Module 2: Cellular Injury

What is cellular injury?

Cell injury occurs when homeostasis fails due to the cell being exposed to harmful stimuli or stressors, leading to cell dysfunction, death, or altered cellular function.

What are 8 causes of cell injury?

1. hypoxia

2. free radical formation

3. chemical agents

4. infectious agents

5. physical or mechanical stress

6. immune reactions genetic factors

7. nutritional imbalance

When does hypoxic cell injury occur?

when there is a lack of sufficient oxygen

What causes hypoxic cell injury?

1.local loss of blood flow

2.low oxygen in the air

3.loss/alteration of hemoglobin

4.decreased rbc’s

5.damage to oxidative enzymes (cytochromes)

6.insufficient systemic respiration

7.insufficient systemic circulation

what is ischemia?

Ischemia is a condition characterized by insufficient blood flow to a tissue, leading to a lack of oxygen and nutrients essential for cellular metabolism. It can result from various factors such as obstruction of blood vessels or low blood pressure.

what is Anoxia?

total lack of oxygen.

example: embolus lodged in a blood vessel, suffocating tissue.

Describe the early stages of hypoxic cell injury in anaerobic glycolysis

blood flow is obstructed or stopped

ischemia

decreased mitochondrial oxygenation

decreased ATP

increased anaerobic glycolysis (decreased glycogen)

increased lactate (lactic acid)

decreased ph (more acidic)

nuclear chromatin clumping

Describe the early stages of hypoxic cell injury in anaerobic glycolysis

blood flow is obstructed or stopped

ischemia

decreased mitochondrial oxygenation

decreased ATP

decreased sodium pump

increased INTRACELLULAR (Na+ and Ca++) increased EXTRACELLULAR K+

increased water

increased acute cellular swelling

How does the does the loss of Na/K pump activity affect the cell?

dilation of endoplasmic reticulum

detachment of ribosomes

decreased protein synthesis

lipid deposition

What happens with prolonged hypoxic cell injury?

the cell blows up, becomes irreversible, DEATH

-continue swelling leads to vacuolation (formation of cellular cavities)

-swelling of lysosomes

-swelling of mitochondria

-calcium activates intracellular enzymes like proteases, phospholipases, and endonucleases

-cell membrane damage

In prolonged hypoxic cell injuries, what do the swelling of lysosomes cause?

digestion of cytoplasm and nuclear components

What is oxidative stress?

oxidative stress is injury caused by ROS (reactive oxygen species)

-free radicals

-inflammatory cells

-excess energy (UV or radiation)

-redox reactions

What does Oxidative stress cause? (think hydrogen peroxide)

causes membrane, organelle, and cell damage

-break down unsaturated fatty acid (peroxidation of lipids)

-alters protiens

-DNA damage

Where does mitochondrial DNA (mtDNA) come from and why?

mtDNA comes from your mom

the ova carries more mitochondria than sperm; when fertilization occurs more mitochondria is from mother (ova)

What are examples of chemicals that can cause cell injury?

-CCl4

-Lead

-carbon monoxide

-ethanol/alchol

-mercury

-drugs

How can we be exposed to chemical injuries?

inhalation, ingestion, absorption

-direct toxicity to cell membranes and/or organelles

-free radicals forming

-alteration of cellular enzymes or proteins (causes cellular functions to be blocked and stops synthesis)

How does reperfusion lead to apoptosis?

• lack of of oxygen in ischemia causes cells to accumulate xanthine and hypoxanthine

• reperfusion introduces oxygen, (O2 combine with xanthine and hypoxanthine) leading to the formation of reactive oxygen species (ROS) and hydrogen peroxide that can damage cells, triggering apoptosis.

• cause cell membrane damage

• mitochondrial calcium overload

  • loss of atp and solutes

What are 4 mechanisms that cause cellular accumulation?

• abnormal metabolism

• defect in protein folding or transport

• enzyme defects

• cellular uptake of substnaces

what are storage diseases?

• accumulation of substances

  • catabolism defect causes metabolic products to accumulate

  • loss of enzyme funciton

• macrophage uptake

Define cellular accumulation

Cellular accumulation is the abnormal buildup of substances within cells due to various mechanisms, including metabolic disruptions, enzyme deficiencies, or impaired substance transport, which can lead to cellular injury