2025 Questions and Answers
When does a cell become irreversibly injured? - ANS 1. The exact point of irreversible injury
can vary based on a variety of factors, and the exact point of irreversible damage is up for
debate. However, structurally, when severe vacuolization of the mitochondria occurs and
calcium moves into the cell, irreversible injury is imminent.
Discuss the pathogenesis of hypoxic injury. - ANS Hypoxia leads to a reduction in ATP levels
which causes the plasma membrane's sodium-potassium (Na+-K+) pump and sodium-calcium
exchange mechanism to fail, leading to an intracellular accumulation of sodium and calcium
and diffusion of potassium out of the cell. Sodium and water then can enter the cell freely. The
entire cell becomes markedly swollen, with increased concentrations of sodium, water, and
chloride and decreased concentrations of potassium. Continued hypoxic injury with
accumulation of calcium subsequently activates multiple enzyme systems resulting in
membrane damage, cytoskeleton disruption, DNA and chromatin degradation, ATP depletion,
and eventual cell death.
What are the mechanisms of ischemia-reperfusion injury? - ANS 1. Restoration of blood flow
and oxygen to ischemic tissues can increase recovery of cells reversibly injured, but
paradoxically result in additional injury known as ischemia-reperfusion injury.
Mechanisms of ischemia-reperfusion injury include:
a. Oxidative Stress: Reoxygenation induces oxidative stress by generating highly ROS and
nitrogen species. These include hydroxyl radical (OH-), superoxide radical (O.2) and hydrogen
peroxide (H202). Nitrogen based free radicals present mostly in the form of nitric oxide (NO)
and are generated by endothelial cells, macrophages, neurons and other cells. The radicals
further damage the already compromised membrane and facilitate calcium overload within the
mitochondria. Additionally, reperfusion injury promotes pro-inflammatory neutrophil adhesion
to the endothelium where they release toxic oxidants and harmful proteases. Antioxidants such
Pg. 1 Copyright © 2025 Jasonmcconell. ALL RIGHTS RESERVED.
, as Vitamin C & E reverse neutrophil adhesion and neutrophol-mediated reperfusion in cardiac
muscle.
b. Increased intracellular calcium concentration - Intracellular and mitochondrial calcium
accumulate within the cell during acute ischemia. Reperfusion results in more calcium influx
because of damaged cell membranes and ROS-mediated injury to the sarcoplasmic reticulum.
The increased calcium enhances mitochondrial permeability; damaged mitochondria have
decreased or ceased production of ATP.
c. Inflammation: Ischemic injury promotes inflammation. Dead cells stimulate immune cells to
release cytokine-mediated danger signals, thus initiating inflammatory response.
d. Complement activation: May exacerbate damage which has occurred secondary to
reperfusion injury.
Why are children more susceptible to the toxic effects of lead exposure? - ANS 1. Children
have an increased hand-to-mouth behavior and thus prone to putting objects found in their
environment into their mouths.
2. The blood-brain barrier in children is immature during fetal development, contributing to
greater accumulation in the developing brain.
3.Infant absorption of lead is greater than adults. In adults, the body burden of lead is found in
bone. In children, growth results in a rapid turnover in skeletal bone causing a continuous
leaching of lead into the bone.
4. In cases of compromised nutrition, where dietary intake of iron and calcium is insufficient,
children are more likely to have elevated lead levels.
Discuss the nutritional implications in chronic alcoholism. - ANS 1. Major nutritional
deficiencies associated with alcohol abuse include those of magnesium, vitamin B6, thiamine,
folic acid and phosphorus.
2. Folic acid deficiency becomes especially serious when alcohol is consumed during pregnancy
and may contribute to fetal alcohol syndrome.
3. Thiamine deficiency results in major neurologic sequele.
4. Increased risk of head and neck cancers
Discuss mechanisms of cell injury related to chronic alcoholism - ANS 1. Protein transport
malfunctions
Pg. 2 Copyright © 2025 Jasonmcconell. ALL RIGHTS RESERVED.