Necrosis and infarction

Necrosis is never physiologic. Membranes rupture, contents leak, and inflammation follows. Two processes compete in dead tissue: denaturation of proteins, which preserves cell outlines, and enzymatic digestion by the cell's own lysosomal enzymes or by those of incoming leukocytes, which dissolves them. Which one wins, and in what setting, gives each pattern.

In ischemic tissue, lactic acidosis denatures structural proteins and enzymes, including lysosomal enzymes, so the dead cells are not digested at first. Their outlines persist for days as firm, eosinophilic “ghosts” whose nuclei have disappeared or are fading (karyolysis). Neutrophils and macrophages coming in from the living edge eventually digest and remove the dead tissue.

An infarct is the gross, naked-eye form of coagulative necrosis caused by sudden occlusion of a vessel. Because arteries branch like a tree, the dead territory is usually wedge-shaped, with its apex at the occlusion and its base at the organ surface.

Here enzymes win. Hydrolytic enzymes from the dead cells themselves or from incoming neutrophils digest the tissue into a liquid. The lecture gives three settings:

• Brain infarct: the brain is rich in lipid and poor in connective tissue, and enzymes from dying cells and microglia liquefy it. Macrophages clear the debris and a cyst, walled off by reactive astrocytes, remains.
• Abscess: neutrophils recruited by bacteria release proteolytic enzymes, producing pus.
• Pancreatitis: activated pancreatic enzymes digest the parenchyma.

Caseous (“cheese-like”) necrosis is soft, white and friable to the eye. Under the microscope it is amorphous, granular pink debris in which cell outlines are lost, so it is often described as combining features of coagulative and liquefactive necrosis. It forms at the centre of granulomas in tuberculosis and some systemic fungal infections such as histoplasmosis, where activated macrophages destroy the organisms and lipid from mycobacterial cell walls contributes to the material.

Fibrinoid necrosis is damage to blood vessel walls in which bright pink, smudgy, protein-rich material, mostly fibrin leaked from plasma, mixed with immune complexes, is deposited. It affects small arteries, arterioles, venules and glomerular capillaries, and can occur in valves, myocardium and subcutaneous tissue. The lecture links it to malignant hypertension and vasculitis such as Henoch–Schönlein purpura (IgA vasculitis).

Gangrene is a clinical term rather than a separate microscopic pattern. Dry gangrene is ischemic coagulative necrosis of a limb or part, which dries and blackens like a mummy with a clear line of demarcation, typically in the toes and feet of people with atherosclerosis or diabetes. When bacteria such as Clostridium perfringens infect the dead tissue, their enzymes and the neutrophil response add liquefaction: wet gangrene, swollen, foul-smelling and spreading. Ischemic bowel tends toward wet gangrene.