NBME form 1 question

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yo. what do y'all think about this question from NBME 1 (old school i know):

45-year-old woman has an acute coronary occlusion. Within seconds, the ischemic region shows mitochondrial swelling and depletion of glycogen granules Which of the following metabolic events is the most likely cause of these cellular changes?

- ATP depletion
- accumulation of free fatty acids
- degradation of membrane phospholipids
- efflux of k
- influx of na

i think it's ATP depletion because of the timing ("within seconds") and swelling (which according to pathoma is reversible) but depletion of glycogen granules means that it's sort of extensive, so maybe degradation of membrane phospholipids.

Degradation of membrane phospholipids to me suggests irreversible injury which would take at least 20 minutes.

Glycogen granules are depleted to produce glucose. That glucose undergoes anaerobic glycolysis to form lactate and ATP. Eventually you run out of glucose, which leads to a depletion of ATP and no other way to produce it. The lack of ATP leads to mitochondrial swelling due to accumulation of intracellular sodium.

Originally Posted by ijn

Degradation of membrane phospholipids to me suggests irreversible injury which would take at least 20 minutes.

Glycogen granules are depleted to produce glucose. That glucose undergoes anaerobic glycolysis to form lactate and ATP. Eventually you run out of glucose, which leads to a depletion of ATP and no other way to produce it. The lack of ATP leads to mitochondrial swelling due to accumulation of intracellular sodium.

OK so then you agree that the correct answer is "ATP depletion"?

yes, A is correct
I saw almost the same question in UW

Originally Posted by The Anhedonia

yo. what do y'all think about this question from NBME 1 (old school i know):

45-year-old woman has an acute coronary occlusion. Within seconds, the ischemic region shows mitochondrial swelling and depletion of glycogen granules Which of the following metabolic events is the most likely cause of these cellular changes?

- ATP depletion
- accumulation of free fatty acids
- degradation of membrane phospholipids
- efflux of k
- influx of na

i think it's ATP depletion because of the timing ("within seconds") and swelling (which according to pathoma is reversible) but depletion of glycogen granules means that it's sort of extensive, so maybe degradation of membrane phospholipids.

confusing q but i think the answer is c. you cannot have mitochondrial swelling without membrane disruption but you can indeed have mito swelling with an overabundance of atp.

edit: to elaborate a bit in case my terse response was confusing (im typing w/phone, apologies): mito swelling is irreversible and atp depletion is not. atp depletion can initialize the multiple pathways leading to membrane disruption (specifically, inner mito membrane), but it's not sufficient to cause swelling by itself (methinks...). Again, membrane disruption is 100% necessary for mitochondrial swelling to occur. the same cannot be said for atp depletion. and if im wrong, its ok, ill just fail the boards nbd.

Originally Posted by teenmachinery1

confusing q but i think the answer is c. you cannot have mitochondrial swelling without membrane disruption but you can indeed have mito swelling with an overabundance of atp.

edit: to elaborate a bit in case my terse response was confusing (im typing w/phone, apologies): mito swelling is irreversible and atp depletion is not. atp depletion can initialize the multiple pathways leading to membrane disruption (specifically, inner mito membrane), but it's not sufficient to cause swelling by itself (methinks...). Again, membrane disruption is 100% necessary for mitochondrial swelling to occur. the same cannot be said for atp depletion. and if im wrong, its ok, ill just fail the boards nbd.

The ATP choice makes more sense. The ischemia is only a few seconds. It takes a good 5 minutes for neurons and cardiac tissue to undergo irreversible damage...and thats neurons and cardiac tissue we are talking about.

ATP depletion

from ROBBINS:Irreversible cell injury: mitochondria swell, lysosomes swell, damage to plasma membrane and lysosomal membranes leads to enzyme leakage; acidosis somewhat protective by inhibiting enzymatic reactions.

so....does this sway anyone's opinion?

You can't have irreversible injury in seconds. One of the distinguishing factors between between angina and myocardial infarction is if the pain lasts longer than 20 minutes.

Mitochondrial swelling is not irreversible at the beginning of ischemia. When you start to disrupt the mitochondrial membrane then it's irreversible. You seemed to think glycogen granule depletion indicated severity. That just indicates a general feature of the first few minutes of ischemia. The cell's initial response to hypoxia is burning fuel via anaerobic glycolysis. Once glycogen stores are depleted then you truly run out of ATP.

Originally Posted by The Anhedonia

from ROBBINS:Irreversible cell injury: mitochondria swell, lysosomes swell, damage to plasma membrane and lysosomal membranes leads to enzyme leakage; acidosis somewhat protective by inhibiting enzymatic reactions.

so....does this sway anyone's opinion?

I am not sure which version of Robbins you have. I have the 8th edition and it says in Ch 1 in the section entitiled "Morphologic Alterations in Cell Injury" in the subsection of "Reversible Injury": "Mitochondrial changes, including swelling and the appearance of small amorphous densities." I am not sure why you claim Robbins says that mitochondria swell in IRREVERSIBLE injury.