Overview of Cell Injury and Cell Death Faculty of Medicine Department of Pathology Hussam Telfah, MBBS, FRCPath

Patterns of tissue necrosis Caseous necrosis: White cheeselike friable necrosis. Tuberculosis Collection of fragmented or lysed cells with amorphous granular eosinophilic debris surrounded by histiocytes (macrophages), known as granuloma.

Patterns of necrosis Fat necrosis: usually used in clinical terms and it is not a specific type. Necrosis (destruction) of fat. Typical example: pancreatic enzymes (lipases) release in acute pancreatitis. The fatty acids result from the breakdown of fat combine with calcium leading to the formation of white chalky areas (Saponification).

Patterns of necrosis Fibrinoid necrosis: immune reactions involving blood vessels. Complexes of antigens and antibodies deposited in the walls of arteries. Immune complexes deposits along with fibrin result in a bright pink material on H&E. Example: vasculitis.

Fate of necrotic tissue Phagocytosis. Replacement by scar. Regeneration. Calcification.

Apoptosis

Apoptosis Pathway of cell death induced by a suicide program in which activation of degrading enzymes takes place. Apoptotic cells break up into fragments called apoptotic bodies which contain portions of the cytoplasm and nucleus. Become targets for phagocytosis before their contents leak out and so there would be no inflammatory reaction.

Apoptosis Occurs normally during development and adulthood and also in pathologic conditions. Physiologic situations: Embryogenesis, involution of hormone-dependent tissues upon hormone withdrawal, cell loss in proliferating cell populations and death of host cells after serving their useful function.

Apoptosis Pathologic situations: (no host reaction) DNA damage, certain infections (viral ones), pathologic atrophy in parenchymal organs after duct obstruction (pancreas, parotid and kidney)

Morphology Cell shrinkage: dense cytoplasm, tightly packed organelles. Chromatin condensation: peripherally under the nuclear membrane. Formation of cytoplasmic blebs and apoptotic bodies: blebbing then fragmentation into membrane bound apoptotic bodies composed of cytoplasm and tightly packed organelles with or without nuclear fragments.

Morphology Phagocytosis of apoptotic cells or cell bodies by macrophages. On H&E apoptotic cell appears intensely eosinophilic.

Feature Necrosis Apoptosis Cell size Enlarged (swelling)   Enlarged (swelling) Reduced (shrinkage) Nucleus Pyknosis → karyorrhexis → karyolysis Fragmentation into nucleosome-size fragments Plasma membrane Disrupted Intact; altered structure, especially orientation of lipids Cellular content Enzymatic digestion; may leak out of cell Adjacent inflammation Frequent No Physiologic or pathologic role Invariably pathologic (culmination of irreversible cell injury) Often physiologic, means of eliminating unwanted cells; may be pathologic after some forms of cell injury, especially DNA damage