DIP Episode 321 - The Clutch Metabolic Acidosis Podcast (for all USMLEs)

Okay, welcome. My name is Divine. This is episode 321 of the Divine intervention podcast. In this podcast I'm going to be talking about metabolic acidosis in relation to the USMLA exams. Now one thing and again I will very likely make other acid-based podcasts in the future but one thing I know that people routinely struggle with is just understanding pathophysiology with metabolic acidosis is something that lots and lots of people struggle with. In fact I have struggle with it at some point in my medical career but you know thankfully at least I will say again I still have a lot to learn but at least you know I know a thing or two. I feel like about a metabolic acidosis that I would like to share share with all of you in this podcast. So this podcast if metabolic acidosis is something you've just struggled with understanding I will give you a very nice framework for understanding it in this podcast. If you understand this podcast then you should be able to pretty much rationalize many of the things you see on exams and as you learn today again many things get a lot easier when you just understand them instead of just committing them to memory and as a reminder for those that are taking the USMLA step two, CK of step three exams soon. I do have an MBA me test against strategy scores taking place next tomorrow that's on Thursday it's from three or five thirty p.m. Pacific Standard Time.

I'll use a lot of MBA me style questions to go over a very logical very methodical approach to answering MBA me questions on those respective exams and then I'll be having a 20-hour review course for again both exams that just case at three on Thursday and on Friday I mean on Friday so hurry on on Saturday this week it'll be 10 hours each day we'll have some breaks in between obviously so that people can relax.

Okay so let's just jump right into it right so we know that whenever there's some kind of acidosis in the body the person's pH is gonna be less than 7.35 I think that's an important thing to keep in mind because sometimes people just want to know like hard and fast numbers or thus as you would see when you get into the clinic or their many exceptions to these roles but basically a normal body pH should be between 7.35 and 7.45 so if your pH is less than 7.35 you have an acidemia but if your pH is greater than 7.45 you have an alkaline right and again you know there are some key differences between acidosis and acidemia but that has clinical context but snow particularly useful on exams so I'm not gonna waste my time on that so what's the framework that I want to use to explain this at a Bologna sedoses business to people well the first thing I think I want you to realize is just to realize that there are two kinds of ions right there are two kinds of ions may also have learned this in general chemistry in college and again don't worry I know some of you are cringing this is like extremely simple BC chemistry that probably even a five-year-old will understand right but there are two kinds of ions in the body they're cations and they're anions right I'll say that again they're cations which are positively charged ions and then they're anions which are negatively charged at ions right so we know that in the body you know the key cations again there is many of them but one which we tend to care about the most is probably like sodium sodium is like the big big one we also care about potassium but the thing is potassium is so minute relative to sodium they're like you know what sodium is like the legit guy so we're gonna worry more about sodium because think about it a normal body sodium is like 140 versus a normal body potassium that's about like four right so if you think

about it if you're kind of looking at it that way it's almost like by a factor of like I don't know if I'm doing my math right by a factor of 35 so you know sodium is probably a lot more important than potassium although if your potassium is really out of whack as you see from my podcast I believe I made a podcast on hyperkelemia or something not too long ago if potassium is out of whack that's a huge problem so sodium is kind of like the big cation we care about now what are the big anions we care about what are the big negatively charged ions we care about well chloride is a big one I mean it kind of almost goes two to two with sodium and all chloride is about like 100 104 right another one we also care about for sure is bicarb right white carb you know normal bicarb is usually right around like 24 right in fact if you see the spread right like the cation in the body is not that far removed from those anions right so those are kind of like the key key cations and key anions although I think one thing I want to mention is that there are many different you know many other anions that we certainly care about we can just ignore them right I mean like things like lactate phosphate sulfate even albuming is an anion right albuming has an over-on-negative charge right so there are all those other anions in the body that matter now one thing then I want to introduce again you may be like well divine come on go ahead and get to the acid based stuff again if you understand these rules that I'm going over these basics then when I'm describing it to you it will make a lot of sense don't worry I'm gonna get there right so one of the principles I think I want to spend some time on is just the principle of electron neutrality it's a very important principle in the body ring the principle of electron neutrality it's a very important principle because basically you don't want to be

electrified as a human being if you can avoid it so your body takes great pains and has multiple molecular mechanisms in place to keep an electron neutral neutral milieu if you may what I mean by that electron neutral milieu basically just means that the number of cations in your body should roughly equal the number of anions in your body so the positives should balance the negatives right and we know some of these mechanisms already right like for example many of us know that many cells on in the body have this hydrogen potassium exchange business right so whenever I'm saying whenever hydrogen ions enter into a cell potassium ions come out of the cell in in exchange right many of us know one that's also pretty useful many of us probably learned it in step studying for step one as the chloride shift or alkaline tide or whatever but basically like whenever your body has a cell that is producing chloride on one side typically on the other side of the cell the body is going to be dumping out by car right so chloride and by car they're almost like interchangeable ions because your body always tries to like if you're losing chloride your body is like I'm going to put by carben response if you're losing by carben I'm going to put chloridion response right so there are these things again all designed to maintain some sort of electron neutrality in the body right so the thing that the reason I'm introducing this principle of electron neutrality is if you keep it in mind you analyze many and you have understanding of the mechanism behind the metabolic acidosis you can easily keep track of oh this would be a nanayan gap metabolic acidosis or oh this would be a normal nanayan gap metabolic acidosis just stuff like that right so just gonna go enough of that right this again same principle of electron neutrality right so I think one thing I want to talk about is just a book keepin

g system right so many of us right like at least I remember back in the day in Nigeria when I rarely grew up I did take a class I believe on book keeping it was part of like my either high school or you know they don't call it high school in Nigeria they call it secondary school but I believe in secondary school I learned about book keeping one of my business studies classes I think I two business studies for like three years back in the day so really the book keeping system is just a nice way of keeping track of what is coming in and what is coming out right if you own a business you definitely want to keep track oh okay this is how much money came in this is how much we sent out an expenses so you can determine your profit but again remember the buddy is a profit less system all the buddy wants is if an anion is going out I want another anion coming in right where I want a cadaion coming in your response again your body just always always always wants to keep things neutral it wants it doesn't want anyone having too much power the positive ions which are the cadaions most balanced the negative ions which are the anions right so the thing is many times in metabolic acidosis right because if you think about it an acid has two parts right it has the hydrogen ion part of it and then it has the anion part of it right and we know that if we're dealing with a Bolicacidosis you know anions are things we care about you really need to keep track of the anion in metabolic acidosis if you can keep track of the anion and do your book keeping correctly you can pretty much always deduce what kind of acidosis what kind of metabolic acidosis you have right so let's say for example you have some kind of acidosis where because again remember I said that the major cadaion right so just backtrack a little bit here just to summarize we said the major cadaion in the body is sodium and the

n we said the major anions in the body are chloride right which is a big one it's usually about 104 another one is bicarb right HCO HCO 3 minus right we do care about that but then we say that again there are some other and because the thing is if you really do the math think about it right let's say a normal body sodium is 140 right and then let's say a normal body chloride is like 104 right and then let's say a normal body bicarb which is an anion is like 24 right if you do the math if you look at it if a normal body sodium is 140 that's a that's a cadaion there and then we have these anions that's add up to you know 104 for chloride 24 for bicarb if I'm doing my math right that's 128 so do you see that you're like to find out you just describe this principle of electronic neutrality this numbers don't seem to add up well let's see right because you have 140 on the positive charge side we have just 128 which is you know 104 plus 24 on the negative charge side so that means there's 12 anions that we seem to not be accounted for right there's 12 anions that we seem to not be accounted for because again we said that your body likes things to be balanced it likes the cadaions to balance the anions right so that 12 which doesn't seem to be made up right is what constitutes the anion gap but the thing is if you really think about it again in terms of this principle of electronic neutrality that I've propounded already those 12 anions must just be some other anion that is not chloride or bicarb right that is the anion gap right and again those negative ions include many different things right like lactate acido acetate right phosphate sulfate those are all anions that fall into that 12 anions that we did not count business so again if you keep all those things in mind you're being good shape right so see for example you have like some kind of asidosis where you look at all

your and again I think one thing I mentioned earlier that I think I just really want to emphasize again is your body in general has this almost like up-down relationship with chloride and bicarb whenever you lose chloride your body will top up bicarb whenever you lose bicarb your body will top up chloride right so basically chloride and bicarb there like there are brothers keepers but again remember whenever you have any changes in your chloride when your bicarb your bookkeeping system needs to still work right your bookkeeping system needs to still work right so you still need to maintain that electronic neutrality so again just always think of this as a balance of power if you do your bookkeeping around I'll give a couple of examples here and you'll be you'll be in good shape right so let's say for example so let's maybe just be going into a bunch of examples a bunch of examples right and then I'll keep talking about this bookkeeping system so by the end you will like okay divine I get it I get it right so let's say for example you have some unusual situation in the body that is making you lose bicarb right not unusual situation in the body that is making you lose bicarb well if you lose bicarb if we're doing a bookkeeping system right we know that the key anions are chloride bicarb and those other guys that make up 12 right so and I've already said that again your body tries to like whenever your body sees that there is a changing bicarb usually tries to compensate for it with a changing chloride so if you think about it if the anion you lose is bicarb well your body is like okay wow my bicarb is not like 24 but something strange happened my bicarb went down to 12 so your body is going to be like okay well the balance of power has shifted away from the anions so we need to put 12 anions back in right so how does your body do that your body does that by putting 12

chloride anions back in right your body puts those 12 chloride anions back in so your chloride will go up as your bicarb is going down right again to maintain that electral neutrality so some of you may be like oh so divine how does this cost an acidosis well look at it you've lost bicarb so your bicarb has gone down if your bicarb is low you have a metabolic acidosis right so you say okay divine what are some of these situations that can cause me to just lose bicarb well if you think about it there is quite a number of them right so let's say for some reason your proximal convoluted tubules don't work right for basically has like fanconies for example if you have fanconies remember the primary side where you reabsorb pretty much all the bicarb here in the front is the proximal tubule right if your proximal tubule does not work well think about it and we're going to be able to reabsorb bicarb so you're going to lose that bicarb if you lose that bicarb again as I said your chloride will rise in response so if you really think about it that thing that I said constitutes the anion gap which is those on measured anions that you know make up 12 since again remember that chloride bicarb relation I talked about you're losing bicarb so your body is like okay I'll replace you so your body is not replacing it with any of those other anions that make up 12 so those other anions I can adjust the in as they are right so your anion gap did not change right so again if your proximal tubule doesn't work you're not going to reabsorb bicarb you're going to lose it that's going to cause a normal anion gap metabolic acidosis again I want to read a read white's a normal anion gap again as your bicarb goes down by a certain amount your chloride will go back up by the exact same amount right because again if you think about it like for example your beta intercalited cells in the nephrine re

member whenever I don't know if many of you still remember the cabonic and hydrae's business right whenever you're losing so much bicarb your body is going to be regaining so much chloride in the kidneys that is one mechanism behind this almost like your your relationship between chloride and bicarb right so again if you're losing a ton of bicarb your chloride will rise proportionately so nothing changes in that other group of unmeasured anions like those lactates and phosphates and sulfates and stuff that we we don't measure that mix up that extra 12 that I cannot talk about at the beginning right so I mean if you have a personal tubule problem that's making you lose bicarb what exactly is that that's a type 2 RTA right that's a cause of a normal anion gap metabolic acidosis right although if you think about it too there's some drugs that can make you not reabsorbed bicarb in the in the nephrine right those are those cabonic and hydrae's inhibitors so drugs like acid azolamide or drosolamide right so if you're not able to reabsorbed bicarb in the proximal convoluted tubule in that bicarb will literally sting your urine right so you're losing that bicarb your body will reach the chloride proportionately right so if your body reaches that chloride proportionately again you're going to have as your bicarb is going down chloride is going up right so everything is being accounted for accounted for right so notice let's see the persons bicarb is 12 as the persons bicarb went down by 12 the chloride must have gone on by 12 so the chloride went from like 104 to 116 right even if the persons bicarb is now 12 right so if the persons bicarb is 12 and chloride is 116 116 plus 12 is 128 if you subtract that from 140 you still have that 12 and we know that those other am ions are still holding the fort right or think about it if a person has diarrhea remember your GI tract your co

lon produces a ton of bicarb literally your colon present ton of bicarb so if you're having a lot of colonic motility you're going to be getting rid of tons and tons and tons and tons of bicarb if you are getting rid of all this bicarb again as bicarb is being pushed out in your poop your body is going to be generating more chloride and reabsorbing it across those intestinal enterocytes right so again your bicarb is going down your chloride is going up but there's nothing happening to that special group I call them let's call them the special group of 12 anions nothing is happening to the special group of 12 anions because the only changes here that are happening are bicarb chloride and whatever decrease happens with your bicarb is going to be accompanied by a commensurate increase in your chloride so the anion gap stays marble right okay or you can think of what are the circumstances can I think of well actually let me go from the other angle well you know what I think let me talk about one more so let's say for example your adrenal cortex doesn't work right let's say a person has adicence disease for person has adicence disease think about it your adrenal cortex is destroyed right and again let me maybe go ahead and say this remember adicence disease is a disease of the adrenal cortex it's not a disease of the adrenal medulla that's a common misnomer among medical students adicence disease does not affect the adrenal medulla adicence disease only affects the adrenal cortex right maybe like what divine is you know the same gland why don't we kill the medulla as well there is no we don't the thing is the adrenal gland is almost like two organs rolling two one the adrenal cortex as we know is derived from misoder right the adrenal cortex as we know is derived from misoder but what is the adrenal medulla derived from the adrenal medulla is actually derived from neurocre

ssels right so the adrenal medulla is derived from neurocressels so because the adrenal medulla is derived from neurocressels those tissues are literally not the same they they don't resemble each other they don't look the same at all right so autoimmune disease against one is very likely you're not going to affect the other right so repression has adicence disease well you know some of the merillosa is not going to be working anymore and that's a problem right because if you think about it if you're not the merillosa doesn't work you're not going to make out a duster and our duster has a couple of jobs let's put it this way our duster and the job is to make you reabsorbed sodium that's one job description second job description is it makes you pee potassium that's another job description and then the third job description is it makes you pee acid hydrogen ions in the body right so I'll say that again our duster and the job description in life is reabsorbed sodium peep protons pee um hold it I want to say what did I just say so pee protons and then pee potassium right so pee potassium pee protons reabsorbed sodium so if you have adicence disease here adrenal cortex doesn't work your zone of glomerulus it doesn't work you have an our duster and deficiency so the opposite of the job description of our duster is what you see lab wise right so since you're not able to reabsorbed sodium you're going to become hypoinitriemic right because you're not getting enough sodium if you cannot pee potassium then you'll keep that potassium in you right so you have hyperkelinia and then if you're not able to pee protons then you keep those protons in you so you have an acidosis right and remember the key places where our duster and those all these things right is the principal cell and the alpha-integrated cell remember the principal cell has an in-ex channel that in-ex channel brings

in sodium our duster and supercharges that in in-ex channel that's how you reabsorbed sodium and the principal cell of the collecting duct you have the wrong key channel the wrong key channel makes you pee potassium that channel is supercharged by our duster so if it's not working it'll not be pee potassium and then the alpha-integrated cell has a proton pump that proton pump is supercharged by our duster and so again if you have an out-duster in deficiency that proton pump is not going to be supercharged so you're going to keep you're going to hang on to those protons right and we know that whenever you hang on to protons well your body is like we we got to neutralize these protons so those protons will marry by carb so that's going to bring your by-carb down because when protons hydrogen ions bind to by-carb right your form carbonych acid which then is converted by carbonych and hydrates to H2 O to that you then blow off right so again whenever your protons are retained your by-carb will decrease and as your by-carb is decreasing remember that we were like said earlier so by-carb is decreasing your body will proportionally increase the chloride right so again the changes that are happening the by-carb if we're doing a bookkeeping right the by-carb is going down the chloride is going up so there's no change in that special anion group of 12 right as I've described a diagnosis right so if you have an aldosterine deficiency if you think about that that's also going to cause a normal anion gap metabolic acid doses because again nothing is happening to that special anion group of 12 in fact that's a type 4 RTA right anything that lowers your aldosterine levels will cause a type 4 RTA right there are many ways you can lower your aldosterine levels you can have other since disease reagental cortex doesn't work you can have you can be taken on aldosterine receptor antagonis

ts believe it or not right where you if they gain like a drug like sperm or lactone for heart failure or a player unknown or they remember you can also use sperm or lactone for if a person has a portal hypertension right that's essentially using pharmacology to replicate an aldosterine deficiency because we're literally blocking our aldosterine receptors right that will know your aldosterine does going to give you that same type 4 RTA business another classic one is if a person has a congenital adrenal hyperplegia right so newborn that is like hypo-neutremic hyperchalemic has a normal anion gap metabolic acid dose as well remember the most common cause of congenital adrenal hyperplegia is 21 hydroxylase deficiency so you're not going to be able to make our aldosterine accordion so again you're going to have an aldosterine deficiency you're going to get a type 4 RTA right or they give you a question about some person some person that you know came in with no core rigidity from like a military base right and then now the person suddenly has hypo-neutremia hyperchalemia metabolic acidosis that's what a house for Dricks and Syndrome right so you have nice seramine giddiness that has pretty much touched the person's adrenal adrenal glands and then has caused the problems right or they can give you a person that was recently started on therapy for paroxysmal nocturnal hemoglobinuria well think about remember P&H the therapy for that is C5 inhibitor aculesumab aculesumab is a monocloryl antibody against the C5 complement protein if you inhibited that protein and you'll never be able to form the membrane attack complex right you're basically using a drug to induce a terminal complement protein deficiency whenever that happens unfortunately unfortunately you're going to be pretty supposed to require nice serine infections like my seramine giddiness right so those people can ge

t meningococcus sepsis that can cause a what a house for Dricks and Syndrome right so again just again many of these things are just based on understanding if you have the understanding you're not from memorizing many many many of these things right you can see pretty much the causes of a normal anion that metabolic acidosis and again it makes sense if you're doing your bokeh in appropriately right so I know some of you are probably itching okay divine and by the way a normal anion that metabolic acidosis the most common causes the area that's very high you'll see most common cause of a normal anion that metabolic acidosis is the area the second most common cause of a normal anion that normal anion that metabolic acidosis this is like a distance second is an RTA correct it's an RTA okay then there's some other lorry of things hyperalimitation pancreatic or anophysiola maybe I'll make a podcast if I if I have the time or I deem it high yield on normal anion that metabolic acidosis in the future just describing the mechanisms of those but again I've kind of described a lot of the probably water represented like 99% of the scenarios you'll see already okay so I've been doing bokeh pain to read that special anion group of 12 doesn't get affected normal anion that metabolic acidosis well this amount of acidosis read that special anion group of 12 gets affected absolutely right absolutely so again let's do some bokeh pain so let's imagine a person that is I don't know is in some kind of shock but you're genetic shock septic shock blah blah blah blah blah like if you don't understand shock just go to I believe I made a podcast on shock recently from non-stickin just go on the spreadsheet on the website on their exam topic lists it would lead you to a google spreadsheet that is non-editable is only me that can edit it because they don't people don't mess it up and go under th

e step two sickest step three tap go under special topics you you'll see the podcast on shock I believe I've made a podcast on shock so say for example representing some kind of shock well if you're in shock or you're hypoxic for whatever reason well your body is really gonna depend very heavily for ATP on anaerobic like colasis right well if anaerobic like colasis is happening what's gonna be building up some elactic acid right or lactic acid as you look at the name lactic acid right it means it has hydrogen ions and lactate okay so those hydrogen ions that are bumped up right because you're building building building of that lactic acid those hydrogen ions will bring down your bicarb right those hydrogen ions will bring down your bicarb so some of me may be like oh okay divine so as the bicarb is going down my chloride must be coming up in response well unfortunately that's not the case so it's not every time that your bicarb goes down that your body raises the chloride in response no right again this is why it's important to not just memorize excuse me this is why it's important to not just memorize lists of things but you need to understand the mechanism behind those lists that you're memorizing right so if you think about it we want to maintain this the principle of electron neutrality just think of it as like a key core principle that body is like I got a stick with so think about it if you're getting lactic acid like a ton of lactic acid that lactic acid is gonna be that the hydrogen ions in that lactic acid will bring down your bicarb right because of that buffering system I've described already with carbonic anhydrous but those hydrogen ions are not the only thing that's in lactic acid there's the anion lactate and that anion is important right but the thing is if you think about it lactate is not chloride lactate is not bicarb so that means it falls on that

that special anion group of 12 right special anion group of 12 so since you're generating a ton of lactate that special anion group of 12 will go up so if you think about it let's say this person started with a bicarb of you know let's see the anomobicarb is 24 right and the normal chloride is 104 and the special anion group of 12 is 12 right all adds up to 140 which is the normal body sodium if your bicarb goes down because you're brushing so many hydrogen ions into the body so let's see the bicarb goes down by 10 from 24 to I don't know um 14 right so your bicarb has gone down by 10 so you need to supply 10 anions from somewhere well the thing is lactic acid comes with 10 hydrogen ions again these things I'm just using these numbers to make it easy to understand so lactic acid comes with 10 hydrogen ions but it also comes with 10 lactate anions those 10 lactate anions need to be accounted for somehow right so the thing is those 10 lactate anions they go to that special anion group of 12 but that special anion group of 12 because they've literally gained 10 lactates it goes from 12 negative charges to 22 negative charges so if we do our bookkeeping now we have 14 for a bicarb we have 22 for a special anion group so 22 plus 14 is 36 your chloride cannot change if you still want to maintain an electron neutrality your chloride still needs to stick to 104 and that 104 plus 36 gives you 140 right so whenever you're bringing whenever you have and so the general principle here is this whenever you have an acidosis because you're bringing in a lot of hydrogen ions that have a non chloride or a non bicarb anion with them that's going to cause that special anion group of 12 to grow and if they grow then your chloride cannot grow if you still want to maintain an electron neutrality because you don't want the number of anions to exceed 140 right again I'm just using these numbe

rs to make this easy to understand this is way more complex than this but if you really understand this you probably understand it better than the vast majority of people involved in medicine to be honest with you right so in that case because that special anion group of 12 is no longer a group of 12 because they're getting 10 extra anions from lactate they now become like 22 do you see that those that special anion group is now numerically higher than it normally is right it's normally like 12 what now it's like 22 right those weird anions that's those special anions right because the number is going up numerically in the presence anion gap has gone up right the presence anion gap has gone up right so of that pi that pi of 140 anions they were trying to keep normally those special anion stick only 12 anions of that pi but now they're taking 22 anions of that pi so the anion gap has gone up right that's a higher anion gap metabolic acidosis that is why for person has lactate acidosis they will have a higher anion gap metabolic acidosis right so what are the things that cause lactate acidosis well if you're in shock right septic shock whatever you can get lactate acidosis if you're now if you're if you're taking a metforming right again I believe I've kind of described the mechanism behind the metforming lactate acidosis but if you really think about it if you're something that's inhibiting hepatic gluconeogenesis then one pathway that will not be working off to snuff is the quarry cycle if your quarry cycle doesn't work very well then your lactate acid is going to build up because remember okay what's the quarry cycle I feel like people listening to this will really want to get this down mainly tissues in your body make lactate acid but you don't know what to do with it so you will ship that lactate acid to the lever and then the lever because it's capable of gluconeo

genesis we convert that lactate acid to pyruvate right and then from pyruvate and convert it back to like phosphoenopyrruvate you know through that pyruvate carboxylics and PPCK business that's not the main topic of discussion is I'm just going to give you that quick and then you make glucose back right so the thing is the mechanism of action literally of metforming is it inhibits hepatic gluconeogenesis so you essentially put in a bottleneck in that process if you put a bottleneck in that process your lactate acid is going to go up right so you're going to have a higher-known gap in a polycacidosis for that reason okay think about a person that has you know the abelic emergency lesity forgot to take the insulin or the runoff of their insulin as many times happens unfortunately then the thing that's going to happen is those people's are you know ketone bodies who build up because of those counter regulatory hormones right so the ketone bodies like acido acetic acid will build up better hydroxybutyric acid will build up if you think about it look at the name acido acetic acid so it's an acid that has hydrogen ions and then the anion with it is acido acetic that anion is a non chloride non-bicarb anion right so again that special anion group of 12 is going to grow right is going to take more of that pie of 140 right so the thing that's going to happen is you're going to have a higher-known gap metabolic acidosis or beta hydroxybutyric acid well as hydrogen ions those hydrogen ions will bring down your bicarb but again the anion you are bringing in big measure into the body is a non chloride non-bicarb anion so your body is like well since the special anion group of 12 is growing then we cannot grow the chloride at the same time right that's going to cause a higher anion gap at a polyacidosis right or if you think about it remember you're whenever you have a lot of urea

the transporters that help you get rid of like urea and also help you get rid of other anions like sulfate phosphate and stuff well if you have kidney disease your urea builds up so much that's just going to make it really really difficult for your body to get rid at least if I'm remembering the mechanism correctly it's going to make it very hard for your body to get rid of sulfate and phosphate if your body cannot get rid of sulfate and phosphate guess what you're going to build up right that's going to increase that that's special anion group of 12 right so that's going to again cause a higher anion gap metabolic acidosis right or if a person is seeking what is it like isonize it right remember isonize it the pleats of it in b6 right and b6 is a very important co-factor for many reactions in metabolism right so again that can cause an acidosis right that can build up again these special anion group of 12 right or if a person is seeking methanol right think about it methanol is converted by alcohol dehydrogenase to formic acid well uh for make acid well let's maybe put it this way methanol is converted by alcohol dehydrogenase to form for milder height and then that for milder height is then converted by uh acetaldehyde dehydrogenase to for make acid right so that for make acid contains hydrogen ions and for meat for meat is a non chloride non-bicarbon ion right so again if you're just thinking about this fixed pie over 140 anions that for meat is going to raise your anion gap right remember people that have methanol poisoning they tend to have like eye problems because it can cause a dimma of the right that's a classic for a phondoscopic exam finding on mbimix amts right or if you think of a person that um that takes uh antifreeze ethylene glycol right well that ethylene glycol is converted to um it can be oxidized right in two sequential steps by alcohol dehydrogen

ase and that's a toutedhyde dehydrogenase right to an acid right so again when you oxidize it to an acid right although the acid in this case happens to be oxalic acid um that oxalic acid has hydrogen ions that will crush your bicarb and oxalic right which will again raise that special anion group of 12 right so do you see again many of these things is just about understanding the mechanisms right again i know many people remember mod piles cut mod piles blah blah blah blah but again if you understand the mechanisms many of these things are just a lot easier than than than than than you think right so how do we calculate the anion gap well it should be completely obvious based on what I've described already right anion gap is basically your sodium right which is the key cation minus your chloride minus your bicarb right so you just basically add up your chloride and bicarb and subtract that number from sodium right that will give you what's in that special anion group which usually should be should be 12 right and then the thing I just want to say is if a person has a metabolic acidosis and after this then I'm saying I'm going to say like maybe two other points just to kind of pull some things together for people listening to this and if a person has a metabolic acidosis you always want to calculate winter's formula it's just a smart thing to do right because winter's formula will show you if you are compensating a property right so for example winter's formula because if you think about it for person has a metabolic acidosis well your body is like okay let's bring the page back to normal by blowing of CO2 right so you look at the presence p CO2 so the winter's formula tells you what you expect that p CO2 should be so what is winter's formula well winter's formula is 1.5 times your bicarb plus 8 plus or minus 2 I mean these are things that actually go through go throu

gh in the in the state to seek is the three-view course with people we go through multiple examples with of this stuff right so 1.5 times your bicarb plus 8 plus or minus 2 right it'll give you a range you basically get a range from that if you expect that if your p CO2 that you calculate is so that from now give you like an expected p CO2 range if the p CO2 that's measured on the patient's AB Gs much what is in that range that means the presence compensating perfectly but if the p CO2 happens to be higher than the range and that means the person is not compensating perfectly so that means they have a complement respiratory acidosis now if the p CO2 happens to be less than the range that means they are blowing off way too much CO2 than they need to right so that means they are over compensating so they will have a concomitant respiratory acidosis right so really really make sure you understand that winter's formula business now what is another thing I wanted to see here I hope I'm trying to get in it well one is this whole concept of if people have a big time acidosis why giving them normal saline is maybe not the smartest again in the world so let's explain why that's the case so again think back to this principle of electron neutrality again your body wants to keep the anion at 140 if you're giving a person a ton of normal saline in the setting of an acidosis well think about it normal saline is sodium chloride as a ton of chloride think about if you give a person a large amount of chloride well as you're giving them large amount of chloride well your body is going to have to depress the bicarb in response right to maintain that pi fixed at 140 because let's say your chloride is normally 104 and it raises to 110 because you're getting a ton of normal saline then your bicarb is going to have to go down commensurately by 6 it's going to have to go down from like 24 to

like 18 surprise surprise you've created a metabolic acidosis for that person essentially right you've created a metabolic acidosis for that person so that's why usually in those circumstances the smart thing to do typically is to give those people lactated ringers when people have an acidosis but again I'm just saying that to explain something that I know many med students have just gen even many people in healthcare believe it or not have just generally never really understood but again I'll see on mbm exams on USML exams if a person has needs fluids normal saline is usually going to be the right answer like 99.9% of the time so that's something I definitely keep keep at the back of your mind if if I were you okay so I think what was the second thing I wanted to say in relation to an acidosis there's one thing I wanted to see but I don't know for some reason it's just not coming to mind right now um it's not coming to mind right now well if it comes to mind maybe I'll discuss it in another podcast but there'll probably be other podcasts in the future on acid-base imbalances but I feel like this should really set people up to just understand acid-base in a very good light especially metabolic acidosis right because that's the one that he tests a lot on exams so again as I do at the end of every podcast I do offer review courses for the USML exams especially step 2ck step 3 um I offer one on one tutoring with on a very limited basis I essentially don't have time for one on one tutoring for the most part um and then if you want to get these episodes you can subscribe to the podcast I have this this podcast on Apple podcasts on Google podcasts and on Spotify at least the most recent 150 it's it's a rule I've tried many times to circumvent this role doesn't work so if you want every episode from episode one all the way to this episode which is episode 321 then you need t

o go to the website and subscribe on the website you don't need any special logins or anything if you subscribe though I mean that subscription definitely helps right but the benefit of subscription is whenever I make a new podcast you you get an email notification but um if you say you don't want to subscribe that that's fine um but if you want everything from a piece of the one to a piece of 321 it's gonna be on the website divineinterventionpodcast.com and then I have a You Tube channel divineintervention usmlypodcasts and videos and that's where I post the videos that I make although again if you want the slides that go with those specific videos that I episodes go on the website you you'll find those there and then one other thing I want to say that I've been advertising a recent times with my podcast is many people you know used to listen to life lessons but uh life lessons that I put at the end of my different podcasts at least some of them so and I've got in tons of emails I to be honest yeah I can't remember exactly how many but I've got in a very decent number of emails or people like divine you know I've been blessed by listening to your life lessons um it's really causing me to like change my behavior in a certain way blah blah blah blah and again as many of you know probably listen to this podcast in a Christian so I decided to make a new website so the divineinterventionpodcast.com that's where I'm going to put in podcasts but I said I'll make a new website just for the life lessons it's called divine intervention life lessons right so divine intervention life lessons is you know so website is a basically an audio podcast as many of you probably recognize I I love teaching I absolutely love teaching even in church I do a ton of teaching so divineinterventionlifelessens.com you'll see episodes there where again you can just listen to the podcast most of th

em are going to be like between five and probably no more than 10 minutes long and they're very short but you'll have like some short Bible based teaching that applies to many of us that are medical professionals but also just to perfect just to any human being right so I'll talk about like a life lesson kind of like I've always talked about at the end of some of my podcasts and again I think you should find that to be to be helpful so again if you if you want to listen to any of those podcasts and I actually have it on Apple Podcasts as well so if you search for divine intervention life lessons it's a podcast on Apple Podcasts so thank you for listening to me today hopefully you found this podcast to be helpful I will see you in the next episode have a wonderful day and God bless you thank you

The principle of electroneutrality; cations must roughly equal anions ($\text{Cation} \approx \text{Anion}$).

Less than $7.35$ (acidemia).

Sodium ($\text{Na}^+$), Chloride ($\text{Cl}^-$), and Bicarbonate ($\text{HCO}_3^-$).

$\text{AG} = \text{Na}^+ - (\text{Cl}^- + \text{HCO}_3^-)$.

The accumulation of unmeasured, non-$\text{Cl}^-$ or non-$\text{HCO}_3^-$ anions (e.g., lactate, ketoacids).

The increased $\text{Cl}^-$ load forces a compensatory drop in $\text{HCO}_3^-$, worsening the acidosis.

Hyponatremia, hyperkalemia, and metabolic acidosis.

Lactic Acidosis $\rightarrow$ High Anion Gap Metabolic Acidosis.

Acetate ($\text{CH}_3\text{COO}^-$) and $\beta$-hydroxybutyrate, which are non-$\text{Cl}^-$ or non-$\text{HCO}_3^-$ anions.

Failure of the proximal convoluted tubule to reabsorb filtered $\text{HCO}_3^-$.

Aldosterone.

Respiratory compensation involves blowing off $\text{CO}_2$ (respiratory alkalosis) to raise $\text{pH}$. The calculation uses Winter's Formula: $1.5 \times \text{HCO}_3^- + 8 \pm 2$.

Lactic acid comes from anaerobic metabolism (shock); Ketoacids come from counter-regulatory hormones/insulin deficiency.

Lactic Acidosis $\rightarrow$ High Anion Gap Metabolic Acidosis.

Acetate ($\text{CH}_3\text{COO}^-$) and $\beta$-hydroxybutyrate, which are non-$\text{Cl}^-$ or non-$\text{HCO}_3^-$ anions.

Failure of the proximal convoluted tubule to reabsorb filtered $\text{HCO}_3^-$.

Aldosterone.

Respiratory compensation involves blowing off $\text{CO}_2$ (respiratory alkalosis) to raise $\text{pH}$. The calculation uses Winter's Formula: $1.5 \times \text{HCO}_3^- + 8 \pm 2$.

Lactic acid comes from anaerobic metabolism (shock); Ketoacids come from counter-regulatory hormones/insulin deficiency.