Necrosis and Oncosis

• Necrosis is a form of cell death involving the breakdown of cell membranes.
• The term "necrosis" originates from the Greek word "Necros," meaning dead body.
• Necrosis typically follows irreversible cell injury.
• Cellular enzymes leak out during necrosis, leading to cell digestion.
• Necrosis is associated with an inflammatory cell response.
• External factors like infection and extreme temperatures can trigger necrosis.
• Internal factors like tissue ischemia can also induce necrosis.

Oncosis

• This begins when toxins or ischemia damage the mitochondria.
• Mitochondrial damage halts ATP synthesis, disrupting ion pump function.
• Disrupted ion pumps cause sodium and water influx, leading to cell swelling and bursting.
• The bursting of cells spills internal contents onto neighboring cells.
• Spilled contents attract immune cells and trigger inflammation.
• Immune cells release proteases and reactive oxygen species (ROS), causing further tissue damage.
• Extensive tissue destruction can result in organ dysfunction.

Coagulative Necrosis

• Typically occurs due to hypoxia caused by ischemia.
• Hypoxia denatures structural proteins and impairs lysosomal enzyme function.
• Affected cells retain some structure, resulting in a gel-like appearance.
• Dead tissue forms a pale, wedge-shaped infarct, with the apex pointing towards the obstruction.
• Reperfusion can cause the tissue to become dark red, resulting in a red infarct.
• Commonly affects the heart, kidneys, and spleen.
• Structural proteins denature before enzymatic digestion, resulting in a firm tissue that preserves tissue architecture.
• Low oxygen (hypoxia) leads to acidic intracellular conditions, causing structural proteins and enzymes to denature.
• Since the enzymes responsible for breaking down the cell are also denatured, enzymatic digestion is delayed.
• The plasma membrane stays relatively intact for some time.
• Dead cells lose their function but maintain their shape, which is why the tissue appears firm instead of liquefied.
• Macrophages and neutrophils arrive later to remove dead cells.
• Lysosomal enzymes from recruited immune cells will finally break down the membranes, leading to full degradation.

Liquefactive Necrosis

• Occurs when hydrolytic enzymes completely digest dead cells.
• Results in a creamy substance composed of dead immune cells.
• Commonly seen in the brain, pancreatic cells, and abscesses.
• Microglial cells in the brain contain hydrolytic enzymes that liquefy the dead brain tissue.
• Pancreatic enzymes like trypsin, activated during chronic inflammation, digest pancreatic tissue.
• Neutrophils in abscesses use proteolytic enzymes to liquefy tissue, forming pus.

Gangrenous Necrosis

• Typically results from hypoxia.
• Affects the lower limbs and gastrointestinal tract.
• Dry gangrene causes tissue to dry up, resembling a mummy.
• Infected dry gangrene can lead to liquefactive necrosis, becoming wet gangrene.

Caseous Necrosis

• A combination of coagulative and liquefactive necrosis.
• Typically occurs due to fungal or mycobacterial infections, such as Mycobacterium tuberculosis.
• Dead cells disintegrate but are not fully digested, resulting in a cottage cheese-like consistency.

Fat Necrosis

• Occurs due to trauma to fatty organs like the pancreas or breasts.
• Trauma ruptures adipose cell membranes, releasing fatty acids into the extracellular space.
• Fatty acids combine with calcium, leading to dystrophic calcifications.
• Calcifications appear as chalk-like deposits in the tissue.
• Pancreatitis can cause lipase to spill, digesting fat in adjacent retroperitoneal tissue.

Fibrinoid Necrosis

• Commonly found in malignant hypertension and vasculitis.
• High blood pressure damages the muscular walls of small arteries.
• Fibrin infiltrates and damages the walls of the damaged blood vessels.
• Vasculitis involves an inflammatory reaction in blood vessel walls, causing destruction.

Necrosis vs Apoptosis

• Nuclear features are key to identifying necrosis
• Pyknosis: The nucleus shrinks and condenses.
• Karyorrhexis: The nucleus breaks or fragments apart.
• Karyolysis: The nucleus fades out.
• Necrosis involves disruption and fading of the cell
• Enzyme digestion occurs due to enzyme leakage.
• Exposed phospholipids attract inflammatory cells.
• Neutrophils and macrophages are recruited.
• Apoptosis involves shrinkage of the cell and fragmentation of the nucleus with no karyolysis.

Clinical Correlation and Lab Tests

• Damaged cell membranes cause leakage of intracellular proteins into the circulation.
• Myocardial infarction causes high levels of troponin and creatine kinase (CK-MB).
• Hepatocyte injury leads to elevated aminotransferases (AST and ALT).
• Bile duct injury results in increased alkaline phosphatase (ALP).
• Skeletal muscle injury releases creatine kinase (CK-MM) and aldolase.

Oncosis vs Necrosis

• Oncosis is a type of necrosis characterized mainly by cell swelling
• Necrosis is a general term for unregulated cell death that can involve various mechanisms and morphological changes.
• Necrosis often leads to inflammation due to the release of cellular contents into the extracellular space
• Oncosis specifically refers to the swelling of cells that may or may not result in such an inflammatory response.
• Oncosis is often used in the context of ischemic injury or hypoxia, where the cell is deprived of oxygen, leading to water influx.
• Necrosis encompasses a wider range of cell death mechanisms, including those triggered by infections, trauma, or toxins.

Exposed Phospholipids

• Exposed phospholipids recruit inflammatory cells that help with the digestion of lysed cells
• Exposed phospholipids serve as an 'eat me' signal, attracting phagocytes like neutrophils and macrophages to the site of cell death.
• The recruitment of inflammatory cells promotes the digestion of cellular debris and contributes to the inflammatory response characteristic of necrosis.