1.2 Cellular Injury

Question 1

Slowly developing ischemia vs Acute ischemia: result?

Answer 1

• slow: atrophy

- fast: cell injury

Question 2

Hypoxia: 3 main categories of causes

Answer 2

1. Ischemia
2. Hypoxemia
3. Decreased O2 carrying capacity

Question 3

Ischemia: 3 main causes

Answer 3

1. Decreased arterial perfusion
2. Decreased venous drainage
3. Shock–hypotension causes poor tissue perfusion

Question 4

Hypoxemia: 4 main causes

Answer 4

1. High altitude (decreased PA O2)
2. Hypoventilation (ex can’t breathe)
3. Diffusion defect (membrane is thickened–eg interstitial pulmonary fibrosis)
4. V/Q mismatch–blood bypasses oxygenated lung (eg R to L shunt), or oxygenated air cannot reach blood (eg atalectasis–lung collapse)

Question 5

Decreased O2 carrying capacity: 3 examples

Answer 5

Think hemoglobin (Hb)

1. Anemia
2. CO Poisoning
3. Methemoglobinemia–Fe in heme is oxidized to 3+, which cannot bind O2.

Question 6

Methemoglobinemia

• cause
• classic finding
• Tx

Answer 6

• causes hypoxia
• Fe in heme is oxidized to 3+, which cannot bind O2.
• cause: oxidant stress (sulfa, nitrate drugs) or in newborns
• classic finding: cyanosis with chocolate-colored blood
• Tx: intravenous methylene blue–reduces 3+ to 2+ Fe.

Question 7

How does hypoxia lead to cell injury? (3 cellular mechs)

Answer 7

Low ATP causes:

1. Na/K pump disrupted, so more Na inside cell and therefore water buildup (swelling)
2. Ca pump disrupted, so Ca buildup
3. Aerobic respiration becomes anaerobic. This increases lactic acid, leading to low pH, which denatures proteins and precipitates DNA

Question 8

Reversible cell injury:

• Main hallmark
• what 2 main things happen

Answer 8

Hallmark: Cell swelling.

1. Loss of microvilli, and membrane blebbing
2. RER swelling makes ribosomes pop off, so decreased protein synthesis

Question 9

Irreversible cell injury:

• Main hallmark
• what 3 main things happen

Answer 9

Hallmark: Membrane damage

1. Plasma membrane damage.
   - cytosol proteins leak out, Ca leaks in
2. Mitochondrial membrane damage
   - loss of ox-phos (inner mito membrane)
   - Cyto C leaks out, activates apoptosis
3. Lysosome membrane damage
   - Hydrolytic enzymes leak into cytosol and are activated by Ca

Question 10

Calcification: 2 types

Answer 10

1. metastatic–from high Ca levels

2. dystrophic–cell injury