PATHOLOGY

Dr. Priyanka Sachdev , MD

 Cell Adaptations

Adaptations →

❑Are reversible

❑Structural responses to physiologic stress (e.g., pregnancy) and

pathologic stress

❑During which new but altered steady states are achieved

❑Allowing the cell to survive and continue to function

 Stress
(Physiological or Pathological)

Cellular adaptation

Cell injury

Reversible Cell injury

“Point of no return “ ------------------

Irreversible Cell injury

 5 Types Of Adaptations

1. Hyperplasia → Increase in number of cells

2. Hypertrophy→ Increase in the size of cells

3. Atrophy → Decrease in the size of cells / shrinkage of cells

4. Metaplasia→ Transformation of one adult cell type with another

5. Dysplasia → ‘Disordered cellular development’

 Hyperplasia

• Increase in the number of cells , not size of cell, resulting in enlargement of

the organ or tissue.
 Physiologic hyperplasia
1. Hyperplasia of female breast at
puberty, pregnancy and lactation

2. Enlarged size of the uterus in

pregnancy → example of
physiologic hypertrophy as well as
hyperplasia.

3. Compensatory hyperplasia →
• Following nephrectomy on one side,
there is hyperplasia of nephrons of
the other kidney
 Pathologic hyperplasia

1. Endometrial hyperplasia following oestrogen

excess

2. Benign prostatic hyperplasia due to DHT

(dihydrotestosterone)

3. Formation of skin warts from hyperplasia of

epidermis due to HPV
 Hypertrophy

• Increase in the size of cells, not number of cells, leading to an

increase in the size of the organ
 Physiologic hypertrophy
1. Enlarged size of the uterus in
pregnancy is an example of
physiologic hypertrophy as well
as hyperplasia.

2. Hypertrophy of skeletal muscle

e.g. hypertrophied muscles in
athletes and manual labourers.
 Pathologic hypertrophy
1. Hypertrophy of cardiac muscle
occurs in Systemic
hypertension, Aortic valve
disease

2. Hypertrophy of smooth muscle

e.g. Cardiac achalasia (in
oesophagus), Pyloric stenosis (in
stomach).
 Atrophy
• Decrease in cell size and number of cells (with or without accompanying
shrinkage of the organ or tissue)

• Atrophied cells are smaller than normal but they are still viable – they do
not necessarily undergo apoptosis or necrosis
 Physiologic atrophy
1. Atrophy of thymus in adult life.

2. Atrophy of ovary after menopause.

3. Atrophy of brain with ageing.

4. Decrease in the size of the uterus that

occurs shortly after parturition
 Uterus

Hypertrophy Atrophy
Hyperplasia

Normal Pregnancy Parturition

 Pathologic atrophy
1. Starvation atrophy → general weakness, emaciation and
anaemia known as cachexia seen in cancer and severely ill
patients.

2. Ischaemic atrophy → atrophic kidney in atherosclerosis of

renal artery, Atrophy of the brain in cerebral
atherosclerosis.

3. Neuropathic atrophy → e.g. Poliomyelitis

4. Disuse atrophy → e.g. Wasting of muscles of limb

immobilised in cast, Atrophy of the pancreas in obstruction
of pancreatic duct.
5. Endocrine atrophy → eg.
Hypopituitarism may lead to atrophy of
thyroid, adrenal and gonads

6. Pressure atrophy → eg. Erosion of

the skull by meningioma , Erosion of the
sternum by aneurysm of arch of aorta

7. Idiopathic atrophy → where no

obvious cause is present
 Metaplasia
• A reversible change in which one mature/adult cell type is replaced by
another mature/adult cell type
 Squamous metaplasia Examples

1. In bronchus (normally lined by pseudostratified columnar ciliated

epithelium) in chronic smokers.

2. In gallbladder (normally lined by simple columnar epithelium) in

cholelithiasis.

3. In prostate (normally lined by simple columnar epithelium) in chronic

prostatitis

4. In uterine endocervix (normally lined by simple columnar epithelium) in

prolapse of the uterus
Smoke

Calcalus

Uterus
Prolapse

Inflammation
 Columnar metaplasia Examples

1. Barrett’s oesophagus → change of normal squamous epithelium to

columnar epithelium due to GERD

2. Cervical erosion → Ectocervix - change of normal squamous epithelium to

columnar epithelium due to increased exposure of the cervical epithelium
to estrogen
 GERD

Hcl Hcl

Normal Barrett’s Oesophagus

 Cervix

Ulterus
Prolapse

Cervical
erosion
(due to
estrogen
exposure
 Dysplasia
• Disordered cellular development
• Characterised by cellular cytologic changes

• Cytological changes →
1. Increased number of layers
2. Disorderly arrangement of cells from basal layer to surface layer
3. Loss of basal polarity i.e. nuclei lying away from basement
membrane
4. Cellular and nuclear pleomorphism
5. Increased nucleocytoplasmic (N/C) ratio
6. Nuclear hyperchromatism
7. Increased mitotic activity
‒ No. of layers normal ‒ No. of layers
‒ Ordered arrangement ‒ Disordered arrangement
‒ Basal Polarity + ‒ Basal Polarity –
‒ Pleomorphism – ‒ Pleomorphism +
𝐍 𝐍
‒ 𝐍𝐨𝐫𝐦𝐚𝐥 ‒
𝐂 𝐂
‒ Hyper chromatism – ‒ Hyper chromatism +
‒ Mitosis normal ‒ Mitosis
• Full thickness dysplasia is known as carcinoma in situ (Precurssor of
cancer)
 Cell Death

• Apoptosis → Suicide

• Necrosis → Murder
 Apoptosis

Cell Suicide

• It is a pathway of cell death that is induced by a tightly regulated

intracellular program in which cells destined to die activate enzymes
(caspase) degrade the cells own nuclear DNA and cytoplasmic proteins.

• The cell is phagoctosed

• There is no leakage outside
• So there is no inflammation
 Mechanism

Extrinsic pathway Intrinsic pathway

Initiation Execution Initiation Execution

 Extrinsic pathway → Initiation phase

• It is initiated through specific receptors called death receptors

1. Fas protein (CD95)

2. TNF receptors
Death receptors
(FAS | CD 95 receptor)
Death receptors
(FAS | CD 95 receptor)
FAS (CD- 95)
 Fas receptor (Death receptor)

Fas protein (CD95) binds with it

Multiple Fas receptors come together

Cytoplasmic death domain FADD formed

Activate pro- caspsase 8 and 10 to active caspase 8 and 10

 Intrinsic pathway → Initiation phase

Stimuli→ DNA damage (beyod repair)

 Cyt. c

DNA
 Cyt. c

DNA
Damage
 Cyt. c

DNA
Damage
 Cyt. 6

DNA
Damage
 Cyt. 6

DNA Active
Damage Caspase 9
 Stimuli (DNA damage)

Anti apoptotic molecules Bcl-2 , Bcl-x ,Mcl -1 are lost

Replaced by pro-apoptotic molecules like Bak, Bax, Bim, Bad

Increased mitochondrial permeability (MPT)

Release to cytochrome C into cytoplasm

Activates Apaf-1 along with procaspase-9

Activated caspase-9
 Execution phase
• It is a convergence point for both extrinsic and intrinsic pathways.
 Activates
CASPASE

Apoptotic bodies
Phagocyte
Morophological changes in apoptosis
 Diagnosis Of Apoptosis
1. Apoptosis markers → Annexin-V is a
recombinant protein with high affinity
for phospholipid like
phosphatidylserine.

2. Agarose gel electrophoresis →

Fragmented DNA shows Step Ladder
Pattern,which is due to internucleosomal
cleavage of DNA by endonuclease
 Apoptosis (Suicide) Necrosis (Murder)

• Single cells or small clusters of cells • Often contiguous cells

• Cell shrinkage • Cell swelling

• Pyknosis and karyorrhexis • Karyolysis, pyknosis,and karyorrhexis

• Intact cell membrane • Disrupted cell membrane

• Cytoplasm retained in apoptotic bodies • Cytoplasm leaked

• Inflammation absent • Inflammation present

 Cell Death

• Apoptosis → Suicide

• Necrosis → Murder
 Necrosis
• Necrosis is death of cells and tissues in the living animal

• Necrosis is defined as a localised area of death of tissue followed later by

degradation of tissue by hydrolytic enzymes liberated from dead cells

• It is invariably accompanied by inflamatory reaction

 Coagulative Liquifactive Casseous Fat Fibrinoid

Introduction

Causes

Gross

Microscopy
 Coagulative necrosis

• Most common type of necrosis

• Architectural outlines persist but

cellular and nuclear details are lost
(Ghost cells / Tombstone)

• Type of tissue can be recognized

 Causes:
1.Ischemia due to thrombosis/ embolism in all organs except brain
(Amongst solid organs brain is the only exception, i.e., it is the only solid
organ in which ischemia leads to liquefactive necrosis and not coagulative
necrosis)

2.Mild burns (thermal injury)

3.Zenker's degeneration necrosis

 Grossly
• Focus in the early stage is pale, firm, and slightly swollen
 Microscopically

Hallmark of coagulative
necrosis is the conversion of
normal cells into their ‘tomb
stones’ i.e. outlines of the
cells are retained and the
cell type can still be
recognised but their
cytoplasmic and nuclear
details are lost
 Liquefactive (Colliquative) necrosis

• Hydrolytic enzymes in tissue

degradation have a dominant role in
causing semi-fluid material

• Their architectural details as well as

cytoplasmic and nuclear details are
lost
 Causes:

1. Pyogenic bacterial infections attract neutrophils. Bacterial and

leukocytic enzymes liquefy dead cells and tissues.

2. Ischemic necrosis of brain

 Gross appearance

• Affected area is soft with liquefied centre containing necrotic debris with
a cyst wall
 Microscopic appearance:

1. The necrotic area usually appears as

a cavity containing a mass of necrotic
neutrophils, bacteria and tissue
debris

2. The entire necrotic mass is

surrounded by a cyst wall formed by
proliferating capillaries and
inflammatory cells
 Caseous necrosis (cheese like)
• Dead tissue is converted into a
homogenous, granular mass
resembling cottage cheese.

• Their architectural details as well as

cytoplasmic and nuclear details are
lost

• Accumulation of amorphous (no

structure) debris within an area of
necrosis
 Cause:

• Mycobacterium tuberculosis
• Syphilis
• Histoplasma
• Coccidioimycosis
 Gross appearance
• Foci of caseous necrosis resemble dry cheese and are soft, granular and
yellowish.
 Microscopically

• Centre contain structureless,

eosinophilic material having
scattered granular debris of
disintegrated nuclei

• The surrounding tissue shows

granulomatous inflammatory
reaction consisting of epithelioid
, giant cells of Langhans’ and
foreign body type and peripheral
mantle of lymphocytes
 Fat necrosis

• Fat necrosis is a special form of cell death occurring at mainly fat-rich

anatomic locations in the body.

• Death of adipose tissue in a living animal

Causes
1. Pancreatic (acute pacreatitis)
2. Breast (Traumatic)
3. Mesentry (Inflammmation)
 Grossly
• Fat necrosis appears as yellowish-white and firm deposits.

• Formation of calcium soaps imparts the necrosed foci firmer and chalky
white appearance
 Microscopically

1. The necrosed fat cells have

cloudy appearance

2. They are surrounded by an

inflammatory reaction.
 Fibrinoid Necrosis

• Fibrinoid necrosis is characterized by

deposition of fibrin-like material which has
the staining properties of fibrin

• Causes → Immunologic injury of vessel wall

(e.g. in immune complex vasculitis,
autoimmune diseases, Arthus reaction etc),
arterioles in hypertension, peptic ulcer etc.
 Microscopically

• Fibrinoid necrosis is identified by

brightly eosinophilic, hyaline-like
deposition in the vessel wall.

• Necrotic focus is surrounded by

nuclear debris of neutrophils
(leucocytoclasis)

• Local haemorrhage may occur due to

rupture of the blood vessel.
 Coagulative Liquifactive Casseous Fat Fibrinoid

- Arch + - Arch - - Arch -

Blood
Introduction - Cyto - - Cyto - gel - Cyto - debries Fat rich locations
vessels
- Nucleus - - Nucleus - - Nucleus -

- Ischemia of - TB - Breast trauma

- Ischemia Brain
all organs - Syphilis - Pancreatitis
Causes - Pyogenic - Vasculitis
(Except - Histoplasma - Mesentry
infection
Brain) - Coccidiomycosis inflammation

- Liq. Centre - Yellowish

Gross - Pale - Dry cheese like -
with Cyst Wall white

Structureless
Tomb- stone Cavity Cont. material with Cloudy Fibrinoid
Microscopy
appearance debries granulomatous appearance (ribbon) like
inflammation
 Gangrene

• Gangrene is necrosis of tissue associated with superadded putrefaction

GANGRENE = Necrosis + Putrefaction

 Types

1.Dry” gangrene → less bacterial superinfection; tissue appears dry

2. “Wet” gangrene → abundant bacterial superinfection; tissue looks wet

and liquefactive

3. A variant of wet gangrene called gas gangrene.

 Feature Dry Gangrene Wet Gangrene

1. Site Commonly limbs Commonly in bowel

2. Mechanisms Arterial occlusion Blockage of both venous drainage

and arterial obstruction
3. Macroscopy Organ dry, shrunken and black Part moist , soft, swollen, rotten and
dark
4. Putrefaction Limited due to very little blood Marked due to stuffing of organ with
supply blood
5. Line of demarcation Present Absent
6. Bacteria Bacteria fail to survive Numerous present
7. Prognosis Better due to little septicaemia Poor due to profound toxaemia

8. Type of necrosis Variant of Coagulative necrosis Liquifactive necrosis is superimposed

on coagulative necrosis
 Gas Gangrene
• Special form of wet gangrene caused by gas-forming clostridia (gram-positive
anaerobic bacteria)

• Swollen, oedematous, painful and crepitant due to accumulation of gas

bubbles of carbon dioxide within the tissues formed by fermentation of
sugars by bacterial toxins
 Pathological Calcification

• Deposition of calcium salts in tissues other than osteoid or enamel is

called pathologic or heterotopic calcification
 Types
Calcium normal Hyper Calcemia
.. . . . . . …………………..

Dead
And Normal
Degenerated tissue
tissue

Dystrophic Metastatic
 Dystrophic Calcification Metastatic Calcification
Calcium deposits in dead and dying tissues Calcium deposits in normal tissues

Normal calcium metabolism Deranged calcium metabolism

Normal serum calcium levels Hypercalcemia

Irreversible Reversible upon correction of metabolic

disorder

Occurs due to increased binding of Increased precipitates of

phosphates with necrotic and degenerative calciumphosphate due to hypercalcemia at
tissue — binds to calcium forming calcium certain sites (lungs, stomach, blood
phosphate precipitates vessels, cornea)
 Sites of dystrophic calcification:
Dead tissues

• Caseation eg. Tuberculosis

• Dead parasites like trichinosis,
Onchocercosis.
• Fat necrosis
• Infarcts
• Thrombi
• Haematoma
Sites of metastatic calcification:
 Special stain for calcification

1. Von Kossa gives a black color

2. Alizarin red S that produces red staining

 1. Dystrophic calcification means-

a) Calcification in destroyed tissue with normal calcium level in blood

b) ↑ level of Ca++ deposits

c) Calcification in normal tissue seen in hyperparathyroidism

d) Calcification in destroyed tissues with hypercalcemia

 General Pathology
1. Cell adaptations,Cell injury, Cell death

2. Inflammation

3. Wound healing and repair

4. Hemodynamics

5. Neoplasia

6. Immunopathology

7. Genetics
 Inflammation

• It is a body defense reaction in order to eliminate or limit the spread of

injurious agent, followed by removal of the necrosed cells and repair of
damaged tissue

• White blood cells or leukocytes are the body’s major infection-fighting cells.
 Classification
Acute Chronic
Rapid onset Late onset
Short duration Longer duration
Odema Granuloma formation
Neutrophils Macrophage, lymphocyte
 Cardinal Signs

Latin English

Rubor : redness
Calor : ↑ed local temperature Celsus
Tumor : swelling
Dolor : pain
Functio laesa: loss of function → Virchow
 Acute inflammation

Vascular events Cellular reaction

 Vascular Events Cellular Events

1.Transient vasoconstriction of arterioles 1. Margination and pavementing

2. Rolling
2.Persistent progressive vasodilatation
3. Adhesion
3.Elevate the local hydrostatic pressure
4. Transmigration (diapedes)
4.Increased vascular permeability
5. Chemotaxis
5.Slowing or stasis 6. Phagocytosis
 1.Transient vasoconstriction of arterioles
• Responsible for blanching seen immediately after injury.

• With mild injury→ 3-5 seconds

• severe injury→ 5 minutes
 2. Persistent progressive vasodilatation
• Vasodilatation results in increased blood volume→ redness(rubor) and
warmth (calor) at the site of acute inflammation.
3. Elevate the local hydrostatic pressure
Starling’s hypothesis
• Transudation of fluid into the extracellular space (Oedema→
Transudate ) → Tumor
 4. Increased vascular permeability

• Hallmark of acute inflammation

• Leads to escape of protein rich fluid (Oedema → Exudate) → swelling
(tumor)
• Most affected vessels are venules
 Remember
• In the initial stage, the escape of fluid is due to Elevation in hydrostatic
pressure.
• This is transudate in nature.

• But subsequently, the escape of fluid is due increased vascular

permeability of Microvasculature
• This is exudate in nature.
Altered Vascular Permeability mechanisms

1. Formation of endothelial gaps

2. Direct endothelial injury

3. Leukocyte mediated endothelial cell injury

4. Increased transcytosis

5. Leakage from new blood vessels

 Mechanism Vasculature Response Pathogenesis

1. Endothelial gaps

2. Direct endothelial injury

3. Leukocyte mediated injury

4. Transcytosis

5. Leaky new blood vessels

 5. Slowing or stasis

• Increased concentration of red cells → raised blood viscosity

 Acute inflammation

Vascular events Cellular reaction

 Cellular Events
1. Margination and pavementing
2. Rolling
3. Adhesion
4. Transmigration (diapedes)
5. Chemotaxis
6. Phagocytosis
 Margination
• The normal axial flow consists of central stream of cells comprised by
leucocytes and RBCs and peripheral cell-free layer of plasma close to vessel
wall.
• WBCs leave the centre and comes at periphery of blood vessel→ Reversal of
axial blood flow
 Rolling
• Peripherally marginated and pavemented neutrophils slowly roll over the
endothelial cells lining the vessel wall due to transient bonds between
them → Rolling
 Adhesion
• Bond between the leucocytes and endothelial cells becoming firmer →
Adhesion
 Complementary adhesion molecules (CAM)
Endothelial Molecule Leukocyte Molecule Major Role

1. P-selectin Sialyl-Lewis X Rolling

2. E-selectin Sialyl-Lewis X Rolling and adhesion

3. GlyCam-1 (CD34) L-selectin Rolling

4. ICAM-1 B2 integrins Adhesion

5. VCAM-1 B1 integrins Adhesion

6. PECAM-1 (CD-31) PECAM-1 (CD-31) Diapedesis

(trasmigration)
 Transmigration (diapedes)
• Escape out into the extravascular space; this is known as transmigration
• Passive phenomenon
• PECAM
 Chemotaxis
• Unidirectional oriented along a chemical gradient

Potent chemotactic substance →

1) LT-B4
2) C3a
3) C5a → most powerful
4) Interleukins (IL-8)
 Phagocytosis
Engulfment of microbes by the WBC’s (cell-eating)

• Cells performing this function are called phagocytes

 Phagocytsis

This sequence was appreciated by Metchnikoff (1880)

1.Recognition and Attachement

2.Engulfment

3.Killing and degradation→ 3 steps

a) MPO-dependent
b) MPO-independent
Chronic Inflammation / Granulomatous Inflammation

• Chronic inflammation is a response of prolonged duration (weeks or

months) in which inflammation, tissue injury and attempts at repair
(fibrosis) coexist, in varying combinations.

1. Inflammation (Mononuclear infiltrate)

2. Tissue injury
3. Attempts at repair (Fibrosis)
 Pathogenesis Of Granuloma
• Formation of granuloma is a type IV hypersensitivity reaction

3 Steps →

1. Engulfment by macrophages

2.Activation of CD4+ T cells

3. Release of Cytokines
 1. Engulfment by macrophages

Macrophages engulf the antigen

Try to destroy it

But antigen is poorly degradable

These cells fail to digest and degrade the antigen

 2.Activation of CD4+ T cells

Macrophages failed to deal with the antigen

Present antigen to CD4+ T lymphocytes

CD4+ T lymphocyte activated

Release lymphokines

IL-1, IL-2, interferon-Y, TNF-α

 3. Release of Cytokines

Interferon-γ activates macrophages and transform it into epitheloid cells

IL-1 and IL-2 stimulate proliferation of more T cells.

TNF-α promotes fibroblast proliferation

 Types of Giant cells
1. Foreign body giant cells
2. Langhans’ giant cells
3. Trouton giant cells
4. Giant cells in tumours
Foreign body giant cells
• These nuclei are scattered throughout the cytoplasm.
• Eg. chronic infective granulomas, leprosy and tuberculosis

Langhans’ giant cells

• Nuclei are arranged either around the periphery in the form of
horseshoe or ring, or are clustered at the two poles of the giant cell.
• Eg. tuberculosis and sarcoidosis.

Touton giant cells

• These multinucleated cells have vacuolated cytoplasm due to lipid
content
• e.g. Xanthoma
Naked Granulomas → not have surrounding rim of
mononuclear cells
• composed of epithelioid histiocytes and multinucleated giant
cells
• e.g. sarcoidosis

Stellate granuloma → Star shaped Granuloma

• Granuloma with central neutrophilic infiltrates.
Examples
• Cat scratch disease
• LGV (lymphogranuloma venereum)

Durck's granuloma→ Seen in cerebral malarial caused by

Plasmodium falciparum.
▪ Blood vessels packed with rings of P. falciparum.
 Examples Of Granulomatous Inflammation

BACTERIAL
1) Tuberculosis Mycobacterium tuberculosis
2) Leprosy Mycobacterium leprae
3) Syphilis Treponema pallidum
4) Granuloma inguinale (Donovanosis) C. donovani
5) Brucellosis (Mediterranean fever) Brucella abortus
6) Cat scratch disease Coccobacillus
7) Tularaemia Francisella tularensis
8) Glanders Actinobacillus mallei
FUNGAL
1. Actinomycosis Actinomycetes israelii
2. Blastomycosis Blastomyces demtitidis
3. Cryptococcosis Cryptococcus neoformans
4. Coccidioidomycosis Coccidioidesimmitis
PARASITIC
1. Schistosomiasis(Bilharziasis) Schistosoma mansoni,
haematobiumjaponicum
MISCELLANEOUS
1.Sarcoidosis Unknown
2.Crohn's disease Unknown
3. Silicosis Silica dust
4.Berylliosis Metallic beryllium
5.foreign body granulomas Talc, suture, oils, wood splinter etc
 General Pathology
1. Cell adaptations,Cell injury, Cell death

2. Inflammation

3. Wound healing and repair

4. Hemodynamics

5. Neoplasia

6. Immunopathology

7. Genetics
 Oedema

• Oedema is defined as abnormal and excessive accumulation of fluid in the

interstitial tissue space
 Effusion
• Effusions is defined as abnormal and excessive accumulation of fluid in body
cavities
Normal fluid exchange
At arterial end→
• Hydrostatic pressure (outward force) > osmotic pressure (inward force)
• Net Outward driving force = 38 - 25 = 13 mmHg
• Fluid comes out from capillary into the interstial space.

At venous end →
• Osmotic pressure (inward pressure) > hydrostatic pressure (outward
pressure)
• Net Inward-driving force = 25 -12 = 13 mmHg
• Fluid comes back in the capillary from interstitial space.
 Pathogenesis of edema

1. Increased capillary hydrostatic pressure

2. Decreased plasma oncotic pressure

3. Lymphatic obstruction

4. Sodium and water retention

5. Increased capillary permeability (Inflammation)

 1. Increased capillary Hydrostatic pressure
• i) Oedema of cardiac disease e.g. in
congestive cardiac failure, constrictive
pericarditis.

• ii) Postural oedema e.g. transient oedema

of feet and ankles due to increased
venous pressure seen in individuals
Whose job involves standing for long
hours such as traffic constables
 2. Decresed plasma oncotic pressure
• The plasma oncotic pressure is exerted by the total amount of plasma
proteins.

• Albumin has four times higher plasma oncotic pressure than globulin
• Thus it is hypoalbuminaemia that results in oedema.

• Edema takes place when →

• Total plasma protein is below 5 gm/dl (normal 6-8 gm/dl)
• Albumin is below 2.5 gm/dl (normal 3.5- 5gm/dl)
 Examples →

1.Inadequate synthesis of albumin →

severe liver diseases (end-stage
cirrhosis)

2.Protein malnutrition

3.Increased loss of albumin →

Nephrotic syndrome in which
albumin leaks into the urine through
abnormally permeable glomerular
capillaries.
 3. Lymphatic Obstruction

• Normally, the interstitial fluid in the tissue spaces escapes by way of

lymphatics.

• Obstruction to outflow of these channels→ oedema, known as

lymphoedema
 Examples →
1.Removal of axillary lymph nodes in
radical mastectomy for carcinoma of
the breast causing lymphoedema of
the affected arm.

2.Inflammation of the lymphatics as

seen in filariasis (elephantiasis)
results in lymphoedema of scrotum
and legs known as elephantiasis

3.Milroy’s disease or hereditary

lymphoedema is due to abnormal
development of lymphatic channels
 4. Sodium And Water Retention
• i) Oedema of cardiac disease e.g. in congestive cardiac failure.

• ii) Oedema of renal disease e.g. in nephrotic and nephritic syndrome.

 5. Increased capillary permeability

Capillary endothelium is injured

Gaps between the endothelial cells

Leakage of plasma proteins into interstitial fluid

Reduced plasma oncotic pressure and elevated

oncotic pressure of interstitial fluid

Oedema
 Examples

• i) Generalised oedema occurring in systemic

infections, poisonings, certain drugs and
chemicals, anaphylactic reactions and anoxia.

• ii) Localised oedema due to allergic reactions,

insect-bite, irritant drugs and chemicals.
 Causes and examples of oedema

Lymphatic
⬆️Hydrostatic ⬇️Plasma
obstruction Sodium retention Inflammation
pressure osmotic pressure
(Lymphedema)
• Acute and
• After breast
• Cardiac failure • Liver cirrhosis • Cardiac failure chronic
surgery
inflammation
• Postural
• Malnutrition • Filariasis • Renal failure
oedema

• Renal failure
• Milroy disease
(Nephrotic syn)
FEATURE TRANSUDATE EXUDATE

Definition Protein-poor , cell-poor fluid Protein-rich , cell-rich fluid

Character Non-inflammatory oedema Inflammatory oedema

Protein content Low (less than 1 gm/dl) High ( 2.5-3.5 gm/dl)

Glucose content Same as in plasma Low (less than 60 mg/di)
Specific gravity Low (less than 1.015) High (more than 1.018)
pH > 7.3 < 7.3
LDH Low High
Cells Few cells Many cells
Oedema in congestive
Examples Purulent exudate such as pus
cardiac failure
 Thrombosis

• Haemostasis occurs after injury to CVS and is

useful as it stop escape of blood and plasma,

• Thrombosis occurs in the unruptured CVS (without

injury) and has harmful effects of ischemia

• Thrombosis is the formation of a blood clot (solid

mass) in the unruptured CVS from the constituents
of flowing blood , obstructing the flow of blood
through the circulatory system
 Pathophysiology
• Virchow described three primary events which predispose to thrombus
formation (Virchow’s triad):

1. Endothelial injury

2. Altered blood flow (Stasis or turbulance)

3. Hypercoagulability of blood
 Types of Thrombi

3 Types depending on site of origin→

1.Cardiac thrombi (vegetations)

2.Arterial thrombi
3.Venous thrombi
 Grossly
• Arterial thrombus known as white thrombi as they contains more platelets
and relatively less fibrin

• Venous thrombi known as red thrombi as they contain more enmeshed red
cells and relatively few platelets.
 Feature Arterial thrombus Venous thrombus
Pathogenesis Endothelial injury or turbulence Stasis

Blood flow Active Sluggish

Sites Coronary, cerebral , femoral arteries Superficial and deep leg veins

Propagation Retrograde manner Antegrade manner

Lines of Zahn Present Absent

Pale platelet layer alternating with dark

RBC mixed with relatively less platelets,
Microscopic red cell layer so also called as white
so also called as red thrombi
thrombi
Occlusion Incomplete Complete

Complications lschemia and infarction Edema and ulceration

 Embolism
• An embolus is a detached intravascular solid, liquid, or gaseous mass that
is carried by the blood from its point of origin to a distant site, where it
often causes tissue dysfunction or infarction.

• The transported intravascular mass detached from its site of origin is

called an embolus
 Depending upon the matter in the emboli

• i) Solid e.g. detached thrombi

(thromboemboli), atheromatous
material, tumour cell
clumps,parasites, bacterial clumps,
foreign bodies.

• ii) Liquid e.g. fat globules, amniotic

fluid

• iii) Gaseous e.g. air

 Types

• These may arise in the→

➢Arterial circulation→ Arterial (systemic) thromboembolism

➢Venous circulation → Pulmonary Thromboembolism

 Effects of arterial emboli

• The effects of arterial emboli depend upon their size, site of lodgement,
and adequacy of collateral circulation

➢Infarction of the organ

➢ Gangrene in the lower limbs

➢Myocardial infarction may occur following coronary embolism.

➢ Sudden death may result from middle cerebral artery embolism

 Effect of venous embolism
• Obstruction of pulmonary arterial circulation leading to pulmonary
embolism
 Pulmonary Thromboembolism

Embolus in vein

Flows through venous drainage into the larger veins (SVC and IVC)

Right side of the heart (RA → RV)

Pulmonary artery

Pulmonary embolism
 Shock
Shock is the clinical syndrome that results from poor tissue perfusion

➢In this condition tissues in the body do not receive enough oxygen and
nutrients to allow the cells to function.

➢This ultimately leads to cellular death

➢ May progress to organ failure

➢ Finally, to whole body failure

➢ Death.
 Classification

1.Hypovolumic shock

2.Cardiogenic shock

3.Septic shock
 Hypovolumic Shock Cardiogenic Shock Septic Shock

Causes

Pathogenesis

Symptoms
 1. Hypovolaemic shock

• Most common form of shock

• Occurs due to decreased blood volume

Causes
1. Acute haemorrhage
2. Dehydration from vomiting's, diarrhoea
3. Burns
4. Excessive use of diuretics
5. Acute pancreatitis
 Symptoms

1. Increased heart rate (tachycardia)

2. Low blood pressure (hypotension)

3. Low urinary output (oliguria to anuria)

4. Alteration in mental state (agitated to confused to lethargic)

 3 stages→
i) Mild hypovolemia or stage I (< 20% volume loss): Only mild
tachycardia is there with normal BP.

ii) Moderate hypovolemia or stage II (20-40% volume loss):

Tachycardia with normal BP in supine position but hypotension in
erect posture.

iii) Severe hypovolemia or stage III (> 40% volume loss): Classical
signs of shock appear e.g. tachycardia, hypotension, disorientation
etc.
 2. Cardiogenic shock

• caused by inadequate pumping action of heart

• Cardiogenic shock occurs when 40% or more of the left ventricle is

destroyed.
 Causes
i. Deficient emptying e.g.
a) Myocardial infarction
b) Cardiomyopathies
c) Rupture of the heart, ventricle or
papillary muscle
d) cardiac arrhythmias

ii. Deficient filling e.g.

a) Cardiac tamponade from
haemopericardium

iii. Obstruction to the outflow e.g.

a) Pulmonary embolism
b) Ball valve thrombus
c) Tension pneumothorax
d) Dissecting aortic aneurysm
 Symptoms
• Decreased cardiac output has its
effects in the form of decreased
tissue perfusion (tissue hypoxia)

• Movement of fluid from pulmonary

vascular bed into pulmonary
interstitial space initially
(interstitial pulmonary oedema)
and later into alveolar spaces
(alveolar pulmonary oedema)
 3. Septic (Toxaemic) shock
• Severe bacterial infections or septicaemia induce septic shock

Causes→

i. Gram-negative septicaemia (endotoxic shock) e.g.

Infection with E.coli, Proteus, Klebsiella, Pseudomonas and
Bacteroides

ii. Gram-positive septicaemia (exotoxic shock) e.g.

Infection with streptococci, pneumococci
 Gram positive bacteria Gram positive bacteria

Lipopolysaccharide (LPS) Lipotheicoic acid

LPS binds to CD14 Lipotheicoic acid binds to ILR -2

Macrophages stimulated

Secrete proinflammatory cytokine ( TNF-α and IL-1)

Vasodilatation and increased vascular permeability

Inadequate perfusion of cells and tissues

Septic Shock
 Septic shock has two different stages

1) Early hyperdynamic stage

• It is characterized by vasodilatation (decreased peripheral resistance),
Tachycardia, normal to increased cardiac output, and warm extrimities.

2) Late hypodynamic stage

• It is characterized by vasoconstriction, decreased output, and oliguria
(renal failure).
 Hypovolumic Shock Cardiogenic Shock Septic Shock

Causes

Pathogenesis

Symptoms
 General Pathology
1. Cell adaptations,Cell injury, Cell death

2. Inflammation

3. Wound healing and repair

4. Hemodynamics

5. Genetics

6. Immunopathology

7. Neoplasia
• Out of a total number of 46
chromosome→

a) 22 pairs of chromosomes are

homologous and are called
autosomes.

b) 23rd pair is alike only in the females

(have 2 similar X chromosomes)
whereas in a male there is one X
chromosome and one Y
chromosome. The X and Y are
therefore referred to as sex
chromosomes.
 Genetic inheritance of Single gene
disorders
• AD
• AR
• XD
• XR
 Autosomal Dominant (AD) Inheritance Diseases

• Mutated genes can express

themselves in heterozygous state.

• Variable onset

• Autosomal dominant traits do not

skip a generation

• Autosomal dominant traits do not

show gender bias.
 Examples
Vo Familial Hypercholesterolemia Autosomal DOMINANT
Vo Hai Disease
Von Willebrand
Familial Familial Adenomatous Polyposis
Hypercholesterolemia Hypercholesterolemia (Familial)
Autosomal Adult polycystic kidney
D Dystrophia myotonica
O Osteogenesis imperfecta
M Marfan syndrome
I Intermittent porphyria
N Neurofibromatosis-1
A Achondroplasia
N Neurofibromatosis – 2
T Tuberous sclerosis
Hai Huntington’s disease; Hereditary spherocytosis
 Autosomal Recessive (AR) Inheritance Diseases
• Mutant genes express themselves
only in Homozygous state.

• Early uniform onset (usually in

childhood).

• Both sexes Involved

• Generations skipped
 Examples
ABCDEFGH SPW
A - Albinism, Alpha 1 Antitrypsin Deficiency
B - Beta Thalassemia
C - Cystic Fibrosis, CGD, CAH
D - Deafness(SNHL), Dubin Johnson
E - Enzyme Deficiencies(Glycogen Storage And
Lysosomal Storage)
F - Friedrich's Ataxia, Fanconi Anemia
G - Galactosemia
H - Hemochromatosis, Hurler syndrome
S - Sickle Cell Disease
P - Phenylketonuria
W - Wilson's disease
 X - Linked Dominant Disorders
• These are the conditions in which
both heterozygous males and
females are affected.

a) Affected male will transmit it to

100% of their daughters and
none of their sons.

b) Affected (diseased) female will

transmit the disease to 50% of
their sons and daughters.
 Examples

FAIR
F - Facial (oro) syndrome
A - Alports
I - Incontinenta pigmento
R - Resistant rickets
 X - Linked Recessive Disorder

a) The mutant recessive gene on the X

chromosome expresses itself in a
male child because it is not
suppressed by a normal allele

b) The mutant recessive gene on the X

chromosome do NOT expresses itself
in a female child because in the
female, the presence of a normal
allele on other X-chromosome
prevents the expression of the
disease So, females only act as
carriers.
 Examples

GRAHAM BELL
G - G6 PD deficency
R - Retinitis pigmentosa
A - Androgen insensitivity
H - Hemophilia A & B, Hydrcephalus
A - Adrenoleucodystrophy
M - Menkes disease
B - Beckers & duchennes musculardystrophy, Blindness
(color blindness)
E - Emery- Dreifuss dystrophy
L - Lesch nyhan syndrome
L - Lowe disease
 Chromosomal Disorders

• The gametes contain half the number of chromosomes (haploid) and are
represented as (23, X) or (23, Y).

• An exact multiple of haploid chromosomes is called Euploidy (2n, 3n, 4n

etc).

• When exact multiple of haploid chromosomes is not present, it is called

Aneuploidy.

• Genome mutations involve loss or gain of whole chromosomes, giving rise

to monosomy or trisomy.
 2n 2n

Normal Meiosis Anaphase lag or Non disjunction

n , n n+1 , n-1

Normal gametes Abnormal gemetes

When these fuse with normal gametes When these fuse with normal gametes

2n 2n 2n+1 2n-1

Normal diploid cells Trisomy Monosomy

 Cytogenetic disorders involving Autosomes

• Down Syndrome (Trisomy 21)

• Patau syndrome (Trisomy 13)

• Edwards syndrome (Trisomy 18)

 General Pathology
1. Cell adaptations,Cell injury, Cell death

2. Inflammation

3. Wound healing and repair

4. Hemodynamics

5. Genetics

6. Immunopathology

7. Neoplasia
Transplant rejection
 Graft Types
• 1) Autograft (autogenic graft): Graft
from self

• 2) Isograft (syngraft): Graft from

genetically identical person, e.g.
identical twin

• 3) Allograft (homograft or allogenic

graft): Graft from genetically unrelated
member of same species

• 4) Xenograft (heterograft): Graft from

different species
 General Pathology
1. Cell adaptations,Cell injury, Cell death

2. Inflammation

3. Wound healing and repair

4. Hemodynamics

5. Genetics

6. Immunopathology

7. Neoplasia
 Neoplasia

• The term ‘neoplasia’ means

new growth

• The new growth produced is

called ‘neoplasm’ or ‘tumour`

• The branch of science dealing

with the study of neoplasms is
called oncology
 Neoplasm
An abnormal mass of tissue

➢The growth of which exceeds and is

uncoordinated with that of the normal
tissues

➢Persists in the same excessive

manner even after cessation of the
stimuli which evoked the change.
 Tetratoma
• Tumors are composed of cells representative of a
single germ layer.

• Teratoma arise from totipotent cells

• Teratomas are germ cell tumors commonly

composed of multiple cell types derived from 3
germ layers → ectoderm, mesoderm and endoderm

• A teratoma is a rare type of germ cell tumor that

may contain immature or fully formed tissue,
including teeth, hair, bone and muscle.

• Teratomas are usually benign but may be malignant

 Benign versus Malignant tumour

1. Rate of growth

2. Clinical features

3. Gross features

4. Microscopic features

5. Spread of tumours

a. Local invasion or direct spread

b. Metastasis or distant spread

 1. Rate of growth

• Benign tumour cells → Less mitotic rate (more doubling time)

• Malignant tumour cells → Increased mitotic rate (less doubling time) and
slower death rate ie. cell production exceeds the cell loss.
 2. Clinical Features

Benign tumours Malignant tumours

• Slow growing • Grow rapidly

• May remain asymptomatic (e.g. • May ulcerate on the surface
subcutaneous lipoma) • Invade locally into deeper tissues
• May produce serious symptoms • May spread to distant sites
(e.g. meningioma in the CNS) (metastasis)
• Systemic features such as weight
loss, anorexia and anaemia.
 3. Gross Features

Benign tumours Malignant tumours

• Spherical or ovoid in shape. • Irregular in shape

• Encapsulated or well- • Poorly-circumscribed
circumscribed • Extend into the adjacent tissues.
• Freely movable • Sarcomas typically have fishflesh
• More firm and uniform like consistency while carcinomas
• Surrounding tissue compressed are generally firm
• Surrounding tissue invaded
 4. Microscopic Features

• Lack of differentiation

OR

• Presence of Anaplasia
 Differentiation

Differentiation is defined as the extent of morphological and functional

resemblance of tumour cells to corresponding normal cells.
 Anaplasia
• Anaplasia is lack of differentiation

• Characteristic feature of malignant tumours

• Anaplasia is considered as a hallmark of malignant transformation,

• It is irreversible
 Features of anaplasia

1. Loss of polarity
2. Pleomorphism
3. N:C ratio
4. Anisonucleosis
5. Hyperchromatism
6. Nucleolar changes
7. Mitotic figures
8. Tumor giant cells
9. Cytoplasm increased mucin
10.DNA anuploidy
 5. Spread Of Tumours
1. Local invasion (direct spread)

2. Metastasis (distant spread)

Invasiveness and metastasis are the two other most important features to
distinguish malignant from benign tumours.

• Benign tumour → Neither show local invasion nor Metastasis

• Malignant tumour → Show local invasion as well as Metastasis

➢Metastasis is the most reliable feature of a malignant tumor

➢Invasiveness is the 2nd most reliable sign of malignancy (after metastasis)
FEATURE BENIGN MALIGNANT
I. Clinical And Gross Features
1. Boundaries Encapsulated or well- Poorly-circumscribed and
circumscribed irregular
2. Surrounding tissue Compressed Invaded
3. Size Usually small Often larger
4. Secondary changes Occur less often Occur more often

II.Microscopic Features

1. Basal polarity Retained Lost

2. Pleomorphism Absent Present
3. N / C ratio Normal Increased
4. Anisonucleosis Absent Present
5. Hyperchromatism Absent Present
6. Mitosis May be present but are always Mitotic figures Increased and are
typical mitoses generally atypical and abnormal
 7. Tumour giant cells May be present but without Present with nuclear atypia
nuclear atypia
8. Chromosomal Infrequent Invariably present
abnormalities

III. Growth Rate Slow Rapid

IV. Local Invasion Compresses the surrounding Infiltrates and Invades the
tissues without Invading or adjacent tissues
lnfiltrating them

V. Metastasis Absent Frequently present

VI. Prognosis Local complications Death by local and metastatic

complications
 Tumour Markers

• Some tumor produce or elicite the production of markers that can be

measured in the serum or urine or other body fluids.

• Tumor markers are biochemical indicators of the presence of a tumor.

Tumor Markers Tumor Types
Hormones
Human chorionic gonadotropin Trophoblastic tumors, nonseminomatous testicular
tumors
Calcitonin Medullary carcinoma of thyroid
Catecholamine and metabolites Pheochromocytoma and related tumors
Oncofoetal Antigens
a-Fetoprotein Liver cell cancer, nonseminomatous germ cell
tumors of testis
Carcinoembryonic antigen Carcinomas of the colon, pancreas, lung, stomach,
and heart
Isoenzymes
Prostatic acid phosphatase Prostate cancer
Neuron-specific enolase Small-cell cancer of lung, neuroblastoma
Specific Proteins
Immunoglobulins Multiple myeloma and other gammopathies
Prostate-specific antigen and prostate- Prostate cancer
specific membrane antigen

Mucins and Other Glycoproteins

CA-125 Ovarian cancer
CA-19-9 Colon cancer, pancreatic cancer
CA-15-3 Breast cancer