Ep 172: A 52-Year-Old Man with an Increased Respiratory Rate

In this episode in our “Physiology at the Bedside” series, we discuss the causes and pathophysiology of acidosis.

Read more on this topic in Harrison's

Harrison's Principles of Internal Medicine, 22nd Edition

Transcript

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[Ms. Heidhausen] This is Katerina Heidhausen, executive editor of Harrison's Principles of Internal Medicine. Harrison's Podclass is brought to you by McGraw Hill's AccessMedicine, the online medical resource that delivers the latest content from the best minds in medicine. And now, on to the episode. 

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[Dr. Handy] Hi everyone, welcome back to Harrison's Podclass. We're your co-hosts. I'm Dr. Cathy Handy. 

[Dr. Wiener] And I'm Dr. Charlie Wiener, and we're joining you from the Johns Hopkins School of Medicine. Welcome to Harrison's Podclass. Today's patient is a 52-year-old with an increased respiratory rate. Cathy, today's episode is the second in our Physiology at the Bedside series. 

[Dr. Handy] Great, bring it. 

[Dr. Wiener] So your patient today is a 50-year-old man with longstanding type 1 diabetes mellitus, complicated by mild diabetic nephropathy. His baseline creatinine is 1.9, with an estimated creatinine clearance of 60 mL/min. His usual medications are insulin by pump and losartan. He has not needed diuretics. He comes in today because over the last one to two days, he feels like he has to hyperventilate at rest, and it's been getting worse with exertion. Years ago, he had an episode of DKA, and he remembers feeling the same. 

[Dr. Handy] I need a little bit more history. So, has he been compliant with his insulin? Any recent illnesses or sick contacts, fevers, respiratory or GI symptoms, or new medications? Does he use illicit drugs or any alcohol? 

[Dr. Wiener] All good questions. He's very careful about his glucose, and his insulin pump is working well. No to any recent illnesses, systemic symptoms, new medications, or supplements or recent illnesses. He drinks a glass of bourbon or rye most nights before bed, but that's all. 

[Dr. Handy] Tell me about his vitals and his physical exam, and labs. 

[Dr. Wiener] He's in no acute distress, but he's clearly huffing and puffing as he walks down the hall to the exam room. 

[Dr. Handy] I'm glad to hear a pulmonologist describe that as "huffing and puffing," because that's my oncology description of breathing sometimes, too. 

[Dr. Wiener chuckles] Okay. He also is afebrile, his heart rate is 105, his blood pressure is 125/75, and his respiratory rate is 26 with an oxygen saturation of 96% on room air. 

[Dr. Handy] Okay, so his respiratory rate is definitely elevated. Anything on physical? 

[Dr. Wiener] No, it's entirely normal with no signs of volume depletion or overload. He has clear lungs, a normal heart, normal abdomen, extremities, and neurologic exam. 

[Dr. Handy] Labs? 

[Dr. Wiener] Because of his respiratory symptoms and history of DKA, you get a stat ABG which shows a pH of 7.34, a PCO2 of 25, and a PO2 of 70. 

[Dr. Handy] Okay, with his low pH and low PCO2, he has an acute metabolic acidosis with partial compensation. The fall in blood pH is accompanied by a characteristic increase in ventilation, which is giving us a lower PCO2. If he was not huffing and puffing, his pH would be about 7.22. That's a real acidosis. 

[Dr. Wiener] How'd you get to 7.22? 

[Dr. Handy] While not exact, generally speaking, an acute 10-millimeter reduction in PCO2 translates into a 0.08 increase in pH. So, if his PCO2 was 40 instead of 25, his pH would be lower by about 0.12, or his pH would end up being 7.22. I find that rule helpful at the bedside to help distinguish between acute and chronic metabolic disturbances. 

[Dr. Wiener] Okay, well, what's next? 

[Dr. Handy] The next step for any metabolic acidosis is to calculate the anion gap. So for that, we need his labs. 

[Dr. Wiener] Okay. His sodium is 140, potassium 5.3, chloride 118, bicarbonate 12, BUN 25, creatinine 2.0. His glucose is 135, and his hemoglobin A1c is 6.2%. And that's going to get us to our question. The question asks, which of the following is the most likely diagnosis? Option A. is alcoholic ketoacidosis. Option B. is diabetic ketoacidosis. Option C. is extensive vomiting. Option D. is type 1 RTA. And option E. is type 4 RTA. 

[Dr. Handy] All right, well first, let's calculate his anion gap, or sodium minus the chloride plus the bicarb. In his case, that equals 10, and that's normal. That immediately rules out options A. and B. Remember, an elevated anion gap is a reflection of unmeasured anions such as lactate or ketones. The four principal causes of a high anion gap acidosis are lactic acidosis, ketoacidosis, ingested toxins, and kidney failure, either acute or chronic. So he has none of those. I'll also add that typically, anion gap acidosis is seen in stage 3B, 4, or 5 kidney failure. Our patient is likely only in stage 2. 

[Dr. Wiener] Okay, so we've established that he has a normal anion gap metabolic acidosis. What causes those? 

[Dr. Handy] Non-anion gap metabolic acidosis is due to a loss of alkali, typically from the gastrointestinal tract as a result of diarrhea, or from the kidneys due to renal tubular abnormalities. In these disorders, reciprocal changes in chloride and bicarb maintain a normal anion gap. 

[Dr. Wiener] You mentioned diarrhea as a cause. Option C. suggested extensive vomiting. 

[Dr. Handy] Yeah, that's wrong. Extensive vomiting may cause a loss of acid and result in a metabolic alkalosis. 

[Dr. Wiener] Okay, so we're down to the RTAs or renal tubular acidoses. Tell me about them. 

[Dr. Handy] RTAs are a set of disorders characterized by renal tubular abnormalities that allow excessive excretion of bicarbonate. Reciprocal changes in serum chloride and bicarb maintain that normal anion gap, like I mentioned before. There are roughly three types of RTA. 

[Dr. Wiener] The question mentions type 1 and type 4. 

[Dr. Handy] Type 1 or distal RTAs may be seen as an acquired or inherited disorder. The features of classical distal RTA include hypokalemia, a non-anion gap metabolic acidosis, low urinary ammonium excretion, a positive urine anion gap, and an inappropriately high urine pH. Collecting a urine sample would be useful. 

[Dr. Wiener] You mentioned that type 1 RTA usually has hypokalemia, but our patient has hyperkalemia. 

[Dr. Handy] Yes, and so that's why I think option D. is false. 

[Dr. Wiener] You mentioned the urine anion gap. What's that? 

[Dr. Handy] Urine anion gap is an indirect estimate of urinary ammonium excretion. The urine anion gap is calculated the same as the serum anion gap. Normally, the urine anion gap should be negative, because urinary chloride is greater than the sum of sodium and potassium in the urine. If a patient has a non-anion gap metabolic acidosis and a negative urinary anion gap, this suggests an extrarenal cause of the acidosis. Diarrhea would be an example of that. Conversely, when the urine anion gap is positive, this suggests a renal tubular origin of the acidosis. 

[Dr. Wiener] Okay, so you think our patient has a type 4 RTA. Tell me what that is, and tell me why. 

[Dr. Handy] Type 4 RTAs are characterized by a non-anion gap metabolic acidosis with hyperkalemia, and that's disproportionate to the accompanying reduction in glomerular filtration rate because of coexisting impairment of potassium and acid secretion. Urinary ammonium excretion is invariably depressed, so the urine anion gap is positive. Diabetic nephropathy is the most common cause, but any disorder with impaired aldosterone secretion or activity may cause a type 4 RTA. 

[Dr. Wiener] So for completeness, and not mentioned in our question, what is a type 2 RTA? 

[Dr. Handy] Type 2 or proximal RTA is not common. It's often due to generalized proximal tubular dysfunction, manifested by glycosuria, generalized aminoaciduria and phosphaturia, or Fanconi syndrome. It's most commonly seen in children. 

[Dr. Wiener] Okay, so let's close this case. The teaching points today are that a non-anion gap metabolic acidosis is caused by an excessive loss of alkaline, usually via the GI or the renal tracts. A positive urinary anion gap suggests a renal tubular defect. Type 4 RTA, which often is seen in patients with diabetic nephropathy, can be distinguished from type 1 RTA by the presence of hyperkalemia. 

[Dr. Handy] You can find this question in other questions like it in the Harrison's Self-Review, and you can learn more about this topic in the Harrison's chapter on acidosis and alkalosis. Visit the show notes for links to helpful resources, including related chapters and review questions from Harrison's, available exclusively on AccessMedicine. If you enjoyed this episode, please leave us a review, so we can reach more listeners just like you. Thanks so much for listening. 

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