Diabetic Ketoacidosis (DKA) Explained Clearly Remastered – DKA Pathophysiology
29
August

By Adem Lewis / in , , , , , , , , , , , , , , , , , , , , , , /


okay well 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 so it behooves us to understand a little bit more about what is DKA how does present and how to treat it the first I want to do is 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 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 I’ll 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 co a so we’ll just do it acid Co Co a massive teal a ok 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 this 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 Paul Mathilde Co a tomatillo Co a through the enzyme palmitoyl Co a transfer ace now no longer being inhibited or being disinhibited and allowing quite a lot of these Paul Mathilde Koei’s 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 these high two carbon units can be used as you know a steel Kawai 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 it 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 OAH 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 there 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 in abyssion of fatty acid transport into matrix of Myto Condrey a– 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 yards 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 and 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 in 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 and 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 d hi guya rhesus 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 bodies show us 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 won’t 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 anti get metabolic acidosis is kind of a surrogate for how big the ketone bodies are but you can actually measure ketone bodies some hospitals measure serum ketones okay and some also measure something called beta hydroxy butyrate you look at 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 bodies 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 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 you’ll also see sometimes a low phosphorous sometimes a normal phosphorous so this is the hallmarks of somebody presenting with DKA let’s talk about how we treat that coming up here next


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