pathoma cell death Flashcards
What is the morphologic hallmark of cell death?
Loss of the nucleus, which occurs via nuclear condensation (pyknosis), fragmentation (karyorrhexis), and dissolution (karyolysis)
Define necrosis.
Death of large groups of cells followed by acute inflammation, due to an underlying pathologic process; it is never physiologic
What are the gross patterns of necrosis?
Coagulative necrosis, liquefactive necrosis, gangrenous necrosis, and caseous necrosis.
Describe coagulative necrosis.
Necrotic tissue that remains firm; cell shape and organ structure are preserved by coagulation of proteins, but the nucleus disappears.
What is a characteristic feature of coagulative necrosis?
It is characteristic of ischemic infarction of any organ except the brain.
What distinguishes red infarction in coagulative necrosis?
It arises if blood re-enters a loosely organized tissue, such as in pulmonary or testicular infarction
What happens to tissue in liquefactive necrosis?
Necrotic tissue becomes liquefied due to enzymatic lysis of cells and proteins.
Give examples of conditions associated with liquefactive necrosis.
Brain infarction: Proteolytic enzymes from microglial cells liquefy the brain.
Abscess: Proteolytic enzymes from neutrophils liquefy tissue.
Pancreatitis: Proteolytic enzymes from the pancreas liquefy parenchyma.
Describe gangrenous necrosis.
Coagulative necrosis that resembles mummified tissue (dry gangrene), often seen in ischemia of the lower limb and GI tract.
What is “wet gangrene”?
If a superimposed infection occurs in gangrenous tissue, liquefactive necrosis ensues, forming wet gangrene
What characterizes caseous necrosis?
Soft, friable necrotic tissue with a “cottage cheese-like” appearance, a combination of coagulative and liquefactive necrosis
What conditions are associated with caseous necrosis?
Granulomatous inflammation due to tuberculosis or fungal infections.
What is fat necrosis?
Necrotic adipose tissue with a chalky-white appearance due to calcium deposition.
What conditions are associated with fat necrosis?
Trauma to fat (e.g., breast) and pancreatitis-mediated damage of peripancreatic fat
What process occurs in fat necrosis involving calcium?
Saponification, where fatty acids join with calcium, forming deposits through dystrophic calcification.
Differentiate between dystrophic calcification and metastatic calcification.
Dystrophic calcification: Calcium deposits on dead tissues with normal serum calcium and phosphate levels.
Metastatic calcification: Calcium deposits in normal tissues due to high serum calcium or phosphate levels (e.g., hyperparathyroidism).
What is fibrinoid necrosis?
Necrotic damage to blood vessel walls, with proteins (including fibrin) leaking into the wall, causing bright pink staining microscopically.
What conditions are associated with fibrinoid necrosis?
Malignant hypertension and vasculitis.
Give examples of physiological apoptosis.
Endometrial shedding during the menstrual cycle.
Removal of cells during embryogenesis.
CD8+ T cell-mediated killing of virally infected cells.
What happens to a cell during apoptosis?
The cell shrinks, making the cytoplasm more eosinophilic (pink).
The nucleus condenses and fragments in an organized manner.
Apoptotic bodies form and are removed by macrophages, without inflammation.
What mediates apoptosis?
Caspases, which activate proteases (to break down the cytoskeleton) and endonucleases (to break down DNA).
How are caspases activated in the intrinsic mitochondrial pathway?
Cellular injury, DNA damage, or decreased hormonal stimulation inactivates Bcl2.
Lack of Bcl2 allows cytochrome c to leak from the mitochondrial matrix into the cytoplasm, activating caspases.
What is the extrinsic receptor-ligand pathway of apoptosis?
1.FAS ligand binds the FAS death receptor (CD95) on the target cell, activating caspases (e.g., negative selection of thymocytes in the thymus).
2.Tumor necrosis factor (TNF) binds to the TNF receptor on the target cell, activating caspases.
What is the cytotoxic CD8+ T cell-mediated pathway of apoptosis?
- Perforins from CD8+ T cells create pores in the target cell membrane.
- Granzyme enters through these pores to activate caspases.
- An example is the killing of virally infected cells by CD8+ T cells
