Basic Concepts

Chapter - 1
BASIC CONCEPTS

I. Cell Membrane:
Thickness 7-10 nm. The fluid mosaic model of membrane structure proposed in 1972 by Singer and Nicolson.
Contain lipids (bilayer), proteins & carbohydrates.

Chapter - 1
Basic Concepts
A. Lipids: 30-40% of cell membrane consists of three classes of amphipathic lipids: phospholipids, glycolipids,
and steroids. The phospholipids are the most abundant. In animal cells cholesterol is normally found
dispersed in varying degrees throughout cell membranes, in the irregular spaces between the hydrophobic
tails of the membrane lipids, where it confers a stiffening and strengthening effect on the membrane. lecithin
is phosphatidylcholine a type of phospholipid which is a integral part of cell membrane. Cell membrane
contains triglycerides close to zero.
B. Carbohydrates: Plasma membranes also contain carbohydrates, predominantly glycoproteins, but with some
glycolipids (cerebrosides and gangliosides). For the most part, no glycosylation occurs on membranes within
the cell; rather generally glycosylation occurs on the extracellular surface of the plasma membrane. The
glycocalyx is an important feature in all cells, especially epithelia with microvilli. The penultimate sugar is
galactose and the terminal sugar is sialic acid. Sialic acid carries a negative chargeQ, providing an external
barrier to –vely charged particles.
C. Proteins: 50-60% of cell membrane. 3 types

Type Examples
1. Integral proteins or transmembrane proteins : Ion channels, proton pumps, G protein-coupled receptor
2. Lipid anchored proteins: : G proteins
3. Peripheral proteins: : Some enzymes & hormones

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 Physiology

II. Cell Junctions

A. Tight junction: membranes fuse tightly, no transport between adjacent cells possible. Eg blood brain
barrier, GIT, Kidney & choroid plexus.
B. Desmosomes : membranes are separated by 15-20 nm, but no transport of substances takes place. Act as
anchoring junctions.
C. Gap Junctions : 2-20 nm separation. Made up of Connexons. Contain ion channels responsible for spread
of impulses, found in cardiac muscles (in intercalated discs- make Cardiac muscle “one unit” or
syncytium), Electrical synapses, Nodal tissue & Single unit (visceral) smooth muscle.

Cytoskeletal system
Cytoskeleton type Diameter (nm) Subunit & Structure function

Cell junctions
A. Microfilaments 6 Made of actin, double helix Muscle Contraction
Slow axoplasmic transport
vimentin (mesenchyme)
B. Intermediate Cell adhesion
10 neurofilament
filaments Maintain cell shape
keratins (epithelial cells)

Intracellular transport
Cilia and flagella.
C. Microtubules 23 α and β-tubulin
Centriole- mitotic spindle.

D. Molecular motors: Cytoskeletal motors & Polymerization motors

1. Cytoskeletal motors
a. Myosin is responsible for muscle contraction
b. Kinesin moves cargo inside cells away from the nucleus along
c. microtubules
d. Dynein produces the axonemal beating of cilia and flagella and
e. also transports cargo along microtubules towards the cell nucleus

2. Polymerisation motors
a. Actin polymerization generates forces and can be used for propulsion. ATP is used.
b. Microtubule polymerization using GTP.
c. Dynamin is responsible for the separation of clathrin buds from the plasma membrane.

3. Fast cytoplasmic transport (20-400mm/day): use molecular motors which run on Microtubule filaments
a. anterograde: This is driven by kinesin
b. Retrograde: This is driven by Dyenin

4. Slow cytoplasmic transport (0.2-4mm/day)

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 Basic Concepts

This is always anterograde. The cytoskeleton (Microtubules) moves as a whole due to the continual
polymerization at the leading end (+ end) and depolymerization at the trailing end (- end).

Concept 1. Body Composition: Values and Measurement

Values
a. Body Composition (as % of Body weight)
Water 60% to 70%
Proteins 18%

Chapter - 1
Minerals 7%
Fats 15%

*Body Water as % Body weight

TBW = 60%
ECF = 20%
Plasma = 5%
Interstitial fluid  15%
ICF = 40%
(Total blood volume = 8% of body weight; since plasma volume is 5% of body weight, blood cell volume = 3% of
body weight)

Basic Concepts
b. Measurement of the various body fluid compartments
This is done by the principle of volume of distribution. (or dye-dilution method)
Q-e = v where
C  = volume
Q = quantity of indicator given
C = concentration of the indicator
e = The amount of indicator which has either been lost or metabolized
c. Indicators
Compartment Indicator used
Plasma volume Evans’ blue (T1824)
RBC volume Tagging RBC with 51Cr, 59Fe, 32P; also antigenic tagging
ECF volume Inulin, sucrose, Mannitol, Sodium thiosulphate, sodium
thiocyanate
Interstitial fluid Cannot be measured directly; can be calculated as ECF volume –
Plasma volume
ICF Cannot be measured directly; can be calculated as Total body
water – ECF
Total body water D2O is most frequent used; also, tritium oxide, aminopyrine

d. Other points
Water content of lean body mass = 71-72 mL/ 100 gm of tissue
(Lean body mass = body mass devoid of fat)
(Note that fat does not hold water)
Total body water

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 Physiology

i. Somewhat lower in women

ii. Tends to decrease with age

Concept 2: Expressing Solute Concentrations

Mole (or mol)
Definition: It is molecular weight of a substance in grams i.e. it is gram molecular weight
Example:
a. Calcium  Molecular weight = 40;; therefore, 40 gm = 1 mol of calcium
b. NaCl  Atomic weight of
Na = 23
CL = 35.5
Therefore, 23+35.5 = 58.5 gm of NaCl = 1 mol of NaCl

Note
1. In S.I. system, mole is the standard used to express amount of any substance
Dalton: It is a unit of mass; 1 Dalton = 1/12th of the mass of carbon atom – 12
2. Molecular weight is a dimensionless ratio.

Equivalent (Eq.)
1 mol of an ionized substance
1 Equivalent = -------------------------------------------
Valence

a. 1 equivalent of calcium = 40/2 = 20gm

b. 1 equivalent of Sodium = 23/1 = 23gm

Osmole
1 OSMOLE = Mol  Number of freely moving particular each molecule liberates in solution
It expresses concentration of osmotically active particles

Examples
1 mol of NaCl = 2 osmoles because each NaCl molecule given one Na+ and one Cl- particle is solution
1 mol of Na2SO4 = 3 osmoles because each Na2SO4 molecule gives 2 Na+ and 1 SO4 is solution
1 mol of CaCl2 = 3 osmoles, because each molecule of CaCl2 give 3 particles (1 calcium and 2 Cl-) in solution
1 mol of Na2SO4 has 4 equivalents and 3 osmoles

Note :
One osmole (or one can say 1 mol of an undissociated substance in an ideal solution ) of any substance has the
following properties :
1. it depresses freezing point by 1.860C*
2. it exerts an osmotic pressure of 22.4 atmospheres
3. it has 6 X 1023, molecules (Avagadro’s number)
*This fact can be used to measure the osmolal concentration of a substance.

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 Basic Concepts

Difference between osmolarity and osmolality

Osmolarity is the number of osmoles per litre of solution;
Osmolality is the number of osmoles per kg of solvent. Osmolality is not affected by changes in volume of solution
or by temperature.

Tonicity
Definition: This is the osmolality of a solution with respect to plasma osmolality

Chapter - 1
Example : 0.9% NaCl is isotonic ; 5% glucose is isotonic initially; later is become hyptomic
Plasma osmolality : 290 mosm
Approximate formula for finding the plasma osmolality:
Plasma osmolality = Na+ concentration (in mEq/l) x 2 + glucose(mg/dL)/18 + BUN (mg/dL)/2.8
Out of the 290 mosm,
1. Na+ and its associated ions (Cl- / HCO3-) = 270 mosm
2. Urea = 5 mosm
3. Glucose = 5 mosm
Osmolal Gap:
1. The most accurate way of finding out the osmolality is by freezing point depression (see above)
2. The approximate formula is as given above

Basic Concepts
3. If there is a difference between the two calculations, it is called osmolal gap. Osmolol gap indicates the
presence of a foreign substance.

ECF Volume Body Osmolarity ICF Volume

Loss of isotonic fluid Hemorrhage Diarrhea ↓ no change no change
Vomiting
Loss of hypotonic fluid Dehydration Diabetes ↓ ↑ ↓
insipidus
Gain of isotonic fluid ↑ no change no change
Gain of hypotonic fluid ↑ ↓ ↑
Gain of hypertonic fluid e.g. mannitol ↑ ↑ ↓

Concept 3: Transport Across Cell Membranes

1. Active : Primary and secondary
2. Passive
3. Exocytosis / Endocytosis (This is an active process)

1. Active Transport
Definition: Energy is used. Against gradient
Types:
a. Primary active transport: Energy is derived directly by hydrolysis of ATP by the transporter itself.
(Note: All transporters ending with “ATPase” are primary active)
Eg. Na+ K+ ATPase pump:
b. Secondary active transport : Energy is derived indirectly
Eg. Sodium – linked glucose transport (i.e. SGLT) in kidney & GIT

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 Physiology

(Note: All transport mechanisms which are linked to Na+ entry or K+ exit are secondary active.eg. Na+-I-
symport)
The secondary active transport can be a
i. Counter transport or antiport (exchanger) where two substance are transported in the opposite
direction
Or
ii. Co- transport (symport) where two substances are transported in the same direction

Na+ K+ ATPase pump: It is a universal pump responsible for maximum energy consumption in basal state. Coupling
ratio of 3:2 i.e. 3 Na+ out and 2 K+ inside the cell. Blocked by digitalis & Ouabain. The Na+/K+-ATPase helps to
generate resting membrane potential(5-10%), active transport (primary as well as secondary active) and regulate
cellular volume(by pumping out Na+ & therefore water-failure will lead to cellular swelling)
2. Passive transport – (No energy required as along gradient)
Diffusion
This can be
a. Simple diffusion
b. Facilitated diffusion
c. Nonionic diffusion

a. Simple diffusion
Characteristics
i.No carrier molecule involved
ii.No Tm (No transport maximum i..e not saturable)
iii.Follows Fick’s law of diffusion
iv.Fick’s Law of diffusion
J= - DA  C
x
Where
J = Net rate of diffusion
D = Diffusion coefficient
A = Area
(Delta C = Concentration difference on the 2 sides of the membrane)
(Delta x = thickness of the membrane)
(The negative sign indicates the direction of diffusion )
(For diffusion from higher to lower concentration, the sign is negative)
The time required for diffusion is directly proportional to the square of the diffusion distance
Example of simple diffusion : O2/CO2 exchange in alveoli

b. Facilitated diffusion
Characteristics -:
i. No energy is required
ii. A carrier molecule is involved to which the substance binds, therefore, it is also called passive carrier –
mediated transport
iii. Has a Tm (it is saturable)

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 Basic Concepts

iv. It can be competitively and noncompetitively inhibited

v. It follows the enzyme – substrate kinetics of Michaelis - Menten
E.g. Glucose transport by glucose transporters (GLUT)

(a)
(a): Simple diffusion
Rate
(b)
(b): Facilitated diffusion

Chapter - 1
Concentration

c. Non – ionic diffusion

i. In case of weak acids or bases, where the acid / base can cross the membrane in the non – ionized form
but cannot cross the membrane in the ionized form
Eg. Ammonia transport in GIT / Kidney. The mucosal toxicity of non – steroidal anti inflammatory drugs
can be explained on this basis.
ii. Osmosis
 Definition: Diffusion of a solvent into a higher concentration of solute to which the membrane is

Basic Concepts
impermeable

 2. Osmotic pressure for an ideal solution is given by

nRT
P=

Where P = osmotic pressure
N = number of particles
R = Gas constant
 = volume
T = Absolute temperature
 Osmotic pressure depends on the number rather than the type of particles in solution. Such
properties which depend on the number the rather than the type of particles in called fundamental
colligative property
 Other examples of fundamental colligative property are:
o Vapour pressure lowering
o Freezing point depression
o Boiling point elevation

iii. Filtration: This is the movement of fluid across capillaries, this is governed by Starling’s forces. The
starling’s forces are
 Hydrostatic pressure (a ‘push’ force) and
 Oncotic pressure (a ‘pull’ force)

iv. Bulk flow or solvent drag

This refers to the movement of particles / solutes along with movement of water

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Vesicular transport: Endocytosis (eg phagocytosis) & Exocytosis. Membrane area increases in exocytosis
and decreases in endocytosis. All require Ca2+. Proteins involved are Clathrin (Receptor mediated
endocytosis), Dynamine, Caveolin etc.

III. ELECTROPHYSIOLOGY OF CELL MEMBRANE

A. Donnan effect / Gibbs – Donnan equilibrium

B. Nernst equation
C. Goldman – Hodgkin – Katz (G-H-K) equation or, Goldman constant field equation or chord conductance
equation

1. Donnan effect
Presence of an impermeant ion (e.g A- in side 2) on one side of the membrane repels similarly charged
permeant ions to the
other side and holds opposite charged permeant ions to the same side.
Side 1 Side 2

Eg.
A-

2. Gibbs – Donnan equilibrium

a. This can be considered as the ‘mathematics’ of the Donnan effect.
b. The effects the presence of the impermeant ion on the distribution of permeant ions are
c. It causes an asymmetric distribution of the permeant ions
d. More osmotically active particle on the side containing the impermeant ion
e. The product of the concentration of the permeant ions on one side equal, the product of the
concentration of the permeant ions on the other side
f. However, the total number of positive charges on one side equals the total number of negative charges.
Illustrate example
Side 1 Side 2

K+ = 9 K+ = 6
Cl- = 4 Cl- = 6
A- = 5

A is the impermeant anion

3. Nernst equation
Gives the value of equilibrium potential or isoelectric potential. (E) Equilibrium potential is the membrane
potential at which equilibrium is reached (i.e. there is no net flux of that ion).
Examples
E Na+ = +60mv(tendency of Na+ is to diffuse in till potential reaches +60 mv)
E K+ = - 90mv(tendency of K+ is to diffuse out till potential reaches -90 mv)
ECl- = - 70mv

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 Basic Concepts

Note: The ECl is the closest to the RMP.

4. Goldman constant Field equation

a. Gives the magnitude of the membrane potential. It depends on;
i. The distribution of Na+, Cl-, K+
ii. Permeability of the membrane to each of these ions
b. Concept: Resting Membrane potential (R.M.P)
Definition: Every cell shows a potential difference, with the inside being negative. Its value varies from

Chapter - 1
cell to cell
c. Genesis of R.M.P.
i. Diffusion of K+ : This is the most important cause as membrane is more permeable to K+ than
Na+ so it diffuses out and membrane potential becomes negative.
ii. Na+ - K+ ATPase: 5-10% of RMP
iii. By itself, it contributes a small percentage; its contribution towards RMP is more in those
cells with low RMP
[Note: Pacemaker tissues have a low RMP]
iv. More importantly, it maintains the diffusion gradient for K+
Donnan effect: This also maintains the diffusion gradient for K+

Basic Concepts
Value (mV) : Neuron – 70, skeletal muscle – 85, SA node –30 to –40, ventricle –90, smooth muscle –30 to –40,
thyroid –50, RBC –10 , Hair cell -50 mV

Effect of change in Na+/K+ on RMP

1. Changes in Na+ : No change in RMP

Reason : Low permeability of membrane to sodium
(Note: However, a decrease in external Na+ concentration decrease the height of the action potential)

2. Change in K+
Increase in K+ concentration in ECF decreases RMP
Eg. From – 70 mV, it may become – 65 mV
(Note: While commenting on the change in the membrane potential (eg. From – 70 mV to – 65 mV) the sign
(positive or negative) has to be ignored. Thus, -70mV to – 65mV should be considered as a decrease in potential or
depolarization. (-70mV to – 90mV is hyperpolarization)
The patch clamp technique is a laboratory technique in electrophysiology that allows the study of single or multiple
ion channels in cells. The technique can be applied to a wide variety of cells, but is especially useful in the study of
excitable cells such as neurons, cardiomyocytes, muscle fibers and pancreatic beta cells. It can also be applied to
the study of bacterial ion channels in specially prepared giant spheroplasts. The patch clamp technique is a
refinement of the voltage clamp. Neher and Sakmann received the Nobel Prize in Physiology or Medicine in 1991
for this work.
Techniques: a. Cell-attached or on-cell patch b. Inside-out patch
c. Whole-cell patch d. Outside-out patch
e. Perforated patch

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Some Important Data

ECF ( in mEq/litre)
Cations Anions
+ -
Na 145 Cl 100
K+ 5 HCO3- 27
++
Ca 2 PO4--- 2
++
Mg 2 SO4-- 1

Organic acids 5
Proteins 19
Total 154 Total 154

ICF ( in mEq/litre)
Cations Anions
Na+ 10 Cl- 10
+ -
K 150 HCO3 10
++
Ca 3 PO4--- 90
+
Mg 15 SO4-- 15
Organic acids -
Proteins 52
Total 177 Total 177

Total Exchangeable
+
Na 3900 mEq (90 gm) 80%
K+ 3400 mEq (90 gm) 95%
*(only one-third of Na in bone is exchangeable
Na+ 3900 mEq in 70 kg or 56 meq/Kg
+
K 3400 mEq in 70 kg or 50 meq/Kg
ELECTROLYTES
Losses
(in mEq/day in a 70 kg man in temperature climate)
Na+ K+ Cl-
Urine 40-90 20-60 40-120
Sweat 50-100 5 50-100
Faeces 1.5 4 0.5
Total 140 (3.2 gm) 60 (2.4 gm) 200 (7 gm)

Recall MCQs

1. ECF is _________% of the total body water

A. 20 B. 40 C. 33 D. 66

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 Basic Concepts

2. All the following can measure ECF except

A. Inulin B. Sucrose C. Mannitol D. Sodium thiosulphate E. Evans’ blue

3. 1 osmole of NaCl is ______ gms of NaCl

A. 58.5 B. 29.25 C. 117 D. None of the above is correct.

4. A solution has a freezing point of –0.93 degree celcius. This has an osmolarity of
A. 50 osmoles B. 500 millisosmoles C. 1 osmole D. 0.5 milliosmole E. cannot comment

Chapter - 1
5. Ammonia transport in the kidney is an example of
A. Non-ionic diffusion B. Facilated diffusion
C. Simple diffusion D. Secondary active transport

6. Isoelectric potential is given by

A. Nernst equation B. GHK equation
C. Fick’s equation D. Gibbs-Donnan equilibrium

7. RMP of a neuron is approximately

A. –90mV B. –90 microvolt C. –40 mV D. –70 mV

Basic Concepts
8. What percentage of ECF sodium is exchangeable?
A. 70 B. 100 C. 33 D. 50

9. Most abundant intracellular anion is

A. Phosphate B. Protein C. Chloride D. Bicarbonate

10. RMP is mostly due to

A. K+ diffusion B. Na+ diffusion C. Na+K+ ATPase D. Donnan effect

Analytical/Conceptual MCQs
1. 1500 ml of water is ingested by an adult. Assuming no water losses, how much water ( in ml) do you think
would have gone into the interstitial fluid compartment after equilibration?
A. 500 B. 375
C. 333.3 D. 225 E. None of the above is correct

2. Calculate the osmolarity (in millisomoles/litre) of a solution having the following composition
i. Serum Na = 135 meq/L ii. Glucose = 90 mg/dL
iii. BUN = 14 mg/dL iv. Bilirubin = 50 milliosmoles/litre
A. 330 B. 289 C. 195 D. 306 E. 289.5

3. The ICF volume is 28 litres. The ECF volume is 14 litres. The osmolarity is 300 milliosmoles/litre. The subject
loses 2 litres of ECF fluid and each litre has 200 milliosmoles. In such a case, which one of the following will be
true?
A. ICFV and ECFV will increase B. ICFV and ECFV will decrease
C. ICFV will increase and ECFV will decrease D. ICFV will decrease and ECFV will increase

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 Physiology

4. A substance has twice the concentration on side A as compared to side B. If the concentration on side A is
made 5 times that in side B, by how many times will the diffusion increase?
A. 3 B. 1/5 C. 4 D. 5

5. Iodide transport in the thyroid cell is an example of

A. Non-ionic diffusion B. Simple diffusion
C. Facilitated diffusion D. Secondary active transport E. Primary active transport

Answer key for Recall MCQs

1.C 2.E 3.A 4.B 5.A
6.A 7.D 8.A 9.A 10.A

Answer key for Analytical /Conceptual MCQs

1. B 2. A 3. B 4. C 5. D

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“Please Read the Preface of this book Before you attempt these questions.”
Explanation of answer start from page no. 24

1 . Which is a non essential mineral (AIIMS NOV.2010) 10. Which of the following is true regarding auto-
A. Copper B. Managanese regulation: (DNB Pattern)
C. Iron D. Lead A. Vary with change in pressure
B. Maintains the blood flow
2 Glucose transporter in myocyte is (AIIMS NOV 2009) C. Well developed in skin
A. GLUT1 B. GLUT2 D. Regulated by local metabolites
C. GLUT3 D. GLUT.4
11. Organ to have the maximum oxygen consumption
3. Pseudohyponatremia is not seen in: after liver is: (DNB Pattern)
A. Hypothyroidism B. Mannitol A. Skeletal muscle B. Kidney
C. Extreme hyperproteinemia D. Severe hyperlipidemia C. Brain D. Heart

4. First change seen with salicylate poisoning is: 12. Which of the following is blocked by tetrodotoxin:
A. Metabolic acidosis B. Respiratory acidosis A. Na during resting state
C. Metabolic alkalosis D. Respiratory alkalosis B. K during resting state
C. K during action potential
5. D2O is used in determination of: (DNB Pattern) D. Na during action potential
A. Total body water B. Plasma volume
C. Extracellular fluid D. Intracellular fluid 13. Deficiency of which of the following leads to
pellagra:
6. Auto-regulation is not seen in: (DNB Pattern) A. Niacin B. Riboflavin
A. Liver B. Cutaneous C. Folic acid D. Pantothenic acid
C. Kidney D. Brain
14. Which of the following is different between saliva
7. The pH of extracellular fluid is:(Latest question) and plasma:
A. 8 B. 6 C. 7.4 D. 5.5 A. Hypotonicity B. HCO3- concentration
C. Aldosterone concentration D. Protease enzyme
8. Which of the following is a high energy compound:
A. ANP B. Adenosine triphosphate 15. Which of the following is true about cell
C. UTP D. GTP membrane transport: (DNB Pattern)
A. Cl- with glucose symport
9. Which of the following statement is false regarding B. Na+ with glucose antiport
Barr body: (DNB Jan – 2007) C. Na+ with glucose symport
A. Drumstick chromatin projecting from the nuclei of D. K+ with glucose symport
1 –15% of polymorphonuclear leucocytes in males
B. One Barr body is present 16. Which of the following transports glucose into a
C. Inactive X chromosome condenses and seen usually
cell: (DNB Pattern)
near the nuclear membrane
D. Barr body for each X chromosome in excess of one in A. Na+ symport B. K+ symport
the cell C. Na+ antiport D. K+ antiport

1.D 2.D 3.A 4.A 5.A 6.B 7.C 8.B 9.A 10.B 11.A 12.D 13.A 14.B 15.C 16.A

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 Basic Concepts

17. Which of the following is the best for measuring 26. Which of the following is/are the force generating
total body water: protein/proteins:
A. Evan’s blue B. I131 A. Myosin and myoglobin B. Dynein
C. Tritium oxide D. P 32 C. Troponin D. Calmodulin

18. Basal metabolic rate is dependent on: 27. After chloride ions, which of the following ion is
A. Body weight the most abundant anion in blood plasma:
B. Surface area A. Phosphates B. Calcium

Chapter - 1
C. Amount of adipose tissue C. Bicarbonates D. Potassium
D. Amount of lean body mass
28. Nitric oxide is released from: (DNB Dec – 2008)
19. Which of the following produce ketone bodies: A. Pericytes B. Smooth muscle cells
A. Liver B. Muscles C. Endothelial cells D. Mesenchymal cells
C. Kidney D. Gastrointestinal tract
29. The cell junctions allowing exchange of
20. Plasma membrane is chiefly made up of: cytoplasmic molecules between the 2 cells are called:
A. Phospholipids B. Protein A. Gap junctions B. Tight junctions
C. Cholesterol D. Carbohydrate C. Anchoring junctions D. Focal junctions

Basic Concepts
21. Which of the following is true 30. Chediak-Higashi syndrome is associated with
A. ECF is rich in K+ B. ECF has high Na+: K+ ratio detect in: (DNB Dec. 2009)
C. ECF is more than ICF D. ECF is rich in organic anion A. Chemotaxis B. Phagocytosis
C. Absorption D. Proton pump
22. Maximum triglycerides are in which fraction:
A. VLDL B. LDL 31. Which of the following is true regarding second
C. HDL D. Chylomicron messenger? (DNB Pattern)
A. Mediates intracellular activities of enzymes and
23. Triple helix structure is seen in: hormones
A. Keratin B. Collagen B. Mediates extracellular activities of enzymes and
C. Elastin D. Cartilage hormones
C. Both
24. EDRF simulates: D. None
A. The action of cAMP B. The action of nitric oxide
C. The action of halothane D. The action of ether 32. The transport of chemicals across cell membrane
against the gradient is mediated by:
25. Which of the following is not a function of nitric A. Voltage gated channels B. Channel proteins
oxide: C. G proteins D. Carrier proteins
A. Kill cancer cells
B. Vasoconstriction 33. Deuterium oxide and inulin are injected into a
C. Relaxation of vascular smooth muscles normal 30-year-old person. The volume of distribution
D. Deficiency may cause clinical hypertension of deuterium oxide is found to be 42L and that of
inulin 14L. Which of the following is TRUE?:

17.C 18.D 19.A 20.B 21.B 22.D 23.B 24.B 25.B 26.B 27.C 28.C 29.A 30.A 31.A 32.D

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 Physiology

A. Intracellular volume is 28 L 40. The endothelial cells produce thrombomodulin,

B. Intracellular volume is 20 L except those found in:
C. Intracellular volume is 40 L A. Hepatic circulation
D. Intracellular volume is 15 L B. Cutaneous circulation
C. Cerebral microcirculation
34. Sodium-potassium-ATPase helps in the mainte- D. Renal circulation
nance of which of the following?
A. Cell surface charge 41. Antigen presenting cells are specialised cells
B. Cell volume present on all of the following except
C. Low extracellular sodium A. Skin B. Lymph node
D. High extracellular potassium C. Spleen D. Kidney

35. Albumin acts as a co-transport for: 42. The following is an example of “Regulated
A. Vitamin K B. Fatty acids pathway”(DNB Pattern)
C. Copper D. Iron A. Constitutive exocytosis
B. Receptor mediated endocytosis
36. Alpha-fetoprotein in maternal serum and/or C. Constitutive endocytosis
amniotic fluid is increased in all, except D. Non constitutive exocytosis
A. Fetal neural tube defects
B. Down’s syndrome 43. The poison cyanide inhibits the reaction between
C. Anencephaly A. Cytochrome oxidase and molecular oxygen
D. Encephalocele B. Cytochrome A and Cytochrome B
C. Phosphofructokinase and glucose oxidase
37. Barr body is found in the following phase of the D. Haemoglobin and oxyhaemoglobin
cell cycle:
A. Interphase B. Metaphase 44. The cell junctions allowing exchange of
C. G1 phase D. Telophase cytoplasmic molecules between the two cells are
called: (DNB Pattern)
38. Oral rehydration mixture contains glucose and A. Gap junctions B. Tight junctions
sodium because both of them: C. Anchoring junctions D. Focal junctions
A. Are needed to maintain the plasma osmolality
B. Are prominent energy source for the body 45. All of the following statements are correct about
C. Facilitate the transport of each other from the potassium balance. Except:
intestinal mucosa to blood A. Most of potassium is intracellular
D. Are required for the activation of sodium potassium B. Three quarter of the total body potassium is found
ATPase in skeletal muscle
C. Intracellular potassium is released into extra-
39. All of the following are examples of tumor cellular space in response to severe injury
markers, except D. Acidosis leads to movement of potassium from
A. Alpha HCG B. Alpha-fetoprotein extracellular to intracellular fluid compartment.
C. Thyroglobulin D. Beta HCG

33.A 34.B,A 35.B 36.B 37.A 38.C 39.A 40.C 41.D 42.D 43.A 44.A 45.D

20
 Basic Concepts

46. A 10°C decrease in temperature causes decrease in 54. Which of the following substance increase the
cerebral metabolic rate by: release of Ca++ from endoplasmic reticulum?
A. 10% B. 30% C. 50% D. 70% A. Inositol triphosphate
B. Parathyroid hormone
47. One of the following is intraneural secondary C. 1, 25-dihydroxy cholecalciferol
messenger: (DNB Pattern) D. Diacyl glycerol
A.. Dopamine B. Cyclic AMP
C. GMP D. Calcium 55. A small Ca binding protein that modifies the

Chapter - 1
activity of many enzymes and other proteins in
48. Number of bonds broken in protein synthesis is response to changes of Ca concentration, is known as:
A. One B. Two C. Four D. Eight A. Cycline B. Calmodulin
C. Collagen D. Kinesin
49. Earliest definite sign of death is:
A. Absent brain stem reflexes 56. The most abundant glycoprotein present in
B. Stoppage of mucosal ciliary action respiratory basement membrane is:
passage A. Laminin B. Fibronectin
C. Retinal anterior column breakdown C. Collagen type 4 D. Heparin sulphate
D. None of these
57. Sweating a result of exertion is mediated through:

Basic Concepts
50. How much amount of energy is yielded by one ml A. Adrenal hormones
of alcohol (per gram) in the body? B. Sympathetic Cholinergic
A. 1 cal B. 4 cal C. 7 cal/gm D. 9 cal C. Sympathetic adrenergic
D. Parasympathetic Cholinergic
51. Various cells respond differentially to a second
messenger (such as increased cAMP) because they 58. True about calcium
have different: (DNB June – 2008) A.. Intracellular anion B. Binds to proteins
A. Receptors B. Enzymatic composition C. Depresses myocardium D. None
C. Nuclei D. Membrane lipids
59. In which of the following conditions the level of
52. if you calculate the plasma osmolality of a child creatinine kinase — I increases?
with plasma Na+ 125 meq/L, glucose 108 mg/dl, and A. Myocardial ischemia B. Brain ischemia
BUN (blood urea nitrogen) 140 mg/dL, the most C. Kidney damage D. Electrical cardioversion
appropriate answer would be:
A. 300 mOsm/kg B. 306 mOsm/kg 60. Acetyl choline is not therapeutic because
C. 312 mOsm/kg D. 318 mOsm/kg A. Indefinite action B. It is rapidly metabolized
C. More effective at NMJ D. All of the above
53. Which of the following is a membrane bound
enzyme that catalyzes the formation of cyclic AMP 61. The first physiological response to high
from ATP environmental temperature is:
A. Tyrosine kinase B. Polymerase A. Sweating
C. ATP synthase D. Adenylate cyclase B. Vasodilatation
C. Decrease heat production
D. Non-shivering thermogenesis

46.D 47.B 48.C 49.A 50.C 51.B 52.B 53.D 54.A 55.B 56.A 57.B 58.B 59.B 60.B 61.B

21
 Physiology

62. Barr body is found in the following phase of the A. RBC rouleux formation
cell cycle (DNB Pattern) B. Increased plasma skimming
A. Interphase B. Metaphase C. Increased number of RBC in capillaries
C. Gi phase D. Telophase D. None

63. Serum angiotensin convertion enzyme may be 71. Content of Na+ in ringer lactate is meq/L
raised in all of the following, except: A. 154 B. 121
A. Sarcoidosis B. Silicosis C. 130 D. 144
C. Berylliosis D. Bronchogenic carcinoma
72. Androgen receptors are coded in
64. In an unacclimatised person suddenly exposed to A. Long arm of X chromosome
cold atmosphere, changes seen are B. Short arm of X chromosome
A. Increase in systolic BP C. Long arm of Y chromosome
B. Shift of blood from shell to core D. Short arm of Y chromosome
C. Non — thermogenic shivering
D. Tachycardia 73. The majority of body sodium is present in:
A. Extra cellular fluid B. Intra cellular fluid
65. False about body temperature: C. Plasma D. Bone
A. Mean Temp. 98.2 ± 0.7°F
B. P.M. Temp > 99.9° F 74. Which one of the following is the correct sequence
C. A.M. Temp. > 98.4°F in increasing order of their basal blood supply
D. Rectal Temp. 0.6°> oral temp (ml/min/100g of tissue)?
A. Heart, brain, kidney B. Brain, kidney, heart
66. ATP needs (DNB June – 2012) C. Kidney, heart, brain D. Brain, heart, kidney
A. Calcium B. Magnesium
C. Manganese D. Zinc 75. An adolescent desirous of increasing his muscle
mass is advised to (DNB Pattern)
67. True regarding Na/K pump is A. Increase protein intake
A. Pumps Na against a gradient B. Take steroids
B. 5 Na exchanged for 2K C. Exercise the muscle
C. Increases in intracellular Na D. Electrically stimulate the muscle
D. Hypocalcemia inhibits the pump
76. Nissl’s substance is composed of:
68. Most permeable capillaries A. Rough endoplasmic reticulum
A. Post pituitary B. Liver B. Nerve cell vesicles
C. Kidney D. Small intestine C. Aggregated mitochondria
D. Deposits of pigmented granules
69. Calmodulin activates
A. Muscle phosphorylase B. Protein kinase 77. Most diffusible ion in excitable tissue is
C. 2,3 DPG D. Glucokinase A. Na+ B. K+ C. PO4- D. Cl-

70. Increased blood viscostiy and slow circulation 78. The state of Iron responsible for O2 transport
causes A. Fe++ B. Fe+++ C. Both D. None
62.A 63.D 64.B 65.C 66.B 67.A 68.C 69.A 70.A 71.C 72.A 73.A 74.D 75.C 76.A 77.B 78.A

22
 Basic Concepts

79. Which of the following is the calcium ion binding 88. W. Milieu interior was coined by–
protein: (DNB Pattern) A. Claude Bernard B. Sherrington
A. Troponin B. Calmodulin C. Both D. None C. Weber D. Huxley

80. The motility of cell is due to 89. In Preload, there is

A. actin B. calmodulin A. isotonic contraction without shortening of muscle
C. tropomyosin D. microfilaments fibres
B. isotonic contraction with shortening of muscle fibres

Chapter - 1
81. Compound action potential is seen in C. isometric contraction without shortening of muscle
A. Motor nerve to spindle B. Slow pain fibres fibres
C. Mixed nerve D. Single axon D. isometric contraction with shortening of muscle
fibres
82. Chronaxie is minimum in?
A. Myelinated.nerve B. Unmyelinated.nerve 90. Osmotic principle was given by-
C. Red muscle fibres D. White muscle fibres A. Bernoulli B. Van’t hoff C. Pascal D. Boyle

83. After chloride ions, which of the following ion is 91. ECF measured by
the most abundant anion in blood plasma: A. Inulin B. D2O
A. Phosphates B. Calcium C. Evans blue dye D. PAH

Basic Concepts
C. Bicarbonates D. Potassium
92. Plasma volume measured by
84. amplitude of action potential can be increased A. Inulin B. D2O
maximally by C. Evans blue dye D. PAH
A. decreased absolute refractory period
B. increased no. of open Na+ channel 93. True regarding G proteins? (AIIMS May 08)
C. increased no. of open K+ channel A. There exists two isoforms of G protein
D. increased frequency of opening of Na+ channel B. Essentially function as “on-off” switches for cell
signaling.
85 which of the following increases particle diffusion C. Receptors coupled to G-proteins are those for
across the cell membrane : catecholamines, Gn RH, beta-adrenergics, and TRH.
A. increasing lipid solubility of the membrane D. Decreased G-protein activity is seen in—
B. increasing the size of molecule Pseudohypoparathyroidism
C. increasing the thickness of membrane
D. all of the above 94. Point the true statement? (AIIMS May 08)
A. Facilitated diffusion does not require energy
86. Thin filament are made up of B. Osmosis is receptor mediated molecule transport
A. Actin B. Tropomyosin C. Passive diffusion helps for signal transmission across
C. Troponin D. All of the above membrane
D. Glucose is transported by passive diffusion
87. Relaxation protein is
A. Tropomyosin B. Actin 95. Not found in cell membrane of animal:
C. Myosine D. Dystrophin A. Lecithin B. Cholesterol
C. Carbohydrate D. TG
79.C 80.A 81.C 82.A 83.C 84.B 85.A 86.D 87.A 88.A 89.B 90.B 91.A 92.C 93.A 94.A 95.D

23
 Physiology

96. The second messengers cyclic AMP and cyclic GMP

(A) Activate the same signal transduction pathways
(B) Are generated by the activation of cyclases
(C) Activate the same protein kinase
(D) Are important only in sensory transduction

97. Several segments of the polypeptide chain of integral membrane proteins usually span the lipid bilayer.
These segments frequently
(A) Adopt an α-helical configuration
(B) Contain many hydrophilic amino acids
(C) Form covalent bonds with cholesterol
(D) Contain unusually strong peptide bonds

98. The electrical potential difference necessary for a single ion to be at equilibrium across a membrane is best
described by the
(A) Goldman equation
(B) van’t Hoff equation
(C) Fick’s law
(D) Nernst equation

99. During regulatory volume decrease, many cells will increase

(A) Their volume
(B) Influx of Na+
(C) Efflux of K+
(D) Synthesis of sorbitol

100. At equilibrium the concentrations of Cl- inside and outside a cell are 8 mmol/L and 120 mmol/L,
respectively. The equilibrium potential for Cl- at 37oC is calculated to be
(A) +4.07 mV
(B) -4.07 mV
(C) +71.7 mV
(D) -71.7 mV

101.The volume of the extracellular fluid is most closely related to the amount of which solute in this
compartment?
(A) HCO3 -
(B) Glucose
(C) K+
(D) Na+

102. Select the true statement about membrane phospholipids.

(A) A phospholipid contains cholesterol
(B) Phospholipids move rapidly in the plane of the bilayer
(C) Specific phospholipids are always present in equal proportions in the two halves of the bilayer
(D) Phospholipids form ion channels through the membrane

96.B 97.A 98.D 99.C 100.D 101.D 102.B

24
 Basic Concepts

103.The diagram below shows what

a. hagen-poisseuille principle

b. stewart-hamilton principle

c. bernoulli's principle

Chapter - 1
d. universal gas equation

Basic Concepts
103.C

25
 Physiology

26
 Basic Concepts

Explanation
Chapter-1 Basic Concepts

1. Ans. D. Lead
(Ref: Ganong 23rd Ed , Chapter 27. Pg 451)
Table 27–3 Trace Elements Believed Essential for Life.
Arsenic Manganese
Chromium Molybdenum

Chapter - 1
Cobalt Nickel
Copper Selenium
Fluorine Silicon
Iodine Vanadium
Iron Zinc
a. Manganese is an essential trace nutrient in all forms of life.
b. The classes of enzymes that have manganese cofactors are very broad and include oxidoreductases,
transferases, hydrolases, lyases, isomerases, ligases, lectins, and integrins.
c. The reverse transcriptases of many retroviruses (though not lentiviruses such as HIV) contain manganese.
d. The best known manganese-containing polypeptides may be arginase, the diphtheria toxin, and Mn-
containing superoxide dismutase (Mn-SOD).

Basic Concepts
2. Ans. D. GLUT 4 Ref: Ganong – 23rd Ed. Pg 338
GLUT 1 Q Basal glucose uptake Placenta, blood-brain barrier, brain, red cells,
kidneys, colon, many other organs

GLUT 2 Q B-cell glucose sensor; transport out of B cells of islets Q, liver Q, epithelial cells of small
intestinal and renal epithelial cells intestine, kidneys

GLUT 3 Basal glucose uptake Brain Q, placenta, kidneys

GLUT 4 Q Insulin-stimulated glucose uptake Skeletal and cardiac muscle, adipose tissue,

GLUT 5 Fructose transport Jejunum, sperm Q

GLUT 6 None Pseudogene

GLUT 7 Glucose 6-phosphate transporter in Liver, other tissues

endoplasmic reticulum

3. Ans. A. Hypothyroidism
A plasma Na+ concentration less than 135 mmol/L Q is known as hyponatremia. In some conditions plasma
osmolality may be normal or increased in cases of hyponatremia, and this condition is known as
pseudohyponatremia. Common, causes of pseudohyponatremia are as under:
Normal plasma osmolality Increased plasma osmolality
• Hyperlipidemia Q • Hyperglycemia Q
• Hyperproteinemia Q • Mannitol Q
Q
• Post-transurethral resection of prostate • Post-transurethral resection of bladder tumor Q

27
 Physiology

• Raised plasma glucose Q • Raised plasma triglyceride Q

4. Ans. A. Metabolic acidosis
Acute salicylate poisoning is more common in children. Serious toxicity occurs when the serum salicylate level is
more than 50 mg/dl. Q As it is an acid it produces METABOLIC ACIDOSIS Q and it directly stimulates the respiratory
centers to produce hyperventilation Q leading to respiratory alkalosis. Other features are:
a. Vomiting Q b. Dehydration Q c. Electrolyte imbalance Q
d. Restlessness Q e. Hyperpyrexia Q f. Seizures Q
g. Coma and death Q

5. Ans. A. Total body water

6. Ans. B. Cutaneous
The capacity of tissues to regulate their own blood flow is known as auto-regulation.
It is well developed in KIDNEY Q, but it has also been observed in the MESENTERY Q, SKELETAL Q MUSCLE Q, BRAIN Q,
LIVER Q and MYOCARDIUM Q. except skin.

7. Ans. C. 7.4
The pH of extra cellular fluid is 7.40 and under normal conditions it usually varies less than +/- 0.05 pH units Q.

8. Ans. B. Adenosine triphosphate

ADENOSINE TRIPHOSPHATE (ATP) is a compound of adenosine which contains three phosphoric acid groups. ATP is
present in all cells but particularly in muscle cells When it is split by enzyme action energy is produced.

9. Ans. A. Drumstick chromatin projecting from the nuclei of 1 – 15% of polymorphonuclear leucocytes in males
a. According to the Lyon hypothesis, one of the two X chromosomes in each somatic cell of the female is
genetically inactivated
b. The BARR BODY REPRESENTS THE INACTIVATED X CHROMOSOME Barr body is the sex chromatin mass
seen near the nuclear membrane of normal female somatic cells
c. Thus, there is a barr body for each X chromosome in excess of one in the cell Q
d. The inactive X chromosome is also visible as a small drumstick of chromatic projecting from the nuclei of 1-
15% of the polymorphonuclear leukocytes in females but not in males.

10. Ans. B. Maintains the blood flow

The capacity of tissues to regulate their own blood supply is known as auto-regulation. This capacity is developed in
kidney but is also seen in mesentery, skeletal muscles, brain, liver and myocardium.

11. Ans. A. Skeletal muscle

Oxygen Consumption of Body
• Whole body 250 ml/minute Q
• Liver 51 ml/minute Q
• Skeletal muscle 50 ml/minute Q
• Brain 49 ml/ minute Q
• Rest of the body 44 ml/minute Q
• Heart muscle 29 ml/minute Q

28
 Basic Concepts

• Kidney 18 ml/minute Q
• Skin 12 ml/minute Q

12. Ans. D. Na during action potential

Sodium channels are blocked by a toxin called TETRODOTOXIN when this toxin is applied to the outside of cell
membrane where sodium activation gates are located.

13. Ans. A. Niacin

Chapter - 1
Clinical deficiency of NIACIN results in dermatitis, glossitis, stomatitis, diarrhea, proctitis, mental depression ,
abdominal pain, vaginitis, dysphagia, and amenorrhea and the condition is known as PELLAGRA.

14. Ans. B. HCO3- concentration

Concentration of potassium and bicarbonate ions in saliva is greater than that of plasma because of their active
secretion Q

15. Ans. C. Na+ with glucose symport

16. Ans. A. Na+ symport

The glucose and sodium ions share the same symport.

Basic Concepts
17. Ans. C. Tritium oxide
Radioactive water (TRITIUM Q) or heavy water (deuterium Q) can be used to measure total body water. Tritium is
also used as a tracer in chemical and biochemical research.

18. Ans. D. Amount of lean body mass

BASAL METABOLIC RATE is the metabolic rate measured under basal conditions which are enumerated below:
a. 12 hr after eating
b. After a restful sleep
c. No exercise or activity preceding test
d. Elimination of emotional excitement
e. In a comfortable temperature
f. Lean body mass
It is expressed in terms of kilocalories per square meter of body surface per hour Q.

29
 Physiology

19. Ans. A. Liver

a. KETONE BODIES increase in the blood as a result of faulty carbohydrate metabolism.
b. They are formed in liver and consist of acid, acetoacetic acid, and acetone.
c. They are increased in patients with untreated or inadequately controlled diabetes mellitus and are the
chief cause of acidosis.
d. They may also occur in other metabolic disorder.

20. Ans. ‘B’ Protein

The plasma membrane is about 40 % lipid and 60 % PROTEIN, but these proportions vary greatly, from 20 to 75%
protein depending on the type of cell. Most of the lipids in the plasma membrane are phospholipids. Q

21. Ans. B. ECF has high Na+: K+ ratio

Distribution of Total Body Water (60% Body Weight)
• INTRACELLULAR SPACE 40% body weight Q
• EXTRACELLULAR SPACE 20% body weight Q
• INTERSTITIAL FLUID 15% body weight Q
• PLASMA VOLUME 5% body weight Q
Constituents of ECF
• Na+ 142 mmol/L Q
+
•K 4.2 mmol/L Q
• Ca++ 1.2mmol/L Q
-
• Cl 108 mmol/L Q
• HCO3- 28 mmol/L Q
• Oxygen 40 mmHg Q
• CO2 40 mmHg Q
• Sugar 58 mg/dL Q
• pH 7.4 Q
• Temperature 98.4°F or 37°C Q

22. Ans. D. Chylomicron

LIPOPROTEIN TRIGLYCERIDE SUM OF FREE AND ESTERIFIED CHOLESTEROL PHOSPHOLIPID
Chylomicrons 80-95 Q 2-7 3-9
VLDL 55-80 5-15 10-20
IDL 20-50 20-40 15-25
LDL 5-15 40-50 20-25
HDL 5-10 15-25 20-30

23. Ans. B. Collagen

a. Collagen is the major macromolecule of connective tissue and is the most common protein in the animal
world Q.
b. The most important property of collagen molecule is their TRIPLE HELIX structure consisting of three
polypeptide subunits. Collagen is of five types.

30
 Basic Concepts

c. Helix, shape in the form of a spiral coil, either cylindrical or conical, along its length.

24. Ans. B. The action of nitric oxide

a. Nitric oxide is a simple molecule with broad and diverse effects in human body.
b. It was reported by Furchgott and Zawadzki in 1980 that a product of the endothelial cell causes
vasorelaxation, and this ENDOTHELIUM-DERIVED RELAXING FACTOR (EDRF) was ultimately found to be
NITRIC OXIDE Q.

Chapter - 1
25. Ans. B. Vasoconstriction
a. The production of NITRIC OXIDE by nitric acid synthetase in macrophages, lymphocytes, and neutrophils is
a vital determinant of immune and inflammatory responses.
b. The bactericidal, fungicidal, viricidal, parasiticidal, and TUMORICIDAL Q activities of macrophages are due
to vigorous elaboration of nitric oxide by nitric acid synthetase.
c. Nitric oxide RELAXES GASTROINTESTINAL SMOOTH MUSCLE Q and leads to reduced motility, relaxation of
the sphincter of Oddi , and relaxation of the lower esophageal sphincter.
d. Nitric oxide is a decisive determinant of basal vascular tone, and a deficiency of nitric oxide is associated
with HYPERTENSION Q .

26. Ans. B. Dynein

Basic Concepts
DYNEIN is a very large protein that has a molecular configuration similar to arms. Contraction of these arms
facilitates the movement of cilia and flagella of bacteria.

27. Ans. C. Bicarbonates

After chloride ions, bicarbonate ions are the most abundant extracellular anion Q.
APPROXIMATE COMPOSITION OF BLOOD PLASMA
Anions Cations
Q
Chloride ions 113 mEq/L Sodium ions 152 mEq/L
Bicarbonate ions 27 mEq/L Q Potassium ions 5 mEq/L
Anionic proteins 16 mEq/L Calcium ions 5 mEq/L
Organic acids 6 mEq/L Magnesium ions 3 mEq/L
HPO4- - 2mEq/L
SO4- - 1 mEq/L
APPROXIMATE COMPOSITION OF INTERSTIAL FLUID
Anions Cations
Chloride ions 117 mEq/L Sodium ions 143 mEq/L
Bicarbonate ions 27 mEq/L Potassium ions 4 mEq/L
Anionic proteins 2 mEq/L Calcium ions 5 mEq/L
Organic acids 6 mEq/L Magnesium ions 3 mEq/L
HPO43- 2mEq/L
SO4-- 1mEq/L

31
 Physiology

28. Ans. C. Endothelial cells

Nitric oxide, a compound released by the endothelium of blood vessels as endothelium derived relaxing factor
(EDRF) is also produced in the brain

29. Ans. A. Gap junctions

a. Two types of ‘junctions’ form between the cells that make up tissue; junctions that fasten the cells to one
another and to the surrounding tissues, and the junctions that permit transfer of ions and other molecules
from one cell to another
b. The junctions that tie cells together are known as tight junctions or desmosomes.
c. The junctions by whom molecules are transferred are known as gap junctions Q

30. Ans. A. Chemotaxis

a. Chediak-Higashi syndrome is a rare disease with autosomal recessive Q inheritance.
b. Neutrophils and all cells containing lysosomes from patients with Chediak-Higashi syndrome
characteristically have large granules.
c. Chediak-Higashi syndrome neutrophils and monocytes have impaired chemotaxis and abnormal rates of
microbial killing slow rates of fusion of the lysosomal granules with phagosomes.
d. Natural killer cell function is also impaired

31. Ans. A. Mediates intracellular activities of enzymes and hormones

32. Ans. D. Carrier proteins

33. Ans. A. Intracellular volume is 28 L

D2O = Total body water = 42L , ECF = 14L
Intracellular volume is 42-14 = 28L.

34. Ans. B >A

a. The sodium-potassium pump is the most commonly active transport mechanism in the body.
b. This pump is present in all cells in body and is responsible for maintaining the sodium and potassium
concentration differences across the cell membrane as well as for establishing a negative electrical
potential inside the cells.

32
 Basic Concepts

c. When 3 sodium ions bind on the inside of this carrier protein and 2 potassium ions on the outside, the
ATPase function of the protein becomes activated Q.
d. This then cleaves 1 molecule of ATP, splitting it to ADP and liberating a high-energy phosphate bond of
energy.
e. This energy is then believed to cause a conformational change in the protein carrier molecule, extruding
the sodium ions to the outside and the potassium ions to the inside.
f. By this process a net of 1 positive charge is moved from the interior of the cell to the exterior for each
revolution of the pump.

Chapter - 1
g. This creates positivity outside the cell but leaves a deficit of positive ions inside the cell; that is, it causes
negativity on the inside.
h. Therefore, the sodium-potassium pump is said to be electrogenic Q because it creates an electrical
potential across the cell membrane as it pumps.
i. One of the most important functions of the sodium-potassium pump is to control the volume of the cells.
Without function of this pump, most cells of the body would swell until they burst Q.

35. Ans. B. Fatty acids

Under normal conditions, about 3 molecules of fatty acid combine with each molecule of albumin, but as many as

Basic Concepts
30 fatty acid molecules can combine with a single albumin molecule when the need for fatty acid transport is
extreme.

36. Ans. B. Down’s syndrome

a. Low levels of maternal serum alpha-fetoprotein (MSAFP) may be associated with chromosomal
abnormalities.
b. Altered levels of human chorionic gonadotropin (hCG) and unconjugated estriol (UE3) also may be
associated with fetal chromosomal abnormalities.
c. A fetus with trisomy 21 results in hCG levels that are higher than expected and UE3 levels that are
decreased Q.
d. A triple panel screen in combination with maternal age can be used to estimate the risk of fetal trisomy
21 for an individual woman.

37. Ans. A. Interphase

The inactivated X is almost entirely late replicating During interphase it is tightly condensed Q and can be visualized
microscopically as sex chromatin’ or the Barr body.

38. Ans. C. Facilitate the transport of each other from the intestinal mucosa to blood
An example is the symport in the intestinal mucosa that is responsible for the co-transport by facilitated diffusion
of Na+ and glucose from the intestinal lumen into mucosal cells
Composition of new WHO low osmolarity ORS
Electrolytes Mmols/litre
Dextrose 75 Q
Sodium 75 Q
Citrate 10 Q

33
 Physiology

Potassium 20 Q
Chloride 65 Q
Osmolarity 245 Mmols/litre Q
Composition of 4. 3 g ORS powder to be dissolved in 200 ml of water
Anhydrous Dextrose IP 2.7 g Q
Sodium Chloride IP 0.52 g Q
Sodium Citrate IP 0.58 g Q
Potassium Chloride IP 0.3 g Q
Excipients q.s. Q

39. Ans. A. Alpha HCG

a. The clinical evaluation of patients with myeloma includes a careful physical examination searching for
tender bones and masses. It is also important to quantitate serum beta microglobulin. Q
b. Prostate, breast, and thyroid carcinomas are suggested, respectively, by a reaction with antibodies to PSA
or prostatic alkaline phosphatase, gross cystic fluid protein, or thyroglobulin. Q
c. The finding of alpha-fetoprotein, beta hCG or placental alkaline phosphatase staining is very helpful in
assigning a germ cell origin Q.

40. Ans. C. Cerebral microcirculation

All endothelial cells except those in the cerebral microcirculation produce thrombomodulin Q. It is a thrombin-
binding protein which expresses it on their surface.

41. Ans. D. Kidney

Antigen presenting cells (APC): -
‘The three cell types that are the primary presenters of antigen peptide fragments to T-cells, are:
a. dendritic/Langerhans cells (in skin),
b. monocytes — macrophages (in lymph nodes, spleen) and
c. B-lymphocytes.”

42. Ans. D. Non constitutive exocytosis

Exocytosis 
a. This extrusion process, requires Ca++ and energy, along with docking proteins.
b. There are two pathway by which secretion from the cell occurs: -
i. Non constitutive pathway  proteins from the golgi apparatus initially enter secretory granules,
where processing of prohormones to the mature hormones occurs before exocytosis.
ii. Constitutive pathway  prompt transport of proteins to the cell membrane in vesicles, with little or
no processing or storage.
c. The non constitutive pathway is sometimes called the regulated pathway, but this term is misleading
because the output of protiens by the constitutive pathway is also regulated.

43. Ans. A. Cytochrome oxidase and molecular oxygen

Cyanide: -
a. Causes histotoxic hypoxia Q, inhibit tissue oxidative process (cellular respiration), by inhibiting cytochrome
oxidase, there by cells can not utilize O2 (histotoxic hypoxia)

34
 Basic Concepts

b. Methylene blue or nitrites are used to treat cyanide poisoning (act as Antidote) Q hyperbaric oxygenation is
also helpful.

44. Ans. A. Gap junctions

Two types of junctins form between the cells that make up tissues.
a. Junctions that fastens the cells to one another and to surrounding tissues.
b. Junctions that permit transfer of ions and other molecules from one cell to another.
The junction that tie cells together and endow tissues with strength and stability include the tight junction, which is
also called zonula occludens Q The desmosomes and zonula adherens holds cells together and the hemidesmosome

Chapter - 1
and focal adhesion attatch cells to their basal laminas. Tight junctins between epithelial cells are also essential for
transport of ions across epithelia. The junction by which molecules are transferred is the gap junction Q.

45. Ans. D. Acidosis leads to movement of potassium from extracellular to intracellular fluid compartment.
a. Potassium is the major intracellular cation. Q The normal plasma concn of K+ is in 3.5 to 5.0 mmol/L, where
as that inside cells is about 150 m mol/L.
b. Tissue destruction or breakdown results in release of the intracellular K+ [leading to hyperkalemia] where
as the production of new cell shift K+ out of ECF. Finally modulate to severe exercise may be associated
with K+ release from muscle, leading to glycogenolysis and local vasodilation.
c. The role of extracellular pH in K+ balance relates to the underlying acid base disorder. In metabolic

Basic Concepts
acidosis 60% of the H+ load is buffered inside cells. To maintain electroneutrality, the H + ion must either be
accompanied by an anion or exchanged for intracellular K+ (leading to hyperkalemia).
d. CMDT 2001, page 877 also writes, that intracellular potassium shifts to the extracellular fluid in
hyperkalemia associated with acidosis. Serum K+ concn rises about 0.7 meq/L for every decrease of 0.1 pH
unit during acidosis. Q
e. Organic acidosis are not usually associated with a pH - related K+ shift, since anions such as lactate and -
hydroxybutyrate can be readily taken up by the cells Q The converse movement of K+ into cells, may be
seen with metabolic alkalosis [i.e. that from extracelluar to intracellular fluid compartment as in option 4].

46. Ans. D. 70%

a. Cerebral O2 consumption is 39% of normal (ie 61 % less than normal) at 30°C and 35% (ie 65% less) at 28 oc.
b. With each fall of 1°C metabolism is reduced by 6.7% so in 10oC fall it will decrease by 70%
c. Other Effects' Q
R - Rise in S. K+ Q
O – O2 dissociation curve shifted to left Q
A - Acidosis Q
D – Duration & magnitude of Block (N-M junction) by depolarizing drugs are increased and non
depolarizing drug is reduced. Q

47. Ans. B. Cyclic AMP

"Dopamine is a Neurotransmitter (Ligands), which binds on D-Receptor and either for  or  cyclic AMP (second
messenger) in the brain.

48. Ans. C. Four

a. Peptide Bond formation (Protein synthesis) : requires hydrolysis of high energy phosphates bonds - as

35
 Physiology

follows
i. The charging of the tRNA molecule with amino acylmoiety require hydrolysis of an A TP to an AMP,
equivalent to the hydrolysis of 2 ATPs to 2ADPs and phosphates.
ii. The entry of the aminoacyl-tRNA into A site results in the hydrolysis of one GTP to GDP (3) The
translocation of the newly formed peptidyl-tRNA in the A site into the P site by eEF-2 similarly
result in the hydrolysis of GTP to GDP and phosphate.
b. "Thus, the energy requirements for the formation of one peptide bond include the equivalent of the
hydrolysis of 2ATP molecules to ADP and 2 GTP molecules to GDP, or the hydrolysis of 4-high energy
phosphate bonds.

49. Ans. A. Absent brain stem reflexes

Brain death:
a. In order to establish brain death, Q the irreversibly comatose pt must be shown to have lost all brain stem
reflex responses, including the pupillary, corneal, oculocephalic, oropharyngeal, and respiratory reflexes;
and should have been in this condition for at least 6 hours.
b. Spinal reflex movements do not exclude the diagnosis, but ongoing seizure activity or decerebrate or
decorticate posturing is not consistent with brain death. Q
c. An isoelectric electroencephalogram, when the recording is made according to the recommendations of
the American electroencephalo-graphic society, is especially helpful in the confirming the diagnosis.
d. Alternatively, the demonstration of an absent cerebral circulation by I.V. radioisotope central angiography
or by four-vessel contrast cerebral angiography can be confirmatory.

50. Ans. C. 7 cal/gm

a. Alcohol gives  7 cal/gm Q
b. Metabolism of alcohol follows zero-order kinetics, i.e. a constant amount (8-12 ml of absolute
alcohol/hour) is degraded in unit time.

51. Ans. B. Enzymatic composition

a. Hormones of drugs require receptors for their action. Some receptors are directly attached to effector
molecules and some receptors are coupled to effector molecules and some receptors are couple to
effectors by second messengers
b. These second messengers are so named because they intervene b/w the original message and the
ultimate effect on the cell.
c. One of the many sequence of events which follows, when a hormone or a drug combines with receptors
coupled to second messengers in given below.

Hormone combines with a receptor


Now receptor changes shape

Combines with Gs protein

Gs protein release GDP and binds GTP

36
 Basic Concepts


The activates adenylate cyclase

ATP converted to cAMP

 cAMP

Activates protein kinase


Chapter - 1
Protein kinase phosphorylase serine or threonine

Phosphorylated proteins

Inactivates or activates enzymes
d. Cells respond differentially to a second messenger because the enzymes present in the cell respond
differentially to increase or decrease in cAMP For e.g.
i. Increase in cAMP will cause activation of those enzymes which require phsophorylation to get
activated where as enzymes which requiring dephospharylation for their active state are inactivated.
e. Many students believe that the answer should be 'receptors'

Basic Concepts
f. Now don't get confused. Note that: second messengers respond differentially to a hormone or drug
because of receptors but cells respond to second messengers differentially because of different enzymes. Q

52. Ans. B. 306 mOsm/kg

a. Osmality (mOsm/kg) Q= 2[Na+ cone. in mEq/l] + 0.55 [Glucose cone. In mg/dl] +.36 [BUN in mg/dl]
b. The values in this child:
- Na+  125 meq/l
- Glucose  108 mg/dl
- BUN  140 mg/dl
c. Putting these values in the equation
d. Osmolality = 2 [125 meq/l] + 0.055 [108 mg/dl]
+ 0.36 [140 mg/dl]
= 250 + 5.94 + 50.4 = 306.34

53. Ans. D. Adenylate cyclase

Adenylate cyclase is a membrane-bound enzyme that converts A TP to 3,5 - adenosine monophosphate (also called
cyclic AMP or cAMP)

54. Ans. A. Inositol triphosphate

a. Inositol, 4, 5-triphosphate (a inositol derivative) bind to receptors on the endoplasmic reticulum, causing a
rapid release of Ca++ from intracellular stores.
b. The resulting increase in intracellular Ca++ permits the formation of a calcium calmodulin complex that
mediates a wide range of effects of ~e intracellular Ca ++
c. Calmodulin is the most widely distributed small calcium-binding proteins.
d. The binding of 4 molecules of Ca++ to calmodulin triggers a conformational change such that the activated

37
 Physiology

Ca ++ calmodulin complex bind to the and activates protein molecules, often enzymes.

55. Ans. B. Calmodulin

56. Ans. A. Laminin

Basement membrane is made of collagen type 4, laminins, fibronectin and proteoglycans. Laminin is glycoprotein
while collagen type 4 is not.

57. Ans. B. Sympathetic Cholinergic

Sweating:
a. Centre is located in Anterior hypothalamus preoptic area.
b. In general, most sweat lands are innervated by sympathetic cholinergic nerve fibers i.e. Ach is
c. the transmitter; therefore sympathetic stimulation causes sweating whereas parasympathetic stimulation
has no effect.
d. But in palms and soles sweat glands are innervated by sympathetic adrenergic nerve fibers. Q

58. Ans. B. Binds to proteins

Calcium metabolism
a. The body of a young adult human contain about 1100 gm calcium (=27.5 mol. of calcium)
i. 99% of calcium is present in bones.
ii. 0.1 % of calcium present in ECF
iii. 0.5 to 1% of skeletal calcium is freely exchangeable with that in the ECF.
iv. Plasma calcium level- 9-11 mg/dL : of which
 50% ionized (diffusible)
 Calcium complexed to anions ( with phosphate, citrate, HC03 - Diffusible) Q
 Protein bound calcium - 41 % (non diffusible) with - Albumin (major) - Globulin
It is free, ionized calcium (Ca++, divalent cation) in the body fluid that is vital second messenger and is
necessary for blood coagulation, muscle contraction (all types) and nerve function.
b. Absorption and Excretion:
i. Intestine: the feedback controlled hormonal regulation of intestinal absorptive efficiency result in a
relatively constant daily net calcium absorption of approximately 200 to 400 mg/day despite large
changes in daily dietary calcium intake.
 Daily intake  400 - 1500 mg/day (Av. = 1000 mg/day)
 On average 350 mg - absorbed
 250 mg/day calcium enters the intestine via secretions and sloughed mucosal cell  lost in faces
 Total ingestion = 1000 mg/day
 Total loss = 650 + 250 = 900 mg/day
 Therefore 90% of daily intake of calcium is excreted in faces. Q

Site  calcium is absorbed in upper small intestine (Duodenum and proximal jejunum) Q
Mechanism of intestinal absorption:
o Active (Transcellular) Mechanism  Main mechanism  controlled principally by Vit D3
o Passive (paracellular) mechanism: accounts for 5%
o Optimal rates of calcium absorption require gastric acid.
o High calcium intake  Serum Ca++   synthesis of Vit D3  intestinal absorption and

38
 Basic Concepts

vice versa.

ii. Renal regulation of calcium metabolism

 Approximately 10% (100 mg/day) of ingested calcium is excreted in urine Q
 99% of filtered calcium is reabsorbed
 In PCT  65% reabsorption  via passive, paracellular route, coupled to con comitant Nacl
reabsorption, not specifically regulated.
o In the cortical thick ascending limb of Henle's Loop (cTAL)  20% reabsorption  via

Chapter - 1
passive paracellular mechanism  it requires paracellin-l for reabsorption of calcium
and is inhibited by  plasma Ca++ and Mg++, acting via CaSR.
o In DCT  10% reabsorbed -7 regulated by PTH (Transcellular active mechanism)

59. Ans. B. Brain ischemia

a. Creatinine Kinase (CPK) - iso-enzymes
i. Three types
ii. Each iso-enzymes is a dimer, composed of two protomers 'M' (muscles) and 'B' (Brain)
iii. CPK (CK) isoenzymes can be separated by
a. Electrophoresis

Basic Concepts
b. Ion exchange chromatography
Types Electrophoretic mobility Distribution in tissues
CPK-1, BB Fast moving (more –ve) Brain
CPK-2, MB ----- Myocardium
CPK-3, MM Slow moving Skeletal muscles
b. Acute coronary syndrome (ACS) : group - into
i. Acute MI with ST-segment Elevation (=STEMI) and
ii. Unstable angina (UA) and non-ST segment elevation MI (UA/NSTEMI)
c. CK-MB (CPK-2) and troponin - a much more specific marker of mycocardial necrosis (MI)
d. The Diagnosis of NSTEMI is established if a patient with the CIF of UA develops evidence of myocardial
necrosis as reflected in elevated cardiac biomarkers. Elevated levels of these markers distinguish patient
with NSTEMI from those with UA.
e. Unstable angina:
a. Diagnosis of UA is based largely on the clinical presentation
b. UA is defined as angina pectoris or equivalent ischaemic discomfort with at least one of three
following features:
i. It occurs at rest (or with minimal exertion) usually lasting> 10 min.
ii. It is severe and of new onset (i.e. within the prior 4 to 6 wk) and/or
iii. It occurs with a crescendo pattern (i.e. distinctly more severe, prolonged or frequent than
previously)
f. Cardia specific troponin (cTnT and cTnI)  their measurement is of considerable diagnostic usefulness and
they are now the Preferred biochemical markers for MI Q. Their levels may remain elevated for 7-10 days
Q
after STEMI.

60. Ans. B. It is rapidly metabolized

"Ach is not used because of evanescent and non-selective action"

39
 Physiology

61. Ans. B. Vasodilatation

a. Temperature Decreasing Mechanism when body is too hot
i. Vasodilation (cutaneous) ii. Sweating iii. Decrease heat production
b. Temperature increasing mechanisms when body is too cold
i. Skin vasoconstriction ii. Pilorection
c. Increase heat production by
i. Shivering
ii. Sympathetic stimulation (via beta 3 receptor, Nor Ad, Non-shivering thermogenesis, chemical
thermogenesis, uncouple oxidative phosphorylation)
iii. Thyroxin secretion.

62. Ans. A. Interphase

a. The two X-chrmosomes in females dipliod somatic cells exhibit striking morphologic and functional
differences:
i.
One X-chromosome is in a highly condensed (Heteropyknotic) state in INTERPHASE and is visible as sex
chromatin (BARR BODY Q. It completes DNA synthesis later than any other chromosome, and the
action of genes located on the precociously condensed segments is suppressed by transcriptional
inactivation.
ii. The other X-chromosome, the single X-chromosome in male somatic cells, is in a highly extended
(isopyknotic) state during INTERPHASE. It completes DNA replication with most of the complement
and is genetically active.
b. The discordant behavior of two homologous X-chromosomes in female somatic cells serves as a
mechanism of dosage compensation.

63. Ans. D. Bronchogenic carcinoma

"Increased serum levels of ACE are suggestive of sarcoidosis but ACE can also be elevated in miliary TB, berylliosis,
asbestosis, and silicosis.

64. Ans. B. Shift of blood from shell to core

Body responses on exposure to cold:
Keep its internal temperature constant by increasing heat production or by reducing heat loos.
a. Heat loss in reduced by cutaneous vasoconstriction this reduces the amount of heat transferred by the blood
from the body core to the body surface (shell). This may raised the B.P. Heat loss is also reduced by piloerection
b. Heat production ed by:
c. es the metabolic rate
d.  Adrenaline secretion  chemical thermogenesis or non shivering thermogenesis from brown fat (by
uncouple oxidative phosphorylation). Since brown fat almost absent in adult, so it is not important in adult.
But important in neonates, in which non shivering thermogenesis, increases the heat production by 100%
i. Increased thyroxin productin as a long term cause of increased Heat production  it requires several weak
ii. Shivering  during maximal shivering body heat production can rise to four to five times normal 
shivering centre located in dorsomedial portion of the posterior hypothalamus
iii. Voluntary muscular activity.

40
 Basic Concepts

65. Ans. C. A.M. Temp. > 98.4°F

Normal body temperature: ~
a. Humans are "warm-blood" (homeothermic)
b. Traditional normal value for oral temp. is 37°C (98.6 oF), but the morning oral temp (in young adult) 
36.7oC with SD of 0.2oC.
c. 95% of all young adult have morning oral temp of 36.3 to 37.1oC (97.3 to 98.8oF; mean  1.96 SD)
d. Extrimites are generally cooler than the rest of the body
e. The temperature of scrotum is 32°C (5oC less than body temp) Q

Chapter - 1
f. The rectal temp is the representative of the temp. at the core of the body and varies least with changes in
environmental temp.
g. Oral temp is normally 0.5oC < rectal temp. Q
h. The Normal human core temp undergoes a regulalar circadian fluctuation of 0.5 to 0.7 oC:
i. Lowest at 6 AM (morning)
ii. Highest at PM (Evening)
iii. Lowest during sleep
i. Hypothalamus regulate the temperature: Q
i. Anterior hypothalamus responses to heat. Q
ii. Posterior Hypothalamus responses to cold Q

Basic Concepts
66. Ans. B. Magnesium
ATP:
a. High energy phosphate (ATP) play a central role in energy capture and transfer.
b. In its reaction in the cell, it function as the Mg++ complex.

67. Ans. A. Pumps Na against a gradient

Na+-K+ ATPase (pump):
a. Na+-K+-ATPase catalyzes the hydrolysis of ATP to ADP and uses the energy to extrude three Na+ from the
cells and take two K+ into the (ells for each mole of ATP. I.e.  the ECF Na+ cone and the K ICF cone or
the ICF Na+ cone.
b. It is an Electrogenic pump, having coupling ratio 3:2 (3Na+: 2K+) Q . Since ECF conc. of Na+ is higher than ICF
 so it pump Na+ outside call angaist conc. gradient and is similar way, the ICF conc. of K+ is more than
ECF, hence pump K+ into the cells agaist the conc. gradient.
c. Active transport of N a + and K+ is one of major energy using processes in the body on the average it
accounts for about 24% of the energy utilized by cells, and in neurons it account for 70%.
d. In Heart muscle, Na+-K+ ATPase indirectly affect Ca++ transport. Normally one Ca++ goes out side the cells
and three Na+ go inside the cells  i.e. Antiport. If the Na+-K+ ATPase activity is inhibited by Quabain and
related digitalis glycoside
i. intracellular Na+ conc. es  the Na+ gradient across the cell membrane decreases  Ca++ extrusion
decreases
ii. result in  intracellular Ca++ conc.  contraction of Heart muscle  positive inotropic effect.
e. Regulation of Na+-K+ ATPase activity:

41
 Physiology

Increased activity of pump Decreased activity of pump

Q
i. Thyroid hormone i. Dopamine inhibit the pump phosphorylation in
ii. Aldosterone Q kidney, thus causes natriuresis Q
iii. Insulin Q ii. Ouabain Q
Q
iv. G-actin
f. Pump activity is affected by second messengers  eg. cAMP and DAG.

68. Ans. C. Kidney

a. The permeability of the glomerular capillaries is about 50 times that of the capillaries in muscles.
b. Kidney can filter 125 ml/min or 7.5 l/h or 180L/day (GFR)  it shows that no organs in the body other than
kidney, permeable to such extent.
c. Since GFR is governed by the size of capillary bed, the permeability of the capillaries, and the hydrostatic and
osmotic pressure gradient across the capillary wall.

69. Ans. A. Muscle phosphorylase

a. Calmodulin-dependent protein kinases:
a. Myosin Light chain kinase b. Phosphorylase kinase
c. Ca++/calmodulin kinase- d. Ca++/Calmodulin kinase-II
e. Ca++/Calmodulin kinase-Ill

b. Calcium-phospholipid dependent protein kinase: - Protein kinase C

c. Glucokinase  present in liver and pancreatic cells  it is activated by Insulin, and its activity is ed by
Glucagon (cAMP)

70. Ans. A. RBC rouleux formation

a. Rouleaux  RBC pile one over another like a pile of coin
b. Visocity of the blood is increased by high hematocrit value (RBC counts, polycythemia) and very low
velocity and vice versa
c. At slower velocities in blood vessels axial flow of the RBC is absent ~ RBC are now scattered and cause
resistance to the movement of the fluid ~ further, at very low velocities (tviscosity) -J Rouleaux formation
of RBC may occurs, further obstructing the flow
d. Newtonian fluid ~
i. Where the viscosity does not change with change of the shearing force (velocity) and
ii. when moves through a tube, shows a laminar (stream line) flow.
e. Blood is a non-Newtonian fluid. Q
f. Fahraeus-LindQvist Effect ~ Blood flow in minute tubes exhibits for less viscous effect than it does in large
vessels.
g. Plasma skimming: (Ref Ganong 22nd)
i. In the vessels, red cells tends to accumulate in the centre (axial flow) of flowing stream
ii. Consequently, the blood along the side of the vessels has a low hematocrit, and branches leaving a
large vessels at right angles may receive a disproportionate amount of Red-cellpoor blood. This is
known Plasma skimming that is why hemotocrit of capillary blood is 25% lower than the 'whole blood
hematocrit. Q
iii. Low viscocity, high velocity ~ Axial flow of RBC ~ dec. Hematocrit ~ plasma skimming.

42
 Basic Concepts

iv. High viscosity, low velocity ~ absent axial flow of RBC ~ inc. Hematocrit ~ plasma skimming.

71. Ans. C. 130

Solution Concentration in meq/L
Na+ K+ Ca++ Cl- Citrate or lactate
Q
Ringer’s lactate 130 4 4 109 28
Darrow’s solution Q 122 36 (highest) Q - 104 54

Chapter - 1
72. Ans. A. Long arm of X chromosome
a. "The androgen receptor is a typical member of the steroid 1 thyroid family of receptors, is encoded by a
gene on the long arm of the X-chromosome" Q
b. During embryonic period, differentiation of the indifferent gonad into a testis is mediated by a single gene
on the short arm of the y-chromosome (SRY).
73. Ans. A. Extra cellular fluid
Distribution of sodium and potassium in the body
Component Amount (% of total) of
Na+ K+
1. Total intracellular 9.0 89.6

Basic Concepts
2. Total extracellular 91.0 10.4
Plasma 11.2 0.4
Interstitial fluid 29 1.0
Dense connective tissue and 11.7 0.4
Cartilage
Bone 36.5 7.6
Transcellular locations 2.6 1.0

 Extracellular fluid = 14L = 20% body weight)

= Plasma (3.5L) + interstitial fluid (10.5L)  Hence total content of sodium in ECF = 11.2%
+ 29.2% = 41.4%  % content of sodium in Bone = 36.5%

74. Ans. D. Brain, heart, kidney

Region Blood flow ' % of Total COP
- ml/min ml/100gm/min -
(1) Liver 1500 57.7 27.8
420
(2) Kidneys 1260 23.3

(3) Brain 750 54 13.9

(4) Heart 250 84 4.7
.: Brain (54) < Heart (84) < Kidneys (420)

75. Ans. C. Exercise the muscle

Muscle: size: ~

43
 Physiology

a. The basic size of a person's muscle is determined mainly by heredity plus the level of testosterone
b. However with training, the muscle can becomes hypertrophied perhaps an additional 30-40%.
c. The athlete who has enlarged his muscles through an exercise training programe likewise will have
increased muscle strength.
d. Increse cortisol for eg cushing's syndrome ~ cause catabolic effect on muscles ~ decrease protein contents
and muscles are poorly developed. (Ganong 22nd)

76. Ans. A. Rough endoplasmic reticulum

The nerve cell body (or soma) of the neuron
Contains:
a. Nucleus ~ Nucleus contain one nucleus and no centrosome..
b. Nissl bodies:
i. also called Tigroid substances Q
ii. present all over the soma except the axon hillock Q, and they extend to some extent in the dendrites.
iii. (Hi) They are basophilic Q granules,
iv. Nissl granules are organelles containing ribosomes (RNA + protein). They are similar to the rough -
surface membranes found in the cytoplasm of most cells which collectively makes up the endoplasmic
reticulum or ergastoplasm of the cell. (Samson Wright 13th/261)
v. Nissl granules disappear or degenerate when the neuron is fatigued, Anoxic or injured - k/a
Chromatolysis. Q
c. Mitochondria ~ present in soma as well as in axon.
d. Golgi apparatus ~ stained by silver chromate impregnation techniques
e. Neurofibrils

77. Ans. B. K+
Most diffusible ion in excitable tissue (nerve, muscle)  K+
Most diffusible ion ion during excitation  Na+

78. Ans. A. Fe++

"Each of four iron atoms of Hb can binds reversibly one molecule of O2. The Iron stays in ferrous state (Fe ++) so
that reaction is an oxygenation, not on oxidation".

79. Ans. C. Both

a. CALMODULIN is an intracellular protein that combines with calcium and activates a variety of cellular
processes.
b. TROPONIN is an inhibitory protein found in muscle fibers. When the action potential at the sarcolemma
causes the sarcoplasmic reticulum to release calcium ions they bind to troponin and shift tropomyosin
away from the myosin-binding sites actin thus permitting contraction.

80. Ans. A. actin

(Ref: Review of Medical Physiology- Ganong’s-23rd Edition, P-24)
a. Actin is the monomeric subunit of two types of filaments in cells: microfilaments, one of the three major
components of the cytoskeleton, and thin filaments, part of the contractile apparatus in muscle cells.

44
 Basic Concepts

b. Thus, actin participates in many important cellular processes, including muscle contraction, cell motility,
cell division and cytokinesis, vesicle and organelle movement, cell signaling,
c. And the establishment and maintenance of cell junctions and cell shape.

81. Ans. C. Mixed nerve

(Ref: Review of Medical Physiology- Ganong’s-23rd Edition, P-88)
a. The compound action potential is graded in nature, in striking contrast to the all-or-none response of
single axons.

Chapter - 1
b. There is a simple explanation for why the response of a nerve is graded and that of a single fiber is all-or-
none.
c. The nerve is composed of many fibers of different diameters, with these different diameters seemingly
distributed at random throughout the nerve.
d. Therefore mixed nerve is the best candidate as it will most likely be having different fibres unlike muscle
spindle motor having only A gamma and Slow pain fibres only C fibres.

Basic Concepts
82. Ans. A. Myelinated.nerve
a. Chronaxie is the minimum time required for an electric current double the strength of the rheobase to
stimulate a muscle or a neuron. Rheobase is the lowest intensity with indefinite pulse duration which just
stimulated muscles or nerves.
b. Chronaxie is dependent on the density of voltage-gated sodium channels in the cell, which affect that cell’s
excitability.
c. Chronaxie varies across different types of tissue: fast-twitch muscles have a lower chronaxie, slow-twitch
muscles have a higher one. There is an inverse relationship between chronaxie and conduction velocity.

83. Ans. C. Bicarbonates

84. Ans B. increased no. of open Na+ channel

(Ref: Ganong’s-23rd Edition, P-82-86)
a. Na+ is critical for the action potential in nerve cells. Action potentials are repeatedly initiated as the
extracellular concentration of Na+ is modified.
b. As the concentration of sodium in the extracellular solution is reduced, the action potentials become
smaller. Same is observed when we block sodium channels.
c. K+ channels are responsible for repolarisation, so they will rather decrease the amplitude of AP, infact if
only sodium channels were there in open state not K+, amplitude would reach close to equilibrium
potential of sodium i.e. +60 mV.
d. The absolute refractory period is a period of time after the initiation of one action potential when it is
impossible to initiate a second action potential no matter how much the cell is depolarized. So, it is not a

45
 Physiology

major factor for amplitude since no AP would occur here and if we shorten it and get 2 nd AP , its amplitude
is always less than the first one.

85. Ans. A. increasing lipid solubility of the membrane

86. Ans. D. All of the above(Ref: Ganong’s-23rd Edition, Pg95)

a. The light I band is divided by the dark Z line, and the dark A band has the lighter H band in
b. its center. A transverse M line is seen in the middle of the H band, and this line plus the narrow light areas
on either side of it are sometimes called the pseudo-H zone. The area between two adjacent Z lines is
called a sarcomere.
c. The thick filaments, which are about twice the diameter of the thin filaments, are made up of
d. myosin; the thin filaments are made up of actin, tropomyosin,and troponin.

87. Ans. A. Tropomyosin

(Ref: Review of Medical Physiology- Ganong’s-23rd Edition, Pg95-96)
a. Troponin is attached to the protein tropomyosin and lies within the groove between actin filaments in
muscle tissue.
b. In a relaxed muscle, tropomyosin blocks the attachment site for the myosin crossbridge, thus preventing
contraction, therefore also called as Relaxation protein

88. Ans. A. Claude Bernard

Milieu intérieur or interior milieu, from the French, milieu intérieur (the environment within), is a phrase coined by
Claude Bernard to refer to the extra-cellular fluid environment, and its physiological capacity to ensure protective
stability for the tissues and organs of multicellular living organisms.

89. Ans. B. isotonic contraction with shortening of muscle fibres (Ref: Ganong’s-23rd Edition, Pg101)
a. A contraction which occur without an appreciable decrease in the length of the whole muscle is called
isometric (“same measure” or length).
b. Contraction against a constant load with a decrease in muscle length is isotonic (“same tension”).
c. In preload , the load acts on the muscle even before contraction, which causes stretching of muscle fibre
and results in increased force of contraction and shortening, called as Frank Starling Law.

90. Ans. B. Van’t hoff

a. The van 't Hoff factor (named after J. H. van 't Hoff) is a measure of the effect of a solute upon colligative
properties such as osmotic pressure, relative lowering in vapor pressure, elevation of boiling point and
freezing point depression.

46
 Basic Concepts

b. The van 't Hoff factor is the ratio between the actual concentration of particles produced when the
substance is dissolved, and the concentration of a substance as calculated from its mass. For most non-
electrolytes dissolved in water, the van' t Hoff factor is essentially 1.

91. Ans. A. Inulin

92. Ans. C Evans blue dye

Plasma Volume (PV). Radiolabeled albumin or Evans Blue Dye (which binds to albumin) are commonly used.

Chapter - 1
93. Ans. A. There exists two isoforms of G protein

94. Ans. A. Facilitated diffusion does not require energy

95. Ans. D. TG

96. The answer is B. Are generated by the activation of cyclases

Ref: Ganong - Review of Medical Physiology 23rd Ed Page 42
 Cyclic nucleotides are generated by the action of either adenylyl or guanylyl cyclase on ATP or GTP, respectively.
 Cyclic AMP and cGMP activate distinct signaling pathways. For example, cAMP can activate protein kinase A, which

Basic Concepts
will phosphorylate its substrates; cGMP activates protein kinase G, which phosphorylates a different set of
substrates.
 Although signal transduction in sensory tissues involves both cAMP and cGMP, cGMP has a more important role in
signal transduction than cAMP.
 Phospholipase C activation is coupled to the activation of a G protein (Gq), not to cAMP or cGMP

97. The answer is A. Adopt an α-helical configuration

Ref: Ganong - Review of Medical Physiology 23rd Ed Page 8,9
 Membrane-spanning segments of integral proteins frequently adopt an α -helical conformation because this
structure maximizes the opportunities for the polar peptide bonds to form hydrogen bonds with one another in the
hydrophobic interior of the lipid bilayer.
 These segments are composed largely of amino acids with nonpolar hydrophobic side chains that interact with the
surrounding lipids.
 There are no covalent bonds with cholesterol or phospholipids, and the peptide bonds are not unusually strong.

98. The answer is D. Nernst equation

Ref: Ganong - Review of Medical Physiology 23rd Ed Page 7
 The Nernst equation calculates the membrane potential that develops when a single ion is distributed at equilibrium
across a membrane.
 The Goldman equation gives the value of the membrane potential when all permeable ions are accounted for.
 The van’t Hoff equation calculates the osmotic pressure of a solution.
 Fick’s law refers to the diffusional movement of solute. The permeability coefficient accounts for several factors that
determine the ease with which a solute can cross a membrane

99.The answer is C. Efflux of K+

Ref: Ganong - Review of Medical Physiology 23rd Ed Page 5
 K+ is the major intracellular ion; efflux of K+ will produce an osmotic flow of water out of the cell.
 Water exit will lead to a decrease in cell volume.
 An influx of Na+ and synthesis of sorbitol do not occur during this process because both processes would increase
intracellular osmolytes and drive water into the cell, increasing cell volume.

47
 Physiology

100. The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 7,8
By substituting in the Nernst equation
Ei – Eo = 61/–1 x log10 120/8
= -61 x 1.176
= -71.7 mV inside the cell.
Note that for Cl-, the value for z (valence) is -1

101.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 913
Na+ is the major osmotically active solute in the ECF and is the major determinant of the amount of water in and, hence,
volume of this compartment.

102.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 13

 Phospholipid molecules can rotate and move laterally within the plane of the lipid bilayer, but movement from one
half of the bilayer to the other is slow because it is an energetically unfavorable process.
 Cholesterol is an example of a separate class of lipids that do not contain fatty acids.
 Many phospholipids are distributed unequally between the two halves of the lipid bilayer. In the red blood cell
membrane, for example, most of the phosphatidylcholine is in the outer half.
 Both ion channels and symporters are membrane proteins, not phospholipids

103.Ans C bernoulli's principle

Bernoulli's principle. When fluid flows through the narrow portion of the tube, the kinetic energy of flow
is increased as the velocity increases, and the potential energy is reduced. Consequently, the measured
pressure (P) is lower than it would have been at that point if the tube had not been narrowed. The
dashed line indicates what the pressure drop due to frictional forces would have been if the tube had
been of uniform diameter. The sum of KE & PE is constant.

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 Nerve - Muscle Physiology

Chapter - 2
Nerve – Muscle Physiology

I. Anatomy Nerve :

Axon hillock : The thickened area of cell body from which axon arises
Initial segment : The first 50 to 100 m of the axon.

Nerve-Muscle Physiology Chapter - 2

Axon telodendria : Also called synaptic knobs or terminal buttons

A. Peculiarities of a neuron:
1. Nissl substance (also called Nissl bodies or granules) Tigroid Body : This is composed of large aggregations
of rough endoplasmic reticulum. The Nissl substance extends into the dendrites but is absent in axon hillock
and axon.
2. Neurofibrils:
These represent the microfilaments and microtubules of other cells of the body. (Forms neurofibrillary
tangles in Alzheimer's Disease.)
3. No centrioles

Myelin formation
i In peripheral nerves : By schwann cells.
Schwann cell forms myelin on one axon
ii In CNS By oligo dendro gliocytes
Oligodendrogliocyte from myelin on many axon

Myelin is absent at
i- Nodes of Ranvier
ii- Axonal endings
iii- Soma
iv- Initial segment

B. Position of cell body

1. It is often at the dendritic zone end of axon
2. Sometimes, it is within the axon eg. auditory nerve
3. Sometime, it is attached to the side of the axon eg. cutaneous nerve

C. Functional Areas of Neuron

Receptor Dendrites
Generation of action potentials The Axon Hillock in spinal motor neuron (More Na+
initial segment Channels initial segment & proximal to
cell body so summation here)
The initial node of Ranvier in cutaneous sensory
neurons(same mechanism)
Transmission of action potential Axonal process

45
 Physiology

Release of synaptic transmitter Nerve endings

D. Axoplasmic Transport
I. Fast (20-400mm/day) use molecular motors II. Slow (0.2-0.4mm/day) by microtubules and neurofilaments
which run on Microtubule filaments themselves

1. Anterograde This is always anterograde

By kinesin Transport of soluble enzymes, tubulins of microtubules etc.
Transport of mitochondria, reticulum, small
vesicles etc.
2. Retrograde
By Dyenin
Transport of proteins, small molecules, also
virus, toxins like tetanus toxin e.g. rabies virus.

E. Nerve degeneration / regeneration

Nerve degeneration Nerve regeneration
1. Anterograde (Wallerian) 1. Anterograde
a. Axoplasm breaks down a. Macrophage eating away the debris, leaving
b. Myelin breaks down an empty endoneureal tube.
b. Schwann cell regeneration
c. Axonal sprouting
2. Cell Body 2. Cell Body
a. Chromotolysis (Nissl bodies break down - a. Nissl bodies and Golgi apparatus gradually
1st change in cell body) reappear
b. Cell swelling b. Cell regains its normal size
c. Nucleus move to periphery c. Nucleus returns to central position

Regeneration occurs at the rate of 1mm/day or 2.5 cm/month

F. Potentials/ Recording
1. CRO (Cathode ray oscilloscope)
This is used to measure electrical events in living tissue; the advantage being that it is an inertia less,
instantaneously responding lever

2. Concept of polarity
All cells have a resting membrane potential (refer : general physiology)
If a cell with a R.M.P. of say, -70mv changes to say –60mv, the cell is said to be depolarized (note that one
has to ignore the negative sign while commenting on the change of polarity)
Other illustrative examples
From To State
-70mv -90mv Hyperpolarized
-70mv +40mv Depolarized (spike Potential)
-70 -40mv Depolarized (threshold)

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 Nerve - Muscle Physiology

3. Changes seen during stimulation of a nerve

One would require a set of stimulating electrodes (S) and a set of (R) recording electrodes

(S) (R)

The recording electrodes can be such that one electrode is on the surface and the other, inside the cell; or

Nerve-Muscle Physiology Chapter - 2

else, both recording electrodes can be on the surface. When both the electrodes are on the surface, a
biphasic action potential is recorded.

Note:
a. Nerve is a poor conductor of electricity
b. Nerve can conduct impulses in both directions
c. However, once it starts going in one direction, it cannot come back because it finds the previous part
refractory.
d. Stimulation almost always occurs at cathode
e. nerve refractory

While stimulating the nerve, the following changes/ events occur

i. Electro tonic potentials

These are potential changes that occur in the nerve due to passive addition of charge; for example, at the
cathode end of the stimulating electrode, negative charge are added on the surface and at the anode end of the
stimulating electrode, positive charges are added
Illustrative examples
RMP -70mv
Addition of ‘1’ negative
charge at cathodal surface -69mv (Depolarized) [-70 –(-1) = -69]
Addition of ‘1’ positive charge -71mv (Hyperpolarized) [-70-1 =-71]
At anode end
Therefore, electrotonic potential, can be either cat-electrotonic or an-electro tonic.

ii. Local response

Upto say –70mv to –63mv, electrotonic potentials can be seen i.e., the addition of ‘7’ negative charge at the
cathode causes exactly 7mv change. However, beyond this, a further addition of ‘1’ negative charge may cause
the potential to change by more than 1 e.g. from –63mv, it may become –61mv. This is called the local response
i.e. the change in the potential is more than what you would expect on the basis of passive addition of charge.
This shows that the membrane is now participating in the process
The local response in due to opening up to some of the voltage gated sodium channels

iii. Action potential

When the local response brings out a change of say 15mv (i.e. from –70mv to –55mv), the firing level is reached
wherein a large number of voltage – gated sodium channels open up and cause the action potential

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 Physiology

To summarise,

Electrotonic potential (is due to) Passive addition of charge

Local response (is due to) Opening up of some of the Na+ channels
Action potential (is due to) Opening up of many Na+ channels

[Difference between Local potentials and Action potential]

(Example of Local potential: EPSP/IPSP, dendritic potentials, Motor End-plate potential, receptor potential,
synaptic potential, generator potential, electrotonic potential)
Local Potential Action potential
1. Does not follow all or none law Follows all or none law
2. Not self – propagating Self – propagating
3. Can summate to produce AP No summation
4. Can be depolarizing/hyperpolarizing Always depolarizing
5. No refractory period, Has refractory period

G. Phases of an action potential

Depolarization in Various Due to

Tissue
1. Nerve Na+
2. Skeletal muscle Non specific
cation channel
3. Na+ channel
4. Smooth muscle Ca++
5. SA Node Ca++
6. Ventricular muscle Na+
7. Endolymphatics K+ influx
potentials

1 = R.M.P.
2. Cat – electrotonic potential
3. Local response
4. Firing level / threshold
5. Depolarization
6. Overshoot /Spike Potential
7. After – Depolarization
8. After – hyperpolarization

Note:
i. During after-depolarization, the excitability of nerve is more than after-hyperpolarization so most
excitable part of refractory period..
ii. During after-hyperpolarization, the excitability of nerve is less, when compared to resting phase.

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 Nerve - Muscle Physiology

Refractory Period has 2 parts :- Absolute refractory period (ARP) & Relative refractory period(RRP)
i. Absolute refractory period: no stimulus can result in 2nd AP. From above firing level depolarization to
1/3rd of repolarisation. Excitability is zero.
ii. Relative refractory period: a strong stimuli can lead to 2 nd AP. From 1/3rd of repolarization to RMP.
Excitability is less. Include after-depolarization (less refractory) & after-hyperpolarization (more
refractory)

Nerve-Muscle Physiology Chapter - 2

H. Strength – duration curve
1. Rheobase The minimum strength of current to stimulate a nerve, regardless of the
time it takes
2. Utilization time Time taken for the rheobase current to stimulate a nerve
3. Chronaxie Time taken for twice the rheobase current to stimulates a nerve
4. Summation 2 subthreshold stimuli can summate to produce AP
Can be Spatial (2 stimuli at 2 different place) or Temporal (2 successive
stimuli one after another)

I. Other terms
1. Biphasic action potential This type of record is obtained when both the recording
electrodes are on the surface of the nerve
2. Compound action potential (multi Seen in a mixed nerve, wherein there may be several fibre
peaked action potential) types
3. Accommodation Slowly rising currents fail to fire (stimulate) the nerve
Cause : The opening of K+ channels balances the gradual
opening of Na+ channels

J. Nerve Fibre Classification

1. Erlanger and Gasser classification

Fibre types Functions Fibre diameter (m) Conduction
velocity (m/s)
A Alpha Proprioception; somatic motor 12-20 70-120
Beta Touch, pressure 5-12 30-70
Gamma Motor to muscle spindles 3-6 15-30
Delta Pain , cold, touch 2-5 12-30
B Preganglionic autonomic <3 3-15
C Dorsal root Pain, temperature, some 0.4-1.2 0.5-2
mechanoreceptor, reflex responses
Sympathetic Postganglionic sympathetic 0.3-1.3 0.7-2.3
& Parasym.
A and B are myelinated; C are unmyelinated

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 Physiology

2. Numerical classification (for sensory neurons only)

Number Origin Fibre type
Ia Muscle spindle, annulo spiral ending A
Ib Golgi tendon organ A
II Muscle spindle, flower-spray ending; touch, pressure A
III Pain and cold receptors; some touch receptors A
IV Pain, temperature and other receptors Dorsal root C

3. Susceptibility to: Most Susceptible Intermediate Least Susceptible

Hypoxia B A C
Pressure A B C
Local anesthetics C B A

Substance p is released in response to vpain in Muscle spindle function is: (AIIMS May 09)
periphery. (AIIMS Nov 09) A. Length B. Stretch
a. Nerve terminals b. Mast cells C. Touch D. Temperature
c. Endothelium d. Plasma
Ans A. Length
Ans A. Nerve terminals

K. Conduction of action potential or nerve impulse

Mechanism
Action potential

Local currents (“current sink”)

Which in turn causes

Action potential and so on

Main factor affecting conduction velocity
1. Axon diameter : More the diameter, more the speed of conduction
2. Myelination : Increases conduction velocity by saltatory conduction

L. C.N.S. glial cells

Oligodendrogliocytes Formation of myelin
Microglia Scavenger (Phagocyic function)
Astrocytes Induce capillaries to develop tight functions to form blood brain
barrier. Also K+ uptake, Embryonal neuronal migration, NGF secretion,
Metabolism of drugs, neurotransmitters etc

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 Nerve - Muscle Physiology

M. MUSCLE – SKELETAL MUSCLE

1. Hierarchy of muscle structure
Muscle
Made up of

Muscle fibre (or muscle cell)

Made up of

Nerve-Muscle Physiology Chapter - 2

Muscle fibril
Made up of

Muscle filaments

(Made up of contractile proteins)

2. Cytoskeletal proteins
a. Contractile
i. Myosin (The type of myosin present in skeletal muscle is myosin II)
ii. Actin
b. Regulatory (‘or relaxing’)
i. Tropomyosin
ii. Troponin
c. Anchoring
i. -actinin ii. Titin iii. Nebulin iv. Dystrophin
d. Bands / Lines
i. Bands – A, I, H ; Lines – Z, M
ii. A band – Dark, made up of myosin
iii. I band – Light, made up of actin, mainly
H – The lighter portion of A band, where there is no overlap of actin and myosin
Z line – The actin filaments get anchored here; the length of the muscle between 2 Z-lines is called s
sarcomere
M line – The central bulge in the myosin filament
When a muscle contracts, the two Z- lines come closer; the length of the A band remains constant whereas the
length of I and H band decreases. The M – line becomes more prominent.

3. Structure of Thick/thin filaments

Thick filament is made up of myosin (myosin II)
Myosin II has 2 globular heads; (Myosin I has one globular head)
The globular head has
i. actin – binding site
ii. Catalytic site for hydrolysis of ATP

51
 Physiology

Thin filament
Is made up of actin (mainly), tropomyosin and troponin (troponin I,T,C) Other proteins: providing stability to
sarcomere
i. Desmin: Desmin is a type III intermediate filament found near the Z line in sarcomeres. These
connections maintain the structural and mechanical integrity of the cell during contraction while
also helping in force transmission and longitudinal load bearing.
ii. Titin :Titin is a large abundant protein of striated muscle. N-terminal Z-disc region and C-terminal
Mline region bind to the Z-line and M-line of the sarcomere respectively, so that a single titin
molecule spans half the length of a sarcomere
iii. Actinin :Actinin is a microfilament protein. α-Actinin is necessary for the attachment of actin
filaments to the Z-lines in skeletal muscle cells

N. Sarcotubular system
Made up of
1. L-tubule (Longitudinal tubule)
This is the sarcoplasmic reticulum.
2. T – tubule (Transverse tubule) this is the invagination of the sarcolemma into the muscle cell
T-tubule

(1)

L-tubule
(2) (Sarco-plasmic
reticulum)
The L-tubule (Sarcoplasmic reticulum) has got ‘distended ends’ called cistern.
The 2 cisterns associated on either side of the T-tubule – is called a triad. There are 2 traids / sarcomere in
skeletal muscle and at A-I junction.

a. Receptors
i. T-tubule has dihydrophyridine receptor [ (1) in the diagram above]
ii. The L tubule cistern has ryanodine receptors [(2) in the diagram above];
b. Ryanodine receptor(RyR) :Ryanodine receptors mediate the release of calcium ions from the sarcoplasmic
reticulum, essential for muscle contraction. In skeletal muscle, it is thought that activation occurs via a
physical coupling to the dihydropyridine receptor.
c. Dihydropyridine receptor :it is a voltage-dependent calcium channel found in the transverse tubule of
muscles. In skeletal muscle it associates with the ryanodine receptor RyR via a mechanical linkage. It senses
the voltage change caused by the end-plate potential.
d. Ca2+- Mg2+ ATPase :moves Ca2+ back into the reticulum, producing relaxation

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 Nerve - Muscle Physiology

Functions of the T – tubule and L –tubule

i. The transverse tubule is continuous with the membrane of muscle fibre. It forms a grid perforating
the individual muscle fibrils. The space between the 2 layers of the T- system is an extension of the
extra cellular space
ii. The T system allows rapid transmission of action potential from cell membrane to all fibres in muscle
The L – tubule
The L-tubule (sacroplasmic reticulum) is concerned with Ca++ movement and muscle metabolism

Nerve-Muscle Physiology Chapter - 2

O. Excitation – contraction coupling :
The process by which depolarization of the muscle fibre initiates contraction is called excitation – contraction
coupling

P. Events :
1. Action potential generated in a nerve has to cause action potential in the muscle cell membrane.
2. In the muscle cell membrane, depolarization normally starts at the motor end plate, the specialized
structure of the muscle cell membrane under the motor nerve ending.
The depolarization at the motor-end plate is called end plate potential (EPP)
3. The depolarization at motor-end plate, if large enough, causes action potential in the adjacent parts of
the muscle cell membrane.
4. The action potential thus generated is able to reach all the muscle fibrils in the muscle cell interior via
the T-tubules.
5. This triggers release of Ca++ from the terminal cisterns of the L-tubule
6. The released, Ca++ binds to troponin – C (There are 3 ‘parts’ of troponin – troponin I, T and C)
(Troponin T : binds the other troponin components to tropomyosin)
(Troponin I : inhibits interaction of myosin & actin)
(Troponin C : has 4 Ca++ binding sites that initiates contraction)
7. This allows he troponin to get ‘lifted off’ the tropomyosin.
8. The tropomyosin ‘moves away’, uncovering the sites where myosin heads bind to actin.
9. This triggers the cross-bridge cycling, including the power-stroke.
10. Relaxation is brought about by the active pumping of Ca ++ back into the sarcoplasmic reticulum
(Note that the troponin – tropomyosin complex is the relaxing protein that inhibits the actin myosin interaction)

II. SARCOLEMMAL PROTEINS

A. Dystrophin–Glycoprotein Complex
The large dystrophin protein forms a rod that connects the thin actin filaments to the transmembrane protein – β
dystroglycan in the sarcolemma by smaller proteins in the cytoplasm, syntrophins.
β dystroglycan is connected to merosin (merosin are basically laminins) in the extracellular matrix by α
dystroglycan. The dystroglycans are in turn associated with a complex of four transmembrane glycoproteins: α, β,
γ and δ sarcoglycan.
This Dystrophin–Glycoprotein complex adds strength to the muscle by providing a scaffolding for the fibrils and
connecting them to the extracellular environment.

53
 Physiology

Extra Edge
 Duchenne Muscular dystrophy : X linked, mutation of dystrophin gene.
 Becker muscular dystrophy – dystrophin altered.
1. Motor Unit
a. Definition: Each single spinal motor neuron along with the muscle fibres it innervates is called a motor
unit.
A motor unit follows the all or none law.
b. Size principle : Slow motor units innervate slow muscle fibres, fast motor units innervate fast muscle
fibres.

2. Henneman principle : In large muscles, the small, slow units are recruited first; then if required, the large
units are recruited
a. Summation : 2 types
i. Temporal = A single motor unit, stimulated many times by the same strength of stimulus
ii. Spatial = Many motor unit, stimulated at the sametime by increasing the strength of the stimulus

B. Muscle fibre types

Type I Type II
Other names Slow, red, Oxidative Fast, White, glycolytic
Function For long, slow contractions For fine, skilled movement
Fatiguability Fatigue late Fatigue early
Myosin ATPase activity Slow Fast
Ca++ pumping capacity of Moderate High
sarcoplasmic reticulum
Diameter Moderate Large
Glycolytic capacity Moderate High
Oxidative capacity High Low
Examples Back muscles Extra ocular muscles

High oxidative slow High oxidative fast Low oxidative fast

twitch twitch twitch

Speed contraction Slow Fast Fast

Myosin ATPase activity Low High High

Primary source of ATP Oxidative Oxidative Anerobic

production phosphorylation phosphorylation glycolysis

Glycolytic enzymes Low Intermediate High

No. of mitochondria Many Many few

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 Nerve - Muscle Physiology

Capillaries Many Many Few

Myoglobin content High High Low

Muscle color Red Red White

Glycogen content Low Intermediate High

Fiber diameter Small intermediate large

Nerve-Muscle Physiology Chapter - 2

Rate of fatigue Small intermediate large

Isometric and Isotonic contraction

Isometric Isotonic
Tension increases Constant tension
Length remains same Length decreases
No external work is done External work is done
Heat released is less; more energy efficient Heat released is more; less energy efficient
e.g. – antigravity muscles maintaining e.g. legs moved in walking posture.
1. Length – Tension Relationship
a. There is definite length – tension relationship in skeletal muscle. There is a particular length at which
the active tension developed is maximum. This is called the optimum length.
b. The tension developed depends upon the number of cross-bridges that can be formed between actin
and myosin. On stretching no of cross-bridges increase thereby active tension is more with increase in
length of muscle. On further stretching the no. of cross-bridges decrease so active tension developed is
decreased. In heart this relation is called Frank Starling Law

2. Energy for muscle contraction

a. ATP stores (last seconds)
b. ATP from creatinine phosphate (min.)
c. ATP from glycolysis (hrs)
d. ATP from aerobic metabolism (days)

3. XI. Fibrillation / Fasciculation

a. Fibrillation : Potentials arising spontaneously in single denervated muscle fibres; Not visible grossly.
fibrillation potential arise at the end plate where increases Ach sensitivity involves the whole of the
muscle end plate. seen in LMN lesion (dennervation hypersensitivity).
b. Fasciculation: Involuntary contraction of a single motor unit; Visible grossly, also seen in LMN lesions,
cause : pathological discharge of spinal motor neurous

MUSCLE – Cardiac Muscle

a. Functional histology
i. Muscle fibres branch and interdigitate.
ii. Intercalated disc are present at Z-lines Intercalated disc is the place of mechanical electrical coupling
of muscle fibres.

55
 Physiology

iii. (Electrical coupling is by means of gap junctions).

iv. The T-tubule system is at Z lines.
v. One traid / sarcomere.

b. Electrical activity
This is different in the
i. Pacemaker cells
And
ii. Contractile cells

 Pacemaker Cells

c
d

(A) b
a
 Contractile Cell
Viz SA node, AV nod

1
2

0 3

4 4

Phase Name Cause

A. Prepotential Cause /Pacemaker potentials Initial rapid
Opening of Na+
a) Early part:  in K+ efflux 0 depolarization and
channels
b) Late part : in Ca++ influx overshoot
(through Ca++ T channels) Initial rapid Closure of Na+
1
repolarisation channels; Efflux of K+
B. Action potential Ca++ influx and K+
2 Plateau
c) Depolarization:  in Ca++ influx efflux
++
(through Ca L channels) 3 Final repolarisation Closure of Ca++
d) Repolarisation:  in K+ efflux 4 channels; K+ efflux
RMP through various types
of K+ channels
C. After depolarization or After potentials:

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 Nerve - Muscle Physiology

1. Introduction: It’s occurrence is abnormal. As the name suggests, these are basically potentials or
depolarisations that develop after a conducted action potential.
2. Classification: Depending on which phase of the ventricular action potential the after depolarisations
occur, it can be classified as
a. Early after depolarisations (EAD)
b. Late after depolarisations (DAD)

3. Significance: Both EAD and DAD can set up tachycardia. They can do this either on their own or because

Nerve-Muscle Physiology Chapter - 2

they can trigger an activity in an already formed automatic tissue (secondary to ischaemia is an infarcted
tissue etc.)

4. EAD: Appears at the end of phase 2 or in phase 3 of the ventricular action potential. They are associated
with prolonged Q-T interval i.e. it tends to occur at slower heart rates. Thus, quinidine, which decreases
the heart rate, can actually set up tachycardia (by causing EADs); this is called torsades de pointes. The
exact cause of EAD is not known.

5. DAD: Appears near the very end of phase 3 or beginning of phase 4 of ventricular action potential. They
are exaggerated by tachycardia. The cause is due to increased intracellular calcium; this induces a
transient diastolic inward current, possibly by promoting Na +Ca++ exchanger. The current causing the
repetitive after depolarization is switched on by an increased intracellular calcium level. Therefore, the
Ca++ antagonist verapamil and a low external Ca++ level both inhibit DAD. DADs are thought to be
underlying the development of ventricular automaticity during digitalis poisoning.

TABLE SHOW CARDIAC ION CHANNELS

Table 2-2 CARDIACION CHANNELS AND CURRENTS
CHANNELS GATING CHARACTERISTICS
Sodium
Fast Na+ (INa) Voltage Phase 0 of myocytes
Slow Na+ (IF) Voltage & Receptor Contributes to phase 4 pacemaker
Current in SA ans AV nodal cells
Calcium
L-type(Ica) Voltage Slow inward, long – lasting current
Phase 2 of myocytes and phases 4
And of SA and AV nodal Cells

T-type(Ica) Voltage Transient current: contributes to phase

4 pacemaker current in SA and AV nodal
Cells
Potassium
Inward rectifier (IK1) Voltage Maintains negative potential in phase 4
: closes with depolarization : its decay
contributes to pacemaker currents

Transient outward(I10) Voltage Contributes to phase 1 in myocytes

Delayed rectifier(Ikr) Voltage Phase 3 repolarization

ATP-sensitive(Ik,ATP) Receptor Inhibited by ATP ; opens when ATP

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 Physiology

Decreases

Acetylcholine activated(Ik,ACH) Receptor Activated by acetylcholine; Gi-protein

coupled

D. Mechanism of contraction
This is similar to skeletal muscle.
The T tubules are wide and filled with mucopoly-saccharide
There is also the phenomenon of calcium triggered calcium release (or calcium-induced calcium release). This
K+ Na+

Ca2+
1
2
Na+
S.R

means that Ca++ entry from ECF into the cardiac muscle cell triggers the release of more Ca ++ from the
sarcoplasmic reticulum
Relaxation
S.R = Sarcoplasmic reticulum
Relaxation is by decreasing the cytosolic Ca++ level by :-
a. Ca++ pump in sarcoplasmic reticulum
b. Ca++ Na+ antiport
c. Na+- K+ ATPase
(Phospholamban inhibits the Ca++ pump in S.R. This activity of phospholamban is inhibited by its
phosphorylation)

1. Relationship between electrical and mechanical events

The action potential in ventricular muscle fibres is prolonged one and therefore the refractory period is also
relatively prolonged. This is the reason as to why cardiac muscle cannot be tetanised

2. Length – tension relationship

Within physiologic limits, force of contraction (as reflected by stroke volume) is directly proportional to the
initial length of the muscle fibre (as determined by the end-diastolic volume). This is known as the Frank-
starling’s law.

3. Muscle – Smooth Muscle:-

a. Nerve supply
The nerve shows varicosities; the nerve establishes functional contact at several points on the muscle as it
courses alongside it; this is called synapse en passant. There can be excitatory or inhibitory functional
potentials.
b. Functional anatomy

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 Nerve - Muscle Physiology

No troponin or tropomyosin
No Z – lines (The anchorage for the actin filaments is provided by structures called dense bodies)
No T-tubule
No (or rudimentary) sarcoplasmic reticulum
Types
1. Visceral (single – unit)
This is the type of smooth muscle present in hollow viscera. There are gap junctions between muscle fibres
2. Multi – unit

Nerve-Muscle Physiology Chapter - 2

Eg. Intraocular muscle of the eye (ciliaris, iris), pilomotor muscle of skin, muscles of blood vessels.
It behaves like skeletal muscle in the sense that its response can be graded.

a. Electrical activity
i. There is no steady resting membrane potential in smooth muscle
ii. There is presence of slow-waves (pacemaker potentials). These are generated in multiple foci that shift
from place to place
iii. Action potentials (spike potentials) are formed  superimposed on the slow-waves

b. Excitation / inhibition in smooth muscle

i. Multi – unit
Can be excited only by nerves
ii. Single unit

The response can be

 Spontaneous
 From adjacent cells (through gap junctions)
 Nerves (i.e. by neurotransmitters)
 Hormones
 Stretch
 Cold

c. Mechanism of contraction
(Excitation contraction coupling in visceral smooth muscle is a very slow process)
i. First Ca++ entry into the cell
ii. Ca++ binds to calmodulin
iii. The Ca++ calmodulin complex activates myosin light chain kinase (MLCK)
iv. Activation of MLCK causes phosphorylation of myosin which causes increased myosin ATPase activity and
binding of myosin to actin
v. This initiates the cross-bridge cycling & contraction
vi. Relaxation is by dephosphorylation of myosin by myosin phosphatase

d. Some unique features of smooth muscle contraction :-

i. The process is slow
ii. It is a low-energy mechanism

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 Physiology

iii. It shows the presence of latching or latch state. This is the state in smooth muscle where, even after
dephosphorylation of myosin, the cross-bridges continue to ‘cling on’ for sometime. The advantage is that
it allows sustained contraction with minimum energy expenditure
iv. There is a higher percentage of shortening
v. There is no fixed length-tension relationship in smooth muscle. It shows the property of plasticity. Eg
urinary bladder- cytometrogram
Smooth muscle can generate as much or even more tension than skeletal muscle/ cardiac muscle.
Force of contraction of smooth muscles : 4-6 kg / cm2
Skeletal muscles : 3-4 kg / cm2

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 Nerve-Muscle Physiology

“Please Read the Preface of this book Before you attempt these questions.”
Explanation of answer start from page no. 64

Section-1 -: Membrane Potentials 8. Synaptic conduction is mostly orthodromic

because: (LQ)
1. Action potential generates in axon hillock due to A. Dendrites cannot be depolarized
(AIPG 2009) B. Once repolarized, an area cannot be depolarized
C. The strength of antidromic impulse is less
A. It has least threshold
D. Chemical mediator is located only in the presynaptic

Nerve -Muscle Physiology Chapter - 2

B. Neurotransmitters produced terminal
C. Unmyelinated
D. Has more Ion channels are 9. Action potential is produced because of:
(LQ)
2. Which is true about presynaptic inhibition? A. Na+ influx B. K+ influx
(AIIMS NOV 2012) C. K+ and Na+ influx D. Mg+ influx
A. Occurs due to hyperpolarisation of presynaptic
10. The permeability to which of the following ions
membrane
increases during depolarization of a nerve fiber:
B. Occurs due to inhibition of release of positive
(LQ)
neurotransmitter from presynaptic terminal
A.Ca++ B. Cl-
C. Produces action potential +
C. Na D. Mg++
D. Occurs due to blockage of presynaptic receptor.
11. Which of the following is not associated with
3. End plate potential follows which law(DNB Dec-
nerve transmission?
2010)
A. Na+ B. Mg+
A. All or none law B. Depolarisation -
C. Cl D. K+
C. Hyperpolarisation D. Propagation
12. Nerve impulse is initiated at axon hillock because:
4. Continuous sub-threshold stimulus leading to
(LQ)
sustained response and increase in threshold for
A. It is un-myelinated
action potential. This is known as? (AIIMS MAY 2013)
B. It has lower threshold than the rest of axon
A. Accommodation B. Adaptation
C. Neurotransmitters are released here
C. Resistance D. Initiation
D. None of the above
5. Fast axonal transport is by all except?
13 . In a motor nerve fiber, lower threshold potential
(AIIMS NOV 2007)
is seen in: (LQ)
A. Dynenin B. Kinesin
A. Axon hillock B. Body C. Axon D. Dendrite
C. Microtubule D. Neurofilaments
14. Initiation of impulse starts in. (DNB June-2011)
6. Rheobase is an indicator of: (DNB Dec-2011)
A. Axon
A. Specificity of impulse transmission
B. Axon hillock + initial segment
B. Magnitude of current
C. Cell body
C. Rate of discharge
D. Dendritic tree
D. Velocity of nerve conduction
15. EPSP is due to(DNB Dec-2012)
7. Antidromic conduction is seen in:
A. K+ influx B. Na+ efflux
A. Axon B. Synapse
C. Both D. None C. Na+ influx D. Ca++ influx

1.D 2.A 3.B 4.A 5.D 6.B 7.A 8.D 9.A 10.C 11.B 12.B 13.A 14.B 15.C

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 Physiology

16. Which of the following statements is true for B. It is decremental in nature

excitatory postsynaptic potentials (EPSP) C. It does not follow all or none law
A. Are self propagating D. It requires a threshold stimulus to be activated
B. Show all or none response
C. Are proportional to the amount of transmitter 23. Synaptic potentials can be recorded by:
released by the presynaptic neuron (DNB Pattern)
D. Are inhibitory at presynaptic terminal. A. Patch clamp technique
B. Voltage clamp technique
17. A traveling nerve impulse does not depolarize the C. Microelectrode
area immediately behind it, because: D. EEG
A. It is hyperpolarized.
B. It is refractory. 24. Neuronal degeneration is seen in all of the
C. It is not self — propogating following, except
D. The conduction is always orthodromic. A. Crush nerve injury
B. Fetal development
18. Which of the following is true regarding Renshaw C. Senescence
inhibition? D. Neuropraxia
A. Collateral causes the inhibition
B. Inhibition of feedback propagation 25. Saltatory conduction in myelinated axons results
C. Both from the fact that
D. None (A) Salt concentration is increased beneath the myelin
segments
19. Renshaw cell inhibition is an example of (B) Nongated ion channels are present beneath the
(DNB Pattern) segments of myelin
A. Feed — forward inhibition (C) Membrane resistance is decreased beneath the
B. Oscillating motor activity segments of myelin
C. Circuitry for bio feedback inhibition (D) Voltage-gated sodium channels are concentrated at
D. All of the above the nodes of Ranvier

20. Resting membrane potential on nerve is 26. Tetanus toxin and botulinum toxin exert their
determined by concentration of (DNB Dec-2010) effects by disrupting the function of SNARES,
A. Calcium B. Potassium inhibiting
C. Chloride D. Magnesium (A) Propagation of the action potential
(B) The function of voltage-gated ion channels
21. The true statement regarding the action potential (C) The docking and binding of synaptic vesicles to the
in a nerve is: presynaptic membrane
A. The depolarization is a result of outward movement (D) The binding of transmitter to the postsynaptic
of potassium ions receptor
B. The action potential occurs due to sudden opening
of Na+ channels 27. What property of the postsynaptic neuron would
C. The action potential occurs when the potential optimize the effectiveness of two closely spaced
reaches a threshold at —65 mV axodendritic synapses?
D. The resting membrane potential is —90 mV (A) A high membrane resistance
(B) A high dendritic cytoplasmic resistance
22. Which of the following are true about nerve action (C) A small cross-sectional area
potential conduction? (D) A small space constant
A. On activation there is influx of potassium and efflux
of sodium

16.C 17.B 18.C 19.C 20.B 21.B 22.D 23.C 24.D 25.D 26.C 27.A

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 Nerve-Muscle Physiology

28. The true statement regarding the action potential

in a nerve is: 3. Which of the following triggers muscle contraction?
(A). The depolarization is a result of outward (AIPG 2008)
movement of potassium ions A.Ca2+ binding tropomyosin
(B). The action potential occurs due to sudden opening B. Ca2+ binding troponin C
of Na+ channels C. ATP breakdown
(C). The action potential occurs when the potential D. Ca2+ binding troponin I
reaches a threshold at —65 mV
(D)). The resting membrane potential is —90 mV 4. All are true regarding cardiac muscle except:

Nerve -Muscle Physiology Chapter - 2

(AIPG 2007)
29. An increase in the action potential frequency in a A. Have multiple nuclei B. Have gap junction
sensory nerve usually signifies C. Acts as a syncytium D. Branched fibres
(A) Increased intensity of the stimulus
(B) Cessation of the stimulus 5. The motor unit consists of:
(C) Adaptation of the receptor A. All muscle fibers in a muscle
(D) A constant and maintained stimulus B. Motor nerve and muscle fibers that it supplies

30. Sensory receptors that adapt rapidly are well C. Afferent neuron center and efferent neuron
suited to sensing D. Single muscle fiber and all neurons that innervate it
(A) The weight of an object held in the hand
(B) The rate at which an extremity is being moved 6. Intercalated disks are found in:
(C) Resting body orientation in space A. Smooth muscle B. Cardiac muscles
(D) Potentially hazardous chemicals in the environment C. Both D. None

7. Myasthenia gravis is a disorder of:

31. Adaptation in a sensory receptor is associated
with a A. Neuromuscular junction
(A) Decline in the amplitude of action potentials in the B. Spinal cord
sensory nerve C. Motor neuron
(B) Reduction in the intensity of the applied stimulus D. Peripheral nerve
(C) Decline in the conduction velocity of sensory nerve
action potentials 8. Contraction of covering binding sites on actin is
(D) Decline in the amplitude of the generator potential prevented by: (DNB Pattern)
A. Tropomyosin B. Troponin
C. Calmodulin D. Thypmosin
Section-2 -: Muscle 9. All are calcium-binding proteins except
1. Muscle's blood supply increases during exercise due A. Calbindin B. Calmodulin
to - (AIPG 2009) C. Tropomyosin D. Troponin
A. Increased blood pressure
B. Accumulation of active metabolites 10. Tropomyosin is involved in:
C. Increase vasodilatation A. Helps in the fusion of actin and myosin
D. Increase heart rate B. Covers myosin and prevents attachments of actin
and myosin
2. Which of the following is NOT a Sarcolemmal C. Slides over myosin
protein? (AIPG 2008) D. Cause Ca release
A.Perlecan B.Dystrophin
C.Dystroglycan D.Sarcoglycan

28.B 29.A 30.B 31.D 1.B 2.A 3.B 4.A 5.B 6.B 7.A 8.B 9.C 10.B

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 Physiology

C. Accumulation of Ca++
11. On which of the following, the muscle contraction D. Depletion of ATP
depends?
A. ATP B. Myosin C. Actin D. Calcium
18. Golgi tendon organ determines?(AIIMS May 08)
12. Which of the following is true regarding excitation- A. Static length
contraction coupling in smooth muscle? B.Muscle action
(LQ) C. Muscle tension
A. Phosphorylation of actin occurs D. Dynamic length
B. Troponin is essential
C. Intracellular calcium is essential to cause contraction
19. Continuous sub-threshold stimulus leading to sustained
D. Increased calcium in sarcoplasmic reticulum causes
response and increase in threshold for action potential. This
sustained contraction
is known as? (AIIMS May 08)
A. Accommodation
13. In isometric exercise the following changes occur
B. Adaptation
EXCEPT: (DNB Dec-2008)
C. Resistance
A. Increase in muscle tone
B.Staircase phenomenon D. Initiation
C. Summation of contractions
D. Relaxation heat 20. Many signaling pathways involve the generation
of inositol trisphosphate (IP3) and diacylglycerol
14. The force of muscle contraction can be increased (DAG). These molecules
by all of the following except: (A) Are first messengers
A. Increasing the frequency of activation of motor units (B) Activate phospholipase C
B. Increasing the number of motor units activated (C) Are derived from PIP2
C. Increasing the amplitude of action potentials in the (D) Can activate calcium calmodulin-dependent protein
motor neurons kinases
D. Recruiting larger motor units
21. Which of the following triggers muscle
15. Amongst the muscles, skeletal muscle is the most contraction?
excitable tissue because (DNB Dec-2009) (A). Ca2+ binding tropomyosin
A. There are two “T: tubules per sarcomere and has (B). Ca2+ binding troponin C
well developed sarcoplasmic reticulum (C). ATP breakdown
B. It is supplied by large myelinated nerve fibres (D). Ca2+ binding troponin I
C. It is nerve regulated
D. None of the above 22. Which type of motor unit is of prime importance
in generating the muscle power necessary for the
16. Duchenne Muscular dystrophy is a disease of maintenance of posture?
(A) Low threshold, fatigue-resistant
(DNB Pattern)
(B) High threshold, fatigable
A. Neuromuscular junction (C) Intrafusal, gamma controlled
B. Sarcolemmal proteins (D) High threshold, high force
C. Muscle contractile protein
D. Disuse atrophy due to muscle weakness 23. Which type of sensory receptor provides
information about the force of muscle contraction?
(A) Nuclear bag fiber
17. In severe exercise muscle spasm occurs due to
(B) Nuclear chain fiber
A. Accumulation of K+
(C) Golgi tendon organ
B. Accumulation of Acetycholine (D) Bare nerve ending

11.D 12.C 13.D 14.C 15.A 16.B 17.A 18.C 19.A 20.C 21.B 22.A 23.C

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Nerve-Muscle Physiology

Nerve -Muscle Physiology Chapter - 2

 Physiology

Explanation
Chapter-2 Nerve - Muscle Physiology

Section-1 -: Membrane Potentials

1. Ans. D. Has more Ion channels. It contains the highest no. of voltage gated sodium channels
(Ref: Ganong – 23rd Ed-79)
a. The axon hillock is the anatomical part of a neuron that connects the cell body (the soma) to the axon.
b. It is described as the location where the summation of inhibitory postsynaptic potentials (IPSPs) and
excitatory postsynaptic potentials (EPSPs) from numerous synaptic inputs on the dendrites or cell body
occurs.
c. It is electrophysiologically equivalent to the initial segment where the summated membrane potential
reaches the triggering threshold, an action potential propagates through the rest of the axon (and
"backwards" towards the dendrites as seen in neural backpropagation).
d. The triggering is due to positive feedback between highly crowded voltage gated sodium channels, which
are present at the critical density at the axon hillock (and nodes of ranvier) but not in the soma.
e. The axon hillock also functions as a tight junction, since it acts as a barrier for lateral diffusion of
transmembrane proteins, GPI anchored proteins such as thy1, and lipids embedded in the plasma
membrane
Functionality
a. When neurotransmitters from the presynaptic neuron attach to the receptor sites on the postsynaptic
dendritic spines, the postsynaptic membrane may become depolarized (more positive).
b. This depolarisation will travel towards the axon hillock, diminishing exponentially with time and distance.
c. It, therefore, takes multiple such events, arriving in close temporal order, to have any significant effect on
the axon hillock.
d. Since the axon hillock has the highest concentration of ion channels, it is almost always the action
potential initiation site.
e. At the axon hillock, the depolarization will activate the voltage gated sodium channels, transporting
sodium ions into the negatively charged cell.
f. As sodium enters the cell, the cell membrane potential becomes more positive, which activates even more
sodium channels in the membrane.
g. The sodium influx eventually overtakes the potassium efflux (via the potassium leak channels), initiating a
positive feedback loop (rising phase).
h. At around +40 mV the voltage gated sodium channels begin to close (peak phase) and the voltage gated
potassium channels begin to open, moving potassium against its electrochemical gradient and out of the
cell (falling phase).
i. The potassium channels exhibit a delayed reaction to the membrane repolarisation, and even after the
resting potential is achieved, some potassium continues to flow out, resulting in an intracellular fluid
which is more negative than the resting potential, and during which, no action potential can begin
(undershoot phase).
j. This undershoot phase ensures that the action potential propagates down the axon and not back up it.
k. Once this initial action potential is initiated, principally at the axon hillock, it propagates down the length
of the axon.

64
 Nerve-Muscle Physiology

l. Under normal conditions, the action potential would attenuate very quickly due to the porous nature of
the cell membrane.
m. To ensure faster and more efficient propagation of action potentials, the axon is myelinated.
n. A myelin sheath ensures that the signal can not escape through the ion or leak channels.
o. There are, nevertheless, gaps in the insulation (nodes of ranvier) which boost the signal strength.
p. As the action potential reaches a node of Ranvier, it depolarises the cell membrane.
q. As the cell membrane is depolarised, the voltage gated sodium ions open and sodium rushes in, triggering
a fresh new action potential.

Nerve -Muscle Physiology Chapter - 2

r. The undershoot phase, thus, guarantees that the action potential can never propagate backwards up
along the axon.

2. Ans. A. Occurs due to hyperpolarisation of presynaptic membrane

+ve
NT
B

Pre – synaptic Inhibition

C

Presynaptic inhibition occurs as follows :

a. The neuron ‘A’ releases an excitatory NT, to excite neuron ‘B’. But neuron ‘C’ ends pre-synaptically on ‘A’
to decrease the release of the excitatory NT.
b. Some of the salient Features of Pre-synaptic Inhibition are :
a. It is example of axoaxonic synapse b. It is stimulated by general anaesthetics
c. It is inhibited by picrotoxin d. It is mostly due to GABA
c. So it occurs due to hyperpolarisation of presynaptic membrane and results in inhibition of release of
positive neurotransmitter from presynaptic terminal (Ref: Ganong, 22nd Edition, Page no 92,)

3. Ans. B. Depolarisation
a. END-PLATE-POTENTIAL: - During the transmission at neuromuscular junction, the binding of acetylcholine
to nicotinic Ach receptors increased the Na+ and K+ conductance of the membrane, and the resultant
influx of the Na+ produces a depolarizing potential Q, called End-plate potential.
b. IPSP  due Hyperpolarization (Influx of cl- or efflux of K+).
c. EPSP  due depolarization (Influx of Na+).

4. Ans. A. (Accommodation) (Ref. Ganong Physiology 23rd ed. 79; Figure 5–3.)
a. Slowly rising currents fail to fire the nerve because the nerve adapts to the applied stimulus, a process
called accommodation.

65
 Physiology

b. It is because slow opening voltage gated K channels also start to open to cause K efflux and balance Na
influx via voltage gated Na channels, this leads increase in threshold for action potential.
c. Once threshold intensity is reached, a full-fledged action potential is produced.
d. Further increases in the intensity of a stimulus produce no increment or other change in the action
potential as long as the other experimental conditions remain constant.
e. The action potential fails to occur if the stimulus is subthreshold in magnitude, and it occurs with constant
amplitude and form regardless of the strength of the stimulus if the stimulus is at or above threshold
intensity.
f. The action potential is therefore "all or none" in character and is said to obey the all-or-none law.

5. Ans. D. Neurofilaments
a. Fast axoplasmic transport (20-400mm/day): use molecular motors which run on Microtubule filaments
i. Anterograde: This is driven by kinesin
ii. Retrograde: This is driven by Dyenin
b. Slow axoplasmic transport (0.2-4mm/day)
c. This is always anterograde. The cytoskeleton (Microtubule & Neurofilament) moves as a whole due to the
continual polymerization at the leading end (+ end) and depolymersation at the trailing end (- end).

6. Ans. B. Magnitude of current

RHEOBASE is the lowest magnitude of current just sufficient to excite a given nerve or muscle.

7. Ans. A. Axon
In lying animals impulses normally pass in one direction along the axons and this conduction is called orthodromic
conduction. Antidromic means that the nerve impulse travels in the opposite direction and it is seen in axons.
Synapses are one way as receptors are present only on post synaptic neuron.

8. Ans. D. Chemical mediator is located only in the presynaptic terminal

a. An axon can conduct the impulse in either direction.
b. When an action potential is initiated in the middle of an axon, 2 impulses traveling in opposite directions
are set up by electronic depolarization on either side of the initial current sink. In living animals, impulses
normally pass in one direction only Q (from synaptic junctions or receptors along axons to their
termination).
c. Such conduction is called orthodromic. Conduction in the opposite direction is called antidromic. Q Since
synapses, unlike axons, permit conduction in 1 direction only, any antidromic impulse that they set up fail
to pass the first synapse they encounter and die out at that point.

9. Ans. A. Na+ influx

10. Ans. C. Na+

11. Ans. B. Mg+

12. Ans. B. It has lower threshold than the rest of axon

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 Nerve-Muscle Physiology

13. Ans. A. Axon hillock

a. One might expect that depolarization at one point on the plasma membrane would generate an action
potent irrespective of inhibitory signals elsewhere However, this is avoided in many neurons by the axon
hillock the region where the axon emerges from the cell body.
b. The portion of the plasma membrane at the axon hillock has:
i. No synapses of its own and
ii. A lower threshold than elsewhere on the cell
c. The action potential is usually generated in the axon hillock Q.

Nerve -Muscle Physiology Chapter - 2

d. Having neither excitatory nor inhibitory synapses of its own, it is able to evaluate the total picture of EPSPs
and IPSPs created in the dendrites and cell body.

14. Ans. B. Axon hillock + initial segment

a. Neuron: - Neuron generally have four important zones: -
i. There is a Receptor, or Dendritic zone, where multiple local potential changes generated by synaptic
connections are integrated (i.e. Non conducted local potentials are integrated in the receptor zone).
ii. A site where propagated action potential are generated (initial segment inspinal motor neurons, the initial
node of Ranvier in cutaneous sensory neurons).
iii. An axonal process that transmits propagated impulses to the nerve endings and
iv. The nerve endings, where action potential cause the release of synaptic transmitters.

b. See the given figure below: -

Figure: Functional organization of neurons.

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 Physiology

Nissi bodies (granules): —are small basophilic granules, membranous organelles containing ribosomes; present
through out the cell body (soma, or perikaryon) except in axon hillock (from where axon arises); flow into the
dendrites but not into axon; they are stained with basic dyes (eg. Methylene blue, thionine or cresyl violet); During
fatigue or injury of neuron, these bodies fragment and disappear by a process called chromatolysis: Q within 48
hours of section of the nerve the Nissi substance begins to disintegrate into a fine duct —chromatolysis).

15. Ans. C. Na+ influx

a. EPSP (Excitatory post synaptic potential) -
i. Definition: the increase in voltage above the normal resting potential — that is to a less negative
value — is called EPSP because if this potential rises high enough, it will elicit on action potential in the
neuron, thus exciting it.
ii. EPSP is due to depolarization Q.
iii. Production  rapid influx of Na+ to the interior neutralised part of the negativity of RMP  RMP ed
from - 65 to 55 EPSP  excite the neuron.
[Note  by openings of Na+ or Ca++ ions channels, producing an inward current].
b. IPSP (Inhibitory post synaptic potential)
i. Definition  increase in negativity beyond the RMP level is called IPSP, that inhibits the neuron to be
excited. Q
ii. Production - opening of the chloride channels will allows negatively charged chloride ions to move to
the interior
CT ions influx)  membrane potential becomes more negative than normal; and opening of K +
channels will have K+ ions to move to the exterior (K+ ion efflux).  make membrane potential more
negative than usual. Thus Cl- influx and K+ efflux increase the degree of intracellular negativity 
called Hyperpolarization Q inhibits the neuron to be excited.
[ Note — In addition IPSP is also produced by K+ eflux and clossure of the Na+ or Ca++ channels]

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 Nerve-Muscle Physiology

Nerve -Muscle Physiology Chapter - 2

16. Ans. C. Are proportional to the amount of transmitter released by the presynaptic neuron
a. EPSP and IPSP 
i. EPSP makes the post synaptic membrane hypopolarised and if sufficiently strong causes an AP to
develop in the post synaptic membrane.
ii. On the other hand IPSP causes hyperpolarisation of the post synaptic membrane that is it makes the
post synaptic membrane resistant to stimulus.
An EPSP is the fore runner of an AP.,
b. Ionic basis of EPSP development is as follows-
The AP comes  synaptic transmitter (ST) released  ST combines with the receptors of the post synaptic
membrane and this combining causes opening of ligand gated Na + and other channels in the post synaptic
membrane
 entry of Na+ and other cations inside the cell from the ECF  hypopolarisation and EPSP in the post synaptic
membrane].
c. Presynaptic inhibition -
i. Another type of inhibition occuring in the CNS is presynaptic inhibition a process mediated by neurons
that end on excitatary ending forming axo-axonal synapses..
ii. Three mechanisms of presynaytic inhibition have been described -
a. First activation of the presynaptic receptors in Cl- conductance and this has been shown to
decrease the size of the action potentials reaching the excitatory ending.

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 Physiology

b. This in turn reduces Ca2+ entry and consequently the amount of the excitatory transmitter
released. Voltage gated K+ channels are also opened, and the resulting K efflux also decreases the
Ca2+ influx.
c. Finally there is evidence for direct inhibition of transmitter release independent of Ca2+ influx into
the excitatory ending.
iii. First transmitter to be shown to produce presynaptic inhibition was GABA. Q
iv. Thus mechanism of presynaptic inhibition is different. Thus option (4) is also excluded.
v. IPSP  Sometimes receptors and the transmitter combination leads to hyperpolarisation. If the value
of the ‘rmp’
vi. was —70mv, as a result of said combination, it now becomes say —80mv. This difference (- l0mv in
this example) is called IPSP. IPSP is caused by influx of Cl- from ECF to ICF and K+ efflux. Q

17. Ans. B. It is refractory.

"Once initiated a moving impulse does not depolarize the area behind it to the firing level, because this area is
refractory" Q

18. Ans. C. Both

Presynaptic and postsynaptic inhibition is usually produced by stimulation of certain ‘systems’ converging on a
give postsynaptic neuron. For example, each spinal motor neuron regularly gives of a recurrent collateral that
synapses with an inhibitory inter-neuron, which terminates on the cell body of the spinal neuron and other spinal
motor neurons.

This inhibitory neuron is known as Renshaw cell after its discoverer.

19. Ans. C. Circuitry for bio feedback inhibition

a. Renshaw cell inhibition: - Negative - feed back inhibition of a spinal motor neuron via an inhibitory
interneurons (Renshaw cell). It is also called Recurrent inhibition Q. Interneuron releases glycine Q which
inhibitory in function. .
b. Feed - forward inhibition: - seen in the cerebellum, stimulation of basket cells produced IPSP, in the
Purkinje cells. Q However, the basket cells and the Purkinje cells are excited by the same parallel fiber
excitatory input. This arrangement, which has been called "feed forward inhibtion.

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 Nerve-Muscle Physiology

20. Ans. B. Potassium

a. "The magnitude of the resting membrane potential is determined primarily by the concentration of extra
cellular K+ because the resting membrane is much more permeable to K+ than it Na+
b. Changes in the external K+ conc. affect the RMP whereas' change in the external Na + conc. affect the
magnitude of the action potential (Ganong 22nd ed.)

21. Ans. B. The action potential occurs due to sudden opening of Na + channels
The action potential occurs due to sudden opening of voltage gated Na + channels. The membrane potential of

Nerve -Muscle Physiology Chapter - 2

large nerves when they are not transmitting nerve signals, that is, when they are in the so called resting’ state is
about —70 millivolts. Q

22. Ans. D. It requires a threshold stimulus to be activated

a. The action potential will not occur until the initial rise in the membrane potential is great enough to create
the vicious cycle.
b. This occurs when the number of sodium ions entering the fiber becomes greater than the number of
potassium ions leaving the fiber A sudden rise of membrane potential by 15—30 mV is usually required.
c. A sudden increase in the membrane potential in a large nerve fiber (from—70 mV to —55 mV) usually
causes the explosive development of the action potential.
d. This level of— 55 mV is known as threshold for stimulation. Q

23. Ans. C. Microelectrode

a. The electrical events in the neurons are rapid being measured in milliseconds; and the potential changes
are small, being measured in millivolts.
b. In addition to development of microelectrodes with a tip diameter of less than one micrometer Q, the
principal advances that made detailed study of the electrical activity in the nerve possible were the
development of amplifiers and cathode ray oscilloscope.

24. Ans. D. Neuropraxia

Neuropraxia (nerve not working) is a local block to conduction of nerve impulses at a discrete area along the course
of a nerve, axons are in continuity and therefore wallerian degeneration does not occur. It is a relatively mild
injury and recovery is complete provided the cause is removed e.g. Qutch palsy.

25. The answer is D. Voltage-gated sodium channels are concentrated at the nodes of Ranvier
Ref: Ganong - Review of Medical Physiology 23rd Ed Page 57
 A specialization occurs in myelinated axons in which the voltage-gated sodium channels are preferentially distributed
to the axonal membrane beneath the nodes of Ranvier.
 Since these channels are required for the generation of an action potential, the action potential jumps from node to
node.
 This process is facilitated by an increased membrane resistance and a decreased capacitance associated with the
myelinated regions of the axon, both of which promote the electrotonic spread of the positive charge that
accumulates beneath one node of Ranvier at the peak of the action potential.
 Nongated ion channels are not involved in the generation of action potential.

26. The answer is C. The docking and binding of synaptic vesicles to the presynaptic membrane
Ref: Ganong - Review of Medical Physiology 23rd Ed Page 87,88

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 Physiology

 SNARE (an acronym derived from "SNAP (Soluble NSF Attachment Protein) REceptor") proteins are a large protein
superfamily consisting of more than 60 members in yeast and mammalian cells.
 The primary role of SNARE proteins is to mediate vesicle fusion, that is, docking and binding synaptic vesicles to the
presynaptic membrane to prepare them for release.
 SNAREs can be divided into two categories: vesicle or v-SNAREs , which are incorporated into the membranes of
transport vesicles during budding, and target or t-SNAREs, which are located in the membranes of target
compartments.
 Recent classification however takes account of the structural features of the SNARE proteins and divides them into
R-SNAREs and Q-SNAREs.
 The best-studied SNAREs are those that mediate docking of synaptic vesicles with the presynaptic membrane. These
SNAREs are the targets of the bacterial neurotoxins responsible for botulism and tetanus.

27. The answer is A. A high membrane resistance

Ref: Ganong - Review of Medical Physiology 23rd Ed Page 85-89
 Spatial summation of synaptic potentials can occur if they are close enough that the space constant spans the two
synapses; therefore, properties of the cell that increase the space constant would optimize the effectiveness of the
two synapses.
 The space constant increases with increasing membrane resistance or decreasing cytoplasmic resistance.
 Cytoplasmic resistance decreases as the cross-sectional area increases.
 Temporal summation could also increase the effectiveness of the two synapses; this would be facilitated by a large
time constant.

28. Ans. is (B) The action potential occurs due to sudden opening of Na + channels
Ref: Ganong, 22nd Edition, Page no 56
The action potential occurs due to sudden opening of voltage gated Na + channels The membrane potential of large nerves
when they are not transmitting nerve signals, that is, when they are in the so called resting’ state is about —70 millivolts Q

29.The answer is A. Increased intensity of the stimulus

Ref: Ganong - Review of Medical Physiology 23rd Ed Page 126
 The intensity of sensory information is encoded in the action potential frequency. Cessation of the stimulus would
lead to a rapid decrease in the action potential frequency, and adaptation of the receptor would also lead to a
decrease in frequency.
 With a constant and maintained stimulus, at least some adaptation would take place, and the frequency would fall
somewhat (and certainly not increase).
 The action potential velocity is a property of the nerve—not the receptor— and it would not be affected.

30.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 124
 Reduction in the intensity of a sensation is largely the result of a decline in the generator potential. In this sense, it
mimics the effects of a reduction in the stimulus intensity.
 Because the action potentials arising in a sensory nerve are all-or-none, their velocity of conduction, amplitude, and
duration of depolarization are not affected by the stimulus intensity; rather, they are properties of the nerve cell.

31. Ans: (B). Ca2+ binding troponin C

•The process by which depolarization of the muscle fiber initiates contraction is called excitation-contraction coupling .
•The action potential is transmitted to all the fibrils in the fiber via the T system .
•It triggers the release of Ca2+ from the terminal cisterns, the lateral sacs of the sarcoplasmic reticulum next to the T system
Ca2+ initiates contraction by binding to troponin C .
In resting muscle, troponin I is tightly bound to actin and tropomyosin covers the sites where myosin heads bind to actin.
•Thus, the troponin-tropomyosin complex constitutes a “relaxing protein ” that inhibits the interaction between actin and
myosin..
•When the Ca 2+ released by the action potential binds to troponin C, the binding of troponin I to actin is presumably
weakened, and this permits the tropomyosin to move laterally.
•This movement uncovers binding sites for the myosin heads.

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 Nerve-Muscle Physiology

•ATP is then split and contraction occurs Seven myosin-binding sites are uncovered for each molecule of troponin that
binds a calcium ion.

Section-2 -: Muscle

1. Ans. B. Accumulation of active metabolites (Ref :-Ganong-23rd Page-93)

The most important factor responsible for the increased blood flow in the exercising muscles is local; there is

Nerve -Muscle Physiology Chapter - 2

accumulation of metabolites which open up the precapillary sphincters, thereby recruiting more capillaries into
circulation. (Ref. Guyton 11th ed. p 247)
a. The tremendous increase in muscle blood flow that occurs during skeletal muscle activity is caused
primarily by chemical effects acting directly on the muscle arterioles to cause dilatation.
b. One of the most important chemical effects is reduction of oxygen in the muscle tissues. That is, during
muscle activity, the muscle uses oxygen rapidly, thereby decreasing the oxygen concentration in the tissue
fluids. This in turn causes local arteriolar vasodilatation both because the arteriolar walls cannot maintain
contraction in the absence of oxygen and because oxygen deficiency causes release of vasodilator
substances.
c. These local metabolites include lactate, adenosine, substance P etc, also ↓ p4, low pO2, high CO2 and
increased temperature results in vasodilation.
d. The most important vasodilator substance is probably adenosine in heart.

2. Ans. A. Perlecan
a. A large protein called dystrophin (MW-427,000)forms a rod that connects the thin actin filaments to the
transmembrane protein dystroglycan in the sarcolemma. This dystrophin-glycoprotein complex adds
strength to the muscle by providing a scaffolding for the fibrils and connecting them to the extracellular
environment.
b. Perlecan is a large multi-domain proteoglycan that binds to and cross-links many extracellular matrix
(ECM)components and cell- surface molecules.
c. Perlecan is synthesized by both vascular endothelial and smooth muscle cells and deposited in the
extracellular matrix.
d. Perlecan is a key component of the vascular extracellular matrix, here it interacts with a variety of other
matrix components and helps to maintain the endothelial barrier function.
e. Perlecan is a potent inhibitor of smooth muscle cell proliferation and is thus thought to help maintain
vascular homeostasis.
f. Perlecan can also promotes growth factor (e.g.,FGF2)activity and thus stimulate endothelial growth and
re-generation.

3. Ans. B. Ca2+ binding troponin C

4. Ans. A. Have multiple nuclei

5. Ans. B. Motor nerve and muscle fibers that it supplies

Motor unit consists of a somatic motor neuron and all the muscle cells it innervates.

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 Physiology

6. Ans. B. Cardiac muscles

INTERCALATED DISKS provide a strong union between cardiac muscle fibers and maintain cell to cell cohesion so
that pull of one contractile unit is transmitted along its axis to the next.

7. Ans. A. Neuromuscular junction

Myasthenia gravis is a disorder of NEUROMUSCULAR JUNCTION characterized by weakness and fatigability of
skeletal muscles. The basic defect is a decrease in the number of available acetylcholine receptors (AChRs) at
neuromuscular junctions Q because of an antibody-mediated autoimmune attack.

8. Ans. B. Troponin
a. In resting muscle fibers Troponin I is tightly bound to Actin while Tropomyosin covers the site where
myosin heads bind the Actin Q.
b. Therefore troponin-tropomyosin complex forms a relaxing protein which prevents interaction between
Actin and Myosin in resting muscles.
c. When Calcium ions are released by action potential they bind to Troponin C.
d. This process weakens the binding of Troponin I with Actin and cause lateral movement of Tropomyosin.
e. This process uncovers the binding sites of Actin and myosin heads leading to contraction.

9. Ans. C. Tropomyosin
Many different calcium-binding proteins have been described, including troponin, calmodulin, and calbindin

10. Ans. B. Covers myosin and prevents attachments of actin and myosin

11. Ans. D. Calcium

12. Ans. C. Intracellular calcium is essential to cause contraction

Excitation-contraction coupling (role of calcium ions):

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 Nerve-Muscle Physiology

a. The actual contractile process in skeletal muscle is activated by calcium ions Q.

b. This is also true in smooth muscles; however, the source of the calcium ions differs in smooth muscle
because the sarcoplasmic reticulum of smooth muscle is poorly developed Q.
c. In ‘some’ types of smooth muscle, almost all the calcium ions that cause contraction enter the muscle cell
from the extracellular fluid at the time of the action potential.
d. Because the smooth muscle fibers are extremely small (in contrast to the sizes of skeletal muscle fibers),
these calcium ions can diffuse to all parts of the smooth muscle and bring about the contractile process.

Nerve -Muscle Physiology Chapter - 2

13. Ans. D. Relaxation heat
"If a muscle that has contracted isotonically is restored to its previous length, extra-heat in addition to heat is
produced (known as Relaxation heat)"
I.e.
a. In Isotonic contraction  both Recovery heat and Relaxation heat (extra heat) are produced that restore
the muscle to its precontraction state. External work must be done on the muscle to return it to its
previous length, and relaxation heat is mainly a manifestation of this work.
b. In Isometric contraction (same length but  in tension) - only Recovery heat is liberated that restore the
muscle to its pre-contraction state.
i. Summation of contractions and Staircaise (Treppe) phenomenon occur in both of muscle contraction"
Work = Force x (distance).
ii. Therefore
 In Isometric contraction
W = Force x a (distance)
= 0 i.e. energy is used with work.
 In Isotonic contraction
W = Force x distance (muscle is shortened)
= Work done.

14. Ans. C. Increasing the amplitude of action potentials in the motor neurons
Force of muscle contraction depends upon
1. Resting length of muscle Q
2. Isometrical contraction Q
3. Recruitment Q
4. Repetition of stimuli Q
5. Fast muscle fibers Q
6. Action potentials are all or none phenomenon.they don’t show increase in amplitude.

15. Ans. A. There are two “T: tubules per sarcomere and has well developed sarcoplasmic reticulum
Mammalian skeletal muscle is organised optimally for rapid excitation of muscle contraction.

16. Ans. B. Sarcolemmal proteins

a. Duchenne and Becker muscular dystrophies  X-linked recessive disorder:
i. Caused by due to production of defective dystrophin or Absence of dystrophin, which is a sarcolemma
protein.

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 Physiology

Normally, the "dystrophin - glycoprotein complex" appears to confers stability to sarcolemma Q  so, in
the cases of these diseases  distruption of the dystrophin-glycoprotein complexes weakens the
sarcolemma causing membrane tears and a cascade of event leading to muscle fibers necrosis.

b. Diseases due to defect of Neuromuscular junction 

i. Myasthenia Gravis  Ach Receptor's number are decreased at the post synaptic muscle membrane;
anti-Ach R antibodies binds to AchRs, and reduces the available numbers of AchRs. Q
ii. Lambert-Eaton Maasthenia syndrome (LEMS)  Presynaptic neuromuscular disorder Q
iii. LMN types paralysis  causes Disuse atrophy of muscles weakness (eg. polio). Q

17. Ans. A. Accumulation of K+

Muscle spasm:
a. Spinal cord reflexes that causes muscle spasm.
b. Muscle cramps (= muscle spasm)  a type of local spam is the typical muscle cramp. Any local iritating
factor or metabolic abnormality of a muscle, such as severe cold, lack of blood flow to the muscle, or over
exercise of the muscle, can elicit pain or other types of sensory impulses that are transmitted from muscle
to the spinal cord, thus causing reflex muscle contraction.
c. During Exercise  Local mechanism maintaining a high blood flow in exercising muscle include a fall tissue
PO2 (hypoxia), arise in tissue PCO2 (H+) an accumulation of K+ and other vasodilator metabolites, Also due
to  in temp.

18. Ans. C. Muscle tension

19. Ans. A. Accommodation

20. The answer is C. Are derived from PIP2

Ref: Ganong - Review of Medical Physiology 23rd Ed Page 38
 Inositol trisphosphate (IP3) and diacylglycerol (DAG) are generated by the action of phospholipase C (PLC) on PIP 2,
phosphatidylinositol 4,5-bisphosphate. IP3 and DAG are second messengers, not first messengers.
 DAG is important for the activation of protein kinase C, not PLC. Tyrosine kinase receptors are activated by the
binding of ligands, such as hormones or growth factors, not by IP3 or DAG.
 IP3 can indirectly activate calcium-calmodulin-dependent protein kinases by causing the release of calcium from
intracellular stores; DAG has no direct effect on these kinases.

21. Ans: (B). Ca2+ binding troponin C

•The process by which depolarization of the muscle fiber initiates contraction is called excitation-contraction coupling .
•The action potential is transmitted to all the fibrils in the fiber via the T system .
•It triggers the release of Ca2+ from the terminal cisterns, the lateral sacs of the sarcoplasmic reticulum next to the T system
Ca2+ initiates contraction by binding to troponin C .
In resting muscle, troponin I is tightly bound to actin and tropomyosin covers the sites where myosin heads bind to actin.
•Thus, the troponin-tropomyosin complex constitutes a “relaxing protein ” that inhibits the interaction between actin and
myosin..
•When the Ca 2+ released by the action potential binds to troponin C, the binding of troponin I to actin is presumably
weakened, and this permits the tropomyosin to move laterally.
•This movement uncovers binding sites for the myosin heads.
•ATP is then split and contraction occurs Seven myosin-binding sites are uncovered for each molecule of troponin that
binds a calcium ion.

22.The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 206-209

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 Nerve-Muscle Physiology

 The maintenance of posture requires continuous muscle action in antigravity muscles of the back.
 The low threshold for activation, fatigue-resistant motor units are the type active in postural control.
 Intrafusal muscle fibers do not contribute to force generation.

23.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 133
 GOLGI TENDON ORGAN – receptor for inverse stretch reflex (3-25 muscle fibres / tendon organ )
 Are in series with muscle fibres
 Stimulated by both passive stretch and active contraction of muscle
 Supplied by ib afferents

Nerve -Muscle Physiology Chapter - 2

 Senses muscle tension & force of muscular contraction
 It acts as a protective reflex to prevent tearing of muscles. As a strong & potentially damaging muscle force reflexly
inhibits the contraction – leading to relaxation instead of trying to maintain the force.
 The nuclear chain and bag fibers, along with type Ia endings, are all components of the muscle spindle which reports
muscle length and velocity of muscle shortening.

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 Kidney

Chapter – 3
Kidney

Each human kidney has about 1 - 1.3 million nephrons. The length of nephron including collecting ducts ranges
from 45- 65mm. The human PCT is about 15 mm long; DCT is about 5 mm long and collecting ducts are 20 mm
long.

Chapter - 3
I. FUNCTIONAL ANATOMY
Nephron = Renal tubule + glomerulus
Glomerulus + Bowman’s capsule = malphigion corpuscle.

Kidney

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 Physiology

A. Glomerular membrane
The barriers through which filtration has to take place
1. Glomerular endothelial cell layer : The glomerular capillaries are fenestrated (most permeable capillaries),
the pore size of the fenestrae is 70 – 90 nm.
2. Basement membrane: Permeability of basement membrane depends on:
a. Size of particle
Neutral substances which are < 4nm are freely filtered; > 8nm are not filtered
Between 4 nm and 8nm, the permeability is inversely proportional to the diameter
b. Charge of the particle
Since the sialoprotein in the glomerular capillary wall are negatively charged, filtration of positively
charged particles is facilitated whereas negatively charged particles are repelled. That why there is
only 0.2% filterability of albumin(negatively charged) although it is filterable by size( effective
diameter of ~ 7 nm.)
c. Visceral epithelial layer of Bowman’s capsule. The visceral epithelial cell is called a podocyte; each
podocyte has many foot processes, which inter digitate to form filtration slits:
The size of filtration slits = 25 nm.

B. Difference between proximal tubular cell and distal tubular cell

PCT CD
1. Brush border present No brush border
2. Carbonic anhydrase present in luminal membrane No carbonic anhydrase in luminal membrane
3. Has ‘leaky’ tight junctions Has ‘tight’ tight junction

C. Difference between cortical and juxtamedullary nephron

Cortical nephron Juxtamedullary nephron
Form 85% of the nephrons Form 15% of the nephrons
Short loop of Henle Long loop of Henle
Peritubular capillary network is short Form vasa recta
Blood flow is large Blood flow is less
O2 extraction is very less O2 extraction is large
PO2 is 50mmHg PO2 is 15mmHg
Role in excretion of waste products in wine Involved in counter current system far formation of
concentrated wine.

D. Special cells in collecting tubule

1. P (Principal) cell: For Na+ reabsorption
2. I (Intercalated) cell: They are present in Cortical Collecting Duct.
Intercalated cells come in α and β varieties and participate in acid-base homeostasis.

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 Kidney

Type of cell Secretes Reabsorbs

acid (via an apical H+-ATPase and H+/K+ exchanger) in the form

α-intercalated bicarbonate (via band 3, a
of hydrogen ions
cells basolateral Cl-/HCO3- exchanger)
also an e.g. of Primary active transport.

β-intercalated
bicarbonate (via Pendrin a specialised apical Cl-/HCO3-) acid (via a basal H+-ATPase)
cells

Chapter - 3
E. Mesangial cells
2 sites :-
1. Intraglomerular mesangial cells (Lying between glomerular capillary loops)
These are contractile cells and play a role in regulation of glomerular filtration
(Note: When these contract, the GFR decreases because the effective area of filtration is reduced)
Agents causing their :-

Contraction Relaxation
Endothelins Dopamine
Angiotensin II ANP
Vasopressin cAMP
Norepinephrine PGE2

Kidney
Platelet activating factor
Platelet derived growth factor
PGF2
Thromboxane A2
Leukotrienes C4 and D4
Histamines

2. Extra glomerular mesangial cells (Lacis cells)

These form part of the juxta – glomerular apparatus.
Secrete mesangial matrix, phagocytic, inflammatory.

F. Juxtaglomerular apparatus
Components are
1. Juxtaglomerular cells (act as baroreceptors)
These are modified smooth muscle cells in the tunica media of the afferent arteriole. The cells have renin
containing granules. Stimulated by low Blood vol., Low BP, Low Na+, Sympathetic stimulation,
Thromboxane A2.
2. Macula densa (act as chemoreceptors)
This is the modified region of the tubular epithelium; it marks the beginning of DCT. Act as sensor for Na+
3. Lacis cells (they are supporting cells)

G. Renal vessels / Renal nerves

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 Physiology

Renal vasodilation: Dopamine, prostaglandins, acetyl choline, high protein diet

Renal vasoconstriction:
1. Angiotensin II
Constricts efferent arteriole more than afferent arteriole so ↓ RBF ↑ GFR
2. Norepinephrine
Constricts afferent arteriole more than efferent arteriole so ↓ RBF ↓ GFR
Effects of sympathetic Nerves to kidney
1. Vasoconstriction (Which decrease renal blood flow and GFR)
2. Increases renin output
3. Increases Na+ reabsorption
Peritubular capillaries secrete Erythropoietin (85%) rest from liver etc

II. KIDNEY: BLOOD FLOW/O2 CONSUMPTION

(WEIGHT = 300 GM)
A. Renal Blood Flow
Total 1260 mL/min
Cortical 5 mL/Gm/min
Outer Medulla 2.5 mL/Gm/min
Inner Medulla 0.6 mL/Gm/min

Effective Renal plasma flow (ERPF) = 625 mL/min

Renal plasma flow (RPF) = 700 mL/min
B. O2 Consumption
Total 18 mL/min
Cortex 9 mL/100 gm/min
Inner Med. 0.4 mL/100 gm/min
(A-V) O2 Diff. = 14 ml/L

OTHER POINTS
1. Total Blood Flow Liver > Kidney > Sk Msl > Brain
(mL/min) (1500) (1260) (840) (750)
(mL/100g/min) Kidney > Heart > Liver > Brain
(420) (84) (58) (54)

2. A-V O2 Diff Heart > Brain > Sk Msl > Liver > Kidney
(mL/L) (114) (62) (60) (34) (14)

3. O2 Consumption Liver > Sk Msl > Brain > Heart > Kidney
(mL/min) (51) (50) (46) (29) (18)

4. O2 Consumption Heart > Kidney > Brain > Liver

(mL/100g/min) (9.7) (6) (3.3) (2.0)

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 Kidney

Glomerular filtration
This is governed by the same forces (Starling’s forces) as that across capillary.
GFR = Kf [ (PGC - PT) + (t - GC)]
Where Kf = filtration coefficient
GC = Glomerular capillary
T = Tubule
P = Hydrostatic pressure

Chapter - 3
 = Oncotic pressure
(Hydrostatic pressure is a ‘push’ force and Oncotic pressure is a ‘retaining’ or pull force)

III. TUBULAR REABSORPTION

A. Sodium reabsorption
It occurs in all parts of the tubule except the thin descending part. It is active reabsorption except in thin
ascending portion (where it is passive).
The various mechanisms in different parts of the tubule are

PCT (Proximal Convoluted tubule) SGLT

Na – Amino acids
Na – Citrate / PO4 / SO4 / Lactate

Kidney
PST (Proximal Straight tubule) Cl- driven Na+ transport
DTS (Descending thin Segment) No reabsorption
ATS (Ascending thin Segment) Passive (no transportation)
TAL (Thick Ascending Limb) Na+- K+ - 2Cl-; Na-H
DCT (Distal convoluted tubule) Na+ - Cl-
CD (Collecting Duct) P cell (ENaC)
(P cell = principal cell; ENaC = Epithelial sodium channel)
(Aldosterone acts on collecting duct to increase Na+ reabsorption. It does this by increasing the number of open
EnaCs and also by increasing the number of Na+ - K+ ATPase)
Other points
Out of the total filtered load of Na+, 99.4% is reabsorbed  65% in PCT; 25% in Henle; 10% in DCT/CT.
Na+ reabsorption is increased by aldosterone (which acts on collecting duct) and by angiotensin II (which acts on
PCT)
Most of the sodium is reabsorbed along with Cl
Natriuresis is caused by PGE2, IL-1, ANP, Quabain, Endothelin

B. Glucose
1. Glucose is reabsorbed by secondary active transport.SGLT-1,2
2. All the glucose is reabsorbed in PCT.
3. The TmG (tubular maximum for glucose i.e. the maximum rate of absorption of glucose by the tubule)
is 375 mg/min in males and 300mg/min in females.

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 Physiology

4. Given that the TmG is 375mg/min in males, by calculation, the renal threshold for glucose in blood
would be
5. 300mg/dL.
6. The actual value of renal Threshold is much less than this; it is 200mg/dL in arterial and 180mg/dL in
venous blood.
7. This deviation in the renal threshold (from the calculated predicted value) in called splay.
8. The reason for splay is heterogeneity of nephrons (i.e. not all nephrons have TmG of 375 mg/min);
further, not all nephrons are maximally active simultaneously

C. Water
Water reabsorption is passive, following the osmotic gradient. The total glomerular filtered load is
approximately 180L/day. Out of this, the amount of urine output can vary from 500mL (osmolality of 1400
mosm/L) to 23.3 Litres (osmolality of 30 mosm/L). Water reabsorption is facilitated by water channels
(aquaporins) There are various types of aquaporins:

Type Site
Aquaporin 1 Luminal membrane of PCT
Aquaporin 2 Luminal membrane of CD
Aquaporin 3 Basolateral membrane of CD
Aquaporin 4 Brain
Aquaporin 5 Salivary, lacrimal, respiratory system

The % of water reabsorption in the various segments is as follows

1. PCT 60-70% 2. Loop of Henle 15%
3. Distal Tubule 20%
a. DCT 5%
b. CT 15%
Cortical CT 10%
- Medullary CT 4.7%
Permeability and Transport in Various Segments of the Nephron.
Permeability

H2O Urea NaCl Active Transport of Na+

Loop of Henle

Thin descending limb 4+ + ± 0

Thin ascending limb 0 + 4+ 0

Thick ascending limb 0 ± ± 4+

Distal convoluted tubule ± ± ± 3+

Collecting tubule

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 Kidney

Cortical portion 3+* 0 ± 2+

Outer medullary portion 3+* 0 ± 1+

Inner medullary portion 3+* 3+ ± 1+

The tonicity of tubular fluid at various segments :-

Water reaborptn in PCT is obligatory ↑ Water reabsorption in CD – Facultative.
1. At the end of PCT : Isotonic

Chapter - 3
2. As it goes down the descending limb : Hypertonic
3. As it goes up the ascending limb : It first, isotonic, then hypotonic.
4. At the top of ascending limb, it is hypotonic
(The ascending limb is called the diluting segment)
Segments to water is as follows:
Water NaCL
A Thin Descending Limb Highly permeable 
B Thin ascending limb Not permeable Highly permeable
C Thick ascending limb (TAL) Not permeable 
+ + -
[However, TAL has Na - K - Cl cotransporter]

5. The DCT is relatively impermeable to water (Therefore, there is continued dilution of the tubular fluid as it goes
along the DCT)

Kidney
6. Collecting Duct
It becomes permeable to water in the presence of ADH; ADH inserts aquaporin 2 channels in the luminal
membrane of collecting duct cells

D. Counter current mechanism

There are 2 counter current mechanisms in kidney

1. Counter current multiplier, in loop of Henle (Produces osmolality gradient of medulla 1200 mosm/L)
2. Counter current exchanger, in vasa recta (Maintains medullary osmolality gradient by selectively reabsorbing
water only.

The counter current mechanism depends on the gradient of osmolality in the medullary interstitium. The medullary
interstitial gradient depends on;
1. Active transport of Na+ at thick ascending limb (by Na+ - K+ - 2Cl- Co- transporter)
2. Passive movement of Na+/Cl- out of thin ascending limb without water
3. (Refer to the permeability characteristics of the tubule)
4. Permeability of thin descending limb to water
5. Urea, also contributes

The inner medullary collect duct is significantly permeable to urea; (ADH increase this permeability).
The longer the loop of Henle, the greater can be the medullary interstitial osmotic gradient created; thus, the
concentration ability is determined by the length of the loop of Henle.

83
 Physiology

Once the interstitial osmotic gradient is established by the counter current multiplier, it is maintained by the
counter current exchange mechanism of the vasa recta; without the counter current exchange mechanism, all the
good work of the counter current multiplier will soon be lost. The counter current multiplier mechanism is active
whereas the counter current exchange mechanism is passive.

Once the medullary interstitial osmotic gradient is established, water can move from the collecting in the presence
of ADH

Note that in the cortical collecting duct segment, the urine can at best be concentrated up to isotonicity only; as it
moves down the medulla collecting duct, the urine can be concentrated up to the maximum limit determined a by
the maximum gradient existing in the medullary interstitium.

Difference between Water and Osmotic diuresis

Water diuresis Osmotic diuresis
This is by inhibition of ADH This is by osmosis
Absorption in PCT is normal Absorption in PCT is decreased
Maximum limit of diuresis is 16ml/min No such limit

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 Kidney

E. Potassium
1. Active reabsorption in PCT; secreted in DCT. K+ secretion is decreased when the amount of Na+ reaching
the DCT is small.
2. K+ secretion is also decreased when the H+ secretion is increased
3. In DCT, Na+ is reabsorbed and K+ and H+ compete for their secretion for the amount of Na+ reabsorbed.
4. K+ is the only electrolyte that is reabsorbed as well as secreted.
5. 65% of the K+ is reabsorbed in PCT, 25% in loop and < 10% reaches the distal rephron

Chapter - 3
6. For K+ and H+, remember the terms ‘hypokalemia i.e. alkalosis and hyperkalemic acidosis’.

F. Hydrogen secretion
Occurs in PCT, DCT and CD
Mechanisms
a. In PCT
i. Na+ - H+ exchanger
ii. For each H+ that is secreted, effectively 1 Na+ and 1 HCO3- is reabsorbed.
(The handling of the secreted H+ in PCT is by carbonic anhydrase)
The secreted H+ in PCT does not acidify the urine; it only helps in the reabsorption of Na+ and HCO3-.
Since the secreted H+ in the PCT is quickly handled, the secretion of H+ in, PCT can be called a high-capacity, low-
gradient system. i.e. the capacity is high but the acidification is not there.

Kidney
In tubular fluid

Na+

H+
H+ Carbonic
anhydrase
HCO3-

Lumen H2CO3

H2O
CO2
H2O + CO2
+
Na
H2CO3
+
H HCO3-

b. In DCT / CD
i. ATP – driven proton (H+) pump
ii. H+ - K+ ATPase
The secreted H+ here helps to acidify the urine. Since the secreted H+ is not as quickly handled (recall that there is
no carbonic anhydrase in the luminal membrane of DCT), the limit of H + secretion is reached quickly. Therefore, the

85
 Physiology

H+ secretion here can be called a low-capacity, high-gradient system. i.e. the capacity is low but the acidification is
significant.

Clearance : Clearance for a substance ‘A’ is

i. Definition: defined as that volume of plasma that is required to contain that much amount of the
substance A which is present in one minute’s urine. Its unit is mL/min.
ii. Formula :-

It is given by the formula:

C= U V
P Where
C = clearance
U = concentration of the substance in the urine
V = urine flow
P = concentration of the substance in the plasma

Uses

If renal clearance is more than GFR.→ Tubular secretion

If renal clearance is less than GFR. → Tubular reabsorption
If renal clearance is same as GFR. → No secretion & no reabsorption

1. Filtered Load = Glomerular Filtration Rate x Plasma Concentration,

2. Tm: no Tm for urea, chloride, water as they are passively reabsorbed.
3. Clearance of Inulin gives GFR (125ml/min)

G. Extraction ratio
1. The fraction of a substance removed from the blood flowing through the kidney or other organ; it is
calculated from the formula (RA—RV)/RA, where A and V, respectively, are the concentrations of the
substance in Renal artery and vein respectively. For instance, para aminohippuric acid (PAH) is almost
completely excreted in the final urine, and thus almost none is found in the venous return (RV ~ 0).
Therefore, the extraction ration of PAH ~1. This is why PAH is used in PAH clearance to estimate renal
plasma flow.
2. Clearance of paramino hippuric acid (PAH) gives renal plasma flow (625 ml/min)
3. Since the extraction ratio of PAH is 0.9 (90%), the value obtained is effective renal plasma flow (ERPF)
ERPF
The actual RPF =
0.9

H. Other Points
Clearance is just a mathematical (theoretical) concept eg. Clearance of glucose is normally zero because there is no
glucose in the urine. It does not mean that there is no glucose in blood !
0

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 Kidney

Chapter - 3
I. Graph showing the effect of increasing plasma concentration on clearance.
1. For a substance that is reabsorbed its Clearance is less than GFR and on increasing its plasma conc. above
renal threshold its Clearance starts increasing. It can become as high as GFR itself but not more than that as
they are always reabsorbed e.g. Glucose.
2. Whereas for any substance that is secreted it has a Clearance more than GFR and on increasing its plasma
conc. its Clearance starts decreasing. It can become as low as GFR again but not less than that.e.g PAH
Clearance.
3. Whereas a substance that as no secretion no reabsorption i.e. GFR= Clearance, increasing the plasma conc.

Kidney
Does not affect Clearance at all it remains same as GFR.

J. Free Water clearance (CH2O)

This is the difference between actual urine output and the urine output calculated based on clearance of osmoles
CH20 = V - Uosm X V where V = actual urine output
Posm
(If the value is positive, the urine is hypotonic; if the value is negative, the urine is hypertomic)

K. Urinary Buffers
Help in acid secretion
Type of buffer PK Sites
Bicarbonate(noninducible buffer) 6.1 In PCT, it is mostly bicarbonate buffer
Phosphate (noninducible buffer) 6.8 In DCT/CD
Ammonia (inducible buffer) 9.0 Both PCT & DCT
1. Ammonia buffer system: The principal reaction producing NH4+ in cells is conversion of glutamine to
glutamate. This reaction is catalyzed by the enzyme glutaminase, which is abundant in renal tubular cells. pK'
of this buffer system is 9.0. In chronic acidosis, the amount of NH4+ excreted at any given urine pH also
increases, because more NH3 enters the tubular urine. The effect of this adaptation of NH3 secretion, is a
further removal of H+ from the tubular fluid and consequently a further enhancement of H + secretion.

2. Limiting pH of urine = 4.5

Factors affecting acid secretion
a. Intracellular PCO2

87
 Physiology

When PCO2 in high, acid secretion is increased

b. K+ depletion
This increases acid secretion
3. Note:
Hypokalemia tends to cause alkalosis and vice versa.
Hyperkalemia tends to cause acidosis and vice versa.
a. If carbonic anhydrase is inhibited, acid secretion is decreased
b. Aldosterone: This increases Na+ reabsorption and increases K+ and H+ secretion
4. Titratable Acid :- This is measured by the amount of alkali to be added to urine to make the pH 7.4. Titratable
acid mainly reflects the buffering by phosphate buffer. pH of filterate does not change till DCT.
a. Net acid excretion: Titratable acid + NH4 excreted – HCO3- excreted.
b. Net HCO3- gain: Same formula as for net acid excretion.

88
 Physiology

“Please Read the Preface of this book Before you attempt these questions.”
Explanation of answer start from page no. 93
because:
Section-1 -: A. Of its high concentration in plasma
Nephron, Blood flow and Glomerular Filtration B. Has molecular weight slightly greater than the
molecules normally getting filtered
1. Angiotensin II causes A/E: (AIIMS MAY 2011, AIPG C. High albumin: globulin ratio
2009) D. Tubular epithelial cells are sensitive to albumin
A. Stimulates release of ADH
B. Increases thirst 8. Which of the following does not form filtration
C. Vasodilation barrier in nephrons: (Latest Questions)
D. Stimulates aldosterone release A. Podocytes
B. Endothelial cells
2. Renal physiology A/E (AIPG 2009) C. Mesangium
A. DCT always receive hypo-osmotic solution D. Basement membrane (basal lamina)
B. Afferent artery supplies glomerulus
C. GFR is controlled by afferent & efferent arteriole 9. Which of the following is NOT secreted in the proximal
tubule?
D. 5% cardiac output is received by kidney.
(A) Organic anions such as bile salts
(B) Hydrogen ions (H+)
3. What is absent in the medulla? (C) Organic cations such as choline
A. Loop of Henle B. Vasa recta (D) Phosphate
C. Collecting duct D. Juxtaglomerular Section-2 -: Transport of various substance
apparatus 1 . Absorption of all occur in PCT except: (AIIMS
NOV 2010)
4. Glomerular filtration rate is best estimated by A. PO4 B. Glucose
-
which of the following: (DNB Pattern) C. HCO3 D. H+
A. MSA
B. Inulin clearance 2. The status of fluid in distal convoluted tubule is
C. Hippuric acid always (AIPG 2009)
D. Creatinine clearance A. Always hypotonic B. Hypertonic
C. Isotonic D. Always hypertonic
5. Relaxation of mesangial cells of kidney is brought
about by (DNB Pattern) 3. Maximum absorption of HCO3 occurs is:
A. cAMP B. Endothelin (AIIMS NOV 2007)
C. PGF2 D. Vasopressin A. PCT B. DCT
C. CT D. ALH
6. GFR increases if(DNB June-2009)
A. Afferent arteriole constricts 4. Which of the following ion is least absorbed in
B. Afferent arteriole dilates tubules:
C. Efferent arteriole constricts A. Sodium B. Urea
D. Efferent arteriole dilates C. Creatinine D. Glucose

7. In renal disease albumin is first to appear in urine

1.C 2.D 3.D 4.B 5.A 6.B&C 7.B 8.C 9.D 1.D 2.A 3.A 4.C

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 Kidney

13. The amount of protein normally excreted in urine

5. In the presence of vasopressin the greatest fraction per day is: (LQ)
of filtrated water is re-absorbed in which part of the A. 100mg B. 300mg
nephron? C. 150mg D. 450mg
A. Proximal tubule B. Distal tubule
14. Tm for glucose is: (DNB Pattern)
C. Loop of Henle D. Collecting duct
A. 500 B. 440 C. 350 D. 150

6. Which of the following is true regarding potassium?

15. Transport maximum (Tm) means (DNB Pattern)

Chapter - 3
(DNB Pattern)
A. Maximum reabsorption & secretion
A. Mainly absorbed in DCT
B. Maximum amount of glomerular filtration/min
B. Absorption depends upon aldosterone
C. Substance cleared from plasma/mm
C. Competes with sodium ion absorption
D. Amount of toxic substances excreted/min
D. Entirely absorbed in PCT

16. True about nephron is (DNB June-2009)

7. Which of the following is not absorbed in DCT?
A. Na is absorbed actively in descending loop of Henle
(DNB Pattern)
A. Sodium B. Water B. 60 to 70% of GFR is absorbed in proximal tubule
C. Potassium D. Chloride C. Absorption of water occurs in ascending loop of
Henle
8. Active potassium excretion occurs at: D. The filtrate reaching distal convoluted tubule is
(DNB Pattern) hypertonic with respect to surroundings
A. Proximal convoluted tubule

Kidney
B. Distal convoluted tubule 17. Potassium is maximally absorbed in which part of
C. Ascending loop of Henle nephron? (DNB Pattern)
D. Descending loop of Henle A. Proximal convulated tubules
B. DCT
9. Maximum absorption of water occurs in: C. Collecting ducts
A. PCT B. DCI D. Loop of Henle
C. Loop of Henle D. Collecting tubules
18. Over half of the Potassium that appears in the
10. Na absorption is maximum at: (Latest Questions) urine of a patient, who has ingested some potassium
A. DC B. PCT salts, is derived from:
C. Loop of Henle D. Collecting tubules A. Glomerular filtrate
B. Secretion by the distal tubule
11. In which of the following the major portion of C. Reabsorption in the proximal tubule
glomerular filtrate is absorbed? (DNB Pattern) D. Secretion by the loop of Henle
A. Collecting duct
B. Distal convoluted tubule Section-3 -: Clearance
C. Loop of Henle 1. Which of the following statement is true ? (AIIMS
D. Proximal segment by active reabsorption of Na+ MAY 2011)
A. Fluid coming from the descending limb of loop of
12. The urine/plasma ratio of sodium ion is: henle is hypotonic
A.0 B.100 C. 10 D. 0.6 B. Descending limb of loop of henle is permeable to
solutes

5.A 6.D 7.C 8.B 9.A 10.B 11.D 12.D 13.C 14.C 15.A 16.B 17.A 18.B 1.C

89
 Physiology

C. If clearance of substance is greater than GFR, then (A) Blood urea nitrogen (BUN)
tubular secretion must be present (B) Endogenous creatinine clearance
D. Clearance of a substance is always less than GFR if (C) Inulin clearance
there is tubular secretion (D) PAH clearance
2. What is true? (AIIMS NOV 2012) 10.Which of the following substances has the highest
A. Clearance of a substance which is freely filtered and renal clearance?
actively secreted is greater than GFR (A) Creatinine
(B) Inulin
B. Clearance of a substance which is filtered and
(C) PAH
C. reabsorbed is greater than the clearance of inulin (D) Na+
D. Descending loop of Henle has hypotonic fluid
E. Descending loop of Henle is permeable to solutes Section-4 -: Counter Current Mechanism
1. Urinary concentrating ability of the kidney is
3. Renal plasma flow is best determined by increased by:
(DNB Pattern) A. ECF volume contraction
A. Inulin B. Creatinine
B. Increase in RBF
C. PAH D. Mannitol
C. Reduction of medullary hyperosmlarity
4. Inulin clearance is equal to
D. Increase in GFR
A. 55m1/min B. 625 ml/min
2. Renal medullar hyperosmolarity is due to:
C. 125m1/min D. 40 ml/min (DNB Pattern)
A. Increased interstitial Na
5. Least clearance is for among these (DNB Pattern) B. Increased interstitial K
A. Glucose B. Insulin C. Increased interstitial Na & urea
C. Urea D. Creatinine D. All of the above
6. PAH (para-aminohippuric acid) clearance is
indicated by which of the following: 3. Which of the following is true regarding nephron
A. Renal plasma flow B. Filtration rate function:
C. Reabsorption rate D.Glomerular filtration rate A. Ascending thick limb is permeable to water
B. Osmolality of intratubular content is more
7. The renal plasma flow (RPF) of a patient was to be C. In PCT 10-20% filtrates are reabsorbed
estimated through the measurement of Para Amino D. In PCT 60-70% filtrates are reabsorbed
Hippuric acid (PAH) clearance. The technician
observed the procedures correctly but due to an error Section-5 -: Acid-Base Balance
in the weighing inadvertently used thrice the
recommended dose of PAH. RPF estimated is likely to 1. Anion gap is mainly due to: (DNB Pattern)
be: A. Sulfate B. Phosphates
A. False — High C. Protein D. Nitrates
B. False — Low
C. False — high or false — low depending on the GFR 2. The enzyme required for the generation of the
D. Correct and is unaffected by the PAH overdose ammonium ion in the kidney is:
8. Free water clearance by the kidney is increased by A. Glutamate dehydrogenase
which of the following? B. Glutamate aspartate transaminase
(A). Diabetes insipidus (B). Renal failure
C. Glutaminase
(C). Diuretic therapy (D). Diabetes mellitus
D. Glutamate carboxylase
9.Which of the following provides the most accurate
measure of GFR?

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 Kidney

3. In which of the following metabolic alkalosis is not

seen: (DNB Pattern), (DNB June-2010)
A. Thiazide therapy
B. Ureterosigmoidostomy
C. Persistent vomiting
D.Cushing syndrome

4. The Henderson-Hasselbalch equation is used for

measuring: (DNB Pattern)

Chapter - 3
A. The sodium potassium balance
B. The acid base balance
C. The kinetics of enzymatic reaction
D. Anion gap

5. Basal acid output is increased by which of the

following?
(A). Acidification of the antrum
(B). Administration of an H2 receptor antagonist
(C). Vagotomy
(D). Alkalinization of the antrum

Kidney

2.A 3.C 4.C 5.A 6.A 7.B 8. A 9. C 10.C 1.A 2.D 3.D 1.C 2.C 3.B 4.B 5.D

91
 Physiology

7. Most accurate measurement of extracellular fluid

(ECF) volume can be done using: (DNB Dec-2009)
6. Following cells are responsible for acid secretion in A. Sucrose B. Mannitol
kidney. (DNB Pattern) C. Inulin D. Aminopyrine
A. I cells B. P cells
C. Masangial cells D. Pericytes 8. Which of the following is false regarding renin?
A. It is secreted by kidney
Section-6 -: endocrine functions of kidney & other B. It is synthesized as pre-prohormone
applied aspects C. It is increased in primary hyperaldosteronism
D. It is a glycoprotein
1. Which of the following hormone is not secreted by
kidney. (AIPG 2011) 9. In micturition reflex, the first change to occur is:
(DNB June-2010)
A. 1,25 dihydroxy cholecalciferol
A. Trigone relaxation
B. Angiotensin I
B. Detrusor contraction
C. Renin
C. Relaxation of perineal muscle
D. Erythropoietin
D.Decreased urethral pressure

2. Ureteric peristalsis is due to (AIIMS NOV 2011) 10. Which of the following methods is not used for
A. Sympathetic innervation measurement of body fluid volumes?
B. Parasympathetic innervation A. Aminopyrine for total body water
C. Both (A) and (B) B. Inulin for extracellular fluid
D. Pace maker activity of the smooth muscle cells in the C. Evans blue for plasma volume
renal pelvis D. I131 albumin for blood volume

3. Sodium is excreted in urine in: 11. Vasopressin secretion is increased by

A. CHF B. SIADH A. Alcohol
C. Aldosterone deficiency D. Shock B. Decreased ECF volume
C. Carbamazepine
4. In which of the following condition, renin secretion D. Procainamide
is inhibited:
A. Cirrhosis B. Exercise 12. In which of the following forms the Anti diuretic
C. Hypervolemia D. Cardiac failure hormone (ADH) is circulated in plasma?
(DNB June-2009)
5. Renin is released when: (DNB Pattern) A. Bound to neurophysin — I
A. Low phosphate B. Low sodium B. Bound to neurophysin —II
C. Bound to plasma albumin
C. High phosphate D. High sodium
D. Free form
13. ADH act at:
6. Which of the following is the renin induced A. Proximal convoluted tubules
hypertension: B. Distal convoluted tubules
A. Renal artery stenosis hypertension C. Collecting tubules
B. Coarctation of aorta D. Loop of Henle
C. Renovascular hypertension 14. Angiotensinogen is produced by: (DNB Pattern)
D. Essential hypertension A. Liver B. Kidney
C. Atrium D. Hypothalamus
6.A 1.B 2.D 3.B 4.C 5.B 6.C 7.C 8.C 9.C 10.D 11.B,C 12.B 13.C 14.A

92
 Kidney

15. Production of aldosterone is stimulated by? 23. Monitoring of serum cystatin levels for
A. Atrial natriuretic peptide A. Renal functions B. Bone disorders
B. Adrenaline C. Muscle disorder D. Liver functions
C. Renin
D. Dopamine
E. Endorphin 24. Which of the following changes tends to increase
peritubular capillary fluid reabsorption? :
16. Several hormones regulate the tubular A. Increased Efferent arteriolar resistance

Chapter - 3
reabsorption of water and electrolytes at different B. Decrease Efferent arteriolar resistance
sites in the nephron. Which of the following C. Increase afferent arteriolar resistance
combination is correct? D. Decrease afferent arteriolar resistance
A. Angiotensin in distal tubule
B. Aldosterone in collecting ducts
C. ADH in proximal tubule 25. Mineralocorticoid receptor are not present on :
D. ANP in loop of Henle (AIIMS Nov 08)
A. Distal nephron
17. The part of Nephron most impermeable to water B. Colon
is C. Liver
A. PCT B. DCT D. Hippocampus
C. Ascending Loop D. CD
26. What is true? (AIIMS Nov 08)
18. In which of the following condition, renin
secretion is inhibited: A. Clearance of a substance which is freely filtered and
actively secreted is greater than GFR

Kidney
A. Cirrhosis B. Exercise
C. Hypervolemia D. Cardiac failure B. Clearance of a substance which is filtered and reabsorbed
is greater than the clearance of inulin
19. Aldosterone does not act on C. Descending loop of Henle has hypotonic fluid
A. PCT D. Descending loop of Henle is permeable to solutes
B. ascending limb of loop of Henle
C. DCT
D. collecting duct

20. ANP acts at which site?

A. Collecting duct
B. Ascending Loop
C. Descending Loop
D. PCT

21. In collecting duct...

A. increased excretion of K+
B. increase excretion of Na+
C. increase excretion of urea
D. increased HCO3- reabsorption

22. An athelete came to casualty with 4 days of

passing red coloured urine, the cause of hematuria is
A.hemoglobin. B.hemosiderin
C.hepatoglobin D. myoglobin
15.C D E 16.B 17.C 18.C 19.A 20.A 21.A 22.A 23.A 24.A 25.C 26.A

93
 Kidney

27.If the plasma concentration of a freely filterable substance is 2 mg/mL, GFR is 100 mL/min, urine
concentration of the substance is 10 mg/mL, and urine flow rate is 5 mL/min, we can conclude that the kidney
tubules
(A) Reabsorbed 150 mg/min
(B) Reabsorbed 200 mg/min
(C) Secreted 50 mg/min
(D) Secreted 150 mg/min

Chapter - 3
28.A man has progressive, chronic kidney disease. Which of the following indicates the greatest absolute
decrease in GFR?
(A) A fall in plasma creatinine from 4 mg/dL to 2 mg/dL
(B) A fall in plasma creatinine from 2 mg/dL to 1 mg/dL
(C) A rise in plasma creatinine from 1 mg/dL to 2 mg/dL
(D) A rise in plasma creatinine from 2 mg/dL to 4 mg/dL

29.Which of the following results in thirst?

(A) Cardiac failure
(B) Decreased plasma levels of angiotensin II
(C) Distension of the cardiac atria
(D) Distension of the stomach

30. In a kidney producing urine with an osmolality of 1,200 mOsm/kg H 2O, the osmolality of fluid collected from
the end of the cortical collecting duct is about

Kidney
(A) 100 mOsm/kg H2O
(B) 300 mOsm/kg H2O
(C) 600 mOsm/kg H2O
(D) 900 mOsm/kg H2O

31.Hypertension was observed in a young boy since birth. Which of the following disorders may be present?
(A) Bartter’s syndrome
(B) Gitelman’s syndrome
(C) Liddle’s syndrome
(D) Nephrogenic diabetes insipidus

32.In a person with severe central diabetes insipidus (deficient production or release of AVP), urine osmolality
and flow rate is typically about
(A) 50 mOsm/kg H2O, 18 L/day
(B) 50 mOsm/kg H2O, 1.5 L/day
(C) 300 mOsm/kg H2O, 1.5 L/day
(D) 300 mOsm/kg H2O, 18 L/day

27.A 28. C 29.A 30.B 31. C 32. A

93
 Physiology

33.The primary reason that the female phenotype develops in an XY male is

(A) The secretion of progesterone
(B) Adrenal insufficiency
(C) The lack of testosterone action
(D) Increased inhibin secretion

34. Renin in synthesized by

(A) Granular cells
(B) Intercalated cells
(C) Interstitial cells
(D) Macula densa cells

35.Arginine vasopressin (AVP) is synthesized in the

(A) Adrenal cortex
(B) Anterior hypothalamus
(C) Anterior pituitary
(D) Collecting ducts of the kidneys

36.A 60-kg woman is given 10 microcuries (μCI) of radioiodinated serum albumin (RISA) intravenously. Ten
minutes later, a venous blood sample is collected, and the plasma RISA activity is 4 μCI/L. Her hematocrit ratio is
0.40. What is her blood volume?
(A) 417 mL
(B) 625 mL
(C) 2.5 L
(D) 4.17 L

37.Which of the following leads to decreased Na+ reabsorption by the kidneys?

(A) An increase in central blood volume
(B) An increase in colloid osmotic pressure in the peritubular capillaries
(C) An increase in GFR
(D) An increase in plasma aldosterone level

38.The nephron segment that reabsorbs the largest percentage of filtered Mg 2+ is the
(A) Proximal convoluted tubule
(B) Thick ascending limb
(C) Distal convoluted tubule
(D) Cortical collecting duct

39.Which of the following causes decreased renin release by the kidneys?

(A) Decreased fluid and solute delivery to the macula densa
(B) Hemorrhage
(C) Intravenous infusion of isotonic saline
(D) Narrowing (stenosis) of the renal artery

33 C 34. A 35 .B 36D 37 A 38B 39.C

94
 Kidney

40.Which of the following may cause hyperkalemia?

(A) Epinephrine injection
(B) Hyperaldosteronism
(C) Insulin administration
(D) Skeletal muscle injury

41.True about Parathyroid hormone (PTH) is

(A) Decreases tubular reabsorption of Ca2+
(B) Decreases tubular reabsorption of phosphate

Chapter - 3
(C) Inhibits bone resorption.
(D) Secretion is decreased in patients with chronic renal failure

42.Aldosterone acts on cortical collecting ducts to

(A) Decrease K+ secretion
(B) Decrease Na+ reabsorption
(C) Decrease water permeability
(D) Increase K+ secretion

43.In response to an increase in GFR, the proximal tubule and the loop of Henle demonstrate an increase in the
rate of Na+ reabsorption. This phenomenon is called
(A) Autoregulation
(B) Glomerulotubular balance
(C) Mineralocorticoid escape
(D) Saturation of tubular transport

Kidney
44.A hypertensive patient is given an angiotensin-converting enzyme (ACE) inhibitor. Which of the following
changes would be expected?
(A) Plasma aldosterone level will rise
(B) Plasma angiotensin I level will rise
(C) Plasma angiotensin II level will rise
(D) Plasma bradykinin level will fall

45.If a person consumes a high-K+ diet, the majority of K+ excreted in the urine is derived from
(A) Glomerular filtrate
(B) K+ that is not reabsorbed in the proximal tubule
(C) K+ secreted in the loop of Henle
(D) K+ secreted by the cortical collecting duct

46.Which of the following set of values would lead you to suspect that a person has syndrome of inappropriate
secretion of ADH (SIADH)?
Plasma Urine
Osmolality Plasma Osmolality
(mOsm/ [Na+] (mOsm/
kg H2O) (mEq/L) kg H2O)
(A) 300 145 100
(B) 270 130 50
(C) 285 140 600
(D) 270 130 450

40.D 41 .B 42 .D 43.B 44. B 45 .D 46.D

95
 Physiology

47.A dehydrated hospitalized patient with uncontrolled diabetes mellitus has a plasma [K+] of 4.5 mEq/L
(normal, 3.5 to 5.0 mEq/L), a plasma [glucose] of 500 mg/dL, and an arterial blood pH of 7.00 (normal, 7.35 to
7.45). These data suggest that the patient has
(A) A decreased total body store of K+
(B) A normal total body store of K+
(C) An increased total body store of K+
(D) Hypokalemia

48. Intravenous infusion of 2.0 L of isotonic saline (0.9% NaCl) results in increased
(A) Intracellular fluid volume
(B) Plasma aldosterone level
(C) Plasma arginine vasopressin (AVP) concentration
(D) Plasma atrial natriuretic peptide (ANP) concentration

49.The kidneys of a person with congestive heart failure avidly retain Na+. The best explanation for this is that
the
(A) Effective arterial blood volume is decreased
(B) Extracellular fluid volume is decreased
(C) Extracellular fluid volume is increased
(D) Total blood volume is decreased

47. A 48. D 49.A

96
 Kidney

50. What is the osmolarity at point “X” in the diagram below if ADH is present?

Chapter - 3
Kidney
a)hypertonic

b) hypotonic

c) isotonic

d) hypertonic if aldosterone is also present

51. The main driving force for water reabsorption by the proximal tubule

epithelium is

(A) Active reabsorption of amino acids and glucose

(B) Active reabsorption of Na+

(C) Active reabsorption of water

(D) Pinocytosis

50. A 51.B

97
 Physiology

52. Renal autoregulation

(A) Is associated with increased renal vascular resistance when arterial blood

pressure is lowered from 100 to 80 mm Hg

(B) Mainly involves changes in the caliber of efferent arterioles

(C) Maintains a normal renal blood flow during severe hypotension (blood pressure, 50 mm Hg)

(D) Minimizes the impact of changes in arterial blood pressure on renal Na+ excretion

52.D

98
 Kidney

Explanation
Chapter-3 Kidney

Section-1 -: Nephron, Blood flow and Glomerular Filtration

1. Ans. C Vasodilation (Ref: Ganong – 23rd Ed-Page-639)

Actions of Angiotensin II
a. Angiotensin II binds to AT1 receptors in the zona glomerulosa which act via a G protein to activate

Chapter - 3
phospholipase C. The resulting increase in protein kinase C fosters the conversion of cholesterol to

Kidney
b. pregnenolone and facilitates the action of aldosterone synthase, resulting in increased secretion of
aldosterone. Angiotensin II is one of the most potent vasoconstrictors in body.
c. Angiotensin II increases thirst sensation through the subfornical organ (SFO) of the brain, decreases the
response of the baroreceptor reflex, and increases the desire for salt.
d. It increases secretion of ADH in the posterior pituitary and secretion of ACTH in the anterior pituitary.
e. It also potentiates the release of norepinephrine by direct action on postganglionic sympathetic fibers.

2. Ans. D. 5% cardiac output is received by kidney.(Ref: Ganong - Review of Medical Physiology 23rd Ed-Page-
639)
a. The descending limb of the loop of Henle is permeable to water, but the ascending limb is impermeable.
b. Sodium, potassium and chloride are co-transported out of the thick segment of the ascending limb.
c. Therefore, the fluid in the descending limb of the loop of Henle becomes hypertonic as water moves into
the hypertonic interstitium.
d. In the ascending limb, it becomes more dilute, and when it reaches the top, it is hypotonic to plasma
because of the movement of sodium and chloride out to the tubular lumen.

99
 Physiology

e. Therefore, the fluid that is delivered to the distal convoluted tubule is always hypotonic.
f. The glomerulus, which is about 200 m in diameter, is formed by the invagination of a tuft of capillaries
into the dilated, blind end of the nephron (Bowman's capsule).
g. The capillaries are supplied by an afferent arteriole and drained by a slightly smaller efferent arteriole. In
a resting adult, the kidneys receive 1.2–1.3 L of blood per minute, or just under 25% of the cardiac
output.
h. The afferent & efferent arteriole control the blood supply as well as the hydrostatic pressure in the
glomerulus,thereby controlling the GFR also.

3. Ans. D. Juxtaglomerular apparatus : (Ref: Ganong 23rd edition, Page 639)

4. Ans. B. Inulin clearance

The GFR can be measured by measuring the excretion and plasma level of a substance that is:
i. Freely filtered through glomeruli Q ii. Not secreted by renal tubules Q
Q
iii. Not reabsorbed by renal tubules iv. Not stored in kidney Q
v. Nontoxic Q vi. Has no effect on GFR Q
INULIN is a product of Dhalia tubers It is a polymer of fructose with a molecular weight of 5200 which meets the
above criteria and is best for measuring GFR Normal GFR of an average man is 125 mI/minute Q

5. Ans. A. cAMP
Mesangial cells: -
a. Contraction of the mesangial cells decrease Kf
b. Kf = “glomerular ultrafiltration coefficient”  is the product of the glomerular capillary wall hydraulic
conductivity (i.e. its permeability) and the effective filtration surface area
c. Kf controls the GFR: -GFR=Kf [(PGC –PT) – (GC – T)]
d. Agents causing contraction or relaxation of mesangial cells: -
6. Ans. B & C : Afferent arteriole dilates, Efferent arteriole constricts
Determinants of the GFR:
a. GFR == Kf x Net filtration pressure
b. Net filtration pressure = (PG - PB - G + B)
i. PG = Glomerular hydrostatic pressure (= 60 mm Hg), promotes filtration
ii. PB = Hydrostatic pressure in Bowman's capsule (=18 mm Hg) which opposes filtration
iii. PG = Glomerular capillary colloid osmotic pressure (=32 mm Hg), which opposes filtration
iv. PB = Bowman's capsule colloid osmotic pressure which promotes filtration, normally its value is zero
v. Therefore
Net filtration pressure = (PG - PB - G + B)
= 60 -18 - 32 + 0
= +10 mm Hg
c. Kf = Glomerular capillary filtration (ultrafiltration) co-efficient Kf is a measure of the product of the
hydraulic conductivity (i.e. its permeability) and surface area of the glomerular capillaries. Its normal value
for kidney is 12.5 ml/min/mm Hg of filtration pressure or 4.2 ml/min/mm Hg per 100 gm of kidney.

Factors that increase or Decrease GFR

a. Kf - "although increased Kf raises GFR, and decreased Kf reduces GFR, changes in Kf probably do not provide

100
 Kidney

a primary mechanism for the normal day to day regulation of GFR Kf- if decreases  GFR
i. Measangial cells  contraction   Kf   GFR; Angiotensin II important regulator of the mesangial
cells contraction  contraction  area available for filtration.
ii. Thickness of the Glomerulary capillary BM i.e.  glom. capi. permeability   Kf  GFR  e.g chr.
HTN, DM Agents causing contraction or Relaxation of measangial cells i.e. , or  Kf i.e. - or  GFR.

b. Glomerular capillary Hydraustatic pressure (PG)

i. Changes in glomerular hydrostatic pressure (PG) serve as the primary means for physiological

Chapter - 3
regulation of GFR
ii.  In PG raises GFR whereas in PG reduces GFR Under physiological condition, PG is determined by
three variable.
 Arterial pressure: due to autoregulation mechanism, kidneys maintain a relatively constant PG
when BP fluctuates, but when the mean systemic arterial pressure drops below 90 mm Hg, there
is a sharp drop in GFR Angiotension II formation increases in cases of  arterial pressure or
hypovolemia  causes constraction of efferent arterioles   PG  tends to maintain GFR
 Afferent arteriolar resistance (RA) Constriction of afferent arterioles   Renal Blood flow  
glomerular hydrostatic pressure (PG) -7 JGFR Dilatation of afferent arterioles   Renal Blood
flow   PG GFR
 Efferent arteriolar Resistance (RE)
Constriction of efferent arterioles has biphasic effects on GFR.
o Moderate constriction: Renal Blood flow does not reduces too much

Kidney
o Severe constriction:  Renal Blood flow  Due to Donnan effect  increase in glomerular
colloid Osmotic pressure exceeds the increase in glomerular capillary hydrostatic pressure,
therefore net filtration force actually decreases  causes in GFR.
Summary of factors that can Decrease the GFR :
Physical determinants Physiological/Pathophysiological causes
a.  Kf  due to DM, Chr. HTN (diffuse glomerular disease)
-  in glomerular Capillary permeability
-  filtration surface area Nephron loss in progressive RF

b.  PB   GFR Urinary tract obstruction

c.  Oncotic pressure G   GFR  Renal blood flow,  plasma proteins – e.g. Hemo
concentration due to severe vol depletion, myeloma or other
dysproteinemias.
d.  PG   GFR  Arterial pressure as in circulatory shock
Dec. afferent diameter, efferent arteriole  Angiotension II (e.g. ACE-inhibitors)
dilation  Sympathetic activity, Vasoconstrictor hormones (e.g NorAdr,
Endothelin)

7. Ans. ‘B’ Has molecular weight slightly greater than the molecules normally getting filtered
a. Functionally, the glomerular membrane permits the free passage of neutral substances upto 4 nm in
diameter and almost totally excludes those with diameter greater than 8 nm. Glomerular wall is negatively
charged with sialoproteins and Heparan sulfate, therefore, due to electrostatic force of repulsion,

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 Physiology

negatively charged substance as albumin (69 kD, 7 nm dia) not filtered.

b. Both charge and size (i.e. mol. wt.) selectively normally prevent virtually all plasma albumin, globulin (mol
wt.  90 kD) and other larger weight proteins from crossing the glomerular wall.
c. Smaller' proteins (<20 kDa) are freely filtered but are readily reabsorbed by the proximal tubules.
d. Normal individual excrete < 150 mg/d of total protein and only about 30 mg/dL of albumin. the remainder
of the protein in the Urine is secreted by tubules (Tamm-Horsfall, IgA, and Urokinase) or represents small
amounts of filtered α2- micro - globulin, apoproteins, enzymes and peptide hormones".
Glomerular proteiuria: any disease 'damage the Glomerular filtration barrer  1st -ve charges are dissipated 
Albumin filtered'  not reabsorbed in proximal tubules due to its larger mol. wt (size)  appear in urine. Q
Tubular proteinuria: In the healthy, large amount of proteins of low mol. wt. than albumin are filtered by the
glomerulus and reabsorbed in the PT. Injury to PT may result in decreased reabsorptive capacity and the loss of
these low mol. wt. proteins in urine. Q
In tubular proteinuria, little or no albumin is detected, whereas in glomerular proteinuria the major protein is
albumin Q
 Conclusion: Normally proteins upto size and mol. wt. of in albumin' are not filtered; and proteins with mol.
wt. < 20 kD are easily filtered but totally reabsorbed in PT. Albumin with mol. wt. 69 kD and larger mol. wt.
proteins, they gets filtered in renal disease that disturbed size and-ve charges of glomerular filteration barrier
 due to their larger mol. wt. they are not reabsorbed in PT  and excreted in urine. There fore answer is (b)
i.e. Albumin is first to appear in urine because, it has mol. wt. slightly> the molecules normally getting
filtered.

8. Ans. C Mesangium
a. Two cellular layers separate the blood from glomerular filtrate in Bowman’s capsule, Capillary
endothelium and specialized endothelium.
b. These two layers are separated by a BASAL LAMINA.
c. Stellate cells called mesangial cells send their processes between endothelium and basal lamina.
d. Cells of epithelium are called podocytes and they send numerous pseudopodia which interdigitate and
form slits along the capillary walls podycytes.

9. Ans. (D). Phosphate

Ref: Ganong, 22nd Edition, Page no 724, 730
Phosphate is reabsorbed in the proximal tubule. It crosses the luminal membrane coupled to a sodium (Na+)/phosphate
cotransporter and then moves from the tubular cell to the peri tubular fluid via facilitated diffusion.
A number of different organic anions (e.g., bile salts, hippurate, oxalate, urate, fatty acids) are secreted in the proximal
tubule. The active step is transport of these molecules from the peritubular space to the tubular cell interior across the
basolateral membrane. The transport molecules involved appear to be rather nondiscriminating in nature, so a variety of
anions can be transported.
The greatest amount of hydrogen ion (H+) secretion occurs in the proximal tubule. Most of this secretion is involved in
the reabsorption of filtered bicarbonate. H+ is transported across the apical membrane by a sodium (Na+)/H+ antiporter.
A number of different organic cations (e.g., choline, creatinine, thiamine, guanidine) are also secreted in the proximal
tubule.
Most ammonium (NH+) that is generated by tubular cells to aid in excretion of an acid load is produced in the proximal
tubule. NH4 + is transported into the proximal tubular lumen across the apical membrane by a sodium (Na+)/NH/
antiporter.

Section-2 -: Transport of various substance

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 Kidney

1. Ans. D. H+
Ganong - 23rd Ed Page-665
a. PCT has maximum ATP ,Oxygen Consumption & Active transport.
b. The reabsorption of almost all substances is maximum in PCT.
c. Maximum secretion of most substances is again seen in PCT like drugs, toxins, organic acids, creatinine etc
d. In PCT there is maximum H+ secretion. Around 4200 mEq/day.
e. Still the pH remains unchanged due to presence of various buffer in PCT like Bicarbonate, Phosphate and

Chapter - 3
Ammonia buffer.

Substance % reabsorbed
salt 60-70%
Water 60-70%
Glucose and Amino acids 100%
potassium 65%
urea 50%

Kidney
phosphate 80%
HCO3- 100%
Ca2+ 80%

2. Ans. A. Always hypotonic

(Ref. Ganong 23rd ed. Page 639)
a. The descending limb of the loop of Henle is permeable to water, but the ascending limb is impermeable.
b. Sodium, potassium and chloride are co-transported out of the thick segment of the ascending limb.
c. Therefore, the fluid in the descending limb of the loop of Henle becomes hypertonic as water moves into
the hypertonic interstitium.
d. In the ascending limb, it becomes more dilute, and when it reaches the top, it is hypotonic to plasma
because of the movement of sodium and chloride out to the tubular lumen.
e. Therefore, the fluid that is delivered to the distal convoluted tubule is always hypotonic.

3. Ans. A. PCT
About 70% of filtered HCO3 occur at PCT. 70% of filtered water. NaCl absorption occur at PCT. 100% of filtered
glucose and amino acid occur at PCT

4. Ans. C. Creatinine
Urinary concentration (U) Plasma concentration (P) U/P ratio
Glucose (mg %) 0 100 0
Sodium ions mE0q/L 90 150 0.6

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 Physiology

Urea (mg%) 900 15 60

Creatinine (mg %) 150 1 150

5. Ans. A. Proximal tubule

a. Maximum water is reabsorbed in proximal tubule (60-70%) is called obligatory water reabsoption (does
not required ADH).
b. Vasopressin or Antidiuretic hormone (ADH) increases the permeability of the collecting ducts of the kidney
so that water enters the hypertonic interstitium of the renal pyramids, the urine becomes concentrated
and its volume decreases. The mechanism by which the vasopressin exerts its antidiuretic effect is
activated by V2 receptors leading to insertion of water channels called aquaporins (main is aquaporin 2) in
luminal membrane. 10-12% water reabsorpt in CD under ADH is called water reaborption facultative.

6. Ans. D. Entirely absorbed in PCT

7. Ans. C. Potassium

8. Ans. B. Distal convoluted tubule

Much of the filtered K+ is removed from the tubular fluid by active reabsorption in the proximal tubules, and K + is
then secreted into the fluid by the distal tubular cells In the distal tubules Na + is generally reabsorbed and K+ is
secreted.

9. Ans. A. PCT
10. Ans. B. PCT
11. Ans. D. Proximal segment by active reabsorption of Na+
a. Many substances are actively transported out of the fluid in the proximal tubule, but fluid obtained by
micropuncture remains essentially isosmotic to the end of the proximal tubule.
b. Therefore in the proximal tubule, water moves passively out of the tubule along the osmotic gradients
setup by the active transport of solute and isotonicity untamed 60— 70% of the filtered solute and 60—
70% of the filtered water have been removed by the time the filtrate reaches the end of the proximal
tubule.

12. Ans. D. 0.6

13. Ans. C. 150mg

The majority of persons excrete between 30 and 150 mg/d of total protein (NORMAL UPPER LIMIT IS 200 mg/d)
and only about 30 mg/d of albumin.

14. Ans. C. 350

a. The renal active transport systems have a maximum rate at which they can transport a particular solute.
b. This is known as TRANSPORT MAXIMUM OR TM for that solute.
c. The Tm of glucose is know as TmG and is 375 mg/min in men and 300 mg/mm in women. Q

15. Ans. A. Maximum reabsorption & secretion

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 Kidney

Transport maximum - (Tm) 

a. Definition  for most substances that are actively reabsorbed or secreted, there is a limit to the rate at which
the solute can be transported, often refered to as the transport maximum (T m)
b. Tm for substances that are actively reabsorbed: -
i. Glucose  320 mg/min
ii. Urate  15 mg/min
iii. Lactate  75 mg/min
c. Tm for substance that are actively secreted: -

Chapter - 3
i. Creatinine  16 mg/min
ii. PAH  80 mg/min

16. Ans. B. 60 to 70% of GFR is absorbed in proximal tubule

a. The Proximal tubules reabsorbes 60% to 65% of the filtered Na Q+, Cl--, HCO3- Q and water Q, and virtually
all the filtered K+ HPO42 - and amino acid Q
b. Segments of nephrons which are impermeable to water: Q
 Ascending loop of Henle (but permeable to Na+ and Cl-) Q
 Early DCT  relatively impermeable to water. Q
c. Hormones that regulate Tubular reabsorption:
Hormones Site of action Effects

Late Distal tubule and collecting duct Q  NaCl, H2O reabsorption

Kidney
Aldosterone
 K+ secretion

Late distal tubule and collecting duct Q

ADH (vasopressin)  H2O reabsorption

d. Late distal tubule and cortical collecting tubule: -

i. They are composed of two distinct cells - Principal cells and Intercalated cells
ii. The principal cells reabsorb Na+ and H2O; and secrete K+
iii. Intercalated cells reabsorb K+ and HCO3- and; secrete H+ (ie. Acid base balance)
e. Na + reabsorption: - "In the PCT, thick portion of the Ascending limb of loop of Henle, DCT, and collecting
duct, Na+ moves by co-transport

17. Ans. A. Proximal convulated tubules

“Much of the filtered K+ is removed from the tubular fluid by active reabsorption in the proximal tubules, and K+ is
then secreted into the fluid by distal tubular cells.”

18. Ans. B. Secretion by the distal tubule

“Virtually all regulation of renal K+ excretion and total body K+ balance occurs in the distal nephron (DCT + CCD)Q

Section-3 -: Clearance

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 Physiology

1. Ans. C. If clearance of substance is greater than GFR, then tubular secretion must be present
(Ref: Ganong - 23nd Ed page 631)
a. The explanation is based on the basic definition and the concept of clearance.
b. The clearance of a substance which is freely filtered and neither secreted nor reabsorbed (e.g. inulin
clearance) gives the value of GFR.
c. Any substance which has a clearance greater than that of inulin must be getting secreted in addition to
being freely filtered.
d. One of the most important aspects of counter-current multiplier system is the differential permeability
characteristic of descending thin segment (DTS) and the ascending thin segment of the loop of Henle
(ATS):
i. DTS : is permeable to water but not solutes
ii. ATS : is permeable to sodium but not water
e. Due to this, the tubular fluid in the descending loop gets hypertonic whereas in the ascending limb, the
tubular fluid becomes dilute.

2. Ans. A. Clearance of a substance which is freely filtered and actively secreted is greater than GFR (refer
above explanation)

3. Ans. C. PAH
a. Renal plasma flow - RPF
i. Can be measured by infusing para-amino hippuric acid (PAH) and determining its urine and plasma
concentration.
ii. 90% of the PAH in arterial blood is removed in a single circulation through the kidney. It is therefore
become common place to calculate the “renal plasma flow” by dividing the amount of PAH in urine
by the plasma PAH level.
iii. Effective renal plasma flow (ERPF): -
ERPF = UPAH X V = Clearance of PAH
PPAH
= 625 ml/min.

iv. Actual - RPF = ERPF = 630

Extraction ratio 0.9
= 720 mI/min.
b. Renal Blood flow -
= RPF x 1
1- Hematocrit
= 700 X 1
0.55
= 1273 ml/mm.
c. “for determination of the GFR do a creatinine or Inulin clearance test and for determination of RBF or RPF
the PAH clearance is to be done”

4. Ans. C. 125mL/min

a. Substances used to measure GFR:

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 Kidney

The substance should be —

 freely filtered
 neither reabsorbed nor secreted
 nontoxic
 not metabolized by the body.
Eg.
i. Inulin: polymer of fructose, meets above these criteria in human and most animals and is extensively
used to measure GFR

Chapter - 3
CINULIN = UINULIN X V
PINULIN
= l26ml/min
= GFR
ii. 51Cr-EDTA is also used but inulin remains the standared substance. Q
iii. Endogenous creatinine clearance is easy to measure (GFR) and is worth while index of renal function
iv. NMS/319  other substances used to measure GFR are  mannitol sorbitol, sucrose (I.V.),
isothalamate, radioactive cobalt labelled vit. B12, radioiodine — labelled Hypaque.
b. Effective RPF = 625 ml/min. = PAH clearance

5. Ans. A. Glucose
a. Renal clearance:
i. Definition: the renal clearance of a substance is the volume of plasma that is completely cleared of

Kidney
the substance by the kidneys per unit time.
ii. Filtration Fraction is calculated:
FF = GFR = 125 = 0.19
RPF 650
b. Comparisons of Inulin clearance with clearances of different substances:
Substances Clearance Rate (ml/min)
Glucose 0
Sodium 0.9
Chloride 1.3
Potassium 12.0
Phosphate 25.0
Inulin 125.0
Creatinine 140.0

c. According to Ganong:
i. Q. Effective RPF = 630 ml/min
ii. Q. Actual RPF = 700 ml/min
iii. Q. Renal Blood flow = 1273 ml/min

6. Ans. A. Renal plasma flow

a. The kidneys get 1.2-1.3 liters (25 %of cardiac output) of blood per minute.

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 Physiology

b. Renal blood flow can be measured by electromagnetic flow meters or by application of Fick’s principle
which states that ‘blood flow equals the amount of a substance absorbed or excreted by an organ (or
whole body) per unit time, divided by the arteriovenous difference of that substance across the organ’.
c. Renal plasma flow is generally measured by injecting PARA-AMINO-HIPPURIC ACID (PAH) and then
determining its urine and plasma concentrations.

7. Ans. B. False — Low

Para aminohippuric acid is used to measure renal plasma flow Q.
a. At low plasma cone of PAH, it is almost completely cleared from the plasma by a combination of
glomerular filtration and tubular secretion, and indicates renal plasma flow.
b. When plasma cone of PAH is elevated beyond 20 mg/dL, the secretary mechanism becomes saturated,
and the transport maximum (Tm) is reached. So the clearance of PAR from plasma is decreased, giving a
false low value of RPF.

8. Ans. (A). Diabetes insipidus

Ref: Ganong, 22nd Edition, Page no 719
Free water clearance is the amount of water excreted in excess of that required to make the urine isotonic to plasma. It is
calculated using the formula: (CH2O = V – Cosm) Free water clearance is positive when the urine is dilute (more than a
sufficient amount of water is excreted), and free water clearance is negative when the urine is concentrated (not enough
water is excreted to make the urine isotonic to plasma). An increase in free water clearance can lead to hypernatremia; a
decrease in free water clearance can lead to hyponatremia. In diabetes insipidus, very little water is reabsorbed in the distal
nephron, and, therefore, the free water clearance is very high. In heart failure or renal failure, very little free water can be
generated even if the urine is dilute because the glomerular filtration rate is decreased. With diuretic therapy, Na+ excretion
is increased. Therefore, the increased water excretion is accompanied by an increased Na+ excretion and the amount of free
water generated is limited. Although the water loss is proportionally greater than the solute loss in diabetes mellitus, the
amount of water excreted is much less and the solute concentration significantly higher than in diabetes insipidus, so the
free water clearance is much less in diabetes mellitus than in diabetes insipidus.

9. The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 866
 Inulin clearance is the standard for measuring GFR.
 Because Inulin is neither secreted nor reaborped, only filtered, so rate of clearance is equal to GFR.
 (Creatinine is slightly secreted from the peritubular capillaries into the tubules)

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 Kidney

 PAH clearance is used to measure renal plasma flow, not GFR.

10.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 863
 The renal clearance of PAH is the highest (it is nearly equal to the renal plasma flow) because PAH is not only filtered
by the glomeruli but is also secreted vigorously by proximal tubules.
 Creatinine is filtered and secreted, to a small extent only, in the human kidney. Inulin is only filtered.
 Urea is filtered and variably reabsorbed; its clearance is always below the inulin clearance in people.
 Na+ has the lowest clearance of all because filtered Na+ is extensively reabsorbed.
 Clearance of glucose is normally zero.
 Note that clearance can never have a negative value

Chapter - 3
Section-4 -: Counter Current Mechanism

1. Ans. A. ECF volume contraction

2. Ans. D. All of the above

a. Urine concentration:
The Basic requirement for forming a concentrating urine are :
i. A high level of ADH (vassopressin)  increases the permeability of the DT and collecting ducts (main
site) to water and
ii. A high osmolarily of the renal medullary interstitial fluid, which provides the osmotic gradient

Kidney
necessary for water reabsorption to occur in the presence of high levels of ADH.
Counter current Mechanism  produces a hyperosmotic Renal Medullary interstitium.
1. The osmolarity of the interstitial fluid in the medulla of the kidney is much high. Increasing
progressively to about 1200-1400 mOsm/L in the pelvic tip of the medulla. Q
The counter current mechanism depends on the special anatomical arrangement of the loops of Henle
and the Vasa recta, the specialized peritubular capillaries of renal medulla. Q
b. In presence of Vaso pressin, maximal antidiuresis, urine conc. is 1400 mOsm/Kg H 2O (in 0.5 L/d urine)
whereas in the absence of vasopressin, urine conc. is 30 mOsm/Kg H 2O (in 23.3 L/d urine) Water balance:
i. Water intake: regulated by the thirst, via osmoreceptor, located in the antero-lateral hypothalamus,
mainly regulated by toxicity of plasma.
ii. Water excretion: The principal determinant of renal excretion is argenine vassopressin (AVP or ADH).
The major stimulus for AVP secretion is hypertoxicity (i.e.  plasma Na+ conc.)  AVP binds on to V2
receptor on the basolateral membrane of principal cells in the collecting duct  activates adenylyl
cyclase  insertion of water channels (Aqua porin-2) on luminal membrane   passive water
reabsorption along a osmotic gradient from the lumen of the collecting duct to hypertonic medullary
interstitium.
c. Regulation of ADH :-
Increase ADH Decrease ADH
(=  urine conc.) (= urine conc, i.e. dilute urine)
 Plasma osmolarity (M.Imp),  Plasma osmolarity,
↑osmotic pressure of plasma  Osmotic pressure of plasma
Blood volume  Blood volume ,  ECF
( = ECF volume contraction)  BP

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 Physiology

 BP Drugs –
Nausea Alcohol
Hypoxia, Pain, emotions, stress,exercise Clonidine
Drugs – Haloperidol
Morphine (Dopamine blockers)
Nicotine
Cyclophosphamide

d. Control of thirst
Increase thirst Decrease thirst
Osmolarity (M.Imp)  Osmolarity
 BP  Blood volume
Blood volume BP
Angiotensin II  Angiotensin II
Dryness of mouth Gastric distention

3. Ans. D. In PCT 60-70% filtrates are reabsorbed

Section-5 -:Acid-Base Balance

1. Ans. C. Protein
Anion gap represents unmeasured anions in plasma and is normally 10 to 12 mmol/L.
AG = [Na+] - [ Cl- + HCO3-]
The unmeasured anions include mainly ANIONIC PROTEINS but phosphate, sulfate, and organic anions also
contribute to it.

2. Ans. C. Glutaminase
Several reaction in the renal tubular cells produce NH4+. NH4+ is in equilibrium with NH3 and H+ in the cells. The
principal reaction producing NH4+ In cells is conversion of glutamine to glutamate and this reaction is catalyzed by
the enzyme glutaminase, which is abundant in the renal tubular cells

3. Ans. B. Ureterosigmoidostomy Causes of Metabolic Alkalosis

a. Exogenous HCO3- loads
b. Acute alkali administration
c. Milk-alkali syndrome
d. Effective ECFV contraction, normotension, Vomiting, Gastric aspiration, Congenital chloridorrhea,
e. K deficiency, and secondary hyperreninemic
f. Villous adenoma
g. hyperaldosteronism
h. Diuretics, Edematous states, Posthypercapnic state,
i. Hypercalcemia/hypoparathyroidism
j. Recovery from lactic acidosis or ketoacidosis, Nonreabsorbable anions including penicillin, carbenicillin,
k. Mg2+ deficiency, K+ depletion, Bartter’s syndrome Gitelman’s syndrome.

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 Kidney

4. Ans. B. The acid base balance

a. Arterial pH is maintained between 7.35 and 7.45 by extracellular and intracellular chemical buffering
together with respiratory and renal regulatory mechanisms.
b. The control of PaCO2 the CNS and respiratory systems and the control of the plasma HCO 3- by the kidneys
stabilize the arterial pH by excretion or retention of acid or alkali The metabolic and respiratory
components that regulate systemic pH are described by the Henderson-Hasselbalch equation: Q

[ HCO3-]

Chapter - 3
pH = 6.1 + log --------------------
PaCO2 x 0.0301

5. Ans (D). Alkalinization of the antrum

Ref: Ganong, 22nd Edition, Page no 491
Alkalinization of the antrum releases the gastrin-containing cells from the inhibitory influences of somatostatin and
increases acid secretion. Acidification of the antrum promotes the release of somatostatin, a paracrine secretion that
inhibits gastrin release. Decreased gastrin release reduces the acid output of the stomach. Acidification of the duodenum
elicits inhibitory neural (enterogastric) and hormonal (enterogastrone) reflexes that also inhibit acid output.
Administration of a histamine antagonist reduces acid secretion by decreasing the stimulatory effect of histamine.

5. Ans. A. I cells

Section-6 -: endocrine functions of kidney & other applied aspects

Kidney
1. Ans. B. Angiotensin I
The kidney produces three hormones:
a. 1,25 dihydroxycholecalciferol
b. Renin
c. erythropoietin
Angiotensinogen is found in the D2 globulin fraction of the plasma. It is synthesized in the liver and is converted to
angiotensin I by renin which is further converted to angiotensin II by the action of ACE in lungs.

2. Ans. D Pace maker activity of the smooth muscle cells in the renal pelvis
a. Explanation: The walls of the ureter contains smooth muscle and are innervated by both sympathetic and
parasympathetic. Nerves fibres as well as by intramural plexus of neurons and nerve fibres that extends
along to entire length of the ureters.
b. As with other visceral smooth muscle peristaltic contractions in the ureter are enhanced by
parasympathetic nerves stimulation and inhibited by sympathetic stimulation.
c. The ureteral musculature behaves as a functional syncytium which permits the spread of electrical
excitation from cell to cell.
d. The origin of this impulse is from the Pacemaker cells present near the renal pelvis. So, we can say that
ureteral peristalsis is an essentially myogenic phenomenon, the influence of the autonomic nerve supply
being limited to modulating peristalsis and influencing ureteral tonus.

3. Ans. B. SIADH

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 Physiology

a. In SIADH SYNDROME the excessive release or an excessive renal tubular effect of vasopressin results in the
excretion of Concentrated urine despite a subnormal plasma osmolality and serum sodium concentration.
b. Sodium excretion in the urine is maintained by hypervolemia, suppression of the renin-angiotensin-
aldosterone system, and an increased plasma concentration of atrial natriuretic peptide.

4. Ans. C. Hypervolemia

5. Ans. B. Low sodium

RENIN is an enzyme that is produced and stored in the granules of the juxtaglomerular cells surrounding the
afferent arterioles of glomeruli in the kidney. Following stimuli increase its secretion: Q
• Sodium depletion • Diuretics
• Hypotension • Hemorrhage
• Upright posture • Dehydration
• Constriction of renal artery or aorta • Cardiac failure
• Cirrhosis

Renin is a glycoprotein syntherized as a preproharmone.

6. Ans. C. Renovascular hypertension

Hypertension can be produced by renal disease. It results due to one of the following factors:
a. A derangement in the renal handling of sodium and fluids which leads to volume expansion.
b. An alteration in renal secretion of vaso-active materials. This results in a systemic or local change in
arteriolar tone
i. Renovascular hypertension for example, pre-eclampsia and eclampsia
ii. renal parenchymal hypertension

Renal vascular hypertension is due to decreased perfusion of renal tissue caused by stenosis of renal artery. This
activates the RENIN-ANGIOTENSIN SYSTEM resulting in elevated circulating angiotensin II which increases arterial
pressure by directly causing vasoconstriction and by stimulating aldosterone secretion which leads to sodium
retention.

7. Ans. C. Inulin

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 Kidney

Perhaps the most accurate’ measurement of extracellular fluid volume is that obtained by using inulin, a
polysaccharide with a molecular weight of 5200.

8. Ans. C. It is increased in primary hyperaldosteronism

9. Ans. C. Relaxation of perineal muscle

a. The first stage of the act of micturition is a relaxation of the perineal muscles, except the sphincter
urethrae, and a contraction of the muscles of the abdominal wall Q.

Chapter - 3
b. This is followed by a firm contraction of the detrusor and relaxation of the sphincter vesicae.
c. The flow of urine begins on subsequent relaxation of the sphincter urethrae, the bladder being emptied by
the contraction of the detrusor assisted by the action of the muscles of the abdominal wall.
d. As the act is completed, the bladder muscles relaxes and the sphincter vesicae contracts.
e. Finally the sphincter urethrae are closed and (in males) the last drops of urine are expelled from the bulbar
portion of the urethra by the action of bulbospongiosus.

10. Ans. D. I131 albumin for blood volume

• Plasma volume Evans blue, radioactive iodine labeled albumin Q
• Extracellular fluid Inulin Q
• Total body water Heavy water (D2O), tritium oxide and aminopyrine Q

11. Ans. B,C. Decreased ECF volume, Carbamazepine

Kidney
VASOPRESSIN
a. It hormone of the posterior pituitary gland, and is synthesized in the cell bodies of the magnocellular
neurons in the supra-optic and paraventricular nuclei of hypothalamus.
b. Because one of its principal physiologic effects is the retention of water by the kidney, vasopressin is often
called the ADH. i.e.  the conc. of urine and the osmolality of the plasma.
c. Its deficiency cause — Diabetes insidipus i.e. polyuria ( =  the conc. of urine, Hypotonic urine) and es the
osmolality of plasma.
d. Summary of stimuli affecting vasopressin secretion
e. Drugs ed vasopressin secretion (SIADH): - chiorpropamide, vincristine, vincristine, cyclophosphamide,
carbamazepine, oxytocin, GA, Narcotics, TAD.

12. Ans. ‘B’ Bound to neurophysin —II

The hormones of the post-pituitary gland (ADH and oxytocin) are synthesised in the cell bodies of magnocellular
neurons in the supraoptic and paraventricular nuclei. Q
a. Vasopressin and oxytocin each have a characteristic neurophysin ass. With them in the granules in the
neurons that secrete them, neurophysin II in case of vaspressin and neurophysin I in case of oxytocin. .
b. ADH secretion is enhanced by angiotensin II, prostaglandins, histamine, neuropeptide Y and Ach and is
inhibited by GABA and ANP.
ADH responsive water channel is collecting ducts of kidney is aquaporin-2 Q

13. Ans. C. Collecting tubules

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 Physiology

Posterior lobe of pituitary secretes two hormones namely oxytocin and vasopressin (ADH). ADH acts by binding to
the V2 receptor on the baso-lateral surface of the principal cell of the renal conducting duct (COLLECTING TUBULES
AND DUCTS). Its action is to conserve water and concentrate the urine.

14. Ans. ‘A’ Liver

Protein synthesized by Liver:
i. Albumin (4.5 - 5.0 gm/dL) Q ii. Orosomucoid (rise in inflammuation) Q
iii. 1-antiprotease Q iv -fetoprotein Q
v 2-macroglobulin Q vi. Antithrombin-III Q
vii. Ceruloplasmin Q viii. C-reactive protein Q
ix. Fibrinogen Q x. Haptoglobin Q
xi. Hemopexin Q xi. Transferrin Q
xiii. Apolipoprotein B Q xiv. Angiotensinogen Q
xv. Coagulatin factors II, VII, IX, X Q xvi. Antithrombin C, Protein C Q
xviii. IGF-I Q xviii. Steroid hormone binding protein Q
xix. Thyroxin-binding globulin Q xx. Transthyretin (Thyroid -binding pre albumin) Q

15. Ans. C,D,E. Renin, Dopamine, Endorphin

a. Regulation of Aldosterone secretion
Three primary mechanism control Aldosterone secretion
i. the Renin-Angiotensin system
ii. Potassium, and
iii. ACTH Of these factors Potassium ion concentration and renin-angiotensin II system are by far the
most potent regulating aldosterone secretion.
b. Factors increase Aldosterone secretion. Q
i. High K+ intake  act by  intracellular Ca++ voltage gated Ca++ channels
ii. Renin-Angiotensin II  acts by  diacylglycerol, protein kinases C.
iii. ACTH  have minor role, acts by  intracellular cAMP, protein kinase A.
iv. Low sodium intake  minor role
v. Others
 Constriction of IVC in thorax
 Standing posture
 Secondary hyperaldosteronism e.g. in CCF, Cirrhosis, and nephrosis
 surgery, Anxiety, physical trauma, Hemorrhage
 Neurotransmitter
 Dopamine
 Endorphin
 mSH (permissive action)
 Endothelin
c. Factors that have inhibitory effect on Aldosterone secretion
i. High Na+
ii. ANP, Quabain like factors
[ANP - inhibits renin secretion and  the responsiveness of the Zona glomerulosa to angiotensin II]

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 Kidney

16. Ans. B. Aldosterone in collecting ducts

Hormones Site of action in kidney
Aldosterone Cortical collecting duct & Distal tubules
ADH Medullary collecting duct
Angiotensin II Constricts efferent arterioles prevents decrease in glomerular hydrostatic pressure and GFR
ANP Collecting ducts

Chapter - 3
17. Ans. C. Ascending Loop (Ref: Ganong’s-23rd Ed, P-653)
Even in the absence of ADH , CD is still more permeable to water than the ascending loop of henle.

18. Ans. C. Hypervolemia

19. Ans. A. PCT

(Ref: Ganong’s-23rd Ed, P-658)
a. Aldosterone is a steroid hormone (mineralocorticoid family) produced by the outer section (zona
glomerulosa) of the adrenal cortex in the adrenal gland.
b. It acts mainly on the distal tubules and collecting ducts of the nephron.
c. Aldosterone tends to promote Na+ and water retention, and lower plasma K+ concentration by the
following mechanisms:
i. Acting on the nuclear mineralocorticoid receptors (MR) within the principal cells of the distal tubule

Kidney
and the collecting duct of the kidney nephron, it upregulates and activates the basolateral Na+/K+
pumps, which pumps three sodium ions out of the cell and two potassium ions into the cell. This
results in reabsorption of sodium (Na+) ions and water (which follows sodium) into the blood, and
secreting potassium (K+) ions into the urine (lumen of collecting duct).
ii. Aldosterone upregulates epithelial sodium channels (ENaCs), increasing apical membrane
permeability for Na+.
iii. Cl- is reabsorbed in conjunction with sodium cations to maintain the system's electrochemical
balance.
iv. Aldosterone stimulates the secretion of K+ into the tubular lumen.
v. Aldosterone stimulates Na+ and water reabsorption from the gut, salivary and sweat glands in
exchange for K+.
vi. Aldosterone stimulates secretion of H+ in exchange for K+ in the intercalated cells of the cortical
collecting tubules, regulating plasma bicarbonate (HCO3−) levels and its acid/base balance.

20. Ans. A. Collecting duct

ANP binds to a specific set of receptors - ANP receptors. Receptor-agonist binding causes a reduction in blood
volume and therefore a reduction in cardiac output and systemic blood pressure.Lipolysis is increased and renal
sodium reabsorption is decreased. The overall effect of ANP on the body is to counter increases in blood pressure
and volume caused by the renin-angiotensin system.
Renal
a. Dilates the afferent glomerular arteriole, constricts the efferent glomerular arteriole, and relaxes
the mesangial cells. This increases pressure in the glomerular capillaries, thus increasing the rate (GFR),
resulting in greater excretion of sodium and water.

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 Physiology

b. Increases blood flow through the vasa recta which will wash the solutes (NaCl and urea) out of the
medullary interstitium.[8] The lower osmolarity of the medullary interstitium leads to less reabsorption of
tubular fluid and increased excretion.
c. Decreases sodium reabsorption in the distal convoluted tubule (interaction with NCC) and cortical
collecting duct of the nephron via guanosine 3',5'-cyclic monophosphate (cGMP) dependent
phosphorylation of ENaC
d. Inhibits renin secretion, thereby inhibiting the renin-angiotensin-aldosterone system.
e. Reduces aldosterone secretion by the adrenal cortex.

Vascular
Relaxes vascular smooth muscle in arterioles and venules by:
a. Membrane Receptor-mediated elevation of vascular smooth muscle cGMP
b. Inhibition of the effects of catecholamines

21. Ans. A. increased excretion of K+There are 2 types of cells in cd

22. Ans. A. hemoglobin.

a. March hemoglobinuria, also known as march hematuria, occurs when blood is seen in the urine after
repetitive impacts on the body, particularly affecting the feet (such as running on a hard road ) and hands.
b. Hematuria after strenuous exercise may also result from athletic nephritis, which is a kidney inflammation
resulting from strenuous exercise, and may cause hematuria (which itself may be called "exertion
hematuria"), proteinuria, and cylinduria. However, athletic nephritis may be secondary to the hemoglobin
load on the kidneys caused by the hemolysis in march hemoglobinuria. In most persons the effects of
athletic nephritis are transient and disappear within hours to days after the end of exercise.

23. Ans. A. Renal functions

a. Cystatin C or cystatin 3 a protein mainly used as a biomarker of kidney function.
b. Cystatin C has a low molecular weight (approximately 13.3 kilodaltons), and it is removed from the
bloodstream by glomerular filtration in the kidneys.
c. If kidney function and glomerular filtration rate decline, the blood levels of cystatin C rise.
d. Serum levels of cystatin C are a more precise test of kidney function (as represented by the glomerular
filtration rate, GFR) than serum creatinine levels.

24. Ans. A. Increased Efferent arteriolar resistance

Increased Efferent arteriolar resistance will lead to more filtration and lower pressure in peritubular capillaries
around the nephron, leading to more reabsorption.

25. Ans. C. Liver

26. Ans. A. Clearance of a substance which is freely filtered and actively secreted is greater than GFR

27. The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 888

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 Kidney

The filtered load of the substance is Px x GFR = 2 mg/mL x 100 mL/min = 200 mg/min. The rate of excretion is UxV=10
mg/mL x5 mL/min = 50 mg/min. Hence, more substance X was filtered than was excreted, and the difference, 200 mg/min
- 50 mg/min = 150 mg/min, gives the rate of tubular reabsorption of substance X.
(Note : amount or quantity = volume x concentration)

28.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 867
There is an inverse hyperbolic relationship between plasma [creatinine] and GFR and, therefore, a rise in plasma
[creatinine] is associated with a fall in GFR . The greatest absolute change in GFR occurs when plasma [creatinine]
doubles starting from a normal GFR and plasma [creatinine].

29.The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 902

Chapter - 3
 Cardiac failure results in a decrease in effective arterial blood volume, which stimulates thirst.
 Because angiotensin stimulates thirst, a low plasma level would have the opposite effect.
 Distension of the atria (increased blood volume) or stomach inhibits thirst. Volume expansion and a low plasma
osmolality both inhibit thirst.

30.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 883,884
 When the kidney is producing maximally concentrated urine, fluid in the cortical collecting duct becomes isosmotic
with the surrounding cortical interstitial fluid.
 (the osmolatity of the cortical interstitium is 300 mOsm/kg water)
 Therefore, the osmolality will be about 300 mosm/kg H2O; it cannot go above this value because hyperosmotic
values (compared to systemic blood plasma) can be produced only in the kidney medulla.

31. The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 890
Liddle’s syndrome is due to excessive activity of the Na+ channel in collecting duct principal cells, leading to salt retention
and hypertension. Bartter and Gitelman syndromes are salt-wasting disorders; blood pressure would tend to be low, not
high. Diabetes insipidus and renal glucosuria produce excessive fluid loss and would not be likely causes of the patient’s

Kidney
hypertension.

32.The answer is A. Ref: Ganong -

In the absence of arginine vasopressin, the kidneys produce a large volume of osmotically dilute urine.

33.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 568
 The female phenotype can develop in an XY male if the biological action of testosterone is absent. This absence can
be due to a lack of testosterone secretion caused by enzyme deficiencies or a lack of the testosterone (DHT)
receptor. In this process, called testicular feminization, a phenotypic female develops in the presence of an XY
karyotype.
 There is a lack of pubic and axillary hair, well-developed breasts (as a result of the conversion of testosterone to
estrogen), with inguinal or abdominal testes, no uterus (because AMH is secreted), underdeveloped male accessory
ducts (lack of testosterone action), and the vagina ends in a blind pouch.
 Progesterone has no effect on phenotype. There is no evidence that adrenal insufficiency (low cortisol and
androgens from the adrenals) have any effect on inducing female phenotype in a male.
 Inhibin would reduce FSH secretion and ultimately reduce adult testis size, but in the fetus there is no effect on the
development of the female phenotype. AMH will prevent formation of the oviducts, uterus, and upper vagina; it
does not increase female characteristics in the male.

34. The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 864
Granular cells (also known as juxtaglomerular cells) are located primarily in the wall of afferent arterioles and are the
major site of renin synthesis and release. (the JG cells are modified smooth muscle cells of the tunica media of the
afferent arteriole; since the muscle cell has been modified to assume secretory function, the JG cells are referred to as
myo-epitheloid cells).

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 Physiology

35.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 352
AVP is synthesized in the cell bodies of nerve cells located in the supraoptic and paraventricular nuclei of the anterior
hypothalamus.

36. The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 5
From the indicator dilution method, the plasma volume = 10 Ci / 4 Ci/L= 2.5 L. If the hematocrit ratio is 0.4, then the
blood volume = 2.5 L plasma / 0.6 L plasma per L blood = 4.17 L.

37.The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 872
An increase in central blood volume will stretch the atria, cause the release of atrial natriuretic peptide, and result in
diminished Na+ reabsorption. All other choices produce increased tubular Na+ reabsorption.

38.The answer is B. Ref: Ganong -

The loop of Henle (mostly the thick ascending limb) reabsorbs about 65% of the filtered Mg2+.

39.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 893
Infusion of isotonic saline tends to raise blood pressure, decrease renal sympathetic nerve activity, and increase fluid
delivery to the macula densa; all of these changes suppress renin release. All other choices result in increased renin
release.

40.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 477
 Skeletal muscle cells contain large amounts of K+; injury of these cells can result in addition of large amounts of K+ to
the ECF.
 Insulin, epinephrine, and HCO3- promote the uptake of K+ by cells.
 Hyperaldosteronism causes increased renal excretion of K+ and a tendency to develop hypokalemia.

41. The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 479,487
PTH inhibits tubular reabsorption of phosphate, stimulates tubular reabsorption of Ca2+, and increases bone resorption.
PTH secretion is increased in patients with chronic renal failure. Its secretion is stimulated by a fall in plasma ionized
Ca2+.

42. The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 889
Aldosterone increases K+ secretion and Na+ reabsorption by cortical collecting ducts. It does not affect water
permeability.

43.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 879
 Autoregulation refers to the relative constancy of renal blood flow and GFR despite changes in arterial blood
pressure.
 Mineralocorticoid escape refers to the fact that the salt-retaining action of mineralocorticoids does not persist but is
overpowered by factors that promote renal Na+ excretion.
 Saturation of transport occurs when the maximal rate of tubular transport is reached. Tubuloglomerular feedback
results in afferent arteriolar constriction when fluid delivery to the macula densa is increased; it contributes to renal
autoregulation.

Glomerulo-tubular balance:
More the filtered load, more the reabsorbed load (load-dependent reabsorption). What is reabsorbed is a constant
percentage and not a constant amount. This helps in preserving the solute.
Possible mechanism for glomerulo-tubular balance :
As more fluid comes out of the glomerulus (due to increase in GFR), the protein concentration and therefore the
oncotic pressure in the plasma increases. When the plasma comes to the peritubular capillaries, there is an increased

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 Kidney

oncotic pressure; this results in pulling the excess water in the tubular lumen into the capillaries. Along with the flow
of water, sodium is also reabsorbed (this is known as bulk flow or solvent drag).

44.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 672
 The inhibitor will block the conversion of angiotensin I to angiotensin II, and therefore, the plasma angiotensin I level
will rise and the plasma angiotensin II and aldosterone levels will fall. The plasma bradykinin level will rise because
the converting enzyme catalyzes the breakdown of this hormone.
 The plasma renin level will rise because
(1) The fall in blood pressure stimulates renin release, and

Chapter - 3
(2) Angiotensin II directly inhibits renin release by acting on the granular cells of afferent arterioles, so that this
inhibition is removed when less angiotensin II is present.

45.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 883
In response to an increase in dietary K+ intake, the cortical collecting duct principal cells increase the rate of K+ secretion,
accounting for most of the K+ excreted in the urine.

46.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 902
The subject in choice D has a low plasma osmolality but inappropriately concentrated urine. The subject in choice A may
have diabetes insipidus. The subject in choice B has a low plasma osmolality, but the urine osmolality is appropriately low.
The subjects in choices C and E are normal, although the subject in choice E is producing concentrated urine and may be
water-deprived.

47.The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 865
 The low blood pH and hyperglycemia (or hyperosmolality) would tend to raise plasma [K+], yet the plasma [K+] is
normal.

Kidney
 These findings suggest that the total body store of K+ is reduced. Remember that most of the body’s K+ is within
cells.
 In uncontrolled diabetes mellitus, the osmotic diuresis (increased Na+ and water delivery to the cortical collecting
ducts), increased renal excretion of poorly reabsorbed anions (ketone body acids), and elevated plasma aldosterone
level (secondary to volume depletion) would all favor enhanced excretion of K+ by the kidneys.
 The person has normokalemia, not hypokalemia or hyperkalemia.

48.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 914
 Isotonic saline does not change cell volume. The plasma AVP level will fall because of volume expansion and
cardiovascular stretch receptor inhibition of its release.
 The plasma aldosterone level will be low because of inhibited release of renin and less angiotensin II formation.
 The plasma ANP level will be increased from stretch of the cardiac atria.
 A large part of the infused isotonic saline will be filtered through capillary walls into the interstitial fluid.

49.The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 821
ECF volume and blood volume are increased, but these should promote Na+ excretion, not lead to Na+ retention by the
kidneys. A decrease in effective arterial blood volume is the best explanation for renal Na+ retention.

50. ans A) hypertonic

If ADH is present CD becomes permeable to water via Aquaporin 2 and cause water
reabsorption resulting in hypertonic fluid in CD and also hypertonic urine. In absence of ADH i.e
DI, there would be hypotonic fluid.

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 Physiology

51.The answer is B. Active reabsorption of Na+, powered by the Na+/K+-ATPase, is the main driving
force for water reabsorption. Reabsorption of amino acids and water is secondary to active Na+
reabsorption. There is no active water reabsorption, and pinocytosis is too

small to account for appreciable water reabsorption. The high colloid osmotic pressure in peritubular
capillaries favors uptake of reabsorbed fluid from the renal interstitial fluid, but does not cause the
removal of fluid from the proximal tubule lumen.

52.The answer is D. In the autoregulatory range, vascular resistance falls when arterial blood
pressure falls. Changes in vessel caliber primarily occur in vessels upstream to the glomeruli (cortical
radial arteries and afferent arterioles). Because autoregulatory range extends from an arterial blood
pressure of about 80 to 180 mm Hg, renal blood flow is not maintained when blood pressure is low;
in fact, the sympathetic nervous system will be activated and cause intense vasocon- striction in the
kidneys. Renal autoregulation does not depend on nerves.

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 Cardiovascular System

Chapter - 4
Cardiovascular System

I. ELECTRICAL EVENTS

The conducting system is made up of modified cardiac muscle. Though there are ‘latent pacemakers’ in other
portions of the conducting system, the SA node is the normal pacemaker of the heart because its prepotential

Cardiovascular System Chapter - 4

(refer- cardiac muscle) is the steepest. The atrial and ventricular muscle normally do not show prepotential. The SA
node is situated at the junction of superior vena cava and right atrium.
(The AV node is situated in the right posterior portion of the inter atrial septum)

A. Innervation of SA node & AV node

SA node AV node
Parasympathetic Right vagus Left vagus
Sympathetic Right stellate ganglion Left stellate ganglion

B. Stimulation of
Right vagus Inhibits SA node es heart rate
Left vagus Inhibits AV node Slows A-V conduction
Right stellate ganglion Stimulates SA node es heart rate
Left stellate ganglion Stimulate AV node Shortens AV conduction time and
refractoriness

C. Conductions speeds & Frequency

Tissue Rate (m/s) Impulse frequency
SA node 0.05 60-100/min
Q
AV node 0.02- 0.05 slowest 40-60/min
Bundle of His 1 40-60/min
Bundle branches 1 20-40/min
Q
Purkinje system 4 Fastest 20-40/min
Note: Conductions speeds in Internodal artial pathways, atrial & Venticular muscles is 1m/sec

D. Spread of cardiac excitation – (Depolarization begins in SA node)

Ventricular depolarization- the first part of the ventricle to get depolarized is the left endocardial surface of the
interventricular system; then the right endocardial surface of the interventricular system. It then passes down and
through the Purkinje system depolarizes the ventricles from endocardium to epicardium. The top of the interve-
ntricular septum and the base of the heart are the last to be depolarized.

Ventricular repolarisation- The apical epicardial surface is the first to repolarise; the base endocardial surface is the
last to repolarise.

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 Physiology

E. ECG – The 12 lead ECG consists of

1. 3 bipolar limb leads viz lead I, II, III (also called standard limb leads) :record activity in vertical plane
2. 3 unipolar (augmented) limb leads viz avR, avL, avF :record activity in vertical plane
3. 6 unipolar chest leads viz V1 to V6: record activity in Horizontal plane(anteroposterior)
4. Unipolar limb leads – the connection of the bipolar limb leads is :
RA - + LA
- -

II III

+ +
LL
LA= Left arm; RA= Right arm ; LL= Left leg

5. For example, Lead I is between LA and RA, with the LA ‘positive’ and RA ‘negative’. The direction of the lead
axis is taken from negative to positive e.g the arrow indicates the direction of lead II.
The basic electrical recording principle are
a. If the direction of the cardiac impulse is towards the recording electrode, a positive (upward)
deflection is recorded; if it is moving away from the recording electrode, a negative (downward)
deflection is recorded.
b. The height of deflection depends on
i. The strength of the cardiac impulse vector.
ii. How the vector is oriented to the lead axis. If it is parallel, it records maximum deflection; if it is
perpendicular, it records minimum deflection.

iii. Calculation of axis- The connections of the bipolar limb leads can be represented in another way;
( (
- - ‘
) ) V
’
 I I
‘ ‘ (
B A(
1 I +
’ ( ’ I
8 + )
I +
0 ) 0 I
0
I )
d I
If one goes ‘clockwise’ from point ‘ A’ to point e‘B’ The vector ‘V’I can be taken as –
0 0
it is( from 0 to +180 ; g 30 or asI +3300.
0

if one goes r
- ‘anticlockwise’ from point ‘A’ to point Similarly, direction of lead II is
0
‘B’ )it is from 0 to –180 .0
e +600 or - 3000
Illustrative example: e

114
 Cardiovascular System

 The normal direction of the mean QRS vector is generally between- 300 to +1100.
 Normally, the maximum deflection is recorded in lead II because the direction of the mean QRS vector is
most parallel to lead II.

Cardiovascular System Chapter - 4

I
I
I
I
 If there is a left ventricular
I hypertrophy, the vector will ‘shift’ in the direction shown by dotted arrow; in
which case, the vector would become most parallel to lead I. So, if one wants to know the value of vector,
the vector can be ‘superimposed’ on the triaxial system.
e.g.
V

I
I

V I
I I I
I I
0 I 0 0
Value of V = 150 I Value of V = 60 or + 300 I
I
 Einthoven’s law : Mean deflection is lead II = Mean deflection in lead I + Mean deflection in lead III i.e II
= I + III
 Augmented unipolar limb leads – the unipolar limb leads are VR (right arm), VL (left arm) and VF (left foot);
the augmented limb leads are aVR, aVL and aVF. The ‘augmentation’ is in terms of amplitude of deflection
i.e aVR amplitude is 1½ times the amplitude in VR (the configuration remains the same). In the unipolar
leads, one electrode that is kept at the point where the potential is to be measured is called the exploring
electrode. The other electrode (called indifferent electrode) is kept at near zero potential by connecting 3
wires from the right arm, left arm and left leg, through a resistance (of say 5 kilo ohm). This is also called
the Wilson’s terminal - Diagram L
R
A A

Wilson
’s
Te
r L
mi L
na
l 5

K
115
 Physiology

 Note that the bipolar leads measure the potential difference whereas the unipolar leads measure the actual
potential at that point.
 Precordial chest leads
o The leads can be divided as lateral leads(left ventricle), anterior,inferior and septal.

F. Normal ECG
1. The P wave is due to atrial depolarization, upright in II, III, and aVF inverted in aVR
2. The PR interval is the interval from the beginning of the P wave to the Q wave(0.12-.20 Sec)
3. The Q wave is the beginning of ventricular depolarization( - ve Wave)
4. The QRS complex represents the depolarization of the ventricles (0.1sec)
5. The QT interval is the interval from the beginning of the Q wave to the end of the T wave (0.4 sec)
6. The ST segment is the segment from the end of the S wave to the beginning of the T wave (0.3 sec)
7. The T wave represents ventricular repolarization.
8. U wave : a small positive wave which may be seen following the T wave . This wave represents the last
remnants of ventricular repolarization. Inverted or prominent U waves indicates underlying pathology or
conditions affecting repolarization.
9. Q-T interval: The Q-T interval represents the time for both ventricular depolarization and repolarization
to occur, and therefore roughly estimates the duration of an average ventricular action potential. This
interval can range from 0.2 to 0.4 seconds depending upon heart rate. At high heart rates, ventricular
action potentials shorten in duration, which decreases the Q-T interval. Because prolonged Q-T intervals
can be diagnostic for susceptibility to certain types of tachyarrhythmias, it is important to determine if a
given Q-T interval is excessively long. In practice, the Q-T interval is expressed as a "corrected Q-T (QTc)" by
taking the Q-T interval and dividing it by the square root of the R-R interval (interval between ventricular
depolarizations). This allows an assessment of the Q-T interval that is independent of heart rate. Normal
corrected Q-Tc intervals are less than 0.44 seconds.

Some generalizations in normal ECG

Lead Feature(s)
aVR All the deflections are negative
aVL / aVF Predominantly positive or biphasic
V1 , V2 No Q wave; deep S wave
V3 , V4 Biphasic
V5 , V6 Small Q wave, Tall R wave
Lead I, II, III All positive deflection; largest in lead II

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 Cardiovascular System

G. ECG in some abnormal condition

1. Accelerated A-V conduction
Wolff- Parkinson White Syndrome : (Here, the abnormal connection is between atria & ventricle, it is called
the bundle of Kent)
a. Short P- R interval
b. Prolonged QRS deflection, which is slurred on the upstroke
c. P- J interval is normal
Lown- Ganong- Levine syndrome : (Here, the abnormal connection is between atria and bundle of
his; if is called James bundle)

Cardiovascular System Chapter - 4

d. Short P - R interval
e. Normal QRS
f. P – J interval is decreases
2. M.I
a. Changes due to current of injury – ST segment elevation. This is most noticeable in chest leads just
over the infarcted area (current of injury due to leakage of intracellular K+: the infarcted area is
negative (extra cellularly) relative to the surrounding area; this results in flow of current into the
infarcted area from the surrounding areas.)
The ST segment elevation is because of 3 basic abnormalities of cardiac muscle in M.I
i. Rapid repolarization (seconds after the infarct)
ii.  in RMP (minutes after the infarct )
iii. Delayed depolarization (half an hour after infarct)
b. Changes due to electrical silence –(after days/ weeks, the infarct becomes electrically silent)
i. Q wave changes
ii. R wave changes (failure of progression)
c. Changes due to conduction abnormalities

H. Heart block
1. Atrioventricular block is blockage of the conduction from the atria to the AV-node.
2. The first-degree AV block is a prolongation of the PR-interval (above 0.2 s) implying a delay of the
conduction - not a real block. All beats are conducted 1:1 ratio.
3. The second-degree AV block occurs when some signals are not conducted so 2:1 or 3:1 pattern. Mobitz I
heart block is characterized by progressive prolongation of the PR interval on the electrocardiogram (ECG)
on consecutive beats followed by a blocked P wave (i.e., a 'dropped' QRS complex). After the dropped QRS
complex, the PR interval resets and the cycle repeats.also called Wenckebach phenomenon. Mobitz II
heart block is mostly a disease of the distal conduction system (His-Purkinje System). It is characterized by
intermittently nonconducted P waves not preceded by PR prolongation and not followed by PR shortening.
4. The third degree AV block (complete AV-block) is a total block of the conduction between the SA node and
the ventricles. A latent AV- or ventricular pacemaker (Mainly bundle of His) maintains Cardiac output with a
spontaneous escape rhythm around 40-50 bpm (Adam-Stokes syndrome)

II. Arrhythmias (due to reentry and increased automaticity)

A. Electrolytes
1. Decrease of Na+: Causes low voltage ECG

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 Physiology

2. Hypothermia  Elevation of the j-point — Osborne wave.

3. Digitalis toxicity —short QT interval with “scooping” of the ST-T wave comples (i.e. Depression of ST-T
segment) Q
4. Sub arachnoid Hemorrhage  “CVAT-wave” pattern  marked QT prolongation with deep wide T-wave
inversions Q
5. Hyper kalemia: Tall peaked T waves. At higher levels, ; Paralysis of atria, prolongation of QRS ventricular
arrhythmia. Since the RMP es as ECF K+ es, eventually heart stops in diastole
6. Hypokalemia:
7. ST 
8. Prominent U waves
9. Increase in Ca++ in ECF : Short QT interval , increases myocardial contractility; if too much calcium, there is
calcium rigor and the heart stops in systole.
10. Decrease in Ca++
a. ST segment prolongation
b. QT interval prolongation

B. HIS Bundle Electrogram (HBE)

1. This is used to study events in the
a. AV node
b. Bundle of His
c. Purkinje system
2. There are 3 waves in HBE:
Wave Denotes
A deflection AV nodal activation
H spike Transmission through bundle of His
V deflection Ventricular depolarization

There are 3 intervals described (marked with the help of HBE and standard (ECG):
Interval From – to Represents
PA (27 ms) First appearance of atrial Conduction time from SA node to
depolarization to ‘A’ wave in HBE AV node
AH (92 ms) ‘A’ wave to start of ‘H’ AV node conduction time

HV (43 ms) Start of ‘H’ to start of QRS Conduction in bundle of His and
branches
[Note that PA ++ AH+ HV internal = PR interval]
From the HBE, a distinction can be made between supra ventricular tachycardia (H spike present) and ventricular
tachycardia (No H spike)

C. Cardiac cycle
Note that mechanical events follow electrical events; atrial systole starts after ‘P’ wave and ventricular systole
starts near the end of ‘R’ wave and ends just after ‘T’ wave.
1. Duration of 1 cardiac cycle = 0.8 second

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 Cardiovascular System

2. Ventricular systole = 0.3 second

3. Ventricular diastole = 0.5 second
4. Atrial systole = 0.1 second
5. Atrial diastole = 0.7 second

Cardiovascular System Chapter - 4

D. Atrial systole :
1. P wave on the ECG precedes atrial systole, which contributes to ventricular filling that causes the fourth
heart sound. duration 0.1 sec.
2. 30% ventricular filling is due to atrial contraction
3. Correlates with a- wave in JVP
4. Ventricular systole: 0.3 sec
a. Isovolumetric contraction – c wave in JVP
b. Rapid ejection x decent in JVP
c. Slow ejection
d. the first heart sound (lub) - this sound is generated by the closing of the AV valves (& this occurs
because increasing pressure in the ventricles causes the AV valves to close) initially there is no change
in ventricular volume (called the period of isovolumetric contraction) because ventricular pressure
must build to a certain level before the semilunar valves can be forced open & blood ejected. Once
that pressure is achieved, & the semilunar valves open, ventricular ejection occurs in rapid (2/3ed of
ejection) and slow ejection.

1. Ventricular diastole: 0.5 sec

a. Isovolumetric relaxation - v wave in JVP

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 Physiology

b. Rapid filling
c. Slow filling (diastasis)
d. the second heart sound (dub)- this sound is generated by the closing of the semilunar valves
e. Ventricular volume increases rapidly (period of rapid inflow) - this occurs because blood that
accumulated in the atria during ventricular systole (when the AV valves were closed) now forces open
the AV valves & flows inside. This causes the third heart sound. After this 'rapid inflow', ventricular
volume continues to increase, but at a slower rate (the period of diastasis).
2. Waves in JVP
a wave Venous distention due to right atrial contraction
c wave Bulging of tricuspid valve into the right atrium during right ventricular isovolumetric
contraction and by the impact of the carotid artery adjacent to the jugular vein.
x descent Atrial relaxation and to the downward displacement of the tricuspid valve during
ventricular systole.
v wave Increasing volume of blood in the right atrium during ventricular systole when the
tricuspid valve is closed
y descent Opening of the tricuspid valve and the subsequent rapid inflow of blood into the
right ventricle.

E. Some abnormalities in JVP

1. Giant ‘C’ wave: Seen in tricuspid regurgitation
2. Giant ‘a” wave (common wave) : Seen in complete heart block

F. Pressures (mmHg)
1. Pulmonary artery 25/10
2. Mean 10-15
3. Aorta 120/80
4. Mean 100
5. Left atrium 5
6. Pulmonary capillaries : 8
7. Left ventricle: 120/ 0
8. Right ventricle: 25/0

G. Parameters
1. Stroke volume (SV): This is the amount of blood ejected by each ventricle per stroke; it is between 70-90 ml
2. End- diastolic volume (EDV): This is the amount of blood in the ventricle at the end of diastole; it is around
130ml
3. End- systolic volume = EDV- SV (it is around 50ml).
4. Ejection fraction: the percentage of EDV that is ejected with each stroke and is about 65%

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 Cardiovascular System

70-90 x 100  65% 130

5. The ejection fraction is a valuable index of the ventricular function
a. Cardiac output = S.V. x Heart rate
b. Blood pressure = C.O x peripheral resistance

H. Heart Sounds
S1: Closure of A-V valves S2: Closure of semilunar valves
S3: Rapid ventricular fillings S4: Forceful atrial contraction

Cardiovascular System Chapter - 4

Arterial pulse- this is because of the pressure wave set up in the walls of the vessels. The rate of the pressure wave
is
1. Aorta 4m/s
2. Large arteries 8m/s
3. Small arteries 16m/s
(Note that the rate of blood flow at the root of the aorta is 40cm/s)
With age, the arteries get thickened and the pressure wave, moves faster. The strength of the pulse is
determined by the pulse pressure (the difference between systolic and diastolic pressure); it bears no relation
to the mean arterial pressure. The dicrotic notch corresponds with the closure of aortic valve.
4. Cardiac output:
Definition: Amount of blood ejected by each ventricle per minute
Value = 5L/ min

Formula= C-O =S.V X H.R

C. O.
Cardiac Index = -----------------------------
Body surface area
Its value is 3.2 L/Sq.m/min

I. Measurement :
1. Fick method
2. Dye dilution / thermo dilution(Stewart Hamilton method)
3. Doppler plus echocardiograph
4. Velocity Encoded phase contrast MRI→ Most accurate method
5. FICK’s PRINCIPLE states that blood flow equals the amount of a substance absorbed or excreted by an
organ (or whole body) per unit time divided by the arteriovenous difference of that substance across the
organ. This principle can be used to calculate the cardiac output by measuring the oxygen consumption of
body per unit time and A-V difference of oxygen across the lung
Oxygen Consumption in both lungs
CO=
(A-V ) O2 difference

1. Thermodilution technique
a. Method - cold saline is injected into the right Atrium. Temperature change in the blood is then
recorded in the pulmonary artery. (10ml of 0.9% Nacl at Room temp. injected over 4 Sec.)
b. Principle - The temperature change is inversely proportional to the amount of blood flowing through

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 Physiology

the pulmonary artery

c. Facts about estimating CO by thermodilution technique :
d. The dilution thermodilution method is least reliable when the cardiac output is low and transit of
cold bolus through right is delayed.

J. Indicator-Dilution techniques – It is based on Stewart – Hamilton Principle.

1. "If for example, there is severe valvular regurgitation or a low cardiac output state in which the washout of
the indicator is prolonged and recirculation begins well before an adequate decline in the indicator curve
occurs, determinations are erroneous. Intracardiac shunts may also greatly affect the shape of curve.
2. Thermo dilution method has several advantages: - it obviates the need for withdrawal of blood from an
arterial site- and Less affected by recirculation. However a significant error occurs in patients with severe
tricuspid regurgitation. Also, in patients with low outputs (esp < 2.5L/rnin), thermodilution tends to
overestimate the cardiac out

K. Regulation of cardiac out put

Since CO = HR X SV, it can be regulated by HR and SV
1. HR: This is influenced by sympathetic and parasympathetic innervation
2. S.V: This can be changed by:-
VR→ Preload
(EDV)
Contractility SV X HR= CO X TPR = BP
Afterloard
(MAP)
1. Heterometric regulation: - This is based on Frank Starling Law; more is the initial length of the cardiac muscle
preload, as indicated by EDV , more will be the SV (with in physiologic limits).
Factors that normally increase or decrease the length of ventricular cardiac muscle fibers:

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 Cardiovascular System

2. Increase
a. Stronger atrial contractions
b. Increased total blood volume
c. Increased venous tone
d. Increased pumping action of skeletal muscle
e. Increased negative intrathoracic pressure

3. B. Decrease

Cardiovascular System Chapter - 4

a. Standing (Lying to standing in position)
b. Increased intrapericardiac pressure
c. Decreased ventricular compliance

4. Homometric regulation:- This S.V can also be changed for the same initial length . This is called homometric
regulation. For example, positively inotropic agents like catecholamines , xanthines , glucagon and digitalis -
increase the S.V; negatively inotropic states like hypercapnia , hypoxias , acidosis , certain drugs ,(eg
barbiturates ,quinidine) heart failure , M.I - decrease the S.V .
5. To summarise, C.O can be either regulated by heterometric regulation (Frank starling law) with regulation
based on a change in initial length or EDV) or by homometric regulation.

6. Venous return: Venous return is equal to CO, it depends on

a. Respiratory pump (negative intrathoracic pressure)
b. Peripheral Muscle pump
c. Cardiac pump
d. Sympathetic tone
e. Venous Compliance
f. Gravity (like posture)
g. Deep fascia
h. Venous valves
i. Venous pressure gradient that is VR = Psf – RAF/ RVR in which VR is venous return, Psf is mean
systemic filling pressure, PRA is right atrial pressure, and RVR is resistance to venous return. Psf in turn
depends on arterial pressure.

 Work done / O2 consumption

a. Work done :- Ventricular work per beat correlates well with O 2 consumption
b. Left ventricular work/ beat = S.V. X M.A.P in aorta
c. Right ventricular work/ beat = S.V. X M.A.P in pulmonary artery
( MAP= Means Arterial pressure)
d. Since aortic pressure is nearly 7 times pulmonary arterial pressure , the left ventricular stroke work is 7
times right ventricular stroke work.
i. Preload: It is the volume that is present in the ventricles before heart contracts or simply EDV. Can
also be said as volume work as more is preload more is the stroke volume (Frank Starling Law).It
depends on ventricular compliance, heart rate, venous return etc. It is increased by: ↑ blood vol., ↑
venous return, MR & AR.

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 Physiology

ii. Afterload: It is the pressure against which ventricles have to contract. Also called pressure work. It is
increased in AS, ↑ MAP or HT, ↑ Resistance to blood flow.
iii. Out of the pressure work and volume work, since work= volume X pressure, the pressure work
(Afterload) produces a greater increase in total work done and O 2 consumption than volume work
(preload).Since work done is asymmetrical there is concentric hypertrophy in AS and Eccentric or
dilatational hypertrophy in AR. Secondly chances of MI are more in AS as compared to AI.

 O2 consumption by the heart:- The beating heart at rest consumes 9 ml / 100g /min of O 2.
a. The arterio – venous O2 difference is maximum in the heart.
b. The O2 consumption is determined by
i. Intra myocardial tension ii. Contractile state of myocardium iii. Heart rate
c. Note:- Myocardial O2 usage is most closely related to the tension time index (TTI).
d. The tension time index is a product of the mean systolic pressure , the duration of systole and the heart
rate
(The higher the heart rate the greater is the myocardial O2 usage, for any given cardiac output.)

1. The pressure volume (PV) loop analysis depicts the relationship between left ventricular volume and
left ventricular pressure during a single cardiac cycle . Opening and closing of the mitral and aortic
valves are represented by the inflection points A, B, C, D respectively:

Fig. Normal pressure-volume (PV) loop and valve positions.

AB = LV filling
BC = Isovolumetric contraction
CD = LV ejection
DA = Isovolumetric relaxation

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 Cardiovascular System

Point-A = Coincides with MV opening, and represents LV end-systolic volume and early diastolic pressure
Point- B = Coincides with MV closure, and represents LV end diastolic pressure (LV EDP) and volume (LVEDV)
Point-C= Represents opening of Aortic valve and coincides with systemic, aortic diastolic pressure
Point-D= is the closure of the Aortic valve and represents LV end systolic pressure and volume, coinciding with the
dicrotic notch in the Aortic pressure tracing
Segment AB => LV compliance is defined by the slope of the filling phase or segment AB  Preload or EDV. The
compliance is decreased when the ventricles become stiff or unable to fill properly e.g. MI, constrictive pericarditis,
pericardial effusion etc and the PV loop(baseline shifts up).
Therefore PV loops analysis  gives information about - LV compliance, Preload, contractility. Stroke volume (SV)

Cardiovascular System Chapter - 4

[SV = EDV - ESV], Ejection Fraction (EF) and various valvular lesions.
Remember: The curve shifts to right side in case of increased preload, Upside in case of increased afterload and
to Left & upside in incase of increased myocardial contractility
o In AS - High LV systolic pressure and an upward and counter clock wise rotation in the end-diastolic
pressure
volume relationship i.e. AB line shifted to upward. indicative of  chamber compliance i.e.  LV compliance.
a. SV and EF are well preserved
b. Contractility – 

o In Aortic Insufficiency (i.e. AR)

Enlarged LV, minimal change in LVEDP despite the large volume preload (Increase compliance).PV curve
shifted to right side.

o In MS
PV loop illustrates hypovolemia Since the predominant impact of MS occurs proximal to the left ventricle, the
PV loop analysis format is less useful.

o In MR
The diastolic PV relationship (line AB) is shifted to the right as it in AI, consistent with a marked increase in
compliance (contractility is decreased)

L. Summary: PV loop (AB line) shifted

1. To slight right and upwards in AS
2. To right in MR
3. To right in AI
4. In MS  left shift but PV loop analysis is less
useful
A = Normal
B = Mitral stenosis
C = Aortic stenosis
D = mitral regurgitation
E = aortic regurgitation

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 Physiology

a. Vessels
i. Wind kessel vessels : show elastic recoil eg aorta, major arteries (2 % in aorta, 8% in rest)
ii. Resistance vessels : innervated, eg arterioles. (max. smooth muscle and wall thickness to lumen
ratio)Rich sympathetic innervation
iii. Precapillary sphincters : not innervated, affected by local metabolites
iv. Exchange vessels : capillaries, not innervated (5 % of blood vol.)
v. Capacitance vessels : veins, thin walled, poor innervation (55 % of blood vol. )
vi. Shunt vessels : A-V anastomoses (bypass capillaries), in skin for temp. regulation
Cross sectional area : is minimum for aorta and maximum for capillaries
Note:- I). Cross sectional area: is minimum for aorta and maximum for capillaries
b. Capillaries:-
3 types
i. Continuous eg. brain, skin
ii. Fenestrated eg. GIT, glomeruli of kidney, endocrine glands, circum ventricular
organs
iii. Discontinuous (Sinusoids) eg. liver, bone marrow
iv. The least permeability of capillaries is that is the brain

Pericytes:
These are associated with capillaries and post capillary venules. They are similar to the mesangial cells in
the renal glomeruli.
i. They are contractile
ii. They release vasoactive agents
iii. They synthesize and release constituents of bone marrow and extra cellular matrix.
One of their functions is to regulate the flow through the junction between the endothelia cells,
especially during inflammation

c. Distribution of Blood
Systemic veins 54%
Pulmonary circulation 18%
Heart cavities 12%
Arteries 8%
Capillaries 5%
Aorta 2%
Arterioles 1%

d. Biophysical principles:-
F=P/R (Where F= flow , P= effective perfusion pressure , R= resistance)
or
R=P/F
If P is expressed in mm Hg and flow is expressed in ml/second, then resistance will be expressed in ‘R’ units
[Or peripheral resistance units (PRU)]

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 Cardiovascular System

e. Blood flow measurement

Direct method Indirect method
i. Electro magnetic flow meters i. Fick method
ii. Doppler flow meter ii. Indicator method eg. Kety method for cerebral
blood flow using N2O
iii. Plethysmography

i. While applying the biophysical principles, one must bear in mind that vessels are not rigid tubes and
that blood is not a perfect fluid. Thus there can be differences between in vivo and in vitro

Cardiovascular System Chapter - 4

conditions.
Flow can be laminar (streamline) or turbulent:
Laminar Turbulent
a. Silent a. Noisy
b. Paraboloid velocity profile – flow is maximum b. No such gradient in flow rate from
in the center of the flow and goes on decreasing towards center of the flow towards the vessel wall exists
the wall
c. More efficient (less energy consumption) c. less efficient

ii. The probability of turbulence in a given flow can be determined by Reynold’s number:
Re= PDV/  (Where Re = Reynold ‘s number, P = Density of the fluid, D= Diameter of the vessel, V=
Velocity of flow and  = Viscosity)
iii. More the Reynold’s number, more the chances of turbulence
If D is measured in cms , V in cm/s,  in poises ,
Then if Re is < 2000 there is usually no turbulence; if Re is > 3000, turbulence almost always there.

f. Average velocity of flow

V= Q/A (Where V= velocity, Q= Quantity / amount of fluid and A= Area)
So , if area is more, velocity is less, Therefore the velocity is least in the capillaries (maximum cross-
sectional area) and maximum in the aorta (least cross-sectional area). Aorta (Max) > Vena cava > Artery >
Arteriole > Capillary

g. Calculation of resistance:
R= 8L/ r 4 (Where R= resistance, = viscosity, L= length of the vessel and r= radius)
Since Flow = Pressure/Resistance
(P1F-P2)  r 4
8Ll
o
w the Poiseuille – Hagen formula
i. The above formula is called
ii. As seen in the calculation of resistance, one of the factors on which resistance depends is the viscosity of
the blood. Viscosity in =
turn depends mostly on haematocrit. However the change in viscosity with
change in haematocrit is much less in vivo than in vitro.
iii. Newtonian and Non- Newtonian fluid: - A Newtonian fluid is a fluid whose viscosity is independent of
the rate of shear eg. Plasma, Saline.

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 Physiology

iv. A non-Newtonian fluid is a fluid in which the viscosity changes with the changes in the shear rate.
v. At very low shear rates, the viscosity is greatly increased; at high rates of flow the fluid behaves
almost as a newtonian fluid. Blood is a non-Newtonian fluid.
vi. Critical closing pressure:- It is the pressure below which flow completely stops; the value of this
pressure is not zero but above zero.
vii. Law of Laplace:- This gives the relationship between the distending pressure (P) , the wall tension (T) ,
the wall thickness (W) and the radius in a hollow viscous organ
T = Pr
W
Law of Laplace helps to explain as to why
Capillaries do not rupture inspite of being thin walled.
Dilated hearts have to work more.
Alveoli do not collapse during expiration
In thin walled structure, ‘W’ can be ignored.
In a spherical structure, P= 2T/r
In a cylindrical structure, P= T/r

B.P.:-
i. Pulse Pressure = Systolic B.P. – Diastolic B.P
ii. Mean Pressure = Diastolic B.P. + 1/3 pulse pressure

 The maximum pressure drop in the vascular circuit is at the level of the arterioles.(as the maximum
 resistance is at the arterioles)
 The arterial blood pressure can be measured by
i) Directly using Intraarterial manometer – most accurate, measure end arterial or Total pressure
(Kinetic + pressure energy)
ii) Indirectly using sphygmomanometer auscultatory method – non invasive, measures only the lateral
pressure i.e Pressure energy. Since the cuff pressure gets dissipated between the cuff and the artery by
the interspersed tissues the blood pressure measured by the sphygmomanometer is always higher than
the intraarterial pressure (False High).
o The cuff pressure at which the sounds are first heard is the systolic pressure.
o As the cuff pressure is lowered further, the sounds become louder, then dull and muffled. Finally in
most individuals, they disappear. The pressure at which they disappear or become muffled is the
diastolic pressure.
o Other points to be noted while measuring BP by sphygmomanometer are:
i. The length of cuff should be 2/3rd of Mid arm circumference
ii. The cuff must be always kept at the heart level & mercury scale at eye level.
iii. False high BP seen in: Obese, small cuff, Thick sclerotic vessel
iv. False low BP seen in: Auscultatory Gap (occurs in very high BP, cause unknown, prevented
by palpatory BP first)
v. Effect of gravity on B.P.: Above the heart level , the B.P. falls and below the heart level , the
B.P increases The value is 0.77 mm Hg per cm. This is true for arterial as well as for venous
pressure.

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III. Cardio vascular regulation:-

A. Auto regulation: - The ability of an organ to regulate its blood flow (on its own independent of nervous
ystemic influences ) with changes in perfusion pressure (with in a range)
Many organs show auto regulation e.g.. Brain, Kidney, Skeletal muscle, liver, heart , etc.
Skin does not show autoregulation.
Theories of auto regulation
1. Myogenic:- This depends upon the inherent property of the smooth muscle to contract ,when stretched.
More the perfusion pressure, the more it contracts to decrease the calibre of the vessel and hence to

Cardiovascular System Chapter - 4

decrease the blood flow
2. Metabolic:- Less the perfusion pressure, more is the accumulation of local metabolites which can dilate
the vessel and thus increase blood flow.
3. Tissue pressure theory – This is applicable in encapsulated organs e.g. kidney Some of the vasodilator
metabolites are  O2, CO2, pH,  Osmolality,  temperature, K+ , Adenosine, Lactate etc.
( Note:- The local effect of hypoxia & hypercapnia is vasodilatation in all the blood vessels except
pulmonary vessels where they cause vasoconstriction)
B. Circulating hormones:
These can be vasoconstrictors / vasodilators.
Circulating hormones
Constriction Dilation
Epinephrine (except in skeletal muscle and liver) Epinephrine in skeletal muscle and liver
Norepinephrine, AVP , Angiotensin II CGRP Substance P, Histamine, ANP, VIP
Neuropeptide Y

C. Examples of vasoconstrictors:
1. Epinephrine /Norepinephrine
2. Norepinephirine causes generalized vasoconstriction where as epinephrine dilates the vessels in skeletal
muscle and liver.
Parameter Norepinephrine Epinephrine
Systolic B.P  
Diastolic B.P.  
Mean arteria
 Only slight 
Pressure
Pulse pressure only slight  
Heart rate Reflex bradycardia 
Cardiac output  
3. Dopamine: Causes vasoconstriction everywhere except in renal vessels where it causes renal vasodilatation
4. Angiotensin II: It causes generalized vasoconstriction , increases water intake and stimulates aldosterone
secretion.
D. Kinin system
1. The kinin system generates vasoactive peptides from plasma proteins, called kininogens, by the action of
specific proteases called kallikreins. Activation of the kinin system results in the release of the vasoactive
nonapeptide bradykinin.

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 Physiology

2. Bradykinin increases vascular permeability and causes contraction of smooth muscle, dilation of blood
vessels, and pain when injected into the skin. These effects are similar to those of histamine.
3. It is triggered by the activation of Hageman factor (factor XII of the intrinsic clotting pathway) upon contact
with negatively charged surfaces, such as collagen and basement membranes.
4. A fragment of factor XII (prekallikrein activator, or factor XIIa)is produced, and this converts plasma
prekallikrein into an active proteolytic form, the enzyme kallikrein. The latter cleaves a plasma glycoprotein
precursor, high-molecular-weight kininogen, to produce bradykinin.
5. Bradykinin is degraded by
a. Kininase I-a carboxy peptidase that removes carboxy terminal Argmine
b. Kininase II-removes Phenylalamine –Argimine from carboxy terminal Kininase II is
c. Sympathetic vasodilator system
i. Site: Vessels of skeletal muscles
ii. Pathway: From the cortex to the vessels .It does not influence the vasomotor center in the medulla.
iii. Neurotransmitter: The neuro transmitter at their postganglionic neurons is acetylcholine.
iv. Functional role: It plays no role in the vasodilation in skeletal muscles during exercise;
v. it may play a role in the vasodilation by the thought of exercise.

E. Triple Response: Red reaction, Wheal & Flare

1. When the skin is stroked more firmly with a pointed instrument, instead of the white reaction there is
reddening at the site that appears in about 10 seconds (red reaction).It is due to release of Histamine. The
initial redness is due to capillary dilation.
2. The, swelling (wheal) is local edema due to increased permeability of the capillaries and postcapillary
venules, with consequent extravasation of fluid. It is again due to release of Histamine, bradykinin etc.
3. The redness spreading out from the injury (flare)is due to arteriolar dilation. Mediated via AXON REFLEX
and substance P.

F. Axon reflex:- Peculiarities /features:

1. It is a local reflex ; the impulse does not reach the spinal cord
2. Antidromic conduction
3. The neurotransmitter is substance P
4. Produces vasodilatation and increased capillary permeability
5. It is responsible for the ‘flare’ of triple reaction
6. Asynaptic
7. It is present even after total sympathectomy. The flare is absent in locally anesthetized skin and in
denervated skin after the sensory nerves have degenerated.

G. Neural regulation: - The main cardiocascular ‘centre’ is in the medulla.

There are 2 ‘centers’ viz
1. Vasomotor centre (VMC)
2. Cardio inhibitory centre (CIC/CVC)
3. The VMC is in the rostral ventrolateral medulla (RVLM); it has connection with the (inter mediolateral grey
horn) of the spinal cord from which sympathetic innervation arises for the heart and blood vessels.
4. The CIC is in fact the nucleus of the vagus . It innervates the heart. The nucleus ambiguus by the vagus is
the CIC

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IV. INPUTS TO THE VMC:

A. Inhibitory inputs
(i) From cortex via hypothalamus (ii). Lungs (iii). Baroreceptors

B. Excitatory inputs
(i) From cortex via hypothalamus (ii) Pain pathways (iii) Chemo receptors

Cardiovascular System Chapter - 4

C. Direct stimulation of VMC by hypoxia and hypercapnia
(
-
)

NTS= Nucleus of tractus solitarius

RVLM = Rostral ventrolateral medulla which is the VMC
CIC = Cardio inhibitory centre

The above structures are bilaterally present. For clarity, structures on only one side are shown.
Related to
i. Inotropic = Force
ii. Chronotropic = HR
iii. Dromotropic = Conduction velocity
iv. Bathmotropic = Excitability
v. Lusiotropic = Relaxation time.(Phospholamban inhibit the sarcoplasmic reticulum calcium pump

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 Physiology

(SERCA) is lost by blocking it beta-adrenergic agonist epinephrine enhance the rate of cardiac myocyte
relaxation. )
Resting Vagal Tone – HR is low due to this, cutting vagus inc. HR to 100/min
Regulation of Arterial B.P

1. Rapidly acting regulating Mechanism: within seconds, Approximately corrects the two-third fall in B.P,
a. Baroreflex
b. Chemoreflex
c. CNS ischemic reflex

2. Intermediate Acting Regulatory Mechanism: take min - hours

a. Capillary fluid shift mechanism
b. Stress relaxation and reverse stress relaxation Mechanism

3. Long term regulatory Mechanism: take days

a. Direct :Renal fluid mechanism
b. Indirect: Hormonal regulation (RAS, Aldosterone)
Baroreceptor Mechanism
i. Arterial baroreceptors: The arch of the aorta, and the carotid sinuses of internal carotid arteries
and Pulmonary trunk
ii. Low pressure baroreceptors: Atriocaval receptor, Pulm. venoarterial receptors, Atrial receptors &
Ventricular receptors
iii. Innervation of baro receptors: Carotid baro receptor -Glossopharyengeal and others by Vagus
nerve
iv. Set point and tonic activation: Most sensitive to MAP. Baroreceptors are tonically active at (MAP)
60 TO 180 mm Hg. Below 60 mm Hg they do not act. Act by inhibiting VMC & stimulating CIC. They
have a value called baroreceptor set point where they tend to maintain the arterial MAP.
Baroreceptor set point is not fixed, in chronic hypertension it increases in chronic hypotension
decreases. When they or their nerve supply cut BP Increases called Neurogenic or experimental
hypertension.

Chemoreceptor reflex
a. Act within 40-60 mm Hg
b. Corrects approx. 2/3 rd of further fall in B.P.
CNS Ischaemic response
The arterial pressure elevation in response to cerebral ischaemia (severely decreased blood flow to VMC, direct
VMC stimulation)
i. Operates between 15-50 mm Hg of Mean BP.
ii. Emergency pressure control system.
iii. Also called the last ditch stand pressure control mechanism.

 INTERMEDIATE MECHANISMS (30% TO 15% CORRECTION)

a. They begin to act within a few minute and reach full function within a few hours.
b. They primarily correct any alteration in b.p. by altering blood volume.

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 Cardiovascular System

 CAPILLARY FLUID SHIFT MECHANISM

a. Increased BP leads to increased filtration at the arterial end.
b. As a result,circulating blood volume decreases and BP comes back to normal.

 STRESS RELAXATION
a. When there is increased BP it causes relaxation of blood vessels by local vascular tone adjustment.
b. Therefore, cardic output decreases and BP. falls back to normal.

Cardiovascular System Chapter - 4

 REVERSE STRESS RELAXATION
a. Fall in BP decreases perfusion pressure in blood storage organs causing constriction of blood vessels
limitations

 EFFECT OF EXERCISE ON BLOOD PRESSURE (B.P)

a. ISOMETRIC CONTRACTION: In this the systolic and the diastolic blood pressure increases in all grades of
exercise.
b. ISOTONIC CONTRACTION:
i. Mild: systolic blood pressure increases but there is no change or a slightly increase in the diastolic
blood pressure.
ii. Moderate: the systolic blood pressure increases but there is no change or a slight decrease in
diastolic blood pressure.
iii. Severe : Systolic increase but diastolic dec due to local metabolites. Pulse pressure widens

 Atrial Stretch receptors

a. Type A : Discharge primarily in atrial systole
b. Type B : Discharge primarily (late in) atrial diastole.
c. The response is vasodilatation and  BP but and increase in heart rate ( not a decrease in heart rate)
d. When ECF volume decreases

sympathetic discharge  central venous pressure

 
 Renin  firing of atrial stretch receptors
 
 Aldosterone  ADH
e. Reflexes:-
i. Bainbridge reflex
ii. Bezold – Jarisch reflex
iii. Cushing’s reflex Or the C.N.S. ischaemic response or Last Ditch effort

f. Bainbridge reflex: -
i. Infusion of blood or saline causes increase in heart rate (if the initial heart rate is low)
ii. Receptors involved: Atrial stretch receptors
iii. Bezold – Jarisch reflex:- (Coronary chemoreflex)

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 Physiology

iv. Injections of veratridine ,serotonin , capsaicin etc into the coronary arteries supplying the left
ventricle causes apnoea followed by rapid breathing ,  in BP and  in heart rate.
v. Receptors involved: Left ventricular (C fibre endings)
vi. Cushing’s reflex:- ( C.N.S. Ischaemic response)
vii. Increase in intracranial pressure causes hypoxia and hypercapnia in medulla, which directly stimulates
the V.M.C.This results in an increase in B.P.
viii. The  in B.P. through the baroreceptor mechanisms causes reflex Bradycardia.
MAREY’S LAW: blood pressure is inversely proportional to heart rate.Due to baroreceptor reflex. Eg Shock : low
BP but Inc.HR & Cushing’s reflex

 Effects of chemoreceptor stimulation of VMC: -

Stimulation of chemoreceptor → Stimulates VMC →  in H.R  in C.O
[Note that the effect of hypoxia on heart rate is an increase (because of hyperapnoea) and a reflex decrease
because of stimulation of VMC. Therefore, its effect on heart rate is variable.
Blood Pressure Waves: -
In direct record (intra arterial) of B.P., many types of waves can be seen;
a. Cardiac waves - These are the waves because of the systolic rise and diastolic fall
b. Traube – Hering (T-H) Waves – These are the fluctuation in the B.P., synchronous with respiration.
c. Mayer Waves – These are seen in conditions like hypotension. The wave pattern is 1 per 20-40 second

The wave patter is 1 per 20 – 40 seconds

Valsalva manoeuvre:-
This is forced expiration against a closed glottis. It is one of the tests used for assessing the baroreceptor
responses. Characteristic changes in heart rate and BP are seen during the various phases of the
Valsalva manoeuvre:
i. At the beginning of the manoeuvre:  in BP
ii. During the maneuver:  in B.P
 in H.R.
iii. Immediately after the end of the manoeuvre  in B.P.
 in H.R.

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 Cardiovascular System

V. REGIONAL CIRCULATION:
A. Coronary Circulation – via R. & L. coronary arteries.
1. Endarteries but anastamosis can be seen in pathological conditions.
2. LAD most commonly involved in CAD.
3. 60-80 ml/100 gm/min or 250 ml/min
4. Maximum A-V O2 Difference & O2 extraction.
5. Phasic i.e supply more during diastole, minimum during systole(zero in subendocardium), so more

Cardiovascular System Chapter - 4

capillaries
6. Autoregulation is present – adenosine (main metabolite), K+, H+, CO2
7. Sympathetic stimulation increases and parasympathetic stimulation decreases coronary blood flow.

B. Cerebral circulation – Circle of Willis

1. 50-60 ml/100 gm/min or 750 ml/min. O2 consumption: 49 ml/min
2. Autoregulation present.
3. Factors regulating cerebral blood flow (CBF):
a. Inc. pCO2 & dec. pO2 cause vasodilatation & vice versa
b. Cerebral metabolism rate
c. Cerebral perfusion pressure: Mean arterial pressure – intracranial pressure
d. Blood viscosity
e. Temperature: Fall in temp. by 1o C decrease CBF by 5-7%

C. The Blood-Brain Barrier and Cerebrospinal Fluid

1. The barrier between cerebral capillary blood and cerebrospinal fluid (CSF) is formed by cerebral capillary
endothelium connected by tight junctions & Astrocytes
2. Water easily diffuses across the BBB; nonionized drugs cross more readily than ionized drugs.
3. Glucose, the primary energy source of the brain, requires carrier-mediated transport (GLUT 1 & 3)
4. Except Co2, Creatinine, Cl- HCO3- & Mg2+ all substances are more in plasma as compared to CSF
5. Most CSF is secreted by the choroid plexus (meningeal vessels). CSF fills the subarachnoid space and
ventricles of the brain. Regulation of pressure is by absorption which occurs in arachnoid villi. (10%
lymphatics also)
6. Normal vol. 150 ml. Daily production 500 ml. Rate 0.2-0.3 ml/min
7. Pressure 50-180 mm H2O or 10 mm Hg. Below 68 mm absorption stops.In sitting more than lying.

Composition of CSF
Osmolarity 292-297 mOsm/L
Sodium 137-145 mmol/L (137-145 mEq/L)
Potassium 2.7-3.9 mmol/L(2.7-3.9 mEq/L)
Calcium 1.0- 1.5 mmol/L(2.1 – 3.0 mEq/L)
Magnesium 1.0-1.2 mmol/L(2.0-2.5 mEq/L)
Chloride 116-122 mmol/L(1 16-122 mEq/L)
CO2 content 20-24 mmol/L(20-24 mEq/L)
PCO2 6-7 kPa (45-49 mmHg)

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 Physiology

pH 7.31-7.34
GLUCOSE 40-70 mg/dL
Lactate 10-20 mg/Dl
TOTAL PROTEIN 20-50 mg/dL
TOTAL LEUKOCYTES <5 per mL
Lymphocytes 60-70 percent
Monocytes 30-50 percent
Neutrophils None

A. Regions lying outside BBB are: post. Pituitary, Area Protrema, OVLT & Subfornical Organ & Median
eminence of hypothalamus Hepatic Circulation : 1500 ml/min, dual via portal vein (80%) % hepatic A. (20%)

Difference between Systemic & Pulmonary circulation

Systemic or greater circulation Pulmonary or lesser circulation

high pressure & high resistance circulation (aortic low pressure & low resistance circulation
pressure- 120/80 mm Hg & average capillary pressure (pulmonary trunk pressure- 25/8 mm Hg &
17) average capillary pressure 7 )
Compliance relatively less It is high-compliance system and The empty vessels
are ready to accommodate either acute or chronic
increases in PBV (recruitment), with little or no
increase in pulmonary arterial driving pressure.
Hypoxia causes vasodilatation (due to ATP sensitive K Hypoxia causes vasoconstriction (due to hypoxia
channels) sensitive K channels). Also decline in pH also
produces vasoconstriction in the lungs, as opposed
to the vasodilatation it produces in other tissues.
The mean velocity of the blood in aorta is about 40 The mean velocity of the blood in the root of the
cm/s. pulmonary artery is the same as that in the aorta. It
falls off rapidly, then rises slightly again in the larger
pulmonary veins.

D. Body responses to exercise:

1. Muscle Blood flow:
a. At rest 2-4ml/100g/min (650ml/min)
b. During maximal exercise  90ml/l00g/min (20850 ml/min) 25 times of normal
c. Local mechanism blood flow (vasodilation)  Po2, Co2 (H+ or pH) and accumulation of K+.

2. Systemic circulatory changes:

i. With the start of an isometric muscle contraction the heart rate rises, largely due to ed vagal tone. Stroke
volume changes relatively little.
ii. Response to isotonic muscle contraction  prompt increase in Heart rate and marked increase in stroke

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 Cardiovascular System

volume, and there is net fall in total peripheral resistance.

a. Cardiac out put:

i. At rest -t 5.5 L/min
ii. During isotonic exercise 35 L/min
b. Heart rate:
 In children  200 or > beats/min

Cardiovascular System Chapter - 4

 In adult rarely exceeds> 195 beats /min
 In Elderly persons  rise is even smaller.
Maximum HR is given by 220-age.so 200 is the best answer

3. Respiratory Response to Exercise :-

a. At start of exercise  ventilation due to psychic stimuli and afferent impulse from proprioceptors in
muscles and tendons.
b. Arterial O2 tension remains in normal range  which is provided by :
i.  Ventilation,  pulmonary blood blow (5.5 L/min at rest to as much as 20-25 L/min in exercise)
ii.  CO
c. Arterial PaCO2  either normal or low in moderate exercise and more vigorous exercise respectively
therefore HCO3 levels of blood is either normal or low.
i. Despite  Co2 production in exercise, Arterial.PaCo2 remain normal or low, due to increased excretion of
Co2 by lungs from 200 ml/min at rest to as much as 8000 ml/min.

d. Other changes in exercise

i.  Body temp.
ii.  Serum K+ level
iii.  lactic acid
e. In moderate exercise  Arterial pH, PCO2 and PO2 remain constant (by increasing ventilation and CO)

f. Effect of exercise on blood flow to various organs

Blood flow during rest ml/min Blood flow during exercise ml/min
Cardiac output 590 24,000
Heart 250 1,000
Brain 750 750
Skeletal muscle 650 20,850
Skin 500 500
Kidney, liver and GIT 3,100 600

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 Physiology

g. Effect on the CVS on changing posture from supine to the upright: -

i. Arterial blood pressure  decrease
ii. Central venous pressure  decrease (3 mmHg)
iii. Heart rate  increase (25)
iv. Abdominal and limb flow'  decrease by 25%
v. Cardiac output  decrease by 25%
vi. Stroke volume  decrease by 40%
vii. Abdominal and limb resistance  increase
viii. Total peripheral resistance  increase by 25%
ix. Small vein pressure  increase 10 min Hg
x. Cerebral blood pool  decrease by 400 ml

Note: Orthopnea never occurs in a normal person due to Reservoir function of pulmonary veins

xi. The pulmonary veins are an important blood reservoir because of their distensibility.
xii. When a normal individual lies down, the pulmonary blood volume increases by up to 400 mL, and when
the person stands up this blood is discharged into the general circulation.
xiii. This shift is the cause of the decrease in vital capacity in the supine position and is responsible for the
occurrence of orthopnea in heart failure.
xiv. Orthopnea is due to increased distribution of blood to the pulmonary circulation while recumbent.
Orthopnea is often a symptom of left ventricular heart failure and/or pulmonary edema.
xv. Mechanism: the Left heart's failure causes congestion of the Left atrium. The Pulmonary Vein and thus the
lungs also will become congested. In a supine position this congestion is compounded with the ease by
which blood can backflow from the atria , against blood coming back from the lungs. When one is sitting
up, gravity helps to keep the congested blood from working as much against the blood returning from the
lungs, allowing less congestion of the lungs itself and thus less difficulty breathing.

Region Blood Flow O2 Consumption Percentage of Totalbody

m
l AV Oxygen
O2
mL/100g Difference mL./l00 Cardiac
mL/min Consumptio
m/min
m mL/L gm/min Output
n
i
n

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 Cardiovascular System

1
5
Liver 55 35 51 2.0 30 20.5
0
0
1
2
Kidneys 420 15 18 6.0 25 7.5
5
0
7
Brain 545 65 49 3.0 15 19.5

Cardiovascular System Chapter - 4

0
4
Skin 135 25 12 0.3 9 5.0
0
8
Skeletal
2-4
0 60 50 0.2 16 20.0
muscle
0
2
Heart muscle 845 100 27 10 5 10.0
0
5
0
Whole body 8-10 50 250 0.4 100 100
0
0

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 Physiology

“Please Read the Preface of this book Before you attempt these questions.”
Explanation of answer start from page no. 147

Section-2-: 8. Which of the following is the correct order of

1. TRUE regarding human heart (AIPG 2010) activation after stimulation of Purkinje fibers:
A. Conduction of impulse from endocardium to A. Endocardium, epicardium, upper most part of
inwards septum
B. During exercise duration of systole is reduced more B. Endocardium, septum, epicardium
than diastole C. Epicardium, endocardium; septum
C. HR increases with parasympathetic denervation D. Epicardium, septum, endocardium
D. Vagal stimulation decreases force of contraction
9. SA node acts as a pacemaker of the heart because
2. Vagal stimulation causes increase in of the fact that it: (LQ)
A. Heart rate B. R-R interval in EC A. Is capable of generating impulses spontaneously
C. Cardiac output (COP) D. Force of contraction B. Has rich sympathetic innervations
C. Has poor cholinergic innervations
3. The maximum conduction rate is at:
D. Generates impulses at the highest rate
A. SA node B. AV node
C. Bundle of His D. Purkinje fiber
10. PR interval indicates which of the following: (DNB
Jun-2009)
4. In which of the following the conduction velocity is
A. AV node conduction time
least (DNB Dec-2010)
B. Ventricular repolarization
A. AV node B. Ventricles
C. Atrial depolarization
C. Bundle of His D. Purkinje fiber
D. Both A and C
5. SA node is the pacemaker of heart because:
A. It generates impulses at a faster rate 11. ST interval indicates which of the following:
B. It generates impulse spontaneously A. Atrial repolarization
C. It is richly supplied by sympathetic nerve B. Ventricular repolarization
C. Atrial depolarization
D. lt is poorly supplied by parasympathetic nerve
D. Ventricular depolarization
6. The pacemaker potential is due to: (LQ)
A. Fast Na+ channel 12. QRS complex indicates which of the following:
B. Decrease in K+ permeability A. Atrial repolarization
C. Slow Ca++ channel B. Ventricular repolarization
D. Rapid repolarization C. Atrial depolarization
D. Ventricular depolarization
7. Calcium enters the cardiac cell during:
A. Rapid upstroke of the action potential 13. Which one of the following is the ECG hallmark of
B. Down slope of the action potential hypothermia? (DNB Dec-2010)
C. Plateau phase of the action potential A. Prominent U wave B. Inverted T wave
D. Slow diastolic depolarization (phase 4) of the action C. Bizarre QRS wave D. Osborne J wave
potential

1.C 2.B 3.D 4.A 5.A 6.B 7.C 8.A 9.D 10.D 11.B 12.D 13.D

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 Cardiovascular System

left
14. A 72-year-old man with an atrial rate of 80
beats/min develops third-degree (complete) AV block. 19. Excitation of the ventricles
A pacemaker site located in the AV node below the (A) Always leads to excitation of the atria
region of the block triggers ventricular activity, but at (B) Results from the action of norepinephrine on
a rate of only 40 beats/min. What would be ventricular myocytes
observed? (C) Proceeds from the subendocardium to
(A) One P wave for each QRS complex subepicardium
(B) An inverted T wave (D) Is initiated during the plateau (phase 2) of the
(C) A shortened PR interval ventricular action potential

Cardiovascular System Chapter - 4

(D) A normal QRS complex
20. Which is true statement about AV nodal cells?
15. To ensure an adequate heart rate, a temporary (A) Exhibit action potentials characterized by rapid
electronic pacemaker lead is attached to the apex of depolarization (phase 0)
the right ventricle, and the heart is paced by (B) Exhibit increased conduction velocity when exposed
electrically stimulating this site at a rate of 70 to acetylcholine
beats/min. When the ECG during pacing is compared (C) Conduct impulses more slowly than either atrial or
with the ECG before pacing, there would be a ventricular cells
(A) Shortened PR interval (D) Are capable of pacemaker activity at an intrinsic
(B) QRS complex similar to that seen with left bundle- rate of 100 beats/min
branch block
(C) QRS complex of shortened duration 21. Stimulation of the parasympathetic nerves to the
(D) P wave following each QRS complex normal heart can lead to complete inhibition of the SA
node for several seconds. During that period
16. What is most responsible for phase 0 of a cardiac (A) P waves would become larger
nodal cell? (B) There would be fewer T waves than QRS complexes
(A) Voltage-gated Na+ channels (C) There would be fewer P waves than T waves
(B) Acetylcholine-activated K+ channels (D) There would be fewer QRS complexes than P waves
(C) Inward rectifying K+ channels
(D) Voltage-gated Ca2+ channels 22.The R wave in lead I of the ECG
(A) Is larger than normal with right ventricular
17. Atrial repolarization normally occurs during the hypertrophy
(A) P wave (B) Reflects a net dipole associated with ventricular
(B) QRS complex depolarization
(C) ST segment (C) Reflects a net dipole associated with ventricular
(D) T wave repolarization
(D) Is largest when the mean electrical axis is directed
18. The P wave is normally positive in lead I of the perpendicular to a line drawn between the two
ECG because shoulders
(A) Depolarization of the ventricles proceeds from
subendocardium to subepicardium 23.During the cardiac cycle, the correct statement is
(B) When the ECG electrode attached to the right arm (A) The aortic and mitral valves are never open at the
is positive relative to the electrode attached to the left same time
arm, an upward deflection is recorded (B) The first heart sound is caused by the rapid ejection
(C) AV nodal conduction is slower than atrial of blood from the ventricles
conduction (C) The mitral valve is open throughout diastole
(D) Depolarization of the atria proceeds from right to (D) Left ventricular pressure is always less than aortic
pressure
14.D 15.B 16D. 17.B 18.D 19.C 20. C 21.C 22. B 23.A

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141
Cardiovascular System Chapter - 4
 Physiology

D. End of diastasis

Section-2-: Cardiac Cycle & JVP Changes Section-3-: Cardiac Output & Ventricular Functions

1 .‘C’ wave in JVP is due to: (AIIMS NOV 2007) 1 . True about myocardial O2 demand is (AIIMS 2011
A. Atrial Contraction MAY)
B. Bulging of the tricuspid value into the right atrium A. Directly proportional to duration of systole
C. Ventricular diastole when the tricuspid valve is B. Inversely proportional to heart rate
closed C. Negligible in quiescent heart
D. Ventricular diastole when the tricuspid valve is open D. Has a constant relation to the external work done by
heart
2. First heart sound occurs due to: (LQ)
A. Opening of semilunar valve 2. Standing to sitting change is: (AIPG JUN 2009)
B. Opening of AV valve A. Immediate Increase in Venous Return
C. Closure of semilunar valve B. Increase in heart rate
D. Closure of AV valve C. Increase epinephrine
D. Increased cerebral blood flow

3. Second heart sound occurs due to: (LQ) 3. When a person changes position from standing to
A. Opening of mitral and tricuspid valve lying down position, following occurs.
B. Opening of aortic and pulmonary valve (AIIMS NOV 2007)
C. Closure of mitral and tricuspid valve A. Heart rate increases and settles at higher level
D. Closure of aortic and pulmonary valve B. Venous return to heart rises immediately
C. Cerebral blood flow become more than that in
4. The iso-volumetric relaxation stops when: standing position settles at a higher level
A. Ventricular volume changes D. Decrease in blood flow to the lung apex
B. Intraventricular volume changes
C. Ventricular pressure falls below atrial pressure 4. About myocardial oxygen demand, true is
D. Beginning of T wave (AIIMS NOV 2007)
A. Inverse relation with heart rate
5. Which of the following marks the end of B. Inverse relation of systemic hypertension
isovolumetric relaxation: (DNB Dec-2008) C. Directly Proportional to ventricle systole
A. C wave in JVP duration
B. Closing of semilunar valve D. Negligible in quiescent heart
C. Opening of semilunar valve
D. Opening of AV valve 5. Cardiac output in liter per minute divided by heart
rate gives:
A Mean arterial pressure
6. During the cardiac cycle the opening of the aortic
B. Cardiac index
valve takes place at the:
C. Cardiac efficiency
A. Beginning of systole
D. Mean stroke volume
B. End of isovolumeric contraction
C. End of diastole
1.B 2.D 3.D 4.C 5.D 6.B 1.A 2.A 3.B 4.C 5.D

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 Cardiovascular System

6. The basal cardiac output in adults is:

A. l0 liter B. 5.5liter
C. 7.5 liter D. 6.5 liter Section-4 -: Principles Of Hemodynamics

7. Fick’s principle is used for measuring: (DNB Dec- 1. Which of the following is false regarding glomerular
2010) capillaries (AIIMS NOV.2011)
A. Blood pressure A. Oncotic pressure is higher in the blood column than
B. Pulse pressure that in glomerular capillaries
C. Lung volumes B. Constriction of the afferent arteriole produces fall in

Cardiovascular System Chapter - 4

D. Cardiac output capillary BP
C. Concentration of glucose is equal in glomerular
8. Starling’s principle is: (DNB Jun-2007) capillaries and ultrafiltrate
A. Muscle fiber length does not affect contraction D. Hematocrit is raised in the glomerular capillaries
B. Contraction is proportional to blood flow
C. Within physiological limits, the force of contraction 2. In standing position venous return affected by a/e?
is proportional to initial length of cardiac muscle fiber (AIPG 2010)
D. Energy of contraction is proportional to afterload A. Arterial pressure
B. Deep fascia
9. Cardiac output measured by thermodilution C. Calf muscles
technique is unreliable in all of the following D. Competent valves of perforator
situations EXCEPT: (DNB Jun-2008)
A. Ventricular septal defect 3. Venous flow depends on the following factors
B. Tricuspid regurgitation EXCEPT? (AIIMS MAY 2008)
C. Low cardiac output A. Calf muscle contraction B. Valves in perforators
D. Pulmonary regurgitation C. Arterial pressure D. Fascial planes

10. Cardiac output =5 lit/min. BSA = 1.7 m2, calculate 4. Which of the following is true about physiological
the cardiac index (LQ) state: (LQ)
A. 5 l/m2 B. 4.81/m2 A. Capillaries contain 5% blood
C. 3.0l/m2 D. 3.71/m2 B. Vein contains 5% of blood
C. Capillaries contain 25% of blood
11. Ejection fraction increases with D. Vein contains 25 % of blood
A. End. Systolic volume
B. End. Diastolic volume 5. Which of the following is true regarding systemic
C. Peripheral vascular resistance veins:
D. Venodilation A. Contain 5% of blood volume
B. Contain 12% of blood volume
12. Oxygen demand of heart: (AIPG JUN 2009) C. Contain 18% of blood volume
A. Increases proportionately with heart rate D. Contain 54% of blood volume
B. Depends upon duration of systole
C. Is negligible when heart is at rest 6. Laminar flow is dependent on: (LQ)
D. Is in constant relation with amount of work done. A. Critical velocity B. Viscosity

6.B 7.D 8.C 9.C 10.C 11.B 12.A 1.A 2.A 3.D 4.A 5.D 6.A

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 Physiology

C. Constant velocity D. Critical closing pressure D. Length of vessel

7. Which of the following provides major part of total 14. Which of the following statements about
peripheral resistance: cutaneous shunt vessels is true (AIIMS 2011 MAY)
A. Venules B. Capillaries A. Perform nutritive function
C. Arterioles D. Small arteries B. Have role in thermoregulation
C. Not under the control of autonomic nervous system
8. Maximum peripheral resistance is at: (DNB Jun- D. These vessels are evenly distributed throughout the
2010) skin
A. Arterioles B. Capillaries
C. Small arteries D. Aorta 15. During Exercise the cardiac output rises upto 5
times, but pulmonary vascular resistance only few
9. Bernoulli’s principle states that: mm hg. Why? AIPG 2010
A. Flow velocity is inversely related to pressure in a A. sympathetic stimulation causing vasodilatation
vessel B. Opening of parallel channels
B. Measure of blood flow C. Pulmonary vasoconstriction
C. Sum of kinetic energy of flow and pressure energy is D. J receptors
constant 16. The data below are from an athletic 70-kg man
D. All are correct during heavy exercise. Which statement is correct?
Oxygen consumption: 4 L/min Arterial oxygen 19
mL/100 mL content: blood Mixed venous oxygen 3
10. Bernoulli’s principal states (DNB Dec-2009)
mL/100 mL content: blood Heart rate: 180 beats/min
A. Sum of kinetic energy of flow and pressure energy is (A) Cardiac output is 12 L/min
constant (B) Cardiac output is 25 L/min
B. Low tones producing maximal stimulation at apex of (C) Stroke volume is 67 mL
cochlea (D) Stroke volume is 100 mL
C. Magnitude of the sensation felt is proportionate to
the log of the intensity of stimulus 17. Which of the following would cause a decrease in
stroke volume, compared with the normal resting
D. Force of contraction is proportional to the stretch of
value?
cardiac muscle (A) Reduction in afterload
(B) An increase in end-diastolic pressure
11. The velocity of blood is maximum in the: (C) Stimulation of the vagus nerves
(LQ) (D) Electrical pacing to a heart rate of 200 beats/min
A. Large veins B. Small vein
C. Venules D. Capillaries

12. Maximum surface area is present in

A. Capillary B. Arterioles
C. Artery D. Vein

13. Blood flow through a vessel varies directly with

A. Resistance
B. Viscosity
C. Pressure of difference Section-5 -: Blood Pressure

7.C 8.A 9.C 10.A 11.A 12.A 13.C 14.B 15.B 16. B 17.D

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 Cardiovascular System

1. Which of these is correct regarding mean blood

pressure? Which of these is correct regarding mean
blood pressure? (AIIMS NOV.2011, MAY 2006)
A. DBP+2SBP/3 B. SBP+2DBP/3
C. DBP+3SBP/2 D. SBP+3DBP/2

2. Mean circulatory pressure is (AIIMS NOV 2008)

a. Average of pulmonary and circulatory pressure

Cardiovascular System Chapter - 4

b. Pressure at any 1 point when the heart is stopped
c. Average of central venous and systemic pressure
d. Diastolic BP + 1/3 pulse pressure

3. The blood pressure measured phygmomanometer

by is (AIPG 2008)
A. Lower than the intraarterial pressure
B. Higher than the intraarterial pressure
C. Same as the intraarterial pressure
D. The same with different cuff sizes

4. Pulmonary wedge pressure corresponds to which of

the following: (DNB Jun-2008)
A. Right ventricular pressure
B. Left ventricular pressure
C. Left atrial pressure
D. Right atrial pressure

1.B 2.B 3.B 4.C

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 Physiology

5. Mean arterial pressure is equal to: (DNB Jun-2009), (DNBB.Dec-2010)

The sitting position
A. Systolic + diastolic pressure/2 C. The standing position
B. Diastolic + 1/3rd Pulse pressure D. Any position as long as the post-flight recording is
C. Systolic + diastolic pressure/3 made in the same position
D. Systolic + 1/4th diastolic pressure
10. Diastolic Pr. In Aorta is maintained by
6. Occlusion of common carotid artery on both sides (AIPG 2009)
leads to A. Elastic recoil of aorta
A. Increases in HR & BP B. Muscular artery
B. Increases in BP & decreases in HR C. Resistance in arterioles
C. Decrease in HR & BP D. Capillaries
D. NO effect on BP & HR
11. Mean circulatory pressure is (AIIMS Nov 08)
7. Carotid sinus baroreceptor is most sensitive a. Average of pulmonary and circulatory pressure
to:(DNB Dec-2010) b. Pressure at any 1 point when the heart is stopped
A. Mean blood pressure c. Average of central venous and systemic pressure
B. Diastolic blood pressure d. Diastolic BP + 1/3 pulse pressure
C. Systolic blood pressure
D. Pulse pressure 12. The pressure measured in either the arterial or the
venous circulation when the heart has stopped long
8. Two students, Vineet and Kamlesh were asked to enough to allow the pressures to equalize is called the
(A) Hemodynamic pressure
demonstrate in dogs the role of sinus nerve in
(B) Mean arterial pressure
hypovolemic shock. Vineet severed the sinus nerve (C) Transmural pressure
when the mean blood pressure (MBP) was 85 mm Hg (D) Mean circulatory filling pressure
and Kainlesh cut the sinus nerve when the mean
blood pressure was 60mm Hg. On cutting the sinus 13. Blood pressure measured using a
nerve: sphygmomanometer
A. Vineet recorded an increase in MBP but Kamlesh (A) May be falsely low with too narrow a cuff
recorded a decrease in MBP. (B) May be falsely low in patients with badly stiffened
arteries
B. Vineet recorded a decrease in MBP but Kamlesh
(C) May be falsely high in obese patients
recorded an increase in MBP (D) Gives a direct reading of mean arterial pressure
C. Both recorded an increase in MBP
D. Both recorded a decrease in MBP. 14. As arterial pressure is raised and lowered during
the course of a day, blood flow through the brain
9. As a part of space research program, a physiologist would be expected to
was asked to investigate the effect of flight induced (A) Change in the same direction as the arterial blood
pressure because of the limited autoregulatory ability
stress on blood pressure. Accordingly, the blood
of the cerebral vessels
pressure of the cosmonauts were to be measured (B) Change in a direction opposite the change in mean
twice: once before the take-off and once after arterial pressure
spacecraft entered the designated orbit around the (C) Remain about constant because cerebral vascular
earth. For a proper comparison, the preflight blood resistance changes in the same direction as arterial
pressure should be recorded in: pressure
(D) Fluctuate widely, as both arterial pressure and
A. The lying down position
5.B 6.A 7.A 8.A 9.A 10.A 11.B 12.D 13.C 14.C

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 Cardiovascular System

brain neural activity status change

15. Blood pressure measured using a

sphygmomanometer
(A) May be falsely low with too narrow a cuff
(B) May be falsely low in patients with badly stiffened
arteries
(C) May be falsely high in obese patients
(D) Gives a direct reading of mean arterial pressure

Cardiovascular System Chapter - 4

16. As arterial pressure is raised and lowered during
the course of a day, blood flow through the brain
would be expected to
(A) Change in the same direction as the arterial blood
pressure because of the limited autoregulatory ability
of the cerebral vessels
(B) Change in a direction opposite the change in mean
arterial pressure
(C) Remain about constant because cerebral vascular
resistance changes in the same direction as arterial
pressure
(D) Fluctuate widely, as both arterial pressure and
brain neural activity status change

15. C 16. C

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 Cardiovascular System

7. A shift of posture from supine to upright posture is

Section-6 -: Cardiovascular Regulatory Mechanisms associated with cardiovascular adjustments. Which of
the following is not true in this context:
1. Which of the following statements about A. Rise in central venous pressure
vasomotor centre (VMC) is true (AIIMS 2011 MAY) B. Rise in heart rate
A. Independent of corticohypothalamic inputs C. Decrease in cardiac output
B. Influenced by baroceptor signals but not by D. Decrease in stroke volume
chemoreceptors
C. Acts along with the cardiovagal centre (CVC) to Section-7 -Special Circulation & APPLIED

Cardiovascular System Chapter - 4

maintain blood pressure
D. Essentially silent in sleep 1. CSF pressure is mainly regulated by (AIIMS 2011
MAY)
2 True for vasomotor centre is: (AIPG 2009) A. Rate of CSF formation B. Rate of CSF absorption
A. Not influenced by cortical centres C. Cerebral blood flow D. Venous pressure
B. Stimulated by baroreceptors from arterial organs
C. In sleep medulla stops sending signals which 2. Orthopnea in congestive heart failure is due to:
explains decrease in B.P (AIPG 2011)
D. Functional interaction with cardio vagal centre A. Reservoir function of pulmonary veins
B. Reservoir function of veins in lower limbs
3. Bradykinin produces all except: (DNB Pattern) C. Pulmonary hypertension
A..Pain D. Systemic hypertension
B..Vasoconstriciton
C..Emigration of leucocytes 3 . Blood brain barrier permeable to all except
D.Increases vascular Permeability (AIIMS Nov.2010)
A. Water B. Gas
4. Pressure on carotid sinus leads to: C. Lipophilic substances D. Protein
A. Tachycardia B. Increased blood pressure
C. Reflex bradycardia D. Brain bridge reflex 4. Main cause of increased blood flow to exercising
muscle is: (AIIMS MAY 2010)
5. Which of the following is not caused by A. Increase BP
sympathetic stimulation: B. increase HR
A. Increased BP C. Vasodilation due to local metabolites
B. Increased heart rate D. increase symp discharge
C. Increased venous capacitance
D. Increased total peripheral resistance 5. Pulmonary circulation differs from Systemic by
which of the following feature? (AIIMS MAY 2011)
6. Carotid sinus stimulation would result in A. In pulmonary circulation, Vasoconstriction In
A. Decreased vagal activity Response To Hypoxia
B. Increased heart rate B. Resistance is more than that in systemic circulation.
C. Decreased sympathetic discharge to heart C. Blood pressure is more in pulmonary circulation
D. Increased vasomotor tone D. Flow velocity is more in pulmonary circulation

1.C 2.D 3.B 4.C 5.C 6.C 7.A 1.B 2.A 3.C 5.A 6.D 7.C 8.C 9.D

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 Physiology

6. Cerebral blood flow is does not depend on? 13. Lymph flow from the foot is (AIPG 2008)
(AIIMS MAY 2008) A. Increased when an individual rises from the supine
A. Cerebral Metabolic rate to standing position.
B. CO2 B. Increased by messaging the foot
C. Blood pressure C. Increased when capillary permeability is decreased
D. K+ D Decreased when the valves of the leg veins are
incompetent
7. Thrombomodulin I is produced by all of the
following EXCEPT (AIPG 2008) 14. Which of the following give rise to Lewis Triple
A. Splanchnic circulation. B. Skin circulation Response? (AIPG 2008)
C. Cerebralcirculation D. Muscle circulation A. Axon reflex
B. Infury to endotheliu
8. Which of the following is TRUE regarding C. histamine
physiological changes in the brain during exercise? D. None of the above
(AIPG 2008)
A. Blood flow is decreased 15. The regional arterial resistance of the mesentry
B. Blood flow is increased and kidney vessels is reduced by
C. Blood flow remains unaltered A. Dopamine B. Dobutamine
D. Blood flow initially is increased and then decreases C. Nor adrenaline D. Isoprenaline

9 Maximum heart rate with exercise 16. Which of the following is true regarding triple
A. 120 B. 140 C. 160 D. 200 response:
A. Axon reflex
10. All are increased during exercise except; B. Flare is due to arteriolar dilation
A. Cardiac output C. Both
B. Venous return D. None
C. Coronary blood flow
D. Peripheral vascular resistance 17 The pressure-volume curve is shifted to the left in:
(DNB Dec-2010)
11. Exercise causes: (AIIMS NOV 2012) A. Mitral regurgitation B. Aortic regurgitation
A. Increased blood flow to the skin C. Mitral stenosis D. Aortic stenosis
B. Increased in cerebral blood flow due to increase in
systolic blood pressure 18. Hypovolemic shock is characterized by all of the
C. Body temperature rise following except (Latest Questions)
D. All of the above A. Hypotension B. Cold and clammy skin
C. Intense thirst D. Inhibition of respiration
12. Blood supply during exercise does not decrease in:
(DNB Pattern) 19. Vagal stimulation causes increase in
A. Coronary circulation (AIIMS Nov 08)
B. Renal circulation A. Heart rate B. R-R interval in ECG
C. Hepatosplanchnic circulation C. Cardiac output (COP) D. Force of contraction
D. Cutaneous circulation
20. A single cell within a culture of freshly isolated
10.D 11.C 12.A 13.B 14.C 15.A 16.C 17.D 18.D 19.B 20.A

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 Cardiovascular System

cardiac muscle cells is injected with a fluorescent dye (C) Exercise

that cannot cross cell membranes. Within minutes, (D) The diving response
several adjacent cells become fluorescent. The most
likely explanation for this observation is the presence 25. A patient suffers a severe hemorrhage resulting in
of a lowered mean arterial pressure. Which of the
(A) Gap junctions following would be elevated above normal levels?
(B) IP3 receptors (A) Splanchnic blood flow
(C) Transverse tubules (B) Cardiopulmonary receptor activity
(D) Desmosomes (C) Right ventricular end-diastolic volume
(D) Heart rate

Cardiovascular System Chapter - 4

21. The volume of an aorta is increased by 30 mL with
an associated pressure increase from 80 to 120 mm 26. A person stands up. Compared with the
Hg. The compliance of the aorta is recumbent position, 1 minute after standing, the
(A) 1.33 mm Hg/mL (A) Skin blood flow increases
(B) 4.0 mm Hg/mL (B) Volume of blood in leg veins increases
(C) 0.75 mm Hg/mL (C) Cardiac preload increases
(D) 0.75 mL/mm Hg (D) Cardiac contractility decreases

22. Which of the following special circulations has the

widest range of blood flows as part of its 27. A manual labourer moves in March from Kashmir
contributions to both the regulation of systemic to Delhi and becomes acclimatized by working
vascular resistance and the modification of resistance outdoors for a month. Compared with his responses
to suit the organ’s metabolic needs? on the first few days in the Delhi, for the same activity
(A) Coronary level after acclimatization one would expect higher
(B) Cerebral (A) Core temperature
(C) Small intestine (B) Heart rate
(D) Skeletal muscle (C) Sweating rate
(D) Sweat salt concentration
23. Which of the following is true with respect to
peripheral chemoreceptors?
(A) Activation is important in inhibiting the diving
response
(B) Activity is increased by increased pH
(C) They are located in the medulla oblongata, but not
the hypothalamus
(D) Activation is important in the cardiovascular
response to hemorrhagic hypotension

24. Parasympathetic stimulation of the heart

accompanied by a withdrawal of sympathetic tone to
most of the blood vessels of the body is characteristic
21.D 22.D 23.D 24 .B 25.D 26.B 27.C

of
(A) The fight-or-flight response
(B) Vasovagal syncope

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 Cardiovascular System

28. In the PV loop below, the EDV is shown at what point?

Cardiovascular System Chapter - 4

a) A

b) B

c) C

d) D

29. In the diagram below A-D represent depolarization of ventricles. Which one represents
“R” wave?

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 Physiology

a) A

b) B

c) C

d) D

30. In the tube in the diagram, the inlet pressure is 75 mm Hg and the outlet pressure at A
and B is 25 mm Hg. Flow is 100 mL/min. The resistance to flow is

(A) 2 PRU

(B) 0.5 PRU

(C) 2 (mL/min)/mm Hg

(D) 0.75 mm Hg/(mL/min)

31.. In the presence of a drug that blocks all effects of norepinephrine and epinephrine on
the heart, the autonomic nervous system can

(A) Raise the heart rate above its intrinsic rate

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 Cardiovascular System

(B) Lower the heart rate below its intrinsic rate

(C) Raise and lower the heart rate above and below its intrinsic rate

(D) Neither raise nor lower the heart rate from its intrinsic rate

32.At a constant blood flow, an increase in the number of perfused capillaries

Cardiovascular System Chapter - 4

improves the exchange between blood and tissue because of

(A) Greater surface area for the diffusion of molecules

(B) Faster flow velocity of plasma and red blood cells in capillaries

(C) Increased permeability of the microvasculature

(D) Decreased concentration of chemicals in the capillary blood

28.B 29.C 30.B 31. B 32.A

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 Physiology

Explanations
Chapter-4 Cardiovascular System

1. Ans. C. HR increases with parasympathetic denervation

a. Impulses in the noradrenergic sympathetic nerves to the heart increase the cardiac rate (chronotropic
effect)and the force of cardiac contraction (inotropic effect).
b. They also inhibit the effects of vagal stimulation, probably by the release of neuropeptide Y, which is a co-
transmitter in the sympathetic endings.
c. Impulses in the cholinergic vagal cardiac fibers decrease the heart rate.
d. A moderate amount of tonic discharge takes place in the cardiac sympathetic nerves at rest, but there is a
good deal of tonic vagal discharge (vagal tone) in humans and other large animals.
e. When the vagi are cut in experimental animals, the heart rate rises, and after the administration of
parasympatholytic drugs such as atropine, the heart rate in humans increases from 70 (its normal resting
value)to 150 –180 beats/min because the sympathetic tone is unopposed.
f. In humans in whom both noradrenergic and cholinergic systems are blocked, the heart rate is approximately
100/min.

2. Ans. B. R-R interval (Ref: Ganong 23rd ed-489)

a. R-R interval is the interval between the peaks of R wave of 2 consecutive QRS complexes.
b. Obviously, the R-R interval bears an inverse relationship with the heart rate.
c. Vagal stimulation causes bradycardia and therefore an increase in R-R interval.
d. Vagal stimulation leads to bradycardia, hat is why in symptomatic bradycardia cases.
e. Patients are treated by giving injection atropine.
f. Vagal stimulation leads to decrease COP & ejection fraction.

3. Ans. D. Purkinje fiber

4. Ans. A. AV node

5. Ans. A. It generates impulses at a faster rate

a. The PACEMAKER function of the heart resides in the sinoatrial (SA) node, It lies at the Junction of the right
atrium and superior vena cava and is approximately 1.5 cm long and 2 to 3 mm wide Q.
b. It is supplied by the sinus node artery which arises from either the right coronary artery (60 percent) or the left
circumflex coronary artery (40 percent) Various parts of conduction system of heart and under abnormal
circumstances even the myocardium is capable of spontaneous discharge.
c. As this SA node normally discharges more rapidly than any other structure it is the normal pacemaker of heart.
Q

6. Ans. B. Decrease in K+ permeability

Pacemaker potentials or Pre potentials:
a. "Rhythmically-discharging cells have a membrane potential that, after each impulse, declines to the firing level.
Thus, this pre potential or pacemaker potential triggers the next impulse. Q
b. At the peak of each impulse, IK begins and brings about repolarization IK than declines, and as K+ efflux
decreases (ie:  in permeability), the membrane begins to depolarize, forming the first part of the pre

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 Cardiovascular System

potential.  Ca++ channels then open  two types - T - channels (transient channels) and L-channels (L =
long-lasting). The calcium current (lca) due to opening of T channels completes the prepotential, and lca due to
opening of L-channels produces the impulse.

7. Ans. C. Plateau phase of the action potential

Action potential in cardiac muscle:

8. Ans. A. Endocardium, epicardium, upper most part of septum

a. Depolarization started from SA node spreads radially all over the atria and converges on AV node arid this

Cardiovascular System Chapter - 4

process takes 0.1 seconds.
b. As the conduction in AV node is slow, wave of excitation spreads to ventricles after another 0.1 second.
c. From top of septum the wave spreads rapidly in Purkinje fibers and ventricles in 0.08 to 0.1 seconds.
d. Ventricular depolarization starts at the left side of interventricular septum and moves to right across the
middle portion of septum.
e. From here it spreads down the septum to the apex of heart and returns along the ventricular wall to the AV
junction. Endocardium is stimulated, then myocardium, and then the epicardium. Last parts of heart to be
depolarized are postero-basal part of left ventricle, pulmonary conus and finally upper most portion of
septum.

9. Ans. D. Generates impulses at the highest rate

a. The various parts of the conduction system of heart and, under abnormal conditions, parts of the myocardium
are capable of spontaneous discharge.
b. However, the SA node normally discharges most rapidly Q, depolarization spreading from it to the other
regions before they discharge spontaneously.
c. The SA node is therefore the normal cardiac pacemaker, its rate of discharge determining the rate at which
heart beats.

10. Ans. D. Both A and C

11. Ans. B. Ventricular repolarization

12. Ans. D. Ventricular depolarization

• PR interval Atrial depolarization and conduction through AV node Q

• QRS duration Ventricular depolarization Q
• QT interval Ventricular depolarization plus ventricular repolarization Q
• ST Interval Ventricular repolarization Q

13. Ans. D. Osborne J wave

14.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 661,662
 The form of the QRS will be normal because electrical excitation of the ventricles occurs over essentially the normal
pathway (i.e., AV node to bundle branches to Purkinje system to myocardium).

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 Physiology

 The T wave will be normal as well. With complete heart block, P waves and QRS complexes are completely
independent of each other.
 Some PR intervals could be shortened by chance, others will be very long; that is, there is no predictable PR interval.
 There will not be a consistent ratio of P waves to QRS complexes because the two are disassociated, but the average
ratio would be 80/40 or 2:1.

15.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 661
 The shape of the QRS complex will be significantly different from normal because depolarization now originates in
the right ventricle and propagates in a retrograde fashion.
 Because the right side of the heart depolarizes before the left, the configuration of the QRS may resemble that seen
with left bundle branch block, another situation in which the right side of the heart depolarizes before the left.
 The duration of the QRS complex will be increased because the specialized conducting system of the ventricles is not
fully employed: Depolarization moves through more slowly conducting muscle instead of the rapidly conducting
Purkinje system.
 Retrograde conduction through the AV node is extremely unlikely, so P waves will not follow each QRS complex.
Because excitation of the atria and ventricles is still independent, there will be no predictable PR interval.

16.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 653
 Voltage-gated Ca2+ channels are primarily responsible for the upswing (i.e. depolarisation phase) of the action
potential (phase 0) of nodal cells.
 Voltage-gated Na+ channels are inactivated because the resting membrane potential in these cells never becomes
sufficiently negative to allow reactivation.
 Acetylcholine-activated K+ channels are important only in mediating the effect of ACh on the pacemaker potential of
nodal cells.
 Inward rectifying K+ channels are responsible for maintaining the resting membrane potential in nonnodal cells but
have a less important role in cells with a pacemaker potential.

17. The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 656
Atrial repolarization normally occurs during the QRS complex. A dipole is created by atrial repolarization but it
is not observed on the ECG because the dipole created by ventricular depolarization is much larger.

18.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 657
 Depolarization of the ventricles proceeds from subendocardium to subepicardium, but this does not result in the P
wave. (On the other hand, repolarisation of the ventricles proceeds from epicardium to endocardium)
 In lead I, when the ECG electrode attached to the right arm is positive relative to the electrode attached to the left
arm, a downward deflection is recorded.
 AV nodal conduction is slower than atrial conduction, but this does not cause the P wave.
 When cardiac cells are depolarized, the inside of the cells is positive or neutral relative to the outside of the cells.

19. The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 657
 Excitation of the ventricles does not ordinarily lead to excitation of the atria because retrograde conduction in the
AV node is unusual.
 Norepinephrine modulates the ventricular force of contraction and conduction velocity and lowers the threshold for
excitation, but it does not, by itself, initiate excitation.
 Excitation of the ventricles is initiated by phase 0 of the action potential. Normal ventricular cells do not exhibit
pacemaker potentials.

20. The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 654
 AV nodal cells exhibit action potentials characterized by slow depolarization (phase 0) because fast voltage-gated
Na+ channels do not participate.
 This is because the diastolic potential of these cells does not become sufficiently negative to allow reactivation of
Na+ channels.

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 Cardiovascular System

 Acetylcholine slows and norepinephrine speeds conduction velocity. AV nodal cells are capable of pacemaker activity
but at a rate of approximately 25 to 40 beats/min.

21.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 655-660
 When stimulation of the parasympathetic nerves to the normal heart leads to complete inhibition of the SA node for
several seconds, nodal escape usually occurs.
 In this situation, pacemaker activity usually is taken over by cells in the AV node or bundle of His.
 QRS complexes are normal because the pacemaker activity is high enough in the conducting system to lead to a
normal pattern of ventricular excitation.
 T waves would be normal for the same reason. Because at least one beat begins without atrial excitation,there

Cardiovascular System Chapter - 4

would be fewer P waves than either QRS complexes or T waves.

22.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 657
The R wave in lead I of the ECG reflects a net dipole associated with ventricular depolarization. Repolarization
causes the T wave. The R wave is smallest when the mean axis is directed perpendicular to a line drawn
between the two shoulders because both electrodes are equally influenced by the negative and positive
sides of the dipole.

23.The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 675,677
 The aortic and mitral valves are never open at the same time. This is the basic principle of the cardiac pump.
 The first heart sound is caused by closure of the mitral and tricuspid valves. The mitral valve is open throughout
diastole except isovolumetric relaxation.
 Left ventricular pressure is less than aortic pressure during diastole and isovolumetric contraction but is greater than
aortic pressure during a substantial period of ventricular ejection.
 Ventricular filling occurs during diastole.

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 Cardiovascular System

Section-2 -: Cardiac Cycle & JVP Changes

1. Ans. B. Bulging of the tricuspid value into the right atrium

2. Ans. D. Closure of AV valve

3. Ans. ‘D’ Closure of aortic and pulmonary valve

Cardiovascular System Chapter - 4

4. Ans. ‘C’ Ventricular pressure falls below atrial pressure

ISO- VOLUMETRIC RELAXATION ends when ventricular pressure tails below atrial pressure and the AV valves
open allowing the ventricles to be filled with blood.

5. Ans. ‘D’ Opening of AV valve

6. Ans. B. End of isovolumeric contraction

At the end of isovolumetric contraction, aortic and pulmonary valves open
Events of the cardiac cycle at a heart rate of 75 beats/min. the phases of the cardiac cycle identified by
the numbers at the bottom are as follows. 1. atrial systole: 2. Isovolumetric ventricular contractions;
3. Ventricular ejection; 4. Isovolumetric ventricular relaxation 5. Ventricular filling.

Mitral and Tricuspid valve close Aortic and pulmonary valve close
 
Isovolumid or Isometric Contraction Isovolumetric or Isometric relaxation
 
Aortic and pulmonary valve open Mitral and tricuspid valve open

Section-3 -: Cardiac Output & Ventricular Functions

1. Ans. A. Directly proportional to duration of systole (Ref: Ganong - 23nd Ed page 516)
About option D: Relationship with external work done is not contant

2. Ans. A. Immediate Increase in Venous Return (Ref: Ganong - 22nd Ed-page489)

a. In the standing position, as a result of the effect of gravity on the blood, the mean arterial blood pressure in
the feet of a normal adult is 180–200 mm Hg and venous pressure is 85–90 mm Hg.
b. The arterial pressure at head level is 60–75 mm Hg, and the venous pressure is zero.
c. If the individual does not move, 300–500 mL of blood pools in the venous capacitance vessels of the lower
extremities, fluid begins to accumulate in the interstitial spaces because of increased hydrostatic pressure in
the capillaries, and stroke volume is decreased.
d. Symptoms of cerebral ischemia develop when the cerebral blood flow decreases to less than about 60% of the
flow in the recumbent position.

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 Physiology

e. If no compensatory cardiovascular changes occurred, the reduction in cardiac output due to pooling on
standing would lead to a reduction of cerebral flow of this magnitude, and consciousness would be lost. So,
under normal conditions the cerebral blood flow remains unchanged.
f. The major compensations on assuming the upright position are triggered by the drop in blood pressure in the
carotid sinus and aortic arch.
g. The heart rate increases, helping to maintain cardiac output. Relatively little venoconstriction occurs in the
periphery, but there is a prompt increase in the circulating levels of renin and aldosterone.
h. The arterioles constrict, helping to maintain blood pressure. So, when the person sits from a standing posture
the venous return increases due to movement of 300-500 ml of blood pooled in the lower extremities
towards the heart.

Effect on the cardiovascular system of rising from the supine to the upright position

3. Ans. B. Venous return to heart rises immediately

a. Immediately on lying from standing position, following occur
i. Increase Venus return ii. Increase cardiac output
b. Gradient from base to apex in perfusion, ventilation intraplerual pressure V/Q ratio, occur only is standing and
sitting position. It does not occur is lying position

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 Cardiovascular System

4. Ans. C. Directly Proportional to ventricle systole duration

5. Ans D. Mean stroke volume

The STROKE VOLUME (about 80 ml) multiplied by the heart rate per minute is equal to the cardiac output.Cardiac
output = stroke volume x heart rate

6. Ans. ‘B’ 5.5liter

1. CARDIAC OUTPUT is defined as the volume of blood pumped into the arterial system per minute (unit time).
2. The stroke volume (about 80 ml) multiplied by the heart rate per minute is equal to the cardiac output.

Cardiovascular System Chapter - 4

3. The normal cardiac output value in healthy adults varies between 2.5 to 6.0 liters per minute (average 5.5
liter).
4. Output per minute per square meter of body surface area is known as CARDIAC INDEX (average 3.2 liter).
5. Some factors affecting cardiac output are given below:
Increase Cardiac Output Decrease Cardiac Output No change
• Anxiety and excitement • Sitting and standing from lying • Sleep
• Eating position • Moderate changes in
• Exercise • Rapid arrhythmias environmental temperature
• High environmental temperature • Heart disease
• Pregnancy
• Epinephrine
• Histamine

7. Ans. ‘D’ Cardiac output

8. Ans. C. Within physiological limits, the force of contraction is proportional to initial length of cardiac muscle
fiber
Frank Starling’s law of heart states that the force of the contraction of myocardium is proportional to the initial
length of the cardiac muscle fibers. Therefore an increase in diastolic filling will increase the force of contraction of
myocardium.

9. Ans. C. Low Cardiac Output (Ref: Textbook of cardiovascular Medicine, Volume 355 Edited by E.J Topal,
Robert M.C
Methods of Measurement of cardiac out:
If Tricuspid regurgitation and pulmonary regurgitation is present or significant left to right shunt present - the
thermodilution technique is less reliable.
Thermal dilution method is used except low cardiac ouput states where Fick's principle is preferred . Q But among
the Provided option C is best to exclude.

10. Ans. C. 3.0l/m2

Cardiac out average = 5.0 L/min Q
a. Cardiac index = cardiac out per square of body surface area.
b. = 5L/min
1.7m2
= 3 lit/min/m2 Q

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 Physiology

11. Ans. B. End. Diastolic volume

12. Ans. A. Increases proportionately with heart rate. (Ref: Ganong – 23rd Ed-page 489)

Changes in Cardiac Function with Exercise.

Work (kg- O2 Usage Pulse Rate (per Cardiac Output Stroke Volume A-V O2 Difference
m/min) (mL/min) min) (L/min) (mL) (mL/dL)

Rest 267 64 6.4 100 4.3

288 910 104 13.1 126 7.0

540 1430 122 15.2 125 9.4

900 2143 161 17.8 110 12.3

1260 3007 173 20.9 120 14.5

Section-4 -: Principles Of Hemodynamics

1. Ans. A. Oncotic pressure is higher in the blood column than that in glomerular capillaries
(Ref: 23rd edition Ganong's Page-507
a. The factors governing filtration across the glomerular capillaries are the same as those governing filtration
across all other capillaries, that is, the size of the capillary bed, the permeability of the capillaries, and the
hydrostatic and osmotic pressure gradients across the capillary wall.
b. For each nephron:

c. Kf, the glomerular ultrafiltration coefficient, is the product of the glomerular capillary wall hydraulic
conductivity (ie, its permeability) and the effective filtration surface area. P GC is the mean hydrostatic pressure
in the glomerular capillaries, PT the mean hydrostatic pressure in the tubule (Bowman's space), πGC the oncotic
pressure of the plasma in the glomerular capillaries, and πT the oncotic pressure of the filtrate in the tubule.
i. Now the oncotic pressure of the glomerular capillaries is the same as in any other systemic capillary i.e. 25
mm Hg
ii. Constriction of the afferent arteriole causes a fall in capillary BP resulting in decreased GFR
iii. Due to filteration of plasma, RBC are more in glomerular capillaries, so the GFR increases
d. Concentration of all freely filtered substances like glucose are equal in glomerular capillaries and ultrafiltrate

2. Ans. A. Arterial pressure

(Ref: Ganong - Review of Medical Physiology 22nd Ed.Pg:595 & Guyton – Textbook of Medical Physiology 10th Ed.
Pg: 176-179)

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 Cardiovascular System

3. Ans. D. Fascial planes (Ref. Ganong Physiology 23rd page-569)

Venous return of flow depends on
a. Respiratory pump
b. Muscle pump
c. Sympathetic tone
d. Cardiac output
e. Gravity
f. Venous pressure gradient that is VR = Psf – RAF/ RVR in which VR is venous return, Psf is mean systemic filling
pressure, PRA is right atrial pressure, and RVR is resistance to venous return. Psf in turn depends on arterial

Cardiovascular System Chapter - 4

pressure.
i. In the limbs, the veins are surrounded by skeletal muscles, and contraction of these muscles during activity
compresses the veins.
ii. Pulsations of nearby arteries may also compress veins. Since the venous valves prevent reverse flow, the
blood moves toward the heart.
iii. During quiet standing, when the full effect of gravity is manifest, venous pressure at the ankle is 85–90
mm Hg.
iv. Pooling of blood in the leg veins reduces venous return, with the result that cardiac output is reduced,
sometimes to the point where fainting occurs. Rhythmic contractions of the leg muscles while the person
is standing serve to lower the venous pressure in the legs to less than 30 mm Hg by propelling blood
toward the heart.
v. This heart ward movement of the blood is decreased in patients with varicose veins because their valves
are incompetent.
vi. These patients may develop stasis and ankle edema.
vii. However, even when the valves are incompetent, muscle contractions continue to produce a basic heart
ward movement of the blood because the resistance of the larger veins in the direction of the heart is less
than the resistance of the small vessels away from the heart.

4. Ans A. Capillaries contain 5% blood

5. Ans. D. Contain 54% of blood volume

6. Ans. A. Critical velocity

a. The flow of blood in the blood vessels is normally laminar (stream line). Within the blood vessels, an infinitely
thin layer of blood in contact with the vessel does not move. The next layer within the vessel has a low velocity,
the next a higher velocity, and so forth, velocity being greatest in the center of the stream.
b. Laminar flow occurs at velocities up to a certain CRITICAL VELOCITY. At or above this velocity flow is turbulent. Q

7. Ans. C. Arterioles

8. Ans. A. Arterioles
Q
The small arteries and ARTERIOLES are also known as resistance vessels because they are the principal site of
peripheral resistance.

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 Physiology

9. Ans. C. Sum of kinetic energy of flow and pressure energy is constant

In a tube or a blood vessel the total energy-the sum of the kinetic energy of flow and the pressure energy-is
constant
(Bernoulli’s principle).

10. Ans. A. Sum of kinetic energy of flow and pressure energy is constant
a. Bernoulli Principle:
i. "In a tube or a blood vessel the total energy - the sum of the kinetic energy of flow and the pressure
energy - is constant." Q
ii. The greater the velocity of flow in a vessel, the lower the lateral pressure distending its walls. Q
b. Frank - Starling law: (Option d)
i. "Energy of the contraction is proportional to the initial length of the cardiac muscle fiber. Q
ii. " For the heart, the length of the muscle fibers (ie. Extent' of the pre-load) is proportionate to the end-
diastalic volume.
iii. Weber-Fechner law - "the magnitude of the sensation felt is proportionate to the log of the intensity of
the stimulus." Q

11. Ans. A. Large veins

a. The average velocity of blood is high in the aorta, declines steadily in the smaller vessels, capillaries Q.
b. The average velocity of blood flow increases again as the blood enters the veins , although not so high as in the
aorta. and is lowest in the venule is relatively high in large veins

12. Ans. A. Capillary

1. Characteristics of various types of blood
Vessels Total cross section area (cm2) Percentage of Blood volume contained
Aorta 4.5 2
Artery 20 8
Arteriole 400 1
Capillary 4500 5
Venule 4000
Vein 40
 54
Vena cava 18
2. The total area of all the capillary wall in the body exceeds 63,00 m 2
3. The arterioles are the major site of the resistance to blood flow, and small changes in their caliber cause large
changes in the total peripheral resistance.

13. Ans. C. Pressure of difference

a. Flow  in any portion of the vascular system is equal to the effective perfusion pressure in that portion divided
by resistance.
 The effective perfusion pressure is the mean intraluminal pressure at the arterial mean minus the mean
pressure at the venous end
Flow = Pressure
Resistance
b. Indirect methods for measuring blood flow — are

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 Cardiovascular System

i. Fick and indicator dilution techniques

ii. Cerebral blood flow  kety N2O method
iii. Renal blood flow  by measuring clearance of PAHA
iv. Blood flow in extrimtes —by Plethysmography

From above it is clear that flow is directly varies with pressure difference and radius (r4) and indirectly varies with
viscosity of fluid, resistance and length of tube Q

14. Ans. B. Have role in thermoregulation (Ref: Ganong - 23nd Ed page 524)

Cardiovascular System Chapter - 4

ARTERIOVENOUS ANASTOMOSES
a. In the fingers, palms, and ear lobes, short channels connect arterioles to venules, bypassing the capillaries.
These arteriovenous (A-V) anastomoses, or shunts, have thick, muscular walls and are abundantly innervated,
presumably by vasoconstrictor nerve fibers.
b. The amount of heat lost from the body is regulated to a large extent by varying the amount of blood flowing
through the skin.
c. Blood flow in response to thermoregulatory stimuli can vary from 1 to as much as 150 mL/100 g of skin/min,
and it has been postulated that these variations are possible because blood can be shunted through the
anastomoses.
d. Therefore they play an important role in regulation of body temperature and one of the earliest changes in Hot
climate is cutaneous vasodilation due to opening of shunt vessels and the reverse occurs in cold weather.

15. Ans. B. Opening of parallel channels

(Ref: Ganong - 23rd Ed Pg: 569)
During exercise there is an increase in CO due to increased HR and SV.
a. Peripheral resistance and DBP also increase due to sympathetic vasoconstriction. Sympathetic cholinergic
system does cause Vasodilatation but only in few organs like Skeletal muscle Q, Uterus and Sweat glands.
b. In Lungs there is not much rise in pulmonary vascular resistance because of opening of precapillary sphincters.
They cause opening of more blood vessels leading to increasing in pulmonary perfusion.
c. But the vessels are arranged in parallel to each other, their resistances are added as

d. So, more is the number of resistances (vessels) in parallel lower is the Total resistance (R T).
e. During exercise this mechanism counters the effect of sympathetic vasoconstriction in lungs and there is only
small rise in pulmonary vascular resistance.

Section-5 -: Blood Pressure

1. Ans. B. SBP+2DBP/3
(Ref: 23rd edition Ganong's Review of Medical Physiology chapter32)
MBP is defined as the average circulatory pressure during cardiac cycle, since diastole is longer it depends primarily
on the DBP.

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 Physiology

MBP = DBP + 1/3 PP

Now if we replace PP = (SBP-DBP)
We get
MBP = DBP + 1/3 SBP-DBP)
= (3DBP + SBP – DBP)/ 3
= (2DBP+SBP)/3

2. Ans. ‘B’ Pressure at any point when the heart is stopped Explanation: Ref. Ganong’s 23 rd ed-Page555
a. Mean systemic filling pressure is slightly different from the mean circulatory filling pressure.
b. It is the pressure measured everywhere in the systemic circulation after blood flow has been stopped by
clamping the large blood vessels at the heart, so that the pressure in the systemic circulation can be measured
independently from those in the pulmonary circulation.
c. The mean systemic pressure, although almost impossible to measure in the living animal, is the important
pressure for determining the venous return.
d. The mean systemic filling pressure, however, is almost always nearly equal to the mean circulatory filling
pressure because the pulmonary circulation has less than one eighth as much capacitance as the systemic
circulation and only about one tenth as much blood volume.

3. Ans. B. Higher than the intraarterial pressure

4. Ans. C. Left atrial pressure

a. PULMONARY WEDGE PRESSURE IS the pressure measured in the pulmonary artery at its capillary end.
b. A catheter (SwanGaz catheter) is positioned in the pulmonary artery, and the distal portion of the catheter is
isolated from pressure behind it in the artery by inflating a balloon .
c. This makes the catheter to float into a” WEDGED POSITION “, and allows sensing of transmission of pressures in
front of the catheter (in the pulmonary capillary bed) by the transducer.
d. Because there is no valve between this location and the left atrium, the measurement reflects LEFT ATRIAL
PRESSURE Q

5. Ans. B. Diastolic + 1/3rd Pulse pressure

• Systolic pressure Peak pressure in aorta during cardiac cycle
• Diastolic pressure Minimum pressure in aorta during cardiac cycle
• Pulse pressure (Systolic pressure) — (diastolic pressure)
• Mean arterial pressure (Diastolic pressure) + (1/3rd pulse pressure)

6. Ans. A. Increases in HR & BP

a. “CNS Ischaemic response  control of arterial pressure by the Brain’s vasomotor centre in response to
diminished brain blood flow”: 
i.  Brain blood flow  cerebral Ischaemia  vasomotor centre excited  Systemic Arterial pressure often
rises to a level as high as heart can possibly pump
ii. sympathetic stimulation  HR
[Note  by occlusion of common carotid artery both side  Brain blood flow  CNS ischaemia] Q

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 Cardiovascular System

b.  Hypoxia  brain affected first c/f 

i. Less severe hypoxia causes - impaired judgement, drowsiness, dulled pain sensibility, excitement,
disorientation, loss of time sense, and Headache.
ii. Other symptoms/signs  Anorexia, nausea, vomiting, Tachy cardia (HR), and when the hypoxia is severe,
Hypertension (B P).

7. Ans. A. Mean blood pressure

Samson Wright : - Effect of common carotid artery occulation  fall in pressure of carotid sinus  baroreceptors
lesen their discharge  medullary cardiovascular centre is inhibited  increase their drive to the sympathetic

Cardiovascular System Chapter - 4

vasoconstriction and to the cardiac sympathetic fibers  BP and HR

8. Ans. A. Vineet recorded on increase in MBP But Kamlesh recorded a decrease in MBP
Arterial Baroreceptor control system:
a. The Baroreceptor are stretch receptors in the wall of the heart and blood vessels. The carotid sinus (small
dilation of the internal carotid artery) and Aortic arch receptors monitor the arterial circulation.
Carotid sinus Aortic Arch
 
Afferents go via-Hering’s nerve Afferent go via vagus nerve
(carotid sinus nerve) via IX CN
 
Reach medullary cardio-vascular centre Reach Medullary Cardio-vascular centre
a. Normally discharge from the carotid sinus inhibit the medullary cardio-vascular centre and thus inhibit the
sympathetic tonic discharge from medullary cardi-vascular centre
b. When BP rises  stretch the carotid sinus and Aaetic arch  Baroreceptor stimulated  Baroreceptor
discharge  inhibits the medullary cardiovascular centre and excite the vagal discharge  thus sympathetic
discharge and  vagal tone  leads to  vasodilation venodilation Bp, Brachycardia and COP.
c. When BP falls  Baroreceptor discharge decreases  inhibition of medullary cardiovascular centre decreases

d. sympathetic discharge  leads to vasoconstriction ( BP),  HR, and  COP.
e. When both carotid sinus nerve are sectioned  loss of inhibitory impulse from carotid sinus nerves - allows
escape of the medullary cardio vascular centre  es sympathetic discharge  leads to vasoconstriction (
BP), HR, and COP.
f. Effect of Bilateral carotid occlusion leads fall pressure in the carotid sinus reduces the stretch on its wall  
Baroreceptor discharge loss of inhibition on medullary cardio-vascular centre   sympathetic discharge
leads to  BP,  HR, and  COP.
g. A mean blood pressure of some 60-70 mm Hg is required in the sinus segment before any reflex inhibition is
exercised upon the medullary cardiovascular centre.
h. The carotid sinus nerves and vagal fibers from the aortic arch are commonly called the Buffer nerves.

9. Ans. A. The lying down position

a. For two values to be comparable (to remove any bias) we must remove as many confounding variable possible
"The confounding variable in this question is gravity.
b. Gravity is present on earth but is not present in space.

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 Physiology

c. So, we have to take the BP in a position which sort of nullifies the effect of gravity on earth.
d. The best position is the lying down position because then the whole body is at the same height with respect to
the heart.

10. Ans. A . Elastic recoil of aorta Ref: Ganong - Review of Medical Physiology 22nd Ed
Due to presence of elastic fibres in the Windkessel vessels there is a elastic recoil during the diastole (they are
stretched during systole), which results in a forward flow and aortic pressure wave called as diastolic pressure.
a. Although the mean velocity of the blood in the proximal portion of the aorta is 40 cm/s, the flow is phasic, and
velocity ranges from 120 cm/s during systole to a negative value at the time of the transient backflow before
the aortic valve closes in diastole. In the distal portions of the aorta and in the large arteries, velocity is also
greater in systole than it is in diastole.
b. However, the vessels are elastic, and forward flow is continuous because of the recoil during diastole of the
vessel walls that have been stretched during systole. This recoil effect is sometimes called the Windkessel
effect, and the vessels are called Windkessel vessels; Windkessel is the German word for an elastic reservoir.
c. Pulsatile flow appears, in some poorly understood way, to maintain optimal function of the tissues.
d. If an organ is perfused with a pump that delivers a nonpulsatile flow, there is a gradual rise in vascular
resistance, and tissue perfusion fails.

Arterial Pressure
a. The pressure in the aorta and in the brachial and other large arteries in a young adult human rises to a peak
value (systolic pressure) of about 120 mm Hg during each heart cycle and falls to a minimum value (diastolic
pressure) of about 70 mm Hg.
b. The arterial pressure is conventionally written as systolic pressure over diastolic pressure—eg, 120/70 mm Hg.
c. The pulse pressure, the difference between the systolic and diastolic pressures, is normally about 50 mm Hg.
d. The mean pressure is the average pressure throughout the cardiac cycle.
e. Because systole is shorter than diastole, the mean pressure is slightly less than the value halfway between
systolic and diastolic pressure.
f. It can actually be determined only by integrating the area of the pressure curve , however, as an approximation,
mean pressure equals the diastolic pressure plus one-third of the pulse pressure.
g. The pressure falls very slightly in the large and medium-sized arteries because their resistance to flow is small,
but it falls rapidly in the small arteries and arterioles, which are the main sites of the peripheral resistance
against which the heart pumps.
h. The mean pressure at the end of the arterioles is 30-38 mm Hg.
i. Pulse pressure also declines rapidly to about 5 mm Hg at the ends of the arterioles.
j. The magnitude of the pressure drop along the arterioles varies considerably depending upon whether they are
constricted or dilated.

11. Ans : ‘B’ Pressure at any point when the heart is stopped

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 Cardiovascular System

12.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 721
 When the heart stops, blood continues to flow from the arteries to the veins until the pressures in the two sides of
the circulation are equal.
 That pressure is mean circulatory filling pressure. Hemodynamic pressure is the potential energy that causes blood
to flow.
 Mean arterial pressure is the average pressure in the aorta or a large artery over the cardiac cycle.
 Transmural pressure is the difference between the pressure inside and outside a blood vessel. Hydrostatic pressure
is the pressure caused by the force of gravity acting on a fluid.

Cardiovascular System Chapter - 4

13.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 726
 If the cuff is too small, it takes a falsely high pressure in the cuff to transmit sufficient pressure to the vessel wall for
total occlusion of the artery.
 Blood pressure may be falsely high in patients with badly stiffened arteries because of the extra pressure needed to
compress the arteries.
 The measurement gives an indirect reading of systolic and diastolic pressure; mean arterial pressure must be
calculated.
As an approximation, the mean arterial pressure is calculated by :
DBP + 1/3rd PP
(DBP = diastolic BP); PP = pulse pressure)

 The measurement depends on the appearance of sound to signal systolic pressure

14.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 767
Brain blood flow is constant despite large changes in the arterial blood pressure because vascular resistance
usually changes in the same direction as the arterial pressure and by almost the same percentage.

15.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 726
 If the cuff is too small, it takes a falsely high pressure in the cuff to transmit sufficient pressure to the vessel wall for
total occlusion of the artery.
 Blood pressure may be falsely high in patients with badly stiffened arteries because of the extra pressure needed to
compress the arteries.
 The measurement gives an indirect reading of systolic and diastolic pressure; mean arterial pressure must be
calculated.
As an approximation, the mean arterial pressure is calculated by :
DBP + 1/3rd PP
(DBP = diastolic BP); PP = pulse pressure)

 The measurement depends on the appearance of sound to signal systolic pressure

16.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 767
Brain blood flow is constant despite large changes in the arterial blood pressure because vascular resistance
usually changes in the same direction as the arterial pressure and by almost the same percentage.

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Section-6 -: Cardiovascular Regulatory Mechanisms

1. Ans. C. Acts along with the cardio vagal centre (CVC) to maintain blood pressure
(Ref: Ganong - 23nd Ed page 478)
a. The main control of blood pressure is exerted by groups of neurons in the medulla oblongata that are
sometimes called collectively the vasomotor area or vasomotor center.
b. As we can see from the table listed below (from Ganong) the VMC can be excited by Cortical signals (example
increased HR & BP during sexual excitement and anger) or inhibited.
c. Also the Baroreceptors are inhibitory to VMC but chemoreceptors are stimulatory.
d. In sleep these centre are working to maintain BP just like respiratory centres are maintaining respiration.
e. The Cardio Vagal Centre (CVC) inhibits the VMC pressor area. And there is a functional interaction between the
CVC and VMC. The pattern of discharge from CVC is not tonic but together they both maintain a normal BP.

Factors Affecting the Activity of the Vasomotor Area in the Medulla.

Direct stimulation
CO2
Hypoxia
Excitatory inputs
From cortex via hypothalamus
From pain pathways and muscles
From carotid and aortic chemoreceptors
Inhibitory inputs
From cortex via hypothalamus
From lungs
From carotid, aortic, and cardiopulmonary baroreceptors

2. Ans. D. Functional interaction with cardio vagal centre.

(Ref: Ganong - 22nd Ed) Page-533

3. Ans. B. Vasoconstriction

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 Cardiovascular System

4. Ans ‘C’ Reflex bradycardia

The BARORECEPTORS are stretch receptors found in the walls of heart and blood vessels. The carotid sinus and
aortic Arch receptors monitor the arterial circulation. Impulses generated in baroreceptors have the following
effect:
Inhibition Excitation
Tonic discharge of vasoconstrictor nerves Q Cardioinhibitory center Q
* Produce vasodilation, venodilation, drop in blood

Cardiovascular System Chapter - 4

pressure and decrease in heart rate and cardiac output

5. Ans C Increased venous capacitance Response to a Sympathetic Stimulation

Radial muscle of iris Contraction Bronchial muscles Relaxation
Ciliary muscle Relaxation Bronchial glands Inhibition
SA node Increased HR Sweat glands Localized secretion in palms
(adrenergic sweating)
AV node Inc. Adrenal medulla No response
conduction velocity
Arterioles β Constriction Detrusor muscle Relaxation
α 2 Dilation

Gallbladder Relaxation Trigone and sphincter

Contraction
Gl tract
Stomach Intestine
Motility Decreased
Decreased
Secretion Inhibition Inhibition
Sphincter Contraction Contraction

6. Ans. C. Decreased sympathetic discharge to heart

7. Ans. A. Rise in central venous pressure

Section-7 -: Special Circulation & APPLIED

1. Ans. B. Rate of absorption

(Ref: Ganong - 23nd Ed-Page-569)
Normal CSF pressure is mainly regulated by rate of absorption by arachnoid villi.
a. The normal rate of CSF formation remains nearly very constant. It is independent of the CSF pressure.
b. Absorption by arachnoid villi is proportionate to the CSF pressure
(Arachnoid villi act like valves and allow CSF fluid to flow into venous sinuses when CSF pressure is about 1.5mm
Hg greater than the pressure of blood in the venous sinuses. If the CSF pressure rises further, the valves open
more widely, so that under normal conditions, the CSF pressure almost never rises more than a few mm of Hg

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 Physiology

higher than the pressure in the cerebral venous sinuses)

CSF formation and absorption in humans at various CSF pressure.

2. Ans . A. Reservoir function of pulmonary veins.(Ref. Ganong 23rd/pg. 603)

3. Ans. C. Lipophilic substances
4. Ans. C. Vasodilation due to local metabolites (Ref: Ganong - 23rd Ed, Page-569)
5. Ans. A. In pulmonary circulation, Vasoconstriction In Response To Hypoxia
(Ref. Ganong Physiology 23rd ed. pg. 664)

6. Ans. D. K+ (Ref, Ganong Physiology 23rd ed. 616)

a. For adequate function of brain, a continuous blood flow is required.
b. Normal cerebral blood flow is 15% of resting cardiac output (750ml /min) or about 50- 55 ml blood /100gm
tissue / min.
c. 50 - 70 % of CSF is formed in the choroid plexuses and the remainder is formed along the ventricular walls and
the blood vessels.
d. VOLUME - 150 ml
e. Rate of CSF production is 550ml / day.
f. The composition of brain CSF is the same as that of brain E.C.F
g. Interruption of CSF for 5-10 seconds causes loss of consciousness and circulatory arrest for only 3-4 min results
in irreversible brain damage.
h. Cerebral perfusion pressure is defined as mean systemic arterial pressure minus intra cranial pressure.
i. Option (3) cerebral autoregulation & effect of B.P
j. If systemic B.P drops cerebral perfusion is preserved through - vasodilatation of arterioles of brain; likewise
arteriolar vasoconstriction occurs at high systemic pressure to prevent hyper perfusion. But cerebral
autoregulation is effective over a range of 80 -180 mm Hg only.
k. Option (2) CBF & effect of pH & CO2
l. CBF increases with hypercapnia & acidosis and decreases with hypocapnia & alkalosis. This forms the basis of
use of hyperventilation to lower intra cranial pressure.

Note: Metabolic acid base imbalances produce opposite changes in CSF.

i. Respiratory acid base imbalances (change in arterial CO2 tension) produce parallel changes in CSF

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 Cardiovascular System

Option (1) CBF & cerebral metabolic rate

ii. Cerebral autoregulation may be disordered focally &unpredictably in disease states such as traumatic
brain injury and severe focal cerebral ischemia.
iii. Since about option (3), (2) & (1) it is clearly mentioned in HARRISON'S; the best answer of exclusion should
be option (4).

7. Ans. C. Cerebral circulation

a. The endothelium of the blood vessels also plays an active role in preventing the extension of clots into blood
vessels. All endothelial cells except those in the cerebral microcirculation produce thrombomodulin, a

Cardiovascular System Chapter - 4

thrombin-binding protein, and express it on their surface. In the circulating blood, thrombin is a procoagulant
that activates factors V and VIII, but when it binds to thrombomodulin, it becomes an anticoagulant in that the
thrombomodulin – thrombin complex activates protein C. Activated protein C (APC),along with its cofactor
protein S, inactivates factors V and VIII and inactivates an inhibitors of tissue plasminogen activator, increasing
the formation of plasmin.
b. Endothelial cells are wide and thin, tile-like and slightly curved to fit the curvature of the vessel.
c. They are somewhat elongated in the direction of blood flow, especially in arteries.
d. Endothelial cells firmly adhere to each other at their edges, so that the lining of the lumen presents no
discontinuity (except in sinusoids).
e. The thickness of endothelial cells is maximal at the level of their nucleus, where it can reach 2 –3 mm, this part
of the cell often bulging slightly into the lumen.
f. Elsewhere, the endothelial cell is thinner and laminar; in capillaries, these portions of the cell are very
attenuated, often measuring as little as 0.2 mm in thickness.
g. The luminal surface of the endothelium is relatively smooth.
h. However, it is common to find endothelial laminar projections into the lumen, especially near the cell junctions.
i. The cell surface is pitted by the numerous caveolae and the membrane is coated by a prominent glycocalyx.
j. The glycocalyx is a highly-charged, polysaccharide-rich felt of glycoproteins, anchored to the cell membrane,
which controls the transport of solutes and may mediate the mechanical effects of blood flow on the
endothelial cells.
k. Because of the high charge density the glycocalyx may contribute to the non-thrombogenic properties of the
surface of the intact endothelium.
l. The glycocalyx is not seen in standard electron micrographs of the endothelium, but can be visualized with
electron-dense substances, such as ruthenium red, which bind specifically to glycoproteins.
m. The abluminal surface is also pitted by caveolae and it rests over a basal lamina.

8. Ans. C. Blood flow remains unaltered

9. Ans ‘D’ 200

Body responses to exercise:
a. Muscle Blood flow:
i. At rest  2-4ml/100g/min (650ml/min)
ii. During maximal exercise  90ml/l00g/min (20, 850 ml/min) 25 x of normal
iii. Local mechanism blood flow (vasodilation)  Po2, Co2 (H+ or pH) and accumulation of K+.

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 Physiology

10. Ans. D. Peripheral vascular resistance

Changes in Exercise:
a. There is a net fall in total peripheral resistance due to vasodilation in exercising muscle.Vasodilation is due to
local changes   tissue Po2, tissues Pco2,-c K+ and temperature  that maintaing a high blood flow.
b. CoP increases from 5.9 L/min at resting to 24L/min in exercise
c. Blood flow increase in:
i. Heart Q (250 ml/min to 1000 ml/min)
ii. Active skeletal (650ml/rnin to 28, 850 ml/min)
d. Blood flow remains unchanged in:
i. Brain Q and
ii. Skin
e. Blood flow decreased in
i. Kidney Q, Liver Q, GIT Q. Etc (3100ml/rnin, to 600 ml/min)
ii. inactive skeletal muscle Q (650ml/rnin to 300 ml/min)
f. There is a great increase in venous returns

11. Ans. C. Body temperature rise

Temperature Regulation
a. During exercise the body temperature rises, and the hypothalamic centers that control heat dissipating
mechanisms are activated.
b. The temperature increase is due in part to the inability of the heat dissipating mechanism to handle the great
increases in heat production, but there is evidence that during exercise there is in addition a resetting of the
thermostat ie an increase in the body temperature at which the heat dissipating mechanisms are activated
sweat seceactin is greatly increased and vaporization of this sweat is the major path for heat loss. The
cutaneous vessels also dilate.
c. The dilation is primarily due to inhibition of vasoconstrictor tone, although local release of vasodilator
polypeptides may also contribute.

12. Ans. A. Coronary circulation

13. Ans. B. Increased by massaging the foot

Explanation
a. Basic anatomy: Lymph is the ultrafiltrate of blood, formed at the tissue level, from the fluid coming out of the
capillaries.
b. Most of the fluid will enter the venules, but some of it remains in the intercellular space and will be taken up by
the lymphatics, as lymph.
c. Lymphatic vessels are just like veins (but are thin walled)and usually will maintain unidirectional flow (due to
valves)towards the heart.
d. Lymphatic flow from the periphery increases upon movements of the structures in the vicinity, e.g., arteries,
veins, etc. Any external compression on the vessels will increase the lymphatic flow (as happens with the
venous return).
e. Lymphatic vessels enter the neck veins; before the neck veins enter the heart (Thoracic duct enters the left
venous angle at the junction of internal jugular and subclavian vein).

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 Cardiovascular System

f. As evident, when an individual rises from the supine to standing position the lymphatic flow from the foot will
decrease and not increase, due to gravity. If we massage the foot we will force the lymphatic flow (as well as
venous return),by forcing the lymph to enter the lymphatic vessels.
g. Lymphatic flow decreases when capillary permeability is decreased Since, less interstitial fluid will be produced
and less interstitial pressure will be generated,(this pressure is essential for lymph movement into the lymphatic
vessels).Less interstitial fluid means less lymph production. When the valves of the leg become incompetent
there will be venous pooling. This pooling causes retrograde pressure in the venules, resulting in reduced entry
of fluid into them (from the tissues). Now, as evident, there will be more of interstitial pressure to drive the
lymph into the lymphatic vessels and push it towards the heart more forcefully. So, lymphatic flow from foot is

Cardiovascular System Chapter - 4

increased, in case there is incompetency of venous valves in the leg.

14. Ans. C. Histamine

15. Ans. A. Dopamine

a. Dopamine:
i. D1 + D2 + . + 1 (not 2)  agonist.
ii. The D1 receptors in renal and mesentric blood vessel are the most sensitive: - I.V. infusion of low dose
dopamine dilates these vessels by cAMP es GFR and Na+ excretion.
iii. Use: - in cardiogenic or septic shock and severe CHF to increase BP and urine outflow.
b. Dobutamine:
i. Relatively selective 1 agonist
ii. Used as inotropic agent in pump failure accompanying M.I., cardiac surgery and short term
a. Isoprenaline:  1 + 2 –sympathomimetic

16. Ans. C. Both

Three Reactions of the Skin to Injury [Response]
• A RED REACTION .ALONG THE LINE OF INJURY
• A RED AREA AROUND THE INJURY (FLARE OR ERYTHEMA)
• AN ELEVATED AREA RESULTING FROM LOCALIZED EDEMA (WELT OR WHEAL)

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 Physiology

17. Ans. D. Aortic stenosis

a. curve is shifted downward and to right ~ means ~ compliance is decreased, e.g. in
- Pulmonary congestion Q-
- Interstitial pulmonary fibrosis Q
- Also less during inflation Q

b. Curve is shifted upward and to left  means compliance of lungs is increased, e.g. in
- Emphysema Q
- Also during deflation Q

[Do not confuse: 

In case of lungs  PV curve, left shift means  compliance of lungs Q, while in case of LV PV loop left shift means 
LV compliance and vise – versa] Q

18. Ans. D. Inhibition of respiration

a. Hypovolemic shock (eg. due to haemorrhage):
i. It is also called "cold shock".
ii. It is characterized by:
i. Hypotension (.JBP) ii. A rapid, thready pulse (Tachycardia)
iii. A cold pale, clammy skin iv. Intense thirst
v. Rapid respiration and vi. Restlessness or torpor (inative, apapthetic)

b. Compensatory reactions activated by haemorrhage (ie. Hypovolemic shock):

i. Vasoconstriction (but sparing the vessels of the heart and brain)
ii. Tachycardia
iii. Venoconstriction
iv. Tachypnea  increased thoracic pumping
v. Restlessness  increased skeletal muscle pumping
vi. Increased movement of intertitial fluid into capillaries
vii. Increased secretion of the Nor-epinephrine and epinephrine
viii. Increased secretion of the vasopressin
ix. Increased secretion of the glucocorticoids
x. Increased secretion of the renin and Aldosterone
xi. Increased secretion of the Erythropoietin
xii. Increased plasma protein synthesis

19. Ans. B. R-R interval

20.The answer is A. Gap junctions

Ref: Ganong - Review of Medical Physiology 23rd Ed Page 16
 Cardiac muscle cells have many gap junctions that allow the rapid transmission of electrical activity and the
coordination of heart muscle contraction.
 Gap junctions are pores composed of paired connexons that allow the passage of ions, nucleotides, and other small
molecules between cells.
 To date, five different functions have been ascribed to gap junction protein:

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 Cardiovascular System

o a) electrical and metabolic coupling between cells

o b) Electrical and metabolic exchange through hemichannels
o c) Tumor suppressor genes (Cx43, Cx32 and Cx36)
o d) Adhesive function independent of conductive gap junction channel (neural migration in neocortex)
o e) Role of carboxyl-terminal in signaling cytoplasmic pathways (Cx43)

21. The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 797
Compliance =∆V/∆P
= 30 mL/40 mm Hg
= 0.75 mL/mm Hg

Cardiovascular System Chapter - 4

The reciprocal of compliance i.e. ∆P/∆V is known as elastance.
22. The answer is D. Ref: Ganong -
The skeletal muscle vasculature has a 20-fold or greater range of blood flows, from minimal perfusion at rest to
very high blood flows during intense exercise. No other organ system has appreciably more than a 4- to 5-
fold change in blood flow from rest to maximum flow.

23.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 839
 Peripheral chemoreceptor activation plays a significant role in enhancing the diving response by enhancing
peripheral vasoconstriction and bradycardia.
 Activation is increased by a decrease in pH and by a lowering of arterial PO2, not oxygen content.
 Peripheral chemoreceptors are located in the aortic and carotid bodies.

24.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 750
 The fight-or-flight response and exercise are characterized by increased sympathetic tone and decreased
parasympathetic tone.
 The diving response is associated with increased parasympathetic and sympathetic tone.
 The cold pressor response is characterized by increased sympathetic activity to the heart and blood vessels.

25.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 682
 The hemorrhage has decreased arterial pressure below normal. The fall in blood volume would result in a fall in
central blood volume, right ventricular end-diastolic volume, and cardiopulmonary receptor activity.
 Carotid baroreceptor activity would be lowered in the presence of a low mean arterial pressure. The resulting
sympathetic activity would cause vasoconstriction in the splanchnic bed, and especially with a lowered arterial
pressure, splanchnic blood flow would be decreased.
 The heart rate would be elevated by the increased sympathetic activity and decreased parasympathetic activity
caused by the baroreceptor reflex.

26.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 750
 Standing up increases the transmural pressure in the veins of the legs. Because the veins are highly compliant, their
volume increases at the expense of central blood volume.
 A lower central blood volume means reduced cardiac filling pressure (preload). Within seconds, the decrease in
preload decreases stroke volume, cardiac output, and arterial pressure.
 However, within the first minute, the arterial baroreflex and the cardiopulmonary reflex work together to increase
sympathetic activity and decrease parasympathetic activity.
 As a result, cardiac contractility and heart rate increase, and cardiac output decreases less than it would have
without compensation. “Noncritical” vascular regions, such as the splanchnic area and skin, constrict in response to
increased sympathetic nervous system activity.
 Brain blood flow changes little because sympathetic nerve activation causes little vasoconstriction in the brain and
autoregulation of blood flow prevents a fall in brain blood flow, even if mean arterial pressure decreases.

27.The answer is C.
 The classic changes observed in heat acclimatization are lower heart rate during exercise;

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 Physiology

 an increased sweating response;

 a lower core temperature during exercise, which is due to both the increased sweating response
 a lower thermoregulatory set point.
 In addition, salt is conserved by a reduced salt concentration in sweat.

28.ans B

AB = LV filling

BC = Isovolumetric contraction

CD = LV ejection

DA = Isovolumetric relaxation

Point-A = Coincides with MV opening, and represents LV end-systolic volume and early diastolic pressure

Point- B = Coincides with MV closure, and represents LV end diastolic pressure (LV EDP) and volume
(EDV)

Point-C= Represents opening of Aortic valve and coincides with systemic, aortic diastolic pressure

Point-D= is the closure of the Aortic valve and represents LV end systolic pressure and volume, coinciding
with the dicrotic notch in the Aortic pressure tracing

Segment AB => LV compliance is defined by the slope of the filling phase or segment AB  Preload or
EDV. The compliance is decreased when the ventricles become stiff or unable to fill properly eg MI,
constrictive pericarditis, pericardial effusion etc and the PV loop(baseline shifts up.

Therefore PV loops analysis  gives information about - LV compliance, Preload, contractility. Stroke
volume (SV) [SV = EDV - ESV], Ejection Fraction (EF) and various valvular lesions.

Remember: The curve shifts to right side in case of increased preload, Upside in case of increased afterload
and to Left & upside in incase of increased myocardial contractility

29.ans C

 Normal Q waves, when present, represent depolarization of the interventricular septum.

For this reason, they are referred to as septal Q waves and can be appreciated in the
lateral leads I, aVL, V5 and V6.

 R wave is due to depolarization of bulk of the ventricles, the R vector moves downwards
towards the apex

 S wave is due to late depol. of posterobasal left ventricle, S vector moves upwards
towards posterobasal ventricle

30.The answer is B.

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 Cardiovascular System

Flow(Q) = pressure difference/ resistance

R= ∆P/Q

where Q= 95 + 5 = 100 mL/min

and ∆P= 75 - 25 = 50 mm Hg.

Cardiovascular System Chapter - 4

R = 50/100 = 0.5 mm Hg/(mL/min) = 0.5 PRU

31.The answer is B. Activation of parasympathetic nerves to the heart would lower the heart rate
below its intrinsic rate. However, with all effects of norepinephrine and epinephrine blocked, the
sympathetic nervous system cannot raise the heart rate above its intrinsic

rate. The withdrawal of parasympathetic nerve tone could only raise the heart rate to the intrinsic
rate.

32.The answer is A. More capillaries in use at a constant blood flow actually slows the flow velocity
in individual capillaries. The distances between capillaries are decreased. The perfusion of additional
capillaries does not influence the permeability of the individual capillaries.

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 Respiration

Chapter - 5
Respiration

I. FUNCTIONAL ANATOMY

A. Weibel’s classification of airway generations: From trachea to alveolar sacs, the airways divide 23 times.
(Trachea is generation ‘0’). The first 16 generations form the conducting zone (consisting of bronchi,

Chapter - 5
bronchioles and terminal bronchioles); the remaining 7 generations are the transitional and respiratory zones
(consisting of the respiratory bronchioles, alveolar ducts and alveoli)

Respiration

B. Presence of cilia, smooth muscle, glands, cartilage in the air passages

Cilia : Present upto respiratory bronchioles

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 Physiology

Cartilage : Only in trachea and bronchi

Glands : Only in trachea & bronchi
Smooth muscle : Maximum in terminal bronchiole

Generation 1 to 10 →Bronchi
Generation 11th to 10th →Terminal Bronchioles
Generation 17th to 18th 19th →Respiratory Bronchioles
Generation 20, 21,22 →Alveolar duet
Generation 23 →Alveoli

1. Types of cells
a. Alveolar epithelial cells
These are of 2 types
i. Type I (There form the main living)
ii. Type II (also called granular pneumocytes), These secrete surfactant
b. Other cells in lungs:-
Pulmonary alveolar macrophages, lymphocyte,
plasma cells, APUD cells, mast cells

2. Bronchoconstriction and dilation

a. Bronchoconstriction : Reflexly (by irritants; this is cholinergically mediated), cool air, exercise,
expiration, leukotrienes, substance P , cholinergic stimulation, early morning (around 6 A.M.)

b. Bronchodilation : Adrenergic stimulation, by non adrenergic – non cholinergic nerve stimulation

(NANC) where the neurotransmitter is VIP, inspiration, in the evening (around 6 P.M.)

3. Gas Laws
a. Dalton’s law of partial pressure: The partial pressure of a gas in a mixture of gases is equal to the
total pressure times its percentage
b. Boyle’s Law: P X 1 / V, if T is constant
c. Charle’s law: P X T (if V is constant) and V X TC if P is constant
d. Henry’s law: The dissolved gas is already proportional to its partial pressure
e. Graham’s law: The rate of effusion is reversely proportional to the square

II. Mechanics
A. Different types of pressures
1. Intrapleural pressure :
This is pressure within the pleural space (also called intrathoracic pressure) Oesophageal pressure measures
intrapleural pressure. This pressure is always negative i.e. – 2 mm Hg because pleural cavity is a closed
cavity and the recoil of lungs and thoracic cavity are in opposite direction.This increases the volume
resulting in fall in pressure. It is more negative at apex (-6 mm Hg) than base(-2 mm Hg).It helps in :
a. Preventing collapse of alveoli due to its –ve pressure (eg pneumothorax- lung collapse)
b. Decreases work of breathing

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 Respiration

c. Some air is always present as it keeps alveoli semi inflated so gas exchange is continous.
During Valsalve maneuver, tension pneumothorax, coughing it can become as high as +100 mm Hg

2. Intrapulmonary pressure
This is the pressure in the airways
The transmural pressure are
a. Transpulmonary : The pressure difference between intrapleural and intrapulmonary
pressure

Chapter - 5
b. Transthoracic : The pressure difference between the intrapleural pressure and
atmospheric pressure
c. Also, one can talk of the pressure difference between the intrapulmonary pressure and atmospheric
pressure

TTP TPP
( (
b a
) ) Airway pressure
(intrapulmon
( ary)

Respiration
c
)

I
n
t
r
B. Inspiration and expiration a
1. Muscles involved in quiet respiration
Inspiration : Diaphragm is the main muscle;p also external intercostal muscle
Expiration : No expiratory muscle (passive)l
e
a. Transpulmonary
u
b. Transthoracic
r
c. Pressure difference between intra pulmonary and atmospheric pressure (Trans respiratory)
a
(Trans respiratory pressure) l
2. Muscles involved in forceful respiration
Inspiration : Scalene, sternocleidomastoid
Expiration : Internal intercostal muscles,
Anterior abdominal muscle
3. Pressure changes during respiration
a. Intrapleural pressure: At the beginning of quiet inspiration, it is – 2.5 mmHg subatmospheric i.e. 2.5
mmHg less than atmospheric pressure of 760 mmHg; at the end of inspiration, it becomes – 6.0 mmHg.

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 Physiology

b. Intra alveolar pressure : At the peak of inspiration, it is – 1 mmHg; at the peak of expiration, it is +1
mmHg. At the beginning and at the end of both inspiration and expiration, the interalveolar pressure is
zero i.e. same as atmosphere pressure

III. Respiratory obstruction

This can be:
Intrathoracic or extrathoracic
Variable or fixed
Flow-volume curve can be used to identify whether a variable obstruction is intrathoracic or extrathoracic. It
cannot identify fixed intrathoracic or extrathoracic.
In variable intrathoracic obstruction, the inspiratory flow-volume curve is less affected than the
expiratory flow-volume curve. In variable extrathoracic, obstruction. The expiratory flow-volume
curve is less affected than the inspiratory flow-volume curve.

(
( 1
a )(
) 2
)

A. Compliance
This is defined as the change in volume for a unit change in pressure.It denotes stretchibility and is inverse of
elasticity.
Compliance =  V
P

A plot of the change in volume with a change in pressure is the volume-pressure curve or the relaxation-pressure
curve. When the relaxation – pressure curve is plotted for the total respiratory system (i.e. taking into account

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 Respiration

the interaction between the recoil of the lungs and recoil of the chest) the volume of the gas in lungs when the
pressure is zero is called the relaxation volume. The relaxation volume equals the functional residual capacity.

B. Types of compliance measurements

1. Static compliance : This is the measurement made without taking into account the effect of the different
phases of respiration. Lungs : 220 ml/cm of H2O Lungs+Thorax : 130 ml/cm of H2O
2. Dynamic compliance : Compliance measurement during the difference phases of respiratory
3. Specific compliance (Independent of lung volume) = Compliance FRC

Chapter - 5
C. Factors affecting compliance
1. Lung volume : Smaller the lungs, smaller is the compliance. Therefore, specific compliance measurement
normalizes the effect of lung size on compliance.
2. For a given lung size, the compliance becomes less at extremes of lung volume.
3. Compliance is more during deflation than during inflation
4. If surface tension is more, compliance is less
5. Compliance at Apex is less than that at Base of lungs.
6. Compliance measured with saline is more than compliance measured with air.

D. Condition in which compliance is affected

1. Compliance decreased : Pulmonary congestion, pulmonary fibrosis etc.

Respiration
2. Compliance increased : Emphysema, old age

E. Alveolar surface tension

This is exerted by the film of fluid that lives the alveoli; this surface tension is less at lower lung volumes (this is
due to the effect of surfactant)

F. Surfactant
1. The surface tension in alveoli is produced due to air-fluid interphase. Surfactant is made up of
PHOSPHOLIPID- DI-PALMITOIL-PHOPHATIDYL-CHOLINE (DPPC) + two major proteins having molecular
weights of 32,000 and 10,000, fibrin etc.
2. It is secreted by TYPE II ALVEOLAR EPITHELIAL CELLS (type II pneumocytes) . It reduces surface tension in
alveoli by not dissolving uniformly in the fluid lining the alveolar surface.
3. Instead, part of the molecule dissolves, while the remainder spreads over the surface of the water in the
alveoli, thereby breaking the structure of water present inside the alveoli.
4. When the lung volume is less, the alveoli are smaller and therefore the concentration Eg. surfactant per
unit area is more so more active during expiration.
5. Stability of alveoli of alveoli is mainly the function of surfactant which prevents their collapse under Surface
tension.
6. Main functions:
a. It increases the Compliance
b. Reduces work of breathing
c. Prevents collapse of alveoli at end of expiration : law of Laplace(P=2T/r)
d. Prevents pulmonary edema by keeping the alveoli dry

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 Physiology

e. Alveolar size regulation: As the alveoli increase in size, the surfactant becomes more spread out over
the surface of the liquid. This increases surface tension effectively slowing the rate of increase of the
alveoli. This also helps all alveoli in the lungs expand at the same rate.
7. It has high concentration in the fetal lungs at 20 weeks of gestation . However, it does not reach the surface
of the lung until 28-38 weeks when it is present in amniotic fluid. .Maximum secretion occurs at 34 weeks
8. When the lung volume is less, the alveoli are smaller and therefore the concentration Eg. surfactant per
unit area is more. Consequently, the surface tension is less at lower lung volumes.

G. Work of breathing
Normal. 0.5 kg/m/min. 2 types
1. Elastic work (65%)
a. Tissue elasticity (1/3rd)
b. Surface tension elasticity (2/3rd)

2. Non-elastic work (35%)

a. Viscous resistance (7%)
b. Airway resistance (28%)
i. The work of breathing can be calculated from the relaxation – pressure curve.
ii. The work of breathing for the lung alone is more than that for the total respiratory system. Since the
airway resistance becomes more during turbulent flow, the work of breathing is more during
turbulent flow than during laminar flow.
iii. The work of breathing is increased in conditions such as emphysema, asthma, congestive heart
failure

H. Hysteresis loop
If there were no frictional resistance due to airway and viscous resistance, the relaxation – pressure curve
would be a straight line. However, because of the frictional resistance, any change in volume which is expected
because of change in pressure does not happen immediately but happens after a time delay. This causes the
relaxation – pressure curve to take a curved shape (instead of a straight line). This is called hysteresis.
1. Ventilation – perfusion ratio
Normal value for entire lung is 0.8. But at Base it is 0.6 and apex 1.3
a. Ventilation per unit lung volume decreases from base to the apex (low due to low compliance)
b. Perfusion decreases from base (more due to gravity) to the apex
c. The ventilation – perfusion ratio increases from base to apex
d. Both Ventilation & perfusion are maximum at base but ratio is less because perfusion is more than
ventilation and at apex reverse is true.
e. As a result of less gas exchange there is wasted ventilation occurring at apex also called Alveolar dead
space & pO2 is also maximum, that’s why TB of apex is more common.

2. Dead space
a. Since gaseous exchange in the respiratory system occurs only in the terminal portions of the airways,
the gas that occupies the rest of the respiratory system is not available for gas exchange with
pulmonary capillary blood this volume is called as anatomic dead space (150ml) Q.

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 Respiration

b. When alveolar dead space (i.e.all the air in the alveoli that is not participating in gas exchange) is
included in the total measurement of dead space, this is called the physiologic dead spaceQ i.e
Anatomic dead space plus alveolar dead space
c. In a normal person, the anatomic and physiologic dead spaces are nearly equal because all alveoli are
functional in the normal lung. Q
d. Normally, physiologic dead space = anatomic dead space = 150 mL.

3. Dead space is decreased in

Chapter - 5
a. Females
b. Children
c. supine position
d. neck fully flexed with depressed chin
e. low lung volumes
f. Expiration
g. Tracheostomy & endotracheal intubationQ (Artificial airway)

4. Dead space increased by

a. Males
b. Old age
c. Inspiration

Respiration
d. Artificial airway with tubeQ (increased mechanical DS due to tube volume)
e. standing positionQ (due to hypoperfusion of apical alveoli)
f. emphysema Q
g. neck extension Q
h. Ipratropium (Bronchodilation)

5. Diffusion capacity of lung

Definition: The diffusion capacity of the lung (DL)is defined as the volume of gas diffusing across the
respiratory membrane in 1 minute when the pressure gradient is 1 mmHg.
Factors
DL = KX AXS
dX w

Where k is proportionality constant

A = Area of the membrane
S = Solubility of the gas
W = molecular weight of the gas
D = thickness of the membrane

S
w is called the diffusion coefficient; the diffusion coefficient is entirely based on the characteristic of
the gas.
Measurement

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 Physiology

Diffusion capacity of carbon monoxide (DLCO) is taken as an index of diffusion capacity as it has a very high
affinity for Hb as a result it is 0% dissolved in blood, Hence PaCO remains zero allowing 100% CO
diffusion. DLO2 is never measured directly, it is expressed with DLCO as the index.

Toxicity of CO is limited to its diffusion d/t (AIIMS Nov 09)

A. The binding capacity of CO to HB with high avidity
B. CO does not diffused across the alveolar capillary membrane
C. Decreased permeability across alveoli-blood membranes
D. Decreased diffusion across blood-brain barrier.

Ans. A The binding capacity of CO to HB with high avidity

6. Factors affecting DLCO
A. Decrease DLCO is decreased in any condition which affects the effective alveolar surface area i.e Diffusion
across respiratory membrane:
1. 1.Hindrance in the alveolar wall. e.g. fibrosis, alveolitis, vasculitis
2. 2.Decrease of total lung area, e.g. Restrictive lung disease.
3. 3.Uneven spread of air in lungs, e.g. emphysema.
4. 4.Pulmonary embolism
5. 5.Cardiac insufficiency
6. 6.Pulmonary hypertension
7. 7.Bleomycin (upon administration of more than 200 units)
8. 8.Anemia-due to decrease in blood volume
However, many modern devices compensates for the hemoglobin value of the patient (taken by blood test), and
excludes it as a factor in the DLCO interpretation.

7. Factors that can increase the DLCO include polycythaemia, asthma (can also have normal DLCO) and increased
pulmonary blood volume as occurs in exercise or congestive heart failure. Other factors are left-to-right
pulmonary shunting that occurs in left heart failure, alveolar hemorrhage, and smoking within 24 hours of the
test.
Value
DLO2 = 25 mL/ min / mm Hg
DLCO2 is 20 times DLO2
Conditions in which DL is affected

8. Perfusion limited Gas exchange: (Perfusion dependent; free flow across membrane)
when the gas passing through equilibrates early in the course through the capillary. now the only way to
increase diffusion is to increase the blood flow through the capillary. eg: O 2 at rest is exchanged by
perfusion limited mechanism .
9. Diffusion limited Gas exchange : (Not dependent on perfusion; diffusion across membrane is hampered),the
gas in the blood and alveoli does not equilibrate even after reaching the end of the capillary. The partial
pressure gradient is present even after passage thru the capillaries. eg: Carbon Monoxide & in case of
restrictive lung disease , the thickening of the alveolar membrane does not allow proper diffusion across it.

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 Respiration

11. Lung volumes, capacities and dead space

Spirometry : Measures all volumes and capacities except those involving measurement of
residual volume; Therefore, it cannot measure residual volume, functional residual capacity and total lung
capacity
A. Respiratory Volumes
1. Tidal volume (TV) - normal volume moving in/out (0.5 L)
2. Inspiratory reserve volume (IRV) - volume inhaled AFTER normal tidal volume when asked to take deepest
possible breath (2.1-3.2 L)

Chapter - 5
3. Expiratory reserve volume (ERV) - volume exhaled AFTER normal tidal volume when asked to force out all
air possible (1.0-2.0 L)
4. Residual volume (RV) - air that remains in lungs even after totally forced exhalation (1.2 L)
5. Closing volume (CV) the lung volume above the residual volume of which the airways in the lower,
dependent parts of the lung begin to close off because of lesser transmural pressure in these areas. This
phenomenon is called as Dynamic Compression of airways). If CV> FRC collapse of lungs takes place
example RDS due to increased Surface tension.
B. Respiratory Capacities: Sum of 2 or more volumes
1. Inspiratory capacity (IC) = TV + IRV (MAXIMUM volume of air that can be inhaled) 3-4 L
2. Functional residual capacity (FRC) = ERV + RV (measured by Helium dilution method, nitrogen washout
method & Plethysmography) 2.5 L. Also called relaxation volume as recoil of chest wall is balanced by lung
recoil at this volume.

Respiration
3. Vital capacity (VC) = TV + IRV + ERV (max. insp. followed by max exp.) 4.8 L in Males & 3.2 Females.
4. Total lung capacity (TLC) = TV + IRV + ERV + RV (the SUM of all volumes; about 6.0 L).Depends on lung
compliance if compliance is more so is the TLC eg. emphysema

Dynamic lung volumes & capacities

1. Forced vital capacity (FVC) - total volume exhaled after forceful exhalation of a deep breath
2. FEV1 amount of air expired in 1st second normal value 80%, FEV2 - 95%, FEV3 – 100%
3. Minute respiratory volume (MRV) or PV - total volume flowing in & out in 1 minute (resting rate = 6 L per
4. Maximum Breathing Capacity (MBC) – Maximum air that can be moved in or out of the lungs per
minute.90-170 Litre/min

Peak This is the speed of the air moving out of your lungs at the beginning of the
PEFR Expiratory expiration, measured in liters per second. It is effort dependent (on strength of
Flow expiratory muscles) 5-15 L/sec

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 Physiology

This is the average flow (or speed) of air coming out of the lung during the middle
Forced Expiratory
MEFR portion of the expiration. It is effort independent and depends on the small
Flow 25–75%
airway resistance. Very sensitive indicator for bronchial asthma.3-5L/sec

Obstructive lung disease Restrictive lung

disease
Residual volume Increase Decrease
FRC Increase Decrease
Total lung capacity Normal to increase Decrease
Diffusion capacity Normal (exceptemphysema) Decreased
Vital capacity Decrease Decrease
FEF 25-75% Decrease Normal
FEV1/FVC (Most Imp) Decrease Normal to increase

Plethysmography
a. Pulmonary plethysmographs are commonly used to measure the functional residual capacity (FRC) of the
lungs—the volume in the lungs when the muscles of respiration are relaxed—and total lung capacity.
b. In a traditional plethysmograph, the test subject is placed inside a sealed chamber the size of a small
telephone booth with a single mouthpiece. At the end of normal expiration, the mouthpiece is closed. The
patient is then asked to make an inspiratory effort. As the patient tries to inhale, the lungs expand,
decreasing pressure within the lungs and increasing lung volume. This, in turn, increases the pressure
within the box since it is a closed system and the volume of the box compartment has decreased to
accommodate the new volume of the subject. And during forceful expiration the lung pressure increases
and chamber pressure decreases as thorax occupies less volume inside the chamber i.e decompression of
chamber.mcq 2011 AIPG
c. Boyle's Law is used to calculate the unknown volume within the lungs. First, the change in volume of the
chest is computed. The initial pressure and volume of the box are set equal to the known pressure after
expansion times the unknown new volume. Once the new volume is found, the new volume minus the
original volume is the change in volume in the box and also the change in volume in the chest. With this
information, Boyle's Law is used again to determine the original volume of gas: the initial volume
(unknown) times the initial pressure is equal to the final volume times the final pressure.
d. The difference between full and empty lungs can be used to assess diseases and airway passage
restrictions. An obstructive disease will show increased FRC because some airways do not empty normally,
while a restrictive disease will show decreased FRC. Body plethysmography is particularly appropriate for
patients who have air spaces which do not communicate with the bronchial tree; in such patients gas
dilution would give an incorrectly low reading.
e. Obstructive lung disease include : Asthma, Bronchiectasis, chronic bronchitis & Emphysema (COPD),
Bronchiolitis, Cystic fibrosis
Restrictive lung disease include :
1. Interstitial lung diseases (the most common of which are sarcoidosis, rheumatoid lung, scleroderma lung, the
pneumoconioses, histocytosis X, lymphangitic carcinomatosis, and idiopathic pulmonary fibrosis)
2. Chest wall deformities (kyphoscoliosis, Ankylosing spondylitis, thoracoplasty)
3. Pleural fibrosis

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4. Alveolar-filling disease (alveolar proteinosis, alveolar cell carcinoma, desquamative interstitial pneumonia,
and alveolar microlithiasis)
5. Neuromuscular disease (e.g., myasthenia gravis, amyotrophic lateral sclerosis,GB syndrome, Diaphragmatic
palsy)

IV. GAS TRANSPORT

A. Symbols P = partial pressure
I = Inspired air

Chapter - 5
E = Expired air
A = Alveolar
a = arterial
v = venous
v = mixed venous
B = Barometric
F = Fractional percentage
PIO2 means partial pressure of O2 in inspired air

B. Partial pressure of O2 / CO2 at different sites (in mmHg)

P I Alveolus Arterial Capillaries Veins E

Respiration
O2 160 150 100 95* 40 40 116
CO2 0.3 0.3 40 40 46 46 32

* The partial pressure of blood leaving the pulmonary capillaries is 97 mmHg but it falls to 95 mmHg in the
systemic arterial blood because of physiologic shunt. The physiologic shunt is due to a part of the bronchial blood
flow and a part of the coronary blood flow which bypasses the pulmonary capillaries
PAO2 is given by alveolar gas equation PAO2 = FiO2 x (PB - PH2O) - PaCO2
RQ
Where:-
PAO2 = PO2 of the alveolar air
FiO2 = Fraction of O2 in the air (Eg 20% in atm or inspired air & 16% in expired)
PB = Barometric pressure (760mmHg)
PH2O = Water vapour pressure (47mm H2O)
PaCO2 = Partial pressure of CO2 ( 40 mm Hg)
RQ = Respiratory quotient

C. O2 transport
Most of the O2 in the blood is carried along with Hb (99%) Each Hb carries 4 molecules of O 2. Hb exhibits the
‘relaxed’ and the ‘tense’ state. When Hb takes up O2 the beta chains move closer and the haem enters the
relaxed state. The relaxed state favours binding of O2 while the tense state decrease binding.
Oxygen – Hb dissociation curve (O-HDC)
This is a plot of the partial pressure of O 2 and the % saturation of Hb with O2 It is normally sigmoid-shaped.
If the OHDC is shifted to the right, it means that the affinity of Hb for O2 has become less (which favours O2
delivery).

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Shift to the right is caused by

1.  pH
2.  in temperature
3.  in 2,3 – DPG (It bind beta chain at 4 sites)

P50 = The partial pressure of oxygen as which Hb is 50% separated. It value = 26 mmHg. (or 3.45 Kpa). When the
OHDC shifts to the right, P50 increases. (1Kpa = 7.5 mmHg)

Factors affecting 2,3 DPG

1. pH Q (acidosis inhibits red cell glycolysis, the 2,3-BPG concentration falls when the pH is low).
2. Thyroid hormones, growth hormone, and androgensQ increase the concentration of 2,3-BPG and the P50.
3. ExerciseQ has been reported to produce an increase in 2,3-BPG
4. Ascent to high altitudeQ triggers a substantial rise in 2,3-BPG concentration in red cells,
5. The affinity of fetal hemoglobin (hemoglobin F) for O2. The cause of this greater affinity is the poor binding
of 2,3-BPG by the polypeptide chains that replace chains in fetal hemoglobinQ.
6. Red cell 2,3-BPG concentration is increased in anemiaQ and in a variety of diseases in which there is chronic
hypoxia
7. In bank blood that is stored, the 2,3-BPG level falls. This decrease, is less if the blood is stored in citrate–
phosphate–dextrose solutionQ rather than the usual acid–citrate–dextrose solution.
8. Inosine increases 2,3 DPG in red blood cells. Q
9. HbF binds 2,3 – DPG poorly; hence it has a greater affinity for O2

D. Effect of pH on O-HDC
1.  pH
a. Direct effect : shift to right
b. By decreasing 2,3 – DPG, shift to left
2.  pH
a. Direct effect : shift to left
b. By increasing 2,3 – DPG, shift to right

E. Bohr effect
There is a decrease in O2 affinity for Hb with a decrease in pH

1. Calculation of O2 carrying capacity of blood

a. 1 gm of Hb, when fully saturated, contains 1.34 ml of O2. At a pO2 of 40 mmHg (as exists in Venous
blood), Hb is only 75% saturated. Therefore, 1 gm of Hb would carry 1.34 X 75 / 100 mL of O2 at pO 2 of
40 mmHg
b. The amount of dissolved O2 in plasma is 0.003/ dL / mmHg of pO2. At a pO2 of 40mmHg, the amount of
dissolved O2 is 0.003 X 40 = 0.12 mL of O2 / dL.
Myoglobin
This is present in skeletal muscles. 1 mole cule (OMDC) of myoglobin binds / 1 molecule of O 2. The shape of O2
myoglobin dissociation curve is a rectangular hyperbola. It lies to the left of the O 2 – Hb dissociation curve.

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Chapter - 5
Respiration
2. CO2 transport
a. Different ways in which CO2 is transported in :
i. Plasma
ii. In dissolved form of
iii. As carbamino compound with plasma proteins
iv. Getting hydrated CO2 + H2O H2 CO3 H+ + HCO3- The H+ gets buffered with plasma
proteins. Since there is no carbonic anhydrase in plasma, the process of hydration is slow.
a. RBC
i. In dissolved form
ii. As carbamino compound with Hb
iii. Getting hydrated
CO2 + H2O H2 CO3 H+ + HCO3- The H+ gets buffered by Hb; 70% the HCO3- enters plasma and Cl-
enters RBC (chloride shift)
(Since there is carbonic anhydrase in RBC, the process of hydration is rapid.)
3. It is clear from the above that for each CO2 molecule that goes into RBC, there is either one HCO3- or one
Cl- inside the RBC; the chloride content of the venous blood RBC is more than that of arterial blood RBC.
Therefore, there is an increase in the volume of RBC in venous blood and hence the haematocrit of venous
blood is more.

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4. Out of the 49ml of CO2 / dL in arterial blood, 2.6 mL is dissolved 2.6 mL of CO2 exists as carbamino
compound and 43.8 mL is transported as HCO3-
5. Haldane effect: loading of O2 causes unloading of CO2.
6. Chloride shift: in venous blood increase in Cl- inside RBCs due to exchange with bicarbonate ions, which are
formed due to increase CO2 levels. RBC volume & PCV increases in venous blood.

V. REGULATION OF RESPIRATION
A. Voluntary control
B. This is from the cortex directly to the spinal cord
C. Automatic control : In medulla & pons
1. MEDULLA – has pre botzinger complex (between nucleus ambiguous and lateral rectal nucleus) which acts
as pacemaker for spontaneous respiration, also contains DRG & VRG (DORSAL &VENTRAL RESPIRATORY
GROUP OF NEURONS)
a. DRG - contains inspiratory neurons which supply inspiratory muscles
b. VRG - both inspiratory & expiratory neurons

2. PONS – contain 2 centres

a. Apneustic centre (in lower pons) : stimulates inspiratory neurons. If not
inhibited by vagus and pneumotaxic
centre will cause apneusis .
b. Pneumotaxic centre (in upper pons) : inhibit apneustic centre .
Near Parabranchial Nucleus (NPBL)

Effect of Lesion/ Transection of brainstem on respiration

Section A: Above pons : Normal tidal respiration but voluntary control is lost. If vagus also cut then slow & deep
breathing because vagus inhibits apneustic centre .

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 Respiration

Section B: At Mid pons : loss of inhibitory action of pneumotaxic centre on apneustic centre there is stimulation of
inspiratory neurons by apneustic resulting in slow and deep breathing. If vagus also cut then APNEUSIS .

Section C: Between Pons & Medulla: Spontaneous respiration continues, although somewhat- irregular and
gasping Q because respiration is produced by medulla but made rhythmic & regular by pontine centres .

Section D: Below medulla: No respiration. Q

Chapter - 5
Factors affecting the respiratory centre
1. Chemical
CO2 / O2 / H+

2. Non – chemical
a. Vagal afferents from airways / lungs
b. Pons / hypothalamus / limbic system
c. Proprioceptors
d. Baroreceptors

Respiration
3. Chemical control
The chemoreceptors for chemical control are the
Peripheral chemoreceptors Viz the carotid and the aortic bodies
Central chemoreceptors situated in the ventral surface of the medulla

1. Peripheral chemoreceptors
These chemoreceptor are located in —(a) Carotid bodies  at the birfurcation of the common carotid artery
(bilaterally)  Afferent fibers via Hering’s Nerve of IX CN to the dorsal respiratory area of the medulla.
a. Aortic bodies  located in arch of Aorta  afferent fiber via X CN to dorsal respiratory area of the medulla.
2. These receptors are stimulated by: -
a. a rise in PCO2 of arterial blood
b. a rise in H+ conc.
c. a decline in the PO2
i. Each carotid and aortic body (glomus) contains 2 types of cells, type I and type II cells. The type I
(glomus cells) respond to hypoxia; they have O2 – sensitive K+ channels
ii. Blood flow in each 2 mg carotid body is about 0.04 mL/min. or 2000 ml/100gm of tissue/min.
iii. Because the blood flow per unit of tissue is so enormous, the O2 needs of the cells can be met
largely by dissolved O2 alone. Therefore, the receptors are not stimulated in conditions such as
Anemia and Carbon Mono oxide poisoning
iv. Maximally stimulated by KCN (cyanides)

4. Central chemoreceptors
There respond to H+ only.
They are sensitive to the H+ in the CSF and the brain interstitial fluid. CO 2 can influence these central

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chemoreceptors only indirectly by getting converted into H+. By virtue of this, CO2 is able to act on both central
(60-70% of the effect of CO2) as well as on peripheral (30-40% of the effect of CO2) chemoreceptors.

Apnea point : pCO2 levels at which respiration stops. A CO2 drive is needed to maintain the respiration. Normal 37
mmHg.

5. Ventilatory response to CO2

The link between metabolism and ventilation is CO2 and not O2
There is a linear relationship between respiratory minute volume and alveolar pCO 2

6. Ventilatory response to O2 lack

There is no increase in ventilation till the PAO2 (alveolar PO2) becomes less than 60 mmHg. The reasons for this
lack of response are :
i. Hb is a weaker acid than HbO2; therefore with less O2, there is more Hb which by being weaker acid
tends to inhibit the ventilation
ii. Also, as ventilation increases, the CO2 that is washed out counters the increase in ventilation

7. Ventilatory response to CO2 and O2

This exhibits a complex relationship, the effect of CO 2 excess and O2 lack is more than additive. If one were to plot
a curve between CO2 and ventilation at different fixed O2 levels, one would get a fan of curves. The slope of the
curve (between CO2 and ventilation) would increase significantly with decreased O2 levels.

pO2 = 80
pO2 = 90
Ventilatio
n pO2 = 100
(L/min)

0 40 80
PACO2
(mmHg)
The intersection of these fan of curves is at one single point.
Since this point of intersection is below the normal value of PACO2 of 40 mmHg, it shows that there is normally a
slight but definite CO2 drive of the respiratory centre.
Ventilatory response to H+ and CO2
Here, the effect is simply additive

8. Breath Holding
The breaking point is the point at which breathing can no longer be voluntarily inhibited (because of increase in
CO2 and decrease in O2)
Breath holding can be prolonged by

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1. Removal of carotid bodies

2. Breathing 100% O2 before breath holding
3. Hyperventilating room air (because of the initial  in CO2 of arterial blood)
4. By breathing gas mixture low in O2 and high in CO2, breath holding can be prolonged for an additional 20
seconds
5. Encouragement

Chapter - 5
Respiration

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B. Non – chemical influences

Responses mediated by receptors in the airways and lungs (all are vagally mediated)
Vagal Type of receptors Location in Stimulus Response
innervation interstitium
Myelinated Slowly adapting Among airway Lung inflation i. Inspiration time ed
smooth ii. Hering - Breuer reflexes
muscle iii. Bronchodilation
iv. Tachycardia
Rapidly adapting Among airway i. Lung hyper i. Hyperpnoea
epithelial cells inflation ii. Cough
ii. Irritants iii. Bronchoconstriction
iv. Mucus secretion
Unmyelinated Pulmonary C fibres (J Close to blood i. Lung hyper – i. Apnoea followed by
C fibres receptors) Bronchial vessels inflation rapid breathing
C fibres ii. Irritants ii. Bronchoconstriction
iii.  HR
iv.  BP
v. Mucus secretion

1. Hering-Breuer Reflexes:
a. Hering-Breur Inflation reflex is an increase in the duration of expiration - produced by steady lung
inflation.
b. Hering-Breuer deflation reflex is a decreased in the duration of expiration produced by marked
deflation of the lung .
2. J-Receptors (Juxtracapillary):They are present in alveolar interstitium, supplied by Unmyelinated C fibres of
vagus. They are stimulated by hyperinflation of the lung, but they respond as well to intravenous or
intracardiac administration of chemicals such as Capsaicin, Increased fluid in alveolar interstitium. The
reflex response that is produced is apnea followed by rapid breathing, bradycardia and hypotension
(pulmonary chemoreflex). Eg. CHF, Pulmonary odema, Heavy exercise etc
3. Head's paradoxical reflex:
a. Inflation of lungs lead to further inflation. Helps in 1st breath of child.
b. Seen during labour. Clamping of umbilical cord results in a fall in arterial oxygen and slight rise in
carbon dioxide tension. These factors stimulate the respiratory centre directly and via the
chemoreceptors in carotid body.

4. Baroreceptors stimulation
Inhibits respiration ; the effect is almost of no physiologic importance

5. Effect of sleep
There is a decrease in sensitivity to CO2 during slow wave sleep; during REM sleep ,there is even further decrease
in sensitivity to CO2

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V. Hypoxia
Hypoxic Anaemic Stagnant Histotoxic
Underlying cause PaO2 is ed Amount of O2 carrying capacity is No utilization at
available Hb normal but O2 delivery tissue level
decreases is decreased
Examples High altitude, lung Anaemic, CO Heart failure shock Cyanide
disease poisoning hemorrhage poisoning
ed

Chapter - 5
PaO2 Normal Normal Normal
O2 Content ed Normal Normal Normal
dissolved
Combined (with ed ed Normal Normal
Hb)
Chemoreceptors Stimulated (+) Not stimulated Strongly stimulated Strongly
stimulation (+++) stimulated (+++)
Amount of ed Total Hb ed, HHb ed ed
reduced Hb ed
Cyanosis Can be present NEVER Can be present NEVER
2. C.O. poisoning

Respiration
Produces anaemic type of hypoxia. The uptake of CO is diffusion limited as it has very high affinity for Hb so it
crosses the alveolar membrane and maximally binds to Hb and very little dissolves in blood. Therefore the partial
pressure of CO in the blood entering the pulmonary capillaries is zero. The affinity of hemoglobin for CO is 210
times its affinity for O2, and COHb liberates CO very slowly .
C.O. poisoning is especially dangerous because
a. Less Hb is available for carrying O2
b. It does not stimulate the chemoreceptors
c. There is a shift of the O2 – Hb dissociation curve to the left

3. High altitude
a. High altitude pulmonary edema is a serious form of mountain sickness  pulmonary edema prone to occurs
in individual who ascend quickly to altitudes above 2500m and engage in heavy physical acitvity during the
first 3 days after arival. It is associated with marked pulmonary hypertension due to vasoconstriction . The
edema is patchy in nature. It is due to increased capillary permeability , increased filtration pressure but left
atrial pressure is normal . Nifedipine, Steroids & Carbonic Anhydrase inhibitor are of value in the t/t and
prevention of the condition, also rest and O2. Q

b. Acute mountain sickness  in unacclimatized persons: -

1. At 3700m (12000 feet)  symptoms :irritability, drowsiness, lassitude, mental and muscle fatigue.
2. Above 18,000 feet  seizures
3. Above 23,000 feet  (conciousness lost)
Cause  cerebral edema due to arteriolar dilation
T/t  for Alkalosis  Acetazolamide and for cerebral edema  gluco-corticoids

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c. Acclimatization refers to changes in the body tissues in response to long term exposure to hypoxia i.e. at
high altitude for days, weeks or years  the person becomes more and more acclimatized to low PO2. The
principal means by which acclimatization comes about are: -
1. A great increase in pulmonary ventilation  on immediate exposure to very low Po2, the hypoxic
stimulation of the chemoreceptors increase alveolar ventilation about 65% above normal. This is immediate
compensation for the high altitude.”
2. Increased in RBC  Due to hypoxia   erythropoietin  polycythemia
3. Increased diffusion capacity of lungs  it increased three folds above the normal; and Increased T.L.
capacity.
4. Pulmonary Hypertension  Note that hypoxia causes vasoconstriction in lungs.
5. Increased vascularity of the tissue  density es in skeletal and cardiac muscle.
6. Increase alkalization of urine.
7. Increased ability of the cells to use O2, despite the low PO2  due to ed conc of oxidative enzymes and
ed density of mitochondria at cellular level.
The alkalosis tends to shift the O-HDC to the left; recall that alkalosis also favours formation of red cell. 2,3
DPG which tends to shift the O-HDC to the right. The net effect is a slight shift of the O-HDC to the right (i.e
the P50 increase slightly)

d. Other points
1. PB (the atmospheric pressure) decrease
2. Composition of the air remains the same
3. PH2O remain the same
4. PAO2 decreases
5. PACO2 decreases (because of hyperventilation)
6. The sensitivity of the carotid body to hypoxia does not increase; in fact, prolonged hypoxia decrease the
sensitivity

4. P(A – a) O2 gradient
This is affected in hypoxic hypoxia, in other types of hypoxia, it is normal
In hypoxic hypoxia due to high altitude and hypoventilation, it is decreased, in hypoxic hypoxia due to diffusional
defect and night to left shunt, it is increased.

9. Latest Trends
I. Hypoxia-inducible factors (HIFs) are transcription factors that respond to HYPOXIA.
a. Hypoxia promotes the formation of blood vessels, and is important for the formation of a vascular
system in embryos. The hypoxia in wounds promotes the formation of blood vessels, but also the
migration of keratinocytes and the restoration of the epithelium.In general, HIFs are vital to
development.
b. Therapeutic Potential: Recently several drugs have been developed which act as selective HIF prolyl-
hydroxylase inhibitors. Eg.FibroGen's compounds FG-2216 and FG-4592. By inhibiting HIF prolyl-
hydroxylase, the activity of HIF-1α in the bloodstream is prolonged, which results in an increase in
endogenous production of erythropoetin.

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II. OXIDATIVE STRESS: It is due to various free oxygen radicals which dameages the lipid membrane, proteins,
nucleus etc.
10. Methods of Measuring Oxidative stress
There are several methods for measuring Oxidative stress that includes
1. The measurement of lipid oxidation products such as malonaldehyde in blood on urine ;
2. In vivo oxidizability of blood fractions (such as LDL)
3. Vitamin E or vitamin C levels in blood fractions (including LDL)
4. Catalase or Superoxide dismutase levels in blood fractions

Chapter - 5
5. Lipid peroxides in blood
6. Volatile compounds such as ethane and pentane in expired breath
7. Glutathione/glutathione disulfide in blood factions
8. Eicosanoids in urine
9. Autoxidative, non-cyclooxygenase-denived eicosanoids in plasma
10. The “TRAP” assay that measures the total peroxyl radical-trapping antioxidant power of blood serum

11. BMR
1. Energy expenditure in resting state is given by RMR or the Resting Metabolic Rate.
2. The metabolic rate determined at rest in a room at a comfortable temperature in the thermoneutral zone
12–14 hours after the last meal is called the basal metabolic rate (BMR).
3. Katch-McArdle formula is most accurate for its calculatiom on the basis of lean body mass:

Respiration
4. P=370 +b(21.6. LBM) where LBM is the lean body mass in kg.
5. This value falls about 10% during sleep and up to 40% during prolonged starvation.
6. The rate during normal daytime activities is, of course, higher than the BMR because of muscular activity
and food intake.
7. The maximum metabolic rate reached during exercise is often said to be 10 times the BMR.
Factors Affecting the Metabolic Rate
The metabolic rate is affected by many factors. One of the most important is muscular exertion. O2 consumption
is elevated not only during exertion but also for as long afterward as is necessary to repay the O 2 debt .
Factors Affecting the Metabolic Rate.
Muscular exertion during or just before measurement
Recent ingestion of food (SDA)
High or low environmental temperature
Height, weight, and surface area
Sex
Age
Growth
Reproduction
Lactation
Emotional state
Body temperature
Circulating levels of thyroid hormones
Circulating epinephrine and norepinephrine levels

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12. Effect of Height, weight, and Body surface area (BSA)on BMR

I. BMR has a stronger correlation with body weight than with any other nutritional anthropometric index
used as a single independent variable.
II. BMR has highest correlation with Lean body mass as compared to Total weight (fat + Lean body weight),
BSA & Height.
III. Since BMR is the energy consumption in resting state in metabolic active tissue i.e lean body mass
(adipose tissue is metabolically inert) BMR depends very much on LBM. By far the main determinant of
resting metabolic rate is fat-free mass
IV. In a very tall thin and short obese person BMR differs but BSA can be similar so low correlation. Same way
BMI depends more on Body weight rather Lean body weight so again low correlation.
a. Recently ingested foods also increase the metabolic rate because of their specific dynamic action
(SDA). The SDA of a food is the obligatory energy expenditure that occurs during its assimilation into
the body.
b. Another factor that stimulates metabolism is the environmental temperature. The curve relating the
metabolic rate to the environmental temperature is U-shaped. When the environmental temperature
is lower than body temperature, heat-producing mechanisms such as shivering are activated and the
metabolic rate rises.
c. When the temperature is high enough to raise the body temperature, metabolic processes generally
accelerate, and the metabolic rate rises about 14% for each degree Celsius of elevation.

13. Nitrogen narcosis

a. Nitrogen narcosis( inert gas narcosis, raptures of the deep, Martini effect) is a reversible alteration in
consciousness that occurs while scuba diving at depth as under high pressure nitrogen becomes
soluble in blood and reaches the brain.
b. Apart from helium, and probably neon, all gases that can be breathed have a narcotic effect, which
is greater as the lipid solubility of the gas increases.
c. The precise mechanism is not well understood, but it appears to be the direct effect of gas dissolving
into nerve membranes and causing temporary disruption in nerve transmissions.
d. Some of these effects may be due to antagonism at NMDA receptors and potentiation of GABA A
receptors. Similar to the mechanism of ethanol's effect, the increase of gas dissolved in nerve cell
membranes may cause altered ion permeability properties of the neural cells' lipid bilayers.
e. An early theory, the Meyer-Overton hypothesis suggested that narcosis happens when the gas
penetrates the lipids of the brain's nerve cells, causing direct mechanical interference with the
transmission of signals from one nerve cell to another.

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“Please Read the Preface of this book Before you attempt these questions.”
Explanation of answer start from page no. 197

Section-1 -: Mechanics of breathing B. Increase surface area by surfactant

C. Negative intra pleural pressure
D. Lung compliance
1. Specific compliance is reduced in the following
except: (AIPG 2011)
2. The mechanism of action of surfactant is:
A. Pulmonary congestion
(AIIMS NOV 2013)
B. Reduced functional pulmonary surfactant
A. Breaks the structure of water in the alveoli
C. Chronic bronchitis
B. Lubricate the flow of Co2 diffusion
D. Pulmonary fibrosis
C. Makes the capillary surface hydrophilic
D. All of the above
2 . Negative intrapleural pressure is due to? (AIIMS
NOV 2010)
3. Surfactant is made up of which of the following:
A. Lymphatic drainage from plural cavity
(DNB Dec-2009)
B. Equally distributed surfactant
A. Degradable products B. Mucoprotein
C. Negative pressure in alveoli
C. Fibrinogen D. Phospholipid
D. presence of cartilaginous ring at the upper airway
4. Which of the following secrete surfactant: (LQ)
3. Muscle of expiration
A. Type II pneumocytes B. Type I pneumocytes
A. Diaphragm
C. Goblet cells D. Paneth cells
B. Internal intercostals
C. External intercostals
5. Surfactant is present in amniotic fluid at:
D. Rect. Abdominis
A. 34 weeks B. 32 weeks
C. 28 weeks D. 36 weeks
4. The intrapleural pressure is negative both during
inspiration and expiration because:
6. Pulmonary surfactant is secreted by:
A. Intrapulmonary pressure is always (DNB Pattern)
negative A. Type I pneumocytes
B. Thoracic cage and lung’s opposite recoil. B. Type II pneumocytes
C. Transpulmonary pressure determines the C. Clara cells
negativity D. Bronchial epithelial cells
D. Surfactant prevents the lungs to collapse
7 Stability of alveoli maintain by. (AIIMS Nov 09)
5 Physiological dead space is increased by all except A. Residual air
(AIIMS May 2009) B. Increase surface area by
A. Artificial airway surfactant
B. Neck extension C. Negative intra pleural pressure
C. Upright position D. Lung compliance
D. Ipratropium
Section-3 -: Ventilation / Perfusion Pressure
Section-2 -: Surface tension & Surfactant

1. Stability of alveoli maintain by 1. In which of the following area of the lung the
ventilation perfusion ratio is maximum:
(AIIMS NOV 2009)
A. Apex of lung B. Base of lung
A. Residual air
C. Equal in all areas D. Right posterior lobe
1.C 2.A 3.B 4.B 5.A 1.B 2.A 3.D 4.A 5.C 6.B 7.B 1.A

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small.
C. The diameter of theses airways is very small.
2. Total alveolar ventilation volume is: (DNB D. The linear velocity of airflow in the small airways
Pattern) is extremely low.
A. 1.5 liter/mm B. 4.2 liter/mm
C. 5.3 liter/mm D. 3.5 liter/mm 3 . In lung True about Hyaline membrane disease is
(AIIMS NOV 2010)
3. Which of the following is true? (DNB Pattern) A. FRC is more than closing volume
A. At base of lung blood circulation is minimum B. FRC is lesser than closing volume
B. Ventilation per unit lung volume maximum at C. FRC is equal to closing volume

Chapter - 5
apex of lung D. FRC variation is more important than closing
C. At base of lung ventilation-perfusion ratio is volume
maximum
D. Alveolar PaO2 is maximum at apex of lung 4. Physiological dead space is increased by
all except (AIIMS MAY 2009)
4. Which of the following is true regarding ideal A. Artificial airway B. Neck extension
alveolar ventilation- perfusion ratio? (DNB Pattern) C. Upright position D. Ipratropium
A. Maximum at apex of lung
B. Minimum at apex of lung 5. Vital capacity is:
C. Maximum at AV shunt A. TV+RV B. IRV+ERV
D. Maximum at base of lung C. TV+IRV+ERV D. TV+IRV

5. Ventilation-perfusion ratio is maximum at apex 6. Anatomic dead space is what % of tidal volume:

Respiration
of lung due to: (DNB Pattern) (DNB Pattern)
A. Blood flow is increased considerably more than A.20% B.30%
ventilation C. 40% D. 50%
B. Blood flow is decreased considerably
more than ventilation 7. FRC is: (DNB Pattern)
C. Base of lung has high ventilation in relation to A. Dead space volume
B. Volume of air present after normal expiration
blood flow
C. Volume of air present after forceful expiration
D. Direct connection with trachea
D. Residual volume
Section-4 -: Lung volume & capacities
8. Normal functional residual capacity is:
1. During plethesmography, which of the following A.2.3L B. 1.3L
occurs as patient expires with closed glottis in the C. 2.9L D. 4.5L
box? (AIPG 2011)
9. Ventilation perfusion Ratio is maximum in (DNB
A. The pressure increases in both
Pattern)
B. The pressure decreases in both
C. The pressure in lungs increases and in the box
decreases A. Base of lung B. Apex of lung
D. The pressure in box increases and in the lungs C. Post lobe of lung D. Middle lobe of lung
decreases
10. Lung diffusion capacity is measured with (DNB
2. Flow in small airways is laminar because: (AIPG Pattern)
2011) A. CO2 B. CO
A. Reynolds number in small airways is more than C. O2 D. H2
2000.
B. The total cross sectional area of small airways is 11. Tidal volume is: (DNB Dec-2009)

2.B 3.D 4.A 5.B 1.C 2.D 3.B 4.A 5.C 6.B 7.B 8.A 9.B 10.B

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 Physiology

A. Total vital capacity + RV D. Haldane effect

B. Functional residual capacity - RV
C. TLC-RV 4. Rise in 2-3 bisphosphoglycerate is seen in all
D. Inspiratory capacity — inspiratory reserve volume except? (AIPG 2009)
A. Chronic anemia B. Chronic hypoxia
12. All of the following are normal values in lung C. Inosine D. Hypoxanthine
measurements except 5. High affinity of HbF with O2 due to:
A. Tidal volume 0.5 liters (AIIMS MAY 2009)
B. Vital capacity 4.5 liters A. Decrease binding with 2,3 DPG
C. Residual volume 2 liters B. Decrease concentration of Hb
D. Inspiratory reserve volume 3.3 liters C. Increase in the Ph
D. Bohr effect
13. Total lung capacity depend on- (DNB Pattern)
A. Size of airway B. Closing tidal volume 6. An increase in which of the following parameters
C. Lung compliance D. Residual volume will shift the O2 dissociation curve to the left: (LQ)
A. Temperature
14. Total lung capacity is B. Partial pressure of CO2
A. 3 — 4 litres B. 4 — 5 litres C. 2, 3 DPG concentration
C. 6 — 7 litres D. 7 — 8 litres D. Oxygen affinity of hemoglobin

15. Vital capacity is 7. Which of the following is the important feature

A. Tidal volume + Expiratory Reserve Volume of 2, 3 diphosphoglycerate:
B. Tidal volume + Inspiratory Reserve Volume A. Higher concentration in blood
C. I.R.V. + E. R.V. B. Bohr effect
D. T.V. + I.R.V. + E.R.V. C. Alters affinity to hemoglobin
E. Tidal volume D. A and C

16. Total lung capacity depend on- 8. Oxygen affinity decreases in (DNB Pattern)
(A) Size of airway (B) Closing tidal volume A. Hypoxia B. Hypothermia
(C) Lung compliance (D) Residual volume C. HbF D. Increase in pH

Section-5 -: Gas Exchange & Transport 9. The normal value of P50 on the oxyhaemoglobin
dissociation curve in an adult is -
1. Gas used to measure diffusion capacity of A. l.8 kPa B. 2.7 kPa C. 3.6 kPa D.4.5 kPa
lung (AIIMS NOV 2010)
A. CO B. NO C. CO2 D. O2 10. Decreased O2 affinity of Hb in blood with
decreased pH: (DNB Pattern)
2. Reason for fast CO2 diffusion in blood (AIIMS
NOV 2010) A. Haldane effect B. Double Haldane effect
A. Less dense B. More soluble in plasma C. Bohr effect D. Double Bhor effect
C. Less molecular weight D. Less pco2 in the alveoli
11. Least amount of CO2 is in
3. Cause of sigmoid shape of O2 curve? (AIPG A. Anatomical dead space — end inspiration phase
2009 ) B. Anatomical dead space — end expiration phase
A. Binding of one O2 molecule increase the affinity of C. Alveoli — end inspiration phase
binding of other O2 molecules. D. Alveoli — end expiration phase
B. Binding of one O2 molecule decrease the affinity of
binding of other O2 molecules. 12. Dissolved oxygen is not dependent on (DNB
C. Bohr effect Pattern)
11.D 12.C 13.C 14.C 15.D 16 .C 1.A 2.B 3.A 4.D 5.A 6.D 7.D,A,C 8.A 9.C 10.C 11.A 12.A

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 Respiration

A. Hb B. Atmospheric pressure C. Pneumotaxic centre

C. Alveolar pressure D. Arterial tension of O2 D. Apneustic centre

13. Carbon dioxide is transported in blood mainly 4. Pace maker of respiration lies at:
as: (DNB Pattern) (AIIMS NOV 2009)
A. DRG B. Pneumotaxic centre
A. Free carbon dioxide B. Bicarbonate C. Apneustic centre D. Pre botzinger complex
C. Carbamino compound D. Plasma protein
5. Transection at mid-pons lead to.
14. The concentration of oxygen provided by (AIIMS NOV 2009)

Chapter - 5
mouth-to-mouth respiration is: A. Rapid, shallow breathing
A. 16% B. 20% C. 25% D. 30% B. Apneusis
C. Hyperventilation
15. One intern calculated the concentration of O2 in D. Deep breathing
blood as 0.0025 ml/ml of blood. Considering
atmospheric pressure as 760 mmHg, how much 6. Central chemoreceptors are most sensitive to:
approx. O2 tension could have been in the blood? (AIIMS 2011, AIPG 2009)
A. 40 mmHg B. 60 mmHg A. Increase in CO2 Tension
C. 80 mmHg D. 100 mmHg B. Decrease in CO2 Tension
C. Low O2 Tension
16. Haemoglobin unlike myoglobin show D. Increase in H+
A. Parabolic curve of oxygen association
B. Positive cooperativity 7. “Inflation of lungs induces further inflation” is

Respiration
C. Dissolved form explained by: (DNB Dec 2012)
D. CO A. Hering-Breuer inflation reflex
B. Hering-Breuer deflation reflex
17. Least amount of CO2 is in C. Heads paradoxical reflex
(A) Anatomical dead space — end inspiration phase D. J-reflex
(B) Anatomical dead space — end expiration phase
(C) Alveoli — end inspiration phase 8. The vasodilatation produced by carbon dioxide is
(D) Alveoli — end expiration phase maximum in one of the following:
A. Kidney B. Brain
Section-6 -: Regulation of Respiration C. Liver D. Heart
1. Loading reflex to monitor tidal volume (AIIMS
NOV.2011) 9. Peripheral chemoreceptors is stimulated
A. Stretch receptors in bronchioles maximally by (DNB Dec-2010)
B. J receptors A. Cyanide B. Anaemia
C. Thoracic muscle spindles C. Hypocapnia D. Alkalosis
D. Carotid and aortic bodies
10. True In Asthma. (AIIMS Nov 09)
2. In resting stage respiration does not depend A. Increased FRC Reduced Residual Volume
upon (AIIMS NOV 2010) B. Increased FRC Increased Residual Vol
A. PCO2 B. PO2 C. Reduced FRC Reduced Residual Volume
C. J receptor D. Stretch receptor D. Reduced FRC Increased Residual Vol
11. Pace maker of respiration lies at: (AIIMS Nov 09)
3. Pacemaker for the start of rhythmic respiration A. DRG B. Pneumotaxic centre
(AIIMS NOV 2010)
C. Apneustic centre D. Pre botzinger complex
A. Dorsal respiratory group
B. Pre – botzinger complex 12. Transection at mid-pons lead to. (AIIMS Nov 09)

12 A 13.B 14.A 15.C 16.B 17.A 1.C 2.C 3.B 4.D 5.D 6.A 7.C 8.B 9.A 10.B 11.D 12.D

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 Physiology

A. Rapid, shallow breathing 7. Cyanosis doesn’t occur in Anemia because.

B. Apneusis (AIPG 2009)
C. Hyperventilation A. Certain min. amount of reduced Hb should be
present
D. Deep breathing
B. In anemia, O2 saturation increases
C. Hypoxia stimulates erythropoietin production
Section-7 -: Applied Respiratory Physiology D. O2 Hemoglobin curve shifts to right

1. Nitrogen narcosis is caused due to (AIIMS 2011 8. Which of the following statement is true for high
MAY) altitude pulmonary edema?
A. Nitrogen inhibits dismutase enzyme A. It reduces after exercise.
B. Increase production of nitrous oxide B. It occurs only in acclimatized individuals.
C. Increased solubility of nitrogen in nerve cell C. It is associated with pulmonary hypertension.
membrane D. It is more likely to occur above the height of 300
D. Decrease in oxygen free radicals m.

2. A 32 years old mountaineer has hematocrit of 9. Earliest change in high alitiude is (DNB Pattern)
60. He is likely to have: (AIPG 2011) A. Hyperventillation B. Decrease in work capacity
A. Progressive hemodilution C. Drowsiness D. Polycythemia
B. High altitude pulmonary edema
C. High altitude cerebral edema 10. During acclimatization to high altitude all of the
D. Polycythemia with possible dehydration following take place except:
A. Increase in minute ventilation
3.Level of Hypoxia is independent of (AIIMS NOV B. Increase in the sensitivity of central
2010) chemoreceptors
A. Hb B. FiO2 C. PCO2 D. Altitude C. Increase in the sensitivity of carotid body to
hypoxia
4. What is the reason that an infant can breathe D. Shift in the oxygen dissociation curve to the left
while suckling breast milk? (AIIMS NOV.2010)
A. Small wide tongue. 11. All of the following are related to oxygen
B. High position of the larynx toxicity except. (AIPG 2007)
C. Small pharynx A. Retinal blindness
D. short soft palate B. Pulmonary edema
C. Decreased cerebral blood flow
5. True In Asthma. (AIIMS NOV 2009) D. Convulsions
A. Increased FRC Reduced Residual Volume
B. Increased FRC Increased Residual Vol 12. An untrained person going to higher altitude for
C. Reduced FRC Reduced Residual Volume training can have maximum anabolic effect by:
D. Reduced FRC Increased Residual Vol (AIPG 2007)
A. Decrease in workload, increase in duration of
6. Toxicity of CO is limited to its diffusion d/t exercise
(AIIMS NOV 2009) B. Decrease in work load
A. The binding capacity of CO to HB with high avidity C. Increase in work load, increase in duration of
B. CO does not diffused across the alveolar capillary exercise
Membrane D. Increase in work load, decrease in duration of
C. Decreased permeability across alveoli-blood exercise
membranes
D. decreased diffusion across blood-brain barrier. 13. Cyanosis which is not corrected by 100% oxygen
therapy is due to: (DNB Pattern)
1.C 2.D 3.C 4.B 5.B 6.A 7.A 8.D 9.A 10.D 11.C 12.A

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 Respiration

A. Chronic obstructive pulmonary disease A. CO2 poisoning B. Met Hb

B. Bronchial asthma C. Cyanide poisoning D. Respiratory acidosis
C. TOF
D. Interstitial lung disease 21. Which of the following is false regarding
respiratory failure type-I? (DNB Pattern)

14. In moderate exercise stimulation of respiration A. Normal A-a gradient B. Normal PaCO2
is due to (DNB June-2011) C. Decreased PaCO2 D. Decreased PaO2
A. Stimulation of J Receptor
B. Stimulation of lung stretch receptor 22. Death due to cyanide poisoning results from

Chapter - 5
C. Joint propioception receptor which of the following types of anoxia? (DNB Dec-
D. Stimulation of medullary centre. 2012)
A. Anoxic anoxia B. Anaemic anoxia
15. Which of the following is the best-known C. Stagnant anoxia D. Histotoxic anoxia
metabolic function of the lung?
A. Inactivation of serotonin
B. Conversion of angiotensin I to angiotensin II 23. In Caissons disease all seen except?
C. Inactivation of bradykinin A. Myonecrosis B. Lymphedema
D. Metabolism of basic drugs by cytochrome P450 C Paraplegia D. None
system
24. Basic respiratory rhythm centre is present in-
16. True about pulmonary circulation: A. dorsal medulla
(DNB Pattern) B. ventral medulla

Respiration
A. It receives 30% of cardiac output C. rostroventrolateral medulla
B. Hypoxia causes vasoconstriction D. Pons
C. Blood volume in lung is 450 ml
D. Pulmonary capillaries contain most of the blood 25. Surfactant is secreted by
volume in lung A. type 2 pneumocytes
e. It has low resistance B. type 1 pneumocytes
C. clara cells
17. Hypoxia causes vasoconstriction in D. APUD cells
A. Muscle B. Lungs C. Liver D. Spleen
26. 100 feet deep under water,what is the pressure
18. Which of the following statement is true for high A. 2 atm B. 4 atm
altitude pulmonary edema? (AIIMS May 08) C. 8 atm D. 12 atm
A. It reduces after exercise.
B. It occurs only in acclimatized individuals. 27. Partial pressure of oxygen in venous blood
C. It is associated with pulmonary hypertension. A. 40 mm Hg B. 60 mm Hg
D. It is more likely to occur above the height of 300 m C. 80 mm Hg D. 95 mm Hg

19. Anoxic hypoxia is because of: (DNB Pattern) 28. Diaphragm is lowest in
A. Decreased pO2 in arterial blood A. sitting B. standing
B. Increased pO2 in arterial blood C. supine D. prone
C. Increased pCO2 in blood
D. Increased pO2 in venous blood 29. normally lungs kept dry by
A. osmotic pressure in interstitium
20. Which of the following conditions leads to tissue B. surfactant
hypoxia without alteration of oxygen content of C. surface tension
blood? D. air water interphase
13.C 14.C 15.B 16.B,C,E 17.B 18.D 19.A 20.C 21.A 22.D 23.B 24.A 25.A 26.B 27.A 28.A 29.A 30.A

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 Physiology

30. Obstructive pattern in spirometry is seen in

A. alpha 1 anti trypsin deficiency
B. kyphoscoliosis
C. pneumonia
D. phrenic nerve injury
31. Anatomic dead space is what % of tidal volume:
A.20% B.30%
C. 40% D. 50%

32. Cavernous respiration is seen in .

A. Asthma
B. Emphysema
C. Consolidation
D. cavitary lesion

33. maximum increase in minute volume is seen in

A. exercise
B. hyperthermia
C. voluntary Ventilation
D. decreased pO2

34. An increase in pulmonary blood flow during

exercise
(A). Causes alveolar oxygen tension to decrease
(B). Causes the V/Q ratio at the top of the lung to
increase
(C). Causes pulmonary arterial resistance to decrease
(D). Causes diffusion capacity to decrease

35. Hyperventilation in response to a stressful

situation leads to which of the following?
(A). A decrease in the blood flow to the brain
(B). An increase in the activity of the central
chemoreceptors
(C). A decrease in pH of the arterial blood
(D). An increase in the resistance of the pulmonary
blood vessels

36. Oxygen affinity decreases in

(A) Hypoxia (B) Hypothermia
(C) HbF (D) Increase in pH

37. Which type of hemoglobin is not normally found

within human erythrocytes?
(A) HbA (C) HbCO
(B) HbA2 (D) HbO2
38. Earliest change in high altitude is
(A) Hyperventilation (B) Decrease in work capacity
(C) Drowsiness (D) Polycythemia

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 Respiration

31.B 32.A 33A 34.C 35.A 36.A 37.C 38.A

39. Hypoxia causes vasoconstriction in
(A) Muscle (B) Lungs
(C) Liver (D) Spleen

40. In healthy individuals, the cause of an (A-a)O2 gradient is

(A) Low diffusing capacity for oxygen compared with that for carbon dioxide
(B) A high A/ ratio in the apex of the lungs

Chapter - 5
(C) Overventilation in the base of the lung
(D) A bronchial circulation shunt

41. Which of the following will not cause a low lung diffusing capacity (DL)?
(A) Decreased diffusion distance
(B) Decreased capillary blood volume
(C) Decreased surface area
(D) Decreased cardiac output

42. With respect to oxygen and carbon dioxide transport,

(A) The slopes of the oxygen and carbon dioxide content curves are similar
(B) Equal amounts of oxygen and carbon dioxide can be carried in 100 mL of blood
(C) The presence of carbon dioxide decreases the P50 for O2
(D) The presence of oxygen lowers carbon dioxide content in the blood

Respiration
43. Which of the following conditions causes a decrease in arterial O2 saturation without a decrease in O2
tension?
(A). Anemia (B). Carbon monoxide poisoning
(C). A low V/Q ratio (D). Hypoventilation

44. Pulmonary vascular resistance decreases if

(A). The lungs are inflated to total lung capacity
(B). Sympathetic stimulation to the pulmonary vessels in increased
(C). Alveolar oxygen tension is decreased
(D). Cardiac output is increased

39.B 40.D 41.A 42.D 43.B 44.D

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 Physiology

45. In the graph below, what are X &Y

A) Emphysema & Chronic bronchitis

B) Emphysema & single lung

C) Restrictive lung disease & Emphysema

D) Restrictive lung disease & single lung

46. A 32-year-old patient has a pulmonary vascular resistance of 4 mm Hg/L per minute and a cardiac output
of 5 L/min. What is her driving pressure for moving

blood through the pulmonary circulation?

(A) 10 mm Hg

(B) 15 mm Hg

(C) 20 mm Hg

(D) 30 mm Hg

45.B 46.C

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 Respiration

Chapter - 5
Explanation
Chapter-5 Respiration

Section-1 -: Mechanics of breathing

Respiration
1. Ans. C. Chronic bronchitis.
(Ref. Ganong Physiology 23rd/pg. 595)
a. Lung compliance refers to the ability of lungs to stretch. However, many normal factors affect lung
compliance and it is best represented by a whole pressure-volume curve.
b. Thus, Lung compliance is the change in lung volume for a given change in pressure.
 Compliance = ΔV / ΔP.
c. The normal compliance of human lungs and chest wall is about 0.2 L/cm H2O.
d. Decreased pulmonary compliance due to lung edema, lung hemorrhage, or loss of surfactant. Compliance
is reduced in restrictive lung disease.

Lung compliance

a. Compliance
i. The slope of the pressure-volume curve at a particular lung volume ΔV => i.e. volume change per
unit of pressure change (mL/cmH2O)
ii. normal value = 200mLs/cmH2O
iii. Lower31.B
compliance = more effort of breathing
32.A 33.A

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 Physiology

b. Specific compliance:
i. = compliance divided by FRC (/cmH2O)
ii. normal value = 0.05/cmH2O
iii. similar values in both sexs and all ages including neonates
iv. measurement of the intrinsic elastic property of the lung tissue
c. Dynamic compliance vs static compliance:
i. Static compliance is the compliance measured when there is no gas flow into or out of the lung.
d. Lung compliance and chest wall compliance:
i. Compliance is made up of lung compliance and chest compliance
ii. => 1/Ct = 1/Cl + 1/Ccw
iii. (Ct = total compliance, Cl = lung compliance, Ccw = chest wall compliance)
e. Factors affecting compliance:
i. Lung elastic recoil
ii. Lung volume
iii. Pulmonary blood flow
iv. History of recent ventilator
v. Bronchial smooth muscle tone
vi. Diseases

a. Lung's elastic recoil

Due to:

i. Surface tension in the alveoli

ii. Stretched elastic fibres in the lung parenchyma
iii. Surface tension accounts for 70% of the elastic recoil
b. Lung volume
i. The slope of the P-V curve is not constant across different lung volumes.
ii. At high lung volumes, compliance is reduced because more pressure is required to stretch the
already stretched elastic tissues further.
iii. At very low volumes, compliance is reduced because of closed airway and collapsed alveoli
 increased surface tension
 increased pressure is needed to re-open the airway/alveoli
 reduced compliance
iv. At the base of the lung, at very low volumes, compliance is even more reduced because of
positive intrapleural pressure
v. Posture affects compliance by affecting the lung volume.
vi. Restriction of chest expansion also affect lung volmen and chest wall compliance.
c. Pulmonary blood flow
i. Contributes to stiffness of the lung, especially in the case of pulmonary congestion
d. History of recent ventilation
i. Prolonged periods of hypoventilation without periodic deep breath may lead to reduced
compliance.
ii. May be related to atelectasis.
e. Bronchial smooth muscle tone

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 Respiration

i. In animal studies, increased bronchocontriction can lower time constant and reduced dynamic
compliance.
ii. Static compliance is probably not affected.
f. Disease
i. In diseased lungs, where time constant for the alveolis are different, units with higher time
constants are slow to fill and empty.
ii. With higher respiratory rate, the problem worsens:
 units with high time constant hypoventilates
 less lung units participate in volume changes

Chapter - 5
 dynamic compliance reduced.
iii. With collapsed alveoli
 greatly increased surface tension
 very high pressure is required to re-open airway/alveoli.

Diseases that REDUCE ▪ Fibrosis

compliance ▪ Pulmonary hypertension/congestion
▪ Alveolar atelectasis
▪ Reduced surfactant (increased surface tension) e.g. artificial ventilation,
prematurity

Respiration
Diseases that INCREASE ▪ Pulmonary emphysema (alteration in elastic tissue) -> static compliance is
compliance: Increased but dynamic compliance is reduced.
▪ Normal ageing (alteration in elastic tissue)
▪ Asthma (reason unknown).

2. Ans. A. Lymphatic drainage from plural cavity

Ganong - Review of Medical Physiology 23rd Ed & West JB. Respiratory physiology—the essentials. Baltimore
(MD): Williams and Wilkins; 1995.Page 378
Pleural cavity is a closed cavity. And the pressure is always negative due to the following factors:
a. The lungs have a tendency to recoil inwards, therefore visceral pleura is pulled inwards.
b. Surface tension also help by creating a inward force in alveoli.
c. The thorax has a tendency to recoil outwards, pulling parietal pleura with it. Therefore the pleural cavity is
stretched on both sides leading to increase in its volume and decrease pressure inside. And it becomes
negative.
d. Also there is a continuous Lymphatic drainage from pleural cavity, which creates a suction force in pleural
cavity, keeping the pressure negative.
Note: Surfactant by decreasing Surface tension actually opposes the negative pressure.. And pressure in alveoli is
same as atmospheric pressure, taken as ZERO.

3. Ans. B Internal intercostals

a. Expiration:
i. During expiration, the diaphragm simply relaxes, and the elastic recoil of the lungs, chest wall, and
abdominal structures compresses the lungs.

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 Physiology

ii. During heavy breathing  Expiration  extra force is achieved mainly by contraction of the
abdominal muscles
iii. Muscles that pull the rib cage down ward are classified as muscle of expiration: - are
 Abdominal recti  powerful effect
 Internal intercostals muscles.
b. Inspiration:-
a. Contraction of Diaphragm is a most important in inspiration.
b. Muscle that elevate the chest cage are classified as Muscles of inspiration:- are
i. External intercostals  most important muscles that raise the rib cage
ii. Sternocleidomastoid, Anterior serrati, and scaleni ~ that help in the raising the ribs cage.

4. Ans. B. Thoracic cage and lung’s opposite recoil.

a. Pleural pressure is the pressure of the fluid in the narrow space between the lung pleura and the chest
wall pleura. This is normally a slightly negative pressure.
b. The normal pleural pressure at the beginning of inspiration is about —5 cmH2O Q, which is the amount of
suction that is required to hold the lung open to their resting level.
c. Then, during inspiration, expansion of the chest cage pulls the surface of the lungs with still greater force
and creates a more negative pressure of about —7.5 cmH2O.

5. Ans. A. Artificial airway

Section-2 -: Surface tension & Surfactant

1. Ans. B. Increase surface area by surfactant

(Ref. Ganong - Review of Medical Physiology 23rd Ed-Page-587)
a. Stability of alveoli of alveoli is mainly the function of surfactant which prevents their collapse under
Surface tension.
b. Factors like Residual air, Negative intra pleural pressure, Compliance mainly affect the inflation and
deflation of lung during respiration.
c. They do have some effect on stability on alveoli but the single most important factor remains the
Surfactant. (Maximum work of breathing is done to oppose Surface tension).
d. The surface tension in alveoli is produced due to air-fluid interphase. Surfactant is made up of
PHOSPHOLIPID- DI-PALMITOIL-PHOPHATIDYL-CHOLINE (DPPC) Q + two major proteins having molecular
weights of 32,000 and 10,000.
e. It is secreted by TYPE II ALVEOLAR EPITHELIAL CELLS (type II pneumocytes) Q. It reduces surface tension in
alveoli by not dissolving uniformly in the fluid lining the alveolar surface.
f. Instead, part of the molecule dissolves, while the remainder spreads over the surface of the water in the
alveoli, thereby breaking the structure of water present inside the alveoli.
g. Main functions:
i. It increases the Compliance Q
ii. Reduces work of breathing Q
iii. Prevents collapse of alveoli at end of expiration : law of Laplace(P=2T/r) Q
iv. Prevents pulmonary edema by keeping the alveoli dryQ

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 Respiration

v. Alveolar size regulation: As the alveoli increase in size, the surfactant becomes more spread out over
the surface of the liquid. This increases surface tension effectively slowing the rate of increase of the
alveoli. This also helps all alveoli in the lungs expand at the same rate.
It has high concentration in the fetal lungs at 20 weeks of gestation Q. However, it does not reach
the surface of the lung until 28-38 weeks when it is present in amniotic fluid. Q .Maximum
secretion occurs at 34 weeks Q

2. Ans. A. Breaks the structure of water in the alveoli

Chapter - 5
Surfactant:
a. The surface tension in alveoli is produced due to air-fluid interphase.
b. The low surface tension when the alveoli are small is due to the presence in the fluid lining the alveoli of
surfactant, a lipid surface –tension-lowering agent. Surfactant is a mixture of DPPC, other lipids, and
proteins.
c. It does this by not dissolving uniformly in the fluid lining the alveolar surface. Instead, part of the molecule
dissolves, while the remainder spreads over the surface of the water in the alveoli,thereby breaking the
structure of water present inside the alveoli.
d. This surface has from one twelfth to one half the surface tension of a pure water surface.
e. If the surface tension is not kept low when the alveoli become smaller during expiration, they collapse in
accordance with the law of Laplace.
f. In spherical structures like the alveoli, the distending pressure equals 2 times the tension divided by the

Respiration
radius (P=2T/r) ; if T is not reduced as r is reduced , the tension overcomes the distending pressure.
Surfactant also helps tp prevent pulmonary edema.
g. It has been calculated that if were not presents, the unopposed surface tension in the alveoli would
produce a 20mm Hg force favoring transudation fluid from the blood into the alveoli.

3. Ans. D. Phospholipid

4. Ans. A. Type II pneumocytes

Surfactant is made up of PHOSPHOLIPID- DI-PALMITOIL-PHOPHATIDYL-CHOLINE (DPPC) Q + two major proteins
having molecular weights of 32,000 and 10,000. It is secreted by TYPE II ALVEOLAR EPITHELIAL CELLS (type II
pneumocytes) Q.

5. Ans. C. 28 weeks
SURFACTANT (Di-Palmitoyl-Phosphatidyl-Choline) is present in high concentration in the fetal lung
homogenates at 20 weeks of gestation Q. However, it does not reach the surface of the lung until 28-38 weeks
when it is present in amniotic fluid. Q

6. Ans. ‘B’ Type II pneumocytes

Surfactant is produced by type-Il alveolar epithelial cells (type-Il pneumocytes).

7.Ans. B. Increase surface area by surfactant

Section-3 -: Ventilation / Perfusion Pressure

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 Physiology

1. Ans. A. Apex of lung

In an upright person, pulmonary arterial flow and alveolar ventilation of APEX OF LUNG are much less than the
lower part. However, the blood flow is much less in comparison to ventilation. Here the
VENTILATION/PERFUSION RATIO IS 2.5 TIMES MORE THAN THE IDEAL VALUE. (Physiological dead space).
PHYSIOLOGICAL SHUNT On the other extreme the ventilation perfusion ratio is 0.6 times the ideal value at
the base of lung and represents a physiological shunt.

2. Ans. B. 4.2 liter/mm

3. Ans. D. Alveolar PaO2 is maximum at apex of lung

4. Ans. A. Maximum at apex of lung

a. The ratio of pulmonary ventilation to pulmonary blood flow for the ‘whole’ lung at rest is about 0.8 Q (4.2
liter/minute ventilation divided by 5.5 liter/minute of blood flow).
b. There are relatively marked differences in ventilation-perfusion ratio in various parts of the normal lung
due to the effect of gravity, and local changes in the ventilation perfusion ratio are common in disease.
c. Ventilation, as well as perfusion, in the upright position declines in a linear fashion from the bases to the
apices of the lungs. However, the ventilation-perfusion ratios are high in the upper portions of the lungs.
d. This high ventilation perfusion ratios at the apices account for the predilection for tuberculosis for this
area of lung because the relatively high alveolar P02 that results provides a favorable environment for the
growth of tubercle bacilli. Q

5. Ans. B. Blood flow is decreased considerably more than ventilation

a. In a normal person in the upright position, both blood flow and alveolar ventilation are considerably less in
the upper part of the lung than in the lower part; however, blood flow is decreased considerable more
than ventilation.
b. Therefore, at the top of the lung, ventilation perfusion ratio is as much as three times as great as the
‘ideal’ value, which causes a moderate degree of physiological dead space in this area of the lung Q.
c. At the other extreme, in the bottom of the lung there is slightly too little ventilation in relation to blood
flow, with ventilation perfusion ratio as low as 0.6 times the ‘ideal’ value.
d. Therefore, in this area a small fraction of the blood fails to become normally oxygenated representing a
physiological shunt.

Section-4 -: Lung volume & capacities

1. Ans. C. The pressure in lungs increases and in the box decreases.

(Ref. H-18th / 1597)
a. It is the most common method of meauring lung volumes.
b. Pressure in the box chnages in an opposite direction to that of the thorax.
c. The thorax expands on inspiration, thereby compressing gas in the box.
d. The opposite occurs on expiration.

Body plethysmography:

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a. It is commonly used alterative method of measuring lung volume that takes advantage of the principle of
Boyle's law, which states that the volume of gas at a constant temperature varies inversely with the
pressure applied to it.
b. The primary advantage of body plethysmography is that it can measure the total volume of air in the
chest, including gas trapped in bullae. Another advantage is that this test can be performed quickly.
c. Drawbacks include the complexity of the equipment as well as the need for a patient to sit in a small
enclosed space. A patient is placed in a sitting position in a closed body box with a known volume.
d. From the FRC, the patient pants with an open glottis against a closed shutter to produce changes in the

Chapter - 5
box pressure proportionate to the volume of air in the chest.
e. The volume measured by this technique is referred to as thoracic gas volume (TGV) and represents the
lung volume at which the shutter was closed, typically FRC.

2. Ans. D. The linear velocity of airflow in the small airways is extremely low.
(Ref. Ganong Physiology, 23rd/ pg.540)
Generally, turbulent flow occurs when Re > 2000, and laminar flow occurs when Re < 2000.Q
Cross-sectional area as a function of airway generation:
a. The total cross-sectional area of the airway tree increases as one moves towards the lung periphery
because of the dichotomous branching system of the human airway tree. Hence, the total number of
parallel airways increases as one moves from the trachea (generation 1) to the lung periphery.

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b. Re is related to flow velocity, which is related to tube diameter.
c. Average velocity (cm/sec) of gas in the tube is calculated by dividing the flow rate (cm3/sec) by tube area
(cm2). Hence, flow is turbulent in the larger airways, but laminar in more peripheral airways, where the
total cross-sectional area is greater.
d. The key point here is the TOTAL cross-sectional area at a given level of the airway tree.
e. So that, even if an individual peripheral airway has a relatively small diameter, the total cross sectional
area of all the airways that comprise that airway generation, will be relatively high.
f. Consequently, the average velocity (ie. flow rate/tube area) will be a relatively small number, and
according to the above equation, Re (Reynold’s number) will be low and flow will be laminar.
g. This explains why flow in peripheral airways is laminar, even though the radius of an individual
peripheral airway is much smaller than that of the main conducting airways.

Poiseuille resistance (R) is thus:

R=8nL/πr4
The key point is that R is proportional to the tube length but inversely proportional to the fourth power of the
tube radius. This means that resistance increases very rapidly as tube radius decreases.
(Ganong 23rd/Chapter 32;pg. 540:)

LAMINAR BLOOD FLOW

a. The flow of blood in straight blood vessels, like the flow of liquids in narrow rigid tubes, is normally
laminar (streamline).
b. Within the blood vessels, an infinitely thin layer of blood in contact with the wall of the vessel does not
move.

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c. The next layer within the vessel has a low velocity, the next a higher velocity, and so forth, velocity being
greatest in the center of the stream. Laminar flow occurs at velocities up to a certain critical velocity.
d. At or above this velocity, flow is turbulent. Streamline flow is silent, but turbulent flow creates sounds.

REYNOLDS NUMBER
a. The probability of turbulence is also related to the diameter of the vessel and the viscosity of the blood.
This probability can be expressed by the ratio of inertial to viscous forces as follows:
o Where,
i. Re is the Reynolds number, named for the man who described the relationship;
ii. p is the density of the fluid;
iii. D is the diameter of the tube under consideration;
iv. V is the velocity of the flow; and is the viscosity of the fluid.
b. The higher the value of Re, the greater is the probability of turbulence. When D is in cm, V is in cm/s–1,
andin poises; flow is usually not turbulent if Re is less than 2000. Q
c. When Re is more than 3000, turbulence is almost always present.
d. Laminar flow is disturbed at branching of arteries, but normally not to the point that turbulence is
produced.
e. Constriction of an artery increases the velocity of blood flow through the constriction, producing
turbulence, and consequently sounds, beyond the constriction.
f. Examples are bruits heard over arteries constricted by atherosclerotic plaques and the sounds of
Korotkoff heard when measuring blood pressure.
g. In humans, the critical velocity is sometimes exceeded in the ascending aorta at the peak of systolic
ejection, but it is usually exceeded only when an artery is constricted. Turbulence occurs more frequently
in anemia because the viscosity of the blood is lower. This may be the explanation of the systolic murmurs
that are common in anemia.
Capillaries have highest total cross-sectional area.Q

3. Ans. B. FRC is lesser than closing volume

(Ref: West JB. Respiratory physiology—the essentials. Baltimore (MD):)
Williams and Wilkins; 1995.
a. Closing Volume or closing capacity (CC) is the volume in the lungs at which its smallest airways, start
closing during expiration due to increased intrathoracic pressure around airways.
b. The closing capacity is usually less than the residual volume (RV). This means that there is normally
enough air within the lungs to keep these airways open throughout both inhalation and exhalation.
c. As the lungs age, there is a gradual increase in the closing capacity.
d. In Hyaline membrane disease FRC is lesser than closing volume. When the FRC drops below the critical
closing volume, alveolar collapse occurs .
e. The closing volume of alveoli is larger than the FRC until 6-8 years of age. This causes an increased
tendency for airway closure at end expiration.
f. With exhalation, intrathoracic pressure changes will result in airway closure. This occurs first in dependent
areas of the lungs around the level of residual volume.
g. During disease states, increased transpleural pressures result in increased closing volumes. These closing
volumes may occur at the level of FRC, which result in atelectasis, subsequent ventilation/perfusion (V/Q)
mismatch, and eventual hypoxemia and heypercapuia.

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h. Continous positive airway pressure is one of the therapies used to increase FRC, prevent atelectasis and
maintain ventilation.

4. Ans. A. (Ref: Ganong - Review of Medical Physiology 23rd Ed, -Page-609

a. Since gaseous exchange in the respiratory system occurs only in the terminal portions of the airways, the
gas that occupies the rest of the respiratory system is not available for gas exchange with pulmonary
capillary blood this volume is called as anatomic dead space (150ml) Q.
b. When alveolar dead space (i.e.all the air in the alveoli that is not participating in gas exchange) is included
in the total measurement of dead space, this is called the physiologic dead spaceQ, in contradistinction to

Chapter - 5
the anatomic dead space.
c. In a normal person, the anatomic and physiologic dead spaces are nearly equal because all alveoli are
functional in the normal lung. Q

Dead space is decreased by

a. supine postionQ
b. neck fully flexedQ with depressed chin
c. low lung volumesQ
d. TracheostomyQ & endotracheal intubationQ (Artificial airway).

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Dead space increased by
a. endotracheal intubation with tubeQ (increased mechanical DS due to tube volume)
b. standing positionQ (due to hypoperfusion of apical alveoli)
c. emphysema Q
d. neck extension Q
e. Ipratropium (Bronchodilation)

So we can see that only artificial airway (considering only tracheostomy& endotracheal intubation no tube which
will add mechanical Dead space) involves decrease in the Physiological dead space
Note: Depression of the jaw with flexion of the neck produced a mean decrease in the dead space of 31.4 ml while
a protrusion of the jaw with extension of the neck increases the dead space by 39.7 ml.

5. Ans. C. TV+IRV+ERV
Various Lung Volumes
Tidal volume The amount of air which moves into the lung with each inspiration (or whic
comes out with each expiration)
Inspiratory reserve volume (IRV) The excess air above the tidal volume which can be inspired with maximum
inspiratory effort. Q
Expiratory reserve volume (ERV) It is the volume of air that can be expelled by an active expiratory effort
after passive expiration Q
Residual volume It is the volume of air that is left in lung after maximum expiratory effort
Vital capacity The maximum amount of air that can be expired after a maximum
inspiratory effort.

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FEV 1 Fraction of vital capacity expired in one second

6. Ans. B. 30%
a. A normal individual at rest inspires about 12 to 16 times/minute and each breath have a tidal volume of
about 500 mL.
b. A portion (more or less 30%) of the fresh air inspired with each breath does not reach the alveoli but
remains in the. conducting airways of the lung.
c. This component of each breath is called the ANATOMIC DEAD SPACE component.

7. Ans. B. Volume of air present after normal expiration

FUNCTIONAL RESIDUAL CAPACITY (FRC Q) is defined as the volume of gas in the lungs at the end of a normal
expiration. During this phase the lungs are partially inflated, so their elastic recoil exerts a force tending to empty
the lungs.

8. Ans. A. 2.3L
Lung Volumes
MEN WOMEN
Total lung capacity 6.4 L 4.9L
Functional residual capacity 2.2 L Q 2.6 L Q
Residual volume 1.5 L 1.2 L
Inspiratory capacity 4.8 L Q 3.7 L Q
Expiratory reserve volume 3.2 L 2.3 L
Vital capacity 1.7 L 1.4 L

9. Ans. B. Apex of lung

Ventilation / perfusion ration (VA/Q):
a. The ratio of pulmonary ventilation to pulmonary blood flow for the whole lung at rest is about 0.8. Q
b. Ventilation, as well as perfusion, in upright position declines in a linear fashion from the bases to the
Apices of the lungs. Q
c. The ventilation/perfusion ratios are high in the upper portion of the lungs (Apices). Q
d. Normally the VA/Q ratio varies from about 0.6 at the base to about 3 at the apex of the lung. Q
e. Due to high VA/ ratio at apices of the lungs, account for the predilection of T.B. for this area because the
relatively high Alveolar Po2, provides favorable environment for the growth to mycobacterium
tuberculosis. Q

10. Ans. B. CO
[Already explained in detail]
a. " The diffusing capacity for CO (DLco) is measured as an index of diffusing capacity of lungs because its
uptake is diffusion limited" Q
b. " Normal value of DLco at rest is about 25ml/min/mm Hg". Q

11. Ans. D. Inspiratory capacity — inspiratory reserve volume

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Chapter - 5
a. The amount of air that moves into the lungs with each inspiration (or that moves out with each
expiration) is known as the tidal volume.
b. The air inspired with a maximal inspiratory effort in excess of the tidal volume is the inspiratory reserve
volume.
c. The volume expelled by an active expiratory effort after passive expiration is the expiratory reserve

Respiration
volume, and the air ‘left’ in the lungs after a maximal expiratory effort is the residual volume.
d. The space in the conducting zone of the airways occupied by the gas that does not exchange with
blood in the pulmonary vessels is the respiratory dead space.
e. The vital capacity is the largest amount of air that can be expired after a inspiratory effort. The vital
capacity equals the inspiratory reserve volume plus the tidal volume plus expiratory reserve volume.

12. Ans. C. Residual volume 2 liters

Male Female
• Inspiratory reserve volume Q 3.3 1.9
• Tidal volume Q 0.5 0.5
• Expiratory reserve volume Q 1.0 0.7
• Vital capacity Q 4.8 3.1
• Residual volume Q 1.2 1.1
• Total lung capacity Q 6.0 4.2

13. Ans. C. Lung compliance

a. TLC  is the maximum valume to which the lungs can be expanded with the greatest possible inspiratory
effort.
b. TLC = IRV +TV + ERV+RV Q= IC + RV Q
c. Compliance (stretchability) of lungs:  is increased in Emphysema (obstructive lungs dis) and decreased
in Interstitial pulmonary fibrosis (Restrictive lung disease). Compliance of lung is change in lung volume
per unit change in airways pressure.
d. TLC is increased in obstructive ling disease (eg. emphysema, CoPD) and decreased in the restrictive lung

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disease (Interstitial pulmonary fibrosis).

14. Ans. C. 6 — 7 litres

Important parameters of lungs:-
a. Vital capacity = IRV + TV + ERV Q = Inspiratory capacity + ERV Q
b. Inspiratory capacity = IRV + TV Q
c. Functional residual capacity = ERV + RV Q
d. Respirator minute volume or Pulmonary ventilation = 6 L/min Q
e. Alveolar ventilation (at rest) = 4.2 L/min Q
f. Maximal voluntary ventilation (BTPS) 125 — 170 L/min Q
g. Timed vital capacity: - 80% of total in 1 second; 97% in 3 seconds Q
h. Work of quite breathing: - 0.5 kg-m/min. Q
i. Maximal work of breathing: - 10kg-m/breath Q
j. TV = 150mL (dead space) + 350 (Alveolar volume) = 500 ml. Q
15. Ans. D. T.V. + I.R.V. + E.R.V.

Fig.: Diagram showing respiratory excursions during normal breathing and during maximal inspiration and
maximal expiration
Lungs capacities

(a) VC = IRV + TV + ERV Q IC = IRV + TV Q

VC=IC+ERV Q FRC = ERV + RV Q

(b) TLC=IRV +TV +ERV +RV Q

or = IC + FRV Q
or=VC +RV Q

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16. Ans. is (C) Lung compliance

1. TLC  is the maximum volume to which the lungs can be expanded with the greatest possible inspiratory effort.
TLC = IRV +TV + ERV+RV Q= IC + RV Q
2.Compliance (stretchability) of lungs:  is increased in Emphysema (obstructive lungs dis) and decreased in Interstitial
pulmonary fibrosis (Restrictive lung disease). Compliance of lung is change in lung volume per unit change in airways
pressure.
3. TLC is increased in obstructive ling disease (eg. emphysema, COPD) and decreased in the restrictive lung disease
(Interstitial pulmonary fibrosis)

Chapter - 5
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Section-5 -: Gas Exchange & Transport

1. Ans. A. CO (Ganong –23rd Ed Page-607)

a. Carbon monoxide (CO) is taken up by hemoglobin in the red blood cells at such a high rate that the partial
pressure of CO in the capillaries stays very low and equilibrium is not reached in the 0.75 s the blood is in
the pulmonary capillaries.
b. Therefore, the transfer of CO is not limited by perfusion at rest and instead is diffusion limited.
c. The diffusing capacity of the lung for a given gas is directly proportionate to the surface area of the
alveolocapillary membrane and inversely proportionate to its thickness.
d. The diffusing capacity for CO (DLCO) is measured as an index of diffusing capacity because its uptake is
diffusion-limited.
e. DLCO is proportionate to the amount of CO entering the blood (VCO) divided by the partial pressure of CO
in the alveoli minus the partial pressure of CO in the blood entering the pulmonary capillaries.
f. The normal value of DLCO at rest is about 25 mL/min/mm Hg. It increases up to threefold during exercise
because of capillary dilation and an increase in the number of active capillaries.

2. Ans. B. More soluble in plasma

(Ref: Ganong - 23rd Page-609)
Definition: The diffusion capacity of the lung (DL)is defined as the volume of gas diffusing across
the respiratory membrane in 1 minute when the pressure gradient is 1 mmHg.
FICK’S LAW
DL = K .A .S
d . MW
Where k is proportionality constant
A = Area of the membrane
S = Solubility of the gas
MW = molecular weight of the gas
D = thickness of the membrane
S
MW is called the diffusion coefficient; the diffusion coefficient is entirely based on
the characteristic of the gas.
DLO2 = 25 mL/ min / mm Hg
DLCO2 is 20 times DLO2 as CO2 is more soluble than O2

3. Ans. A Binding of one O2 molecule increase the affinity of binding of other O2 molecules. This is also called
relative affinity
a. Hemoglobin contains four globin chains and the oxygenation of each chain causes structural changes that
increase the affinity of the haem of the remaining chains for oxygen.
b. This increases oxygen affinity, as oxygen loads is the cause of the sigmoid shape of the dissociation curve.
Initially the slope is flat as affinity is low then due to “relative affinity” the slope increases and then as the
Hb gets saturated the slope again becomes flat (plateau phase).

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Chapter - 5
Oxygen-hemoglobin dissociation curve
4. Ans. D Hypoxanthine (Ref: Ganong – Review of Medical Physiology 22nd Ed)
Factors affecting the concentration of 2,3-BPG in the red cells include pH. Because acidosis inhibits red cell
glycolysis, the 2,3-BPG concentration falls when the pH is low.
a. Thyroid hormones, growth hormone, and androgens increase the concentration of 2,3-BPG and the P50.

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i. Exercise has been reported to produce an increase in 2,3-BPG within 60 minutes, although the
rise may not occur in trained athletes.
ii. The P50 is also increased during exercise, because the temperature rises in active tissues and CO 2
and metabolites accumulate, lowering the pH. In addition, much more O2 is removed from each
unit of blood flowing through active tissues because the tissues' PO2 declines.
iii. Finally, at low PO2 values, the oxygen–hemoglobin dissociation curve is steep, and large amounts
of O2 are liberated per unit drop in PO2.
iv. Ascent to high altitude triggers a substantial rise in 2,3-BPG concentration in red cells, with a
consequent increase in P50 and increase in the availability of O2 to tissues.
v. The affinity of fetal hemoglobin (hemoglobin F) for O2, which is greater than that for adult
hemoglobin (hemoglobin A), facilitates the movement of O2 from the mother to the fetus.
vi. The cause of this greater affinity is the poor binding of 2,3-BPG by the polypeptide chains that
replace chains in fetal hemoglobin.
vii. Red cell 2,3-BPG concentration is increased in anemia and in a variety of diseases in which there
is chronic hypoxia.
viii. This facilitates the delivery of O2 to the tissues by raising the PO2 at which O2 is released in
peripheral capillaries.
ix. In bank blood that is stored, the 2,3-BPG level falls and the ability of this blood to release O2 to
the tissues is reduced.
x. This decrease, which obviously limits the benefit of the blood if it is transfused into a hypoxic
patient, is less if the blood is stored in citrate–phosphate–dextrose solution rather than the usual
acid–citrate–dextrose solution.
xi. Inosine is a nucleoside involved in the formation of purines and a compound with possible roles
in energy metabolism.

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xii. It is a precursor to adenosine, an important energy molecule, and plays many supportive roles in
the body, including releasing insulin, facilitating the use of carbohydrate by the heart, and,
potentially, participating in oxygen metabolism and protein synthesis.
xiii. Many of the effects attributed to inosine stem from its potential role in increasing levels of a
compound known as 2,3 DPG in red blood cells.
xiv. An enhanced 2,3 DPG level would allow an easier release of oxygen from the blood cells to the
tissues.
Hypoxanthine is not mentioned in any of the available literature as having a role in increasing
the 2,3 DPG level.So, by exclusion it becomes the correct answer.

5. Ans. A. Decrease binding with 2,3 DPG (Ref: Ganong – Review of Medical Physiology 22nd Ed)
a. The affinity of fetal hemoglobin (hemoglobin F) for O 2, which is greater than that for adult hemoglobin
(hemoglobin A), facilitates the movement of O2 from the mother to the fetus.
b. The cause of this greater affinity is the poor binding of 2,3-BPG by the polypeptide chains that replace
chains in fetal hemoglobin.
c. Some abnormal hemoglobins in adults have low P 50 values, and the resulting high O2 affinity of the
hemoglobin causes enough tissue hypoxia to stimulate increased red cell formation, with resulting
polycythemia .
d. It is interesting to speculate that these hemoglobins may not bind 2,3-BPG.
e. Factors affecting the concentration of 2,3-BPG in the red cells include
i. pH Q (acidosis inhibits red cell glycolysis, the 2,3-BPG concentration falls when the pH is low).
ii. Thyroid hormones, growth hormone, and androgensQ increase the concentration of 2,3-BPG and the
P50.
iii. ExerciseQ has been reported to produce an increase in 2,3-BPG
iv. Ascent to high altitudeQ triggers a substantial rise in 2,3-BPG concentration in red cells,
v. The affinity of fetal hemoglobin (hemoglobin F) for O2. The cause of this greater affinity is the poor
binding of 2,3-BPG by the polypeptide chains that replace chains in fetal hemoglobinQ.
vi. Red cell 2,3-BPG concentration is increased in anemiaQ and in a variety of diseases in which there is
chronic hypoxia
vii. In bank blood that is stored, the 2,3-BPG level falls. This decrease, is less if the blood is stored in
citrate–phosphate–dextrose solutionQ rather than the usual acid–citrate–dextrose solution.
viii. Inosine increases 2,3 DPG in red blood cells. Q

6. Ans. D. Oxygen affinity of hemoglobin

a. The decrease in oxygen affinity of hemoglobin when the pH of blood falls is known as Bohr effect.
b. Hydrogen ions alter the structure of hemoglobin and increase the release of oxygen.
c. A rise in temperature, CO2 concentration and 2,3 DPG concentration shifts the curve to the right.
d. When curve is shifted to right a higher PO2 is required to bind a given amount of oxygen to hemoglobin.

7. Ans. D’ A and C
2, 3-diphosphoglycerate is an organic phosphate found in RBCs. It alters the affinity of hemoglobin for oxygen.

8. Ans. A. Hypoxia
a. Factors that shift O2- Hb dissociation curve to right - ie. Decrease O2 affinity with Hb:

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i. ed in H+ cone. (pH, Bohr effect) Q

ii. ed CO2 (O2, Hypoxic condition) Q
iii. ed in temperature. Q
iv. ed DPG. Q

b. Factors that shift O2-Hb dissociation curve to the left side ie. increase the O2 affinity with Hb
a. Just reverse of the right b. in temperature c. in pH (7.6) Q
Q Q
shift (Hypothermia)

Chapter - 5
d.  HbF (fetal Hb) Q e. CO poisoning Q

9. Ans. C. 3.6 kPa

a. P50 is the PO2 at which hemoglobin is half (50%) saturated with O2
b. It is the index of affinity of hemoglobin for oxygen Q. Higher the P50, the lower the affinity of hemoglobin
for Oxygen.
c. Under normal conditions
i. When Hb is normal ii. PaCO2 is 110 mm Hg
o
iii. 'Temperature is 37 C iv. 2, 3 DPG is 15 mol/gm of Hb
d. The value of P50 is 25 mm Hg - 3.6 kPa.
e. Note 1 mm Hg = 0.14 kPa

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10. Ans. C. Bohr effect
a. Bohr effect:
i. Definition  the decrease in O2 affinity of Hb when the pH of the blood falls is called the Bohr effect Q
ii. Deoxy Hb binds H+ more actively than does oxy Hb.
iii. PH of blood falls as its CO2 content increases so that when the PCO2 rises the curve shifts to the right
and the P50 rises  this is Bohr effect.
b. Haldone effect:  CO2 transport in blood: 
i. Definition  the ability of deoxygenated - blood to carry more CO2 than oxygenated Hb. Q
ii. Deoxygenated Hb (weak acid) binds more H+ than oxy Hb (stronger acid) does and forms carbamino
compound (Hb-CO2).
iii. Venous blood carries more CO2 than Arterial blood and CO2 uptake is facillated in tissues and CO2
release is facilitated in the lungs.
iv. Thus the Haldane effect aproximately doubles the amount of CO2 released from the blood in the
lungs and approximately doubles the pickup of CO2 in the tissues Q.

11. Ans. A. Anatomical dead space — end inspiration phase

a. During inspiration atmospheric air enters into respiratory passage (that contain O 2, 20.84%, and CO2,
0.04%)  that air in the respiratory passages before entering the alveoli, becomes humified (i.e. at the
end of inspiratory phase, anatomical dead space contain humified air that contains O2, 19.67% and CO2,
0.04 %)
b. During expiration: Expired air is a combination of dead space air and alveolar air.
i. First portion of expired air, is the dead space air, and is typically humified air.
ii. Then progressively more and more alveolar air becomes mixed dead space air until all the dead space

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air has finally been washed out and nothing but alveolar air is expired at the end of expiration.
Therefore
i. Dead space (Anatomical)  At the end of inspiration contains hummed air i.e. O219.69% (or 149.3mmHg),
CO2 - 0.04% (or 0.3 mmHg) and N2 -74.09% (or 563 mm Hg)
ii. Alveoli  alveolar air composition remains relatively constant either during expiration or inspiration i.e.
Alveolar air contain O2 13.6% (or 104 mm Hg), CO2 5.3% (or 40 mm Hg)
iii. Dead space at the end of expiration: contains alveolar air Le. O2 13.6%, and CO2 5.3%.
Therefore Ans is Dead space at the end of inspiration contains least amount of CO2. Q

12. Ans. A. Hb

13. Ans. B. Bicarbonate

a. The solubility of carbon dioxide in blood is about 20 times that of oxygen Q, so that there is considerably
more carbon dioxide than oxygen in simple solution at equal partial pressures.
b. The carbon dioxide that diffuses into RBCs is rapidly hydrated to H2CO3 because of the presence of
carbonic anhydrase. Q
c. The H2CO3 dissociates to H+ and H2CO3 , and the AH+ is buffered, primarily by hemoglobin, while the HCO3-
enters the plasma ‘Some’ of the carbon dioxide in the ABCs reacts with the amino groups of proteins
principally hemoglobin, to form carbamino compounds.

14. Ans. A. 16%

Affective ventilation in a child can be achieved by mouth-to-mouth breathing with nose seal which can provide the
victim a FiO2 (fraction of oxygen in inspired air) of about 0.16— 0.17

15. Ans. C. 80 mmHg

According to Henry’s Law Q
a. When pressure is expressed in atmospheric (1 atmospheric = 760 mmHg) and conc. is expressed in
volume of gas dissolved in each volume of water, the solubility coefficient for gases at body temperature.
b. In these question
c. Conc Of O2 in blood
= 0.025 ml/ml
= 2.5 ml/L
d. We know that normal dissolved O2 is 0.3 ml% gives a PaO2 of around 95-98 mm Hg( ~ 100 mm Hg)
e. So, 0.25ml% would give roughly 80 mm Hg.

16. Ans. ‘B’ Positive cooperativity

a. Hb - O2  dissociation curve  sigmoid curve Q
b. Myoglobin - O2  dissociation curve  Rectangular hyperbola Q
c. Hb combines with 4 mole of O2 Q
d. Myoglobin combines with 1 mole of O2 Q
e. (Cooperative effect to combine O2) Q
f. Unlike Myoglobin, hemoglobin shows: Q
i. Tetrameric structure Q
ii. Can bind four O2 molecule Q

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iii. Sigmoid saturation kinetics Q

iv. Co-operativity (positive) or co-operative binding kinetics, a property that permits it to bind a maximal
quantity of O2 at the respiratory organ and to deliver a maximal quantity of O 2 at peripheral tissue.
Here binding of heme in Hb molecule with O2 facilitates/promotes binding of other O2 molecule thus
positive co-operativity. Q

17. Ans. is (A) Anatomical dead space — end inspiration phase

Ref: Ganong, 22nd Edition, Page no 658

Chapter - 5
1. During inspiration ~ atmospheric air enters into respiratory passage (that contain O2, 20.84%, and CO2,
0.04%)  that air in the respiratory passages before entering the alveoli, becomes humified (i.e. at the end
of inspiratory phase, anatomical dead space contain humified air that contains O2, 19.67% and CO2, 0.04
%)
2. During expiration: Expired air is a combination of dead space air and alveolar air.
a. First portion of expired air, is the dead space air, and is typically humified air.
b. Then progressively more and more alveolar air becomes mixed dead space air until all the dead
space air has finally been washed out and nothing but alveolar air is expired at the end of
expiration.
Therefore
1. Dead space (Anatomical)  At the end of inspiration contains hummed air i.e. O219.69% (or
149.3mmHg), CO2 - 0.04% (or 0.3 mmHg) and N2 -74.09% (or 563 mm Hg)
2. Alveoli  alveolar air composition remains relatively constant either during expiration or
inspiration i.e. Alveolar air contain O2 13.6% (or 104 mm Hg), CO2 5.3% (or 40 mm Hg)
3. Dead space at the end of expiration: contains alveolar air Le. O2 13.6%, and CO2 5.3%.

Respiration
Therefore Ans is Dead space at the end of inspiration contains least amount of CO2. Q

Section-6 -: Regulation of Respiration

1. Ans. C Thoracic muscle spindles (Ref: 23rd edition Ganong's Page-625)

a. Regulation of Respiratory Activity
i. A rise in the PCO 2 or H+ concentration of arterial blood or a drop in its PO 2 increases the level of
respiratory neuron activity in the medulla, and changes in the opposite direction have a slight
inhibitory effect.
ii. The effects of variations in blood chemistry on ventilation are mediated via respiratory
chemoreceptors—the carotid and aortic bodies and collections of cells in the medulla and elsewhere
that are sensitive to changes in the chemistry of the blood.
iii. They initiate impulses that stimulate the respiratory center. Superimposed on this basic chemical
control of respiration, other afferents provide non-chemical controls that affect breathing in
particular situations.

Table 37–1 Stimuli Affecting the Respiratory Center.

Chemical control
CO2 (via CSF and brain interstitial fluid H+ concentration)

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O2 (via carotid and aortic bodies)

H+
Non-chemical control
Vagal afferents from receptors in the airways and lungs
Afferents from the pons, hypothalamus, and limbic system
Afferents from proprioceptors
Afferents from baroreceptors: arterial, atrial, ventricular, pulmonary

b. J receptors :
i. They are stimulated by hyperinflation of the lung, but they respond as well to intravenous or
intracardiac administration of chemicals such as capsaicin.
ii. The reflex response that is produced is apnea followed by rapid breathing, bradycardia, and
hypotension (pulmonary chemoreflex). A similar response is produced by receptors in the heart
(Bezold–Jarisch reflex or the coronary chemoreflex).
iii. The physiologic role of this reflex is uncertain, but it probably occurs in pathologic states such as
pulmonary congestion or embolization, in which it is produced by endogenously released
substances
c. Stretch receptors in bronchioles : cause Hering–Breuer reflexes
i. The shortening of inspiration produced by vagal afferent activity is mediated by slowly adapting
Stretch receptors.
ii. The Hering–Breuer inflation reflex is an increase in the duration of expiration produced by steady
lung inflation, and the Hering–Breuer deflation reflex is a decrease in the duration of expiration
produced by marked deflation of the lung.
iii. They limit the inspiration and expiration therefore help in maintain normal tidal resting respiration
(AIIMS nov 2010)
d. Proprioceptors : Muscle spindles, Golgi tendon organs etc
i. Carefully controlled experiments have shown that active and passive movements of joints stimulate
respiration
ii. Presumably because impulses in afferent pathways from proprioceptors in muscles, tendons, and
joints stimulate the inspiratory neurons.
iii. This effect probably helps increase ventilation during exercise.
e. Muscle spindle cause Stretch reflex or the “Loading reflex” their stretching during inspiration leads to
“loading” of spindle and help in sensing “inspiratory volume”

2. Ans. C. J receptor (Ref: Ganong –Page-625)

a. Factors affecting the respiratory centre
i. Chemical
CO2 / O2 / H+: via chemoreceptors. infact CO2 is the main drive for respiration.
ii. Non – chemical
 Vagal afferents from airways / lungs : Via Stretch receptors called as Hering-Breuer Reflexes
o Hering-Breur Inflation reflex is an increase in the duration of expiration - produced by

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 Respiration

steady lung inflation.

o Hering-Breuer deflation reflex is a decreased in the duration of expiration produced by
marked deflation of the lung .
They maintain normal tidal, resting ventilation and prevent hyperinflation & collapse of lungs.
 OTHER FACTORS
o Pons / hypothalamus / limbic system
o Proprioceptors
o Baroreceptors

Chapter - 5
b. J-Reflex (J receptors or Juxtracapillary receptors):
i. They are present in alveolar interstitium, supplied by Unmyelinated C fibres of vagus.
ii. They are stimulated by hyperinflation of the lung, but they respond as well to intravenous or
intracardiac administration of chemicals such as Capsaicin, Increased fluid in alveolar interstitium.
iii. The reflex response that is produced is apnea followed by rapid breathing, bradycardia and
hypotension (pulmonary chemoreflex). Eg. CHF, Pulmonary odema, Heavy exercise etc.
iv. They have no role in physiological conditions so are not required to maintain resting respiration.

3. Ans. B. Pre – botzinger complex (Ref: Ganong – 23rd Ed. Pg 625, 10th Ed & Samson Wright Applied
Physiology13th ED.Pg 168.)
a. MEDULLA – has pre botzinger complex Q (between nucleus ambiguous and lateral rectal nucleus) which

Respiration
acts as pacemaker for spontaneous respiration, also contains DRG & VRG (DORSAL &VENTRAL
RESPIRATORY GROUP OF NEURONS).
i. DRG - contains inspiratory neurons which supply inspiratory muscles.
ii. VRG - both inspiratory & expiratory neurons.
b. PONS – contain 2 centres
i. Apneustic centre (in lower pons) : stimulates inspiratory neurons. If not inhibited by vagus and
pneumotaxic centre will cause apneusis Q.
ii. Pneumotaxic centre (in upper pons) : inhibit apneustic centre Q. Near Parabranchial Nucleus (NPBL) Q

4. Ans. D. Prebotzinger complex Ref: Ganong - Review of Medical Physiology 23rd Ed. Pg 629
a. MEDULLA – has pre botzinger complex which acts as pacemaker for spontaneous respiration, also contains
DRG & VRG (DORSAL &VENTRAL RESPIRATORY GROUP OF NEURONS).
i. DRG - contains inspiratory neurons which supply inspiratory muscles.
ii. VRG - both inspiratory & expiratory neurons.
b. PONS – contain 2 centres
i. Apneustic centre (in lower pons) : stimulates inspiratory neurons. If not inhibited by vagus and
pneumotaxic centre will cause apneusis.
ii. Pneumotaxic centre (in upper pons) : inhibit apneustic centre.

5. Ans. D. Deep breathing

(Ref: Ganong – 23rd Ed. Pg 625
MEDULLA – has pre botzinger complex Q (between nucleus ambiguous and lateral rectal nucleus) which acts as
pacemaker for spontaneous respiration, also contains DRG & VRG (DORSAL &VENTRAL RESPIRATORY GROUP OF
NEURONS)

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a. DRG - contains inspiratory neurons which supply inspiratory muscles

b. VRG - both inspiratory & expiratory neurons
PONS – contain 2 centres
a. Apneustic centre (in lower pons) : stimulates inspiratory neurons. If not inhibited by vagus and
pneumotaxic centre will cause apneusis Q.
b. Pneumotaxic centre (in upper pons) : inhibit apneustic centre Q. Near Parabranchial Nucleus (NPBL) Q

1. Effect of Lesion/ Transection of brainstem on respiration

a. Section A: Above pons : Normal tidal respiration but voluntary control is lost. If vagus also cut then
slow & deep breathing because vagus inhibits apneustic centre Q.
b. Section B: At Mid pons : loss of inhibitory action of pneumotaxic centre on apneustic centre there is
stimulation of inspiratory neurons by apneustic resulting in slow and deep breathing. If vagus also cut
then APNEUSIS Q.
c. Section C: Between Pons & Medulla: Spontaneous respiration continues, although somewhat-
irregular and gasping Q because respiration is produced by medulla but made rhythmic & regular by
pontine centres Q.
d. Section D: Below medulla: No respiration. Q

6. Ans. A. Increase in CO2 Tension. (Ref: Ganong - Review of Medical Physiology 22nd Ed)
Central chemoreceptors :
a. The chemoreceptors that mediate the hyperventilation produced by increases in arterial PCO2 after the
carotid and aortic bodies are denervated are located in the medulla oblongata and consequently are called
medullary chemoreceptors.
b. They are separate from the dorsal and ventral respiratory neurons and are located on the ventral surface
of the medulla.
c. The chemoreceptors monitor the H + concentration of CSF, including the brain interstitial fluid.

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d. CO2 readily penetrates membranes, including the blood–brain barrier, whereas H+ and HCO3– penetrate
slowly.
e. The CO2 that enters the brain and CSF is promptly hydrated.
f. The H2CO3 dissociates, so that the local H+ concentration rises. The H+ concentration in brain interstitial
fluid parallels the arterial PCO2.
g. Experimentally produced changes in the PCO2 of CSF have minor, variable effects on respiration as long as
the H+ concentration is held constant, but any increase in spinal fluid H+ concentration stimulates
respiration.
h. The magnitude of the stimulation is proportionate to the rise in H+ concentration.

Chapter - 5
i. Thus, the effects of CO2 on respiration are mainly due to its movement into the CSF and brain interstitial
fluid, where it increases the H+ concentration and stimulates receptors sensitive to H+.
Regulation of respiratory activity
a. A rise in the PCO2 or H+ concentration of arterial blood or a drop in its PO2 increases the level of
respiratory neuron activity in the medulla, and changes in the opposite direction have a slight inhibitory
effect.
b. The effects of variations in blood chemistry on ventilation are mediated via respiratory chemoreceptors—
the carotid and aortic bodies and collections of cells in the medulla and elsewhere that are sensitive to
changes in the chemistry of the blood.
c. They initiate impulses that stimulate the respiratory center.
d. Superimposed on this basic chemical control of respiration, other afferents provide nonchemical controls

Respiration
that affect breathing in particular situations
Chemical control of breathing
a. The chemical regulatory mechanisms adjust ventilation in such a way that the alveolar PCO2 is normally
held constant, the effects of excess H+ in the blood are combated, and the PO2 is raised when it falls to a
potentially dangerous level.
b. The respiratory minute volume is proportionate to the metabolic rate, but the link between metabolism
and ventilation is CO2, not O2.
c. The receptors in the carotid and aortic bodies are stimulated by a rise in the PCO2 or H+ concentration of
arterial blood or a decline in its PO2.
d. After denervation of the carotid chemoreceptors, the response to a drop in PO 2 is abolished; the
predominant effect of hypoxia after denervation of the carotid bodies is a direct depression of the
respiratory center.
e. The response to changes in arterial blood H+ concentration in the pH 7.3-7.5 range is also abolished,
although larger changes exert some effect.
The response to changes in arterial PCO2, on the other hand, is affected only slightly; it is reduced no more than 30-
35%.

7. Ans. C. Low O2 Tension

a. Hering-Breuer Reflexes:
i. Hering-Breur Inflation reflex is an increase in the duration of expiration - produced by steady lung
inflation. Q
ii. Hering-Breuer deflation reflex is a decreased in the duration of expiration produced by marked
deflation of the lung .Q
b. J-Receptors (Juxtracapillary):

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They are stimulated by hyperinflation of the lung, but they respond as well to intravenous or intracardiac
administration of chemicals such as Capsaicin. The reflex response that is produced is apnea followed by rapid
breathing, bradycardia and hypotension (pulmonary chemoreflex). Q
c. Head's paradoxical reflex:
i. With the completion of second stage of labour, certain events play a major role in the initiation of
respiration
ii. Clamping of umbilical cord results in a fall in arterial oxygen and slight rise in carbon dioxide tension.
These factors taken together stimulate the respiratory centre directly and via the chemoreceptors in
carotid body.
iii. Sensory impulses from changes in skin temperature and proprioceptive impulse from joints directly
stimulate the respiratory centre.
iv. With inflation of the lungs there is augmentation of respiratory effort - Head's paradoxical reflex.

8. Ans. B. Brain
An increase in CO2 concentration causes moderate vasodilatation in most tissues and marked vasodilatation In the
brain.

9. Ans. A. Cyanide
[A] Peripheral chemoreceptor system for control of Respiratory activity: -
a. These chemoreceptor located in —
i. Carotid bodies Q  at the birfurcation of the common carotid artery Q (bilaterally)  Afferent fibers
via Hering’s Nerve of IX CN Q to the dorsal respiratory area of the medulla.
ii. Aortic bodies  located in arch of Aorta Q  afferent fiber via X CN Q to dorsal respiratory area of the
medulla.
b. These receptors are stimulated by: -
i. A rise in PCO2 of arterial blood Q
ii. A rise in H+ conc. (ie in PH i.e. Metabolic acidosis) of arterial blood and Q
iii. A decline in the PO2 of arterial blood. Q
[If these changes in opposite direction, have a slight inhibitory effect on respiration]
c. These carotid and Aortic bodies  contain type I cells (glomus) and Type II cells. On stimulation by
hypoxia and cyanide release catecholamine  Dopamine is the principle transmitter.
d. Blood flow in each 2 mg carotid body is about 0.04 mL/min. or 2000 ml/100gm of tissue/min.
e. Because the blood flow per unit of tissue is so enormous, the O2 needs of the cells can be met largely by
dissolved
f. O2 alone. Therefore, the receptors are not stimulated in conditions such as Anemia and Carbon
Monooxide poisoning, in which the amount of dissolved O2 in the blood reaching the receptor is generally
normal even though the combined O2 in the blood is markedly decreased.
g. The receptors are stimulated when the arterial PO2 is low (i.e. Hypoxic Hypoxia) or when, because of
vascular stasis, the amount of O2 delivered to the receptor perunit time is decreased (i.e. stagnant or
Ischemic hypoxia)
h. Powerfull stimulatin of receptors is also produced by drugs such as cyanide, which prevent O 2 utilization at
the tissue level (Histotoxic hypoxia).

10. Ans. B- Increased FRC Increased Residual Vol

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11. Ans. D -Prebotzinger complex

12. Ans. D. Deep breathing

Section-7 -: Applied Respiratory Physiology

1. Ans. C. Increased solubility of nitrogen in nerve cell membrane

a. Nitrogen narcosis( inert gas narcosis, raptures of the deep, Martini effect) is a reversible alteration in

Chapter - 5
consciousness that occurs while scuba diving at depth as under high pressure nitrogen becomes soluble in
blood and reaches the brain.
b. Apart from helium, and probably neon, all gases that can be breathed have a narcotic effect, which is
greater as the lipid solubility of the gas increases.
c. The precise mechanism is not well understood, but it appears to be the direct effect of gas dissolving into
nerve membranes and causing temporary disruption in nerve transmissions.
d. Some of these effects may be due to antagonism at NMDA receptors and potentiation of GABA A receptors.
Similar to the mechanism of ethanol's effect, the increase of gas dissolved in nerve cell membranes may
cause altered ion permeability properties of the neural cells' lipid bilayers.
e. An early theory, the Meyer-Overton hypothesis suggested that narcosis happens when the gas penetrates
the lipids of the brain's nerve cells, causing direct mechanical interference with the transmission of signals

Respiration
from one nerve cell to another.

2. Ans. D. Polycythemia with possible dehydration.

(Ref. H-18th /pg. 130, 362)
a. Hematocrit levels >50% in men or >45% in women may be abnormal. Hematocrits >60% in men and >55%
in women are almost invariably associated with an increased red cell mass.
b. Polycythemia can be spurious (related to a decrease in plasma volume; Gaisbock’s syndrome), primary, or
secondary in origin.
c. The secondary causes are all associated with increases in EPO levels: either a physiologically adapted
appropriate elevation based on tissue hypoxia (lung disease, high altitude, CO poisoning, high-affinity
hemoglobin- opathy) or an abnormal overproduction (renal cysts, renal artery stenosis, tumors with
ectopic EPO production).
d. A rare familial form of polycythemia is associated with normal EPO levels but hyperresponsive EPO
receptors due to mutations.
e. Hypoxia is the principal stimulus for causing an increase in red blood cell production.
f. Ordinarily, when a person remains exposed to low oxygen for weeks at a time, the hematocrit rises
slowly from a normal value of 40 to 45 to an average of about 60, with an average increase in whole
blood hemoglobin concentration from normal of 15 g/dl to about 20 g/dl.
g. In addition, the blood volume also increases, often by 20 to 30 per cent, and this increase times the
increased blood hemoglobin concentration gives an increase in total body hemoglobin of 50 or more per
cent.

Chronic mountain sickness or Monge disease

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 Physiology

a. An increase in RBC production and resulting polycythemia are normal responses to high altitude. However,
some high-altitude residents become severely symptomatic as a result of excessive polycythemia. This
condition has been called chronic mountain sickness, or Monge disease.
b. Symptoms of Monge disease range from diminished mental and physical capacity to headaches,
personality changes, unconsciousness, and coma.
c. Healthy men at 4540 m (14,900 ft) have hematocrits of approximately 60% and hemoglobin values of 19
g/dL.
d. Patients with Monge disease may have hematocrits as high as 84% and hemoglobin concentrations of 28
g/dL.
e. Normal arterial saturation at that altitude (ie, 81%) may fall as low as 60% in affected individuals.

ADAPTATION TO HIGH ALTITUDE

a. Partial pressure of oxygen falls with increasing altitude
b. Results in acute / chronic hypoxia with adaptation

Acute
a. Alveolar PO2 needs to fall to 60mmHg and below to stimulate ventilation via the carotid body *
b. As ventilation increases, CO2 is lost and the fall in PCO2 reduces respiratory drive from the central
chemoreceptors, off-setting the carotid body response *
c. Carotid bodies also elicit reflex vasoconstriction with increased heart rate and cardiac out-put. Blood is
diverted from the skin and splanchnic circulations to vital organs *
d. The fall in PCO2 increases the ability of Hb to bind oxygen (reverse Bohr effect) – resulting in a higher Hb
saturation for a given alveolar PO2 *
e. Mountain sickness is characterised by headache, nausea, giddiness, GI disturbance, fatigue and impaired
mental function.
f. Sleep apnoea occurs at altitudes > 4000m and pulmonary oedema may occur above 3000m.

Chronic
a. Increased minute respiratory volume – the respiratory alkalosis caused by hyperventilation is
compensated by excretion of bicarbonate by the kidneys. Plasma pH is restored to normal within 1 week
of ascent.
b. Increased red cell mass – stimulated by erythropoietin secreted by the kidneys in response to low PO 2.
c. Increased production of 2,3-diphosphoglycerate by red cells resulting in a right shift of the oxygen
dissociation curve.
d. Increased cardiac out-put.
e. Increased vascularization of tissues.
f. Relative polycythemia is an apparent rise of the erythrocyte level in the blood; however, the underlying
cause is reduced blood plasma.
g. Relative polycythemia is often caused by loss of body fluids, such as through burns, dehydration and
stress. Rarely, relative polycythemia can be caused by apparent polycythemia also known as Gaisböck's
syndrome.
h. Apparent polycythemia primarily affects middle-aged obese men and is associated with smoking,
increased alcohol intake and hypertension.

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3. Ans. C. Ref: Ganong - 23rd Ed. –Page-625

a. Hypoxia is O2 deficiency at the tissue level. Traditionally, hypoxia has been divided into four types.
i. The four categories are
b. Hypoxic hypoxia, in which the PO2 of the arterial blood is reduced; so, depends on FiO2 in inspired air.
c. Anemic hypoxia, in which the arterial PO 2 is normal but the amount of hemoglobin available to carry O2
is reduced; so, it depends on amount of Hb.
d. Stagnant or ischemic hypoxia, in which the blood flow to a tissue is so low that adequate O2 is not
delivered to it despite a normal PO2 and hemoglobin concentration; and

Chapter - 5
e. Histotoxic hypoxia, in which the amount of O2 delivered to a tissue is adequate but, because of the action
of a toxic agent, the tissue cells cannot make use of the O2 supplied to them.

Hypoxic Anaemic Stagnant Histotoxic

Underlying cause PaO2 is ed Amount of O2 carrying capacity is normal No utilization at
available Hb but O2 delivery is decreased tissue level
decreases
Examples High altitude, Anaemic, CO Heart failure shock Cyanide
lung disease poisoning hemorrhage poisoning
PaO2 ed Normal Normal Normal
O2 Content dissolved ed Normal Normal Normal
Combined (with Hb) ed ed Normal Normal

Respiration
Chemoreceptors Stimulated (+) Not stimulated Strongly stimulated (+++) Strongly
stimulation stimulated (+++)
Amount of reduced ed Total Hb ed, ed ed
Hb % of reduced Hb
ed
Cyanosis Can be present NEVER Can be present NEVER

SO, Level of hypoxia depends on Hb( anemic hypoxia), FiO2 HYPOXIC HYPOXIA) & Altitude (HYPOXIC HYPOXIA) but
not pCO2. infact high p CO2 can lead to hyperventilation and increase oxygen supply.
But if the question is about hypoxaemia , then Ans. Will be Hb Hypoxaemia →↓PaO2 of blod or decrease O2
tension

4. Ans. B. High position of the larynx

(REF: Endoscopic evaluation and treatment of swallowing disorders. Susan 6
In infants, the larynx is in a high position in the neck, residing adjacent to the cervical vertebrae C1-3, in contrast to
position in adults, at the C6-7 vertebral level (Fig. 13-21.
a. As a consequence of the high resting level of the larynx, the epiglottis passes superiorly to the free margin
of the soft palate and projects into the nasopharynx.
b. The high position of the larynx func-tionally separates the respiratory and digestive tracts until 4 to 6
months postnatally by minimizing the overlap of the hypopharyngeal airway and the esoph-ageal inlet
tracts

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 Physiology

c. This positioning forces a bolus to divert around the epiglottis as the pharynx fills with the bolus and
contracts sequentially for swallowing .
d. The close proximity of hypopharyngeal structures re-quires cessation of respiration during swallowing to
minimize the risk of aspiration (Ardran et al, 1958; Bosma, 1985; Koenig et al)

5. Ans. B. Increased FRC Increased Residual Vol

(Ref: Ganong - Review of Medical Physiology 23rd Ed, Harrison - principles of internal medicine 17th ed.)
Obstructive lung disease Restrictive lung disease
Residual volume Increase Q Decrease Q
FRC Increase Q Decrease Q
Total lung capacity Normal to increase Q Decrease Q
Q
Diffusion capacity Normal (except emphysema) Decreased Q
Vital capacity Decrease Q Decrease Q
FEF 25-75% Decrease Q Normal Q
Q
FEV1/FVC (Most Imp) Decrease Normal to increase Q

Obstructive lung disease include Q: Asthma, Bronchiectasis, chronic bronchitis & Emphysema
(COPD),Bronchiolitis, Cystic fibrosis
Restrictive lung disease include Q:
a. Interstitial lung diseases (the most common of which are sarcoidosis, rheumatoid lung, scleroderma lung, the
pneumoconioses, histocytosis X, lymphangitic carcinomatosis, and idiopathic pulmonary fibrosis)
b. Chest wall deformities (kyphoscoliosis, Ankylosing spondylitis, thoracoplasty)
c. Pleural fibrosis
d. Alveolar-filling disease (alveolar proteinosis, alveolar cell carcinoma, desquamative interstitial pneumonia,
and alveolar microlithiasis)

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 Respiration

e. Neuromuscular disease (e.g., myasthenia gravis, amyotrophic lateral sclerosis,GB syndrome, Diaphragmatic
palsy)

6. Ans. A. The binding capacity of CO to HB with high avidity

(Ref: Ganong - Review of Medical Physiology 23rd Ed. Pg:625)
a. The uptake of CO is diffusion limited Q as it has very high affinity for Hb Q so it crosses the alveolar
membrane and maximally binds to Hb and very little dissolves in blood. Therefore the partial pressure of
CO in the blood entering the pulmonary capillaries is zero except in habitual cigarette smokers.
b. The affinity of hemoglobin for CO is 210 times its affinity for O2, and COHb liberates CO very slowly Q.

Chapter - 5
c. CO is toxic because it reacts with hemoglobin to form carbon monoxyhemoglobin (carboxyhemoglobin,
COHb), and COHb cannot take up O2.
d. Carbon monoxide poisoning is often listed as a form of anemic hypoxia Q because the amount of
hemoglobin that can carry O2 is reduced, but the total hemoglobin content of the blood is unaffected by
CO.
e. An additional difficulty is that when COHb is present the dissociation curve of the remaining HbO 2 shifts to
the left, decreasing the amount of O2 released. This is why an anemic individual who has 50% of the
normal amount of HbO2 may be able to perform moderate work, whereas an individual whose HbO 2 is
reduced to the same level because of the formation of COHb is seriously incapacitated Q.
f. The diffusing capacity for CO (DLCO) is measured as an index of diffusing capacity because its uptake is
diffusion-limited Q.

Respiration
Perfusion limited Q: (Perfusion dependent; free flow across membrane) when the gas passing through
equilibrates early in the course thru the capillary. now the only way to increase diffusion is to increase the
blood flow thru the capillary. eg: O2 at rest is exchanged by perfusion limited mechanism Q.

Diffusion limited Q: (Not dependent on perfusion; diffusion across membrane is hampered),the gas in the
blood and alveoli does not equilibrate even after reaching the end of the capillary. The partial pressure
gradient is present even after passage thru the capillaries. eg: Carbon Monoxide & in case of restrictive
lung disease Q, the thickening of the alveolar membrane does not allow proper diffusion across it.

7. Ans. A. Certain min. amount of reduced Hb should be present.

(Ref: Ganong - Review of Medical Physiology 23rd Ed-609)
a. Cyanosis is a blue colouration of the skin and mucous membranes due to the presence of > 5g/dl reduced
hemoglobin in blood vessels near the skin surface.Now since in anemia the total amount of hemoglobin is
decreased, the amount of reduced Hb to produce Cyanosis is not sufficient eg.
b. Suppose Hb is 8 gm% and 50% of Hb is reduced then we will have reduced Hb of 4 gm% and no cyanosis

8. Ans. D. It is associated with pulmonary hypertension. (Ref. Ganong Physiology 21st ed. pg. 690)
a. Small percentage of people who ascend rapidly to high altitudes become acutely sick and can die if not
given oxygen or removed to a low altitude.
b. The sickness begins from a few hours up to about 2 days after ascent. It is called acute mountain sickness
and more common in Unacclimatized individuals, after exercise and if ascend is done without rest.
c. Acute mountain sickness presents with acute pulmonary edema.

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 Physiology

d. The severe hypoxia causes the pulmonary arterioles to constrict potently, but the constriction is much
greater in some parts of the lungs than in other parts, so that more and more of the pulmonary blood flow
is forced through fewer and fewer still unconstricted pulmonary vessels.
e. The capillary pressure in these areas of the lungs becomes especially high (so associated with pulmonary
hypertension) and local edema occurs. Extension of the process to progressively more areas of the lungs
leads to spreading pulmonary edema and severe pulmonary dysfunction that can be lethal. Allowing the
person to breathe oxygen usually reverses the process within hours. So high-altitude pulmonary edema is
a patchy edema of the lungs that is related to the marked pulmonary hypertension that develops at high
altitude.

9. Ans. A. Hyperventillation
Effect of decreased Barometric pressure  due to increasing (high)altitude  Lead to  PO2
a. At 3000m (10,000 feet) — Po is 6OmmHg (above the sea level) Hypoxic stimulation of chemo receptors
 es ventilation (Hyper ventilation Q) fall in arterial PCO2 —Respiratory alkalosis Q
b. Acute Hypoxic symptoms -Acute mountain sickness  in unacclimatized persons: -
i. At 3700m (12000 feet)  symptoms :irritability, drowsiness, lassitude, mental and muscle fatigue.
ii. Above 18,000 feet  seizures
iii. Above 23,000 feet  (conciousness lost)
c. Delayed effects of high altitude -
This syndrome develops 8-24 hours after arrival and last 4-8 days. It is C/B: -
i. Headache, irritability, insomnia, breathlessness and nausea and vomitting. Q
ii. Cause  cerebral edema due to arteriolar dilation Q
iii. T/t  for Alkalosis  Acetazolamide and for cerebral edema  gluco-corticoids Q
iv. High altitude pulmonary edema is a serious form of mountain sickness  pulmonary edema prone to
occurs in individual who ascend quickly to altitudes above 2500m and engage in heavy physical
acitvity during the first 3 days after arival. It is associated with marked pulmonary hypertension.
Nifedipine is of value in the t/t and prevention of the condition, also rest and O 2. Q
d. Acclimatization refers to changes in the body tissues in response to long term exposure to hypoxia i.e. at
high altitude for days, weeks or years  the person becomes more and more acclimatized to low PO2. The
principal means by which acclimatization comes about are: -
i. A great increase in pulmonary ventilation Q  on immediate exposure to very low Po2, the hypoxic
stimulation of the chemoreceptors increase alveolar ventilation about 65% above normal. This is
immediate compensation for the high altitude.”
ii. Increased in RBC Q  Due to hypoxia   erythropoietin  polycythemia
iii. Increased diffusion capacity of lungs Q  it increased three folds above the normal; and Increased
T.L. capacity.
iv. Pulmonary Hypertension Q  Note that hypoxia causes vasoconstriction in lungs.
v. Increased vascularity of the tissue Q  density es in skeletal and cardiac muscle.
vi. Increased ability of the cells to use O2, despite the low PO2 Q  due to ed conc of oxidative
enzymes and ed density of mitochondria at cellular level.

10. Ans. D. Shift in the oxygen dissociation curve to the left

Ascent to high attitude triggers a substantial rise in 2,3-DPG concn in RBC, with a consequent increase in P50 and
increase in availability of O2 to tissues (O2 dissociation curve shift to right).

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 Respiration

Right shifting of O2, dissociation curve Q

a.  Temperature b.  H+ conc ( pH value) c.  2, 3 – DPG
d. CO2 e. Exercise f. High altitudes
g. Hypoxia

11. Ans. C. Decreased cerebral blood flow

Oxygen toxicity refers to high P02 at cellular level which can damage intracellular enzymes and may form highly
reactive ionic species. The tissues most susceptible to oxygen toxicity are:

Chapter - 5
a. CNS (as nerve cells-.are most sensitive to hypoxia): Most prominent neurological symptom is convulsions
followed by unconsciousness.
b. Lungs (they are first to be exposed): The lungs have a very large area in contact with the breathing gas and
contain thin membranes with limited antioxidant defenses, making them particularly susceptible to damage by
oxygen. Pulmonary toxicity occurs with prolonged exposure of 16–24 hours or more to elevated concentrations of
oxygen greater than 50%. Prolonged exposure produces pulmonary fibrosis leading to diffusion defect & Pulmonay
Odema.
c. Eyes: can lead to retrolental fibroplasia or retinopathy of prematurity (ROP) in infants
The effect of hyperbaric oxygenation on the cerebral blood flow have been well studied. It has been demonstrated
that in response to hyperbaric oxygenation cerebral blood flow is decreased because of cerebral vasoconstriction
13,19,28,49
.Debate exists as to whether the vasoconstriction is a result of blood oxygen per se or a secondary change
in carbon dioxide48 .Even in the presence of cerebral vasoconstriction, the total amount of the oxygen available to

Respiration
the brain is believed to be increased4,12,14,29,46,50,51.However it can be argued that the relief of cerebral anoxia may
be completely negated by the decrease in blood flow5,20.In quantitative terms ,Lembertsen31 and Jacobson19 have
shown that blood flow is decreased by approximately 25%. At three atmosphere absolute the additional oxygen is
dissolved in the plasma is increased by 100% in terms of normal arteriovenous oxygen extractions, thereby
increasing available oxygen25,26
So, there is decreased cerebral blood flow in oxygen toxicity but it is protective in nature and not a part of disorders
seen in O2 toxicity.

12. Ans. A. Decrease in work load, increase in duration of exercise.

a. Exercise increases oxygen requirement while at high altitudes the oxygen availability is poor.
b. Exercise performed at high altitudes hastens the process of acclimatization
c. Exercise performance is impaired at high altitude even after short term acclimatization.
d. Regular maximal strength exercise induces synthesis of more myofibrils and hence hypertrophy of active
muscle cell, thereby producing maximal anabolic effect.
e. One of the cardinal principles of muscle development during athletic training is the following:

i. Muscles that function under no load, even if they are exercised for hours on end, increase little in strength.
At the other extreme, muscles that contract at more than 50 per cent maximal force of contraction will
develop strength rapidly even if the contractions are performed only a few times each day. Using this
principle, experiments on muscle building have shown that six nearly maximal muscle contractions performed
in three sets 3 days a week give approximately optimal increase in muscle strength, without producing chronic
muscle fatigue.(Ref: GUYTON Textbook of Medical Physiology 11th ed. Pg 1060)
ii. But for better acclimatization there should be decrease in workload (resistance) and increase in duration of
exercise which increases the endurance.

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Endurance exercise or endurance training consists of performing low- to medium-intensity exercise for long
periods of time. If the workload is increased it leads to increased oxygen demand and results in low exercise
capacity due to low oxygen availability.

13. Ans. C. TOF

100% OXYGEN INHALATION improves cyanosis in every case except when there is right to left shunting of blood so
that deoxygenated blood bypasses the lung and goes into the systemic circulation as in the case seen in TOF and
various other congenital heart diseases with right to left shunt.

14. Ans. C. Joint propioception receptor

Effects of exercise on Respiration:-
a. There is an abrupt increase in the ventilation, at the start of the exercise is presumply due to psychic stimuli
and afferent impulses from propioceptors in muscles, tendons, and joints; with moderate exercise, the
increase is due mostly to an increase in the depth of respiration.
b. The more gradual increase is presumbly humoral even though arterial pH, PCO2 and PO2 remain constant
during Moderate exercise.
c. It currently appears that a no. of different factors combine to produce the increase in ventilation seen during
moderate exercise for ego  body temp. plasms K+ cone that stimulate peripheral chemoreceptor, 
sensitivity of Respiratory centre to CO2.
d.
During severe exercise  in ventilation is due to  Lactic acid, pH Q  (H+) and  CO2

J-receptor (Juxtacapillary)  they are C-fibers ending (unmyelinated Q)  close to pulmonary vessels  stimulated
by: Hyper inflation of lungs, when pulmonary capillaries are engorged with blood or pulmonary edema (as in CCF)
or IV/Intracardiac capsaicin  The reflex response (pulmonary chemoreflex) that is produced in Apnea_followed by
rapid breathing (tachypnea), brady cardia and Hypotension.

15. Ans. B. Conversion of angiotensin I to angiotensin II

a. The lungs also activate one hormone; physiologically inactive angiotensin lis converted into the pressor,
aldosterone stimulating angiotensin II in the pulmonary circulation.
b. Large amounts of angiotensin-converting enzyme (ACE) responsible for this activation are located on the
surface of the endothelial cells of the pulmonary capillaries.

16. Ans. B,C,E : Hypoxia causes vasoconstriction, Blood volume in lung is 450 ml, It has low resistance
Pulmonary circulation:
a. The blood flow through the lungs is essentially equal to cardiac out
b. The blood volume of the lungs is about 450 ml. about 9% of the total blood volume of –the circulation.
Approximately 70 ml of this is in the pulmonary capillaries, and the remainder is divided about equally
between the arteries and the veins.
c. The pulmonary veins are an important blood reservoir because of their distensibility. When a normal
individual lies down, the pulmonary blood volume increases by up to 400 mi, and when the person stands
up this blood is discharged into general circulation. This shift is the cause of the les in vital capacity in the
supine position and is responsible for the occurance of orthopnea in heart failure.
d. The entire pulmonary vascular system is a distensible low pressure system.
a. Pul. arterial pressure  24/9  Hg and mean pressure is about 15 mm Hg

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 Respiration

b. Pul. capillary pressure  10 mm Hg.

e. Hypoxia ( O2 tension) pH, and  CO2 conc.  causes Vasoconstriction in lungs.

17. Ans. B. Lungs

“O2 deficiency (Hypoxia), Accumulation of CO2,  PH  produce vasoconstriction in the lungs. While these are in
the other tissues, produce vasodilation.

18. Ans. D. It is associated with pulmonary hypertension.

Chapter - 5
19. Ans. A. Decreased pO2 in arterial blood
ANOXIC HYPOXIA Hypoxia due to disordered pulmonary mechanisms of oxygenation. It may be
due to reduced oxygen supply, respiratory obstruction, reduced pulmonary
function or inadequate respiratory movements PO2 of arterial blood is
reduced. Q
ANEMIC HYPOXIA Hypoxia due to a decrease in hemoglobin concentration or in the number of
erythrocytes in the blood. Here pO2 is normal but there is hypoxia due to
reduced oxygen carrying capacity of blood. Q
STAGNANT HYPOXIA Hypoxia due to insufficient peripheral circulation as occurs in cardiac failure
shock arterial spasm and thrombosis In this condition there is normal p02 and
hemoglobin concentration Q

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HISTOTOXIC HYPOXIA In this kind of hypoxia Oxygen delivery to the tissues is adequate but due to
action of sometoxic agent (e g cyanide) tissues are unable to use it Q

20. Ans. C. Cyanide poisoning

Hypoxia due to inhibition of tissue oxidative process is most commonly the result of cyanide poisoning as it inhibits
the enzyme cytochrome oxidase and possibly other enzymes.

21. Ans. A. Normal A-a gradient

Types of Respiratory Failure Q
Type PaO2 PaCO2 PA-aO2
I Low Normal or low High
II Low High Normal
III Low High High
a. Respiratory failure is the ‘primary’ indication for initiation of mechanical ventilation Q.
b. Hypoxemic respiratory failure Q1) is defined as a PaO2 less than 60 mmHg with fraction of oxygen in
inspired air (FiO2 greater than 0.6 (in the absence of cyanotic heart disease Q), and hypercarbic respiratory
failure (type 2) is defined as an acute PaCO2 Greater than 50 mmHg Q.
c. Hypoxemic respiratory failure most commonly results from pulmonary conditions such as severe
pneumonia, pulmonary edema pulmonary hemorrhage and RDS causing ventilation perfusion mismatch
and shunt.
d. Hypoxemic respiratory failure is present when arterial oxygen saturations of less than 90 % are observed
despite an inspired oxygen fraction of greater than 0.6.
e. The goal of ventilator treatment in this setting is to provide adequate arterial oxygen saturation.
f. Hypercarbic respiratory failure results from disease states causing either a decrease in minute ventilation
or an increase in physiologic dead space.

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 Physiology

g. Common conditions associated with hypercarbic respiratory failure include ‘neuromuscular-diseases’,

such as myasthenia gravis, ascending polyradiculopathy, and myopathies, as well as diseases that cause
respiratory muscle fatigue due to increased workload, such as bronchial asthma, COPD, and restrictive
lung disease.
h. Acute hypercarbic respiratory failure is present when arterial PaCO 2 values exceed 50 mmHg and the
arterial pH is below 7.30.
i. Chronic hypercarbic respiratory failure is characterized by arterial PaCO 2 values of greater than 50 mmHg
and an arterial pH above 7.30.

22. Ans. D. Histotoxic anoxia

Hypoxia or Anoxia  O2 deficiency at the tissue level
Type:
a. Hypoxic Hypoxia (anoxic anoxic)  a.  PO2 of arterial blood Q
 b. Chemoreceptor stimulated Q
b. Anaemic Hypoxia 
i. Arterial PO2 is normal but amount of Hb available to carry O2 is reduced Q
ii. Chemoreceptors are not stimulated, since dissolved O2 in blood is enough to keep these receptor
normal. Q
c. Stagnant or ischemic hypoxia 
i. Normal PO2 and Hb conc. Q
ii. Blood flow to tissue is so slow that adequate O2 is not delivered Q
iii. Chemoreceptor are strongly stimulated. Q
d. Histotoxic Hypoxia:-
i. Caused by Canide, that inhibit cytochrome oxidase (cyt aa3), so that tissue cells cannot make use of
O2 . Q
ii. O2 delivery to tissue is normal. Q
iii. Chemoreceptor are strongly stimulated. Q

23. Ans. B. Lymphedema

a. Effects of increased Barometric pressure: on N2 As in case of Diving deep in sea:
i. If a diver breaths compressed air (under high pressure) the amount of N2 dissolved in the body fluid
become great, the increased PN2 can cause Nitrogen narcosis, a condition also known as.
b. Rupture of the deep.
i. S/S - (with increasing pressure i.e. with increasing depth in sea) due to Nitrogen narcosis :
Euphoria  then symptoms resemble alcohol intoxication  Intectual function are impaired but
manual dexterity is maintained.
ii. Prevention: The problem of Nitrogen narcosis can be avoided by breathing mixtures of Oxygen and
helium and deeper dives can be made.
iii. Helium is used instead of N2 because:
 Only l/5th the narcotic effect of N2
 Only 1/2 as much volume of helium dissolves in the body tissues as N2, and volume that dissolve
diffuses out of the tissues several times as rapidly as does N2, thus reducing the problem of
depression sickness.
 Low density of helium (l/7th of N2) keeps the airway resistance for breathing at a minimum.
c. Decompression sickness

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 Respiration

(Also known as Bends, compressed Air Sickness, Caisson Disease, Diver's Paralysis, or Dysbarism)
a. As a diver breathing 80% N2 ascends from a dive the elevated alveolar PN2 falls. N2 diffuses from the
tissues into the lungs along the partial pressure gradient. Bubbles form in the tissues and blood
(blocking the blood vessels) and causing symptoms of decompression sickness or the Bends or Caisson
disease. Q
b. Symptoms commonly appear 10-30 min after the diver resurfaces and they progress. Q
c. Symptoms:
i. Bubbles in tissues causes:

Chapter - 5
Severe pain particularly around joints (known as Bends) and in muscles (in 85 to 90% cases) and
neurological symptoms that includes - Paresthesia and Itching
ii. Bubbles in blood stream, which occurs in most severe cases, obstruct the arteries to brain
(collapse, dizziness, unconciousness); and spinal cord (m.c. and can lead to Paralysis and
respiratory failure
iii. Micro Bubbles plugging the capillaries in lungs  causes CHOKES, which c/b Dyspnea, (serious
shortness of breath), often followed by severe pulmonary edema and occasionally death.
d. Management:
a. Uses of mixtures of O2 and Helium before diving. Q
b. Decompression (resurfaces) is gradual no harmful effects are observed. Q
c. t/t  of this Caisson disease is prompt recompression in a pressure chamber followed by slow
decompression Q

Respiration
24. Ans. A. dorsal medulla
a. MEDULLA – has pre botzinger complex (in dorsal part) which acts as pacemaker for spontaneous
respiration, also contains DRG & VRG (DORSAL &VENTRAL RESPIRATORY GROUP OF NEURONS)
i. DRG - contains inspiratory neurons which supply inspiratory muscles
ii. VRG - both inspiratory & expiratory neurons
b. PONS – contain 2 centres
i. Apneustic centre (in lower pons) : stimulates inspiratory neurons. If not inhibited by vagus and
pneumotaxic centre will cause apneusis.
ii. Pneumotaxic centre (in upper pons) : inhibit apneustic centre.

25. Ans. A. type 2 pneumocytes

a. Pulmonary surfactant is a surface-active lipoprotein complex (phospholipoprotein) formed by type II
alveolar cells.
b. The proteins and lipids that comprise the surfactant have both a hydrophilic region and a hydrophobic
region.
c. By adsorbing to the air-water interface of alveoli with the hydrophilic head groups in the water and the
hydrophobic tails facing towards the air, the main lipid component of surfactant,
dipalmitoylphosphatidylcholine (DPPC), reduces surface tension.

26. Ans. B. 4 atm

a. Assuming the density of seawater to be 1025 kg/m³ (in fact it is slightly variable), pressure increases by 1
atm with each 10 m of depth. 1 feet = 0.3048 meter, 100 feet = 30.48 m
b. So, pressure increased is 3 atm , and add 1 for the normal pressure of atmosphere = 4 atm

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27. Ans. A. 40 mm Hg ( Ref: Review of Medical Physiology- Ganong’s-23rd Edition, Pg661)

Venous blood has around 40 mmHg pO2. see the table below

28. Ans. A. sitting (Ref: Gray's Anatomy, 40th edition )

a. Skiagraphy shows that the height of the diaphragm in the thorax varies considerably with the position of
the body.
b. It stands highest when the body is horizontal and the patient on his back, and in this position it performs
the largest respiratory excursions with normal breathing.
c. When the body is erect the dome of the diaphragm falls, and its respiratory movements become smaller.
d. The dome falls still lower when the sitting posture is assumed, and in this position its respiratory
excursions are smallest. These facts may, perhaps, explain why it is that patients suffering from severe
dyspnœa are most comfortable and least short of breath when they sit up.
e. When the body is horizontal and the patient on his side, the two halves of the diaphragm do not behave
alike.
f. The uppermost half sinks to a level lower even than when the patient sits, and moves little with
respiration; the lower half rises higher in the thorax than it does when the patient is supine, and its
respiratory excursions are much increased.

29. Ans. A osmotic pressure in interstitium

a. The low intracapillary hydrostatic pressure, a consequence of the low pulmonary arterial pressure, means
that normally the osmotic force tending to move fluid into pulmonary capillaries is greater than the
hydrostatic pressure moving fluid out.Thus, interstitial space is small and the alveoli are "moist" but not
"wet".

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 Respiration

Chapter - 5
Pc = capillary hydrostatic pressure
πc = capillary osmotic pressure (due to plasma protein, oncotic pressure)
Pt = tissue hydrostatic pressure
πt = tissue osmotic pressure
b. Note: Hydrostatic pressure difference (Pc - Pt) tends to move fluid out of capillaries
Note: Osmotic pressure difference (πc - πt) tends to move fluid into capillaries
c. surface tension of fluid lining the alveoli is an inward force which pull fluid from alveolar wall by average
pressure= -3 mmHg in normal lung , but without surfactant it's increased to -20 mmHg , thus decreased
surfactant leads to pulmonary edema, but the main factor is low pressure in pulmonary capillaries and
interstitium prevent filteration of fluid.
d. Therefore both surfactant and osmotic pressure as answers are correct ,but better answer is pressure in

Respiration
interstitium.

30. Ans. A. alpha 1 anti trypsin deficiency

a. Emphysema is a disease of the lung tissue caused by destruction of structures feeding the alveoli, in some
cases owing to the consequences of alpha 1-antitrypsin deficiency.
b. It leads to decrease in FEV1% which is the most important parameter for obstructive lung diseases.

31. Ans. B. 30%

a. A normal individual at rest inspires about 12 to 16 times/minute and each breath have a tidal volume of
about 500 mL.
b. A portion (more or less 30%) of the fresh air inspired with each breath does not reach the alveoli but
remains in the. conducting airways of the lung. This component of each breath is called the ANATOMIC
DEAD SPACE component.

i. Dead space is decreased by

 supine postionQ
 neck fully flexedQ with depressed chin
 low lung volumesQ
 TracheostomyQ & endotracheal intubationQ (Artificial airway)
ii. Dead space increased by
 endotracheal intubation with tubeQ (increased mechanical DS due to tube volume)
 standing positionQ (due to hypoperfusion of apical alveoli)

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 emphysema Q
 neck extension Q
 Ipratropium (Bronchodilation)

32. Ans. A. Asthma

a. Experienced physicians could discriminate between consolidation and cavitation by noting the quality of
bronchial breathing.
b. In consolidation, the bronchial breathing is low pitched and sticky and is termed tubular type of bronchial
breathing.
c. In cavitary disease, it is high pitched and hollow and is called cavernous breathing.

33. Ans. A. exercise (Ref: Review of Medical Physiology- Ganong’s-23rd Edition, P-534)
a. In voluntary Ventilation, there is a increase in minute volume (TV x RR) but it is not much because of CO2
washout depressing the respiratory centres.
b. This is absent in exercise since there is increased CO2 production in body due to exercising muscle’s
metabolism.
c. Hypoxia is less effective stimulus than hypercapnia( primary drive for respiration). Hyperthermia is a minor
factor affecting respiration.

34. Ans. (C). Causes pulmonary arterial resistance to decrease

The increase in blood flow through the pulmonary circulation during exercise increases the diameter of the pulmonary
vessels and therefore decreases their resistance. The decrease in resistance can occur because the pulmonary vessels are
very compliant and are large enough to prevent an increase in pulmonary artery blood pressure when cardiac output
increases. The increased blood flow to the lung evens out the V/Q ratio, decreasing it at the top of the lung and
increasing it at the bottom. Making the V/Q ratio more similar throughout the lung may decrease some of the shunting
effect that normally occurs at the base of the lung where the V/Q ratio is quite low and may actually increase the oxygen
saturation of arterial blood. The increased blood flow will also increase the surface area for respiratory exchange and
therefore increase the diffusing capacity.

35. Ans. (A). A decrease in the blood flow to the brain

Hyperventilation, by definition, reduces the arterial PCO2 below normal, that is, to a value less than 40 mmHg.
Low arterial PCO2 in the blood perfusing the brain causes vasoconstriction of the cerebral vasculature, leading to
a lowering of blood flow to the brain. The low arterial CO2 will increase the pH of the arterial blood (i.e.,
produce a respiratory alkalosis) and decrease the activity of the central chemoreceptors. Pulmonary vasculature,
unlike the systemic vasculature, is dilated by low PCO2 and high PO2 and constricted by high PCO2 and low
PO2. The respiratory alkalosis will cause Ca2+ to bind to plasma proteins, lowering the concentration of ionized
Ca2+. Low concentrations of ionized Ca2+ increase the excitability of nerve and muscle membranes, causing
them to contract spontaneously or with minimal stimulation. The increased contractile activity of skeletal muscle
produced by low concentration of ionized Ca2+ is called tetany.

36. Ans. is (A) Hypoxia

1. Factors that shift O2- Hb dissociation curve to right - ie. Decrease O2 affinity with Hb:
(i) ed in H+ cone. (pH, Bohr effect) Q
(ii) ed CO2 (O2, Hypoxic condition) Q

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 Respiration

(iii) ed in temperature. Q

(iv) ed DPG. Q

2. Factors that shift O2-Hb dissociation curve to the left side ie. increase the O2 affinity with Hb
(i) Just reverse of the right shift Q (ii) in temperature (Hypothermia) Q
(iii) in pH (7.6) Q (iv)  HbF (fetal Hb) Q
Q
(v) CO poisoning

Chapter - 5
37. The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 694
Adult erythrocytes normally do not contain any carboxyhemoglobin, which is formed when hemoglobin binds
carbon monoxide. Adult erythrocytes possess two distinct types of hemoglobin, HbA and HbA 2. These
hemoglobin molecules may be saturated with oxygen (HbO2 ) or reduced to Hb when oxygen is released to cells
within tissues.

38. Ans. is (A) Hyperventilation

Effect of decreased Barometric pressure  due to increasing (high)altitude  Lead to  PO2
[A] At 3000m (10,000 feet) — Po is 6OmmHg (above the sea level) Hypoxic stimulation of chemo receptors
 es ventilation (Hyper ventilation Q) fall in arterial PCO2 —Respiratory alkalosis Q

[B] Acute Hypoxic symptoms -Acute mountain sickness  in unacclimatized persons: -

Respiration
(i) At 3700m (12000 feet)  symptoms :irritability, drowsiness, lassitude, mental and muscle
fatigue.
(ii) Above 18,000 feet  seizures
(iii) Above 23,000 feet  (conciousness lost)

[C] Delayed effects of high altitude -

This syndrome develops 8-24 hours after arrival and last 4-8 days. It is C/B: -
(i) Headache, irritability, insomnia, breathlessness and nausea and vomitting. Q
(ii) Cause  cerebral edema due to arteriolar dilation Q
(iii) T/t  for Alkalosis  Acetazolamide and for cerebral edema  gluco-corticoids Q
(iv) High altitude pulmonary edema is a serious form of mountain sickness  pulmonary edema prone
to occurs in
individual who ascend quickly to altitudes above 2500m and engage in heavy physical acitvity during
the first 3 days after arival. It is associated with marked pulmonary hypertension. Nifedipine is of
value in the t/t and prevention of the condition, also rest and O2. Q
[D] Acclimatization refers to changes in the body tissues in response to long term exposure to hypoxia
i.e. at high altitude for days, weeks or years  the person becomes more and more acclimatized to
low PO2. The principal means by which acclimatization comes about are: -
1. a great increase in pulmonary ventilation Q  on immediate exposure to very low Po2, the hypoxic
stimulation of the chemoreceptors increase alveolar ventilation about 65% above normal. This is
immediate compensation for the high altitude.”
2. Increased in RBC Q  Due to hypoxia   erythropoietin  polycythemia
3. Increased diffusion capacity of lungs Q  it increased three folds above the normal; and Increased
T.L. capacity.
4. Pulmonary Hypertension Q  Note that hypoxia causes vasoconstriction in lungs.
5. Increased vascularity of the tissue Q  density es in skeletal and cardiac muscle.
6. Increased ability of the cells to use O2, despite the low PO2 Q  due to ed conc of oxidative
enzymes and ed density of mitochondria at cellular level.

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39. Ans. is (B) Lungs

“O2 deficiency (Hypoxia), Accumulation of CO2,  PH  produce vasoconstriction in the lungs. While these are
in the other tissues, produce vasodilation.

40.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 804
The (A-a)O2 gradient in a healthy person is due to both a low VA/Q˙ ratio at the base of the lungs and a small
shunt from the bronchial circulation.
(A = alveolus; a = arterial)

41.The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 804
A decrease in the diffusion distance will lead to an increase in DL. A decrease in capillary blood volume, surface
area, cardiac output, and blood hemoglobin concentration will decrease DL.

42. The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 818
The equilibrium curves are not similar; that for CO2 is steeper and more linear. The blood carries more CO2 than
O2. The presence of CO2 will increase the P50. Although red cells carry most of the O2, the plasma carries the
majority of the CO2 (mainly as bicarbonate).

43. Ans. (B). Carbon monoxide poisoning

A rise or fall in the oxy gen saturation of hemoglobin is caused by a decrease in the arterial O2
tension, which can result from a low V/Q ratio, hypoventilation, or an anatomical right-to-left
shunt. Because carbon monoxide (CO) competes with O2 on the hemoglobin molecule, CO
poisoning can cause a decrease in hemoglobin’s saturation even when the Po2 is normal. In
anemia, oxygen saturation is unchanged but the concentration of hemoglobin is less than
normal, reducing the oxygen content.
44. Ans. (D). Cardiac output is increased
Ref: Ganong, 22nd Edition, Page no 661
Pulmonary vascular resistance is affected by cardiac output, pulmonary artery pressure, lung volume, and O2 tension.
Increasing cardiac output or pulmonary artery pressure causes the pulmonary vasculature to expand, thereby
decreasing PVR. At high lung volumes, intrapulmonary blood vessels are stretched and compressed, increasing PVR.
At low lung volumes, extrapulmonary blood vessels are compressed, increasing PVR. The lowest PVR occurs near
FRC. Decreasing PO2 or increasing Pco2 or H+ concentration causes PVR to rise. The sympathetic nervous system
has little direct effect on PVR.

45.Ans B) Emphysema & single lung

The graph shows static compliance curves. X shows increased compliance i.e Emphysema and Y show decreased
could be Restrictive lung disease, single lung etc. In Chronic bronchitis compliance is normal.

46.The answer is C.

∆P = R xQ ˙ = 4 mm Hg/L/min x

5 L/min = 20 mm Hg.

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 Central Nervous System

Chapter - 6
Central Nervous System

Neurotransmitters:
A. Monoamines
 Catecholamines (Dopamine, Norepinephrine, Epinephrine),Indolamines (Serotonin)
B. Amino Acids


Central Nervous System Chapter - 6

GABA, Glutamate, Glycine, Aspartate
Peptides (examples)
 Opiods: enkephalins, Neurohypophyseals: vasopressin, oxytocin, Secretins: corticotropin-releasing
factor, Insulins: insulin, insulin growth factors, substance P
C. Acetylcholine (ACh)
1. In CNS and brain, influences alertness, attention, and memory
2. Formed by combination of acetyl CoA + choline (enzyme choline acetyltransferase)
3. Does not undergo reuptake; action is terminated by cholinesterase
4. Found in:
a. Neuro-muscular junction
b. Post ganglionic parasympathetic nerve endings
c. All preganglionic nerve endings of ANS
d. Some of the post ganglionic neurons of sympathetic N.S
e. Large pyramidal cells (BETZ CELLS) of motor cortex
f. By many different neurons in basal ganglia
i. Two receptor types: Nicotonic (movement) Muscarinic (autonomic)
ii. Mysthenia Gravis characterized by defect in Ach transmission.
iii. Botulinum toxin prevents release of Ach; Black widow spider venom stimulates release;
Curare blocks Ach nicotine receptors

D. Serotonin (5-HT, or 5-hydroxytryptamine)

1. Behavioral effects are complex
2. Plays a role in regulation of mood; control of eating, sleep, and arousal; and pain
3. Raphe Nuclei (in brainstem)  entire CNS
4. Tricyclic antidepressants (eg, imipramine,) block both Serotonin and NE uptake

E. Dopamine (DA)
1. Generally associated w/ motor disorders and neuropsychiatric problems (schizophrenia, ADHD, tics), as well
as modulation of reward centre.
2. Conditions due to defects in dopamine synthesis include PKU, Parkinson’s
3. Excessive dopamine produced by coke, amphetamine, L-dopa; can lead to visua006C hallucinations,
hyperkinetic movement disorders
4. Midbrain (substantia nigra pars compacta and ventral tegmental)  striatum, prefrontal, limbic, amygdala.
3 well-known pathways:
a. Nigrostriatal – major component of extrapyramidal motor system; decreased DA here causes rigidity,
tremor, and akinesia; excess causes dyskinesia

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b. Mesolimbic – probably propagates positive symptoms of psychosis; rewarding effects of certain stimuli
including drugs; ventral tegmental areas (midbrain) to amygdala/limbic
c. Mesocortical – probably propagates some negative symptoms of psychosis; planning, strategy
preparation; ventral tegmental to frontal cortex.
5. Dopamine has 5 receptor. D1& D5 act by increasing cAMP (via adenylyl cyclase) & D2,D3 & D4 act by
decreasing cAMP
6. Phenyalanine  tyrosine  DOPA  Dopamine (tyrosine hydroxylase rate-limiting)
7. Terminate process: reuptake, monoamine oxidase (MAO), etc.

F. Norepinephrine (NE) (noradrenalin)

1. Functions helps regulate mood, memory, hormones, blood flow, and motor behavior
2. Also thought to increase vigilance; role in sexual behavior and control of appetite
3. Locus Ceruleus (pons)  entire CNS
4. Tricyclic antidepressants (eg, imipramine, clomipramine) block both Serotonin and NE uptake

G. Epinephrine (adrenalin)
1. Hormone produced by adrenal medulla
2. Also produced in brain, but minor importance compared with NE
3. Stimulates sympathetic division of ANS to produce “flight or fight”

H. GABA Cell bodies in entire CNS project to entire CNS

1. Principal inhibitory transmitter substance in brain.
2. Synthesised from glutamic acid through the activity of glutamic acid decarboxylase (GAD) is used as marker
of GABA secreting neurons
3. On GABA A receptors – acts by increasing Cl- conductance
4. On GABA B receptors- increasing K+ efflux, mediator for presynaptic inhibition
5. Enhanced activity produces sedative, anxiolytic, and anticonvulsant effects

I. Glutamate Cell bodies in entire CNS project to entire CNS

1. Principal excitatory transmitter (along with aspartate) substance in brain and cord
2. Implicated in neural plasticity, learning, and memory
3. Four types of glutamate receptors, one being the NMDA receptor

J. Glycine Inhibitory neurotransmitter in spinal cord and lower brain

1. May play a modulatory role at interneurons in cord
2. acts by increasing Cl- conductance
3. Blocked by strychnine

K. PEPTIDES : project to entire CNS; no mechanism for reuptake once released; deactivated by enzymes
Substance P – mediator of inflammation, carrying pain signals(Tachykinins)
Vasopressin facilitate water reabsorption by kidneys; may play a role in memory consolidation
Somatostatin – modulation of heat, pain, sleep; also reduced in cortex of Alz pts
Angiotensin II- central actions include stimulation of pressor responses and drinking
Opoids (Enkephalin)- pain perception, stress, respiratory regulation, temperature control

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μ (mu) k (kappa) δ(delta)

(↑k+ conductance) (Closes Ca2+ channels) Ca2+ channel close

Analgesia Analgesia Analgesia

Resp depression Dieresis
Constipation Meiosis
Euphoria Sedation

Central Nervous System Chapter - 6

Sedation Dysphoria
Meiosis

1. Tachykinins are peptides that excite neurons, evoke behavioral responses, are potent vasodilators and
contract (directly or indirectly) many smooth muscles.Until now, only three tachykinins have been isolated
and sequenced from mammalian tissues: SP, NKA (neuromedin L, neurokinin, and substance K), and NKB
(neurokinin and neuromedin k). Substance P is found in high concentration in the endings of primary
afferent neurons in the spinal cord, and it is probably the mediator at the first synapse in the pathways for
slow pain, is responsible for the axon reflex. In the intestine, it is involved in peristalsis.
2. Orexins, also called hypocretins, are the common names given to a pair of excitatory neuropeptide
hormones (Orexin-A and B). Produced by lateral and posterior hypothalamus. The orexin/hypocretin
system is involved in the stimulation of food intake. In addition, it stimulates wakefulness and energy
expenditure. People lacking the orexin/hypocretin neuropeptide itself also have narcolepsy.
3. Neurotrophins are proteins necessary for survival and growth of neurons. Some of these neurotrophins
are products of the muscles or other structures that the neurons innervate, but others are produced by
astrocytes. These proteins bind to receptors at the endings of a neuron. They are internalized and then
transported by retrograde transport to the neuronal cell body, where they foster the production of proteins
associated with neuronal development, growth, and survival.They have trk receptors which dimerizes, and
this initiates autophosphorylation in the cytoplasmic tyrosine kinase domains of the receptors.

Neurotrophin Receptor
Nerve growth factor (NGF) trk A

Brain-derived neurotrophic factor (BDNF) trk B

Neurotrophin 3 (NT-3) trk C, less on trk A and trk B

Neurotrophin 4/5 (NT-4/5) trk B

Schwann cells and astrocytes produce ciliary neurotropic factor (CNTF). This factor promotes the survival of
damaged and embryonic spinal cord neurons and may prove to be of value in treating human diseases in which
motor neurons degenerate
NOTE: Autoimmunity to GAD appears to cause the stiff-man syndrome (SMS), a disease characterized by
fluctuating but progressive muscle rigidity and painful muscle spasms, presumably due to GABA deficiency.

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GABA is formed by decarboxylation of glutamate. The enzyme that catalyzes this reaction is glutamate
decarboxylase (GAD), which is present in nerve endings in many parts of the brain. GABA is metabolized
primarily by transamination to succinic semialdehyde and thence to succinate in the citric acid cycle. GABA
transaminase (GABA-T) is the enzyme that catalyzes the transamination. Pyridoxal phosphate, a derivative of
the B complex vitamin pyridoxine, is a cofactor for GAD and GABA-T.

SYNAPSE : Junction between two neurons, where information from one neuron is transmitted or relayed
to another neuron, but there is no protoplasmic connection between the two neurons.Types
1.AXO-DENDRITIC (Most common)
2. AXO-SOMATIC
3. AXO-AXONAL

SYNAPTIC TRANSMISSION
Sequence of events:
A. Arrival of message in form of Action potential.
B. Opening of voltage gated Ca2+ channels.
C. Fusion of vesicles with cell membrane & exocytosis.
D. Development of Post synaptic potential.
E. Post Synaptic potentials are integrated at axon hillock.
F. AP in the axon of the Post synaptic neuron

1. Postsynaptic potentials are either brief depolarizations or hyperpolarizations of postsynaptic membrane

kept brief by reuptake (rapid removal of transmitter substance by terminal button) and enzymatic
deactivation (enzyme destroys transmitter - occurs for acetyclcholine by way of acetylcholinesterase)
2. Nature of postsynaptic potential depends on type of ion channel opened by postsynaptic receptors at
particular synapse
Excitatory potentials (EPSP)occur when Na+ or Ca2+ enters cell
Inhibitory potentials (IPSP) produced by opening of K+ or Cl- channels
A. EPSP
Type Timing Cause Site
1. EPSP Latency : 0.5 ms Na/Ca influx
Peak : 0.5 – 1.5 ms
Time Constant : 3 ms
2. Slow Latency : 100 – 500 ms  K efflux AutonomicGanglia
Lasts : Several Seconds cardiac muscle,
smooth muscle,
cortical neurons
3. Late slow Latency : 1-5 Sec  K efflux Symp. Ganglia
Lasts : 10 – 30 min

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B. IPSP
Type Timing Cause Site
IPSP Latency 0.5 ms Cl- influx
Peaks: 0.5 –1.5 ms  K+ efflux
Time consistent: 3 ms Na+/Ca++ closure
Slow Latency 100 – 500 ms K efflux Auto. Ganglia,
Lasts : Several seconds cardiac
muscle,smooth

Central Nervous System Chapter - 6

muscle,cortical
neurons

C. Aid to memory
1. Timing of EPSP & IPSP : Same
2. Slow EPSP & IPSP : cause is K+
3. No late slow IPSP.

Fast & slow responses & post ganglionic neurons in sympathetic ganglia:
EPSP Type Duration NT Receptor
1. Fast 30ms Ach Nicotinic
2. Slow 30 S Ach M2
3. Late slow 4 min GnRH GnRH
IPSP Slow 2S Dopamine D2

D. SNARE PROTEINS: Main proteins that interact to produce synaptic vesicle docking and fusion in nerve endings
i.e Synaptobrevin (V- snare protein) in vesicle membrane locks with Syntaxin (t- snare protein) in cell
membrane
1. Tetanus Toxin  act on Synaptobrevin ,block presynaptic release of inhibitory neurotransmitter in spinal
cord leading to SPASTICITY
2. Botulinum Toxins B,D,F,G  act on Synaptobrevin
i. C  act on Syntaxin
AB  act on SNAP – 25
Block release of Ach at NM junction : FLACCID PARALYSIS
Uses: to relieve achalasia (in LES ), to remove wrinkles (in facial muscles)
E. PROPERTIES OF SYNAPTIC TRANSMISSION
1. Synaptic delay (0.5 ms)
2. Spatial summation & Temporal summation
3. Facilitation-subliminal fringe
4. Occlusion
5. Fatigue
6. Synaptic plasticity (For memory & learning a)Post tetanic potentiation b)habituation(inactivation of Ca 2+
channels, decreased response) c) sensitization d)Long term potentiation e)LTD - Long term depression

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RECEPTORS
Receptors can be classified as:-
i. Tactile receptors
ii. Thermo receptors
iii. Nociceptors
iv. Proprioceptors

F. Thermoreceptors and nociceptors are mainly naked nerve endings.

Proprioceptors : are stimulated by changes of position of body
i. Muscle spindle
ii. Golgi tendon organ
iii. Joint receptors
iv. Vestibular receptors
Receptors can be further classified as on the basis of receptor adaptation as
 Rapidly Adapting
 Slowly Adapting
Adaptation is decrease in frequency of action potentials despite the maintenance of a constant strength
stimulus
 Rapidly Adapting (or phasic )
These include
o Pacinian corpuscles
o Meissner’s corpuscles
o Krause’s end bulb
 Slowly Adapting (or tonic)
These include
o Merkel’s disc
o Ruffini endings
o mechanoreceptors

CUTANEOUS RECEPTORS
A. MEISSENER’S CORPUSCLES: TACTILE RECEPTORS
1. Encapsulated endings
2. Ellipsoidal structure
3. Occur in groups
Found on : skin of finger tips, Lips, nipples, Orifices of body

B. PACINIAN CORPUSCLES : Quickly adapting receptors responds to deformity caused by firm pressure
1. Encapsulated & spherical
2. Located in: Subcutaneous tissue: Pressure
3. Neighbourhood of tendons & joints: Vibrations

C. END BULB OF KRAUSE: MECHANORECEPTORS:

1. Encapsulated & spherical

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2. Found in : Papillae of lips, tongue, skin of genetalia, in sheaths of nerves.

3. FIBRE: A-GROUP (δ)

D. ORGAN OF RUFFINI: mechanorecetors/degree of warmth, cold

1. Expanded ends of sensory nerve fibres
2. Slowly adapting touch receptors
3. Found in dermis
4. Nerve fibre type associated with these receptors are A δ Type or C

Central Nervous System Chapter - 6

E. MERKELS DISC: TACTILE RECEPTORS
1. Expanded tips
2. Grouped together in a single receptor organ – Iggo Dome receptor
3. Under epithelium of skin

F. FREE NERVE ENDINGS [UNCAPSULATED]

1. Responds to noxious stimuli- pain
2. Also responds to touch & temperature
3. Fibre: terminal branches of thin myelinated A δ(Fast pain) & unmyelinated C fibres(slow pain)

Transient receptor potential (TRP) ion channel: The TRP channels are a family of 6 transmembrane spanning
domain proteins expressed in low numbers per cell to yield small net inward currents. Humans use TRP channels
to appreciate sweet, bitter and umami (amino acid) tastes, and to discriminate warmth, heat and cold. The TRPV
(use pepper derived vanilloid compound capsaicin as a ligand) subfamily involved in neuronal pain pathways,
sense heat and osmolarity. The TRPM (long TRPC, Melastatin) subfamily involved in Ca 2+ dependent signaling,
control of cell cycle progression, division or migration, and thermosensation.

JOINT RECEPTORS
GOLGI END ORGANS: in ligaments of joints, respond to position of joint
END ORGAN OF RUFFINI: In the capsule responds to movements of joints.
PACINIAN CORPUSCLE: in the ligaments very sensitive to quick movements & vibrations
Rapidly adapting receptors sense vibration;
Slowly adapting receptors sense pressure.
Rapidly adapting receptors are encapsulated nerve endings.
Slowly adapting receptors are expanded nerve endings.
Itch is carried by C-mechanoreceptors.

Function of spinocerebellar tract (AIIMS May 09)

A. Planning & programming of movement
B. Coordination & smoothing of movement
C. Equilibrium
D. Vibration
Ans B Coordination & smoothing of movement

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A. Sensory Pathways
1. Anterolateral system: crossed tract
2. Dorsal (or posterior) column system: uncrossed
3. SPINOCEREBELLAR TRACT : Unconscious proprioception
(Anterior or Ventral & Posterior or Dorsal)

B. Anterolateral system:
This includes
1. Anterior (or ventral)
Spinothalamic tract: This carries crude touch
2. Lateral Spinothalamic tract: This carries pain and temperature

C. Pain innervation of the viscera. Pain afferents from structures between the pain lines reach the CNS via
sympathetic pathways, whereas, they traverse parasympathetic pathways from structures above the thoracic
pain line and below the pelvic pain line.

D. Gate Control Theory & Lateral inhibition

1. Stimulation of skin at the site of pain also gives some pain relief. The relief may result from inhibition of
pain pathways in the dorsal horn gate by stimulation of large-diameter touch-pressure afferents.
2. Collaterals from these myelinated afferent fibers synapse in the dorsal horn. These collaterals inhibit the
input from nociceptive afferent fibres that also synapse in the dorsal horn. This is called the gate-control
hypothesis.
3. The same mechanism is probably responsible for the efficacy of counterirritants, Hot water bags etc .
Stimulation of the skin over an area of visceral inflammation produces some relief of the pain due to the
visceral disease by inhibiting C unmyelinated Adrenergic fibres from GIT carrying visceral pain.
4. Afferent fibers from visceral structures reach the CNS via sympathetic and parasympathetic nerves. Their
cell bodies are located in the dorsal roots and the homologous cranial nerve ganglia.
5. Specifically, there are visceral afferents in the facial, glossopharyngeal, and vagus nerves; in the thoracic
and upper lumbar dorsal roots; and in the sacral roots .
6. Vagal connections provide a massive sensory link for "physiological information", while sympathetic
unmyelinated C fibres provide sensations of visceral pain.
E. Dorsal column
This carries the rest of the sensations e.g. proprioception, vibration, fine touch, etc.

F. Spinocerebellar Tract
1. The kinesthetic & proprioceptive information from the body relayed via spinocerebellar tracts are used for
coordination.
2. The copy of motor plan relayed from motor cortex via pontocerebellar tract is matched with the actual
muscle movements information relayed via spinocerebellar tract (Comparator Servo Mechanism).Then
prompt correction are made to coordinate and smoothen the ongoing activity.
3. Dorsal spinocerebellar is uncrossed and reaches cerebellum via inferior peduncle.
4. Ventral spinocerebellar is mostly crossed and reaches cerebellum via superior peduncle.

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G. Diagram Showing the Dorsal Col. Pathway

Central Nervous System Chapter - 6

Fig. Ascending tracts carrying sensory information from peripheral receptors to the cerebral cortex. (a)
Dorsal-column pathway mediating touch, vibratory sense, and proprioception. (b) Ventrolateral
spinothalamic tract mediating pain and temperature.

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Law of reciprocal innervation of agonist antagonist muscles/ (AIIMS May 08)

1. Hering's law
2. Sherrington's law
3. Laplace’s law
4. Hick’s law

Ans. 2. Sherrington's law

This is hemi-section of the spinal cord

H. Brown Sequard Syndrome
Opposite side:
1. Loss of pain and temperature sensation
Same side:
1. Other sensations lost (except touch)
2. LMN type of paralysis or the level of lesion
3. UMN type of paralysis below the level of lesion

LAWS RELATED TO SENSORY PHYSIOLOGY

A. Muller’s Doctrine of specific nerve energies:

No matter where along the nerve pathway one
stimulates, the type of sensation will depend on which part of the brain is finally going to be stimulated.
B. Law of Projection:
No matter where along the nerve pathway one stimulates, the
sensation will be felt at the site of the receptor. Eg PHANTOM LIMB
C. Weber Fechner Law & Stevens’ power law
These two laws relate the sensation felt (S) to the intensity of the stimulus (I).
S = K log I – Weber-Fechner Law
S = KIa – Steven’s Power Law
D. Bell-Magendie Law
This law states that the dorsal root is sensory and ventral root is motor
E. Labelled – line theory
All the sensations from the different parts of the body travel along specified paths.
e.g.
i. In the lateral spinothalamic tract, fibers from the lower parts of the body are placed laterally.
ii. In the posterior column, fibers from the lower parts of the body are placed medially.

A. SENSORY CORTEX
1. Present in Postcentral Gyrus area 3,1,2
2. Body is represented Vertical & upside down called as Sensory homunculus.
3. Not only is there detailed localization of the fibers from the various parts of the body in the postcentral
gyrus, but also the size of the cortical receiving area for impulses from a particular part of the body is
proportionate to the use of the part.

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4. The cortical areas for sensation from the trunk and back are small, whereas very large areas are concerned
with impulses from the hand and the parts of the mouth concerned with speech.

Representation in Cerebral cortex is : (AIIMS May 09)

A. Vertically
B. Horizontally
C. Tangentially
D. Tandem

Central Nervous System Chapter - 6

Ans. A Vertically

B. LESION OF POST CENTRAL GYRUS

1. Decreases the sensations, but do not entirely abolish them.
a. Fine touch & proprioception are almost totally lost.
b. Temp. sensibility less affected.
c. Pain sensibility only slightly affected.
NOTE:A certain degree of perception is possible in the absence of cortex.

C. Upon Recovery:
a. Pain sensibility returns first.
b. Followed by temperature sense.
c. & finally proprioception & fine touch.

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Types of Inhibition

A A

+ve NT +ve
N
B B
T

Direct or post – synaptic inhibition Pre – synaptic Inhibition

‘A’ ‘B’

This is because of the release of an inhibitory Pre-synaptic Inhibition

neurotrasmitter (NT) from neuron A; this produces ‘A’ releases an excitatory NT, to excite B. But ‘C’ ends
an IPSP in neuron B. presynaptically as ‘A’ to decrease the release of the
excitatory NT. Salient Features of Presynaptic Inhibition
a. It is example of axo-axonic synapse
b. It is stimulated by general anaesthetics
c. It is inhibited by picrotoxin
d. It is mostly due to GABA

A
B
+
(+)
B (+) Muscle)
- A
(-)
C

Eg. Basket / Stellate cell inhibiting the purkinje cell in the cerebellum

Feedback or Renshaw cell inhibition

‘A’ stimulate the muscle. However, a collateral
Feed-forward inhibition
from A (‘B’) ends on an inhibitory interneuron (C)
‘A’ stimulates ‘B’; but ‘B’
in the anterior horn of the spinal cord. This
inhibits ‘C’
inhibitory interneuron is called a Renshaw cell.

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Lateral or afferent or surround inhibition

This is one of the cornerstones of sensory physiology. Stimulation of required neuron inhibits the adjacent
neurons (by a collateral). This enhances contrast and sharpens the image.

REFLEXES
A. Asynaptic reflex e.g. Axon reflex
B. Monosynaptic reflex e.g. Stretch reflexes (deep tendon reflexes)
C. Di or Bi-synaptic reflex e.g.

Central Nervous System Chapter - 6

1. Inverse stretch reflex.
2. Reciprocal innervation.
D. Polysynaptic reflex e.g.
1. Superficial reflexes.
2. Withdrawal response
3. Flexor
4. Crossed – extensor

A. Stretch reflex
It is responsible for contraction of muscle when stretched. Receptor is muscle spindle.Muscles have 2 type of
fibres one outside the capsule of muscle spindle called EXTRAFUSAL MUSCLE FIBRE.They are contractile,
supplied by αMotor neurons from ventral horn, resulting in shortening of muscle proper. The

B. INTRAFUSAL MUSCLE FIBRE are present inside the spindle, they too are contractile supplied by γ motor
neurons. Unlike extrafusal when they contract they lead to activation of muscle spindle as they stretch the
centre of muscle spindle.So the function of γ motor discharge is maintaining spindle sensitivity.
1. There are two types of intrafusal fibers in muscle spindles. The first type contains many nuclei in a dilated
central area and is therefore called a nuclear bag fiber.
2. Typically two nuclear bag fibers occur per spindle: nuclear bag fiber 1 with a low level of myosin ATPase
activity and nuclear bag fiber 2 with a high level of myosin ATPase activity. The second fiber type, the
nuclear chain fiber, is thinner and shorter and lacks a definite bag.
3. There are two kinds of sensory endings in each spindle. The primary (annulospiral) endings are the
terminations of rapidly conducting group Ia afferent fibers supplying central portion of bothnchain & Bag
fibres. The secondary (flower-spray) endings are terminations of group II sensory fibers and are located
nearer the ends of the intrafusal fibers but only on nuclear chain fibers.

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4. The nerves from the endings in the nuclear bag region show a dynamic responseQ; ie, they discharge most
rapidly while the muscle is being stretched and less rapidly during sustained stretch.
5. The nerves from the primary endings on the nuclear chain fibers show a static responseQ; ie, they discharge
at an increased rate throughout the period when a muscle is stretched. Thus, the primary endings respond
to both changes in length and changes in the rate of stretch.

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6. Stretching of spindle activates the α motor neuron via Ia & II afferents leading to muscle
contraction.

Central Nervous System Chapter - 6

7. Functions of Muscle spindle
8. Sensing and Maintaining normal muscle length (By Length servo and Follow up servo mechanism)
9. Stretch Reflex
10. Muscle tone (Due to Gamma efferent discharge)
11. Body Posture (Postural reflex at spinal cord level)
So both stretch and length are functions of muscle spindle but the primary function is maintenance of length.

MUSCLE TONE
It is due to asynchronous gamma motor neuron discharge which increases sensitivity of muscle spindle and
their discharge increases. As a result α Motor neurons are activated and lead to muscle
contraction(involuntary). These contractions result in increased tension in muscle even when not contracting
called resting muscle tone. Increase gamma discharge leads to increased muscle tone called Hypertonia is of 2
types
Rigidity: Both flexors & Extensors are hypertonic. Seen in Extrepyramidal lesion like Parkinsons.
Spasticity:Only 1 group of muscle is hypertonic.eg. Pyramidal lesion

A. Gamma motor neuron discharge Regulation:

1. DESCENDING TRACTS : from number of areas in brain – they control the sensitivity of muscle spindle & hence
stretch reflexes of various parts of body – to meet the needs of posture control.Mainly inhibitory so when
cut leads to increased γ discharge & Rigidity occurs called release phenomenon.eg. Decerebrate rigidity.
2. ANXIETY : ↑ γ motor neuron discharge
↓
Hyper active tendon reflexes

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3. STIMULATION OF SKIN BY NOXIOUS AGENT : ↑ γ motor discharge to ipsilateral flexor muscle spindles,
Withdrawl reflex activated.
4. Pain: ↑ γ motor discharge. Eg Gaurding seen in Acute abdomen due to increased γ discharge of abdominal
muscles.
4. JENDRASSIK’S MANEUVER: trying to pull the hands apart when flexed fingers are hooked together – ↑ γ
efferent discharge – facilitates Knee jerk reflex

B. Summary of Stretch Reflex

Inverse Stretch reflex (autogenic inhibition)

C. GOLGI TENDON ORGAN – receptor for inverse stretch reflex (3-25 muscle fibres / tendon organ )
1. are in series with muscle fibres
2. high threshold receptors
3. stimulated by both passive stretch and active contraction of muscle
4. supplied by Ib afferents
5. senses muscle tension
6. It acts as a protective reflex to prevent tearing of muscles. As a strong & potentially damaging muscle force
reflexly inhibits the contraction – leading to relaxation instead of trying to maintain the force.
7. Pneumonic: Golgi tendon organ is for tension (t for tension, t for tendon)
Muscle spindle is for length

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RETICULAR FORMATION
It is a network of nerve cells and fibers in the central core of the brainstem (It is present in the mid ventral portion
of the medulla, pons and midbrain). It is a complex poly-synaptic pathway and has many of the important centers in
the medulla viz deglutition center , vomiting center , respiratory center , center for cardiovascular regulation
Connections
A. Afferents
Collaterals from the specific sensory pathways (ascending sensory tracts)
Cerebral cortex (corticofugal fibres)

Central Nervous System Chapter - 6

Cerebellum
Basal ganglia
Efferents from reticular formation
Ascending pathway – the ascending reticular activating system (ARAS) to the cerebral cortex (via the thalamus – cf
thalamus)
Descending pathway- the reticulo spinal tract

B. Functions of the reticular system

Maintenance of sleep / wakefulness cycle : stimulation of ARAS causes arousal, awakefulness and alertness
Modulation of muscle tone :
Reticular formation is one of the supraspinal influences for the stretch reflex (e.f. regulation of posture)
It is the location of all the vital centers as mentioned above
EEG
1. it is concerned with synchronization / desynchronisation of E.E.G waves
2. stimulation of reticular formation : desynchronisation of EEG
3. inhibition of reticular formation : synchronization of EEG
4. Sensation
5. it modulates / controls sensory input to CNS eg supraspinal control of pain (gate control theory of pain)
6. it modulates sensory impulses of muscle spindle
7. it has role in focusing of attention (selective attention ) probably by cutting off all other signals
It is necessary for learning and conditioned reflex

THALAMUS
A. Classification of thalamic nuclei
1. Non-specific nuclei - These are the midline and intralaminar nuclei . these project diffusely and non-
specifically to the whole of the neocortex. These nuclei receive input from the reticular formation (the
ARAS). Impulses from the nuclei are responsible for the diffuse secondary response ( EEG) . The alerting
effects of reticular activation, are relayed through them.

2. Specific nuclei
a. Sensory relay nuclei
b. Medial geniculate body (concerned with hearing)
c. Lateral geniculate body (concerned with vision)
d. Ventro posterior lateral and ventro-posterior medial :

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e. These nuclei are the sites of termination of the ascending somatic afferent tracts the medial lemniscus
(carrying sensation from all parts except the face) ends in the ventroposterior lateral ; the trigeminal
leminscus (carrying sensations from face and taste sensation ) ends in the ventroposterior medial nucleus
f. Nuclei concerned with control of posture and movement
g. Ventrolateral nucleus -This is the chief motor nucleus of the thalamus. It receives fibres from the
cerebellum (the dentato – thalamic fibres cf cerebellum). Fibres from the ventrolateral nucleus project to
the primary motor cortex (area 4) and pre- motor cortex (area 6)
h. Ventro anterior nucleus -It receives fibres from the cerebellum and basal ganglia. It projects to the
premotor cortex.

B. Nuclei concerned with visceral efferent control mechanism

a) Fornix Maxillary bodies of

Via Hippocampus
hypothalmus

Via
Mamillo-thalamic tract (bundle of vicq d’ Azyr)

Cingulate gyrus (area 24) Anterior thalamic nuclei

The above circuit is called the papez circuit
b). Lateral dorsal nucleus -Its connections are similar to anterior thalamic nuclei.
c) Dorsal – medial nucleus

Hypothalamus Dorsal medial Frontal

nucleus cortex
C. Thalamic nuclei serving integrative and perceptual function:
1. Pulvinar and lateral posterior nucleus:
Superior collius nucleus / Pretectal nucleus

Pulvinar & lateral posterior nucleus

Parieto – occipito – temporal cortex
(which is intercalated between the somatic, visual and auditory cortex)
2. Reticular nucleus

D. Functions of thalamus
These can be predicted from the connections mentioned above
1. It is a great sensory relay station
It is an important relay station for all sensory systems except smell
2. Motor function
It is also a relay station for the motor fibres from the basal ganglia and cerebellum on their way to the cerebral
cortex

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3. It also relays a part of the ARAS

E. EEG
Hans Berger made the first systematic analysis of EEG
1. Waves in the EEG
Delta , theta , alpha , beta (from delta to beta , the frequency increases and the amplitude decreases)

2. Salient features of the different waves

Alpha rhythm -this is the wave seen at rest , with the eyes closed and the mind wandering .Its frequency is

Central Nervous System Chapter - 6

8-12 /second and the amplitude is 50-100 v . it is most marked in the parieto – occipital lobe. The
frequency of the alpha rhythm is decreased by
a. low blood glucose
b. low body temperature
c. low level of adrenal glucocorticoid hormones
d. high Paco2

F. Alpha block
(also called arousal response / alerting response / desynchronisation)
Alpha rhythm can be made to disappear by focused attention, by mental concentration and sensory
stimulation.
(the ascending reticular formation activity is responsible for the EEG alerting response ; stimulation of ARAS
causes the EEG rhythm to change from slow to high frequency small waves )
Beta rhythm -it has a frequency of 18-30 / second. It is seen over the frontal region. It is the wave seen when
the eyes are opened; It is the wave seen in the alerting response
Theta rhythm-frequency is 4-7/second. It has large amplitude. It occurs in children and in the hippocampus.
Delta rhythm -frequency is < 4/second, large amplitude
Gamma oscillations : 30-80 HzQ when individual aroused and focuses attention on something.
G. Sources of EEG
It is due to the constantly shifting / fluctuating dipole between the dendrites of the cortical cells and the cell
bodies

H. Evoked cortical potential

This is an EEG change produced by some form of stimulation.

Evoked cortical potential consist of :-

1. Primary evoked potential This consist of positive and a small negative wave. It has a latency of 5-12 ms. It is
highly specific in its location (over the primary receiving area of the cortex for the particular sensory pathway
that has been stimulated to evoke). It is produced by conduction of sensory signal through specific sensory
pathway.

2. Diffuse secondary response

This consists of a larger, more prolonged positive deflection . It has a latency of 20-80 ms and may last 30
seconds. Its activity can be recorded form most of the cerebral cortex. It is produced due to spread of impulses
through the ARAS to cerebral cortex.

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 Physiology

I. Sleep
NREM sleep (slow-wave sleep)-4 stages
REM sleep

Characteristics
Stage 1 of NREM Low amplitude, high frequency EEG activity
Stage 2 of NREM Sleep spindles (alpha – like 10-14 /seconds , 50 v
amplitude), K complexes
Stage 3 of NREM Low frequency , increased amplitude
Stage 4 of NREM Maximum slowing , (least frequency ), large waves
(rhythmic slow waves, synchronized )
REM Rapid , low voltage EEG

All the stages of sleep are reversible except the stage from REM to awake state
Duration / percentage of various stages
Percentage of REM out of total sleeping time
- Premature infants =80%
- Full term neonates =50%
- 20-65 years = 25%
- After 65 years, it decrease (in elderly = 15%)

J. Genesis of sleep
1. REM
The mechanism that triggers REM sleep is located in the pontine reticular formation. PGO spikes originate in the
lateral pontine tegmentum. The spikes are due to discharge of cholinergic neurons
2. NREM

K. Stimulation of certain sleep zones can produce sleep

1. Diencephalic sleep zone
(In the posterior hypothalamus and the near by intralaminar and anterior thalamic nuclei )
for producing sleep it requires low frequency stimulation
2. Medullary synchronizing zone
(In the reticular formation of the medulla oblongata at the level of the nucleus of the tractus solitarius)
This also requires low frequency stimulation for producing sleep
3. Basal forebrain sleep zone (includes preoptic area and the diagonal band of Broca)
This can produce sleep by both low as well as high frequency stimulation

L. Control of posture and movement

Posture control
Stretch reflex is fundamental to posture control. The major factor in posture control is by a change in the
threshold of the stretch reflex. This can be achieved
1. Directly by a change in the excitability of the motor neuron
2. Indirectly by change in the rate of discharge of gamma efferent nerve to muscle spindle

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There are 6 supraspinal influences on the stretch reflex viz

a. Cortex =inhibits gamma motor neuron
b. Basal ganglia=inhibits gamma motor neuron
c. Cerebellum= inhibits gamma motor neuron
d. Reticular formation (facilitatory area tonic ally active)= stimulates gamma motor neuron
e. Reticular formation (inhibitory area)= inhibits gamma motor neuron
f. vestibular nuclei = stimulates alpha motor neuron
Stretch reflex can be made hyperactive either by increasing gamma stimulation or by increasing alpha stimulation

Central Nervous System Chapter - 6

1. Transection at various levels helps to find out the role of each structure
a. SPINAL COMPONENTS -(only the spinal cord intact , transection above the spinal cord) there is initially
a period of spinal shock during which all spinal reflexes are profound depressed

b. Features after the spinal shock is over

Hyperactive stretch reflexes
Presence of positive supporting reaction (magnet reaction)and negative supporting reaction
when suitably stimulated , spinal animals can even produce walking movements indicating the presence of
loco- motor pattern generators .However the spinal locomotor pattern generator needs to be turned on by
the mesencephalic locomotor region
Automatic reflexes
i. Reflex contraction of the urinary bladder and rectum can occur
ii. BP is generally normal at rest but there are wide swings
iii. Bouts of sweating and blanching of the skin occur
Sexual responses -Erection and ejaculation is possible by local stimulation
Mass reflex -Irradiation from one reflex center to another can occur . Minor stimulation of skin can cause
evacuation of the urinary bladder rectum, sweating , pallor , BP swings, in addition to withdrawal response

M. MEDULLARY COMPONENTS - transection at the superior border of the pons causes decerbration. It leaves
the following components intact. the spinal cord, medulla , pons and cerebellum
1. Features
a. No stage of spinal shock decerebrate rigidity immediately occurs. The reason for this is increased
general excitability of the motor neuron pool
b. Increased discharge of gamma motor neurons (because the inhibitory influence of the cerebral cortex
and basal ganglia on the gamma motor neuron is removed)
c. (Although the cerebellum also has an inhibitory influence on gamma motor neuron , removal of the
cerebellum in humans causes hypotonia )
d. The decerebrate rigidity in animals is most marked in the antigravity muscle. However, in humans the
pattern of decerebrate rigidity is extensor in all the 4 limbs
(note that in decorticate rigidity, there is extensor rigidity in the legs and moderate flexion in arms )
e. tonic labyrinthine and tonic neck reflexes are present: these reflexes are responsible for the change in
the pattern of rigidity with change in the position. They are not righting reflexes
f. righting reflexes are absent

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N. MID BRAIN COMPONENTS Here , the transection is made at the superior border of the mid brain
1. Features
a. extensor rigidity is seen only when the animal lies quietly on its back
b. the animal can rise to standing position walk , and right itself
c. righting reflexes are present. All the righting reflexes (except the optical righting reflex, which is
cortical) are integrated at the mid brain (the righting reflexes operate to maintain the normal standing
position and keep an animal head upright)
d. grasp reflex present
e. pupillary light reflex present (if the optic nerves or intact)
f. nystagmus present
g. vestibular placing reaction present.

O. CORTICAL COMPONENTS: decortication in many species of animals causes little motor deficiency.In
primates , the deficit is more severe but movement in still possible

1. Features
a. Because the hypothalamus is present , temperature regulation and other visceral and homeostatic
functions are present.
b. Inability to react in terms of past experience
c. Decorticate rigidity: this is because of loss of cortical inhibition of gamma motor neuron
d. As in mid brain , the rigidity is present only when the animals is at rest
e. Hopping and placing reaction absent

2. Postural reflexes
Reflexes Integrated in
Antigravity reflexes, attitudinal reflexes, (ie. Tonic Medulla
labyrinthine & tonic neck reflexes)
Locomotor Mid brain, thalamus
Righting reflexes (except optical righting reflex) Mid brain
Optical righting reflex Cortex
Visuo spinal reflex Mid brain
Conditioned reflex Cortex

CONTROL OF MOVEMENT
Some general schemes
Commands for voluntary movement originates in the cortical association areas (this is any area in the brain that is
lying between and connecting on sensory projection area with another )
A. The movements are planned in the cortex , basal ganglia and neocerebellum
B. From the basal ganglia and neocerebellum (via the thalamus), there is projection to Premotor and motor
cortex
C. From the motor cortex (via the corticospinal tract and corticobulbar tract ) there is projection to spinal
motor neurons and homologous cranial nerve nuclei and there is movement

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D. There is feedback information of the movement (via the sensory input)

E. The spinocerebellum in turn projects to the brain stem (via the rubro spinal , reticulospinal , tecto spinal and
vestibulo spinal) for posture & coordination
F. In the brains stem and the spinal cord,
 The medial (or ventral , pathways / neurons subserve the muscles of the trunk and proximal portions of
limbs )
 The lateral pathways / neurons subserve the distal portions of the limbs
Thus,

Central Nervous System Chapter - 6

1. The medial portions of anterior horns
2. The ventral corticospinal tract and
3. The medial descending pathways of brain stem (viz the tectospinal , retciulospinal and vestibulo spinal
tracts )
4. Are concerned with adjustment of proximal muscles and posture
Whereas,
5. The lateral corticospinal tract and
6. The rubrospinal tract are concerned with distal limb muscles (for skilled voluntary movements)
a. The pyramidal tracts are the corticospinal tracts; strictly speaking it is only the lateral corticospinal
tract, which should be called the pyramidal tract because it is only the lateral corticospinal tract that
forms pyramids in the medulla. The extra pyramidal tracts are the rest of the descending pathways
from the brainstem.
b. Cortical motor areas Motor cortex (the primary motor cortex). This is in the precentral gyrus (area 4)
premotor cortex (area 6)
c. Supplementary motor area (in the medial side of the hemisphere on and above the superior bank of the
d. cingulated sulcus)
e. Somatic sensory area I (in post – central gyrus )
f. Somatic sensory area II (in the wall of the sylvian fissure )
i. Representation In the precentral gyrus
ii. There is a point to point representation in the precentral gyrus. The arrangement is such that the feet
is represented at the top and the face at the bottom. Except the face area (which has bilateral
representation), the rest of the representation is unilateral to the opposite side musculature)
iii. The size of the representation is proportional to the skill involved in voluntary movement e.g the
speech and hand has a large area of representation.
iv. The premotor cortex may be concerned with setting posture at the start of planned movement
7. Supplementary motor area
i. This is involved primarily in programming motor sequences
ii. The posterior – parietal cortex (somatic sensory areas)
iii. This provides the origin of 40% of corticospinal and corticobulbar tracts. It also projects to premotor
area. Its lesion results in inability to execute learned sequence of movements
(Lesions of the left motor cortex causes motor dysfunction of left and right hand whereas lesions of right
motor cortex has little effect on right hand)
[Function of area 5: aiming of hands towards an object and manipulating it ]
[Function of area 7 : hand - eye coordination ]

G. Corticospinal / corticobulbar tracts

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1. Origin:
a. 30% from motor cortex b. 30% from premotor cortex
c. 40% from parietal lobe , especially somatic sensory ones
(The corticospinal fibres from parietal lobe is presumably concerned with direct sensory motor coordination)
Functions: - the corticospinal and corticobulbar tracts are the primary pathway for initiation of skilled voluntary
movement
2. Lesions:
a. Lesion of lateral corticospinal tract
i. LOSS of control of distal muscles of limbs (which is concerned with fine, skilled movements )
ii. Hypotonia
iii. Extensor plantar response (Babinski’s sign)
b. Lesions of ventral corticospinal tract this causes axial muscle deficits (difficulty with balance , walking
and climbing )
c. Lesion of extrapyramidal (posture – regulating pathways) : causes spastic paralysis

3. Rubrospinal tract:
a. Origin: Red nucleus (of the midbrain) b. Crossed pathway
c. Afferents to red nucleus come from:
i. Cerebral cortex ii. Inhibits antigravity muscles (or extensors) iii. For fine, skilled movement

4. Tectospinal tract
Origin: superior colliculus of the midbrain
Crossed pathway
Afferents to superior colliculus come from:-
a. Cerebral cortex (especially from occipital lobe

FUNCTION
Reflex movement of the head and arms in response to visual and exteroceptive stimuli

A. Vestibulospinal tract
1. Uncrossed pathway 2. 2 ‘types’
3. Lateral vestibulospinal tract 4. Medial vestibulospinal tract

B. Lateral vestibulospinal tract

1. Origin: Lateral vestibular nucleus (also called Deiter’s nucleus)
2. Afferents to lateral vestibular nucleus come from
3. Vestibular nerve – Fastigial nucleus of the cerebellum

C. Medial vestibulospinal tract

1. Origin: Medial vestibular nucleus
2. Function of vestibulospinal tract
Excitatory to antigravity muscles (stimulates the extensors and inhibits the flexors) of neck and back muscles.

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D. Reticulospinal tract
1. It is a rely station for descending motor commands
2. Origin: from reticular formation
3. Afferents to reticular formation come from : a. Cerebral cortex b. Intermediate nuclei of cerebellum
4. 2 ‘types’: a. Lateral reticulospinal tract b. Medial reticulospinal tract

E. Lateral reticulospinal tract

1. Both crossed and uncrossed pathway
2. Origin: reticular formation in medulla

Central Nervous System Chapter - 6

3. Function
4. Facilitatory influence on flexors; inhibitory influence on extensors

F. Medial reticulospinal tract: 1. Crossed pathway 2. Origin: from reticular formation in pons
G. Function
Inhibitory influence on flexors, facilitatory influence on extensors
H. Basal ganglia
(There is one on each side )
It consist of
1. Caudate nucleus 2. Putamen 3. Globus pallidus
I. Plus the functionally related
1. Subthalamic nucleus (body of Luys)
2. Substantia nigra
The caudate nucleus and putamen is referred to as the striatum and the putamen and the globus pallidus as the
lenticular nucleus

CONNECTIONS OF THE BASAL GANGLIA

A. Afferents
1. From cerebral cortex (all parts )to striatum
2. From the centromedian nucleus of thalamus to striatum
so the afferents to the basal ganglia end in the striatum
B. Efferent
1. Mainly from the internal segment of globus pallidus to the ventro lateral , ventroanterior and centromedian
nuclei of thalamus
2. From substantia nigra to the thalamus
3. Inside connection

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A : direct pathway – causes disinhibition of thalamus (and stimulation of cortex )

B:- Indirect pathway : causes inhibition of thalamus (and inhibition of cortex)

C. Functions of basal ganglia

1. Planning and programming of movements
basal ganglia via thalamus motor cortex

cortico – spinal tract

motor neurons
2. Role in cognitive processes (especially that of the caudate nucleus )
3. ON/OFF Controller of movement
4. Helps in learning of Skilled movements

D. Lesion of Basal ganglia:

1. Hemiballismus  due to lesion in subthalamic nucleus
2. Huntington’s disease/chorea:- Due to abnormal gene  many times repeating codon, CAG- “The abnormal
movements are believed to be caused by loss of most of the cell bodies of GABA-secreting neurons in the
caudate nucleus and putamen (= Striatum) and acetyl choline secreting neurons in many part of the brain”
3. Parkinson’s disease (Paralysis agitans) Q\ - “results from widespread destruction of that portion of the
substantia nigra Q, the pars compacta, that sends dopamine-secreting nerve fibers to the caudate nucleus and
putamen (= striatum) - C/F — Cog-wheel or lead pipe rigidity, Involuntary tremor (3-6 cycles/sec) and Akinesia.
4. Athetosis (Writhing movement)  due to lesion in the globus pallidus.

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Cerebellum
A. Divisions (anatomical)
1. It has a central vermis (made up of 10 lobules)
2. 2 lateral cerebellar hemispheres- these have many foldings and therefore have a large surface area.
The 10 lobules of the vermis are:
I : Lingula
II & III : Centralis
IV & V : culmen

Central Nervous System Chapter - 6

VI : Lobulus simplex
VII : Folium, tuber
VIII : Pyramis
IX : uvula
X : Nodulus
B. Functional divisions
1. Spinocerebellum \vermis\ paleocerebellum
2. Cerebrocerebellum (or neocerebellum)
3. Vestibulocerebellum \Archicerebellum\ flocculonodular lobe

(1)
a

(2) c

3 d
a. To medial descending systems
for motor execution
b. To lateral descending system
c. To motor and premotor cortex – for motor planning
d. To vestibular nuclei – for balance and eye movements

The constituents of 3 parts of the cerebellum are:

Part Constituents Connections Functions

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Spinocerebellum Vermis (except the Afferent By comparing plan with

nodulus ) and the Proprioceptive input from performance,it
adjacent medial body smoothens and
portions of the Copy of the motor plan coordinates
hemispheres movements
Efferent
From vermis
 to
Brains stem area (for axial
and proximal limb
muscles)
From the hemispheres
 to
brain stem area ( For
distal muscles)
Cerebro cerebellum The lateral portions of Intract with motor cortex Planning and
(or neocerebellum) hemispheres programming movements
Vestibulo The nodulus and Vestibular Equilibrium
cerebellum (or the flocculus Learning induced change
floculo- nodular in vestibulo ocular reflex.
lobe)

C. Structure
The cerebellum is organized as
a. An outer cerebellum cortex, separated by
b. White matter from the
c. Deep cerebellar nuclear

c
The cerebellar cortex has 3 layers and 5 types of cells :
The 3 layers are
1. The outer molecular
2. Middle purkinje
3. Inner granular

The 5 cells are:

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1. Purkinje
2. Granular
3. Golgi
4. Stellate
5. Basket

Location of the cell bodies of the cells:

Stellate, Basket : Outer molecular layers
Purkinje : Middle Purkinje layer

Central Nervous System Chapter - 6

Golgi, Granular : Inner granular
(also, the ‘glomeruli’ lie in the inner granular)

The deep nuclei are (4 on each side)

i) Dentate ii) Emboliform iii) Fastigial iv) Globose
(the emboliform and globose are together referred to as the Inter positus)

D. Connections
1. Afferent
There are 2 main primary afferent inputs
a. Mossy fibres
b. Climbing fibres
i. Both of these are excitatory; they send collateral to the deep nuclei & pass to the cerebellar cortex.
ii. The climbing fibres ends on the Purkinje cell; the mossy fibres also end on the Purkinje cell, but
through the granule cell.
iii. The input to the Purkinje cell from the climbing fibre is 1:1; it is a stong excitatory input and
produces a complex spike whereas the input to the Purkinje cell from the mossy fibre is 1 million : 1;
it is a weak input and produces a simple spike.
iv. What do the mossy and climbing fibres convey ?
v. Climbing Fibres = They come from one single source viz the inferior olivary nuclei. The climbing
fibres convey proprioceptive inputs from all over the body

Purkinje cell

Climbing fibres

Inferior olivary nuclei

Proprioceptive input from all over the body

Mossy fibres: They come from many sources. The fibres first end on the dendrites of the granule cells in
“glomeruli”. The mossy fibres conveys proprioceptive input from all parts of the body and also input from the
cerebral cortex via pontine nuclei to the cerebellar cortex.

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The various tracts carried by the climbing and mossy fibres are:
1. Vestibulo- cerebellar Vestibular impulses from labyrinth.
Direct and via vestibular nuclei (Ipsilateral)
2. Dorsal spinocerebellar Proprioceptive and exteroceptive impulses from body
(trunk/ leg) (Ipsilateral)
3. Ventral spinocerebellar Proprioceptive and exteroceptive impulses from body
(trunk/ leg) (Contralateral)
4. Cuneo cerebellar Proprioceptive impulses from head and neck
(Ipsilateral)
5. Olivo cerebellar Proprioceptive impulses from all over body through
relay in inferior olive
6. Tecto – Cerebellar Auditory and visual impulses via inferior and superior
colliculi
7. Ponto- cerebellar Impulses from motor and other parts of cerebral
cortex via pontine nuclei (From Opposite cerebral
cortex)
8. Rubro- cerebellar Impulses from opposite red. Nucleus
9. Reticulo- cerebellar Impulses from brain stem reticular formation

- The olivo cerebellar pathway projects to cerebellar cortex via climbing fibres.
- The rest of the listed pathways project via mossy fibres.
[ The sensory input to the cerebellum is mostly ipsilateral]
[the dentatothalamo– cortical pathway crosses to the opposite side; further; the corticospinal tract also crosses
to the opposite side. Therefore, the cerebellum regulates the activity of the SAME side of the body. In
cerebellar lesions, there is a  in muscle tone on the same side and the patient tends to fall on same side.
2. Efferent (output ) cerebellum
e. From vestibulo cerebellum – directly to the brain stem (not via the deep nuclei)
f. From spinocerebellum

From the medial portions of the spinocerebellum to Fastigial nuclei

Then to
Brainstem
From adjacent hemispheric portions of the spinocerebellum to Emboliform and globose nuclei
Then to
Brainstem
ii) From neocerebellum – to the denatate nucleus

Then to (directly / indirectly by)

Ventrolateral nucleus of Thalamus

Cortex
(the dentato thalamocortical pathway)
(Note that only the output from the vestibulo cerebellum does not go via the deep nuclei )

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Vestibulo-
Cerebellum Rest of the cerebellum
Cerebellar cortex
Deep nuclei
(Cerebellar output)
Direct (to brainstem) Via the deep nuclei (to brainstem/ thealamus)

[Note that the afferent inputs go both to the cerebellar cortex and to the deep nuclei. In other words, deep

Central Nervous System Chapter - 6

nuclei receive input from the cerebellar cortex (except vestibulocerebellum) as well (as via the collateral) from
the afferent inputs of the cerebellum]

3. Inside connections
a) Purkinje cell – (recall that the climbing fibres end directly on the Purkinje cell; the mossy fibres end on the
Purkinje cell through the granular cell.) The Purkinje cell projects to the deep nuclei; the deep nuclei then gives its
output out of the cerebellum. The input from the Purkinje cell to the deep nuclei is inhibitory; however, the deep
nuclei output is always excitatory. Even at rest deep nuclei continuously discharge excitatory inputs. When
movement occurs, the deep nuclei discharge increase at first; within a few milliseconds, inhibition of this discharge
occurs by the Purkinje cell. This allows damping.

b) Granule cell : - output from the granule cell axons bifurcate and give rise to parallel fibres. The granule cell
stimulates the Purkinje cell; however, the granule cell also ends at basket/ stellate cells and stimulates them. But
the basket and stellate cells in turn inhibit the Purkinje cell (this inhibition by the basket/ stellate cell is an example
of feed forward inhibition). The granule cell itself is inhibited by the Golgi cell
The granule cell synthesizes glutamate but has GABA receptor on it. The Golgi cell inhibits granule cell via the
GABA receptors.
(Note that out of the 5 cells in the cerebellar cortex only the output from the granule cell is excitatory the
output from the rest of the cells is inhibitory.
a. Granule cell Stimulates the Purkinje, Basket and stellate cells
b. Purkinje cell Inhibits deep nuclei
c. Golgi cell Inhibits granule cell
d. Basket cell Inhibits Purkinje cell
e. Stellate cell Inhibits Purkinje cell

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4. Functions
a. Maintenance of equilibrium – this is the function of the vestibulo cerebellum (i.e. the flocculonodular
lobe). There is inter connection between the vestibular apparatus and the flocculonodular lobe.
b. Role in regulation of tone/ posture – the effects of the cerebellum on the stretch reflex are complex.
With cerebellar disease one would expect an increased in tone. But in humans, hypotonia occurs in
cerebellar disease. The spinocerebellum projects on
i. The alpha motor neurons (through efferent output to vestibular nuclei)
ii. The gamma motor neurons (through efferent output to reticular formation)
There is a perfect co ordination between the alpha and gamma motor neuron discharge (the
alpha- gamma linkage). The linkage exists at the level of the spinal cord; the ‘switch’ for the
linkage is in the cerebellum.
c. Error control function / effects on movement- By comparing plan with performance, (the cerebellum
gets input from the cortex as well as various sensory inputs) the cerebellum makes anticipatory
corrections.
d. Planning functions – This is the function of the neocerebellum
e. Role in learning: The cerebellum is concerned with learned adjustments to repetitive tasks.

5. Cerebellar lesions/ disease

1. Features
a. No paralysis
b. No sensory deficit
c. No abnormalities at rest (except the changes in stretch reflexes)
d. Ataxia (drunken gait)

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e. Slurred/ scanning speech

f. Dysmetria (past- pointing)
g. Intention tremor
h. Rebound phenomenon
i. Adiadokodinesia
j. Decomposition of movement
[Electrical activity in cerebellum: the basic electrical of frequency rhythm of the cerebellar cortex is of frequency
150- 300/ S and 200v amplitude. Superimposed on this basic rhythm is a 1000-2000/s component of

Central Nervous System Chapter - 6

smaller amplitude.

Upper motor neuron lesions Lower motor neuron lesions

Paralysis of movements rather than muscles Individual muscle or muscle group affected
Slight disuse atrophy Marked wasting
Hypertonia Hypotonia
Clasp knife spasticity Flaccid paralysis
Tendon reflexes increased (clonus may be present) Tendon reflexes decreased or absent
Positive Babinski sign Negative Babinski sign

Circadian rhythm is controlled by (AIIMS Nov 08)

1. Supraoptic nucleus
2. Suprachiasmatic nucleus
3. Paraventricular nucleus
4. Median eminence
Ans. (B) Suprachiasmatic nucleus

HYPOTHALAMUS
a. Circadian rhythm : Suprachiasmatic nuclei
b. Temperature
i. Heat response : mediated by anterior hypothalamus
ii. Cold response: mediated by posterior hypothalamus
6. Thirst
Lateral preoptic area
7. Hunger
a. Feeding center: lateral hypothalamus
b. Satiety center: ventromedial hypothalamus
c. Leptin is a 16 kDa protein hormone that plays a key role in regulating energy intake and energy
expenditure, including appetite and metabolism. Leptin is one of the most important adipose derived
hormones. The Ob(Lep) gene is located on chromosome 7 in humans. Leptin binds to the ventromedial
nucleus of the hypothalamus, known as the "appetite center." Leptin signals to the brain that the body
has had enough to eat, or satiety. The circulating leptin levels give the brain input regarding energy
storage so it can regulate appetite and metabolism. Leptin works by inhibiting the activity of neurons that
contain neuropeptide Y (NPY) and agouti-related peptide (AgRP), and by increasing the activity of neurons

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expressing α-melanocyte-stimulating hormone (α-MSH).Leptin resistance can lead to Obesity in which

incresed Leptin levels are present. Leptin receptors: especially in arcuate nuclei and paraventricular nuclei

Principal Polypeptides and Proteins That May Be Involved in Regulation the Appetite for Food.

Increase food intake (orexigenic) Decrease food intake (antiorexigenic)

AGRP Bombesin
-Endorphin CART
Galanin CCK
Ghrelin CRH
GHRH CGRP
MCH Glucagon
Neuropeptide Y GLP-1, 2
Orexin A GRP
Orexin B Leptin
Neurotensin
Oxytocin
Peptide YY
Somatostatin
-MSH

d. Sexual behavior : Anterior ventral hypothalamus, piriform cortex (in male)

e. Catecholamines: dorsal and posterior hypothalamus

8. Control of pituitary hormones

a. Anterior
i. CRH: Paraventricular nuclei
ii. GnRH : preoptic area
iii. PIH/PRH (Prolactin)
b. Posterior
i. ADH/ Oxytocin: supraoptic and paraventricular nucleus
ii. Both nuclei secrete both hormones; however,
iii. Paraventricular: mainly oxytocin
iv. Supraoptic: mainly ADH
Osmoreceptors : Anterior hypothalamus
9. Pyrogens
These release cytokines from macrophages etc.  act on preoptic area of hypothalamus  release local
prostaglandins  fever

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10. Autonomic nervous system

Stimulation of
a. The anterior hypothalamus
Causes parasympathetic response like contraction of the urinary bladder
b. Lateral areas of the hypothalamus
Produces sympathetic responses such as rise in BP, pupillary dilation, piloerection, increased adrenal
medullary secretion etc. this is the kind of response seen in animals exposed to stress (the fight or the
flight reaction)

Central Nervous System Chapter - 6

c. Mid-dorsal area of the hypothalamus
Causes cholinergic sympathetic vasodilatation
d. Dorsomedial nuclei and posterior hypothalamic areas
Produces increased adrenal medullary secretion which is one of the physical changes associated with rage
and fear.
MELATONIN
A. Melatonin is synthesized by pineal parenchymal cells and secreted by them into the blood and CSF.
B. It is synthesized from serotonin by N-acetylation and O-methylation. Q
C. Formation and metabolism of melatonin -
Tryptophan 5-Hydroxytryptophan 5-Hydroxytryptamine (Serotonin)
|
N-Acetyl —5-methoxytryptamine  N-Acetyl-Serotonin
(Melatonin)

 Metabolism
6-Hydroxymelatomn (in Liver)
and other metabolites (in brain)

A. ReguIation of Melatonin Secretion

1. In humans and all other species studied to date, melatonin synthesis and secretion are increased during
the dark period of the day and maintained at a low level during the day-light hours. The remarkable
diurnal variation in secretion is brought about by training of the hypothalamus to the light-dark cycle via
retino-hypothalmic nerves
2. The hypothalamus in turn cause norepinephrine secretion by the postganglionic sympathetic nerves (nervi
conari) that innervate the pineal gland.
3. The norepinephrine acts via adrenergic receptors in the pineal gland to increase interacellular cAMP, and
the cAMP in turn produced a marked increase in N-acetyl transferase activity. This results in increased
melatonin synthesis and secretion.

Exposure to darkness


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Retinohypothalamic fibers

supra chiasmatic nuclei in hypothalamus

Preganglionic sympathetic neurons in spinal cord

Postganglionic sympathetic nerves (nervi conarii) arising in superior cervical ganglion

norepinephrine secretion in pineal gland

intracellular cAMP

N-Acetyltransferase activity

Hydroxyindole- O methyl transferase activity

Melatonin

B. Higher Functions of CNS

1. Cortical organization (Cerebral cortex)
a. The neocortex is generally arranged in six layers
b. The neurons are mostly pyramidal cells with extensive vertical dendritic trees
c. Afferents from the specific nuclei of the thalamus terminate primarily in cortical layer 4 , where the
non specific afferent are distirubted to layers 1 to 4.
2. Histological structures of cerebral cortex:
a. Most of the cells are three types: -
i. Granular (stellate) cells
ii. Fusiform cells and
iii. Pyramidal cells
b. Granule cells — short axon function mainly as intracortical interneurons. Some are excitory (releasing
—glutamate) and others are inhibitory (releasing  GABA)
c. Pyramidal cells and fusiform cells: 
i. They give rise to almost all the out put fibers from the cortex.
ii. Pyramidal cells are larger and more numerous than fusiform cells
iii. Pyramidal cell are the source of long large nerve fibers that go all the way to the spinal cord and also
give rise to most of the large subcortical association fiber bundles that pass from one major part of
the brain to the other.

C. BRODMANN’S AREAS
S. No. Area

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Primary sensory area

1. = 3, 1, 2
(Post central gyrus)
Primary Motor area
2. = 4
(Pre – central gyrus)

3. Premotor area = 6

4. Frontal eye field = 8

Central Nervous System Chapter - 6

5. Sensory association area = 5, 7

Primary visual area = 17

6.
(Visual association area) = 18,19
Primary auditory area = 41
7.
Auditory association area = 41, 42
Broca’s area = 44
8.
Wernicke’s area = 22
Cingulete gyrus = 24
9.
Angular gyrus = 39

D. Applied:
1. Prosopagnosia  the inability to recognize faces due to lesion in the fusiform gyrus on the inferior surface
of the right temporal lobe.
2. Acalculia  a-selective impairment of mathematical ability (calculation), due to lesion in the inferior
portion of the left frontal lobe.
3. Construction Apraxia : - Lesions that involves the posterior parietal cortex in the right hemisphere lead to
severe difficulties in copying-simple line drawings.
4. Anosmia  inability to smell.

E. Prosopagnosia and visual agnosia:

1. Prosopagnosia - no difficulty with the generic identification of face as face or of a car as a car, but they
cannot recognize the identify of individual face or the make of an individual car.
2. Visual obiect agnosia: when recognition problems become more generalized and extend to the generic
identification of common objects, the condition is known as visual object agnosia; the pateint is unable
either to name a visually presented object or to describe its use.
3. The characterstic lesions in prosopagnosia and visual object agnosia consists of bilateral infarctions in the
territary of the posterior cerebral arteries and involve the lingual and fusiform gyri of occipitotemporal
cortex. Q\

F. Balint's syndrome: - (Severe spatial disorientation) 

1. This syndrome is a combination of :

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 Physiology

a. Oculomotor apraxia (deficit in the orderly visuo-motor scanning of the environment)

b. Optic ataxis (Deficits in accurate manual reaching towards visuat target) and (c) Simultanganosia: - (an
inability to integrate visual information in the centre of gaze with more peripheral information for eg -
the patient "misses the forest for the trees".
2. Balint's syndrome results from bilateral dorsal parietal lesions Q, common settings include:
a. Water - shed infarction between the middle and posterior cerebral artery territories,
b. Hypoglycemia
c. Sagittal sinus thrombosis or
d. Degenerative disease such as Alzheimer disease.

G. Gerstmann's syndrome: -
1. It is a combination of:
a. Acalculia (impairment of simple arithmetic)
b. Dysgraphia (impaired writing)
c. Fingeranomia (inability to name individual fingers)
d. Right Left confusion (an inability to tell whether a hand, foot or arm of the patient a examiner is an
right or left side of the body)
2. Cause; - Gerstmann's syndrome is commonly associated with damage to the inferior parietal lobule
(=Angular gyrus) in the left hemisphere (Dominant side)

H. Cerebral dominance: Specialization of one hemisphere.

1. Left hemisphere (Dominant or Categorical hemisphere):
a. More adept in language and analytical abilities.
b. Damage:
c. Severe speech problems.
2. Right hemisphere (Representational hemisphere):
a. Most adept at visuospatial tasks,Emotion, Non verbal communication
b. Damage:

• Difficulty finding way around house.

I. Language:

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 Central Nervous System

1. Broca’s area: Inferior frontal gyrus Area 44

a. Involves articulation of speech.
b. Broca’s area sends fibers to the motor cortex which directly controls the musculature of speech.
c. In damage less speech but comprehension is unimpaired. MOTOR or FLUENT APHASIA
2. Wernicke’s area: Superior Temporal Gyrus Area 22
a. Involves language comprehension.
b. In damage, language comprehension is destroyed, but speech is rapid without any
meaning(senseless). SENSORY or FLUENT APHASIA
3. Angular gyrus:

Central Nervous System Chapter - 6

a. Center of integration of auditory, visual, and somatesthetic information.
b. Damage produces aphasia.
4. Arcuate fasciculus:
To speak intelligibly, words originating in Wernicke’s area must be sent to Broca’s area. Connects the two
structures.

J. Limbic System
The limbic system is applied to the part of brain that consist of a rim of cortical tissue around the hilum of
cerebral hemisphere and a group of associated deep structures.
Also called rhinocephalon & is phylogenetically the oldest part of cerebral cortex (allocortex) It consists of:
1. Cingulate gyrus
2. Septal nuclei
3. Hippocampal formation:Hippocampus & Dentate nucleus
4. Amygdala
5. Median forebrain bundle (MFB) act as pleasure centre
Papez circuit links limbic system to hypothalamus & thalamus and is concerned with Emotions & Memory
Fornix from hippocampus  mamillary body of hypothalamus  Anterior nucleus of thalamus

K. Function of limbic system

1. Role in Olfaction related memory
2. Emotional and Behavioural responses
3. Autonomic responses
4. Limbic system with Hypothalamus ~ it concerned with ~ sexual behaviour , the emotion of rage and
fear and motivation
5. Rage responses - minor stimuli evoke violent episodes - are observed after removal of the neocortex
and after destruction of ventro-medial hypothalamic nuclei and septal nuclei in animal with intact
cerebral cortices. i.e. emotional effect to a physical stimuli (Rage) is given by cerebral cortices.
6. Learning & Memory

Emotions have 3 components

1. Cognition: Awareness 2. AFFECT: feeling itself
3. Conation: desire to act 4. Peripheral Expression: via Hypothalamus i.e HR, BP etc

The nucleus accumbens is a collection of neurons within the forebrain. It is thought to play an important role
in reward, laughter, pleasure, addiction, fear, and the placebo effect. The principal neuronal cell type found in

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 Physiology

the nucleus accumbens is the medium spiny neuron. The neurotransmitter produced by these neurons is
gamma-aminobutyric acid (GABA). Major inputs to the nucleus accumbens include prefrontal association
cortices, basolateral amygdala, and dopaminergic neurons located in the ventral tegmental area (VTA).
Dopaminergic input from the VTA is thought to modulate the activity of neurons within the nucleus
accumbens. These terminals are also the site of action of highly-addictive drugs such as cocaine and
amphetamine, which cause a manifold increase in dopamine levels in the nucleus accumbens.

Kluver-Bucy syndrome (KBS) has been considered a direct consequence of bilateral anterior temporal lobe
damage resulting from disease or injury.
Features: Hyperphagia, Hypersexuality, Fearlessness, Decreased Emotions, Agnosia & Rage

MEMORY
A. Memory is of following types:-
1. Short term memory: lasts seconds to hours. Due to synapses.
2. Long term memory: Days or can last for lifetime. long term memory involves formation of new synaptic
connection and synthesis of new proteins"
3. Recruitment of neurons is called Cortical plasticity and is a established mechanism of Memory & learning

B. Recent memory: Short-term memory. Also called working memory.

C. Working memory is a form of short-term memory that keeps information available, usually for very short
periods, while the individual plans action based on it.
Capacity: About 7 plus or minus 2 "chunks" of information (Miller, 1956)
Duration: About 18 to 20 seconds (Peterson & Peterson, 1959)

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 Central Nervous System

D. Long-term memory is the relatively permanent memory store. Also called remote memory. Duration: Up to a
lifetime.
E. Delayed memory This term is used to describe the experience of an individual who recalls a memory for
which he or she was previously amnestic. The recollection may occur spontaneously or in the context of
therapy.

F. Memory function includes:

1. Registration (acquisition)
2. Conversion of Short-term memory to Long term memory

Central Nervous System Chapter - 6

3. Retention (storage or consolidation)
4. Stabilization
5. Retrieval (decoding or recall)

G. The process of Conversion of Short-term memory to Long term memory occurs in hippocampal cortex
while the process of retreival requires the frontal lobe. When the subject recalls words there is increased
activity in their right frontal lobe and para hippocampal cortex on both sides.
H. The encoding process for short term explicit memory involves the hippocampus, long term memory is stored
in various part of neocortex.
I. The dominant source of input to the hippocampus is the entorhinal cortex (EC). Within the hippocampus, the
flow of information is largely unidirectional, with signals propagating through a series of tightly packed cell
layers, first to the dentate gyrus, which projects to the CA3 layer, which projects to the CA1 layer, which
projects to the subiculum, which projects out of the hippocampus to the EC. Theta rhythm is produced by
Hippocampus. long-term potentiation (LTP) is produced here which involves NDMA receptors.
J. Note: Acc. to current views information from the senses is temporarily stored in various parts as working
memory which is relayed to the medial temporal lobe, and specifically to the parahippocampal gyrus From
there, it enters the hippocampus. Output from the hippocampus leaves via subiculum and the entorhinal
cortex and somehow binds together and strengthens the circuit in neocortex forming over time the stable
remote memories.'

Learning: By Reinforcement (reward & punishment mechanism) & conditioned reflex

Conditioned reflex is a example of associative learning.eg Pavlov's classic experiments.
1. meat in front of dog : unconditioned stimulus (US)
2. Innate response : salivation with food
3. The conditioned stimulus (CS) : bell ringing
4. Conditioned Reflex : Salivation on ringing of bell alone

Mirror neuron is a neuron which fires both when an animal acts and when the animal observes the same action
performed by another animal (especially by another animal of the same species). Thus, the neuron "mirrors"
the behavior of another animal, as though the observer were itself acting. These neurons have been directly
observed in primates, and are believed to exist in humans and other species including birds. In humans, brain
activity consistent with mirror neurons has been found in the premotor cortex and the inferior parietal cortex.
Mirror neurons might be very important in imitation and language acquisition

AUTONOMIC FUNCTION TESTING

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 Physiology

Sympathetic Functions Para Sympathetic Functions

Handgrip dynamometry Valsalva ratio (Max.RR/Min. RR Interval) N>1.2
SL Ratio E:I Ratio (Exp./Insp)
Cold Pressor test
Galvanic Skin Resistance
Sweat test
Quantitative Sudomotor Axon Reflex Testing (QSART)
Quantitative Sudomotor Axon Reflex Testing (QSART): The QSART test measures the autonomic nerves that
control sweating. The QSART measures the volume of sweat produced by stimulation.

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 Physiology

“Please Read the Preface of this book Before you attempt these questions.”
Explanation of answer start from page no. 284
8. Exposure to darkness leads to increased melatonin
Section-1, General, Neurons, Neurotransmitters secretion. It is brought about by:
A. Decreasing the activity of suprachiasmatic nuclei
1. Pain insensitive structure in brain is (AIIMS MAY B. Increasing the serotonin N-acetyl transferase
2010) C. Decreasing the hydroxy-indole-O-methyl
A. falx cerebri transferase activity
B. dural venous sinuses D. Blocking the release of norepinephrine from
C. choroid plexus sympathetic nerve terminals
D. middle meningeal A.
9. Melatonin is
2. Memory cells escape apoptosis because of? A. Serotonergic B. Dopaminergic
(AIIMS NOV 2009) C. Adrenergic D. Estrogenic
A. Nerve growth factor
B. Platelet derived growth factor 10. Which of the following is a preganglionic sympathetic
C. Fibroblast growth factor neurotransmitter:
D. Insulin like growth factor A. Glycine B. Adrenaline
C. Norepinephrine D. Acetylcholine
3. Substance p is released in response to pain in
periphery. (AIIMS NOV 2012) 11. Which of the following is excitatory:
A. Nerve terminals B. Mast cells A. Gamma-amino-butyric acid
C. Endothelium D. Plasma B. Glycine
C. Glutamate
4. In Central nervous system the myelin sheath is D. Lysine
formed by:
A. Oligodendrogliocytes 12. Renshaw cell inhibition is a typical example of
B. Schwann cells inhibition: (DNB Jun-2012)
C. Microglia A. Direct B. Recurrent
D. Astrocytes C. Indirect D. Presynaptic

5. Inhibitory neurotransmitter of central nervous 13. In the postnatal period the greatest growth in the
system is: (DNB Jun-2011) grey matter of the C.N.S. is of
A. Aspartate A. Neuron cell number
B. Gamma-aminobutyric acid B. Length of axon
C. Glutamate C. Dendritic tree
D. Acetylcholine D. Size of Perikaryon

6. Which of the following is not a feature of neuroglia: 14. Phagocytosis in the CNS is done by(DNB Dec-
A. Protoplasmic astrocytes are found in grey matter 2011)
B. Oligodendrocytes are derived from ectoderm A. Astrocytes B. Schwann cells
C. Microglia is of mesodermal origin C. Microglia D. Oligocytes
D. Central neuroglia cells are derived from Schwann
cells 15. In CNS the phagocytosis is done by:
A. Oligodendroglia B. Microglia
7. Sine qua non for cerebral cortex C. Astrocytes D. All of the above
A. Stellate cells B. Pyramidal cells
C. Granular cells D. Basket cells 16. Which of the following is the inhibition substance
in spinal cord:
1.C 2.A 3.A 4.A 5.B 6.D 7.B 8.B 9.A 10.D 11.C 12.B 13.C 14.C 15.B

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 Central Nervous System

A. Gamma-amino butyric acid

B. Glycine 24.Persons with mild cognitive impairments who
C. Dopamine smoke may experience a worsening of symptoms if
D. 5-hydroxytryptamine they stop smoking. This worsening of symptoms is
because nicotine acts as an agonist for receptors of a
17. Not an example of excitatory transmitter: particular neurotransmitter. That neurotransmitter is
A. Gamma-amino-butyric acid (A) Acetylcholine
B. Glutamate (B) Dopamine
C. Adrenaline (C) Neuropeptide Y
D. Acetylcholine (D) Nitric oxide

Central Nervous System Chapter - 6

18. The inhibitory neurotransmitter in central nervous
system is:
Section- 2: Sensory System , Spinal Cord & Tracts
A. Glutamate B. Aspartate
1. Not true for myelopathy (AIIMS NOV.2011)
C. Gamma-aminobutyric acid D. Taurine A. Sensory loss of facial area
B. Brisk Jaw jerk
19. Gamma neurons innervate: (DNB Pattern)
C. Brisk pectoral jerk
A. Extrafusal muscle fibers
D. Bladder and bowel involvement
B. Intrafusal muscle fibers
2. Due to a central cord lesion, dissociative sensory
C. Primary motor innervations to skeletal muscles
loss seen due to (AIIMS NOV 2009)
D. Inhibit antagonistic muscles
A. Decussating branches of lateral spinothalamic tract
B. Dorsal column
20. The brain neurons may get irreversibly damaged
C. Anterior spinothalamic tract
if exposed to significant hypoxia for:
D. Cilioretinal pathway
A. 8 minutes. B. 20 min
C. 5 sec. D. 15 sec.
3. Function of spinocerebellar tract
(AIIMS MAY 2009)
21. Function of dendrites. (PGI June-2012)
A. Planning & programming of movement
A. It generates the action potential
B. Coordination & smoothing of movement
B. Wave activity in E.E.G.
C. Equilibrium
C. Increased retrograde firing
D. Vibration
D. Decreased retrograde firing
E. Involved in memory
4. In Brown-Sequard’s syndrome there is:
A. Ipsilateral loss of pain sensation
22.Which class of neurotransmitter would be most B. Ipsilateral loss of temperature sensation
affected by a toxin that disrupted microtubules C. Ipsilateral loss of proprioception
within neurons? D. Ipsilateral loss of crude touch sensation
(A) Amino acid transmitters
(B) Catecholamine transmitters
(C) Membrane-soluble transmitters 5. Which of the following carries conscious proprioception:
(D) Peptide transmitters (DNB Pattern)
A. Spinocerebellar tract
23. A chemist is trying to produce a new neuroleptic B. Ponto cerebral tract
drug. To be an effective neuroleptic, the new C. Anterior spinothalamic tract
compound must target D. Dorsal column
(A) Acetylcholine receptors
(B) Dopamine receptors
(C) Neuropeptide Y receptors
(D) Norepinephrine receptors 6. Fine touch is transmitted via: (DNB Dec-2007)

16.B 17.A 18.C 19.B 20.A 21.B,D,E 22.D 23.B 24.A 1.B 2A 3.B 4.C 5.D

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 Physiology

A. The dorsal lemniscal system

B. The anterior spinothalamic tract 14. Which of the following phrase adequately
C. The lateral spinothalamic tract describes Pacinian corpuscles
D. The cerebellopontine tracts A. A type of pain receptors
B. Slowly adapting touch receptors
7. Stereoanesthesia is due to lesion of- C. Rapidly adapting mechanoreceptors
A. Nucleus Gracilis B. Nucleus cuneatus D. Located in the joints
C. Spinoreticular tract D. Spinothalamic tract
15. Phantom limb phenomenon can be described by:
8. True about weber Fechner law? (DNB Dec-2010)
(AIIMS NOV 2012) A. Weber Fechner law B. Power law
A. It states that localization of two pts depends on the C. Bell-Magendie law D. Law of projection
magnitude of the stimulus. 16. The distance by which two touch stimuli must be
B. Intensity of stimulus is proportional to sensational separated to be perceived as two separate stimuli is
feel. greatest:
C. Dorsal columns are sensory and ventral columns are A. The lips
mortal B. The palm of the hand
D. Stimulus of sensation is directly proportional to C. The back of scapula
stimulus applied. D. The dorsum of the hand.
17. Massage and the application of linaments to
9. As per Weber Fechner law, sensation is proportional to painful areas in the body relieves pain due to-
which of the following: A. Stimulation of endogenous analgesic system
A. Number of sensory fibers stimulated B. Release of endorphins by the first order neurons in
B. Logarithm of stimulus strength the brain stem
C. Square root of area stimulated C. Release of glutamate and substance P in the spinal
D. Amplitude of receptor potential cord
D. Inhibition by large myelinated afferent fibres
10. Intensity and amplitude are proportional to
(DNB Pattern) 18. If a single spinal nerve is cut, the area of tactile
A. Weber-Frechner law loss is always greater than the area of loss of painful
B. Starling’s law sensations, because
C. Poiseuille-Hagen-formula law A. Tactile information is carried by myelinated fast
D. Hardy’s ,law conducting fibres
B. Tactile receptors adapt quickly
11. Destruction of sensory area 1 of brain leads to loss of C. Degree of overlap of fibres carrying tactile sensation
which sensations?
is much less
A. Pain D. In the primary sensory cortex tactile sensation is
B. Touch represented on a larger area
C. Stereognosis gone but 2 point discrimination
retained 19 . Hot water bag use in intestine colic works by
D. Stereognosis & 2 point discrimination
inhibiting- AIPG 2010
A. Adrenergic receptors
12. A person with intractable pain over the right leg B. Cholinergic receptors
is benefited by: C. Cold receptor in skin
A.Right spinothalamic tract cordectomy D. Due to increased temp of peritoneal membr
B. Left Spinothalamic tract cordectomy
C. Right hemicordectomy
D. Left hemicordectomy
13. Sensation transmitted by pacinian corpuscles is:
A. Cold B. Warmth
6.A C. Touch
7.B 8.B 9.B D. Vibration
10.A 11.D 12.B 13.D 14.C 15.D 16.C 17.D 18.C Motor
Section-3: 19.A System & Reflexes

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 Central Nervous System

1. Muscle spindle function is: (AIIMS MAY 2009) B. Thermoregulation

A. Length B. Stretch C. Planning of voluntary movements
C. Touch D. Temperature D. Past memory

2. Golgi tendon organ determines? (AIIMS MAY 2008) 2. In substantia nigra, the major neurotransmitter is:
A. Static length B. Muscle action A. Dopaminergic B. Acetylcholine
C. Muscle tension D. Dynamic length C. Noradrenaline D. GABA

3. Which of the following is involved in amyotrophic lateral 3. Functions of Basal ganglia include
sclerosis? A. Gross motor movements

Central Nervous System Chapter - 6

A. Raphae nucleus B. Skilled motor movements
B. Lower motor neuron C. Maintenance of equilibrium
C. Posterior column D. Emotional response
D. Anterior and posterior column E. Cortical arousal

4. Which of the following is the twitch of a single 4. Huntington’s disease is due to the loss of:
motor unit? A. Nigrostriatal dopaminergic neurons
A. Chorea B. Fasciculation© B. Intrastriatal cholinergic neurons
C. Tremor D. Myoclonic jerk C. Intrastriatal GABAergic neurons
D. Intrastriatal cholinergic and GABAergic neurons
5. Skilled voluntary movement is initiated at
A. Cerebral Cortex (motor cortex) 5. A disease that produces decreased inhibitory input
B. Basal ganglia to the internal segment of the globus pallidus should
C. Cortical association areas have what effect on the motor area of the cerebral
D. Cerebellum cortex?
(A) Increased excitatory feedback directly to the cortex
6. Pyramidal fibers are: (B) No effect
A. Projection fibres (C) Decreased excitatory output from the thalamus to
B. Association fibres the cortex
C. Commissural fibres (D) Increased excitatory output from the putamen to
D. Association & commissural fibres the cortex
7. Lesions of pyramidal tract do not present with:
6. The basal forebrain nuclei and the
A. Exaggerated reflex B. Positive Babinski sign
pedunculopontine nuclei are similar in that neurons
C. Clasp knife rigidity D. Abnormal movements
within them
8. With which one of the following lower motor neuron (A) Are major inputs to the striatum
lesions are associated? (DNB Pattern) (B) Receive innervation from the cingulate gyrus
A. Flaccid paralysis B. Hyperactive stretch reflex (C) Process information related to language
C. Spasticity D. Muscular incoordination construction
(D) Utilize acetylcholine as their neurotransmitter
9. Crossed extensor reflex is a
A. Withdrawal reflex B. Postural reflex Section-5-: Cerebellum
C. Monosynaptic reflex D. Sympathetic 1. Which of the following exclusively involve neurons
(AIIMS NOV.2011)
Section-4-: Basal Ganglia A. Supra nuclear palsy
B. Spinocerebellar ataxia
C. Corticobasilar degeneration
1. Basal ganglion is related with:
D. Multiple system atrophy
A. Sleep
2. Which of the following clearly states the role of

1.A 2.C 3.B 4.B 5.A 6.A 7.D 8.A 9.A 1.C 2.A 3.B 4.C 5C 6.D 1.B

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cerebellum in motor performance?

A. Planning and programing of movement
B. Convert abstract thought into voluntary action
C. Initiation of skilled voluntary action
D. Smoothens and coordinates ongoing movements

3. True about cerebellum

A. Cerebral cortex have mostly inhibitory effects
A. Stage I B. Stage II C. Stage III D. Stage IV
B. Co-ordination
C. Planning of motor movements
3. A person with eyes closed and mind wandering will
D. Decreased tone
have the following wave in EEG
E. Excitatory effect from deep nuclei
A. Beta waves B. Alpha waves
C. Delta waves D. Theta waves
4. All of the following manifestations are seen in
cases of cerebellar damage in human beings except
4. Waves seen in EEG at the Hippocampus
A. Loss of non-declarative/reflexive memory
A. Alpha B. Beta C. Theta D. Delta
B. Loss of adjustment of vestibulo-ocular reflex
5. Nightmares are seen in (LQ)
C. Static tremor and rigidity
A. REM sleep B. NREM stage II
D. Ataxia, atonia and asthenia
C. NREM stage III D. NREM stage IV
5. Archicerebellum is: (DNB Pattern)
5. In which of the following is blood flow not
A. Declive
increased in REM sleep?
B. Flocculus
(A). Primary visual cortex (B). Anterior cingulate
C. Central lobule
cortex
D. Olive nucleus
(C). Pons (D). Amygdala
6.Which cerebellar component would be abnormal in
a degenerative disease that affected spinal sensory
Section-7-: Hypothalamus
neurons?
1. Which is not occurring in child exposed to cold
(A) Purkinje cells
climate (AIIMS NOV.2011)
(B) Mossy fibers
A. Shivering
(C) Parallel fibers
B. Cutaneous vasoconstriction
(D) Climbing fibers
C. Flexion of body like fetus position
Section-6-: EEG & Sleep
D. Production of noradrenaline to release energy
1. In EEG, delta waves are seen: (AIPG 2007)
from brown adipose tissue
A. Due to reticular system
B. When the thalamus is cut off from pons
2. Which deleterious effect is least likely to occur in
C. In deep sleep
hypothermia (AIIMS NOV.2011)
D. These originate from thalamocortical area
A. Cardiac arrhythmia
B. Decreased peripheral resistance
2. The EEG record shown below is normally record
C. Reversible coagulation
able during which stage of sleep?
D. Renal failure
3. All can increase appetite except (AIIMS MAY
2010)
A. α MSH
B. Melanocyte concentrating hormone
C. Neuropeptide Y
D. AGRP

2.D 3.B 4.C 5.B 6B 1.C 2.B 3.B 4.C 5.A 6. A 1.A 2.B 3.A

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4. Sleep is primarily regulated by? (AIPG 2009)

A. Thalamus B. Hypothalamus
C. Putamen D. Limbic cortex

Central Nervous System Chapter - 6

10. Drinking can be induced by:
5. Satiety center is located in: (LQ)
A. Electrical stimulation of the posterior hypothalamus
A. Lateral hypothalamic area
B. Perifornical region B. Osmotic stimulation of supraoptic nucleus
C. Ventromedial nucleus of hypothalamus C. Lesions in the paraventricular nucleus
D. Dorsomedial nucleus of hypothalamus D. Electrical stimulation of the preoptic nucleus

6. Thermoregulatory center is located at: 11. Osmoreceptor is located at which site

A. Anterior hypothalamus B. Renal medulla
A. Pons B. Hypothalamus
C. Carotid body D. Atrial chamber
C. Medulla D. Pituitary

7. Primary motor area for shivering is: 12 .10 Not a Direct function of hypothalamus:
A. Dorsomedial posterior hypothalamus A. Food intake
B. Ventromedial anterior hypothalamus B. Heart rate increased with exercise
C. Red nucleus C. Control of various endocrine and activity rhyt
D. Motor cortex D. Temperature regulation

8. Thirst is activated by: (DNB Jun-2009) 13. Osmoreceptors are present in:
A. Increased Angiotensin I level A. Pons B. Medulla
B. Extracellular hyperosmolarity C. Anterior hypothalamus D. Posterior pituitary
C. Increased ANP levels
D. Increased renin levels 14. True about non shivering thermogenesis
A. Glucose converted to lactate
B.Fatty acids show uncoupled oxidative
9. Circadian rhythm is controlled by (AIIMS NOV phosphorylation
2008) C. ADP is burnt into heat
A. Supraoptic nucleus D. Adipose tissue is entirely absent
B. Suprachiasmatic nucleus
C. Paraventricular nucleus
D. Median eminence 4.B 5.C 6.B 7.A8.B 9.B 10.D 11.A 12.B
13.C 14.B

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 Physiology

5. Papez circuit in limbic system involves. (AIPG 2007)

15. In animals with chronic exposure to cold what is A. Anterior thalamic nuclei
true (AIIMS MAY 2011) B. Pulvinar nuclei
A. Sympathetic tone to heart is not much affected C. Anterior hypothalamic nuclei
B. Free insulin is increased D. Interlaminar nuclei
C. Vagal inhibition of heart is reduced
D. Perfusion of adipose tissue is decreased 6. Prosopagnosia is: (DNB Jun-2010)
A. Inability to recognize colors
16. About neuropeptide Y an orexin {appetite B. B. Inability to recognize faces
stimulant}:all are TRUE except: (AIIMS NOV 20100 C. Unable to correct grammatical errors
A. it is mediated under the effect of melanocortin D. Inability to recognize voices
B. decreases thermogenesis
C. its level increases during starvation 7. Lesion of which of the following structure leads to
D. contains 36 aa residues Kluver-Bucy syndrome?
A. Amygdala B. Hippocampus
17. Stomach secretes which of the following which C. Hypothalamus D. Temporal lobes
controls appetite (AIIMS nov 2010)
A. CCK B. Ghrelin 8. Emotional effect to a physical response is given by:
C. Orexin D. insulin like growth factor A. Amygdaloid B. Cortex
C. Cerebellum D. Hippocampus
Section-8-: Higher Functions
Q.9 Arousal response in mediated by
1. Remembering things a week old is A. Dorsal column
A. recent memory B. Reticulo activating system
B. remote memory C. Spinothalamic tract D. Vestibule cerebellar tract
C. delayed memory
D. working memory 10. Prosapagnosia is
A. Inability to recognise faces B. Inability to draw
2. Representation in Cerebral cortex is : C. Inability to count D. Inability to smell
A. Vertically B. Horizontally
C. Tangentially D. Tandem 11. The following is true about brain metabolism
except
3. Memory formation process in the CNS involves all A. Use fatty acid in starvation
except (AIPG 2007) B. In resting state 60% of total energy utilised
A. It involves change in neurotransmitter release at C. Ketone bodies are used in starvation
the synapse. D. Has no energy store.
B. Increase in no. of synapses and dendrites
C. Recruitment of neurons and involvement of more 12. Part of brain most sensitive to hypoxia is?
neurons in a particular function as in somatosensory A. Thalamus B. Hippocampus
area of cortex. C. Cerebellum D. Pons
D. Allocation of specialized nerve cells as occurs in
hippocampus. 13. Who described conditioned reflex:
A. Pavlov B. Salk
4. Conversion of short term - memory into long term C. Sherington D. Priestly
memory occurs in: (AIPG 2007) 14. When a dog is given food after a bell and this is
A. Amygdala B. Hippocampus repeated several times, he will salivate just on hearing the
C. Frontal cortex D. Hypothalamus bell. This is an example of:
A. Reinforcement B. Conditioned reflex
C. Unconditional reflex D. Enforcement
15.C 16.A 17.B 1.B 2.A 3.D 4.B 5.A 6.B 7.A 8.D 9.B 10.A 11.AB 12.B 13.A

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Section-9-: Speech & Aphasia C. 1-6mmHg

D. 9-lOmmHg
1. Broca's area is involved in: (AIPG 2010) 5. The arachnoid villi responsible for CSF absorption
A. Word formation B. Word interpretation protrude mainly in the: (LQ)
C. Word comprehension D. Word understanding A. Superior sagittal sinus
B. Inferior sagittal sinus
2. Broca’s area of speech is located in: (LQ) C. Straight sinus
A. Superior temporal gyrus D.Transverse sinus
B. Posterior border of frontal lobe
C. Inferior border of frontal lobe 6. Which of the following is a pain sensitive intracranial

Central Nervous System Chapter - 6

structure:
D. Superior border of frontal lobe
A. Pia mater B. Dura mater
3. Motor aphasia is: (LQ) C. Pial veins D. Brain
A. Verbal comprehension
B. Unable to express the words 7. All the following are more in CSF compared to
C. Verbal expression plasma except (LQ)
D. Peripheral speech apparatus involvement A. Mg B. Cl C.HCO3 D. Glucose

4. Language and speech require the participation of 8. CSF production per minute. (LQ)
both Wernicke’s area and Broca’s area. These two A. 0.30—0.35 ml./min B. 0.5ml/min
regions of the brain communicate with each other via C. 2mllmin D. 1 ml/mm
a fiber bundle called
(A) The thalamocortical tract 9. True statement. regarding CSF is
(B) The reticular activating system A. Daily production < 700 ml
(C) The prefrontal lobe B. CSF analysis rules out active secretion as a cause of
(D) The arcuate fasciculus formation of CSF
C. It flows from III ventricle to the IV ventricle
D. Produced only by choroid plexus
Section-10-: CSF
1. CSF pressure depends primarily upon? (AIIMS NOV 10. Blood brain barrier is deficient at
2008) (LQ)
A. Rate of formation from choroid plexus A. Area postrema B. Thalamus
B. Rate of absorption C. Meta thalamus D. Cerebellum
C. Cerebral blood flow
D. Blood pressure Section-11-: autonomic nervous system
1. Increased vagal tone leads to:
2. With CSF all are true except? (AIIMS NOV 2012) A. increased refractory period of atria
A. Persistent leakage causes headache B. Increased ventricular contractibility
B. Neutrophils are normally not presents C. Increased ectopic beats
C. p H is less than that of blood D. Decreased AV conduction
D. Secreted by the arachnoid villi
2. Autonomic ganglion is mainly
3. CSF plasma glucose ratio is: A. Cholinergic B. Adrenergic C.
A. 0.44 B. 0.64 C. 0.54 D. 0.74 Dopaminergic D. Serotonergic

4. Normal pressure of CSF in adult is: (Latest 3. Group B fibre are

Questions) A. Sympathetic preganglionic
A. 6-l2mmHg (50-l80mmH2O) B. Sympathetic post ganglionic
B. 10-l2mmHg C. Parasympathetic preganglionic
D. Parasympathetic post ganglionic
14.B 1.A 2.C 3.C 4.D 1.B 2.D 3.B 4.A 5.C 6.B 7.D 8.A 9.A 10.A 1.D 2.A 3.A C

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4. Parasympathetic stimulation will cause: 17. Ablation of the ‘somatosensory area 1’ of the
A. Bronchodilation B. Decrease GI secretions cerebral cortex leads to:
C. Pupillary constriction D. Decrease sweat secretion A. Total loss of pain sensation
B. Total loss of touch sensation
5. Sensory fiber with maximum conduction C. Loss of tactile localization but not of two point
velocity: discrimination
A. C- fiber B. Alpha fiber D. Loss of tactile localization and two point
C. Beta fiber D. Gamma fiber discrimination

6. sympathetic ganglia arises from 18. Non shivering thermogenesis in adults is due to:
A. Lumbosacral B. Thoracolumbar A. Thyroid hormone
C. Craniosacral D. Thoracosacral B. Brown fat between the shoulders
C. Adrenaline from adrenal medulla
7. Degeneration of corpus striatum cause D. Muscle metabolism
A. Parkinson disease. B. chorea
C. hemiballismus D. Athetosis
19. Due to a central cord lesion, dissociative sensory
8. Umami taste is due to loss seen due to. (AIIMS Nov 09)
A. glutamate B. sodium C. H+ D. K+
A. Decussating branches of lateral spinothalamic tract
9. Burst suppression is seen in B. Dorsal column
A. GA B. Hypothermia C. Anterior spinothalamic tract
C. Coma D. All of the above D. Cilioretinal pathway

10. REM sleep not seen 20. CSF pressure depends primarily upon? (AIIMS Nov
A. Beta waves B. PGO spikes 08)
C. Alpha waves D. delta waves
A. Rate of formation from choroid plexus
11. Otoaccoustic emissions are related to B. Rate of absorption
A. outer hair cells B. Inner hair cells C. Cerebral blood flow
C. Othlith organs D. Spiral ganglia D. Blood pressure

12. Nociceptin acts via 21. At which location along the basilar membrane are
A. Opoid receptors B. Orphanin receptors the highest-frequency sounds detected?
C. GABA receptors D. Substance P receptors (A) Nearest the oval window
(B) Farthest from the oval window, near the
13. Acetyl choline is secreted by which cells of retina helicotrema
A. ganglion cell B. amacrine cells (C) Uniformly along the basilar membrane
C. unipolar cells D. horizontal cells (D) At the midpoint of the membrane

14. Transducin protein is seen in

A. vision B. hearing C. balance D. smell

15. Nerve fibres affected mainly by local anaesthetic 22. Motion of the endolymph in the semicircular
A. A B. Autonomic fibres C. B D. C canals when the head is held still will result in the
perception of
16. In damage to Preoptic area in hypothalamus (A) Being upside-down
A. Hypothermia B. Hyperthermia (B) Moving in a straight line
C. Loss of appetite D. Increase appetite (C) Continued rotation
4.C 5.B 6.B 7.B 8.A 9.D 10.D 11.A 12.B 13.B 14.A 15.C 16.B 17.D 18.C 19.A 20.B 21.A

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(D) Being upright and stationary

23. The cyclical flexion and extension motions of a leg

during walking result from activity at which level of
the nervous system?
(A) Cerebral cortex
(B) Cerebellum
(C) Globus pallidus
(D) Spinal cord

Central Nervous System Chapter - 6

24. Which brainstem-derived descending tract
produces action similar to the corticospinal tract?
(A) Vestibulospinal
(B) Reticulospinal
(C) Spinocerebellar
(D) Rubrospinal

25. Concurrent flexion of both wrists in response to

electrical stimulation is characteristic of which area of
the nervous system?
(A) Postcentral gyrus
(B) Vestibulospinal tract
(C) Dentate nucleus
(D) Supplementary motor cortex

26.A viral infection causes damage to both

hippocampi in a patient. This damage would cause
the patient to exhibit functional deficits in
(A) Recalling an old declarative memory
(B) Recalling an old procedural memory
(C) Forming a new short-term memory
(D) Forming a new long-term memory

22.C 23.D 24.D 25 D 26.D

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27. A neural tracer technique labels the axon and

cell body when it is applied to any part of a 32. Disruption of the hypothalamic pituitary portal
neuron. Where labelled cell bodies are most likely system will lead to
to be found after the tracer substance is injected (A) High circulating levels of PRL, low levels of LH and
into the wall of the stomach? FSH, and ovarian atrophy
(A) Prefrontal cortex (B) Enhanced follicular development as a result of
(B) Intermediolateral horn of spinal cord increased circulating levels of PRL
(C) Dorsal vagal complex (C) Ovulation, followed by increased circulating levels
(D) Hypothalamus of progesterone
(D) A reduction of ovarian inhibin levels, followed by
28. An electrophysiological study of a neuron in the increased circulating FSH
ENS detects a fast EPSP. Which is the most likely
property associated with the EPSP?
(A) Acetylcholine (ACh) receptors
(B) Suppression of hyperpolarizing after-potentials
(C) Receptor activation of adenylyl cyclase
(D) Hyperpolarization of the membrane potential

29. The application of norepinephrine (NE) to the ENS

suppresses cholinergically mediated EPSPs but has no
effect on depolarizing responses to applied
acetylcholine (ACh). This finding is best interpreted as
(A) Postsynaptic excitation
(B) Slow synaptic inhibition
(C) Presynaptic inhibition
(D) Postsynaptic facilitation

30. Which of the following is true regarding auto-

regulation:
(A). Vary with change in pressure
(B). Maintains the blood flow
(C). Well developed in skin
(D). Regulated by local metabolites

31.When the sympathetic nervous system is

activated,
(A) Norepinephrine is released by the vascular smooth
muscle cells
(B) Acetylcholine is released onto vascular smooth
muscle cells
(C) Norepinephrine is released from axons onto the
arteriolar wall
(D) The arterioles constrict because nitric oxide
production is suppressed

27. C 28. A 29. C 30.B 31. C 32.A

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Explanations
Chapter-6 Central Nervous System):

Section-1-: General, Neurons, Neurotransmitters etc

1. Ans. C. choroid plexus. Ref: Gray's anatomy: Page 404.

1. Pain sensitive cranial structures are: - 
a. The scalp and Aponeurotica Q b. Middle meningeal artery Q
c. Dural-sinuses Q d. Falx cerebri and Q
e. The proximal segments of the large pial arteries Q

Q
2. Pain insensitive cranial structures:
a. Ventricular ependyma Q b. Choroid plexus Q
c. Pial veins and Q d. Much of the brain parenchyma Q

2. Ans. A. Nerve growth factor

a. Memory cells behave like immortalized cells, with no requirement for antigen signaling to survive. These
cells can respond more rapidly to antigen.
b. These characteristics of memory cells are potentially due to an altered chromatin state of cytokine genes,
a higher expression of adhesion factors which helps to lower the threshold needed for signaling, and a
higher expression level of anti-apoptotic factors such as Bcl-2 Q.
c. Growth factors can work to inhibit the apoptotic pathways. For example, some growth factors activate PI3
kinase, which activates Akt. The activated protein Akt inactivates procaspase-9 & inhibits FasL synthesis.
d. The most important growth factor in this regard is Nerve growth factor(NGF). Although others like
IGF,PDGF & FGF can also prolong the survival.
Survival of memory B lymphocytes is tightly linked to the integrity of the Bcl-2 protein and is regulated
by a nerve growth factor (NGF) autocrine circuit

3. Ans A. Nerve terminals (Ref: Ganong –23rd Ed. Pg:112)

a. Substance P is found in high concentration in the endings of primary afferent neurons in the spinal cord Q,
and it is probably the mediator at the first synapse Q in the pathways for pain transmission in the dorsal
horn.
b. It is also found in high concentrations in the nigrostriatal system Q, where its concentration is proportional
to that of dopamine, and in the hypothalamus, where it may play a role in neuroendocrine regulation.
c. Upon injection into the skin, it causes redness and swelling, and it is the mediator released by nerve fibers
that is responsible for the axon reflex Q.
d. In the intestine, it is involved in peristalsis Q.
e. It has recently been reported that a centrally active NK-1 receptor antagonist has antidepressant activity in
humans.

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4. Ans. A. Oligodendrogliocytes
Apart from neurons, CNS also contains glial cells known as neuroglia. Number of glial cells is five times that of
neurons Q. Schwann cells found in peripheral nervous system are also glial cells. In the CNS there are three
types of glia:
MICROGLIA Scavenger cells which enter the CNS from blood vessels Q
OLIGODENDROCYTES Involved in myelin formation Q
ASTROCYTES Produce substances that are trophic to neurons but their exact role is not
known Q

Central Nervous System Chapter - 6

5. Ans. B. Gamma-aminobutyric acid
GAMMA-AMINOBUTYRIC ACID is an inhibitory neurotransmitter found in brain and retina which is responsible
for presynaptic inhibition. Q

6. Ans. D. Central neuroglia cells are derived from Schwann cells

NEUROGLIA is also known as glia. It includes astrocytes, oligodendroglias, microglia (mesoglia), ependyma,
Schwann cells and satellite (capsule) cells surrounding cranial and spinal ganglia. All except the microglia
are derived from ectoderm. Mesoglia is of mesodermal origin. Schwann cells are glia like cells found along
peripheral nerves. Q

7. Ans. B. Pyramidal cells

[Sine qua non = indispensable condition or, qualification]

8. Ans. B. Increasing the serotonin N-acetyl transferase

a. First Lets see the synthesis of melatonin from sertonin
i. Serotonin
ii. N. Acetyl transferase + Acetyl CoA
iii. N-Acetyl serotonin
iv. J, Hydroxy indole – O- methyl transferase + S-Adenosylmethionine
v. Melatonin (N -acetyl- 5-methoxytryptamine)

9. Ans. A. Serotonergic

10. Ans. D. Acetylcholine

ACETYLCHOLINE (ACh) is the preganglionic neurotransmitter for both sympathetic and parasympathetic Q
divisions of the autonomic nervous system as well as the postganglionic neurotransmitter of the
parasympathetic neurons. Norepinephrine is the neurotransmitter of the post gurgulionis sympathetic
neurons.

11. Ans. C. Glutamate

GLUTAMATE is a widely used excitatory Q neurotransmitter in brain and is supposed to be found in more than
50% neurons in CNS. Gamma-amino-butyric acid and Glycine Q are inhibitory Q neurotransmitters.

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12. Ans. B. Recurrent

RENSHAW CELL is a small cell with a short axon that connects motor nerve axons with each other. Stimulation
of each motor neuron inhibits the surrounding motor neuron and this effect is known as recurrent
inhibition Q.

13. Ans. C. Dendritic tree

14. Ans. C. Microglia

15. Ans. B. Microglia

The reticuloendothelial system (R.E.S)comprises monocyte-derived phagocytic cells that are lymph nodes and
several other organs. The reticuloendothelial system comprises monocyte-derived phagocytic cells that are lymph
nodes several other organs.

RES.
• LIVER KUPFFER CELLS Q
• LUNG ALVEOLAR MACROPHAGES Q
• SPLEEN, KIDNEY MESANGIAL CELLS Q
• BRAIN MICROGLIA Q

16. Ans. B. Glycine

GLYCINE is the mediator responsible for direct inhibition in the spinal cord

17. Ans. A. Gamma-amino-butyric acid

a. The a motor neurons in the spinal cord receive direct postsynaptic inhibition from Renshaw cell
interneurons, which release glycine Other inter neurons produce pre synaptic inhibition on dorsal horn
neurons through release Of GAMMA- AMINOBUTYRIC ACID (GABA) which indirectly inhibits the alpha and
gamma motor neurons.
b. Glutamate is a widely used excitatory neurotransmitter in brain and is supposed to be found in more than
50% of neurons in CNS. Q

18. Ans. C. Gamma-aminobutyric acid

a. The first neurotransmitter to be shown to produce presynaptic inhibition was gamma-aminobutyric acid
(GABA). It acts via GABAA receptors; GABA increases chloride conductance Q.
b. GABAB receptors are also present in the spinal cord and appear to mediate presynaptic inhibition via a G-
protein that produces an increase in potassium ion conductance.
c. Baclofen, is a GABAB agonist Q and is effective in treatment of spasticity of spinal cord injury and multiple
sclerosis. Q

19. Ans. B. Intrafusal muscle fibers

a. In addition to the alpha motor neurons that excite contraction of the skeletal muscle fibers, about one half
as many much smaller gamma motor neurons are located along with the alpha motor neurons in the
anterior horns. Q

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b. These transmit impulses through type-A gamma fibers, averaging 5 micron in diameter, to very small,
special skeletal muscle fibers called intrafusal fibers, present in the muscle spindle.

20. Ans. A. 8 minutes.

"The cerebral cortex can tolerate the acute hypoxia due to complete circulatory arrest for 5-10 min at 28° CQ, 20
min at 20° Q and 50 min at 15°C° Q.

21. Ans. B,D,E

Central Nervous System Chapter - 6

22.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 98
 Most neurotransmitters are synthesized locally within the axon terminals from precursors available at the terminals,
using enzymes that reside in the terminals.
 However, peptides must be synthesized by ribosomes, which are not found in axons or terminals.
 The supply of peptide transmitters in the axon terminal must be continuously replenished via axoplasmic transport
from the cell body.
 Microtubules are an essential component of axoplasmic transport; disrupting their integrity would diminish axonal
transport and deplete the peptide transmitter from the terminal.

23. The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 533
Neuroleptics drugs ameliorate the symptoms of psychosis in disorders such as schizophrenia. While the etiology of
schizophrenia is far from understood and many transmitter systems may be involved, all neuroleptics block
dopamine receptors.

24. The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 185
 Acetylcholine is critical for cognitive function because of the cholinergic neurons in the basal forebrain that relay
hippocampal information to the rest of the cortex.
 Nicotine activates cholinergic receptors. The only effective drugs for the treatment of cognitive deficits in
Alzheimer’s disease are cholinergic, although cognition clearly involves neurons in many regions of the brain that
utilize a variety of transmitters.

SECTION-2-: : Sensory System , Spinal Cord & Tracts

1. Ans. B. Brisk Jaw jerk

(Ref: Wheeless' Textbook of Orthopaedics 7th ed Page 342)
a. Myelopathy
Spinal cord compression by degenerative spine disease is one of the more common causes of myelopathy,
however tumors or other masses can also cause myleopathies. Intraspinal tumors may originate in the
substance of the spinal cord (intramedullary tumors) or compress it from the outside (extramedullary
tumors).
b. Clinical Findings:
i. upper motor neuron findings such as hyper-reflexia, clonus, or Babinski's sign may be present;
ii. funicular pain, characterized by central burning and stinging with or w/o (Lhermitte's
phenomenon – radiating lightening like sensations down back with neck flexion) may also be
present with myelopathy;
iii. upper extremity: - mixed upper and lower motor neuron findings;

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iv. myelopathy can initially present w/ hand dysfunction w/ loss of fine motor function such as
writing;
v. lower extremity - upper motor neuron signs;
vi. lateral cord involvement: causes spasticity, hyper-reflexia, and frank clonus in lower extremities;
vii. posterior cord involvement: causes decline in ability to walk, apparent ataxia;
viii. loss of lower extremity proprioception;
c. Babinski's sign:
a. may not be present until myelopathy becomes severe;
b. upper motor neuron findings such as hyper-reflexia, clonus, or Babinski's sign may be present;
d. Remember, lesions of the spinal cord rostral to the sacral cord result first in a flaccid (atonic; acute)
bladder, followed by a spastic (chronic) bladder. Lesions from S1 down, and involving all of the various
nerves, result in ONLY a flaccid bladder.
i. The trigeminal nucleus extends throughout the entire brainstem, from the midbrain to the medulla,
and continues into the cervical cord, where it merges with the dorsal horn cells of the spinal cord.
ii. The nucleus is divided anatomically into three parts, visible in microscopic sections of the brainstem.
From caudal to rostral (i.e., going up from the medulla to the midbrain) they are the spinal trigeminal
nucleus, the main trigeminal nucleus, and the mesencephalic trigeminal nucleus.
iii. The three parts of the trigeminal nucleus receive different types of sensory information. The spinal
trigeminal nucleus receives pain/temperature fibers. The main trigeminal nucleus receives
touch/position fibers. The mesencephalic nucleus receives proprioceptor and mechanoreceptor fibers
from the jaws and teeth.
iv. Therefore pain and temp can be lost over face in cervical myelopathy due to spinal trigeminal
nucleus, but Jaw jerk would not be involved.

2. Ans. A. Decussating branches of lateral spinothalamic tract

(REF:Current diagnosis & treatment in orthopedics 3RD ED.Page 265)
Neurology in clinical practice - Page 360 4TH ED.
Dissociated sensory loss is a pattern of neurological damage caused by a lesion to a single tract in the spinal
cord which involves selective loss of fine touch and proprioception without loss of pain and temperature, or
vice-versa.
Central cord syndrome
a. Central cord syndrome (CCS) is an acute cervical spinal cord injury (SCI).
b. Central cord syndrome is observed most often in cervical spondylosis, syringomyelia, hydromyelia, and
trauma.
c. Hemorrhage and intramedullary tumors such as central canal ependymoma are other causes.
d. Because central cord syndrome is more common in the cervical cord, the arms are often weak with
preservation of strength in the legs ("man-in-a-barrel syndrome"). Considerable recovery is common.
e. This syndrome is associated with variable sensory and reflex deficits; often the most affected sensory
modalities are pain and temperature because the lateral spinothalamic tract fibers cross just ventral to the
central canal.
f. This is sometimes referred to as dissociated sensory loss and is often present in a capelike distribution.
g. Lateral extension can result in ipsilateral Horner syndrome (because of involvement of the ciliospinal
center), kyphoscoliosis (because of involvement of dorsomedian and ventromedian motor nuclei supplying
the paraspinal muscles) and spastic paralysis (because of corticospinal tract involvement).

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h. Dorsal extension can result in ipsilateral position sense and vibratory loss due to involvement of dorsal
column.

3. Ans. B. Coordination & smoothing of movement. Ref: Ganong – Ed, Page 203

4. Ans. C. Ipsilateral loss of proprioception

Hemiparesis due to a lesion in the high cervical spinal cord, associated with ipsilateral loss of proprioception and
contralateral loss of pain and temperature sense constitute BROWN-SEQUARD’S SYNDROME. Its features
are:

Central Nervous System Chapter - 6

a. Paralysis on the same side as the lesion
b. Loss of position and vibratory sense and ataxia on the same side as the lesion
c. Loss of pain on the side opposite the lesion
d. Loss of temperature sensitivity on the side opposite the lesion

5. Ans. D. Dorsal column

The proprioceptive impulses are transmitted up the spinal cord in the dorsal columns Q. Much of these inputs
go to the cerebellum but some pass to the cerebral cortex via medial lemnisci and thalamic radiations.

6. Ans. A The dorsal lemniscal system

a. Lateral spinothalamic tract carries pain and temperature; Q
b. Anterior spinothalamic tract carries crude touch; Q
c. All other sensations are carried by dorsal lemniscal. Q

7. Ans. B Nucleus cuneatus

a. Stereognosis  The ability to identify objects by HANDLING them without looking at them is called
stereognosis
b. This information is earned by Posterior column (dorsal column) to the cerebral cortex.
c. Posterior column has two components:
i. Gracile faciculus  carries information from sacral and lumbar regions.
ii. Cuneate fasiculus  carries information from cervical and thoracic regions.
Hence, as definition, stereognosis is the ability to identify objects by handling, and the information from hand
goes through cervical and thoracic parts i.e. cuneate fasiculus, therefore lesion of cuneate fasiculus, causes
stereoanesthesia. Note that stereognosis has large cortical component, therefore impaired stereognosis is
an early sign of damage to cerebral cortex.
i. Dorsal column (Posterior column)  carries sensations for Touch (Fine), pressure, vibration, joint
position (proprioception), and two point discrimination.
ii. Spinothalamic tract carries sensation for Pain and temperature (by lateral spino thalamic tract); and
crude touch and pressure (by ventral spino thalamic tract)

8. Ans. B. Intensity of stimulus is proportional to sensational feel.

a. Phantom limb is a phenomenon seen in amputees. The patient complains of pain and proprioceptive
sensation sin the absent limb. This is because, the ends of the nerves cut at the time of amputation, are
stimulated by pressure on them or may even spontaneously. The impulse generated in these nerve fibers

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previously came from sense organs in the amputated limb, thus the sensations felt are projected to where
the receptors used to be.
b. Power Law
c. States that a person interprets changes in intensity of sensory stimuli approximately in proportion to a
power function of the actual intensity.
d. Its given by formula.

Interpreted signal strength = K x (stimulus – K) y

(In this formula the exponent y and the constant K and k are different for each type sensation)
(Ref: Ganong , 23rd Editon, Page 128, Guyton, 10/e, p548) )

9. Ans. B. Logarithm of stimulus strength

WEBER FECHNER LAW states that gradations of stimulus strength are discriminated in proportion to the
logarithm of stimulus strength. Q

10. Ans. A. Weber-Frechner law

a. Weber-Fechner Law Q: - "It has been taught that the magnitude of the sensation felt is proportionate to
the log of the intesity of the stimulus".
b. "The frequency of the action-potential generated by a stimulus to a sensory nerve fiber is also related to
the intensity of the initiating stimulus by a power function"
c. Starling's Law of the Heart or Frank-starling law Q
(length-tension relationship in cardiac muscle): - states that "the energy of contraction is proportional to the
initial length of the cardiac muscle fiber" for the heart, the length of the muscle fibers (i.e. the extent of
preload) is proportionate to the end-diastolic volume.
2. Poiseuille-Hagen-formula Q  shows the relation between the flow (F) in the long narrow tube (L) the
viscosity () of the fluid, and the radius ® of the tube.

11. Ans. D. Stereognosis & 2 point discrimination

a. Two somatic sensory areas of the cortex: -

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 Central Nervous System

i. Somatic sensory area I (S.I)  in the post central gyms and corresponds to Brodmann’s area 1, 2 and
3. Ablation of S 1 in animal causes deficit in position sense and in the ability to discriminate size and
shape
ii. Somatic sensory area II (S.II)  the wall the sylvian fissure. Ablation of S-II causes deficient in learning
based on tactile discrimination.

b. Cortical lesions do not abolish somatic sensation

i. Proprioception and fine touch are most affected by cortical lesions Q
ii. Temperature sensibility is less affected, and pain sensibility is only slightly affected. Q

Central Nervous System Chapter - 6

iii. Thus, perception is possible in the absence of cortex. Q

12. Ans. B. Left Spinothalamic tract cordectomy

a. Spinothalamic tract
i. Touch sensation - by ventral spinothalamic tract Q
ii. Pain and temperature - by lateral spinothalamic tract Q
b. Fibers of spinothalamic tract cross in the anterior commissure of the cord to the opposite Q
c. That is why, intractable pain over the right leg is benefited by left spino thalamic tract cordectomy.

13. Ans. D. Vibration

SENSE ENDINGS ACTIVATED
• Pain Cutaneous nociceptors Q
• Temperature, heat Cutaneous thermoreceptors for hot Q
• Temperature, cold Cutaneous thermoreceptors for cold Q
• Touch Cutaneous mechanoreceptors, also naked endings Q
• VIBRATION Mechanoreceptors, especially PACINIAN CORPUSCLES (Pressure also) Q
• Joint position Joint capsule and tendon endings, muscle spindles Q

14. Ans. C. Rapidly adapting mechanoreceptors

a. Pacinian corpuscles are present in the skin, some mucous membranes, etc.
b. They are mechanoreceptors Q, responding to pressure, or any kind of mechanical stimulus causing a
deformation of the corpuscle.
c. The Pacinian corpuscle has a single afferent nerve fiber Its end is covered by a sensitive receptor
membrane whose sodium channels will open when the membrane is deformed in any way It is surrounded
by several concentric capsules of connective tissue with a viscous gel between them.

15. Ans. D. Law of projection

a. The Law of Projection: “No matter where a particular sensory pathway is stimulated along its course to
the cortex, the conscious sensation produced is referred to the location of the receptor.”
b. For example, when the cortical receiving area for impulses from the left hand is stimulated, the patient
reports sensation in the left hand, not in the head.

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c. Another dramatic example is seen in amputees. Some of these patients may complain, often bitterly, of
pain and proprioceptive sensations in the absent limb (phantom limb).

16. Ans. C. The back of scapula

a. Two-point discrimination
a. The minimal distance by which two touch stimuli must be separated to be perceived as separate is called
the two-point threshold. It depends upon touch plus the cortical component of identifying one or two
stimuli.
i. a. Smallest where the touch receptors are most abundant as on finger tips Q where two stimuli be
resolved if they are separated as little as 3 mm. Q
ii. Largest where the touch receptors are scarse as on the back Q where two stimuli must be separated by
65 mm or more before they can be distinguished as separate points.

17. Ans. D. Inhibition by large myelinated afferent fibres

a. Pain:
Receptors: naked nerve ending (free nerve ending  found in almost every tissues of the body.
& Tract  Antolateral-
spinothalamic tract

Types of Pain Nerve fiber involved in Synaptic transmitors

transmission
1. Fast mild pain (first Small diameter myelinated A Ii Glutamate
or fast pain) fibers; terminate primarily on
neurons in laminas I and V of
dorsal horn
2. Slow severe pain Unmyelinated C-fiber; terminate Substance –P
(slow or second pain) primarily on neurons in laminas I
and II of dorsal hom

b. Gate system for Pain control:

i. "The synaptic junctions between the peripheral nociceptor fibers and the dorsal horn cells in the spinal
cord are the sites of considerable plasticity. For this reason, the dorsal horn. has been called a gate, where
pain impulse can be "Gated" - i.e. modified.
ii. For example: Stimulation of large diameter afferent fibers (i.e. AP fibers, touch receptors) from an area
from which pain is being initiated reduces the pain. Collateral branches from the touch fibers (i.e. large
diameter Aα-myelinated fibers) in the dorsal columns enter the substantia gelatinosa, and it has been
postulated that impulses in these collaterals or interneurons on which they end inhibit transmission from
the dorsal root pain fibers to the spinothalamic neurons.
iii. Mechanism:-Presynaptic inhibition at the endings of the primary afferent's that transmit pain impulses.
iv. "Stimulation of large type A β sensory fibers (i.e. Large myelinated A β-fibers) from the tactile receptors
can depress the transmission of pain signals. This effect presumably result from local lateral inhibition

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(Presynaptic inhibition) in the spinal cord. It explains why rubbing the skin near painful area or application
of liniments to painful area relieves the' pain" "Accupuncture, touching or shaking relieves pain in similar
manner"
v. "Stimulation with electrical vibrator at the site of pain also relieves pain".

18. Ans. C. Degree of overlap of fibres carrying tactile sensation is much less
a. Sensory changes due to interruption of a single peripheral nerve vary, depending on whether the nerve
involved is predominantly muscular, cutaneous or mixed.
b. "Following injury to a cutaneous nerve the area of sensory loss is always less than its anatomic distribution

Central Nervous System Chapter - 6

because of overlaps from adjacent nerve".
c. "The area of tactile loss, is greater than that of pain relates both to a lack of collateralization
(regeneration) from adjacent tactile fibres (in contrast to rapid collalteral regeneration of pain fibres) and
to a greater overlap of pain sensory units".

19. Ans . A. Adrenergic receptors

(Ref: Ganong - 23rd Ed.Pg:143-144 )
a. Afferent fibers from visceral structures reach the CNS via sympathetic and parasympathetic nerves. Their
cell bodies are located in the dorsal roots and the homologous cranial nerve ganglia.
b. Specifically, there are visceral afferents in the facial, glossopharyngeal, and vagus nerves; in the thoracic
and upper lumbar dorsal roots; and in the sacral roots .
c. Vagal connections provide a massive sensory link for "physiological information", while sympathetic
unmyelinated C fibres provide sensations of visceral pain.
Pain innervation of the viscera. Pain afferents from structures between the pain lines reach the CNS via
sympathetic pathways, whereas, they traverse parasympathetic pathways from structures above the
thoracic pain line and below the pelvic pain line.

Section-3-: Motor System & Reflexes

1. Ans . A Length (Ref: Ganong – 23rd Ed)

Functions of Muscle spindle
a. Sensing and Maintaining normal muscle length (By Length servo and Follow up servo mechanism)
b. Stretch ReflexQ
c. Muscle tone Q (Due to Gamma efferent discharge) Q
d. Body Posture (Postural reflex Q at spinal cord level)
So both stretch and length are functions of muscle spindle but the primary function is maintenance of length.
Pneumonic: Golgi tendon organ is for tension (t for tension, t for tendon) Muscle spindle is for length

2. Ans. C. Muscle tension

(Ref. Ganong Physiology 23rd ed. 93)

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 Physiology

a. The Golgi tendon organ is an encapsulated sensory receptor, made of 10 to 15 muscle fibers connected in
series with in muscle tendon.
b. Golgi tendon organ detects muscle tension . When this small bundle of muscle fibers is “tensed” by
contracting or stretching the muscle, it gets stimulated and elicit protective disynaptic spinal reflex called
Golgi tendon reflex which relaxes the muscle. Sensory innervation of the organ is by Ib nerves.

c. This means up to a point, the harder a muscle is stretched, the stronger is the reflex contraction by stretch
reflex.
d. When the tension becomes great enough, contraction suddenly ceases and the muscle relaxes.
e. This relaxation in response to strong stretch is called the inverse stretch reflex or autogenic inhibition or
golgi tendon reflex.
f. The major difference in excitation of the Golgi tendon organ versus the muscle spindle is that the muscle
spindle detects muscle length (static length) and changes in muscle length (dynamic length), whereas the
tendon organ detects muscle tension.

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3. Ans. B. Lower motor neuron

a. Amyotrophic lateral sclerosis is the most common form of progressive motor neuron disease Q.
b. The pathology of motor neuron degenerative disorders involve lower motor neurons Q (consisting of
anterior horn cells in spinal cord and their brainstem homologues innervating bulbar muscles) and upper
or corticospinal motor neurons (emanating from layer 5 of motor cortex to descend via the pyramidal tract
to synapse with lower motor neurons, either directly or indirectly via interneurons).

4. Ans. B. Fasciculation
When an abnormal impulse occurs in a motor nerve fiber its whole motor unit contracts. This often causes

Central Nervous System Chapter - 6

sufficient contraction in the muscle that one can see a slight ripple in the skin over the muscle. This is
known as fasciculation.

5. Ans. A. Cerebral Cortex (motor cortex)

Control of posture and movement -
a. Commands for voluntary movement originate in cortical association area (motor cortex).
b. The movements are planned in the cortex as well as in the basal ganglia and the lateral portions of the
cerebellar hemispheres.
c. Motor commands from motor cortex are relayed in large part via the corticospinal tract to the spinal cord and
corticobulbar tract to motor neurons in the brain stem  the corticospinal and corticobulbar system is the
primary pathway for the initiation of skilled voluntary movement
d. The main brain stem pathways that are concerned with posture and co-ordination are the rubrospinal,
reticulospinal, tectospinal, and vestibulospinal tracts, and corresponding projections to motor neurons in the
brain stem.

6. Ans. A. Projection fibres

White matter of cerebrum:
The white matter of cerebrum is composed mostly of myelinated nerve fibers, and comprises of three groups:
a. Association fibers or Arcuate fibers:
Association (Arcuate) fibers connect different cortical areas of the same hemisphere to one another. All
are ispilateral. They are short and long arcuate fibers.
The long association (Arcute) fibers are:
i. Uncinate fasciculus ii. Cingulum iii. Superior longitudinal fasiculus
iv. Inferior longitudinal fasiculus iv. Fronto-occipital fasiculus
b. Commissural fibers: - Connects the two hemispheres to each other Q, linking corresponding or homotopic
loci and also heterotopic loci they are:
i. Corpus callosum ii. Anterior commissure iii. Commissure of fornix
iv. Posterior commissure v. Habenular - commissure
c. Projection fibers: - Connect the cerebral cortex with the grey matter of the brainstem and spinal cord and
comprises of both incoming and out goings fibers (=tract). Most of the projection fibers form internal
capsule. Many important tracts e.g. corticospinal (pyramidal tract) and cortico pontine are made up of
projection fibers (Note ~ Tract = bundle of fibers)

7. Ans. D. Abnormal movements

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8. Ans. A. Flaccid paralysis

a. The lower motor neuron may be injured or diseased in the cranial nerve nuclei or spinal anterior horn
cells, in the anterior nerve root, or in the nerves themselves.
b. A common acute lesion of anterior horn cell used to be poliomyelitis in which fever was accompanied by
signs of meningeal irritation. In a few days a flaccid paralysis occurred.

9. Ans. A. Withdrawal reflex

a. Spinal Reflex:
i. Monosynaptic reflex- ~ The simplest reflex arc is one with a single synapse between the afferent and
efferent neurons. They are monosynaptic. Eg. stretch reflexes (Knee jerk, ankle jerk etc) ~ Muscle spindle is
the receptor for stretch reflex. Q
ii. Polysynaptic reflex ~ Reflex are, in which one or more intemeurons are interposed between the afferent
and efferent neurons.
Eg. i. Withdrawal reflex Q ii. Abdominal reflex Q iii. Cremastric reflex etc. Q
b. Withdrawal reflex:
i. The withdrawal reflex is a typical polysynaptic reflex Q that occurs in response to a noxious and usually
painful stimulation of the skin or subcutaneous tissues and muscles.
ii. The response is flexor muscle contraction and inhibition of extensor muscles.
iii. When a strong stimulus applied to a limb, the response includes not only flexion and withdrawal of that
limb but also extension of the opposite limb. This is called crossed extension response, which is properly
part of the with drawl reflex
c. Bell-Magendie Law: - in the spinal cord the dorsal roots are sensory and the ventral roots are motor.

Section-4-: Basal Ganglia

1. Ans. C. Planning of voluntary movements

BASAL GANGLIA are involved in the planning and programming of movement. Q

2. Ans. A. Dopaminergic
a. There is a system of dopaminergic neurons in nigrostriatal dopaminergic system with cell bodies in
substantia nigra and axon endings in caudate nucleus Q.
b. In Parkinson’s disease there is loss of dopaminergic cells in the substantia nigra Qwhich leads to striatal
dopamine depletion.
c. As DOPAMINE activates excitatory Dl receptors in the direct pathway and represses inhibitory D2
receptors in the indirect pathway, this depletion leads to decreased activity of the direct pathway and
increased activity of the indirect pathway.

3. Ans. B. Skilled motor movements

Basal ganglia:
a. It consists of five nuclei -

a. Caudate nucleus Q b. Putamen Q c. Globus pallidus Q

d. Subthalamic nucleus Q e. Sustantia nigra Q
* Striatum = caudate nucleus +

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Putamen
* Lenticular, = putamen + Globus
pallidus

B. The hypothalamus and limbic systems are intimately concerned with emotional expression and the
genesis of emotions.
C. Cerebellum and vestibular system of innerear are concerned with equilibirium.

Central Nervous System Chapter - 6

4. Ans. C. Intrastriatal GABAergic neurons
Huntington’s disease is a genetic, autosomal dominant Q, degenerative brain disorder. The two clinical
hallmarks of the disease are chorea and behavioral disturbance. Neurochemically there is a marked
decrease of gamma-aminobutyric acid (GABA) Q and its synthetic enzyme glutamic acid decarboxylase
throughout the basal ganglia Q. There is gliosis and neuronal loss, especially of medium-sized spiny neurons
in the caudate and putamen. There is relative sparing of large cholinergic aspiny neurons.

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5. The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 214
Decreased inhibitory input to the GPi from the putamen, would enhance inhibitory output from the GPi to the thalamus.
The result is inhibition of excitatory output from the thalamus back to the cortex.

Diagrammatic representation of the principal connections of the basal ganglia. Solid lines indicate excitatory
pathways,
dashed lines inhibitory pathways. The transmitters are indicated in the pathways, where they are known. Glu,
glutamate; DA, dopamine. Acetylcholine is the transmitter produced by interneurons in the striatum. SNPR,
substantia nigra, pars reticulata; SNPC, substantia nigra, pars compacta; ES, external segment; IS, internal
segment; PPN, pedunculopontine nuclei.

6. The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 101-104
 The basal forebrain nuclei and the pedunculopontine nuclei are major sources of distributed cholinergic innervation
in the CNS.
 These cell groups are functionally dissimilar. Neither is a major input to the striatum or involved in language
construction. Only the basal forebrain nuclei receive input from the cingulate gyrus.
 Although not known for certain, it is unlikely that either of these cell groups is atrophied in schizophrenia, which
appears to be a disorder of dopaminergic function.

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Section-5-: Cerebellum

1. Ans. B. Spinocerebellar ataxia

(Ref: Textbook of Clinical Neurology by Christopher G. Goetz page 374)
a. Spinocerebellar ataxia : It involves only the neurons whereas in other lesion cells like glial cells etc can also
be involved.
b. Corticobasilar degeneration
Corticobasilar degeneration is a rare condition that causes symptoms like PSP but can be unilateral

Central Nervous System Chapter - 6

(affecting only one side of the body) and eye movement may not be affected. Cortico-basilar
degeneration: severe cell loss in the pre- and post-central parietal area. Symptoms include stiffness,
ataxia, choreiform movements, flexion dystonia, vertical gaze palsy, parkinsonian features and cerebellar
and pyramidal tract signs.
c. Steel-Richardson-Olszewski syndrome or progressive supranuclear palsy (PSP): first described in the
1960s, this symmetrical disease is characterised by rigidity, falls (backward), a fixed facial expression,
inability to look down and speech and swallowing problems. Tremor is rare and then only during
movement.
d. Multiple system atrophy Multiple system atrophy (MSA) is a rare condition that causes symptoms similar
to Parkinson's disease. However, patients with MSA have more widespread damage to the part of the
nervous system that controls important functions such as heart rate, blood pressure, and sweating.

2. Ans. D. Smoothens and coordinates ongoing movements

By comparing plan with performance spinocerebellum smoothes and coordinates movements that are ongoing.

3. Ans. B Co-ordination

4. Ans. C. Static tremor and rigidity

5. Ans. B. Flocculus
The cerebellum can be divided into 2 fundamental parts known as flocculonodular lobe and the corpus
cerebelli, the later comprising an anterior and middle lobe. Certain sectors of the cerebellum are
phylogenetically older than the rest. The flocculonodular lobe together with the lingula constitutes the
oldest part of the cerebellum (archicerebellum) Q.

6.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 220
Spinal input, such as from the spinocerebellar tracts, enters the cerebellum on the mossy fibers. The climbing fibers originate
from the inferior olivary nucleus of the medulla (the olivo-cerebellar tract). The other components are intrinsic to the
cerebellum.

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Diagram of neural connections in the cerebellum. Plus (+) and minus (–) signs indicate whether endings are
excitatory or
inhibitory. BC, basket cell; GC, Golgi cell; GR, granule cell; NC, cell in deep nucleus; PC, Purkinje cell.

31. Ans. is (C) Lung compliance

1. TLC  is the maximum volume to which the lungs can be expanded with the greatest possible inspiratory effort.
TLC = IRV +TV + ERV+RV Q= IC + RV Q
2.Compliance (stretchability) of lungs:  is increased in Emphysema (obstructive lungs dis) and decreased in Interstitial
pulmonary fibrosis (Restrictive lung disease). Compliance of lung is change in lung volume per unit change in airways
pressure.
3. TLC is increased in obstructive ling disease (eg. emphysema, COPD) and decreased in the restrictive lung disease
(Interstitial pulmonary fibrosis)

Section-6-: EEG & Sleep

1. Ans. C. In deep sleep

Frequency
Type Location Normally Pathologically
(Hz)

frontal, high
 adults  subcortical lesions
amplitu
Delta up to 3  deep sleep  diffuse lesions
de (20-
 infants
200 μV)

Parietal and
 young children
tempor  focal subcortical lesions
Theta 4 - 7 Hz  drowsiness(early
al
sleep)
regions

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Parietal and
Frequency decreases in : hypoglycemia,
occipita  closing the eyes and
Alpha 8 - 12 Hz hypothermia,
l(50- by relaxation.
hypercapnia,GA,sleep,coma
100 μV)
Frontal
region;
low  active, busy or
Beta 12 - 30 Hz amplitu anxious thinking,  sedatives

Central Nervous System Chapter - 6

de active concentration
waves
10 μV

2. Ans. B. Stage II

3. Ans. B. Alpha waves

Sleep pattern –
a. Types —
i. REM Sleep, or D-sleep (desynchronized, or dreaming sleep) or active sleep or paradoxial sleep
ii. NREM sleep or quiet sleep or orthodox sleep or S-sleep (synchronized sleep)
b. As the person falls asleep, the person first passes through, stages of NREM sleep.
c. Over all REM sleep constitues 20 to 25% of total sleep and NREM Sleep stages (1 and 2) are 50 to 60
persent. Q
d. NREM sleep: 4 stages (1 to 4)  C/B 
i. Wakefulness -
 Alert wakefulness with Eye open  -wave
 Quiet wakefulness with eye closed  -waves
ii. Stage — 1  theta () activity Q
iii. Stage —2  Sleep spindle (13-15 cycles/sec) and K-complexes (high voltage spikes) Q
iv. Stage 3  theta and delta activity Q
v. Stage 4 (Deep sleep or cerebral sleep)  Delta activity () predominate Q
vi. Stage 3 and 4 togather called slow-wave sleep Q
vii. Disorders of the NREM stage 4 and 3 sleep: - i.e. during deep sleep Q

Sleep walking (somnabulism)
 Sleep terrors or night terrors (Pavor nocturnus)  C/B  Autonomic sympathetic activity
 the dream is not remembered.
 Sleep-related enuresis (but CMDT says that it is not limited to a specific stage of sleep)
 Bruxism (tooth grinding)
 Sleep talking (Somniloquy)

e. REM sleep (Paradoxical sleep)  C/B 

i. EEG resembles  stage I NREM sleep  theta activity REM sleep is c/b a low amplitude, mixed
frequency EEG similar to NREM stage I
ii. Associated with active dreaming (remember on wakening) Q

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iii. Muscle tone depressed (paralysis)

iv. HR and Resp. rate  irregular
v. Few irregular muscle movement occurs.
vi. Brain metabolism may increased by 20%
[Note  another characteristic of REM sleep is the occurance of large phasic potentials, in groups of 3
—5, that originate in the pons and pass rapidly to LGB and from there to the occipital cortex, and
therefore, they are called Ponto-geniculo-occipital (PGO) spikes]
vii. Sleep disorder of REM sleep or Penile erection: - eg.
 Narcolepsy: [(Sleep attack (m.c.), cataplexy, Hypnagogic hallucinations, sleep paralysis
(least common)]
 Night mares  dream is remembered

4. Ans. C. Theta
5. Ans. A. REM sleep
6. Ans. (A). Primary visual cortex
Genesis of REM Sleep
 The low-voltage rapid rhythm of the cerebral cortex during REM sleep resembles that during the EEG alerting
response and is presumably generated in the same way.

 The main difference between REM sleep and wakefulness is that dream consciousness is characterized by
bizarre imagery and illogical thoughts, and dreams are generally not stored in memory.

 However, PET scanning of humans in REM sleep shows increased activity in the pontine area, the amygdalas,
and the anterior cingulate gyrus but decreased activity in the prefrontal and parietal cortex. Activity in visual
association areas is increased, but there is a decrease in the primary visual cortex.

Section-7-: Hypothalamus

1. Ans. A. Shivering (Ref: 23rd edition Ganong's Page-273)

Temperature-Regulating Mechanisms
a. The reflex and semireflex thermoregulatory responses in humans are listed in Table 18–4.
b. They include autonomic, somatic, endocrine, and behavioral changes.
c. One group of responses increases heat loss and decreases heat production; the other decreases heat loss
and increases heat production.
d. In general, exposure to heat stimulates the former group of responses and inhibits the latter, whereas
exposure to cold does the opposite.

Table 18–4 Temperature-Regulating Mechanisms.

Mechanisms activated by cold

I. Shivering
II. Hunger
III. Increased voluntary activity

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Increased secretion of norepinephrine and epinephrine

Decreased heat loss
Cutaneous vasoconstriction
Curling up
Horripilation
Mechanisms activated by heat

Central Nervous System Chapter - 6

I. Increased heat loss
II. Cutaneous vasodilation
III. Sweating
Increased respiration
Decreased heat production
Anorexia
Apathy and inertia
i. Curling up "in a ball" is a common reaction to cold in animals and has a counterpart in the position some
people assume on climbing into a cold bed. Curling up decreases the body surface exposed to the
environment.
ii. Shivering is an involuntary response of the skeletal muscles, but cold also causes a semiconscious general
increase in motor activity.
iii. Increased catecholamine secretion is an important endocrine response to cold. Mice unable to make
norepinephrine and epinephrine because their dopamine β-hydroxylase gene is knocked out do not
tolerate cold; they have deficient vasoconstriction and are unable to increase thermogenesis in brown
adipose tissue through UCP 1.
iv. TSH secretion is increased by cold and decreased by heat in laboratory animals, but the change in TSH
secretion produced by cold in adult humans is small and of questionable significance
v. Thermoregulatory adjustments involve local responses as well as more general reflex responses.
vi. When cutaneous blood vessels are cooled they become more sensitive to catecholamines and the
arterioles and venules constrict. This local effect of cold directs blood away from the skin.
vii. In new born and children immature temperature regulating mechanism and Shivering is absent among
newborns
viii. The main mechanism of heat production is through increased noradrenaline to release energy from brown
adipose tissue

2. Ans. B. Decreased peripheral resistance

Rosen's emergency medicine: concepts and clinical practice.
a. Hypothermia is a condition in which core temperature drops below the required temperature for normal
metabolism and body functions which is defined as 35.0 °C (95.0 °F).
b. Body temperature is usually maintained near a constant level of 36.5–37.5 °C (98–100 °F) through biologic
homeostasis or thermoregulation.

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c. If exposed to cold and the internal mechanisms are unable to replenish the heat that is being lost, a drop
in core temperature occurs.
d. As body temperature decreases, characteristic symptoms occur such as shivering and mental confusion.
e. The classical ECG finding of hypothermia is the Osborn J wave. Also, ventricular fibrillation frequently
occurs at <28°C (82.4°F) and asystole at <20°C (68°F).
f. The Osborn J may look very similar to those of an acute ST elevation myocardial infarction.Thrombolysis
as a reaction to the presence of Osborn J waves is not indicated, as it would only worsen the underlying
coagulopathy caused by hypothermia.
g. Hypothermia is also associated with a lower clotting threshold and reversible coagulation.
h. Peripheral resistance is increased due to vasoconstriction caused by hypothermia.

3. Ans. A. MSH Ref: Ganong - 23rd Ed 429

4. Ans. B. Hypothalamus
Posterior nucleus→ wake promoting area and
Ventero Lateral Pre-optic area
↓
Sleep Promotion area

5. Ans. C Ventromedial nucleus of hypothalamus

Regulators of Hunger

6. Ans. B. Hypothalamus
Thermoregulatory center is a center located in the HYPOTHALAMUS that regulates heat production especially
heat loss. It is found in the anterior portion of the hypothalamus, especially the preoptic area.

7. Ans. A. Dorsomedial posterior hypothalamus

a. Primary motor center for shivering is located in the DORSOMEDIAL PORTION OF POSTERIOR
HYPOTHALAMUS near the wall of third ventricle.
b. This area is excited by cold signals from skin and spinal cord and inhibited by signals by heat centers Q from
hypothalamus.
c. During maximum shivering body heat production raises about five times the normal. Q

8. Ans. B. Extracellular hyperosmolarity

a. Drinking is regulated by plasma osmolality and extracellular fluid volume in much the same way as
vasopressin secretion.
b. Water intake is increased by increased effective osmotic pressure of the plasma, by decrease in
extracellular fluid volume, and by psychologic and other factors.
c. Injection of hypertonic saline into the anterior hypothalamus causes drinking in animals by acting on
osmoreceptors. Q

9. Ans. B. Suprachiasmatic nucleus (Ref: Ganong 23rd edition Page 235)

10. Ans. D. Electrical stimulation of the preoptic nucleus

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The same area along the anteroventral wall of the third ventricle Q that promotes ADH release also stimulates
thirst. Located anterolaterally in the preoptic nucleus Q is another small area that, when stimulated electrically,
causes immediate drinking that continues as long as the stimulation lasts. All these areas are known as thirst
center together Q.

11. Ans. A. Anterior hypothalamus

Function Integrating Area of hypothalamus
Osmoreceptor Anterior Hypothalamus Q
Temperature regulation Q Anterior hypothalamus response to heat and posterior

Central Nervous System Chapter - 6

hypothalamus response to cold Q
Hunger Anterior ventral hypothalamus plus, in the male piriform cortex Q
Sexual behavior Anterior ventral hypothalamus plus, in the male, piriform cortex Q
Circardian Rhythm Supra-chiasmatic nuclei Q

12. Ans. B. Heart rate increased with exercise

Main Functions of Hypothalamus
• Temperature regulation • Neuroendocrine control of catecholamines
• Appetitive behavior Thirst and hunger • Neuroendocrine control of vasopressin
• Defensive reactions Fear and rage • Neuroendocrine control of oxytocin
• Sexual behavior • Neuroendocrine control of TSH via TRH
• Control of various endocrine activity, • Neuroendocrine control of FSH, LH via LHRH
rhythm
• Neuroendocrine control of prolactin via PIH and PRH
• Neuroendocrine control of GH via somatostatin and GRH

13. Ans. C. Anterior hypothalamus

a. AVP release is regulated primarily by OSMORECEPTORS found in the HYPOTHALAMUS.
b. Changes in the concentration circulating plasma solutes to which the cellular membrane is impermeable
bring about alterations in the volume of the osmoreceptor cells, which in turn change the electric activity
of the neurons and control both the synthesis and release of AVP. As a consequence of this mechanism
between effective plasma osmolality and AVP release, plasma osmolality is generally maintained within a
very narrow range.

14. Ans. B. Fatty acids show uncoupled oxidative phosphorylation

a. Sympathetic stimulation- “Non-shivering thermogenesis” (= Chemical thermogenesis):
Steps are -
a. Stimulation of the sympathetic nervous system  liberate — nor epinephrine and epinephrine 
metabolic rate
b.  Glycogenolysis and a more important effect on brown fat in causing marked liberation of heat
c. Brown fat contains large numbers of mitochondria and many small globules of fat  when these cells
are stimulated by sympathetic nerves heir mitochondria produce a large amount of heat but almost
no ATP (i.e. the process of oxidative phosphorylation in mitochondria is mainly uncoupled)

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 Physiology

d. The neonate has a considerable no. of such fat cells (brown fat) and maximal sympathetic stimulation
can increase the child’s metabolism more than 100% (this is called non-shivering thermogenesis) Q
Non-shivering thermogenesis may also serve as a buffer against obesity.

b. Non-shivering thermogenesis
Cold stress

Sympathetic stimulation — Q to Brown fat

Release of Norepinephrine Q

acts via 3-adrenergic receptors Q

Increases lipolysis and increases fatty acid oxidation in mitochondria, increases heat production (uncoupled
oxidative phosphorylation — i.e. production of heat without ATP generation Q

a. Mechanism of uncoupling
i. Short-circuit conductance  by uncoupling proteins
 UCP-1 — in Brown fat
 UCP-2 — in both white and Brown fat
ii. A thermogenic uncoupling protein:
 Thermogenin  acts as a proton conductance pathway dissipating the electro-chemical potential
across the mitochondrial membrane.
b. “Therefore Non-shivering thermogenesis is mediated via Norepinephrine,β3 , receptor, UGP-1, UGP-2
and thermogenin Q
i. It increase melanocortin secretion but its action are not affected by melanocortin.
ii. High levels of glucocorticosteriods causes an increase of NPY by directly activating type II
glucocorticosteriods receptors and, indirectly, by abolishing the negative feedback of CRF on NPY
synthesis and release.
iii. Neuropeptide Y (NPY)-ergic neurons of the hypothalamic arcuate nucleus (ARC) that project to the
paraventricular nuclei (PVN) and dorsomedial nuclei (DMH) control energy balance by stimulating
feeding and inhibiting thermogenesis, especially under conditions of energy deficit.
iv. Its levels are increased in starvation, anorexia nervosa etc.

15. Ans. C. Vagal inhibition of heart is reduced

(Ref: Animal adaptation to cold. Lawrence C. H. Wang, J. A. Boulant 1st ed. Page 25,36,102-107)
a. Several studies indicate that chronic exposure to cold activate some adaptive mechanisms characterized
by a diminution of the sympathetic response and a concomitant enhancement of the vagal activation. As a
result the heart rate decreases.
b. The various other studies and their results suggest that cold depresses blood insulin levels through
activation of the α-adrenergic inhibition of the pancreatic insulin response.
c. There is a increased blood flow to adipose tissue to increase thermogenesis in adipose tissue (primarily in

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16. Ans. A. it is mediated under the effect of melanocortin

(REF: Drug Discovery and Evaluation: Pharmacological Assays - Page 1645)
a. Neuropeptide Y (NPY) is a 36-amino acid peptide neurotransmitter found in the brain and autonomic
nervous system.
b. The main effect is increased food intake and decreased physical activity.
c. NPY is secreted by the hypothalamus, and, in addition to increasing food intake, it increases the
proportion of energy stored as fat and blocks nociceptive signals to the brain.
d. NPY also augments the vasoconstrictor effects of noradrenergic neurons

Central Nervous System Chapter - 6

e. NPY into the PVN results in an acute release of corticotropin-releasing hormone (CRH) in the rat brain,
proving that NPYergic activity directly stimulates the release and synthesis of CRF.

17. Ans. B. Ghrelin

(Ref: Lippincott. Principles of pharmacology: Page 473 & Ganong - Review of Medical Physioloy 23rd Ed, Page-
429)
a. Ghrelin is a hormone produced mainly by P/D1 cells lining the fundus of the human stomach and epsilon
cells of the pancreas that stimulates hunger.
b. Ghrelin levels increase before meals and decrease after meals.
c. It is considered the counterpart of the hormone leptin, produced by adipose tissue, which induces
satiation when present at higher levels.
d. In some bariatric procedures, the level of ghrelin is reduced in patients, thus causing satiation before it
would normally occur.
e. Ghrelin is also produced in the hypothalamic arcuate nucleus, where it stimulates the secretion of growth
hormone from the anterior pituitary gland.
f. The ghrelin receptor is a G protein-coupled receptor. Receptors for ghrelin are expressed by neurons in
the arcuate nucleus and the lateral hypothalamus.
g. brown fat through UCP 1.

Mechanisms activated by cold in body

a. Shivering b. Hunger
c. Increased voluntary activity d. Increased secretion of norepinephrine and epinephrine
e. Decreased heat loss f. Cutaneous vasoconstriction
g. Curling up h. Horripilation

Section-8-: Higher Functions

1. Ans. B remote memory

a. Recent memory: Short-term memory. Also called working memory.
i. Capacity: About 7 plus or minus 2 "chunks" of information (Miller, 1956)
ii. Duration: About 18 to 20 seconds (Peterson & Peterson, 1959)
b. Long-term memory is the relatively permanent memory store. Also called remote memory. Duration: Up
to a lifetime.

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c. Delayed memory This term is used to describe the experience of an individual who recalls a memory for
which he or she was previously amnestic. The recollection may occur spontaneously or in the context of
therapy.

2. Ans. A. Vertically

3. Ans. D. Allocation of specialized nerve cells as occurs in hippocampus.

Memory is of types
a. Short term memory
b. Long term memory
"Short term memory involves modulation of synaptic transmission by modification of pre existing proteins
whereas long term memory involves formation of new synaptic connection and synthesis of new proteins"
Recruitment of neurons is called Cortical plasticity and is a established mechanism of Memory & learning.
There is no concept of memory cells or specialized nerve cells and also hippocampus doesnot store
memory. So the best answer is D.

4. Ans. B Hippocampus

5. Ans. A. Anterior thalamic nuclei

a. The fornix connects the hippocampus to the mamillary bodies which are in turn connected to the anterior
thalamic nuclei of the thalamus by mammillothalamic tract.
b. The anterior nuclei of thalamus project to the cingulate cortex and from there connections to the
hippocampus complete a complex closed circuit."
c. This circuit was originally described by Papez and has been called Papez circuit.

6. Ans. B. Inability to recognize faces

The patient with PROSOPAGNOSIA are unable recognize familiar faces Q, including, sometimes, the reflection of
his or her own in the mirror.

7. Ans. A. Amygdala
a. Classic Kluver-Bucy syndrome (KBS) has been considered a direct consequence of bilateral anterior
temporal horn damage resulting from disease or injury.
b. Hayman et al recently described a case with MRI evidence of bilateral damage to the basolateral Q
amygdala Unfortunately no autopsy was reported

8. Ans. D. Hippocampus
"Emotions, behaviour; and "Limbic system"
a. Hypothalamus and limbic system are intimately concerned with emotional expression and with the genesis
of emotions.
b. Limbic system is applied to the part of brain that consists of a rim of cortical tissue (Allocortex and juxtacortex)
around hilum of cerebral hemisphere Amygdala Hippocampus and Septal nuclei
c. The major - connections of the limbic system are forming a closed circuit known as Papez circuit;
d. one characteristic of the limbic system is the paucity of connections between it and the neocortex
e. Another characteristic of limbic circuit is their prolong after discharge following stimulation.

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9. Ans. B. Reticulo activating system

[A] RAS (Reticulo-Activating system):
a. RAS fibers convey impulses upwards to the thalamus and cerebral cortex.
b. RAS fibers are multisynaptic path beginning at the medulla and pass upward via pons and mid brain to
reach the thalamus.
c. Function of RAS ~ when the RAS is stimulated, there is wakefulness and alertness of the subject and the
subject becomes fully conscious.

Central Nervous System Chapter - 6

[B]Dorsal columns - Medial Lemniscal system:
a. Carries sensation of
i. Fine touch ii. Two point discrimination iii. Pressure vibration iv. Joint position
b. Courses  I st order neurons passes through posterior column  do not cross at the spinal cord level 
ascends, and terminate into the Dorsal column nuclei (nucleus cuneatus and nucleus gracilis)  from
there 2nd order neuron arises and, cross to the opposite side (in the medulla)  then ascends through
medial lemnisci  ends in the thalamus  from here 3rd order neurons arise and ends in the cerebral
cortex.

[D] Clinical points:

1. Dissociative anaesthesia: ~in syringomyelia ~ loss of pain and temperature while touch, vibrations
joint and position senses are normal.
2. Brown-sequard syndrome (Ref. Guyton 9th ed./617) If only one half of the spinal cord is transected in a
single side (hemisection), the so-called Brown-sequard occurs :
a. All motor junctions are blocked on the side of the transection in all segments below the level of
the transection i.e. due to pyramidal tract injury ~ same side ~since it crosses in the medulla. '
b. Sensation of the pain and temperature (cold and Heat) are lost on the opposite side of the body in
all dermatomes two to six segments below the level of transection. Since pain and temp sensations
are carried by spino-thalamic tract, which is cross to opposite side at the same level of the cord.
c. Kinesthetic and position sensation, vibration sensation discrete localization, and two poin
discrimination -f are lost on the same side of the transection in all dermatomes below the level of
the transection since all these sensations are carried by dorsal and dorsolateral columns, which do
not cross in the spinal cord, instead they cross to opposite side in medulla
[E] Vestibulocerebellar tract  Concerned with equilibrium and learning induced changes in VOR.

10. Ans. A. Inability to recognise faces

11. Ans. A,B. Use fatty acid in starvation, In resting state 60% of total energy utilised
a. Brain metabolism:
b. Major substrates for brain are
i. Glucose, Amino acid, and ketone bodies (in starvation)
ii. Polyunsaturated fatty acids in neonate
c. Brain has no stored energy
d. Brain tissue normally use glucose as an exclusive fuel except during starvation when it can adapt to use
ketone bodies.

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e. Under resting condition, the metabolism of the brain accounts for about 15% of the total metabolism in
the body.
Therefore, under resting condition, brain metabolism is about 7.5 times the average metabolism in the rest
of the body. It means that the brain uses 15% of total energy at resting condition.
f. O2 consumption by the human brain (=cerebral metabolic rate for O 2, CMRO2) is average 3.5 ml/100gm/of
brain/min or 49ml/min for whole brain. Or 20% of the total body resting O2 consumption
g. Glucose enters the brain via GLUT-l in cerebral capillaries. It is independent of insulin.

12. Ans. B. Hippocampus

Hypoxic-Ischemic Encephalopathy
a. This occurs from lack of delivery of 02 (=Hypoxia) to the brain because of hypotension or respiratory
failure
b. Pathologic findings
i. Principal histological findings are extensive multifocal or diffuse laminar cortical necrosis, with
almost invariable involvement of the hippocampus.
c. "The hippocampal CA1 neurons are vulnerable to even brief episodes of hypoxia (ischemia) Q, perhaps
explaining why selective persistent memory deficits may occur after brief cardiac arrest".
d. Scattered small areas of infarction or neuronal loss may be present in the basal ganglia, hypothalamus
e. or brainstem.
f. In some cases, extensive bilateral thalamic scarring may affect pathways that mediate arousal.

13. Ans. A. Pavlov

IVAN PETROVICH PAVLOV was a Russian physiologist. He won the Nobel Prize in medicine in 1904. He is
remembered particularly for his work on conditioned response.

14. Ans. B. Conditioned reflex

Classical conditioning was accidentally discovered by Russian physiologist Ivan Pavlov in the 1900s. During his
work on salivation Pavlov used to give his dog some food and measured the amount of saliva the dog
produced while eating the meal. After the dog had gone through this procedure a few times, however, he
began to salivate even before receiving any food. Pavlov spent the rest of his life studying this basic type

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of associative learning, which is now called classical conditioning or Pavlovian conditioning.

Section-9 -: Speech & Aphasia

Central Nervous System Chapter - 6

1. Ans. A. Word formation
a. An essential function of this area is to transform neural word representations into their articulatory
sequences so that the words can be uttered in the form of spoken language.
b. The sequencing function of Broca's area also appears to involve the ordering of words into sentences that
contain a meaning appropriate syntax (grammar).
c. Wernicke's and Broca's areas are interconnected with each other and with additional perisylvian,
temporal, prefrontal, and posterior parietal regions, making up a neural network subserving the various
aspects of language function.
d. Wernicke's area situated at the posterior end of superior temporal gyrus is concerned with
comprehension of auditory and visual information i.e
i. Word interpretation. ii. Non fluent speech
iii. Good comprehension iv. Poor repetition

2. Ans. C. Inferior border of frontal lobe

BROCA’S AREA IS the area of the left cerebral hemisphere Q at the POSTERIOR END OF THE INFERIOR FRONTAL
GYRUS. It contains the motor speech area and controls movements of tongue, lips, and vocal cords.

3. Ans. C. Verbal expression

In MOTOR APHASIA, patients know what they want to say but cannot say it due to inability to coordinate the
muscles controlling speech. Broca’s area is involved in this condition.

4. The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 378 The arcuate fasciculus
 The arcuate fasciculus is the fiber bundle connecting Broca’s and Wernicke’s areas.
 The fornix connects the hippocampus with the hypothalamus and basal forebrain.
 The thalamocortical tract connects the thalamus with the cortex and the reticular activating system connects the
brainstem with the thalamus and cortex.
 The prefrontal cortex is not a fiber bundle.

Section-10 -: CSF

1. Ans. B. Rate of absorption

Normal CSF pressure is mainly regulated by rate of absorption by arachnoid villi.
a. The normal rate of CSF formation remains nearly very constant. It is independent of the CSF pressure.
b. Absorption by arachnoid villi is proportionate to the CSF pressure

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(Arachnoid villi act like valves and allow CSF fluid to flow into venous sinuses when CSF pressure is about
1.5mm Hg greater than the pressure of blood in the venous sinuses. If the CSF pressure rises further, the
valves open more widely, so that under normal conditions, the CSF pressure almost never rises more than
a few mm of Hg higher than the pressure in the cerebral venous sinuses)

CSF formation and absorption in humans at various CSF pressure.

2. Ans. D. Secreted by the arachnoid villi

Cerebrospinal Fluid
a. Formation & Absorption: CSF fills the ventricles and subarachnoid space. In humans, the volume of CSF is
about 150ml and the rate of CSF production is about 550mL/d.
b. Thus the CSF turns over about 3.7times a day In experiments on animals, it has been estimated that 50-
70% of the CSF is formed in the choroids plexuses and the remainder is formed around blood vessels and
along ventricular walls.
c. Presumably, the situation in humans is similar.
d. The CSF in the ventricles flows through the foramens of Magendie and Luuschka to the subarachnoid
space and is absorbed through the arachnoid villi into veins, primarily the cerebral venous sinuses.
e. The villi consist of projection of the fused arachanoid membrane and endothelium of the sinuses into the
venous sinuses.
f. These are similar, smaller villi projecting into veins around spinal nerve routes.
g. In a poorly understood way, these projections acts as valves which permits bulk flow (direct flow) of CSF
into venous blood.
h. Bulk flow through these villi is about 500ml/d, with the addition small amounts of CSF being absorbed by
diffusion into cerebral blood vessels.
i. Concentration of Substances in human CSF and plasma.
Substance CSF Plasma
pH 7.33 7.40

3. Ans. B. 0.64
CSF glucose Plasma glucose CSF plasma glucose ratio
64mg% 100 mg% 0.64

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4. Ans. A. 6-l2mmHg (50-l80mmH2O)

Composition of CSF

Osmolarity 292-297 mOsm/L Q

Sodium 137-145 mmol/L (1 37-145 mEq/L) Q
Potassium 2.7-3.9 mmol/L(2.7-3.9 mEq/L)
Calcium 1.0- 1.5 mmol/L(2.1 – 3.0 mEq/L)
Magnesium 1.0-1.2 mmol/L(2.0-2.5 mEq/L)
Chloride 116-122 mmol/L(1 16-122 mEq/L)

Central Nervous System Chapter - 6

CO2 content 20-24 mmol/L(20-24 mEq/L
PCO2 6-7 kPa (45-49 mmHg)
PH 7.31-7.34
GLUCOSE 40-70 mg/dL Q
Lactate 10-20 mg/dL
TOTAL PROTEIN 20-50 mg/dL
CSF pressure 50-180 mm H2O Q
CSF volume (adult) About 150 mL Q
TOTAL LEUKOCYTES <5 per mL Q
Lymphocytes 60-70 percent
Monocytes 30-50 percent
Neutrophils None

5. Ans. C. Straight sinus

a. The arachnoid granulations are small fleshy looking elevations, collected in clusters, which are present in
the vicinity of the superior sagittal, transverse, and some other sinuses Q.
b. Arachnoid granulations are macroscopic enlargements of minute projections of the arachnoid matter,
termed arachnoid villi, which are normally present in great number in young subjects.
c. The cerebrospinal fluid is a clear, slightly alkaline fluid, with a specific gravity of about 1007 Q.
d. It is secreted into the ventricles of the brain by the choroid plexus and into the subarachnoid space by the
plexuses sited in the lateral recesses of the 4th ventricle.
e. From the ventricles it passes through the median aperture and the foramina of the lateral recesses of the
4th ventricle and so gains the subarachnoid space in the cerebello medullary cistern and the pontine
cistern.
f. Within the cranium the CSF flows upwards through the gap in the tentorium and then forwards and
laterally over the inferior surface of cerebrum.
g. Finally it ascends over the lateral aspect of each hemisphere to reach the arachnoid villi associated with
the superior sagittal sinus, and so is able to pass back again into the bloodstream.

6. Ans. B. Dura mater

7. Ans. D. Glucose
CSF:
1. CSF has more concentration than plasma for following: 

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 Physiology

CSF Plasma
++ Q
(a) Mg (meq/Kg H2O) 2.2 1.6
- Q
(b)Cl (meq/kg H2O) 113.0 99.0
Q
(c) HC03- (meq/L) 25.1 24.8
(d) PC02 (mmHg) Q 50.2 39.5
Q
(c) creatinine (mg/dL) 1.5 1.2

2.  pH of CSF = 7.33 Q
3.  Osmolality of CSF is equal to the plasma = 289 mOsm/kg/H2O Q
4.  Glucose of CSF = 6.4 mg/dL (or 2/3rd of plasma) Q
5.  protein of CSF = 20mg/dL (Plasma protein = 6 ~m/dL) Q
6. Lumbar CSF pressure normally 70-180 mm H2o CSF Q
7.  At a pressure of 112 mm H2o CSF, filtration and absorption of CSF are equal.
8. Below 68mm H2o CSF pressure absorption stops.
9.  Total volume of CSF  150ml and the rate of CSF production is about 550 ml/day

8. Ans. A. 0.30—0.35 ml./min

Rate of daily production CSF = 550 ml. Q
Rate of daily production i.e. = 550 ml/24 hr
= 550 ml/24 x 60 min
= 0.30 – 0.35 ml/min

9. Ans. ‘A’ Daily production < 700 ml

CSF:
a. Total volume 150ml. Q
b. Daily Production is about 550ml Q
c. 50-70% of CSF is formed in the choroid plexuses and the remainder is formed around blood vessels and along
ventricular wall. Q
d. The process of formation of CSF includes both filtration and secretion. Q
e. circulation of CSF  CSF passes from lateral ventricle to 3rd ventricle though the foramen monro  then 3rd to
4th ventricle though aqueduct of Sylvius  then 4th ventricle to subarachnoid space via the foramina of Luschka
and Magendie Q
f. CSF is absorbed via the arachnoid villi (in sagittal sinus) into the venous blood of cranium and spinal cord. Q
g. CSF is also absorbed partly by the perineural Lymphatics around 1st 2nd 7th & 8th cranial nerves

10. Ans. A. Area postrema

 The structures which are outside the BLOOD- BRAIN- BARRIER: - (All have fenestrated capillaries. and deficits
Blood-brain-barrier): -are
a. Circumventricular organs:
i. Posterior pituitary (Neurohypophysis) Q
ii. Median eminence of Hypothalamus Q
iii. Area postrema Q
iv. Organum-vasculosum of the lamina terminalis (OVLT, supra optic crest) Q

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v. Sub fornical organ (SFO) Q

b. Pineal gland and Anterior pituitary

SECTION-11 -: AUTONOMIC NERVOUS SYSTEM

Central Nervous System Chapter - 6

1. Ans. D. Decreased AV conduction
Stimulation of cholinergic vagal fibers to nodal tissue leads to hyperpolarization of membrane. This action is
mediated by muscarinic receptors and result in DECREASE IN RATE OF FIRING OR CONDUCTION.

2. Ans. A. Cholinergic
ANS (Autonomic Nervous system)  Parasympathetic and sympathetic
a. Chemical transmission at autonomic junction: -(between pre and post-ganglionic neuron; and between the
postganglion neurons and the autonomic effectors) “The principal transmitter agents involved are Acetyl
choline and Non-epinephrine, although Dopamine is also secreted by interneurons in the sympathetic ganglia
and GnRH is secreted by some of the preganglionic neurons
b. On the basis of the chemical mediator, ANS is divided into: I- Cholinergic division (Ach transmitter) And II-
Nor-adrenergic division (Nor Ad transmitter)
c. Examples of cholinergic neurons:- (Ach transmitter)
a. All preganglionic neuron Q
b. Parasympathetic postganglionic neurons Q

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c. Sympathetic post ganglion neurons which innervate sweat gland Q

d. Sympathetic neurons which ends in the blood vessels (= produce vasodilation) Q
d. Remaining post ganglionic sympathetic neurons are Noradrenergic Q
e. The highest seat regulating ANS is in hypothalmus; posterior and lateral nuclei and primarily sympathetic while
anterior and medial nuclei are primarily parasympathetic
f. ICA cells (intrinsic cardiac Adrenergic cells)  Epinephrine (Adenergic) arid norepinephrine.
g. The adrenal medulla is essentially a sympathetic ganglion in which the post ganglion cells have lost their axons
and secrete norepinephrine, epinephrine, and some Dopamine directly into the blood stream.
h. Difference between sympathetic and paraysmpathetic division of ANS: -

Trait Sympathetic Parasympathetic

1. Origin Q Dorso-lumbar (T1 to L2 or L3) Craniosacral (III, VII, IX, X, S2-S4)
2. Ganglia Q Away from the organ On or close to organ
3. Distribution Q Wide Limited to head, neck and trunk
4. Post ganglionic fibers Q Long Short
5. Pre: Postganglionic fibers ratio Q 1:20 to 1:100 11 to 1:2 (except in enteric plexus)
6. Transmitter Q Nor adrenaline (major) Acetyl choline
Acetyl choline (Minor)
7. Function Q Tacking stress and emergency Assimilation of food conservation
of energy

3. Ans. A, C Sympathetic preganglionic, Parasympathetic preganglionic

Nerve fiber Types & Function:
a. Erlanger and Gasser divided mammalian nerve fibers into A,B and C groups.
A groups is further divided into α, β, γ and δ fibers. A and B fibers are myelinated while C-fibers are
unmyelinated
b. A fibers  thickest nerve fibers, (Dia. 12-20 υm), and have highest conduction velocity (70-120 m/s)
Function  Propioception, somatic motor.
Distribution  Muscle spindle, Annulospinal ending, (Ia) and Golgitendon organ (Ib)
c. B-Groups  Preganglionic autonomic (either sympathetic or parasympathetic)
Note  same thing is written in Neuro-anatomy book.
d. C-groups 
i. Dorsal root  Pain and temperature and
ii. Postganglionic sympathetics
e. Susceptibility of the Nerve fibers:

Note  for pain and temperature  Sensations carries by both Aδ and C Nerve fibers

4. Ans. C. Pupillary constriction

Response to a Cholinergic Impulse from Parasympathetic Stimulation

Sphincter of Iris Contraction Bronchial muscles Contraction

Ciliary muscle Contraction Bronchial glands Stimulation

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SA node Decreased HR Sweat glands Secretion

AV node Decrease in conduction Adrenal medulla Secretion of
velocity Epinephrine & NE
Arterioles Dilation Detrusor muscle Contraction
Gall bladder Contraction Trigone and sphincter Relaxation
GI tract
Stomach Intestine
Motility Increased Increased

Central Nervous System Chapter - 6

Secretion Increased Increased
Sphincter Relaxation Relaxation

5. Ans. B. Alpha fiber

(Ref: Review of Medical Physiology- Ganong’s-23rd Edition, P-215)
Alpha fibers are thickly myelinated (12-20 micrometer in diameter) & conduct at rates of 70-120m/s, which is
the maximum with lowest in C fibres at 0.7-2.3 m/sec.

6. Ans. B. Thoracolumbar
(Ref: Review of Medical Physiology- Ganong’s-23rd Edition, P-263)

7. Ans. B chorea
a. Parkinson occurs in damage to niagrostriatal pathways (dopamine)
b. Chorea in caudate nucleus lesion
c. Hemiballismus in subthalamic N. lesion (glutamate)
d. Athetosis in lenticular N (putamen + GP)
e. Huntington in intrastriatal GABAergic and cholinergic pathway disruption

8. Ans. A. glutamate
(Ref: Review of Medical Physiology- Ganong’s-23rd Edition, P-223)
a. Umami is one of the five basic tastes, together with sweet, sour, bitter and salty. The human tongue has
receptors for L-glutamate, which is the source of umami flavor.

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 Physiology

b. Saltiness is a taste produced primarily by the presence of sodium ions

c. Sourness is the taste that detects acidity.
d. Sweetness is produced by the presence of sugars and a few other substances. Sweetness is often
connected to aldehydes and ketones, which contain a carbonyl group. Sweetness is detected by a variety
of G protein coupled receptors coupled to the G protein gustducin found on the taste buds.

9. Ans. D. All of the above

(REF: Benbadis SR. Introduction to EEG. In: Lee-Chiong T, ed. Sleep: A Comprehensive Handbook. Hoboken, NJ:
Wiley & Sons; 2006:989-1024.)
a. Burst suppression is an electroencepholagram (EEG) pattern in which high-voltage activity alternates with
isoelectric quiescence.
b. It is characteristic of an inactivated brain and is commonly observed at deep levels of general anesthesia,
hypothermia, and in pathological conditions such as coma and early infantile encephalopathy.

10. Ans. D. delta waves

(Ref: Review of Medical Physiology- Ganong’s-23rd Edition, P-265)

11. Ans. A. outer hair cells

a. There are two types of otoacoustic emissions: spontaneous otoacoustic emissions (SOAEs), which can
occur without external stimulation, and evoked otoacoustic emissions (EOAEs), which require an evoking
stimulus.
b. OAEs are considered to be related to the amplification function of the cochlea. In the absence of external
stimulation, the activity of the cochlear amplifier increases, leading to the production of sound.
c. Several lines of evidence suggest that, in mammals, outer hair cells are the elements that enhance
cochlear sensitivity and frequency selectivity and hence act as the energy sources for amplification.
d. One theory is that they act to increase the discriminability of signal variations in continuous noise by
lowering the masking effect of its cochlear amplification

12. Ans. B. Orphanin receptors

(Ref: Okuda-Ashitaka E, Minami T, Tachibana S, Yoshihara Y, Nishiuchi Y, Kimura T, Ito S. "Nocistatin, a
peptide that blocks nociceptin action in pain transmission." Nature. 1998 Mar 19; 392(6673):286-9)
a. Nociceptin or orphanin FQ, a 17 amino acid neuropeptide, is the endogenous ligand for the nociceptin
receptor (NOP, ORL-1).
b. Nociceptin is an opioid-related peptide, but it does not act at the classic opioid receptors (namely, mu,
kappa and delta opioid receptors) and its actions are not antagonized by the opioid antagonist naloxone.
Nociceptin is a potent anti-analgesic.
c. Nociceptin acts at the Nociceptin receptor (NOP1), formerly known as ORL-1. The receptor is also widely
distributed in the brain, including in the cortex, anterior olfactory nucleus, lateral septum, hypothalamus,
hippocampus, amygdala, central gray, pontine nuclei, interpeduncular nucleus, substantia nigra, raphe
complex, locus coeruleus, and spinal cord.

13. Ans. B amacrine cells

(Ref: Masland RH, Tauchi M. The cholinergic amacrine cell. TINS. 1986;9:218–223.)

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 Central Nervous System

a. The classic fast excitatory neurotransmitter of the peripheral nervous system, acetylcholine (ACh), is found
in a mirror symmetric pair of amacrine cells in the vertebrate retina.
b. One of the mirror pair occurs in the amacrine cell layer with dendrites in sublamina of the IPL.
c. The other of the pair has its cell body displaced to the ganglion cell layer.

14. Ans. A. vision

a. Transducin (Gt) is a heterotrimeric G protein with three polypeptide chains characterized into two
subunits: α, β and γ. Transducin is naturally expressed in vertebrate retina rods and cones, with different α
subunits in rod and cone photoreceptors.Transducin is a very important G-protein in vertebrate

Central Nervous System Chapter - 6

phototransduction.
b. Heterotrimeric Transducin is activated by metarhodopsin II, a conformational change in rhodopsin caused
by the absorption of a photon by the rhodopsin moiety retinal.
c. The light causes isomerization of retinal from 11-cis to all-trans. Isomerization causes a change in the opsin
to become metarhodopsin II.
d. When metarhodopsin activates transducin, the GDP bound to the α subunit (Tα) is exchanged for GTP from
the cytoplasm. The α subunit dissociates from the βγ subunits (Tβγ.)
e. Activated transducin α-subunit activates cGMP phosphodiesterase. cGMP phosphodiesterase breaks
down cGMP, an intracellular second messenger which opens cGMP-gated cation channels.
f. Phosphodiesterase hydrolyzes cGMP to 5’-GMP. Decrease in cGMP concentration leads to decreased
opening of cation channels and subsequently, hyperpolarization of the membrane potential.

15. Ans. C. B Autonomic Fibres

(Ref: Review of Medical Physiology- Ganong’s-23rd Edition, Pg90)
C fibres are most affected by LA, A fibres the least.

Table 4-3 Relative susceptibility of Mammalian A,B and C never fibers to conduction block produced by various
agents.
Susceptibility to: Most Susceptible Intermediate Least Susceptible
Hypoxia B A C
Pressure A B C
Local anesthetics C B A

16. Ans. B. Hyperthermia

a. Thermoregulatory center is a center located in the HYPOTHALAMUS that regulates heat production
especially heat loss. It is found in the anterior portion of the hypothalamus, especially the preoptic area.
Damage can lead to hyperthermia.

Endotoxin
Inflammation
Other pyrogenic stimuli

Monocytes
Macrophages

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 Physiology

Kupffer cells

Cytokines
Preoptic area
Of hypothalamus

Prostaglandins
Raise temperature
Set point

Fever

b. Primary motor center for shivering is located in the DORSOMEDIAL PORTION OF POSTERIOR
HYPOTHALAMUS near the wall of third ventricle.
c. This area is excited by cold signals from skin and spinal cord and inhibited by signals by heat centers Q from
hypothalamus.
d. During maximum shivering body heat production raises about five times the normal. Q

17. Ans. D Loss of tactile localization and two point discrimination

Lesion of post central gyrus ( SSA -1)
a. Decreases the sensations, but do not entirely abolish them.
i. Fine touch & proprioception are almost totally lost.
ii. Temp. sensibility less affected.
iii. Pain sensibility only slightly affected. Q
NOTE:A certain degree of perception is possible in the absence of cortex. Q
b. Upon Recovery:
i. Pain sensibility returns first. Q
ii. Followed by temperature sense.
iii. & finally proprioception & fine touch. Q

18. Ans. C. Adrenaline from adrenal medulla

β3-adrenoceptor is the most significant in mature brown adipocytes . β3-adrenergic receptors are also present in
white adipocytes. These receptors are stimulated by NE and cause lipolysis which helps in heat production

19. Ans a. Decussating branches of lateral spinothalamic tract

20. Ans. B. Rate of absorption

21.The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 179
 The movements of the foot plate of the stapes set up a series of traveling waves in the perilymph of the scala
vestibuli. As the wave moves up the cochlea, its height increases to a maximum and then drops off rapidly.
 The distance from the stapes to this point of maximum height varies with the frequency of the vibrations initiating
the wave.

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 Central Nervous System

 High-pitched sounds generate waves that reach maximum height near the base of the cochlea; low-pitched sounds
generate waves that peak near the apex.
 As the frequency response of the basilar membrane changes steadily from high to low along its length, so that high
frequencies are detected close to the oval window and low frequencies are detected at the other end, near the
helicotrema.

22.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 183,184

Central Nervous System Chapter - 6

 Relative motion between the endolymph and the cupulae of the semicircular canals is due to the inertia of the
endolymph, whether the body motion is starting or stopping.
 As the fluid continues to move when the head has stopped moving, the cupulae will be stimulated, producing the
sensation of rotary motion.
 Moving in a straight line, without acceleration, will produce no fluid movement and no sensation.
 The sensation of static body position is accomplished by the maculae, which are sensitive to gravity but not
endolymph motion.

23. The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 209
 The spinal cord has the intrinsic circuitry in the form of central pattern generators to produce the basic motions of
walking. Circuits intrinsic to the spinal cord can produce walking movements when stimulated in a suitable fashion
even after spinal cord transection in cats and dogs.
 There are two locomotor pattern generators in the spinal cord: one in the cervical region and one in the lumbar
region. However, this does not mean that spinal animals or humans can walk without stimulation; the pattern
generator has to be turned on by tonic discharge of a discrete area in the midbrain, the mesencephalic locomotor
region, and, of course, this is only possible in patients with incomplete spinal cord transection.
 Interestingly, the generators can also be turned on in experimental animals by administration of the norepinephrine
precursor L-dopa (levodopa) after complete section of the spinal cord.
 All the other listed areas may influence the local pattern generators.

24.The answer is D. Ref: Textbook of Anatomy with Colour Atlas by Inderbir Singh - Page 1007
 The rubrospinal tract descends in the lateral spinal cord and influences distal muscle function. This is also the
function of the corticospinal tract.
 The vestibulospinal and reticulospinal tracts descend medially and influence proximal muscle action.
 The spinocerebellar tract is an ascending pathway.

25.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 205
 For the most part, the supplementary motor area projects to the motor cortex. This region also contains a map of
the body, but it is less precise than in M1.
 It appears to be involved primarily in organizing or planning motor sequences, while M1 executes the movements.
Lesions of this area in monkeys produce awkwardness in performing complex activities and difficulty with bimanual
coordination.
 When human subjects count to themselves without speaking, the motor cortex is quiescent, but when they speak
the numbers aloud as they count, blood flow increases in M1 and the supplementary motor area.
 Thus, the supplementary motor area as well as M1 is involved in voluntary movement when the movements being
performed are complex and involve planning.
 Blood flow increases whether or not a planned movement is carried out. The increase occurs whether the movement
is performed by the contralateral or the ipsilateral hand.
 The supplementary motor area tends to produce bilateral motor responses when stimulated. The other areas would
tend to produce unilateral responses.

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 Physiology

26.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 372
 The hippocampus is crucial for the formation of long-term (declarative) memory.
 Without the hippocampus, short-term memory is intact but the conversion to long-term does not take place.
 The retrieval of stored declarative memory does not require the hippocampus.
 The hippocampus is not needed for the formation or retrieval of procedural memory.

27.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 577
Of the possible choices, only cell bodies in the dorsal vagal nucleus have axons ending in the wall of the stomach.

28.The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 342
Fast EPSPs in the ENS are mediated mainly by nicotinic receptors for ACh. Hyperpolarizing after-potentials reduce
excitability. Metabotropic receptors stimulate adenylyl cyclase. Fast EPSPs are not hyperpolarizing potentials.

29.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 168
Suppression of EPSPs by NE could be through an action at the presynaptic site of ACh release or an action at the
postsynaptic membrane. The finding that NE does not affect the action of exogenously applied ACh, blocking the fast
EPSP indicates that the mechanism of suppression of the EPSPs is suppression of ACh release at the synapse.

30. Ans. is (B) Maintains the blood flow

The capacity of tissues to regulate their own blood supply is known as auto-regulation. This capacity is developed in
kidney but is also seen in mesentery, skeletal muscles, brain, liver and myocardium.

31.The answer is C.
Ref: Ganong - Review of Medical Physiology 23rd Ed Page 289
Nerve fibers, not vascular smooth muscle, release norepinephrine. The norepinephrine from the sympathetic nerves
simply diffuses from the axons and binds to specific receptors on smooth muscle cells.

32.The answer is A.
 Disruption of the hypothalamic-pituitary portal system leads to a lack of dopamine and GnRH reaching the pituitary.
Because dopamine inhibits PRL secretion, PRL levels will increase. In addition, the lack of GnRH will lead to reduced
secretion of LH and FSH, reduced ovarian function, and eventual ovarian atrophy.
 PRL will have no effect on the ovary or inhibit ovarian follicle development. Disruption of the hypothalamic-pituitary
axis will lead to reduced follicular development, lack of ovulation, and low circulating progesterone.
 Inhibin levels will decrease, but FSH will not increase because there is no GnRH reaching the pituitary from the
disrupted axis. Excessive ovarian androgen usually occurs in the presence of excessive LH secretion or an androgen
tumor in the ovary. LH secretion is reduced by the lack of GnRH.

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 Vision

Chapter - 7
Vision & Hearing

I. THE FUNCTION OF THE 3 LAYERS:

A. Sclera: Protective
B. Uvea : Vascular (nutritive)
C. Retina : Light- sensitive

Chapter - 7
D. The retina lines the post 2/3rd of the choroids. The lens ligament (zonule) is attached to the lens and to the
ciliary body.
E. The aqueous humour is formed in the ciliary body. The normal intraocular pressure is 10-20 mmHg.
The refractory power of eye is expressed in diopters
1
No. of diopters = ------------------------------------
Focal length in meters

Normal is 59 D (44 by conea & 15 by Lens)

1. Accomodation- In accommodation, only the anterior curvature of the lens changes.
Near response consists of
a. Accommodation
b. Convergence of the eyes

Vision
c. Papillary constriction
The pupils can constrict as a part of the near response; the pupils also constrict as a part of the light reflex

2. Reduced or Schematic eye- Since there are many places in the eye where refraction of the light rays takes
place, for simplicity, (to make ray diagrams) we can assume that all refraction takes place at the anterior
surface of the cornea. (Most of the refraction occurs at the cornea). The wavelengths of visible light range
from approximately 397–723 nm

3. RETINA
There are 10 layers in the retina. The neural cells in the retina are the receptor cells (rods & cones), the
bipolar cells, the ganglion cells, the horizontal and the amacrine cells. There are 6 million cones and 120
million rods. The glial cells are the Muller cells. There are gap junctions from one retinal neuron to another.

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 Physiology

The horizontal cells (H) join one receptor( R) cell to another; the amacrine (A) cells join one ganglion cell to another.
H R H

B polar cell

A G A
(Ganglion cell)
The rods have connection with bipolar cell. which in turn has connection with ganglion cell. The axons of the
ganglion cell form the optic nerve. Many receptor ( R) cells converge an one bipolar cell and many bipolar cells
converge on one ganglion cell; there is overall convergence from the receptor cell to the ganglion cell.
a. Amacrine cells: are involved in signal processing via lateral inhibition(secrete Ach). They Modulates colour
contrast & luminosity under various light conditions. Also Increase visual acuity.
b. Muller Cells: Are retinal Glial cells. Gives rise to b wave of ERG. K+ & Neurotransmitter uptake
(Note that the direction of the light rays is from that
ganglion cell bipolar cell receptor cell )
At the posterior pole of the eye, the macula lutea (with fovea centralis ) is present. The unique features of the
fovea centralis are
i. It is rod- free; only cones present
ii. The cones here are densely packed there are very few other cells
iii. There are no blood vessels overlying the receptors
iv. It is the point of highest visual acuity.
Note that action potentials are formed only in the ganglion cells; in the other retinal neural cells only local
potentials are formed.
The primary visual area (area 17) lies on the sides of the calcarine fissure in the occipital lobe.
The visual pathway has connections, which subserve
i. Vision
ii. Pupillary reflex
iii. Superior colliculus
iv. Suprachiasmatic nucleus of the hypothalamus
Fibres from ipsilateral temporal hemiretina end in lamina 2,3,5& Fibres from contralateral nasal hemiretina end in
lamina 1,4,6.
The rods are more sensitive (lower threshold) than the cones. The visual spectrum is from 393nm to 727 nm.

Photoreceptor mechanism – All or none action potentials are seen only in the ganglion cells. In all others, there are
local, graded potentials.
 Rods/ cones/ horizontal cells: Hyperpolarising potentials
 Bipolar cells : Hyper or hypopolarising
 Amacrine: Depolarizing.
 Ganglion cells: Action Potentials
o The photosensitive pigment in the rods is rhodopsin. It consists of 11-Cis retinal bound to protein
opsin. Its peak sensitivity to light at a wavelength of 505 nm.

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o When rhodopsin is exposed to light 11-Cis retinal is converted to all trans retinal, which activates a G
protein

Transducin.
a. Regeneration of rhodopsin requires isomerization of all trans retinal back to 11-Cis retinal by rhodopsin
Kinase.
b. The sodium channels in the outer segment of the receptor cell are open in the dark; in the dark; there is a
steady release of neurotransmitter resulting in dark currents.

Chapter - 7
c. When light falls, Transducin closes the sodium channels. Causing hyperpolarisation and a decrease in the
neurotransmitter release. One photon of light is enough to stimulate the rod.
d. The cones are for color vision and respond maximally to light at wavelengths of 440, 535, and 565 nm
e. The retina has 2 types of ganglion cells:
 Magnocellular: for movement, Flicker & Stereopsis (Depth of Perception)
 Parvocellular: for color, texture and shape.
f. True Stereopsis is due to Binocular vision & False is due to Relative sizes , Angles, Parallax etc
g. The primary colors are blue, red and green. For any color, there is a complementary color that when properly
mixed with it, produces a sensation of white. Colour Blobs (V8) are cells in the visual cortex associated with
colour vision.

4. Color defects
Weakness- is called anomally

Vision
Blindness- is called anopia
‘Prot’ refers to red
‘Deuter’ refers to green
‘Tri’ refers to blue
Trichromats have all the 3 types of cones
Dichromats have a 2-cone system
If ‘red’ absent- Protanopia
If ‘green’ absent- Deuteranopia
If ‘blue’ absent- Tritanopia
Monochromats have only 1-cone system.

Cell LGB Visual cortex Function

P(or parvocellular cell) Parvo portion Layer Deep & C Colour, texture, shape
(Layers 3-6) Layer 2,3 (blobs) Colour
Interlaminar region
M (or magnocellular Magnocellular portion Layer superficial Movement, depth,
cell) (Layers 1 and 2) 4C Flicker & spatial
organization

5. Electroretinography measures the electrical responses of various cell types in the retina, including the
photoreceptors (rods and cones), inner retinal cells (bipolar and amacrine cells), and the ganglion cells.
Electrodes are usually placed on the cornea and the skin near the eye. During a recording, the patient's eyes

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are exposed to standardized stimuli and the resulting signal is displayed showing the time course of the signal's
amplitude (voltage). a-, b- and c-waves are observed in the ERG.
The a-wave is a corneo-negative waveform both rods and cones contribute to the a-wave.
The second wave which is corneo-positive, is the b-wave. its origin is from the Müller's cells. The c-wave is positive
like the b-wave, but otherwise is considerably slower. It is generated by the retinal pigment epithelium (RPE) as a
consequence of interaction with the rods.

6. ERG can be useful in:

a. Retinitis pigmentosa and related hereditary degenerations
b. Leber's congenital amaurosis , Choroideremia

AUDITORY SYSTEM
For hearing- the external, middle and inner ear.
For equilibrium- the semicircular canals (SC), the utricle and saccule of the inner ear
a. Semicircular canals sense rotational acceleration
b. The utricle senses linear (horizontal) acceleration
c.The saccule senses linear (vertical) acceleration.
The receptors for both hearing as well as equilibrium are the hair cells. There are 6 groups of hair cells in each ear
viz 3 in semicircular cells, 1 each in the utricles saccule and cochlea.

II. FEATURES OF MIDDLE EAR

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 Vision

A. It is air- filled space in the temporal bone

B. The auditory tube (also called eustachean tube, pharyngotympanic tube) connects the middle ear cavity (also
called cavity) with the nasophanynx. The auditory tube in usually closed; it opens during swallowing, chewing,
yawning. When the tube opens, there is equalization of pressures on the two sides of the tympanic membrane.
C. There are 3 bones- malleus, incus and stapes.
D. There are 2 muscles – tensor tympani and stapedius.
E. The tympanic membrane functions as a resonator that reproduces the vibrations of the sound source. The
motions of the tympanic membrane are imparted to the manubrium of malleus to the incus to the foot plate of
the stapes at oval window. The auditory ossicles thus function as a lever system and increase the sound

Chapter - 7
pressure that arrives at the oval window, because the lever action of the malleus and incus multiplies the
force 1.3 times and the area of the tympanic membrane is much greater than the area of the foot plate of the
stapes.This is called IMPEDENCE MATCHING

III. TYMPANIC REFLEX

A. When the middle ear muscles (tensor tympani and stapedius) contract, they pull the manubrium of the
malleus inward and the footplate of the stapes outward. Loud sounds initiate a reflex contraction of these
muscles called the tympanic reflex. Its function is protective. The reaction time for the reflex is 40 to 160 ms.

Vision

B. Inner ear (Labyrinth) – the inner ear is designed in the form of a tube (membranous labyrinth) encased in a
bony tube (the bony labyrinth).

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 Physiology

C. There is endolymph within the membranous labyrnith and perilymph surrounding the membranous
labyrinth. There is no communication between endo and perilymph. 3 parts of the bony labyrinth house
(contain) 3 parts of the membranous labyrinth;

Bony labyrinth Membranous labyrinth

Bony cochlea Membranous cochlea (also called cochlear duct, scala media)
Vestibule Saccule, utricle
Semicircular canals Semicircular ducts

Cochlea- Its length in 35mm. It has 2 ¾ turns. Divided into three chambers by Basilar & Reissner’s membrane
1. Scala vestibuli (filled with perilymph )
2. Scala tympani (filled with perilymph )
3. Scala media (filled with endolymph )
The perilymph resembles ECF (high Na+, less K+)
Whereas the endolymph resembles ICF (More K+, less Na+).The K+ is secreted actively by Stria Vascularis
Organ of corti – This is the sense organ for hearing. It is situated on the basilar membrane. The receptor for hearing
are the hair cells .

The hair cell processes are bathed in endolymph. Whereas the hair cell bases are bathed in perilymph. There are 4
rows of hair cells – 3 outer and 1 inner.

IV. OUTER HAIR CELLS

A. Acoustic amplifiers” of the cochlea
B. In three rows along the length of the cochlea
C. About 10000 in number
D. Innervated by type II nerves (about 2000 of them)

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 Vision

E. OHCs provide positive feedback into the motion of the basilar membrane- “Tuning of Cochlea”
F. Contain Prestin protein - responsible for electromotility of OHC

V. INNER HAIR CELLS

A. Detect the sound (sound transduction)
B. In a single row along the length of the cochlea
C. About 3000 in number

Chapter - 7
D. Innervated by type I nerves (about 27000 of them)
E. 90 to 95% of the afferent neurons arise from the inner hair cells; only 5-10% arise from the outer hair cells (In
contrast, most efferent neurons [the olivocochlear bundle] end on the outer hair cells). The cell bodies of the
afferent neurons are in the spiral ganglion.

1. Mechanotransduction – is by the bending of the stereocilia which has ‘ tiplinks’ leads to opening of K+
Channels leading to depolarization of Hair cells and release of NT.
(Note that the scala media is electropositive with respect to the scala vestibuli and scala tympani)
Auditory pathway
Auditory (cochlear) division of vestibulo cochlear nerve

Cochlear nuclei in the medulla

Inferior colliculi (the centers for auditory reflexes)

Vision

Medial geniculate body

Auditory cortex (Area 41) (In superior portion of the temporal lobe in the sylvian fissure).
The efferent olivocochlear bundle arises from the superior olivary complex and ends primarily in the outer hair cells
of the organ of cortex.
2. Loudness/ pitch/ timbre
Loudness is related to the amplitude
Pitch is related to frequency
Timbre (quality) is related to overtones (the number of harmonic vibrations)
Loudness is measured in decibels (dB)

Intensity of sound Pressure of sound

dB = 10 log ------------------------------------------------ or db = 20 log ----------------------------------------------
Intensity of standard sound Pressure of standard sound

Note that the average auditory threshold for humans is zero decibel.
The frequency range for hearing is from 20-20000 Hz. The greatest sensitivity lies between 1000- 4000 Hz. The
pitch discrimination is between 1000-3000Hz
Tympanic reflex (attenuation reflex) – Loud sounds cause reflex contraction of the tensor tympani and stapedius
muscles, decreasing sound transmission.
Theories of Hearing
3. Place theory – Frequency discrimination is dependent on the exact place on the basilar membrane. Which
is most stimulated. (It has been known from Von Be’ Ke’s ys travelling wave theory that high- pitched

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 Physiology

sounds reach maximum height near the base of the cochlea and low- pitched sounds reach maximum
height near the apex of the cochlea) Place theory helps to explain high frequency discrimination.
4. For explaining pitch discrimination in the low- frequency range (say 20 to 2000), there is the volley or the
frequency principle. That is, low frequency sounds can cause volleys of impulses synchronised at the same
frequencies and these volleys are transmitted by the cochlear nerve into the cochlear nuclei of the brain.
VI. TUNING FORK TESTS / TYPES OF DEAFNESS
There are 2 types of deafness
A. Conductive : Problem in conduction (e.g wax, destruction of ossicles, thickening of tympanic membrane etc.)
from external ear up to inner ear.
B. Neural : due Hair cell degeneration, nerve damage.

VII. TUNING FORK TEST:

A. Rinne’s test
1. Normal: Air conduction is more than bone conduction
2. Conduction deafness: BC> AC
3. Neural deafness: AC>BC (as long as the nerve deafness is partial)

B. Weber’s test
1. In nerve deafness: Lateralisation towards normal side (i.e. the subject hears better on the normal side ear
during the test)
2. In conduction deafness: Lateralisation is towards damaged side

C. Schwabach’s test (Absolute bone conduction test)

1. Conductive deafness: >normal
2. Neural deafness: < normal

VIII. VESTIBULAR APPARATUS CONSISTS OF

A. Semicircular canals
B. Utricle
C. Saccule
The receptor structure of the semicircular canals is the crista ampullaris in the ampulla. Each crista has hair cells
and sustentacular cells surrounded by a gelatinous partition (cupula) that closes off the ampula. The utricle and
saccule have otolith organ or macula. The macula has hair cells surrounded by an tolithic membrane in which are
embedded crystals of calcium carbonate (otoliths)
Position of macula in utricle and saccule:
D. In utricle: Floor of the utricle
E. In saccule: wall of the saccule in a semi vertical position.

IX. PATHWAY
A. The cell bodies of the neurons supplying the cristae and maculas on each side located in the vestibular
ganglion. Each vestibular nerve terminates in the
1. Ipsilateral 4- part vestibular nucleus and in the
2. Flocculonodular lobe of the cerebellum.
B. The 2nd order neurons from the vestibular nuclei
1. Pass down the spinal cord in the vestibulo spinal tracts (concerned primarily with postural adjustments)
2. Ascend through the medial longitudinal fasciculi to the motor nuclei of the cranial nerves concerned with
control of eye movements viz 3rd, 4th and 6th cranial nerves (largely concerned with eye movements)

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 Vision

C. Nystagmus – It is actually reflex; it helps in visual fixation. It has a slow component (labyrinth) and a quick
component (brain stem) the direction of nystagmus is given by the quick component.

Chapter - 7
Vision

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 Vision

“Please Read the Preface of this book Before you attempt these questions.”
Explanation of answer start from page no. 330

Special Senses 8. The parvocellular pathway from lateral geniculate

nucleus to visual cortex is most sensitive for the
1. VIII nerve receives afferents of (AIIMS MAY 2011) stimulus of:
A. Taste B. Balance A. Color contrast B. Luminance contrast
C. Hearing D. Equilibrium C. Temporal frequency D. Saccadic eye movements

Chapter - 7
2. Taste buds responsible for carrying bitter taste
sensation are located at: 9. Amacrine cells are seen in: (Latest Questions)
A. Posterior aspect of the tongue A. Retina B. Skin in the axilla
B. At the tip of the tongue C. Inner ear D. Blood
C. Just behind the tip of the tongue
D. At the sides of the tongue 10. The only sensory modality which does not reach
the thalamus directly is:
3. Bitter taste is mediated by action of A. Proprioception B. Taste
A. Guanyl cyclase B. G protein C. Olfaction D. Pain and temperature
C. Tyrosine kinase D. Epithelial Na chain
11. Receptor which itself is a dendrite of a nerve
4. Which of the following spectrum of colour is A. Olfactory B. Gustatory C. Visual D. Hearing
highest visualized due to central cones?
A. Red Blue B. Blue Red
C. Blue Green D. Red Green

Vision
5. While seeing a colour chart a colour blind male has
decreased vision for red light colour which appear
very light than that of other colors. Which of the
following is the likely anomaly in him?
A. Protanomaly B. Dutanomaly
C. Tritanomaly D. Butanomaly

6. The rod receptor potential differs from other

sensory receptors in that it shows
A. Depolarization
B. Decreased negativity
C. Increased conductance of Sodium
D. Hyperpolarization

7. During the dark phase of visual cycle, which form

of vitamin A combines with opsin to make Rhodopsin
A. All trans-Retinaldehyde
B. all trans-Retinol
C. 11-cis-Retinaldehyde
D. 11-cis-Retinol

1.C 2.A 3.B 4.D 5.A 6.D 7.C 8.A 9.A 10.C 11.A

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 Physiology

Explanation
Special Senses

1. Ans. C Hearing. (Ganong - 23rd Ed, Page-203)

a. The vestibulocochlear nerve (also known as the auditory or acoustic nerve) is the eighth cranial nerves,
and is responsible for transmitting sound and equilibrium (balance) information from the inner ear to the
brain.
b. This is the nerve along which the sensory cells (the hair cells) of the inner ear transmit information to the
brain. It consists of the cochlear nerve, carrying information about hearing, and the vestibular nerve,
carrying information about balance.
c. Some older texts call the nerve the acoustic or auditory nerve, but these terms have fallen out of
widespread use because they fail to recognize the nerve's role in the vestibular system, Vestibulocochlear
nerve is therefore preferred by most.
d. So, options B,C & D all are correct as far as function of VIII Nerve is concerned, but the best would be C i.e.
Hearing as Balance & Equilibrium are same functions.

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 Vision

2. Ans. A. Posterior aspect of the tongue

BASIC TASTES AREAS OF TONGUE

• Sweet At the tip of the tongue Q
• Sour Along the edges of the tongue Q
• Bitter On the back of the tongue Q
• Salt On the anterior dorsum of the tongue Q

Chapter - 7
3. Ans. B. G protein

a. Taste pathways: -

Vision
b. Receptor stimulation: -
i. For sour  Via mammalion degenerin-I and by activating H+ -gated cation channels
ii. For salt  Via Epithelium sodium channels (ENaC) by direct application amiloride (diuretic) on tongue,
inhibits the ENaC and abolishes the ability to taste salt.
iii. For Sweet  activating adenyl cyclase. via a heterotrimeric G-protein and the resulting increase in
intracellular cAMP reduces K+ conductance
iv. For bitter: - By reducing cAMP via a heterotrimeric G-protein; and Increase IP3 and DAG. A novel G-
 that activates
phosphodiesterase  causing a decrease in intracellular cAMP

4. Ans. D. Red Green

a. Colour vision:-
i. The appreciation of colours is a function of the cones and occurs only in photopic vision.
ii. Young — Helmholtz theory of the colour vision: -
b. Three types of cones: -
i. Short wave pigment or Blue sensitive or cyanolabe  absorbs Light maximally in blue- violet portion
spectrum.
ii. Middle wave or green sensitive or chlorolabe — absorbs maximally in green portion
iii. Long wave pigment or red sensitive or Erythrolable  absorbs maximally in the yellow portion
c. “Blue, green and red are the primary colours but the cones with their maximal sensitivity in the yellow
portion of sensitive enough in red portion to respond to red light at a lower threshold than green”.
d. Ref. Samson  Written that 

331
 Physiology

i. “The peak sensitivity of scotopic vision (twilight vision, function of rods) is approximately 500 nm Q,
whereas that of photopic vision (daylight, function of cones) lies at about 560 nm Q ” This differenece
accounts for the so called Purkinije-shift Q— a difference in the luminosity of colours in light of
different intensity.
ii. Wavelength spectrum of colour 

Violet  400nm
Blue  450 nm
Blue green  500 nm
Greenish yellow  550 nm
Orange  600 nm
Red  650—700mn

e. Red + green = yellow: Blue + yellow. = white

f. The colors best appreciated by central cones of foveo-macular area are Red and green Q
g. Conclusion
Since peak sensitivity of photopic vision (cones) lies at about 560 um (yellow — colour) Q and yellow= Red +
green, Q Hence answer is Red — green
h. Colour blindness: -
a. Red — green blindness is more common in congenital type.
b. Protonope  red sensation missing Q
i. Deuteranope  green sensation missing Q
ii. Tritanope  blue sensation missing Q
c. Test for colour blindness
i. Isihara’s test  for routine testing particularly for —green blindness. Q
ii. Farnsworth Munsell 100 hue test  Scientifically most accurate
iii. Edridge - Green - Lantern test  mainly important for engine drivers
iv. Holmgren’ s wools test
v. Negel’s anomaloscope

5. Ans. A. Protanomaly
a. Some other important points -
i. Visual cortex of the occipital lobe - Q
 Primary visual cortex  V1 area
 Color vision  V8 area Q

ii. Lesions of V8  achromatopsia Q

iii. Color blindness  x-linked recessive disorder Q

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 Vision

6. Ans. D. Hyperpolarization
Sequence of events involved in photo transduction in RODs,and CONES:
Incident light
Structural change in the Retinene 1 of photo pigment

Conformational change of photo pigment

Activation of transduction


Chapter - 7
Activation of phosphodiesterase

Decreased intracellular cGMP

Closure of Na+ channels

HYPER POLARIZATION

Decreased release of synaptic transmitter

Response in bipolar cells and other neural elements
7. Ans. C. 11-cis-Retinaldehyde
First know about the forms of Vitamin A
a. Retinol : A primary alcohol containing a bionone ring with an unsaturated side chain.
b. Retinal: It is an aldehyde which is derived from the oxidation of alcohol. It can exist in two forms

Vision
i. 11-cis retinal
ii. 11-trans retinal
c. Retinoic acid  The acid derived from oxidation of retinal
(Oxidation) (Oxidation)
Retinol --------------- Retinal ------------------------ Retinoic acid
(Retinaldehyde)
Visual cycle .
a. Retinal is a component of the visual pigment of rods and cone cells.
b. Rhodopsin is the visual pigment present in rod cells of the retina during the dark phase. Q Rhodopsin
consists of 11-cis retinal specificany bound to the protein opsin.
c. When rhodopsin is exposed to light a series of photochemical isomerization occurs resulting in the
bleaching of the visual pigment and release of all Trans retinal and opsin.
d. This process triggers a nerve impulse that is transmitted by the optic nerve to the brain. Regeneration of
rhodopsin requires isomerization of all transretinal back to 11-cis retinal. Trans retinal after being released
from rhodopsin is isomerized to 11-cis retinal which spontaneously combines with opsin to form
rhodopsin thus completing the cycle.
e. Similar reactions are responsible for color vision in the cone cells. Q

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 Physiology

All trans retinol


All trans retinal

11 cis retinal
  Opsin
Rhodopsin
Light   Opsin

All trans retinal

f. So, the crux is

i. In the dark phase  11 cis retinal exists with opsin Q
ii. In the light phase  11 trans retinal exists with opsin Q

8. Ans. A. Color contrast

Pathways to the cortex (Visual pathways)
a. The axons of retinal ganglion cells project a detailed spatial representation of the retina on the lateral
geniculate body Q
b. Each geniculate body contains six well defined layers .
a. Layers - 1 and 2 : have large cells, called Magnocellular (provides rapidly' conducting pathway to visual
cortex and transmit only white and black information)
b. Layers 3 - 6 : have small cells called Parvocellular (transmit colour and convey accurate point to point
spatial information) Q
c. On each side (Lateral geniculate body)
a. Layers 1, 4 and 6 : Receive input from contralateral eye i.e. from Nasal retina because only nasal (medial)
side of optic nerve crosses to opposite side.
b. Layers 2, 3 and 5 : Receive input from Ipsilateral eye i.e. from Temproal retina (lateral half of retina)
because optic nerves that originates from Temporal side does not crosses to opposite side.
d. Retina have two kinds of ganglion cells :
a. Y-Retinal ganglion or Large ganglion cells or Magno or M-cells : which add responses from different kinds
of cones and are concerned with movement, flicker and stereopsis; M-cells project to Magnocellular
portion of LGB.
b. X-retinal ganglion or small ganglion cells or Parvo or P-cells : which substract input from one type of cone
from input from another and are concerned with color, texture and shape; P-cells project to parvocellular
portion of LGB.
e. 5. From Lateral geniculate body (nucleus) ; pathways project to visual cortex (area 17): Q
a. Magnocellular pathway: arises from Layers 1 and 2 and carries signals for detection of movement, depth
and flicker.
b. Parvocellular pathway: arises from lavers 3, 4, 5 and 6 and carries signals for Color vision. texture, shape
and fine details.
Cell in the interlaminar region of LGB (nucleus)  receive input from P-ganglion cells  they project via a
separate component of the P pathway to blobs in the visual cortex (necessary for detection of color) (end in
layer 2 and 3 of visual cortex)

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 Vision

Visual area
Primary visual cortex: area 17  visual pathways (Magnocellular and parvocellular) end in the layer 4C of visual
cortex. It is also known as VI. Q V8-color vision Q

Chapter - 7
Vision
Fig. : Ganglion cells projection from the right hemiretina of each eye to the right LGB and from this nucleus to the
right primary visual cortex Q. Note that six layers of the geniculate; P-ganglion cells (also known as X-ganglion),
project to layers 3-6 and M ganglion cells (also known as Y ganglion) project to layers 1 and 2. The ipsilateral (I) and
contralateral (C) eyes project to alternate layers.

Functions of LGB
a. Relay function - is very accurate, exact point to point transmission with high degree of spatial fidelity all
the way from retina to the visual cortex.
b. Gate the transmission of signals to visual cortex.

9. Ans. A. Retina
a. A special category of micro-neurons, lacking an obvious axon, consists of amacrine cells.
b. In these cells Q nervous conduction is apparently possible in either direction along their dendrite-like
processes.
c. Amacrine cells have long been known in the retina Qwhere they lie in synaptic contact with ganglion and
other cells but their presence is also indicated in other parts of the central nervous system, including the
olfactory bulbs (granule cells) and possibly, the lateral geniculate body.

10. Ans. C. Olfaction

"Smell pathways (olfaction) have no relay in the thalamus; & there is no neocortical projection area for olfaction. Q

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 Physiology

11. Ans. A. Olfactory

Olfaction (sense of smell)
a. The smell receptors are distance receptor (teleceptors)
b. The smell pathway, is the only sense, have no relay in the thalamus and there is no neocortical projection area
for olfaction. Q
c. The olfactory receptor are located in a specialized portion of the nasal mucosa, the yellow brown pigmented
olfactory mucous membrane. The general lining of the olfactory area (mucosa) is pseudostratified columnar
epithelium.
d. Olfactory mucous membrane is small in microsmatic animals such as human, covering an area of 5cm2 in the
roof of the nasal cavity near the septum (cribriform plate)
e. There total 10.20 milion of factory cells in human, which are surrounded by sustentacular (supporting) cells.
f. Each olfactory receptor is a neuron, each neuron (receptor) has a short, thick dendrite with an expanded end
called an olfactory rod, from these each rod, 10-20 cilia project
g. Bowman's glands are located just under the basal lamina of the olifactory mucous membrane, which secrete
mucus.
h. From these receptor (neurons), emerge axon fibers, pierce the cribriform plate of the ethamoid bone and
enter the olfactory bulbs. This axon fibers are 20 in numbers, and are 1st order neurons.
i. From Glomeruli (mitral cells and tuft cells) of olfactory bulb  2nd order neurons arises  and forms the
olfactory tract  and ends as follows: in
i. Medial olfactory stria  cross opposite side and
ii. Lateral olfactory stria  terminates chiefly in ;
 Primary olfactory cortex  consists of pro-pyriform area pyriform cortex and olfactory tubercle,
olfactory cortex lies in the frontal lobe of brain and
 Amygloid complex
j. Olfactory tuburcle may be related to abnormal olfactory perceptions in schizophrenia.
k. Efferent fibers of the olfactory tubercle goes to limbic system ~ thus smell is associated with emotion and
behaviors.
l. Efferent fibers from amygdala go to the hypothalamus ~ thus olfaction is associated with appetite and social
behavior.
m. Note:
i. Olfactory neurons (receptor)  bipolar neurons.
ii. To reach primary olfactory cortex, therefore only two neurons (1st order and 2nd order) are required,
which is rather exceptional in sensory physiology.

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 Endocrinology

Chapter - 8
Endocrinology

Mechanism of hormone action: hormones(1st messengers) can act directly inside the cell (group 1) or via cell
surface receptors (group 2).

Group 1 Group 2
Solubility Lipid soluble water soluble

Chapter -8
Transport by plasma Yes No
protein
Plasma half life Long (due to protein binding) Short
Mechanism of action Receptor - hormone complex Cell surface receptor via 2nd
messenger(eg. cAMP,DAG)
Eg. 1.Sex Steroids LH, FSH, TSH, Insulin, Catecholamines
2.Gluco corticoids & mineralocorticoids
3.Vitamin D
4Thyroid hormones

Endocrinology
5.Vitamin A

A. Nuclear receptors: Thyroid Hormones

B. Cytoplasmic receptors: Sex Steroids , Vitamin D, Gluco corticoids & mineralocorticoids
C. Cell surface receptor: Can act via either G proteins or Tyrosine Kinase mechanism.

G proteins :
G proteins are present inside the cell coupled to the cell membrane receptor.
1. They are made up of three subunits designated αβ & γ.
2. The α subunit is bound to GDP. When Hormone binds to the receptor GDP is exchanged for GTP and α
subunit separates.
3. This can either stimulate (Gs) or inhibit(Gi) membrane bound enzymes like Adenyl Cyclase(cAMP),
Guanylyl cyclases (cGMP) & phospholipase C via Gq (DAG & IP3).
4. The intrinsic GTPase activity of the α subunit then converts GTP to GDP & terminate the action. DAG acts
by activating protein kinase C & IP3 by increasing Ca2+.

Tyrosine Kinase: The Cell surface receptor has enzyme Tyrosine Kinase which phosphorylate receptor and then a
no. of cytoplasmic proteins resulting in its action. Remember almost all GROWTH FACTORS act via Tyrosine Kinase
using JAK-STAT pathway.eg NGF, IGF -1,2, PDGF, EDF etc

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 Physiology

cAMP cGMP IP3/DAG Tyrosine Kinase

CRH ANP Oxytocin Growth hormone
FSH NO GnRH Erythropoietin
MSH AT II (vascular & smooth muscle) Prolactin
TSH Substance P Insulin
LH Gastrin IGF -1,2
HCG Cholecystokinin hCS
ACTH Muscarinic M1 & M3(Acetylcholine) Growth Factors
Secretin ADH (V1 receptor) Adiponectin
PTH TRH Leptin
ADH (V2 receptor) α1 adrenergic
1

Glucagon
Calcitonin
AT II (EPITHELIUM)
(-)
α 2(-) & β adrenergic
Somatostatin (-)
M2 Muscarinic (-)

Note: (-) denotes inhibit Adenyl Cyclase.

Pituitary Gland: Growth Hormone & Prolactin

1. The pituitary gland, or hypophysis, is an endocrine gland present in sella turcica covered by a dural fold
(diaphragma sellae).
2. The pituitary fossa, in which the pituitary gland sits, is situated in the sphenoid bone in the middle cranial
fossa. It Develops from called Ratheke's pouch.
3. It has 3 divisions: Adenohypophysis (Anterior Pituitary), Intermediate lobe( secrete α MSH) &
Neurohypophysis (Posterior Pituitary which secrete Oxytocin & ADH).
4. Anterior has 2 type of cells ACIDOPHILS [secrete Growth hormone from Somatotrope (most common cell
type) & Prolactin from Lactotrope] & BASOPHILS (secrete ACTH, TSH, LH & FSH).

Growth Hormone
1. The long arm of human chromosome 17 contains gene for growth hormone and hCS.
2. The plasma growth hormone level is less than 3 ng/mL.
3. The half-life of circulating growth hormone in humans is 6–20 min.
4. Daily growth hormone output is 0.2–1.0 mg/day in adults.
5. It acts via Tyrosine Kinase using JAK-STAT pathway

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 Endocrinology

Actions:
1. Increases the mineralization of bone & epiphyseal growth
2. Ketogenic and increases circulating free fatty acid (FFA) levels
3. Promotes lipolysis & decrease in plasma cholesterol
4. Increases protein synthesis and increases muscle mass
5. GI absorption of Ca2+ is increased and produces a positive nitrogen & phosphorus balance
6. Stimulates the growth of all internal organs excluding the brain
7. Reduces liver uptake of glucose, decreased insulin sensitivity (diabetogenic)

Chapter -8
8. Promotes gluconeogenesis in the liver
9. Excretion of the amino acid 4-hydroxyproline is increased(collagen synthesis)
Stimulators of GH secretion include: Inhibitors of GH secretion include:
Hypoglycaemia REM Sleep
Propranolol (by inhibiting somatostatin) Somatostatin from the periventricular nucleus
Deep sleep Circulating concentrations of GH and IGF-1
Pyrogens Hyperglycemia
Protein diet & amino acids like arginine Glucocorticoids
Vigorous exercise FFA
ADH, Glucagon, Ghrelin

Endocrinology
GHRH also known as somatocrinin
Increased androgen & estrogen secretion
Clonidine and L-DOPA by stimulating GHRH release
10. GH stimulates production of somatomedin insulin-like growth factor 1 (IGF-1) from liver

1. The effects of growth hormone on growth, cartilage, and protein metabolism depend on an interaction
between growth hormone and somatomedins, which are polypeptide growth factors secreted by the liver
and other tissues.
2. The first of these factors isolated was called sulfation factor because it stimulated the incorporation of
chondroitin sulfate into cartilage.
3. However, it also stimulated collagen formation, and its name was changed to somatomedin. It then became
clear that there are a variety of different somatomedins and that they are members of an increasingly large
family of growth factors that affect many different tissues and organs.

4. The principal (and in humans probably the only) circulating somatomedins are insulin-like growth factor I
(IGF-I, somatomedin C) and insulin-like growth factor II (IGF-II). These factors are closely related to insulin,
except that their C chains are not separated
Important: Hypophysectomized animals have a tendency to become hypoglycemic, especially when fasted.
Hypophysectomy ameliorates diabetes mellitus and markedly increases the hypoglycemic effect of insulin. This is
due in part to the deficiency of adrenocortical hormones, but hypophysectomized animals are more sensitive to
insulin than adrenalectomized animals because they also lack the anti-insulin effect of growth hormone.

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 Physiology

Prolactin
1. It is a luteotropic hormone & gene encoding prolactin is located on chromosome 6.
2. The normal plasma prolactin concentration is approximately 5 ng/mL in men and 8 ng/mL in women.
3. Secretion is tonically inhibited by hypothalamic prolactin-inhibiting hormone (PIH) i.e.dopamine from
tuberoinfundibulum (TIDA) neurons of the arcuate nucleus.
4. It stimulates the mammary glands to produce milk (lactation)
5. Prolactin provides the body with sexual gratification after sexual acts. The hormone counteracts the effect
of dopamine, which is responsible for sexual arousal. This is thought to cause the sexual refractory period.
6. Unusually high amounts are suspected to be responsible for impotence and loss of libido.
7. Prolactin also stimulates proliferation of oligodendrocyte precursor cells.
8. Prolactin increases surfactant synthesis of the fetal lungs
9. Factors increasing its production are: Sleep, Nursing, Breast stimulation, Stress, Hypoglycemia, Strenuous
exercise, Sexual intercourse in women, Pregnancy (maximum), Estrogens (maximum), Hypothyroidism,
TRH, Opioids & Somatostatin.

Important: High prolactin levels tend to suppress the ovulatory cycle by inhibiting the secretion of both follicle-
stimulating hormone (FSH) and gonadotropic-releasing hormone (GnRH). They also result in decreased levels of
both testosterone and estrogens.

Kisspeptin the product of the gene Kiss1 is a G-protein coupled receptor ligand for Kiss1 was originally identified as
a human metastasis suppressor gene that has the ability to suppress melanoma and breast cancer metastasis. It is
recently become clear that kisspeptin-GPR54 signaling has an important role in initiating GnRH secretion at
puberty. Before puberty the GnRH neurons are under inhibition by GABA.mcq

THYROID HORMONE

A. Thyroid hormone synthesis occurs in colloid & follicular cells. Thyroxin secretion begins by 20th week.
Inactive Active
Colloid Abundant Scalloped/ reabsorption Lacunae
Follicle Large Small
Cells Flat Columnar

B. The minimum daily iodine intake for normal thyroid function is 150 µg in adults.
C. About 120 µg/d taken up by thyroid gland.
D. The thyroid secretes 80 µg/d in the form of T3 and T4 , while 40 µg/d diffuses back into the ECF.
E. Net loss of I– in the stool of approximately 20 µg/day & rest is excreted in the urine.
F. Iodine uptake occurs in thyroid gland, salivary gland, mammary gland, gastric mucosa, placenta, choroids
plexus via Na+ /I- symporter which is a secondary active transport.

1. Thyroid Hormone Synthesis & Secretion

a. Organification: iodide is oxidized to iodine, and then incorporated into the carbon 3 position of tyrosine
residues of a glycoprotein called thyroglobulin in the colloid.
b. Thyroglobulin is synthesized and secreted by the thyroid cells.

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 Endocrinology

c. The oxidation and reaction of iodide with the secreted thyroglobulin is mediated by thyroid peroxidase, a
membrane-bound enzyme in apical membrane.
d. The first product of iodination is monoiodotyrosine (MIT). MIT is next iodinated on the carbon 5 position to
form diiodotyrosine (DIT).
e. Two DIT molecules then undergo an oxidative condensation to form T4, T3 is formed by condensation of
MIT with DIT. A small amount of RT3 is also formed, probably by condensation of DIT with MIT.
f. Colloid is internalized by the thyrocytes by endocytosis. The peptide bonds of thyroglobulin are hydrolyzed,
and free T4(80 µg) ,T3(4 µg) & RT3(2µg) are secreted.

Chapter -8
2. Transport & Metabolism of Thyroid Hormones
a. Thyroid hormones in blood are transported combined with plasma proteins.
b. Normally 99.98% of T4 & 99. 8%T 3 in plasma is protein bound. Plasma protein which bind T4 & T 3 are:
i. Albumin
ii. Thyroxine binding prealbumin (TBPA or transthyretin)
iii. Thyroxine binding globulin (TBG)

Protein Plasma Concentration T4 binding % T3 binding %

(mg/dl)
67max

Endocrinology
TBG 2 46
Transthyretin (TBPA) 15 20 1min
Albumin 3500 13 min 53 max

c. Estrogens, methadone, heroin, major tranquilizers, clofibrate increase concentrations of Thyroid Hormone-
Binding Proteins but the Free Plasma T4, T3, RT3 remains normal and person is euthyroid.
d. Glucocorticoids, androgens, danazol, asparaginase decrease conc. of Thyroid Hormone-Binding Proteins but
again the Free Plasma T4, T3, RT3 remains normal and person is euthyroid.
e. T4 and T3 are deiodinated in the liver, the kidneys, and many other tissues. One third of the circulating T4 is
normally converted to T3 in adult humans, and 45% is converted to RT3. Only about 13% of the circulating
T3 is secreted by the thyroid while 87% is formed by deiodination of T4.
f. Three different deiodinases: D1, D2, and D3. All contain selenium. D1 is present in in the liver, kidneys,
thyroid and pituitary. D2 is present in the brain, pituitary and brown fat. D3 is present in the brain and in
reproductive tissues.
g. T4 and T3 are conjugated in the liver to form sulfates and glucuronides. These conjugates enter the bile and
secreted in intestine. The thyroid conjugates are hydrolyzed, some are reabsorbed (enterohepatic
circulation) and some are excreted in the stool.
h. Various drugs inhibit deiodinases, producing a fall in plasma T3 levels and a reciprocal rise in RT3. Selenium
deficiency has the same effect. A wide variety of nonthyroidal illnesses also suppress deiodinases. These
include burns, trauma, advanced cancer, cirrhosis, renal failure, MI and febrile states.
i. In fasting: T3,  RT3 (Which helps in energy conservation) & T4 ( Free & Bound) remains normal
j. In Over feeding: T3,  RT3

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 Physiology

T4 T3
Total 8ng/dl 0.15 ng/dl
Free 2ng/dl 0.3ng/dl
% Bound 99.98 99.8
% Free 0.02 0.2
T½ Longer 6-7 days Shorter 1-2 days
Binding More Less
Maxm binding TBG (67%) Albumin (53%)
Action Slower Much more rapid
In colloid More (25%) Less (7%)
In secretion More (80 µg/d) Less (4µg/d)
Reverse Form No RT4 RT3 is present
Potency Less 3-5 times more potent
Binding to nuclear receptors Less More

3. Thyroid hormone actions:

Thyroid hormones enter cells and binds to thyroid receptors (TR) in the nuclei. The hormone-receptor complex
then binds to DNA via zinc fingers and affects transcription of a no. of proteins.
Target Tissue Effect Mechanism
Heart Chronotropic Increased number of β-adrenergic receptors
Inotropic
Enhanced responses to circulating catecholamines, Increased Cardiac output
Increased proportion of α-myosin heavy chain (with higher ATPase activity)
Adipose tissue Catabolic Stimulated lipolysis, lower circulating cholesterol levels
Muscle Catabolic Increased protein breakdown
Bone Developmental Promote normal growth and skeletal development (can also accelerate bone
resorption)
Nervous Developmental Promote normal brain development , can cause rapid mentation, irritability, and
system restlessness, reaction time of reflex decreased
Gut Metabolic Increased rate of carbohydrate absorption, stimulate motility
Lipoprotein Metabolic Formation of LDL receptors
Metabolic hepatic conversion of carotene to vitamin A, carotenemia in hypothyroidism
Other Calorigenic Stimulated oxygen consumption by metabolically active tissues (exceptions:
testes, uterus, lymph nodes, spleen, anterior pituitary)
Increases metabolic rate by stimulating Na+K- ATPase
Increased heat production: Peripheral resistance decreases because of
cutaneous vasodilation

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 Endocrinology

4. TSH
a. Human TSH is a glycoprotein encoded by a gene on chromosome 6 and chromosome 1.
b. The biologic half-life of human TSH is about 60 min. Secretion is pulsatile, and mean output starts to rise at
about 9:00 PM, peaks at midnight.
c. The normal secretion rate is about 110 g/d. The average plasma level is about 2 g/mL
d. Because the subunit in hCG is the same as that in TSH, large amounts of hCG can activate thyroid receptors
nonspecifically.

Chapter -8
e. It increases iodide trapping & binding; synthesis of T3, T4 and iodotyrosines; secretion of thyroglobulin and
endocytosis of colloid.
f. Inhibited by Stress, Dopamine, Somatostatin, Glucocorticoids & T3 T4

5. Thyroid Resistance

Type of resistance State T3/T4 TSH Whether TSH is

suppressible by external
T3/T4
Peripheral tissue + Not clinically High Inappropriately high No
pituitary hypothyroid

Endocrinology
Pituitary only Hyper thyroid High Inappropriately normal / No
high
Peripheral tissue Hypothyroid Normal Normal Yes
only

a. Wolff–Chaikoff effect: High iodine conc. inhibiting formation of thyroid hormones due to down-regulation
of sodium-iodide symporter.
b. Jod-Basedow effect: This phenomenon is an iodine-induced hyperthyroidism, typically presenting in a
patient with endemic goiter

INSULIN & GLUCAGON

Pancreatic Cell Secretion

α cells Glucagon
β cells (most common 60-75%) Insulin
 cells Somatostatin
F cells Pancreatic Polypeptide
D1 cells VIP
Epsilon cells Ghrelin

A. Insulin is a polypeptide anabolic hormone containing two chains of amino acids linked by disulfide bridges
B. Insulin secretion begins at 12 weeks.
C. Beef insulin differs by three amino acids from a human, Pork insulin differs from human insulin by only one
amino acid.
D. Insulin is synthesized in the rough endoplasmic reticulum of the B cells. It is then packaged in Golgi apparatus

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 Physiology

and expelled by exocytosis.

E. Insulin is synthesized as part of a larger preprohormone. The gene for insulin is located on the short arm of
chromosome 11 in humans.
F. Preproinsulin has a 23-amino-acid signal peptide removed as it enters the endoplasmic reticulum. The
remainder of the molecule is then folded, and the disulfide bonds are formed to make proinsulin.
G. The peptide segment connecting the A and B chains, the connecting peptide (C peptide), facilitates the
folding and then is detached in the granules before secretion.
H. Normally, 90–97% of the product released from the B cells is insulin along with equimolar amounts of C-
peptide

1. Peptide.
a. C peptide level in blood provides an index of B cell function in patients receiving exogenous insulin.
b. The half-life of insulin in the circulation in humans is about 5 min
c. The normal concentration of insulin in fasting normal humans is 0–70 U/mL. The amount of insulin secreted
in the basal state is about 1 U/h, with a fivefold to tenfold increase following ingestion of food. The average
amount secreted per day in a normal human is about 40 U.

GLUT Transporter for facilitated diffusion of glucose

GLUT 1 Basal glucose uptake Placenta, blood-brain barrier, brain, red cells, kidneys,
colon, many other organs
GLUT 2 Act as B-cell glucose sensor B cells of islets , liver
GLUT 3 Basal glucose uptake Brain, placenta, kidneys
GLUT 4 Insulin-Dependent glucose uptake Skeletal and cardiac muscle, adipose tissue,
GLUT 5 Fructose transport Jejunum, sperm
GLUT 6 None Pseudogene
GLUT 7 Glucose 6-phosphate transporter in Liver, other tissues
endoplasmic reticulum

Glucose transporter in myocyte is (AIIMS Nov 09)

a. GLUT1 b. GLUT2
c. GLUT3 d. GLUT.4

Ans-GLUT 4

2. Mechanism of secretion
a. Glucose enters β cells via GLUT 2 transporters, which is metabolized to produce ATP.
b. Increased ATP inhibits ATP sensitive K+ channels, resulting in ↓ K+ efflux which depolarizes the β cells.
c. This opens voltage-sensitive Ca2+ channels. The Ca2+ influx causes insulin release by exocytosis.

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 Endocrinology

Chapter -8
Endocrinology
STIMULATORS INHIBITORS
Glucose Somatostatin
Mannose 2-Deoxyglucose
Amino acids (leucine, arginine, others) Mannoheptulose
Intestinal hormones (GIP, GLP-1, gastrin, secretin, CCK) α Adrenergic stimulators
β Keto acids β Adrenergic blockers
Acetylcholine Diazoxide
Glucagon Thiazide diuretics
Cyclic AMP and various cyclic AMP-generating substances K+ depletion
β-Adrenergic stimulators Phenytoin
Theophylline Insulin
Sulfonylureas Microtubule inhibitors

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 Physiology

3. Insulin Receptors: The insulin receptor is a tetramer made up of two α and two β glycoprotein subunits.
a. The gene for the insulin receptor is located on chromosome 19.
b. The α subunits bind insulin and are extracellular, whereas the β subunits span the membrane.
c. The intracellular portions of the β subunits have tyrosine kinase activity
d. Binding of insulin triggers the tyrosine kinase activity of the β subunits, producing autophosphorylation of the
β subunits on tyrosine residues.
e. Insulin receptor substrate (IRS-1) mediates some of the effects in humans but there are other effector systems
also

ACTIONS OF INSULIN

A. Adipose tissue: Increased glucose entry via GLUT 4 (rapid action), Increased fatty acid synthesis, Increased
glycerol phosphate synthesis, Increased triglyceride deposition, Activation of lipoprotein lipase, Inhibition of
hormone-sensitive lipase, Increased K+ uptake (rapid action)
B. Muscle : Increased glucose entry via GLUT 4 (rapid action), Increased glycogen synthesis , Increased amino
acid uptake, Increased protein synthesis in ribosomes, Decreased release of gluconeogenic amino acids,
Increased ketone uptake, Increased K+ uptake (rapid action)
C. Liver : Decreased ketogenesis, Increased protein synthesis, Increased lipid synthesis, increased glucose
uptake by Glucokinase stimulation. Decreased glucose output due to decreased gluconeogenesis, increased
glycogen synthesis, increased glycolysis.

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 Endocrinology

D. ADIPOKINES: are cytokines secreted by adipose tissue.

Agent Effect on Insulin Resistance
Leptin Decreases
TNF α Increases
Adiponectin Decreases
Resistin Increases

Chapter -8
Chemerin Decreases

GLUCAGON
A. Human glucagon is produced by A cells of the pancreatic islets and the L cells of upper GIT.
B. Glucagon secretion begins by 8th week.
C. In L cells, it is processed primarily to glicentin, a polypeptide that consists of glucagon plus glucagon-like
polypeptides 1 and 2 (GLP-1 and GLP-2). Some oxyntomodulin is also formed.
D. Glicentin has some glucagon activity. GLP-1 is a potent stimulator of insulin secretion .
E. GLP-2 lowers food intake. Oxyntomodulin inhibits gastric acid secretion & Appetite.
F. Glucagon is glycogenolytic, gluconeogenic, lipolytic, and ketogenic

Endocrinology
G. Glucagon has a half-life in the circulation of 5 to 10 min.
H. Stimulators are: Amino acids, CCK, gastrin, Cortisol, Exercise, Infections, Stress, β-Adr. stimulator & Ach
I. Inhibitors are: Glucose, Somatostatin, Secretin, FFA, Ketone, Insulin, Phenytoin, α- Adr. stimulator, GABA

Hyperglycemic Hormones are

Glucagon Cortisol
Catecholamines GH Thyroid hormones

ADRENAL HORMONES
A. Adrenal Cortex: 3 layers
1. The zona glomerulosa makes up 15% of the adrenal gland: ALDOSTERONE
2. the zona fasciculata, 50% : Glucocorticoids
3. the zona reticularis, 7% : Sex Steroids

C27 : Cholesterol (Main precursor)

C21 : 17 Hydroxy corticosteroids:- Progesterone & Corticosteroids
C19 : 17- Ketosteroids:- Androgens
C18 : Estrogens
C17 : CPPP ring
Adr. Cortex secretes mainly C21 , C19
C19 : Androgenic activity
C21 : Mineralocorticoid activity
&
Glucocorticoid activity

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 Physiology

GLUCOCORTICOIDS

1. Cortisol 2. Corticosterone

A. Mineralocorticoids
1. Aldosterone 2. Deoxy corticosterone

B. Androgens
1. DHEA 2. Androsteine dione
(Cortisone : From cortisol, in liver. Does not come into circulation)
Corticosterone : Has mineralocorticoid Activity)

Dehydroepiandrosterone sulphate (DHEAS) is main secretion by cortex.

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 Endocrinology

TRANSPORT, METABOLISM, & EXCRETION

A. Cortisol is bound in the circulation to an globulin called transcortin . Normal levels of total plasma cortisol is
(13.5 µg/dL or 375 nmol/L). Half-life is 60-90 min.
B. Cortisol is metabolized in the liver, which is the principal site of glucocorticoid catabolism. Most of the cortisol
is reduced to dihydrocortisol and then to tetrahydrocortisol, which is conjugated to glucuronic acid and
excreted in urine.

Chapter -8
Actions of Glucocorticoids
1. Protein: Cortisol promotes degradation and increased delivery of amino acids.
2. Lipids: Cortisol promotes lipolysis and increased delivery of free fatty acids and glycerol.
3. Carbohydrate: Cortisol raises blood glucose. Cortisol inhibits glucose uptake in most tissues (muscle,
lymphoid, and fat), Cortisol increases hepatic output of glucose via gluconeogenesis from amino acids in
particular (not from liver glycogenolysis). Glucocorticoids exert an anti-insulin action in peripheral tissues
and make diabetes worse. However, the brain and the heart are spared.
4. Permissive Actions of Cortisol: Cortisol enhances the action of glucagon and catecholamines
5. Increases vascular reactivity.
6. CNS: adrenal insufficiency causes irritability, apprehension, and inability to concentrate. Slow EEG

Endocrinology
waves
7. BLOOD CELLS & LYMPHATIC ORGANS: Except BEL(basophil, eosinophil & Lymphocytes) all other are
increased. They reduce secretion of cytokines by inhibiting the effect of NF- κB on the nucleus. Inhibit
degranulation of Mast cell.
8. Adrenal insufficiency is characterized by an inability to excrete a water load, causing water intoxication
9. RESISTANCE TO STRESS: stress is defined as any change in the environment that changes or threatens to
change an existing optimal steady state. Increased ACTH leads to increased glucocorticoid level.
10. Glucocorticoids accelerate the maturation of surfactant in the lungs, decrease GH, TSH.

ACTH
ACTH is a single-chain polypeptide originate from proopiomelanocortin (POMC) in the pituitary, its half-life in the
circulation in humans is about 10 min. In humans, maximum production of cortisol occurs between 4:00 AM and
10:00 AM.A second smaller peak occurs in evening time. It stimulates the secretion of Cortisol (and adrenal
androgens) of adrenal cortex. Cortisol suppresses the release of ACTH by acting on the hypothalamus and anterior
pituitary.
Corticotropin-Releasing Hormone (CRH): Secretion of CRH increases in response to stress & in the early morning. It
then increase ACTH level.
Note : POMC is the precursor of ACTH as well as several other peptides, including melanocyte stimulating
hormone (MSH), β-lipotropin, β -endorphin etc.

ALDOSTERONE
A. The primary target tissue for aldosterone is the kidney, where its most important action is to increase Na +
reabsorption by the principal cells (P cells) of the kidney's collecting ducts.
B. Aldosterone also promotes the secretion of H+ by the intercalated cells of the collecting duct, and K + secretion
by the principal cells.

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 Physiology

C. The Na+-conserving action of aldosterone is also seen in salivary ducts, sweat glands, and the distal colon.

TRANSPORT, METABOLISM, & EXCRETION

Aldosterone is bound to protein to only a slight extent, and its half-life is short (about 20 min). The amount
secreted is small and the total plasma aldosterone level in humans is normally about 0.006 g/dL (0.17 nmol/L).
Much of the aldosterone is converted in the liver to the tetrahydro glucuronide derivative, but some is changed in
the liver and in the kidneys to an 18-glucuronide.
1. Increased Aldosterone Secretion: Decreased pressure in the renal artery (e.g., hemorrhage, shock,
dehydration, sweating) will activate the renin-angiotensin system, increase aldosterone secretion, and increase
sympathetic stimulation to return blood pressure toward normal.
2. Decreased Aldosterone Secretion: Any condition that increases blood pressure in the renal artery, eg HT,
weightlessness.
3. ESCAPE PHENOMENON: Odema due to Na+ and water retention is prevented by "Na+ escape" in primary
hyperaldosteronism. It is because of atrial natriuretic peptide.
Clinical Aspect of Adrenal Glands:
i. In human, the ratio of secreted cortisol to corticosterone is approx. 7: 1
ii. M.C. cause of CAR (virilization) is 21 α-hydroxylase deficiency
iii. Circadian rhythm  for corticol (ACTH)
The biological clock responsible for the diurnal (circadian) ACTH rhythm is located in the
suprachiasmatic nuclei of hypothalmus. Highest cortisol (ACTH) level is in the early morning (ie. 4 to
10 AM) Least cortisal (ACTH) level is in the evening
iv. Cushing's syndrome ~ due excess of glucocorticoids (cortisol)
v. Addison's disease ~ due to Adrenocortical insufficiency.

ATRIAL NATRIURETIC PEPTIDE (ANP)

ANP is the hormone secreted by the right atrium. The stimuli that release ANP (two peptides are released) are:
1. Stretch, an action independent of nervous involvement
2. Increased salt intake
ANP increases sodium loss (natriuresis) and water loss by the kidney because of, in part, an increase in glomerular
filtration rate due to:
ANP-mediated dilation of the afferent arteriole
ANP-mediated constriction of the efferent arteriole

All use cAMP as second messenger except (AIIMS Nov 09)

A. Corticotropin B. Dopamine
C. Glucagon D. Vasopressin

Ans .D. Vasopressin

Adrenal Medulla
1. 28% of the mass of the adrenal gland
2. In normal individuals 90% of output from adrenal medulla is epinephrine & only 10% is norepinephrine.
Adrenal Medulla also secretes Dopamine (50%), Chromogranin A, Opioid peptides &
3. Adrenomedullin

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 Endocrinology

4. Extradrenal sources (sympathetic ganglia): Mainly norepinephrine & 50% of Dopamine

5. Pheochromocytoma are catecholamine secreting tumour of chromaffin cells derived from adrenal medulla
or extradrenal sources (chromaffin cells in sympathetic ganglia).Output in Pheochromocytoma is mainly
norepinephrine
6. Norepinephrine is formed by hydroxylation and decarboxylation of tyrosine, and epinephrine by
methylation of norepinephrine.
7. Phenylethanolamine-N-methyltransferase (PNMT), catalyzes the formation of epinephrine from
norepinephrine, is found in brain & adrenal medulla.

Chapter -8
8. Adrenal medullary PNMT is induced by glucocorticoids. So, after hypophyrsectomy epinephrine synthesis
decreases.
9. The catecholamines have a half-life of about 2 min in the circulation. They are methoxylated and then
oxidized to vanillylmandelic acid [VMA].
10. About 50% of the secreted catecholamines appear in the urine as free or conjugated
11. metanephrine and normetanephrine, and 35% as VMA
12. Catecholamines increase alertness, epinephrine usually evokes more anxiety and fear.
13. Epinephrine and norepinephrine both cause glycogenolysis.
14. Norepinephrine and epinephrine also produce a prompt rise in the metabolic rate
15. When injected, epinephrine and norepinephrine cause an initial rise in plasma K+ because of release of K+
from the liver and then a prolonged fall in plasma K+ because of an increased entry of K+ into skeletal

Endocrinology
muscle
16. Adrenalectomy: Free E in plasma becomes zero NE unchanged

Exercise : NE >> E

Asphyxia/Hypoxia : NE > E
Familiar Stress : NE > E
(Unfamiliar Stress : E > NE

Hormones involved in Calcium Homeostasis

1. There is approximately 1 kg of calcium in the human body. About 99% exists in the bone and 1% in the extra
cellular fluid. Plasma calcium exists in 3 forms:
2. Complexed with organic acids
3. Protein bound
4. Ionized
5. The ionized calcium is maintained at a concentration between 1.1 and 1.3 mmol/L. If the ionic calcium levels
fall the organism develops hyper excitability and develops tetanic convulsions. A marked elevation may result
in death owing to muscle paralysis and coma.

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 Physiology

RELATIONSHIP BETWEEN CALCIUM AND PHOSPHATE

There is a chemical equilibrium between calcium and phosphate. Thus, calcium homeostasis cannot be considered
without understanding the relationship between calcium and phosphate.
A. Bone is a complex precipitate of calcium and phosphate called hydroxyapatite, which is laid down in a protein
(osteoid) matrix. Bone formation or resorption depends on the product of their concentrations called solubility
product
2+
[Ca ] X [PO4] > solubility product = bone deposition
[Ca2+] X [PO4] < solubility product = bone resorption
Thus, a decrease in the interstitial concentration of either Ca2+ or phosphate promotes the resorption of these salts
from bone (demineralization). It is the free Ca2+, not the phosphate, that is regulated so precisely. Hormonal control
of free Ca2+ levels is almost entirely achieved via parathyroid

B. Bone Cells
1. Osteoblasts: (bone forming) arise from osteoprogenitor cells of mesenchymal origin.
2. Osteocytes: Osteoblasts become entrapped in mineralized bone differentiate into osteocytes.
3. Osteoclasts (resorb bone) arise from monocytes that migrate to bone. Several monocytes fuse to form the
multinucleated osteoclasts.

C. PARATHYROID HORMONE (PTH)

PTH is a peptide hormone released from the parathyroids in response to lowered interstitial free Ca2+.
The function of PTH is to raise free Ca2+, which it does by several mechanisms.

D. Actions of Parathyroid Hormone

1. Receptor on Osteoblasts not Osteoclasts.
2. PTH increases Ca2+ reabsorption in the distal tubule of the kidney and decreases phosphate reabsorption in the
proximal tubule.
3. By decreasing renal phosphate reabsorption, PTH lowers plasma phosphate. This causes the product of the
Ca2+ and phosphate concentrations to be less than the solubility product. This, in turn, promotes the resorption
of these ions from bone and raises their concentration in the circulating blood.
4. PTH slowly increases the formation and activity of osteoclasts indirectly, which resorb bone, releasing Ca 2+ via
RANK receptors. These receptors are activated by RANK ligand present on osteoblasts which is induced by PTH.
5. PTH increases the formation of 1,25 di-OH (active vitamin D) in the proximal tubules of the kidney, which leads
to increased absorption of Ca2+ and phosphate from the small intestine.

E. CALCITONIN
Calcitonin (CT) is a peptide hormone secreted by the parafollicular cells (C cells) of the thyroid gland. It is released
in response to elevated free calcium. Calcitonin lowers plasma calcium by decreasing the activity of osteoclasts,
thus decreasing bone resorption. Its receptor is on Osteoclasts.

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 Endocrinology

F. VITAMIN D3 (CHOLECALCIFEROL)

Chapter -8
1. The synthesis of 1,25 di-OH D3 occurs sequentially in the skin —> liver -» kidney.
2. After its conversion to the 25 OH form in the liver, it can be stored in fat tissue. The serum levels of 25 OH

Endocrinology
vitamin D represent the best measure of the body stores of vitamin D when.
3. Most of the 25 OH form, which is the immediate precursor of 1,25 di-OH D3 is converted to the inactive
metabolite, 24,25 di-OH D3
4. The normal plasma level of 25-hydroxycholecalciferol is about 30 ng/mL, and that of 1,25-
dihydroxycholecalciferol is about 0.03 ng/mL (approximately 100 pmol/L).

G. Actions of 1,25 di-OH D3

1. Under normal conditions, vitamin D acts to raise plasma Ca2+ and phosphate. Thus, vitamin D
promotes bone deposition. This is accomplished by:
a. 1,25 di-OH D3 increases the absorption of Ca2+ and phosphate by the intestinal mucosa by
increasing the production of Ca2+-binding proteins(Calbindin).
b. The resulting high concentrations of Ca2+ and phosphate in the extracellular fluid exceed the
solubility product, and precipitation of bone salts into bone matrix occurs.
c. 1,25 di-OH D3 increases the reabsorption of Ca2+ by renal distal tubule.
2. Receptors for 1,25 di-OH D are on the nuclear membranes of osteoblasts.

Which of the following is not true regarding Vitamin D? (AIIMS May 08)
A. 1 hydroxylation occurs in kidney.
B. 25-hydroxylation takes place in the liver.
C. In absence of sunlight 200-400 IU of vitamin D is the daily required.
D. William’s syndrome is characterized by precocious puberty, obesity and mental retardation.

Ans.3. In absence of sunlight 200-400 IU of vitamin D is the daily required.

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 Physiology

H. Other Hormones
1. Glucocorticoids lower plasma Ca2+ levels by inhibiting osteoclast formation and activity, but over long
periods they cause osteoporosis by decreasing bone formation and increasing bone resorption.
2. Growth hormone increases calcium excretion in the urine, but also increases intestinal absorption of Ca 2+,
resultant action is positive calcium balance.
3. Insulin-like growth factor I (IGF-I) stimulates protein synthesis in bone.
4. Thyroid hormones cause hypercalcemia, hypercalciuria and osteoporosis.
5. Estrogens prevent osteoporosis by inhibiting the stimulatory effects of certain cytokines on osteoclasts.
6. Insulin increases bone formation, and there is significant bone loss in untreated diabetes.

Summary:
PO43-
Ca++

1,25 DHCC  
Calcitonin  
PTH  

Disorder of parathyroid PTH Serum Calcium Serum PO4

Primary Hypo Decreased Decreased Increased
Pseudo Hypo Increased Decreased Increased
Pseudo-pseudo Hypo Normal Normal Normal
Secondary Hypo Decreased Increased Increased
Primary Hyper Increased Increased Decreased
Pseudo Hyper PTH-rP increased Increased Decreased
Secondary Hyper (Due to Increased Decreased Increased (due to
chronic renal failure) decreased GFR)
Secondary Hyper (due to Increased Decreased Decreased
other causes)
Tertiary Initially like secondary, later like primary

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 Endocrinology

“Please Read the Preface of this book Before you attempt these questions.”
Explanation of answer start from page no. 368

Section- 1-:General & Mechanism of Hormones Action 7. Which of the following is the site of estrogen
action:
1. Adrenaline, noradrenaline, dopamine, serotonin act A. Mitochondria
through (AIIMS NOV.2011) B. Cell membrane
A. 1pass receptor B. 4 pass receptor C. Nucleus
C. 7pass receptor D. Ligand gated channel D.Cytoplasmic receptors

Chapter -8
2. Which of the pairs regarding vasopressin is 8. Which of the following’s receptor is present
incorrect: (AIIMS NOV.2010) intracellularly in muscle cells? (DNB Pattern)
A. v1- vascular smooth muscles A. Insulin B. Corticosteroid
B. v2-distal collecting ducts C. Epinephrine D. Glucagon
C. v3-anterior pituitary
D. v4-CNS 9. All of the following act on cell membrane receptors
except (DNB Dec-2010)
3. All use cAMP as second messenger except A. Cortisol B. Insulin C. FSH D. TSH
(AIIMS NOV 2009)

Endocrinology
A. Corticotropin B. Dopamine 10. Which among the following are polypeptides?
C. Glucagon D. Vasopressin A. LHRH B. FSH C .LH
D. Prolactin E. Estrogen
4. Steroid receptors bind to the following except?
(AIIMS MAY 2008) Section-2 -: Pituitary Gland:
A. Transcription mediators Growth Hormone & Prolactin
B. Transcription promoters
C. Transcription repressors 1. HIGH prolactin is associated with: (AIIMS NOV
D. Steroid response elements 2009)
A. Increase FSH
5 Regarding nitric oxide, false is: B. Increase estradiol
(AIIMS NOV 2007) C. Increase testosterone
A. Seen in the lung of smokers D. Increase libido
B. Increases cAMP levels
C. Used to treat hypertension 2. In obstructive azoospermia (AIPG 2009)
D. All are true A. FSH & LH Both increase
B. FSH & LH Both normal
6. cAMP is a second messenger of: (DNB Jun-2008) C. FSH decrease but LH increases
A. GH D. FSH & LH both decrease
B. Thyroxin
C. Insulin 3. The secretion of prolactin is controlled by:
D. Follicle stimulating hormone (DNB Pattern)
A. Serotonin B. GABA
C. Somatostatin D. Dopamine

1.C 2.D 3.D 4.C 5.B 6.D 7.C 8.B 9.A 10.A,D 1.B 2.B 3.D

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 Physiology

4. Which of the following is responsible for 13. Posterior pituitary stores and releases which of
menopausal hot flashes: (DNB Dec-2009) the following hormones?
A. Decreased progesterone B. Decreased estrogen A. TSH and GH B. TSH and LH
C. LH surge D. FSH surge C. ADH and prolactin D. Oxytocin and vasopressin

5. Which of the following secretes antidiuretic

14. Follicle stimulating hormone is produced by:
hormone:
A. Basophil of pituitary B. Neutrophil of pituitary
A. Anterior pituitary B. Posterior pituitary
C. Acidophil of pituitary D. Theca cells
C. Thyroid D. Hypothalamus
15. Which of the following is false regarding oxytocin?
6. Transaction of pituitary stalk leads to: (DNB Pattern)
A. Increase in ACTH A. It causes milk ejection reflex
B. Increase in prolactin B. It is least sensitive to uterus in pregnancy
C. Increase in growth hormone C. May also involved in luteolysis
D.Increase in TSH D. It triggers increase in intracellular level of Ca++

7. Which of the following is not caused by Oxytocin: 16. Estrogens are not produced by:
(DNB June-2009) A. Pituitary B. Ovary
A. Milk ejection
C. Adrenal D. Placenta
B. Lactogenesis
C. Contraction of uterine muscles
17. In the neurohypophysis, secretory granules
D. Myoepithelial cell contraction
accumulate in:
A. Pituicytes
8. Acromegaly occurs due to:
B. Nerve endings
A. Drugs B. Chromophobe adenoma
C. Intercellular spaces
C. Acidophilic adenoma D.Basophilic adenoma
D. Capillary endothelium

9. Pituicyte is located in: (DNB Dec-2009)

18. Insulin stress test assay estimates (DNB Dec-2010)
A. Pars intermedia B. Pars tuberalis
A. Diabetes mellitus B. Growth hormone
C. Neurohypophysis D. Adenohypophysis
C. Glucagon assay D. Catecholamines

10. Which of the following secretes melatonin:

19. True about Growth Hormone is that
A. Adrenal cortex B. Adrenal medulla
A. It prevents diabetes mellitus resistant to insulin
C. Pineal gland D. Melanocytes
B. Causes hyperglycemia
C. Enhances lipogenesis
11. Apart from TSH, TRH also stimulates the release
D. Causes hypoglycemia
of: (LQ)
A. Prolactin B. GH
C. Oxytocin D. Gonadotropin Section-3 -: Thyroid Gland

12. Which of the following is secreted by pineal gland? 1. BMR is closely dependent on (AIIMS MAY 2011,
A. Melanin B. Melatonin AIPG 2010,2011)
C.ANP D. GH A. BSA B. lean body mass
C. BMI D. Height

4.C 5.B 6.B 7.B 8.C 9.C 10.C 11A 12.B 13.D 14.A 15.B 16.A 17.B 18.B 19.B 1.B

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 Endocrinology

2 . BMR is low in (AIPG 2010) 2 . All changes occur in Joints due to aging except?
A. Hyperthyroid B. Obesity (AIIMS MAY 2010)
C. Feeding D. Exercise A. Water level decreases
B. Proteoglycan production decrease
3. Energy expenditure in resting state depends upon: C. Proteoglycan degradation increase
(AIPG 2009) D. Keratin level decrease
A. Lean body mass B. Adipose tissue
C. Heart Rate D. None of the above 3 . Which of the following decreases insulin release?

Chapter -8
(AIPG 2010)
4. The hormones associated with cold adaptation is: A. Gastrin B. Epinephrine
A. GH C. Secretin D. Growth Hormone
B. Thyroxine
C. Insulin 4. Which of the following is not secreted by endocrinal
D. Melanocyte stimulating hormone part of pancreas:
A. Somatostatin B. Insulin
5. T3 level gives an indication of: (DNB Dec-2010) C. Chymotrypsin D. Glucagon
A. Metabolic state
B. Thyroid state 5. Delta cells or ‘D’ cells of pancreas: (DNB Dec-2009)
C. Pituitary function state A. Secrete glucagon

Endocrinology
D. Does not indicate anything B. Secrete somatostatin
C. Secrete insulin
6. Which of the following is false regarding T3 and T4. D. Secretepancreatic polypeptide
(DNB Pattern)
A. T3 has short half-life than T4 .6. Human insulin differ from beef insulin by: (DNB
B. T3 is more potent than T4 June-2008)
C. T4 binds to prealbumin more tightly than T3 A. 1 Amino acid
D. T4 is completely converted to T3 in peripheral tissue B. 3 Amino acid
C. 4 Amino acid
7. Iodine uptake is seen in the following organs D. 6 Amino acid
A. Ovary B. Thyroid
C. Parathyroid D. Salivary gland 7. Insulin does not cause:
E. Mammary gland A. Increase glycogen synthesis
B. Increase protein synthesis
8. “C” cells are found in: (Latest Questions) C. Increase potassium uptake
A. Pituitary B. Thyroid
D. Lipolysis
C. Thymus D. Parathyroid
8. Glucose increases plasma insulin by a process that
Section-4 -: Section: Pancreas
involves: (DNB Pattern)
A. GLUT1 B. GLUT2 C. GLUT3 D. SGLT1
1 . Somatomedin mediates: (AIIMS MAY 2010)
A. Lipolysis
9. Hormone which does not cross placenta:
B. Decreased rate of glucose uptake by cells.
A. Thyroxine B. Oestrogen
C. Deposition of chondroitin sulphate.
C. Insulin D. None
D. Gluconeogenesis.

2.B 3.A 4.B 5.B 6.D 7.B,D,E 8.B 1.C 2.D 3.B 4.C 5.B 6.B 7.D 8.B 9.C

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10. HbA1c level in blood explains:(LQ) 6. Endocrine functions associated with kidney include
A. Acute rise of sugar all of the following except
B. Long term status of blood sugar A. Erythropoietin secretion
C. Hepatorenal syndrome B. Natriuretic peptide secretion
D. Chronic pancreatitis C. 1 ,25-dihydroxycholecalciferol
D. Renin secretion
11. A 62-year-old woman eats a high carbohydrate
meal. Her plasma glucose concentration rises, and this 7. Non-shivering thermogenesis in adults is due to:
results in increased insulin secretion from the (DNB Pattern)
pancreatic islet cells. The insulin response is an A. Thyroid hormone
example of
B. Brown fat between the shoulders
(A) Chemical equilibrium
(B) End-product inhibition C. Noradrenaline
(C) Feedforward control D. Muscle metabolism
(D) Negative feedback
Section-5 -: Section: Adrenals Section-6 -: Section: Calcium And Potassium
1. Mineralocorticoid receptor are not present on :
(AIPG 2011, AIIMS NOV 2008) 1. Which of the following is false regarding PTH
A. Distal nephron B. Colon secretion (AIIMS NOV.2011)
C. Liver D. Hippocampus A. Non ionic calcium is most important stimulus for
PTH secretion
2. Which of the following is the principal metabolite in B. Mg stimulates PTH secretion in the same way as Ca
norepinephrine metabolism excreted in urine: C. Hypercalcemia in cancer patients is due to
A. Metanephrine B. Homogentisic acid parathormone related protein.
C. Aspartic acid D.Vanillylmandelic acid D. Parathyroid senses calcium through calcium
sensing receptor
3. In the adrenal gland, androgens are produced by
the cells in the 2. Marker of bone formation are all except
A. Zona glomerulosa B. Zona reticularis (AIIMS NOV. 2011)
C. Zona fasciculate D. Medulla A. Hydroxyproline B. Procollagen residue
C. Alkaline phosphatase D. Osteocalcin
4. The mechanism that protects normal pancreas from
autodigestion is: (DNB Pattern)
3. Which of the following is the active form of calcium
A. Secretion of biocarbonate
in the body? (AIPG 2008)
B. Protease inhibitors present in plasma.
A.Lonized calcium
C. Proteolytic enzymes secreted in inactive form.
B.Complexed with phosphate
D. The resistance of pancreatic cells.
C.Coplexed with oxalates
D.Bound to albumin
5. Which of the following secretes aldosterone:
A. Adrenal medulla
4. A patient is on a Low calcium diet for 6 weeks. He is
B. Zona reticularis
most likely to have:
C. Zona glomerulosa
A. Raised parathyroid hormone levels
D.Zona fasciculata
B. Raised calcitonin levels
C. Increased phosphate levels

10.B 11.D 1.C 2.D 3.B 4.C 5.C 6.B 7.C 1.A 2.A 3.A 4.A 5.A

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 Endocrinology

D. None of the above

12. Osteomalacia is associated with:
5. The mechanism by which hyperventilation may A. Decreases in osteoid volume
cause muscle spasm is: (DNB Pattern) B. Decreases in osteoid surface
A. Decreased calcium B. Decreased carbon dioxide C. Increase in osteoid maturation time
C. Decreased potassium D. Decreased sodium D. None

6. A polypeptide causing decrease in serum calcium is: 13. Main mineral salt of bone (AIIMS MAY 2010)
A. Vitamin D B. Parathyroid hormone

Chapter -8
A. CaCl2 B. Hydroxyapatite
C. Calcitonin D. Steroid C. CaCO3 D. Ca Oxalate

7. Osteoclast has specific receptor for: 14. Which of the following is not true regarding
A. Parathyroid hormone B. Calcitonin Vitamin D? (AIIMS MAY 2008)
C. Thyroxin. D. Vit D3. A. 1 hydroxylation occurs in kidney.
B. 25-hydroxylation takes place in the liver.
8. Sudden decrease in serum calcium is associated C. In absence of sunlight 200-400 IU of vitamin D is
with: the daily required.
A. Increased thyroxine and PTH D. William’s syndrome is characterized by precocious
B. Increased phosphate puberty, obesity and mental retardation.

Endocrinology
C. Increased sensitivity of muscle and nerve
D. Cardiac conduction abnormality Section-7: Reproduction & Related Hormones

9. Which one of the following acts to increase the 1. A male received testosterone for a long time. It may
release of Ca 2+ from endoplasmic reticulum? cause? (AIIMS NOV 2010)
(DNB Pattern) A. Azoospermia
A. Inositol triphosphate
B. Increase sperm motility
B.Parathyroid hormone
C. Increase spermatogenesis
C. 1, 25-di Hydroxy cholecalciferol
D. Increase gonadotropin
D. Diacyl glycerol

2. Capacitance of sperm takes place in (AIIMS MAY

10.Hypocalcemia - all are seen except: (DNB Pattern)
2010)
A. Numbness and tingling of circumoral regio
A. Seminiferous tubules
B. Hyperactive tendon reflexes and positive chvostek’ s
B. Epididymis
sign
C. Vas deference
C. Shortening of Q-T interval in ECG
D. Uterus
D. Carpopedal spasm

3. Best indicator for ovarian reserve (AIIMS MAY 2010)

11. Parathyroid hormone is responsible for: (DNB Dec-
2009) A. LH B. FSH
A. Increased production of 1, 25
dihydroxycholecalciferol in kidney
B. Increase in number of osteoblasts
C. Decreased reabsorption of calcium ions in kidney
D. Decreased urinary phosphate excretion

6.C 7.B 8.C 9.A 10.C 11.A 12.C 13.B 14.C 1.A 2.D 3.B 4.C

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 Physiology

C. FSH/LH ratio D. Estradiol C. Genital tract female D. Epididymis

4. Estrogen action on carbohydrate metabolism 11. Which of the following hormone is secreted by
(AIIMS MAY 2009) Sertoli cells:
A. Worsening of NIDDM A. Testosterone B. Inhibin
B. Increase uptake of glucose through increase in C. Estrogen D. Androstenedione
insulin sensitivity
C. Glycolysis increase 12. Antibodies against sperms develop:
D. Increasing central adipose deposition A. After infection B. After vasectomy
C. After orchidectomy D. None of the above
5. Sertoli cells are associated with (AIPG 2009) 13. Which of the following causes increase in basal
A. Spermiogenesis body temperature during ovulation:
B. Secretion of seminal fluid A. Progesterone
C. Production of testosterones B. Estrogen
D. Production of sperm C. Luteinizing hormone
D. Follicle stimulating hormone
6. Which of the following is TRUE regarding
requirement of temperature for spermatogenesis? 14. In postmenopausal women, estrogen is
(AIPG 2008) metabolized mostly into:
A. Requires temperature higher than core temperature A. Estriol B. Estrone
B. Required temperature should be conducive C. Estradiol D. Androstenedione
C. Requires temperature lower than core temperature
D. Requires temperature equal to core temperature 15. Elasticity of cervical mucous is seen at time of
A. Proliferative B. Midcycle
7. Correct sequence of sperm movement is C. Luteal stage D. Menstruation
(AIPG 2008)
A. Rete testis – straight tubules –different tubules 16. Which of the following secrete testosterone: (DNB
B. Straight tubules – rete testis – efferent tubules Pattern)
C. Straight tubules – efferent tubules – epididymis A. Leydig cells B. Sertoli cells
D. Straight tubule – rete tests epididymis C. Adrenal medulla D. Pituitary

8. Sertoli cells in the testis have receptors for? 17. The correct position of OH groups in estradiol are:
(AIIMS NOV 2012) A. C3 and Cl7 B. C7 and Cl6
A. FSH B. LH C. C3 and Cl9 D. C7 and Cl9
C. Inhibin D. All of the above
18. Which of the following is the site of estrogen
9. Sperms acquire motility in: (DNB Pattern) action: (DNB Dec-2008)
A. Epididymis B. Testis A. Mitochondria B. Cell membrane
C. Vas deferens D. Seminal vesicle C. Nucleus D. Cytoplasmic receptors

10. The capacitance of sperm is attained in: (DNB 19. Which of the following is true regarding polycystic
June-2009) ovary disease:
A. Fallopian tube B. Vagina
A. Low progesterone
5.A 6.C 7.B 8.A 9.A 10.C 11.B 12.B 13.A 14.B 15.B 16.A 17.A 18.C19.B20.A 21.B

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 Endocrinology

B. Normal or elevated LH/FSH

C. High LH, FSH and estradiol 28. The enzyme associated with the conversion of
D. Low LH, FSH and estradiol androgen to oestrogen in the growing ovarian follicle
is:
20. Gene coding for androgen receptors is situated in: A. Desmolase B. Isomerase
(DNB Pattern) C. Aromatase D. Hydroxylase
A. Long arm of X chromosome
B. Short arm of X chromosome 29. Blood testis barrier is formed by (LQ)

Chapter -8
C. Long arm of Y chromosome A. Sertoli cells B. Leydig cells
D. Short arm of Y chromosome C. Epididymis D. Ves deferens
21. Which of the following is inhibited by Inhibin: 30. Prostaglandins found in the seminal fluid are the
A.LH B.FSH C. ACTH D. PTH secreting products of
A. Prostate gland . B. Seminal vesicle
22. After formation, the sperms are stored in: C. Leydig cells D. Sertoli cells
A. Rete testis B. Seminal vesicles
C. Sertoli cells D. Epididymis 31. The laboratory report shows values of
gonodotropin and ovarian hormones of the blood
23. Which of the following statements can be sample taken on day 20 of the menstrual cycle of a
regarded as primary action of inhibin? young woman. Whether her cycle was ovulatory or

Endocrinology
A. It inhibits secretion of prolactin not may be validly assessed by the reported serum
B. It stimulates synthesis of estradiol level of:
C. It stimulates secretion of TSH A. FSH B. LH
D. It inhibits secretion of FSH C. Oestradiol. D. Progesterone

24. Meiosis occurs in human males in: 32. Apoptosis can occur by changes in hormone levels
A. Epididymis B. Seminiferous tabules in the ovarian cycle. When there is no fertilization of
C. Vas deferens D. Seminal vesicle the ovum, the endometrial cells die
because:
25. Features of HCG A. The involution of corpus luteum causes estradiol and
A. Is a glycoprotein progesterone levels to fall dramatically
B. Levels increases in third trimester B. LH levels rise after ovulation
C. Alpha subunit is specific for HCG C. Estradiol levels are not involved in the LH surge
D. Secreted by Trophoblasts phenomenon
E. Has 2 subunits D. Estradiol inhibits the induction of the progesterone
receptor in the endometrium
26. Length of spermatozoa
A. 50  B. 100  C. 120 D. 500  33. Before the onset of puberty, the GnRH neurons
are under the inhibitory control of: (DNB Pattern)
27. Sertoli cells have receptors for: A. Glycine
A. Inhibin B. Glutamate
B. Luteinising hormone C. Gamma amino butyric acid (GABA)
C. Follicle stimulating hormone D. Beta-endorphin
D. Melatonin
22.D 23.D 24.B 25.A,E 26.A 27.C 28.C 29.A 30.B 31.D 32.A 33.D 34.D 35.A

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 Physiology

34. All are steroids except?

A. Testosterone B. cortisol 45. GnRH acts via
C. Progesterone D. Centchroman A. Camp B. cGMP
C. Tyrosine kinase D. Phospholipase C
35. Prolactin secretion is decreased by
A. Dopamine B. PRL 46. Glucose mediated insulin release is mediated
C. TRH D. All of the above through:
A. ATP sensitive K+ channels
36. Cortisol secretion results in B. cAMP
A. decrease ACTH B. increased ACTH
C. Increased CRH D. No effect on CRH C. Carrier modulators
D. Receptor phosphorylation
37. Hormone responsible for initiation of ovulation
A. LH B. progesterone THYROID GLAND
C. Estrogen D. Prolactin
1. With respect to inactive follicles, active thyroid
38. Pancreatic β cell are freely permeable to glucose follicles
via A. Have abundant colloid B. Are large
A GLUT1 B GLUT2 C GLUT3 D GLUT 4 C. Have columnar cells D. Both A and C

39. Insulin stimulated glucose entry is seen in 2. Reabsorption Lacunae in thyroid are seen in
A. cardiac muscle B. Brain A. Colloid, in active follicles
C. Smooth muscles D. Intestines B. Colloid, in inactive follicles
C. Cells, in active follicles
40. Fructose is secreted by D. Cells, in inactive follicles
A. seminal vesicle B. prostate
C. epididymis D. sertoli cells 3. All the following are functions of thyroid cells
except.
41. Hormone acting on adjacent cells is called A. Collect and transport Iodine
A. autocrine B. paracrine B. Synthesize thyroglobulin
C. endocrine D. neurocrine C. Secrete the thyroid hormones
42. Premenopausal peripheral conversion of D. Synthesize thyroid hormones
estrogen precursors in the obese patient results in the
formation of 4. All the following take place in colloid except
A. Estriol B. Estradiol A. Oxidation of I  I2
C. Estrone D. Androstenedione B. Binding of I2 to thyroglobulin
C. ‘Coupling Reaction’
43. Insulin secretion is inhibited by D. Thyroglobulin synthesis
A. Hypokalemia B. Glucose
C. Glugacon D. GLP-1 5. The R.M.P of thyroid cell is approximately
A. – 70mv B. – 50mv
44. Epiphyseal closure is due to C. – 90mv D. –10mv
A. thyroxine B. GH
C. Androgen
36.A 37.A 38.B 39.A
D.40.A
Cortisol
41.B 42.C 43.A
6.
44.C
Iodide46.A
45.D
uptake into thyroid cell is an5.B
1.C 2.A 3.D 4.D
example of
6.B 7.E

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 Endocrinology

A. Primary active transport C. 5’ – deiodinase forms RT3 from T4

B. Secondary active transport D. There is much more RT3 (than T3) is foetal life
C. Facilitated Diffusion
D. Non-1onic diffusion 14. Deiodinase Deiodizes all the following except
A. T4 B. T3
7. The minimum % of Iodinated compounds in C. RT3 D. DIT
thyroid cell colloid is that of
A. MIT B. DIT 15. T3 is decreased and RT3 is increased in

Chapter -8
C. T4 D. T3 E. RT3 A. Fasting B. Foetus
C. Selenium deficiency D. All of the above.
8. The minimum amount in thyroid secretion is that
of 16. T4 has calorigenic action all the following
A. T4 B. T3 tissues/organs except
C. RT3 D. MIT A. Adipose tissue B. Muscle
C. Heart D. Anterior Pituitary
9. All the following are thyroid binding proteins
except (in plasma) 17. All the following are physiologic effects of thyroid
A. Albumin B. Transthyretin hormones except
C. TBG D. Thyroglobulin A. Positive chronotropic effect

Endocrinology
B. Positive inotropic effect
10. In the thyroid, ‘coupling reaction’ forms all the C. Stimulates lipolysis in tissues
following except D.  ES proten breakdown
A. T3 B. T4 E.  ES rate of carbohydrate absorption in G.I.T.
C. RT3 D. DIT F. Stimulates formation of LDL respectors

11. In estrogen – treated individuals, all the following 18. All the following have Identical X-subunit except
regarding thyroid status are correct except. A. LH B. FSH
A. Concentration of binding proteins is high C. TSH D. Hcg
B. Total plasma T3,T4,RT3 is normal or low E. ACTH
C. Free plasma T4, T3, RT3, is normal
D. Plasma TSH is normal 19. TSH is inhibited by all the following except
E. They are euthyroid A. Stress B. Dopamine
C. Somatostatin D. Glucocorticoids
12. When compared to T4, all the following are true of E.  In T3 F.  T4
T3 except.
A. Total plasma level is fess 20. T/2 is least for
B. Free plasma level is less A. 123
I
C. % of free plasma level is more B. 131
I
D. Less binding to proteins C. 127
I
E. Maximum binding to TBG D. 125
I

13. All are true of RT3 except 21. An increase in both TSH as well as thyroid
A. It is insert hormones can be encountered in
B. 95% of RT3 in circulation is formed from T4 A. Estrogen – Treated Individuals

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 Physiology

B. Androgen – Treated Individuals E. Increase Not reabsorption in kidney

C. Graves’ Disease
D.T3, T4 resistance 8. In all the following situations,  in epinephrine is
more than  in norepinephrine except
ADRENAL GLANDS A. Haemorrhage B. Hypoglycaemia
C. Ketoacidosis D. Pheaochromocytoma
1. In the adrenal medulla,
A. 90% of cells are of epinephrine secreting type
B. 90% cells are of norepinephrine secreting type 9. 17-Ketosteroids are how many carbon atoms ?
C. 90% cells are of dopamine secreting type A. C19 B. C17
D. 45% cells are of epinephrine secreting type C. C21 D. C18

2. Most of the total mass of adrenal gland is made 10. 17- Hydroxy Corticosteroids are
up of A. C19 B. C21
A. Zona glomerulosa B. Zona fasciculate C. C17 D. C18
C. Zona reticularis D. Adrenal medulla
11. Transcortin (CBG) is  ED in all except
3. On standing, the levels of all the following increase A. Nephrosis B. Cirrhosis
except C. Multiple myeloma D. Pregnancy
A. Norepinephrine B. Epinephrine
C. Aldosterone D. Renin 12. The commonest cause of congenital adrenal
hyperplasia is due to deficiency of
4. For which of the following is adrenal medulla the A. 11- Hydroxylase B. 21 Hydroxylase
main source C. 17- Hydroxylase D. Cholesterol desmolase
A. Norepinephrine B. Epinephrine
C. Dopamine D. B & C 13. The % of urinary ketosteroids from adrenal cortex
(either directly Eg. DHEA or from cortisol metabolism)
5. The cardiovascular effects of norepinephrine would in men is
include A significant  in all the following except. A. Two-Thirds B. Three-Fourths
A. S.B.P. B. D.B.P. C. One-Third D. 100%
C. M.A.P. D. P.P.
14. Secretion of adrenal androgens is controlled
6. ACTH secretion produces hypertrophy of mainly by
A. Zona fasciculate B. Zona reticularis A. ACTH B. Pituitary-Adrenal
C. Zona Glomerulosa D. A & B C. FSH D. LH
E. A, B & C
15. Permissive action(s) of glucocorticoid include.
7. All are actions of dopamine except A. Glucagon & Catecholamines for calorigenic effects.
A. Renal vasodilatation B. Catecholamines for lipolytic effects
B. Vasodilatation in mesentery C. Catecholamines for pressor responses
C. Vaso constriction elsewhere D. Catecholamines for bronchodilatation
D. Positively inotropic effect E. All of the above.

1.A
8.D 2.B
9.D 3.B
10.D 4.B
11.B 5.D
12.E 6.D
13.C 7.E 14.D8.D 9.A
15.D 10.B
16.D 11.D
17.E 12.B
18.E 13.A
19.F 14.A
20.A 15.E
21.D

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 Endocrinology

except.
16. All the following can be features of adrenocortical A. In K+ in plasma
Hypofunction except B. In plasma Na+
A. Na+ Loss with circulatory insufficiency C. In plasma HCO3
B. Decreased vascular responsiveness to D. Escape phenomenon’ is seen beyond a certain
epinephrine/norepinephrine ECF volume, so, no oedema in normal individuals
C. Person can be ‘normal’ as long as there is
adequate caloric intake

Chapter -8
D. Uncontrolled diuresis, leading to excessive water 23. Aldosterone secretion is controlled by
loss and water deprivation A. ACTH B. Angiotensin II
+
C. Electrolytes Na /K D. All
17. Glucocorticoids decrease all the following except.
A. Basophils B. Eosinophils 24. Glucocorticoids do not usually have mineralo-
C. Lymphocytes D. Monocytes corticoid effects because
A. Clucocorticoids do not bind to mineralocorticoid
18. Glucocorticoids act as anti-inflammatory / anti- receptors
allergic agents because they B. Normally, there is enough aldosterone for
A. Affect combination of antigen with antibody competitive inhibition
B. Influence the effects of histamine on the tissues

Endocrinology
C. Mineralcocrticoid – sensitive cells have 11 –
C. Prevent release of histamine/cytokines hydroxy steroid dehydrogenase
D. Cause all of the above. D. All of the above

19. ACTH bursts are maximum 25. ACTH  ES

A. Early morning B. Afternoon A. Aldosterone B. Glucocorticoids
C. Evening D. Night, around 10.00 pm C. Deoxycorticosterone D. All of the above

20. All the following can be stimulatory afferent input 26. Primary hyperaldsteronism (‘Conn’s syndrome’)
to CRH release from para ventricular nuclei of may cause all the following in otherwise ‘normal’
hypothalamus except individuals except.
A. Amygdaloid nuclei A. Oedema B. Weakness
B. Suprachiasmatic nuclei C. Hypertension D. Tetany
C. Baroreceptors, via N.T.S. E. Polyuria F. Hypkalemia
D. Nociceptive pathways & reticular formation G. Alkalosis

21. The effects of aldosterone on kidney include 27. Within the endocrine system, specificity of
A ED Nat reabsorption communication is determined by
B. ED K + excretion (A) The chemical nature of the hormone
(B) The distance between the endocrine cell and its
C. ED H+ excretion
target cell(s)
D. only A & B (C) The presence of specific receptors on target cells
E. A, B & C (D) Anatomical connections between the endocrine
and target cells
22. All are true of primary hyperaldosteronism

16.D 17.D 18.C 19.A 20.C 21.E 22.B 23.D 24.C 25.D 26.A 27.C

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 Physiology

28. The primary form of cortisol in the plasma is that 33. Through what “permissive action” do
which is glucocorticoids accelerate gluconeogenesis during
(A) Bound to albumin fasting?
(B) Bound to transthyretin (A) Glucocorticoids stimulate the secretion of insulin,
(C) Free in solution which activates gluconeogenic enzymes in the liver
(D) Bound to corticosteroid-binding globulin (CBG) (B) Glucocorticoids inhibit the use of glucose by skeletal
muscle
29. Which of the following sources of cholesterol is (C) Glucocorticoids maintain the vascular response to
most important for sustaining adrenal steroidogenesis norepinephrine
when it occurs at a high rate for a long time? (D) Glucocorticoids maintain the intracellular
(A) De novo synthesis of cholesterol from acetate concentrations of many of the enzymes needed to
(B) Cholesterol in LDL particles carry out gluconeogenesis through effects on
(C) Cholesterol in the plasma membrane transcription
(D) Cholesterol in lipid droplets within adrenal cortical
cells PANCREAS

30. Congenital adrenal hyperplasia is most likely a

1. Blood from one of the following endocrine glands
result of
(A) Defects in adrenal steroidogenic enzymes drains into hepatic portal vein
(B) Addison’s disease A. Islet Cell B. Thyroid
(C) Defects in ACTH secretion C. Adrenal cortex D. Adrenal Medulla
(D) Defects in corticosteroid-binding globulin E. Testis

31. Which of the following is most likely to result in a

decreased rate of aldosterone release?
(A) An increase in renin secretion by the kidney
(B) A rise in serum potassium
(C) A fall in blood pressure in the kidney
(D) A decrease in IP3 in cells of the zona glomerulosa

32. The rate-limiting step in the synthesis of cortisol is

catalyzed by
(A) 21-Hydroxylase
(B) 3β-Hydroxysteroid dehydrogenase
(C) Cholesterol side-chain cleavage enzyme
(D) 11β-Hydroxylase

28.D 29.B 30.A 31. D 32.C 33.D 1.A

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 Endocrinology

2. All are true of glucose absorption in GIT/Kidney 8. In severe acidosis, all the following can be
Except observed except.
A. It is Via SGLT A. Total body Na+ is ed
B. No phosphorylation is required B. Plasma Na+ may be ed (If not loss > water loss}
C. Inhibited by Phlorhizin C. Total body k+ is also low
D. Affected by insulin D. Plasma k+ ised
9. All the following are actions of glucagon in liver
3. In insulin deficiency absorption through/uptake except

Chapter -8
by all the following is normal except. A. Glycogenolytic B. Gluconeogenetic
A. Adipose Tissue B. Intestine C. Lipolytic D. Antiketotic
C. Kidney PCT D. Brian uptake
E. RBC uptake 10. All the following stimulate insulin secretion
except
4. One of the following statements is false A. Glucagon B. Secretin
A. Insulin causes K+ to enter cells, ing K+ in CEF C. CCK D. Gastrin
B. Insulin receptors are ed in starvation E. GIP F. GLP-1
C. Affinity of insulin receptors is ed in adrenal G. K+ H. Depletion
insufficiency

Endocrinology
D. Alloxan/streptozotocin 11. The overall/net effect of sympathetic/
parasympathetic stimulation on insulin/ glucagon
5. In Hyperglycaemia there can be all except secretion is all of the following except
A. Osmotic dieresis A. Sympathetic (+) : es Glucagon
B. Polydipsia B. Vagal (+) :  es Glucagon
C. Loss of urinary Na+ C. Sympathetic (+) :  es Insulin
D. ed urinary K+ reabsorption D. Vagal (+) : es Insulin

6. Hyperphagia of diabetes mellitus may be due to 12. Glucagon secretion is stimulated by all except
A. Efficient glucose utilization in the cells of A. Aminoacios B. Gastrin
ventromedian nuclei of hypothalamus C. CCK D. Exercise
B. Deficient glucose utilization in cells of lateral E. Secretin
hypothalamus
C.  ed Glucose utilization in cells of ventromedian 13. Paracrine control in islets includes all except.
nuclei of hypoth. A. Insulin (-)s Glucagon
D. ed Glucose utilization in cells of lateral B. Somatostatin (-)s Glucagon
hypothalamus C. Somatostatin (-)s insulin
D. Glucagon (+)s insulin
7. The enzyne that controls entry of glucose into E. Glucagon (-)s somatostatin
circulation from liver is
A. Phosphoenol pyruvate carboxykinase 14. Somatostatin – secreting pancreatic tumors can
B. Glucose – 6 phosphotase cause all the following except.
C. Pyruvate carboxylase A. Hypoglycaemia
D. Phospho fructokinase B. ed Gastric – emptying time

2.D 3.A 4.B 5.D 6.A 7.B 8.D 9.D 10.H 11.C 12.E 13.E 14.A

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 Physiology

C. ed Gastric-acid secretion

D. Gall stones 7. Mechanism of action of VIT D/1,25 DHCC
A. Camp B. cAMP
PARATHYROID GLANDS C. IP3 D. Genomic
1. Which of the following regarding actions on
plasma Ca++ and PO4- is true 8. In the regulation of 1,25 DHCC, all are true except.
A. 1,25 DHCC :  Ca++,  PO43- A. 1,25 DHCC (-) PTH
B. Calcitonin :  Ca++,  PO43- B. 1,25 DHCC (-) 1, hydroxylase
C. PTH :  Ca++, PO43- C. 1,25 DHCC (+) 24  hydroxylase
D. None of the above D. PO43- (+) 1  hydroxylase

2. Main effect of VIT.D. (1,25 DHCC) is

A. es intestinal absorption of Ca++
B. es bone resorption (net effect)
C. es Ca++ reabsorption in kidney
D. es bone formation (net effect)

3. PTH has all the following actions except

A. es bone Resorption
B. Phosphaturic action
C. es Ca++ Resorption in DCT
D. es formation of 1,25 DHCC
(and thus es Ca++/PO43- absorption from intestine)
E. es Ca++ excretion in urine

4. All are true of Ca++ absorption in intestine except

A. Active
B. Mainly from duodenum
C. Shows adaptation
D. In renal failure, absorption is ed

5. The major site(s) for control of body’s

phosphorous is/are
A. Kidney B. GIT
C. Bone D. All of the above

6. The major storage form of VIT. D is

A. 25 OHCC (calcidiol)
B. 1,25 DHCC (calcitriol)
C. 24, 25 DHCC
D.VIT.D3 (cholecalciferol)

1.D 2.A 3.E 4.D 5.A 6.A 7.D 8.D

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 Physiology

Reproduction & Related Hormones

1. Estriol production during pregnancy requires:

(A) Androgens produced from cholesterol in the placenta
(B) Estradiol as a precursor from the mother’s ovary
(C) Androgens substrates from the fetus
(D) Androgens from the ovary of the mother

2. A major causal factor in some cases of hypogonadism is

(A) Reduced secretion of gonadotropin-releasing hormone (GnRH)
(B) Hypersecretion of pituitary LH and FSH as the result of increased GnRH
(C) Excess secretion of testicular activin by Sertoli cells
(D) Failure of the hypothalamus to respond to testosterone

3. The major function of follistatin is

(A) Bind FSH and increase FSH secretion
(B) Inhibit the production of seminal fluid
(C) Reduce testosterone secretion by Leydig cells
(D) Bind activin and thus decrease FSH secretion

4. A major function of the epididymis is

(A) Storage and transport of mature sperm
(B) Initiating the development of spermatozoa
(C) Secretion of estrogens
(D) Production of inhibin

5. The production of mature spermatozoa from spermatogonia

(A) Takes 32 days
(B) Takes 70 days
(C) Takes 150 days
(D) Is unaffected by Kallmann’s syndrome

6. The first enzymatic reaction, which is the rate-limiting step, in the production of testosterone
(A) Occurs in the mitochondria
(B) Occurs in the ribosomes
(C) Involves aromatization
(D) Generates progesterone as the immediate derivative

7. which of the following statements about Testosterone is correct

(A) Bound to high-density lipoprotein (HDL)
(B) Bound to activin
(C) Converted to dihydrotestosterone in the prostate
(D) Converted to 17- hydroxyprogesterone in the liver

1.C 2.A 3. D 4. A 5.B 6.A 7.C

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 Endocrinology

8. Which is true about Sex hormone-binding globulin (SHBG)

(A) Binds testosterone with a higher affinity than estradiol
(B) Reduces the total amount of circulating testosterone
(C) Decreases the half-life of testosterone
(D) Stimulates the secretion of inhibin

9. The production of estradiol by the testes requires

(A) Sertoli cell follistatin

Chapter -8
(B) LH and Leydig cells
(C) Activin but not LH
(D) Leydig cell, Sertoli cells, LH, and FSH

10. Estradiol synthesis in the graafian follicle involves

(A) Activation of LH-stimulated granulosa production of androgen
(B) Stimulation of aromatase in the granulosa cell by FSH
(C) Decreased secretion of progesterone from the corpus luteum, resulting in increased LH
(D) Inhibition of the LH surge during the preovulatory period

11. Granulosa cells do not produce estradiol from cholesterol because they do not have an active

Endocrinology
(A) 17α-Hydroxylase
(B) Aromatase
(C) 5α-Reductase
(D) Sulfatase

12. A clinical sign indicating the onset of the menopause is

(A) The onset of menses near age 50
(B) An increase in plasma FSH levels
(C) An excessive presence of corpora lutea
(D) An increased number of cornified cells in the vagina

13. Increased progesterone during the postovulatory period is associated with

(A) Proliferation of the uterine endometrium
(B) Enhanced development of graafian follicles
(C) Luteal regression
(D) An increase in basal body temperature by 0.5 to 1.0C

14. The theca interna cells of the graafian follicle are distinguished by
(A) Their capacity to produce androgens from cholesterol
(B) The lack of cholesterol side-chain cleavage enzyme
(C) Aromatization of testosterone to estradiol
(D) The lack of a blood supply

8.A 9D 10. B 11. A 12.B 13.D 14.A

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 Physiology

15. Polyspermy block occurs as a result of the

(A) Cortical reaction
(B) Enzyme reaction
(C) Acrosome reaction
(D) Decidual reaction

16. The next ovulatory cycle after implantation is postponed because of

(A) High levels of PRL
(B) The production of hCG by trophoblast cells
(C) The production of prostaglandins by the corpus luteum
(D) The depletion of oocytes in the ovary

17. Spinnbarkeit formation is induced by

(A) Secretory endometrium
(B) Progesterone action on the uterus
(C) Androgen production from the ovaries
(D) Estrogen action on the vaginal secretions

18. When does the Implantation occur

(A) On day 4 after fertilization
(B) After the endometrium undergoes a decidual reaction
(C) When the embryo is at the morula stage
(D) Only after priming of the uterine endometrium by progesterone and estrogen

19. Successful fertilization is most likely to occur when the oocyte is in

(A) The oviduct and has entered the second meiotic division
(B) The uterus and has completed the first meiotic division
(C) Metaphase of mitosis
(D) The graafian follicle, which then enters the oviduct

20. The enzyme, 5α-reductase is responsible for

(A) Conversion of cholesterol to pregnenolone and enhancing steroidogenesis
(B) Conversion of testosterone to dihydrotestosterone
(C) Aromatization of testosterone to estradiol
(D) Increasing the synthesis of LH

21. Regarding suckling reflex, which of the following is true

(A) Has afferent hormonal and efferent neuronal components
(B) Increases placental lactogen secretion
(C) Increases the release of dopamine from the arcuate nucleus
(D) Triggers the release of oxytocin by stimulating the supraoptic nuclei

22. Upon contact between the sperm head and the zona pellucida, penetration of the sperm into the egg is
allowed because of
(A) The acrosome reaction (B) The zona reaction
(C) The perivitelline space (D) Pronuclei formation

15 .A 16 .B 17 .D 18.D 19.A 20.B 21.D 22.A

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 Endocrinology

23. Inhibin is an ovarian hormone that

(A) Inhibits the secretion of LH and PRL
(B) Is produced by granulosa cells and inhibits the secretion of FSH
(C) Only has local ovarian effects and no effect on the secretion of FSH
(D) Has two forms, A and B, with the same subunits but distinct subunits

24. Oral steroidal contraceptives are most effective in preventing pregnancy by

(A) Blocking ovulation
(B) Altering the uterine environment
(C) Thickening the cervical mucus

Chapter -8
(D) Reducing sperm motility

25. An index of the binding affinity of a hormone for its receptor can be obtained by examining the
(A) Y-intercept of a Scatchard plot
(B) Slope of a Scatchard plot
(C) Maximum point on a biological dose-response curve
(D) X-intercept of a Scatchard plot

26. Most peptide and protein hormones are synthesized as

(A) A secretagogue

Endocrinology
(B) A pleiotropic hormone
(C) Proopiomelanocortin (POMC)
(D) A preprohormone

23.B 24.A 25. B 26.D

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Explanation
Chapter-8 Endocrinology

Section-1 -: General & Mechanism of Hormones Action

1. Ans. C. Seven pass receptor (Ref: 23rd edition Ganong's Page-301)

G Protein-Coupled Receptors
a. All the heterotrimeric G protein-coupled receptors (GPCRs) that have been characterized to date are
proteins that span the cell membrane seven times. Because of this structure they are alternatively
referred to as seven-helix receptors or serpentine receptors.
b. A very large number have been cloned, and their functions are multiple and diverse.
c. These receptors further assemble into a barrel-like structure. Upon ligand binding, a conformational
change activates a resting heterotrimeric G protein associated with the cytoplasmic leaf of the plasma
membrane.
d. Activation of a single receptor can result in 1, 10, or more active heterotrimeric G proteins, providing
amplification as well as transduction of the first messenger.
e. Bound receptors can be inactivated to limit the amount of cellular signaling. This frequently occurs
through phosphorylation of the cytoplasmic side of the receptor.

Table 2–5 Some of the Ligands for Receptors Coupled to Heterotrimeric G Proteins.

Class Ligand
Neurotransmitters Epinephrine
Norepinephrine
Dopamine
5-Hydroxytryptamine
Histamine
Acetylcholine
Adenosine
Opioids
Tachykinins Substance P
Neurokinin A
Neuropeptide K
Other peptides Angiotensin II
Arginine vasopressin
Oxytocin
VIP, GRP, TRH, PTH
Glycoprotein hormones TSH, FSH, LH, Hcg
Arachidonic acid derivatives Thromboxane A2

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 Endocrinology

2. Ans. D. v4-CNS (REF: Ref: Ganong - 23rd Ed -301)

There are three receptors of vasopressin: VH1A, VH1B( called VH3) & VH2
There is no V4 receptor of ADH.

Receptor Gene G protein Functions

Arginine vasopressin receptor 1A AVPR1A Gq Vasoconstriction
Arginine vasopressin receptor 1B
AVPR1B Gq Neural
also called Arginine vasopressin receptor 3

Chapter -8
Arginine vasopressin receptor 2 AVPR2 Gs Antidiuretic

Second
Type messenger Locations Actions
system
vasoconstriction, gluconeogenesis, platelet
liver, kidney, peripheral
AVPR1A IP3/calcium aggregation, and release of factor VIII and von
vasculature, brain
Willebrand factor
AVPR1B IP3/calcium pituitary gland, brain ACTH secretion in response to stress

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basolateral membrane of the cells
insert aquaporin-2 (AQP2) channels
AVPR2 cAMP lining the collecting ducts of the
Release of von Willebrand factor
kidneys

3. Ans. D .Vasopressin
(Ref: Ganong – 23rd Ed. Pg:98,243)
a. Corticotropin Q & Glucagon Q both act by stimulating adenylyl cyclase which in turn increase cAMP.
b. Dopamine has 5 receptor. D1& D5 act by increasing cAMP Q (via adenylyl cyclase) & D2,D3 & D4 act by
decreasing cAMP Q.
c. Whereas ADH has 2 receptors VR 1(A & B) acts via IP3/DAG mechanism Q and VR2 which acts by increasing
cAMP Q in tubular cells, it is important for water reabsorption in Collecting duct (by aquaporin 2) Q. Other
Hormones acting via cAMP are
CRH, FSH, MSH Q, TSH Q, LH Q ,α2 & β adr. receptors Q ,PTH Q ,ADH, AT II (epithelium), Secretin, HCG,
Glucagon somatostatin, Lipotropin, Calcitonin

4. Ans. C. Transcription repressors

a. Steroid hormone receptors are intracellular receptors (typically cytoplasmic) that perform signal
transduction for steroid hormones.
b. Steroid hormone receptors are part of the nuclear receptor family that include a group of homologous
structured receptors (type II receptors) that bind to non-steroid ligands such as thyroid hormones and
vitamin A, as well as to vitamin D, and orphan receptors.
c. All these receptors are transcription factors. Depending upon the steroid hormone that they bind, they are
either located in the cytosol and move to the cell nucleus upon activation, or spend their life in the nucleus
waiting for the the steroid hormone to enter and activate them.

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 Physiology

d. This uptake into the nucleus has to do with Nuclear Localization Signals (NLS) found in a region of the
receptor. In most cases this signal is covered up by heat shock proteins which bind the receptor until the
hormone is present.
e. Upon binding by the hormone the receptor undergoes a conformational change, the heat shock proteins
come off, and the receptor together the with bound hormone enter the nucleus to act upon transcription.

Type I Receptors
 Sex hormone receptors (sex hormones)
a. Androgen receptor b. Estrogen receptor
c. Progesterone receptor d. Glucocorticoid receptor (glucocorticoids)
e. Mineralocorticoid receptor (mineralocorticoids)

Type II Receptors
a. Vitamin A receptor (Vitamin A) b. Vitamin D receptor (Vitamin D)
c. Retinoid receptor d. Thyroid hormone receptor
e. Orphan receptors
a. Steroid hormone receptors are proteins that have a binding site for a particular steroid molecule.
b. Their response elements are DNA sequences that are bound by the complex of the steroid bound to its
receptor.
c. The response element is part of the promoter of a gene.
d. Binding by the receptor activates or represses, as the case may be, the gene controlled by that promoter.
e. It is through this mechanism that steroid hormones turn genes on (or off).
f. For a steroid hormone to the nucleus, moving from the cytosol if necessary bind to its response element
activate other transcription factors to start transcription.

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 Endocrinology

5. Ans. B. Increases cAMP levels

a. Many different stimuli act on the endothelial cells to produce endothelium-derived relaxing factor (EDRF),
a substance that is now known to be nitric oxide (NO).
b. NO is synthesized from arginine in a reaction catalyzed by nitric oxide synthase (NO synthase, NOS). three
isoforms of NOS have been identified: NOS 1, found in the nervous system; NOS 2, found in macrophages
and other immune cells; and NOS 3, found in endothelial cells. NOS 1 and NOS 3 are activated by agents
that increase intracellular Ca2+ concentration, including the vasodilators acetylcholine and bradykinin.
c. The NOS in immune cells is not induced by Ca2+ but is activated by cytokines.

Chapter -8
d. The NO that is formed in the endothelium diffuses to smooth muscle cells, where it activated soluble
guanylyl cyclase, producing cGMP, which in turn mediated the relaxation of vascular smooth muscle. NO is
inactivated by hemoglobin.

6. Ans. D. Follicle stimulating hormone

Some Hormones and Related Substances that Act by Altering Intracellular camp
Increase cAMP Q
• ACTH • Calcitonin
• Catecholamines (β1, β 2 receptors) • Chorionic gonadotropin
• FSH • Glucagon

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• LH •LHRH
• Lipotorpin • Melanocyte stimulating hormone
• Nerve growth factor • Parathyroid hormone
• Prostaglandin El • Thyrotropin releasing hormone
• TSH • Vasopressin
Q
Decrease cAMP
• Catecholamines (α2 receptors) • Dopamine (D2 receptors)
• Somatostatin

7. Ans. C. Nucleus
a. Hormonal steroids and thyroid hormones exert their main physiological effects by acting directly on the
NUCLEI their target cells to increase transcription of selected mRNAs.
b. Like other steroids estrogen combines with an intracellular protein receptor and this complex binds to
DNA.
c. This promotes formation of mRNAs which in turn direct the formation of new proteins which modify the
cell function.

8. Ans. B. Corticosteroid

9. Ans. A. Cortisol
Hormones that bind to Intracellular receptors
• Estrogens • Glucocorticoids
• Progestins • Mineralocorticoids
• Androgens • Calcitriol (1, 25 (OH)
• Thyroid hormones (T3 and T4)

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 Physiology

Hormonal steroids and thyroid hormones exert their main physiological effects by acting directly on the nucleus of
their target cells to increase transcription of the selected messenger RNAs QProteins polypeptides, and most
ligands in the extracellular fluid act in a different way they bind to receptors on the membranes of their target
cells, and trigger changes in the concentration of substance inside the cell that produce the physiological effects.
The extracellular ligands are called the first messengers while the intracellular mediators are called second
messengers.

10. Ans. A, D. LHRH, Prolactin

a. Anterior pituitary hormones  6 hormones -
b. “ACTH, prolactin, and growth hormones are simple polypeptides or proteins, whereas TSH, LH, and FSH are
glycoprotein)
c. Estrogen  steroid hormone.
d. LHRH  from Hypothalamus  polypeptide.

Section-2 -: Pituitary Gland: Growth Hormone & Prolactin

1. Ans. B - Increase estradiol

Factors Affecting the Secretion of Human Prolactin and Growth Hormone.

Factor Prolactin Growth Hormone

Sleep ↑↑ ↑↑ Q
Nursing ↑↑↑↑ No change
Breast stimulation in nonlactating women ↑ No change
Stress ↑↑ ↑↑ Q
Hypoglycemia ↑ ↑↑ Q
Strenuous exercise ↑ ↑Q
Sexual intrcourse in women ↑ No change
Pregnancy Q ↑↑↑↑ No change
Q
Estrogens ↑↑↑↑ ↑
Hypothyroidism ↑↑↑↑ No change
TRH ↑↑ No change
Opioids ↑ ↑
Somatostatin Q No change ↓↓ Q
L-Dopa ↓ ↑↑
High prolactin levels tend to suppress the ovulatory cycle by inhibiting the secretion of both follicle-stimulating
hormone (FSH) and gonadotropic-releasing hormone (GnRH).They also result in decreased levels of both
testosterone and estrogens. This tends to decrease libido.

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2. Ans. B. FSH & LH Both normal

FSH & LH Both normal. Both FSH & LH are a marker of testicular function, which tends to be normal in most cases
of obstructive azoospermia so, the chances of finding normal FSH & LH levels are maximum. In fact some studies
also pinpoint the same fact.

Chapter -8
a. For most infertile men, the semen analysis is the only test which needs to be done - after all, the only job
of a man is to provide sperm to fertilize the egg ! For men with a low sperm count, there is no need to do
any other tests, since these do not provide any useful information.
b. However, many doctors still do blood tests for measuring the levels of key reproductive hormones, such as

Endocrinology
prolactin, FSH, LH and testosterone.
c. These are just a waste of time and money since they provide no useful information and do not alter the
treatment plan.
d. For men with azoospermia ( zero sperm count), additional blood tests may be useful .
e. The serum FSH (follicle-stimulating hormone) level test is a useful one for assessing testicular function.
f. If the reason for the azoospermia is testicular failure, then this is reflected in a raised FSH level.
g. This is because, in these patients, the testis also fails to produce a hormone called inhibin (which normally
suppresses FSH levels to their normal range).
h. A high FSH level is usually diagnostic of primary testicular failure, a condition in which the seminiferous
tubules in the testes do not produce sperm normally, because they are damaged.
i. This test is done by a radioimmunoassay or chemiluminescent assay, and since it is a sophisticated test, it
is best done in a specialized laboratory.
 Abnormal test results should be repeated and rechecked for confirmation.
j. The other reason for a high FSH level in some men is the consumption of clomiphene (a medicine often
prescribed for the empiric treatment of oligospermia).
k. This is why the test should be done only when no medication is being taken.
l. While a high FSH level is diagnostic of testicular failure, a normal FSH level provides no useful information.
m. Thus, men with complete testicular failure may also have normal FSH levels.
n. While a high FSH level suggests primary testicular failure, it cannot differentiate between partial testicular
failure and complete testicular failure.
o. This means that even men with very high FSH levels can have occasional areas of sperm production in their
testes, and these testicular sperm can be used for TESA-ICSI ( testicular sperm aspiration and
intracytoplasmic sperm injection) treatment.
p. Rarely, the FSH level may be low. A low FSH level is found in patients with hypogonadotropic
hypogonadism.

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 Physiology

q. Hypogonadotropic hypogonadism is an uncommon (but treatable!) cause of azoospermia.

r. Along with an FSH level test, most doctors also do a LH (luteinizing hormone) level test, which provides
mostly the same information.
s. A testosterone level test provides information on whether or not the testes are producing adequate
amounts of the male hormone, namely, testosterone.
t. Most infertile men have normal testosterone levels, because the compartment for testosterone
production is separate from the compartment which produces sperm, and is usually intact in infertile men.
u. A low testosterone level causes a decreased libido and this can be treated by testosterone replacement
therapy in the form of tablets or injections.
v. Of course, this therapy will not increase the sperm count.
w. For men with azoospermia and erectile dysfunction, measuring the prolactin level will help to detect men
who have hyperprolactinemia ( high prolactin levels).
x. Though this is a rare problem, they can be effectively treated with medical therapy with bromocriptine
and the results are very gratifying.
(Ref- Male Infertility Tests. Beyond the Semen Analysis (Page 2) :How to Have a Baby: Overcoming Infertility by
Dr. Aniruddha Malpani, MD and Dr. Anjali Malpani, MD)

3. Ans. D. Dopamine
The major hypothalamic inhibitory factor for prolactin is DOPAMINE

4. Ans. C LH surge
a. The most common menopausal symptoms are vasomotor instability (hot flashes), atrophy of the
urogenital epithelium and skin, decreased size of the breasts, and osteoporosis.
b. HOT FLASHES (FLUSHES) may start with an aura preceding abdominal discomfort quickly followed by a
feeling of heat moving toward the head.
c. Next the face becomes red, and then there is sweating followed by exhaustion.
d. The pathogenesis of the hot flash is uncertain.
e. There is a close Relationship between the onset of the hot flash and pulses of LH secretion.
f. LH is secreted in episodic bursts at intervals of 30-60 minutes, and in the absence of gonadal hormones,
these burst are large.
g. EACH HOT FLASH BEGINS WITH THE START OF A BURST.

5. Ans. B. Posterior pituitary

Some Hormones Secreted by Pituitary Gland
Anterior lobe Q Intermediate lobe Q Posterior lobe Q
TSH α & β melanocyte stimulating Vasopressin (ADH)
hormone
ACTH γ lipoprotein (γ-LPH) Oxytocin
Growth hormone (somatotropin) Corticotropin like intermediate lobe
peptide (CLIP)
FSH Fragments of pro-opiomelanocortin
LH β-endorphin
Prolactin
γlipoprotein (γ-LPH)
melanocyte stimulating hormone (α
-MSH)

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 Endocrinology

6. Ans. B. Increase in prolactin

a. The pituitary is under the control of the hypothalamus, which produces a number of chemical mediators.
b. These hormones are synthesized in the hypothalamus and enter the portal vascular system, which carries
them through the PITUITARY STALK to the anterior lobe Interruption of the pituitary stalk is followed by
reduction in the release of Growth Hormone, luteinizing hormone, Follicle Stimulation Hormone, thyroid-
stimulating hormone, and adrenocorticotropic hormone, from the anterior pituitary.
c. In contrast the LEVEL OF PROLACTIN RISES after interruption of the stalk, implying that the normal
hypothalamic influence on prolactin secretion is inhibitory Q

Chapter -8
7. Ans. B. Lactogenesis
a. OXYTOCIN causes contraction of the myoepithelial cells that line the ducts of the breast.
b. This squeezes the milk out of the alveoli of the lactating breast into the large ducts and then Out of nipple
(milk ejection)
c. Oxytocin also causes contraction of smooth muscle of uterus. Helps in parturition.

8. Ans. C. Acidophilic adenoma

If an ACIDOPHILIC TUMOR occurs in pituitary after adolescence, i.e. after the fusion of epiphyses of long bones with
shafts, the person cannot grow taller, but the soft tissues can continue to grow and bones can grow in thickness.
This is known as acromegaly.

Endocrinology
9. Ans. C. Neurohypophysis
PITUICYTE is a modified branched neuroglia cell characteristic of pars nervosa of the posterior lobe of the pituitary
gland (neurohypophysis) and it is also present in the infundibular stalk.

10. Ans. C. Pineal gland

MELATONIN is a hormone produced by the pineal gland. Its synthesis occurs in pineal parenchymal cells. It is
involved in the onset of puberty and may influence sleep-waking cycles.

11. Ans. A. Prolactin

Thyrotropin-releasing hormone (TRH) controls TSH release and may also influence prolactin release.

12. Ans. B. Melatonin

Pineal gland secretes melatonin and several other similar substances. Either melatonin, or one of the other
substances then passes either by the way of the blood, or through the fluid of the third ventricle to the anterior
pituitary gland to control gonadotropic hormone secretion.

13. Ans. D. Oxytocin and vasopressin

The 2 hormones secreted by the posterior pituitary are antidiuretic hormone (vasopressin) and oxytocin.

14. Ans. A. Basophil of pituitary

Cell type Hormone secreted Stain affinity
• Somatotrope Growth hormone Acidophilic
• Lactotrope Prolactin Acidophilic
• Corticotrope ACTH & beta-LPH Basophilic
• Thyrotrope TSH Basophilic
• Gonadotrope FSH & LH Basophilic

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15. Ans. B. It is least sensitive to uterus in pregnancy

a. Oxytocin acts on the membranes of myometrial and myoepithelial cells to cause an increased force of
contraction.
b. The sensitivity of the myometrium to oxytocin Increases with the duration of pregnancy, and a role for
oxytocin in the initiation and maintenance of labor is probable.
c. It also contracts myoepithelial cells in the breasts, thereby expressing milk from the breasts when the baby
suckles.

16. Ans. A. Pituitary

In the normal non-pregnant female, estrogens are secreted in major quantities only by the ovaries, though minute
amounts are also secreted by the adrenal cortices. In pregnancy, tremendous quantities are also secreted by the
placenta, as well.

17. Ans. B. Nerve endings

a. Pituitary eland (Hypophysis) : two portions:
i. Anterior Pituitary (or Adenohypophysis): - originates from Rathke's pouch (which is an embryonic
invagination of the pharyngeal epithelium)
ii. Posterior pituitary (or Neurohypophysis)  which is an outgrowth of the hypothalamus.
b. Neurohypophysis 
i. Connects with Hypothalamus via nerve fibers  forming track called hypo-thalamico Hypophysial
tract"
ii. Fibers of tract contain granules called neurosecretory granules or Gomori bodies which are stored,
the hormones.
iii. Two hormones of neurohypophysis vasopressin (ADH) and oxytocin. "These hormones are
synthesized in the cell bodies of the magnocellular neurons in the supra-optic nuclei (mainly ADH) and
paraventricular nuclei (mainly oxytocin) of the hypothalamus and transported in combination with
"carrier" protein called neurophysin, down the axons of these neurons to their nerve endings in the
neurohypohysis.
c. Adenohypophysis: - histologically consists of 30-40% somatotropes (Acidophils, secretes GH), 20% of
corticotropes (ACTH) and 3 to 5% of thyrotropes (TSH), Gonadotropes (LH, FSH) and lactotropes (protectin)
d. Pituicytes: - Neurohypophsis composed mainly of glial like cells called pituicytes. The pituicytes do not secrete
hormones, they act simply as a supporting structure for large number of terminal nerve fibers and terminal
nerve endings.

18. Ans. B. Growth hormone

a. Insulin Tolerance Test:
i. uses for  assessment of the hypothalamic - pituitary axis and assessment of GH deficiency.
ii. C/I  IHD, Epilepsy and severe Hypopituitarism
iii. AIM  To produce adequate hypoglycemia
iv. Result  Normal subject GH > 20 mU/L
Normal subject cortisol> 550 mU/L.

b. Tests of GH secretion (stimulation test)

i. I hour after going to sleep

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ii. Frequent sampling during sleep

iii. Post excercise
iv. Insulin induced hypoglycemia
v. Clonidine
vi. Arginine
vii. Glucagon
c. ACTH stimulation test  used for diagnosis of Primary or secondary Adrenal insufficiency (Addison's dis) Q

Chapter -8
19. Ans. B. Causes hyperglycemia

Section-3 -: Thyroid Gland

1. Ans . B. lean body mass (Ref: Ganong - 23rd Ed. Pg:281-82,)

a. Energy expenditure in resting state is given by RMR or the Resting Metabolic Rate.
b. The metabolic rate determined at rest in a room at a comfortable temperature in the thermoneutral zone
12–14 hours after the last meal is called the basal metabolic rate (BMR).
c. Katch-McArdle formula is most accurate for its calculatiom on the basis of lean body mass:
P= 370+(21.6.LBM) where LBM is the lean body mass in kg.

Endocrinology
d. This value falls about 10% during sleep and up to 40% during prolonged starvation.
e. The rate during normal daytime activities is, of course, higher than the BMR because of muscular activity
and food intake.
f. The maximum metabolic rate reached during exercise is often said to be 10 times the BMR.
Factors Affecting the Metabolic Rate
a. The metabolic rate is affected by many factors. One of the most important is muscular exertion. O 2
consumption is elevated not only during exertion but also for as long afterward as is necessary to repay
the O2 debt .
Factors Affecting the Metabolic Rate.

Muscular exertion during or just before measurement

Latest ingestion of food (SDA)
High or low environmental temperature
Height, weight, and surface area
Sex
Age
Growth
Reproduction
Lactation
Emotional state
Body temperature
Circulating levels of thyroid hormones
Circulating epinephrine and norepinephrine levels

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Effect of Height, weight, and Body surface area (BSA)on BMR

a. Comparison of the correlation coefficients obtained by both Schofield and by Soares & Shetty (1988)
shows that BMR has a stronger correlation with body weight than with any other nutritional
anthropometric index used as a single independent variable.
b. Schofield, Soares & Shetty (1986,88) demonstrated an r = 0.80 for body weight accounting for 64% of the
variance while BMI had an r = 0.64 and height an r = 0.57.
c. Miller and Blyth assessed different means of adjusting basal metabolic rate (BMR) for different body
size parameters. The correlation between BMR and lean body mass(LBM) was r = 0 .92, greater than
that for BSA ( r = 0.84) and body mass (r = 0.85).
d. So, we can see that BMR has highest correlation with Lean body mass as compared to Total weight (fat +
Lean body weight), BSA & Height.
e. Since BMR is the energy consumption in resting state in metabolic active tissue i.e lean body mass
(adipose tissue is metabolically inert) BMR depends very much on LBM. By far the main determinant of
resting metabolic rate is fat-free mass (Miller & Blythe, 1953; Webb, 1981)
f. In a very tall thin and short obese person BMR differs but BSA can be similar so low correlation. Same way
BMI depends more on Body weight rather Lean body weight so again low correlation.
g. Latestly ingested foods also increase the metabolic rate because of their specific dynamic action (SDA).
The SDA of a food is the obligatory energy expenditure that occurs during its assimilation into the body.
h. Another factor that stimulates metabolism is the environmental temperature. The curve relating the
metabolic rate to the environmental temperature is U-shaped. When the environmental temperature is
lower than body temperature, heat-producing mechanisms such as shivering are activated and the
metabolic rate rises.
i. When the temperature is high enough to raise the body temperature, metabolic processes generally
accelerate, and the metabolic rate rises about 14% for each degree Celsius of elevation.

2. Ans. B. Obesity
(Ref: Ganong - 23rd Ed. Pg:281-82
a. In Hyperthyroid, Feeding (SDA) & exercise BMR increases (see table in previous Q.)
b. In case of obesity the BMR can be very different. Low BMR (Hypothyroidism) can lead to weight gain.
c. There is little evidence that obese subjects are characterized by an inherently low metabolic rate. Indeed,
it has been repeatedly demonstrated that under standardized conditions the obese have higher absolute
energy requirements than do the lean, due to the greater mass of metabolically active tissue.
d. As weight is gained both fat and fat-free mass are gained. However, this does not occur at a linear rate
as body size increases. As the body gets fatter, a greater ratio of fat to lean tissue is deposited (Forbes,
1982, 1987). Thus adipose tissue expands faster than lean tissue.
e. The metabolic rate of adipose tissue is very low compared with that of lean tissue (Miller & Blythe,
1953). By far the main determinant of resting metabolic rate is fat-free mass (Miller & Blythe, 1953;
Webb, 1981).
f. BMR per kg of body weight is lower than that of the normal subject (due to the lower percentage of fat-
free mass contributing to body weight). By the same argument the BMR per kg fat-free mass for most
subjects is very similar.

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 Endocrinology

3. Ans. A. Lean body mass

a. Energy expenditure in resting state is given by RMR or the Resting Metabolic Rate.
b. The metabolic rate determined at rest in a room at a comfortable temperature in the thermoneutral zone
12–14 hours after the last meal is called the basal metabolic rate (BMR).
c. This value falls about 10% during sleep and up to 40% during prolonged starvation.
d. The rate during normal daytime activities is, of course, higher than the BMR because of muscular activity
and food intake.
e. The maximum metabolic rate reached during exercise is often said to be 10 times the BMR, but trained

Chapter -8
athletes can increase their metabolic rate as much as 20-fold.
f. The BMR of a man of average size is about 2000 kcal/d. Large animals have higher absolute BMRs, but the
ratio of BMR to body weight in small animals is much greater.
g. The relation of BMR to body weight (W) is
h. However, repeated measurements by numerous investigators have come up with a higher exponent,
averaging 0.75.
i. So Energy expenditure in resting state would depend very much on body weight, thereby lean body mass
which is around 80-85% of total body weight is the correct answer.

4. Ans. B. Thyroxine

Endocrinology
Temperature increasing mechanism when body is too cold:
a. Skin vasoconstriction
b. Piloerection
c. Increased heat production by
i. Shivering -  heat production 4 to 5 times of normal
ii. Sympathetic excitation -  Nor-adrenaline  Non-shivering thermogenesis
iii. Thyroxine secretion - a long term cause of  heat production
Shivering  primary motor centre for shivering is located in the Dorsomedial portion of the posterior
hypothalamus.

5. Ans. B. Thyroid state. It is a part of thyroid function test. BMR depends on a lot of other factors also.

6. Ans. D. T4 is completely converted to T3 in peripheral tissue

7. Ans. B,D,E. Thyroid, Salivary gland, Mammary gland

a. Iodine Traping (Iodine pump)
b. Iodide uptake is a critical first step in the thyroid hormone synthesis by the thyroid.
i. Iodide uptake from circulation, is mediated by Na+/I- symporter (NIS), which is expressed at the
basolateral membrane of the thyroid follicular cells. It is an example of secondary active
transport.
c. The rate of iodide trapping by the thyroid is influenced by several factors, the most important being the
cone of TSH (i.e. TSH stimuliltes iodide uptake)
d. Low Level of NIS are also present in the salivary glands, lactating breast and placenta.
e. "The salivary glands, the gastric mucosa, the placenta, the ciliary body of the eye, the choroid plexus. and
the mammary glands also transport iodide against a concentration gradient but their uptake is not

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 Physiology

affected by TSH. Diiodotyrosine is formed in mammary tissues but T4 and T3 are not".
f. Low Iodine levels increase the amount of NSI and stimulate uptake, whereas high iodine levels suppress
NIS expression and uptake.
g. Excess iodide transiently inhibits thyroid iodide organification, a phenomenon known as the
i. WOLFF-CHAIKOFF-EFFECT. Q
h. Another iodide transporter, PENDRIN, is located on the apical surface of thyroid cells and mediates iodine
EFFLUX into the lumen. Mutation of the PENDRIN gene causes Pendred syndrome Q, a disorder C/B a.
defective organification of iodide b. goiter, and c. SN deafness.

8. Ans. B. Thyroid
THYROID contains a small population of C cells. They are the source of calcitonin and may give rise to medullary
thyroid carcinoma when they undergo malignant transformation.

Section-4 -: Pancreas

1. Ans. C. Deposition of chondroitin sulphate.

2. Ans. D. Keratin sulphate level decrease

(Ref: Dynamics of bone and cartilage metabolism. M. J. Seibel, Simon P. Robins Ed. 2006 Page 442)
a. Proteoglycans are a part of matrix which is secreted by chondrocytes.
i. half life of three months
ii. provide compressive strength
iii. regulate matrix hydration by providing a porous structure to trap and hold water
iv. composed of subunits of glycosaminoglycans (GAG’s - disaccharide polymers)
i. chondroitin-4-sulfate (decreases with age)
ii. chondroitin-6-sulfate
iii. keratin sulfate (increases with age)
b. Changes With Ageing
With ageing cartilage becomes hypocellular and has decreased elasticity.
c. Chondrocytes
i. increase in size
ii. increased lysosomal enzymes
iii. cartilage becomes hypocellular (cells stop reproducing)
d. Matrix
i. Proteoglycans
 decrease in mass and size - decreased length of chondroitin sulfate chains
 change in proportion - increased keratin sulphate
 Increase in enzymatic degradation
ii. Water content decreases
iii. Protein content increases
So, during ageing there is decrease in water content, decrease production of proteoglycans and also increased
degradation of proteoglycans resulting in decrease in their levels. But the proportion of proteoglycans also changes
with Increased in keratin sulphate and decreased chondroitin sulphate levels.

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3. Ans . B. Epinephrine (Ref: Ganong - Review of Medical Physiology 22nd Ed.Pg:345 & Berne & Levy physiology
5th Ed.

4. Ans. C. Chymotrypsin

5. Ans. B. Secrete somatostatin

6. Ans. B. 3 Amino acid

Chapter -8
a. Insulin is a polypeptide containing two chains of amino acids linked by 2 disulphide bridges between A7 to
B7 and A20 to B19.
b. A third disulphide bridge connects A6 and All .A chain has 21 amino acids and B chain has 30 amino acids.
c. Half life of insulin in circulation is 5 minutes There is a close similarity between human, porcine and bovine
insulins.
d. The porcine insulin differs only by a single amino acid from human insulin as it has Alanine in place of
Threonine at B 30 position.
e. The BOVINE INSULIN DIFFERS FROM HUMAN INSULIN ONLY BY 3 AMINO ACIDS.

Difference from human amino acid sequence

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A chain B chain
Amino acid position 8 9 10 30
Human insulin Threonine, Serine Isoleucine Threonine
Pig and dog insulin Threonine Serine Isoleucine Alanine
Cattle and goat insulin Alanine Serine Valine Alanine

7. Ans. D. Lipolysis
8. Ans. B. GLUT2
Mechanism of Insulin secretion by Beta cells :- .
a. Glucose is the key regulator of insulin secretion by pancreatic Beta cells, others are – amino acids, ketones,
various nutrients, GIP, and neurotransmitters.
b. Glucose stimulation of insulin secretion begins with its transport into beta cells by the GLUT-2 glucose
transporter.
c. Glucose phosphorylation by glucokinase is the rate-limiting step that controls glucose regulated insulin
secretion.
d. ATP sensitive K+ Channel

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i. Consists of two proteins

 SUR (Sulphonyl Urea Receptor) and
 Inwardly rectifying K+ channels.
ii. Insulin secretagogues :
Sulphonyl Urea and Non Sulphonyl Urea
(Repaglinide, Nateglinide) increase insulin secretion by binding with SUR of ATP sensitive -K+ channel
 inhibit it  reducing conductance of the K+-channel depolarization  influx of Ca++  insulin
secretion Insulin stimulates glucose uptake through GLUT-4 transporter in the skeletal muscle, cardiac
muscle and adipose tissues.
 SGLT-1 transporter
o Sodium dependent unidirectional transporter
o Secondary active transport .
o Present in small intestine and kidney
o Mediates active uptake of glucose from the lumen of the intestine and reabsorption of
glucose in PCT of kidney against a conc. gradient.
 GLUT-I-transporter (facilitated diffusion) :
o Mediates basal uptake of glucose (independent of insulin) in the Placenta, BBB, Brain, RBC,
Kidney, Colon, many other organs.

9. Ans. C. Insulin
Treatment of Diabetes in pregnancy
a. Oral antidiabetics should not be used during pregnancy these drugs cross the placenta and may have
teratogenic effect or produce neonatal hypoglycemia. That is why, insulin is used
b. A post prandial plasma glucose level of more than 140 mg% even on diet control is an indication of insulin
therapy.

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 Endocrinology

10. Ans. B. Long term status of blood sugar

Glycated Hb is abnormally high in diabetic with chronic hyperglycmeia and reflects their metabolic control.
Glycated Hemoglobin (HbA1)
a. It is produced by nonenyzmatic condensation of glucose molecules with free amino groups on the globin
component of Hb.
b. The major form of glycohemoglobin in termed Hb Alc, which normally comprises only 4-6% of total Hb.
c. The remaining glycohemoglobins (2-4% of total) consist of phosphorylated glucose or fructose and are
termed HbA1a and Hb Alb

Chapter -8
Since, glycohemoglobin circulate within RBCs whose 'life "span lasts upto 120 days, they generally reflect the state
of glycemia over the preceding 8-12 Weeks Q
In Hb AIC, a glucose attached to the NH2 group of terminal valine in each β chain. Q

11.The answer is D. Negative feedback

 The increase in plasma insulin lowers the plasma glucose concentration back to normal and is an example of negative
feedback. Negative feedback opposes change and results in stability.
 Positive feedback would produce a further increase in plasma glucose concentration.
 In other words, in negative feedback, the stimulus and response are in the opposite direction e.g. if T3 increases
(stimulus), the response is decrease in T3 and if T3 decreases, the response is increase in T3. In positive feedback, the
stimulus and response are in the same direction.
 Chemical equilibrium indicates a condition in which the rates of reactions in forward and backward directions are

Endocrinology
equal.
 End-product inhibition occurs when the products of a chemical reaction slow the reaction (for example, by inhibiting
an enzyme) that produces them.
 Feedforward control involves a command signal and does not directly sense the regulated variable (plasma glucose
concentration).

Section-5 -: Adrenals

1. Ans. C. Liver
a. Aldosterone’s and other steroids with mineralocorticoid activity increase the reabsorptions of Na+ from
the urine, sweat, saliva, and gastric juice.
b. Sodium ions move out of the urine (Or saliva, sweat, or gastric juice) into the surrounding epithelial cells
and are actively transported from these cells into the interstitial fluid.
c. The amount of Na+ removed from these fluids is proportionate to the rate of active transport of Na+.
d. Thus, mineralocorticoids cause retention of Na+ in the ECF. In the kidneys, they act primarily on the
epithelium of the cortical collecting ducts.
e. They may also increased the K+ and decreased the Na+ levels in muscle and brain cells.
f. Under the influence of aldosterone, increased amounts of Na+ are in effect exchanged for K+ and H+ in the
renal tubules, producing a K+ diuresis and increase in urine acidity.
(Ref: Ganong, Page 375, 23rd Edition)

2. Ans. D. Vanillylmandelic acid

Epinephrine and nor-epinephrine are metabolized to inactive products by either oxidation or methylation.
VANILLYLMANDELIC ACID is the most plentiful catecholamine metabolite found in urine.

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 Physiology

3. Ans. B. Zona reticularis

4. Ans. C. Proteolytic enzymes secreted in inactive form.
a. The pancreatic enzymes have the capability of digesting the pancreas itself (mainly proteases) (Auto
digestion of pancreas is considered to be the main pathogenic mechanism for pancreatitis).
b. Normally, auto digestion of pancreas is prevented by several means:
i. The enzymes are synthesized as inactive pro enzymes (with the exception of amylase and lipase)
ii. They are sequestered in membrane bound zymogen granules in acinar cells
iii. Activation of pro enzymes requires conversion of inactive trypsinogen to active trypsin by duodenal
enteropeptidase.
iv. Trypsin inhibitors are present within acinar and ductal secretions.
v. Intra pancreatic release of trypsin activates an enzyme or enzymes that degrades other enzymes to
inert products.
vi. (t) Lysosomal enzymes are capable of degrading zymogen granules when normal acinar secretion is
impaired or blocked.
vii. Acinar cells are remarkably resistant to the action of trypsin, chymotrypsin and phospholipase A2 .

c. Regarding option 'a' pancreatic enzymes require alkaline medium for their activity so bicarbonate
secretion will help in their activity.

5. Ans. C. Zona glomerulosa

Separate zones of the adrenal cortex synthesize specific hormones. The outer ZONA GLOMERULOSA contains the
enzymes for aldosterone biosynthesis, and the inner Zona fasciculata and Zona reticularis is the site of cortisol and
androgen biosynthesis.

6. Ans. B. Natriuretic peptide secretion

The kidneys produce 3 hormones viz 1 ,25-dihydroxycholecalciferol, renin, and erythropoietin.
7. Ans. C. Noradrenaline
a. Stimulation of the sympathetic nervous system, with liberation of norepinephrine and epinephrine
increases the metabolic rate of many tissues of the body.
b. These hormones have a ‘direct’ effect on the muscle and liver cells in causing glycogenolysis, and this,
along with other intracellular effects, increases cellular activity.
c. Even more important is the effect of sympathetic stimulation on a certain type of tat tissue called brown
fat Qin causing marked liberation of heat.
d. The newborn child has a considerable number of such fat cells, and maximal sympathetic stimulation can
increase the child’s metabolism more than 100%. Q This is known as non-shivering thermogenesis.
e.
The magnitude of this effect in the adult human being is in question-probably less than 10— 15%- though
this might be increase following cold adaptation.

Section-6 -: Calcium And Potassium

1. Ans A. Non ionic calcium is most important stimulus for PTH secretion
(Ref: 23rd edition Ganong's-301)
a. Circulating ionized calcium acts directly on the parathyroid glands in a negative feedback fashion to
regulate the secretion of PTH. The key to this regulation is a cell membrane Ca2+ sensing receptor, CaR.

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 Endocrinology

b. Activation of this G-protein coupled receptor leads to phosphoinositide turnover in many tissues. In the
parathyroid, its activation inhibits PTH secretion.
c. In this way, when the plasma Ca2+ level is high, PTH secretion is inhibited and the Ca2+ is deposited in the
bones. When it is low, secretion is increased and Ca2+ is mobilized from the bones.
d. Mg2+ works in the similar fashion and when it is low, PTH secretion is increased
e. Parathyroid hormone-related protein (or PTHrP) is a protein member of the parathyroid hormone family.
It is occasionally secreted by cancer cells (breast cancer, certain types of lung cancer including squamous
cell carcinoma).

Chapter -8
f. PTHrP acts as an endocrine, autocrine, paracrine, and intracrine hormone. It regulates endochondral bone
development by maintaining the endochondral growth plate at a constant width.
g. It also regulates epithelial-mesenchymal interactions during the formation of the mammary glands.
h. PTHrP is related in function to the "normal" parathyroid hormone. When a tumor secretes PTHrP, this can
lead to hypercalcemia. As this is sometimes the first sign of the malignancy, hypercalcemia caused by
PTHrP is considered a paraneoplastic phenomenon.
i. PTHR1 is responsible for most cases of humoral hypercalcemia of malignancy

2. Ans. A. Hydroxyproline
(Ref: 23rd edition Ganong's Page-301)
a. Biochemical markers of bone formation are

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i. serum alkaline phosphatase,
ii. osteocalcin, and
iii. the carboxy-terminal extension peptide of pro-collagen 1.
b. Osteocalcin is secreted solely by osteoblasts and thought to play a role in the body's metabolic regulation
and is pro-osteoblastic, or bone-building, by nature.It is also implicated in bone mineralization and calcium
ion homeostasis.
c. Procollagen 1 Carboxyterminal Peptide (P1CP) is the precursor of collagen, synthesized in osteoblasts and
fibroblasts and subsequently converted to form collagen by procollagen peptidase.

3. Ans. A. Ionized calcium

There is approximately 1 kg of calcium in the human body. About 99% exists in the bone and 1%in the extra
cellular fluid. Plasma calcium exists in 3 forms:
a. Complexed with organic acids b. Protein bound c. Ionized
The ionized calcium which is maintained at a concentration between 1.1 and 1.3 mmol/L is biologically the most
active fraction. The organism has very little tolerance for significant deviation from this normal range. If the ionic
calcium levels fall the organism develops hyper excitability and develops tetanic convulsions. A marked elevation
may result in death owing to muscle paralysis and coma.

4. Ans. A. Raised parathyroid hormone levels

a. Circulating ionized calcium acts directly on the parathyroid glands in a negative feedback fashion to
regulate the secretion of PTH.
b. The key to this regulation is a cell membrane Ca2+ receptor.
c. This serpentine receptor is coupled via a G protein to phosphoinositide turnover and is found in many
tissues.
d. In the parathyroid its its activation inhibits PTH secretion is habited and the Ca 2+ is deposited in the bones.

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e. When it is low, secretion is increased and Ca2+ is mobilized from the bones.

5. Ans. A. Decreased calcium

Detrimental Effects of Hyperventilation
1 Dizziness 5 Visual impairment
2 Cardiac arrhythmias 6 Myocardial ischemia
3 Seizure activity secondary to decreased 7 Muscle weakness secondary to hypophosphatemia
cerebral free serum calcium
4 Carpopedal spasm and tetany secondary to 8 Paresthesias secondary to decreased free serum calcium
decreased free serum calcium

6. Ans. C. Calcitonin
a. Calcitonin is a hypocalcemic peptide hormone that acts as the ‘physiologic-antagonist’ to parathyroid
hormone.
b. The hypocalcemic activity is accounted for primarily by inhibition of osteoclast-mediated bone resorption
and secondarily by stimulation of renal calcium clearance.
c. These effects are mediated by receptors on osteoclasts and renal tubular cells.

7. Ans. B. Calcitonin
Hormones Bone cells on which their receptors are present
Calcitonin Osteoclasts  Directly inhibit its function (i.e. Resorption)
Parathyroid  Osteoblasts  Activate its function
Vitamin D  Osteoblasts  Activate its function

8. Ans. C. Increased sensitivity of muscle and nerve

a. The concentration of Ca in the extracellular fluid has profound effect on the voltage level at which the Na
channels become activated.
b. When there is a deficit Ca the sodium channels become activated (opened) by ‘very little’ change of the
membrane potential from its normal very negative resting level to a less negative level. As a result the
nerve fiber becomes highly excitable, sometimes discharging repetitively without provocation instead of
remaining in the resting state.
c. The probable way in which Ca++ affect the sodium channels is that calcium ions bind to the exterior surface
of the sodium channel protein molecule.
d. The positive charges on these Ca++ in turn alter the electrical state of the channel protein itself, increasing
the voltage level required to open the gate

9. Ans. A. Inositol triphosphate

The link between membrane binding of a ligand that acts via Ca++ and the prompt increase in the cytoplalsmic Ca++
concentration is often inositol triphosphate.

10. Ans. C. Shortening of Q-T interval in ECG

"In Hypocalcemia QT interval in ECG is prolonged.
CIF Features of Hyeocalcemia
a. Extensive spasm of skeletal muscle causes cramps and tetany. Q

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b. Carpopedal spasm, facial grimacing, and in extreme cases Laryngeal spasm and convulsion. Q
c. Paresthesias of lips and extremities, and Abdominal pain. Q
d. 4. JVP with papilledema in long standing hypocalcaemia. Q
e. Mental changes include - irritability, depression and psychosis. Q
f. QT interval on ECG is prolonged (in contrast shortening in hypercalcemia) Q
g. Chvostek's sign (contraction of the facial muscles in response to tapping the facial nerve anterior to ear)
and Trousseau's sign (carpal spasm occurring after occlusion of the brachial artery with blood pressure cuff
for 3 minutes) are usually readily elicited. Q

Chapter -8
h. In chronic hypoparathyroidism (= chr. Hypocalcemia),cataracts and calcification of Basal ganglia. Q

11. Ans. A. Increased production of 1, 25 dihydroxycholecalciferol in kidney.

12. Ans. C. Increase in osteoid maturation time

Osteomalacia is characteristically described as a 'mineralisation disorder' manifested exclusively by defect in
mineralization of newly forming bone.
Abnormal minieralization / decrease in deposition of mineralized bone (i.e. decrease in mineratzation apposition
rate)


Endocrinology
Matrix continues to be secreted but is not mineralized.
(i.e. osteoid does not mature or increased osteoid maturation time)

Increased thickness of osteoid

Increased volume of osteoid
Increase is bone surface covered by osteoid.

13. Ans. B. Hydroxyapatite Ref: Ganong - Review of 23rd Ed-Page-303

a. The main salt in bone extracellular matrix is hydroxyapatite. This is made up of calcium ions and
phosphate ions Ca10(PO4)6(OH)2.
b. Most of the weight of bone is due to its extracellular matrix, and 70% of that weight is due to inorganic
salts.
c. Up to fifty percent of bone is made up of a modified form of the inorganic mineral hydroxylapatite (known
as bone mineral).
d. Carbonated calcium-deficient hydroxylapatite is the main mineral of which dental enamel and dentin are
comprised.
e. Hydroxyapatite crystals are also found in the small calcifications (within the pineal gland and other
structures) known as corpora arenacea or 'brain sand'.
14. Ans. C. In absence of sunlight 200-400 IU of vitamin D is the daily required.
(Ref. Ganong Physiology 23rd ed. pg 363)

Section-7 -: Reproduction & Related Hormones

1. Ans. A. Azoospermia

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 Physiology

(Ref: Lippincott. Principles of pharmacology: the pathophysiologic basis of drug therapy)

By David E. Golan. Page 515 & Ganong - Review of Medical Physiology 23rd Ed.
Testosterone, the principal hormone of the testes, is a C19 steroid with an –OH group in the 17 position. It is
synthesized from cholesterol in the Leydig cells and is also formed from androstenedione secreted by the adrenal
cortex.
a. ACTIONS
i. Testosterone is necessary for normal sperm development. It activates genes in Sertoli cells, which
promote differentiation of spermatogonia.
ii. Regulates acute HPA (Hypothalamic–pituitary–adrenal axis).
iii. Maintenance of muscle trophism.
iv. Testosterone regulates the thromboxane A2 receptors on megakaryocytes and platelets.
v. Libido as evinced in clitoral engorgement/penile erection frequency.
b. Regulation:
i. Castration is followed by a rise in the pituitary content and secretion of FSH and LH, and hypothalamic
lesions prevent this rise.
ii. Testosterone inhibits LH secretion by acting directly on the anterior pituitary and by inhibiting the
secretion of GnRH from the hypothalamus.
iii. As a consequence, endogenous testicular production of testosterone is reduced. Spermatogenesis is
also reduced, and if administration is continued, azoospermia and infertility may result.
iv. Peripheral aromatization of androgens to estrogens can cause gynecomastia.
v. Cessation of exogenous androgen treatment in normal males usually results in restoration of normal
sperm levels over a 6-month period.
c. Uses
i. Infertility
ii. Hypogonodism
iii. lack of libido or erectile dysfunction,
iv. osteoporosis,
v. bone marrow stimulation for anemia.

2. Ans D. Uterus (Ref: Ganong - 23rd Ed-Page391)

a. Spermatozoa leaving the testes are not fully mobile. They continue their maturation and acquire motility
during their passage through the epididymis.
b. Their capacity to produce fertilization is further enhanced if they spend more additional time in the
FEMALE REPRODUCTIVE TRACT mainly uterus.
c. The initial process occurring in the female reproductive tract is known as capacitation Q. It makes the
spermatozoa better able to adhere to the ovum. Q.
d. Note: Spermatozoa are stored in epididymis. Spermatozoa maturation and motility acquired during their
passage through epididymis.

3. Ans. B. FSH (Ref: Reproductive Endocrinology & Infertility By Daftary & Patki, Page 250.)
Ovarian reserve is a term used to describe the functional potential of the ovary and reflects the number and quality
of oocytes within it.
Tests of ovarian reserve:

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 Endocrinology

a. Cycle day 3 FSH. Many studies have shown that an increasing FSH level is associated with a decreased
pregnancy rate. Women in their early 40s were found to have elevated FSH levels associated with
accelerated follicular phases of the menstrual cycle compared to younger patients.
b. Clomiphene Citrate Challenge Test. This simple test involves a day 3 FSH level, 100 mg clomiphene from
day 5-9, and a day 10 FSH level. An abnormal test is an elevated day 10 FSH level. An elevated day 3 FSH is
a positive test. This is a ‘provocative test’, which will unmask patients which might be missed with a day 3
FSH level. It is 2-3 times more sensitive than a day 3 FSH level. This may be the best screening test to date.
A positive or abnormal test is associated with a poor chance to conceive (<5%).

Chapter -8
Results FSH <15 good
FSH >15<20 borderline
FSH >20 poor
c. Serum inhibin levels. Inhibin is a protein that is secreted by the follicles of the ovary to inhibit FSH
secretion by the pituitary. An ovary with decreased ‘reserve’ will secrete less inhibin and thus will have a
higher day FSH level and worse prognosis. This blood test is done in research labs, at present.

d. Ovarian volume/follicles. Several studies have shown that patients with decreased ovarian volume and
baseline follicles have decreased reserve. Using ultrasound scanning to count the number of antral follicles
in the ovary is more accurate than measuring ovarian volume to assess ovarian reserve.

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4. Ans. C. Glycolysis increase.
(Ref: Ganong - Review of Medical Physiology 22nd Ed, Guyton – Textbook of Medical Physiology 10th Ed, and
various other textbooks & Journals etc.)
a. A number of studies say that the HRT has no highly deleterious effect in patients with NIDDM or with
IGT(Impaired Glucose Tolerance TEST). The data studied do not support the hypothesis of an impaired
oestrogen effect in patients with NIDDM. Infact HRT is significantly associated with lower HbA1c levels in
NIDDM pateints. In some cases where there was worsening it was associated more with progesterone in
OCP.
b. Estrogen is also shown to modulate insulin sensitivity possibly by altering insulin related gene expression.
Infact estrogen α receptor knock out mice shows insulin resistance (Barros et. al. 2006) whereas β
receptor decreases insulin sensitivity.
c. At physiological levels, testosterone and oestradiol are thought to be involved in maintaining normal
insulin sensitivity. However, outside this 'physiological window' these steroids may promote insulin
resistance. For eg a study stated that intake of Oral Contraceptives for 3 cycles induced glucose
intolerance, hyperinsulinaemia and insulin resistance in normal menstruating Chinese women. These
changes occurred in association with elevated plasma triglyceride concentrations.
d. Estrogen-induced growth requires continuous replenishment of energy, predominantly generated by
glycolysis. Estrogen-induced changes in glycolysis appeared to be mediated via its regulation of GLUT 1
expression & Glycolytic enzyme induction. Estradiol promotes the energetic capacity of mitochondria by
maximizing aerobic glycolysis.
e. Alterations in the composition of the plasma lipids caused by estrogens are characterized by an increase
in the high-density lipoproteinsQ, a slight reduction in the low-density lipoproteinsQand a reduction in
plasma cholesterol levelsQ. Plasma triglyceride levels are increasedQ due to lipolysis and increase synthesis
of triglyceridesQ.

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 Physiology

So, The best answer would be increased glycolysis (Option C) as relation of estrogens with insulin sensitivity is
ambivalent (Option B) and most studies show that it does not worsen NIDDM ((Option A). Infact new studies
have shown that post-menopausal women who take estrogen replacement therapy (ERT) are less likely to
develop diabetes and, if they do have the disease, are better able to maintain good blood sugar control .And
question is about carbohydrate metabolism not lipid metabolism where it causes lipolysis (Option D). Estrogen
causes fat to be stored in the buttocks, thighs, and hips in women. Men are more likely to have fat stored in
the abdomen due to sex hormone differences. When women reach menopause and the estrogen produced by
ovaries declines, fat migrates from their buttocks, hips and thighs to their waists; later fat is stored in the
abdomen (central obesity).

5. Ans. A Spermiogenesis.Sertoli cells are associated with maturation phase of Spermiogenesis

Spermiogenesis is the final stage of spermatogenesis which sees the maturation of spermatids into mature, motile
spermatozoa.
The process of spermiogenesis is traditionally divided into four stages: the Golgi phase, the cap phase, the
acrosomal phase, and the maturation stage.
a. Golgi phase
i. The spermatids, which up until now have been mostly radially symmetrical, begin to develop
polarity.
ii. The head forms at one end, and the Golgi apparatus creates enzymes that will become the
acrosome.
iii. At the other end, it develops a thickened mid-piece, where the mitochondria gather and form an
axoneme.
iv. Spermatid DNA also undergoes packaging, becoming highly condensed.
v. The DNA is packaged firstly with specific nuclear basic proteins, which are subsequently replaced
with protamines during spermatid elongation.
vi. The resultant tightly packed chromatin is transcriptionally inactive.
b. Cap phase
The Golgi apparatus surrounds the now condensed nucleus, becoming the acrosomal cap.
c. Acrosomal phase
i. One of the centrioles of the cell elongates to become the tail of the sperm. A temporary structure
called the "manchette" assists in this elongation.
ii. During this phase, the developing spermatozoa orient themselves so that their tails point towards the
center of the lumen, away from the epithelium.
d. Maturation phase
The excess cytoplasm, known as residual bodies, is phagocytosed by surrounding Sertoli cells in the testes.
Sertoli cell is a 'nurse' cell of the testes.It is activated by follicle-stimulating hormone, and has FSH-
receptor on its membranes. Its main function is to nurture the developing sperm cells through the stages
of spermatogenesis.
Sertoli cells also act as phagocytes, consuming the residual cytoplasm during spermiogenesis.
e. Sertoli cells secrete the following substances:
i. Anti-Müllerian Hormone (AMH) - secreted during the early stages of fetal life.
ii. inhibin and activins - secreted after puberty, and work together to regulate FSH secretion

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iii. Androgen binding protein - facilitate spermatogenesis and sperm maturation estradiol - aromatase from
Sertoli cells convert testosterone to 17 beta estradiol to direct spermatogenesis
 Glial Cell Line-Derived Neurotrophic Factor (GDNF) - has been demonstrated to function in promoting
undifferentiating spermatogonia, which ensures stem cell self-renewal during the perinatal period.
o The ETS related molecule (ERM transcription factor) - needed for maintenance of the
spermatogonial stem cell in the adult testis.

6. Ans. C. Requires temperature lower than core temperature

Chapter -8
a. Spermatogenesis requires a temperature considerably lower than that of the interior of the body.
b. The testes are normally maintained at a temperature of about 32 °.
c. They are kept cool by air circulating around the scrotum and probably by heat exchange in a
countercurrent fashion between the spermatic arteries and veins.
d. When the testes are retained in the abdomen or when, in experimental animals, they are held close to the
body by tight cloth binders, degeneration of the tubular walls and sterility result.
e. Hot baths (43 –45 ° for 30 minutes per day)and insulated athletic supporters reduce the sperm count in
humans, in some cases by 90%.However,the reductions produced in this manner are not consistent
enough to make the procedures reliable forms of male contraception.
f. In addition, evidence suggests a seasonal effect in men, with sperm counts being greater in the winter

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regardless of the temperature to which the scrotum is exposed.

7. Ans. B. Straight tubules–rete testis–efferent tubules

a. The sperms are formed in the seminiferous tubules (spermatogenesis) and pass on to the straight tubules
(tubuli recti).
b. They then enter a network of tubules (rete testis),where they are exposed to high concentration of
estrogen.
c. The sperms get concentrated in the rete testis, and if they don ’infertility can result (due to diluted
semen).
d. Now, the sperms reach efferent ductules. The efferent ductules are lined by ciliated columnar epithelium,
the cilia help in the mass movement of sperms.
e. And finally, the sperms reach the epididymis. Epididymis is lined by pseudo-stratified columnar epithelium
with stereo-cilia.
f. Stereo-cilia are also seen in the internal ear hair cells and are believed to absorb the fluids (Cilia is a
misnomer).
g. The sperms will be stored in the epididymis till their ejaculation.

8. Ans. A. FSH
Explanation: FSH helps in maintaining the spermatogenic epithelium by stimulation of Sertoli cells in the male. FSH
acts on the sertoli cells to facilitate the late stages of spermatid maturation. In addition, it promotes the production
of ABP
a. Sertoli cell (a kind of sustentacular cell) is a 'nurse' cell of the testes which is part of a seminiferous tubule.
b. It is activated by follicle-stimulating hormone, and has FSH-receptor on its membranes.
c. FSH binds to Sertloi cells stimulate testicular fluid production and synthesis of intracellular androgen
receptor proteins. Sertoli cells secrete anti- mullerian hormone and activins also.

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d. LH binds to receptors on interstitial cells of Leydig and stimulate testosterone production, which in turn
binds to Sertoli cells to promote spermatogenesis.
e. Inhibin is a hormone that inhibits FSH production. It is secreted from the Sertoli cells, located in the
seminiferous tubule inside the testes.

9. Ans. A. Epididymis
Spermatozoa leaving the testes are not fully mobile. They continue their maturation and acquire motility during
their passage through the EPIDIDYMIS.

10. Ans. C. Genital tract female

a. Spermatozoa leaving the testes are not fully mobile.
b. They continue their maturation and acquire motility during their passage through the epididymis. Their
capacity to produce fertilization is further enhanced if they spend more additional time in the FEMALE
REPRODUCTIVE TRACT.
c. The initial process occurring in the female reproductive tract is known as capacitation Q. It makes the
spermatozoa better able to adhere to the ovum. Q

11. Ans. B. Inhibin

SERTOLI CELLS are the supporting elongated cells of the seminiferous tubules of the testes to which spermatids
attach to be nourished until they become mature spermatozoa. Sertoli cells produce the hormone inhibin, which is
a polypeptide that inhibits FSH.

12. Ans. B. After vasectomy

Vasectomy causes an autoimmune response to sperm. Blocking of the vas causes reabsorption of spermatozoa and
subsequent development of antibodies against sperm in the blood. About 54% of men who have had vasectomies
develop antibodies against their own sperm.

13. Ans. A. Progesterone

a. Biphasic changes in BASAL BODY TEMPERATURE are typical of the ovulatory cycle and are mediated by
alterations in PROGESTERONE levels.
b. An increase in basal body temperature by 0.3 to 0.5°C begins after ovulation, persists during the luteal
phase, and returns to the normal baseline (36.2 to 36.4°C) after the onset of the subsequent menses.

BIPHASIC CHANGES IN BASAL BODY TEMPERATURE DURING A MENSTURAL CYCLE

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 Endocrinology

14. Ans. B. Estrone

Circulating estrogens In the ovulating woman are derived from two sources:
a. Sixty percent of mean estrogen formation during the menstrual cycle is in the form of estradiol Q, formed
primarily by ovaries.
b. Remainder is estrone formed mainly in extraglandular tissues from androstenedione.
c. After menopause extraglandular estrogen formation is the major pathway for estrogen synthesis Q
Estrogen production by the menopausal ovary is minimal Plasma levels of estradiol are lower in
postmenopausal women than levels of estrone The rate of peripheral formation of estrone increases in

Chapter -8
menopausal women so that estrone production is only slightly less than it was prior to the menopause
despite the fall in plasma androstenedione. The predominant estrogen formed is ESTRONE rather than
estradiol. Q
15. Ans. B. Midcycle
a. Estrogen:
i. Estrogen makes the cervical muscus thinner and more alkaline, changes that promote the survival and
transport of the sperm.
ii. The mucus is thinnest at the time of ovulation and its elasticity, or spinnbarkeit, increases so that by
midcycle, a drop can be streched into a long, thin thread that may be 8-12cm or more in length.
(Estrogenic effect).
iii. Fern like pattern (Estrogenic effect).

Endocrinology
b. Progesterone:
i. Progesterone makes cervical mucus, thick, tenacious and cellular.
ii. Fails to form fern pattern.

16. Ans. A. Leydig cells

a. TESTOSTERONE is a steroid produced by the interstitial cells of Leydig of the testicles.
b. This hormone is also normal produced by the adrenal cortex of both human males and females.

17. Ans. A. C3 and Cl7

Chemical name of estradiol is 1, 3, 5, (10)-Estratriene-3, 17b-diol.

18. Ans. C. Nucleus

a. Hormonal steroids and thyroid hormones exert their main physiological effects by acting directly on the
NUCLEI their target cells to increase transcription of selected mRNAs.
b. Like other steroids estrogen combines with an intracellular protein receptor and this complex binds to
DNA.
c. This promotes formation of mRNAs which in turn direct the formation of new proteins which modify the
cell function.

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 Physiology

19. Ans. B. Normal or elevated LH/FSH

a. POLYCYSTIC OVARIAN DISEASE is the most common cause of ovarian hyper-androgenism.
b. The salient feature of the disease is the pubertal onset of chronic anovulation and hirsutism. Stein-
Leventhal syndrome (Enlarged cystic ovaries, obesity, and amenorrhea) is present in about 50% of women
with this disorder but is not required for the diagnosis.
c. The fundamental abnormality in polycystic ovarian disease is not fully known, but ELEVATED LEVELS OF

Polycystic ovary Ovarian Congenital

Disease tumor Adrenal
hyperplasia
Urinary17-ketosteroids, plasma
DHEA sulfate Normal or elevated Normal Normal or elevated
Plasma testosterone Normal or elevated Much Normal or elevated
elevated
LH/FSH ratio Normal or elevated Normal Normal
Precursors of cortisol biosynthesis:
:Basal
:Following ACTH infusion Normal Normal Normal or elevated
Normal Normal Much elevated
Cortisol following overnight
dexamethasone suppression test Normal Normal Normal
PLASMA LH lead to enhanced androgen secretion by stromal and thecal cells of the ovary. Q

20. Ans. A. Long arm of X chromosome

ANDROGEN RECEPTOR is encoded by a gene on the long arm of the X chromosome. Q

21. Ans. B. FSH

INHIBIN is a peptide hormone produced by the testicular Sertoli cell and ovarian granulosa cell. It is a potent
inhibitor, of FSH (but not LH) release. Q

22. Ans. D. Epididymis

a. A small quantity of sperm can be stored in the epididymis, but most sperm are stored in the vas deferens
and the ampulla of the vas deferens.
b. They can remain stored, maintaining their fertility, in the genital ducts for several months, though it is
doubtful that during normal sexual activity such prolonged storage ordinarily occurs.

23. Ans. D. It inhibits secretion of FSH

Inhibin is a peptide hormone produced by the testicular Sertoli cell and ovarian granulosa cell. It is a potent
inhibitor of FSH (but not LH) release.

24. Ans. B. Seminiferous tabules

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 Endocrinology

The spermatogonia, the primitive germ cells next to the basal lamina of the seminiferous tubules, mature into
primary spermatocytes The primary spermatocytes undergo meiotic division, reducing the number of
chromosomes.

25. Ans. A,E. Is a glycoprotein, Has 2 subunits

a. HCG ( Human chorionic Gonadotrophin):-
i. HCG is a glycoprotein, mol. wt = 36000 — 40000 daltons
ii. Is secreted by the syncytiotrophoblast of the placenta

Chapter -8
iii. HCG has two subunit: - α and β
 (a subunit  non specific biochemically and functionally similar to LH, FSH and TSH Q
 subunit  specific and unique to HCG.
iv. By radioimmuno assay it can be detected in the maternal serum or urine as early as 8-9 days
following ovulation
v. In the early pregnancy, the doubling, time of HCG conc. in plasma is 1.4 to 2 days.
vi. Conc.of HCG in blood and urine: - (During pregnancy)
 Maximum level (100 IU to 200 IU/ml)  at 60-70 days of pregnancy
 Slowly falling to 10 to 20 I.U/ml  100-130 days of pregnancy
 After that, remains constant with a slight secondary peak at  32 weeks

Endocrinology
 HCG disappear from the circulation within 2 weeks following delivery
 HCG-conc:  Peak  5 mg/ml  during 1st trimester
vii. HCG level  in 
 Multiple pregnancy Q
 Hydatiform mole Q
 Chorio carcinoma Q
 Down’s synd: -for downs synd:  Triple test   Maternal alpha protein,  HCG, and unconjugated-
oestriol (E3) Q

b. Human placental Lactogen or, human chorionic somatomammotropin -

i. Synthesized by syncytiotrophoblast of placenta.
ii. Similar to growth hormone and prolactin.
iii. Function  Increase carbohydrate metabolism  it causes mobilization of FFA from maternal fat deposit
and shift glucose towards utilization by growing foetus. Due to its anti-insulin effect, protein synthesis is
increased as maternal insulin level is high.
iv. Values of HPL less than 5 g after the 35 weeks indicates the possibility of fetal distress and neonatal
asphyxia after delivery.

26. Ans. A. 50 
“A matured spermatozoon is about 60 µ long and consists of a head and a tail”.

27. Ans. C. Follicle stimulating hormone

Sertoli cells have receptors for FSH Q stimulated by FSH Q and secretes the inhibin.
Sertoli cells

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 Physiology

a. Large, complex glycogen - containing cells Q

b. They provide nutrition to the developing sperm cells. Q
c. They phagocytoze the injured or dead sperm cells Q
d. They are the basis: of blood testis barrier Q
e. They secrete androgen-binding protein (ABP), inhibin and MIS. Q
f. They do not synthesize androgens, but they contain aromatase, the enzyme responsible for conversion of
androgens to, estrogens and they can produce estrogens. Q

Note:
i. ABP probably functions-to maintain a high, stable supply of androgen in tubular fluid.
ii. Inhibin inhibits FSH secretion
iii. MIS causes regression of the mullerian ducts is in males during fetal life.

Leydig cells (Interstitial Cells)


They are nest of cells present between the seminiferous tubules in testes. They secrete testosterone into
Q
bloodstream.
Note:
a. Spermatozoa are stored in epididymis.
b. Spermatozoa maturation and motility acquired during their passage through epididymis.
c. Further maturation and capacitance occur within female genital tract.

28. Ans. C. Aromatase

Aromatase is the enzyme that catalyzes the conversion of androstenedione to estrone and the conversion of
testosterone to estradiol. (Aromatization)

29. Ans. A. Sertoli cells

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 Endocrinology

Blood - Testis - Barrier: - Tight junctions between adjacent sertoli cells near the basal lamina form a blood - testis
barrier Q, that prevents many large molecules from passing from the intertitial tissue and the part of the tubule
near the basal lamina to the region near the tubular lumen (adluminal comportment) and the lumen.

30. Ans. B. Seminal vesicle

a. Sertoli cells secretes:
i. Androgen - binding protein (ABP)
ii. Inhibin (It is also secreted by granulosa cell; inhibin inhibits FSH secretion)

Chapter -8
iii. MIS (cause regression of the mullerian duct)
iv. Sertoli cells also contain Aromatase the enzyme responsible for conversion of androgens to
estrogens..
v. Serotoli cells forms the Blood - Testis Barrier.
b. Leydig cells ~ synthesized testosterone.
c. Semen:
i. Amount  2.5-3.5ml per ejaculate after several days of continence. Q
ii. Seminal vesicle contributes 60% of total volume. Q
iii. Seminal vesicles secretes  fructose, citric acid, and large amount of prostaglondin as well fibrinogen.
Fructose major source of energy for sperm. Q
iv. Prostate: contributes 20% total volume  and secretes  citrate ions, Ca++, phosphate ions, a

Endocrinology
clotting enzyme and a profibrinolysin. Q
v. pH of semen  7.35 to 7.50 Q
vi. Sperm count  avg. 100 milion/ml. Q
vii. Human sperms move at a speed of about 3mm/min through the female genital tract, and reach the
uterine tube 30-60 minutes after copulation. Q
viii. Spermatozoa acquire full motility during their-passage through epididymis; capacitation takes place in
female genitalia; Spermatogenesis takes 74 days to form a mature sperm Qfrom, primitive germ cells.
The Length of a mature sperm is about 65 m. (Head – 5m, middle piece 5m, principal piece –
50m, and end piece – 5m) Q
i. Life expectancy of ejaculated sperm in the female genital tract is only 1-2 days Q(Guyton) [upto 120 hours -
Ganong] and ovum lives for approximately 72 hours after it is extruded from the follicle. Q

31. Ans. D. Progesterone

The level of progesterone rises in latter half of the menstrual cycle. Because progesterone is secreted by
corpus luteum.

32. Ans. A. The involution of corpus luteum causes estradiol and progesterone levels to fall dramatically
a. About 2 days before the end of the monthly cycle, the corpus leatum suddenly involutes and ovarian
hormones estrogen and progesterone decrease sharply to low levels of secretion.
b. Menstruation is caused by this sudden reduction of the estrogens and progesterone, especially the
progesterone, at the end of the monthly ovarian cycle.
i. Life cycle of Corpus Luteum
 Stage of proliferation  Stage of Maturation
 Stage of Vascularization  Stage of Regression
ii. The changes in endometrium occur in the following order

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 Physiology

 Stage of regeneration
 Stage of proliferation
 Secretory phase- due to effect of progesterone on receptors that were ,induced by estrogen.
 Menstrual phase
o Regression of corpus lutuem with fall in level of oestrogen and progesterone is an invariable
proceeding feature.
o As a result of withdrawal of hormone support, there is retrogressive changes in the endometrium.

33. Ans. D. Beta-endorphin

Control of the onset of puberty
a. The factors that normally activate or restrain the hypothalamic neurons responsible for GnRH secretion
are unknown.
b. It is clear that GnRH is the major, if not the only, hormone responsible for the onset and progression of
puberty.
c. During the period from birth to puberty, a neural mechanism is operating to prevent the normal pulse
release of GnRH. The nature of the mechanism inhibiting the GnRH pulse generator is unknown.
d. Conversely, opioid peptides such as the enkephalins and -endorphin reduce the frequency of. GnRH
pulses
e. The release of hypothalamic GnRH is also inhibited by melatonin (Samson wright)
Norepinephrine and possibly epinephrine in the hypothalamus increas

34. Ans. D. Centchroman

a. Centchroman(ormeloxifene) is one of the selective estrogen receptor modulators, or SERMs, a class of
medication which acts on the estrogen receptor.
b. It is best known as a non-hormonal, non-steroidal oral contraceptive which is taken once per week. In
India, ormeloxifene has been available as birth control since the early 1990s, and it is currently marketed
there under the trade name Saheli

35. Ans. A. Dopamine

(Ref: Ganong’s-23rd Ed, P-458)
a. Dopamine is the primary neuroendocrine inhibitor of the secretion of prolactin from the anterior pituitary
gland.
b. Dopamine produced by neurons in the arcuate nucleus of the hypothalamus is secreted into the
hypothalamo-hypophysial blood vessels of the median eminence, which supply the pituitary gland.
c. The lactotrope cells that produce prolactin, in the absence of dopamine, secrete prolactin continuously;
dopamine inhibits this secretion.
d. Thus, in the context of regulating prolactin secretion, dopamine is occasionally called prolactin-inhibiting
factor (PIF), prolactin-inhibiting hormone (PIH).

36. Ans. A. decrease ACTH CRH increase ACTH and ACTH increase glucocorticoids.
(Ref: Review of Medical Physiology- Ganong’s-23rd Then via feedback loop glucocorticoids inhibit both
Edition, P-345) ACTH & CRH.

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 Physiology

37. Ans. A. LH
(Ref: - Ganong’s-23rd Ed, P-415)
a. The process of ovulation is controlled by the hypothalamus of the brain and through the release of
hormones secreted in the anterior lobe of the pituitary gland, luteinizing hormone (LH) and follicle-
stimulating hormone (FSH).
b. In the pre-ovulatory phase of the menstrual cycle, the ovarian follicle will undergo a series of
transformations called cumulus expansion, which is stimulated by FSH.
c. After this is done, a hole called the stigma will form in the follicle, and the ovum will leave the follicle
through this hole.
d. Ovulation is triggered by a spike in the amount of FSH and LH released from the pituitary gland.

38. Ans. B. GLUT2

(Ref: - Ganong’s-23rd Ed, P-320)

39. Ans. A. cardiac muscle

GLUT 4 is induced by insulin in adipose tissue, skeletal muscle and cardiac muscle (see the GLUT table)

40. Ans. A. seminal vesicle

(Ref: - Ganong’s-23rd Ed, P-405)

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 Physiology

The thick secretions from the seminal vesicles contain proteins, enzymes, fructose, mucus, vitamin

C, flavins, phosphorylcholine andprostaglandins.

41. Ans. B. paracrine
a. autocrine — the cell signals itself through a chemical that it synthesizes and then responds to. Autocrine
signaling can occur
i. solely within the cytoplasm of the cell or
ii. by a secreted chemical interacting with receptors on the surface of the same cell
b. paracrine — chemical signals that diffuse into the area and interact with receptors on nearby cells.
Examples are:
i. The release of cytokines that cause an inflammatory response in the area.
ii. The release of neurotransmitters at synapses in the nervous system.
c. endocrine — the chemicals are secreted into the blood and carried by blood and tissue fluids to the cells
they act upon.

42. Ans. C. Estrone

(Ref: - Ganong’s-23rd Edition, P-403)
a. Androstenedione (also known as 4-androstenedione and 17-ketoestosterone) is a 19-carbon steroid
hormone produced in the adrenal glands and the gonads as an intermediate step in the biochemical
pathway that produces the androgen testosterone and the estrogens estrone and estradiol.
b. Aromatase is localized in the endoplasmic reticulum where it is regulated by tissue-specific promoters that
are in turn controlled by hormones, cytokines, and other factors.

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 Endocrinology

c. It catalyzes the last steps of estrogen biosynthesis from androgens (specifically, it transforms
androstenedione to estrone and testosterone to estradiol).
d. These steps include three successive hydroxylations of the 19-methyl group of androgens, followed by
simultaneous elimination of the methyl group as formate and aromatization of the A-ring.
e. During the reproductive years, most estradiol(main form of estrogen) in women is produced by the
granulosa cells of the ovaries by the aromatization of androstenedione (produced in the theca folliculi
cells) to estrone, followed by conversion of estrone to estradiol by 17β-hydroxysteroid dehydrogenase.

Chapter -8
43. Ans. A. Hypokalemia (Ref: Ganong’s-23rd Edition, Pg326)

44. Ans. C. Androgen

a. Most of the effect of GH to stimulate growth at the epiphyseal plate is indirect.
b. GH stimulates production of insulin-like growth factor-1 (IGF-1), and it is IGF-1 that directly stimulate
chondrocyte cell division and bone growth.
c. IGF-1 can be considered to act as both a hormone and a paracrine.
d. Some of the IGF-1 is produced by the liver, and travels to the growth plate via the circulation, while some
of the IGF-1 is produced locally by chondrocytes in the growth plate.
e. Thyroid hormone is important for growth because it promotes growth hormone synthesis. Gonadal
steroids, whose secretion increases at puberty, initially promote growth by increasing GH secretion, and

Endocrinology
then subsequently cause growth to end by causing the closure of the epiphyseal growth plates.
f. Cortisol, which is released in response to stress, causes an inhibition of growth.

45. Ans. D. Phospholipase C

a. GnRH is secreted in the hypophysial portal bloodstream at the median eminence. The portal blood carries
the GnRH to the pituitary gland, which contains the gonadotrope cells, where GnRH activates its own
receptor.
b. Gonadotropin-releasing hormone receptor (GnRHR), a seven-transmembrane G-protein-coupled receptor
that stimulates the beta isoform of Phosphoinositide phospholipase C, which goes on to mobilize calcium
and protein kinase C.
c. This results in the activation of proteins involved in the synthesis and secretion of the gonadotropins LH
and FSH.

46. Ans. A. ATP sensitive K+ channels

(Ref: - Ganong’s-23rd Edition, Pg327)

THYROID (T1 TO T11)

1. Ans. C. Have columnar cells

2. Ans. A. Colloid, in active follicles
3. Ans. D. Synthesize thyroid hormones
4. Ans. D. Thyroglobulin synthesis

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 Physiology

5. Ans. B. – 50mv
6. Ans. B. Secondary active transport
7. Ans. E. RT3
8. Ans. D. MIT
9. Ans. D. Thyroglobulin
10. Ans. D. DIT
11. Ans. B. Total plasma T3,T4,RT3 is normal or low
12. Ans. E. Maximum binding to TBG
13. Ans. C. 5’ – deiodinase forms RT3 from T4
14. Ans. D. DIT
15. Ans. D. All of the above.
16. Ans. D. Anterior Pituitary
17. Ans. E.  ES rate of carbohydrate absorption in G.I.T.
18. Ans. E. ACTH
19. Ans. F.  T4
20. Ans. A. 123I
21. Ans. D. T3, T4 resistance

ADRENALGLAND (TAG1 TO TAG15)

1. Ans. A. 90% of cells are of epinephrine secreting type

2. Ans. B. Zona fasciculate
3. Ans. B. Epinephrine
4. Ans. B. Epinephrine
5. Ans. D. P.P
6. Ans. D. A & B
7. Ans. E. Increase Not reabsorption in kidney
8. Ans. D. Pheaochromocytoma
9. Ans. A. C19
10. Ans. B. C21
11. Ans. D. Pregnancy
12. Ans. B. 21 Hydroxylase
13. Ans. A. Two-Thirds
14. Ans. A. ACTH
15. Ans. E. All of the above.
16. Ans. D. Uncontrolled diuresis, leading to excessive water loss and water deprivation
17. Ans. D. Monocytes
18. Ans. C. Prevent release of histamine/cytokines
19. Ans. A. Early morning
20. Ans. C. Baroreceptors, via N.T.S.
21. Ans. E. A, B & C
22. Ans. B. In plasma Na+
23. Ans. D. All
24. Ans. C. Mineralcocrticoid – sensitive cells have 11 – hydroxy steroid dehydrogenase

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 Endocrinology

25. Ans. D. All of the above

26. Ans. A. Oedema
27.The answer is C.
Ref: Ganong - Review of Medical Physiology 23rd Ed Page 342
Hormones produce their effects on target cells by interacting with specific receptors. Hormone binding to its receptor
generally initiates a cascade of events that lead to biological effects in the target cells.

28.The answer is D.
Ref: Ganong - Review of Medical Physiology 23rd Ed Page 454
Cortisol, like other steroid hormones, is carried in the blood largely bound to carrier proteins, although a small

Chapter -8
percentage exists free in solution. The majority of cortisol is bound to a specific carrier protein, corticosteroid-binding
globulin (CBG), while smaller amounts are bound nonspecifically to albumin. Few, if any, cortisol receptors would be
expected in the plasma and transthyretin binds primarily thyroxine.

29.The answer is B.
Ref: Ganong - Review of Medical Physiology 23rd Ed Page 455
 Cholesterol esters in LDL are the most important source of cholesterol for sustaining adrenal steroidogenesis when it
occurs at a high rate over a long time. This cholesterol can be used directly after release from LDL and not stored. De
novo synthesis of cholesterol from acetate is a minor source of cholesterol in humans.
 Cholesterol from the plasma membrane or endoplasmic reticulum is not used for steroidogenesis.
 Cholesterol esters in lipid droplets within adrenal cortical cells would be used first and depleted during periods of

Endocrinology
high adrenal steroid hormone synthesis.
30.The answer is A.
Ref: Ganong - Review of Medical Physiology 23rd Ed Page 453,526
 Congenital adrenal hyperplasia is the result of genetic defects that affect adrenal steroidogenic enzymes, producing
an impaired formation of cortisol. Low serum cortisol is a stimulus for ACTH release from the hypothalamus. The
increase in ACTH has a proliferative effect on the adrenal gland, resulting in hyperplasia.
 Addison’s disease is the result of pathological destruction of the adrenal glands by microorganisms or autoimmune
disease and would, therefore, not result in adrenal hyperplasia. ACTH stimulates the growth of the adrenal gland. A
reduction in ACTH in the blood would result in atrophy of the adrenal gland. Corticosteroid-binding globulin
noncovalently binds steroid hormones in plasma; defects in this protein are not associated with adrenal hyperplasia.
 Cushing’s disease results from a pituitary ACTH-secreting tumor; adrenal hyperplasia is secondary, not congenital, in
this disease. Aldosterone synthesis is regulated by the renin-angiotensin system. Defective aldosterone synthesis
would, therefore, not lead to increased ACTH and adrenal hyperplasia.
31.The answer is D.
Ref: Ganong - Review of Medical Physiology 23rd Ed Page
 IP3 is one of the second messengers in the cells of the zona glomerulosa that signals for aldosterone release. A
decrease in IP3 would result in less signal for aldosterone synthesis and release. The rate of aldosterone secretion
would increase in response to an increase in renin release from the kidney.
 Renin catalyzes the rate-limiting step in the conversion of angiotensinogen to angiotensin II, which is a stimulus for
ldosterone synthesis and release.
 A rise in serum potassium or renal sympathetic nerve activity, a fall in blood pressure in the kidney, or a decrease in
tubule fluid sodium concentration at the macula densa would stimulate aldosterone synthesis and release.

32.The answer is C.
Ref: Ganong - Review of Medical Physiology 23rd Ed Page 451
The first and rate-limiting step in all steroid biosynthesis is catalyzed by cholesterol sidechain cleavage enzyme, resulting
in pregnenolone and isocaproic acid. 17α-hydroxylase, 3β-hydroxysteroid dehydrogenase, 21-hydroxylase, and 11β-

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 Physiology

hydroxylase are all involved in the synthesis of cortisol, but are not rate-limiting. 3-Hydroxy-3-methylglutaryl CoA
reductase catalyzes the rate-limiting step in de novo cholesterol synthesis.
33.The answer is D.
 Glucocorticoids maintain the transcription of genes and, therefore, the intracellular concentrations of many of the
enzymes needed to carry out gluconeogenesis in the liver and kidneys.
 Glucocorticoids maintain the liver and kidneys in a state that makes them capable of accelerated gluconeogenesis
when fasting occurs.
 Glucocorticoids inhibit insulin release. Insulin inhibits gluconeogenic enzymes in the liver. The glucocorticoid-induced
inhibition of glucose utilization by skeletal muscle does not stimulate gluconeogenesis but provides glucose for
utilization by the CNS.
 Inhibition of glycogenolysis by glucocorticoids does not occur in fasting. Glucocorticoids do not inhibit, but actually
permit, lipolysis and the release of fatty acids from adipose tissue.

PANCREAS (P1-10)

1. Ans. A. Islet Cell

2. Ans. D. Affected by insulin
3. Ans. A. Adipose Tissue
4. Ans. B. Insulin receptors are ed in starvation
5. Ans. D. ed urinary K+ reabsorption
6. Ans. A. Efficient glucose utilization in the cells of ventromedian nuclei of hypothalamus
7. Ans. B. Glucose – 6 phosphotase
8. Ans. D. Plasma k+ ised
9. Ans. D. Antiketotic
10. Ans. H. Depletion
11. Ans. C. Sympathetic (+):  es Insulin
12. Ans. E. Secretin
13. Ans. E. Glucagon (-)s somatostatin
14. Ans. A. Hypoglycaemia

Parathyroid
1. Ans. D. None of the above
2. Ans. A. es intestinal absorption of Ca++
3. Ans. E. es Ca++ excretion in urine
4. Ans. D. In renal failure, absorption is ed
5. Ans. A. Kidney
6. Ans. A. 25 OHCC (calcidiol)
7. Ans. D. Genomic
8. Ans. D. PO43- (+) 1  hydroxylase

Reproduction & Related Hormones

1.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 565

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 Endocrinology

 The placenta cannot make androgens from progestin precursors because it lacks 17α-hydroxylase. DHEAS from the
fetal adrenal glands is converted to 16OH-DHEAS by the fetal liver and then to estriol by the placenta; this reaction is
substantial and is an indicator of fetal stress (estriol low) or well-being (estriol high).
 The mother’s adrenal can also make DHEAS, which can be converted to 16-(OH)DHEAS by 16-hydroxylase in the fetal
liver, but this reaction is limited (10%).
 Androgens cannot be produced from cholesterol in the placenta; the placenta lacks 17-αhydroxylase. Estradiol is
generally not converted to estriol.
 Androgens from the ovary are generally not converted to estriol.

Chapter -8
2.The answer is A.
 Reduced secretion of GnRH will result in extremely low levels of circulating LH and FSH, causing testicular atrophy, as
in Kallmann’s syndrome.
 Hypersecretion of LH and FSH, increased activin, and an increased number of FSH receptors all lead to hyperfunction
of the testis, not hypofunction.
 A failure of the hypothalamus to respond to testosterone increases LH, leading to increased Leydig cell androgens
and testicular hypertrophy

3.The answer is D.
Ref: Ganong - Review of Medical Physiology 23rd Ed Page 543
Follistatin is a binding protein for activin. Activin cannot increase FSH secretion when follistatin is bound to it, so FSH

Endocrinology
secretion decreases. Follistatin does not bind FSH, does not inhibit seminal fluid production and Leydig cell testosterone
secretion, and does not stimulate the production of spermatogonia.

4.The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 536
 The epididymis and vas deferens are major storage sites of spermatozoa. Spermatozoa develop in the in the
seminiferous tubules. Sertoli cells, not the epididymis, secrete estrogens and inhibin.
 The prostate gland, seminal vesicles, and bulbourethral glands secrete the seminal fluids.

5.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 536
 It takes approximately 65 to 70 days to develop spermatozoa from the earliest stages of spermatogonia. Because the
production of sperm depends on LH and FSH, a lack of GnRH (Kallmann’s syndrome) will reduce the production of LH,
FSH, and sperm. Temperature is important in regulating sperm production.
 Optimal sperm production occurs at 2 to 3_C lower than body temperature.

6.The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 539
The initial reaction and the rate-limiting step in the production of testosterone is the conversion of cholesterol to
pregnenolone, which is regulated by

7.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 539
 The enzyme 5α-reductase is found in the prostate and converts testosterone to dihydrotestosterone. Testosterone
does not bind HDL; HDL is a source of cholesterol. Activin does not bind testosterone.
 Testosterone cannot be converted directly to 17-hydroxyprogesterone, which is derived from progesterone and is
converted to androstenedione. The side-chain cleavage enzyme converts cholesterol to pregnenolone.

8.The answer is A. Ref: Ganong -

Sex hormone-binding globulin binds to both testosterone and estradiol, but it binds with higher affinity to testosterone.
The bioactivity of testosterone is reduced by SHBG because testosterone cannot bind to its receptor when bound by
SHBG. SHBG increases the circulating half-life of testosterone by slowing the clearance and metabolism of testosterone.
SHBG does not alter the secretion of inhibin or androgen-binding protein.

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 Physiology

9.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 542
 The production of estradiol requires Leydig cells, under the influence of LH, which stimulates androgen production.
The androgen diffuses to Sertoli cells, which contain aromatase, the enzyme that converts androgens to estrogens
under the influence of FSH. Therefore, Leydig cells, Sertoli cells, LH, and FSH are required.
 Follistatin binds activin and would reduce FSH secretion, an essential component for estradiol production. Estradiol is
not produced by Leydig cells.
 Activin would increase the secretion of FSH, which is a necessary component for estradiol, but other cells and
hormones are required. Similarly, Leydig cells would need LH to stimulate the production of the androgen precursor
of estrogen. Sertoli cells, under the influence of FSH, are needed to aromatize androgen from Leydig cells.

10.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 553
 Aromatase is present only in granulose cells and is regulated mainly by FSH. Although LH may stimulate aromatase in
granulosa cells, granulose cells do not produce androgens.
 Estradiol synthesis in the graafian follicle is unrelated to progesterone synthesis in the corpus luteum and does not
increase LH during this phase. Estradiol increases LH secretion during the LH surge.
 There is no evidence for synergy between FSH and progesterone in regulating estradiol secretion by the graafian
follicle.

11.The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 553
 Granulosa cells do not have the enzyme called 17α-hydroxylase, which converts progesterone to 17β-
hydroxyprogesterone. Aromatase is the enzyme that converts androgens to estrogens. 5α-Reductase converts
testosterone to dihydrotestosterone.
 Sulfatase is an enzyme that conjugates steroids with sulfate for subsequent excretion in the urine. Steroidogenic
acute regulatory protein transports cholesterol from the outer to the inner mitochondrial membrane.

12.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 554
 One of the first clinical measures for menopause is an increase in the serum concentration of FSH (and LH), indicative
of the lack of ovarian function. Menses starts at age 12, not age 50, and its onset at this time would not indicate
menopause.
 Excessive corpora lutea would likely indicate multiple ovulations or a failure of luteal regression.
 Increased vaginal cornification is an indicator of estrogen secretion, which does not occur in menopause. Menstrual
cycles become irregular at menopause.

13.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 551,557
 Progesterone has a thermogenic effect on the hypothalamus, increasing the basal body temperature for a few days
after ovulation. Women who, because of ovulatory problems, are having trouble getting pregnant are sometimes
asked to record their daily oral temperatures and look for the increase in basal body temperature, indicating an
increase in progesterone (which indicates ovulation).
 Progesterone induces a secretory type of endometrium, whereas estrogens induce a proliferative type.
 During the luteal phase, when progesterone is increasing, graafian follicles are not present. Progesterone levels
decrease during luteal regression. FSH decreases when progesterone is rising.

14.The answer is A.
Theca interna cells produce androgens under the influence of LH, whereas granulose cells do not produce androgens.
Theca interna cells do contain cholesterol side-chain cleavage enzyme, which converts cholesterol to pregnenolone.

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 Endocrinology

Because theca cells do not express aromatase, they cannot convert testosterone to estradiol. The theca interna has a rich
blood supply. Granulosa cells produce inhibin.

15.The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 563
 Fertilization by more than one sperm is prevented by the cortical reaction. Cortical granules containing proteolytic
enzymes fuse just beneath the entire surface of the oolemma.
 The proteolytic enzymes are released to the perivitelline space, destroy the sperm receptors, and harden the zona,
preventing other sperm from penetrating the fertilized ovum. Enzyme reaction is a nonspecific term with little
meaning for polyspermy.

Chapter -8
 The acrosome reaction allows the sperm to penetrate the zona. The decidual reaction is an inflammatory-like
reaction that occurs simultaneously with implantation of the blastocyst into the uterine endometrium.

16.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 564
 The production of hCG by trophoblast cells stimulates the corpus luteum to continue to produce progesterone so
that luteal regression does not occur at the end of the anticipated cycle. Although PRL levels increase throughout
pregnancy, PRL is not responsible for maintenance of the corpus luteum of pregnancy.
 Prostaglandins are generally luteolytic, causing regression of the corpus luteum, termination of the luteal phase, and
return to the next cycle; they do not prolong the cycle or postpone it. Oocytes are not depleted after implantation.
 In fact, pregnancy tends to preserve oocytes, as ovulation ceases during pregnancy. Plasma progesterone levels are
high during pregnancy as a result of activation of the corpus luteum and placental production of progesterone.

Endocrinology
 Elevated progesterone blocks follicular development and the ensuing LH surge; low levels of progesterone would
permit a return to cyclicity.
17.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 550
 Estrogen induces the formation of a stringy vaginal secretion that is called spinnbarkeit, observed in the late
follicular phase. The secretory endometrium is under the influence of progesterone; therefore, spinnbarkeit would
not be present.
 Spinnbarkeit is not produced in response to progesterone, androgen, or prolactin.

18.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 563
 Under normal circumstances, the uterus must be primed with both progesterone and estrogen for successful
implantation. Implantation occurs on day 7 after fertilization.
 The decidual reaction occurs as the result of the implanting blastocyst.
 The embryo is in the blastocyst stage of development at the time of implantation.
 A morula does not implant.
 The developing embryo enters the uterus on day 3 or 4, it remains suspended in the uterus for 3 or 4 more days, and
implantation occurs on day 7.
19.The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 563
 Fertilization occurs in the oviduct. The oocyte must have entered a second meiotic division to reduce the
chromosome number of the oocyte to a haploid state (n) so that it may fuse with the sperm (also haploid), producing
a 2n zygote.
 Fertilization does not occur in the uterus, especially not after the first meiotic division when the chromosome
number is 2n. In the adult ovary, oocytes do not undergo mitosis. Graafian follicles do not enter the oviduct and are
not fertilized.
 Fertilization does not occur in the uterus, and the oocyte does not implant. The blastocyst will implant in the uterus.
In addition, extrusion of the polar body is associated with fertilization, but this event occurs within the oviduct.

20.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page

5 α -Reductase is the enzyme that converts testosterone to dihydrotestosterone. 5 α –Reductase is associated with
increasing the most potent androgen, dihydrotestosterone, and reducing LH secretion. Estrogens are associated with female
secondary sex characteristics, although some androgens regulate pubic hair development.

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21.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 567
 Suckling involves hormonal and neuronal components, but the hormonal component is efferent and the neuronal
component is afferent.
 When the baby suckles, neural signals from the nipple travel via nerves to the spinal cord and up to the brain
(afferent component), which triggers the release of oxytocin from the supraoptic nuclei (efferent component).
 Oxytocin enters the circulation, enters the breasts, and causes contraction of the myoepithelial cells.
 Placental lactogen is no longer present after parturition; it is a placental hormone.
 Dopamine release is decreased by suckling, and as a result, PRL secretion is increased.

22.The answer is A.
 The acrosome reaction causes a fusion of the plasma membrane and the acrosomal membrane of the sperm, with
subsequent release of proteolytic enzymes that help the sperm enter the ovum.
 The zona reaction and pronuclei formation occur after the sperm has entered the ovum. Sperm enter the
perivitelline space after penetration; there is no evidence that this space has any role in penetration.

23.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 560
Inhibin is produced by granulosa cells and inhibits the secretion of FSH. Inhibin does not inhibit the secretion of LH and
PRL. Although inhibin can have local ovarian effects, it has profound inhibitory effects on FSH secretion. Inhibin has two
forms, A and B; the α subunits are the same, whereas the β subunits are different. Inhibin binds activin and decreases FSH
secretion.

24.The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page

 Oral steroidal contraceptives generally contain progesterone and estrogen-like molecules, which feed back
negatively on the hypothalamic-pituitary axis and reduce the secretion of LH and FSH; this is the primary mechanism
of action in preventing pregnancy.
 Choices B, C, and D are not the best answers, although oral contraceptives do alter the uterine environment, thicken
the cervical mucus, and reduce sperm motility.
 If ovulation were not blocked, the other parameters would not be effective in blocking pregnancy. Oral
contraceptives block the LH surge; they do not induce a premature surge.

25.The answer is B.
Ref: Harper’s Illustrated Biochemistry 25th ed
Scatchard plots of hormone-receptor binding data give information regarding the number of receptors and the affinity of
the hormone for its receptor. The x-intercept provides data regarding total receptor number, and the slope is equal to
the negative of the association constant (-Ka).

26.The answer is D.
Ref: Ganong - Review of Medical Physiology 23rd Ed Page 357
Preprohormones are the gene products for most peptide and protein hormones. These are rapidly cleaved to form
prohormones. POMC and propressophysin are two examples of specific prohormones.

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Chapter - 9
GIT
I. GASTROINTESTINAL MOTILITY
A. Peristalsis
This is a reflex contraction of the gut wall to stretch (e.g. by food). It is present throughout the GIT (from the
oesophagus to the rectum). Stretching the gut wall causes a wave of contraction and relaxation viz. an area of
circular contraction behind the stretch and an area of relaxation in front of it. The wave moves from an oral to
caudal direction and helps in moving the contents of the GIT (at a rate of 2 to 25 cm/s).

Chapter - 9
B. Cause/mechanism :
Peristalsis occurs due to the integrated activity of the intrinsic i.e. the enteric nervous system; however, the input
from the extrinsic autonomic nervous system can increase/decrease it. If a segment of intestine is removed and
the cut ends are joined in their original position, peristalsis still occurs. However, if the ends are reversed and
then joined, peristalsis does not occur.

C. Possible sequence of events

Stretch  releases serotonin  stimulates the myenteric plexus  from the myenteric plexus, cholinergic
neurons go two directions :
1. in a retrograde direction to activate neurons that release substance P and acetylcholine  these cause the
contraction.
2. In an anterograde direction to activate neurons that release NO and VIP  these cause the relaxation in
front of the stimulus.

GIT
D. BER (Basic Electric Rhythm)
1. Definition :
The smooth muscle of the GIT show a spontaneous, rhythmic fluctuations in their membrane potentials
(between –65 mV to –45 mV); this is called basic electrical rhythm or BER.
2. Site :
BER is present throughout GIT except the oesophagus and proximal portion of the stomach.
3. Cause :
BER is caused by pacemaker cells called the interstitial cells of Cajal.
Location of the cells of Cajal :
a. stomach and small intestine  outer circular muscle layer near the myenteric plexus
b. colon  submucosal border of the outer circular muscle layer
Rate of BER:
BER Rate (per min)
Stomach 4
Duodenum 12
Proximal Jejunum 12
Distal Ileum 8
Caecum 9
Sigmoid Colon 6 to16 (MAXIMUM MOTILITY)
BER: Absent in Oesophagus and proximal colon

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 Physiology

Note : The rate decreases in the stomach and small intestine and increases in the large intestine.

E. Function
1. Coordination of peristalsis and other motor activity of the GIT. Proof : vagotomy or transection of the
stomach
2. wall causes the peristalsis in the stomach to become irregular.
3. The BER by itself rarely causes muscle contraction; however, the spike potentials superimposed on the most
depolarizing portions of the BER waves cause contraction and increases muscle tension. The depolarizing
phase of these spike potentials is due to calcium influx and their repolarisation phase is due to potassium
efflux.

F. Factors affecting BER

Acetylcholine increases the number of spike potentials (and thus increases muscle tension) whereas epinephrine
decreases the number of spike potentials (and thus decreases muscle tension)

G. Migrating motor complex

1. Definition
The motor and electrical activity of smooth muscle in GIT that occur during fasting (between periods of
digestion) are called migrating motor complex or MMC. They are so called because the motor activity starts
from the stomach and migrates to the distal ileum.

2. Rate
During the period of fasting, MMCs move down the GIT at a regular rate of approximately 5 cm/min. They are
completely inhibited by a meal; they resume 90 to 120 minutes after the meal.and occur at intervals of about 90
minutes till the next meal.

3. Phases of the MMCs

Phase I : This is the first phase; it is the quiescent period with no spike potentials and no contractions
Phase II : this is a period of irregular spike potentials and contractions
Phase III : this is the last phase; it is a period of regular spike potentials and contractions
Function
This is not fully clear. There is an increase in pancreatic and gastric secretion as well as bile flow during each
MMC. The function of MMC may be to clear the contents of the stomach and small intestine in between the
meals. On taking food, MMC stops immediately and is replaced by peristalsis and other forms of BER and spike
potentials.

Reflexes
1. Gastroileal
2. Gastrocolic
3. Enterogastric
4. Intestino – intestinal
5. Rectosphincteric
6. Colono – ileal

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II. GASTROINTESTINAL HORMONES

A. Classification
The GI peptides can be classified as below :
1. Gastrin family :
The primary hormones in this group are gastrin and cholecystokinin (CCK)
2. Secretin family :
The primary hormones in this group are secretin, glucagon, glicentin (GLI), VIP, and gastrin inhibitory
peptide (GIP).

Chapter - 9
3. Others
Many of the GI peptides do not belong to the above two groups e.g. somatostatin, motilin, substance P,
guanylin, neuropeptide YY etc.

B. The GI cells secreting the GI peptides can be classified as

1. Enterochromaffin (or ECL)cells :
These cells secrete serotonin also (in addtion to secreting polypeptides)

2. APUD (or amine precursor uptake and decarboxylase) cells :

These cells secrete amines also (in addition to secreting polypeptides). Apart from the GIT, APUD cells can also
be found in other organs e.g. lungs. Carcinoid tumors arise from APUD cells.

The important GI hormones are discussed below :

Gastro – Intestinal Hormones

GIT
Gastrin CCK – PZ Secretion GIP
Structure Micro and macro Micro and Only one from
heterogeneci heterogencity
ty
Site G – cells, antrum I – cells – Upper SI S cells – upper SI K cells – upper
S1
Actions Stimulates acid Stimulates GB; relaxes Stimulates secretion of In large dose it
and pepsin; sphincter of Oddi; pancreatic juice inhibits
stimulates stimulates (alkaline); inhibits gastric
gastric pancreatic juice gastric acid secretion; motility
motility; (rich in enzymes); may stimulate pyloric and
stimulates inhibits gastric A1 sphincter; stimulates inhibits
insulin; emptying; may insulin; augments CCK; gastric
stimulates stimulate pyloric action of secretion is to secretion;
glucagons; sphincter; decrease H+ in SI stimulates
closure of G-E stimulates insulin insulin
and glucagons;
trophic to
pancreas;
increases
enterokinase; may

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 Physiology

increase motility of
SI and colon;
augments
secretion
Factors Increased by: Increased by peptides, Increased by products of Increased by
peptides, aminoacids, fatty food digestion, acid in fatty
distension, acids (not duodenum acids,
vagus, cold, triglycerides) amino
epinephrine acids,
decreased by glucose
calcitonin,
acid,
somatostatin,
secretion,
GIP, VIP

VIP Somatostatin Motilin Neurotensin

Nerves D cells of GIT EC cells duodenum Nerve in ileum
Stimulates intestinal Inhibits secretion of gastrin, VIP, Contraction of Inhibits
secretion of GIP, secretion, motilin; intestinal gastrointestina
electrolytes and inhibits pancreatic exocrine smooth muscle; l motility;
water; relaxation of secretion; inhibits gastric regulator of increase ileal
intestinal smooth secretion and motility; MMC (migrating blood flow
muscle; dilation of inhibits gall bladder motor complex)
peripheral blood contraction; inhibits
vessels; inhibits absorption of aminoacids,
gastric acid secretion triglycerides, Increased by
– stimulated gastric acid in lumen; decreased by
acid secretion; vagus
potentiates action of
acetylcholine on
salivary glands;
stimulates
pancreatic
bicarbonate
secretion and
inhibits H secretion
Increased by fat in Increased by acid in lumen
jejunum decreased by vagus

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 GIT

III. GASTRIN
A. Site of production :
G cells present in antral portion of stomach.
Other sites where gastrin is found :
Foetal islets of pancreas, pituitary gland (anterior and intermediate lobes), hypothalamus, medulla oblongata,
vagus and sciatic nerves
B. Actions
1. Stimulation of gastric acid and pepsin secretion

Chapter - 9
2. Trophic action : gastrin stimulates the growth of mucosa of stomach, small and large intestines
3. Stimulation of gastric motility
4. Stimulation of insulin secretion; a protein meal (but not a carbohydrate meal) releases the amount of
gastrin that is required to stimulate insulin secretion

C. Factors affecting gastrin secretion

1. Factors stimulating gastrin secretion
a. Gastric distension e.g. by food
b. Protein digestion products in the stomach viz. peptides and amino acids (the amino acids
phenylalanine and tryptophan are very effective stimulants)
c. Vagal stimulation; note that in the G cell, vagus releases the neurotransmitter GRP (or gastrin releasing
peptide) and not acetylcholine; hence, the gastrin response to vagal stimulation is not abolished by
atropine.
d. Calcium, epinephrine

GIT
2. Factors inhibiting gastrin secretion
a. Acid :
Acid in the antrum inhibits gastrin secretion; this is another example of negative feedback control as
shown below :
Gastrin  increases acid production  but, acid feeds back to inhibit further gastrin secretion
In pernicious anemia, there is damage to the acid-secreting cells of the stomach. Hence, the negative
feedback inhibition of gastrin by acid is not there; thus, the gastrin levels are increased in such cases.
Acid inhibits gastrin secretion in two ways :
i. directly, by acting on G cells
ii. indirectly, by releasing somatostatin (which is a potent inhibitor of gastrin secretion)
b. secretin, GIP, VIP, glucagons, calcitonin

IV. CHOLECYSTOKININ-PANCREOZYMIN (CCK-PZ)

CCK-PZ (or more commonly called CCK) is a single hormone. It is called so because, initially, it was thought that
CCK and PZ were two separate hormones having two different actions; later on, it was found that both the
hormones were one and the same.

A. Site of production
I cells of the upper small intestine.

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 Physiology

B. Other sites where CCK is found

1. nerves in distal ileum and colon (and also in nerves in other parts of the body)
2. neurons in the brain (particularly in the cerebral cortex)

C. Actions
1. contraction of the gall bladder
2. secretion of pancreatic juice rich in enzymes
3. augments the action of secretin in producing secretion of an alkaline pancreatic juice
4. inhibits gastric emptying
5. has a trophic effect on the pancreas
6. increases the secretion of enterokinase
7. may increase motility of small intestine and colon
8. together with secretin, it may increase the contraction of the pyloric sphincter (thus, preventing the reflux
of duodenal contents into the stomach
9. CCK (and gastrin) stimulate glucagons secretion (note that the secretion of both CCK and gastrin increases
after a protein meal.
10. CCK in the brain may have a role in regulation of food intake; it may also have a role in the production of
anxiety and analgesia.

D. CCK receptors
1. Types :
CCK-A and CCK-B receptors.
Site :
CCK-A receptors are mainly located in the periphery, whereas both CCK-A and CCK-B are found in the brain.
2. Mechanism of action :
Both activate phospholipase C (PLC), causing increased production of IP 3 and DAG.
Food digestion products and CCK secretion
Products of food digestion, particularly peptides and amino acids, increase CCK secretion. Fatty acids (with
more than 10 carbon atoms) also increase CCK secretion.
3. Positive feedback mechanism
CCK  increases bile and pancreatic juice secretion  more digestion of protein and fat  further increases
CCK secretion
This positive feedback mechanism stops when the products of food digestion move on to the lower portions of
the GIT.

4. Secretin
Secretin was the first hormone to be discovered (by Bayliss and Starling in the year 1902; Starling coined the
term ‘hormone’).
a. Structure :
It is a polypeptide; M.W. : 5000, consists of 27 amino acids. Its structure is different from that of gastrin and
CCK but similar to that of glucagon, VIP, GLI, and GIP. There is only one form of secretin (in other words, it
does not show microheterogeneity). It is secreted as prosecretin (inactive); it gets converted by gastric HCl
and salts of fatty acids (soaps) into secretin (active).

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 GIT

b. Site of secretion:
Secretin is secreted by S cells present in the upper small intestine. The half-life of secretin is 5 minutes.

E. Actions
1. It acts on the duct cells of the pancreas and that of the biliary tract to increase bicarbonate secretion.
2. Thus, it produces a watery alkaline pancreatic juice, but poor in enzymes. Its effect on the pancreas is
mediated by cAMP.
3. The volume of the flow of juice is directly proportional to the dose of secretin given intravenously. As the
volume of pancreatic secretion increases, its chloride concentration falls and bicarbonate concentration

Chapter - 9
rises. This is because, bicarbonate is secreted in the small ducts but is reabsorbed in the large ducts in
exchange for chloride. The magnitude of this exchange is inversely proportional to the rate of flow.
4. It potentiates the action of CCK (thus, helping in production of pancreatic secretion rich in enzymes)
5. It decreases gastric acid secretion (secretin is the body’s natural antacid)
6. It may cause contraction of the pyloric sphincter and thus delay gastric emptying. This may prevent the
reflux of duodenal contents into the stomach.

F. Factors increasing secretin secretion

1. Products of protein digestion
2. Acid in the upper small intestine
3. Acid released from the stomach reaches the upper small intestine and causes increased secretion of
4. secretin; this is another example of negative feedback control as shown below :
5. Acid  increases secretin secretion  which causes secretion of alkaline pancreatic juice  this
neutralizes the acid  decreases secretin secretion

GIT
G. Note :
CCK-PZ acts on acinar cells of pancreas and stimulates secretion of enzyme-rich pancreatic juice
Secretin acts on the duct cells of the pancreas and stimulates secretion of alkaline (bicarbonate-rich), watery
pancreatic juice.

V. VASOACTIVE INTESTINAL PEPTIDE (VIP)

A. Structure
It is a peptide having 28 amino acids. It is formed from its precursor prepro-VIP. Prepro-VIP has VIP and another
peptide resembling VIP called PHM-27.

B. Site
VIP is found in the nerves in the GIT, blood (where its T1/2 is 2 minutes), brain and autonomic nerves. In the brain
and autonomic nerves, VIP is often found along with acetylcholine.
C. Actions
1. markedly increases the intestinal secretion of electrolytes and water
2. relaxes the intestinal smooth muscle, including the sphincters
3. inhibits gastric acid secretion
4. increases action of acetylcholine on salivary glands. VIP and acetylcholine co-exist in the nerves to the
salivary glands; they do not exist together in other nerves of the GIT.

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 Physiology

5. dilates peripheral blood vessels

6. VIP secreting tumours (called as VIPomas) cause severe diarrhea

VI. ENTEROGASTERONE
This is a putative (meaning as yet chemically unidentified) hormone; it could be the same as peptide YY.

1. Actions
It inhibits gastric acid secretion and motility; it inhibits gastrin-stimulated acid secretion.
Fat causes its release from the jejunum.

VII. GIP (GASTRIC INHIBITORY POLYPEPTIDE)

A. Structure
Like VIP, GIP is a peptide having 43 amino acids.
B. Site
It is produced by K cells in the duodenum and jejunum in the presence of glucose and fat.

C. Actions
1. inhibits gastric juice secretion and motility; hence called GIP. However, this action of GIP is seen only in
high (supraphysiological) doses
2. stimulates insulin secretion.
Response to oral glucose
a. On giving oral glucose, GIP gets secreted and in turn causes release of insulin from the beta cells of the
pancreas. For this reason, GIP is also called as glucose-dependent insulinotropic polypeptide
b. the hormones gastrin, CCK, secretin, and glucagons) are also known to release insulin; however, on
giving oral glucose, they do not get secreted in enough amounts to cause insulin release
c. the hormone called GLP –1 (7 –36) is a glucagon derivative. In response to oral glucose, it gets secreted
from GIT; in turn it causes release of insulin. Its action in releasing insulin is more potent than that of
GIP.
MCQ tip
The GIT hormones, which release significant insulin on giving oral glucose are GIP and GLP-1 (7-36)

IX. MOTILIN

a. Structure
Motilin is a polypeptide having 22 amino acids.
b. Site
It is secreted by enterochromaffin cells and Mo cells in the stomach, small intestine and colon.
c. Actions
i. causes contraction of the smooth muscles of the stomach and intestine

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 GIT

ii. it is the main regulator of the migrating motor complexes (MMCs); MMCs control the
gastrointestinal motility between meals (i.e. in the inter-digestive phase). The blood level of motilin
increases at intervals of about 100 minutes in the inter-digestive phase.
d. Mechanism of Actions
Motilin acts on G protein-coupled receptors present on the neurons in the duodenum and colon.
erythromycin binds to these motilin receptors; thus, it may be useful in patients with decreased
gastrointestinal motility.

Neurotensin

Chapter - 9
a. Structure
Neurotensin is a polypeptide having 13 amino acids.
b. Site
It is secreted from neurons and cells in ileum; its release is stimulated by fatty acids
Actions
i. inhibits GI motility
ii. increases blood flow in ileum

X. SOMATOSTATIN
A. Structure
There are two forms : somatostatin 14 and somatostatin 28.

B. Site

GIT
It is secreted by D cells in the islets of pancreas and by similar D cells in the GI mucosa.
(Somatostatin, which is the growth hormone-inhibiting hormone was originally isolated from the hypothalamus).
Somatostatin is secreted more into the GI lumen than into the bloodstream; this is true of other GI hormones
also.
C. Actions
1. Inhibits
a. the secretion of gastrin, VIP, GIP, secretin, and motilin
b. pancreatic exocrine secretion
c. gastric acid secretion and motility
d. gall bladder contraction
e. the absorption of glucose, amino acids and triglycerides
f. as mentioned under gastrin, acid inhibits gastrin secretion; one of the ways may be as follows :
Acid  stimulates somatostatin secretion  this in turn inhibits gastrin secretion Ghrelin

2. Structure
It is a polypeptide having 28 amino acids.
a. Site
It is secreted primarily from the stomach.
b. Actions
i. it may play an important role in the central control of food intake
ii. stimulates growth hormone secretion (by a direct action on the receptors in the pituitary)

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 Physiology

XI. PEPTIDE YY
A. Structure
It is a polypeptide having 36 amino acids. It is closely related to pancreatic polypeptide and to neuropeptide Y
(which is found in the brain and autonomic nervous system). All these peptides end in tyrosine and are
Amidated at their carboxyl terminal.

B. Site
It is secreted from the jejunum; its secretion is stimulated by fat

C. Actions
1. it inhibits food intake
2. it inhibits gastric acid secretion and motility

XII. GUANYLIN

1. Structure
It is a peptide having 15 amino acids. It is so named because it binds to guanylyl cyclase. Certain strains of E.
coli which produce diarrohoea secrete an enterotoxin which has a structure close to guanlyin; this toxin
acts on the intestinal guanylin receptor (see below) to produce diarrhoea.
2. Site
It is secreted by intestinal cells, from the pylorus to the rectum.
3. Mechanism of action
Guanylin acts on guanylin receptors. It stimulates guanylyl cyclase  this increases the concentration of
intracellular cGMP  this increases the activity of the cystic fibrosis-regulated chloride channel  which
causes increased secretion of chloride into the intestinal lumen
4. Actions
a. it increases chloride secretion into the intestinal lumen and thus may regulate fluid movement. It acts
in the GIT in a paracrine fashion.
b. Guanylin receptors are also found in the kidneys, the liver, and the female reproductive tract; here, it
may be act in an endocrine fashion to regulated fluid movement in these tissues.

XIII. MICROHETEROGENEITY
This general term refers to a polypeptide hormone that is secreted in different forms due to derivatisation
( e.g. addition of a sulphate ) of a single amino acid residue; thus the number of amino acids is the same in these
different forms. For example, there are two groups of gastrins : one in which the tyrosine (in the 6 th position from
the carboxyl terminal) is sulphated and the other in which it is not . In other words, there are sulphated and non-
sulphated gastrins. In the case of gastrins, the sulphated and the non-sulphated forms are in equal amounts and
they are equally active.

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GIT SECRETIONS

Gastrointestinal Secretion

Saliva Gastric secretion Pancreatic Bile

secretion
Main Hypotonic; high HCl; pepsinogen; High bicartonate, Bile, salts, bilirubin,
characteristic bicarbonate; high intrinsic factor isotonic, pancreatic phospholipids,
K+; alpha amylase, lipase, pancreatic cholesterol

Chapter - 9
lingual lipase amylase, proteases
Factors Stimulated by HCl: stimulated by Bicarbonate: CCK: stimulates GB;
stimulating parasympathetic histamine, stimulated by CCK, parasympathetic:
and sympathetic; acetylcholine, secretion and stimulates GB
by food in gastrin: parasympathetic;
stomach Pepsinogen: enzymes:
stimulated by stimulated by CCK,
parasympathetic secretion
parasympathetic
Factors By sleep, Inhibited by HCl Inhibited by ileal
inhibiting dehydration, resection
atropine

Volume Osmolality pH Na+ K+ Cl- HCO3

GIT
(in L/day)
Plasma 3 300 7.4 150 5 110 24
Saliva 1.5 100 7.5 40 15-30 25 30
Gastric Juice 3 200 1 50 10 100 0
Pancreatic Juice 1.5 300 7.8 140 5 70 80
Bile 0.5 300 7.5 140 5-12 80 20

At the end of Volume (L/day) Na K+ Cl- HCO3

Duodenum 9.2 55 15 55 12
Jejunum 3.2 145 8 95 35
Ileum 1.2 135 7 55 75
Colon 0.2 35 85 10 25

XIV. PANCREAS
The pancreas has portions : exocrine and endocrine. In this section, the exocrine portion is discussed.
The exocrine portion secretes the pancreatic juice which contains enzymes important in digestion .

A. Functional anatomy
The exocrine cells have abundant rough endoplasmic reticulum and zymogen granules at the apexes of the
cells. The zymogen granules contain the enzymes. Secretion from them is emptied (by exocytosis) into small

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ducts; these small ducts join to form the pancreatic duct of Wirsung. The duct of Wirsung joins the common
bile duct to form the ampulla of Vater. The ampulla of Vater opens into the duodenum through the duodenal
papilla. The opening of ampulla of Vater is surrounded by a sphincter called the sphincter of Oddi. Some
individuals have an accessory pancreatic duct (called the duct of Santorini); the duct of Santorini opens into
the duodenum proximal to the opening of the ampulla of Vater.

B. Pancreatic juice
It is a colourless, odourless watery secretion isotonic with plasma. It is alkaline with a high bicarbonate content
of about 113 meq/L. (plasma bicarbonate content is about 24 meq/L). About 1500 mL of pancreatic juice is
secreted per day.
The alkaline pancreatic juice, along with bile and intestinal juice (which are also neutral or
alkaline), helps in neutralizing the gastric acid and raising the pH of the duodenal contents to about 6.0 to 7.0.
Thus, by the time the chyme reaches the jejunum, its reaction is nearly neutral, but the intestinal contents are
rarely alkaline.
Composition of the pancreatic juice
1. Inorganic constituents :
a. Cations : Na+, K+, Ca2+, Mg2+
b. Anions : HCO3-, Cl -, SO42-, HPO42-

2. Organic constituents
a. mucous
b. enzymes (refer chapter )
c. trypsin inhibitor
Conversion of the inactive proenzymes into active enzymes
The enzymes of the pancreatic juice are secreted as inactive proenzymes as follows :

3. Trypsinogen  to tryspin
Trypsinogen is converted to the active enzyme trypsin by the brush border enzyme enteropeptidase
(enterokinase) when the pancreatic juice enters the duodenum. Enteropeptidase has a high polysaccharide
content (of about 40%); this high polysaccharide content apparently prevents it from being digested itself
before it can exert its effect.

4. Conversation of other inactive pancreatic proteases into active forms

a. All the other inactive forms (e.g. chymotrypsinogens, proelastase, procarboxypeptidases) are converted
into
b. their active forms by trypsin. Trypsin can also activate trypsinogen; therefore, once some trypsin is
formed,
c. there is an auto-catalytic chain reaction.
d. Enteropeptidase deficiency occurs as a congenital abnormality and leads to protein malnutrition.

5. Trypsin inhibitor
This is secreted by the pancreas in the pancreatic juice. It is a polypeptide with a molecular weight of about
5000 to 6000.
Action : It inhibits both trypsin and chymotrypsin.

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6. Function
Trypsin is a very powerful enzyme by itself and also converts the other inactive pancreatic enzymes into their
powerful active forms. The conversion of trypsinogen to trypsin occurs in the duodenum by enteropeptidase.
However, it is possible that some trypsin may get activated within the pancreas itself. This would lead to
autodigestion of the pancreas. Trypsin inhibitor prevents this autodigestion by trypsin.

7. Trypsin and acute pancreatitis

a. One of the enzymes activated by trypsin is phospholipase A2. Phospholipase A2 converts lecithin to
lyso-lecithin, (by removing a fatty acid). Lysolecithin damages cell membranes.

Chapter - 9
b. Lecithin is a normal constituent of bile. It is possible that acute pancreatitis, phospholipase A 2 is
activated in the pancreatic ducts; this in turn forms lysolecithin from lecithin. Lysolecithin damages
the pancreatic tissue.
c. Small amounts of pancreatic digestive enzymes normally leak into the circulation, but in acute
pancreatitis, the circulating levels of the digestive enzymes rise markedly. Measurement of the
plasma amylase or lipase concentration is therefore of value in diagnosing the disease.

C. Regulation of pancreatic secretion

Secretion of pancreatic juice is primarily under the hormonal control of secretin and CCK-PZ.
1. Actions of secretin :
a. Acts on the pancreatic ducts to cause copious secretion of a very alkaline pancreatic juice that is rich
in HC03 and poor in enzymes; its effect is mediated by cAMP.
b. Stimulates bile secretion.

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2. Actions of CCK-PZ
Acts on the acinar cells and causes discharge of the zymogen granules; it causes low volume secretion of
pancreatic juice that is rich in enzymes; its effect is mediated by phospholipase C
Other hormones/factors
3. Gastrin
This plays a minor role in pancreatic secretion. It acts in two ways :
a. Direct action : it stimulates the pancreatic acinar cells directly and increases acinar secretion
b. Indirect action : it stimulates the parietal cells and increases HCl secretion; HCl in turn enters the
duodenum and releases both secretin and CCK-PZ. This causes increase in enzymes, bicarbonate and
water output.

4. VIP
VIP stimulates pancreatic secretion mainly rich in enzymes. It also stimulates intestinal secretion of
electrolytes and water.

5. Vagal stimulation
This causes secretion of a small amount of pancreatic juice rich in enzymes. The acetylcholine released acts
directly on the acinar cells to cause discharge of the zymogen granules; like CCK, acetylcholine acts on via
phospholipase-C. There is evidence for vagally mediated conditioned reflex secretion of pancreatic juice in
response to the sight or smell of food.

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XV. SALIVARY SECRETION

A. This is the first juice coming in contact with food. It is secreted by the salivary glands. The salivary glands are
located outside the GIT. Food mixes with the saliva on chewing (or mastication).
B. The main salivary glands are the parotid, submaxillary (also called submandibular) and sublingual glands.
The minor salivary glands are lingual, labial, buccal and palatine glands.
C. Depending on the secretion and histological appearance, there are two types of acini in the salivary glands.
These are

1. Serous acini:
Their cells have round nuclei with collection of secretory (zymogen) granules at their apices; these secrete thin
watery saliva rich in enzymes (ptyalin) .

2. Mucous acini :
Their cells have flattened basal nuclei; these secrete thick viscous saliva rich in mucin
Demilunes : sometimes, the mucous acini have caps of serous acini over them; these caps (crescentic in shape)
of serous acini over the mucous acini are called demilunes.
Table showing the histological type and the percentage contribution of the different salivary glands to total saliva

Gland Histological type Secretion % contribution of total saliva

Submaxillary Mixed Viscous 70
Parotid Serous Watery 20
Sublingual Mucous Viscous 5
Other glands 5

3. Composition of saliva
Volume
This is about 1.5 litres/24 hours at a rate of about 1ml/min. The rate of secretion is maximum during meals and
minimum during sleep

pH
Resting salivary glands : slightly less than 7
During active secretion : approaches 8

4. Hypotonic to plasma
Constituents
Water : 99.5%
Solids : 0.5%
Organic : 0.3 %
Inorganic : 0.2%

5. Ductal modification
a. The salivary juice formed in the acini first drains into ducts called intercalated ducts. The intercalated

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ducts drain the salivary juice into another type of ducts called striated ducts; these finally open into the
oral cavity. As the saliva flows through these ducts, its composition gets modified.
b. The saliva first formed in the acini (also called as primary secretion) is isotonic with plasma and its ionic
composition is approximately same as that of plasma. However, as this saliva flows through the ducts,
i. Na and Cl gets absorbed
ii. K and HCO3- is added
iii. It becomes hypotonic (this is because the ducts are relatively impermeable to water)
c. Thus, the final composition of the saliva secreted in the oral cavity depends on the rate of salivary flow
through the ducts. More the rate of flow, less will be the ductal modification.

Chapter - 9
i. At low rates
The saliva is hypotonic, slightly acidic, and rich in K; but has less Na and Cl
ii. At high rates
The saliva is still hypotonic (but closer to isotonic), with higher concentrations of Na and Cl.
iii. Effect of aldosterone on ductal modification
Its action on the salivary ducts is similar to its action on the collecting ducts of the kidney i.e. it increases Na
absorption and increases K secretion. Thus aldosterone increases the K concentration and decreases the Na
concentration of saliva. In Addison’s disease (where aldosterone is less), there is a high Na/K ratio in the saliva.

6. Enzymes in the saliva

a. Salivary alpha amylase or ptyalin :
This is produced by the salivary glands; it acts on starch and converts it into alpha limit dextrins and maltase. Its
optimum pH is 6.8 and it is activated by chloride ions.

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b. Lingual lipase
This is produced by the Ebners glands present on the dorsum of the tongue. It becomes active in the stomach
and can digest as much as 30% of ingested triglycerides.
Other constituents of the saliva
i. Mucins :
These are glycoproteins produced by the mucous acini of the salivary glands. Their function is to
lubricate the food and help in food bolus formation; they also bind bacteria and protect the oral
mucosa.
ii. IgA
The secretory immunoglobulin IgA is present in the saliva; it helps to fight against bacteria and
viruses.
iii. Lysozymes :
These are groups of enzymes which attack the walls of bacteria and destroy them
iv. Lactoferrin :
This binds iron and is bacteriostatic
v. proline-rich proteins
These protect tooth enamel and bind toxic tannins
vi. Kallikrein
This enzyme present in the saliva acts on alpha 2 globulin to produce bradykinin; bradykinin is a
polypeptide which causes vasodilatation.
vii. Nerve growth factor

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 Physiology

This is a polypeptide produced by the submaxillary salivary gland. It is useful for the growth and
maintenance of the sympathetic and sensory nerves.
viii. Sialogastrin
This is a gastrin-like substance present in the saliva

7. Functions of saliva
a. Preparation of the food for swallowing (bolus formation) :
Saliva mixes well with the food and the mucus present in the saliva acts as a lubricant. Food is made into a
bolus, which can be easily swallowed.
b. Solvent
To appreciate the sensation of taste, food has to be dissolved. Saliva acts as a Solvent which dissolves the
food materials and helps in stimulating the taste buds.
c. Speech
Saliva keeps the oral cavity moist; it helps in the movements of the lips and tongue. These factors help in
speech.
d. cleansing action
Continuous secretion of saliva washes off the food residues, bacteria and desquamated epithelial cells.
Lysozymes present in the saliva destroy bacteria. Thus, saliva cleans the oral cavity/teeth and helps in oral
hygiene. Patients suffering from xerostomia or atyalism (deficient salivation) have more chances of dental
infection than normal people.
e. Digestion
Salivary alpha amylase helps in starch digestion
f. Excretion
Saliva excretes mercury, lead and KI compounds.
g. Buffers in saliva
These help to maintain the oral pH at about 7.0. They also help neutralize gastric acid and relieve heartburn
when gastric juice is regurgitated into the oesophagus.

XVI. REGULATION OF SALIVARY SECRETION

Salivary secretion is exclusively under neural control; both sympathetic and parasympathetic nerves supply the
salivary glands.
A. Sympathetic nerves
These fibres arise from T1 to T4 segments of the spinal cord and reach the superior salivary ganglion. Post-
ganglionic fibres start here and run along the blood vessels and supply all the salivary glands. The sympathetic
fibres supply the blood vessels, the myoepithelial (or basket) cells and acinar cells.

B. Actions
1. Sympathetic stimulation causes secretion of small amounts of thick, viscous saliva rich in organic
constituents from the submandibular glands. Increased salivary secretion
a. Mechanism of action
Sympathetic stimulation /circulating catecholamines stimulate salivary secretion rich in enzymes through alpha
and beta receptors. Alpha receptor action is mediated through calcium ions and beta receptor action ismediated
through cyclic AMP.

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b. Vasoconstriction
The norepinephrine released brings about vasoconstriction and decreased blood flow; thus, the water content
of the secretion is less.
2. The myoepithelial (or basket) cells contract under the influence of norepinephrine and cause expulsion of
the already secreted saliva from the acinus.
B. Parasympathetic nerve fibers
These come from a nucleus present at the junction of the medulla and pons near the tractus solitarius. The
nucleus has got two parts :
1. The caudal part (called inferior salivary nucleus) :

Chapter - 9
This provides parasympathetic nerve fibres to acinar cells and blood vessels of parotid gland. These fibres
pass via the IX (i.e. glossopharyngeal ) nerve
2. The superior part (called superior salivary nucleus) :
This provides parasympathetic fibres to the acinar cells and blood vessels of the submaxillary and
sublingual glands. These fibres pass through the VII (i.e. facial ) nerve and the chorda tympani nerve.
Pain afferents from these glands run in the parasympathetic nerves.

3. Actions
Stimulation of the parasympathetic nerve fibres results in profuse secretion of watery saliva with a relatively low
content of organic material. Along with this secretion, there is a significant vasodilation in the salivary glands;
the vasodilation is likely to be due to VIP. (VIP is a co-transmitter with acetylcholine in some of the post-
ganglionic parasympathetic neurons). Atropine and other cholinergic blocking agents reduce salivary secretion.

4. Mechanism of action of parasympathetic nerves

GIT
1. Acetylcholine (Ach) released from the nerve endings directly act on the acinar cells and stimulate enzyme
secretion
2. Ach activates kallikrein; kallikrein in turn activates kininogen and converts it into bradykinin. Bradykinin
produces vasodilatation and increases the blood flow to the gland
3. VIP is a co-transmitter released along with Ach and causes vasodilatation.

C. Types of salivary secretion

1. Spontaneous or resting salivary secretion
Saliva is secreted continuously even in the absence of any known stimulus; this is called spontaneous or resting
salivary secretion. This is possibly due to release of minute amounts of acetylcholine into the gland. However,
spontaneous secretion cannot be blocked by atropine. It can, however, be blocked by metabolic poisons like
cyanide. This indicates that the spontaneous salivary secretion depends upon the metabolic activity of the
salivary glands. This type of secretion is responsible for keeping the oral cavity moist all the time.

2. Reflex secretion
This occurs in response to a stimulus. The reflex secretion can be further subdivided into
a. unconditioned (or inherent)reflex secretion
Food (and other substances) in the mouth causes reflex secretion of saliva (also, stimulation of the vagal
afferent fibres at the gastric end of the oesophagus results in reflex secretion of saliva)

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D. Pathway
Food in the mouth  stimulates the trigeminal, glossopharyngeal and vagal nerves  impulses in them are
carried to the superior and inferior salivary nucleus  reflex salivation
1. conditioned (or acquired) reflex secretion
2. Salivary secretion can be easily conditioned (as shown by Pavlov); the sight, smell or even thought of food
causes salivary secretion.
3. Deglutition or Swallowing
4. This is the process by which the chewed food is emptied form the mouth into the stomach. It is initiated
voluntarily but is completed reflexly.

 Pathway
Deglutition is initiated by afferent impulses in V, IX and X cranial nerves  impulses from there are carried and
integrated in the nucleus of the tractus solitarius and the nucleus ambiguus  from here, efferent fibres pass to
the muscles of the pharynx and tongue via the V, VII and XII cranial nerves.

 Mechanism
Swallowing is initiated by the voluntary action of passing the bolus of food with the help of the tongue to the
pharynx; thereafter, the process occurs reflexly. When food reaches the pharynx, it starts a wave of involuntary
contraction in the pharyngeal muscles; this pushes the food into the oesophagus. Peristalsis in the oesophagus
pushes the food down the oesophagus at a rate of about 4 cm/second. However, in the upright position, gravity
pulls the liquid/semisolid food to the lower end of the oesophagus faster than the wave of peristalsis.

 Other components of the swallowing reflex

1. inhibition of respiration
2. closure of glottis

XVII. GASTRO-OESOPHAGEAL JUNCTION

This performs the function of a sphincter. Its functions are
A. to cause orderly flow of food from the oesophagus into the stomach
B. to prevent reflux of gastric contents into the oesophagus

A. The gastro-oesophageal junction is made up of 3 components :

1. Intrinsic sphincter or the lower oesophageal sphincter (LES) :
This is formed by the oesophageal smooth muscle at its lower end; the LES (unlike the rest of the
oesophagus) is tonically active; however, it relaxes on swallowing. The tonic activity of the LES (in between
meals) prevents reflux of gastric contents into the oesophagus.
2. extrinsic sphincter
This is made up of skeletal muscle fibres of the crural portion of the diaphragm; these fibres surround the
oesophagus (at the point where it enters the diaphragm) and exert a pinchcock-like action on the
oesophagus.
3. Flap valve :
The oblique (or sling) fibres of the stomach wall create a flap valve at the gastrooesophageal junction; this
valve helps to close the junction whenever the intragastric pressure rises (and thus prevents regurgitation)

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B. Control of the gastro-oesophageal junction

This is under neural control.
1. Control of internal sphincter i.e. LES
The tone of LES is under neural control from the vagus.
a. the vagal endings which release acetylcholine  cause contraction of the internal sphincter
b. the vagal endings (via interneurons) which release NO and VIP  cause relaxation of the internal
sphincter

Chapter - 9
2. Control of external sphincter i.e. the crural portion of the diaphragm
This is under neural control from the phrenic nerves. The contraction of the crural portion of the diaphragm
is coordinated with respiration and contractions of the chest and abdominal muscles.

Note: Esophageal peristalsis can be initiated by deglutition ("primary" peristalsis) or local distention
("secondary" peristalsis).
Clinical correlates
3. Achalasia
This is the name given to the condition in which food accumulates in the oesophagus; due to this, the oesophagus
becomes dilated.
a. Cause :
i. the myenteric plexus of the oesophagus at the LES is deficient
ii. there is defective release of NO and VIP.
b. Because of the above,

GIT
i. there is increased resting tone in the LES
ii. the LES does not relax fully on swallowing
c. Management
i. pneumatic dilation of the LES
ii. myotomy (incision of the oesophageal muscle)
iii. injection of botulinum toxin into the LES (this acts by inhibiting release of acetylcholine)
4. Gastro-oesophageal reflux disease (GERD)
As the name suggests, in this condition there is reflux of acid gastric contents into the oesophagus. It is
due to LES incompetence (thus, it is the opposite condition to achalasia, in which there is increased tone
of LES).
a. Symptoms
i. heart burn and oesophagitis
ii. there can be ulceration and stricture formation (due to scarring of the tissue) in the oesophagus
iii. in severe cases, the internal/external sphincter are weak
iv. in less severe cases, there are intermittent periods where there is less neural drive to these
sphincters; the cause of this is not known.
b. Treatment
i. H2 receptor blockers (omeprazole) : this inhibits acid secretion
ii. Fundoplication : In this surgical procedure, a portion of the fundus of the stomach is wrapped
around the lower oesophagus  thus, the oesophagus is made to lie inside a short tunnel of
stomach

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 Physiology

5. Pharyngo-oesophageal sphincter
1. The sphincter at the upper end of the oesophagus is called the pharyngo-oesophageal sphincter. It is
formed by the tonic contraction of the crico-pharyngeus muscle. It is normally closed except during
swallowing. It prevents the entry of air from the mouth into the oesophagus. However, during the act of
swallowing (e.g. drinking, eating) some air is swallowed; this is called aerophagia (‘air eating’). Out of the
air that is swallowed, some is regurgitated through the mouth during belching, some is absorbed but much
of it is passed on to the colon. In the colon, some oxygen from the swallowed air is absorbed; colonic
bateria act on carbohydrate and other substances to produce hydrogen, hydrogen sulphide, carbon
dioxide, and methane. These latter gases are thus added to the air and passed as flatus. The smell in the
flatus is mostly due to the sulphides. Normally, the GIT has about 200 ml of gas; about 500 to 1500 ml of
gas is produced/day. In some individuals, gas in the intestine can cause cramps, rumbling noises (these
rumbling noises are called as borborygmi) and abdominal discomfort.

XVIII. STOMACH
A. Parts of the stomach
Cardia or cardiac orifice :
The part where the oesophagus enters the stomach is called the cardiac orifice or cardia. Fundus :
The portion of stomach which lies above the cardiac orifice is called the fundus.
1. Body :
The portion of the stomach below the fundus is called the body of the stomach.
Pyloric antrum or antrum/pyloric sphincter
At the end of the body of the stomach is the pyloric antrum or simply called the antrum. The pyloric antrum
leads into the pyloric canal. The pyloric canal opens into the duodenum and the opening is guarded by a
sphincter called pyloric sphincter.
2. Incisura angularis
A small notch on the lesser curvature between the body and the pyloric antrum is called incisura angularis.
A straight line from the incisura angularis to the greater curvature separates the pyloric antrum from the body.

3. Gastric glands
The shape and structure of the gastric glands is different in different parts of the stomach. In the fundus and the
body, the glands are long and straight. In the pylorus and in the cardiac area, the glands are short and tortuous.

Four different types of cells are present in the gastric glands; these are :
a. Parietal or oxyntic cells
b. Chief or zymogen cells
c. Mucous cells
d. Argentaffin cells
i. In the cardiac and pyloric regions
Here, the glands secrete mucous

ii. In the body and fundus

Here, the glands also contain
parietal (or oxyntic cells)  which secrete HCl and intrinsic factor and

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chief or zymogen or peptic cells  which secrete pepsinogens

These secretions mix with mucus secreted by the cells in the neck of the glands. Many such glands open
on the gastric pit; the gastric pit in turn opens on the surface of the mucosa.

iii. Surface epithelium

The surface epithelium contains mucous cells; these secrete mucous and bicarbonate.
Food is stored in the stomach, mixed with acid, mucus and pepsin, and released at a controlled steady
rate into the duodenum.

Chapter - 9
4. Function of HCl
a. Kills many ingested bacteria
b. Provides the necessary PH for pepsin to start protein digestion
c. Stimulates the flow of bile
d. Activates pepsinogen to pepsin

5. Blood supply and lymphatic supply

The stomach has a very rich blood and lymphatic supply. Blood is supplied by the cardiac arteries. Lymph drains
into the gastro-duodenal group and celiac group of lymph glands.
Nerve supply

6. Sympathetic
This is from the celiac plexus; the sympathetic supply causes
a. Relaxation of the muscle

GIT
b. Contraction of the sphincters
c. Vasoconstriction

7. Parasympathetic
This comes from the dorsal nucleus of the vagi located in the floor of the fourth ventricle. The right vagus
supplies the posterior surface and the left vagus supplies the anterior surface. They synapse with the myenteric
and Meissner’s plexuses. Post-ganglionic fibres start from here and supply the gastric glands.

8. The parasympathetic supply causes

a. Contraction of the muscle
b. Relaxation of the sphincter
9. Local nervous system
These are the myenteric and Meissner’s plexuses. Peristalsis is mainly coordinated by the local plexus.
Gastric juice Amount = about 2500 ml per day;
During meals, the gastric secretion is maximum and during sleep, it is minimum.
pH = about 1.0
Composition

The contents of the normal gastric juice in the fasting state are
a. Inorganic :
Cations are Na, K, Mg, H;

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 Physiology

Anions are Cl-, HPO42-SO42-

b. Organic
Pepsins, lipase, mucus, intrinsic factor

HCl secretion
As mentioned above, HCl is secreted by the parietal cells.
Content of HCl in parietal cell secretion
Pure parietal secretion has pH of about 0.87 and contains 0.17 N HCl. It is isotonic with plasma (with 150 meq of
H and 150 meq of Cl per liter).

Note
The pH of the cytoplasm of the parietal cells is 7.0 to 7.2
Plasma : H concentration = 0.00004 meq/L ; Cl concentration = 100 meq/L
The above-mentioned figures show that there is a very large H gradient against which the parietal cell has to
secrete H; thus, the transport mechanism is active. The active transporter is H – K ATPase.
Structure of the parietal cell
The parietal cell has
i. Apical membrane
This faces the lumen of the gastric glands; it contains the H-K ATPase
ii. Canaliculi
The resting cell has intracellular canaliculi, which open on the apical membrane of the cell
iii. Tubulo-vesicular structures
At rest
The parietal cells contain abundant tubulo-vesicular structures; these structures contain H-K ATPase in their
walls.

10. During stimulation of the parietal cells

a. The tubulovesicular structures move to the apical membrane and fuse with it; this helps in inserting many
more H+K+ ATPase molecules into the apical membrane. These H-K ATPase molecules are now exposed to the
K+ in the ECF; this activates the H+K+ ATPase and the H-K exchange begins.
b. Many microvilli project into the canaliculi; this greatly increases the surface area of the cell membrane in
contact with the gastric lumen.
Basolateral membrane
This is in contact with the interstitial fluid.

11. Mechanism of HCl secretion

a. Secretion of H secretion
As mentioned above, this is done by H+ -K+ ATPase.
The H+ is initially formed inside the parietal cell as follows :
CO2 + H2 O -- H2 CO3 -- H+ + HCO3-

The above reaction is catalyzed by carbonic anhydrase; the parietal cells a high content of carbonic anhydrase.
The HCO3- is extruded from the basolateral membrane into the interstitial fluid in exchange for Cl - (by HCO3 – Cl

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antiport).
Because of the efflux of HCO3 into the blood, the stomach has a negative respiratory quotient; in other words,
the amount of CO2 in the arterial blood is greater than the amount in gastric venous blood. When gastric acid
secretion is elevated after a meal, sufficient H may be secreted to raise the pH of systemic blood and make the
urine alkaline (post-prandial alkaline tide)

b. Secretion of Chloride
i. Chloride is extruded down its electrochemical gradient into the lumen through channels that are activated
by cAMP.

Chapter - 9
ii. In the gastric lumen, the H+ and Cl+ combine to form HCl.

12. Factors affecting HCl secretion

a. HCl stimulants
i. Histamine
This stimulates acid secretion by acting via H2 receptors  the H2 receptors stimulate Gs protein 
increases adenylyl cyclase activity  increases intracellular cAMP  stimulates protein kinases 
stimulates H-K ATPase  increases HCl output
ii. Acetylcholine
This stimulates acid secretion by acting via M3 muscarinic receptors  this in turn increases intracellular
free calcium  stimulates protein kinases  stimulates H-K ATPase  increases HCl output.
iii. Gastrin
Gastrin increases HCl output in two ways :
iv. Direct action :

GIT
via the gastrin receptors on the parietal cells  this in turn increases intracellular free calcium 
stimulates protein kinases  stimulates H-K ATPase  increases HCl output.

v. Indirect action (via ECL cells)

This is the main way by which gastrin increases HCl secretion.
Gastrin stimulates the gastrin receptors on the enterochromaffin-like (ECL) cells.

13. ECL cells :

a. These are the vesicle- and granule containing cells; the ECL cells are the predominant endocrine cell type
in the
b. acid-secreting portion of the stomach.
c. Stimulation of ECL cells  stimulates histamine secretion  which in turn stimulates HCl secretion.
d. ECL cells undergo hypertrophy when gastric acid secretion is suppressed for prolonged periods.
e. The different intracellular mediators interact with each other; thus, activation of one receptor type
potentiates
f. the response of another receptor type.
HCl inhibitors
 Somatostatin : this inhibits ECL cells.
 PGE2 : acts via Gi to decrease adenylyl cyclas222e activity and decrease intracellular cAMP.
 EGF and TGF : these also act via Gi.
 High acidity, H2 blockers, and atropine also decrease

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 Physiology

HCl secretion.

B. Organic constituents of the gastric juice

1. Mucous
This is of two types
a. insoluble or visible mucous : it is a polymer of glycoprotein with a high viscosity; it is secreted by the surface
epithelial cells and forms a 0.5 to 2.5 mm thick layer. It protects the gastric mucosa from the acid.
b. Non-parietal secretion includes the mucous, enzymes, and electrolytes. When HCl combines with either salts
or other substances, it gets neutralized and produces neutral chloride.

c. soluble mucous : this is secreted by the mucous neck cells and acts as a vehicle for HCl and other enzymes
secreted by the gastric glands.

2. Intrinsic factor
This is secreted by the parietal cells. It is a glycoprotein required for the absorption of vitamin B12. Its deficiency
leads to pernicious anaemia. Its secretion is stimulated by acetylcholine, gastrin and histamine.

3. Enzymes : pepsin, gelatinase, carbonic anhydrase, rennin, lipase, urease

a. Pepsin : this is secreted by the chief cells in the inactive form as pepsinogen. Pepsinogen is activated to
pepsin by HCl and pepsin itself. Molecular weight = 35000; optimum pH for activity is 1. 5 to 3.5. Beyond
3.5, pepsin is inactivated. Secretion of pepsin is stimulated by vagus, acetylcholine, gastrin, histamine and
insulin. Pepsin is an endopeptidase; it acts on denatured proteins and converts them into proteoses,
peptones and a few amino acids. It attacks the peptide linkages in which the amino groups are attached to
the aromatic amino acids.
b. Rennin : this is important in calves and human infants. Origin is not known. It is suggested to be produced
by chief cells. It acts on milk in the presence of calcium and causes its precipitation. It is absent in adult
humans and cows where its function is taken over by HCl and pepsin
c. Gelatinase : causes digestion of gelatin
d. Lipase : acts chiefly on tributyrin and other low molecular weight triglycerides. Its origin in humans is not
known. It is active between 4 to 5 pH and is inactive below pH 2.5. It is a weak fat-splitting enzyme and
becomes important for fat digestion only when there is pancreatic insufficiency.
e. Carbonic anhydrase : derived from the parietal cells
f. Urease : origin not known; converts urea into ammonia
Note : Salivary amylase can act in the stomach and converts starch into maltose till it is inactivated by gastric
acidity. It is inactivated within 30 to 60 minutes.

4. Gastric mucosal barrier

This protects the stomach from getting damaged by the acid in gastric juice. The mucosal barrier is made by The
mucus and The HCO3 -.
a. Mucus :
Source :
i. Neck cells of the gastric glands and
ii. surface mucosal cells.

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 GIT

Composed of Mucus is made up of glycoproteins called mucins; the mucins form a flexible gel on the
gastric mucosa.
b. HCO3-
Source :
Surface mucosal cells
HCO3- trapping
Most of the secreted HCO3 is trapped in the mucus gel.
Because of this, a pH gradient is established at the epithelial cells as follows :
a. on the luminal side : the pH is 1.0 to 2.0

Chapter - 9
b. at the surface of the epithelial cells : the pH is 6.0 to 7.0.
c. HCl secreted by the parietal cells in the gastric glands crosses this barrier in finger-like channels, leaving the
rest of the gel layer intact.
d. Mucus and HCO3- secreted by mucosal cells also play an important role in protecting the duodenum from
e. damage when acid-rich gastric juice is secreted into it.
f. Factors affecting mucus/HCO3- secretion
g. Prostaglandins stimulate mucus secretion.
h. HCO3- secretion is also stimulated by prostaglandins and by local reflexes.
i. Other factors which protect the gastric mucosa
j. Trefoil peptides
k. Some of the resistance of the mucosa of the GIT to autodigest is also provided by trefoil peptides in the
gastric mucosa.
These are of several types and are acid-resistant.
5. Other places where trefoil peptides are found :

GIT
a. Hypothalamus
b. Pituitaryand
c. In rapidly proliferating tissues.

6. Structure
They are characterized by a three-loop structure that looks like a three-leaf clover.
In mice in which the gene for one of these peptides has been knocked out, the gastric and intestinal mucosa are
histologically abnormal and there is a high incidence of benign and malignant mucosal tumours.

7. Factors which tend to damage the mucosal barrier

a. Regurgitated bile salts acting as detergents
b. Alcohol
c. Nicotine
d. Salicylates and other drugs that decrease mucus and hco3- secretion
e. Lyso lecithin in the regurgitated food
f. Ischaemia of gastric mucosa
g. adrenergic agonists like adrenaline and noradrenaline by decreasing HCO3- secretion.

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 Physiology

8. Gastric Motility
a. Receptive relaxation
b. When food enters the stomach, the fundus and the upper portion of the body of the stomach relax and
accommodate the food (without any increase of pressure). This relaxation of the stomach is called receptive
relaxation.
9. Mechanism
Receptive relaxation is vagally mediated; it is triggered by movement of the pharynx and oesophagus.

10. Peristalsis
a. This is controlled by the gastric BER. Peristalsis begins immediately after the receptive relaxation and
helps in mixing and grinding the food.
b. Peristalsis begins in the lower portion of the body and goes toward the pylorus. The contraction of the
distal stomach caused by each wave is called antral systole; the contraction waves occur at the rate of 3
to 4 per minute and each contraction wave can last up to 10 seconds.

11. Regulation of gastric emptying

a. For this, the antrum, pylorus, and upper duodenum function as a unit. First, there is contraction of the
antrum; this is followed by sequential contraction of the pyloric region and then the duodenum.
b. Importance of the initial antral contraction
c. The initial contraction of the antrum prevents solid masses from entering the duodenum; instead of
being ‘prematurely’ pushed into the duodenum, the food particles are allowed to be mixed and
crushed. Thus, the more liquid gastric contents are sent in small quantities into the duodenum.
d. Normally, there is no regurgitation of food from the duodenum; the reasons are :
i. The contraction of the pyloric segment persists slightly longer than that of the duodenum
ii. CCK and secretin may constrict the pyloric sphincter.

12. Hunger Contractions

These are the gastric contractions that occur between meals; they are presumably associated with the
migrating motor complexes (MMCs). Hunger contractions can sometimes be felt and may even be mildly
painful. They are so called because they are associated with the sensation of hunger. However, they have
no role in the regulation of food intake.

13. Regulation of Gastric motility and secretion

This is by neural and humoral mechanisms.
Neural mechanisms :
This is by
a. local autonomic reflexes (involving cholinergic neurons) and
b. impulses from the CNS by way of the vagus nerves.
Vagal stimulation increases gastrin secretion by release of GRP (see above). Other vagal fibers release
acetylcholine; the released acetylcholine acts directly on the cells in the glands in the body and the fundus to
increase acid and pepsin secretion. Stimulation of the vagus nerve in the chest or neck increases acid and
pepsin secretion, but vagotomy does not abolish the secretory response to local stimuli.

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 GIT

Humoral mechanisms
Discussed above.
Gastric juice is secreted continuously throughout the day. During the resting state, only a small amount is
secreted ; during digestion, the secretion increases.

14. Gastric juice secretion can thus be divided into two main phases :
a. Digestive phase
b. Inter-digestive (or resting) phase

Chapter - 9
15. The digestive phase is further sub-divided into
a. Cephalic phase
b. Gastric phase
c. Intestinal phase
Both neural and humoral mechanisms regulate the secretion of gastric juice during the digestive phase. Neural
control mechanisms dominate in the cephalic phase; humoral control mechanisms dominate in the gastric
phase.

a. Cephalic phase
This is the initial reflex phase. These are vagally mediated responses induced by activity in the CNS.
The presence of food in the mouth reflexively stimulates gastric secretion. The efferent fibers for this reflex are in
the vagus nerves. Thus, even before the food enters the stomach, there is stimulation of gastric secretion.
This vagally mediated reflex can be easily conditioned. For example, the sight, smell, and thought of food
increase gastric secretion. Cephalic influences are responsible for one third to one half of the acid secreted in

GIT
response to a normal meal.

i. Psychological states
Psychologic states can affect gastric secretion and motility; these changes are mediated principally via the
vagi.
ii. William Beaumont made observations on a patient called Alexis St. Martin. Martin (a Canadian) had a
permanent gastric fistula resulting from a gunshot wound; thus, William Beaumont could study the stomach in
various psychological states of the patient. He noted the following :
 anger and hostility :
 This was associated with turgor, hyperemia, and hypersecretion of the gastric mucosa
 fear and depression :
 This was associated with decrease in gastric secretion, blood flow and gastric motility.
Note : vagotomy abolishes the cephalic phase.

b. Gastric phase
The gastric phase of secretion begins when the food enters the stomach. Food in the stomach potentiates the
increase in gastric secretion produced by the sight and smell of food and the presence of food in the mouth.

Mechanisms
The gastric phase is controlled by both neural and humoral mechanisms.
Neural mechanisms

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 Physiology

i. Presence of food in the stomach stretches the gastric mucosa. This leads to stimulation of secretion in
two ways :
a) long vago-vagal reflex mechanism
b) Vagal nerve endings are stimulated  impulses travel via vagal afferents to the vagal nucleus 
then relayed through vagal efferents  to stimulate gastric juice secretion
c) local gastric reflexes in the intrinsic submucous (or Meissner’s) plexus
Receptors in the gastric mucosa are activated by stretch and chemical stimuli, mainly amino acids and
related products of digestion. This in turn activates the submucous (or Meissner’s) plexus and causes
acid secretion.
The products of protein digestion also bring about increased secretion of gastrin, and this augments
the flow of acid.
Note :
Thus, stretch stimulates gastric secretion by
i. long vago-vagal reflex
ii. local reflex
iii. Humoral mechanisms
Discussed above (see the effects of gastrin, histamine and acetylcholine)

c. Intestinal influences
i. Although gastrin-containing cells are present in the mucosa of the small intestine as well as in the
stomach, instillation of amino acids directly into the duodenum does not increase circulating gastrin
levels.
ii. Fats, carbohydrates, and acid in the duodenum inhibit gastric acid secretion, pepsin secretion and
gastric motility via neural and hormonal mechanisms. The hormone involved is probably peptide YY.
Gastric acid secretion is increased following removal of large parts of the small intestine. The
hypersecretion, which is roughly proportionate in degree to the amount of intestine removed, may be
due in part to removal of the source of peptide YY.

iii. Other Influences

 Hypoglycemia
This acts via the brain and vagal efferents to stimulate acid and pepsin secretion.
 Caffeine and alcohol
These act directly on the mucosa to increase gastric secretion.
 Smoking
Nicotine present in the smoke stimulates gastric secretion. Light smoking stimulates and heavy smoking
inhibits secretion due to excess nicotine.

Regulation of Gastric Motility & Emptying

Rate of gastric emptying
This depends on
i. the type of food ingested :
 Carbohydrate-rich food : leaves the stomach in a few hours.
 Protein-rich food : leaves more slowly(3-4 hrs)
 Fat-rich food : leaves most slowly(5-6 hrs)

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 GIT

ii. the osmotic pressure of the material entering the duodenum :

Hyperosmolality of the duodenal contents decreases gastric emptying. The hyperosmolality is sensed by
"duodenal osmoreceptors"; the effect is probably neural in origin.

C. Peptic Ulcer
Localised erosion and destruction of gastric or duodenal mucosa is called peptic ulcer.
Causes
1. Breakdown of gastric mucosal barrier
Peptic ulcer is primarily due to breakdown of the gastric mucosal barrier. The breakdown can be due to

Chapter - 9
i) Infection with the bacterium Helicobacter pylori
ii) Aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs)
These inhibit the production of prostaglandins and consequently decrease mucus and HC03 secretion (see
above).

2. Excess acid secretion

E.g. Zollinger-Ellison syndrome. This syndrome is seen in patients with gastrinomas. Most of the gastrinomas
are found in the pancreas (although they can occur in the stomach and duodenum). The gastrin causes
prolonged hypersecretion of acid. Lipids and protein digestion are affected due to the high acidity and
there is steatorrhoea and diarrhoea.

3. Chronic stress

4. Ischemia of gastric mucosa

GIT
Treatment
1. Inhibition of acid secretion by :
a. H2 histamine receptors blockers
Drugs e.g. cimetidine block the H 2 histamine receptors on parietal cells.
b. Omeprazole
This inhibits the H+-K+ ATPase on the parietal cell.
c. H. pylori can be eradicated with antibiotics
d. Ulcers which are due to NSAIDs can be treated by stopping the NSAID; if for some reason, this is not
advisable, then treatment can be done with the prostaglandin agonist misoprostol.

Functions of the Stomach

1. Storage function : the stomach receives large quantities of food taken in a short time and stores it for 2 to
3 hours.
2. Digestive function : The stomach mainly helps in the digestion of proteins; pepsin in the gastric juice is an
important proteolytic enzyme
3. Mechanical churning or grinding action : food is broken into smaller particles and converted into chyme;
this facilitates the digestive process
4. Produces intrinsic factor (IF) : IF is 49-kDa glycoprotein ; it binds to cyanocobalamin (vitamin B 12) and is
necessary for its absorption from the small intestine.
5. Bacteriolytic : The HCl that is produced in the stomach kills bacteria

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 Physiology

6. Absorption : water, alcohol, saline are absorbed in the stomach to some extent.
7. Conversion of ferrous to ferric ion : iron present in the colloidal form is liberated from the food. Then it is
oxidized to ferric from the ferrous state. This is done by the acid and is later reduced to ferrous by ascorbic
acid.
Cyanocobalamin is a cobalt-containing vitamin. Deficiency of this vitamin causes megaloblastic anaemia and
deterioration of certain sensory pathways in the CNS. If the deficiency of cyanocobalamin is due to lack of
the intrinsic factor, oral administration of cyanacobolamin will not be effective but parenteral
administration will be effective.
Deficiency due to an inadequate dietary intake of cyanocobalamin is very rare; this is probably because the
minimum daily requirements are quite low and the vitamin is found in most foods of animal origin.

D. Mechanism of Vitamin B12 reabsorption

1. Vitamin B12 normally binds to intrinsic factor and forms a complex with it; this complex is taken up by a
protein called cubilin; cubulin is a high-affinity apolipoprotein in receptors in the distal ileum. This
triggers absorption of the complex by endocytosis.
2. In the ileal enterocytes, the cyanocobalamin is transferred to transcobalamin II; transcobalamin II is a
cyancobalamin transport protein that transports the vitamin in plasma.

3. Causes of cyanocobalamin deficiency

a. gastrectomy : this removes the intrinsic factor-secreting tissue pernicious anemia,
b. In this disease, there is autoimmune destruction of the parietal cells.
c. diseases of the distal ileum.

4. Effects of gastrectomy
a. pernicious anaemia develops; as mentioned above, in such cases, the cyanocobalamin deficiency
can only be treated by parenteral injection of cyanocobalamin.
b. Digestion of food : the gastric juice contains pepsin, which helps in protein digestion; however, the
pancreatic enzymes can digest the proteins and thus nutrition can be maintained. Thus, protein
digestion is not affected.
c. These patients are prone to develop iron deficiency anemia and other abnormalities, and they must

eat frequent small meals.

d. Dumping syndrome
Patients with gastrectomy or gastrojejunostomy may have symptoms of weakness, dizziness and sweating
after meals; this is referred to as the dumping syndrome. The reasons for the symptoms are :
Hypoglycaemia
a. This occurs because of the following sequence of events
b. In gastrectomized patients  there is rapid absorption of glucose from the intestine  the hyperglycemia
causes abrupt rise in insulin secretion  thus they may develop hypoglycemic symptoms about 2 hours
after meals.
c. Rapid entry of hypertonic meals into the intestine  this cause the movement of a lot of water into the
gut  there is significant hypovolemia and hypotension
d. stimulation of the autonomic reflexes : this occurs secondary to distension of the small intestine and
release of hormones from the gut due to rapid entry of gastric contents into the duodenum and jejunum

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 GIT

e. small stomach syndrome

5. This occurs when partial gastrectomy is done. The symptoms are

a.there is distension and discomfort on food intake; thus, food intake decreases with consequent loss of
weight
b. vomiting may occur due to entry of bile into the stomach
c. diarrhoea and steatorrhoea may occur due to failure of fat digestion
d. palpitation and flushing

Chapter - 9
6. Small Intestine
3 regions: duodenum, jejunum, and ileum
a. Mucosa (tunica mucosa): villi (supported by lamina propria) + glands (open into intervillar spaces;
embedded in lamina propria) epithelium: wet surface epithelia + goblet (oligomucous) cells (produce
mucinogen > mucus). villi: simple columnar; surface absorptive cells with with microvilli forming brush
(striated) border and glycocalyx (rich in disaccharidases and dipeptidases); manufacture secretory protein
and protein J binding IgA. Glands: simple tubular (= crypts of Lieberkühn)
b. Epithelium: simple columnar (resemble surface absorptive cells)
basal exocrinocytes (Paneth) cells (apical eosinophilic granules)
APUD cells (endocrinocytes; clear cytoplasm; vesicular basal nuclei): Amino Precursor Uptake and
Decarboxylation: peptide or amine-secreting cells of gastrointestinal tract and other endocrine organs
c. lamina propria: underlying loose ct: lacteals take up lipids; capillaries take up amino acids and
carbohydrates.
d. Gut-Associated Lymphoid Tissue (GALT): lymphoid elements (scattered B and T cells, plasma cells, mast

GIT
cells, macrophages), indivual lymphnodules and aggregated lymnodules in ilium.
e. muscularis mucosae: thin layer smooth muscle may run up into villi; movement in mucosa
f. Submucosa: fibroelastic ct; spiral plicae circulares (= folds) especially in jejunum; glands (in duodenum);
submucosal (Meissner) nervous plexuses (small parasympathetic ganglia)
g. functions: absorption of monosaccharides and amino acids via active transport; bile salts emulsify fatty
acids and monoglycerides forming micelles which along with glycerol move through sER of surface cells
where they are reesterified to triglycerides and coated with protein to form chylomicrons (lipoprotein
droplets) that exit cells and are taken up in lacteals (= chyle)
h. BRUNNER’S GLANDS are compound glands of the duodenum and upper jejunum. They are embedded in
the submucous tissue and lined with columnar epithelium They secrete a thick clear alkaline mucinous
solution which helps in protecting the duodenal mucosa from gastric acid.
i. Paneth cells—endocrine cells located in the depths of the crypts of Lieberkuhn—secrete defensins,
naturally occurring peptide antibiotics that are also secreted elsewhere in the body .
j. Defensins: The principal defense molecules secreted by Paneth cells are alpha-defensins, also known as
cryptones. These peptides have hydrophobic and positively-charged domains that can interact with
phospholipids in cell membranes. This structure allows defensins to insert into membranes, where they
interact with one another to form pores that disrupt membrane function, leading to cell lysis. Due to the
higher concentration of negatively-charged phospholipids in bacterial than vertebrate cell membranes,
defensins preferentially bind to and disrupt bacterial cells, sparing the cells they are functioning to protect.
Paneth cells are stimulated to secrete defensins when exposed to bacteria (both Gram positive and
negative types) or such bacterial products as lipopolysaccharide, muramyl dipeptide and lipid A.

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 Physiology

k. Other secretions: In addition to defensins, Paneth cells secrete lysozyme, zinc and phospholipase A2,
which have clear antimicrobial activity. This battery of secretory molecules gives Paneth cells a potent
arsenal against a broad spectrum of agents, including bacteria, fungi and even some enveloped viruses.
l. Paneth cells secrete a number lysozymes into the lumen of the crypt, thereby contributing to maintenance
of the gastrointestinal barrier
m. Muscularis externa: two or more muscle layers (inner circular [tight helix]; outer longitudinal [loose helix]);
myenteric (Auberbach) plexuses between muscle layers

E. Large Intestine
1. No pitts or villi; divided into cecum, appendix, ascending, transverse, descending, and sigmoid colons,
rectum, and anal canal. Functions in absorption of water, electrolytes, some vitamins, remaining amino
acids, lipids, and carbohydrates; compacts feces.
2. Mucosa : epithelium simple (surface epithelial cell) columnar absorptive epithelium with abundant goblet
(oligomucous) cells, lamina propria: underlying loose ct; glands (= crypts of Lieberkühn) simple columnar
epithelium, regenerative cells, and APUD (enteroendocrinocytes) cells in base release paracrine hormones
muscularis mucosae: thin layer smooth muscle
3. Muscularis externa:two muscle layers (inner circular [tight helix; modified in anal sphincters]; outer
longitudinal [loose helix]) modified as taniae coli: 3 thickening separate haustra coli (Roman device for
hauling water; sacculations); (Auberbachs) myenteric plexuses; sympathetic ganglia and fibers between
muscle layers; peristaltic action independent.
4. Serosa (Adventitia): irregular dense ct surrounded by mesothelium (serosa) or bound to body wall
(adventitia); appendices epiploicae = small fat-filled pouches
5. Appendix: surface epithelium with many goblet cells; glands relatively shallow; lamina propria infiltrated
with lymphoid cells; lymph nodules in submucosa
6. Anorectal junction: abrupt change at anal valves from simple columnar of rectum to stratified squameous
epithelium (keratinizing type) of anal canal; rectal glands short; lamina propria infiltrated by lymphoid cells.
7. Anal Canal: anal columns = longitudinal folds joined at orifice to form anal valves and anal sinuses.
8. Circumanal glands, hair follicles, and sebaceous glands. Spinincters formed by muscularis externa.

XIX. CARBOHYDRATES
A. Dietary carbohydrates
These are :
1. Monosaccharides : fructose, glucose
2. Disaccharides : lactose (milk sugar), sucrose (cane sugar or table sugar)
3. Polysaccharides :

The only digestible polysaccharides in humans are the starches (starches are polymers of glucose). Dietary
starches can be of :
a. Animal origin :
i. Glycogen :
Glycogen is mostly straight in structure (with glucose molecules attached to each other by 1:4 alpha linkage);
there is some side-branching also (here the linkage is by 1:6 alpha linkage)
b. Plant origin :

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 GIT

i. Amylopectin :
This is the main dietary starch (constituting more than 80 to 90%).This is just like glycogen, with even fewer side
branches.

ii. Amylose :
This has no side branches.

iii. Cellulose :
This cannot be digested in humans.

Chapter - 9
iv. Digestion
Final end products :
The end products of carbohydrate digestion are the monosaccharides fructose, glucose and galactose. Only
monosaccharides can be absorbed from the GIT.

B. Site :
Although starch digestion begins in the mouth (by salivary alpha amylase), almost all starch digestion occurs in
small intestine.

C. Enzymes :
1. Salivary alpha amylase (ptyalin)
2. Pancreatic alpha amylase
3. Small intestine brush border enzymes :

GIT
Alpha-dextrinase (also called isomaltase), sucrase, maltase, lactase, trehalase
(Note : alpha-dextrinase and sucrase are separate subunits of a single protein)
Alpha amylase (salivary and pancreatic) digestion :
The alpha amylase acting on starch can break only the 1:4 alpha linkages;
They cannot break 1:6 alpha linkages, terminal 1:4 alpha linkages and 1:4 alpha linkages next to branching points.
Thus, the end products of amylase digestion are not monosaccharides; the end products are :
i. Oligosaccharides
ii. Maltose (a disaccharide)
iii. Maltriose (a trisaccharide)
iv. Alpha-dextrins (these are glucose polymers containing on an average 8 glucose molecules containing 1:6
alpha linkages)
The above end products are further digested by the brush border enzymes.

Note : the activator for salivary alpha amylase is chloride ion.

Brush border enzyme digestion

437
 Physiology

This is shown in the table below :

Enzyme Acts on End products
Alpha dextrinase or isomaltase Alpha dextrins, maltose, maltriose Glucose
(this is the main enzyme for
breaking 1:6 alpha linkages)
Sucrase Sucrose, maltose, maltriose Sucrose : glucose and fructose
Maltose : 2 glucose
Maltriose : 3 glucose
Maltase Maltose, maltriose, alpha dextrins Glucose
Lactase Lactose Glucose, galactose
Trehalase Trehalose (this is a 1:1 alpha 2 glucose
linkage dimer of glucose

D. Absorption
Site :
Absorption of the monosaccharides occurs in the small intestine.
Amount of monosaccharides that can be absorbed:
Absorption is not regulated. The intestine can absorb more than 5 kg of dietary sucrose/day. Almost all the
glucose and galactose present in the intestine can be absorbed. The maximal rate of glucose absorption from
intestine is about 120 gram/hr.

‘GLUT’ SERIES (Glucose Transporters)

GLUT 1 Blood brain barrier, brain, placenta, kidney etc
GLUT 2  cells of is lets of pancreas, liver, epithelial cells of small intestinal / renal
tubules
GLUT 3 Brain, placenta, kidney etc
GLUT 4 Insulin – stimulated glucose uptake in skeletal muscle / adipose tissue
GLUT 5 Fructose transport in jejunum / sperm
GLUT 6
GLUT 7 Liver, G-6-P in Endoplasmic reticular

Glucose absorption
Site Transport mechanism Insulin
Intestine SGLT No effect
Kidney SGLT No effect
Muscle (SK muscle / cardiac GLUT 4 Favour
muscle)
Adipose GLUT 4 Favour
Liver (Hexokinase) Favour
Insulin does not affect the absorption of glucose in:
Kidney, intestine, RBC, brain.

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 GIT

E. Mechanism
1. Glucose/galactose (hexoses)
a. From lumen to enterocyte
These are absorbed by sodium-dependent secondary active transport (the transporter is a symport and is
called SGLT or sodium linked glucose transport)

F. Salient features of SGLT:

1. Just like the GLUT series of transporters, SGLT also crosses the membrane 12 times (with its COOH and NH2
terminals on the cytoplasmic side of the membrane)

Chapter - 9
2. It is present in the kidney and intestine
3. It is not affected by insulin
4. It transports glucose and galactose
5. It has 3 binding sites :
a. 2 for sodium and
b. 1 for glucose or galactose

From enterocyte to the interstitium

This is by GLUT 2. From the interstitium, it diffuses into blood.
a. Fructose (hexose)
Its absorption is independent of sodium. It is transported by facilitated diffusion by GLUT series of transporters. 2
GLUT series of transporters are involved :
i. from lumen to enterocyte : GLUT 5
ii. from enterocyte to interstitium : GLUT 2

GIT
Fructose absorption occurs rapidly because most of the fructose is converted into glucose and lactic acid within
the enterocyte; this maintains a high concentration gradient for diffusion.
b. Pentoses
These are absorbed by simple diffusion.

XX. PROTEINS
A. Digestion
Generally, proteins must be digested into small polypeptides before being absorbed.
Enzymes responsible for protein digestion

1. Gastric enzyme : viz pepsins

a. The pepsin precursors are pepsinogens. Pepsinogens are converted into pepsins by gastric HCl.
Pepsinogens are ssecreted by the chief cells of the stomach.
b. Pepsins break peptide bonds adjacent to aromatic amino acids (e.g. next to phenylalanine, tyrosine);
their break down products are polypeptides of different sizes.
c. Importance of protein digestion in stomach :
d. Although only 10-15% of the protein digestion occurs in stomach, these protein digestion products act
as secretogogues; these secretogogues stimulate secretion of proteases by the pancreas.

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 Physiology

2. Pancreatic and intestinal enzymes

The pancreatic and intestinal enzymes involved in protein digestion are shown below; the table also shows the
site of break down of the peptide bonds by these enzymes:

Enzymes Site of break down of peptide bonds

Pancreatic enzymes
i. Trypsin Carboxyl side of basic amino acids (arginine or lysine)
ii. Chymotrypsins Carboxyl side of aromatic amino acids
iii. Elastase Carboxyl side of aliphatic amino acids
iv. Carboxypeptidase A Carboxyl terminal amino acids that have aromatic or branched aliphatic side
chains
v. Carboxypeptidase B Carboxyl terminal amino acids that have basic side chains
Intestinal brush border enzymes
i. Aminopeptidases Amino terminal amino acid
ii. Carboxypeptidases Carboxy terminal amino acid
iii. Endopeptidases Midportion of peptide molecules
iv. Dipeptidases Two amino acids

The pancreatic protein digestion enzymes mentioned above exist as their inactive precursors :
Inactive precursor Active enzyme
Trypsinogen Trypsin
Chymotrypsinogens Chymotrypsins
Proelastase Elastase
Procarboxypeptidase A Carboxypeptidase A
Procarboxypeptidase B Carboxypeptidase B

B. Activators :
1. Trypsinogen is converted into trypsin by enteropeptidase (previously called enterokinase)
2. Trypsin in turn converts :
a. More trypsinogen into trypsin (autocatalysis)
b. The other inactive precursors mentioned above into their active form

C. Endo- and exopeptidases

1. Endopeptidases
Trypsin, chymotrypsins and elastase are called endopeptidases; this is because they break the interior
peptide bonds in the peptide molecules.
2. Exopeptidases
The carboxypeptidases and aminopeptidases are called exopeptidases; this is because they break the
terminal amino acids.

D. Absorption
Mechanisms
From lumen to enterocyte

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 GIT

1. For amino acids

a. Na+ - amino acid secondary active transport
b. Na+ Cl- - amino acid secondary active transport
c. Na+ - independent transport of amino acid
2. For di-and tripeptides
H – dependent transport mechanism

3. Proteins
1. Although polypeptides with greater than 3 peptides are poorly absorbed, some proteins can still be

Chapter - 9
absorbed, especially in infants. For instance, the secretory immunoglobulins (IgAs) in the maternal colustrum
are absorbed by endocytosis from the intestine and then into circulation by exocytosis. Protein absorption
decreases with age
2. but still it persists in adults. Absorption of certain food protein antigens from the intestine can cause allergy.
3. Absorption of protein antigens (especially bacterial/viral proteins) occurs in M or microfold cells; M cells are
4. specialized intestinal epithelial cells that overlie the Peyer’s patches (Peyer’s patches are aggregates of
lymphoid tissue in the intestine)

a. Secretory immunity
Antigen  from the M cells go to  lymphoid cells and activate the lymphoblasts  these enter the
circulation  and reach the intestinal mucosa and other epithelia. Now, if these lymphoblasts are exposed
again to the same antigen, IgA is secreted.

b. Protein in stools

GIT
All the ingested protein is absorbed (95 to 97 % in the small intestine and the remaining 2 to 5 % is digested by
bacterial action in colon and then absorbed). Thus, there is no ingested protein in stool. The protein in stool is
thus derived from :
i. bacteria within the colon
ii. cellular debris
Absorption from the enterocyte to interstitium
The amino acids and peptides are transported across the basolateral membrane of the enterocytes by
facilitated diffusion or by simple diffusion. They they enter the capillaries of the villus by simple diffusion

Amino acid ------ Amino acid --------- Amino acid

Peptide ----------- Peptide --------------- Peptide

Enterocyte
Absorption of amino acids is rapid in duodenum/jejunum but slow in ileum.
E. Source of proteins
1. Exogenous (or dietary) proteins : 50%
2. Endogenous proteins : 50%
a. From secretory proteins in digestive juices (25% )
b. From desquamated cells (25% )

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 Physiology

Is protein absorption from intestine regulated

Unlike absorption of carbohydrate, absorption of proteins from the intestine seems to be regulated. For example,
in starvation ( or if the intestine is partly resected), the brush border enzyme activity increases.

F. Nucleic Acids
1. Nucleic acids are digested by the pancreatic nucleases (viz. ribonuclease and deoxyribonuclease) into
nucleotides. The nucleotides are further split into nucleosides and phosphoric acid by intestinal enzymes. In
turn, nucleosides are split into their sugars and purine/pyrimidine bases. The purine/pyridmidine bases are
absorbed by active transport.

G. Fats and lipids

1. Digestion
Fat digestion starts primarily in the duodenum. Digestion is by lipase; lipase comes from three sources
a. Lingual lipase
This is secreted by Ebner’s glands present on the dorsal surface of the tongue; lingual lipase can digest up
to 30% of the dietary triglycerides. Lingual lipase acts on triglycerides to give fatty acids and 1,2 –
diacylglycerols.
b. Pancreatic lipase
This is the most important enzyme for lipid digestion; it acts on triglycerides to give fatty acids and
monoglycerides.

H. Gastric lipase
This is not important in humans except in pancreatic insufficiency; it acts on triglycerides to give fatty acids and
glycerol.
1. Pancreatic lipase
Types of pancreatic lipase
a. Colipase-activated pancreatic lipase
Colipase is a pancreatic enzyme; it activates pancreatic lipase. Colipase itself is secreted as
procolipase; trypsin activates procolipase to colipase.
This type of pancreatic lipase can only split triglycerides.
b. Bile salt-activated pancreatic lipase
This is less active (about 10 to 60 times) than colipase-activated pancreatic lipase. However, it can split
triglycerides, cholesterol esters, esters of fat-soluble vitamins and phospholipids.

2. Action
Pancreatic lipase splits the fatty acids in position 1 and 3 of the triglycerides but not the fatty acid in position 2.
Thus, it splits triglycerides into 2 fatty acids and 2-monoglyceride.

I. Emulsification :
1. Meaning :
The process of break down of fat into small fat droplets (less than 1 micrometer in diameter) is called
emulsification.

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 GIT

2. Carried out by :
Bile salts, lecithin and monoglycerides.

3. Importance :
Fats must first be emulsified before pancreatic lipase can act on them.
Other pancreatic enzymes for fat digestion

4. 2.Cholesteryl ester hydrolase :

This acts on dietary cholesteryl esters and splits it into cholesterol.

Chapter - 9
5. 3.Phospholipase A2
a. This exists as pro-phospholipase A2; it gets activated by trypsin into phospholipase A2. It acts on
phospholipids to liberate fatty acids and lysophospholipids.
b. End products of fat digestion in the intestinal lumen
c. Fatty acids, monoglycerides, cholesterol and lysophospholipids.

J. Micelle formation
1. What is a micelle ?
A micelle (approx. 5 nm in diameter) is a spherical aggregate consisting of 2 ‘parts’

2. A central lipid phase (hydrophobic) :

a. The center of the micelle has digested end products of fat (viz. fatty acids, monoglycerides, cholesterol,
lysophospholipids); it also has the fat-soluble vitamins.

GIT
b. The fat products have their hydrophobic chains facing the interior and their polar ends facing the water
phase outside.

3. A peripheral water phase (hydrophilic):

a. The center is surrounded by a peripheral water phase consisting of bile salts.
b. (Thus, micelle is formed by digested end products of fat in the center and bile salts in the periphery).
c. Importance of micelle formation
d. There is a water layer called the unstirred water (USW) layer in between the intestinal lumen and the
intestinal cell. Since fats do not dissolve in water, micelle formation helps in passing through the USW
layer to reach the enterocyte. This is because the fat products are kept in the center of the micelle and
the water-soluble bile salt is in the periphery.
e. The micelle moves down its concentration gradient to reach the surface of the enterocyte; here, the fat
products are released from the micelle. Since the fat products are released close to the cell membrane,
they can diffuse into the cell.
f. The bile salt is released into the lumen; here, it helps in forming more micelle formation. Finally, the
bile salt is absorbed only in the terminal ileum by a sodium-dependent active transport and thus re-
used.
g. The rate-limiting step in lipid absorption is the migration of micelles from the intestinal lumen to the
intestinal cell surface.

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 Physiology

K. Absorption
1. For the end products of fat digestion to cross the unstirred water layer, they must first be made soluble in
water; this is done by micelle formation with the help of bile salts (see above)
2. Micelles help in crossing the unstirred water layer to reach the cell surface; here, micelles break into :
3. Digested lipid end products.
4. Bile salts

1. Lipid end products

Site :
Almost all the digested lipids are totally absorbed by the time the chyme reaches the mid-jejunum; most of the
absorption occurs in the duodenum.. Lipids enter the enterocyte by passive diffusion.

2. Bile salts
a. Site :
i. Bile salt absorption does not occur much in the jejunum. It remains in the intestinal lumen (this is an
advantage because here it helps in forming new micelles) till it reaches the terminal ileum; absorption occurs
in the terminal ileum by a sodium-dependent active transport.
b. Fat in stools
i. Normally, almost all (95%)of the ingested lipid is absorbed; thus, fat present in the stool is mostly derived
from the intestinal flora.
ii. Fate of the digested end products of lipid in the enterocyte
iii. Once inside the enterocyte, the digested lipids enter the smooth endoplasmic reticulum (SER) where they
are re-constituted. Only fatty acids with less than 10-12 carbon atoms pass from the mucosal cell directly
into the portal blood where they are transported as free (unesterified) fatty acids.

3. Reconstitution in SER
a. fatty acids (with more than 12 carbon atoms) : are re-esterified to triglycerides.
How?
MGT
2-monoglyceride ----------------------- 1-2 diglyceride
Fatty acid
(acylation)
DGT
1-2 diglyceride ------------------------------ 1-2, 3 triglyceride
Fatty acid
(acylation)

MGT : monoacyl glycerol acyl transferase

DGT : diacylglycerol acyl transferase
ester
b. Cholesterol -------------------- cholesteryl ester

fatty acids
c. lysophospholipids -------------- phospholipids

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 GIT

Note :
Some of the triglycerides in the cell is formed from glycerophosphate (which is a product of glucose metabolism);
this occurs in rough endoplasmic reticulum (RER).
acylation
Glucose ---- glycerophosphate--------------- triglycerides
The reconstitution inside the enterocyte helps in maintaining the concentration gradient for diffusion from lumen
to cell.
Chylomicrons

Chapter - 9
L. Formation :
Site : enterocyte
How formed :
i. The reconstituted triglycerides and cholesteryl esters coalesce within the SER to from small lipid droplets
(approx. 1mm diameter).
ii. They are then coated with a layer of proteins (beta lipoproteins) and phospholipids to form chylomicrons.
iii. The chylomicrons formed in RER move to Golgi apparatus, where carbohydrate moieties are added there.

M. Transport
The chylomicrons are transported out of the cell by exocytosis.

1. Importance of beta lipoproteins

Beta lipoproteins (which are synthesized by the enterocyte in the RER) covers the surface of the chylomicrons. In
the absence of beta lipoproteins, exocytosis will not occur and the enterocyte becomes engorged with lipids.

GIT
(Note : The acylation of glycerophosphate and the formation of lipoproteins occurs in the RER).
2. Transport of lipids in circulation

What are they ?

These fatty acids are made up of 2 to 5 carbon chains.
a. Content
Their average concentration in lumen is 80 mmol/L.
b. Consist of
i. They consist of acetate (60%), propionate (25%) and butyrate (15%). Formation
ii. They are formed by the action of colonic bacteria on dietary fibre.
iii. Dietary fiber is the material that escapes digestion in the upper GIT and enters the colon; it consists of
complex
iv. carbohydrates, resisitant starches etc. Colonic bacteria act on dietary fibre to give rise to SCFAs.

c. Importance/functions of SCFAs
a. the absorbed SCFAs from colon are metabolized and contribute significantly to the total calorie intake.
b. The SCFAs are trophic to the colonic epithelial cells
c. They fight inflammation
d. Acid-base balance : since a part of the SCFA is absorbed in exchange for hydrogen, it helps in acid-base
balance

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 Physiology

e. Helps sodium absorption by an unknown mechanism.

3. Absorption of cholesterol and other sterols

This occurs in the small intestine. (Sterols of plant origin are poorly absorbed; further, they decrease absorption
of cholesterol). The reconstituted cholesterol in the cell is converted into chylomicrons and enters the circulation
via the lymphatics.

N. Electrolytes
1. Sodium transport
Site : this occurs throughout the small and the large intestine.
Mechanisms
a. diffusion : some sodium diffuses into (or out of) the small intestine, depending on its concentration
gradient.
b. Secondary active transport :
i. The basolateral membrane of the enterocyte has Na+ - K + ATPase
ii. The luminal membrane has the following secondary active co-transport mechanisms
SGLT (Sodium-glucose)
Sodium-amino acid
Sodium-(di or tri) peptide
Sodium- chloride

2. Chloride transport
Chloride gets absorbed mostly by passive diffusion down its electrochemical gradient; the electrochemical
gradient is established secondary to the active transport of sodium.

3.Potassium
a. Potassium is absorbed from the small intestine; it is secreted into the colon when the luminal potassium
concentration is low. Most of the potassium movement in GIT is due to diffusion.
b. In the distal colon, there is a H+ - K + - ATPase in the luminal membrane of cells; it moves K+ from lumen into
the cell and H+ from cell into the lumen. In spite of the H+ - K + - ATPase in the distal colon, loss of colonic or
ileal fluids
c. In chronic diarrhoea can cause severe hypokalaemia.
d. What happens when dietary K + is high for a long time?
High K + in the diet ---- aldosterone gets secreted -- inserts more Na+ – K + ATPase in the basolateral
membrane of the intestinal cell --- more K + moves into the cell from the interstitium --- K +S moves out
of the cell into the lumen by passive diffusion -- more K + enters the colon.

O. Important MCQ Tips

1. Saliva contains 25-30 mEq/L K+ at low flow rate & 15-20 mEq/L at high flow rate
2. The concentration of K+ in pancreatic juice is same as plasma i.e. around 4.5 mEq/L
3. Liver bile contains 5-6 mEq/L whereas Gall Bladder bile has 12 mEq/L
4. In ileum the concentration rises due to exchange of potassium with Na+ (K+ absorption also occurs). It
normally is around 10-12 mEq/L.
5. As it reaches rectum the conc. of K+ rises to 85 mEq/L due to colonic secretion of K+.

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 GIT

6. Normal stool K+ excretion is 5-10 mEq a day and volume is 100-200 grams.
7. So max conc. is seen in stool or in colon but maximum levels or secretion is seen in saliva (since volume
secreted is 1.5 L/day as compared to 100-200 ml of stool)

P. Water
Water movement in the intestine is passive, moving down its osmotic gradient.
1. Tonicity of chyme in GIT
a. Duodenum : Hypo- or hypertonic (depending upon the type of food taken)
b. Rest of the intestine: isotonic. There is an active absorption of electrolytes and nutrients ; this creates

Chapter - 9
an osmotic gradient due to which water moves rapidly, resulting in osmotic equilibrium. Thus, fluid in
the intestine is always isotonic to plasma. In other words, there is iso-osmotic reabsorption of
electrolytes/nutrients in the intestine.
Mechanism of action of saline cathartics (e.g. magnesium sulphate) as laxatives :
Unlike sodium chloride, these salts are poorly absorbed from GIT; thus, .they retain water in the intestine and act
as laxatives.

Q. Mechanism of diarrhoea in cholera

Basic facts regarding the enterocyte
a. the basolateral membrane has Na +– K +– Cl- cotransporter (note : in the renal tubules, Na +– K +– Cl- is in the
luminal membrane)
b. the luminal membrane has various Cl- channels which are regulated by protein kinases
c. from the Na +– K +– Cl- in the basolateral membrane, Cl- enters the cell from the interstitium; from the cell, Cl -
enters the lumen by Cl- channels

GIT
In cholera, one type of Cl- channel in luminal membrane is activated by protein kinase A and therefore by c
AMP.
R. Reasons for diarrohoea in cholera :
1. Increased chloride secretion into the lumen :
In cholera, the c AMP concentration in the cell is increased (and therefore, many of the chloride channels
remain open and chloride moves into the lumen). Although the vibrio cholerae as such stays in the lumen, a
part of its toxin moves into the cell and increases the c AMP concentration in the cell. How? This can be
explained in the following steps :
a. the cholera toxin binds to a receptor (called GM-1 ganglioside receptor) on the enterocyte
b. due to this, an activated subunit of the toxin (called A1 peptide) moves into the cell
c. this A1 subunit transfers ADP ribose to the alpha-subunit of G s protein; this results in inhibition of the
inherent GTPase activity of the Gs protein
d. thus, once the G s protein is activated, it remains active for a long time (because of inhibition of its
inherent GTPase) activity
e. this causes continuous stimulation of adenylyl cyclase and thus marked increase in intracellular
concentration of c AMP
2. Decreased absorption of sodium from the lumen
a. This occurs due to increase in c AMP.
b. Because of the above reasons, there is an increased sodium chloride content in lumen, which results in
diarrhoea.
c. How is ORS (oral rehydration solution) helpful in cholera ?

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 Physiology

d. The cholera toxin does not affect either the Na+-K+-ATPase or the SGLT. Thus, ORS (which contains sodium
and glucose and uses the SGLT secondary active cotransport) is effective.

XXI. VITAMINS
A. Fat soluble vitamins (i.e. A, D, E and K)
Along with the lipids, these are absorbed as a part of micelles (see above) in the upper small intestine.

B. Water soluble vitamins

Most are absorbed in the upper small intestine; vitamin B12 is absorbed in the ileum.
Vitamin B12 and folate absorption is sodium-independent ; other water soluble vitamins
are absorbed by a sodium-dependent mechanism.
Vitamin B12
The gastric parietal cells secrete a vitamin B12- binding protein called intrinsic factor (IF). The IF-vitamin B12
complex binds to a receptor on ileal enterocyte and the complex is absorbed.

C. Calcium
Calcium absorption in the small intestine is regulated to maintain calcium balance. For example, absorption is
increased in calcium deficiency and decreased in calcium excess. This regulation is mediated by 1,25 DHCC (this is
the active derivative of vitamin D). Normally, the dietary intake of calcium is about 1000 mg; normally, about 25
to 80 % of this is absorbed. Main site is proximal intestine (jejunum).

D. Mechanism
Calcium absorption occurs via a membrane-bound carrier; the carrier is activated by 1, 25 DHCC
Factors affecting calcium absorption
1. 1, 25 DHCC :
1.25 DHCC enters the enterocyte, where it inserts the calcium carrier in the luminal membrane of the
enterocyte.
2. Calcium (and also magnesium) absorption is increased by protein
3. Calcium absorption is inhibited by phosphates and oxalates (because these form insoluble salts with
calcium)

E. Iron
Site of absorption :
Almost all of iron absorption occurs in the duodenum.
Forms in which iron is absorbed :
Iron can be absorbed as :
1. Haem (as present in meat)
2. Free ion
Ferrous ion (Fe++) is absorbed much more efficiently than ferric ion (Fe3+). Most of the dietary iron is in the ferric
form. Thus, it needs to be converted into ferrous form for absorption.

1. Conversion of ferric to ferrous : This occurs in

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 GIT

a. Stomach : The stomach acid tends to break the insoluble iron complexes within the chyme and thus
releases the iron from the complexes. Once the iron is free, it is converted from ferric to ferrous in the
presence of ascorbic acid (vitamin C)
b. Intestine : In the enterocyte brush border, the transporter for iron (called DMT 1) has ferric reductase
activity.

2. Mechanism of iron absorption from lumen to cell :

a. Haem is absorbed by a haem transporter called HT
b. Ferrous ion is absorbed by a iron transporter called DMT 1 transporter.

Chapter - 9
c. Inside the cell :
i. Haem oxidase acts on haem to release ferrous ion and porphyrin ferrous ion
ii. Some ferrous ion is converted to ferric ion; the ferric ion ‘combines with’ an iron-binding protein
called apoferritin to form ferritin (see below).

a. From cell to interstitium :

The ferrous ion which is not converted into ferric ion is transported across the basolateral membrane by a
transporter called ferroportin 1; a protein called hephaestin (or Hp) helps ferroportin 1 in the basolateral
transport of ferrous ion.

b. In the plasma :
Here, ferrous ion is converted into ferric ion and is bound to the transport protein called transferrin; transferrin is
a beta-1 globulin.

GIT
MCQ tip
Ferrous form :
Only this form can get across the cell membrane ; the iron in haem is in ferrous form
Ferric form :
This forms most of the dietary protein, present in ferritin, hemosiderin, transferrin.

F. Regulation of iron absorption

1. Normal absorption :
Iron absorption is necessary for maintaining normal iron balance. Very little (0.75 mg in males and 1.5 mg in
females) of the 15-25 mg of iron ingested each day is actively absorbed (approximately 3 to 6% of the ingested
iron is absorbed).

2. Iron absorption from intestine is regulated :

In iron deficiency, more iron is absorbed; in iron excess, less is absorbed. There is a close association between
iron levels and the amount of ferritin and transferrin.as shown below:
a. High iron levels cause ferritin to increase and transferrin to decrease.
b. Low iron levels cause ferritin to decrease and transferrin to increase.

3. Dietary factors affecting iron absorption :

Phytic acid (which is found in cereals), phosphates and oxalates form insoluble compounds with iron in the
intestine; thus, they decrease iron absorption.

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 Physiology

4. Ferritin micelle :
Ferritin is the tissue storage form of iron; it is present in enterocytes and other cells.
The ferric ion and the protein apoferritin together form ferritin micelles; ferritin micelles consist of ferric ion (in
the form of ferric hydroxyphosphate) in the center surrounded by 24 subunits of apoferritin. Each ferritin micelle
contains some 3000 to 4500 ferric atoms.

5. Significance of ferritin
i. Normally, there is very little ferritin in the plasma. However, in patients with excess iron, the amount of
ferritin in the plasma increases. The amount of ferritin in the plasma can be used as an index of body iron
stores.
ii. Ferritin can be easily seen under electron microscope; thus, it can also be used as a marker for phagocytosis
etc.
6. Hemosiderin molecule
This consists of aggregated deposits of partly degraded ferritin molecules in lysosomal membranes. It contains
much more iron than ferritin molecule.
Ferritin molecule contains 23% iron whereas the haemosiderin molecule may contain 50% iron.

450
 GIT

“Please Read the Preface of this book Before you attempt these questions.”
Explanation of answer start from page no. 460

Section-1 -:Salivary Glands, Oesophagus and Stomach 9. In stomach the acid is secreted by:
A. HCO3- is exchanged for K+ B. H+, Na+
C. Active secretion D. Passive secretion
1. Chymotrypsinogen is a (AIIMS NOV.2011)
A. Carboxypeptidase B. Zymogen 10. The requirement of folic acid during pregnancy
C. Transaminase D. Elastase is……………………….g. (DNB Pattern)

Chapter - 9
A.600 B.300 C. 150. D. 900
2. Max potassium ions present in : (AIIMS MAY 2009)
A. Colon B. Jejunal secretions 11. Pepsinogen is converted to pepsin because of:
C. Stomach D. Saliva (DNB Dec-2010)
A. Enterokinase B. Trypsin
3. Intrinsic factor of castle is + in C. Chymotrypsin D. Low pH (Gastric acid)
(AIPG 2009)
A. Chief cells B. Fundus cells 12. Gastrin regulates the gastric acid secretion at:
C. Goblet cells D. Parietal cells (DNB Pattern)
A. Gastric cardia
4. Deglutition peristalsis of oesophagus: (AIPG B. Antrum
2009) C. Pyloric canal
A. Primary B. Secondary D. First part of duodenum
C. Tertiary D. Quaternary
13. Which of the following mediates cephalic phase
5. Prostaglandin that helps in protecting GI mucosa is: of gastric secretion: (DNB Pattern)
(AIPG 2007) A. Parasympathetic nerve

GIT
A. PGE2 C. PGF2 B. Sympathetic efferent nerve
B. PGI1 D. None of the above C. Chemical agents
D. Neurohormones of hypothalamus
6. Which of the following is correctly matched?
(AIIMS NOV 2007) 14. Gastric juice contains all of the following except
A. Cells- Somatostatin A. Na+ B.Ca++ C. Mg++ D.K+
B. D. cells-Insulin
C. G cells- Gastrin 15. Oxyntic cells are found in:
D. K cells- CCK-PZ A. Stomach B. Duodenum
C. Pancreas D. Intestine
7. Bitter taste is perceived mainly by which part of 16. Which one of the following is the primary site of
the tongue production of gastrin?
A. Anterior 1/3 B. Posterior 1/3 A. Pylorus B. Antrum
C. Lateral aspect D. Tip C. Pancreas D. Small intestine

8. All of the following are functions of saliva except 17. Mixing waves of stomach (DNB Pattern)
A. Acts as lubricant for mastication A. Originates in body of stomach
B. It helps in perception of taste by dissolving B. Originates in fundus of stomach
C. It helps in digestion of carbohydrates C. Originates at incisura angularis
D. It helps in digestion of proteins D. Originates in any part of stomach

1.B 2.D 3.D 4.A 5.A 6.C 7.B 8.D 9.C 10.B 11.D 12.B 13.A 14.B 15.A 16.B 17.A

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 Physiology

18.The best description of the lag phase of gastric (A) Carbon dioxide from carbon and oxygen
emptying is the time required for (B) Carbonic acid from carbon dioxide and water
(A) Conversion from the interdigestive to the digestive (C) Bicarbonate ion from carbonic acid
enteric motor program (D) Hydrochloric acid
(B) Maximal stimulation of gastric secretion
(C) Return of the emptying curve to baseline 24. Parasympathetic stimulation induces salivary
(D) Reduction of particle size to occur acinar cells to release the protease
(A) Bradykinin (B) Kallikrein
19.When elevated in an ingested meal, the factor with (C) Kininogen (D) Kinin
the greatest effect in slowing gastric emptying is
(A) pH 25. Which protein is absent in saliva?
(B) Carbohydrate (A) Lactoferrin (B) Amylase
(C) Protein (C) Mucin (D) Intrinsic factor
(D) Lipid
26. After the ingestion of a meal, the pH in the
20.On a return visit after receiving a diagnosis of stomach lumen increases in response to the dilution
functional dyspepsia, a 35- year-old woman reports and buffering of gastric acid by the arrival of food. The
sensations of early satiety and discomfort in the pH in the stomach lumen in the fasting state is usually
epigastric region after a meal. These symptoms are between?
most likely a result of (A) 1 to 2 (B) 4 to 5
(A) Malfunction of adaptive relaxation in the gastric (C) 6 to 7 (D) 9 to 10
reservoir
(B) Elevated frequency of contractions in the antral 27. Unlike other GI secretions, salivary secretion is
pump controlled almost exclusively by the nervous system
(C) An incompetent lower esophageal sphincter and is significantly inhibited by
(D) Premature onset of the interdigestive phase of (A) Atropine (B) Pilocarpine
gastric motility (C) Cimetidine (D) Aspirin
21. Most of the following GI secretions have a basal
output during the interdigestive period (between 28.The chief cells of the stomach secrete
meals). However, the sight and smell of a tasty meal (A) Intrinsic factor
stimulates GI secretions. Of the various GI secretions, (B) Hydrochloric acid
which is the most stimulated? (C) Pepsinogen
(A) Gastric secretion (D) Gastrin
(B) Intestinal secretion
(C) Pancreatic secretion 29.The interaction of histamine with its H2 receptor in
(D) Salivary secretion the parietal cell results in
22. Gastric acid secretion is stimulated during several (A) An increase in intracellular sodium concentration
phases associated with the ingestion and digestion of (B) An increase in intracellular cAMP production
a meal. Which phase is associated with the bulk of (C) An increase in intracellular cGMP production
acid secretion? (D) A decrease in intracellular calcium concentration
(A) Cephalic
(B) Esophageal 30.When the pH of the stomach lumen falls below 3,
(C) Gastric the antrum of the stomach releases a peptide that
(D) Intestinal acts locally to inhibit gastrin release. This peptide is
(A) Enterogastrone
23. Carbonic anhydrase is an enzyme that occurs in (B) Intrinsic factor
plants, bacteria, and animals and is involved in the (C) Secretin
formation of which chemical? (D) Somatostatin
18.D 19.D 20.A 21.D 22 .C 23. B 24.B 25.D 26 .A 27 .A 28.C 29 B 30.D

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 GIT

31. Stimulation for gastric emptying:

A. Secretin B. CCK C. Gastrin D. Distension 7. Which inhibits gastric secretion?
A. Secretin
32. Intrinsic factor is secreted by: (AIIMS MAY 2010) B. High gastric Ph
A. Chief cell B. Parietal cell C. Insulin
C. G cells D. None of the above D. Calcium
8. The mechanism that protects normal pancreas from
33. Parietal cells in the stomach secrete a protein autodigestion is:
crucial for the absorption of vitamin B12 by the ileum. A. Secretion of bicarbonate
What is this protein? B. Protease inhibitors present in plasma

Chapter - 9
(A) Intrinsic factor (B) Gastrin C. Proteolytic enzymes secreted in inactive form
(C) Somatostatin (D) Cholecystokinin (CCK) D. The resistance of pancreatic cells

Section-2 -: Gall Bladder, Liver, Pancreas & Bile 9. All of the following enzymes are secreted by the
pancreas except (DNB Pattern)
1. All are actions of cholecystokinin except A. Enterokinase B. Chymotrypsin
A. Increase gastrin secretion C. Carboxypeptidase D. Lipase
B. Increase lower esophageal sphincter pressure
C. Stimulation of pancreatic enzyme 10. Which is increased in blood level hepatectomy:
D. Stimulation of gallbladder A. Fibrinogen
B. Lipoprotein
2. Which of the following stimulate gallbladder C. Angiotensin
contraction: (DNB Pattern) D. Estrogen
A. Gastrin B. Vagus C. CCK D. Secretin
11. Which of the following has highest pH:
3. Which of the following is the most important A. Pancreatic juice

GIT
stimulus for the secretion of bile: B. Gastric juice
A. Bile salts B. Bile acid C. Gallbladder bile
C. Secretin D. CCK D. Saliva

4. Which of the following is major difference between 12.Which hormone stimulates pancreatic secretion
hepatic bile and gallbladder bile: (DNB Dec-2009) that is rich in bicarbonate?
A. Bicarbonates B. Bile acid (A) Somatostatin
C. Chloride D. Cholesterol (B) Secretin
(C) CCK
5. Action of cholecystokinin include all of the (D) Gastrin
following except:
A. Contraction of gall bladder 13.A patient suffering from Zollinger- Ellison
B. Secretion of panacreatic juice rich in enzymes syndrome would be expected to have
C. Increases the secretion of enterokinase (A) Excessive acid reflux into the esophagus, resulting
D. Augments the action of secretion of gastrin in esophagitis
E. Stimulated gastric emptying (B) Excessive secretion of CCK, causing continuous
contraction of the gallbladder
6. Which of the following is not caused by CCK? (C) A gastrin-secreting tumor of the pancreas, causing
(DNB Pattern) excessive stomach acid secretion and peptic ulcers
A. Contraction of gallbladder (D) Low plasma lipid levels, due to failure of the liver to
B. Decreases tone of sphincter of Oddi secrete VLDLs
C. Pancreatic enzyme secretion
D. Increases gastrin secretion
31.C 32.B 33.A 1.A 2.C 3.A 4.C 5.E 6.D 7.A 8.C 9.A 10.D 11.A 12.B 13.C

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 Physiology

14. The arterial blood glucose concentration in normal (C) The liver can no longer efficiently convert vitamin D
humans after a meal is in the range of to 25- hydroxycholecalciferol
(A) 30 to 50 mg/dL (D) The liver can no longer efficiently convert
(B) 50 to 70 mg/dL cholecalciferol to 1,25-dihydroxycholecalciferol
(C) 120 to 150 mg/dL
(D) 220 to 250 mg/dL
21.The liver removes LDLs in the blood by the LDLs
15. Both the liver and muscle contain glycogen, yet, binding to
unlike liver, muscle is not capable of contributing (A) LDL receptors and then internalizing them
glucose to the circulation because muscle (B) HDL receptors and then internalizing them
(A) Does not have the enzyme glucose-6-phosphatase (C) The albumin present on LDLs and then internalizing
(B) Glycolytic activity consumes all of the glucose it them
generates (D) The transferrin present on LDL and then
(C) Does not have the enzyme glucose-1-phosphatase internalizing them
(D) Does not have the enzyme glycogen phosphorylase
22. Compared to an unacclimatized person, one who
16. The hepatocyte is compartmentalized to carry out is acclimatized to cold has
specific functions. In which subcellular compartment (A) Higher metabolic rate in the cold, to produce more
does fatty acid synthesis occur? heat
(A) Cytoplasm (B) Mitochondria (B) Lower metabolic rate in the cold, to conserve
(C) Nucleus (D) Endosomes metabolic energy
17. Because free ammonia in the blood is toxic to the (C) Lower peripheral blood flow in the cold, to retain
body, it is transported in which of the following non- heat
toxic forms? (D) Various combinations of the above, depending on
(A) Histidine and urea the environment that produced acclimatization.
(B) Phenylalanine and methionine
(C) Glutamine and urea
(D) Lysine and glutamine 23. What is the mechanism through which
catecholamines stabilize blood glucose concentration
18. Which protein is made by the liver and carries iron in response to hypoglycemia?
in the blood? (A) Catecholamines stimulate glycogen phosphorylase
(A) Hemosiderin (B) Haptoglobin to release glucose from muscle
(C) Transferrin (D) Ceruloplasmin (B) Catecholamines inhibit glycogenolysis in the liver
(C) Catecholamines stimulate the release of insulin
19. The level of drug metabolizing enzymes in the liver from the pancreas
determines how fast a drug is removed from the (D) Catecholamines stimulate gluconeogenesis in the
circulation. Therefore, it would be expected to find liver
drug metabolizing enzymes
(A) Higher in smokers than in nonsmokers 24. Bile acid uptake by hepatocytes is dependent on
(B) Similar in smokers and nonsmokers (A) Calcium
(C) Lower in smokers than in nonsmokers (B) Iron
(D) Stimulated by malnutrition (C) Sodium
20.The level of circulating 1,25- (D) Potassium
dihydroxycholecalciferol is significantly reduced in
patients with chronic liver disease because
(A) The liver can no longer efficiently convert 25-
hydroxycholecalciferol to 1,25-dihydroxycholecalciferol
(B) The liver can no longer efficiently convert vitamin D
to cholecalciferol

14.C 15.A 16. A 17. C 18.C 19.A 20. C 21.A 22. D 23.D 24.C

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 GIT

Chapter - 9
Section-3 -: Small and Large Intestine

1. Function of gut flora, which of the following is not

the primary function of gut flora? (AIIMS NOV.2011)
A. Fermentation of mucus
B. Synthesis of short chain fatty acids
C. Synthesis of vitamin K
D. Regeneration of the epithelium
.
2 . Nitric Oxide In GIT acts Primarily By (AIPG 2010)
A. Smooth Muscle relaxant
B. Secretomotor
C. Vasodilator

GIT
D. Vasoconstrictor

3. Highest concentration of potassium is seen in-

(AIIMS NOV 2009)
A. Bile B. Pancreatic juice
C. Terminal ileum D. Rectum

4. PANETH cells are rich in:(AIPG 2009)

A. Zinc B. Lysozyme
C. Mucus D. Intrinsic factor

1.A 2.A 3.D 4.A B

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 Physiology

5. Which of the following have maximum Post 12. Which of the following is true regarding Brunner’s gland:
prandial contractibility: (AIIMS MAY 2011, NOV (DNB Pattern)
2013) A. Secretion of enzymes
A. Transverse Colon B. Ascending Colon B. Water and electrolyte secretion
C. Descending colon D. Sigmoid colon C. Mucus production to protect intestine from aci
D. All of the above
6. TRUE about secretin includes all of the following
EXCEPT (AIPG 2008) 13. Which of the following is the function of M cells in
A. It increases the acidity of biliary and pancreatic intestine: (DNB Dec-2008)
secretions A. Antigen presenting cells
B. It decreases gastric acid secretion B. Meisner plexus cells
C. It decreases gastrin secretion and gastric emptying C. Mucous secreting glands
D. Increases flow and velocity of bile D. All of the above

7. Enzymes not stable at acidic pH are all except 14. Which of the following is not present in pancreatic
(AIPG 2007) juice: (DNB Pattern)
A. Trypsin B. Chymotrypsin A. Elastase B. Colipase
C. Pepsin D. Carboxypeptidase C. Aminopeptidase D. Ribonuclease

8. All of the following statements regarding small 15. Acid secretion is not increased by:
intestinal motility are true except? (AIPG 2007) A. Vagus stimulation B. Gastrin
A. Completely independent of stomach motility C. Food in stomach D. Somatostatin
B. CCK increases small intestinal motility
C. Abdominal distension increases motility 16. The most important stimulus for release of
D. Increased motility by acetylcholine secretin is: (DNB June-2008)
A. Amino acids B. Vitamin D
9. Which of the following does not stimulate C. Wheat D. Hydrochloric acid
enterogastric reflex? (LQ)
A. Products of protein digestion in the duodenum 17. Following are gastrointestinal hormones except
B. Duodenal distension A. CCK-PZ B. GIP
C. H + ions bathing duodenal mucosa C. Motilin D. Chymotrypsin
D. Hormones
18. Short chain fatty acid produced by bacteria are
10. Which of the following enzyme is secreted by maximally absorbed in (DNB Pattern)
intestine: A. Duodenum B .Colon
A. Trypsin C. Ileum D. Jejunum
B. Elastase
C. Dipeptidase 19. Intestinal absorption is faster for
D. Phospholipase A2 A. Hexoses
B. Dissacharides
11. Which of the following is the most important C. Oligosaccharides
stimulus for the release of secretin from duodenal D. Polysaccharides
mucosa:
A. Acidity of chyme 20. Hirschsprung disease is due to (AIIMS NOV 2012)
B. Vagus nerve stimulation A. Loss of ganglion cells in sympathetic chain
C. Duodenal distention B. Failure of migration of neural crest cells from cranial
D. Protein contents of chyme to caudal direction
C. Atrophy of longitudinal muscles
D. Loss of vagal innervation of myenteric plexus

5.D 6.A 7.C 8.A 9.D 10.C 11.A 12.C 13.A 14.C 15.D 16.A 17.D 18.B 19.A 20.B

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 GIT

21. Fat in duodenum results in: B. The extrinsic sympathetic nervous system
A. Gall bladder contraction C. Both
B. CCK inhibition D. None
C. Increased secretion
D. Increased propulsive movements
32. What is true regarding gastrin ?
22. Antiperistalsis is normally seen in: A. It shows macroheterogeneity
A. Colon B. Jejunum C. Duodenum D. Ileum B. It shows microheterogenity
C. It is mainly inactivated in the kidney and small
23. Maximum absorption of water occurs in (AIPG

Chapter - 9
intestine
2010, 2011) D. It is formed from its precursor, preprogastrin
A. stomach B. ileum C. colon D. jejunum
E. All
24. Gastric secretions decreased by:
A. Somatostatin B. Gastrin 33. Which of the following is/are true regarding CCK?
C. Histamine D. Ach A. Like gastrin, it shows micro- and acroheterogeneity
B. Its T/2 is about 5 minutes
25. Calcium absorption in Gut is increased in – C. It is secreted by I cells in the upper small intestine D.
A. acidic Ph B. Alkaline pH All
C. Neutral pH D. Not affected by pH
changes
34. Vagal stimulation increases gastrin secretion. This
26. Transit time is slowest in is mediated by
A. stomach B. colon A. GRP or gastrin-releasing peptide
C. jejunum D. ileum B. Acetylcholine
C. Glucagon

GIT
27. Fe2+ conversion from Fe 3+ enzyme responsible is?
D. Substance P
A. Reductase B. DMT 1
C. DMT 2 D. Oxidase
35. Intravenous injection of secretin will cause the
28. Chylomicrons function is following changes in the pancreatic juice secretion
A. Transport lipids B. lipid storage except
C. emulsification of fat D. lipid excretion A. Secretion of copious volume of pancreatic
secretion
29. Massive small bowel resection, the intestine
B.Bicarbonate content increased markedly
compensate by :
A. Lengthened individual villi C. Chloride content decreases markedly
B. increased enzymes D. Amylase content increases markedly
C. increase number of villi E. Potassium content does not change much
D. Increased life span for absorptive cells
36. Max potassium ions present in : (AIIMS May 09)
30. In the GIT, skeletal muscle is present in A. Colon B. Jejunal secretions
A. Stomach B. Oesophagus
C. Stomach D. Saliva
C. Small intestine D. Large intestine
37. Regarding swallowing, which is/are true?
31. The innervation of the intestinal blood vessels is A. it is almost impossible to swallow when the mouth is
from kept open
A. The intrinsic enteric nervous system B. a normal adult swallows about 600 times per day
21.A 22.A 23.D 24.A 25.B 26.B 27.A 28.A 29.A 30.B 31.C 32.E 33.D 34.A 35.D 36.D

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 Physiology

C. During swallowing, there is cessation of respiration 46. The final digestion of proteins to amino acids can
D. All occur in
A. Intestinal lumen
38. Which part of the stomach secretes gastrin? B. Brush border
A. Body B. Antrum C. Inside the intestinal mucosal cell
C. Fundus D. Cardia D. All

39. Enzymes from which one of the following can 47. Passive absorption is for
digest carbohydrate, lipid, protein and nucleic acids? A. Carbohydrate B. Lipids
A. Salivary glands B. Stomach C. Proteins D. All
C. Pancreas D. Intestine
48. The maximum contribution to the total
40. From the lumen of the small intestine to the small endogenous water secretion in GIT is from
intestinal cell (called enterocyte), the barriers to A. Salivary glands B. Stomach
diffusion is/are C. Bile D. Pancreas
A. Brush border B. Glycocalyx E. Intestine
C. Unstirred water layer D. Mucous coat
E. All 49. Maximum water is absorbed from
A.Jejunum B.Ileum
41. Main enzyme for digestion of alpha-dextrin is C.Colon D.Stomach
A. isomaltase B. maltase
C. sucrose D. lactase 50. Which of the following is absorbed from colon?
A. Long-chain fatty acids B. Bile salts
42. All are true of glucose absorption in the intestine C. Sugars D. Sodium
except
A. It is dependent on insulin 51. Substances absorbed mostly from lower small
B. It does not require phosphorylation intestine include
C. It is competitively inhibited by the drug phlorhizin A. Bile salts
D. It occurs via SGLT B. Vitamin b12
C. Antibodies in the new born
43. The acid-secreting regions of the stomach secrete D. All
A. Pepsinogen I B. Pepsinogen II
C. Both D. None 52. Which substance is not absorbed from lower small
intestine?
44. The optimum pH for pepsin action is A. Sugars
A. 1.6 to 3.2 B. 2 to 4 C. 6.5 D. 8 B. Vitamins (except vitamin b12) and sulphate
C. Amino acids
45. All the following enzymes are found in the human D. Sodium
stomach except
A. Pepsins B. Gelatinase 53. The duodenum differs from the jejunum in that
C. Lipase D. Chymosin (also called rennin) the duodenum
A. Does not absorb sugars

37. D 38.B 39.C 40.E 41.A 42.A 43.A 44.A 45.D 46.D 47.B 48.B 49.A 50.D 51.D 52.B

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 GIT

B. Does not absorb amino acids C. SGL T-1 D. SGLT-2

C. Secretes bicarbonate E. Simple diffusion only in the presence of insulin
D. Does not absorb vitamins
62. Protein digestion begins in
54. Most of the iron in the body is in A. Saliva
A. Ferritin B. Haemoglobin B. Stomach
C. Myoglobin D. Transferrin C. Duodenal Cap
D. At the attachment of ligament of Treitz

Chapter - 9
55. From the lumen to the enterocyte, the barrier to
diffusion include 63. Maximal acid secretion correlates with levels of
A. Glycocalyx B. Brush Border A. Pepsinogen 4 B. Pepsinogen 2
C. Unstirred Layer D. Mucous Coat C. Pepsinogen 2 D. Pepsinogen 4
E. Villous membrane F. All of the above
64. All the following enzyme are present in stomach
56. Optimum pH for salivary  amylase (ptyalin) is except
A. 6.7 B. 7.8 C. 8.6 D. 1.2-2.4 A. Pepsin B. Chymosin
C. Lipase D. Gelatinase
57. Mal triose is
A. 3 glucose B. 2 Glucose + Lactose 65. Digestion of proteins occurs at
C. 2 glucose + fructose D. 3 galactose A. Intestinal lumen
B. Brush Border
58. Salivary -amylase can hydrolyze polysaccharides) C. Cytoplasm of mucosal cells
A. 1:4  D. All of the above.

GIT
B. 1:6 
C. 1:4B 66. Di- and tripeptides are transported into
D. Terminal 1:4  enterocytes by a system that requires
E. 1:4  next to branching point A. H+ B. Na+
F. A, D and E C. Cl- D. Independent of A, B, C

59. Isomalase (  dextrinase) can split 67. Absorption of one of the following can occur
A. -dextrins B. Maltriose without being broken down
C. Maltose D. All of the above A. Protein
B. Triglycerides, although this seen only in infants
60. All are true of carbohydrate absorption except C. -Dextrins
A. Principal end products of CHO digestion in lumen are D. Sucrose
oligosaccharides/ disaccharides
B. -dextrinase an split 1:6  linkages 68. Ebner’s glands secrete
C. Trehalase is an enzyme in brush border A. Ptyalin B. Lingual lipase
D. Some CHO can get absorbed as lactose C. Mucus D. Colipase

61. Fructose is absorbed by 69. Most fat digestion begins in

A. Simple Diffusion B. Facilitated Diffusion A. Stomach B. Saliva/ Mouth

53.C 54.B 55.E 56.A 57.A 58.A 59.D 60.D 61.B 62.A 63.A 64.B 65.D 66.A 67.A 68.B

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 Physiology

C. Duodenum D. 1leum A. Hemoglobin B. Ferritin

C. Myoglobin D. Transferrin
70. Pancreatic lipase acting on triglycerides can split
A. All 3 bonds B. 1 and 3 79. Auerbach’s plexus is concerned primarily with
C. 1 and 2 D. 2 and 3 A. Motor control B. Secreting activity
C. Blood flow D. Sensory function
71. Bile-salt activated pancreatic lipase can split
A. Triglycerides 80. True about extrinsic innervation of gut is
B. Cholesterol esters A. PS generally (+) SM of wall and (-) sphincters
C. Esters of fat-soluble vitamins B. PS generally (-) SM of wall and (+) sphincters
D. Phospholipids C. S generally (+) SM of wall and (-) sphincters
E. All of the above D. S generally (-) SM of wall and (-) sphincters

72. Emulsification of fat is by 81. All are true of peristalsis except

A. Bile salts B. Lecithin A. It is a reflex response
C. Monoglycerides D. All of the above B. It occurs in all parts of GIT (from oesophagus to
rectum)
73. Lipids form micelles by interacting with C. Its activity can be  ed ored by extrinsic innervation
A. Bile salts B. Lecithin D. B.E.R. coordinates peristaltic activity
C. Monoglycerides D. All E. It does not require the enteric nervous system.

74. Bile salts are maximally absorbed in

A. Duodenum B. Jejunum
C. Ileum D. Colon
82. Basic electrical rhythm (B.E.R.) is seen in all the
75. Cholera toxin acts on following except
A. Cl with channel in luminal membrane A. Oesophagus B. Stomach
B. Na+-K+-2CC with cotransporter in luminal membrane C. Ileum D. Colon
C. Na+-K+ ATP ase
D. SGLT1 83. The rate of B.E.R. is minimum in
A. Stomach B. Duodenum
76. The contents are essentially isotonic in all the C. Caecum D. Sigmoid
following except
A. Duodenum B. Jejunum 84. All are true of migrating motor complex except
C. Ileum D. Colon A. These cycles of motor activity migrate from stomach
to distal ileum
77. One of the following water soluble vitamins does B. They migrate ab orally at  5 cm/min
not require Na+ for its absorption C. Occur at intervals of – 90 min
A. Vit B12 B. Thiamine D. Gastric secretion, bile flow, pancreatic secretion
C. Riboflavin D. Ascorbic acid increase during each MMC
E. They are present during fasting and are immediately
78. Most of the iron in the body is in stopped on ingestion of food

69.C 70.B 71.E 72.D 73.A 74.C 75.A 76.A 77.A 78.A 79.A 80.A 81.E 82.A 83.A 84.F

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 GIT

F. Gastric may have a role in its generation 89. All are true of G.I.P. except
A. Secreted by K cells of Duod. & jejunum
85. All the following hormones (G.I) belong to B. (+)ed by glucose, fat in the duodenum
secretion family except C. In large doses, it (-)s gastric secretion and mobility
A. Glucagon B. Glicentin D. It stimulates insulin secretion
C. V.I.P. D. G.I.P. E. Belongs to gastrin family of G.I. hormones.
E. CCK
90. V.I.P., all are true except.
A. Markedly es intestinal secn. of electrolytes

Chapter - 9
86. All are true of gastrin except
A. Secreted by G cells of antrum B. Relaxes intestinal smooth muscle and sphincters
B. G cells are APUD cells C. Dilates peripheral blood vessel
C. Gastrin shows micro and microheterogeneity D. It is found in nerves of GIT
D. Vagal (+) releases gastrin from G cells, Ach being the E. (+)s gastric acid secretion
mediator F. Potentiates action of Ach. On salivary glands.
E. The AAS phenylalanine and tryptophan is stomach
are potent stimuli for gastric secretion 91. All are true of somatostatin except
F. H+ in antrum (-) gastrin secretion is ed A. Produced by D cells of GI mucosa
B. Generally, inhibitory in its actions on GI
87. All are true regarding CCK-PZ except C. It is (+) ed by acid in stomach
A. Secreted by I cells in upper SI D. Only form of somatostatin is seen in tissue
B. Like gastrin, it shows micro/microheterogeneity
C. Causes contraction of G.B. and secretion of 92. ‘Receptive relaxation’ is seen in
pancreatic juice rich in Enzymes A. Oesophagus B. Stomach

GIT
D. es gastric motility D. Duodenum D. Caecum
E. CCK (+)’s glucagon secretion
F. es secretion of enterokinase 93. Regarding salivary juice, only one of the
G. Its secretion is  ed by peptides, AAS, fatly acids in following is true :
duodenum A. The salivary juice output from the duct is always
hypotonic
88. Regarding secretin, the following statements are B. Maximum contribution of total saliva is by parotid
true except. gland
A. Secreted by S cells of upper small intestine. C. It secretion is controlled by G.I. hormone
B. Only one form of secretin has been isolated, unlike C. (PS) (+)  es and (S) (+)  es its secretion
CCK and gastrin E. Regardless of flow rate, its ionic composition
C. es secretion of HCO-3 by the duct cells of the remains the same.
pancreas and biliary duct F. Aldosterone does not affect its ionic composition.
D. Augments the action of CCK
E. es gastric acid secretion by an action on G cells (via 94. The cells of the stomach can secrete all the
gastrin) following except
F. Secretion of secretion is ed by products of protein A. Pepsin B. HCL
digestion and by acid in duodenum . C. Intrinsic factor D. Mucus
E. HCO3-

85..E 86.D 87.D 88.E 89.E 90.E 91.D 92.B 93.A 94.A

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 Physiology

95. Postprandial alkaline tide can be attributed to

A. Oxyntic Cells B. Peptic Cells 102. All are true of ileocecal valve except
C. Paneth Cells D. M Cells A. It is normally closed and opens only when a
peristaltic wave reacts it
96. All the following inhibit gastric motility except B. It gets opened by gastroileal reflex
A. Hyposmolarity of duodenal contents C. Sympathetic (+) increase its contraction
B. Products of protein digestion in duodenum D. It is also a part of the gastrocolic reflex where in it
C. H+ in Duodenum relaxes.
D. Enterogastric reflex
E. Distension of duodenum 103. The following are stimuli for release of CCK
F. Peptide YY except
G. Vagotomy A. Peptides B. AAS
C. Fatty acid D. Monoglycerides
97. Enteropeptidase act on E. Triglycerides
A. Polypeptides B. Dipeptides
C. Trypsinogen D. Starch 104. Gastric inhibitory peptide is secreted by
A. Oxyntic cells of stomach
98. The primary bile acids are B. Chief cells of stomach
A. Deoxycholic acid and lithocholic acid C. Surface epithelial cells of stomach
B. Cholic acid and deoxycholic acid D. Upper SI
C. Cholic acid and chenodeoxycholic acid
D. Cholic acid and lithocholic acid 105. The only G.I. hormone that is released in
response to fat, protein and carbohydrate is
99. Critical micelle concentration refers to the A. CCK-PZ B. Secretin
critical levels of C. G.I.P. D. V.I.P.
A. Cholesterol B. Bile salts
C. Phospholipids D. Free fatty acids 106. All the following are contained in micelles except
A. Glycerol B. Cholesterol
100. All the following are true of bile secretion except C. Monoglycerides D. FAS
A. Increased by (+) of vagus
B. Increased by secretin 107. Hirschsprung disease is due to (AIIMS Nov 09)
C. The bile salts reabsorbed from intestine actually A. Loss of ganglion cells in sympathetic chain
inhibit synthesis of new bile acids B. Failure of migration of neural crest cells from cranial
D. Bile salts decrease bile flow to caudal direction
C. Atrophy of longitudinal muscles
101. Valvula conniventes (3), villi (10) and microvilli D. Loss of vagal innervation of myenteric plexus
(20) increase the absorptive surface of SI by above 108. Which of the following does not stimulate
A. 200 times B. 100 times enterogastric reflex?
C. 600 times D. 1500 times (A) Products of protein digestion in the duodenum
(B) Duodenal distension
(C) H+ ions bathing duodenal mucosa
(D) Cholecystokinin

95.A 96.A 97.C 98.C 99.B 100.D 101.C 102.D 103.E 104.D 105.C 106.A 107.B 108.D

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109. A mouse with a new genetic mutation is discovered not to have electrical slow waves in the small intestine.
What cell type is most likely affected by the mutation?
(A) Enteric neurons
(B) Inhibitory motor neurons
(C) Enterochromaffin cells
(D) Interstitial cells of Cajal

Chapter - 9
110.The absence of intestinal motility in the normal small intestine is best described as
(A) A migrating motor complex
(B) An interdigestive state
(C) Segmentation
(D) Physiological ileus

111.Examination of the properties of a normal sphincter in the digestive tract will show that
(A) Primary flow across the sphincter is unidirectional
(B) The lower esophageal sphincter is relaxed at the onset of a migrating motor complex in the stomach
(C) Blockade of the sphincteric innervation by a local anesthetic causes the sphincter to relax
(D) The manometric pressure in the lumen of the sphincter is less than the pressure detected in the lumen on
either side of the sphincter

112. A disease that results in the loss of enteric inhibitory motor neurons to the musculature of the digestive
tract will most likely be expressed as
(A) Rapid intestinal transit
(B) Accelerated gastric emptying

GIT
(C) Gastroesophageal reflux
(D) Achalasia of the lower esophageal sphincter

113.The instillation of markers in the large intestine is used to evaluate transit time in the large intestine and
diagnose motility disorders. In healthy subjects, dwell-times for instilled markers in the large intestine are
greatest in the
(A) Ascending colon
(B) Sigmoid colon
(C) Descending colon
(D) Transverse colon

114.Lactase is a brush border enzyme involved in the digestion of lactose. The digestion product or products of
lactose are
(A) Glucose
(B) Glucose and galactose
(C) Glucose and fructose
(D) Galactose and fructose

115.Maltase hydrolyzes maltose to form

(A) Glucose
(B) Glucose and galactose
(C) Glucose and fructose
(D) Galactose and fructose
109 D 110.D 111.A 112.D 113.D 114.B 115.A

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116.Which sugar is taken up by enterocytes by facilitated diffusion?

(A) Glucose
(B) Galactose
(C) Fructose
(D) Xylose
117.Dietary triglyceride is a major source of nutrient for the human body. It is digested mostly in the intestinal
lumen by pancreatic lipase to release
(A) Lysophosphatidylcholine and fatty acids
(B) Glycerol and fatty acids

Chapter - 9
(C) Diglyceride and fatty acids
(D) 2-Monoglyceride and fatty acids

118.After a meal, dietary lipid is absorbed by the small intestine and transported in the lymph mainly as
(A) VLDLs
(B) Free fatty acids bound to albumin
(C) Chylomicrons
(D) LDLs
119.What would you expect to find in a sample of hepatic portal blood after protein has been digested and
absorbed by the GI tract?
(A) Free amino acids
(B) Dipeptides and tripeptides
(C) Free amino acids and dipeptides
(D) Free amino acids and tripeptides
120.Which one of the following vitamins stimulates calcium absorption by the GI tract?
(A) Vitamin E (B) Vitamin D

GIT
(C) Vitamin A (D) Vitamin K

121.Which vitamin is transported in chylomicrons as an ester?

(A) Vitamin E (B) Vitamin D
(C) Vitamin A (D) Vitamin K

122.Potassium is absorbed in the jejunum by

(A) Active transport
(B) Facilitated transport
(C) Passive transport
(D) Active and passive transport
123.Ascorbic acid is a potent enhancer of iron absorption because it
(A) Enhances the absorption of heme iron
(B) Enhances the activity of heme oxygenase
(C) Is a reducing agent, thereby helping to keep iron in the ferrous state
(D) Decreases the production of ferritin by enterocytes

124.The first step in alcohol metabolism by the liver is the formation of acetaldehyde from alcohol, a chemical
reaction catalyzed by
(A) Cytochrome P450
(B) NADPH-cytochrome reductase P450
(C) Alcohol oxygenase
(D) Alcohol dehydrogenase
116.C 117.D 118.C 119.A 120.B 121.C 122.C 123 .C 124.D

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 Physiology

125. The small intestine secretes various triglyceride-rich lipoproteins, but the liver secretes only
(A) Chylomicrons (B) VLDLs
(C) LDLs (D) HDLs

126.See the diagram below of a intertinal cell. Where is it most likely present?

a) Duodenum

b) Ileum

c) Colon

d) Jejunum

125.B 126.A

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 Physiology

Explanation
Chapter-9 GIT

Section-1 -: Salivary Glands, Oesophagus and Stomach

1. Ans. B. zymogen
(Ref: Ref: 23rd edition Ganong's Page-429)
a. A zymogen (or proenzyme) is an inactive enzyme precursor.
b. A zymogen requires a biochemical change (such as a hydrolysis reaction revealing the active site, or
changing the configuration to reveal the active site) for it to become an active enzyme.
c. The biochemical change usually occurs in a lysosome where a specific part of the precursor enzyme is
cleaved in order to activate it.
d. The amino acid chain that is released upon activation is called the activation peptide.
e. The pancreas secretes zymogens partly to prevent the enzymes from digesting proteins in the cells in
which they are synthesised.
f. Fungi also secrete digestive enzymes into the environment as zymogens.
g. The external environment has a different pH than inside the fungal cell and this changes the zymogen's
structure into an active enzyme.

Examples of zymogens:
a. Angiotensinogen b. Trypsinogen
c. Chymotrypsinogen d. Pepsinogen
e. Most proteins in the coagulation system f. Some of the proteins of the complement system
g. Caspases h. Proelastase
i. Prolipase j. Procarboxypolypeptidases

2. Ans. D. Saliva
(Ref: Ganong - 23rd Ed)
Daily Secretion of GIT
Daily Volume (ml) pH
Saliva 1000Q 6.0–7.0
Gastric secretion 1500 1.0–3.5
Pancreatic secretion 1000 8.0–8.3Q
Bile 1000 7.8
Small intestine secretion 1800Q 7.5–8.0
Brunner’s gland secretion 200 8.0–8.3
Large intestinal secretion 200 7.5–8.0
Total 6700

a. The concentration of K+ in pancreatic juice is same as plasma i.e. around 4.5 mEq/L Q
b. Liver bile contains 5-6 mEq/L whereas Gall Bladder bile has 12 mEq/L Q
c. In ileum the concentration rises due to exchange of potassium with Na+ (K+ absorption also occurs). It
normally is around 10-12 mEq/L.

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 GIT

d. As it reaches rectum the conc. of K+ rises to 75 mEq/L Q due to colonic secretion of K+.
e. Normal stool K+ excretion is 5-10 mEq a day Q and volume is 100-200 grams.
f. Saliva contains 25-30 mEq/L at low flow rate Q & 15-20 mEq/L at high flow rate
g. So max conc. is seen in stool Q or in colon Q but maximum levels or secretion is seen in saliva Q (since
volume secreted is 1.5 L/day Q as compared to 100-200 ml of stool)

3. Ans. D. Parietal cells

Chapter - 9
GIT
4. Ans. A. Primary (Ref: Ganong – 23rd Ed-page-469)
a. Esophageal peristalsis can be initiated by deglutition ("primary" peristalsis) or local distention ("secondary"
peristalsis).
b. Deglutition is one of the most complex reflex neural activities.
c. The initial phase is voluntary when food is chewed, mixed with saliva and formed into a bolus before being
pushed to the posterior pharynx by the tongue. Receptors in the posterior pharynx are then activated to
initiate the involuntary phase of deglutition, which involves carefully sequenced contraction of numerous
head and neck muscles.
d. Secondary peristalsis refers to peristalsis activated by esophageal distention.
e. This can occur physiologically by food left behind after the primary peristaltic wave has passed, or by
refluxed contents from the stomach.
f. Unlike primary peristalsis, secondary peristalsis is not accompanied by deglutition with associated
pharyngeal and upper esophageal sphincter motor function.
g. In the striated muscle esophagus, distention activates a peristaltic reflex that is mediated by central
mechanisms; distention activates vagal afferents, which in turn leads to sequential vagal efferent
discharge to the striated musculature of the proximal esophagus.

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 Physiology

5. Ans. A. PGE2
Type Receptor Function
 vasodilation
PGI2 IP  inhibit platelet aggregation
 bronchodilatation
 bronchoconstriction
EP1
 GI tract smooth muscle contraction
 bronchodilatation
EP2  GI tract smooth muscle relaxation
 vasodilatation
 ↓ gastric acid secretion
PGE2  ↑ gastric mucus secretion
 uterus contraction (in pregnancy)
EP3
 GI tract smooth muscle contraction
 lipolysis inhibition
 ↑ autonomic neurotransmitters
 hyperalgesia
Unspecified
 pyrogenic
 uterus contraction
PGF2α FP
 bronchoconstriction

6. Ans. C. G cells- Gastrin

Explanation
a. B cells secrete insulin, D cells secrete somatostatin, K cells of upper small intestine secrete GIP
b. Gastrin is a hormone that stimulates secretion of gastric acid by the parietal cells of the stomach. It is
released by G cells in the stomach and duodenum.
i. Somatostatin- Delta cells (delta-cells or D cells) are somatostatin producing cells.
c. They can be found in the stomach, intestine and the Islets of Langerhans in the pancreas.
i. Insulin is synthesized in the pancreas within the beta cells (beta-cells) of the islets of Langerhans.
ii. One to three million islets of Langerhans (pancreatic islets) form the endocrine part of the pancreas,
which is primarily an exocrine gland. The endocrine portion only accounts for 2% of the total mass of
the pancreas. Within the islets of Langerhans, beta cells constitute 60–80% of all the cells.

7. Ans. B. Posterior 1/3

“Bitter substances are tasted mostly on the back of the tongue, sour along the edges, sweet at the tip, and salt on
the dorsum anteriorly”.

8. Ans. D. It helps in digestion of proteins

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 GIT

9. Ans. C. Active secretion

The last step in hydrogen ion ACTIVE SECRETION is achieved by an H +, K+ - ATPase “proton pump” which is
located in the apical microvillus membrane and tubovesicular apparatus of the parietal cells of stomach. This
PROTON PUMP exchanges hydrogen for potassium across the microvillus membrane.

10. Ans. B. 300

Daily Folic Acid Requirement
Category Weight kg Folate µg

Chapter - 9
Infants 6 25
9 35
Children 13 50
20 75
28 100
Males 45 150
66 200
72 200
79 200
77 200
Females 46 150
55 180
58 180
63 180

GIT
65 180
Pregnant 400
Lactating 280
260

11. Ans. D. Low pH (Gastric acid)

Gastric acid catalyzes the cleavage of inactive PEPSINOGEN into proteolytically active pepsins, and also provides
the low pH required for pepsin activity.

12. Ans. B. Antrum

GASTRIN is produced by G cells located in the lateral walls of the glands situated in the antral portion of the gastri
mucosa. It is released in response to partially digested protein, ethyl alcohol in about 10% concentration, and,
distention of the antrum of the stomach.

13. Ans. A. Parasympathetic nerve

14. Ans. B. Ca++
Contents of Gastric Juice (pH1)
a. Water Pepsin
b. Intrinsic factor H+
c. Mucus Na+, K+ Mg+
d. Gelatinase Cl-, HPO4 , SO4-

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 Physiology

15. Ans. A. Stomach

In the body of the stomach, including the fundus, the glands contain parietal (oxyntic) cells, which secrete
hydrochloric acid and intrinsic factor, and chief ( peptic) cells, which secrete pepsinogens.

16. Ans. B. Antrum

17. Ans. A. Originates in body of stomach

a. Mixing: wave of stomach: when the stomach contains food, weak peristaltic constrictor waves, called
mixing waves, begin in the mid portion of stomach wall and move towards the antrum along the stomach
wall about once every 15 to 20 seconds.
b. Peristalsis begins in the lower portion of the body, mixing and grinding. the food and permitting small,
semiliquid portions of it to pass through pylorus and enter the duodenum.

18. The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 629
 Gastric emptying of particles greater than about 7 mm does not occur during the digestive state. The lag phase is the
time required for the stomach to grind large particles into smaller particles in this size range.
 Choice A is not correct because conversion from interdigestive to digestive states occurs immediately upon the first
few swallows of a meal.
 Choice B is incorrect because cephalic and gastric phases of acid secretion reach maximum near the onset of the lag
phase.
 Choice C is incorrect because the lag phase is at the beginning of the emptying curve, not at the end.

19. The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 629
Lipids (fats) have the greatest effect in slowing gastric emptying because they have the highest caloric content. Decreased
pH in the duodenum is also a powerful suppressant of gastric emptying. However, the question asks about an ingested
meal, not conditions in the duodenum.

20. The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page
 As the gastric reservoir fills during a meal, mechanoreceptors signal the CNS. When the limits of adaptive relaxation
in the reservoir are reached, signals from the stretch receptors in the reservoir’s walls account for the sensations of
fullness and satiety.
 Overdistension is perceived as discomfort. Adaptive relaxation appears to malfunction in the forms of functional
dyspepsia characterized by the symptoms described in this question.
 If adaptive relaxation is compromised (e.g., by an enteric neuropathy), mechanoreceptors are activated at lower
distending volumes and the CNS wrongly interprets the signals as if the gastric reservoir were full.
 None of the other choices would be expected to activate mechanosensory signaling of the state of fullness of the
gastric reservoir.

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 GIT

21.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 573
 Salivary secretion is exclusively under neural control.
 The others need both neural and hormonal stimulation and are, therefore, only partially stimulated by the sight,
smell, and chewing of food (cephalic phase).
 The sight, smell, and chewing of food stimulate the parasympathetic nervous system, which stimulates salivary
secretion.

22.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 595
Although the cephalic and intestinal phases stimulate gastric secretion, the gastric phase is, by far, the most important.

Chapter - 9
23.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 816
Carbonic anhydrase catalyzes the formation of carbonic acid from carbon dioxide and water. It is not involved in the
formation of carbon dioxide from carbon and oxygen, bicarbonate ion from carbonic acid, hydrochloric acid, or
hypochlorous acid.

24.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 757
 Parasympathetic stimulation induces the release of kallikrein by the salivary acinar cells, which converts kininogen to
form lysyl-bradykinin (a potent vasodilator).
 Bradykinin is a vasoactive peptide.
 Kininogen is the precursor for kinins.
 Kinins include bradykinin and lysyl-bradykinin.

25.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 573
Intrinsic factor is secreted by the parietal cells of the stomach and is not secreted by the salivary glands. Lactoferrin,
amylase, mucin, and muramidase are found in saliva.
26.The answer is (A) 1 to 2. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 577

GIT
In the fasting state, the pH of the stomach is low, between 1 and 2.

27.The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 572
 Salivary secretion is inhibited by atropine.
 Atropine is an anticholinergic drug that competitively inhibits ACh at postganglionic sites, inhibiting parasympathetic
activity. Pilocarpine actually stimulates salivation because of its muscarinic action.
 Cimetidine is an antagonist for the histamine H2 receptor.
 Aspirin is the most widely used analgesic (pain reducer), antipyretic (fever reducer), and anti-inflammatory drug.

28.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 575
The chief cells of the stomach secrete pepsinogen, and the parietal cells of the stomach secrete hydrochloric acid and
intrinsic factor. Gastrin and CCK are secreted by specialized endocrine cells.

29.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 579
Histamine interacts with its receptor in parietal cells to increase the intracellular cAMP. Histamine does not cause an
increase in intracellular sodium or cGMP or a decrease in intracellular calcium.

30.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 595,599
 When the pH of the stomach falls below 3, the antrum secretes somatostatin, which acts locally to inhibit gastrin
release; therefore, somatostatin inhibits gastric secretion. Enterogastrones are hormones produced by the
duodenum that inhibit gastric secretion and motility. Intrinsic factor is involved in the absorption of vitamin B12 and
is not involved in the release of gastrin.
 Secretin is a hormone secreted by the duodenal and jejunal mucosa when exposed to acidic chyme and is
responsible for stimulating pancreatic secretion rich in bicarbonate.
 CCK stimulates the gallbladder to contract and the pancreas to secrete a juice rich in enzymes.

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 Physiology

31. Ans. C. Gastrin

32. Ans. B. Parietal cell Ref: Ganong - 23rd Ed –Page-45

33.The answer is A.
Ref: Ganong - Review of Medical Physiology 23rd Ed Page 576
Intrinsic factor is critical for the absorption of vitamin B12 by the ileum. None of the other substances is secreted by
parietal cells. Gastrin, somatostatin, and CCK are secreted by specialized GI endocrine cells, whereas chylomicrons are
produced by enterocytes

Section-2 -: Gall Bladder, Liver, Pancreas & Bile

1. Ans. A. Increase gastrin secretion

Actions of CCK Q
CONTRACTION OF GALLBLADDER SECRETION OF PANCREATIC JUICE
Inhibits gastric emptying Exerts atrophic effect on the pancreas
Increases the secretion of enterokinase Augments the action of secretin in producing secretion
of an alkaline pancreatic juice
Enhances the motility of small intestine and colon CCK and gastrin stimulate glucagon secretion
Augments the action of secretin in contracting the
pyloric sphincter

2. Ans. C. CCK

3. Ans. is ‘A’ Bile salts

Cholagogues Q Choleretics Q
Substances that cause contraction of gall bladder Substances that increase the secretion of bile (bile
(CCK) salts are most potent)

4. Ans. C. Chloride
Composition of Bile
Ingredients Hepatic bile Gallbladder bile
• Water 97.5 gm/dL Q 92.0 gm/dL Q
• Bile salts 1.10 gm/dL Q 6gm/dL Q
• Bilirubin 0.04 gm/dL 0.30 gm/dL
• Cholesterol 0.10 gm/dL 0.30-0.90 gm/dL
• Fatty acids 0.12 gm/dL 0.30-0.
• Lecithin 0.04 gm/dL 0.30 gm/dL
• Sodium ions 145 mEq/L 130 mEq/L
• Potassium ions 5 mEq/L 12 mEq/L
• Calcium ions 5 mEq/L 23 mEq/L

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 GIT

• Chloride Ions 100 mEq/L 25 mEq/L

• Bicarbonate ions 28 mEq/L Q 10 mEq/L Q

5. Ans. E. Stimulated gastric emptying

6. Ans. D. Increases gastrin secretion

7. Ans. A. Secretin

Chapter - 9
Factors that stimulate gastric secretion (Acid)
a. Gastrin Q b. Histamine Q c. Acetyl choline Q
d. Gastrin releasing peptide Q e. CCK Q

Factors that inhibit gastric secretion (Acid) -

a. Somatostatin Q b. Secretin Q c. Enteroglucagon Q
d. Prostaglandins Q e. Neurotensin Q f. GIP Q
g. PYY Q.

a. Low pH directly inhibits HCI and gastrin secretion (NMS physiology 91)
b. Principal action of gastrin — stimulation of gastric acid and pepsin secretion  gastrin secretion is
increased by the following factors and there by HCI secretion: -
i. Luminal  peptides and amino acids, Distension
ii. Neural  increased vagal stimulation via GRP
Blood borne  calcium and Epinephrine

GIT
iii.

8. Ans. C. Proteolytic enzymes secreted in inactive form

9. Ans. A. Enterokinase
Enterokinase, an enzyme found in the duodenal mucosa, cleaves the lysine-isoleucine bond of trypsinogen to
form trypsin.
10. Ans. D. Estrogen
i. Fibrinogen, Lipoprotein and angiotensinogen (that converted into Angiotensin) are synthesized by liver. So
after hepatectomy, their levels are decreased.
ii. Estrogens are mainly catabolized by liver, so their levels increased after hepatectomy.

11. Ans. A. Pancreatic juice

Body secretion pH
• Pancreatic juice 8
• Gastric juice 1
• Saliva 7
• Hepatic duct bile 7.8-8.6
• Gallbladder bile 7.0-7.4

12.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 596,647

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 Physiology

Secretin stimulates secretion of a bicarbonate- rich pancreatic juice. Somatostatin, gastrin, and insulin do not. CCK
stimulates a pancreatic secretion rich in enzymes and potentiates the action of secretin.

13.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 574
Excessive production of gastrin results in acid hypersecretion and peptic ulcer disease. Patients with Zollinger-Ellison
syndrome do not suffer from excessive acid reflux, excessive secretion of CCK, failure of the liver to secrete VLDLs, or
failure to secrete a bicarbonate-rich pancreatic juice

14.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page

 Unlike patients who have diabetes, healthy humans are capable of keeping their blood glucose within a relatively
narrow range after a meal, 120 to 150 mg/dL.
 Blood levels of 30 to 50 mg/dL and 50 to 70 mg/dL indicate hypoglycemia, and blood levels of 220 to 250 mg/dL and
300 to 350 mg/dL indicate hyperglycemia.

15.The answer is A.
Ref: Ganong - Review of Medical Physiology 23rd Ed Page 640
 The liver has the enzyme glucose-6- phosphatase, but muscle does not.
 Consequently, muscle is incapable of releasing glucose from glucose 6- phosphate.
 Glucose undergoes reactions other than glycolysis.
 Both liver and muscle have glucose-1- hosphatase and glycogen phosphorylase enzymes.
 The synthesis of glucose, called gluconeogenesis, is carried out mostly in the liver and, to some extent, in the
kidneys.

16.The answer is A.
Ref: Ganong - Review of Medical Physiology 23rd Ed Page 637
Fatty acid synthesis occurs only in the cytoplasm. Mitochondria are involved in fatty acid oxidation rather than synthesis.
Fatty acid synthesis does not occur in the nucleus. Endosomes and the Golgi apparatus are not involved in fatty acid
synthesis.

17.The answer is C.
Ref: Ganong - Review of Medical Physiology 23rd Ed Page 644
Both urea and glutamine play an important role in the storage and transport of ammonia in the blood. Histidine,
phenylalanine, methionine, and lysine are not involved in ammonia transport.

18.The answer is C.
Ref: Ganong - Review of Medical Physiology 23rd Ed Page 704
 The liver makes transferrin to carry iron in the blood.
 Hemosiderin is an intracellular complex of ferric hydroxide, polysaccharides, and proteins.
 Haptoglobin binds free hemoglobin in the blood.
 Ceruloplasmin is a circulating plasma protein involved in the transport of copper.

19.The answer is A.
Ref: Ganong - Review of Medical Physiology 23rd Ed Page 565
Smokers inhale polycyclic aromatic hydrocarbons, which stimulate drug-metabolizing enzymes. Therefore, smokers have
higher levels of hepatic drug-metabolizing enzymes than nonsmokers. The level of drug-metabolizing enzymes in the liver
is lowered by malnutrition and is lower in the newborn.

20.The answer is C.
Ref: Ganong - Review of Medical Physiology 23rd Ed Page 613
 A healthy liver converts vitamin D (cholecalciferol) to form 25-hydroxycholecalciferol, but a diseased liver has a
reduced capacity to do so.
 The kidney, not the liver, is responsible for the conversion of 25-hydroxycholecalciferol to 1,25-
dihydroxycholecalciferol.

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 GIT

 Vitamin D, not 1,25-hydroxycholecalciferol

, is absorbed by the small intestine

21.The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 647
LDLs are removed from the blood by the liver by binding to LDL receptors, followed by endocytosis of the LDL-receptor
complex. LDLs do not bind to HDL receptors, albumin, transferrin, or ceruloplasmin.

22.The answer is D.
Ref: Ganong - Review of Medical Physiology 23rd Ed Page 334
Acclimatization to cold produces several different (and contrasting) sets of changes, depending on the acclimatizing

Chapter - 9
environment (and, perhaps, on characteristics of the population being acclimatized).

23.The answer is D.
Ref: Ganong - Review of Medical Physiology 23rd Ed Page
 Catecholamines stimulate glycogenolysis and gluconeogenesis in the liver, causing glucose to be synthesized and
released into the blood.
 Catecholamines stimulate glycogen phosphorylase in muscle to free glucose for use by the muscle. Muscle cannot
release glucose to the circulation because it lacks glucose-6-phosphatase. However, the muscle can release lactate,
which can be used in gluconeogenesis by the liver.
 Catecholamines inhibit the release of insulin from the pancreas. Insulin would be
 counterproductive to attempts to increase blood glucose.
 Catecholamines increase the release of fatty acids from the adipose tissue, to be used in gluconeogenesis by the
liver.

24.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 643
The uptake of bile acid by hepatocytes is sodium-dependent and is not dependent on calcium, iron, potassium, or
chloride.

GIT
Section-3 -: Small and Large Intestine
1. Ans. A. Fermentation of mucus
( Ref: 23rd edition Ganong's Page-451)
Research suggests that the relationship between gut flora and humans is not merely commensal (a non-harmful
coexistence), but rather a symbiotic relationship.Though people can survive without gut flora, the microorganisms
perform a host of useful functions,
a. Functions
i. producing vitamins for the host (such as biotin and vitamin K).
ii. Bacteria turn carbohydrates they ferment into short chain fatty acids, or SCFAs
iii. These materials can be used by host cells, providing a major source of useful energy and
 nutrients for humans,as well as helping the body to absorb essential dietary minerals such as
 calcium, magnesium and iron.
iv. Gases and organic acids, such as lactic acid, are also produced by saccharolytic fermentation.
 Acetic acid is used by muscle, propionic acid helps the liver produce ATP, and butyric acid
 provides energy to gut cells and may prevent cancer.
v. Another, less favorable type of fermentation, proteolytic fermentation, breaks down proteins like
 enzymes, dead host and bacterial cells, and collagen and elastin found in food.
vi. Another important role of helpful gut flora is that they prevent species that would harm the host from
colonizing the gut through competitive exclusion, an activity termed the "barrier effect.

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 Physiology

vii. Gut flora have a continuous and dynamic effect on the host's gut and systemic immune systems. The
bacteria are key in promoting the early development of the gut's mucosal immune system both in
terms of its physical components and function and continue to play a role later in life in its operation.
viii. The bacteria stimulate the lymphoid tissue associated with the gut mucosa to produce antibodies to
pathogens.
b. MUCUS
a. In the digestive system, mucus is used as a lubricant for materials that must pass over membranes,
 e.g., food passing down the esophagus. A layer of mucus along the inner walls of the stomach is
vital to protect the cell linings of that organ from the highly acidic environment within it.
b. Mucus does not digested in the intestinal tract.
c. Mucus is also secreted from glands within the rectum due to stimulation of the mucous membrane
within

2. Ans. A. Smooth Muscle relaxant

(Ref: Ganong – 23rd Ed.Pg:345)
a. NO is a very important inhibitory neurotransmitter in the GIT, released from non-adrenergic non-
cholinergic neurons.
b. NO acts as an intra- and extracellular signalling molecule in vascular and smooth muscle GIT cells and it is
an important mediator in numerous physiological and pathophysiological conditions.
c. NO is synthesized from L-arginine by the action of NO synthase (NOS) that is present in nitrergic neurons
of GIT.
d. The most widely reported action of NO in the gut is relaxation of smooth muscle through activation of
soluble guanylate cyclase and the accumulation of cyclic guanosine 3 ', 5'-monophosphate (cGMP).
e. Deficiency of nitrergic innervations has been shown in gastrointestinal Tissues of patients with various
diseases such as are Achalasia and Hirschsprung's disease.
f. Peristalsis is an excellent example of the integrated activity of the enteric nervous system. It appears that
local stretch releases serotonin, which activates sensory neurons that activate the myenteric plexus.
g. Cholinergic neurons passing in a retrograde direction in this plexus activate neurons that release substance
P and acetylcholine, causing smooth muscle contraction.
h. At the same time, cholinergic neurons passing in an anterograde direction activate neurons that secrete
NO, vasoactive intestinal polypeptide (VIP), and adenosine triphosphate (ATP), producing the relaxation
ahead of the stimulus

3. Ans. D. Rectum(Ganong – 23rd Ed.Pg:345)

Daily fluid Turnover (mL) in the Gastrointestinal Tract.
Ingested 2000
Endogenous secretions 7000
Salivary glands 1500
Stomach 2500 Q
Bile 500 Q
Pancreas 1500
Intestine +1000
Total input 9000

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 GIT

Reabsorbed 8800
Jejunum 5500 Q
Ileum 2000
Colon +1300
Balance in stool 200
4. Ans. Both A. and B. Zinc, Lysozyme
Paneth cells—endocrine cells located in the depths of the crypts of Lieberkuhn—secrete defensins, naturally

Chapter - 9
occurring peptide antibiotics that are also secreted elsewhere in the body .
a. Defensins: The principal defense molecules secreted by Paneth cells are alpha-defensins, also known as
cryptones. These peptides have hydrophobic and positively-charged domains that can interact with
phospholipids in cell membranes. This structure allows defensins to insert into membranes, where they
interact with one another to form pores that disrupt membrane function, leading to cell lysis. Due to the
higher concentration of negatively-charged phospholipids in bacterial than vertebrate cell membranes,
defensins preferentially bind to and disrupt bacterial cells, sparing the cells they are functioning to protect.
Paneth cells are stimulated to secrete defensins when exposed to bacteria (both Gram positive and
negative types) or such bacterial products as lipopolysaccharide, muramyl dipeptide and lipid A.
b. Other secretions: In addition to defensins, Paneth cells secrete lysozyme, zinc and phospholipase A2,
which have clear antimicrobial activity. This battery of secretory molecules gives Paneth cells a potent
arsenal against a broad spectrum of agents, including bacteria, fungi and even some enveloped viruses.
c. Paneth cells secrete a number lysozymes into the lumen of the crypt, thereby contributing to maintenance
of the gastrointestinal barrier.

GIT
5. Ans. D. Sigmoid colon
(Ref: Ganong -23nd Ed page 386)

6. Ans. A. It increases the acidity of biliary and pancreatic secretions

7. Ans. C. Pepsin : The site of action of trypsin, chymotrypsin and carboxypeptidase is small intestine which has

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 Physiology

the a pH of around 8 and hence these act best in alkaline pH where as pepsin acts mainly in stomach at a pH
of around 2.0. Thus pepsin is the obvious answer.

8. Ans. A. Completely independent of stomach motility

a. Increase in the gastric motility increases intestinal motility.
b. Though the process is not well understood but there are some cells in the smooth muscle of GI mucosa
K.a. intestinal cell of cajal which generate basic electrical rhythm (BER) and act as a pacemaker and
regulate the motility.
c. These BERs rarely cause muscle contraction but spike potential superimposed on the most depolarizing
portion increases muscle tension.
d. Acetyl choline increase the no. of spikes and tension developed in smooth muscles, hence increases
motility.

9. Ans. D. Hormones Enterogastric reflex -

a. Definition  signals from the colon and small intestine to inhibits stomach motility and stomach
secretion. Q
b. “Products of protein digestion and hydrogen ions (H+) bathing the duodenal mucosa initiate a neurally
mediated decrease in gastric mortality, the Enterogastric reflex. Distention of the doudenum also initiates
this reflex” (Ganong 22nd) also the degree of osmolality of the chyme initiates the reflex.

10. Ans. C. Dipeptidase

Enzymes Secreted by Intestinal Mucosa
• Enteropeptidase • Aminopeptidases
• Dipeptidases • Maltase
• Lactase • Sucrase
• α limit dextrinase • Nuclease and related enzyme

11. Ans. A. Acidity of chyme

SECRETIN is secreted by glands of mucosa of upper pancreatic juice Secretion of secretin is stimulated part of
small intestine. It causes secretion of a watery, alkaline by products of protein digestion and acid

12. Ans. C. Mucus production to protect intestine from aci

BRUNNER’S GLANDS are compound glands of the duodenum and upper jejunum. They are embedded in the
submucous tissue and lined with columnar epithelium They secrete a thick clear alkaline mucinous solution which
helps in protecting the duodenal mucosa from gastric acid.

13. Ans. A. Antigen presenting cells

a. Absorption of protein antigens (bacterial and viral proteins) takes place in the large MICROFOLD CELLS OR
M CELLS.
b. These M cells are specialized intestinal epithelial cells which pass the antigen to lymphoid cells and
lymphoblasts.
c. These activated lymphoblasts enter the circulation and return to intestinal mucosa to secrete IgA in
response to subsequent exposure from same antigen.

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 GIT

14. Ans. C. Aminopeptidase Enzymes Secreted by Exocrine Pancreas

15. Ans. D. Somatostatin

16. Ans. A. Amino acids

The secretion of secretin is increased by the products of protein digestion and by acid bathing the mucosa of the
upper small intestine.
17. Ans. D. Chymotrypsin

Chapter - 9
18. Ans. B. Colon

19. Ans. A. Hexoses

20. Ans. B. failure of migration of neural crest cells from cranial to caudal direction

(Ref: 7th Ed-Page-295)

a. Hirschsprung's disease, or congenital aganglionic megacolon, involves an enlargement of the colon, caused
by bowel obstruction resulting from absence of normal peristaltic activity Q.
b. According to latest research, Hirschsprung's is caused by the interaction between two proteins encoded by
two variant genes. The RET proto-oncogene on chromosome 10 was identified as one of the genes
involved Q.
c. The protein with which RET has to interact in order for Hirschsprung’s disease to develop is termed EDNRB
and is encoded by the gene EDNRB located on chromosome 13.
d. The authors conclude that the mode of inheritance for Hirschsprung’s is oligogenic. This means that two

GIT
mutated genes interact to cause a disorder. Variations in RET and EDNRB have to coexist in order for a
child to get Hirschsprung’s.
e. RET codes for proteins that assist cells of the neural crest Q (which later become ganglion cells) in their
movement through the digestive tract during the development of the embryo from cranial to caudal
direction. EDNRB codes for proteins that connect these nerve cells to the digestive tract.

21. Ans. A. Gall bladder contraction

FATTY ACIDS in duodenum release CCK which causes gallbladder contraction, Acid, products of protein digestion
and calcium ions also stimulate CCK secretion.

22. Ans. A. Colon

ANTIPERISTALSIS or reversed peristalsis refers to a wave of contraction in the GI tract which moves toward the
oral end, when it occurs in duodenum it leads to vomiting but in the ascending colon it occurs normally Q.

23. Ans. D. Jejunum

(Ref: Ganong - Review of Medical Physiology 22nd Ed. Pg:476)
The intestines are presented each day with about 2000 mL of ingested fluid plus 7000 mL of secretions from the
mucosa of the gastrointestinal tract and associated glands. Ninety-eight percent of this fluid is reabsorbed, with a
daily fluid loss of only 200 mL in the stools. Maximum reabsorption occurs in Jejunum around 5500 ml.
24. Ans. A. Somatostatin Ref: Ganong’s-23rd Edition, P-434

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25. Ans. B. Alkaline pH

(Ref: Ganong’s-23rd Edition, P-458)
a. absorption of calcium increased by
Vitamin D is an important co-factor in the intestinal absorption of calcium, as it increases the number of
calcium binding proteins.

b. absorption of calcium decreased by

i. "Unesterified long-chain saturated fatty acids, i.e. palmitic acid
ii. Phytic acid binding to calcium
iii. Oxalic acid binding to calcium
iv. Cortisol binding to calcium
v. Low pH food and proteins

26. Ans. B. colon

(Ref: Ganong’s-23rd Edition, P-475)
a. The first part of a test meal reaches the cecum in about 4 h, and all the undigested portions have entered
the colon in 8 or 9 h.
b. On average, the first remnants of the meal traverse the first third of the colon in 6 h, the second third in 9
h, and reach the terminal part of the colon (the sigmoid colon) in 12 h. From the sigmoid colon to the
anus, transport is much slower.
c. When small colored beads are fed with a meal, an average of 70% of them are recovered in the stool in 72
has but total recovery requires more than a week.
d. The time taken for food or other ingested objects to transit through the gastrointestinal tract varies
depending on many factors, but roughly, it takes 2.5 to 3 hours after a meal for 50% of stomach contents
to empty into the intestines and total emptying of the stomach takes 4 to 5 hours. Subsequently, 50%
emptying of the small intestine takes 2.5 to 3 hours. Finally, transit through the colon takes 30 to 40 hours

27. Ans. A. Reductase

(Ref: Ganong’s-23rd Edition, Pg458-9)
a. Most of the iron in the diet is in the ferric (Fe3+) form, whereas it is the ferrous (Fe 2+) form that is
absorbed. Fe3+ reductase activity is associated with the iron transporter in the brush borders of the
enterocytes .
b. Gastric secretions dissolve the iron and permit it to form soluble complexes with ascorbic acid and other
substances that aid its reduction to the Fe 2+ form.
c. The importance of this function in humans is indicated by the fact that iron deficiency anemia is a
troublesome and relatively frequent complication of partial gastrectomy.
d. Almost all iron absorption occurs in the duodenum. Transport of Fe 2+ into the enterocytes occurs via
divalent metal transporter 1 (DMT1).

28. Ans. A. Transport lipids

a. Chylomicrons are lipoprotein particles that consist of triglycerides (85-92%), phospholipids (6-12%),
cholesterol (1-3%) and proteins (1-2%).

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 GIT

b. They transport dietary lipids from the intestines to other locations in the body. Chylomicrons transport
exogenous lipids to liver, adipose, cardiac, and skeletal muscle tissue, where their triglyceride components
are unloaded by the activity of lipoprotein lipase.
c. As a consequence, chylomicron remnants are left over and are taken up by the liver.Chylomicrons are a
type of structure that includes lipoprotein produced in absorptive cells of small intestines, specifically, the
epithelial cells within the villi of the duodenum.

Chapter - 9
29. Ans. A. Lengthened individual villi
a. When a massive small bowel resection is necessary, the body attempts to adapt by increasing digestion
and absorption of nutrients.
b. This is accomplished by lengthening the individual villi and the number of active cells on the villous
surface, which effectively increases the absorptive area available.
c. The individual epithelial cell does not increased life span, and since the villi and cells are decreased post
resection synthesis of digestive enzymes is not increased.

30. Ans. ‘B’

Upper 1/4th of oesophagus : has striated muscle
Middle portion : has both striated and smooth muscle
Distal portion : has only smooth muscle

31. Ans. ‘C’

The extrinsic sympathetic fibres :

GIT
These secrete norepinephrine and cause vasoconstriction.
The intrinsic enteric nervous system fibres :
These secrete many different substances. For example, many of them secrete VIP and NO; these cause the
hyperemia that occurs during digestion of food.

32. Ans. ‘E’

D. Macroheterogeneity :
1. This general term refers to a polypeptide hormone that is secreted in different forms due to the difference
in the number of amino acids in them . For example, gastrin is secreted in many forms (all these forms
have the same carboxyl terminal configuration) :
2. G 14, G 17 and G 34 are the main forms (the number refers to the number of amino acid residues in the
gastrin molecule); G 17 is the main form with respect to gastric acid secretion.
T/2 of
G 14 and G 17 : 2 to 3 minutes
G 34 : 15 minutes
a. One form has more than 45 amino acids
b. Another form is the carboxyl terminal tetrapeptide ( this has all the actions of gastrin; however, it is only
1/10th as potent as G 17)

33. Ans. ‘D’

CCK is formed from its precursor prepro-CCK. The various forms of CCK are :

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 Physiology

CCK 58, CCK 39, CCK 33, CCK 12, CCK 8, CCK 4 (the numbers indicate the number of amino acids);
Unlike gastrin, the non-sulphated form of CCK is not found in the tissues.
The CCK secreted in the duodenum and jejunum is mostly CCK 8 and CCK 12.
The enteric and pancreatic nerves contain primarily CCK.
CCK 58 and CCK 8 are found in the brain.

34. Ans. ‘A’

The vagal endings on the gastrin-producing G cells secrete GRP and not acetylcholine; the GRP mediates the
gastrin release from the G cells. GRP has 27 amino acids; out of this, the 10 amino acids at the carboxyl terminal
are almost same as bombesin (a peptide found in amphibians).
Substance P is found in cells and neurons of the GIT; it increases the motility of the small intestine.
(Both GRP and substance P may enter the circulation)
Apart from the pancreas, glucagon is secreted by the GIT; this may be partly responsible for the hyperglycemia
that occurs after pancreatectomy.

35. Ans. ‘D’

As the volume of pancreatic secretion increases, its Cl - concentration falls and its HC03 concentration
increases. Why? This is because although HC03 is secreted in the small ducts, it is reabsorbed in the large ducts in
exchange for Cl-. The magnitude of the exchange is inversely proportionate to the rate of flow.
The enzyme content in the pancreatic juice decreases with secretin.

36. Ans. D Saliva

37. Ans. ‘D’

Total number of swallows per day Out of this, : 600
1. along with eating/drinking : 200
2. while awake without food : 350
3. while sleeping : 50

38. Ans. ‘B’

Body (and also fundus )
Have
i) Parietal (or oxyntic) cells which produce HCl and intrinsic factor
ii) Chief (or peptic or zymogen) cells which produce pepsinogens
Mucus is secreted in all parts of the stomach.

39. Ans. ‘C’. Pancreas

Enzymes from Help in digestion of
Salivary and lingual glands Carbohydrates and fats
Stomach Proteins and fats
Exocrine pancreas All
Cell membrane of enterocytes Carbohydrates and proteins
Cytoplasm of enterocytes (has peptidases) Di- and tri- and tetrapeptides.

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 GIT

40. Ans. ‘E’. All

The luminal side of enterocyte is lined by brush border (made up of microvilli);
in turn, the microvilli is ‘covered’ by 2 layers (from lumen towards the cell) viz. :
- unstirred water layer
- glycocalyx layer (this is rich in neutral and amino sugars)
Thus, for a substance to enter the cell from the lumen, it has to cross the unstirred water layer, glycocalyx, brush
border and the mucous layer.

Chapter - 9
41. Ans. ‘A’. Isomaltase
Isomaltase is also known as alpha-dextrinase
Substrate Digested by (bracket shows % contribution to digestion by the enzyme)
Alpha dextrins Alpha dextrinase (95), maltase (5)
Maltose Alpha dextrinase (50), maltase (25), sucrase (25)
Maltriose Alpha dextrinase (50), maltase (25), sucrase (25)

42. Ans. ‘A’

Glucose absorption in intestine and kidney have the features mentioned above; further, they are insulin-
independent.

43. Ans. ‘A’ Pepsinogen I

Two types of pepsinogen are secreted by the stomach viz. pepsinogen I and II.

GIT
Pepsinogen I is secreted by acid-secreting regions of the stomach;
Pepsinogen II is secreted by acid-secreting regions as well as pyloric regions.
Maximum acid secretion correlates with pepsinogen I levels.

44. Ans. ‘A’. 1.6 to 3.2

Thus, pepsins get inactivated when the gastric contents mix with the alkaline pancreatic juice in the
duodenum/jejunum.
The pH of intestinal contents
- in the duodenal cap : 2 to 4
- rest of the duodenum : 6.5 (approx.)

45. Ans. ‘D’. Chymosin (also called rennin)

Chymosin is a milk-clotting enzyme found in young animals but is not present in humans.

46. Ans. ‘D’. All

Absorption of proteins can occur as
- Amino acids
- Di- and tripeptides; inside the enterocyte, they are then broken down to amino acids by the intracellular
peptidases
- (note : protein can be absorbed as such also)

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 Physiology

47. Ans. ‘B’. Lipids

48. Ans. ‘B’

Salivary glands (1500 ml), stomach (2500 ml), bile (500 ml), pancreas (1500 ml), intestine (1000 ml), Total
endogenous secretions (7000ml); exogenous i.e. ingested water (2000 ml)

49. Ans. ‘A’

Jejunum (5500 ml), ileum (2000 ml), colon (1300 ml); total (8800 ml)
Very small movement of water occurs in the stomach.
Thus, out of the total input of 9000 ml of water, 8800 is absorbed; 200 ml is lost in stools. In other words, nearly
98% of the total input is absorbed. About 7500 ml gets absorbed in small intestine and only 1500 ml goes to the
colon; out of this 1500 ml, 1300 ml gets absorbed in the colon.

50. Ans. ‘D’. Sodium

Small intestine
Most substances are absorbed from small intestine.
Colon
Substances absorbed from colon :
Sodium is absorbed in significant amounts in colon; in fact sodium (and also chloride) is absorbed throughout the
small intestine and colon
Chloride is absorbed to some extent
Short-chain fatty acids are absorbed from colon
(Note : long-chain fatty acids are absorbed from small intestine)
Substance secreted into colon
Potassium : this is secreted into the colon when the luminal K + is low.

51. Ans. ‘D’

52. Ans. ‘B’. Vitamins (except vitamin b12) and sulphate

1. All vitamins (except vitamin B12) ( and also sulphate) are absorbed in the upper and mid small intestine.
2. Calcium, ferrous and chloride are absorbed to some extent in the lower small intestine

53. Ans. ‘C’. Secretes bicarbonate

Another difference is that there is very little absorption of NaCl in the duodenum

54. Ans. ‘B’. Haemoglobin

Percentage of total body iron
Haemoglobin 70
Myoglobin 3
Ferritin 27

55. Ans. E . Villous membrane

To enter the enterocyte (which is the columnar cell on the villous cell membrane), A to D are barriers except

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 GIT

56. Ans. A. 6.7

For salivary -amylase, the optimum pH is 6.7. It does not (it cannot) act in the acidic pH of the stomach. For
pepsins, optium pH is 1.6 to 3.2
(pH in the duodenal cap = 2- 4, pH of the rest of the duodenum is 6.5 approximately)

57. Ans. A. 3 glucose

Chapter - 9
Maltriose = 3 Glucose
Maltose = 2 Glucose
Suerose = Glucose + fructose
Lactose = Glucose + galactose
Trahalose = 2 Glucose (a 1 : 1  - linked di chain of glucose)

58. Ans. A. 1:4 

There are no -linkage splitting enzyme in humans ( linkages are found in cellulose etc) Salivary and
pancreatic  anylase can only hydrolyse 1 : 4  linkage in the straight chain but they cannot hydrolyse the
terminal 1 : 4 linkages, the 1 : 4 linkages next to branching or the 1 : 6 linkage

59. Ans. D. All of the above

Isomaltase (or dextrinase) can split  - dextrins, maltose and maltriose

GIT
60. Ans. D. Some CHO can get absorbed as lactose
In the human, the amylase can split carbohydrates only upto oligosaccharides / disacc harides
Lactose cannot be absorbed as such (it has to be split by the lactase enzyme in the membrane)

61. Ans. B. Facilitated Diffusion

Fructose gets absorbed by facilitated diffusion. The transporters involved are
i. E try of fructose from the luminal side into the cell is by GLUT 5 transporter
ii. Exit of fructose from the basolateral membrane to the interstitium is by GLUT 2 transporter

Glucose transporters
There are 2 series of glucose transporters
a. SGLT series (Sodium linked Glucose Transporter) : These are present in the kidney and is the intestine
Features of the SGLT series
i. It is not affected by insulin
ii. No phosphorylation is required
iii. It is inhibited by phlorhizin
b. Glut series (Glucose Transporters)

62. Ans. A. Stomach

Saliva has -amylase (for stract digestion) and also has lipase; it does no have enzymes for digesting proteins. The
duodenal cap or bulb is the first portion of dudenum, it is a common site of peptic ulceration the duodenum
becomes the jejunem at the ligament of Treitz.

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 Physiology

63. Ans. A. Pepsinogen 4

Pepsinogens of gastric mucosa is of 2 groups, immuno histochemically viz
Pepsinogens I - found only in acid – secreting regions
Pepsinogens II - It is found in pyloric region as well

64. Ans. B. Chymosin

(Chymosin, also known as rennin, is found in the stomach of young animals but is probably absent in human)

65. Ans. D. All of the above Protein digestion in stomach is up to polypeptides level. In the intestine, the
intestinal mucosal enzymes and the pancreatic enzymes further digest the polypeptides. The intestinal rush
border has aminopeptidases, carboxypeptidases, endopeptidases and dipeptidases
The pancreatic enzymes for protein digestion are:
Trypsin
Chmotrypsins Which are endopeptidases (Which act on interior peptide bonds)
Elastase
Carboxypeptidases : Which are exopeptides
Further, they are intracellular peptidases in the mucosal cells

66. Ans. A. H+
Aminoacids are transported mostly with Na+ (these are many different transporters). But the di / tripeptides
transporter system requires H+ and not Na+

67. Ans. A. Protein Absorption of undigested protein can occur, especially in infants. This decreases with age.
However, adults can still absorb undigested protein. The M cells (microfold cells) overlying the Payer’s
patches absorb antigens

68. Ans. B. Lingual lipase

Lingual lipase - is secreted by glands of the tongue (Ebner’s glands)
Salvary  amylase - is secreted by salivary glands
Gastric lipase - is not an important enzyme except in pancreatic in sufficiency
But
Lingual lipase is an important enzyme and can digest as much as 30% of diatary triglycerides

69. Ans. C. Duodenum

Beginning of digestion of
i. Carbohydrate - in saliva
ii. Protein - in stomach
iii. fat - in duodenum

70. Ans. B. 1 and 3

Triglyceride = 3 fatty acids + glyecrol (FA = fatty acid)
i.e.

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 GIT

CH2 OH - FA Ist bond

|
CHOH - FA 2nd bond
|
CH2 OH - FA 3rd bond
Pancreatic lipase splits 1st and 3rd bond to give monoglycoride (1 fatty acid + glycerol)
i.e.

Chapter - 9
CH2 OH
|
CHOH - FA (2 monoglyceride)
|
CH2 OH
In Short,
Triglycerides 2 Monoglyceride
Pancreatic lipase and 2 fatty acid

71. Ans. E. All of the above

Pancreatic lipase is the enzyme far fat digestion
(But, first the fats have to be emulsified) There are 2 types of pancreatic lipase (depending on how they can get
activated / facilitated) :
i) Colipase – Facilitated pancreatic lipase
ii) Bile – salt activated pancreatic lipase

GIT
Colipase in obtained from procolipase by action of trypsin
i.e. Trypsin
Procolipase Colipase
Colipase – activated pancreatic lipase Bile – salt activated pancreatic lipase
i) 10-60 times more active
but
ii) Can oplit only triglycerides Can catalyse the hydrolysis of cholesterol esters,
esters of fat – soluble vitamins, phosptolipids
and triglycerides

72. Ans. D. All of the above

73. Ans. A. Bile salts
74. Ans. C. Ileum
75. Ans. A. Cl with channel in luminal membrane

K+
cAMP Cl-
Na+
Cl-

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 Physiology

Choleratoxin activates CAMP, causing more secretion of CL -. It also hampers Na+ carrier in mucosa and thus also
decreases NaCl absorption
Cl- enters enterocytes from the basoleteral membrane and gets secreted by Cl- channel in luminal side

76. Ans. A. Duodenum

The contents of the duodenum may be hyper or hypotonic but the contents of the jejunum is almost isotonic
and this isotonicity of the contents is maintained throughout the small intestine

77. Ans. A Vit B12 is absorbed in ileum; most other vitamins are absorbed in upper small intestine
Vit B12 and folate absorption are Na+ - independent; but absorption of all others (options B,C,D,E,F) are by Na+-
cotransport mechanism

78. Ans. A 70% of iron in body is in Hb

3% in Myoglobin
27% in ferritin
Ferritin is found in enterocytes and other cells. It is the principal tissue storage form of iron

79. Ans. A. Motor control

i. Submucons (or Meissner’s) plexus in the submucosa is concerned with control of intestinal secretion,
blood flow of gut and sensory function.
ii. Myenteric (or Auerbach) plexus is concerned mainly with motor activity (motility)

80. Ans. A. PS generally (+) SM of wall and (-) sphincters

i. Sympathetic stimulation : Stimulates sphincters -: inhibits smooth muscle in walls
ii. Parasympathetic stimulation : inhibits sphincters; stimulate, smooth muscle in wall

81. Ans. E. It does not require the enteric nervous system

Peristalsis is a reflex response to stretch. The stretch causes a circular contraction behind the stimulus and
an area of relaxation in front of it

82. Ans. A. Oesophagus

i. Peristalsis - is seen from oesophagus to rectum
ii. BER - is seen everywhere in GIT except in oesophagus and
proximal portions of stomach
(iii) MMC (Migrating Motor complex) - migrates from the stomach to distal ileum
BER is initiated by the interstitial cells of Cajal (Which are the pacemaker cells)
The ‘spikes’ on the BER are increased by acetylcholine and decreased by epinephrine

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 GIT

83. Ans. A.

84. Ans. F. Gastric may have a role in its generation

Motilin is responsible for MMC (migrating motor complex). It is secreted by EC cells and Mo cells in stomach,
small intestine colon. It causes contraction of smooth muscle in stomach / intestine

85. Ans. E. CCK

Chapter - 9
There are 2 families of gastro intestinal hormones:
i. Gastrin family  includes gastrin, CCK – PZ
ii. Secretin family  includes secretin, glucagon, glicentin VIP, GIP

86. Ans. D. Vagal (+) releases gastrin from G cells, Ach being the mediator
Gastrin is also secreted by ‘TG’ cells which are present throughout the stomach and small intestine
Entero endocrine cells are cells of GIT which secrete hormones (peptides). If these cells also secrete serotomin,
they are called EC (entero chromaffin) cells; if they secrete amines (in addition to peptide secretion), are called
APUD (amine precursor uptake and decarboxylate) cells
i.e. EC cells – secrete peptide plus Serotonin
APUD cells – secrete peptides plus amines
Gastrin has 3 forms : G14, 17 and 34
The principal form with respect to gastric acid secretionis G17
Macroheterogeneity : is varying lengths of amino acids
Microheterogeneity : is same length of amino acid but difference of single amino acid

GIT
residues
Vagus stimulates gastrin release; the neurotran mitter is gastrin – releasing peptide (GRP) and not acetyecholine
In pernicious anaemia, there is gastric atrophy therefore, there is no acid production. Thus, the negative feedback
effect of acid on gastrin secretion is not there, so, there is more gastrin.

87. Ans. D. es gastric motility

CCK- PZ inhibits gastric motility

88. Ans. E. es gastric acid secretion by an action on G cells (via gastrin)
Secretin is “anti – acid” in its actions

89. Ans. E. Belongs to gastrin family of G.I. hormones.

GIP is secreted by K cells of jejunum and duodenum.
Previously, it was called gastric – inhibitory peptide. Now, it is called glucose – dependent insulinotropic
polypeptide (the two names indicate its two actions)

90. Ans. E. (+)s gastric acid secretion

Most of the gastro intestinal hormones inhibit gastric acid motility and secretion
Gastrin is inhibited by : somatostatin, secretin VIP, GIP, glucagon calcitonin

91. Ans. D. There are 2 forms of somatostatin in tissues viz somatostatin 14 and 28

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 Physiology

92. Ans. B. Stomach

93. Ans. A. The salivary juice output from the duct is always hypotonic
Maximum contribution to total saliva is by submaxillary gland
i. Submaxillary gland : Mixed secretion
ii. Perotid gland : serous secretion
iii. Sublingual : Mucous secretion
Salivary secretion is controlled by parasympathetic reflexes and not by gastointestime harm ones.
Both sympathetic as well as parasympathetic stimulation increase salivary secretion; parasympathetic stimulation
causes watery saliva, relatively less in organic constituent and causes vasodiletation (VIP mediated). Sympathetic
stimulation*. The salivary juice gets modified as it flows through the salivary ducts. Nacl is absorbed and KHCO3 is
seoreted into the duct. With increased flow rate, the ductal modification of the salivary juice decreases. With
decreased flow rate, less NaCL and more KHCO3 appears

NaCL
KHCO3
The salivary juice is always hypotonic, because the duct is more permeable to NaCL than it is to water
[*Causes secretion of small amounts of saliva, rich in organic constituents, from the submaxillary glands. It also
causes vasoconstriction]

94. Ans. A. Pepsin

The body of the stomach has parietal cells (also called oxyntic cells) which secrete HCl and intrinsic factor The
chief cells (also called zymogen cells, peptic cells) secrete pepsinogen (and not pepsin)

95. Ans. A. Oxyntic Cells

H HCO3+
L H +
+
U K H2CO3
M HCO3-

E Cl-
N

When H+ is secreted by the oxyntic (partial cells) is response to food HCO3- is added to the blood.
Paneth cells are endocrine cells located in the crypts of Lieberkihn of smell intestine. They may produce guanylin.

Guanylin (+) guanylyl cyclase ed cGMP

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 GIT

ed Cl- secretion into lumen  activity of CFTR Cl- channel

96. Ans. A. Hyposmolarity of duodenal contents

Hyperosmolality rather than hypoasmolality of the duodenal contents inhibit gastric motility

97. Ans. C. Trypsinogen

Chapter - 9
Enteropeptidase has also been known as enterokinase. But eince the enzyme is not a kinase (as was formerly
thought) but a peptidase, it is correct to call it entero peptidase

98. Ans. C. Cholic acid and chenodeoxycholic acid

Primary bile acids Secondary bite acids
1. cholic acid Deoxycholic acid
2. Chenideoxycholic acid Lithocholic acid

99. Ans. B.
Above a certain concentration called the critical micelle concentration all bile salts added to a solution form
micelles

100. Ans. D. Bile salts decrease bile flow

The bile salts reabsorbed from the intestine actually inhibit the synthesis of new bile acids but they themselves
are promptly secreted and they markedly increase bile flow.

GIT
101. Ans. C. 600 times
i. Valvulae connivents : increase the absorption surface 3 times
ii. Villi (on the valvulae conniventes) : increase the absorption surface 10 times
iii. Microvilli (on the villi) : increase the absorption surface 20 times

So, the total increase in

absorption surface due to
all three = 3 X 10 X 20 =
600

102. Ans. D. It is also a part of the gastrocolic reflex where in it relaxes.

Gastrocolic reflex : Distension of the stomach by food initiates contraction of the rectum and frequently a
desire to defecate.

103. Ans. E. Triglycerides

104. Ans. D. Upper SI
105. Ans. C. G.I.P.
106. Ans. A. Glycerol

107. Ans. B failure of migration of neural crest cells from cranial to caudal direction

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 Physiology

108. Ans. is (D) Cholecystokinin

Enterogastric reflex -
1. Definition  signals from the colon and small intestine to inhibits stomach motility and stomach secretion. Q
2. “Products of protein digestion and hydrogen ions (H+) bathing the duodenal mucosa initiate a neurally mediated
decrease in gastric mortality, the Enterogastric reflex. Distention of the duodenum also initiates this reflex” also the
degree of osmolality of the chyme initiates the reflex.

109.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 625
Interstitial cells of Cajal are pacemaker cells that generate electrical slow waves. The other cell types do not generate
electrical slow waves.

110. The answer is D. Ref: Guyton – Text book of Medical Physiology 10th Ed Page 567
Physiological ileus is defined as the absence of contractile activity. It is a significant behavior pattern, requiring a
functional ENS. Each of the other neurally programmed patterns involves contractile behavior and motility.

111. The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 627
 Choice A is correct because sphincters function to prevent reflux; therefore, flow across a sphincter is generally
unidirectional.
 Choice B is not correct because tone in the lower esophageal sphincter is increased during the MMC (i.e. migrating
motor complex) in the stomach.
 Choice C is incorrect because the sphincter cannot be relaxed after blockade of the inhibitory innervation by a local
anesthetic.
 Choice D is incorrect because pressure in the sphincter is higher than in the two compartments it separates.

112.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 163,628
 Rapid transit is not likely because the loss of inhibitory motor neurons results in delayed transit (i.e.,
pseudoobstruction).
 Accelerated gastric emptying does not occur mainly because pseudoobstruction in the duodenum presents a high
resistance to inflow from the stomach.
 Gastroesophageal reflux is not correct because in the absence of inhibition, the lower esophageal sphincter remains
contracted and is a barrier to reflux.

113.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 632
Observations on the transit of markers after instillation in the human cecum show that the markers remain for the
longest time in the transverse colon. Transit is significantly faster in the other parts of the large intestine.

11.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 606
Lactase hydrolyzes lactose to form both glucose and galactose. None of the other combinations is correct.

115.The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 606
Maltase hydrolyzes maltose to form glucose. Because maltose does not contain galactose or fructose, none of the other
choices is correct.

116.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 608
Fructose is taken up by enterocytes by facilitated diffusion. Both glucose and galactose are taken up by enterocytes
through a sodium-dependent transporter (secondary active transport). Xylose and sucrose are not taken up by
enterocytes.

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 GIT

117.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 611
 Pancreatic lipase hydrolyzes triglyceride to form 2-monoglyceride and two fatty acids. The hydrolysis of
phosphatidylcholine, not triglyceride, results in the formation of lysophosphatidylcholine. Although diglyceride is an
intermediate in the hydrolysis of triglyceride by pancreatic lipase, the hydrolysis continues until 2-monoglyceride and
fatty acids are formed.
 Pancreatic lipase does not hydrolyze triglyceride totally to form glycerol and fatty acids.

118.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 612
 The small intestine transports dietary triglyceride as chylomicrons in lymph. VLDLs are secreted by the small intestine
during fasting.

Chapter - 9
 Although some dietary fatty acids are transported in the portal blood bound to albumin, it is not the predominant
pathway for the transport of dietary lipids to the circulation by the small intestine.
 The intestine does not secrete LDLs, and although it does secrete HDLs, they are not used as a vehicle for
transporting dietary lipids to the blood by the small intestine.
119.The answer is A. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 609
Dietary protein is transported in the portal blood as free amino acids. Although dipeptides and tripeptides are taken up
by enterocytes, they are hydrolyzed by the brush border membrane, as well as by cytoplasmic peptidase to form free
amino acids.

120.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 613
Vitamin D plays an important indirect role in the absorption of calcium by the GI tract. The other vitamins listed are not
involved in the absorption of calcium.

121.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 620,622
Vitamin A is transported in chylomicrons as ester. Vitamins D, E, and K are transported in the free form associated with
chylomicrons. Vitamin B12, a water-soluble vitamin, is transported in the blood bound to transcobalamin.

GIT
122.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 608
Potassium is passively absorbed by the jejunum. The other choices do not apply to the absorption of potassium by the
small intestine.

123.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 613
Ascorbic acid enhances iron absorption mostly by its reducing capacity, keeping iron in the ferrous state. Ascorbic acid
does not enhance heme iron absorption, nor does it affect heme oxygenase activity or the production of ferritin or
transferrin.

124.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page

 Alcohol dehydrogenase catalyzes the conversion of alcohol to acetaldehyde, which is then converted to acetate.
 Acetate is then metabolized by hepatocytes. Cytochrome P450 is a primary component of the oxidative enzyme
system involved in the metabolism of drugs.
 NADPH-cytochrome P450 reductase is an enzyme involved in phase I reactions of drug metabolism.
 There is no such enzyme as alcohol oxygenase.
 Glycogen phosphorylase is an enzyme involved in glycogen breakdown, not alcohol metabolism.

125.The answer is B.
Ref: Ganong - Review of Medical Physiology 23rd Ed Page 647
Although both chylomicrons and VLDLs are triglyceride-rich lipoproteins, the liver, unlike the small intestine, produces
only VLDLs. LDLs and HDLs are not triglyceride-rich lipoproteins. Chylomicron remnants are generated in the circulation
by
the metabolism of chylomicrons.

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 Physiology

126. Ans A

Absorption of iron in Duodenum

Most of the iron in the diet is in the ferric (Fe3+) form, whereas it is the ferrous (Fe2+) form that is
absorbed. There is Fe3+ reductase activity associated with the iron transporter in the brush borders
of the enterocytes

Almost all iron absorption occurs in the duodenum. Transport of Fe2+ into the enterocytes occurs via
DMT1 . Some is stored in ferritin, and the remainder is transported out of the enterocytes by a
basolateral transporter named ferroportin 1. A protein called hephaestin (Hp) is associated with
ferroportin 1.In the plasma, Fe2+ is converted to Fe3+ and bound to the iron transport protein
transferrin. Fe3+ is converted to Fe2+ by ferric reductase, and Fe2+ is transported into the enterocyte
by the apical membrane iron transporter DMT1. Heme is transported into the enterocyte by a
separate heme transporter (HT), and heme oxidase (HO) releases Fe2+ from the heme. Some of the
intracellular Fe2+ is converted to Fe3+ and bound to ferritin. The rest binds to the basolateral Fe2+
transporter ferroportin (FP) and is transported to the interstitial fluid. The transport is aided by
hephaestin (Hp). In plasma, Fe2+ is converted to Fe3+ and bound to the iron transport protein
transferrin (TF).

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Chapter - 10
Blood

I. Plasma Proteins
A. Composition of plasma
Water : 91.5%
Solutes : 8.5%

Chapter - 10
B. The solute fraction consists of
Proteins
The relative percentage of the plasma proteins are
1. Albumin (55%)
2. Globulins (38%)
3. Fibrinogen (7%)

C. Non-protein nitrogenous substances

- Nitrogen, urea, uric acid, creatinine, ammonium salts
Regulatory substances
- Enzymes and hormones
Electrolytes

Blood
-
Na, K, Mg, Ca, Cl, HPO4 - , HCO3-
Amino acids, glucose
Total plasma proteins = 6.4 gm to 8.3 gm /dL (average = 7.4 gm /dL)

Albumin = 3.5 to 5.2 gm/dL

Globulins = 1.7 to 3.2 gm/dL
Fibrinogen = 0.2 to 0.4 gm/dL

The normal albumin : globulin ratio (A : G ratio) : about 1.7

D. Classification of plasma proteins

1. Classical or Howe method
In this method, the plasma proteins are classified into 3 major groups :
albumin, globulins and fibrinogen; the globulin fraction is further subdivided into other components

2. Some fractions of globulins are :

- Lipoproteins, glycoproteins, interleukins, haptoglobulins, cortisol-binding globulin, ceruloplasmin,
transferrin, immunoglobulins

3. Electrophoretic method
By this, the plasma proteins can be separated into 5 fractions viz. albumin, alpha 1, alpha 2, beta and gamma
fractions.

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 Physiology

E. Functions of plasma proteins

1. Maintenance of colloidal osmotic pressure
The osmotic pressure exerted by the plasma protein colloids is also called as oncotic pressure. The plasma
proteins are able to exert osmotic pressure because the capillary walls are relatively impermeable to
plasma proteins.
Value of this oncotic pressure : about 25 mm Hg

2. Maintenance of blood pH
The plasma proteins can combine with acids or bases to maintain the pH of blood. The plasma proteins are
also responsible for 15% of the buffering capacity of the blood. How? There is weak ionization of their
carboxyl (COOH) and amino (NH2) groups; these are capable of combining with acids or bases and buffer
them. At the normal plasma pH of 7.40, the proteins are mostly in the anionic form

3. Blood clotting
Plasma proteins contain a large number of proteins called clotting factors (viz. fibrinogen, prothrombin).
Fibrinogen is converted into fibrin during the process of blood coagulation.

4. Carriers
Plasma proteins act as carriers of metals, hormones (e.g. thyroid, adrenocortical, gonadal etc.), lipids, fat-
soluble vitamins and drugs.

F. Advantage of the protein binding

1. Prevents filtration of the bound hormones through the glomeruli
2. Acts as a reservoir of the hormones

Albumin acts as a non-specific transport protein for a number of substances e.g. metals, ions, fatty acids,
amino acids, steroids, vitamins, hormones, bilirubin, enzymes, and drugs.

5. Defence mechanism
Immunoglobulins (also called gamma-globulins) and complement system are the plasma proteins responsible
for body defence mechanism.

G. Production of plasma proteins

1. Plasma cells
Circulating antibodies in the gamma globulin fraction of the plasma proteins are manufactured in the plasma
cells
2. Liver
Most of the other plasma proteins are synthesized in the liver.
Properties of the individual plasma proteins
i) Albumin
Molecular weight = 70,000
Half-life = about 10 days
Synthesis : in liver

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Function
It is responsible for the carriage in the plasma of most of the bilirubin and of non-ionized calcium

 Metabolism
In normal adult humans,
a. The plasma albumin level = 3.5-5.0 g/dL
b. The total exchangeable albumin pool = 4.0-5.0 g/kg body weight

Chapter - 10
c. 38-45% of this albumin is intravascular
d. Much of the extravascular albumin is in the skin.
e. Between 6% and 10% of the exchangeable pool is degraded per day
f. The degraded albumin is replaced by hepatic synthesis of 200-400 mg/kg/d.

 Regulation
Albumin synthesis is carefully regulated. It is decreased during fasting and increased in conditions such as
nephrosis in which there is excessive albumin loss.

ii) Globulins
Molecular weight = 90,000 to 1,56,000

Components

Blood
The globulins consist of alpha 1, alpha 2, beta 1, beta 2, gamma 1, and gamma 2 fractions; the gamma
globulins consist of the antibodies

Synthesis
Gamma globulin : in plasma cells
Other globulins : liver

iii) Fibrinogen
Molecular weight = 5,00,000
Synthesis : liver
The plasma fibrinogen concentration is raised in almost all diseases in which raised ESR is found,
particularly in acute infections and in pregnancy.

F. Applied aspects
1. Causes of hypoproteinemia
a. Prolonged starvation
b. Malabsorption syndrome
c. Liver disease (because hepatic protein synthesis is decreased)
d. Nephrosis (because of increased loss of albumin in urine)
Because of the decrease in the plasma oncotic pressure, edema tends to develop

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 Physiology

2. Afibrinogenemia

Causes
- Congenital
This can occur as a rare congenital abnormality; here, there is congenital absence fibrinogen
- Severe liver disease
- In pregnancy, as a complication of detachment of placenta
It is characterized by defective blood clotting.

Q. The plasma volume in a 60-kg man will be approximately

A. 3 L B. 4 L C. 5 L D. 1.5 L

Ans. ‘A’ 3L
Plasma volume = 5 % of body weight
So, in a 60-kg man, it will be 5/100 x 60 = 3 L

Q. All the following are true statements except

A. Plasma clots on standing
B. Serum = whole blood minus clot
C. Serum does not contain fibrinogen, clotting factors II, V and VIII
D. Serum has a lower serotonin content than plasma

Ans. ‘D’
Plasma remains fluid only if an anticoagulant is added.
Composition of serum and plasma
Serum has the same composition as plasma except
- That serum does not have fibrinogen and clotting factors II, V, and VIII
- It has a higher serotonin content than plasma; this is because of the breakdown of platelets during
clotting.

More text through MCQs

All the following plasma proteins are produced mainly in the liver except
A. Albumin B. Fibrinogen C. Haptoglobin D. Immunoglobulins
Ans. ‘D’
Immunoglobulins are produced by the plasma cells. Most other plasma proteins are produced by the liver.

The Hb transport protein in the plasma is

A. ceruloplasmin B. haptoglobin C. hemopexin
D. C-reactive proteins (CRP) E. Transferrin F. Transthyretin

Ans. ‘B’
Haptoglobulin
This binds and transports the cell-free Hb. One molecule of haptoglobin binds one molecule of Hb.

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 Blood

OTHER OPTIONS :-

Hemopexin
This binds and transports porphyrins, especially heme. One molecule of hemopexin binds with one molecule of
heme.

Ceruloplasmin
This transports copper. One mole of ceruloplasmin binds 6 copper atoms

Chapter - 10
CRP
a. This is one of the acute phase proteins. It plays a role in tissue inflammation; it binds complement C1q.
Its level increases in inflammation. Called CRP because it reacts with the C polysaccharide of
pneumococcus. Reference Values Normal
b. <1.0 mg/dL, or <l0 mg/L by rate nephelometry for CRP
c. <0. 1 mg/dL or < 1 mg/L by immunoturbidimetric assay for hs-CRP
d. Clinical Implications
1. The traditional test for CRP has added significance over the elevated erythrocyte sedimentation rate (ESR),
which may be influenced by altered physiologic states. CRP tends to increase before rises in antibody titers
and ESR levels occur. CRP levels also tend to decrease sooner than ESR levels.
2. The traditional test for CRP is elevated in rheumatic fever , RA , myocardial infarction , malignancy, bacterial
and viral infections, and postoperatively (declines after fourth postoperative day).

Blood
3. A single test for hs-CRP may not reflect an individual patient's basal hs-CRP level; therefore, follow-up tests or
serial measurements may be required in patients presenting with increased hs-CRP levels.
4. CRP levels may predict future cardiovascular events , diabetes, & hypertension and can be used as a
5. screening tool.
6. One of the minor criteria of Modified Jones criteria

Transferrin
This transports iron. One mole of transferring binds 2 iron atoms.

Transthyretin
The other name for this is thyroid-binding prealbumin. It binds and carries thyroid hormones. The other
thyroid hormone- binding protein is thyroid-binding globulin.

Q. The following blood clotting factors are produced in the liver except
A. factor 2 B. factor 3
C. factor 7 D. factor 9 E. factor 10

Ans. ‘B’. . factor 3

Which of the following plasma proteins is structurally similar to albumin?

A. Alpha-fetoprotein B. protein C C. apolipoprotein B
D. Alpha2-macroglobulin E. antithrombin III F. alpha 1-antiprotease

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 Physiology

Ans. ‘A’. Alpha-fetoprotein

All the above proteins are produced in the liver. The function of alpha-fetoprotein is not exactly known. Like
albumin, it may function as an osmotic regulator and as a non-specific carrier protein (for hormones, amino
acids etc). It is found normally in fetal blood; hence, the name.
Alpha2-macroglobulin binds and inhibits serum endoproteases.
Antithrombin III is a protease inhibitor of the intrinsic clotting system. One molecule of antithrombin III binds
one molecule of these proteases.
Protein C (also, anti-thrombin C) inhibit blood clotting.
Apolipoprotein B is a plasma lipid carrying protein.
Alpha1-antiprotease : this is a trypsin and general protease inhibitor.

The plasma or serum concentration of which of the following proteins is maximum?

A. Fibrinogen B. albumin C. haptoglobin D. C-reactive proteins

Ans. ‘B’. albumin

The plasma levels of some plasma proteins are :
Plasma protein Plasma/serum concentration (mg/dL)
Albumin 3500 to 5000
Fibrinogen 200 to 450
Globulins (total) 1700 to 3200
Alpha 2 macroglobulin 150 to 420
Haptoglobin 40 to 180
Hemopexin 50 to 100
Ceruloplasmin 15 to 60
Transferrin 3 to 6.5
Antithrombin III 15 to 30
Clotting factors 2, 7, 9 and 10 20
TBG (thyroid-binding globulin) 1.5
TBPA (thyroid-binding prealbumin) or transthyretin 25

 Hemoglobin
Molecular weight = 64450.

 Structure
It is a globular protein. Each molecule of Hb has 4 subunits.
Each subunit has :
1. Pigment heme conjugated to
2. a polypeptide.
Thus, there are 4 polypeptide chains in each Hb molecule; the polypeptide chains are collectively called ‘globin’.

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 Blood

 Heme
This is an iron-containing porphyrin known as iron-protoporphyrin IX. The porphyrin nucleus consists essentially of
4 pyrrole rings joined together by 4 methine (=CH-) ‘bridges’; the porphyrins are thus tetrapyrroles. The iron in
heme is in the ferrous (Fe2+ ) form.

 The iron in heme is attached to the

a. N of each pyrrole ring
b. N of the imidazole group of the associated globin

Chapter - 10
Synthesis of heme
(Hb appears in the intermediate stage of erythropoiesis in the bone marrow).
Heme is synthesized from glycine and succinyl CoA as shown below :

 Steps
1. Succinyl CoA + glycine  alpha amino beta keto adipic acid
2. Alpha amino beta adipic acid  delta levulinic acid + CO2
3. Delta levulinic acid (2 molecules)  porphobilinogen
4. Porphobilinogen (4 molecules)  protoporphyrin
5. Protoporphyrin IX + Fe 2+ + globin  Hb

 A single Hb molecule has

Blood
- 4 protoporphyrin IX molecules
- 4 ferrous atoms
- 4 polypeptide chains

1 gram of Hb has about 3.34 mg of ferrous ion.

1 gram of Hb, when fully saturated, carries 1.34 ml of oxygen.
Different states of Hb
OxyHb (HbO2)
Oxygen binds loosely and reversibly with Hb; this Hb is called oxyHb. The oxygen attaches to the ferrous ion in the
heme.
2-3 DPG and H+ compete with oxygen for binding to the deoxygenated Hb; thus, increase in 2-3 DPG and
temperature shift the oxygen-Hb curve to the right.
The affinity of CO to Hb is 210 times the affinity of oxygen for hemoglobin.

1. DeoxyHb (Hb or HHb)

Hb to which oxygen is not attached is called deoxy Hb. It is also called reduced Hb.

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 Physiology

High affinity of HbF with O2 due to: (AIIMS May 09)

A. Decrease binding with 2,3 DPG
B. Decrease concentration of Hb
C. Increase in the pH
D. Bohr effect

Ans. A

2. Carbamino compound :
This is a compound of Hb with carbon dioxide

3. Sulphaemoglobin :
This is a compound of Hb with hydrogen sulphide
4. CarboxyHb
This is a compound of Hb with CO; it is better called as carbonmonoxy Hb.
Oxidised Hb (HbOH) or Methaemoglobin :
In this form of Hb, the ferrous (Fe2+ ) ion gets oxidized to ferric ion
(Fe 3+ )
When reduced or oxygenated Hb is treated with an oxidizing agent, the ferrous ion gets oxidized to ferric ion; this
state of Hb is called as methaemoglobin. The disadvantage of this methaemoglobin is that it cannot unite reversibly
with oxygen.
MetHb is represented like ‘HBOH’; because, here the ferric ion is attached to OH group
The iron in Hb in the normal state is in the ferrous form. Drugs and oxidizing agents convert the ferrous to ferric
form, making it methaemoglobin. Methaemoglobin is dark coloured and when present in large quantities causes a
dusky discolouration of skin resembling cyanosis.
Hb (Ferrous ion) - oxidized (ferric ion)  gives methaemoglobin
Hb MetHb
Iron Ferrous form Ferric form
State of Hb Reduced form Oxidised form
Colour Red Darker
Binding to oxygen reversible irreversible
5. Note
Oxygenated Hb = HbO2; oxidized Hb = MetHb (HBOH)
Glycosylated or glycated Hb (HbAic)
When blood glucose enters the RBCs, the glucose gets attached to Hb at various positions ; this Hb is called
glycated Hb. One of the glycosylated/glycated Hbs is HbAic. This glycated Hb has a glucose attached to the terminal
valine in each beta chain.

The percentage of glycosylated Hb = 50 %. This percentage is directly proportional to blood glucose concentration.
Since the half-life of RBC is 60 days, the level of glycated Hb (HbAic) reflects the mean blood glucose concentration
over the preceding 6 to 8 weeks. So, its estimation is important in management of diabetes mellitus.

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6. Different types of Hb
In the different types of Hb, the heme portion is identical; physical and chemical differences are due to variations in
the composition of the peptides of the globinfraction.

7. HBA (alpha2, beta 2) :

This is the normal and main form of adult Hb; it has 2 alpha and 2 beta chains. Each alpha chain has 141 amino
acids; each beta chain has 146 amino acids.

Chapter - 10
8. HbA2 (alpha 2, delta 2)
This constitutes about 2.5% of the normal adult Hb. It has 2 alpha and 2 delta chains. Each delta chain has 146
amino acids (but 10 amino acids are different from those of beta chains)

9. HbF or foetal Hb(alpha 2, gamma 2)

This occurs in foetal RBCs; it usually disappears by 2-3 months after birth. Since 2-3 DPG has less affinity to bind to
HbF, HbF has greater affinity for oxygen. So, at a given pO2, the percentage saturation of HbF with oxygen is more
than that of HbA.

10.Importance
This increased affinity helps in uptake of oxygen from maternal to foetal circulation.
HbF is much more resistant to alkali than HbA.
1. Fate of RBC/Hb
At the end of their life span, RBCs are destroyed in the reticuloendothelial system (nowadays called as tissue

Blood
macrophage system) and Hb is released from the RBC.
In the tissue macrophage system, the globin and heme portion are split off. The heme is oxidized (by heme
oxygenase) to biliverdin. In this process, CO is formed.
Most of the biliverdin is reduced (by biliverdin reductase) to bilirubin and is excreted in the bile. The iron released
from the heme is reused for Hb synthesis.
1 gram of Hb gives 35 mg of bilirubin. About 250 to 375 mg of bilirubin is produced per day (mostly from Hb; also
from ineffective erythropoiesis and from other heme proteins such as cytochrome P 450)
Exposure of the skin to white light converts bilirubin to lumirubin, which has a shorter half-life than bilirubin.
Other heme containing compounds

11. Myoglobin
Heme is present in myoglobin also. It is found in the red (slow) muscles.Has very high affinity for O 2 acts as O2
storing protein. Binds 1 mole of O2 only. O2 dissociation curve is rectilinear parabole.

12. Neuroglobin
This is an oxygen-binding globin in the brain; its function may be to supply oxygen to neurons.
Cytochrome C
This is a respiratory chain enzyme; it contains heme.

1. More text through MCQs

Q. HbF is
A. alpha 2, beta 2 B. alpha 2, gamma 2

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 Physiology

C. alpha 2, delta 2 D. alpha 2, zeta 2 E. epsilon 2, zeta 2

Ans. : ‘B’ alpha 2, gamm 2

Gamma chain has 146 amino acids (like beta chain, which also has 146 amino acids); however, 37 amino acids are
different.
Epsilon 2, zeta 2 : Gower 1 Hb
Alpha 2, epsilon 2 : Gower 2 Hb
Gower 1 and Gower 2 Hb present in the young embryo; thus, epsilon and zeta chains are embryonic.
Alpha chain gene is present on chromosome 16; the gene for other chains (beta, gamma, delta, epsilon, zeta) are
present on chromosome 11.
Espison, zeta : disappear at approximately 3 months of intrauterine life

2. Gamma
Maximum percentage (about 45%) occurs at about 3 months of intrauterine life; its percentage starts decreasing
just before birth and gets decreased to very low level by about 3 months after birth; it almost completely
disappears at 6 months after birth.

3. Beta chain
The graph for beta chain is almost a mirror image of gamma chain. It starts increasing just before birth; reaches
very high level (about 45 %) at about 3 months after birth and almost 50% at 6 months (that is the maximum
percentage possible because the other 50% is alpha chain)

4. Alpha chain
This reaches 50% at about 3 months of intrauterine life and remains so throughout life.
5. Delta chain
This starts appearing just before birth and becomes maximum (about 2%) at about 6 months after birth.

MCQ round up
At 3 months of intrauterine life
- Zeta, epsilon chains disappear
- Alpha chain percentage becomes maximum (about 50%)
- Gamma chain percentage becomes maximum (about 45%)

At 3 months after birth

- Gamma decreases to very low level
- Beta increases to very high level

At 6 months after birth

- Gamma almost disappears
- Beta becomes almost maximum

6. Alpha chain
Becomes maximum at about 3 months of intra uterine life; thereafter, it remains so throughout.

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Physiology of Hemostasis

Definition of hemostasis
Hemostasis literally means stoppage of bleeding.
Processes
When a blood vessel is cut or damaged, the following 3 basic processes prevent blood loss :
A. Vasoconstriction

Chapter - 10
This is due to serotonin and other vasoconstrictors released from the platelets.

B. Temporary platelet plug formation

This is formed by a loose aggregation of platelets. How? The damaged vessel exposes the collagen; the
platelets bind to the exposed collagen. The bound platelets release ADP; ADP in turn attracts more platelets
and helps in platelet aggregation.
C. Blood coagulation
The clotting mechanism forms fibrin, fibrin reinforces the loose platelet plug. Thus, the loose temporary plug is
converted into a definitive plug.

D. Physiology of coagulation
The process of clotting is called coagulation. The various coagulation factors (also called clotting factors) bring
about the coagulation. Many of the coagulation factors are present in the plasma; some are released from the
platelets.

Blood
E. Coagulation factors
The following are the coagulation factors in the blood and their synonyms :
Factors
Synonyms
(symbol)
I Fibrinogen
II Prothrombin
III Tissue thromboplastin (TPL), Tissue factor
IV Calcium
V Proaccelerin, labile factor, accelerator globulin (Ac-globulin, Ac-G)
VII Proconvertin, Serum Prothromobin Conversion Accelerator (SPCA), stable factor
VIII Anti-hemophilic factor (AHF), anti-hemophilic factor A, anti-hemophilic globulin (AHG)
IX Plasma thromboplastin component (PTC), Christmas factor, anti-hemophilic factor B
X Stuart factor, Stuart Prower factor
XI Plasma thromboplastin antecedent (PTA), anti-hemophilic factor C
XII Hageman factor, glass contact factor
XIII Fibrin-stabilizing factor, Laki-Lorand factor
HMW-K High-molecular weight kininogen, Fitzgerald factor
Pre-Ka Prekallikrein, Fletcher factor
Ka Kallikrein
PL Platelet phospholipid

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 Physiology

Note : there is no factor VI (it is not a separate entity and therefore it is not listed); it was earlier called as accelerin.

F. Mechanism of blood coagulation

Enzyme cascade mechanism
The ultimate aim of the clotting mechanism is to form insoluble fibrin from the soluble fibrinogen. The
clotting mechanism consists of a cascade of reactions in which inactive enzymes are activated; these
activated enzymes in turn activate other inactive enzymes.
A. Steps involved in conversion of fibrinogen to fibrin
1. Formation of fibrin monomer from fibrinogen
Fibrinogen is made up of three types of polypeptide chains viz. alpha, beta and gamma polypeptide
chains.

As a first step, two pairs of polypeptides are released from each fibrinogen molecule; the remaining portion
is the fibrin monomer.
2. Formation of loose fibrin mesh
The fibrin monomer polymerizes with other monomer molecules to form fibrin. This fibrin is initially a
loose mesh of interlacing strands.

3. Formation of tight fibrin mesh

The loose fibrin mesh is converted into a tight, dense mesh by the formation of covalent cross-linkages;
this process is called stabilization. The stabilization reaction is catalyzed by activated factor XIII and
requires calcium.

 Details of conversion of fibrinogen to fibrin

1. Role of thrombin
a. Thrombin catalyzes the conversion of fibrinogen to fibrin. Thrombin is a serine protease; it is formed from its
circulating precursor, prothrombin. Prothrombin is converted to thrombin by the action of activated factor X.
b. Other actions
Activation of platelets, endothelial cells, and leukocytes via a G protein-coupled receptor.

2. Factor X activation
There are 2 pathways for activation of factor X
a. intrinsic pathway b. extrinsic pathway

3. Intrinsic pathway for factor X activation

Steps
a. Conversion of inactive factor XII to active factor XII
activated factor XII)

This is the initial reaction in the intrinsic pathway.

This activation is catalyzed by high-molecular-weight (HMW) kininogen and kallikrein. Kallikrein is a protease
present in small amounts in the plasma; it is formed from pre-kallikrein. As soon as factor XIIa is produced, it causes

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the conversion of prekallikrein to kallikrein; kallikrein in turn activates XII. Thus, it is another example of positive
feedback mechanism.
The activation of factor XII in vitro and in vivo occurs as follows :
a. in vitro Factor XII can be activated in vitro by exposing the blood to electronegativelv charged wettable
surfaces such as glass and collagen fibers.

b. in vivo Activation of factor XII in vivo occurs when blood is exposed to the collagen fibers underlying the
endothelium in the damaged blood vessels

Chapter - 10
c. Activation of factor XI
Active factor XIl (i.e. XII a) in turn activates factor XI
XII a
XI ------------- XI a

d. Activation of factor IX
Active factor XI activates factor IX.
XI a
IX ------------- IX a

e. Activated factor IX forms a complex with active factor VIII

Factor VIII is activated when it is separated from von Willebrand factor.

Blood
f. Activation of factor X
- The complex of IXa and VIIIa activate factor X.
- Phospholipids from aggregated platelets (PL) and calcium are necessary for full activation of factor X.

 Extrinsic pathway for factor X activation

Steps
1. The initial step is the release of tissue thromboplastin (TPL) (also called tissue factor) from damaged tissue;
TPL is a protein-phospholipid mixture containing proteolytic enzymes. tissue thromboplastin activates factor VII.
2. The tissue thromboplastin forms an active complex with factor VII; this complex activates factors 1X and X.
The activation of factor X by this complex of VIIa and TPL requires the presence of calcium and platelet
phospholipid (PL).

1. Common pathway beyond formation of X a

The ultimate aim of both the intrinsic and extrinsic pathway is to activate factor X. Once activated factor Xa is
formed, the remaining coagulation pathway is the same for both intrinsic and extrinsic pathways as given below:
a. Activated factor X (i.e. X a) converts prothrombin to thrombin (the activation requires the presence of platelet
phospholipid i.e. PL, calcium and factor V
b. Thrombin
i. Converts fibrinogen to fibrin monomer polymerization of fibrin monomer to form loose fibrin mesh
ii. Activates factor XIII (to form XIII a)
c. Factor XIII a causes stabilization of the loose fibrin mesh to form tight fibrin mesh

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 Physiology

The extrinsic pathway is inhibited by a tissue factor pathway inhibitor by forming a quaternary structure with TPL,
factor VIla, and factor Xa.

Blood coagulation is an example of positive feedback mechanism; formation of active factor in one step stimulates
its own catalyst. Because of this, very little initiation in the system can produce an immense response.
Most of the coagulation factors in their active state are serine proteases whose active site contains a hydroxyl
group.

 Anti clotting Mechanisms

Introduction
Clotting is essential for stopping bleeding due to injury. However, clotting should not occur inside the blood vessels.
For preventing clotting inside the blood vessels, there are anti-clotting mechanisms. The anti-clotting mechanisms :
1. prevent clotting inside the blood vessels
2. if any clot does form, it breaks the clot

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1. The various anti-clotting mechanisms are :

a. Balance between thromboxane A2 and prostacyclin :
- Thromboxane A2 causes platelet aggregation
- Prostacyclin inhibits platelet aggregation

The balance between the two allows clots to form at the site of injury but prevents clot within the lumen of the
vessel.

Chapter - 10
b. Antithrombin III (also called heparin cofactor II)
This is a circulating protease inhibitor; it binds to the serine proteases in the coagulation system. As
mentioned above, most of the active forms of the clotting factors are serine proteases; thus, anti-thrombin III
blocks the activity of these clotting factors.

Anti-thrombin III inhibits the active forms of factors IX, X, XI, and XII.

Heparin increases the action of anti-thrombin III. How? Heparin increases the binding of anti-thrombin III to the
serine proteases. (Heparin is a naturally occurring anticoagulant; it is a mixture of sulphated polysaccharides with
molecular weights between 15,000-18,000).

c. The endothelium of the blood vessels

The endothelium is another important anti-clotting mechanism; it plays an active role in preventing the

Blood
extension of clots into blood vessels.

B. Thrombomodulin
What is it?
This is a thrombin-binding protein, expressed on the endothelial cells.

Site of production
All endothelial cells except those in the cerebral microcirculation produce thrombomodulin and express it on
their surface.
Mechanism of action
In the circulating blood, thrombin is a pro-coagulant that activates factors V and VIII; however, when thrombin
binds to thrombomodulin, it becomes an anticoagulant. How?
The thrombomodulin-thrombin complex activates protein C. The activated protein C (APC), along with its
cofactor protein S:
- inactivates the activated factors V and VIII
- inactivates an inhibitor of t-PA (tissue plasminogen activator); thus, it increases the formation of plasmin
from plasminogen.

1. Fibrinolytic system
Clots formed in the tissues have ultimately to be disposed of as healing takes place; the dissolution of the clot is
called fibrinolysis and is due to the action of the proteolytic enzyme called plasmin or fibrinolysin.

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 Physiology

Plasmin (also called fibrinolysin)

There is no free plasmin in the blood; the blood contains its inactive precursor called plasminogen (also called
profibrinolysin).
Plasmin lyses fibrin and fibrinogen; this produces fibrinogen degradation products (FDP); the fibrin degradation
products inhibit thrombin.
How is the active plasmin formed from its inactive precursor, plasminogen?
This occurs by the action of
- thrombin
- tissue-type plasminogen activator (t-PA).
- also by urokinase-type plasminogen activator (u-PA).

2. Evidence
Effect of knock out of either the t-PA gene or the u-PA gene in mice :
- Some fibrin deposition occurs
- and clot lysis is slowed.

3. Effect of knock out of both the t-PA and u-PA genes :

- there is extensive spontaneous fibrin deposition
- there is delayed wound healing
- there are defects in growth and fertility (this is because the plasminogen system not only lyses clots but
also plays a role in cell movement and in ovulation).

4. Other actions of plasmin

In addition to its fibrinolytic activity, plasmin can form plasma kinins (bradykinin, kallidin) and thus contribute to
the vascular and sensory features (pain) of the inflammatory response to injury.

5. Structure of human plasminogen

It consists of a
- heavy chain (560-amino-acid) and
- a light chain (241-amino-acid)
6. The heavy chain
- Has glutamate at its amino terminal
- It is folded into five loop structures, each held together by three disulfide bonds. These loops are called
kringles because of their resemblance to a Danish pastry of the same name.

7. Kringles
The Kringles are lysine-binding sites by which the plasminogen molecule attaches to fibrin and other clot
proteins (kringles are also found in prothrombin)
Plasminogen is converted to active plasmin when t-PA hydrolyzes the bond between Arg 560 and Val 561.

8. Plasminogen receptors :

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 Blood

These are located on the surfaces of many different types of cells and are plentiful on endothelial cells. When
plasminogen binds to its receptors, plasminogen becomes activated; thus, clot formation does not occur in the
intact blood vessel walls

9. The protein C pathway

Three protein factors – protein C, protein S and thrombomodulin – constitute an important negative feedback
pathway to keep the clotting mechanism under control.

Chapter - 10
 Thrombomodulin
As mentioned above, it is a protein present on the vascular endothelium; all endothelial cells except those in the
cerebral microcirculation produce thrombomodulin and express them on their surface

 Protein C and protein S : these are plasma proteins

 How does the system work?
a. thrombin binds to thrombomodulin
b. the thrombin-thrombomodulin complex activates protein C
c. In combination with protein S, the activated protein C (APC) inactivates factor V a and VIIIa
d. Because of the inactivation of factors Va and VIIIa, the clotting process is checked.

 Applied aspects
With the help of recombinant DNA techniques, human t-PA is now being produced for clinical use. It lyses clots

Blood
in the coronary arteries if given to patients soon after the onset of myocardial infarction. Streptokinase, a
bacterial enzyme, is also fibrinolvtic and is also used in the treatment of early myocardial infarction
 Annexins
These are a group of proteins which are associated with coagulation and fibrinolysis. About 10 annexins have
been described in mammals.

 Possible role of annexins

1. Annexin II
This forms a platform on endothelial cells on which components of the fibrinolytic system interact, producing
fibrinolysis.
2. Annexin V
This forms a shield around phospholipids involved in coagulation and exerts an antithrombotic effect.

Platelets (Thrombocytes)
A. Structure
These are colourless, non-nucleated, granulated, spherical, oval or rod-shaped bodies.
Diameter : 2 to 4 micrometer
Number : 1.5 to 4 lakhs per cu mm
Half-life : 4 days; average life span : about 10 days

B. Formation
Site : Bone marrow

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 Physiology

C. Development :
Platelets are formed from giant cells called megakaryocytes. The megakaryocytes themselves are formed
from stem cells called megakaryoblasts. The megakaryoblasts  become promegakaryocyte, which become
 megakaryocyte  which form platelets.

D. Release into circulation

The platelets are formed in the cytoplasm of the megakaryocytes; bits of cytoplasm get detached and are
released into the circulation.
Platelets reside in the spleen for a short period prior to circulation in the blood stream.
Percentage of the released platelets in the circulating blood : 60% and 75%
Out of the rest 25 to 40%, most of them are in the spleen; thus, removal of the spleen increases the platelet
count.
E. Ultrastructure
Platelet membrane
The platelet membrane is highly invaginated and has a canalicular system; the canaliculi are in contact with
the ECF

F. Receptors on the membrane

The platelet membrane contain receptors for collagen, ADP, vessel wall von Willebrand factor and fibrinogen.
Microtubules
A ring of microtubules is present around the periphery of platelets.
G. Cytoplasm
The platelet cytoplasm contains actin, myosin, glycogen, lysosomes, and granules.

The platelet granules are of 2 types :

1. Dense granules
These contain the non-protein substances that are secreted in response to platelet activation; the
substances include serotonin, ADP, and other adenine nucleotides,

2. Alpha -granules,
These contain secreted proteins other than the hydrolases in lvsosomes. These proteins include clotting
factors and platelet-derived growth factor (PDGF).

H. PDGF
Structure
It is a dimer made up of A and B subunit polypeptides. Both homodimers (viz. AA and BB) and heterodimer
(viz. AB) are produced.

I. Function
1. stimulates wound healing
2. it is a potent mitogen for vascular smooth muscle.

J. Von Willebrand factor

This is a protein present in the vessel wall and in plasma; it is produced by

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- the endothelial cells of blood vessels

- platelets

K. Function
1. helps the platelets to adhere to damaged vessel wall
2. regulates circulating levels of factor VIII.

L. Role of platelets in hemostasis

Chapter - 10
Steps :
1. Platelet binding
When a blood vessel is injured, platelets bind to
- the exposed collagen
- and to the von Willebrand factor in the wall
The receptors on the platelet membrane help in this binding.
2. Platelet activation
Binding produces platelet activation  this causes release of the contents of their granules; ADP is also
one of the released substances
3. Platelet aggregation
This is mediated by :

a. ADP
The released ADP acts on the ADP receptors in the platelet membranes  this produces further accumulation

Blood
of more platelets (platelet aggregation).

Platelet ADP receptors :

These are P2Y1 , P2Y2 , and P2X1.

b. Platelet activating factor (PAF)

What is PAF?
It is a cytokine secreted by neutrophils, monocytes and platelets. It is an ether phospholipid, 1-alkyl-2-
acetylglyceryl-3-phosphorylcholine; it is produced from membrane lipids. It acts via a G protein-coupled
receptor to increase the production of arachidonic acid derivatives, including thromboxane A.

Actions of PAF :
- It helps in platelet aggregation
- It has inflammatory activity.

M. Factors regulating platelet production :

1. Colony-stimulating factors (CSF): these control the production of megakaryocytes
2. Thrombopoietin :
This is a circulating protein factor.
Production
It is produced constitutivelv by the liver and kidneys,

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 Physiology

Role
 It helps in maturation of megakaryocytes
 It helps in feedback regulation of platelet production :
There are thrombopoietin receptors on platelets.
When the number of platelets is low  the free circulating thrombopoietin is increased (because less
thrombopoietin is bound to the platelets)  this increases production of platelets.

When the number of platelets is high  the free circulating thrombopoietin is decreased (because more
thrombopoietin is bound to the platelets)  this decreases production of platelets.
- The amino terminal portion of the thrombopoietin molecule has the platelet-stimulating activity
- whereas the carboxyl terminal portion contains many carbohydrate residues and is concerned with the
bio-availability of the molecule.

N. Applied aspects
Thrombocytopenic purpura
This occurs due to low platelet count.

O. Features :
- clot retraction is deficient
- there is poor constriction of ruptured vessels.
- easy bruisability and multiple subcutaneous hemorrhages.

Thrombasthenic purpura
In this condition, the platelet count is normal but the platelets are abnormal

RBC (Erythrocytes)

The RBCs carry haemoglobin (Hb).

Morphology and dimensions
A. Shape :
Biconcave, non-nucleated, very elastic and highly flexible when going through capillaries
B. Diameter :
6.5 to 8.8 micron (average = 7.5 micron)
C. Thickness :
at the center : 1 micron
at the periphery : 2.2 microns
average thickness : 2 microns.
D. Surface area :
135 to 140 square microns; the surface area is greatly increased by the biconcave shape (The surface area is much
greater than if its volume were contained in a sphere).
Volume : 90 cubic microns.
E. Advantage of biconcave shape
It is more resistant to fragility

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 Blood

1. it does not get damaged as it passes through capillaries (it assumes a sausage or parachute shape while going
through capillaries)
2. its surface area increases; it helps in more efficient gas exchange.

F. Average life span in the circulation : 120 days; half-life : 60 days.

Count
Male : 5.4 millions/cumm of blood
Female : 4.8 millions/cumm of blood

Chapter - 10
(note : 1 cumm = 1 microlitre)
Each RBC has 20 pg of Hb.
In adult man has 3 x 1013 RBCs and about 900 gm of Hb.

G. Energy supply
Energy to the RBC is provided by :
- glycolysis ( 80 %)
- pentose phosphate pathway ( 20%)
Energy is required to maintain the ionic gradient across its membrane and to keep the iron in the ferrous (Fe 2+)
state.

H. Permeability of the RBC membrane

The viability of RBC depends on the integrity of its membrane. It is freely permeable to water, sodium, potassium

Blood
and chloride. But a Na-K pump keeps the intracellular sodium low and potassium high. The energy for the pump is
provided by the membrane ATPase which requires magnesium, sodium and potassium for full activation. ATP is
formed during glycolysis and its hydrolysis provides the energy for the sodium pump. When RBC metabolism ceases
(as in cold-stored blood), the ions move between plasma and cells according to their concentration gradients.

I. Production of RBC
The production and maturation of RBC is called erythropoiesis.
Site
Foetus
First trimester
In the early embryo, blood formation takes place first in the mesoderm of the yolk sac (the area vasculosa) and
later in the body of the foetus. It is called as the mesoblastic stage of erythropoiesis.

In the mesoblastic stage, the erythropoiesis takes place intravascularly; the endothelial cells themselves get
converted into nucleated RBC and get released in the circulation; in the circulation, they lose their nuclei.

J. Note :
Mesoblastic stage is the only stage where RBC is formed intravascularly; later, it is extravascular.

K. Second trimester
This stage of erythropoiesis is called the hepatic stage. In this stage, the sites of production are spleen and liver
(especially liver). Nucleated RBCs develop from the mesenchyme between the blood vessels and the tissue cells.

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 Physiology

L. Third trimester
About the middle of foetal life, the bone marrow begins to act as a blood-forming organ. After this, the function of
the bone marrow (in RBC production) increases and that of the liver decreases.

M. Adult
1. The only site of production is the bone marrow, however, if bone marrow is destroyed, then extramedullary
erythropoiesis takes place in the liver and spleen. Before it enters the circulation from the bone marrow, it
loses its nucleus. Thus, the peripheral blood has non-nucleated RBCs.
2. At birth, all the bones are filled throughout their length with red marrow. With increasing age, the marrow
becomes more fatty (i.e. red marrow becomes yellow marrow). This process first starts in the distal bones of
limbs (tarsus and carpus); then in the intermediate bones (tibia, fibula, radius and ulna); finally, in the proximal
bones (femur and humerus).
3. At age 20 years, all marrow in the long bones is yellow except in the upper end of the femur and humerus.
4. In adults, red marrow persists mainly in the vertebrae, sternum, ribs, skull and pelvis bones.
5. Weight for weight, children have more red marrow than adults. If one wishes to study extension of
haemopoiesis, one can study the shaft of long bone.

N. Stages in the development of RBCs or erythrocytes

1. From the pleuripotent hematopoietic stem cell (HSC) (refer)  committed stem cells are formed . The
committed stem cells in the RBC series are of 2 types :
a. BFU-E (or burst forming unit –erythrocyte)
b. CFU-E (or colony forming unit –erythrocyte)

2. BFU-E gives rise to  CFU-E cells

3. CFU-E cells give rise to  proerythroblast (or pronormoblast)
4. The stage from proerythroblast to RBC is shown in the following table :
Stage Name Size of Cytoplasmic Mitosis Nucleus No. per 100
cell (µm) staining nucleated
cells in the
bone marrow
I Pro-normoblast 15 to 20 Deep violet Only Nucleus is 12 µm; it has 1 to 3
or blue during many nucleoli; chromatin is
proerythroblast (Basophilic) stress fine and stippled; No Hb
II Early Somewh Basophilic Active No nucleoli; Hb appears, 1 to 3
normoblast at chromatin is fine and shows
smaller a few nodes of
(10 to condensation (Hb is formed
17) from stage II to stage IV)
III Intermediate Still Polychromat Active The resting nucleus shows 4 to 8
normoblast smaller ophil further condensation of
(10 to 14 chromatin. Hb increases; its
µm) eosinophilic staining gives
the cytoplasm a
polychramtic appearance

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 Blood

IV Late 7 to 10 Eosinophilic No Nucleus is small; the 8 to 16

normoblast µm condensed chromatin
(orthochromati shows ‘cart-wheel’
c normoblasts) appearance; finally it
becomes uniformly deeply
condensed and stained (this
state of the nucleus is called
pyknosis; pyknosis =

Chapter - 10
thickened and shrunken
nucleus). Pyknosis is a stage
in the degeneration of the
nucleus. The nucleus finally
breaks up and is extruded
out
Reticulocyte Slightly Eosinophilic No nucleus; Hb synthesis
larger (also continues in this stage.
than the basophilic
mature reticulum is
RBCs present)
Mature RBC 7.2 µm Fully
eosinophilic

Blood
(no
reticulum)

O. Duration
The entire process of erythropoiesis takes about 7 days. Out of this, time taken for conversion from proerythroblast
to reticulocyte is 3 days; time taken for reticulocyte to become matured RBC is 4 days. Out of these 4 days, the last
one day is spent in the peripheral circulation by the reticulocytes.

P. Note :
Maturation of the erythroblasts involves
1. a decrease in the size of the cell
2. increased condensation and finally pyknosis and disappearance of the nucleus
3. accumulation of Hb
4. a change in the staining of the cytoplasm from basophil via polychromatophil to eosinophil (initially the
cytoplasm is basophilic due to plenty of RNA; later it turns eosinophilic due to accumulation of Hb and also due
to decrease in RNA)

Q. Reticulocyte
This is the name given to the young red cell; it is so called because on vital staining with cresyl blue, it shows a
network of basophilic reticulum in the cytoplasm.
All the nucleated precursors of the reticulocyte (i.e. the normoblasts) also give this staining reaction.

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 Physiology

R. The reticulum
This probably consists of remnants of the basophil cytoplasm of the immature cell (chemically, the reticulum is
made up of RNA).
If red cells are stained with eosin and methylene blue, the presence of the reticulum in the young cells (i.e. the
reticulocytes) leads to a diffuse mauve staining of the cell; this is called polychramtophilia. (The cytoplasm is
stained eosinophilic due to Hb and the reticulum is stained basophilic due to RNA)

S. Importance
1. In pathological states, this stained basophil material is sometimes present in clumps which appear as discrete
blue particles. This finding known as basophil punctation (or punctate basophilia) is especially obvious in lead
poisoning.
2. As the red cell ages, the reticulum disappears. In the newborn, 2 to 6 % of the red cells in the circulation are
reticulated; the number falls during the first week to less than 1%, at which level it remains throughout life.
Their number is increased whenever red cells are being rapidly manufactured. In such cases, 25 to 35 % of the
circulating cells can be reticulocytes. An increase in the reticulocyte count (reticulocytosis) is the first blood
change noted when pernicious anaemia is treated with vitamin B12.

T. Spleen as a blood filter

It removes spherocytes and other abnormal RBCs. Abnormal RBCs are removed if they are not as flexible as the
normal RBCs; if they are not flexible, they are not able to go between the endothelial cells that line the splenic
sinuses. Thus, they get trapped and are removed.
Spleen also contains many platelets; it also plays a significant role in immunity.
RBC membrane fragility.

U. This can be classified as under :

A. Mechanical fragility
When RBCs are shaken with glass beads for one hour, about 2 to 5 % of the cells get lysed. In some hemolytic
anaemia, the % is more.

B. Autohemolysis
If normal blood with an anticoagulant is kept at 37 degree centigrade for 24 hours, less than 0.5 % cells get
hemolysed. A higher percentage is seen in some hemolytic anaemia.

C. Osmotic fragility
1. If RBCs are suspended in hypertonic solution, they shrink. If suspended in hypotonic solution, they swell,
become spherical (from disc-shaped) and eventually break and lose their Hb (haemolysis). The Hb of the
hemolysed cells dissolves in the plasma, colouring it red.
2. 0.9 % NaCl solution is isotonic with plasma
3. Values of normal RBC osmotic fragility
4. Haemolysis begins in 0.5% saline; 50 % lysis occurs in 0.40 to 0.42 % solution and complete haemolysis occurs
at 0.3 % solution.
5. In hereditary spherocytosis (also called congenital haemolytic icterus)
6. The cells are already spherocytic in the normal plasma and not disk-shaped; thus, their osmotic fragility is more
(i.e. they start getting hemolysed at less hypotonic or more hypertonic solutions than the normal cells).

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Therefore, hereditary spherocytosis is one of the most common causes of hereditary hemolytic anaemia.
7. Why are the cells spherocytic in hereditary spherocytosis,
8. Here, there is defect in the RBC membrane; there is abnormality in the protein network that normally
maintains the shape and flexibility of RBC membrane.
9. The RBC membrane skeleton is normally made up of the following proteins :
10. spectrin, band 3 protein and ankyrin
a. Spectrin is anchored to the trans-membrane protein band 3 by ankyrin.
11. (the band 3 protein also functions as an anion exchanger)

Chapter - 10
12. Hereditary spherocytosis can occur due to defects in spectrin, band 3, or ankyrin.
13. RBC of venous blood are slightly more fragile than those of arterial blood in normal persons.
14. Osmotic fragility is related to the shape of the RBC; the more spherical it is, the greater the fragility i.e. the
higher the concentration of saline at which hemolysis occurs.

D. Drugs and infections

Hemolysis of RBC can occur due to drugs and infections. Deficiency of G-6-P-D increases the susceptibility to
hemolysis by these agents. Why? G-6-P-D catalyses the first step in the oxidation of glucose via the hexose
monophosphate shunt (HMS) pathway. This pathway generates NADPH; NADPH is required for the integrity of the
normal red cell membrane.
Severe G-6-P-D deficiency also inhibits the killing of bacteria by granulocyte (and so predisposes to severe
infections)

Blood
1. RBC indices
Adult men Adult women Children 1 year
Direct measures
1. Red cell count (RCC) (in millions per 5.5 4.8 4.4
cumm)
2. Hb (gm/dL) 15.5 14 12
3. Mean corpuscular volume (MCV)(in 85 85 85
fL)
4. Packed cell volume (PCV) or 47 42 40
hematocrit (%)
Derived measures
MCH (in pg) 29 29 27
MCHC (g/dL) 33 33 33
2. Note :
1 microlitre = 1 cu mm
1 fl = 10-15 litre
1 pg = 10 –12 gram
MCH = mean corpuscular Hb; it is the average amount of Hb in one RBC
Hb
MCH = ------
RCC
RBC

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 Physiology

3. Formula for calculating MCH

Hb (g/dL)
MCH = ---------------------- --------------------------- x 10
RBC (as so many millions) per cumm

MCV = mean corpuscular volume; it is the average volume of one RBC

PCV
MCV = --------
RBC

4. Formula for calculating MCV

PCV (as percentage)

MCV = ---------------------- --------------------------- x 10
RBC (as so many millions) per cumm

MCHC = mean corpuscular hemoglobin concentration

This gives the amount of hemoglobin in one RBC as per its volume

MCH
MCHC = -------------
MCV

Since MCH = Hb/RBC and MCV = PCV/RBC,

Hb
MCHC can be expressed as = -------------------------------------
MCV x RBC
5. Formula for calculating MCHC

Hb (in g/dL)
MCHC = ----------------------- x 100
PCV (%)
MCV
> 95 fl = macrocytes
< 80 fl = microcytes
MCH
< 25 pg = hypochromic

6. ‘D’ Blood Groups

The membranes of human red cells contain a variety of blood group antigens, which are also called
agglutinogens. The most important are ABO system

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 Blood

7. ABO System
a. The ABO locus is located on chromosome 9
b. The H antigen is an essential precursor to the ABO blood group antigens. The H locus is located on
chromosome 19
c. The A allele encodes a glycosyltransferase that bonds α-N-Acetylgalactosamine to D-galactose end of H
antigen, producing the A antigen.
d. The B allele encodes a glycosyltransferase that joins α-D-galactose bonded to D-galactose end of H antigen,
creating the B antigen.

Chapter - 10
e. They are IgM antibodies. Anti-A and anti-B antibodies are not present in the newborn, appear in the first years
of life.
f. Acquired via cross reaction to food or bacterial antigen.
g. Most Common blood group in India is B
h. Persons with type AB blood are "universal recipients" because they have no circulating agglutinins and can be
given blood of any type without developing a transfusion reaction due to ABO incompatibility.
i. Type O individuals are "universal donors"
j. In individuals who are “secretors”, a soluble form of the ABO blood group antigens is found in saliva and in all
bodily fluids (Semen, Sweat, Saliva) except for the cerebrospinal fluid.

V. THE RH GROUP
a. The Rh factor (named for the rhesus monkey) is a system composed primarily of the C, D, and E antigens.
b. The system has not been detected in tissues other than red cells. D is by far the most antigenic component.

Blood
c. Rh-positive means that the individual has antigen D. The Rh-negative individual has no D antigen and forms the
anti-D agglutinin only when exposed with D-positive cells (Exception to Landsteiners Law i.e is antigen is
absent antibody against the antigen are present in serum).
d. Eighty-five percent of Caucasians are D-positive and 15% are D-negative; over 99% of Indians are D-positive.
e. When Rh-negative mother carries an Rh-positive fetus it can result in hemolytic disease of the newborn
(erythroblastosis fetalis)

Leucocytes (White Blood Corpuscles or cells - WBCs)

A. Introduction
The leucocytes are also called white blood corpuscles (WBS) or simply white cells of the blood but they are not
white but colourless. The WBCs defend the body against diseases by fighting infections (bacterial, viral, parasitic ,
etc.), antigens and also against malignancy.
B. Types
WBCs can be divided into
1. Granulocytes
These WBCs have granules in their cytoplasm. The granulocyte WBCs are : neutrophils, eosinophils and
basophils
2. Agranulocytes
These WBCs do not have granules in their cytoplasm. The agranulocyte WBCs are : monocytes and
lymphocytes

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 Physiology

Normal values with range

Cell Absolute value Range (cells/cu.mm.) Percentage of the total
(Cells/cu.mm.) WBCs
Total WBC 9000 4000 to 11000
Neutrophils 5400 3000 to 6000 50 to 70
Eosionophils 275 150 to 300 1 to 4
Basophils 35 0 to 100 0.4
Lymphocytes 2750 1500 to 4000 20 to 40
Monocytes 540 300 to 600 2 to 8

Note : 1 cu mm = 1 microlitre

Morphology of the nuclei

Nuclei
C. Granulocytes
Young granulocytes : horseshoe-shaped nuclei
Older granulocytes : multilobed nuclei
D. Agranulocytes
Lymphocytes : large round nuclei, scanty cytoplasm
Monocytes : kidney-shaped nuclei, abundant cytoplasm
E. Development of leucocytes (WBCs)
1. Leucocytes develop from the same single type of pleuripotent hematopoietic stem cells (HSCs) from
which all the blood cells develop. The HSCs give rise to committed stem cells (also called progenitor
cells or colony-forming units or CFUs). The committed stem cells are separate for each type of
leucocyte except for the neutrophil and monocyte; neutrophil and monocyte develop from a
common committed stem cell.
2. Stages in the development of neutrophil
3. Pluripotent hematopoietic stem cell  give rise to committed stem cell ; the committed stem cells go
through the following stages :

1. Myeloblast
1. Diameter : 12 to 18 µm;
Nucleus
2. It is purple-blue, large and round with finely stippled chromatin with several nucleoli.
Cytoplasm
3. This consists of a narrow blue rim without granules. Protein synthesis is very active, as shown by a highly
developed endoplasmic reticulum. The cells show active mitosis.

2. Promyelocytes
These show primary granules in the cytoplasm (azurophilic granules). Nucleoli decrease in number. Nucleus is
round, chromatin has started to condense. Mitosis is seen at this stage also.

3. Myelocyte
Diameter : 10 to 15 µm

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 Blood

Cytoplasm
This is more extensive and less basophilic than myeloblast. It has granules; the colour of the granules
classifies them as neutrophil , eosinophil or basophil myelocytes. Primary granules are no longer visible; in
this stage, the secondary or specific granules (for three different granulocytes i.e. neutrophilic, eosinophilic
and basophilic granules) appear. The cytoplasm is still basophilic. Mitosis is observed in this stage also.

F. Nucleus
Smaller and more basophilic than myeloblast. There are no nucleoli; chromatin is coarser and it is further

Chapter - 10
condensed.

1. Metamyelocyte
These cells have deep indented nuclei. The specific granules are plenty and they cytoplasm is yellow-pink.
Mitosis is not seen; chromatin is highly condensed.

2. Band form or juvenile neutrophil

Nucleus becomes horse-shoe or crescent shaped. Specific granules are in plenty. In case of increased
production of neutrophils, this form is also released into the circulation.

3. Segmented form or the mature neutrophils

It is a mature stage and the morphology is like a matured neutrophil. The cells have acquired all the
properties of a neutrophil i.e. phagocytosis, chemotaxis etc. and also the surface receptors. The cells pass into

Blood
the sinusoids to go into circulation.

G. Duration. From the stage of myeloblast to the stage of matured neutrophil it takes about 10 days, out of
which half is required for development up to the stage of myelocyte (mitotic pool) and the other half is
spent from metamyelocyte to matured neutrophil (maturation pool).
This time period is decreased during an acute infection when more neutrophils are needed. The matured
neutrophils stay in the circulation for a short time (half life = 6 hours). Then the cells enter the tissues and die
after 3 to 4 days. The neutrophils are destroyed by the RE cells, eliminated via GIT and via the respiratory
tract secretions. Bone marrow contains 3 days reserve of matured neutrophils.

H. Eosinophils and basophils

These develop with their specific granules in the same way as the neutrophils.

1. Monocytes
These are produced from the same committed stem cells from which the neutrophils develop. The stages of
development are :
Pluripotent hematopoietic stem cell  committed stem cell  monoblast  promonocyte  monocyte. The
monocyte after a short stay in the circulation pass to the tissues and are then called macrophages.

2. Neutrophils
a. These contain neutrophilic granules. They are the most numerous WBCs.
b. Diameter : 10 to 15 microns

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 Physiology

c. Lobes in the nuclei

d. Their nucleus shows variable number of lobes (2 to 7); hence, they are called as polymorphonuclear
leucocytes. The number of lobes increases as the neutrophil gets older.
e. Cytoplasm : pink
f. Granules :
g. fine violet (red-brown); amphophilic granules i.e. the granules take up both acidic and basic stains; thus
although they are called neutrophils, their granules are not neutral.
h. Nucleus : purple blue; chromatin is coarse and ropy

i. Average half-life of a neutrophil in the circulation : 6 hours.

ii. (thus, in order to maintain the normal circulating blood level, it is necessary to produce more than
100 billion neutrophils per day).
iii. The neutrophils are most numerous and are of shortest life span; therefore, their rate of formation
is also high. The bone marrow contains the highest number of neutrophils in different stages of
development and also the matured ones.

I. Neutrophil pool
The neutrophils are divided into different pools or collections, depending on the site.
1. The bone marrow pool
This represents the neutrophils present in bone marrow; it constitutes the largest pool viz. 90%

2. Circulation
This represents the neutrophils present in the circulation; it constitutes 3%; out of this 3%
a. 1.5% are in actual circulation and
b. 1.5% are attached to the endothelium; this is called the. marginal pool.

3. Tissue pool
This represents the neutrophils present in the tissues; it constitutes 7%;
Function
a. Neutrophils are also called as microphages; this is because they engulf small-sized particles (the
monocytes are called macrophages ; this is because they engulf large-sized particles).
b. Neutrophils are called the body’s first line of defence; this is because they are the first to move towards
the invading the bacteria.
How do the neutrophils leave the capillaries and enter the tissues?
Many of the neutrophils enter the tissues.

1. Attraction towards the endothelium :

At first, the neutrophils get attracted to the endothelial surface by selectins and they roll along the
endothelium.

2. Binding to the endothelium:

Next, they bind to the endothelium with the help of neutrophil adhesion molecules of the integrin family.

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 Blood

3. Diapedesis:
a. The neutrophils have contractile proteins e.g. actin, myosin I etc. in their cytoskeleton. With the help of
these contractile proteins, they come out of the walls of the capillaries by passing in between the
endothelial cells. This process is called diapedesis.

J. Note :
a. Many of the neutrophils that come out of the circulation enter the gastrointestinal tract and are lost
from the body.

Chapter - 10
b. Inflammatory response of the neutrophils to bacterial invasion
c. Invasion of the body by bacteria triggers the inflammatory response.

1. Stimulation of the bone marrow

The bone marrow is stimulated to produce and release large numbers of neutrophils.

2. Chemotaxis
Chemical agents move the neutrophils towards the infected area ; such movement of neutrophils is called
chemotaxis. The chemical agents responsible for chemotaxis are called as chemotactic agents.

K. Chemotactic agents
Bacterial products interact with plasma factors and cells to produce these agents The chemotactic agents are a
part of a large family of chemokines .

Blood
The chemotactic agents include :
a. A component of the complement system (C5a);
b. Leukotrienes;
c. Polypeptides (from lvmphocytes, mast cells, and basophils).

Gc- globulin
This is a plasma protein that increases the effect of C5a; the neutrophil membranes also contain this protein.
It also binds and transports vitamin D in the plasma.

1. Opsonization
Coating of the bacteria by certain plasma factors helps the neutrophils in attacking the bacteria. The coating
makes the bacteria “tasty” for the neutrophils. This process of coating of the bacteria is called opsonization.
The factors used for coating are called opsonins. The principal opsonins are the IgG immunoglobulins and
complement proteins.
2. Phagocytosis
a. The opsonized bacteria bind to the receptors on the neutrophil cell membrane
b. This binding to increases the motor activity of the neutrophil via a hetero trimeric G protein .
c. The increased motor activity leads to prompt ingestion of the bacteria by the neutrophil
(phagocytosis) forming a phagocytic vacuole containing the bacteria

3. Degranulation

515
 Physiology

The neutrophil granules discharge their contents into the phagocytic vacuoles (and also into the interstitial
space); this process is called as degranulation.
The granules release
a. various proteolytic enzymes and
b. defensins : these are anti-microbial proteins; the defensins are of two types - alpha and beta.(Secreted by
Paneth cells in GIT)

4. Activation of NADPH oxidase

a. The neutrophil cell membrane-bound enzyme NADPH oxidase is also activated; this leads to production of
toxic oxygen metabolites.

b. The combination of proteolytic enzymes from the granules and the toxic oxygen metabolites help in killing
and digestion of the bacteria.

5. Respiratory burst
Activation of NADPH oxidase (present on the neutrophil cell membrane) results in :
a. a sharp increase in O2 uptake and metabolism in the neutrophil; this is called as respiratory burst)
b. generation of O2 -by the following reaction:
NADPH + H + +202  NADP + + 2H+ +202 -

6. Killing and digestion of the bacteria by :

a. Oxidants : These are :-
b. 02 - (also called superoxide):
This is s a free radical formed by the addition of one electron to O2.
 H2O2
2 02 - react with two H+ to form H2O2 ; this reaction catalyzed by the cytoplasmic form of superoxide
dismutase (SOD-1):

SOD-1
02 - + 02 - + H+ + H+ ------- H2O2 + O2

Both the oxidant 02 - and H2O2 are effective bactericidal agents; however, H2 02 is converted to H2 0 and O2 , by
the enzyme catalase.

SOD-1
a. The cytoplasmic form of SOD contains both Zn and Cu. It is found in many parts of the body.
b. Defective SOD
c. This can occur due a gene mutation; the defective SOD is the cause of a familial form of amyotrophic
lateral sclerosis (ALS).
d. Because of the deficiency of SOD, it is possible that 02 - accumulates in motor neurons and kills them in
at least one form ALS.
e. Two other forms of SOD encoded by at least one different gene are also found in humans.

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 Blood

L. HOCl, HOBr
These are also effective oxidants.How are they produced?
Neutrophils have an enzyme called myeloperoxidase; this enzyme catalyzes the conversion of CI-, Br, I-, and
SCN- to the corresponding acids (HOCI, HOBr, etc). These acids are also potent oxidants. Since CI- is present in
greatest abundance in body fluids, the principal product is HOCI.

1. Other agents in neutrophils that destroy bacteria :

Neutrophil granules have defensins, an elastase and two metalloproteinases that attack collagen, and a

Chapter - 10
variety of other proteases; all these help in destroying the invading organisms. These enzymes act in a
cooperative fashion with the oxidants mentioned above to kill the bacteria.

2. Note:
In certain diseases, e.g. rheumatoid arthritis, the neutrophils may also cause local destruction of host tissue.

3. Role of microtubules and microfilaments

These play a role in
1. movement of the cell in phagocytosis
2. migration of the cell to the site of infection

Proper function of the microfilaments involves the interaction of the actin they contain with myosin-I on the
inside of the cell membrane.

Blood
M. Eosinophils
They are called so because they have eosinophilic granules; these get stained with acidic dyes.

1. Characteristic features :
Eosinophils show many of the features of neutrophils. For example, they a short half-life in the circulation; they
are attracted to the surface of endothelial cells by selectins; they bind to integrins which attach them to the
vessel wall; they enter the tissues by diapedesis. Like neutrophils, eosinophils also show chemotaxis.

2. Sites
Eosinophils are especially abundant in
1. The mucosa of the gastrointestinal tract; here, they defend against parasites.
2. In the mucosa of the respiratory and urinary tracts.

N. Functions
1. Phagocytic function
Like neutrophil, eosinophils are also phagocytic; however, eosinophils are less motile than neutrophils. Like
neutrophil granules, eosinophil granules are also lysosomal in nature and contain most of the enzymes
found in neutrophil granules. Eosinophil granules have a very high peroxidase content which partly
accounts for their parasiticidal action e.g. versus schistosomes.

517
 Physiology

2. Allergic reactions
Eosinophils collect at the site of allergic reactions. It has been suggested that they limit the effects of
mediators (e.g. histamine, bradykinin) of some types of antigen-antibody reaction. The aryl-sulphatase-B
present in the eosinophil inactivates the slow reacting substance (SRS) released from mast cells and
prevents anaphylaxis (anti-allergic reaction). Furthermore, histaminase etc. from eosinophils destroy the
substances released from mast cells. Because of its phagocytic action, it takes up antigen-antibody
complexes.
3. Eosinophils contain a major basic protein (MBP) which damages the larvae of parasites.
4. There is one eosinophilic cation protein which probably neutralizes heparin..
5. Eosinophils also contains peroxidase.

O. Factors and conditions affecting eosinophil activation

1. Their maturation and activation in tissues is particularly stimulated by IL-3, IL-5, and GM-CSF.
2. The level of circulating eosinophils is reduced by adrenal corticosteroids and hence by secretion of ACTH.
The eosinopenia is caused by sequestration of eosinophils in the lungs and spleen and by their
destruction in the circulating blood.
3. Circulating eosinophils are increased in
a. allergic diseases such as asthma and
b. in various other respiratory and gastrointestinal diseases.

P. Basophils
Basophils also enter tissues and release proteins and cytokines. They are also motile and phagocytic. They
resemble but are not identical to mast cells. Like mast cells, basophils contain histamine and heparin. They
release histamine and other inflammatory mediators when activated by a histamine releasing factor secreted
by T lymphocytes; they are essential for immediate-type hypersensitivity reactions. These reactions range
from mild urticaria and rhinitis to severe anaphylactic shock.

Q. Mast Cells
What are they?
Mast cells are heavily granulated wandering cells
Sites where found
They are found in areas rich in connective tissue, and they are abundant beneath epithelial surfaces.
Contents of their granules
Their granules contain heparin, histamine, and many proteases. The heparin appears to play a role in granule
formation.
R. Role
1. In acquired immunity
Mast cells have IgE receptors on their cell membranes; like basophils, they degranulate when IgE-coated
antigens bind to their surface. They are involved in inflammatory responses initiated by immunoglobulins
IgE and IgG. The inflammation fights invading parasites.
2. In natural immunity
Mast cells release TNF-alpha in response to bacterial products by an antibody-independent mechanism;
thus they participate in the nonspecific natural immunity that fights infections. Marked mast cell
degranulation produces clinical manifestations ranging from allergy to anaphylaxis.

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 Blood

3. histamine released from the mast cells of the GIT(and from other gastrointestinal immune cells)
stimulates GIT secretion of water and electrolytes
4. primed mast cells play a central role in the gastrointestinal response to antigen. A primed mast cell is one
that carries antibody on its surface. When the antibody “recognizes” its particular antigen, the mast cells
degranulate and release many different mediators. Several of these mediators induce hypersecretion of
salts and water by the epithelial cells as well as hypermotility. Mast cells also release cytokines that recruit
other mucosal immune cells to the response. These cells may then also release secretogogues.

Chapter - 10
S. Monocytes
Life span of monocytes
1. In the circulation,
Monocytes enter the blood from the bone marrow and circulate for about 72 hours.
2. In the tissues;
3. After about 72 hours in the circulation, monocytes enter the tissues and become tissue macrophages
4. Their life span in the tissues is unknown; studies suggest that they persist for about 3 months. It appears
that they do not reenter the circulation.
5. Some monocytes become the multinucleated giant cells seen in chronic inflammatory diseases such as
tuberculosis.
6. Monocyte- macrophage system;
As mentioned above, monocytes after a short stay in the circulation enter the tissues and becomes tissue
macrophages. These tissue macrophages are found in many organs and are known by different names :

Blood
Tissue macrophage in Known as
Liver Kupffer cells
Connective tissue Histiocytes
Lymph nodes Dendritic cells
Spleen Dendritic cells
Bone marrow Dendritic cells
Adrenal glands Endothelial cells
Pituitary Endothelial cells
CNS Microglia
Alveoli Pulmonary alveolar macrophages (PAMS)
Skin Langerhans cells
Bone Osteoclasts

The monocyte-macrophage system was previously known as reticuloendothelial system.

Functions of tissue macrophage system
1. Phagocytic
The macrophages become activated by lymphokines from T lymphocytes. The activated macrophages mi-
grate in response to chemotactic stimuli phagocytose invading bacteria. The steps in phagocytosis is similar
to that in neutrophils.
2. They play a key role in immunity.
3. They secrete many different substances e.g.

519
 Physiology

a. substances that affect lymphocytes and other cells

b. prostaglandins of the E series
c. clot promoting factors etc.

Factors stimulating/activating the cells of the bone marrow

The hematopoietic stem cells (HSC) in the bone marrow (refer page ) are the pleuripotent uncommitted
stem cells; they give rise to committed stem cells (also called progenitor cells). As the name suggests,
committed stem cells produce one type of blood cell.

a. Interleukins
Interleukins IL-1 and IL-6 followed by IL-3 act in sequence to convert pluripotential uncommitted stem cells
to committed progenitor cells .IL-3 is also known as multi-CSF. (CSF = colony stimulating factor)

b. Colony-stimulating factors (CSF)

CSFs are factors which stimulate/activate a particular committed stem cell. They are so called because these
factors forms colonies of the committed stem cell in soft agar culture medium.
The various CSFs are
a. Granulocyte-macrophage CSF (GM-CSF)
b. Granulocyte CSF (G-CSF)
c. Macrophage CSF (M-CSF).

T. Function of interleukins and CSFs

1. Each of the CSFs stimulates mainly one type of stem cell
2. In addition, each of the CSFs (as well as the interleukins) are capable of stimulating other stem cells as
well.
3. The interleukins and CSFs also they activate and sustain mature blood cells.
The genes for many of these factors are located together on the long arm of chromosome 5. Basal
hematopoiesis is normal in mice in which the GM-CSF gene is knocked out; this indicates that loss of one
factor can be compensated for by others. However, the absence of GM-CSF causes accumulation of surfac-
tant in the lungs.

U. Source of these factors

The factors are produced by macrophages, activated T cells, fibroblasts, and endothelial cells. Mostly, the factors
act locally in the bone marrow.
(Note : The RBC stimulating hormone, erythropoietin, is produced in part by kidney cells and is a circulating
hormone).
V. Applied aspects
To fight invading bacteria, the phagocytic mechanism has to be intact.. If there is a defect in this mechanism, it
can make the person prone to infections. The various defects in the phagocytic mechanism are as follows :
1. Hypomotility of neutrophils
In this condition, actin in the neutrophils does not polymerize normally; as a result, the neutrophils move
slowly.
2. Congenital deficiency of integrins in the leukocyte
3. Chronic granulomatous disease

520
 Blood

In this condition, there is a failure to generate O 2 - in both the neutrophils and monocytes; thus, there is
inability to kill many phagocytosed bacteria.
4. Severe congenital glucose 6-phosphate dehydrogenase deficiency
In this condition, there is failure to generate NADPH; as mentioned above, NADPH is required for producing
O2 - ; consequently, the patient has multiple infections because of failure to generate O 2 -
5. Congenital myeloperoxidase deficiency,
In this condition, hypohalite ions are not formed; thus, there is decrease in ability to attack microbes.

Chapter - 10
Lymphocytes
A. Site of production of lymphocytes after birth
1. Some lymphocytes are formed in the bone marrow.
2. However, most are formed in the lymph nodes, thymus, and spleen. The precursor cells are originally
from the bone marrow; these precursor cells then get processed either in the thymus or bursal
equivalent. These processed precursor cells move to the lymph nodes, thymus and spleen.

B. Release into the circulation

From their site of production, the lymphocytes enter the bloodstream mostly via the lymphatics. At any given
time, only about 2% of the body lymphocytes are in the peripheral blood. Most of the rest are in the
lymphoid organs. Approximately, 3.5 x 1010 lymphocytes per day enter the circulation via the thoracic duct
alone; however, this count includes cells that reenter the lymphatics and thus traverse the thoracic duct more
than once.

Blood
C. Function
Lymphocytes play a very important role in immunity.

521
 Physiology

“Please Read the Preface of this book Before you attempt these questions.”
Explanation of answer start from page no. 525

1. Which of the following is not true? (AIPG 2011) (AIPG 2007)

A. Factor X is common to both extrinsic and intrinsic A. Thrombin B. Factor VIII
pathway. C. Factor V D. Factor VII
B. Calcium is essential for coagulation pathway.
C. Negatively charged surface proteins are required for 9. HB estimation is not done by (AIIMS NOV 2007)
activation of extrinsic pathway. A. Drabkin’s method B. Sahli’s method
D. Intrinsic pathway can occur in vitro. C. Spectrophotometry D. Wintrobe method

2. A 9 year old boy with elevated both PT and aPTT. 10. All of the following occur when the blood flow
What is the diagnosis? (AIIMS NOV 2010) through to capillaries except
A. Defect in extrinsic pathway A. Increase in hematocrit
B. Defect in Intrinsic pathway B. HB curve shift to the left
C. Platelet function defect C. Increased protein content
D. Defect in common pathway D. Decrease in pH

3. What does "C" in CRP stand for? (AIIMS NOV 2009) 11. The life span of RBC is:
(Latest Questions) A. 70 days B. 150 days
A. C- polysaccharide of Pneumococcus C. 120 days D. 110 days
B. Chondroitin Sulfate in series with ARP, BRP
C. Concanavalin A 12. Glycophorin is present in: (DNB Jun – 2010)
D. Cellular A. Entrocytes B. Hepatocyte
C. Erythrocyte D. Lymphocyte
4. ABO antigens not found in (AIIMS NOV 2009)
A. CSF B. Semen 13. In hemopoiesis G-CSF and GM-CSF causes:
C. Sweat D. Saliva A. Leucopenia B. Granulocytosis
C. Erythrocytosis D. Thrombocytosis
5. Which is not involved in intrinsic pathway?
(AIPG 2009) 14. Which of the following is false regarding spectrin:
A. Factor XII B. Factor XI A. Protein in nature
C. Factor IX D. Factor VII B. Functions are similar to ankyrin
C. Deficiency leads to hereditary spherocytosis
6. Rh factor is (AIPG 2008) D. It is responsible for primary structure of cell wall
A. IgM antibody B. Mucopolysaccharide
C. IgG Antibody D. Fatty acid 15. Deficiency of factor does not cause an
abnormality of intrinsic pathway:
7. Which of the following helps in bridging the fibrin A. Factor VIII B. Factor XI
in a clot and stabilizing the clot? (AIPG 2008) C. Factor VII D. Factor IX
A. Factor III B. Factor V
C. Factor VIII D. Factor XIII 16 Cell type, which lacks HLA antigen, is: (DNB Dec. –
8. Clotting factor present in both plasma and serum is 2008)
1.C 2.D 3.A 4.A 5.D 6.B 7.D 8.D 9.D 10.A 11.C 12.C 13.B 14.D 15.C

522
 Blood

A. Monocyte B. Thrombocytes 24. Immune complexes are removed from blood by;
C. Neutrophil D. Red blood cell A. B cell B. Basophil
C. Plasma cell D. Kupffer cell
17 The function common to neutrophils, moncyte &
macrophage is 25. Which of the following promotes platelet
A. Immune response aggregation: (DNB Dec-2007)
B.Phagocytosis A. Adenosine diphosphate B. Interleukin
C. Liberation of histamine C. Thromboxane A2 D. Thrombin

Chapter - 10
D. Destruction of old erythrocytes
26. Which of the following promotes erythropoiesis:
18 In which Hb iron is in Fe3+ form: A. Erythropoietin B. Interleukin 5
A. HbF B. HbA-2 C. Colony stimulating factor D. Interleukin 4
C. Hb gower D. Meth HB
27. Which secretes thymopoietin: (DNB Dec-2009)
19 The blood in the vessels normally does not clot A. Pancreas B. Liver C. Thymus D. Spleen
because:
A. Vitamin K antagonists are present in plasma 28. Which of the following secrete thromboxane A
B. Thrombin has positive feedback on plasminogen A. ABCs B. Neutrophils
C. Sodium citrate in plasma chelates calcium ions. C. Platelets D. WBCs
D. Vascular endothelium is smooth and coated with
glycocalyx 29. Erythropoietin is secreted when:
A. Hemoglobin increases

Blood
20. During homeostasis, platelet affects the B. Increased tissue pCO2 concentration
coagulation by: (PGI May-2011) C. Decreased tissue pO2 concentration
A. Platelet adhesion to exposed endothelium D. Increased tissue pH
B. Clot retraction
C. Activation of prothrombinase complex 30. Which of the following is required for the
D. Vasoconstriction conversion of prothrombin to thrombin:
E. Conversion of fibrinogen to fibrin A. Factors VII, X, V and Ca++
B. Factors X, V and Ca++
21. ‘Aggregins’ are C. Factors X, V
A. Meant for platelet aggregation D. Ca++ only
B. For adhesion of cells to basement membrane
C. For adhesion of fibrinogen receptors to platelets 31. Which of the following clotting factor is not
D. For platelet adhesion to endothelium formed by liver: (DNB Dec-2009)
A. II B.VI C. X D. IX
22. Secondary granules of neutrophils contain
A. Lactoferin 32. In clotting mechanism which of the following
B. Catalase factor is absent: (LQ)
C. Myeloperoxidase A.VI B. III C. IV D. II
D. Nucleotidase
23. B lymphocytes are associated with (LQ) 33. A 55-year-old male accident victim in casualty
A. CD19 B. CD27 C. CD4 D. CD35 ‘urgently’ needs blood. The blood bank is unable to
16.D 17.B 18.D 19.D 20.ABCD 21.A 22.A 23.A 24.D 25.C 26.A 27.C 28.C 29.C 30.B 31.B 32.A

523
 Physiology

determine his ABO group, as his red cell group and 38. Which is Vitamin K dependent clotting
plasma group do not match. Emergency transfusion of factor? (AIIMS NOV 2010)
patient should be with: A. Factor VII B. Factor I
A. RBC corresponding to his red cell group and C. Factor XI D. Factor XII
colloids/crystalloid
B. Whole blood group corresponding to his plasma 39. Hematopoiesis in yolk sac start at
group A. 3rd week B. 8th week
C. O Negative RBC and colloids/crystalloid C. 12 th week D. 15th week
D. AB negative whole blood
40. Interleukin specific for eosinophil is
34. Stored blood as compared to fresh blood has: A. IL-1 B. IL-3 C. IL-5 D. IL-6
A. More 2,3 DPG
B. High extracellular K+ 41. Major basic protein secreted by-
C. High extracellular Hb A. neutrophils B. basophils
D. Increased platelets C. eosinophils D. plasma cells

35. Although more than 400 blood groups have been 42. PDGF (or platelet-derived growth factor) is
identified, the ABO blood group system remains the secreted from
most important in clinical medicine because.: A. alpha granules of platelets
A. It was the first blood group system to be B. dense granules of platelets
discovered. C. both
B. It has four different blood groups A, B, AB, O(H). D. none
C. ABO (H) antigens are present in most body tissues
43. Which of the following would be expected to
and fluids.
contain relatively high numbers of functional
D. ABO (H) antibodies are invariably present in plasma hematopoietic cells?
when persons RBC lacks the corresponding (A) Adult liver
antigen. (B) Umbilical cord blood
(C) Adult circulating blood
36. The true statement about stem cells include? (D) Adult spleen
A. They divide to form different cell lines
B. They are used in gene therapy 44. What is the process that amplifies the number of
T cells or B cells programmed to respond to a specific
C. They are terminally differentiated cells
infectious stimulus?
D. They are present in peripheral circulation (A) Hematopoiesis
E. They are incapable of division (B) Hematotherapy
(C) Inflammation
37. Heme is converted to bilirubin mainly in: (D) Clonal selection
A. Kidney
45. The response to the antigen used in the
B. Liver
tuberculosis skin test, PPD, is not noticeable until 24
C. Spleen to 48 hours after injection because
D. Bone marrow (A) It takes that long for B cells to respond
(B) It takes that long for T cells to respond
(C) It takes that long for neutrophils to arrive at the site
(D) It takes that long for eosinophils to respond

33.C 34.B 35.D 36.A,B 37.D 38.A 39.A 40.C 41.B 42.A 43.B 44.D 45.B

524
 Blood

46. Antibody specificity is determined by the amino

acid sequence within the
(A) Fc region
(B) Constant region
(C) Variable region
(D) Fc receptors

47. The first step in the extrinsic coagulation pathway

is

Chapter - 10
(A) Activation of factor X
(B) Activation of factor XII
(C) Conversion of prothrombin to thrombin
(D) Release of tissue thromboplastin

48. A reactant generated by neutrophils that plays an

important role in bacterial killing is
(A) NADPH oxidase
(B) Hexose monophosphate shunt
(C) G proteins
(D) Superoxide anion

49The first step for lymphatic vessels to remove

excess fluid from interstitial tissue spaces is by?
(A) Generating a lower intravascular than tissue

Blood
hydrostatic pressure
(B) Contracting and forcing lymph into larger
lymphatics
(C) Opening and closing one-way valves in the lymph
vessels
(D) Lowering the colloid osmotic pressure inside the
lymph vessel

50. Which of the following ranges of hemoglobin O2

saturation from systemic venous to systemic
arterial blood represents a normal resting
condition?

(A) 25 to 75%

(B) 40 to 75%

(C) 40 to 95%

(D) 75 to 98%

46.C 47.D 48.D 49.A 50.D

525
 Blood

Explanations
Chapter-10 Blood

1. Ans. C. Negatively charged surface proteins are required for activation of extrinsic pathway.
(Ref: Ganong - 23rd Ed , Page 489)

2. Ans. D. Defect in common pathway

(Ref: Hematology: Page-719-53. )

Chapter - 10
a. The prothrombin time (PT) and its derived measures of prothrombin ratio (PR) and international
normalised ratio (INR) are measures of the extrinsic pathway of coagulation.
b. They are used to determine the clotting tendency of blood, in the measure of warfarin dosage, liver
damage, and vitamin K status.
c. PT measures factors I, II, V, VII, and X.
d. The partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT or APTT) is a
performance indicator measuring the efficacy of both the "intrinsic" (now referred to as the contact
activation pathway) and the common coagulation pathways.
e. It is also used to monitor the treatment effects with heparin, a major anticoagulant. 4
f. It is used in conjunction with the prothrombin time (PT) which measures the extrinsic pathway.
g. Incase both are increased it indicates defect in common pathway.
Condition Prothrombin time Partial thromboplastin time Bleeding time Platelet count
Vitamin K deficiency or warfarin prolonged prolonged unaffected unaffected

Blood
DIC prolonged prolonged prolonged decreased
Von Willebrand disease unaffected prolonged prolonged unaffected
Haemophilia unaffected prolonged unaffected unaffected
Aspirin unaffected unaffected prolonged unaffected
Thrombocytopenia unaffected unaffected prolonged decreased
Early Liver failure prolonged unaffected unaffected unaffected
End-stage Liver failure prolonged prolonged prolonged decreased
Uremia unaffected unaffected prolonged unaffected
Congenital afibrinogenemia prolonged prolonged prolonged unaffected
Factor V deficiency prolonged prolonged unaffected unaffected
Factor X deficiency prolonged prolonged unaffected unaffected
Glanzmann's thrombasthenia unaffected unaffected prolonged unaffected
Bernard-Soulier syndrome unaffected unaffected prolonged decreased

3. Ans. A. C- polysaccharide of Pneumococcus

(Ref: Tillett WS, Francis Jr T (1930). "Serological reactions in pneumonia with a nonprotein somatic fraction of
pneumococcus" J Exp Med 52: 561–585.)
a. C-reactive protein was originally discovered by Tillett and Francis in 1930 as a substance in the serum of
patients with acute inflammation that reacted with the C polysaccharide of pneumococcus. Q
b. Its physiological role is to bind to phosphocholine expressed on the surface of dead or dying cells (and
some types of bacteria) in order to activate the complement system via c1q. Q

525
 Physiology

c. CRP is synthesized by the liver in response to factors released by fat cells (adipocytes). It is a member of
the pentraxin family of proteins.
d. CRP rises up to 50,000-fold in acute inflammation, such as infection. It rises above normal limits within 6
hours, and peaks at 48 hours. Its half-life is constant, and therefore its level is mainly determined by the
rate of production
e. There are two types of CRP assays. One measures a wide range of CRP levels to include those found in
patients with acute infections.
f. The second is a high-sensitivity CRP (hs-CRP) assay. The latter can detect a lower level of CRP to include
those that may be of value in measuring the risk for a cardiac event. The hs-CRP is useful, therefore, for
assessment of risk for developing myocardial infarction in patients presenting with acute coronary
syndromes.

4. Ans. A. CSF
(Ref: Wintrobe's Clinical Hematology, 11th ed.Volume 1 Pg 636)
a. Although the ABO blood group antigens are regarded as RBC antigens, they are actually expressed on a
wide variety of human tissues and are present on most epithelial and endothelial cells.
b. Each human RBC expresses about 2 million ABO blood group antigens. Other blood cells, such as T cells, B
cells, and platelets, have ABO blood group antigens that have been adsorbed from the plasma.
c. In individuals who are "secretors" Q, a soluble form of the ABO blood group antigens is found in saliva Q and
in all bodily fluids (Semen, Sweat Q, Saliva) except for the cerebrospinal fluid.

5. Ans. D Factor VII

The clotting mechanism. a, active form of clotting factor; HMW, high-molecular-weight; PL, platelet phospholipid;
TPL, tissue thromboplastin. TFI, tissue factor pathway inhibitor

6. Ans. B. Mucopolysaccharide
a. Most of the blood group antigens are proteins or mucopolysaccharides, so most likely Rh factor is a
Mucopolysaccharide.

7. Ans. D. Factor XIII

Explanation
a. The fundamental reaction in the clotting of blood is conversion of the soluble plasma protein fibrinogen to
insoluble fibrin.
b. The process involves the release of two pairs of polypeptides from each fibrinogen molecule.
c. The remaining portion, fibrin monomer then polymerizes with other monomer molecules to form fibrin.
d. The fibrin is initially a loose mesh of interlacing strands.
e. It is converted by the formation of covalent cross-linkages to a dense, tight aggregate (stabilization ).
f. This latter reaction is catalyzed by activated factor XIII and requires Ca 2+ .

8. Ans. D Factor VII

a. Fluid portion of blood (Blood minus cells) is known as plasma and if the whole blood is allowed to clot and
the clot is removed, the remaining fluid is called serum.
b. Serum has essentially the same composition as plasma except that fibrinogen and clotting factor II, V and
VIII have been removed.

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 Blood

c. It also has a high serotonin content due to break down of platelets during clotting.
d. Tip to remember - vit K dependent factors do not get consumed during clotting except factor II.

9. Ans. D. Wintrobe method

Explanation.
a. Sahli’s method: Hb estimation by converting a known volume of blood into acid heamatin by addition of
dilute HCl and subsequence comparison with a suitable standard
b. Spectrophotometry: This involves the use of photoelectric colorimeter that measure the amount of light

Chapter - 10
absorbed by a solution. The light used is these instrument is of limited wave band and this band is chosen
to correspond with the part of the spectrum that is maximally absorbed by the solution being tested.
c. The one that is commonly used is cyanmethemoglobin method. Here Hb is converted into
cyanmethemoglobin by Drabkin’s reagent (NaHCO3, 1 gm potassium cyanide 50 mg, potassium ferric
cyanide 200mg and distill water 1 litre)
d. Wintrobe’s tube: This is for estimation of ESR and PCV and not for Hb

10. Ans. A. Increase in hematocrit

a. While blood flows through a narrow vessal, the RBS’s take up the axial stream, so in the periphery ie.
b. Near the vessel wall the blood contains mostly plasma (ie cell poor).
c. Now small vessel arising from the side of the above vessel will have more plasma and a low hematocrit
value.
d. This is called plasma skimming. For this reason, viscosity in the smaller vessels as in capillaries, will be less
and will help in flow.

Blood
e. This is called Fahraeus- Lindqvist effect. So, the hematocrit value is always low in capillaries. In systemic
capillaries there is a decrease in pH & Hb curve shift to the left.
f. In endocrine gland, liver capillaries due to protein secretion protein content increases.

11. Ans. C. 120 days

The average life span of red blood cells (RBCs) in the circulation is 90 TO 120 DAYS.

12. Ans. C. Erythrocyte

a. GLYCOPHORIN is a glycoprotein that spans the bilipid layer of the RBC membrane.
b. Its outside end contains blood group antigens and sites to which some viruses attach.
c. This protein provides the channel through which anions pass in and out of the red blood cell.

13. Ans. B. Granulocytosis

Four glycoproteins that regulate the production of GRANULOCYTES and monocytes are secreted by different
tissues of body and they are called colony stimulating factor.
• Granulocyte macrophage colony stimulating factor (GM-CSF)
• Granulocyte colony stimulating factor (G-CSF)
• Multipotent colony stimulating factor (Multi-CSF)
• Macrophage colony stimulating factor (M-CSF)
G-CSF and GM-CSF stimulate neutrophil production and are used in cancer patients. Q
• G-CSF: 5 pg/kg per day subcutaneously • Start 24-72 h after chemotherapy
• GM-CSF: 250 pg/m per day subcutaneously • Continue until absolute neutrophil count is 1 0,000/ml

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 Physiology

14. Ans. D. It is responsible for primary structure of cell wall

a. The molecular defect in hereditary spherocytosis involves the proteins of the underlying cytoskeleton Q.
b. Nearly 100% patients have a considerable deficiency of SPECTRIN Q.
c. Spectrin is the major skeletal protein of filamentous nature.
d. It consists of two polypeptide chains a and which are intertwined.
e. It is connected laterally via two additional proteins namely protein 4.1 and actin.
f. This two dimensional cable meshwork is tethered (bounded) to the cell membrane by another protein
called ANKYRIN which forms a bridge between spectrin and cell membrane protein 3.
g. About 50% of patients have a defect in ankyrin Q.

15. Ans. C. Factor VII

16. Ans. D. Red blood cell

a. Antigen presenting cells include specialized cells called dendritic cells in the lymph nodes and spleen and
the Langerhans dendritic cells in the skin Macrophages and B cells themselves can also function as antigen
presenting cells.
b. In antigen-presenting cells, polypeptide products of antigen digestion are coupled to protein products of
the major histocompatibility (H LA) complex genes and presented on the surface of the cells.
c. The products of the MHC genes are called human leukocyte antigens (HLA) The genes of the HLA are
located on the short arm of chromosome 6 Q, encode glycoproteins and are divided in two classes based
on their distribution and function.
d. The class I antigens are found on all ‘nucleated’ cells while the class II antigens are present in antigen-
presenting cells including B cells and activated T cells. Q

17. Ans. B. Phagocytosis

Metnikoff discovered the phenomenon of phagocytosis Q. Phagocytic cells are the mononuclear macrophages (of
blood and tissues) and polymorphonuclear microphages (e.g. Nuetrophils, Eosinophilis and Basophils)

18. Ans. D. Meth HB

a. Normally Fe remains in Hb as Fe++ (ferrous) form.
b. When blood is exposed to various drugs and other oxidizing agent in vitro or in vivo, the ferrous iron
(Fe++) that is normally in the molecule is converted to ferric iron (Fe+++) forming Methemoglobin (Met
Hb).

19. Ans. D. Vascular endothelium is smooth and coated with glycocalyx

a. Intact endothelial cells serves primarily to inhibit platelet adherence and blood clotting.
b. Injury or activation of endothelial cells, however, results in a procagulant phenotype that augments local
clot formation. Role of vascular endothelium in hemostasis
c. The vascular endothelium acts as a barrier between the thrombogenic subendothelial tissue and the
blood
d. The smoothness of endothelial cells hinder platelet aggregation
e. They manufactures heparin and 2 macroglobulin which are coagulation inhibitors.
f. These cells manufactures' PGI2 (prostacyclin) which opposes platelet aggregation.

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 Blood

Factors opposing coagulation existing clots and platelets plugging and accruing naturally
A. Opposing coagulation Q B. Causing lysis of existing clot Q C. Opposing platelet aggregation
 Antithrombin III Plasminogen activators Endoperoxidase from platelets
 Heparin Prostacyclin
 Macroglobulin
 Proteins C
Note
a. Vit K dependent factor II, VII, IX, X, CS Q

Chapter - 10
b. Factor II (prothrombin), VII, IX, and X. Protein C and proteins S Q
c. Factors synthesis by liver 2, 7, 9,10, CS + 1,5,11 Q
d. Factor I (fibrinogen), II (Prothrombin), V, VII, IX, X, XI Q
e. Protein C and proteins S Q
f. Antithrombin III and heparin Q

20. Ans. A,B,C,D

21. Ans. A. Meant for platelet aggregation

22. Ans. A. Lactoferin

Neutrophil:
1. Constituents of specific granules (secondary granules) of neutrophils:
a. Lactoferrin b. Lysozyme c. Alkaline phosphatase

Blood
d. Type IV collagenase e. Leukocyte Adhesions molecules f. Plasminogen activation
g. Phospholipase A2

2. Constituents of Azurophil granules (Primary granules of neutrophil

a. Myeloperoxidase b. Lysozyme  Bactericidal factor c. Cationic protein
d. Acid hydrolases e. Elastase f. Non - specific collagenase
g. BPI (Bactericidal permeability i. Phospholipase A2
increasing protein Defensins)
h. Cathepsin G

23. Ans. A. CD19

a. [A] T-cells: - (Markers) .
i. CD3  Pan-T-cell marker Q
ii. CD2  Receptor for sheep Erythrocyte (E-rosette) Q
iii. CD4  T-helper-inducer cells  Binds to MHC class II Q
iv. CD8  T-cytotoxic -suppressor cells  Binds to MHC calls I. Q
v. Surface Antigen receptor (TCR) is attached to CD3. Q
b. [B] B-cells 
i. CD19  Pan B-cell marker. Q
ii. CD2o/21/22  B-cell markers Q
c. [C] CD34  stem cell markers.
d. [D] Hairy cells  usually B-lymphocytes  but characteristically express CD25 and FMC7 and Acid

529
 Physiology

phosphatase staining resistant to the action of tartrate,

e. [E] NK cells 
i. CD56 and CD16 are NK cell marker Q
ii. Large granular Lymphocytes Q
iii. Kills the viral infected and tumor cell in the absence of prior sensitization and without MHC. Q

24. Ans. D. Kupffer cell

a. Monocytes-macrophages
i. Tissues macrophages arise by migration of monocytes from the circulation.
ii. Common locations of tissue macrophages - are lymph node, spleen, BM, perivascular connective
tissue, serous cavities such as peritoneum, pleura, skin connective tissue, lung (Alveolar
macrophages), Liver (kupffer cells) bone (osteoclast), CNS (microglia) and synovium (type A lining cell)
iii. Monocytes - macrophages mediate effector functions such as destruction of antibody coated bacteria,
tumor cells, or even normal hematopietic cells in certain types of antoimmune cytopenias.
b. B-cells 
i. Mediate humoral immunity
ii. B-cells differentiate into plasma cells and memory B cells. Plasma cells secretes
immunoglobulin
c. Basophils  release histamine

25. Ans. C. Thromboxane A2

Thromboxane A2 is an important mediator of platelet secretion and aggregation. Q

26. Ans. A. Erythropoietin

When the hemoglobin level falls below 9 gm%, erythropoietin levels increase thus stimulating the erythroid
marrow to proliferate and increase red blood cell production several times.

27. Ans. C. Thymus

THYMOPOIETIN is a protein which is produced by the THYMUS and it stimulates differentiation of thymocytes

28. Ans. C. Platelets

ThromboxaneA2 is synthesized in PLATELETS and other cells from a prostaglandin, PGH2. It acts to aggregate
platelets and is a potent vasoconstrictor.

29. Ans. C. Decreased tissue pO2 concentration

Levels of ERYTHROPOIETIN are raised by hypoxia, and its production is regulated by the balance between tissue
oxygen supply and demand.

30. Ans. B. Factors X, V and Ca++

The following factors are required to convert prothrombin into thrombin Q
a. Activated factor X b. Factor V c.Ca++ d. Platelet phospholipids

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 Blood

31. Ans. B. VI
Synthesized in liver Q Vitamin K-responsive
• Factor I (Fibrinogen) • Factor II Q
• Factor II (Prothrombin) • Factor VII Q
• Factor V • Factor IX Q
• Factor VII • Factor X Q
• Factor VIII
• Factor IX

Chapter - 10
• Factor X
• Factor XII
• Factor XIII Mnemonic
2 + 7 = 9 and 10

32. Ans. A. VI

33. Ans. C. O Negative RBC and colloids/crystalloid

a. Dangerous hemolytic transfusion reactions occur when blood is transfused into an individual with an
incompatible blood type (an individual who has agglutinins against the ABCs in the transfusion).
b. The plasma in the transfusion is so diluted in the recipient that it rarely causes agglutination even when
the titer of agglutinins against the recipient’s RBCs is high.
c. However, when the recipient’s plasma has agglutinins against the donor s RBCs the cells agglutinate and
hemolyze liberating free hemoglobin into the plasma.

Blood
d. The seventy of transfusion reaction varies from an asymptomatic rise in plasma bilirubin to severe
jaundice and renal tubular damage, with an anuria and death Type 0 individuals are ‘universal-donors’
because there are no regular anti-C agglutinins, and type O blood can be given to anyone without
producing a transfusion reaction due to ABO incompatibility. Q
e. This does not mean however that blood should ever be transfused without being cross-matched except in
the most extreme emergencies since the possibility of reactions or sensitization due to incompatibilities
other than ABC incompatibilities always exists.

34. Ans. B. High Extracellular KT

Blood storage And Transfusion:
a. In bank blood that is stored, the 2,3-DPG level falls and the ability of this blood to release O2 to the tissue is
reduced.
b. Cellular metabolism, membrane ion pump failure and Hemolysis during blood storage  leads to  Hyper
kalemia and Acidaemia with rapid blood transfusion
c. At 4°C (in stored blood), the survival of platelets is considerably reduced and few are functionally useful after
24 hours Q
d. Clotting factors VIII and V are liable and their level fall quickly in stored blood
e. Each unit contain - 450 ml of blood and 60ml CPD solution (citrate - phosphate - dextrose)
f. One unit of whole blood will raise the Hb% by Igm/dL
g. CPD blood has shelf-life of 3 weeks while - CPD-A (Adenosine) has 1 -5 weeks.
h. Blood transfusion in anaesthetized pts especially in children, are vulnerable to hypothermia
i. Blood filters remove micro-aggregates of more than 20m diameter during transfusion. The ordinary infusion

531
 Physiology

set-filter pore size is about 170m,

j. Definition of the massive blood transfusion:
i. 5 units blood in 1 hours in 70kg adult.
ii. or, total blood volume replacement by stored blood in under 24 hours.
k. Acid-citrate dextrose (ACD) blood stored for 21 days while CPD blood can be usefully stored for 35 days Q

35. Ans. D. ABO (H) antibodies are invariably present in plasma when persons RBC lacks the corresponding
antigen.
a. The basic difference between ABO blood group system and other blood group systems (such as Rh, Kell,
Duffy, MNSs blood groups), which makes the ABO group so important is that.
i. preformed ABO antibodies are present in persons plasma when his RBCs lack the corresponding
antigen (ie. Anti. B antibody would be present in a person of type A and type O blood groups. These
two blood groups do not have the 'B' antigen on the RBCs).
ii. This is not the case with other blood groups. Preformed antibodies are not present. They are formed
only after an exposure to the antigen, for example Rh negative person do not have anti. Rh
antibodies, these antibodies are formed only after an exposure to Rh positive blood (by a blood
transfusion, i.e. this makes the first blood transfusion safe even if mismatched).
b. These preformed antibodies, rapidly destroy the RBCs of any mismatched blood transfusion.
c. Read the following lines from the journal of hematology
"In clinical transfusion practice, the ABO blood groups are the most important and can never be ignored in
red cell transfusion, because individuals who genetically lack any antigen, have antibodies against the red
cell types that they have not inherited. These antibodies can destroy red cells rapidly in circulation".
But the question arises - why are these agglutinins (antibodies against AB antigen) produced in people
who do not have the respective agglutinogens (A or B antigens) on their RBCs?
d. The answers is that Small amounts of group A and B antigen enter the body in food, in bacteria, and in
other ways, and these substances initiate the development of the anti-A and anti-B agglutinins.

36. Ans. A,B They divide to form different cell lines, They are used in gene therapy
Stem cells: "Ideal target for gene therapy approach"
a. Stem cell replacement involves the administration of pluripotent renewable cells to organs irreversibly
damaged by disease. The disciplines of gene and cell therapy are now converging, offering unique
opportunity to translate new knowledge of genetics and stem cell biology into the clinical setting.
b. The use of stem cell therapy addresses several of the shortcoming of gene therapy, including the need to
express genes in specific types of host cells, such as erythrocytes or neurons, and the need to regulate
gene expression in response to physiological signals.
c. Characteristics of Stem cells
i. Stem cells are the undifferentiated progenitors that can develop into highly specialized cells that
form the various organs.
ii. Stem cells vary in their replicative capacity and in their differentiation potential.
iii. Stem cells are self-renewing while at the same time generating daughter cells that are more
differentiated.
iv. The expression of telomerase, an enzyme critical for maintaining the telomeres, is consistent with
the self-renewing feature of stem cells.

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 Blood

4. Classification of stem cells

a. Totipotent stem cells:
i. Can form a placenta and can develop into a complete embryo
ii. e.g. the cells derived from the first few division of the fertilized oocyte
b. Pluripotent stem cells
i. capable of forming tissues derived from all three major germline layers endoderm, mesoderm,
and ectoderm. i.e. contribute to all tissues
ii. ego cells derived from the inner cell mass of the blastocyst (= Embryonic stem cells).

Chapter - 10
c. Multipotent stem cells:
i. are the progenitors of cells in particular tissues
ii. give rise to multiple cell types characteristic of a particular tissue
iii. Tissues such as BM, skin, GIT, and Liver have tremendous regenerative potential and continuously
renew their cell population.
[The term oval cell is often used to refer to stem cells in the liver, but other pluripotent cells also appear capable
of liver regeneration]

37. Ans. D. Bone marrow

a. When the RBCs have lived out their life span (average 120 days) and have become too fragile to exist
longer in the circulation, their cell membrane ruptures and the released hemoglobin is phagocytized by
tissue macrophages (also known as the reticuloendothelial system) throughout the body.
b. Here, the hemoglobin is first split into globin and heme, and the heme ring is opened to give free iron that
is transported in the blood by transferrin and a straight chain of four pyrrole nuclei that is the substrate

Blood
from which bilirubin is formed
c. The combination of monocytes, mobile macrophages, fixed tissue macrophages, and a few specialized
endothelial cells in the bone marrow, spleen, and lymph nodes is also called the reticuloendothelial
system.

38. Ans. A. Factor VII (REF: Ganong, 23rd ed-Page521 )

Vitamin K is involved in the carboxylation of certain glutamate residues in proteins to form gamma-
carboxyglutamate residues (abbreviated Gla-residues). It play key roles in the regulation of three physiological
processes:
a. Blood coagulation: (prothrombin (factor II), factors VII, IX, X, protein C, protein S, and protein Z
b. Bone metabolism: osteocalcin, also called bone Gla-protein (BGP), and matrix gla protein (MGP).
c. Vascular functions.

39. Ans. A. 3rd week (Ref: Hematology of the newborn, Williams Hematology)
a. Human hematopoiesis is initiated in the yolk sac during the third week of development.
b. The liver serves as the primary source of red cells from the 9th to the 24th weeks of gestation.
c. Hematopoietic cells are first seen in the marrow of the 10- to 11- week embryo, and they remain confined
to the diaphyseal regions of long bones until 15 weeks gestation.Initially there are approximately equal
numbers of myeloid and erythroid cells in the fetal marrow.
d. However, myeloid cells predominate by 12 weeks gestation, and the myeloid to erythroid ratio approaches
the adult level of 3 to 1 by 21 weeks gestation.

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 Physiology

e. Macrophage cells in the fetal marrow, but not in the fetal liver, express the lipopolysaccharide receptor
CD14.The marrow becomes the major site of hematopoiesis after the 24th week of gestation.

40. Ans. C. IL-5 (Ref: Ganong’s-23rd Edition, Pg66)

The factors stimulating the production of committed stem cells include granulocyte–macrophage CSF (GM-CSF),
granulocyte CSF (G-CSF), and macrophage CSF (M-CSF). Interleukins IL-1 and IL-6 followed by IL-3 (Table 3–1) act in
sequence to convert pluripotential uncommitted stem cells to committed progenitor cells. IL-3 is also known as
multi-CSF.

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 Blood

Chapter - 10
41. Ans. B basophils

Blood
a. Proteoglycan 2 also called (natural killer cell activator, eosinophil granule major basic protein).
b. PRG2 is a 117-residue protein that predominates in eosinophil granules.
c. It is a potent enzyme against helminths and is toxic towards bacteria and mammalian cells in vitro.
d. The eosinophil major basic protein also causes the release of histamine from mast cells and basophils,
activates neutrophils and alveolar macrophages, and is directly implicated in epithelial cell damage,
exfoliation and bronchospasm in asthma.
e. eosinophils degranulate to release an array of cytotoxic granule cationic like:
i. Major basic protein (MBP)
ii. Eosinophil cationic protein (ECP)
iii. Eosinophil peroxidase (EPO)
iv. Eosinophil-derived neurotoxin (EDN)

42. Ans. ‘A’. alpha granules of platelets

Note : PDGF is also produced by macrophages and endothelial cells

43. The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 689
 Umbilical cord blood, derived from the circulating blood of newborn infants, possesses high levels of hematopoietic
progenitors.
 Levels of circulating progenitors rapidly decrease after birth, depleting the progenitor content within the circulating
blood of adults.
 The spleen of adult humans functions as a hematopoietic organ in certain disease states, such as leukemia.

535
 Physiology

 However, in other animals and in developing human fetuses, the spleen plays an important role in the hematopoietic
response.
 While the liver and the thymus are important in hematopoiesis and immune reconstitution prior to birth, these
organs are not involved in hematopoiesis in adult humans.

44.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 100
 When specifically programmed T cells or B cells of the adaptive immune system first recognize specific antigens, they
begin to divide rapidly, generating several copies of cells similarly programmed against the inciting stimulus.
 Hematopoiesis involves the nonspecific generation of all cells in blood, including leukocytes, erythrocytes, and
platelets.
 Hematotherapy is a therapeutic process in which specifically amplified cells are infused in patients to increase
resistance to infection or to restore hematopoiesis.
 Inflammation is not a specific response against individual antigenic determinants and does not require T cell or B cell
amplification.
 Similarly, innate immunity does not require amplification of T cells or B cells as a result of interaction with an
invading stimulus but is affected by cells present and programmed to respond to specific stimuli.

45.The answer is B. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 102
 Delayed-type hypersensitivity reactions to PPD and other specific antigens develop slowly over 24 to 48 hours as T
cells become activated and secrete factors that effect the skin response.
 B cells play no role in this type of reaction; instead, they produce antibodies involved in more immediate responses.
 Neutrophils do not arrive at sites of delayed type hypersensitivity in large numbers.
 Eosinophils play a role in immediate hypersensitivity to many antigens that cause symptoms of allergy, such as
sneezing and stuffy nose, but do not participate in the delayed response.
 Finally, the response to PPD is driven by cells programmed to respond specifically to this antigen derived from the
bacteria that cause tuberculosis, and not by a metabolite of this protein.

46.The answer is C. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 104
 Antibody specificity is dictated by the sequence of amino acids within the variable regions of the light and heavy
chains.
 The Fc region is a site for antibody docking to effector cells and does not play a role in antigen binding.
 The constant region has a similar structure in antibodies of widely divergent specificity and, therefore, does not
dictate specificity.
 Fc receptors are sites on immune effector cells that interact with the Fc region of the antibody molecule and do not
define an antibody’s specificity.
 The J chain is a unique portion of secreted IgA molecules that allows the molecule to move from the circulation
through mucous membranes.

47.The answer is D. Ref: Ganong - Review of Medical Physiology 23rd Ed Page 706
 The extrinsic coagulation pathway is activated when tissue thromboplastin (tissue factor) is released from injured
tissues.
 Activation of factor X occurs later and is a step involved in the activation of both the intrinsic and the extrinsic
pathways.
 Activation of factor XII is the first step in activation of the intrinsic coagulation pathway.
 Conversion of prothrombin to thrombin and conversion of fibrinogen to fibrin are the final steps that lead to clot
formation by either the intrinsic or the extrinsic pathway.

48.The answer is D.
Ref: Ganong - Review of Medical Physiology 23rd Ed Page 478
 Superoxide anion is generated when oxygen is reduced by cytoplasmic NADPH.

536
 Blood

 The reduction is carried out by the enzyme NADPH oxidase, which is not a reactant but a catalyst activated in cells
responding to bacteria.
 The hexose monophosphate shunt is an enzyme cascade (not a reactant) that functions to provide high levels of
reduced NADPH to drive this reaction.
 G proteins are not reactants, but play an essential role in the activation of this cellular cascade.
Similarly, the enzyme myeloperoxidase is not a reactant; it enhances the ability of reactants, such as hydrogen
peroxide, to exert a lethal effect on invading bacteria

Chapter - 10
49.The answer is A.
Although all of the choices are events that happen in lymph vessels, the first key event is lowering the lymphatic
hydrostatic pressure to enable tissue fluid to enter the lymphatic vessel.

The answer is D.

In a normal resting condition, the blood leaving the lungs is 98% saturated with oxygen, and the blood
returning to the lungs is 75% saturated with oxygen. With vigorous exercise, blood leaving the lungs is still
98% saturated, but blood returning is

usually less than 75% saturated because more oxygen is unloaded from hemoglobin in exercising
muscles

Blood

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