Introduction to pathology
USMLE® Step 1 style questions USMLE
A 57-year-old man presents to the emergency department due to acute-onset right lower extremity pain. The symptoms began two hours ago. Past medical history is notable for atrial fibrillation and hypercholesterolemia. Temperature is 37.0°C (98.6°F), blood pressure is 158/83 mmHg, and pulse is 117/min. The right lower extremity is cold to touch below the knee on physical examination. The suitable posterior tibial and dorsalis pedis pulses are absent. Which of the following histological findings, if present, is most suggestive of irreversible cellular injury in the affected extremity?
Content Reviewers:Rishi Desai, MD, MPH, Tanner Marshall, MS
So by this point, you’re probably aware that your body needs oxygen to survive, right?
In fact, every cell in your body needs that precious oxygen.
Those cells use the oxygen to produce energy in the form of ATP, or adenosine triphosphate, a super super important molecule, sometimes even called “the molecular unit of currency”.
The cells use it to basically pay the molecules inside the cell to do their specific jobs.
It’s like one big factory with a bunch of workers that all have specific jobs needed to run the factory, and they only take ATP as payment.
Now the mitochondrion of the cell takes in oxygen and makes ATP to pay the workers, through a process called oxidative phosphorylation, the mitochondrion’s like the factory’s payroll department, right?
When the cell doesn’t get enough oxygen, and so payroll can’t produce the ATP that they need to pay the workers to do their jobs, the whole cellular factory can be damaged or even die, and we call that process hypoxia, where hypo means “less than normal” and oxia means “oxygenation”.
When the oxygen comes in, typically it goes straight to payroll, specifically to the inner mitochondrial membrane where oxidative phosphorylation takes place.
Oxygen’s used in one of the last steps, and serves as an electron acceptor, and this allows the process to finish and produce ATP.
So without oxygen, we can’t finish oxidative phosphorylation and produce ATP.
But why does the whole factory fall apart when payroll stops making ATP? Why don’t they just pause for a bit? Take a little break?
Well, when certain workers stop doing their jobs...things get a little out of hand.
One super important worker is the sodium potassium pump on the cell’s membrane, pretty much like the bouncer that makes sure there isn’t too much sodium diffusing into the cell, basically by pumping it back out every time it diffuses in and maintaining a concentration gradient, this process also keeps too many water molecules from passively diffusing into the cell; think of it like this: water molecules want to go every which way and are constantly moving back and forth, inside and outside the cell, but the all these sodium ions on this side tend to physically block more of them from leaving that side, so over time more water molecules get retained, or almost trapped, on the side with more sodium—in short, the more sodium molecules: the more water molecules.
But, our pump doesn’t do all this for free, and it needs ATP.
So without ATP, it stops pumping sodium back out, and sodium diffuses in...and keeps diffusing in and the concentration gradient goes away, now with less sodium particles on the outside blocking the water molecules from going into the cell, water follows sodium in, which causes the cell to swell up.
When the cell swells up, a couple things happen.
First, usually you have these really tiny microvilli on the cell’s membrane, which look sort of like little fingers that help increase the cell’s surface area and therefore help the cell absorb more things, when the cell swells up and gets all bloated, the water sort of fills these little fingers and reduces the surface area, which makes it harder to absorb molecules since there’s less surface area, right?
Also, sort of along the same lines, the cell can bleb, or bulge outward from all this water, this is a sign that the cell’s cytoskeleton or this structural framework is beginning to fail, and is letting water slip through.
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