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

[0:06]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 mitochondria of the cell takes in oxygen and makes ATP to pay the workers through a process called oxidative phosphorylation. So the mitochondria is 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 or 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 all these sodium ions on this side tend to physically block 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 starts to diffuse in. And it keeps diffusing in, and the concentration gradient goes away. Now, with less sodium molecules in the outside blocking the water molecules from going into the cell, water follows the sodium in, which causes the cell to swell up. And when the cell swells up, a couple things start to happen. First, usually it has these really tiny microvilli on the cell's membrane, which sort of look 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 the 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 two ATP molecules per glucose, whereas oxidative phosphorylation makes about 30 to 36. So it helps a little, but what also happens is it produces a byproduct called 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 happened to the cell is that they're potentially reversible, meaning that if we all of a 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 is not 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 the lactic 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 cutting everything in sight and basically start digesting the cell from the inside.

[6:22]Finally, let's jump back to calcium. Enzyme activation isn't the only effect calcium can have. Calcium can actually get into the mitochondria, causing a cascade that leads the mitochondrial membrane to be more permeable to small molecules. And so it lets a molecule that usually stays in the mitochondria, cytochrome c, to leak out into the cytosol. And 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, apoptosis, or programmed cell death, or basically cellular suicide.

[7:00]At this point, the cell's not in good shape, right? And all this happened eventually because of a lack of oxygen, or because of hypoxia.