Detective Nephron: 70-year-old with serum potassium level of 2.6 mmol/L, experiencing fatigue and muscle weakness


Detective Nephron, world-renowned for expert analytical skills, trains budding physician-detectives on the diagnosis and treatment of kidney diseases. L.O. Henle, a budding nephrologist, presents a new case to the master consultant.

Nephron (nervously) My apprentice is late… should be here with a case he has been struggling with.
Henle enters the room looking confused.
Nephron So… what have you got, my friend?
Henle I… have a case for us.
Nephron Why are you confused?
Henle This is a tough one!
Nephron (with ease) Nothing new… pick one abnormal value, and let’s take it from there.
Henle A 70-year-old female was seen recently for fatigue and muscle weakness and found to have a serum potassium (K) level of 2.6 mmol/L.
Nephron Good! Hypokalemia is a good start.
Henle (with She has known hypertension for the last 10 years.
a curious look) She is not on any diuretics, or
any other medications. Did I mention she has had abdominal pain, as well?
Nephron Ahah! This is going to be fun.
Henle Just some more information, if you will allow me, sir…
Nephron (chuckling) No, you’ve already given me enough.
Henle The medical student couldn’t make it today.
Nephron So, it’s just you and me, partner.
Henle (smirking) You seem to be in a good mood today. Your coffee must be quite strong!
Nephron Let’s go back to your case. Since you evaluated her, what is your biggest worry about her presentation?
Henle Clinically, I was worried about a cardiac arrhythmia, but her electrocardiogram was normal. I was trying to find out whether this abdominal pain was leading to some vomiting episodes. And perhaps her losses are gastrointestinal in origin.
Nephron Maybe she just eats less potassium?
Henle That’s not that common. Renal and gastrointestinal losses are more common. Also, a shift is more common from extracellular compartment to intracellular compartment. Things that can do that are insulin, catecholamines, and metabolic alkalosis. She is not diabetic, and she is not in a high catecholamine state (beta adrenergic state). Her urine toxicology screen was negative.
Nephron Great job… let’s move on. Why can’t she have an insulinoma?
Henle (sarcastically) Of course she could in your world; that’s more common than diuretic abuse. However, her sugars are normal, within the 90 to 130 range… so I don’t think so.
Nephron You mentioned she had alkalosis?
Henle I’m getting to that point. No, she didn’t. But she did have acute kidney injury with a creatinine level of 5.1 mg/dL and BUN level of 89 mg/dL. Her bicarbonate was 23 mmol/L and chloride (Cl) level was 78 mmol/L, with a sodium (Na) level of 134 mmol/L. Her magnesium levels were in normal range.
Nephron As much as I love hyperkalemia without renal injury, I think hypokalemia with renal injury is also fascinating. I strongly urge you to focus on her extracellular fluid status.
Henle I did. Her blood pressure was 80/56 and heart rate was approximately 100 beats per minute. Her hematocrit level is 17 g/dL, suggesting severe volume depletion.
Nephron Are you sure? Go back and check again. It’s very important to make sure.
Henle exits, and Detective Nephron decides to make some coffee. Henle returns shortly thereafter.
Nephron You’re back.
Henle (excited) Yes, and I have confirmed that she is hypovolemic.
Nephron What are her urine Na and K levels?
Henle Interestingly, they both are low. Her fractional excretion of sodium is <1 percent as well.
Nephron Stop right there. So now you’re telling me that the kidney is doing its job correctly. This does not seem like a kidney problem to me.
Henle Correct.
Nephron So what is it?
Henle Well… if I just take her hypokalemia, and since it’s not her intake, there are no medications, we ruled out shifts (hormones, alkalosis, adrenergic states), we are then left with increased urine K losses or gastrointestinal (GI) or skin K losses. Again, I confirmed no diuretic use. Given her hypertension, she could have Liddle’s syndrome, but that’s rare. She could have Conn’s syndrome, but her urine K level would be high in that setting. She is not getting amphoterecin B, which would cause it. I doubt we would have another case of adrenocorticotropic hormone–producing tumor like last time, given she is not alkalotic. However, I think we need to hydrate her first with NaCl and K repletion, then readdress her laboratory data and see if she has any hidden disorders. Her arterial blood gas showed….
Nephron That’s enough… I don’t need an arterial blood gas measurement or any more laboratory data. To me, this seems to be a GI loss. We’re looking in the wrong organ.
Henle leaves to look for other clues.
Nephron Hmm… I doubt this is a kidney problem. The kidney is in prerenal success here. There is appropriate metabolic acidosis, and I think that her acid base status might resolve with hydration… then let’s see if we’re left with hypokalemia.
Henle returns two days later, looking even more puzzled.
Henle You were right, sir: her kidney function is now normal, but her K level is still within the 2.6 to 3.0 mmol/L range.
Nephron Does she have diarrhea or vomiting?
Henle Neither… that’s the confusing part. She does have some intermittently mucus-like loose stools on further questioning, in addition to mild abdominal pain.
Nephron Image her abdomen and ask for a colonoscopy. Something is causing a GI loss in her lower GI tract. Usually with hypokalemia, there are two ways it can proceed: an upper GI problem causing vomiting and subsequent metabolic alkalosis and renal loss of potassium, or metabolic acidosis, a non-gap type due to loose stools and GI losses of potassium.
Henle So… when she first presented, her arterial blood gas showed a pH of 7.38 and a pCO2 of 38. She had an anion gap of 33 from severe renal failure and lactic acidosis. She had anion gap metabolic acidosis and a metabolic alkalosis. After her renal function normalized, she has diarrhea and a non-anion gap metabolic acidosis.
Nephron, Regardless of those specifics, she has shown you that it’s not her kidneys.
Henle Her computed tomography scan of the abdomen showed a rectal mass.
Nephron Aha! You are hiding the right information from me, my friend. Please have her get a colonoscopy soon… she likely has a villous adenoma. Also, have her get an upper GI evaluation including a barium swallow. She might have a condition even more serious than cancer. She might have polyps everywhere!
Henle Sure will!
Henle returns to the office a few days later.
Nephron What do you have for me, my friend?
Henle She had an aggressive tubulo-villous adenoma. She also had multiple polyps in her lower GI tract, but her upper GI tract was spared.
Nephron (confidently) She has McKittrick-Wheelock syndrome.
Henle (surprised) What?
Nephron This eponymous syndrome was first described in 1954. Patients usually have aggressive villous adenomatous polyps in the sigmo-rectal area with diarrhea, dehydration, electrolyte depletion, and acute renal injury. The condition results from elevated adenylate cyclase, cAMP, and prostaglandin E2 levels in the mucosa, which inhibit Na absorption and increase water and Cl secretion. Villous adenomas are usually reported to be 7 to 18 cm and are situated primarily in the rectum. Distal location and large size limit the colon’s ability to reabsorb. Usually, patients present with typically watery mucinous tumors. Initially, fluid/electrolyte losses are easily compensated for by increased PO intake and renal regulation. Patients may deny GI disturbances and can be found to pass mucus from the rectum. Sometimes, they present with severe cases like this one, with volume depletion, hypokalemia, and either metabolic alkalosis or acidosis.
Henle Her cancer is being surgically removed, and all her polyps are slowly being removed.
Nephron Remember, this patient presented with hypokalemia. We often assume that just because there is an electrolyte problem, it’s the kidney’s fault… but this is not the case the majority of the time. Here a systematic approach led us to pursue a GI route, and a prompt diagnosis was made. Well done, apprentice! From an initial diagnosis of hypokalemia, you eventually made a diagnosis of a life-threatening cancer. Always be a good detective. Observe, think, read, and apply. If it doesn’t cross your mind, you will never diagnose it. Great case, Henle. Now let’s go get some real coffee.
This case was submitted by Mohini Alexander, MD, at New York Downtown Hospital, Weill Cornell Medical Center, New York, NY
Detective Nephron was developed by Kenar Jhaveri, MD, FASN, assistant professor of medicine at Hofstra Medical School and an attending nephrologist at North Shore University and Long Island Jewish Medical Center in Great Neck, NY. The column was inspired by Muthukumar Thangamani, MD, and Alan Weinstein, MD, both of Cornell University, and Mitch Halperin, MD, of the University of Toronto. Send correspondence regarding this section to or