Necrosis and Apoptosis

Absolutely — I’ll make it Anki-ready, with Front [TAB] Back, and one flashcard per line so you can copy-paste directly into Anki.

```text

What is necrosis?

Necrosis is the morphologic changes that follow cell death in living tissue, resulting from progressive degradation of cellular structures by enzymes.

What is the main mechanism of necrosis?

Severe irreversible cell injury → cell death → membrane damage/rupture → enzymatic digestion → leakage of cellular contents → inflammation.

What is the main feature distinguishing necrosis from apoptosis?

Necrosis usually involves loss of membrane integrity and inflammation, whereas apoptosis maintains membrane integrity and usually causes little or no inflammation.

What are the major causes of necrosis?

Ischemia/hypoxia, infections, toxins, chemical injury, physical agents, and severe cellular injury.

What happens to the cytoplasm in necrosis?

The cytoplasm becomes more eosinophilic (pink), homogeneous, and may become swollen.

Why does necrotic cytoplasm become more eosinophilic?

RNA is degraded, reducing basophilia, while denatured proteins contribute to increased eosinophilia.

What are the three major nuclear changes in necrosis?

Pyknosis → karyorrhexis → karyolysis.

What is pyknosis?

Nuclear shrinkage with increased chromatin condensation, making the nucleus small and intensely basophilic/dark.

What is karyorrhexis?

Fragmentation of the pyknotic nucleus.

What is karyolysis?

Dissolution and disappearance of the nucleus due to enzymatic degradation of DNA.

What is the sequence of nuclear changes in necrosis?

Pyknosis → karyorrhexis → karyolysis.

Why does necrosis cause inflammation?

Cell membrane rupture releases intracellular contents and DAMPs (damage-associated molecular patterns), which activate inflammatory responses.

What are DAMPs?

Damage-associated molecular patterns; intracellular molecules released from injured/necrotic cells that trigger inflammation.

What is coagulative necrosis?

A pattern of necrosis in which tissue architecture is preserved for several days despite cell death.

What is the most common cause of coagulative necrosis?

Ischemia due to interruption of blood supply.

What are classic examples of coagulative necrosis?

Myocardial infarction, renal infarction, and splenic infarction.

What is the major exception to ischemic coagulative necrosis?

Ischemia in the brain produces liquefactive necrosis instead.

Why is tissue architecture preserved in coagulative necrosis?

Protein denaturation, including denaturation of cellular enzymes, slows enzymatic digestion of the dead cells.

What is liquefactive necrosis?

A pattern of necrosis in which dead cells are completely digested, transforming the tissue into a liquid or viscous mass.

What are the classic causes of liquefactive necrosis?

Brain infarction and bacterial or fungal infections.

Why does a brain infarct undergo liquefactive necrosis?

The dead tissue is digested by hydrolytic enzymes, resulting in liquefaction.

Why do bacterial infections commonly cause liquefactive necrosis?

Neutrophils and microorganisms release hydrolytic enzymes that digest the tissue.

What is pus in relation to liquefactive necrosis?

Pus consists largely of neutrophils, cellular debris, and liquefied tissue produced during an inflammatory response.

What is gangrenous necrosis?

Gangrene is a clinical term for extensive tissue necrosis, usually involving a limb or other large area of tissue.

Is gangrene a distinct microscopic pattern of necrosis?

No. Gangrene is a clinical term rather than a specific microscopic pattern.

What is dry gangrene?

Extensive ischemic coagulative necrosis, typically involving a limb.

What is wet gangrene?

Gangrenous tissue complicated by bacterial infection and liquefactive necrosis.

What is caseous necrosis?

A pattern of necrosis with a soft, white, cheese-like appearance in which tissue architecture is completely destroyed.

What disease is classically associated with caseous necrosis?

Tuberculosis.

What is seen microscopically in caseous necrosis?

Amorphous, granular, eosinophilic debris surrounded by granulomatous inflammation.

What is fat necrosis?

A pattern of necrosis involving destruction of adipose tissue, often with release of fatty acids and formation of calcium soaps.

What are the two classic causes of fat necrosis?

Acute pancreatitis and traumatic injury to fatty tissue, such as the breast.

How does acute pancreatitis cause fat necrosis?

Pancreatic lipases break down triglycerides into free fatty acids, which combine with calcium to form calcium soaps.

What is saponification?

The formation of calcium soaps when free fatty acids released from fat combine with calcium.

What is fibrinoid necrosis?

A pattern of necrosis involving blood vessel walls in which the wall becomes intensely eosinophilic and fibrin-like due to deposition of immune complexes and plasma proteins.

What condition is classically associated with fibrinoid necrosis?

Vasculitis and other immune-mediated vascular injuries.

What is apoptosis?

Apoptosis is a regulated mechanism of cell death in which cells activate enzymes that degrade their own nuclear DNA and cellular proteins.

What is the key concept of apoptosis?

The cell actively dismantles itself in a controlled manner while maintaining membrane integrity, resulting in little or no inflammation.

What are the two broad types of apoptosis?

Physiologic apoptosis and pathologic apoptosis.

What is physiologic apoptosis?

Regulated cell death that occurs normally to eliminate unwanted or unnecessary cells.

What are examples of physiologic apoptosis?

Embryonic development, elimination of self-reactive lymphocytes, involution of hormone-dependent tissues, endometrial cell loss, and removal of excess immune cells after an immune response.

How does apoptosis contribute to embryonic development?

It removes selected cells to sculpt developing organs, such as removing tissue between developing digits.

How does apoptosis help prevent autoimmunity?

It eliminates self-reactive lymphocytes that could attack the body's own tissues.

What is pathologic apoptosis?

Regulated cell death caused by cellular injury or disease, such as severe DNA damage, accumulation of misfolded proteins, or certain viral infections.

What are important causes of pathologic apoptosis?

DNA damage, misfolded proteins/ER stress, and some viral infections.

What happens to the cell during apoptosis?

The cell shrinks, chromatin condenses, the nucleus fragments, and the cell breaks into membrane-bound apoptotic bodies.

What are apoptotic bodies?

Small membrane-bound fragments of an apoptotic cell containing cellular organelles and nuclear material.

What happens to apoptotic bodies?

They are rapidly phagocytosed by macrophages or neighboring cells.

Why does apoptosis usually not cause inflammation?

The cell membrane remains intact and cellular contents are packaged into apoptotic bodies, preventing significant leakage of inflammatory intracellular contents.

What is the major morphologic difference between necrosis and apoptosis?

Necrosis causes cell swelling and membrane rupture, whereas apoptosis causes cell shrinkage, chromatin condensation, and formation of apoptotic bodies with an intact membrane.

What is the intrinsic pathway of apoptosis?

The mitochondrial pathway of apoptosis, activated by intracellular stress such as DNA damage, growth factor withdrawal, and misfolded proteins.

What is the major organelle involved in the intrinsic pathway?

The mitochondrion.

What are important triggers of the intrinsic pathway?

DNA damage, growth factor withdrawal, misfolded proteins, and severe cellular stress.

What protein family regulates the intrinsic pathway?

The BCL-2 family.

What are anti-apoptotic BCL-2 family proteins?

BCL-2 and BCL-XL.

What is the function of BCL-2 and BCL-XL?

They inhibit apoptosis by maintaining mitochondrial membrane integrity.

What are important pro-apoptotic BCL-2 family proteins?

BAX and BAK.

What is the function of BAX and BAK?

They promote mitochondrial outer membrane permeabilization, allowing cytochrome c to escape.

What happens when mitochondrial outer membrane permeabilization occurs?

Cytochrome c is released from the mitochondria into the cytosol.

What is cytochrome c's role in apoptosis?

It binds APAF-1 and contributes to formation of the apoptosome.

What is APAF-1?

Apoptotic protease-activating factor 1; it combines with cytochrome c to form the apoptosome.

What is the apoptosome?

A protein complex formed by cytochrome c and APAF-1 that activates initiator caspase-9.

Which initiator caspase is activated by the intrinsic pathway?

Caspase-9.

What are initiator caspases?

Caspases that are activated early in apoptotic signaling and activate downstream executioner caspases.

What are executioner caspases?

Caspases that cleave cellular and nuclear proteins and execute the final stages of apoptosis.

What are the major executioner caspases?

Caspase-3, caspase-6, and caspase-7.

What is the intrinsic apoptosis sequence?

Cell stress → BAX/BAK → mitochondrial membrane permeabilization → cytochrome c → APAF-1 → apoptosome → caspase-9 → executioner caspases → apoptosis.

What is the extrinsic pathway of apoptosis?

Apoptosis initiated by activation of cell-surface death receptors by extracellular ligands.

What are important death receptors?

Fas (CD95) and TNF receptor.

What activates Fas?

Fas ligand (FasL).

What happens when FasL binds Fas?

Fas recruits signaling proteins and forms the DISC, which activates caspase-8.

What is DISC?

Death-inducing signaling complex; a signaling complex formed following activation of death receptors that activates initiator caspases.

Which initiator caspase is activated by the extrinsic pathway?

Caspase-8.

What is the extrinsic apoptosis sequence?

FasL → Fas → DISC → caspase-8 → executioner caspases → apoptosis.

What is the cytotoxic T-cell pathway of apoptosis?

A pathway in which cytotoxic T lymphocytes kill target cells using perforin and granzymes.

Which cells use the perforin-granzyme pathway?

Cytotoxic T lymphocytes (CD8+ T cells).

What is perforin?

A protein released by cytotoxic T cells that helps deliver granzymes into target cells.

What are granzymes?

Proteases released by cytotoxic T cells that enter target cells and activate apoptotic pathways, including caspases.

What is the perforin-granzyme sequence?

Cytotoxic T cell → perforin → granzyme entry → caspase activation → apoptosis.

What are caspases?

Proteolytic enzymes that cleave specific proteins during apoptosis.

What does the term caspase refer to?

Cysteine-dependent aspartate-specific protease.

Which caspase is associated with the intrinsic pathway?

Caspase-9.

Which caspase is associated with the extrinsic pathway?

Caspase-8.

Which major executioner caspase should you remember for exams?

Caspase-3.

What happens to phosphatidylserine during apoptosis?

It becomes exposed on the outer surface of the plasma membrane.

What is the significance of phosphatidylserine exposure?

It acts as an "eat me" signal that promotes recognition and phagocytosis of apoptotic cells.

What happens to DNA during apoptosis?

DNA is cleaved in a controlled manner by activated nucleases, producing characteristic DNA fragmentation.

What happens to DNA during necrosis?

DNA is degraded more randomly by nucleases after membrane and organelle damage.

What happens to the cell membrane during necrosis?

The membrane loses integrity and eventually ruptures.

What happens to the cell membrane during apoptosis?

The membrane remains intact, although the cell undergoes surface changes that promote phagocytosis.

Does necrosis usually affect individual cells or groups of cells?

It commonly affects groups of cells within a tissue.

Does apoptosis usually affect individual cells or groups of cells?

It usually affects individual cells.

Is apoptosis energy-dependent?

Yes. Apoptosis is an active, regulated process requiring cellular energy.

Is necrosis a regulated programmed process?

Classic necrosis is generally an uncontrolled consequence of severe cell injury, although regulated forms of necrotic cell death also exist.

Which type of cell death is more strongly associated with inflammation?

Necrosis.

Which type of cell death is associated with little or no inflammation?

Apoptosis.

What is the classic example of coagulative necrosis?

Myocardial infarction.