Multidisciplinary Dialogue: Clinical Rounds and Case Reviews, Ep. 4

A Patient With Metabolic Alkalosis

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 a patient with metabolic alkalosis, including the criteria, the most common causes, and the phases of metabolic alkalosis. 

For more cardiometabolic risk content, visit the Resource Center.

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 program director for the internal medicine residency program and the ambulatory care director at Touro University and St. Joseph 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 metabolic alkalosis. The views of the speakers are their own and do not reflect the views of their respective institutions or the views of Consultant360.

Dr Paul Shiu: Good morning folks! Good morning, Dr. Harrison.

Dr Anil Harrison: Hi Paul. Good morning.

Dr Paul Shiu: Because I was thinking about it, I was getting very sentimental. We were trying to celebrate our fourth episode anniversary. I was at the Hallmark store the other day, and I saw this card that said, "People are making end-of-the-world jokes like there is no tomorrow." I thought this is a clever and witty thing to put on a card. So what's the topic today, Dr. Harrison?

Dr Anil Harrison: I think, Paul, we are supposed to talk about metabolic alkalosis.

Dr Paul Shiu: And what is metabolic alkalosis? Well, folks, we're going to elucidate that during today's episode of this multi-part series on acid-base. So I actually had a patient and I wanted to run it by you, Dr. Harrison. A 51-year-old presenting with a history of hyperlipidemia, and uncontrolled hypertension for the past 2 years. He's on amlodipine, metoprolol, and these are his labs: a sodium of 135, potassium of 4, a chloride of a hundred and a bicarb of 32.

Okay. So for those out there in the podcast world, the criteria for alkalosis, pH is greater than 7.45, a bicarb greater than 28. These are the criteria that confirm that the patient has metabolic alkalosis. And if you recall, our patient actually has a bicarb 32. So now we're on this trajectory of metabolic alkalosis. Dr Harrison, would you walk us through the common causes, please?

Dr Anil Harrison: Yeah, Paul. The most common causes for metabolic alkalosis are vomiting, NG suctioning, and diuretics. People start talking about Bartter's and Gitelman's. I just want to mention that they're not that common.

Dr Paul Shiu: Oh.

Dr Anil Harrison: So now you think about it, our patient had neither of the above. He wasn't vomiting. He didn't have an NG. And supposedly he's not been on any diuretics. Now that is what he tells us, no diuretics.

Dr Paul Shiu: Right.

Dr Anil Harrison: So you think about metabolic alkalosis and there are actually 2 stages. There's the acute phase, also called the generation phase. For example, a person who has just started vomiting or who is undergoing nasogastric suctioning. The second stage is the maintenance phase where the kidneys, for some reason, are unable to get rid of the excessive bicarbonate.

Dr Paul Shiu: Wait, Dr. Harrison, can you go through the pathophysiology to explain all this?

Dr Anil Harrison: Sure. So let us elaborate on this. If you take GI issues such as excessive vomiting or nasogastric suctioning or congenital chloride diarrhea and VIPomas, what happens over there is, there is a loss of hydrogen ions and chloride ions, of course. And of course, there is loss of volume. With the loss of hydrogen ions one can get alkalosis and of course, with volume loss, one can get contraction alkalosis. With conditions of low volume states, what happens is that renin gets stimulated in the juxtaglomerular operators, which stimulates the cascade of angiotensinogen and you have angiotensin one, and then you get angiotensin two. Angiotensin two does two things.

Firstly, in the proximal convoluted tubule, it causes retention of sodium and bicarbonate. And secondly, in the distal convoluted tubule, it stimulates aldosterone. "Wakey, wakey, aldosterone!" And what aldosterone does, it causes sodium and chloride retention along with potassium and hydrogen ion excretion, thus explaining how volume contraction and intravascular volume loss results in a metabolic alkalosis. In this scenario, Paul, you would agree that the urine chloride would be low.

Dr Paul Shiu: Yeah. I'm starting to see what you mean here, but I have a question for you. How does severe hypokalemia cause metabolic alkalosis though?

Dr Anil Harrison: Sure. So what happens with severe hypokalemia, the intracellular potassium ions from within the cell, they move to outside the cell in exchange for an influx of hydrogen ions, causing a metabolic alkalosis. So hydrogen ions get into the cell from outside and potassium comes out.

Dr Paul Shiu: It's like you're trying to maintain electro neutrality.

Dr Anil Harrison: Correct.

Dr Paul Shiu: Ah. Okay. So now I have another question for you. Why is the urine chloride low in edematous states, such as congestive heart failure, cirrhosis and chronic renal failure or necrosis?

Dr Anil Harrison: Good question. So if you consider these edematous states, either the hydrostatic pressure is elevated or the oncotic pressure is low, which causes externalization of fluid resulting in edema, but the effective intravascular volume is low and hence, angiotensin two and aldosterone are active just as with the low volume states we discussed a minute ago.

Dr Paul Shiu: So just exactly how do you approach a patient with metabolic alkalosis then? Do you have a method to go about sorting through the various categories?

Dr Anil Harrison: The very first thing is I would recommend doing a thorough history and physical and assessing the volume status of the patient. The blood pressure is low normal. Therefore, it makes sense that we need to consider contraction alkalosis, vomiting, nasogastric suctioning, diuretics, Bartter's and Gitelman's syndrome in the differential diagnosis.

If the volume status is normal to high, the important thing is to check blood pressure and serum potassium. If the blood pressure and potassium are normal, you might want to consider Milk-Alkali syndrome. If the blood pressure is normal and the potassium is low, the metabolic alkalosis could be because of hypokalemia. If a person has low potassium because as you know, low potassium also causes in the proximal convolute tubal to reabsorb by carbonate while also excreting hydrogen ions in the collecting duct. So severe hypokalemia can give you a metabolic alkalosis because of this. Going further, if the blood pressure is high and the potassium is low, this possibly represents mineralocorticoid excess.

So the next thing would be to check renin and aldosterone levels. If the renin is low, but the aldosterone is elevated, this probably is primary hyperaldosteronism. But if both renin and aldosterone are elevated, both of them are elevated, then this possibly is secondary hyperaldosteronism. If both renin and aldosterone are normal, this could be Cushing syndrome. And if both renin and aldosterone are low, consider that the person might be getting exogenous steroids or might be consuming licorice, or the patient might have Liddle syndrome. L-I-D-D-L-E, Liddle syndrome.

Dr Paul Shiu: You mentioned something earlier, Dr Harrison, about Milk-Alkali syndrome. Would you please elaborate more on that?

Dr Anil Harrison: Yes. So in the past folks who had symptoms of Peptic Ulcer Disease, they used to consume milk along with sodium bicarbonate, which-

Dr Paul Shiu: Baking soda.

Dr Anil Harrison: Yeah. Baking soda.

Dr Paul Shiu: You're kidding.

Dr Anil Harrison: I'm not.

Dr Paul Shiu: Oh.

Dr Anil Harrison: So this would cause alkalosis and that is why the term Milk-Alkali syndrome comes about. And having mentioned that, folks who actually take excessive calcium can also get something very similar to a Milk-Alkali syndrome.

Dr Paul Shiu: Is it because they took something like calcium carbonate?

Dr Anil Harrison: Correct.

Dr Paul Shiu: Oh, okay.

Dr Anil Harrison: Absolutely. Absolutely.

Dr Paul Shiu: This is all making so much sense now, Dr Harrison. So we've talked about assessing, always stressing the physical exam. The next thing is, could you elaborate on diuretic use, Bartter's and Gitelman as causes from metabolic alkalosis?

Dr Anil Harrison: Sure. Absolutely. So diuretic use is one of the most common causes for metabolic alkalosis. And as I mentioned before, Gitelman's and Bartter's are rare. If you consider the structure of a nephron, Bartter's syndrome functions very similar to loop diuretics, acting on the ascending thick limb of Henle, where one sodium, one potassium and two chloride ions are reabsorbed. There is a defect in the protein with Bartter's syndrome and hence, you have increased urinary chloride, normal blood pressure with elevated renin and aldosterone levels, with increased calcium levels, urinary calcium levels. Remember you use Furosemide, or Lasix, in folks with increased volume, such as congestive heart failure, renal failure, who have hypercalcemia, right?

Dr Paul Shiu: Mm.

Dr Anil Harrison: Now sodium and chloride are reabsorbed in the early distal convoluted tubule and the absence of that protein results in Gittleman's syndrome. The function is very similar to how Thiazide diuretics work. Once again, you have elevated urine chloride levels, normal blood pressure, elevated renin and aldosterone, but low urine calcium levels. Remember, Thiazides cause calcium reabsorption in the tubules.

Dr Paul Shiu: Beautiful. And I think we exploited this also in gout, is that correct?

Dr Anil Harrison: Absolutely.

Dr Paul Shiu: Ah, see? All these connections. Maybe we can have an episode gout, too.

Dr Anil Harrison: Absolutely. You could.

Dr Paul Shiu: All right. So our patient is one with metabolic alkalosis. Both renin and aldosterone were elevated with an aldosterone renin ratio of significantly less than 20:1. Therefore, we are looking for causes for secondary hyperaldosteronism, such as renal artery stenosis.

Dr Anil Harrison: Absolutely, Paul. Given his age, the risk factors, that could be a possibility for the secondary hyperaldosteronism, renal artery stenosis.

Dr Paul Shiu: That's perfect. So what are your thoughts on a high urine chloride with a low normal BP?

Dr Anil Harrison: So if you have a high urine chloride and a low normal volume status, low normal blood pressure without any extra cellular fluid or edema, the most common cause in this category is diuretic use. Once and only once this has been ruled out, then you consider, or you could consider, Bartter's syndrome or Gittleman's syndrome. Bartter's syndrome, as I mentioned, behaves very similar to furosemide, while Gitelman's behaves more like thiazide diuretics. Remember the urine chloride in these conditions is going to be elevated.

Dr Paul Shiu: What are your thoughts on the high urine chloride with a normal high BP blood pressure?

Dr Anil Harrison: Sure. So with a high urinary chloride, high blood pressure, extracellular fluid is often absent. One needs to consider mineralocorticoid excess, both endogenous and exogenous along with Liddle syndrome in the differential.

Dr Paul Shiu: Hmm. So question is why isn't there edema with the aforementioned?

Dr Anil Harrison: That's a great question, Paul. This occurs actually because of a mechanism that is called aldosterone escape. With excessive aldosterone, sodium and bicarbonate are reabsorbed, and then the excessive sodium then causes a salt diuresis and hence, there is no edema in these states.

Dr Paul Shiu: That actually makes sense.

Dr Anil Harrison: Good.

Dr Paul Shiu: Dr Harrison, this is a very succinct and thorough review of metabolic alkalosis and the workup for you folks out there in the interwebs and the podcast world of the other verses, I want to say thank you so much for your support and for tuning in. I hope that this helped you in your journey to becoming a better physician. There's more to just metabolic alkalosis than looking at bicarb. There's an entire workup. And I think Dr Harrison has shown us that it is definitely possible for us to thoroughly evaluate our patients. Wouldn't you say that, Dr. Harrison?

Dr Anil Harrison: Yes. I agree, Paul, and thank you for your kind words.

Dr Paul Shiu: Please tune in on our next episode, podcast five.

Dr Anil Harrison: Thank you, everybody.

Dr Paul Shiu: Thank you, everybody.