly have amenorrhea for 25 – 30 weeks (who do not - up to 6 weeks)
-Lactational amenorrhoea-
After resumption, there are anovulatory cycles in the first 6 months
If no lactation, menstruation returns 6/52 postpartum.
Lactation has a high influence by the brain centres.

Ascending Tracts
Sensory Afferent Pathways
To sensory cortex and other cortical areas
• Cranial nerves ascending pathways sensory cortex

• Dorsal spinal nerves ascending tracts in spinal cord thalamus sensory cortex
Results in organized higher order responses/memory
Primary afferents/ first order neurons (receptor to the second order neuron)
- Sensory fibers from head area (trigeminal) join the anterolateral and lemniscal systems in the
brain stem
- Rest of the body – along spinal nerves
Secondary afferents/ second order neurons (along ascending tracts of the spinal cord to thalamus)
Tertiary afferents/ third order neurons (thalamus to sensory cortex)
Physiological classification of nerve fibers that transmit different types of sensation
Number Origin Fiber Type

Ia Muscle spindle, Annulo-spiral ending, Mechanical Aα
Ib Golgi tendon organ, Muscle spindle, Flower-spray Aα
II ending, Mechanical Aβ
III Pain and cold receptors, some touch receptors Aδ
IV Pain, Temperature and other receptors Dorsal root C
Carry information to the central integrating areas
Dorsal horn of spinal cord
Dorsal horn acts as a ‘gate` - Action potentials in sensory nerve fibers translated into Action
potentials in ascending tracts; passage dependent on the nature and pattern of impulses –
modified by the inputs from the descending tracts

Fine touch – Dorsal column/Lemniscal system
- First order neurons ascend in dorsal columns (collaterals to SG)

- Synapse with second order neurons in the medulla (gracile and cuneate nuclei)
- Cross the midline – ascend in the medial lemniscus
- Synapse in the thalamus – third order neurons to sensory cortex
- Lesions in the dorsal column won’t cause total loss of ‘touch’ – Crude touch preserved
Dorsal columns – detailed localization, spatial and temporal pattern of touch
Other forms of touch – Anterolateral system
- First order neurons synapse with second order neurons in the dorsal horn
- Second order neurons cross the midline and ascend in the ventral spinothalamic tract
Ventral spinothalamic – poorly localized gross tactile sensation
Pain and temperature – Anterolateral system
- First order neurons synapse with second order neurons in the dorsal horn
- Second order neurons cross the midline and ascend in the lateral spinothalamic tract
Lateral spinothalamic tract – Pain and temperature – discrete pathways in the tract
Proprioception/ Vibration – Dorsal Columns
- First order neurons ascend in dorsal columns

- Synapse with second order neurons in the medulla (gracile and cuneate nuclei)
- Cross the midline – ascend in the medial lemniscus
- Some fibers end in cerebellum
Dorsal Columns – Joint position sense/ Vibration
What happen when the dorsal columns are destroyed??
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Descending tracts
Motor Unit
− Functional unit of motor control system which is responsible in carrying out a

movement
− Components - each single motor neuron and all the muscle fibers innervated by it
− The number of muscle fibers in a motor unit varies (muscles concerned with fine
movements - lesser number of fibers for each motor neuron and vice versa
− Each motor neuron innervates only one kind of muscle
Voluntary motor activity
Idea and complex plane (memory, emotions, motivation etc…. Areas - supplementary and
association cortex……)
Transfer of the complex plan to programs (sensorimotor cortex, basal ganglia, lateral
cerebellum)
Brain stem thalamus
Spinal cord spinal cord
Actions (skeletal muscles) receptors
Descending motor pathways
Descending motor
Pyramidal tracts Extrapyramidal tracts
Corticospinal tract Corticobulbar tracts

Pyramidal tracts
All pyramidal fibers converge from the surface of the brain like a fan - corona radiata
These come down and join together to form the internal capsule at the level of the thalamus
Some fibers are densely packed in the internal capsule, lesions in this region produce dense
weakness (paresis) of the contralateral side
Pyramidal tracts start crossing to the opposite side at the level of medulla
• 80% cross to the opposite side - lateral corticospinal tracts

• 20% remain uncrossed - anterior corticospinal
Distal muscles are supplied by lateral corticospinal tract and responsible for fine, skilled
movements
Axial muscles supplied by anterior corticospinal tract – Gross, posture maintaining

movements
Extra pyramidal system
Descending motor pathways other than the corticospinal tracts
Components - red nucleus, substantia nigra, reticular formation, vestibular nuclei (inputs
from basal ganglia and cerebellum)
Extra pyramidal projections to lower motor neurons
Rubrospinal tract – lateral Excites the flexors and inhibit the extensors
Reticulospinal tract
Tectospinal tract medial
Vestibulo spinal tract Excites proximal limb extensors/ anti-gravity muscles
Involved in - autonomic motor movements (facial expressions)
- control of proximal muscles ( so gross rather than fine movements)

control of posture

SENSORY DIVISION OF THE NERVOUS SYSTEM.
Sensory modality / Stimulus
Changes in the external and internal environment.
Sensory Receptor
Transducers which convert various forms of energy into action potentials in neurons.
Adequate stimulus
The perticular form of energy to which a receptor is most sensitive
Different types of sensations (modality)
• Cutaneous :- touch, pressure, pain( nociception ), temperature

• Special :- smell and taste, vision, hearing,
Acceleration rotational
Linear vertical
Horizontal
• Synthetic :- vibration, two point discrimination
Stereognosis
• Visceral :- proprioception, chemical composition…etc.
• Other :- tickle , itch
Different types of receptors according to their function
• Teleceptors :- for vision, smell (stimulus- at a distance)

• Cutaneous :- free nerve endings are more in dermis than epidermis
Pacinian corpuscles are more in superficial fascia
(stimulus- in the external environment near at hand)
• Interoceptors:- visceral (stimulus- in the internal environment)
• Proprioceptors:-muscle tendon, inner ear (monitor body position)
Different types of receptors according to the sensory modality
• Touch and pressure :-

Fast adapting Meisner’s Texture and slow vibration
Pacinian corpuscle Deep pressure and fast vibration
Slow adapting Ruffini’s Sustained pressure
Merkel cells Sustained pressure and touch
Hair end organ Motion
• Pain and temperature :- free nerve endings
• Hearing and acceleration :- hair cells

Sensory unit :- single sensory axon with all its peripheral branches and it is sensitive to one type of
sensation( modality )
Receptive field :-the area of the sensory unit that produces a response
Generation of an Action potential in a sensory receptor
• Stimulus acts on the unmyelinated nerve end / Receptor
• Changes in the receptor membrane occur (ex: mechanical deformation)
• Opening of Na +/ Ca2+ channels or,
• Inhibition of K+ channels or,
• Inhibition of Na+/K+ ATPase pump, may lead to produce non propogated receptor potential
• Magnitude of the receptor potential α log [intensity of the stimulus ]
• Receptor potential reaches the threshold
• Propogating action potentials are produced in the first node of Ranvier
• Action potentials are produced as long as the receptor potential is above threshold
• Frequency of the propogating AP α magnitude of the receptor potential α Intensity of

stimulus
Intensity of the stimulus α generator potential amplitude

Intensity of the stimulus α Action potential frequency
Sensory coding
Converting a receptor stimulus to a recognizable sensation

Brain identifies four aspects of the stimulus
• Type of stimulus (modality)
• Intensity of stimulus
• Location of stimulus
• Duration of stimulus
Cortical plasticity and Adaptation of sensory receptors affect these functions
Identifying the type of a stimulus

1. Doctrine/law of specific nerve energies
• says that,Specific receptors for one type of sensory modality
• Their associated fibers carry the nerve impulse to the spinal cord
• The impulse is transmitted to a specific sensory pathway
• Ends in a specific area of the brain
• Type of the stimulus is identified
• Stimulation of this pathway anywhere from the receptor to the area of the brain, makes
the person to feel the particular type of sensation that it normally transmits.

2. Adequate stimulus
• is the type of energy that a receptor is most sensitive
• receptors has a very high threshold for another modality while lowest threshold is for
the adequate stimulus
Identifying the location of a stimulus
• Law of projection
• Lateral inhibition
• Sensory unit & receptive field
1. Law of projection
• The sensory pathway extends from the receptor to the cortex
• If we stimulate anywhere along this pathway
• The conscious sensation produced is always referred to the location of the receptor
Phantom limb phenomenon
• Amputation of a limb/part of a limb
• neuromas are formed on the cut end of nerve fibers
• They spontaneously discharge or discharge when pressure is applied
• Earlier these fibers transmitted impulses coming from the amputated limb
• Pain and proprioception sensations felt
• As if coming from the absent limb
• Cortical plasticity is also involved here. How??
2.Lateral inhibition
• Process where axons with the greatest activity are highlighted by the inhibition of adjacent less
active axons
• Improves discrimination and sharpens the edges of a stimulus
• Collateral nerves at different levels inhibit adjacent neurones
• Can occur at any level from the receptor to the cortex

Identifying the intensity of a stimulus
• Number of activated receptors/sensory units.
• Variations in the frequency of action potentials.
1.Number of activated receptors
• Receptors for one modality can have very high threshold for another modality
• Weak stimulus activates low threshold receptors
• Moderate stimulus activates low and high threshold receptors of same modality
• Strong stimulus activates receptors of same and different sensory modalities
• When the number of activated receptors increase, more afferent pathways are activated
• Spatial summation occurs
• When magnitude of the stimulus rises rate of discharge by same pathway increases.
• Temporal summation occurs
• Sensory units of same as well adjacent overlapping receptive fields get stimulated.
• This is known as recruitment of sensory units
• Due to these intensity of the sensation felt increases
2.Variation in the frequency of Action Potential
• Increase in the frequency of the AP - brain interprets as increase in intensity
• Log [intensity of stimulus] α magnitude of receptor potential α frequency of AP

(above threshold level)
Cortical plasticity
• Neurons in the cortex have high degree of convergence and divergence

• Which can become strong with use and weak with disuse
Eg:-
1. Increased afferent information in a sensory pathway - expansion of the cortical area receiving
that input
2. Amputation of a limb
Cortical area receiving inputs from that limb becomes silent
Adjacent cortical areas spread into it
Makes use of that area
• Stroke
Damaged area spreads into adjacent cortical areas
Loss of function is partially regained

Adaptation (Desensitization)
• when a stimulus of constant strength is applied to a receptor, the frequency of action potential
generation decreases over time
• Receptor sensitivity decreases
Degree of adaptation
Slowly adapting (tonic receptors) Rapidly adapting (phasic receptors)

:- baroreceptors, proprioceptors, nociceptors :- pasinian corpuscles,Meisner’s
some mechanoreceptors (merckel cells, ruffini olfactory receptors,taste receptors
endings)
• Adaptation occurs due to,

- Accommodation - progressive inactivation of Na+ channels in the receptor membrane
-Change in the structure of the receptor - stimulus intensity on the receptor reduces
with this (morphological change) eg- pacinian corpuscles
PAIN PERCEPTION AND MODULATION
Pain
Fast pain slow pain
Sharp, pricking pain Aching, burning pain
Well localized Diffuse
A δ fibers C fibers
Glutamate at dorsal horn Substance P at dorsal horn
Pain types
Site of pain Cause of pain
Somatic pain Ischemic pain
Deep pain Inflammatory pain
Muscle pain Neuropathic pain
Visceral pain
Ischemic pain/ muscle pain

• Decreased blood supply results muscle ischaemia
• Causes accumulation of P factor (K+?)
• Stimulates pain fibers
• No pain when the blood supply is restored.
Ex: Angina pectoris, imtermittent claudication
Inflammatory pain
• Due to tissue damage
• Chemical mediators like bradykinn, cytokines, prostaglandins are released
• They act on pain receptors and dorsal horn, producing,

Hyperalgesia – Exaggerated response to minor painful stimuli due to chemical mediators
like bradykinin,cytokines,prostaglandins,substance P,CGRP
allodynia – Pain to innocuous stimuli(touch)

Due to sprouting and formation of new synapses by touch fibers(Aα and Aβ)
and autonomic fibers onto pain conducting fibers.
Neuropathic pain
• Due to damage or inflammation of nerves
• Hyperalgesia and allodynia - abnormal connections by sprouting Aα and Aβ in dorsal horn
• Occurs in various forms
Eg:-
• Pain in the phantom limb
• Causalgia – burning pain long after a trivial injury
• Reflex Sympathetic Dystrophy – after damage to a peripheral nerve trunk, noradrenergic
sympathetic fiber may over grow to the dorsal root ganglia. Sympathetic discharge gives
pain.
Deep somatic pain
• Pain from injured bones, tendons, joints
• Poorly localized & slow pain
• Accompanied by autonomic symptoms: - sweating, nausea, vomiting, pallor, change in BP
• Pain from deep structures results in painful skeletal muscle spasms (setting up a vicious cycle)
Visceral pain
• Due to distension, spasms, ischemia, inflammation in visceral organs
• Afferents come via sympathetic and parasympathetic fibers
• Pain is poorly localized(carried out by C fibers)
• Associate with autonomic symptoms
• Causes reflex spasms in nearby skeletal muscles - guarding
• Radiates or referred to other area
• Radiation of pain – pain felt in the viscus spreads to another somatic area
REFERRED PAIN
• Irritation of a viscus or a deep somatic structure produces pain perception in another distant
somatic area
Eg:- myocardial pain is referred to the arm and neck
Pain in the knee joint is referred to the hip joint
Dermatomal Rule of referred pain

The structure where the pain originates and the dermatomal segment where the pain is
referred have the same embryonic origin

The cause of referred pain
• Convergence of peripheral and visceral pain fibers on the same second order neuron.(In the
dorsal horn)
• Somatic pain is more common than visceral pain
• Brain has learnt that impulses coming in this pathway as produced by the somatic structure
• When the visceral pain fibers discharge, the brain cannot differentiate
• And identifies as coming from the somatic structure
• And also pain can be referred to scars in that dermatome (sites where there was previous pain)
• This is due to plasticity of the brain
• Also visceral pain may facilitate the firing of the somatic nerve ending which in turn stimulate
the 2nd order neurons. thus brain identify it as coming from the somatic fibres.
Pain modulation
• Physical (Dorsal horn gate) 2. Release of opioids 3. Psycological methods 4.other
Gate control theory of pain

• Rubbing the site of pain temporally relieves the pain.
• Small diameter pain fibers (Aδ and C ) transmit impulses to the second order neuron at the
dorsal horn
• This transmission can be inhibited by the activity of large diameter sensory fibers ( Aα and Aβ
carrying touch, pressure )
• These fibers conduct impulses faster than Aδ fibers.
When Aα and Aβ are stimulated they inhibit pain transmission pre synaptically and post synaptically via
an inhibitory interneuron.

• Activity of the descending serotonergic pathways may also be involved in this (Descending
analgesic system)
Stimulation of periaqueductal grey matter (PAG)(by higher centers and by pain conducting C fibers via
Hypothalamus)in mid brain activates Enkephalin releasing neurons that project to,
Neucleus of raphe magnus & Rostral ventro medial medulla(RVMM)
Seratonin Catacholaminergic/noradrenergic
Inhibitory inter neurons that release

endogenous opioids, enkephalin or dynorphin.
Eg:-
o Rubbing on the site of pain
o Acupuncture
o Psychological factors
Release of opioids
• Opioids are peptides
• Endogenous opioids are enkephalin and endorphin
• Exogenous opioids are morphin, pethidine… etc.
• They bind to opioid receptors
• Opioid receptors are produced in dorsal root ganglia cells
• And transported centrally and peripherally along their nerve fibers
Mainly are 3 sites where opioids act,

• At the site of injury,
• Inflammation causes production of opioid peptides by immune cells
• They act on the opioid receptors in the afferent nerve fiber
• Open K+ channels/ Close Ca2+ channels
• Decreases the transmissionof impulses in that nerve
• At the dorsal horn
• Act presynaptically. close Ca2+ channels
• Reduce release of substance P & glutamate
• Act post synaptically. open K+ channels
• Thereby reduce the transmission of pain impulse
placebos and acupuncture results release of endogenous opioids

Psychological methods
• Distraction
• Stress analgesia
Other
• Aspirin(NSAIDs) and paracitamol
• Cannabinoids
SPECIAL SENSATIONS
Itch and Tickle
• Specific receptors are present

• Pathway – spinothalamic tract, thalamus and cortex
• has an emotional component
Vibration
• Stimuli – A pattern of rythemic preassure stimuli
• Pacinian corpuscles – fast vibration Meissner’s corpuscles – slow vibration
• Pathway – dorsal column, thalamus, cortex
• Tested by using 128 Hz tuning fork to the skin of finger tip, tip of toe or a bony prominence
• Loss of vibration(associated with proprioception) is an early sign of degeneration of dorsal
columns.
Eg:- DM, Pernicious aneamia
Two point discrimination

• Ability to distinguish simultaneous two touch stimuli as coming from two different areas
• Has both cortical and receptor component
• Depend on the size of the receptive fields of sensroy units & receptor density
Stereogonosis
• Ability to identify objects by handling without looking at them
• Touch, pressure and large cortical component
• Affected when dorsal column or parietal cortex is damaged
Sensory cortex
Primary sensory Cortex (SI) – Post central gyrus
Secondary sensory cortex (SII) – Walls of sylvian fissure
SI projects to SII
Sensory homounculus
Thalamic projections are arranged representing body parts
Legs on the top and head at the foot of the gyrus
size of the cortical area proportional to the number of receptors in the part (large area for hand)

Face bilaterally represented
Cells are arranged in vertical columns responding to specific sensory modality from a particular region
Information mainly from opposite side of the body
Projections of sensory cortex

• To association areas - meaningful identification
• motor areas - control motor function
• feedback to thalamus
Lesions in the sensory cortex

S l :- deficits in proprioception, stereognosis, fine touch
Pain and temperature, crude touch slightly affected
Affects S ll functions
S ll :- deficits in learning based tactile discrimination
No effects on S l
Association area:- deficits in spatial orientation of the other side

ORGANIZATION OF MOTOR CORTEX
Supplementary motor area

- Involved in planning learned sequences of movements
- Projects to motor cortex
- Somatotopically organized
- Both sides of body are represented
- Reciprocal connections with basal ganglia
Premotor cortex
- Sets posture at the start of a movement
- Organized somatotopically
- Projects into brain stem, motor cortex, descending motor pathways
Primary motor cortex

- Located in precentral gyrus
- Somatotopically organized
- Representation is contralateral & inverted. Face bilateral representation
Anterior edge - axial & proximal limb muscles
Posterior edge - distal limb muscles
- Both muscles & movements are represented – size & skill
- Cortical area representing the body part is proportionate in size to the skills done by that
part
- Cells arranged in coloumns
Plasticity
Ability of an area of motor cortex to expand as a skill is learnt & mastered. (detectable at 1
week maximal at 4 weeks)
Damage to small area of the motor cortex results in taking over the area by the adjacent undamaged
cortex with return of function
Posterior parietal cortex

- Aids in executing learned sequences of movements
- Somatic sensory area
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Reflex motor activity
Reflex: an automatic response to a stimulus occurring by a relatively simple neuronal network
Stimulus Receptor Afferent pathway Integrating station
Effect Effector Efferent pathway
Reflexes
Monosynaptic reflexes Polysynaptic reflexes
Stretch reflex Withdrawal reflex
Reaction time – time between the application of the stimulus and response
Central delay – Time taken for the reflex activity to transverse the spinal cord
Stretch Reflex – maintain the muscle length
• Stimulus - stretch
• Sensory organ - muscle spindle
• Intrafusal fibres are parallel with extrafusal fibres.
Nuclear bag fibres Ia afferents (Aα)

Nuclear chain fibres II afferents
γ efferents
• Intrafusal fibers - Only ends are contractile

- Extrafusal fibres are supplied by α fibres
- γ afferents supply only intrafusal fibers
- β fibres supply both Nuclear bag fibers are two types.
1. Static nuclear bag fibers

2. Dynamic nuclear bag fibers
II afferents supply static bag fibers

and chain fibers
Ia afferents supply all 3 types
Dynamic nuclear bag fibers show a

dynamic response.
They discharge more rapidly when

the muscle is being stretched and
less rapidly during sustained
stretch.
Static bag fibers and chain fibers

show a static response
Inverse stretch reflex (tension monitoring)
Golgi tendon organ.

Maintain the muscle length
Supplied by Ib fibres
Tension up to a certain level Stretch of tendon (up to a limit)
Golgi tendon organ is stretched Stretching of extrafusal fibres
Ib fibres Stretch of muscle spindle (parallel to

Extrafusal fibres)
Inhibitory interneuron muscle relaxes
Distortion of sensory endings
Reciprocal
Contraction of contractile ends Action potentials innervation
In sensory fibres (Ia) Collateral
Sensitivity of Synaptic Inhibitory

muscle spindle Transmission interneuron
(Glutamate) (Glycin)
Spontaneous γ discharge Stimulation of Inhibition of

discharge keeps (α) efferents to efferents to
the ‘muscle tone’ α-γ linkage Protagonist antagonist
Servo-assist
mechanism Protagonist Antagonist
γ tone (spasticity) Contracts relaxes
γ tone
When cut - hypotonia
Increase Decrease
- Anxiety descending fibres from,

- Stimulation of - Motor cortex
Skin by - Basal ganglia
noxious agents - cerebellum
- Jandrassik’s - reticular inhibitory area
Maneuver
descending fibres from
- Reticular facilitatory area
- Vestibular nuclei

α-γ linkage / α-γ servo-assist mechanism
Stimulated α motor neurons activate ϒ motor neurons via collaterals.This increases spindle
sensitivity.
α-γ co-activation
Descending tracts from higher centers will stimulate both α and ϒ motor neurons simultaneously.
Stimulation of γ efferents
Shortening of contractile ends of intrafusal fibers
Stretching of nuclear bag portion of the spindle
Distortion of annulospiral endings
Afferent impulses via Ia fibers
Contraction of extrafusal fibers
Net effects –
1. contraction of muscle (Poor)

2. Increase sensitivity of the muscle spindle to stretch
Muscle tone
Resistance of a muscle to stretch is referred as its tone.
Due to spontaneous discharge of the γ efferents.
Hypotonia Normal tone Hypertonia
Flaccid Spastic
Occurs when the motor nerve to Occurs when the γ efferent discharge is high
muscle is cut.

Polysynaptic reflexes
- Withdrawal reflex
- Shorter pathways initiate the reflex.
Longer pathways maintain the reflex.
• Stimulus - noxious (painful)

• Receptors - nociceptors(free nerve endings)
• Afferents - Aδ, C fibres
• Effect - flexor contracts
Extensor relaxes
Strength of the stimuli crossed extensor response supports the body
A pre-potent reflex
Ant other reflex activity taking place at that spinal level at that moment is suppressed.
After discharge
Continuation of reflex withdrawal even after cessation of sensory receptor firing. (By the
reverberating circuits)
Local sign
Ability to confine withdrawal to portion of the body affected with appropriate response
Irradiation
Spread of excitatory impulses up and down the spinal cord to recruit more motor neurons
(Recruitment of motor units)
Stance reflex
Postural reflexes Static
(Spinal cord Righting reflex
Brain stem)
Stretch Other
(Most important postural reflex) Placing reaction
Phasic
(cortex) Hopping reaction

Lesions in the motor system
Upper motor neuron lesion -A lesion above anterior horn cell

• Corona radiata - mild contralateral hemiparesis
• Internal capsule - dense contralateral hemiparesis
• Brain stem - above pyramidal decussation- contralateral hemiparesis
• Spinal cord above AHC - ipsilateral spastic hemiparesis
Features
- Weakness of voluntary movements -Paresis
- Muscle tone -Spasticity
- Lengthing reaction
- Exaggerated tendon reflexes
- Ankle clonus Babinski sign is seen in
- Babinski sign/ Flexor plantar response
children. Why??
- No muscle
Complete transection of spinal cord

02 phases
1. Spinals shock
2. Appearance of the signs of an UMN lesion
Spinal shock
• Paralysis of skeletal/ smooth muscles below the level of lesion
• Loss of tone in skeletal muscles
• Loss of bladder, bowel function – due to interruption of descending autonomic pathways
• Loss of sensation below the level of lesion
• Loss of tendon reflexes
Reason - cessation of excitatory inputs on stretch reflex by descending pathways

Duration of spinal shock depends on the degree of encephalization of motor
functions (human normally 2 weeks)
Reasons for 2nd phase - Removal of inhibitory influences

Denervation hypersensitivity
Sprouting of excitatory collaterals
- Bladder, bowel function become automatic
- No return of sensory deficits
Mass reflex
• Stroking any part of the limb or perineum cause evacuation of bladder and bowel.
• Due to afferent stimuli irradiating to the autonomic centers of bladder and bowel function
• Intentional mass reflex

Decerebrate rigidity
Separation of brainstem between the levels of superior and inferior colliculi
Inhibition of cerebral cortex/ corticospinal tract, basal ganglia, rubrospinal tract on γ discharge
γ motor discharge due to the hyperactivity of the medial tracts (vestibular nuclei and reticular
facilitatory area)
extensor muscle hyperactivity is exaggerated
Extension of all 4 limbs (mostly the proximal muscles)
Destruction of dorsal horns – theses hyperactivity of the extensors is gone

Also there’s a direct activation of α motor neurons independent of γ loop
Decerebrate rigidity seen in uncal herniation
Decorticate rigidity
Separation of brainstem above the level of midbrain,removal of cerebral cortex.
E.g. – At the internal capsule cause hemi decorticate rigidity
- Flexion of the upper extremities, extensor hyperactivity of the lower extremities
Flexion of the upper extremities – Facilitation of flexors in upper limb by rubrospinal pathway
Extension of the lower limb – Facilitation of extensors in lower limb by reticulospinal pathway
 Reticulospinal facilitatory and inhibitory tracts are intact ascending sensory fibers activate
the reticulospinal facilitatory tract.

Basal Ganglia
Basal ganglia consist of
1. Caudate nucleus
2. Putamen
3. Globus pallidus - Internal and external segments
4. Subthalamic nucleus
5. Substantianigra - pars compacta
Pars reticulata
Lenticular nucleus = Globus palidus + putamen

Striatum = Caudate nucleus + putamen
•Parts of the thalamus are intimately related to the basal ganglia
Basal ganglia Connections

• These nuclei have complex interconnections
No direct connection with the spinal cord
Afferents
1. Corticostriate projections - from cortex
2. Thalamostriate projections - from thalamus
Both ends in striatum and are excitatory
Interconnections between basal ganglia

1. Nigrostriatal dopaminergic system
From substantia nigra to striatum
2. GABA-ergic system
3. Intrastriatal cholinergic system
Efferents
Thalamus receives inhibitory impulses from globus pallidus and substantia nigra, which in turn project to the
cerebral cortex completing the feedback loop.
Functions of basal ganglia

1. Planing and programming of the movements
2. Postural adjustments
3. Monitoring the progress of a movement
4. Involved in cognition (Caudate nucleus)
Movements influenced by the basal ganglia

a. Postural Movements
b. Automatic movements (swinging arms while
walking)
c. Skilled, volitional movements of trunk and
limbs
d. Eye movements
Diseases of the basal ganglia

Produce marked and characteristic abnormalities of the motor functions
Generally, two types of motor disorders
Hyperkinetic
Hypokinetic

Hyperkinetic disorders
there are excessive abnormal movements
include
 Chorea – rapid involuntary dancing movements
 Athetosis – continuous, slow writhing movements
 Balisum – sudden, intense, violent jerky movements of the body
Hypokinetic disorders
Poverty of movement
 Akinesia-difficulty of initiating movements

 Bradykinesia-slowness of movements
Parkinson disease
-common neurodegenerative disorder
-Degeneration of nigrostriatal dopaminergic system
-imbalance between excitation and inhibition
-Has both hypo and hyperkinetic features
-Hyperkinetic features are
• Tremor at rest – regular alternating contraction of antagonist
• Muscle Rigidity (Lead pipe /cogwheel)-increased motor neuron discharge to both
extensors and flexors
-Hypokinetic features are
• Akinesia
• bradykinesia
-Postural instability(gait)
-Decreased associated movements
-Lack of facial expressions and gestures
Treatment
Dopamine does not cross blood brain barrier
Therefore, L-dopa is used as it crosses the blood brain barrier
Huntington disease
-Autosomal dominant disorder

-Loss of intra-striatal cholinergic and GABAergic neurons.
-Releasing of inhibition
-Hyperkinetic features- chorea

Cerebellum
Has two lateral cerebellar hemispheres joined by a medial vermis
Anatomically divided in to
• anterior lobe
• posterior lobe
• flocculonodular lobe
Organization of the cerebellum

Cerebellum has,
-an external cortex-gray matter
-four deep cerebellar nuclei in the internal white matter
Deep cerebellar nuclei

1.dentate
2.globose
3.emboliform
4.fastigial
Functional Divisions
Vestibulocerebellum
• Includes nodulus in vermis and flocculus in hemispheres
• Has vestibular connections
• concerned with equilibrium and eye movements
Spinocerebellum
• Formed by rest of the vermis and adjacent medial portions of the hemispheres
• Receives proprioceptive inputs from the body and copy of motor plan from motor cortex
• Compares the plan with performance and smoothes and coordinates the movements
• Vermis is concerned with the control axial and proximal limb muscles
• Hemispheres are concerned with the control of distal limb muscles
Neocerebellum
• Formed by the rest of the lateral portions of the hemispheres
• Concern with the planning and the programming of the movements
Afferents to the cerebellum

• from brain stem and cerebral cortex
• from Periphery-Tracts are
1. anterior and posterior spinocerebellar tracts
2. Cuneocerebellar tract
3. vestibulocerebellar tract
4. Pontocerebellar tract
5. Tectocerebellar tract
6. Olivocerebellar tract

Efferents from cerebellum
Leave from deep nuclei
Spinocerebellum via
-fastigial
-emboliform
-globose nuclei
Neocerebellum via
-dentate nucleus
Vestibulocerebellar out puts directly to the brain stem
Functions of the cerebellum

• Plans and programs the movements
• Compares the intended movement with the actual movement
• By comparing plan with performance, smoothes and coordinates the ongoing movements
• Coordinates sequential motor activities
• Maintain the posture and equilibrium
• Maintains the muscle tone via stretch reflexes
• Therefore, it plays a role in maintaining the muscle tone
• Maintaining the posture and equilibrium
• Planning and execution of motor movements
• Also involved in learning motor activities
Features of cerebellar disease (occurs in same side of the body, No paralysis, No sensory loss)
1. Ataxia
Incoordination of the movements
lateral lobe lesions produce - ataxia of the limbs
Midline lesions in vermis produce- truncal ataxia\
Not made worse by closing the eyes
2. Disturbances of posture and gait
• head tilted to the side of the lesion, patient tend to fall to the side of the lesion-
‘drunken gait’
3. Dysathria/scanning speech (slurred speech) - defects of skilled movements
4. Dysmetria
• inability to predict the extent of a movement
• also called past pointing
• when attempting to touch an object with the finger overshooting to one side
5 Intention tremor
6. Rebound phenomenon
• inability to stop the movements suddenly
7. Dysdiadochokinesia
• inability to perform rapid alternating opposite movements
8 Nystagmus
• involuntary movements of the eye balls
9. Muscle hypotonia
10 Pendular knee jerk
11 Decomposition of the movements
• inability to perform movements involving more than one joint

Muscle Spindle - Efferents
Vision
Structure of eye
From outer to inner,
1. Sclera - anteriorly replaced by cornea

2. Choroid – anterorly forms ciliary body
3. Retina – posterior 2/3 containing photo
receptors
Optic fundus
Forvia centralis Optic disk
Optic disc - Optic nerve leaves & retinal blood vessels enter the eye ball
Forvia centralis - sensitive to bright light & colours

- Highest visual acuity
- Rod free &densely packed cones
- No blood vessels overlying receptors
Aqueous humour - produced by cilliary body continuously

- Flows through pupil from posterior to anterior chamber
- Reabsorbed through network of trabeculae to canal of schlemm
- Supply nutrition for lens & cornea
- Intraocular pressure – 10-20mmHg
Glaucoma ( intra ocular pressure damages retinal glial cells)
Open angle Glaucoma Angle closure Glaucoma

Reduced permeability through narrowing of anterior chamber angle
Trabeculae (between iris &cornea)
Treated with
Carbonic anhydrase inhibitors – Both decrease the aqueous production

Why in a visual cortex lesion macular is spared??
Photo Receptors
• Na+ channels of outer segment open at dark.

• So, a current flow from inner to outer segment & to
synaptic terminal.
• Release of synaptic transmitter (glutamate) is constant in
the dark
Na+ – Dark current.
K+
Glutamate
When light falls on the outer segment of photo receptor

11-cis retinal in rhodopsin Cyclic GMP regeneration
all trans retinal Light reduces concentration of
changes in opsin Na+
Ca2+ in photo receptors
Activation of transducin Retinal separates from opsin(bleaching)
Bind GTP to the G protein [transducin]

Activates guanylyl cyclase
Activate phosphodiesterase Inhibits phosphodiesterase
Decreased intracellular cGMP
cGMP dependent Na+ channel of outer segment blocked Generates cGMP
Hyperpolarization
Decreased release of glutamate
Neural response
Photo pigment
Rods & Cones
Rodopsin Opsin is a G protein coupled receptor. The
G protein is called Transducin
Opsin Retinal
Protein aldyhide of vit A

Dark adaptation
Moving from
Bright lit dimly lit area
-retina slowly becomes more sensitive to light.
-This decline in visual threshold is called Dark adaptation.
Max 20 min
Light adaptation
Due to disappearance of dark adaptation.
Visual threshold rises. Occurs over 5 mins.
Red goggles – Allow cones to work well but don’t stimulate rods significantly
Thus time for dark adaptation is reduced.
Night blindness
Decreased vit. A level
Inadequate reforming of rhodopsin from retinal
Difficult to see at night
RODS CONES
Low threshold (extremely sensitive) High
Scotopic vision Photopic vision
vision in dark bright light
Can’t determine Can
Details
Boundaries
Colours (black & white vision)
Less visual acuity Greater visual acuity
Image formation
Hyperpolarising
R C
Hyperpolarising or
B Depolarising
B
A Depolarising
G
G

1St image light on photo receptors
H
2nd image bipolar
A
3rd image ganglion cells
Axons of ganglion cells forms optic nerve (only ganglion cells produce action potentials)
Chiasma
Optic tract
LGB
Optic radiation
Visual cortex
Refraction in the eyes
Allow focusing of image on retina
Occur at two structures
• Cornea (3/4 of the refraction)

• Lens (1/4 of the refraction)
Refractive power measured in diopters – Increases when the curvature
Refractive power in diopters α 1/Principal focal length
- When the ciliary muscles contract near objects focus on the retina, distant objects focus in
front of the retina.
- When the cilary muscles relax distant objects focus on the retina, near objects focus behind
the retina.
However, human can see the both objects due to the accommodation.
Accommodation
Process by which the curvature of the lens is increased (up to 12 in youth)

Done by the ciliary muscles.
• When the ciliary muscles contract lens relaxes and curvature increased.
• When the ciliary muscles relax lens tenses and curvature decreased.
Near point of vision
• is the nearest point to the eye at which an object can be brought in to clear focus by
accommodation
• Reduces throughout the life – Cause presbyopia
• Headache occurs with aging

Hyperopia/ Far sightedness Myopia/ Near sightedness
Short eyeball Long eyeball
Partially corrected by sustained accommodation Associated with sleeping in lighted rooms <2 yrs
May lead to strabismus Too much studying in childhood
 Astigmatism – Curvature of the lens is not uniform

 Amblyopia – Refractive error in one eye
 Strabismus (Squint) – Misalignment of eye
Strabismus (squint)
Visual images do not fall on corresponding retinal points. (misalignment of eyes)
Chronic – one visual image If not corrected before age 6 permanent loss of vision in one eye
Is suppressed (In children)
(Cortical effect)
Amblyopia
Refractive error in image is blurred Decreased vision in affected eye
one eye & distorted (permanent)
Binocular vision
Defect cause diplopia
Direct reflex & consensual light reflex
Ciliary ganglion Occulomotor nerve
Edingar-Westphal nucleus
Optic nerve
LGN Pre-tectal nucleus

Mapping the visual field
Peripheral - perimeter, this process is called perimetry
Nasal fields
Temporal fields
Central - tangent screen
Damage to Result
Left optic nerve total blindness of left eye
Optic chiasma Bitemporal heteronymous hemianopia
Left optic tract right homonymous hemianopia
Left geniculo-calcarine tract right homonymous hemianopia
Left Visual cortex right homonymous hemianopia with macular
sparing

Near response
3-part response occurring when an individual looks at a near object
• Accommodation
• Convergence of axes
• Pupillary constriction
Pupillary constriction pathway
Sight Eye Optic tract LGN
Optic radiation
Pupillary
constriction
Visual cortex
Edingar-westphal
Lens thickness nucleus
Frontal cortex
Convergence of Medial rectus CN III motor

ocular axes nucleus
Colour vision
Colours have 3 attributes
- Hue
- Intensity
- Saturation
* Complimentary colour when properly mixed with the counterpart, forms white
Red
Primary colours Green
Blue
Young-Helmholtz theory
• 3 kinds of cones
• each have a different photo pigment maximally sensitive to one of the primary colours.
• Colour perception determined by relative frequency of impulses from different cones.

Colour blindness
Red-Green colour blindness shows X linked recessive transmission
8% of males
0.4% females
Colour weakness - anomaly
Colour blindness - anopia
Trichromats - has all 3 cone systems.

May have an anomaly
Dichromats - only 2 cone systems.
Can match their colour spectrum by mixing only2 primary colour systems.
Monochromats - only 1 cone system.
Match their colour spectrum by varying intensity of only 1.
Ishihara chart is used to test for colour blindness
Vision
1. Visual acuity – Snellen chart
Shortest distance by which two lines can be separate & still be perceived as two lines.
Visual acuity
Distance at which the subject reads the chart
=
Greatest distance from the chart at which a normal person can read the smallest line
Normal visual acuity = 6/6 m 20/20 ft

Subnormal = 6/9 or 6/60
Better than normal = 6/5
Tested by using Snellen letter charts
Factors affecting visual acuity

1) Optical factors - State of image forming mechanism
2) Retinal factors – State of cones
3) Stimulus factors – illumination
- Brightness of the stimulus
- Contrast between the stimulus & the background
- Length of time the subject is exposed to the stimulus
If the patient can’t recognize any of the letters, numbers or shapes at 6m, 3m, 1m distances due
to poor vision,
1. Finger counting
2. Perception of light sources
3. Detecting hand movements
are done.

2. Optic tract lesions
Right uniocular blindness – damage to R

optic nerve
Bitemporal hemianopia – damage to optic

chiasma
Left Homonymous hemianopia – damage

to R optic tract
Left upper quadrant hemianopia
Left homonymous hemianopia with

macular sparing
3. Pupillary light reflex

4. Colour vision – Ishihara pseudo isochromic charts
5. Near response
Looking at a
near object
- Ability to increase the refractive power of the lens by contraction of

ciliary muscles.

Hearing and Equilibrium
Hearing
Sound conduction
1. Ossicular conduction – transmission of sound via tympanic membrane, ossicles to cochlea via oval
window
2. Bone conduction – transmission of sound via bone to inner ear
3. Air conduction – by vibrating secondary tympanic membrane of round window
Middle ear
• Sound is multiplied by,

1. Lever action of ossicles
2. Surface area difference of tympanic membrane and oval window
• Middle ear muscles
1. Tensor tympani – Attached to malleus
Pulls malleus medially
2. Stapedius – Attaches to stapes
Pulls stapes laterally out of oval window
• Tympanic reflex
Very loud voices
Contraction of both tensor tympani and stapedius
Makes ossicles relatively rigid
Protects from excessive stimulation by very loud sounds
Inner ear
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Cochlea
Perilymph Endolymph
↑[Na+] ↓[K+] ↓ [Na+] ↑ [K+]
Composition similar to CSF, serum & ECF Composition similar to ICF
Within scala vestibule and scala tympani Within membranous labyrinth
Organ of Corti
Inner hair cells – Primary receptor cells

Outer hair cells – Help in increasing amplitude
Auditory cortex
• hearing- B41 (localization and sensitivity of sound)

• discrimination of sound- area 41,42,22, planum temporale
• complex sounds/languages - Iry(B41,42) and IIry(B22) auditory cortices
• bilaterally represented
• tonotopic organization

Detection of qualities of sound
1. Frequency
• Point of maximum vibration of the basilar membrane.
• Cochlear base: high frequencies Cochlear apex: low frequencies
2. Loudness
• As sounds become louder amplitude of vibration of basilar membrane and hair cells increases.
• More hair cells are stimulated.
• Outer hair cells are also stimulated.
Sound Localization
1. Time difference between two ears (for lower frequencies)

2. Loudness difference between two ears (for higher frequencies)
3. Shape of pinna (front and behind)
4. Reflection from pinnal surface and movement of sound waves up and down (vertical plane)
• Markedly disrupted by lesions in auditory cortex.
Masking
• Presence of one sound decreases the ability to hear other sounds.
• Due to the relative or absolute refractoriness of previously stimulated receptors and nerve fibers to
the other stimuli.
• The degree to given tone masks others are related to its pitch.
Hearing deficits
Hearing deficits
Conductive deafness Sensorineural deafness

• Impaired conduction of sound • Damage to sensory components of ear or neural
from exterior to cochlea pathway
• Lower frequencies are affected. • Higher frequencies more affected.
• Ex: wax in ear, otitis externa, • Ex: Tumors of VIII nerve or cerebellopontine
d angle
Hearing tests
Weber Rinne
Method Tuning fork on vertex Tuning fork on mastoid then in air
near the ear
If normal Both ears heard normally Vibration in air heard after bone
conduction is over
Conduction deafness Louder in that side Vibration of air not heard after bone
conduction is over
Sensorineural deafness Louder in contralateral side Not heard anything
Partial sensorineural deafness Louder in contralateral side Vibration in air heard after bone
conduction is over
Pure tone audiometry
• To detect a hearing loss
• Sound proof room
• Pure tones tested
Equilibrium
Inputs from,
1. Vestibular system
2. Proprioception
3. Vision
4. Cutaneous exteroreceptors
5. Cerebellum
Vestibular system
• Maintains position of head in static and dynamic states.

• 5 groups of hair cells,
1. Utricle
Maculae (hair cells & otolithic membrane)
2. Saccule
3. 3 semicircular canals – Crista ampularis
• Utricle – macula lies horizontally

Orientation when upright and horizontal acceleration.
• Saccule – macula lies vertically

Orientation when supine and vertical acceleration.
• Semicircular canals – detect rotational acceleration.

Cannot sense the effect of gravity
Central connections
• Vestibulocerebellar –Balance
• Vestibulospinal – Send impulses to motor neurons & facilitates tone of extensors
• Vestibulothalamocortical –Conscious awareness of position & movement of head
• Vestibulo-ocular pathway – medial longitudinal fasciculus
Vestibulo-ocular reflex
• Stimulation of vestibular receptors evokes eye movements of equal magnitude in the direction opposite to
movement of head to maintain the visual field.
Nystagmus
• Repetitive jerky movements of the eye (horizontal/ vertical/ rotatory)
• fast and slow components
• can be seen after rotational movements of the head-normal
• caused by persistent stimulation of hair cells in ampulla
• caloric test (COWS): use nystagmus to access integrity of vestibular system.
Vertigo
• Sensation of rotation in the absence of rotation due excessive stimulation of the vestibular system.
Motion sickness
• Due to prolonged and excessive stimulation of the system

Taste and Smell
Smell
- Receptor – Receptor cells in olfactory mucosa
- No relay in thalamus
- Centre – Olfactory cortex
Adaptation to the taste occurs very rapidly
Taste
-Receptor – taste bud Supertasters – Particular to bitter taste
- Relay in thalamus
- Centre – Past central gyrus
Taste Bud
• Sense organ for taste.
• Adults - 3000-10,000 taste buds (child >>elderly)
Tongue – vallate and fungiform papilla
Pharynx, Palate, epiglottis, proximal esophagus
• Composed of gustatory receptors and sustentacular cells.
Mechanism of taste perception
Gustatory Receptor
Binding of the taste

chemical
Receptor potential
initiated
Post-Receptor
actions
Stimulation of taste afferent

fibres
Taste chemicalgrdually washed away from the taste

villus by saliva (stimulus removed)
VIIth Cranial Taste Pathway

nerve - Ant 2/3
tongue Posteriomedial
IXth- Post 1/3 NTS ventral nucleus of Postcentral gyrus
tongue thalamus
Xth - larynx,
Pharunx
Basic taste modalities

• Sweet – sugar, Alcohol, glycols etc. – Act via G protein gustducin
• Sour – acids (H+)
• Bitter – quinine, caffeine, nicotine – some act via G protein gustducin
• Salt – NaCl (Na+)
• Umami – Monosodium glutamate
 All modalities sensed from all parts of the tongue.
 Afferent nerves contain fibers from all types of taste buds – No clear localization.
Taste threshold
 Different substances have different thresholds.
 Crude intensity discrimination – needs 30% change
Flavor - Mainly synthesized from basic 5 tastes, Smell, Pain, Consistency, Temperature

Smell
 Humans recognize > 10,000 odors. (high discrimination of type. But poor intensity discrimination)
 Strong odor – more lipid/ water soluble.
 Odorant Binding Protein- Concentrates & transfers molecule to receptors.
Olfactory mucous membrane
 Contains olfactory receptor cell, Supportive cells & Progenitor cells.
 Olfactory receptor cells – Bipolar neurons
 Small in humans – Micro-osmic
Olfactory pathway
Olfactory receptor cells Mitral & tufted cells
Olfactory Cortex
(Bipolar cells) (Olfactory bulb)
Olfactory cortex
• Piriform cortex – Primary olfactory cortex
• Lateral & anterior orbitofrontal gyri – Olfactory discrimination
• Amygdala – emotional responses to smell
• Entorhinal cortex – olfactory memories
Olfactory thresholds
 Increase with age.
 Methyl mercaptan can be smelled when 1/25million gram per ml.
All odorant receptors
coupled to G proteins
cAMP
Smell also has a Phospholipase C
products of phosphatidyl inositol hydrolysis
rapid adaptation
Most open cation channels
Depolarization of membrane
Generates action potential in olfactory

neuron
Signal transduction
Complex odor discrimination
 About 1000 odorant receptors
 One type of olfactory receptors project into one olfactory glomerulus
Vomeronasal organ –
 Each olfactory neuron carries only one odor.
 Lateral inhibition by periglomerular & granule cells.
Perception of odors that act as
Abnormalities
pheromones.
Taste Smell Closely related with sexual
• Ageusia • Anosmia function
• Hypogeusia • Hyposmia / Hypero-osmia
• Dysgeusia • Dysosmia Poorly developed in human
• Drugs
Smell more in women
T/F
a) Monosodium glutamate is used as an artificial sweetener
b) Receptors for bitter taste are localized to the posterior aspect of the tongue
c) Taste fibers relay in the nucleus of tractus solitarus
d) Taste perception has a high intensity of discrimination
e) Vagus carries afferent from taste receptors

TEMPERATURE REGULATION
Poikilothermic (cold blooded) – mechanism rudimentary
Vertebrates – can adjust their
body temperature Homeothermic (warm blooded) – mechanism well developed
Invertebrates – cannot adjust their body temperature
• Core temperature (36.3 – 37.1 0c) is closely represented by rectal temperature – varies least with
environmental changes
Oral temperature
Rectal temperature
∗ Core temperature > rectal temperature > oral temperature > surface temperature
Factor Temperature change
variation in body /core physiological Age ↑

temperature
Gender Males > females
Exercise ↑
Emotional excitement ↑
Diurnal Variation 6PM-highest

6AM-lowest
Sleep ↓
After Meals ↑
Female after ovulation ↑
Pathological Hyperthyroidism ↑
Lesion to brain ↑
Infection ↑
Hypothyroidism ↓
Lesion to hypothalamus ↓
∗ The normal human core temperature undergoes a regular circadian fluctuation of 0.5 – 0.7 0C
Heat production –
• basic metabolic process Brown adipose tissue is important in
• food intake
generation of heat in new born
• muscular activity (mainly) ∗
infants
• hormones
• radiation from environment

Heat loss –
Conduction to air (3%)
Evaporation (22%)
Radiation (60%)
Conduction to solid subjects (15%)
Regulation of body temperature
• Autonomic eg: Shivering

• Somatic eg: stamping, dancing
• Endocrine eg:
Catecholamines – produce a rapid short-lived increase in heat
TSH – produce a slowly developing prolonged increase in heat
• Behavioral eg: Wearing suitable clothes when expose to cold weather
Hypothalamic Regulation of Body Temperature

cold cold
cold Posterior
Heat sensitive neurons hypothalamus
hot hot cold
cold cold
hot Anterior
hot cold sensitive neurons
hypothalamus
hot hot
• Integration is done by hypothalamus in response (reflex) to information from sensory

receptors in the skin, brain, deep tissues & etc.
• In these places there are more cold receptors than hot receptors.
• There are threshold temperatures for each of the main temperature regulating responses
and when threshold is reached, the response begins.
Shivering
Hunger
Increase Heat
Voluntary activity ↑
Production
Sympathetic activity ↑
(Secretion of catecholamine) ↑
Stimulation of Heat Gain center

Exposure to “Cold”
(Posterior hypothalamus)
Cutaneous vasoconstriction
Decrease Heat Curling up
loss Horripilation
Decrease Heat Anorexia
Production Apathy & Inertia
Stimulation of Heat Loss center

Exposure to “HOT”
(Anterior hypothalamus)
Cutaneous vasodilation
Increase Heat Sweating
loss Increased respiration
Fever
“as if thermostat is reset” - to a new point above normal body temperature
Inflammation
Endotoxins from bacteria
Pyrogens released from degenerative tissues
Acts on monocytes, Kupffer cells, macrophages
Cytokines (act as endogenous pyrogens)
Activate pre-optic area of hypothalamus
Prostaglandins released
Raise temperature set point
Heat conservation & increase in heat production
Fever
Hyperthermia
• It occurs as a response to infection

• Rise in temperature inhibits the growth of microorganisms
• Antibody production is increased
• Slows growth of some tumors
• Temperature more than 410c is harmful
Hypothermia
• Metabolic & physiologic processes will slow down

• Respiration and heart rate are slow
• Blood pressure is low
• Consciousness is lost
• Useful to do open heart surgeries & to perform brain operations
Thermogenic function of Brown Fat
Brown fat,
• More abundant in infants
• Located - between the scapula, at the nape of the neck & along the great vessels in the thorax &
abdomen
Brown Fat White Fat
• Fat cells contain several small droplets of fat • Fat cells contain only a single large droplet
of fat
• Fat cells as well as blood vessels have an
extensive sympathetic innervation • Principal sympathetic innervation is solely
on blood vessels
• Fat cells contain many mitochondria
• 1 method of oxidation which generates
• 2 methods of oxidation ATP
• Oxidative phosphorylation which
generates ATP
• Uncoupled oxidative phosphorylation
which doesn’t generate ATP, but
produce HEAT
• Heat stroke – Body temperature higher than 41.10c. Neurological dysfunction occur.

1
Micturition
Is the process by which the urinary bladder empties when it becomes filled.
• Step1: progressively fill till threshold is reached.
• Step 2: Initiation of micturition reflex, conscious desire to urinate.
Micturition reflex: an autonomic spinal cord reflex, facilitated and inhibited by higher brain centers in the
cerebral cortex or brain stem.
 self – regenerative reflex
∴ Cycle
1. progressive & rapid ↑ of pressure
2. sustained pressure
3. return to basal tone
Urine is made in the kidneys and comes down to the bladder for storage.
Oblique passage through the bladder wall keeps the ureters closed except during peristaltic waves which bring in
urine.
∴ During contraction of detrusor muscle reflux of urine is prevented.
Of course abnormally short oblique passage, valve malfunctions & vesicouereteral reflux occurs.
Innervations
- Pelvic nerves (S2 , S3 ,S4 ) - preganglionic parasympathetic
Sensory → detect degree of stretch of bladder wall
Motor → (parasympathetic) postganglionic fibers to detrusor muscle
- Pudendal nerve (S2 , S3 , S4) – skeletal motor fibers to external sphincter

- Hypogastric nerves - sympathetic innervations (No part in micturition)
Sphincters – Internal muscle bundle on either side of urethra prevent reflex of semen in to the
Bladder during ejaculation (sympathetic innervations)
External ring of skeletal muscles, voluntary control of micturition
Pressure of the bladder is investigated using cystometrogram.
Voluntary micturition – voluntary contraction of abdominal muscles
↑ Pressure in bladder → stretch receptors stimulated →Micturition reflex excited → ext. sphincter inhibited →
voiding of urine
Lowering of pelvic floor & contraction of detrusor muscle
During micturition – Perineal muscles are relaxed

Lowering of pelvic floor
External urethral sphincter relaxed
Detrusor muscles contract
After urination - Female - urethra empties by gravity

Male- expelled by several contractions of bulbocarvernosus muscle

2
Mitcurition reflex
Stimulus - stretch in the posterior urethra @ the back of the bladder

Afferent - pelvic nerves (sensory)
Coordinating centre - sacral portion of the spinal cord
Higher center inputs - facilitatory centre in the pons (PMC), inhibitory area in midbrain, cortex
Efferents - pelvic nerve (motor)
Effector – Detrusor
Voiding can be initiated without straining even when the bladder is nearly empty
Ureterorenal reflex ----when a ureter becomes blocked (eg-: urethral stone)

Incense reflex contraction + pain
Causes sympathetic reflex
Constricts renal arterioles of kidney of same side
Prevents excessive flow of fluid into the pelvis of the kidney with a blocked ureter.
Cystometrogram –By cystometry

Plot of intra-vesicular pressure vs. volume of urine in bladder as it fills.
Cystometrogram has 3 phases

1. Initial slight rise – Due to increase
in urine volume (till 50ml)
2. Long flat segment – Law of
laplace (till 40ml)
3. Sharp rapid rise (over 400ml)
Initial slight rise in pressure when volume is 1st increased

Long nearly a flat segment
Sudden sharp rise as micturition reflex is triggered
Flat segment is a manifestation of the law of Laplace

P=2T\R
As T rises so does R ∴P remains constant

Cerebrospinal Fluid
• Fluid present around the brain and spinal cord
Formation: -
• Choroid plexus of lateral ventricles / other ventricles
• Ependymal surfaces of ventricles
• Perivascular spaces
∗ Formed by passive filtration of plasma and transfer of ions and water into the filtrate. (Mainly active)
∗ Rate of CSF formation is constant. It is independent of intra ventricular pressure
∗ CSF volume 150ml circulation / daily production is 550ml / daily turnover 3.7 times per day
Absorption: -
• Through arachnoid villi  into cerebral venous
• Smaller villi  into spinal veins
• Through the cribriform plate  into cervical lymphatics
∗ Rate of absorption depends on intra ventricular pressure
∗ Absorption is unidirectional
∗ When CSF pressure is elevated
o Possibly increased expression of aquaporin channels in choroid plexus and cerebral micro
vessels.
o More and more arachnoid villi open up
Absorption ∝ intra ventricular pressure
Absorption
Flow Formation
ml/min 0.4
0 68 112 outflow pressure [ mm CSF]
Circulation: - Lateral ventricle 3rd ventricle 4th ventricle

interventricular foramen cerebral aqueduct
foramen of Magendi & Luschka
cerebral venous sinuses arachnoid villus Subarachnoid space
Composition
• CSF is almost identical with perilymph
 Color of CSF – “clear”, Plasma – “yellow”
 protein in CSF [20 ml] <<<< blood [ 6000ml ]
 Na+, K+, Glucose in CSF < blood
 osmolality in blood = CSF
 pH CSF < blood (due to CO2 in CSF)

Function of the CSF
• Protection of brain
o Cushioning effect
o Brain floats in CSF suspended by arachnoid trabeculae, blood vessels & nerve fibres
o Any movement of the brain within the cranial cavity is gently slowed
CSF pressure
• Lumbar CSF pressure 70 – 180 mmH2O
• CSF pressure can go up by laughing, sneezing, coughing & straining
Head injuries
Cerebral damage results with blows to the skull
Mild/ moderate moderate/severe
CSF protects brain by cushioning effect

coup injury contrecoup injury
damage to the damage to the opposite

same side of the brain side of the brain
Raised Intracranial Pressure

Cerebral perfusion pressure = Mean arterial Pressure – Intracranial Pressure
Raised intracranial pressure leads to,

 decreased cerebral perfusion & cerebral ischemia  shift of cerebral contents within the skull
hypoxia mid line shift
hypercarbia herniation
hypoglycemia cranial nerve palsies
cerebral vasodilation pressure on vital centers
cerebral oedema irregular HR, RR
convulsion loss of consciousness
loss of consciousness death
death
Lumbar puncture
• Safest level to enter the needle to withdraw CSF is between L4 – L5
• 5 ml is maximum volume
• In increased ICP lumbar puncture should not be preformed
• Headache after lumbar puncture due to traction of vessels & nerve roots from which the brain
hangs stimulate pain fibres
• Pain relieved by sterile isotonic saline into subarachnoid space

Clinical Relevance
Hydrocephalus - accumulation of large amount of CSF
 external hydrocephalus  internal hydrocephalus

communicating hydrocephalus non communicating hydrocephalus
re-absorptive capacitive of arachnoid villi ↓ block of the foramen Magendie & Luschka
• Infection/inflammation of the meninges – meningitis (eg: bacterial meningitis-turbid appearance)

• Bleeding into CSF (immediately red, later yellow)
BLOOD BRAIN BARRIER

• Cerebral capillaries do not allow certain substance to pass through them into CSF & brain ECF
• Due to presence of tight junctions between,
o Capillary endothelial cells
o Epithelial cells in the choroid plexus
• Passive diffusion is restricted, specific transport systems present
• Uniquely limited exchange of substances into the brain is referred to as BBB
BBB is not seen in,

 Posterior pituitary & median eminence
 Area postrema Circumventricular organs
 SFO, OVLT
∗ Allow hormones to enter general circulation - Posterior pituitary

∗ Contains chemical receptors = chemoreceptor trigger zone
o Initiation of vomiting/CVS regulation – area postrema
o Water intake – SFO, OVLT
Penetration of substances through the BBB
• Freely permeable – CO2, O2, Alcohol, Anesthetics

• Specific transport systems – Na+, K+, Cl-
• Impermeable – plasma proteins, water, non-lipid soluble large organic molecules
 Transporters
o Facilitate passive penetration into the brain tissue
Eg: glucose – GLUT1
 Reverse Transporters
o Transports drugs and peptides back into the cerebral vessels
Eg: P – glycoprotein (multi drug nonspecific transporter)
Effects of inhibition of this transporter??

Functions of BBB
• Maintains homeostasis of brain ECF
• Prevent entry toxic substances to brain
• Prevent escape of neurotransmitters
Clinical Relevance
 Immature BBB
• Neonatal jaundice – kernicterus
• Occurs due to elevation of unconjugated bilirubin
 Disruption of the BBB
• Head injuries
• Cerebral Infections
• Tumors
 Selectivity of the BBB
• Pharmacological agents – degree of penetration
o Antibiotics for cerebral infections
o Anesthetics
o L-Dopa
o CNS side effects of drugs – eg: antihistamine
o Drugs that act outside BBB

SLEEP & EEG
• Consciousness
- being awake & responding to ones surrounding
• Coma Sensory stimulation
Complete loss of consciousness ↓
Ascending activity
• Pathway activated in arousal ↓
Specific pathways
Reticular activating system (In reticular formation) ↓
• RAS situated in midventral brainstem Collaterals to RAS
• Activated by nonspecific stimuli ↓
• State of thalamocortical neurons determines the sleep-awake status. Intra laminar nuclei of thalamus
Hyperpolarize - sleep ↓
Depolarize (partially) - awake Project to cortex
EEG / Electro encephalogram

• Electrical events of the brain are recorded patterns. (Doesn't record the action potentials)
RAS is located in the reticular

formation.
Reticular formation also contains

areas concerned with regulation of
HR, BP and RR.
δ θ α β Υ
<4 7-8 8-12 18-30 30-80
α -awake, eyes closed, mind wondering

- marked in parieto-occipital area
α Block / desynchronization - by opening eyes. (Replace α waves with fast irregular waves of low voltage)
β - Mentally alert & in infants
- Marked in frontal region.
Υ - Focusing attention.
Θ - in children. large amplitude
δ - In deep sleep & small children.
- Abnormal if in adults in awareness (raised ICP)
Waves seen in childhood (without sleeping)

• β Rhythm
• θ Rhythm
• δ Rhythm
α frequency
Low blood glucose
Low body temperature
↑ Pa co2 opposite
↓cortisol
- Hyper ventilation brings out hidden EEG abnormalities

Arousal Sleep
• Sensory system stimulation * stimulation of sleep zones
Up to midbrain level -slow wave sleep
• Activation of MB reticular area * pontine reticular area
• Mid-thalamic neurons are partially depolarized * Mid-thalamic neurons are hyperpolarized.
(Electrical state of the thalamo-cortical neurons influences the sleep-wake cycle)
Sleep
REM NREM
• Rapid eye movement
• Occurs after 90m of onset of sleep 4 stages
• Voluntary activity of muscle 1 - drowsy, α waves start to disappear, law
Inhibited voltage fluctuations, theta waves, δ waves
• Tone of neck muscles reduced intermittent
• Snoring 2 - light sleep, sleep spindles - short bursts of
• Tooth grinding waves
• Bizarre dreams 3 - δ waves appear, dreams, deep sleep
Digestive system activity decreased. 4 - very deep sleep δ waves prominent. No dreams
• Body temperature, BMR, HR, RR, BP BMR, sympathetic activity
• O2 consumption in brain Vital signs decline (BP, HR, RR) - stage 3 & 4
• EEG pattern is very irregular (Rapid low voltage) has skeletal muscle activities
• Sleep is not interrupted & threshold for
Arousal increased. (Paradoxical sleep)
Sleep cycle
• Sleep starts off with NREM

NREM REM NREM……….
- 4-6REM periods per night.
- Cycle repeated-90min intervals
- More REM & less Stage 3,4 towards morning
• % of REM ↓ with age
- Premature infants 80%
- Full term neonates 50%
- Adults 25%
Factors influencing sleep wake cycles -

 circadian rhythm – Regulated by suprachiasmatic nucleus (SCN) of hypothalamus according to the
impulses coming from retino-hypothalamic tract.
 Neurochemical mechanisms
 Melatonin – Secretion regulated by efferents from SCN
Circadian rhythm & sleep
- Sleep become synchronized to day night light cycle.

-Rhythm operated by suprachiasmatic nuclei of hypothalamus
- CNS receive information via retinohypothalamic fibers
Origin of REM sleep

 Pontine reticular formation
 Spike discharge in cholinergic neurons
 Noradrenergic neurons in locus ceruleus and serotonergic neurons in mid brain raphe become silent
 Shifting of balance of neurotransmitters

RAS nuclei
- Increased N & S Decreased N & S
Decreased ACh Increased ACh
Awake NREM sleep REM sleep
Agonist & Antagonists of sleep
PGD2 Serotonin
PGE2
Caffeine
Children need more sleep than adults

• New born 16-18 hrs.
• Teenagers 8-10 hrs.
• Old adults 6 hrs.
Why do we sleep??
What happen after sleep deprivation??
Disorders of sleep
- Insomnia-insufficient or nonresponsive sleep in spite of adequate opportunities
- Narcolepsy - sudden onset of REM sleep
- Sleep walking - during NREM
- Sleep apnoea - Day time sleepiness due to fragmented sleep at night, caused by upper airway obstruction.

HYPOTHALAMUS
• Part of the limbic system.
• Neural pathways are mostly unmyelinated.
• Hypothalamus connects with –ant. pituitary via portal vascular connections
-post. Pituitary via neural connection
Functions of Hypothalamus
1) Controls ant. Pituitary secretions
 CRH, TRH, GHRH, GnRH, GHIH-somatostatin, PIH-dopamine
2) Controls post. Pituitary secretions.
 Vasopressin (ADH)
 Oxytocin
*synthesized in supraoptic (ADH) & paraventricular nuclei (Oxytocin)
3) Control of autonomic nervous system
 Post. & lateral nuclei during stress conditions
Produces sympathetic discharge
 Adrenal medullary catecholamine secretion.
 Ant. Group of nuclei (supra optic & paraventricular nuclei)
Produce parasympathetic discharge
4) Cardiovascular regulation
 Post. & lateral nuclei- HR & BP
 Pre-optic area- HR & BP
5) Regulation of body temp
 Heat activates- ant. Hypothalamus heat loss
 Cold activates- post. Hypothalamusheat gain
6) Regulation of sleep & wakefulness
 Sleep ant. Hypothalamus
 Wakefulness mamillary body
7) Regulation sexual behavior
 Ant. Ventral hypothalamus
 Piriform cortex- in male
8) Role of defensive reactions
 Two centers (diffuse in the limbic system & hypothalamus)
 Reward center- satisfaction / punishment center- displeasure
9) Role of circadian rhythm / rhythmic fluctuations
 Occurs in response to light dark cycle in the environment
 Circadian rhythm synchronized by pair of Suprachiasmatic nuclei (SCN) in
hypothalamus
 It receives afferent info. from retina Via retino-hypothalamic fibers
 Efferents from SCN Neural and hormonal signals Synchronize many
circadian rhythms
 Rhythms-
1. Secretion of ACTH & other pituitary hormones
2. Sleep- wake cycle
3. Secretion of pineal hormones- melatonin (nocturnal peaks)
4. Activity patterns
10) Regulation of water balance
 In lateral superior hypothalamus
 2 mechanisms - thirst mechanism, ADH mechanism

Thirst mechanism
 Center- anterolateral areas of hypothalamus
 Stimuli
a) Plasma osmolality (Hypertonicity)- via osmo-receptors in ant.
hypothalamus
b) ECF volume(hypovolemia)- via baroreceptors in heart & blood vessels
-via angiotensin II (acting on subfornical organ & OVLT)
c) Dryness of pharyngeal mucosa/ mouth
d) Psychological factors
e) Social factors
f) Prandial drinking-intake of water is increased during eating
This increase due to
• Learned or habit response
• plasma osmolality when food is absorbed. When protein
uptake, products of protein metabolism causes an osmotic
dieresis. So, amount of water need is large.
• Due to action of one or more GIT hormones on the hypothalamus
Summary
Osmolality, hyper tonicity ex: -vomiting hypovolemia ex: -blood lose

High pressure
Osmo- receptors baro-receptors, angiotensin II
ADH hypothalamus Low pressure
Thirst
11) Regulation of food intake – to maintain the body weight in a given set point
 Orexigenic stimuli stimulate food intake, circulating levels during fasting
• NPY- neuropeptide Y
• MCH- melanin concentrating hormone
• AGRP
• Orexin A & B
• Ghrelin (release from stomach when it is empty)
 Anorexigenic stimuli inhibit food intake
• α- MSH- melanin stimulating hormone
• CART- cocaine & amphetamine regulating transcript
• CRH- corticotrophin releasing hormone
• PYY- peptide YY
• CCK
• GLP-Glucagon like peptide
• Leptin
• Insulin
Inputs to regulate food intake
Neural signals
-GIT (via vagus) regarding stomach filling
-cerebral cortex (smell, sight, taste)
Chemical signals Thermal signals

-nutrients in blood HYPOTHALAMUS
-exposure to heat or cold
Hormonal signals
GIT – CCK, PYY, Insulin
Adipose tissue - Leptin

 Regulation is mainly by 2 centers & facilitated by others
1) Feeding center
- Always active, temporally inhibited by satiety center after food intake.
- In lateral nuclei
- Stimuli- desire to eat
- Destruction- anorexia
2) Satiety center
- Ventromedial nuclei
- Stimuli sense of satisfaction
- Destruction- Hyperphagia - hypothalamic obesity
Afferent mechanisms which regulate food intake- 4 hypothesis
2) Lipostatic hypothesis
1) Glucostatic hypothesis Hypothalamus

Food intake
Food intake (-)
Blood glucose levels
Fat deposition
Stimulate glucostats in satiety
center Leptin synthesis
Inhibiting feeding center

Activation of hypothalamic Leptin recept
Stop food intake
3) Gut peptide hypothesis
Food in gut
4) Thermostatic hypothesis
↑Secretion of polypeptides
↓Body tempstimulate appetite
Inhibit feeding center
↑Body tempinhibit appetite
Inhibit food intake
 Cyclical phenomenon
• Circadian rhythm – 24 hours length cycles
– Entrained by SCN (supra chiasmatic nucleus)
Secretion of ACTH and other pituitary hormones

+
Photosensitive Sleep-wake cycle
retinal Afferents SCN
ganglion cells Activity patterns
Retino-hypothalamic
fibers - Secretion of ‘Melatonin’ from pineal gland

Memory and Learning
 Different forms
1. Explicit memory- associated with consciousness
hippocampus/medial temporal lobe is involved
•Semantic-related to facts
•Episodic-related to events
2. Implicit memory- not associated with consciousness
• Priming - neocortex
• Procedural (skills and habits) - striatum
• Associative learning - emotional: amygdala
Skeletal muscle: cerebellum
• Non-associative learning (habituation & sensitization)-reflex pathways
 Explicit memory initially required for a task can become implicit when a task is learnt.
Eg: riding a bicycle
A. Short term memory Explicit & many forms of Implicit memory
B. Long term memory are associated
 Hippocampus convert short term memory to long term memory
 Working memory-form of short-term memory. Keep information available for a very short time
while action is planned.
Eg: remembering a phone number before texting
Neural basis of learning (converting short term to long term memory)
• Strengthening the existing synapses
 activation of genes
 protein synthesis
 Increase in neurotransmitters & post synaptic receptors
• LTP (long term potentiation)- persistent increase in synaptic strength following high-frequency
stimulation of a chemical synapse.
 Protein synthesis of pre & post synaptic neurons
 Accumulation of Ca2+
 accumulation of neurotransmitters
• LTD (long term depression)- reduction in the efficacy of neuronal synapses lasting hours or
longer following a long-patterned stimulus
• Formation of new synapses
Memory disorders
• Amnesia (Retrograde & anterograde)
• Dementia - Alzheimer’s
- Senile dementia
Anterograde amnesia - Due to a damage to the hippocampus or medial temporal lobe. Can't covert the
short term memory to long term memory. Stored long term memory is not affected.
Retrograde amnesia - After a sudden shock, trauma to head or after being anesthetized people forget
what happened just before the incident.
Neurogenesis occurs in brain mainly in hippocampus & olfactory bulb throughout the life.

Language and speech
1. Sensory association areas
2. Wernicke’s area-sensory area of speech -comprehension of auditory and visual information
3. Broca’s area- motor area of speech -convert received information to a pattern of vocalization
An individual who learns a new language in adulthood has two Broca's areas adjacent to each
other. But in contrast a child who speaks two languages has only one Broca's area
The Wernicke’s area and the Broca's area are connected together by arcuate fasciculus
Cerebral dominance
 Neocortical function
• Categorical hemisphere-categorization and symbolization (language function,
mathematical problem solving)
• Representational hemisphere- spatiotemporal relations (recognizing objects, places,
faces, music etc.)
 Hemispheric specialization is related to the handedness
Features of lesions
Categorical hemisphere Representational hemisphere
• Language disorders • Astereognosis
• Fluent non fluent and anomic aphasia • Agnosia
• Acalcuia • Unilateral inattention and neglect
• difficulty in mathematics • prosopagnosia
Patients are disturbed and often depressed about Patient are unconcerned and euphoric about their
their disability disability
Limbic system
Includes,
1. Hippocampus
2. Hypothalamus
3. Amygdala
4. Olfactory bulb
5. VTA (ventral tegmental area)
Functions
1. Involved in emotions
• Cognition (higher functions) –as an awareness of sensation and cause
• Affect-the feeling itself
• Conation-the urge to take action
• Physical changes-BP, PR, sweating
2. Autonomic responses
3. Sexual behavior
4. Rage and fear
5. Motivation and addiction
6. Connections-learning and memory

biochemistry
practicals
(1) Fouchet’s Test – Bile Pigments (5) Benedict’s Test – Reducing substances
1. 5ml of urine (a drop of dil. acetic acid) + 1. 5ml of Benedict’s reagent + 8 drops of
3ml of BaCl2 urine
2. Mix and filter using a filter paper 2. Add porcelain pieces
………………………………………………………………… 3. Boil in direct flame for 2 minutes
3. Place filter paper on another filter paper
4. Add a drop of Fouchet’s Reagent to the (6) Barfoed’s Test – For Monosaccharides
precipitate at the centre 1. 2ml of Barfoed’s reagent + 8 drops of
urine
(2) Test for Haemoglobin (2 tubes) 2. Add porcelain pieces
1. 2ml of urine in tube A 3. Boil in direct flame for 30 seconds
2ml of distilled water in tube B …………………………………………………………………
2. Boil both. 4. Observe after few minutes
cool ………………………………………………………
3. Add 4 drops of orthotoluidine + 4 drops (7) Sulphosalicylic Acid Test – For Proteins
of H2O2 1. 3ml of urine + 3ml of sulphosalicylic acid
4. Mix and leave it 2. Mix
3. Turbidity (intensifies when warming)
…………………………………………………………………
5. Observe within 2 minutes
(8) Heat Coagulation Test – For Proteins
𝟑
1. Fill 𝟒 of tube with urine
(3) Gerhardt’s Test – For acetoacetic acid and
salicylate (2 tubes) 2. Do NOT add porcelain
1. 2 tubes – 3ml of urine in each. Label A 3. Hold tube at an angle and boil ONLY the
and B. upper layer
2. Boil tube B for 1 minute (Do not boil tube 4. Observe for turbidity against a dark
A) background
3. Cool
4. Add FeCl3 dropwise Shake and observe
after each drop.
(4) Rothera’s Test – For acetoacetic acid and

acetone
1. 5ml of urine
2. Saturate with ammonium sulphate
(NH4)2SO4
3. Add 6 drops of sodium nitroprusside
4. Mix
5. Carefully place 2ml of conc. ammonia as
a layer over it (observe purple ring not
brown)
2015 A/L repeat campaign

TEST OBSERVATION INFERENCE
A) Proteins
1) Sulphosalicylic 1. Turbidity develops; on warming turbidity Protein may be present
acid test increases
2. No change occurs Proteins are absent
2) Heat coagulation 1. Turbidity develops Proteins are present
test 2. No change occurs Proteins are absent
B) Sugar
3) Benedict’s test for 1. A brick red colour precipitate develops Reducing substances are present
reducing substances 2. no change occurs (no brick red Reducing substances are absent
precipitate)
4) Barfoed’s test for 1. Brick red colour precipitate develops Monosaccharide is present
monosaccharides 2. no change occurs (no brick red Monosaccharide is absent
precipitate)
C) Ketone Bodies
5) Rothera’s test for 1. A purple ring develops Acetoacetic acid and/or acetone
acetoacetic acid and is present
acetone 2. Purple ring does not appear Acetoacetic acid and/or acetone
is absent
6) Gerhardt’s test for 1. A tube – Purple colour develops Salicylate is present
acetoacetic acid and B tube – Purple colour develops (Acetocetic acid may also be
salicylate (Boiled tube) present)
2. A tube – Purple colour develops Acetoacetic acid is present
B tube – No colour change
(Boiled tube)
3. A tube – No colour change Both salicylate and acetoacetic
B tube – No colour change acid are absent
(Boiled tube)
D) Blood Pigments
7) Test for 1. A tube – Blue colour develops Haemoglobin present
haemoglobin B tube – No colour change/blue colour
may develop (Control tube)
2. A tube – No colour change Haemoglobin absent
B tube – No colour change/blue colour
may develop (Control tube)
E) Bile Pigments
8) Fouchet’s test 1. A green or blue colour change develops Bile pigments present in urine
at the centre
2. No colour change Bile pigments absent in urine
2015 A/L repeat campaign

(4) Rothera’s test
(2)
(3) Gerhardt’s test
(8)
physiology
practicals
Physiology – Practical
Blood
Identification Increased in
Neutrophil Nucleus with 3-5 lobes, Bacterial infection
granulated (decreased- viral infection, TB)
Eosinophil Nucleus with 2 lobes, reddish Chronic hypersensitivity – asthma, parasitic infections
orange staining granules
Basophil Highly dense granules, deep Immediate hypersensitivity – allergy
purple or blue granules, small Viral infection
marginal cytoplasm Malignancy
Monocyte Kidney shaped nucleus, Bacterial infection(acute and chronic)
granulated cytoplasm Malignant disease
Lymphocyte Large round nucleus, thin non Viral infection, chronic lymphocytic leukaemia
granulated cytoplasm (decreased: AIDS, lymphocytopenia)
Packed Cell Volume (PCV)

Items needed – Wintrobe tube, Anticoagulant (EDTA)
Reading – Fraction / Percentage – when taking the reading buffy coat should be excluded
Normal range – males: 40% - 54% females: 37%-47%
Increased in – physiological-high altitudes (due to acclimatization)
Pathological-Dengue (due to haemoconcentration), polycythaemia, dehydration (diarrhoea,
vomiting)
Decreased in – Physiological- Pregnancy (due to haemodilution)
Pathological- anaemia
Blood sample should not be haemolysed as it will yield falsely low results.
Microhaematocrit method
Items needed – capillary haematocrit tube (heparinised), micro haematocrit reader, microhaematocrit centrifuge
Erythrocyte Sedimentation Rate (ESR)

Used to detect presence of inflammation
RBC has net negative charge (zeta potential), so they repel each other, RBC columns form
rouleaux formation of red blood cells
Items needed – Westergren tube, Anticoagulant (sodium citrate)
Reading – mm/1st hour (height of the buffy coat should not be included in the reading)
Normal range –males: 0-10 mm /1st h females: 0-14 mm / 1st h
ESR increase with age, females > males, pregnancy (due to increase in fibrinogen concentration)
Increased in – severe anaemia, tuberculosis, rheumatic fever, malignancies
Decreased in – polycythaemia, sickle cell anaemia, protein abnormalities
• Heparin should not be used as an anticoagulant as it alters the zeta potential of RBCs.
• The tube should not be kept in direct sunlight or path of draughts, surface on which the stand is kept should
be flat, horizontal and should not vibrate.
Osmotic Fragility Test

Items needed – serial dilutions of NaCl (hypotonic)
Reading – where haemolysis begins (appearance of reddish colour) and completes (disappearance of RBC button)
Normal range – begins at 0.45 – 0.5% completed at 0.3% NaCl solution
Increased in – Hereditary Spherocytosis, G6PD Deficiency
Decreased in – Sickle cell anaemia, thalassaemia

0.9% NaCl solution is isotonic to plasma
• Heparin should be used as an anticoagulant.
• Na/ K oxalates, Tri Sodium citrates should not be used as they add salts to the solution
Blood Grouping
Clumping of RBC observed after adding antisera

Anti A- Blue Anti B- Yellow Anti D – colourless
ABO system is inherited in mendelian codominant
Blood Count – WBC and RBC
Items needed – Haemocytometer (clotting chamber) microscope, cover slip, mouthpiece, lancet, cotton wool,
disinfectant
WBC
RBC
For RBC count – RBC pipette (red colour ball inside)

For WBC count – WBC pipette
Hb Concentration – Drabkin’s Test

Items needed – colorimeter, Drabkin’s solution (CN- present, yellow, with blood turns orange)
Bleeding Time Test

Tests vascular and platelet response
Items needed – circular filter paper, stopwatch, sterile blood lancet
Reading – I min + (no. of gaps x 30s)
Normal range – 1 – 5 minutes
Increased in – blood vessel defects, abnormalities in platelet number/quality, (dengue haemorrhagic fever),
VWF deficiency
Hess’ Test
Tests vascular integrity
Bedside test
Items needed- sphygmomanometer, stopwatch, stethoscope, coin, pen
Cuff inflated between systolic and diastolic pressure
Reading – number of haemorrhagic patches in 1 inch diameter circle
10 minutes for patches to appear
If no. of patches > 10 then Hess test is (+) positive
Increased in – dengue haemorrhagic fever, scurvy/ vitamin C deficiency, thrombocytopenia
Clotting Test
Prothrombin time test – extrinsic (and common pathway)
Items needed – anticoagulant (tri sodium citrate), tissue thromboplastin calcium reagent
Normal range – 12 – 15 seconds
International normalized ratio used
Used for – monitoring oral anticoagulant therapy (warfarin), detection of clotting factor deficiencies
Increased in – vit. K deficiency, I, II, V, VII, X deficiency, warfarin therapy, liver disease

Activated Partial Thromboplastin Time (APTT)– intrinsic and common pathway
Whole Blood clotting time test – Intrinsic pathway

Items needed – water bath at 370C, stopwatch, 2 glass test tubes
Normal range – 6 – 10 min
CVS
Electrocardiogram (ECG)
10 mm height – 1Mv – calibration wave
Small square – 0.04 s
Large square – 0.2 s
Heart rate - 1500 300
No. of small squares in RR interval no. of large squares in RR interval
Pulse
• Rate
• Rhythm
• Volume
• Character
• Radio-femoral delay coarctation of aorta
Draw an ECG.
Blood Pressure Measurement

Items needed – sphygmomanometer, stethoscope
Method – using Korotkoff sounds
Systolic pressure (maximum pressure in systole) – pressure when 1st sound appears
Diastolic pressure (minimum pressure in diastole) – sounds disappear
With stethoscope – diastolic pressure
Without stethoscope – systolic pressure
Pulse pressure = systolic pressure – diastolic pressure
Mean arterial pressure = diastolic pressure + 1/3 pulse pressure
Valsalva Manoeuvre
Straining – increased intrathoracic pressure
• Pressure added to aorta blood pressure elevated
• Compression of veins venous return reduced BP reduced
• Baroreceptor inhibition tachycardia, increased peripheral resistance
Glottis opened – intrathoracic pressure back to normal
• Aortic compression removed
• Vein compression removed
• Baroreceptor stimulation
The Valsalva manoeuvre graph.

1. Electrocardiogram (ECG)
HR =1500/No. of small squares in RR interval
HR = 300/ No. of large squares in RR interval
2. Blood pressure measurement
Items needed: sphygmomanometer, stethoscope

Method:
1. The patient should either be seated or lying comfortably. He should have rested for
at least 3 minutes prior to blood pressure measurement.
2. The sphygmomanometer is placed at the same level of the cuff on the patient’s arm
and the observer’s eye level.
3. The arm should be horizontal.
4. The canter of the bladder should be positioned over the line of the artery.
5. Feel the patient’s brachial (or radial) pulse and inflate the cuff to a pressure above
which pulse can no longer be felt.
The point of disappearance of pulse represents the systolic pressure.
6. Place the stethoscope gently over the brachial artery.
7. Inflate the cuff further to raise the pressure to 30 mmHg above the systolic blood
pressure as estimated by palpation.
8. Deflate the cuff at 2-3mmHg per second, listening carefully to the appearance of
Korotkoff sounds.
Phase 1
Appearance of tapping sound
Indicates systolic pressure
Phase 2 and 3
Sounds get louder as more blood enters brachial artery
Phase 4
Sounds become muffled
Phase 5
Sounds disappear
Indicates diastolic pressure
Pulse pressure = systolic pressure – diastolic pressure
Mean arterial pressure = diastolic pressure + 1/3 of pulse pressure

3. Valsalva Manoeuvre
Attempt to exhale against closed glottis and mouth.
Pressure on aorta suddenly increases 1.Arterial BP increases

Intra thoracic pressure increases
Pressure acts on great veins Venous return reduces
Decreased pressure is identified by

BP gradually increases
baroreceptors and HR increases 2. CO decreases & BP decreases
3. BP suddenly deceases Sudden increase in HR

Glottis opened & intra thoracic pressure
suddenly decreases
Venous return increases

4. Raise of BP
HR returns to normal level

Respiratory system
1. Lung volumes and capacities
Total ventilation (Respiratory minute volume) = RR × TV
Alveolar ventilation = (TV – RV) × RR
• RV and total lung capacity cannot be measured by spirometer

• Measured by body plethysmography, helium dilution method
2. Peak Expiratory Flow Meter (PEFM)

Used to monitor the progress of obstructive lung diseases. Ex: Asthma
Unit: l/min
Normal rate: 400l/min (varies with age, gender, height and ethnicity)
Method
1. Should hold the peak flow meter horizontally.
2. Do not block the indicator with your fingers.
3. Mouth piece and lips should be sealed.
4. Inhale deeply then blow as fast as possible.
5. Do this three times and take the highest reading as the result.
Q. Compare and contrast obstructive and restrictive lung diseases.
Obstructive Restrictive
Caused by airway obstruction Caused by stiff lungs
FEV1 decreases FEV1 decreases
VC unchanged VC decreases
FEV1 / VC ratio less than 75% FEV1 / VC ratio normal or higher than 75%
Ex; Asthma, COPD Ex; Lung fibrosis
3. Voluntary hyperventilation
• Increased rate and depth of breathing.

• Increased PO2
• Decreased PCO2  Increased pH
• Cerebral vasoconstriction  dizziness, paresthesia, light headedness
• Peripheral vasoconstriction  cold extremities
• Decreased pH, H+ released from proteins exposing negative sites, Ca2+ binds with
those negative sites, hypocalcaemia
• hypocalcaemia  increased tissue excitability  Chvostek sign
Trousseau’s sign (carpopedal spasm)
• After hyperventilation
Period of apnoea  shallow breathing  Period of apnoea  shallow breathing……….
This happens periodically until PCO2 level become normal.
Exercise physiology
1. Harvard step test
• A moderate isotonic exercise
• Items required:
1. Harvard stool
2. Metronome
3. Stop watch
4. Mercury thermometer
5. Measuring tape
6. Stethoscope
7. Sphygmomanometer

• Physiological parameters checked:
1. Pulse rate
2. Blood pressure
3. Respiratory rate
4. Oral temperature
5. Calf circumference
• These parameters will be checked:
1. Before the exercise.
2. Immediately after exercise.
3. Five minutes after exercise.
• Results
1. Pulse rate: heart rate increases from the beginning by decreasing parasympathetic
stimulation on SA node.
2. Blood pressure: Systolic blood pressure increases as CO increases. But vasoactive
metabolites cause vasodilatation resulting decreased diastolic blood pressure. Due to
persistence of accumulated vasoactive metabolites vessels remain dilated causing further
fall in diastolic blood pressure as CO decreases.
3. Respiratory rate:

4. Oral temperature: Total heat production of the body exceeds increased total body heat
dissipation. So core temperature will increase.
5. Calf circumference: Fluid transduction to interstitial fluid increases. Despite of increased
lymph flow, calf circumference still increases
Renal system
1. Urinometer
• Measures specific gravity of urine.
• Reading: 1.0_ _ (normal: 1.002 – 1.035)
• Instructions: Urinometer should not touch the bottom or sides of the cylinder.
Taking measurement should be done at eye level.
• Temperature correction,
For every 30C increase, 0.001 has to be added.
• If the urine sample is not enough,
Equal volume of distilled water could be added to the sample. Last two digits of the
reading should be multiplied by 2 in order to get the correct reading.
Q. Name another method used to measure specific gravity of urine?

-------------------------------------------------------------------------------------------------------------------------------
Reproduction
Contraceptive methods
Contraceptive methods
Natural methods Artifeticial methods
Periodic Coitus Lactational

Temporary Permanent
Abstinence Interruptus Amenorrehoea
Basal Body Temperature

Method
Male Female Male Female
Barrier
Ryhthm/calander method Condoms
Methods
Hormonal IUCD Vasectomy LRT
Subdermal
Cervical Mucus method Condoms OCP DMPA
Implants
Symto-thermal Method Diaphragm COC
Spermicidal
POP
Creams
Emergency CP

Method Advantages Disadvantages Examples
1. Natural Methods
2. Barrier Methods
3. COC
4. POP
5. Emergency CP
6. DMPA
7. Subdermal Implants
8. IUCP
9. Permanent Methods
Menstrual Cycle
LH serge happens just before

the ovulation & triggers it

Vision
1. Visual acuity – Snellen chart
Visual acuity = Distance at which the subject reads the charts

Distance at which a normal person can read the smallest line the subject reads
6/12 6/9 6/24
If the patient can’t recognize any of the letters, numbers or shapes at 6m, 3m, 1m distances due to
poor vision,
1. Finger counting
2. Perception of light sources
3. Detecting hand movements
are done.
2. Optic tract lesions
Right uniocular blindness – damage to R

optic nerve
Bitemporal hemianopia – damage to optic

chiasma
Left Homonymous hemianopia – damage

to R optic tract
Left upper quadrant hemianopia
Left homonymous hemianopia with

macular sparing

3. Pupillary light reflex
4. Colour vision – Ishihara pseudo iso-chromic charts

5. Near response
Looking at a near object
- Ability to increase the refractive power of the lens

by contraction of ciliary muscles.

Hearing
Types of deafness
1. Conduction deafness
Ex: i. Obstruction of the external auditory canal (ear wax, infections, foreign bodies)
ii. Damage to the tympanic membrane.
iii. Obstruction of the middle ear. (infections, fluid)
iv. Ossicular chain disruptions.
v. Otosclerosis
2. Sensorineural deafness
Ex: i. Damage to hair cells, cochlear nerve or/and organ of Corti.
ii. Acoustic neuroma
iii. Hereditary defects
iv. Infections, Inflammations (mumps, meningitis)
v. Transverse facture of the petrous temporal bone
Hearing tests

-
Audiogram, Audiometer is used

CNS
Equipment for sensory modality test
1. A key/ a coin – for stereognosis
2. Tuning fork – for vibration
3. Cotton wool – for touch
4. Toothpick – for pain
5. Divider – for two point discrimination
6. Hot and cool water - for temperature
Stretch reflex
Equipment – Tendon hammer
Components of stretch reflex:
Receptor: Muscle spindle
Afferents: IA & II
Central integrating area: spinal chord
Efferent: α to extrafusal fibers
Β to both
ϒ to intrafusal fibers

VIVA IN ANATOMY

UPPER LIMB
VIVA IN ANATOMY
Humerus
1. Describe the humerus
(Describe the upper end of humerus/Describe the spiral groove)
2. How did u side determine the humerus?
3. Describe the muscle attachments of upper end of humerus
4. Point out the places where fractures can take place in humerus and name those fractures.
Ans: Surgical neck fracture, mid shaft fracture, supracondylar fracture (3 bony points are in
usual equilateral triangle), medial epicondylar fracture
5. Nerves closely related to humerus and location. Which nerve get damaged in mid shaft
fracture/surgical neck fracture/medial epicondylar fracture?
Ans: surgical neck-axillary nerve
Mid shaft posteriorly (in the radial groove)-radial nerve
Supracondylar region anteriorly-median nerve
Posterior to medial epicondyle-ulnar nerve
6. What structures can be damaged in the supracondylar fracture?
Ans: Median nerve& brachial artery
7. Complications after the brachial artery damage at the elbow
Ans: Volkmann’s ischaemic contracture
Ischaemia of forearm muscles fibrosis& contraction of long flexors & extensors
Flexors are bulkier than extensors wrist-flexed
MP joints-extended
IP joints-flexed
Scapula
8. Describe the scapula
9. Describe the muscle attachments of scapula
(Describe the muscle attachments of coracoid process/Name the muscles attached to the
medial border of scapula/what are the muscles attached to scapula that go into upper limb?)
10. Show the insertion of serratus anterior muscle on scapula. What is the clinical condition that
occurs when this muscle get paralyzed? Cause and clinical testing
Ans: Whole of the medial border of the costal surface of scapula
Winging of the scapula
Cause- damage to long thoracic nerve (ex: mastectomy)
Clinical- medial border of the scapula is unduly prominent; becomes more prominent when
the patient tries to push against the wall; arm can’t be abducted beyond 90°
11. Describe the scapular movements and name one muscle responsible for each movement
12. Describe the scapular anastomosis. Pulsating scapula
Ans: In cases of coarctation of aorta distal to the origin of subclavian artery, blood will be
diverted to the descending aorta through the scapula anastomosis posterior intercostal
arteries. So, pulsation can be felt at the scapular region
Clavicle
13. Describe the clavicle
14. Describe the muscle attachments of clavicle
15. Commonest site of clavicular fracture. What happens to medial and lateral segments?
Ans: Junction of the middle & outer third (weakest part)
Medial segment displaces upwards by the action of sternocleidomastoid. Lateral segment
displaces downwards by the weight of the upper limb and drawn medially by the shoulder
adductors (teres major, latissimus dorsi & pectoralis major). Characteristics feature of the
patient-supporting his sagging upper limb with his opposite side hand.
16. Articulate clavicle with scapula. What is the joint? Main stabilizing factor of that joint?
Shoulder joint
17. Articulate humerus with scapula
18. Describe the shoulder joint.
19. What are the stabilizing factors of shoulder joint?
(Reason for less stability of shoulder joint/ Compare the stability of shoulder joint with hip
joint/ which is the strongest stabilizing factor and describe that/ Name the ligaments)
20. Describe the rotator cuff
21. In which direction shoulder dislocation is more common? Reason for that?
22. Which nerve can be damaged in the dislocation of shoulder?
Radius, Ulna & Wrist joint
23. Side determination of the radius. Features used. Articulate radius with ulna.
Ans: Radius consists of head, neck, shaft and expanded lower end. styloid process is in the lateral aspect
Superior radioulnar joint –head of the radius with radial notch of the ulnar

Inferior radioulnar joint –head of ulnar and ulnar notch of radius
Interosseous membrane- runs upwards and laterally from ulnar to radius
24. Name the most common fracture of the radius in elderly people. Location?
Ans: Colle’s fracture – the radius fractures 2.5 cm / 1 inch proximal to the wrist
joint. Distal fragment is displaced posteriorly and proximally
Reason – fall on outstretched hand
25. What are the bones which participate in forming the wrist joint?
26. Complication after the scaphoid fracture. Reason for that. How it is clinically
presented?
Ans: Scaphoid is the most fractured carpal bone. Fracture occurs after a fall on
outstretched hand, in which position the scaphoid lies directly facing the radius.
Proximal part undergoes avascular necrosis due to interruption of its blood supply
Characteristic tenderness is felt over the anatomical snuff box (the scaphoid is felt at the base of
the thenar eminence and within the anatomical snuff box)
Axilla
27. Describe the axillary lymph nodes
28. Describe the brachial plexus from roots to chords.
(Name the nerves arising from medial/lateral/posterior chord. / How does axillary artery
relate to the brachial plexus?)
29. Erb’s paralysis/ Klumpke’s paralysis. Affected part of brachial plexus. Cause & deformity.
Breast
30. Describe the blood supply of the breast.
31. Describe the lymphatic drainage of the breast.
32. What are the nerves that can be damaged in mastectomy?
Nerves
33. Where does the ulnar nerve most commonly get damaged? What happen if the ulnar nerve
gets damaged there?
Ans: At medial epicondyle produce ulnar claw hand
Claw hand – hyperextension at m/p joints due to paralysis of interossei &lumbricals
Flexion at I/P joints (mainly little and ring fingers)
Sensory loss- medial 1/3rd of palm and medial 1 ½ fingers on both sides
Vasomotor and trophic changes
34. What is ulnar paradox?
35. Clinical test for ulnar nerve damage.
Ans: NERVE TESTS
Ulnar nerve – paper test
36. Most common site where median nerve get damaged? What’s the related clinical condition?
Ans: At wrist (lies beneath palmaris longus tendon in the carpal tunnel)
Carpal tunnel syndrome (compression of median nerve within carpal tunnel)
Causes – dislocation of lunate, bursitis of ulnar and radial bursa
37. Clinical test for median nerve damage
Ans: 1. Pen test (for abductor pollicis brevis)
2. Unable to pick a pin with thumb and index finger (inability to oppose thumb)
38. What would happen if the main trunk of median nerve gets damaged at the wrist? Why does
cutaneous innervation over the thenar eminence not affected in the carpal tunnel syndrome?
39. What are the things you can observe when there is a damage to radial nerve in the mid-shaft
fracture of the humerus? Sensory loss location?
40. How can you differentiate radial nerve damage at mid-shaft from the damage at axilla?
Reason for that?
Ans: at axilla - complete paralysis of triceps& unable to extend the elbow (crutch palsy,
Saturday night palsy). At mid shaft- triceps is not completely paralyzed as medial& long
heads are already supplied by the branches given at axilla & extension of elbow is possible
41. Axillary nerve motor and sensory supply
42. Axillary nerve clinical. Causes, disability, Sensory loss (regimental badge sign), Intramuscular
injection.
Ans: Intra muscular injection – upper part of the deltoid (lateral aspect of the bulge of the
shoulder, no more than 4 cm below the lower border of the acromion.as the anterior branch
of the axillary nerve curls forward round the back of the humerus 5 cm below the acromion)
Hand
43. What are the structures that form the floor and roof of the carpal tunnel?
44. What are the structures that passing through the carpal tunnel?
(What are the structures that passing over the flexor retinaculum?)
45. Describe the muscles of hand. Innervation of those muscles.
46. Describe the actions of lumbricals and interossei

47. Surface mark the superficial palmar arch, proximal border of the flexor retinaculum,
metacarpophalangeal joints on your hand.
Ans: Superficial palmar arch- level of distal border of fully extended thumb
Proximal border of flexor retinaculum- Distal skin crease of wrist
MP joints- distal skin crease of palm
48. Describe the articulated hand (with bone)
Clinical (extras)
49. Describe Dupuytren’s contracture
Ans: Thickening& contraction of palmar aponeurosis. Proximal & later middle phalanx
become flexed. Ring finger most commonly involved
50. What is annular ligament? Describe subluxation of head of radius
Ans: Ligament that encircles the head of the radius and attached with notch of ulnar at
both ends. Continuous with radial collateral ligament of elbow joint capsule. Subluxation of
radius is when the head is dislodged from the grip of annular ligament. Common in children
when lifting them by holding the forearm
51. What are miner’s elbow, tennis elbow & golfer’s elbow?
Ans: Miner’s elbow- inflammation of the olecranon bursa. Caused by resting the weight of
the body on the elbow. Also called student’s elbow.
Tennis elbow- Inflammation of the common extensor origin of forearm muscles. Causes
pain at lateral epicondyle.
Golfer’s elbow- Inflammation of the common flexor origin of forearm muscles. Causes pain
at medial epicondyle.
52. Pulp space infection & complications. Reason for avascular necrosis of only distal part of
terminal phalanx. Why infection not usually spreads from pulp space to the next
compartment?
Ans: rising pressure causes severe pain. Occlusion of vessels by pressure. Avascular necrosis
of distal 4/5th of terminal phalanx. Proximal 1/5th escapes because its artery doesn’t
traverse the compact space.
At each skin crease of fingers, skin is bound down to underlying flexor sheath so usually
infection doesn’t spread to next compartment
53. Why infection of the little finger can easily spread to forearm unlike other fingers?
Ans: Ulnar bursa is in direct continuity with the synovial sheath of little finger unlike other
fingers. Ulnar bursa is proximally connected to forearm space of Parona.
54. What’s painful arc syndrome? Related tendon& bursa?
Ans: Painful when abducting the shoulder between 60° to 120°. Called shoulder impingement. In
supraspinatus tendinitis (tearing of supraspinatus tendon) subacromial bursa becomes connected
with synovial cavity of shoulder joint causes painful arc syndrome.
LOWER LIMB
Femur
1. Describe the femur
2. Describe the proximal part of the femur with its muscle attachments
Ans: Greater trochanter- gluteus medius, gluteus minimus,
Trochanteric fossa-piriformis, gemelli, obturator internus & externus
Lesser trochanter- ilacus, psoas major
Gluteal tuberosity- gluteus maximus (greater part of it inserted to iliotibial tract)
Quadrate tubercle- quadratus femoris
3. Blood supply of the head of the femur (differences in adults and children)
4. Types of fractures of the proximal part of the femur and its clinical importance
5. Describe the trochanteric anastomosis
6. Importance of the angle between the head and the neck of the femur
Ans: Normal angle is 135° (angle is smaller in females because of wider pelvis). In children
normally 160°.Angle is decreased in coxa vara deformity results from adduction fractures.
Increased in coxa valga deformity results from abduction fractures. In x-ray films Imaginary
smooth continuous line along lower border of superior pubic ramus & inferomedial border of neck
of femur is called Shenton’s line. This line is disturbed in neck fractures & hip dislocation.
7. Describe the muscle compartments and relevant nerve supply, blood supply & movements
Ans: Anterior/Extensor compartment of thigh- Femoral nerve- extension of knee, flexion of
hip joint
Posterior/Flexor compartment of thigh- Sciatic nerve- flexion of knee, weak extension of
hip joint
Medial/Adductor compartment of thigh- Obturator nerve- adduction of hip joint
*Thigh muscles are mainly supplied by the profunda femoris artery.
8. Show the adductor tubercle and its importance

Tibia and Fibula
9. Describe the articulated tibia and fibular (side determination of fibula)
10. What is the nerve that is closely related to the neck of the fibula, when it can be damaged,
clinical signs (gait of a patient with damaged common peroneal nerve)
Ans: paralysis of muscles of extensor compartment & lateral compartment. Followed by foot
drop & inversion of foot because of the unopposed actions of plantar flexors & invertors.
Deformity-Talipes equinovarus (plantarflexed & inverted foot). Abnormal gait (steppage
gait). the patient raises the foot higher than usual and bring it down suddenly making
flapping noise. Otherwise his toes/tip of the shoe scratches the ground.
11. What are the sensory supplies of the deep peroneal nerve and superficial peroneal nerve?
Ans: deep peroneal nerve –small area of skin in the web between the 1st and 2nd toes
Superficial peroneal (fibular) nerve –skin of the distal 2/3 of anterolateral aspect of leg and
dorsum of foot. apart from area supplied by the deep peroneal nerve, sural nerve &
saphenous nerve.
12. Describe the compartments of the leg
Ans: anterior compartment – nerve supply; deep peroneal nerve, blood supply; anterior
tibial artery. Posterior compartment; nerve supply; tibial nerve, blood supply; posterior
tibial artery / lateral compartment; nerve supply; superficial peroneal nerve, blood supply;
peroneal artery via perforators
13. Name few muscles in those compartments
14. Describe Compartment syndrome (causes, nerves get affected, surgically how the pressure
is released)
Ans: Deep fascia covering the compartments is an inelastic sheet. Any condition that leads
to an increase in the volume of the compartmental contents is therefore likely to result in
a rise in intra compartmental pressure. Such conditions include haemorrhage, muscle
swelling and local infection. If unrelieved, the increased pressure leads to compression of
the vessels in the compartment and secondary ischaemic damage to the nerves and
muscles of the compartment. This phenomenon is known as compartment syndrome,
and involves, most commonly, the compartments of the leg (especially, the anterior
compartment of leg). Compartment syndrome is a surgical emergency and is treated by
performing a fasciotomy; a procedure in which a generous incision is made in the deep
fascia overlying the compartment in order to decompress the compartment.
15. Name and show two muscles which groove the lower end of the leg
Ans: tibialis posterior- medial malleolus, Peroneus longus & breves- lateral malleolus
Hip joint
16. Describe the hip joint
17. What is the Capsular attachment of hip joint
18. Describe the muscles which produce movement of the hip joint
19. Describe the stabilizing factors of the hip joint
Ans: Bony factors
Muscular factors
Ligamentous factors- pubofemoral, Ishciofemoral, strongest- iliofemoral ligament
20. Differences between the acetabulum and the glenoid fossa
Knee joint
21. Describe the patella (patella development, attachments)
22. Major movements in the knee joint and related muscles)
23. Bursae related to patella
24. Which bursae get affected in clergymen and housemaid knee
Ans: clergymen’s knee –infra patella bursa
Housemaid’s knee- prepatellar bursa
25. Stabilizing factors of knee joint
26. Locking and unlocking mechanism of the knee joint
27. Name the intra capsular and extra capsular structures of the knee joint (intra - cruciate
ligaments, menisci, popliteus tendon/ extra –tibial and fibular collateral ligaments)
(regarding menisci – which one is more prone to damage and how it can be damaged)
Ankle joint
28. Describe the joint (type, movements, bones which contribute)
Foot
29. Describe the bones of the foot
30. Describe the subtalar joint and its movements
31. Avascular necrosis of talus and scaphoid bones
Ans: In both bones, arteries enter distal surface. So, in the fracture, proximal part undergoes avascular
necrosis.
32. Muscles which are responsible to eversion and inversion

33. Describe the Arches of foot (bones which make the arches, summit, functions)
Other
34. Venous drainage of lower limb (superficial, deep, perforators / muscle pump) (clinical
importance of long saphenous vein)
Ans: Because of the constant position of the great saphenous vein lying
immediately in front of the medial malleolus, it can be used for urgent transfusions
even in collapsed & obese persons. Occasionally, accompanying saphenous nerve
can be damaged.
35. Where can you feel the pulse in lower limb (name the arteries)
Ans: Mid inguinal point- femoral artery
Popliteal fossa- popliteal artery
Behind the medial malleolus- posterior tibial artery
Between EHL & EDL tendons on navicular bone- dorsalis pedis artery
36. What is femoral canal, what can you find in femoral canal
37. About femoral hernia (from where does it emerge, pathway, how the pressure is
released, what is the danger of the process)
Thorax
1. Describe the first rib. What are the special features of 1st rib?
2. Describe the relations of 1st rib. Muscle attachment.
3. Describe the features of a typical rib. (parts, articulation)
4. Name the atypical ribs and reasons for that.
5. Name the articular surfaces and the type of the following joints.
(Manubriosternal, costovertebral, costotransverse, costochondral, chondrosternal, interchondral)
6. Describe the muscle attachment of a rib.
7. Name the contents of a costal groove.
8. Describe the intercostal space.
9. Articulate a rib with a corresponding vertebra.
Ans: lower facet of head of the rib should be articulated with the upper costal demi facet of
the numerically corresponding vertebra & tubercle should be articulated with the costal
facet of the transverse process of the same vertebra.
10. Describe the sternum
11. Name all joints formed by the sternum and variety of each.
Ans: manubriosternal & xiphisternal joints- 2ry cartilaginous, 1st rib with manubrium- 1ry
cartilaginous, sternoclavicular- atypical synovial ball & socket, chondrosternal joints of 2-7th
costal cartilages- synovial (2nd with manubrium & body. All others with body)
12. Name the muscles involve in quiet inspiration& expiration. Active/passive?
13. Name the muscles involve in deep inspiration and expiration.
14. Describe the thoracic movement during respiration. (How vertical, transverse & AP diameters increase?)
15. Describe bucket handle& pump handle movements. (axis, which diameter increases, upper/lower ribs)
16. Describe the azygos system.
Ans: Azygos, hemiazygos & accessory hemiazygos veins. Their formation tributaries and drainage.
17. Name the attachments of the suprapleural membrane.
18. Name the structures pass through the openings in the diaphragm and its levels.
19. Describe the innervation of the diaphragm.
20. Briefly describe the development of the diaphragm.
21. State the reason for the unusual pathway of the phrenic nerve.
Ans: Septum transversum initially lies opposite cervical segments. Nerve components of 3rd,
4th, 5th cervical segments grow into it to their respective myotomes. Later the septum
descends to the thoracic region due to rapid growth and folding of the dorsal part of the
embryo. Phrenic nerve is dragged along with it.
22. How do you surface mark the heart?
23. Describe the blood supply of the heart.
24. Describe ventricles.
25. Describe the development of interatrial septum
26. What are the foetal structures that form median umbilical lig, medial umbilical lig, ligamentum
teres hepatis, ligamentum arteriosum & venosum, foramen ovale?
27. Describe the origin, course, distribution of the internal thoracic artery.
28. Define bronchopulmonary segment, Arterial & venous distribution, Clinical importance.
Ans: Segment of the lung supplied by a single segmental/tertiary bronchus. Each segment has its own
separate end artery but not a separate vein. Veins lie at intersegmental planes and supply more than
one segment. Mostly infection of a bronchopulmonary segment remains restricted to it and facilitates
surgical resection of particular lung segment without affecting normal functioning of rest of the lung. It
is the smallest segment of the lung which can be surgically removed with minimal bleeding and damage.

29. Which lung, lobe& segment has more tendency for lodging of aspirated foreign bodies?
Reason?
30. Surface marking of sternal angle of Louis. Name few structures in that plane.
Clinicals
31. Describe the reason why the rib fractures are more common in adults.
Ans: In children chest wall is highly elastic. So, fractures are rare
32. What is the condition known as the cervical rib?
Ans: Cervical rib is a bony/fibrous connection between C7 transverse process & first rib.
Located above the 1st rib as an extra rib. Abnormality in 0.5% of subjects. Fibrous band cause
more complications than the bony rib
33. Name the structures that affected in cervical rib condition. Complications?
34. Describe about diaphragmatic hernia.
35. Describe the process of paracentesis thoracis. Layers pierced.
36. What is safety triangle? Boundaries?
37. What is mediastinal syndrome? Complications & reason for each complication.
Abdomen
Anterior & posterior abdominal walls
1. Name the muscles of anterolateral abdominal wall muscles superficial to deep. Fiber direction
2. What structures form median, medial& lateral umbilical ligaments?
3. Describe rectus sheath. Contents. Say something about midline incision& paramedian incision.
Ans: Midline incision is through linea alba. No major vessels/nerves involved. Simplest incision
with less bleeding. Takes time to cure. In paramedian incision, rectus sheath is incised and rectus
abdominis muscle is retracted laterally. Bleeding occurs but quickly cures.
4. Describe thoracolumbar fascia (layers, compartments& contents)
5. How anterior abdominal wall is divided into quadrants? Name them. In which quadrant liver/
stomach/ appendix is positioned?
6. What is transpyloric plane? Related structures.
Ans: Lower border of L1 - pylorus of the stomach, fundus of the gall bladder, neck of the
pancreas, termination of the spinal cord
Inguinal hernia
7. What is the clinical importance of inguinal region/ lower anterior abdominal wall?
Ans: indirect and direct inguinal hernia
8. Describe the inguinal canal. Boundaries, surface marking of deep& superficial rings.
Ans: deep ring- half inch above mid inguinal point. Superficial ring-medial & above the pubic tubercle.
9. Describe the inguinal hernia. Name the types and define them.
10. Boundaries of Hassel Bach’s triangle
11. How to differentiate an inguinal hernia from a femoral hernia?
12. In which gender the inguinal herniation is more common? Reason?
Ans: Inguinal hernias are 10 times more likely to develop in males than in female. (femoral
hernia is more common in females)
Because of the descent of testis in males, gaps are created in the abdominal muscles after birth.
Abdominal muscles become weaker.
Peritoneum
13. What is epiploic foramen? Name the boundaries of it.
14. Relations of the structures passing through the anterior boundary of epiploic foramen. What is
Pringle’s manoeuvre?
Ans: Haemorrhage during cholecystectomy may be controlled by compressing the hepatic artery
(which gives off the cystic branch) between the index finger and thumb where it lies in the
anterior wall of the foramen of Winslow
15. Describe the attachment of the lesser omentum. Name the structures inside. Embryology of lesser
omentum.
16. Describe gastrosplenic & lienorenal ligaments. Contents & embryology.
17. What is hepato-renal pouch of Morrison? Clinical importance
Ans: It is right sub-hepatic space behind the right lobe of liver & in front of right kidney. It is the
most dependent part of the peritoneal cavity in the supine position. So intra peritoneal fluids
accumulate here.
Liver, spleen, pancreas & extra hepatic biliary system
18. Describe the Relations of the spleen.
19. Describe the Blood supply of the spleen.
20. Describe the Blood supply of the gallbladder.
21. Surface marking of fundus of gallbladder. What’s murphy’s sign?
Ans: Murphy’s sign- pain is felt when pressing at tip of 9th costal cartilage (fundus of gall bladder
lies beneath this point). This occurs when gall stones are developed.

22. What is the difference between it and the blood supply of the appendix & why it is clinically
important?
Ans: Gall bladder is supplied by both cystic artery & arteries from the liver bed. So, there is an
anastomosis. Gangrene of the gall bladder is rare because even if the cystic artery become
thrombosed in acute cholecystitis there is a rich secondary blood supply. But appendicular
artery is an end artery. If it is thrombosed in appendicitis, Gangrene forms. So appendicectomy is
performed. Cholecystectomy is not done in the cholecystitis.
23. Boundaries of Calot’s triangle. Name structures inside.
24. Describe gall stone ileus.
Ans: A gall stone may be extruded from fundus of a chronically inflamed gall bladder into the
duodenum. The gall stone may then impact in the lower ileum as it traverses the gut to produce
intestinal obstruction.
25. Surface marking of the liver. Where is it exposed outside the rib cage? Can normal liver be palpated
26. Relations of the structures in porta hepatis. Describe the formation of the Bile duct starting from liver.
27. Describe the course & important relations of bile duct.
28. Describe the blood supply of pancreas
29. How pancreas opens into duodenum?
Kidney & ureter
30. Describe the course of right/left ureter.
31. Where are the constrictions of ureter? Clinical importance of them.
Ans: Pelviureteric junction
Pelvic brim
Ureteric orifice (narrowest at all)
Ureteric stones (calculus) lodge in constricted sites of ureter.
32. How can u easily identify the ureteric colic in an X-ray? How to differentiate it from a gall stone?
Ans: postero-anterior view – at the tips of the transverse process of lumbar vertebra.
Lateral view –Ureteric & kidney stones-on the body of vertebra / GB stones – anterior to the
body of vertebra
33. Neurological basis of loin to groin radiating pain in the ureteric colic.
34. What is Gerota’s fascia? Attachments & continuations of it.
Ans: renal fascia / false capsule is known as the Gerota’s fascia
35. What is renal angle? Clinical importance. Why deep inspiration is needed for the palpation of
enlarged kidney?
Ans: Angle between lower border of the 12th rib and outer border of erector spinae muscle.
lower poles of the enlarged kidneys are bimanually palpated, on deep inspiration (hard to
palpate during expiration as it is under cover the ribs)
Gastro intestinal tract
36. Describe the blood supply of stomach. Relate with the supply of superior & inferior mesenteric
arteries, boundaries between foregut, midgut & hindgut
37. Describe the lymphatic drainage of stomach. Why lump in lower neck is seen in stomach cancer?
Ans: in stomach cancer left supraclavicular node is enlarged. (troisier’s sign)
38. Describe the blood supply of small intestine
39. How can u differentiate ileum& jejunum by looking at their mesenteries?
40. How can u differentiate intestine& colon in an X-ray film?
Ans:
Large bowel Small bowel
Peripheral Central
Presence of haustrations Valvulae conniventes are present
No gas is seen
41. Describe physiological herniation in the midgut development? What is the abnormality if the
retraction is failed? (omphalocele) Differentiate it from Gastroschisis.
Ans: physiological herniation – (6th week) rapid growth and expansion of the liver causes the
abdominal cavity become too small to contain all intestinal loops. because of these intestinal loops
bulge out through the umbilicus. if it remains, without retraction (10th week) –omphalocele
Gastroschisis -protrusion of abdominal content through body wall, directly into amniotic cavity due
to abnormal closure of body wall around the connecting stalk. lateral to umbilicus (usually right).
viscera are not covered by peritoneum or amnion
42. What is Meckel’s diverticulum? Features of it, complications.
Appendicitis
43. Name the common positions of appendix
44. Surface marking of McBurney’s point
Ans: junction between the lat 1/3 and medial 2/3 of line joining the umbilicus and the right
anterior superior iliac spine
45. Neurological basis of referred pain in appendicitis

Portal system
46. Define portal system. Where are the portal systems in the body?
Ans: in portal venous system a capillary bed pools into another capillary bed through veins
without first going through heart.
E.g. – blood from GI tract to liver
Hypophyseal portal system
47. Name the places of portosystemic anastomosis. Describe one of them (around the
umbilicus/lower end of oesophagus/anal canal). What is the related clinical condition in portal
hypertension at that area? Or (Where can u observe varicose veins in the abdomen/ How
oesophageal varices are formed?)
Ans: varicose veins are developed in lower abdomen
48. Describe the course & important relations of portal vein
Pelvis & perineum

Bones, joints & muscles of pelvis
1. Describe the pelvic bone/ articulated pelvis
2. Describe the anatomical position of the articulated pelvis.
3. Describe the differences between male & female pelvis. (features & reason)
(Identifying the bone male/female and give reasons)
4. Describe the sacrum. (male, female differences)
5. What is true pelvis & false pelvis? Structures forming the boundaries of pelvic inlet (pelvic brim)/
pelvic outlet.
6. Describe the muscle attachments of pelvic bone. (or specifically ask muscles of lower limb/ pelvic
diaphragm/ anterior & posterior abdominal walls/ gluteal muscles)
7. Describe the Pubic symphysis, Sacroiliac joint, lumbosacral joint. Name associated ligaments
Ans: pubic symphysis – secondary cartilaginous joint
Sacroiliac joint –sacroiliac ligament (ant, post, interosseus (strongest))
Lumbosacral joint – iliolumbar ligament
8. Explain the ligaments attached to pelvic girdle.
9. Attachment of inguinal ligament. Differentiate mid inguinal point & midpoint of inguinal ligament.
10. Surface marking of posterior superior iliac spine
Ans: S2 level (sacral dimples in back)
11. Describe pelvic diaphragm.
12. Functions of pelvic diaphragm
13. What happens in weakening of pelvic diaphragm in females?
Rectum & Anal canal
14. Describe the peritoneal coverings of the rectum.
15. Describe the Denonvillier’s fascia. Clinical importance.
Ans: in excising rectum the plane pass through this fascia, without damaging prostate and
rectum. This fascia act as a barrier of spreading carcinoma of prostate to rectum
16. Anterior relations of the rectum in males & females.
17. What are the structures can be palpated in per rectal examination in males & females? What
abnormalities can be found?
Ans: normal - both sexes- anorectal ring, coccyx, sacrum, ischioanal fossa, ischial spines
male- prostate, rarely the healthy seminal vesicles
female - perineal body, cervix, ovaries
abnormalities detected - within lumen - faecal impaction, foreign bodies
in the wall - rectal growths, strictures, granulomata
18. Describe about anal canal (parts, epithelium, nerve supply, blood supply, relate with embryology)
19. How haemorrhoids are formed? Differentiate external & internal haemorrhoids (pain, nerve
supply, bleeding, location)
Male & female reproductive systems
20. Describe the spermatic cord & contents (coverings, contents)
21. What is tunica vaginalis & tunica albuginea? Describe about hydrocele.
Ans: tunica vaginalis (parietal and visceral layers)- remnant of processus vaginalis
Tunica albuginea –thick covering of white fibrous tissue
Hydrocele – fluid accumulation in processes vaginalis
22. Describe the blood supply of the testis (arterial & venous). Lymphatic drainage of testis & why it’s
different from other perineal structures.
Ans: lymph drain into para aortic lymph nodes (L2) as it follows the artery
23. What is undescended testis? Differentiate it from ectopic testis (locations where they can be found)
Ans: Undescended testis – can be found anywhere along its migratory pathway
Ectopic testis – not in the migratory pathway – lower abdomen, thigh
24. Prostatic venous plexus & spread of prostatic carcinoma.

25. What are rectouterine & vesicouterine pouches? Clinical importance of rectouterine pouch
26. Development of female & male internal genitalia (mesonephric& paramesonephric ducts)
27. Explain anteversion & anteflexion of uterus.
Ans: angle of anteversion -90° (axis of the cervix and axis of vagina)
Angle of anteflexion - 170° (axis of uterus and axis of internal os)
28. Describe the broad ligament, round ligament of uterus, ligament of ovary & suspensory ligament
of ovary.
Perineum & urethra
29. Describe the course of male urethra. Most dilatable & least dilatable parts?
Ans: most dilatable part –openings of the ejaculatory ducts
Least dilatable part- membranous part of urethra
30. Describe external urethral sphincter. Concept of Rabdo’s sphincter
Ans: External urethral sphincter (sphincter urethrae) muscle surrounds the membranous part of
the urethra. Supplied by pudendal nerve and voluntarily controlled. Previously it is described as
horizontally arranged muscle inside the deep perineal pouch. But the new Rabdo’s sphincter
concept says that it is an intrinsic part of the urethral wall and vertically arranged mainly
surrounds the membranous urethra but also extends upwards into prostatic urethra &
downwards into bulbar urethra.
31. Extravasation of urine in damage to urethra at superficial perineal space. (attachments of Colle’s
fascia)
32. Describe the course of pudendal nerve. Name the branches. Motor & sensory supply of inferior
rectal nerve.
Head and neck

Parotid gland
1. Surface mark the parotid gland
Ans: 1. upper border of the head of the mandible
2. center of the masseter muscle
3.posteroinferior to the angle of mandible
4.upper part of the anterior border of the mastoid process
2. Describe the parotid gland (serous gland, capsule, contents < superficial to deep >, nerve supply)
3. Surface mark the parotid duct
Ans: from lower border of tragus to point between ala of nose & red margin of lip (midpoint of philtrum)
4. Can stones block the parotid duct, what is the name for the condition.
Ans: Sialolithiasis (salivary calculi)
5. Describe the pathway of parotid duct.
Ans: From anterior margin runs forward on the masseter.
Relations – superior – accessory parotid gland
Upper buccal nerve
Transverse facial artery
– inferior – lower buccal branch
At the anterior border of masseter turns medially and pierce buccal fat pad, buccopharyngeal fascia,
buccinator muscle
Opens opposite the crown of the 2nd upper molar tooth
6. Where does the parotid duct open?
Submandibular and sublingual glands
7. Where are submandibular and sublingual glands located
Ans: sublingual gland –above the medial 1/3 of the mylohyoid line of the mandible
Submandibular gland – below the lateral 2/3 of the mylohyoid line of the mandible
8. Where do their ducts open in the mouth?
Ans: sublingual- open separately into the floor of mouth on either side or the frenulum linguae
Submandibular-frenulum of the tongue
9. Describe the relations of submandibular duct, relation to lingual nerve
Ans: It runs forward superficial to hyoglossus muscle deep to mylohyoid. Lingual nerve is
above & hypoglossal nerve is below it. Lingual nerve double crosses the duct. First medial
to lateral above the duct then lateral to medial below the duct.
10. Name the branches of external carotid artery
11. Name the branches of subclavian artery
Thyroid gland
12. Describe the thyroid gland (location, shape, capsule, blood supply, lymphatic drainage)
13. What is the pyramidal lobe
Ans: An inconstant lobe projects upwards from the isthmus. If it presents, generally lies left
of the midline. It is derived from the caudal end of the thyroglossal duct.

14. What is suspensory ligament of Berry
Ans: Thickened part of pretracheal fascia which connects inner surface of the gland to
cricoid cartilage. Recurrent laryngeal nerve is closely related to this ligament. Accounts
for the upward movement of thyroid gland during deglutition.
15. How do you clinically differentiate thyroid lump and thyroglossal cyst?
Ans: Thyroid lump Ascends upwards with deglutition because of attachment of its false
capsule to the laryngeal cartilages and trachea. Thyroglossal cyst is a remnant of
thyroglossal duct. Thyroglossal duct arises from the floor of the tongue (foramen cecum).
So thyroglossal cysts moves upwards when tongue is protruded.
16. How do thyroid arteries ligate during thyroidectomy?
Ans: Superior thyroid arteries are ligated near the gland so preserve the external laryngeal
nerves which are closely related to the artery away from the gland. Inferior thyroid
arteries (only branches to thyroid gland) are also ligated near the gland to preserve the
branches of it which gives sole blood supply to the parathyroid glands although the
recurrent laryngeal nerve is closely related to the artery near the gland.
17. Describe para thyroid glands, their embryological development
18. What happens during recurrent laryngeal and external laryngeal nerve damages during surgery
Ans: External laryngeal nerve supplies cricothyroid muscle which tenses the vocal chords. In external
laryngeal nerve damage, cricothyroid is paralyzed so high pitch can’t be achieved. Recurrent
laryngeal nerve supplies all the muscles of the larynx (Except cricothyroid) which are responsible for
the movement of vocal chords by the action of abductors & adductors of the chord. In unilateral
recurrent laryngeal nerve damage, hoarseness of voice results. But when both nerves are
completely damaged, phonation is lost. In partial damage to recurrent laryngeal nerves, vocal
chords become completely adducted because of the paralysis of the abductor muscle (posterior
cricoarytenoid) which is supplied by the peripheral fibres of the nerve. Breathing is lost in partial
recurrent laryngeal nerve damage. So partial damage is more harmful than complete damage
(called Semon’s law/ paradox)
19. What are the layers incised during thyroidectomy?
Ans: From superficial to deep – skin, superficial fascia with platysma, investing layer of
deep cervical fascia, Strap muscles, Pretracheal layer of deep cervical fascia (false
capsule), and true capsule of thyroid gland
• If parathyroid glands get damaged in thyroid surgery, Parathormone secretion is
impaired and hypocalcaemia results.
Tongue
20. Describe the nerve supply of tongue
Ans: ant. 2/3 – lingual nerve + chorda tympani
Post 1/3 – glossopharyngeal nerve (pre sulcal and vallete area include)
All the extrinsic / intrinsic muscles are supplied by – hypoglossal nerve
Except Palatoglossus – supplied by pharyngeal plexus.
21. Describe the embryological development of tongue.
Mandible
22. Describe the mandible
23. Show the muscle attachment of mandible
24. Name the muscles of mastication and their innervation.
Ans: temporalis
Masseter anterior division of mandibular nerve (V3)
Lateral pterygoid
Medial pterygoid - main trunk of mandibular nerve
25. Describe the temporo-mandibular joint (type, why it is atypical, articular surfaces, capsular
attachments, most stable position, movements, muscles involved)
26. Why TM joint is most commonly anteriorly dislocated
Ans: When the mouth is widely open, the condylar process of the mandible slides forwards
onto the articular eminence; thence, a blow, or even a yawn, may cause forward
dislocation into the infratemporal fossa on one or both sides.
27. Describe the inferior alveolar nerve, its branches and its clinical significance
Ans: It supplies teeth & gingiva of lower jaw. So inferior alveolar nerve block is done in
dental surgeries
28. Which nerve has to be blocked in local anesthesia during dental surgery
Ans: Inferior alveolar nerve (mostly anesthetized nerve in the body)
Skull
29. Point out foramen in the skull and ask what are the structures pass through it
30. Identify the stylomastoid foramen, structures pass through it
31. Briefly explain the pathway of facial nerve

32. What is bell’s palsy
Ans: It is a lower motor neuron lesion of facial nerve in which the nerve gets compressed
inside the facial canal because of the swelling of the nerve. All the muscles of facial
expression of ipsilateral side paralyzed.
33. Name the terminal branches of the facial nerve and muscles supplied by each branch
34. Show the exact point where the abducent nerve related to the petrous part
Ans: Apex of the petrous temporal bone (medial part of the superior border of petrous
temporal bone)
35. Briefly describe the bones of the skull
36. Describe the relations of the pituitary fossa
37. What is the thinnest part of the skull
Ans: Pterion
38. How you differentiate extradural, subdural and subarachnoid hemorrhage in MRI scans
Ans: Extradural hemorrhage is lens shaped in radiological images. It is because of the
attachment of endosteal layer of dura matter to the sutures & the hemorrhage is
between it and the bone. Subdural hemorrhage is crescent shaped and extends from
anterior cranial fossa to posterior cranial fossa because it is between meningeal layer of
dura matter and arachnoid mater which are not attached with each other. So, the
subdural hemorrhage is not limited by any attachments. In sub arachnoid hemorrhage,
CSF is contaminated with blood and blood spreads into ventricles
39. What is known as cephalo-hematoma
Ans: Collection of fluid deep to pericranium. This takes the shape of the bone because
pericranium is attached to the sutures of the skull. Common in neonates during delivery.
40. Show the pharynx position in the skull
41. Describe cranial fossae
42. What happens during anterior, middle and posterior cranial fossa fractures
43. What is pterion, related artery, clinical importance, how to surface mark it, why it is easily get
fractured (frontal branch of middle meningeal artery, extra Dural hemorrhage)
44. Describe the blood supply of the spinal cord
45. Describe the blood supply of brain (ask them to draw the circle of wills)
46. Name the branches of basilar artery
47. Name the structures supplied by vertebral arteries
48. Describe the clinical symptoms of occlusion of vertebral artery.
Ans: Lateral medullary syndrome
Venous sinus
49. Describe the venous drainage of the skull (sinus, their location)
50. Describe the cavernous sinus
51. What happens in carotido-cavernous fistula
Ans: In head injury, a communication between cavernous sinus and internal carotid artery
may occur. Eye ball protrudes and pulsates with each heartbeat.
Orbit
52. Name the extra ocular muscles, movements, innervation
53. What happens if the lateral rectus gets paralyzed
Ans: Abducent nerve paralysis – can’t look out wards, diplopia.
54. What is known as bi temporal hemi anopia / causes
Ans: Occurs when the optic chiasma is damaged e.g.- pituitary stalk
55. What are the structures pass through superior and inferior orbital fissure / optic canal?
Scalp
56. Name the layers of the scalp
57. What is known as the danger area of scalp and why
Ans: loose areolar tissue, because emissary veins open here and infections can easily spread
58. Define the danger area of face
Ans: Triangular area of face consists from bridge of the nose to upper corners of mouth
59. Describe the course of recurrent laryngeal nerve in both sides, reason for the different
pathways
60. In C6 cross section, name the structures you can identify
61. Ask to draw cervical plexus / Ansa cervicalis
62. What are the structures pass through carotid sheath?
63. Describe the deep cervical fascia, pre-tracheal, prevertebral fascia
64. Name the triangles of the neck.
65. What is the nerve supply for anterior and posterior digastric muscles?
66. Name the paranasal sinuses
67. Name the structures which open to superior middle and inferior meatus

68. What is waldeyer’s ring. name where the lymphoid nodes located?
Ans: Ringed arrangement of lymphoid tissue in the pharynx. Ring consist of lingual tonsil,
palatine tonsil, tubal tonsil and pharyngeal tonsil
69. Where does the auditory tube open?

70. What is known as true and false vocal cords
Ans: false vocal cords – lower free border of the quadrangular membrane
True vocal cords- upper free border of the cricothyroid membrane/vocal ligament
71. Name the muscles which tense the vocal cords
Ans: cricothyroid, vocalis
72. Name the muscles which abduct and adduct the vocal cords
Ans: Abduct vocal cords – post. Cricoarytenoid
Adduct vocal cords – lat. Cricoarytenoid, transverse arytenoid, oblique arytenoid
Relax vocal cord – thyroarytenoid
73. Name laryngeal cartilages and type of their cartilage
Ans: paired – Arytenoid hyaline cartilage – Thyroid, hyoid, arytenoid (basal part)
Corniculate elastic - elastic
Cuneiform
Unpaired – Thyroid
Cricoid
Epiglottic
74. What is otitis media, name the causes?
75. What is known as hyperacusis, in which condition does it occur
Neuroanatomy
76. Describe the embryological development of fore, mid and hind brain and the structures
develop from each part
77. Name the structures affected in medial and lateral medullary syndrome
78. Describe ventricular system
79. Name the cranial parasympathetic ganglia in ANS
Ans: Ciliary – Orbit/ between lateral rectus and optic nerve/ functional – occulomotor/ nucleus
Edinger Westphal
Otic – Infratemporal fossa/ below the foramen Ovale between tensor vali palatini and
mandibular nerve/ functional – Glossopharyngeal /Nucleus – Inferior Salivatory
Pterygopalatine – Pterygopalatine fossa / lateral to sphenopalatine foramen below maxillary artery
anterior to the pterygoid canal / Functional – Facial / Nucleus – lacrimatory
Submandibular – just above the deep part of the submandibular gland suspended from
the lingual nerve/ Functional – Facial/ Nucleus – Superior Salivatory
80. Describe the parasympathetic pathway of parotid gland, submandibular/sublingual glands
Ans: Parotid gland
Inferior salivatory nucleus→Glossopharyngeal nerve tympanic branch→tympanic
plexus→lessor petrosal nerve→otic ganglion→auriculotemporal nerve
Submandibular/sublingual gland
Superior salivatory nucleus→Nervous intermedius→Facial Nerve→Corda Tympani + Lingual
nerve→Submandibular ganglion→parasympathetic post ganglionic fibres via lingual nerve
81. Name a cranial nerve and ask its intra cranial and extra cranial pathway. common sites where
it can get affected.

VIVA IN ANATOMY
Vertebral column
1. Name the curvatures of the vertebral column, number of each vertebra

Ans: in the fetus – C shaped
Secondary curvatures – cervical and lumbar region
Primary curvatures – thoracic and sacral region
C-7, T-12, L-5, S-5, Co-4
2. Name the structures which travel through the foramen transversarium
Ans: vertebral artery ,with its accompanying sympathetic nerve fibers ,vertebral venous
plexus.
3. Name the joints between the vertebra and their joint types, articular surfaces
Ans : intervertebral disk – secondary cartilaginous joint (symphysis )/ between the adjacent
vertebral bodies
Zygapophyseal joint ( facet joint) – synovial joint / between the superior and inferior
articular facets
Special vertebral joints
Atlanto-occipital joint - synovial joint ( ellipsoid ) / convex occipital condyle and
concave facets on lateral mass of the atlas
Median atlantoaxial joint – synovial joint ( pivot ) /between dens and the anterior arch
of the atlas
4. Describe the intervertebral disk.
Ans: consists of annulus fibrosus and nucleus pulposus
Annulus fibrosus-has a narrow outer collagenous zone and inner wider fibrocartilaginous
zone
Nucleus pulposus : lie inside the annulus as a bubble of semiliquid gelatinous substance .
Derived from the embryonic notochord
5. What happens during the disk prolapse ( common sites, direction )
Ans : Nucleus pulposus herniate through the annulus
L4/L5 ,L5/S1 , postero lateral aspect
6. What are the abnormalities of vertebral column
Ans :
CERVICAL
7. Describe the atlanto axial joint ( type , articular surfaces , functions )
8. Describe the 7th cervical vertebra ( important features )
Ans : C7 – vertebra prominens – long spine is not bifid , foramen in the transverse process
doesnot transmit the vertebral artery , suprapleural membrane is attached to it.
9. Movements in the cervical region related to joints
Ans :Atlanto-occipital – nodding of head
Atlantoaxial- rotational movements
Flexion and extension ( pure rotation is impossible )
10. In which bone we find the vertebral body of Atlas .
11. Ligaments which contribute to form the median atlanto axial joint, its movement.
Ans: transverse ligament , apical ligament , alar ligament

12. Describe the vertebral venous plexus ( importants , where does it emerges )
Ans: They emerge from the posterior surface of the vertebral body
These are valveless veins,malignant disease may spread from prostate ,kidney,breast ,
bronchus ,and thyroid gland to the bodies of the vertebra.
THORACIC
13. Describe the features of typical thoracic vertebra
Ans: A pair of semi-circular demifacets on each side of the body , costal facet for the rib in
the transverse process, superior articular facets face – backwards and lateraly / inferior
articular facets – forwards and medially
14. Ask the student to identify a typical thoracic vertebra and ask him/ her to articulate with a
typical rib
LUMBAR
15. Movements of the lumbar region
Ans: The articular facets lie in an anteroposterior plane ,rotation is limited greatly, flexion
extension , lateral flexion
16. Describe charateristics of a typical Lumbar vertebra ,Give reasons for the large vertebral
body.
17. Describe the level which does the lumbar puncher ,purpose
Ans : L4/L5 , Purpose – obtain CSF to introduce drugs ( antibiotics , anaesthetics ,

chemotherapeutic agents
Structures which pierced – skin , superficial fascia ,supraspinous ligament, interspinous
ligament, ligamentum flavum, areolar tissue with the internal vertebral venous plexus , dura
mater, arachnoid mater subarachnoid space
SACRUM
18. Describe the sacrum ( foramens ,caudal anesthesia )

Ans:
Pelvic surface is concave and smooth.
Anterior projecting edge is known as the sacral promontory
Lateral to the body there is wing like structure ala of the sacrum on each side ,consist of
fused costal elements and transverse process
Anteriorly there are four sacral foramina .
Dorsal surface
Sacral hiatus below
Median sacral crest
Inter mediate sacral crest
Lateral sacral crest
Sacral conu

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1 © 2015 A/L Repeat Campaign

- winging of the scapula - due to paralysis of the serratus

Navy under the bridge (superior transverse scapular ligament)

Army over the bridge

2 © 2015 A/L Repeat Campaign

Upper End Shaft Lower End

1) Head of humerus Rounded in the upper half and triangular Articular

Posterior aspect bears radial groove

Lower -Teres minor

5) Intertubercular sulcus has medial and

6)surgical neck- related to axillary nerve

- Surgical neck – Axillary nerve

Common sites of FRACTURE

- Surgical neck – axillary nerve more prone to damage

3 © 2015 A/L Repeat Campaign

• Commonly fractured 1” proximal to the

• Green stick fractures (common in children)

4 © 2015 A/L Repeat Campaign

Muscle Origin Insertion Innervation Function

Muscles of posterior scapular region

Muscle Origin Insertion Innervation Function

Muscles of anterior wall

Muscle Origin Insertion Innervation Function

2 © 2015 A/L Repeat Campaign

Muscle Origin Insertion Innervation Function

Muscles of the lateral and posterior wall of the axilla

Muscle Origin Insertion Innervation Function

Muscle Origin Insertion Innervation Function

3 © 2015 A/L Repeat Campaign

Muscle Origin Insertion Innervation Function

4 © 2015 A/L Repeat Campaign

Muscle Origin Insertion Innervation Function

Muscle Origin Insertion Innervation Function

5 © 2015 A/L Repeat Campaign

Muscle Insertion Innervation Function

6 © 2015 A/L Repeat Campaign

A. Muscles of pectoral girdle

1) Pectoralis Major- For the

2) Trapezius- The shoulder is

3) Latissimus Dorsi- The arm is

4) Serratus Anterior- With the arm

1) Supraspinatus- The arm is abducted against resistance and the muscle

8 © 2015 A/L Repeat Campaign

C. Anterior compartment of the arm

D. Posterior compartment of the arm

E. Anterior compartment of the forearm

3) Flexor Digitorum Superficialis- The fingers are flexed at the proximal

F. Deep muscles of the forearm

G. Posterior compartment of the forearm

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Transverse section of the forearm

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Muscle origin Insertion innervation Action

1 © 2015 A/L Repeat Campaign

Midaxillay line lateral border of

- Lies within superficial fascia--------- EXCEPT – small

• Medial 2/3 – on Pectoralis major muscle

2 © 2015 A/L Repeat Campaign