Diabetic Ketoacidosis (DKA) Explained Clearly – Diabetes Complications

Welcome to another MedCram lecture, we’re, going to talk about diabetic, ketoacidosis DKA. Now DKA is a pretty significant illness that accounts for about a hundred and thirty-five thousand hospital admissions every year in the United States, and it has an estimated cost of about 2.

4 billion u.s. dollars every year. So pretty sizable 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 kind of take you to the cellular level, so Over here I will show you our cell wall and on it it’s, got a insulin receptor.

Also inside the cell. You ‘ Ll recall that we have mitochondria, and you ‘ Ll recall that there is a inter 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 will draw a fatty acid here you’ll recall This is where Krebs cycle occurs.

I’ll abbreviate that as KC – and this is where you have beta-oxidation. Remember these a fatty acids move inside the cell. You ‘ Ll also recall that glucose, once it gets inside, the cell is going to undergo glycolysis and that 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.

So, 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 a process of beta oxidation.

So, in the normal situation, what you have is you’ve got insulin, hitting receptor, causing glucose to go into the cell. Glycolysis is occurring which the end result is pyruvate pyruvate, then moves into the mitochondria Krebs cycle occurs and you get boom ATP great.

In the situation with diabetes, mellitus type 1, where you have no insulin being 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’s. The key point here glucose can no longer come into the cell. There is no glycolysis, there is no pyruvate, then mode of energy source is cut off.

Similarly, insulin is no longer available to prevent beta oxidation, and so what you get at that point is 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 is that they are chopped up into two carbon units so that’s called beta oxidation.

So chop chop chop, chop, chop chop, and so you’re, getting quite a bit of two carbon units in here and this these high two carbon units can be used. As you know, Acetyl CoA in Krebs cycle to make energy it’s, not the best way of making energy, but they can make energy and 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 a result of these two carbon units coming together and the breaking up of ketone bodies, and so all of these actually are ketone bodies.

Acetone is very volatile, and so it can turn into a gas, and this is what you smell on the breath of somebody who is in ketoacidosis. You get this acetone smell, but particularly the thing I want you to pay attention to here is this carboxylic acid chain – and this is the whole carboxylic acid group right here, but particularly this, OH group, because 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 your anion gap, and if you want more information on the anion gap, please see our lectures on ABG interpretations and medical acid-base.

So I think I want to review that and tell you exactly what I’m thinking. They’re number one in DKA. We have a lack of insulin and, 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 is that there is no inhibition of fatty acid transport into 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, as you as you recall, beta oxidation is simply when you have these 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’s, so many of them they start combining and forming these ketone bodies and these ketone bodies are acidic.

So, where’s, the acid coming from the acid is coming from the ketone bodies, which are coming from the acid 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 okay. So let’s review that number one. What we’re going to see here is low insulin and 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 an ion gap acidosis, which is going to lead to increased potassium now.

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 have 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, and why is it going to do that? Well, because the glucose levels become so high that they exceed the reabsorption threshold and the kidneys, and so what you get then is a osmotic diuresis.

That simply means that there’s 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.

That 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 kind of then leads back into this. But then as well, you get a total body.

Potassium depletion, even though your 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 and Along that, you can also put total body phosphate depletion as well.

Now the dehydration can lead to increased creatinine because of renal failure, and so 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 an anion gap metabolic acidosis, again, look at our lecture on acid-base, but what ketone body show up is: is the anion gap metabolic acidosis? What that means is the anion gap, which is, if you look at the chem 7 sodium subtracted the chloride and the bicarb will be greater than 12 and that’s.

Usually the first sign you’ll have so you’ll, have an anion gap metabolic acidosis and that anion gap, metabolic acidosis is kind of a surrogate for how big the ketone bodies are, but you can actually measure ketone body, some hospitals Measure, serum ketones, okay and some also measure something called beta.

Hydroxybutyrate you get the acidosis as mentioned. Sometimes you’ll, see a high potassium. Usually you’ll, see a high potassium. But again the total body potassium is depleted because a lot of those 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 a high glucose, which is one of the things that we All look for, but may not be there.

We also see sometimes a low phosphorus, sometimes a normal phosphorus. So this is the hallmarks of somebody presenting with DKA. Let’s. Talk about how we treat that coming up here. Next