Irreversible Cellular Damage

Question 1

What are some causes of cell injury?

Answer 1

Hypoxia

Ischemia

Chemicals, drugs and toxins

Infection

Nutritional imbalances

Immune system reactions

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

Question 2

What is the difference between hypoxia and ischemia?

Answer 2

Ischemia = loss oxygen and nutrients (decreased blood flow)

Hypoxia = decreased oxygen availability

Question 3

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?

Answer 3

• 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

Question 4

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

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

Answer 4

Troponin

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

Question 5

Explain generally what the message of this diagram is.

Answer 5

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.

Question 6

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

Answer 6

Question 7

Explain the cellular mechanisms that lead to injury upon reperfusion.

Answer 7

Question 8

What are the categories of cell death?

Answer 8

Question 9

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

Answer 9

Bcl X_L

Bcl-w

Question 10

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

Answer 10

Bax

Bak

Bad

Bid

Bim

Bik

Question 11

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

Answer 11

2, 8, 9, 10

Question 12

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

Answer 12

3, 6, 7

Question 13

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

Question 14

Review the intrinsic and extrinsic pathways of apoptosis.

Answer 14

Question 15

Which proteins are pro-survival with respect to apoptosis?

Which are pro-apoptotic?

Answer 15

Bcl-2; Bcl-XL; Bcl-w

Bim; Bik; Egl-1; BH3

Question 16

What morphological changes are characteristic of cells under going apoptosis?

Answer 16

Question 17

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

Answer 17

False - the opposite

Question 18

What are the morphologic differences between apoptosis and necrosis?

Answer 18

Question 19

Coagulative necrosis

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

Answer 19

Question 20

What are the different subtypes of necrosis?

Answer 20

Coagulative

Liquefactive

Caseous

Fat

Fibrinoid

Gangrenous

Question 21

Liquefactive Necrosis

• Architecture of tissue?
• Where is this most commonly seen?

Answer 21

Question 22

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”?

Answer 22

ALWAYS THINK OF TUBERCULOSIS

Question 23

Fat Necrosis

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

Answer 23

Question 24

Fibrinoid Necrosis

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

Answer 24

Arterioles in people with lupus

Malignant Hypertension

Question 25

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?

Answer 25

* See slide * Wet = superimposed infection with liquefactive necrosis * Dry = coagulative necrosis; no infection * Feet, bowel

Question 26

PAMPS are on the surface membrane of [...] DAMPS are located in the [...] of [...] cells

Answer 26

Resident dendritic cells and macrophages Cytosol; resident dendritic cells

Question 27

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

Answer 27

IL-1 Local recruitment of neutrophils Fever

Question 28

Describe the hosts inflammatory response to necrosis.

Answer 28