1 - Cell Injury Flashcards
Why is damage to lysosomal membranes so damaging to cells?
Leakage of lysosomal enzymes will digest cellular components (autodigestion).
What is the meaning of the term hypoxia?
Diminished availability of oxygen to the body tissues
What is cellular hydropic degeneration, and what does it imply?
Cellular hydropic degeneration is when cells become pale, swollen and vacuolated after acute cell injury. The presence of hydropic degeneration implies that acute cell injury has occurred.
What is the correct term for “oxygen deficiency” resulting in diminished availability of oxygen to the body tissues?
Hypoxia
Which extracellular ion, when allowed to leak into an injured cell, activates destructive enzymes causing membrane, cytoskeleton and nuclear damage as well as ATP depletion?
Calcium / Ca2+
Why is ischemia more deleterious to tissues than hypoxia?
Hypoxia results in reduced O2 availability to cells. Ischemia results not only in reduced O2 availability but also reduced delivery of nutrients, water, hormones, growth factors etc. In addition, CO2 and cellular waste products are not removed. Ischemic cells die much more rapidly than hypoxic cells.
Which is more deleterious to tissues: hypoxia or ischemia?
Ischemia.
(Hypoxia results in reduced O2 availability to cells. Ischemia results not only in reduced O2 availability but also reduced delivery of nutrients, water, hormones, growth factors etc. In addition, CO2 and cellular waste products are not removed. Ischemic cells die much more rapidly than hypoxic cells.)
Free radicals are highly reactive and damaging to cells. What are four ways in which they are generated in cells?
(1) Normal oxidative metabolism (i.e., being alive!)
(2) Exposure to toxins, radiation, chemicals, drugs …
(3) Reperfusion injury
(4) Inflammation (phagocytic inflammatory cells release them deliberately)
After cellular injury, levels of calcium within the cytosol often rise. What are two mechanisms by which this rise in cytosolic calcium happens?
(1) Extracellular Ca2+ enters the cell due to membrane pump failure, usually caused by ATP depletion or direct membrane damage.
(2) Intracellular Ca2+, which is sequestered within organelles in healthy cells, leaks into the cytosol from damaged organelles.
Why is it important in cells to keep iron and copper bound to storage or transport proteins?
Iron and copper can catalyze formation of free radicals. Being bound to storage and transport proteins reduces this ability.
What are the three main ways in which the generation or persistence of free radicals within cells is minimized?
(1) Antioxidants that block formation of, or inactivate, free radicals
(2) Enzymes that inactivate free radicals
(3) Storage and transport proteins that bind iron and copper (Fe and Cu can catalyze formation of free radicals)
One effect of cellular injury is loss of cellular calcium homeostasis, with leakage of calcium into cells. What are the two main ways in which this is harmful to cells?
(1) Ca2+ activates four types of destructive enzymes -> membrane, cytoskeleton & nuclear damage and ATP depletion
(2) Ca2+ also stimulates inflammation -> further tissue damage
Which of the following is the most common and important cause of cellular injury and death?
(a) Direct damage to cellular processes, including DNA damage, by intracellular microbial pathogens
(b) Hypoxia
(c) Ultraviolet radiation injury
(b) Hypoxia
Roughly how long does it take after cellular injury before clinicopathologic (i.e., blood or urine test) changes can be detected?
(a) up to 2 hours
(b) 4-12 hours
(c) 12-24 hours
(d) 4-7 days
(a) up to 2 hours
At the basic level, most cellular injury results from (some or all of) three processes. What are these three processes?
Hypoxia
Ischemia
Membrane damage
Superoxide and peroxide are examples of what?
Free radicals, or reactive oxygen species (ROS)
Describe the characteristic microscopic appearance of an acutely injured cell with hydropic degeneration.
Cells have a pale, slightly granular appearance. As the process continues, cells become markedly swollen and vacuoles appear in the cytoplasm.
Hypoxia may result from oxygen not getting into the blood in sufficient amounts. Name three situations / diseases that could cause this.
Lung disease
Suffocation or asphyxiation
Low 02 environment (e.g., drowning, high altitude)
Hypoxia may result from oxygen not being delivered to cells by the blood. Name three situations / diseases that could cause this.
Heart disease (blood not moved effectively)
Anaemia (reduced 02 carrying capacity of blood)
Blood vessel blockage by thrombosis, compression, torsion etc. (downstream ischemia)
Carbon monoxide poisoning (reduced 02 carrying capacity of blood)
Roughly how long does it take after cellular injury before light microscopic changes can be detected?
(a) up to 2 hours
(b) 4-12 hours
(c) 12-24 hours
(d) 4-7 days
(b) 4-12 hours
Name two important enzymes used by cells that inactivate free radicals.
Superoxide dismutase (SOD)
Glutathione peroxidase
Roughly how long does it take after cellular injury before gross (naked eye) changes can be detected?
(a) up to 2 hours
(b) 4-12 hours
(c) 12-24 hours
(d) 4-7 days
(c) 12-24 hours
Roughly how long does it take after cellular injury before ultrastructural (i.e., electron microscopic) changes can be detected?
(a) up to 2 hours
(b) 4-12 hours
(c) 12-24 hours
(d) 4-7 days
(a) up to 2 hours
What is the term used for the acute cell swelling seen as an early, fundamental expression of cell injury?
Hydropic degeneration
What is the term for reduced blood flow to a region of the body, usually because of obstruction of the blood supply?
Ischemia
Hypoxic or toxic insults to cells often result in reduced ATP levels. Explain the pathogenesis whereby this can result in cell swelling.
Hypoxia -> reduced ATP -> membrane Na+/K+ pumps fail -> Na+ moves into cell -> water follows along osmotic gradient -> cell swells. [In other words, cell volume control is an energy dependent process relying on membrane pumps that keep sodium outside and potassium inside the cell. When these pumps fail, cell swelling results by osmotic movement of water into the cell from the extracellular space.]
Name four cell types that are very susceptible to hypoxic injury, and may die within minutes of oxygen deprivation.
Neurons, myocardial cells, renal epithelial cells, hepatocytes
What is the fundamental microscopic change seen in acutely injured cells?
Swelling (acute cell swelling or hydropic degeneration)
Rank the following cell types in DEscending order of susceptibility to hypoxia (i.e., most susceptible to least susceptible):
(a) Epidermal cells
(b) Hepatocytes
(c) Neurons
[Most susceptible] (c) Neurons -> (b) Hepatocytes -> (a) Epithelial cells [Least susceptible]
Which three cellular structures, when injured, cause the most serious effects to the cell, including possible cell death?
Nucleus / DNA
Membranes (plasma and organelle)
Mitochondria
What is the meaning of the term ischemia?
Ischemia is reduced blood flow to a region of the body, usually because of obstruction of the blood supply
Name two important antioxidants used by cells.
[Any 2]
Vitamin E
Vitamin A
Vitamin C
Selenium
Are intracellular calcium levels normally higher or lower than extracellular calcium levels?
Lower. And even within the cell, calcium within the cytosol is kept to a minimum by being sequestered inside organelles.
