Cell Death

4 examples of pathological causes of apoptosis

Organ not receiving stimulus (portosystemic shunt)

Cells containing infectious agent

Cell and/or DNA irreparably damaged

Cell is cancerous

Histological morphology of apoptosis (5)

shrunken cell

loss of adhesions to nearby cells and basement membrane

pyknotic, with chromatin condensed around periphery

no/minimal inflammation

cytoplasmic blebs = apoptotic bodies

3 main causes of necrosis

Loss of blood supply = hypoxia/anoxia

Living agents (pathogens) that damage the cell

Non - living agents (chemicals, ROS, physical injuries)

Histological changes seen with necrosis

Nuclear changes:

• Karyorrhexis (nucleus broken up into pieces)

• Karyolysis (faint nucleus due to break down)

• Pyknosis

Inflammation

• white blood cell influx seen grossly and histologically

What nuclear change is seen in this necrotic image?

Karyolysis

What nuclear change is seen in this necrotic image?

Karyorrhexis

How does anoxia/hypoxia lead to necrosis

Reduction of ATP production = active pumps stop working

• Na+/K+ pumps

• Calcium efflux pumps = intracellular calcium accumulation causes cell damage = hypercalcaemia (poor prognostic indicator)

= oncotic necrosis - cells swelling due to water following sodium

= hyperkalaemia

Increase in anaerobic glycolysis

= increased lactic acid and decreased pH = damaged cellular enzymes and DNA

4 ways cell membranes can be directly damaged

Pore-forming infectious agents/toxins

ROS

Phospholipase activation

Protease activation

Name a popular pore-forming bacteria

Clostridium perfringens - many types, produce different toxins

In what ways can viruses cause membrane damage?

Enveloped virus takes host membrane. Some can leave host cell intact whilst others cause cell lysus

Non-enveloped virus can only leave cell by lysis of the cell

Cell lysis caused by disruption to the cytocavitary network and other homeostatic mechanisms

Can induce apoptosis

What are free radicals and their causes? How are they controlled?

Any molecule with a free electron. Can be reactive oxygen species or reactive nitrogen species

Produced by oxidative metabolism (mitochondria usually) but can damage mitochondria if cannot be removed

Constantly produced by all cells

Free radicles neutralised by Vitamin E and selenium

What are the 4 gross morphologies of necrosis

Lytic/liquefactive

Coagulative

Caseous

Gangrenous

What is this type of necrosis, its causes, and describe the gross and histo features

Coagulative necrosis - basic outline of necrotic cells is preserved

• hypoxic injury - infarction

Gross:

• well demarcated (infarction), rim of inflammation

• Firmer and dryer

Histo:

• preserved tissue architecture - basement membrane often intact

• necrotic cells

• inflammation

• early attempts at healing

What type of necrosis is this? Causes. Describe the gross and histological appearance. Give example causative agents

Chronic coagulation necrosis

Body unable to remove agent e.g. intracellular bacteria or fungi

Birds and reptiles more common due to heterophils producing solid pus (reduced myeloperoxidase)

Gross:

• friable, granular, white appearance

• usually encapsulated

Histo:

• loss of architecture

• central accumulation of remnants of lysed leukocytes

• may have granulomatous inflammation and outer fibrous tissue

• usually have dystrophic calcification centrally

Causative agents:

= Corynebacterium pseudotuberculosis (lymphadenitis in ruminant and horse)

= mycobacterium tuberculosis

What is this type of necrosis? What is the cause? Describe the gross and histological appearance.

Liquefactive/lytic necrosis

cells lysed and necrotic tissue converted to a fluid phase

Caused by bacteria, fungi (cryptococcus neoformans), thiamine deficiency (CNN in ruminants)

mostly affects CNS

Gross:

• soft, viscous

• usually has cavity containing pus

• poorly demarcated boundaries

Histo:

• eosinophilic fluid, cell debris

• messy, hard to orientate in high magnification

• no background supportive tissues

What is gangrenous necrosis and cause?

Sequel of coagulative necrosis

Associated with loss of blood flow to a tissue

Type of gangrenous necrosis. What are its causes (4) and features?

Dry

Caused by coagulation necrosis followed by mummification (no water)

Usually affects the lower portion of extremities

No bacterial proliferation

Features: dry, shrivelled, brown/black. May slough

Cause:

• Ingested toxins

• Frostbite

• Peripheral arteriolar constriction and damage to capillaries

• Thrombosis and infarction

Type of gangrenous necrosis and what are the features?

Wet/moist

Areas of necrotic tissue are further degraded by liquefaction action of saprophytic bacteria = sloughing of tissue

Death can occur from toxaemia (E.coli/lipopolysaccharide)

Gross appearance: soft, moist, red/brown/black, may have gas, putrid odour (hydrogen sulphide)

Type of gangrenous necrosis and explain how it occurs and its gross features.

Gaseous

Bacteria, usually anaerobic, proliferate and produce toxins in necrotic tissue

Bacteria introduced by penetrating wounds

Gross = dark red/black, gas bubbles, fluid and haemorrhagic exudate.

What type of necrosis is this? 4 possible causes. Describe the gross and histological features.

Fat necrosis

• nutritional (yellow fat disease) from high unsaturated fats and low vitamin E

• enzymatic (pancreatitis- enzyme release causes liquefaction of adipocytes)

• traumatic (crushing)

• idiopathic e.g. Jersey and Guernsey cattle can cause stricture and stenosis