Cell injury and death II Flashcards by tcarlso 3

What is coagulative necrosis? How does it appear histologically?

the outline of the dead cells are maintained and the tissue is somewhat firm. Nucleus disappears, and there is a wedge shaped and pale area where clot was

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What is liquefactive necrosis?

the dead cells undergo disintegration and affected tissue is liquified via enzymatic lysis

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What is caseous necrosis?

Accumulation of mononuclear cells that mediate the chronic inflammatory reaction and granuloma formation to an offending organism. The lipid in the wall of the organism can’t be fully broken down. The dead cells persist indefinitely as amorphous, coarsely granular eosinophilic debris

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What is fat necrosis?

enzymatic digestion of fat via lipases. The FAs that are released react with Ca to form a soap-like substance

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What is gangrenous necrosis?

Not a specific pattern of cell death, but usually describes limb loss due to lack of circulation

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What type of cell injury results in coagulative necrosis?

Ischemia

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What causes the maintenance of the outline of coagulative cells?

The CT framework

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Why doesn’t the brain undergo coagulative necrosis? What type of necrosis does it undergo?

There is no CT framework, thus undergoes liquefaction necrosis

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What type of necrosis occurs in abscesses? Why?

Liquefactive, b/c center made up of PMNs (thus no CT)

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How does Liquefactive necrosis appear under the microscope?

Amorphus, granular

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What is an abscess filled with? Does it have vascular supply?

Area filled with PMNs.

No vascular supply

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How does caseous necrosis appear grossly?

Grayish, whitish or yellowish

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What are the two organisms that cause caseous necrosis?

Fungi (especially histoplasmosis)

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What does caseous necrosis appear like beneath the microscope?

Granulated material with surrounding giant cells

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What does enzymatic fat necrosis look like grossly?

White, chalky

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What does enzymatic fat necrosis look like microscopically?

Stuff in fat cells rather than their normal, clear appearance

Potentially basophilic if there is enough Ca

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In what disease does enzymatic fat necrosis usually take place? Why?

In pancreatitis

Because lipases produced solely in the pancreas

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Why is fat necrosis seen more often in pts with hyperthyroidism?

Increased Ca in the blood activates enzymes

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What is fibroid necrosis?

Injury in blood vessels with accumulation of plasma proteins causing the wall to stain intensely eosinophilic

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What causes fibroid necrosis?

Antigen-ab complexes activated clotting cascade

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What is wet gangrene?

Combination of gangrene with superimposed bacterial infection

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Green discoloration around a wound indicates what?

Pseudomonas

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What causes reperfusion injury?

lack of enzymes that reduce ROS, leading to a sudden burst of ROS

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What are the three things that ROS damage?

Membranes (via lipd radicals)

Protein (abnormal folding)

DNA (mutations)

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What are the two findings of reperfusion injury besides increased ROS?

1. Expression of cytokines and cell adhesion molecules | 2. Activation of complement pathway

What are the proteins that activate apoptosis?

Caspases

What happens to the plasma membrane in apoptosis?

Remain intact, but it is altered such that the cell and its fragments become targets for phagocytes

What are the stages of apoptosis?

1. Signal to initiate 2. Intracellular signals 3. Execution phase via caspases 4. Removal of dead cells

What is function of caspases in apoptosis?

Catabolize the cytoskeletons and activate endonucleases

What are the two pro-apoptotic proteins in a cell that form holes in the mitochondria? What does this cause?

Bax Bak Causes cyt C to leak out and activate initiator caspases

What is the function of Bcl-2 and Bcl-X?

Block Bax and Bak, thereby inhibiting the apoptosis pathway

What is the ligand used for the extrinsic apoptotic pathway? What happens when this is bound to a signalling protein?

Fas ligand.TNF receptor Causes adaptor proteins to activate the initiator caspases

Where do the intrinsic and extrinsic pathways of apoptosis converge? What happens after this?

Activation of initiator caspases Leads to executioner caspases

What is the role of p53 in apoptosis?

Activates Bax and Bak to start the intrinsic pathway

What are the morphological changes in apoptosis? (4)

1. Shrinkage of cells 2. Condensation of chromatin 3. Formation of apoptotic bodies 4. Phagocytosis of apoptotic bodies

Swelling is seen in what, and shrinkage is seen in what (necrosis/apoptosis)?

``` Apoptosis = shrinkage necrosis = swelling ```

What are the changes in the nucleus for necrosis?

Pyknosis to karyorrhexis to karyolysis

What are the changes in the nucleus for apoptosis?

Fragmentation

What happens to the plasma membrane in necrosis? Apoptosis?

``` Necrosis = Disrupted Apoptosis = intact ```

What happens to the cellular contents in necrosis?

Enzymatic digestion; may leak out of cell

What happens to the cellular contents in apoptosis?

Intact; may be released in apoptotic bodies

Which has inflammation: necrosis or apoptosis?

Necrosis

How can a virus-infected cell undergo apoptosis via the intrinsic pathway?

Activation of p53

What are the cells that destroy virus-infected cells?

Granzymes (cytotoxic T cells)

How can meds indirectly kill cells?

metabolites

What is the MOA of acetominphen causing cell death?

Produces a highly reactive quinone that reacts with proteins/DNA and causes oxidative stress

What is the MOA of CCl4?

CCl4 goes through p450. Metabolite CCl3 radical reacts with apoproteins in the liver, causing FAs to build up

Where do heavy metals affect cells?

ETC in mito

What is the MOA of phalloidin and paclitaxel?

Binds and inhibits cytoskeleton

Which zone of hepatocytes are most affected by drugs? Why?

Zone 3--farthest from initial site of contact with metabolizing hepatocytes

Name the type of necrosis: the outline of the dead cells are maintained and the tissue is somewhat firm.

Coagulative necrosis

Name the type of necrosis:the dead cells undergo disintegration and affected tissue is liquified.

Liquifactive necrosis

Name the type of necrosis: a form of coagulative necrosis (cheese-like). Example: tuberculosis lesions.

Caseous necrosis

Name the type of necrosis: enzymatic digestion of fat. Example: necrosis of fat by pancreatic enzymes.

Fat necrosis

Name the type of necrosis: Necrosis (usually secondary to ischemia) affecting multiple tissue types (skin, nerve, muscle, etc). It can be dry where the tissue is mummified or wet (usually with superimposed infection). Example: necrosis of distal limbs, usually foot and toes in diabetes.

Gangrenous necrosis

What is the effect of caspases?

Cleavage of proteins

What is the crucial event in apoptosis?

abnormal mitochondrial membrane permeability which allows escape of cytochrome-c into the cystosol which, in turn, activates proteolytic enzymes (caspases)

What does coagulative necrosis look like histologically?

Increased acidophilic uptake

What is the order of protein degradation and enzymatic degradation in coagulative vs liquefactive necrosis?

``` Coag = Proteins denature first, then enzymatic destruction Liq = Enzymes first, then protein denaturation ```

What is the histological appearance of fatty necrosis?

Blue staining d/t Ca deposits

How does fibrinoid necrosis appear histologically?

Amorphous and pink

Reversible or irreversible: ATP depletion cell injury

Reversible

Reversible or irreversible: mito swelling

Reversible

Reversible or irreversible:membrane blebing

Reversible

Reversible or irreversible: Nuclear pyknosis/karyorrhexis/karyolysis

Irreversible

Reversible or irreversible: lysosomal rupture

Irreversible

Reversible or irreversible: increased mitochondrial permeability

Irreversible

What are red infarcts seen in? White?

``` Red = multiple blood supply (red = reperfusion) White = Solid tissues with single blood supply ```

What is the most damaging ROS?

OH* radical

What are the three causes of decreased oxygen in a tissue?

1. Ischemia (lowered blood flow) 2. Hypoxemia (pO2) 3. Anemia/CO binding

What are the three membranes that are damages in Irreversible injury?

Plasmalemma Mitochondrial inner membrane Lysosomal

What are the two signs of CO poisoning?

HA | Cherry red face

What does the blood look like in methemoglobinemia?

Chocolate-colored

Is apocrine metaplasia a risk for CA?

What is keratomalacia?

Loss of Vit A, leading to loss of conjunctiva

What is myositis ossificans?

Mesenchymal tissues undergone metaplasia to bone.

Streak injury in an ovary = ?

Turner's syndrome

Is metaplasia reversible?

yes