General Pathology
(PATH 303)
Lecture # 8

APOPTOSIS
Apoptosis or programmed cell death (apoptosis –a
falling away from)
 It is a genetically controlled homeostatic mechanism to
remove unwanted cells. Death genes give rise to
proteins which direct executioner molecules to:
1. Break chromosomes
2. Depolymerize the cytoskeleton
3. Cause mitochondria to release cytochrome-c and
4. Cytoplasmic blebs and pyknotic nuclei are shed from
cell as apoptotic bodies

Significance
Critical processes :
 Programmed cell death (PCD) is essential for:
 Gene - directed cell deletion in
embryogenesis.
 Physiological involution such as during
menstrual cycle in humans
 Removal of neoplastic cells with lethal
mutations.
 Deletion of cells damaged by toxins and
infectious agents.
Caspases (cystein –containing aspartate
specific proteases).
 Most of cellular changes in PCD are brought
about by protein cleaving enzymes known as
caspases. There are two groups:
 Initiator caspases: Caspase 8 and 10
respond to death signals and activate the
second group i.e.
 Execution caspases: caspases 3, 6 and 7
enzymes that make specific cuts in key
proteins that are required for cell survival.
Mechanism:

Initiation: Signals that initiate the process of PCD
may be extra- or intracellular.



In embryogenesis, atrophy and neoplasia, the initiating
signals arise from within the cell.
Toxins, drugs, cytokines and steroid hormones can all initiate
PCD via specific signals that occur at the cell surface.
Execution: Caspase cascade:
 The death and survival of cell depends on the ratio of
two genes:
a) BAX- a gene that lead to death of the cell.
b) BCL-2 genes that are death repressor genes
 Mitochondrial shutdown: Mitochondria play a critical
role in caspase cascade pathway to PCD.

Cytochrome-c released from
mitochondria binds to a critical protein
apoptotic protease activating factor- 1
(Apaf -1) which in turn binds to and
activates caspse-9
Mitochondrial release of cytochrome- c
Cytochrome -c binds to Apaf-1
Caspase 9 activation
Caspase 3 activation
DNA cleavage
Cytoskeletal
depolymerization
Mitochondrial
breakdown
Comparison between Coagulative necrosis and apoptosis
Coagulative necrosis
Apoptosis
1. Stimuli
Hypoxia , toxins
Physiological and
Pathological factors
2. Microscopic
appearance
Cellular swelling,
Coagulative necrosis ,
disruption of organelles
Single cell, chromatin
condensation, apoptotic
bodies
3. DNA breakdown
Random ,diffuse
Inter-nucleosomal
4. Mechanisms
ATP depletion,
Membrane injury, free
radical damage
Gene activation,
endonucleases,
proteases
5. Tissue reaction
Inflammation
No inflammation,
phagocytosis of
apoptotic bodies.
Gangrene
It is invasion and putrefaction of
necrotic tissues by saprophytic
bacteria
Types
Gangrene may be dry or moist depending
upon the moisture (blood circulation) and
temperature in the tissues
1-Dry Gangrene

Observed in the extremities, legs, ears,
tail, comb, wattle etc.
Causes
1.
2.

Certain drugs like ergot and molds
growing on grasses and wheat straw as
in Deg Nala disease in Pakistan
Freezing and subsequent invasion by
saprophytes
In the extremities, blood circulation is
limited and the temperature is also
lower, therefore, the invasion and
spread of bacteria is slow.
Gross Appearance
The affected part is dry, shriveled,
mummified as a result of dehydration.
 The color may be light or dark grey
according to the amount of iron sulphide
(pseudomelanosis)
 A sharp line of inflammation (redness)
separates the affected area from healthy
tissues

Microscopic Appearance
The dead tissue appears homogenous
without cellular details
 Saprophytic bacteria are usually present
 A few gas bubbles may be present as
clear spaces
 Acute inflammatory reaction may be
present at the junction of dead and live
tissues

2-Moist Gangrene
It occurs in internal organs where
moisture and temperature are favorable
for bacterial growth
 Death occurs rapidly from septicemia,
toxemia and shock

Causes

In lungs:
By faulty drenching and wrong insertion of
stomach tube
Irritating medicines cause necrosis (drenching
pneumonia) and gangrene
In intestine:
Gangrene occurs due to malpositions e.g.
torsion, volvulus, hernia and intussusceptions
 Necrosis is caused due to venous obstruction and
congestion
 Presence of bacteria in the intestinal ingesta allows
rapid spread of moist gangrene
Gross Appearance
The gangrenous part is moist, red, green
or black as a result of iron sulphide
formation.
 The intestine is usually distended with
gas formation.
 There is bad odour from hydrogen
sulphide (rotten eggs) and putrefaction.

Microscopic Appearance

Same as autolysis, with many gas
bubbles and saprophytic bacilli
Gas gangrene, malignant edema
and black quarter disease

These are fatal disease conditions caused by different
species of spore forming bacteria- Clostridium
(C. septicum, C. perfringens and C. chauvei)
 These organisms are anaerobic, spore forming, soil
inhabitant and cause diseases as wound infections.
 Under anaerobic conditions the organisms multiply,
produce toxins causing tissue digestion like lecithinase
and collagenase
 The organisms produce edema and gas in the affected
tissues and spread to surrounding tissues and cause
death of the animal
Results of necrosis and gangrene

1.
2.
3.
4.
5.
Necrosis may terminate in several ways:
Liquefaction and removal by neutrophils,
lymph or blood- (small areas)
Liquefaction and cyst formation- (large
areas). Fibrous capsule may be formed
Liquefaction , abcessation and discharge(invasion by pyogenic bacteria)
Encapsulation without liquefaction(coagulation and caseous necrosis)
Sloughing and desquamation- (on external
surfaces)
Results of necrosis and gangrene
6.Organization of necrotic tissue
7.Dystrophic calcification
8-Death of animal – usually in case of
moist gangrene
Post- mortem changes

Postmortem changes may be
distinguished from lesions of the disease
Factors affecting the onset of
postmortem changes
1.
2.
Environmental temperature
Size, insulation and nutritional status of
the animal
Autolysis:

Digestion of tissues by their own cellular
enzymes
Putrefaction

Decomposition of tissues by enzymes of
saprophytic bacteria
Rigor mortis

It is the stiffening and immobilization of body due to
the muscular contraction after death
 Rigor mortis begins in the anterior part and progresses
towards the posterior direction ( head, neck, trunk and
limbs) and disappears in the same order.
 It appears 1 to 8 hours after death and disappears 2030 hours after death
 Rigor mortis appears earlier when there is high
external temperature or violent exercise (racing,
fighting etc.) and it is retarded by low temperature and
emaciation
Postmortem clotting of blood
Endothelial cells in the blood vessels
release thromboplastin which causes
clotting of blood in the heart and blood
vessels
 Clotting fails in anthrax due to fibrinolysin
produced by B. anthracis and in sweet
clover poisoning due to inhibition of
prothrombin activity

Imbibition with hemoglobin

Erythrocytes are hemolyzed after death
and hemoglobin diffuses into the
surrounding tissues staining them red
Hypostatic congestion

Blood accumulates in the ventral parts of
organs and the carcass due to gravity
Pseudomelanosis

It is the appearance of grey, green or
black pigment in tissues after death.
Hydrogen sulphide produced by
putrefaction combines with iron to form
iron sulphide – a black pigment
Imbibition of bile

This is yellow pigmentation of tissue
around the gallbladder due to the
diffusion of bile after death
Postmortem emphysema

Accumulation of gas in the tissues as a
result of bacterial fermentation. Bloat
may occur in ruminants after death
Rupture and displacement

Accumulation of gas due to postmortem
fermentation may cause rupture of
stomach or intestine. Intussusception
(telescoping) can also occur in terminal
condition. There are no circulatory
changes in such cases