Hypoxia & cellular injury – causes, symptoms, diagnosis, treatment & pathology

Hypoxia & cellular injury – causes, symptoms, diagnosis, treatment & pathology

August 14, 2019 83 By Bertrand Dibbert


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. Finally, the rough endoplasmic reticulum,
or the rough ER, also swells when the cell swells. And remember that the rough ER has all these
little ribosomes on its outside, and these are really important for the cell in making
proteins, but when the rough ER swells, they detach, and stop making proteins, so protein
synthesis goes down. All the ATP isn’t immediately lost though
when you lose oxygen and oxidative phosphorylation stops, luckily your cell can make ATP another
way, called anaerobic glycolysis, anaerobic meaning in the absence of oxygen. This is like the backup ATP generator, which,
isn’t nearly as efficient and only produces a net of about 2 ATP molecules per glucose,
whereas oxidative phosphorylation makes about 30-36… So it helps a little, but what also happens
is it produces the byproduct lactic acid, which lowers the pH inside the cell. This more acidic environment can denature
or essentially destroy proteins and enzymes. Now, up to this point, it’s not all bad,
because one super important thing about these processes that happen to the cell, is that
they’re potentially reversible, meaning that if we all the sudden get oxygen again
and start making ATP, then these changes aren’t necessarily permanent. After enough time, though, irreversible damage
can happen to the cell. Kind of like the sodium potassium pump, there’s
also a calcium pump that helps keep too much calcium from getting in, and if that stops
working, then calcium starts to build up, which isn’t a great thing. First, calcium can activate certain enzymes
that you might not necessarily want to activate, like proteases that can slice up proteins
and damage the cell’s cytoskeleton, which remember is the structural framework that
keeps the cell together. Also, endonucleases can be activated, which
can cut up DNA, the cell’s genetic material. And if we get back to thelactic acid, as more
lactic acid builds up and the environment gets more acidic, the lysosomal membrane can
be damaged as well, which usually houses these hydrolytic enzymes whose job is basically
to grind up large molecules, and when they get out, well, they’re also activated by
calcium and then they just start cuttin’ everything in sight, and basically start digesting
the cell from the inside. Finally, the phospholipase enzyme, which basically
splits phospholipids, gets activated…since the cell’s membrane’s made of phospholipids,
these can destroy the cell membrane, which is probably the most important sign of irreversible
damage. When the membrane’s destroyed, those enzymes
we just listed, along with others, can leak out into the blood and continue wreaking havoc. Finally, let’s jump back to calcium. Enzyme activation isn’t the only effect
calcium can have; calcium can get into the mitochondria, causing a cascade the leads
the mitochondrial membrane to be more permeable to small molecules and so it lets a molecule
that usually stays in the mitochondrial, cytochrome c, to leak out into the cytosol. This is a big big red flag to the cell that
things have gone south, and is kind of analogous to the self-destruct button, and activates a process called apoptosis,
or programmed cell death. This is a bit like cellular suicide. At this point, the cell’s not in good shape,
right? And all this happens eventually because of
a lack of oxygen, or because of hypoxia.