# Metabolic Acidosis

In this episode, Dr Harrison speaks with Paul Shiu, DO, about metabolic acidosis and alkalosis, including confirming the patient's serum bicarbonate is low, calculating the anion gap, calculating the serum osmolality, calculating the delta gap, and more.

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

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

**TRANSCRIPTION:**

**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 Touro University and Saint 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 metabolic acidosis. The views of the speakers are their own and do not reflect the views of their respective institutions.

**Dr Paul Shiu: **Good morning, Dr Harrison.

**Dr Anil Harrison: **Hi, Paul.

**Dr Paul Shiu: **It seems like such a long time since we recorded our first podcast. How have you been?

**Dr Anil Harrison: **I've been well, Paul. Just waiting for the second one to happen, so I'm excited.

**Dr Paul Shiu: **I think that's what we're here for today and I'm very pleased to, I guess, pick up where we left off. Remind us again, what our topic is today, Dr Harrison.

**Dr Anil Harrison: **I thought, Paul, you mentioned we needed to talk about metabolic acidosis, both the high and the normal anion gap.

**Dr Paul Shiu: **That is right, we're picking up exactly where we left off. Without further ado, Dr. Harrison, I actually went to start off our metabolic acidosis with a very relevant case that I actually had. Do you mind?

**Dr Anil Harrison: **Yes, absolutely.

**Dr Paul Shiu: **Okay. I saw this 18-year-old with Type 1 diabetes, presenting with a fever, diarrhea, and altered mental status. His labs revealed a blood sugar of 700. Just for emphasis, 700 folks. A sodium of 130, a potassium of 4, a chloride of a 100, a bicarb of 12 and a BUN of 20, creatinine of 1. His serum sodium is positive for ketones and measured serum osmolality of 304. Blood gas has revealed a pH of 7.27, a posture pressure of CO2 of 27, posture pressure of O2 of 85 millimeters of mercury and a bicarb of 12. What is going on, Dr Harrison?

**Dr Anil Harrison: **Okay. If you think about it, Paul, what I would like to do before we get into solving this case, I would like to give you, in chronological order, how to go about metabolic acidosis.

Which is basically low serum bicarb. The first thing you do is to confirm that the serum bicarb is low. If one has blood gases, it would point towards a pH of less than 7.35. Then the next thing to do is to calculate the anion gap, which is sodium minus chloride minus bicarbonate. A normal anion gap is 12+/-4, which means an anion gap of 8 to 16 is about normal. Therefore, with a low bicarb, you could either get a high anion gap metabolic acidosis, which is greater than 16 or a normal anion gap, which is less than 16. In other institutions, an anion gap of 8 to 12 is normal due to the methods involved with calculations.

The next step is to calculate the serum osmolality, which is two x serum sodium + blood sugar/18 + bun/2.8 and compare it to the lab-measured serum osmolality. If the gap is greater than 10, this is significant and relates to other Osmo's, which are contributing to the elevated serum osmolality with metabolic acidosis. Things like methanol and ethylene glycol need to be considered. If you have a high anion gap metabolic acidosis or HAGMA. The next step is to calculate the delta gap, which equals the patient's anion gap minus a normal anion gap of 12. Following this to see what the expected serum bicarbonate ought to be. There are several ways of doing this, but this is how I do it. You take the normal bicarb of 25 and subtract the delta gap from this.

The question is, why do we do this? The reason we do this as mentioned in podcast 1, one could have more than one metabolic component going on. After you've done this, then you compare the expected or the calculated bicarb with the laboratory-measured serum bicarb. If the patient's measured serum bicarb is greater than the expected bicarb, this tells you besides having a high anion gap metabolic acidosis, there are bicarbonate ions that are retained, signifying a metabolic acidosis. Conversely, if the measured serum bicarbonate is lower than the expected serum bicarbonate, this signifies that there is NAGMA or a normal anion gap metabolic acidosis. In addition to the HAGMA or the high anion gap metabolic acidosis that the patient has. If the anion gap is normal and the serum bicarbonate is low, this is NAGMA. Denoting that either bicarbonate is being lost or there is a problem generating hydrogen ions in the kidneys pointing either to a problem in the gut or within the kidneys. Most often you will see that chloride is elevated. This is also called hyperchloremic non-anion gap metabolic acidosis.

**Dr Paul Shiu: **What we see here is, that we have a patient young sick male with Type 1 diabetes and he's in ketoacidosis. The question is whether there is more to the actual picture, the measure of serum osmolality was 3 0 4, and we calculate the serum osmolality to be 3 0 2. Therefore, there is no osmolar gap. Conditions like methanol, ethylene, and glycol ingest have been ruled out, essentially.

**Dr Anil Harrison: **Absolutely.

**Dr Paul Shiu: **We see the criteria for metabolic acidosis being a pH of less than 7.35 and bicarb less than 22. Our patient clearly has a metabolic acidosis with a pH of 7.27 and a bicarb of 12.

**Dr Anil Harrison: **Correct.

**Dr Paul Shiu: **What should we do next then?

**Dr Anil Harrison: **We know how to calculate the serum anion gap. The serum anion gap is sodium minus chloride minus bicarb. Normal anion gap is 12+/-4. If the gap is elevated, we will call it a high anion gap metabolic acidosis, or a HAGMA and if it's a normal anion gap, we'll call it NAGMA. With NAGMA the utility of a urine and anion gap, which is sodium plus potassium minus chloride. The actual number is zero on this or it could be slightly negative. This has the greatest utility with a normal anion gap metabolic acidosis. We are not going to discuss it right now because we are dealing with a high-end gap metabolic acidosis.

**Dr Paul Shiu:** So our patient clearly has a high anion gap of 18. We abbreviate it as HAGMA. It's so fun to say, isn't it, Dr. Harrison?

**Dr Anil Harrison: **Absolutely. Yes, HAGMA.

**Dr Paul Shiu: **Whenever someone has a HAGMA think of the pneumonic "cat mudpiles." What a funny thing. Can you imagine cat mud piles? I'd just think of cat as in C stands for carbon monoxide, cyanide, congenital heart disease associated failure, A for aminoglycosides, T for theophylline and toluene. Glue sniffing, right?

**Dr Anil Harrison: **Correct.

**Dr Paul Shiu: **M is for methanol, U is for uremia, D is for diabetic ketoacidosis, alcohol and starvation ketoacidosis, P is for propofol, paraldehyde, phenformin, paracetamol, or here in The States, we call it acetaminophen. Then I for iron overload, isoniazid, inborn errors of metabolism, L represents lactic acidosis, E for ethylene glycol and S stands for salicylates.

**Dr Paul Shiu: **Dr Harrison, I noticed that methanol and ethylene glycol are on this list and takes us back to the osmolar gap that we're talking about earlier, right?

**Dr Anil Harrison: **Correct.

**Dr Paul Shiu: **Okay.

**Dr Anil Harrison: **Correct. Because we had no or smaller gap, we could say that the possibility of methanol and ethylene glycol aren't really there in our patient.

**Dr Paul Shiu: **Oh, absolutely.

**Dr Anil Harrison: **What I would like to point out, Paul, is that the anion gap is dependent on a normal serum albumin. A normal ion gap of about 12 is within normal with a normal serum bicarb of 25. One would therefore reason as the bicarb goes down, for example, 10 points. It goes from 25 to 15, the anion gap would widen from 12 to the number 22. What we did over here was we added 10 bicarbonate to the number 12 and we came up with 22. Unfortunately, this does not always happen, especially if there is another metabolic problem going on, such as either a normal anion gap metabolic acidosis or a metabolic alkalosis.

To ascertain if there is another metabolic problem such as NAGMA or a metabolic alkalosis going on. In addition to the HAGMA one calculates the expected bicarb, which equals a normal bicarb 25 minus the delta anion gap. If there is only a high ion gap, and metabolic acidosis, you are expected by a carbon should equal the measured lab bicarbonate value. If the measured or patients by carbon is significantly more than the expected or calculated bicarbonate, this denotes an additional metabolic alkalosis.

On the other hand, if the patient's bicarbonate is less than the expected bicarbonate, there is NAGMA also going on. Therefore, in our patient who has a sodium of 130, a potassium 4, a chloride of a 100 and a Bicarb of 12. Clearly, he has a high anion gap metabolic acidosis with anion gap of 18. His delta gap is 18 minus 12, which equals six. The expected bicarb therefore should be your normal bicarbonate of 25 minus the delta anion gap of 6, which equals 19.

If you actually look at the patient's bicarb, his bicarb is only 12. Signifying that the patient's bicarb is lower than the calculated or expected bicarb. This clearly tells you that this patient also has MAGMA also called a normal anion gap metabolic acidosis. I think this is possibly secondary to his diarrhea with loss of bicarbonate.

**Dr Paul Shiu: **So, recapping for our audience here, there's a lot of good information here.

We have an 18-year-old with Type 1 diabetes on insulin presented with fever, diarrhea, and alter mental status. He has a high anion gap metabolic acidosis, secondary to DKA, diabetic ketoacidosis and a normal, anion gap metabolic acidosis, possibly secondary to diarrhea. His lungs are actually functioning well blowing off CO2. We see the bicarb is 12 plus 15, otherwise known as equal to 27.

As we remember from a previous episode, there exists a relationship between the carbon dioxide CO2 and bicarb. They're always around 15 of each other, where the 27 came from. Then as we recap our approach of metabolic acidosis, the first thing you should do, we should all do, is to confirm that the serum bicarb is low. Number one, if one has blood acids issued point towards a pH of less than 7.35.

**Dr Anil Harrison: **Correct?

**Dr Paul Shiu: **The next step is to calculate the anion gap, which is sodium minus chloride minus bicarb. Now, in some hospitals, I just want to point this out, they sneak in potassium. Be sure to calculate the anion gap for yourself, at least the first time, and see if it corresponds to the anion gap calculated in the labs in your EHR.

Once again, it's sodium minus chloride minus bicarb. A normal anion gap is 12+/-4, which means an anion gap of 8 to 16 is about normal. Now there's a huge caveat here. Once again, that Dr. Harrison mentioned this normal anion gap of 12+/-4 is based off of a normal albumin. Keep that in mind as well. But a good ballpark figure is 12+/-4. Therefore, with a low bicarb, you could either get a high anion gap greater than 16 or a normal anion gap, which is less than 16.

The next step is to calculate the serum osmolality, which is two times sodium because you want to account for the sodium chloride go together. So two times sodium plus sugar divide by 18, bun divide by 2.8.

**Dr Anil Harrison: **Correct.

**Dr Paul Shiu: **Compare that to the lab-measured serum osmolality. If the gap is greater than 10, this is significant. It relates to other Osmo's, which are contributing to the elevated serum osmolality with the metabolic acidosis, such as the toxic alcohols, which we also mentioned in our first podcast.

Those of you who did not listen to the first podcast, this is a shameless promotion for you to also check us out on our first podcast.

There's methanol, ethylene, and glycol. Okay. If you have a high anion gap metabolic acidosis or HAGMA, the next step is to calculate the delta gap, which equals the patient's anion gap minus in normal anion gap 12.

The next step is to see what the expected serum bicarb ought to be. There are several ways of doing this, and this is how Dr. Harrison does it and how I choose to do it as well. You take the normal buy carb of 25 and then you subtract it from the delta gap.

I'm sure all these inquisitive minds out there, all these budding, Dr. Harrison's are probably wondering, why do we do this? What an arbitrary formula, normal bicarb with 25 minus the delta gap. The reason why we do this as mentioned once again, in podcast one. One could have more than one metabolic component going on, you compare the expected and calculate bicarb to the laboratory-measured serum bicarb. If the patient's laboratory measures serum bicarb is greater than the expected to calculate bicarb. This tells us besides having a HAGMA, there has to be bicarb ions starting with pain. This, of course, signifies metabolic alkalosis. You have excess bicarb. `That creates an alkalotic picture, hence metabolic alkalosis.

Conversely, if the measured serum bicarb is lower than the expected in calculus serum bicarb ratio. This signifies that there is a NAGMA in addition to a HAGMA, right?

**Dr Anil Harrison: **Correct.

**Dr Paul Shiu: **Because if we don't have an excess in bicarb, it's normal anion gap. If the anion gap is normal and the serum bicarb is low, this is a NAGMA denoting that either bicarb is being lost or there's a problem generating hydrogen irons in the kidney, pointing either to a problem in the guts, ne-gut-ive and this is a preview for those of you who have no idea why it just emphasized ne-gut-ive, negative or within the kidneys. Most often you would see that the chloritus elevated also called hyperchloremic non-anion gap metabolic acidosis.

**Dr Anil Harrison: **Both of us know anion gap is useful when you have a patient with a metabolic acidosis and you want to know if it's a high anion gap metabolic acidosis or a normal anion gap metabolic acidosis. The way to calculate anion gap is your sodium minus chloride plus bicarbonate.

You had a great question, there're certain institutions that use anion gap which is from 8 to 16. But there are other institutions where depending on the way that it's check, the anion gap is 8 to 12. As you know, the anion gap also depends on the serum albumin. If you've got a normal serum albumin of four and you multiply this by 2.5, you get in a anion gap of 10. If the albumin is low, your anion gap also gets lower. For every gram of albumin that is below normal, you have to deduct about 2.5 milli equivalent per liter on the anion gap. I hope I've answered that question.

**Dr Paul Shiu: **Anion gap is one of those things that I think we'd definitely take for granted, in some systems, especially the institution where I train. The way anion gap is calculated, incorporates potassium, right?

A lot of people simplify the anion gap calculation. Sodium plus potassium becomes sodium minus chloride plus bicarb, right?

**Dr Anil Harrison: **Correct.

**Dr Paul Shiu: **The reason why that is also because sodium is the dominant cat ion. Potassium really doesn't contribute much, but if you dolo potassium that alters your gap a little bit. Then on top of that, the albumin is also a much-neglected protein in the blood. Even though it's not in the equation, it's a large contributor towards what is considered normal range. That's the reason why Dr. Harrison wanted to also clarify this particular point.

**Dr Anil Harrison: **Absolutely, Paul. Normal anion gap reflects the concentration of non-bicarbonate anion buffers, such as albumin, phosphate, sulfate, and other organic acids. Albumin, which has a net negative charge is the single largest contributor to the anion gap.

**Dr Paul Shiu: **So folks you have sodium on the other side and you have albumin on the other side.** **Without further banter, I invite you guys to revisit podcast 1 and definitely revisit podcast 2, because there's a lot of good information here. Podcast 3, will be out very shortly, we try to have regular uploads.

**Dr Anil Harrison: **Well, thank you so much, Paul. It's always a pleasure doing this with you.

**Dr Paul Shiu: **Likewise, pleasure is all mine. Thank you, Dr Harrison.

**Dr Anil Harrison: **Thank you.