Diabetic Ketoacidosis (DKA) Explained Clearly Transcript


We’re gonna talk about diabetic ketoacidosis – DKA. DKA is a pretty significant illness that accounts for about 135.000 hospital admissions every year in the United States and it has an estimated cost of about 2.4 billion US dollars every year. So, a pretty sizeable chunk of cash is used to treat these patients and so, it behooves us to understand a little bit more about what is DKA, how does it present and how to treat it.

First, I want to take you to the cellular level. Over here, I will show you our cell wall and on it, it’s got an insulin receptor. Also, inside the cell, you recall that we have mitochondria and you’ll recall that there is an inner-membrane space, along with the matrix. The matrix is that inner part. Now, remember where things are. You’ve got glucose outside the cell, that wants to move inside, and you’ve got fatty acids as well.

We’ll draw a fatty acid here. You recall that this is where Krebs cycle occurs; I’ll abbreviate that as KC. This is where you have beta-oxidation. Remember these? Fatty acids move inside the cell. You’ll also recall that glucose, once it gets inside the cell, is going to undergo glycolysis and it will also go inside the cell in the form of pyruvate, which will eventually get broken down to the same product and enter Krebs Cycle as Acetyl-CoA.

In the normal situation, you’ve got insulin. Insulin binds to its receptor and insulin also prevents, for the most part, fatty acids from moving on into the cell for the process of beta-oxidation. So, in the normal situation, you’ve got insulin hitting a receptor, causing glucose to go into the cell, glycolysis is occurring and the end result is pyruvate; pyruvate then moves into the mitochondria, Krebs Cycle occurs and you get, boom, ATP.

In the situation with diabetes mellitus type 1, where you have no insulin secreted, or in the case of diabetes type 2, where you have a very strenuous state, high glucagon levels, high epinephrine, low insulin levels, what you have then is, in either of these cases, no insulin secretion or insulin resistance, in which case… And here is the key point here – glucose can no longer come into the cell. There is no glycolysis, there is no pyruvate. This mode of energy source is cut off.

Similarly, insulin is no longer available to prevent beta-oxidation. At that point, you get quite a lot of Palmitoyl-CoA through the enzyme Palmitoyl-CoA-transferase, now no longer being inhibited or being disinhibited and allowing quite a lot of these Palmitoyl-CoAs to go inside the cell, and of course, what happens there, they are chopped up into two-carbon units. That’s called beta-oxidation. And so, you’re getting quite a bit of two-carbon units in here and these can be used as Acetyl-CoA in Krebs Cycle to make energy. It’s not the best way of making energy, but they can make energy. Those ketone bodies are acetone, which looks like this, as you might recall, acetoacetate, which looks like this, and something called beta-hydroxybutyrate, which looks like this.

As you can see, these are results of these two-carbon units coming together and the breaking up of the ketone bodies. All of these, actually, are ketone bodies. Acetone is very volatile and so, it can turn into gas and this is what you smell on the breath of somebody who is in ketoacidosis; you get this acetone smell.

Particularly, the thing I want you to pay attention to is this carboxylic acid chain. This is the whole carboxylic acid group, right here, but particularly this –OH group, cause this proton comes off very nicely, and when it does, what you have left behind is the conjugate base, which is negatively charged, which is what’s going to account for you anion gap. If you want more information on the anion gap, please see our lectures on ABG interpretations and medical acid-base.

I think I want to review that and tell you exactly what I’m thinking there. Number one, in DKA, we have a lack of insulin. As a result of that, we see blood sugars go up, yes, but I think the biggest thing that you ought to pick up from that is number two, there is no inhibition of fatty acid transport into the matrix of mitochondria. That’s important because this means that fatty acids are pouring into the matrix of the mitochondria, as we showed you on the last slide. That means beta-oxidation is occurring, which are you recall, beta-oxidation is simply when you have this long-chain fatty acids getting chopped up into two-carbon units; these two-carbon units are then being fed into the Krebs Cycle, but, because there is so many of them, they start combining and forming these ketone bodies, and these ketone bodies are acidic.

So, where is the acid coming from? The acid is coming from the ketone bodies, which are coming from the Acetyl-CoA, which are coming from the fatty acids, which are coming from the outside, which are being transported because there is no insulin. That’s very important.

Let’s review that. Number one – what we’re going to see here is low insulin. As a result of that, this is what we’re going to see: low insulin leads to ketone bodies, which is going to lead to acidosis, specifically, an anion gap acidosis, which is going to lead to increased potassium. Why does that potassium go up in this case? It goes up in this case because there is a proton-potassium exchange mechanism between the cells and so, as protons are being increased in the serum and they go into the cells, potassium has to leave the cells and go into the serum, to replace them. So, you’ll see an increased potassium level, at least initially.

Now, decreased insulin also leads to high glucose. High glucose is going to lead to dehydration. Why is it going to do that? The glucose levels become so high that they exceed the re-absorption threshold in the kidneys and so, what you get then is an osmotic diuresis. That simply means that there are too many particles in the urine because of the excess glucose that the kidney can’t reabsorb at all and that excess osmotic pressure causes fluid to go with it and that causes dehydration.

Dehydration is going to do a couple of things. It’s going to make all your potassium shift out of your cells and get dumped and so, this then leads back into this, but then, as well, you get a total body potassium depletion. Even though the potassium level in your serum is high, you’re being depleted of your total body potassium.

So, what have we seen here? We’ve seen ketone bodies, we’ve seen hyperglycemia, we’ve seen acidosis, we’ve seen dehydration, we’ve seen osmotic diuresis and we’ve seen total body potassium depletion. Along that, you could also put total body phosphate depletion, as well. The dehydration can lead to increased creatinine because of renal failure.

This is what you typically see in a patient who comes in with DKA. They are at risk because they have low insulin. You can test their blood by checking for ketone bodies and because of this, you’ll see a anion gap metabolic acidosis. Again, look at our lecture on acid-base, but what ketone bodies show up as is an anion gap metabolic acidosis. What that means is that the anion gap, which is sodium subtracted the chloride and the bicarb won’t be greater than 12 and that’s usually the first sign. You’ll have anion gap metabolic acidosis and that anion gap metabolic acidosis is kind of a surrogate for how big the ketone bodies are.

You can actually measure ketone bodies; some hospitals measure serum ketones and some also measure beta-hydroxybutirate. You look at the acidosis, sometimes you’ll see high potassium, usually you’ll see a high potassium, but again, the total body potassium is depleted because a lot of the body’s potassium has been depleted outside of the cells and into the serum. You see these patients very dehydrated, with maybe sometimes hypotension and tachycardia, because of the osmotic diuresis. You’ll see an increased creatinine because of dehydration and of course, you’ll see high glucose, which is one of the things we all look for, but may not be there. You’ll also see sometimes a low phosphorus, sometimes a normal phosphorus.

This is the hallmark of somebody presenting with DKA. Let’s talk about how we treat that! Coming up here next.

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