Cell injury and death

Question 1

List several major causes of cell injury.

Answer 1

Physical agents - trauma, extreme temperatures, radiation

Chemical agents and drugs - toxins, pollutants, alcohol

Biological agents - viruses, bacteria, fungi, parasites

Nutritional imbalances - deficiencies or imbalances

Hypoxia/ Ischemia - oxygen deprivation from reduced blood flow or inadequate oxygen supply.

Immune reactions - autoimmune diseases, hypersensitivity reactions

Genetic abnormalities - mutations, chromosomal defects

Question 2

Describe the key mechanisms of cell injury:

Answer 2

ATP depletion - results from mitochondrial dysfunction, impairs energy-dependent processes like ion pumps

Oxidative stress - excess reactive oxygen species (ROS) cause damage to lipids, proteins, and DNA

Calcium dysregulation - increased intracellular calcium activates harmful enzymes

Membrane damage - loss of membrane integrity due to lipid peroxidation or mechanical disruption

DNA and protein damage - irreparable DNA damage leads to cell cycle arrest or apoptosis

Question 3

Describe reversible cellular appearances after injury:

Answer 3

Cellular swelling (hydropic change).
Fatty change (lipid vacuoles in cytoplasm).
Plasma membrane blebbing.
Loss of microvilli

Question 4

Describe irreversible cellular appearances after injury

Answer 4

Membrane rupture.
Mitochondrial swelling with amorphous densities.
Nuclear changes: Pyknosis (condensation), karyorrhexis (fragmentation), karyolysis (dissolution).

Question 5

Define necrosis and its causes and characteristics:

Answer 5

Uncontrolled cell death caused by external damage,
leading to inflammation

Causes - Ischemia, toxins, trauma

Characteristics;
- enlarged cell size
- nucleus changes from Pyknosis → Karyorrhexis → Karyolysis
- disrupted membrane integrity
- inflammation present

Question 6

Define apoptosis, its causes and its characteristics:

Answer 6

Programmed cell death, a regulated process to eliminate unwanted cells without inflammation

Causes - developmental signals, DNA damage, infection, immune regulation

Characteristics;
- reduced cell size
- fragmentation of nucleus
- intact membrane
- absence of inflammation

Question 7

Describe the mechanisms of apoptosis:

Answer 7

Intrinsic pathway (mitochondrial);
- triggered by DNA damage, oxidative stress, or lack of survival signals.
- release of cytochrome c from mitochondria activates caspase-9

Extrinsic pathway:
- triggered by external signals (e.g., Fas ligand, TNF-α)
- activates caspase-8 through receptor-ligand interaction

Execution phase:
- both pathways converge to activate executioner caspases (e.g., caspase-3)
- caspases cleave cellular components, leading to apoptotic body formation

Question 8

What is the physiological and pathological relevance of Apoptosis ?

Answer 8

Physiological Roles:

• Embryogenesis (e.g., limb development).
• Immune system regulation (e.g., elimination of autoreactive T-cells).
• Maintenance of tissue homeostasis.

Pathological Roles:
- Excessive apoptosis: neurodegenerative diseases, ischemic injury.
- Insufficient apoptosis: cancer, autoimmune diseases.

Question 9

What are the differences between necrosis and apoptosis

Answer 9

Trigger;
- apoptosis uses internal and external signals
- necrosis is severe external injury

Energy dependence:
- apoptosis uses ATP
- necrosis none

Morphology:
- apoptosis, shrinkage (apoptotic bodies)
- necrosis, swelling + lysis

Inflammation;
- necrosis present
- apoptosis absent