Irreversible Cellular Damage Flashcards
What are some causes of cell injury?
Hypoxia
Ischemia
Chemicals, drugs and toxins
Infection
Nutritional imbalances
Immune system reactions
Physical agents (trauma, hot/cold, pressure, radiation, electricity, etc.)
What is the difference between hypoxia and ischemia?
Ischemia = loss oxygen and nutrients (decreased blood flow)
Hypoxia = decreased oxygen availability
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?
- 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
[…] is measured in the blood to detect an MI.
Why isn’t this compound immediately detectable in the blood?
Troponin
Goes to lymphatics first –> enters interstitial fluid and then lymphatics before going to blood
Explain generally what the message of this diagram is.
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.
Explain on a cellular level why ischemia leads to increased Ca++ and cell death.
Explain the cellular mechanisms that lead to injury upon reperfusion.
What are the categories of cell death?
There is a family of signals called Bcl-2 that are involved in apotosis. Which proteins in this family are anti-apototic?
Bcl XL
Bcl-w
There is a family of signals called Bcl-2 that are involved in apotosis. Which proteins in this family are pro-apototic?
Bax
Bak
Bad
Bid
Bim
Bik
There is a family of signals called caspases that are involved in apoptosis. Which of these caspases are initiator caspases?
2, 8, 9, 10
There is a family of signals called caspases that are involved in apoptosis. Which of these caspases are executioner caspases?
3, 6, 7
There is a family of signals called caspases that are involved in apoptosis. Which of these caspases are inflammatory caspases?
Review the intrinsic and extrinsic pathways of apoptosis.
Which proteins are pro-survival with respect to apoptosis?
Which are pro-apoptotic?
Bcl-2; Bcl-XL; Bcl-w
Bim; Bik; Egl-1; BH3
What morphological changes are characteristic of cells under going apoptosis?
True/False: Necrosis does not illicit an inflammatory response, but apoptosis does.
False - the opposite
What are the morphologic differences between apoptosis and necrosis?
Coagulative necrosis
- Architecture of cells
- How they appear on histology
- What is the usual cause
What are the different subtypes of necrosis?
Coagulative
Liquefactive
Caseous
Fat
Fibrinoid
Gangrenous
Liquefactive Necrosis
- Architecture of tissue?
- Where is this most commonly seen?
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”?
ALWAYS THINK OF TUBERCULOSIS
Fat Necrosis
- What the cause is
- Most common disease caused by this
*
Fibrinoid Necrosis
- What are the 2 situations that cause this to happen?
- What are the 2 common “classical” examples of this type of necrosis?
Arterioles in people with lupus
Malignant Hypertension
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?
- See slide
- Wet = superimposed infection with liquefactive necrosis
- Dry = coagulative necrosis; no infection
- Feet, bowel
PAMPS are on the surface membrane of […]
DAMPS are located in the […] of […] cells
Resident dendritic cells and macrophages
Cytosol; resident dendritic cells
When a DAMP is activated, what cytokine does it produce and what effect does this have on the body?
IL-1
Local recruitment of neutrophils
Fever
Describe the hosts inflammatory response to necrosis.
