1.2 Cellular Injury

Question 1

What type of ischemia occurs with Budd-Chiari syndrome?

Answer 1

Decreased venous drainage
Often happens because of polycythemia vera leading to viscous blood that doesn’t drain well
Also happens in Lupus and other hypercoaguable states

Question 2

Explain the relationship between FiO2, PAO2, PaO2, SaO2 and what might cause hypoxemia by affecting each value.

Answer 2

FiO2 is the fraction of O2 in the inspired air
PAO2 is the O2 pressure in the alveoli, decreased by high altitude, also by hypoventilation–increaeses PACO2 resulting in lower PAO2
PaO2 is the O2 pressure in the arteries, interstitial pulonary fibrosis prevents efficient transfer of PAO2 into blood, also decreased by V/Q mismatch
SaO2 is the O2 saturation of the RBC’s

Question 3

What are three primary causes of decreased O2 carrying capacity leading to hypoxia? Describe each.

Answer 3

Anemia: decreased RBC mass, PaO2 is normal, SaO2 normal
CO poisoning: CO binds Hb 100x better than O2, PaO2 normal, SaO2 low, cherry red skin and blood, headache, coma, death
Methemoglobinemia: Iron heme oxidized to Fe3+ which cannot bind O2, PaO2 normal, SaO2 low, seen with oxidant stress (sulfa and nitrate drugs), and in newborns, presents with cyanosis and chocolate colored blood, treat with IV methylene blue which helps reduce Fe back to Fe2+

Question 4

Explain the pathophysiology of hypoxia leading to the changes seen in reversible cellular damage

Answer 4

Low O2 impairs the production of ATP
Low ATP disrupts: Na/K pump resulting in Na and water buildup in cell causing swelling, Ca pump causing increased intracellular Ca over-activating enzymes, switch to anaerobic glycolysis lowering pH that denatures proteins and causes DNA precipitation

Question 5

What is the hallmark of reversible cellular injury?

Answer 5

Cellular swelling that leads to loss of microvilli and presence of membrane blebbing, also swells the ER causing ribosome dissociation and cessation of protein synthesis

Question 6

What is the hallmark of irreversible cell damage?

Answer 6

Membrane damage:
Plasma membrane leading to leakage of enzymes into serum and increased intracellular Ca
Mitochondrial membrane leading to loss of ETC and leakage of Cyt C leading to apoptosis
Lysosomal membrane leaking hydrolytic enzymes into the cytosol and with enhanced activation by increased Ca leads to cellular damage