Cellular Injury and Death: MRCOG Part 1 questions and key facts

Tuberculosis, caused by infection with Mycobacterium tuberculosis, classically induces a specific type of granulomatous inflammation characterised by caseating granulomas. These granulomas are aggregates of immune cells (macrophages, lymphocytes) attempting to contain the infection. Caseation necrosis refers to the central area of necrosis within these granulomas, which appears amorphous, eosinophilic, and 'cheese-like' (caseous) on histological examination due to the destruction of tissue and accumulation of cellular debris.

Sarcoidosis is characterised by non-caseating granulomas, which lack the central necrotic core seen in tuberculosis. Crohn's disease, an inflammatory bowel disease, can also feature granulomas, but these are typically non-caseating. Syphilis (specifically tertiary syphilis) can cause gummas, which are a form of granulomatous inflammation but differ histologically from typical caseating granulomas. Leprosy also involves granulomas, but their morphology varies depending on the type of leprosy (tuberculoid vs lepromatous) and they are not primarily defined by caseation.

The description of cell death involving chromatin condensation, nuclear fragmentation into membrane-bound bodies, and the absence of inflammation is characteristic of apoptosis. Apoptosis, or programmed cell death, is a highly regulated energy-dependent process used by multicellular organisms to eliminate unwanted or damaged cells cleanly, without eliciting an inflammatory response. Follicular atresia, the process by which ovarian follicles degenerate before reaching maturity, is a classic example of physiological apoptosis.

Necrosis, in contrast, is typically pathological cell death resulting from acute injury (like ischaemia or toxins). It involves cell swelling (oncosis), loss of membrane integrity, leakage of cellular contents, and initiation of an inflammatory response. Coagulative necrosis and liquefactive necrosis are morphological patterns of necrosis. Autolysis refers to the enzymatic digestion of cells by their own enzymes, usually occurring after somatic death.

Liquefactive necrosis is characteristic of hypoxic injury within the central nervous system (CNS). Following events like a stroke (cerebral infarction), the affected brain tissue undergoes degradation by hydrolytic enzymes released from neutrophils and microglia. Unlike other tissues, the brain has relatively little connective tissue stroma to support the necrotic cells, and it is rich in lipids and enzymes, leading to the digestion of the tissue into a semi-liquid, viscous mass. This often results in cyst formation after the liquefied debris is removed by phagocytes.

Coagulative necrosis is typically seen in solid organs like the heart, kidneys, or spleen following ischaemia. The underlying tissue architecture is preserved for some days due to denaturation of both structural proteins and enzymes, resulting in a firm texture. Fat necrosis occurs in fatty tissue, often due to enzymatic digestion (e.g., pancreatitis releasing lipases) or trauma, resulting in saponification and chalky white deposits. Caseous necrosis, classically associated with tuberculosis, presents as 'cheese-like' (friable, white/yellow) material resulting from a combination of coagulative and liquefactive necrosis within a granuloma. Gangrenous necrosis usually applies to limbs that have lost blood supply, starting as coagulative necrosis (dry gangrene) which may become liquefactive if a bacterial infection is superimposed (wet gangrene).