06 Apoptosis and Gangrene

8/12/2019 06 Apoptosis and Gangrene

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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

06 Apoptosis and Gangrene

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