Understanding Necrosis: Mechanisms and Types

• Necrosis is a form of cell death that involves the breakdown of cell membranes, usually following irreversible cell injury.
• It is derived from the Greek word "Necros," meaning dead body.

Key Differences from Apoptosis

• Necrosis involves leakage of cellular enzymes and an inflammatory response, unlike apoptosis, which is a clean cell death with packaging of cell contents into apoptotic bodies.

Mechanisms of Necrosis

• Necrosis can start via oncosis, which begins when toxins or ischemia damage the mitochondria, stopping ATP synthesis.
• The failure of ionic pumps leads to sodium and water influx, causing cell swelling and rupture.
• Immune cells release proteases and reactive oxygen species (ROS), which degrade proteins and damage tissues, leading to an inflammatory response.
• Tissue destruction from necrosis can lead to organ dysfunction.

Types of Necrosis

Coagulative Necrosis

• Hypoxia, usually from ischemia, is the cause.
• Structural proteins denature and lysosomal enzymes become ineffective.
• Dead tissue remains somewhat intact, appearing gel-like.
• Pale, wedge-shaped infarcts occur with the apex pointing toward the obstruction.
• Sometimes, reperfusion injury can cause red infarcts.
• It commonly occurs in the heart, kidneys, and spleen.
• Acidic intracellular conditions result from low oxygen (hypoxia).
• These acidic conditions denature proteins, including enzymes.
• Denatured enzymes cannot digest the dead cells right away, so the structural framework remains intact.
• The dead tissue stays firm and solid until immune cells eventually break it down.
• This differs from liquefactive necrosis because hydrolytic enzymes remain active and quickly digest membranes and cell contents in liquefactive necrosis, turning tissue into liquid pus.

Liquefactive Necrosis

• It is caused by hydrolytic enzyme activity.
• Enzymes digest cells into a creamy substance full of dead immune cells.
• Microglial cells in the brain liquefy necrotic tissue.
• Pancreatic enzymes (like trypsin) digest pancreatic cells in pancreatitis.
• Neutrophils liquefy tissue in abscesses, forming pus.
• It commonly occurs in the brain, pancreas, and abscesses.
• Neurons have high lipid content and less connective tissue.
• Enzymes that Microglial cells release completely digest dead neurons.

Gangrenous Necrosis

• Hypoxia affecting extremities or the gastrointestinal (GI) tract is the cause.
• Dry gangrene resembles coagulative necrosis with mummified tissue.
• If infected, it leads to liquefactive necrosis, becoming wet gangrene.

Caseous Necrosis

• Fungal or mycobacterial infections, classically Mycobacterium tuberculosis, are the cause.
• Dead cells disintegrate but are not fully digested.
• The tissue has a characteristic cottage cheese consistency.

Fat Necrosis

• Trauma to fatty organs (pancreas, breast) is the usual cause.
• Adipose cells rupture, releasing fatty acids that bind calcium, forming dystrophic calcifications (chalky deposits).
• In pancreatitis, lipase digests surrounding fat.
• Lipases break down triglycerides into free fatty acids.
• Fatty acids bind calcium through saponification, forming chalky white deposits. Lipase leaks into surrounding fat, digesting it into free fatty acids, which bind calcium.

Fibrinoid Necrosis

• Malignant hypertension and vasculitis are the causes.
• High blood pressure damages arterial walls, allowing fibrin deposition.
• Vasculitis causes inflammation and vessel destruction.
• Autoimmune reactions or high blood pressure damage vessel walls, allowing plasma proteins (especially fibrin) to leak out.

Necrosis vs. Apoptosis

Necrosis

• Nuclear changes include pyknosis (nuclear shrinkage), karyorrhexis (fragmentation), and karyolysis (nuclear fading).
• Cell membrane breakdown, enzyme leakage, and inflammation occur.

Apoptosis

• Shrinkage and fragmentation of the nucleus occur, but there is no karyolysis.
• No inflammation occurs; apoptotic bodies are phagocytosed cleanly.

Clinical Correlation and Lab Tests

• Leakage of intracellular proteins can be measured to indicate specific tissue damage.
• Myocardial infarction leads to elevated troponin and creatine kinase-MB (CK-MB).
• Hepatocyte injury leads to elevated AST and ALT.
• Bile duct injury leads to elevated alkaline phosphatase (ALP).
• Skeletal muscle injury leads to elevated creatine kinase-MM (CK-MM) and aldolase.