Multidisciplinary Dialogue: Clinical Rounds and Case Reviews, Ep. 3

A Patient With a Normal Anion Gap Metabolic Acidosis

Anil Harrison, MD

This podcast series aims to highlight the prevention, diagnosis, and treatment of patients with diseases commonly seen in internal medicine. Host, Anil Harrison, MD, discusses patient cases with residents and with prominent experts to help educate clinicians in treating patients using a multidisciplinary approach.

In this episode, Dr Harrison speaks with Paul Shiu, DO, about interpreting arterial blood gases, including calculating a high anion gap metabolic acidosis (HAGMA), a normal anion gap metabolic acidosis (NAGMA), a urinary anion gap, renal tubular acidosis, and their possible causes.

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Anil Harrison, MD

Anil Harrison, MD, is the associate program director of the internal medicine residency program and the ambulatory care director at Touro University and St Joseph’s Medical Center-Dignity Health (Stockton, CA). Dr Harrison is board certified in India and the United States.

Paul Shiu, MD
Paul Shiu, DO, is a second-year internal medicine resident at St Joseph's Medical Center (Stockton, CA).

Dharminder Singh, MD

Dharminder Singh, MD, is an internal medicine chief resident at St Joseph’s Medical Center (Stockton, CA).


Moderator: Hello everyone. And welcome to Multidisciplinary Dialogue: Clinical Rounds and Case Reviews with your host, Dr. Anil Harrison, who is the Associate Program Director for the Internal Medicine Residency Program and the Ambulatory Care Director at Toro University and St. Joseph's Medical Center, Dignity Health in Stockton, California.

Today, we have a case review that Dr Harrison and Dr Paul Shiu will analyze and provide treatment insights. Dr Shiu is a second-year internal medicine resident at St. Joseph's Medical Center in Stockton, California. In this episode, we'll discuss HAGMA and NAGMA. The views of the speakers are their own and do not reflect the views of their respective institutions or the views of Consultant 360.

Dr Paul Shiu: Dr Harrison, how are you doing this morning?

Dr Anil Harrison: I'm doing well, Paul. It's a beautiful day. Very good morning to you.

Dr Paul Shiu: Very good morning to you. For our new listeners, you may not know this, but Dr Harrison and I, we like to start off our podcast with a joke. And in this case, it's not so much of a joke as much of it, it is an observation. People tell me not to eat late at night for many reasons, but if there is an issue of eating at night, why do they have light bulbs in the refrigerator, Dr Harrison?

Dr Anil Harrison: Search me, Paul.

Dr Paul Shiu: So today we're going to talk about metabolic acidosis, high and normal anion gap. So this is the third part to a series long on arterial blood gasses. We're building the foundation to interpret arterial blood gasses. The topic here is HAGMA and NAGMA. And I actually had a case, Dr Harrison, and I was wondering if you can help me out on it.

Dr Anil Harrison: I'd be happy to, Paul.

Dr Paul Shiu: We have a 40-year-old found to have the following labs upon evaluating of history of recurrent kidney stones. Sodium was 133. Potassium is 3.2. Chloride is 110. Bio carb is 15. A blood sugar of 100. A BUN of 20. A creatinine of 1. His measured serum osmolality by the lab is 280. And then if we calculate serum osmolality, which is sodium times two, plus glucose divided by 18, plus BUN divided by 2.8, we get a calculated serum osmolality of 278. This tells us there is a metabolic acidosis and there is no osmolar gap.

Dr Anil Harrison: Yes, you're right on that. So we have somebody with a metabolic acidosis and no osmolar gap. So if you think about it, Paul, if there is no osmolar gap, we probably can rule out methanol and ethylene glycol. Right? There is no osmolar gap.

Dr Paul Shiu: Correct.

Dr Anil Harrison: So our patient also meets the criteria for metabolic acidosis with a bicarb of 15. Normal bicarb is between 22 to 28. So what we need to do next is to determine if this person has an anion gap, which is sodium minus chloride minus bicarbonate. Our patient has an anion gap of eight, confirming that this is a normal anion gap metabolic acidosis.

So you think about it, what are the etiologies for a normal anion gap metabolic acidosis? And it's a simple mnemonic, which is called HARD UP. H stands for hyperalimentation, A for acetazolamide and other carbonic anhydrase inhibitors, such as topiramate, renal tubular acidosis Type I, IV, and II, ureterosigmoid fistula, and pancreatic fistulas because you lose bicarbonate. All these need to be entertained in the differential. However, if you think about it, our patient did not receive hyperalimentation. This patient is on no medications, has had no prior surgeries, and gives us no history of diarrhea. Therefore, I have a feeling that this might be pointing towards a renal tubal acidosis.

Dr Paul Shiu: So then if you notice, at least with our patient's labs, though, the bicarb is low, the chloride is high. I believe another term for this would be hyperchloremic metabolic acidosis.

Dr Anil Harrison: You're correct, Paul. Yes. So what is the pathophysiology for what actually happens with a normal anion gap metabolic acidosis is there is acidosis or retention of hydrogen ions, or there could be a loss of bicarbonate, which is alkaline. And while losing the bicarbonate, there is retention of chloride. Acid in the blood, in the form of hydrogen ions is excreted in the kidneys. As with an acid load, there is an increased production of ammonium by the nephrons, which combine with the hydrogen ions to form NH4. It is this NH4 that binds with chloride and is then excreted.

Because ammonia in the urine is difficult to measure, it's surrogate, which is chloride is therefore measured instead. The urine anion gap, which is urinary sodium plus urinary potassium minus urinary chloride is usually zero or has a slightly negative number. Remember, instead of measuring ammonia, we are going to measure its surrogate, which is urinary chloride. If the urine anion gap, which is urine sodium plus potassium minus chloride, if it has a negative value, if it has a neg-gut-ive value, you think of a gut problem.

Dr Paul Shiu: Ha-ha. This is serendipitous that the gut just fits into negative.

Dr Anil Harrison: Kind of.

Dr Paul Shiu: Very easy to remember. Thank you, Dr Harrison.

Dr Anil Harrison: Absolutely. But another reason for a negative urine anion gap could be a proximal renal tubular acidosis, which is a Type II. Now, what happens if the urine anion gap is positive? This points to the kidneys, especially, it's either a distal Type I or a Type IV renal tubular acidosis. If you remember with proximal Type II and distal Type I renal tubular acidosis, the serum potassium is low, but with a Type IV renal tubular acidosis, because of aldosterone deficiency or resistance, the serum potassium is elevated. Paul, if you agree, in another presentation, we could discuss renal tubular acidosis and we can go into the details of the various abnormalities that are seen with the different types of RTAs.

Dr Paul Shiu: It's funny, we had a morning report just today and we were talking about, we had a really good case on renal tubular acidosis or a discussion rather on renal tubular acidosis. And for the audience tuning in, who weren't fortunate enough to join us on the Morning Report here, why do we have renal tubular acidosis, 1, 2, and 4? What happened to three? I feel like renal tubular acidosis 3 is like Pluto. It's been kicked off. So hopefully, if Dr Harrison agrees, we can perhaps talk more about renal tubular acidosis as well as talk about what happened to 3.

Dr Anil Harrison: Yeah, poor little 3.

Dr Paul Shiu: Poor little 3. As a refresher, our patient has a urine anion gap that was positive, a urine pH which was 6.2. He had a low serum potassium. Therefore, his diagnosis points towards a Type I distal renal tubular acidosis.

Dr Anil Harrison: Spot on. Spot on, Paul. So to summarize, a 40-year-old patient with a history of recurrent kidney stones and labs to suggest a normal anion gap metabolic acidosis, who also had a positive urine anion gap, a urine pH of 6.2, I think would lead us to believe that he has a distal Type I renal tubular acidosis, which is sometimes associated with kidney stones.

Dr Paul Shiu: This whole business with reoccurring kidney stones, would you elucidate the connection between Type I RTA and kidney stones, please?

Dr Anil Harrison: Absolutely, Paul. This happens due to a lack of urine acidification by the distal nephron and due to a lack of urinary citrate. And that is why the treatment is potassium because these people have hypokalemia and you give them citrate. So potassium citrate is a treatment to replenish potassium as well as citrate and citrate gets converted into bicarbonate.

Dr Paul Shiu: A stroke of brilliance, folks. Well, Dr Harrison, we're very lucky to have you on board here to help us understand NAGMA and HAGMA and very useful mnemonics at that. Last time we talked about CAT-MUDPILES. Today, we talked about HARD UP. I don't know what acronym we have next coming up, but I do know because we're talking about kidney stones that we are just a stone’s throw away from our next podcast.

Dr Anil Harrison: That's a good one, Paul.

Dr Paul Shiu: I tried, Dr Harrison, just trying to keep up with you. So folks, thank you so much for tuning in for yet another podcast with Dr Harrison and me, and we hope that you continue to tune in. And for those who are just joining us, we invite you to listen to podcast one and two, because this is a longstanding series on understanding arterial blood gasses and acid base. And we implore you to listen, give us feedback and we'll get back to you. And if you ask a really, really, really difficult question and make us really scratch our heads, Dr Harrison will send you a personal message via email. Thank you, folks. Really do appreciate you.

Dr Anil Harrison: Thank you, everyone.