Irreversible Cellular Damage Flashcards

1
Q

What are some causes of cell injury?

A

Hypoxia

Ischemia

Chemicals, drugs and toxins

Infection

Nutritional imbalances

Immune system reactions

Physical agents (trauma, hot/cold, pressure, radiation, electricity, etc.)

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2
Q

What is the difference between hypoxia and ischemia?

A

Ischemia = loss oxygen and nutrients (decreased blood flow)

Hypoxia = decreased oxygen availability

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3
Q

In the case of coronary artery disease where a person encounters a blockage of the LAD:

  • Which part of the heart muscle wall is affected by this loss of oxygen most?
  • What is an early sign of blockage on EKG?
  • What is a late sign of blockage on EKG?
A
  • Endocardium and purkinje cells
  • Non-STEMI –> ST depression or T wave inversion –> indicative of loss of oxygen to endocardial surface not whole myocardium
  • STEMI –> ST elevation, Q wave formation –> indicative of full involvement / blockage of oxygen to the myocardium from that vessel
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4
Q

[…] is measured in the blood to detect an MI.

Why isn’t this compound immediately detectable in the blood?

A

Troponin

Goes to lymphatics first –> enters interstitial fluid and then lymphatics before going to blood

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5
Q

Explain generally what the message of this diagram is.

A

Ischemia ultimately causes a rapid decline in pH leading to Ca++ overload and activation of proteases that degrade the cellular structure and cause cell death. If a person experiences ischemia for a long enough time or that is severe enough in its impact on all organ systems, they can die.

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6
Q

Explain on a cellular level why ischemia leads to increased Ca++ and cell death.

A
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7
Q

Explain the cellular mechanisms that lead to injury upon reperfusion.

A
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8
Q

What are the categories of cell death?

A
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9
Q

There is a family of signals called Bcl-2 that are involved in apotosis. Which proteins in this family are anti-apototic?

A

Bcl XL

Bcl-w

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10
Q

There is a family of signals called Bcl-2 that are involved in apotosis. Which proteins in this family are pro-apototic?

A

Bax

Bak

Bad

Bid

Bim

Bik

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11
Q

There is a family of signals called caspases that are involved in apoptosis. Which of these caspases are initiator caspases?

A

2, 8, 9, 10

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12
Q

There is a family of signals called caspases that are involved in apoptosis. Which of these caspases are executioner caspases?

A

3, 6, 7

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13
Q

There is a family of signals called caspases that are involved in apoptosis. Which of these caspases are inflammatory caspases?

A
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14
Q

Review the intrinsic and extrinsic pathways of apoptosis.

A
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15
Q

Which proteins are pro-survival with respect to apoptosis?

Which are pro-apoptotic?

A

Bcl-2; Bcl-XL; Bcl-w

Bim; Bik; Egl-1; BH3

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16
Q

What morphological changes are characteristic of cells under going apoptosis?

A
17
Q

True/False: Necrosis does not illicit an inflammatory response, but apoptosis does.

A

False - the opposite

18
Q

What are the morphologic differences between apoptosis and necrosis?

A
19
Q

Coagulative necrosis

  • Architecture of cells
  • How they appear on histology
  • What is the usual cause
A
20
Q

What are the different subtypes of necrosis?

A

Coagulative

Liquefactive

Caseous

Fat

Fibrinoid

Gangrenous

21
Q

Liquefactive Necrosis

  • Architecture of tissue?
  • Where is this most commonly seen?
A
22
Q

Caseous Necrosis

  • What is the appearance of the tissue?
  • When is this most commonly seen?
  • What disease should you always think of when someone says “caseous necrosis”?
A

ALWAYS THINK OF TUBERCULOSIS

23
Q

Fat Necrosis

  • What the cause is
  • Most common disease caused by this
    *
A
24
Q

Fibrinoid Necrosis

  • What are the 2 situations that cause this to happen?
  • What are the 2 common “classical” examples of this type of necrosis?
A

Arterioles in people with lupus

Malignant Hypertension

25
Q

Gangrenous necrosis

  • What does this refer to?
  • What is the difference between wet and dry gangrene?
  • Where in the body is this seen most often?
A
  • See slide
  • Wet = superimposed infection with liquefactive necrosis
  • Dry = coagulative necrosis; no infection
  • Feet, bowel
26
Q

PAMPS are on the surface membrane of […]

DAMPS are located in the […] of […] cells

A

Resident dendritic cells and macrophages

Cytosol; resident dendritic cells

27
Q

When a DAMP is activated, what cytokine does it produce and what effect does this have on the body?

A

IL-1

Local recruitment of neutrophils

Fever

28
Q

Describe the hosts inflammatory response to necrosis.

A