06 apoptosis and gangrene
TRANSCRIPT
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General Pathology(PATH 303)
Lecture # 8
APOPTOSIS
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Apoptosis or programmed cell death(apoptosis afalling away from)
It is a genetically controlled homeostatic mechanism toremove 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 fromcell as apoptotic bodies
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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.
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Caspases (cystein
containing aspartatespecific proteases).
Most of cellular changes in PCD are broughtabout by protein cleaving enzymes known as
caspases. There are two groups: Initiator caspases: Caspase 8 and 10
respond to death signals and activate thesecond group i.e.
Execution caspases: caspases 3, 6 and 7enzymes that make specific cuts in keyproteins that are required for cell survival.
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Mechanism:
Initiation: Signals that initiate the process of PCDmay 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 oftwo 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.
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Cytochrome-c released from
mitochondria binds to a critical protein
apoptotic protease activating factor- 1
(Apaf -1) which in turn binds to andactivates caspse-9
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Caspase 9 activation
Cytochrome -c binds to Apaf-1
Mitochondrial release of cytochrome- c
Caspase 3 activation
DNA cleavageCytoskeletal
depolymerizationMitochondrial
breakdown
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Comparison between Coagulative necrosis and apoptosis
Coagulativenecrosis Apoptosis
1. Stimuli Hypoxia , toxins Physiological andPathological factors
2. Microscopic
appearance
Cellular swelling,
Coagulative necrosis ,disruption of organelles
Single cell, chromatin
condensation, apoptoticbodies
3. DNA breakdown Random ,diffuse Inter-nucleosomal
4. Mechanisms ATP depletion,
Membrane injury, freeradical damage
Gene activation,
endonucleases,proteases
5. Tissue reaction Inflammation No inflammation,phagocytosis of
apoptotic bodies.
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Gangrene
It is invasion and putrefaction of
necrotic tissues by saprophytic
bacteria
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Types
Gangrene may be dry or moistdepending
upon the moisture (blood circulation) and
temperature in the tissues
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1-Dry Gangrene
Observed in the extremities, legs, ears,
tail, comb, wattle etc.
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Causes
1. Certain drugs like ergot and moldsgrowing on grasses and wheat straw asin Deg Nala disease in Pakistan
2. Freezing and subsequent invasion bysaprophytes
In the extremities, blood circulation is
limited and the temperature is alsolower, therefore, the invasion andspread of bacteria is slow.
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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
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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 bepresent at the junction of dead and live
tissues
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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
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Causes
In lungs:
By faulty drenching and wrong insertion ofstomach tube
Irritating medicines cause necrosis (drenching
pneumonia) and gangreneIn 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
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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.
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Microscopic Appearance
Same as autolysis, with many gas
bubbles and saprophytic bacilli
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Gas gangrene, malignant edema
and black quarter disease
These are fatal disease conditions caused by differentspecies 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 lecithinaseand collagenase
The organisms produce edema and gas in the affectedtissues and spread to surrounding tissues and causedeath of the animal
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Results of necrosis and gangrene
Necrosis may terminate in several ways:
1. Liquefaction and removal by neutrophils,lymph or blood- (small areas)
2. Liquefaction and cyst formation- (largeareas). Fibrous capsule may be formed
3. Liquefaction , abcessation and discharge-(invasion by pyogenic bacteria)
4. Encapsulation without liquefaction-
(coagulation and caseous necrosis)5. Sloughing and desquamation- (on external
surfaces)
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Results of necrosis and gangrene
6.Organization of necrotic tissue
7.Dystrophic calcification
8-Death of animal
usually in case ofmoist gangrene
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Post- mortem changes
Postmortem changes may be
distinguished from lesions of the disease
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Factors affecting the onset of
postmortem changes
1. Environmental temperature
2. Size, insulation and nutritional status of
the animal
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Autolysis:
Digestion of tissues by their own cellular
enzymes
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Putrefaction
Decomposition of tissues by enzymes ofsaprophytic bacteria
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Rigor mortis
It is the stiffening and immobilization of body due tothe muscular contraction after death
Rigor mortis begins in the anterior part and progressestowards the posterior direction ( head, neck, trunk and
limbs) and disappears in the same order. It appears 1 to 8 hours after death and disappears 20-
30 hours after death
Rigor mortis appears earlier when there is highexternal temperature or violent exercise (racing,fighting etc.) and it is retarded by low temperature andemaciation
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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. anthracisand in sweet
clover poisoning due to inhibition ofprothrombin activity
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Imbibition with hemoglobin
Erythrocytes are hemolyzed after death
and hemoglobin diffuses into the
surrounding tissues staining them red
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Hypostatic congestion
Blood accumulates in the ventral parts of
organs and the carcass due to gravity
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Pseudomelanosis
It is the appearance of grey, green or
black pigment in tissues after death.
Hydrogen sulphide produced by
putrefaction combines with iron to formiron sulphide a black pigment
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Imbibition of bile
This is yellow pigmentation of tissue
around the gallbladder due to the
diffusion of bile after death
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Postmortem emphysema
Accumulation of gas in the tissues as a
result of bacterial fermentation. Bloat
may occur in ruminants after death
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Rupture and displacement
Accumulation of gas due to postmortem
fermentation may cause rupture of
stomach or intestine. Intussusception
(telescoping) can also occur in terminalcondition. There are no circulatory
changes in such cases