Lecture 3: Cell injury- cell death, necrosis, apoptosis

What are the two major types of cell death and how do they differ in cause?

Programmed cell death: Essential for maintaining homeostasis; normal part of development.

Pathogenic cell death: Occurs in response to severe cell injury.

What are the two major forms of cell death?

Apoptosis and necrosis.

Which type of cell death is typically physiologic, and which is invariably pathologic?

Physiologic: Apoptosis (though can be pathologic after some injuries, e.g., DNA damage).

Pathologic: Necrosis (culmination of irreversible cell injury).

What is necrosis, and what cellular process is often involved in its initiation?

Death of a cell due to swelling (oncosis) leading to eventual rupture of the plasma membrane.

How does necrosis trigger inflammation?

Ruptured plasma membrane releases cell contents into the extracellular matrix, eliciting an inflammatory reaction.

How was necrosis historically viewed vs. current understanding?

Historically thought unregulated; now known it can be regulated (necroptosis) or unregulated.

What is apoptosis and what happens to the cell membrane during the process?

Programmed cell death with condensation and shrinkage of the cell, breakdown into membrane-bound apoptotic bodies; membrane remains intact but with altered lipid orientation.

What are the two main pathways for apoptosis?

Extrinsic and intrinsic pathways.

What is autophagy and does it always result in cell death?

Cell self-digestion; can be adaptive and does not always result in cell death.

Compare cell size changes in necrosis vs. apoptosis.

Necrosis: Cell enlargement (swelling).

Apoptosis: Cell shrinkage (reduced size).

Compare nuclear changes in necrosis vs. apoptosis.

Necrosis: Pyknosis → karyorrhexis → karyolysis.

Apoptosis: Fragmentation into nucleosome-sized fragments.

Compare plasma membrane integrity in necrosis vs. apoptosis.

Necrosis: Disrupted membrane.

Apoptosis: Intact but altered structure (lipid orientation changes).

Compare fate of cellular contents in necrosis vs. apoptosis.

Necrosis: Enzymatic digestion; may leak out of cell.

Apoptosis: Intact; packaged into apoptotic bodies for phagocytosis.

Compare inflammatory response in necrosis vs. apoptosis.

Necrosis: Frequent inflammation.

Apoptosis: No inflammation.

What is coagulative necrosis and its most common causes?

Necrosis with denaturation of cytoplasmic proteins and retention of cell membranes, almost always due to hypoxia, ischemia, or toxic injury.

What process in coagulative necrosis delays membrane breakdown?

Cellular acidosis denatures lysosomal enzymes, delaying proteolysis.

Why do nuclei disappear in coagulative necrosis despite membrane retention?

Nucleic acid degradation is not hindered, leading to pyknotic, karyorrhectic, or absent nuclei.

Give an example of coagulative necrosis.

Renal infarction with a pale wedge-shaped cortical/medullary region bordered by a red hyperemic rim.

What is caseous necrosis and how does it relate to coagulative necrosis?

A type of coagulative necrosis representing an older lesion with complete loss of cellular architecture, often with a cheese-like gross appearance.

Gross appearance of caseous necrosis?

Crumbly, granular, or laminated yellow-white material; may be calcified.

Common conditions associated with caseous necrosis?

Granulomas, pyogranulomas, abscesses.

Example of caseous necrosis in veterinary pathology?

Lymph node from an ox with tuberculosis (Mycobacterium bovis) showing off-white/tan crumbly material.

Histologic features of caseous necrosis in tuberculosis?

Central area of degenerate/l ysed cells lacking cellular integrity, bordered by degenerate neutrophils and epithelioid macrophages with lacy cytoplasm.

How does Mycobacterium bovis induce caseous necrosis?

Replicates inside macrophages, resists lysosomal killing via cell wall properties; cytotoxic T lymphocytes destroy infected macrophages, leading to necrosis.

What is liquefactive necrosis?

Necrosis where cells are lysed and converted to a liquid phase.

Why is liquefactive necrosis common in the CNS?

Lack of fibrous interstitium to maintain structure, high lipid content, and abundance of lytic enzymes.

Gross term for liquefactive necrosis in the brain?

Malacia (softening).

Early vs. late gross appearance of CNS liquefactive necrosis?

Early—translucency; late—yellowing, softening, swelling.

What is gangrenous necrosis and where does it typically occur?

A type of coagulative necrosis most often affecting distal extremities (limbs, tail, pinnae) or dependent portions of organs (mammary gland, lungs).

What are the four major types of necrosis recognized in veterinary pathology?

Coagulative, caseous, liquefactive, and gangrenous necrosis.

Gross features of coagulative necrosis?

Retention of general tissue architecture with pale, firm areas; cell outlines preserved, membranes retained.

Gross features of caseous necrosis?

Crumbly, granular, or laminated yellow-white material with complete loss of cellular architecture; may be calcified.

Gross features of liquefactive necrosis?

Tissue becomes liquefied/softened; in CNS termed malacia; early translucency, later yellow, soft, swollen.

Gross features of gangrenous necrosis?

Necrosis of distal extremities or dependent organ portions; appearance varies by wet, dry, or gas type.

What are the three forms of gangrenous necrosis?

Wet gangrene, dry gangrene, and gas gangrene.

What causes wet gangrene and its gross appearance?

Infection of necrotic tissue by saprophytic bacteria (e.g., Clostridia); red-black, wet tissue.

Mechanism of dry gangrene?

Decreased vascular perfusion from loss of blood supply or intense vasoconstriction, leading to tissue mummification.

Gross appearance of dry gangrene?

Red-black and dry, typically affecting extremities.

What causes gas gangrene and how is it detected grossly?

Saprophytic bacteria produce gas within necrotic tissue (often Clostridia); palpable crepitus.

What are the four types of fat necrosis?

Enzymatic, traumatic, nutritional, and idiopathic.

What causes enzymatic fat necrosis and in which species is it most common?

Release of pancreatic enzymes (lipases, amylases) into peripancreatic fat during pancreatitis; most common in carnivores.

What causes traumatic fat necrosis and give an example?

Pressure-induced injury or ischemia; example—"downer cow" injury from prolonged recumbency.

What causes nutritional fat necrosis and what is its gross appearance?

Diet high in polyunsaturated fatty acids and low in vitamin E/antioxidants → lipid peroxidation and reactive oxygen species formation; fat appears yellow.

What causes idiopathic fat necrosis and in which species is it most common?

Unknown cause; most common in abdominal fat of overconditioned cattle and in falciform fat of horses/ponies.

What inflammatory cells are recruited in fat necrosis histologically?

Macrophages and neutrophils.

Histologic appearance of necrotic adipocytes in fat necrosis?

Pale eosinophilic to pale basophilic cytoplasm instead of clear vacuolated cytoplasm.