U01.04.004 Necrosis

Necrosis is a form of cell injury that results from exogenous factors leading to irreversible damage to the plasma membrane. This damage causes the cell to undergo enzymatic degradation and protein denaturation, with intracellular components leaking out, triggering a local inflammatory response, which is a key distinction from apoptosis.

Types of Necrosis

1. Coagulative Necrosis

Seen In: Ischemia/infarcts in most tissues (except the brain)
Cause: Ischemia or infarction that denatures enzymes, leading to blocked proteolysis
Histology:
- Preserved cellular architecture (cell outlines are visible)
- Nuclei disappear
- Cytoplasmic binding of eosin stain results in increased eosinophilia (red/pink color)

2. Liquefactive Necrosis

Seen In: Bacterial abscesses, brain infarcts
Cause: Neutrophils release lysosomal enzymes that digest the tissue
Histology:
- Early: Cellular debris and macrophages are present
- Late: Cystic spaces and cavitation, especially in the brain
- Neutrophils and cell debris are seen with bacterial infection

3. Caseous Necrosis

Seen In: Tuberculosis (TB), systemic fungal infections (e.g., Histoplasma capsulatum), Nocardia
Cause: Macrophages wall off the infecting microorganism, leading to granular debris
Histology:
- Fragmented cells and debris surrounded by lymphocytes and macrophages, forming a granuloma

4. Fat Necrosis

Seen In:
- Enzymatic: Acute pancreatitis (saponification of peripancreatic fat)
- Nonenzymatic: Traumatic injuries (e.g., breast tissue injury)
Cause: Damaged pancreatic cells release lipase, which breaks down triglycerides, releasing fatty acids that bind calcium, leading to saponification
Histology:
- Outlines of dead fat cells without peripheral nuclei
- Saponification of fat (combined with calcium) appears dark blue on H&E stain

5. Fibrinoid Necrosis

Seen In: Immune vascular reactions (e.g., Polyarteritis Nodosa), nonimmune vascular reactions (e.g., hypertensive emergency, preeclampsia)
Cause: Immune complex deposition (Type III hypersensitivity reaction) and/or plasma protein (e.g., fibrin) leakage from damaged vessels
Histology:
- Vessel walls appear thick and pink

6. Gangrenous Necrosis

Seen In: Distal extremities and gastrointestinal (GI) tract, typically after chronic ischemia
Types:
- Dry Gangrene: Resulting from ischemia, showing coagulative necrosis
- Wet Gangrene: Superinfection on top of coagulative necrosis, leading to liquefactive necrosis

Points to Remember

Necrosis differs from apoptosis in that it triggers a local inflammatory response.
Histological patterns vary by the type of necrosis, providing clues to the underlying cause.
Gangrenous necrosis can present as dry (coagulative) or wet (liquefactive) depending on the presence of superinfection.

Table of Necrosis Types

Type	Seen In	Cause	Histology
Coagulative	Ischemia/infarcts (except brain)	Ischemia or infarction; enzyme denaturation	Preserved cell outlines, nuclei disappear, increased eosinophilia (red/pink color)
Liquefactive	Bacterial abscesses, brain infarcts	Lysosomal enzyme release by neutrophils	Early: Cellular debris and macrophages; Late: Cystic spaces, cavitation, neutrophils, and cell debris
Caseous	TB, systemic fungi, Nocardia	Macrophage-mediated walling off	Fragmented cells and debris surrounded by lymphocytes and macrophages (granuloma)
Fat	Acute pancreatitis, traumatic fat injury	Lipase release, saponification	Dead fat cells without nuclei, saponification with dark blue staining on H&E
Fibrinoid	Immune/nonimmune vascular reactions	Immune complex deposition, fibrin leakage	Thick, pink vessel walls
Gangrenous	Distal extremity, GI tract (chronic ischemia)	Dry: Ischemia; Wet: Superinfection	Dry: Coagulative necrosis; Wet: Liquefactive necrosis superimposed on coagulative

Table of Necrosis Types

USMLE Step 1 Review Series

Curriculum

U01.04.004 Necrosis

Types of Necrosis

1. Coagulative Necrosis

2. Liquefactive Necrosis

3. Caseous Necrosis

4. Fat Necrosis

5. Fibrinoid Necrosis

6. Gangrenous Necrosis

Points to Remember

Table of Necrosis Types

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