Learn how to use the GOLDMARK mneumonic for all things AGA!


How do you think about metabolic acidosis with a high anion gap? Today, let’s break down the top causes of anion gap acidosis. Using the GOLDMARK mnemonic. I like to write GOLDMARK like this. It helps us group the mnemonic in a way that’s easier to digest. I’ll show you. Let’s start at the top, G and M.

Let’s start with G, which stands for the glycols, ethylene and propylene glycol. These are compounds found in products such as  coolants, antifreeze, or nail polish remover.   If ingested, it can lead to a high anion gap acidosis. And also, these compounds can crystallize in renal tubules and  cause kidney damage. Now, M stands for methanol. That’s a compound found in certain fuels. If ingested, in addition to acidosis, it can lead to  blindness. So altogether, this is the alcohol box. That will prompt you to think about alcohols that aren’t listed here, but can cause an anion gap acidosis, like isopropyl alcohol or ethanol.

Okay, so how do we know if our patient’s anion gap is from an alcohol? Well, we can take advantage of the fact that alcohols are osmotically active, meaning they increase the osmolarity of the blood.

So let’s say you have a patient with alcohol toxicity and then you  calculate the osmolarity of their blood but then you actually also directly measure it.  You’re gonna find the measurement is actually higher than what you calculated because those calculations usually don’t include alcohols.  That’s called the osmolarity gap and can be a sign that your patient’s anion gap might be from alcohol toxicity.

Let’s move on down to the next box, O and A. O is for oxyproline and all you need to know is that that’s a metabolite of  Tylenol. Or Tylenol, if you want to stress the O to make it stick.  A is for aspirin,  but use this to remind yourself that other salicylates can cause an anion gap acidosis too. This includes bismuth subsalicylate, or Pepto Bismol,  and  methyl salicylate, which is found in some topical pain medications like Bengay.

So this is the OTC, or over the counter medication box. Over ingestion of these medications can lead to acidosis in the blood, and sending an early serum tox screen is important to make an accurate diagnosis. Now we’re actually going to flip things a bit for the next box, L and D. L and D stand for, brace yourself, L and D lactate. Those are the two isomers of lactate. Let’s start by talking about the one that we might be more familiar with, L lactate. So L lactate is a byproduct of anaerobic respiration in the body. But did you know that there are two different ways it can build up?

So the first is type A lactic acidosis.  Think A for anoxic. When oxygen isn’t getting to cells, they’re undergoing anaerobic respiration instead.  No oxygen means mitochondria aren’t working, means anaerobic respiration and lactate. So what if oxygen’s getting to our cells just fine, but something else is causing lactate to build up? Well that’s type B lactic acidosis, and think B for build up. This can be for three major different reasons. The first is if the mitochondria just aren’t working, which can happen from different medications or toxins. The next can be if cells are using energy faster than mitochondria can handle. That happens in certain cancers, and it’s called the Warburg effect. Finally, it can happen if you’re making lactate at a normal rate, but it’s just not being cleared quickly enough. Which you can see in things like cirrhosis.

Finally, we have D lactate. Now think D for diarrhea. This actually isn’t a product of our cells, but of the bacteria that live in our gut. If a patient has a disorder where carbohydrates build up in the gut, such as those with a history of GI surgery, or carbohydrate malabsorption, then bacteria will eat those carbohydrates instead and turn them into D lactate.

Now this is lactate, it does get absorbed by our blood, and it can cause an acidosis. But most lab assays for lactate won’t pick this up. So, in those who have a history of GI surgery or carbohydrate malabsorption, you have to maintain a high clinical suspicion if you see acidosis. Okay, on to our final box, R and K are in the metabolic box.

Now, renal failure can cause an anion gap acidosis two major ways. The first, and one that you might be more familiar with, is a buildup of nitrogen waste products, like blood urea nitrogen in the blood. But don’t forget that normal metabolism produces organic acids, which can build up in renal failure and cause an anion gap acidosis.

Finally, K stands for ketones. When we’re low on energy, our body will break down fats to create acidic ketones in the body for energy.  Then when we eat, insulin is released, and that shuts off the production of ketones. So there are three common scenarios for ketone production in the body. One is that you  aren’t eating and you need more energy, such as in starvation. The second is heavy alcohol use.  The mechanism can get a bit complicated, but essentially these patients often present with starvation as well. But alcohol byproducts worsen the ketogenic effect of starvation and actually cause direct fat breakdown itself. And the third is if you don’t have enough insulin to tell ketone production to stop, like in diabetes. Now ketones can be detected in the urine, but generally they should be confirmed and actually quantified with blood testing. The most common test is for beta hydroxybutyrate, which is a byproduct of the ketone acetoacetate.

Alright, and there you have it. This is a breakdown of some of the most common causes of high anion gap acidosis, their etiologies, and how to test for it. I hope this helps you out the next time that you need to mind the gap.

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