Cellular Injury

Question 1

Cell injury occurs when stress ______ cell’s ability to adapt

Answer 1

EXCEEDS

Question 2

Causes of Cellular Injury

Answer 2

1) Inflammation
2) Hypoxia
3) Nutritional excess/deficiency
4) Trauma
5) Genetic mutations

Question 3

Hypoxia =

Answer 3

Low oxygen delivery to tissue. Oxygen is the last electron acceptor in the transport chain that allows for the generation of ATP. Low oxygenation impairs oxidative phosphorylation which results in low ATP (essential energy source)

Question 4

Causes of Hypoxia

Answer 4

• Ischemia (decreased blood flow through an organ from decrease arterial perfusion, decreased venous drainage or shock)
• Hypoxemia (low partial pressure of O2 in the blood, SaO2 <90%, PaO2 <60mmHg)
• Decreased O2 carrying capacity of the blood (ex. anemia, CO poisoning, methemoglobinemia)

Question 5

Classic finding of patient with carbon monoxide (CO) poisoning?

Answer 5

Cherry red appearance of the skin (hgb so tightly bound reflects red light). Early sign of exposure if headache.

Question 6

Causes of Hypoxemia

Answer 6

1) High altitude (Decreased FiO2)
2) Hypoventilation (increased PaCO2 leads to decreased PaO2)
3) Diffusion defect (PAO2 not able to push much O2 into the blood due to a thicker diffusion barrier
4) V/Q mismatch (blood bypasses oxygenated lung (circulation problem), or oxygenated air cannot reach blood (ventilation problem)
5) Shunt (ex. Pulmonary embolism)

Question 7

Describe dilemma in Methemoglobinemia

Answer 7

Iron in heme is oxidized to Fe 3+ (instead of Fe2+), which cannot bind oxygen - PaO2 normal but SaO2 decreased. Seen in oxidant stress (sulfa and nitrate drugs) or in newborns

Question 8

Classic finding in Methemoglobinemia

Answer 8

Cyanosis with chocolate-colored blood

Question 9

Treatment of Methemoglobinemia

Answer 9

IV methylene blue - helps reduce iron back to its 2+ state

Question 10

ATP is necessary for key cellular function including (include 3)

Answer 10

1) Na+/K+ pump maintenance
2) Ca2+ pump maintenance
3) Aerobic glycolysis

Question 11

Disruption of the cellular function of the below in the setting of low ATP leads to

1) Na+/K+ pump maintenance
2) Ca2+ pump maintenance
3) Aerobic glycolysis

Answer 11

1) Sodium and water buildup in the cell (cellular swelling)
2) Ca 2+ buildup in the cytosol leading to undesirable enzyme activation
3) Switch to anaerobic glycolysis. Lactic acid buildup results in low pH, which denatures proteins and precipitates DNA

Question 12

Effects of cytosol swelling in the initial phase of cellular injury

Answer 12

• Loss of microvilli
• Membrane blebbing from loss of membrane integrity
• Swelling of the rough endoplasmic reticulum (RER) results in dissociation of ribosomes and decreased protein synthesis

Question 13

Hallmark of

1) Reversible cell injury?
2) Irreversible cell injury?

Answer 13

1) Cellular Swelling
2) Membrane damage (1) Leaking of cytosolic enzymes into the serum (ex. cardiac troponin) and additional Ca entering the cell; 2) mitochondrial damage –>loss of electron transport chain in the inner mitochondrial membrane and leaking of cytochrome C that was protected in the mitochondria into the cytosol which activates apoptosis); 3) Lysosome membrane damage results in hydrolytic enzymes leaking into the cytosol, which, in turn are activated by the high intracellular calcium