 Our next lecture is going to be on hyperkalemia that is absolutely important that you understand this topic. But before we move on, what is normal potassium? What is normal concentration of potassium? Well, this potassium is three ranges from 3.5 to 5.0. I have to warn you. This is the potassium that's actually found in the extracellular fluid compartment. Not the intracellular fluid in the extracellular fluid compartment. That is what we're measuring. Because inside the extracellular fluid is about 130 to 140 because potassium is the major cation that lives inside the house. So when we measure and we draw out blood in the hospital, we are looking at the concentration of potassium inside the extracellular fluid and specifically we're looking at what is inside your blood vessel intravascularly. However, what is the definition of hyperkalemia? Well, if the highest range you can get is 5, when potassium concentration is greater than 5.0, that means you have hyperkalemia. So how do we know what causes hyperkalemia? We're going to go through a nice chart to be able to break them down one by one. So how do we evaluate? Well, hyperkalemia. There's different ways by which we can develop hyperkalemia in the body. Remember, the kidney is the only organ that 90% of the potassium in our body is excreted out of. If you don't know, go back to the chapter. We talked about potassium physiology. Since the kidney is involved, patients that have renal failure, you're going to see them all the time. There's a lot of patients that have renal failure chronically, patients on dialysis, they come in and their blood potassium is about 8. It's just simply because the kidney cannot filter the potassium through the system. So I want you to first notice what is the most common before I start to break it down into what this is, what is causing it, what is causing that. So renal failure is one of the most common causes of hyperkalemia. So that's to put that acute or chronic renal failure. We will talk about the mechanism when we get to how we evaluate patients. So lab errors, lab error is another very common cause of hyperkalemia. So how are we going to look at hyperkalemia? Now that we know the two most common ways we develop hyperkalemia, although we're going to talk about the pathophysiology behind them, we're going to look at, if somebody's potassium is very high, could it be spurious, could it be caused by red blood cells, lysine inside a test tube, because we caused it when we try to draw blood, or it's a redistribution process. So let's start. If the problem is spurious or artifact, let's call it artifact, or redistribution, the potassium is redistributed from the intracellular compartment to the extracellular compartment. So since I said at the beginning when you see a patient with a level of potassium that's very high, first thing you think about, was this a lab error? If it's a lab error, it's usually due to hemolysis, hemolysis. Why is it hemolysis? Because red blood cells, red blood cells has a lot of potassium in them. And when the lysine's open, when the lysine's open they're going to release all that potassium into the bloodstream, they're going to release all that potassium into the bloodstream, and then you develop hyperkalemia when potassium is greater than five. Another way we can develop it is you have thrombocytosis. Thrombocytosis, thrombo means what? From platelets, you have a lot of platelets running around, you can develop hyperkalemia. So patients that have platelet count of like 500,000 or 600,000, that is a lot that can cause them to develop hyperkalemia, or you can have leukocytosis, leukocytosis, that's a high white count, very, very high white count. So if you can, all you just need to know is look, these are all the blood cells. If the red blood cells are lysine, yeah, we're going to develop hyperkalemia, if you have a lot of platelets and a lot of white blood cells floating around, that would give us a spurious picture of hyperkalemia. Or another very common form is prolongatronicate. So when you want to draw blood in the hospital, they put proternatronicate around and they tie it, and they try to allow blood to be able to get drained out of your veins. If it stays there for so long, what happens to the tissue? Well you develop ischemia, this ischemia to the tissue is going to cause the cells to break out and die and release potassium into the blood. So when you're drawing the blood, you might think, oh, this potassium is high, but it's because the ischemic tissue, the tissue cells die from ischemia, decrease blood flow to the cells and thus decide to release all their content. Thus what is one of the content, potassium leaves inside the cell. Remember, you don't even have to, whether you clench your fist or you don't, you can develop hyperkalemia from ternicate use. So this is called a spurious form of hyperkalemia. Usually last but not the least, lab error, right? Somebody decides to put the, after they draw blood, they put it on the rack for so long and it starts to break down and release the potassium. So if you get back a lab error or it was due to what, hemolysis or proternatonicate use, all you have to do is repeat potassium level, repeat the potassium level. That's all you have to do. Just redraw the blood and recheck it again and the potassium is fine. Now let's talk about the rich distribution. The mnemonic for redistribution is AIDS, wow, AIDS. That is how potassium is redistributed. How do we explain this? Well, let's speak it one at a time. A for acidosis. Which kind of acidosis? Metabolic acidosis. Now let's revisit metabolic acidosis again. When you have metabolic acidosis using our nice shooting formula. What happens? It's metabolic. The bicarb is low. Because the pH of the blood is acidemic. What happens when the blood pH is low? Well, let's take a look. Here's a cell that's actively pumping out sodium. And for every three sodium, two potassium is pumped back in. However, in the presence of acidosis, in the presence of acidosis, what happens? You have low bicarb and a lot of hydrogen ions. You have a lot of hydrogen ions flowing around. What happens when you have a lot of hydrogen ions floating inside the blood? They're going to go inside the cell and they cause lysis. And the cell basically are going to release all the potassium content straight up into the bloodstream. Those potassium start to leak out. Potassium start to leak out and you develop hyperkalemia. So acidosis, metabolic acidosis, you develop hyperkalemia because the way I think about it, if I have an acid and I pour it on the cell, the cell is going to release all its contents. So whatever is inside the content of the cell, which is usually potassium, it's going to go out into the bloodstream. Those cells have what? Potassium in them. So in the acidotic state, they're going to release all that potassium into the body. That's A4 acidosis. Let's talk about the next one, I. Insulin, insulin deficiency, interesting. Well, how does insulin work? Well, this is how insulin works. Let's talk about the mechanism. So here's the cell, we're going to pick a muscle cell. And in the muscle cell, we have sodium, potassium, ATPase pump, sodium, potassium, ATPase pump, right? And this pump's job is to pump out sodium and bring in potassium. So how does insulin work? When you have insulin, insulin comes and binds to the ATPase pump, the sodium, potassium, ATPase pump. And when it binds, right there, this is insulin, it's going to cause potassium to float inside the cell. It's going to cause potassium, let's use blue so we can see better, it's going to cause the potassium to not flow inside the cells. So what happens if I have insulin deficiency? What does this process cause people to have insulin deficiency? Diabetes, maledicts, type one, right? They have autoimmune destruction of their pancreas so they can make an insulin. So what happens? Insulin can bind, potassium can come in, and also that allows what? Glucose to be reabsorbed back into the body, right? That's how glucose comes in, and potassium comes in also. So but when you have insulin deficiency, when I don't have this insulin anymore, all of a sudden my potassium now stays outside and patients can develop hyperkalemia. What does the D stand for? So for my mnemonic aids, D for drugs. The drugs that we're talking about, digitalis, digitalis, digitalis is what is one of the drugs that can cause you to develop hyperkalemia. How does digitalis or de-joxin, de-joxin, right? Digitalis or de-joxin cause hyperkalemia, let's check it out. So finally, sodium and potassium are usually actively pumped in and out of the cell. Sodium, and this is the cell, okay, and this is the cell membrane. This is the cell membrane. So potassium always get actively pumped into the cell because that's where most of the potassium lives, and sodium is always actively pumped outside of the cell by which protein the sodium potassium ATPase, sodium potassium ATPase pump, NA plus K plus ATPase pump, which means we're using energy to actively work hard to keep sodium outside of the cell and keep potassium inside the cell. De-joxin mechanism of action, what it does is it competes with potassium at the sodium potassium ATPase pump. So we're going to use potassium as black. So rather than potassium coming in, here's de-joxin is going to come and take this spot of potassium, thus decreasing the amount of potassium coming inside the cell. What happens to the potassium now? Now all the potassium will start staying, all the potassium will start staying outside of the cell, which is not going to be in plasma causing you to develop hyperkalemia, hyperkalemia. Now why did I draw this little extra pump here? Well, that is the sodium calcium exchanger that's found on the cell membrane potential of cardiac muscle. So it's just not hanging out there for fun. It's because typically the way the mechanism of action of de-joxin is when it inhibits the sodium potassium ATPase pump, normally, as you can see, sodium with the red line usually comes inside the cell. However, when sodium comes inside the cell, that is the only way calcium can be pumped out by the sodium calcium channel. So how does digitalism work again? Well, if sodium potassium ATPase pump does what happens, we're going to be keeping all the sodium inside the cell. Well, if there's too much sodium inside the cell and it's not being pumped out, we cannot pump calcium out because we need to keep pumping the sodium outside of the cell. So does digitalism cause you to retain more calcium indirectly to the cell, inside the cell of the cardiac myocyte, allowing you to have more contractility because when there's more calcium trapped inside the cell, the actin myosin filament, the actin myosin filament, right, the actin myosin filament actually can form cross bridges, can form nice cross bridges, and then you can have active myocardial contraction. That's why they give digitalists to patients that have severe congestive heart failure because they allow the cardiac myosin to contract. However, when you have de-jaxin overdose, when you have overdose of the drug, calcium is going to have to stay outside of the cell and you develop hyperkalemia. So that is the mechanism of action. What other drugs can cause hyperkalemia? Soxenylcholine, it kind of sucks, but soxenylcholine, well, what do we use soxenylcholine for? Soxenylcholine is a drug we use to paralyze patients when we have to intubate them especially in the emergency room. However, one of the side effects is causing hyperkalemia. The mechanism of action is because soxenylcholine causes up-regulation, up-regulation of nicotinic acetylcholine receptors, receptors on the muscle membrane. But usually patients that have increased risk of developing hyperkalemia is patients that have injuries, burns, crush injuries, trauma. Well if you already have trauma, what happens, your cells, your cells that normally contains a lot of potassium are getting crushed. They're getting crushed. So all of a sudden, they're leaking out a lot of potassium and then you up-regulate the amount of receptors on the muscle membrane and then cause e-flux, e-flux of potassium outside into the plasma causing them to develop hyperkalemia. What other drug can cause hyperkalemia? Bitter blockers. What? Are you serious? Bitter blockers, that's one of my favorite drugs. Yeah, let's talk about the mechanism by which bitter blockers actually cause hyperkalemia. But before I tell you, normally when somebody has hyperkalemia, we will talk about the treatment. We give them beta-2 agonists. We give beta-2 agonists. We always give beta-2 agonists and let's draw a cell membrane and put a nice little receptor and here will be the pocket with the beta-2 agonist. So this is a beta-receptor, a beta-2 receptor and let's put the drug in there. This is an agonist that actually binds and make things happen. Well when the beta-2 agonists happen, what will happen inside the cell is there will be activation of cyclic AMP. Cyclic AMP will be activated by the second messenger system and cyclic AMP is going to activate protein kinase A. Protein kinase A. And this protein kinase A, what do they do? Because they have kinases, they phosphorylate, they phosphorylate stuff. So when the phosphorylate is going to have a phosphate to which protein, our favorite protein of all time. Sodium potassium ATPase pump, we're going to need to activate the sodium potassium ATPase pump. Thus allowing us to pump out sodium and bring in potassium. However, when you give a patient beta-blocker, let's put a beta-blocker in there. When you put in a beta-blocker, let's use, this is the beta-blocker. Now you cannot activate cyclic AMP, you can activate protein kinases and thus you cannot phosphorylate the sodium potassium ATPase pump, thus preventing what? What is going to happen? Well, now that we cannot pump out sodium and we cannot pump in the potassium, automatically potassium has to stay outside of the cell. Now there's so many potassium outside of the cell because normally they usually pump in, but since we're not phosphorylating the sodium potassium ATPase pump, we develop hyperkalemia. We develop hyperkalemia. Now I want you to remember that the beta-blockers that actually at most risk that causes patients to actually develop hyperkalemia are non-selective beta-blockers. When I mean by non-selective, they don't care if you have beta-1 or beta-2. Which drugs are we talking about? We're talking about labetolol, carbadolol, and also propanolol, or natolol. So these drugs, these medications, labetolol, carbadolol, propanolol, and natolol, all these drugs are non-selective and when they bind, they cause you to get an increased risk of developing hyperkalemia.