pathoma cell death

Question 1

What is the morphologic hallmark of cell death?

Answer 1

Loss of the nucleus, which occurs via nuclear condensation (pyknosis), fragmentation (karyorrhexis), and dissolution (karyolysis)

Question 2

Define necrosis.

Answer 2

Death of large groups of cells followed by acute inflammation, due to an underlying pathologic process; it is never physiologic

Question 3

What are the gross patterns of necrosis?

Answer 3

Coagulative necrosis, liquefactive necrosis, gangrenous necrosis, and caseous necrosis.

Question 4

Describe coagulative necrosis.

Answer 4

Necrotic tissue that remains firm; cell shape and organ structure are preserved by coagulation of proteins, but the nucleus disappears.

Question 5

What is a characteristic feature of coagulative necrosis?

Answer 5

It is characteristic of ischemic infarction of any organ except the brain.

Question 6

What distinguishes red infarction in coagulative necrosis?

Answer 6

It arises if blood re-enters a loosely organized tissue, such as in pulmonary or testicular infarction

Question 7

What happens to tissue in liquefactive necrosis?

Answer 7

Necrotic tissue becomes liquefied due to enzymatic lysis of cells and proteins.

Question 8

Give examples of conditions associated with liquefactive necrosis.

Answer 8

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.

Question 9

Describe gangrenous necrosis.

Answer 9

Coagulative necrosis that resembles mummified tissue (dry gangrene), often seen in ischemia of the lower limb and GI tract.

Question 10

What is “wet gangrene”?

Answer 10

If a superimposed infection occurs in gangrenous tissue, liquefactive necrosis ensues, forming wet gangrene

Question 11

What characterizes caseous necrosis?

Answer 11

Soft, friable necrotic tissue with a “cottage cheese-like” appearance, a combination of coagulative and liquefactive necrosis

Question 12

What conditions are associated with caseous necrosis?

Answer 12

Granulomatous inflammation due to tuberculosis or fungal infections.

Question 13

What is fat necrosis?

Answer 13

Necrotic adipose tissue with a chalky-white appearance due to calcium deposition.

Question 14

What conditions are associated with fat necrosis?

Answer 14

Trauma to fat (e.g., breast) and pancreatitis-mediated damage of peripancreatic fat

Question 15

What process occurs in fat necrosis involving calcium?

Answer 15

Saponification, where fatty acids join with calcium, forming deposits through dystrophic calcification.

Question 16

Differentiate between dystrophic calcification and metastatic calcification.

Answer 16

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).

Question 17

What is fibrinoid necrosis?

Answer 17

Necrotic damage to blood vessel walls, with proteins (including fibrin) leaking into the wall, causing bright pink staining microscopically.

Question 18

What conditions are associated with fibrinoid necrosis?

Answer 18

Malignant hypertension and vasculitis.

Question 19

Give examples of physiological apoptosis.

Answer 19

Endometrial shedding during the menstrual cycle.

Removal of cells during embryogenesis.

CD8+ T cell-mediated killing of virally infected cells.

Question 20

What happens to a cell during apoptosis?

Answer 20

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.

Question 21

What mediates apoptosis?

Answer 21

Caspases, which activate proteases (to break down the cytoskeleton) and endonucleases (to break down DNA).

Question 22

How are caspases activated in the intrinsic mitochondrial pathway?

Answer 22

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.

Question 23

What is the extrinsic receptor-ligand pathway of apoptosis?

Answer 23

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.

Question 24

What is the cytotoxic CD8+ T cell-mediated pathway of apoptosis?

Answer 24

1. Perforins from CD8+ T cells create pores in the target cell membrane.
2. Granzyme enters through these pores to activate caspases.
3. An example is the killing of virally infected cells by CD8+ T cells

Question 25

What are free radicals?

Answer 25

Chemical species with an unpaired electron in their outer orbit

Question 26

How are free radicals physiologically generated?

Answer 26

During oxidative phosphorylation, cytochrome c oxidase transfers electrons to oxygen, partially reducing it to form superoxide (O2−), hydrogen peroxide (H2O2), and hydroxyl radicals (OH).

Question 27

List the pathologic causes of free radical generation.

Answer 27

1.Ionizing radiation: Hydrolyzes water to form hydroxyl free radicals.

2. Inflammation: NADPH oxidase generates superoxide ions during oxygen-dependent killing by neutrophils.

3.Metals (e.g., copper, iron): Fe2+ generates hydroxyl radicals (Fenton reaction).

4.Drugs and chemicals: Liver P450 system metabolizes drugs (e.g., acetaminophen) to produce free radicals.

Question 28

How do free radicals cause cellular injury?

Answer 28

Through lipid peroxidation and oxidation of DNA and proteins, with DNA damage being implicated in aging and oncogenesis.

Question 29

What are the mechanisms for free radical elimination?

Answer 29

1.Antioxidants (e.g., glutathione, vitamins A, C, and E).

2.Enzymes:
Superoxide dismutase: Converts superoxide to H2O2.
Glutathione peroxidase: Neutralizes free radicals.
Catalase: Converts H2O2 to oxygen and water.

3.Metal carrier proteins (e.g., transferrin, ceruloplasmin).

Question 30

What is carbon tetrachloride (CCl4) toxicity?

Answer 30

1. CCl4, used as an organic solvent in dry cleaning, is converted to CCl3 free radical by hepatocyte P450 enzymes.
2. Results in RER swelling, ribosome detachment, impaired protein synthesis, and decreased apolipoproteins, causing fatty liver changes.

Question 31

What is reperfusion injury?

Answer 31

1. When blood returns to ischemic tissue, O2-derived free radicals are produced, causing further tissue damage.
2. Leads to a continued rise in cardiac enzymes (e.g., troponin) after reperfusion of infarcted myocardial tissue.