Cell Injury and Cell Death I and II Flashcards

1
Q

Why is an elevated blood level of cardiac troponin used as an indicator of a myocardial infarct?

A
  • cardiac troponin is normally found inside cardiac muscle cells
  • when the cells infarct, they lyse and release the protein in the blood stream
  • since this protein is not normally found in the blood, and is not found in any other tissue, it can be measured to determine if a myocardial infarct is occurring or has recently occurred

*at least two hours after injury

0.07 spike for minor myocardial infarction
50 spike for acute MI
myocarditis: trop level stays around 0.05 limit

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2
Q

What are the three types of irreversible nuclear changes?

A
  • pyknosis
  • karyorrhexis
  • karyholysis
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3
Q

What happens to the nucleus in pyknosis?

A

nucleus compacts

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4
Q

What happens to the nucleus in karyorrhexis?

A

chromatin breaks into smaller pieces

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5
Q

What happens to the nucleus in karyolysis?

A

chromatin begins to dissolve

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6
Q

What are possible causes of hypoxia without ischemia?

A
  • high altitude
  • sickle cell anemia
    (shows as bright red blood in CO poisoning)
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7
Q

What are the six types of necrosis?

A
  • coagulation necrosis
  • liquefactive necrosis
  • fat necrosis
  • caseous necrosis
  • fibroid necrosis
  • gangrenous necrosis
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8
Q

What are the etiology and morphologic features of coagulation necrosis?

A

Cause: hypoxic cell of death

Grossly: 
appear white (lighter than the normal tissue) and wedge-shaped from the point at which the ischemia occurred

Microscopically:

  • cells maintain structure but lack nuclei (or have nuclear changes indicative of cell death)
  • very eosinophilic (red=death)
  • protein denaturation is the dominant feature (red!)
  • neutrophils present to clean
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9
Q

What are the etiology and morphologic features of liquefactive necrosis?

A

Cause: focal infection by bacteria or fungi due to accumulation of inflammatory cells (neutrophils)

Grossly:
appears as abscess (pus collection)

Microscopically:

  • appears as though cells are digested
  • neutrophils and debris are present
  • tissue digestion is the dominant feature
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10
Q

What are the etiology and morphologic features of fat necrosis?

A

Cause: acute pancreatitis or trauma leads to digestion of fat cell membranes and the triglycerides stored in fat cells
(issue with diseased neighboring tissue –> cells die, release contents which attack adjacent adipose tissue)

Grossly:
tissue looks chalky due to saponification (combination of fat tissue with calcium)

Microscopically:
- vague outlines of fat cells are present

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11
Q

What are the etiology and morphologic features of caseous necrosis?

A

Cause: chronic inflammation, certain infections (ex: TB, valley fever-coccidioides immitis) that the body can’t fight are walled off in the body, forming granulomas

Microscopically:

  • granulomas - center part becomes filled with dead cells and debris
  • cells do not retain their outlines and appear as granular eosinophilic cell debris
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12
Q

What are the etiology and morphologic features of fibrinoid necrosis?

A

Cause/Location: injured blood vessels

Microscopically:

  • tissue appears bright pink and granular, resembling fibrin
  • composed of fibrin, plasma proteins, and complement

(fibrin: acute inflammation for forming clots)

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13
Q

What are the etiology and morphologic features of gangrenous necrosis?

A

Ischemic necrosis

Cause: low blood flow; usually portion of lower extremities (similar to coagulative, but due to location, called gangrenous)

If bacterial and inflammatory cells are less involved: resembles coagulative necrosis
(dry gangrene; ex: frost bite)

If bacterial and inflammatory cells are recruited: resembles liquefactive necrosis
(wet gangrene; ex: diabetes)

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14
Q

Summarize the molecular changes occurring in cells exposed to hypoxia and relate these changes to the microscopic appearance of reversibly, and irreversibly, injured cells.

A
  • lack of oxygen prevents mitochondria from generating ATP via oxidative phosphorylation
  • as ATP production falls, sodium and potassium pumps shut down. Sodium and calcium enter the cell; potassium leaves. Water also enters the cell, causing swelling
  • ATP is now produced by glycolysis; lactic acid accumulates in the cell. The lower cell pH causes changes in chromatin (clumps) and proteins
  • ribosomes detach from the RER; protein synthesis is compromised; lipids accumulate in cell –> lipoproteins not formed b/c protein synthesis decreased
  • the extra water in the cell that causes swelling also effects the ER and mitochondria. This change is reversible if oxygen is returned to the cell
  • if oxygen does not return, the chromatin will condense into a very dense state before breaking up into chunks and then nucleic acids
  • the presence of calcium in the cells over physiologic levels activates enzymes that will break down cellular components
  • the membranes will lyse, including that of the mitochondria, ER, and Golgi
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15
Q

Due to ATP production by glycolysis and lactic acid accumulation in the cell, pH is lowered (cell more acidic). What happens to the nucleus?

A
  • chromatin clumps
    if oxygen does not return to cell, chromatin will condense into a very dense state before breaking up into chunks and then nucleic acids
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16
Q

The presence of calcium in the cells over physiologic levels causes what?

A
  • the presence of calcium in the cells over physiologic levels activates enzymes that will break down cellular components
  • the membranes will lyse, including that of the mitochondria, ER, and Golgi
17
Q

What is the method by which cyanide injures cells?

A
  • cyanide binds to complex IV: cytochrome oxidase
  • this blocks the electron transport chain and the effect of cytochrome C
  • ATP production through oxidative phosphorylation is halted and the cell dies
18
Q

What is the role of glutathione in cells?

A
  • glutathione (GSH) is major intracellular redox buffer
  • non-enzymatic antioxidant (defense against reactive oxygen species)

when GSH depleted, free radical causes oxidative damage to proteins, DNA, lipids

19
Q

Why is N-acetylcysteine used to treat acetaminophen poisoning?

A
  • N-acetylcysteine can be taken up by hepatocytes (liver cells) and provide the cysteine needed for glutathione syntehsis
  • glutathione takes up the free radical that is generated during the metabolism of acetaminophen
  • glutathine itself cannot be taken up by hepatocytes, but is needed to clear the radical
20
Q

What are two types of chemical injury?

A
  • direct toxicity (cyanide injured cells)

- conversion to toxic metabolites (acetomenophin toxicity)

21
Q

Describe the function of Bcl-2 in relation to apoptosis and cancer

A
  • Bcl-2 inhibits the release from mitochondria of apoptotic factors. In a normal cell, small amounts of Bcl-2 are produced, but if conditions dictate that the cell should die then Bcl-2 production will stop and the cell will undergo apoptosis
  • in a cancer cell, the cell machinery has gone haywire but there is so much Bcl-2 present that the mitochondria cannot release any apoptotic factors
22
Q

Necrosis vs. Apoptosis

cellular swelling or condensation? ATP?

A

Necrosis:
- cellular swelling due to ATP depletion

Apoptosis:
- cellular condensation; requires ATP

23
Q

Necrosis vs. Apoptosis

What are they the result of?

A

Necrosis:
- result of sever cell/tissue injury

Apoptosis:
- regulated process

24
Q

Necrosis vs. Apoptosis

What happens to cell membranes?

A

Necrosis:
- broken cell membranes

Apoptosis:
- intact cell membranes

25
Q

Necrosis vs. Apoptosis

Detectable in tissue?

A

Necrosis:
- readily apparent in the tissue

Apoptosis:
- difficult to detect in the tissue

26
Q

Necrosis vs. Apoptosis

Inflammatory response?

A

Necrosis:
- inflammatory response

Apoptosis:
- no inflammatory response