Microscopic changes in necrosis

Microscopic changes in necrosis

Necrotic cells are more eosinophilic, with a homogenous glassy appearance of the cytoplasm, which looks vacuolated after enzymatic digestion. Myelin figures may appear. They are whorled phospholipid masses that are seen following necrosis. Local calcification may follow. Electron microscope will show damage to cell and mitochondrial membrane, swollen mitochondria with amorphous deposits, myelin figures, and fluffy aggregates of denatured protein. Nuclear pyknosis, karyorrhexis, and karyolysis are seen.

Types of necrosis

1. Coagulative necrosis: In this type of necrosis, the lytic enzymes themselves get denatured so that the outline of the cell is still preserved. A classic example is myocardial infarction and most solid organ infarcts. Coagulative necrosis is seen in response to hypoxic cell death in all tissues except the brain. Dry gangrene of the limbs is an example of coagulative necrosis.

2. Caseous necrosis: This is a special type of coagulative necrosis that is seen in infections with M.tuberculosis. It is characterized by a cheesy, waxy necrotic debris derived from mycolic acid degradation in the mycobacterial cell wall.

3. Liquefactive necrosis: In this type, the necrotic cells are liquefied by enzymes leading to softening of tissue. It is seen in hypoxic injury of the brain or following bacterial and fungal infections. Pus is a result of liquefactive necrosis. Liquefactive enzymes are derived from lysosomes or neutrophils. When infection is superimposed on dry gangrene (originally coagulative necrosis), the local tissue undergoes liquefactive necrosis and is called “wet necrosis”.

This higher-power photomicrograph of the lung demonstrates the edge of the abscess. Note the loss of material from the center of the abscess (1) and loose necrotic material that has not been expelled (2). This material is made up of inflammatory cells (primarily dead white blood cells) and necrotic lung tissue.

4. Fat necrosis: It is seen in the setting of acute pancreatitis with the release of activated pancreatic lipases, which cause necrosis of the pancreas and surrounding peritoneal structures. The lipases also break down stored triglycerides to release free fatty acids which combine with calcium to form chalky white soap deposits in the pancreas, a process called fat saponification. Calcium deposits appear basophilic on microscopy.

5. Fibrinoid necrosis: It is a special type of necrosis seen in small blood vessels like muscular arteries, arterioles and glomeruli in vasculitis associated with autoimmune diseases like SLE and in malignant hypertension. The vessel walls show fibrin deposits and appear homogeneously red or eosinophilic.

Response of subcellular organelles to injury: Heterophagy is the digestion of extracellularly ingested materials by lysosomes. It is seen in phagocytes like neutrophils and macrophages. Autophagy is the digestion of a cell’s own components by lysosomes. Auto-phagolysosomes are seen in autophagy. It is associated with atrophy, fasting, removal of damaged cell components, and tissue remodeling. Carbon particles from inhaled air or carbon pigment from tattoo ink can persist in the phagolysosomes of macrophages for decades. Chloroquine raises the pH inside the lysosome, inactivating lysosomal enzymes. Certain drugs and toxins, like barbiturates, alcohol, etc., can induce the smooth endoplasmic reticulum (SER) and cause SER hypertrophy. Mitochondria may abnormally swell to large, irregular shapes and sizes called megamitochondria as a result of free radical injury associated with alcoholism, hydrazine, and chloramphenicol. Large mitochondria with abnormal cristae are seen in mitochondrial myopathies.

Disorders of the cytoskeletal structures

*Keratin, neurofilaments, desmin, vimentin, and glial filaments are also called intermediate filaments.

Section D: Intracellular accumulations