In 2012, something unusual happened. For the first time since 1868, the year the Detroit Medical College (the future Wayne State University School of Medicine) was founded, a new medical school was opening in the Detroit area. Detroit would no longer hold the distinction of being the largest American city with only a single medical school.
As Oakland University William Beaumont School of Medicine assembled its inaugural faculty, academic appointments materialized from thin air. I was handed the title of Assistant Clinical Professor of Medicine. It felt like a gift.
Over the years, though, that “assistant” began to weigh heavily on me. By 2024, I committed to upgrading that qualifier and pursue promotion. I had no idea just how arduous the process would be. My promotion packet eventually included:
A five-page Achievements in Service letter
A 100-page Achievements in Education dossier, anchored by an eight-page letter and 92 pages of artifacts
A 37-page Achievements in Scholarship document, with a 13-page letter and 24 pages of supporting materials
A two-page Achievements in Patient Care letter
A three-page Personal Statement
My CV
And a list of a dozen associate professors and professors across North America willing to review and score my work
In July of 2024, I submitted well over 150 pages of narrative, documentation, and supporting evidence to OUWB’s Promotion and Tenure Committee.
A few weeks ago, I received the news I had been hoping for: my promotion was granted. As of July 1, I am officially an Associate Professor of Medicine.
It feels good. More than that, it feels validating. I am grateful that Oakland University viewed my work in social media and medical education not as a novelty, but as serious, productive scholarly activity worthy of recognition.
I hope you are well. I have a clarification question regarding milk alkali syndrome. In this disease mechanism, since you have a loop diuretic like effect on the NKCC2 transport proteins, will you have both hypercalcemia AND hypercalciuria?
Best,
XXXXXXXX MS2
This question asks about the urine calcium level and yes in this conditionyou will have both hypercalcemia and hypercalciuria.
The elevated calcium binds the calcium sensing receptor on the basal lateral side of the thick ascendig loop of Henle tubule cell. This signals a decrease in activity of the ROM-K channel on the apical side of the tubular epithelial cell.
The Na-K-2 Cl channel (NKCC) of the thick ascending limb depends on ROM-K to allow potassium to be recycled. Sodium and chloride are found at way higher concentrations in the tubular fluid than potassium, so without recycling the potassium, the NKCC would grind to a halt for want of K. Since the K that is reabsorbed by the NKCC is able to leave the cell via ROM-K there is always plenty of K available to keep the NKCC turning. It does however make the seemingly electroneutral NKCC (2 cations and 2 anions) become electrogenic, because the potassium just leaks out down its concentration gradient so there is only 1 net cation reabsorbed compared to 2 anions. This makes the tubule electropositive and provides the energy to drive the paracellular reabsorption of magnesium and calcium (and probably some sodium as well).
Following the Ca sensing receptor shuting down ROM-K, the NKCC slows for want of K, and the tubule loses its positive charge. This prevents calcium and Mg reabsorption leading to increased urinary calcium as well as loss of Na in the urine.
Note that this is an appropriate change in calcium handling to help restore a normal calcium level. The high calcium itself shuts down calcium reabsorption. However this is inadequate to normalize calcium in milk-alkali syndrome since the acute kidney injury lowers the GFR so far that not enough calcium escapes to normalize the serum calcium.
I hope you are doing well! My name is XXXXXX and I am a second year medical student at OUWB. Thank you for your excellent lectures [ed: I added the bold because I love flattery] that you gave yesterday on sodium and water metabolism. During the second lecture, I did get a little confused on some of the core concepts regarding hyponatremia. I am trying to conceptually understand why your urine volume decreases when you have low solute and high amounts of water intake.
I can see why you are confused, let me try to reteach this.
This slide is supposed to demonstrate how the kidney handles water and solute.
In the absence of kidney failure, solute absorption = solute kidney excretion. Often this will be abbreviated solute in = solute out since our indescrimnate GI tracts pretty much absorb all the minerals and protein they are exposed to and, besides the kidney, no other organ system does meaningful solute excretion. In fact, a failure of solute in = solute out to hold true is a pretty good functional definition of kidney failure.
For people on a western diet (i.e. omnivorous) solute intake can be estimated at 10 mOsm per Kg body weight. So for the 70 kg adult, estimate solute load at 700 mOsm per day.
The kidney can get rid of that solute load in a variable amount of urine. If the person is drinking a lot of water, lowering body osmolality, the hypothalamus will detect this and decrease ADH resulting in dilute urine as indicated on the left side of the slide (absence of ADH, urine osm of 50) and get rid of that solute load with 14 liters of water. The loss of 14 lite3rs of water will increase the serum osmolality back toward normal.
If the patient has a low water intake (which will push the serum osm up) or high serum osmolality, the hypothalamus will release ADH and the urine osm will increase so the body will excrete that same osmolar load of 700 mOsm in only 0.6 liters, retaining any water intake in excess of this 0.6 liters. This retained water will dilute the serum osmolality back toward normal.
This is supposed to demonstrate that the kidney can get rid of the daily osmolar load in a wide range of urine volume to balance water intake and excretion in order to maintain homeostasis.
The next slide shows what happens when the patient is not on a normal western diet. In this case instead of eating 700 mOsm a day the patient is only taking in 100 mOsm a day
Now with ADH turned down to zero, and the urine osmolality bottoming out at 50 mOsm/Kg H2O the maximum amount of urine the body can produce is only 2 liters, an amount that people may exceed with normal, habitual fluid intake. The serum osmolality is low and the body wants to get rid of excess water, but turning down urine osmolality does not produce the expected copious amount of dilute urine needed to correct this situation, because the urine volume is limited by a lack of ingested solute. To increase the urine output to 3 liters would require 150 mOsm of solute (3 L x 50 mOsm/g H2O) but they are only eating 100 mOsm! So while in most cases urine volume is determined by ADH, with increasing urine volume with decreasing urine Osm, once the daily osmolar load is excreted no more urine can be produced.
If the patient has hyponatremia, wouldn’t the interstitial medullary gradient not form due to little sodium being filtered in the tubules at all and thus leading to low amounts of sodium leaving the NKCC2 proteins, thus leading to lower amounts of water being reabsorbed (this is how I’m currently thinking and why I am getting so confused)?
This is not proper thinking. An example of severe case of hyponatremia would be a sodium of 110 mEq/L. Given a GFR of 100 ml/min (0.1 L/min), this is still:
110 x 0.1 L/min x 1440 min/day = 15,840 mEq of Na filtered.
Plenty of Na to keep the medullary interstitium fully concentrated. Also remember half of the osmoles in the medullary interstitium are urea which is not really affected by the hyponatremia (not entirely true, but true enough for MS2s)
I am also aware that ADH is still going to be low here because you wouldn’t want to continue reabsorbing water with hyponatremia,
True
so this is also why I got confused and thought you’d be producing a higher volume of urine rather than a lower one. With the patient drinking lots of water AND having low sodium (hyponatremia), can you reiterate what happens?
When the osmolality is low the body will suppress ADH, unless there is some other stimuli of ADH: volume depletion (hypovolemic hyponatremia) decreased perfusion (hypervolemic hyponatremia from cirrhosis or heart failure) or SIADH. THe lack of ADH increases urine production until all of the daily solute is excreted. With a normal diet, the 700 mOsm will allow the production of 14 liters of dilute urine, enough to correct just about any hyponatremia. But if the patient is drinking 15 liters of water, even with maximally dilute urine there will be progressive hyponatremia, must have fluid intake below excretion to normalize serum Na.
We had a patient with an active infection and bilateral below the knee amputations. The Creatinine was obviously going to over estimate kidney function due to the low muscle mass and I wasn’t prepared to trust the cystatin C in the presence of active inflammation. What to do? Can we McGyver the GFR by looking at the fall in vanco levels over time? Yes, of course we can.
Here’s how it works. Vancomycin is primarily eliminated by glomerular filtration, so its clearance approximates the GFR.
1. Get two vanco levels
You need two vancomycin concentrations drawn after the distribution phase (ideally 1–2 hours post-dose and a trough) and without an additional dose in between.
2. Calculate the Elimination Rate Constant (ke)
This gives you the rate at which the drug is disappearing from the plasma.
3. Estimate vancomycin Clearance
Vancomycin’s volume of distribution (Vd) is about 0.7 L/kg.
4. Convert to GFR (mL/min)
Since vancomycin is almost entirely renally cleared, its clearance approximates GFR.
The vanco clearance calculated above is in liters per hour, so to get conventional GFR units, multiply by 1000 and divide by 60
5. Caveats
This only works if renal function is stable (no AKI or wild fluid shifts)
Must use post-distribution levels
Non-renal clearance of vancomycin is minimal but not zero
Vd can be wildly off in critical illness, obesity, or fluid overload
Bottom Line
You can use vancomycin estimate GFR. It’s not perfect, but in the right context it’s a clever way to triangulate kidney function when the usual suspects lie.
I find using LLMs is a bit like skipping stones on a lake – in the right domain with the correctly-worded prompt, you can sometimes get impressive output.And sometimes you get an utterly unceremonious "kerplunk".
I had a patient’s potassium pop from 3.1 to 5.1. It struck a half-remembered dream of a mentor teaching me that the most common cause of hyperkalemia was the treatment of hypokalemia. It is one of those internship myths that are recited mostly just to scare caution into over eager interns. So I asked Bluesky if anyone knew about this.
I once was told that the most common cause of hyperkalemia was mistreatment of hypokalemia. Anyone know of a reference to support that?
I then immediately, I went to Chat GPT4o and asked the same question. I hit the right domain with a correctly-worded prompt and the rock skipped clear across the lake.
Looking at my choices, I went with the middle one, because it had a DOI and I don’t have a subscription to UpToDate.
And being from 1998 made it contemporary with the pearl of wisdom in question.
The NEJM review of Hypokalemia by G. John Gennari was part of a review series on Fluids and Electrolytes the NEJM ran around the turn of the century. They were foundational articles for me as a fellow from 2001-2003. And on page 6 of an 8 page review of hypokalemia he drops this bomb.
Principles of Potassium Replacement Potassium replacement is the cornerstone of therapy for hypokalemia. Unfortunately, supplemental potassium administration is also the most common cause of severe hyperkalemia in patients who are hospitalized,53 and this risk must be kept in mind when one is initiating treatment. The risk is greatest with the administration of intravenous potassium, which should be avoided if possible. When potassium is given intravenously, the rate should be no more than 20 mmol per hour, and the patient’s cardiac rhythm should be monitored. Oral potassium is safer, because potassium enters the circulation more slowly.
In that study he combed the lab computer to find every case of hyperkalemia over 5.9 in a year. He found 300 and examined every case. Forty-eight of them were associated with new medications. Here was his list of meds that could cause hyperkalemia
Notice he doesn’t include ACEi as a group. He uses group names for beta-blockers and potassium sparing diuretics. But he lists captopril as a single agent because there were no other ACEi. This is an old study.
Of those 300, 172 had sustained hyperkalemia. He found 43 to have a single etiology of hyperkalemia (Group 1). And of those 43, potassium chloride was the sole etiology in 29 patients. Renal insufficiency was right behind at 24, followed by digoxin at 21. Did I mention this was an old study?
The whole study sounds pretty flimsy and polluted with biases. It stinks of post hoc choices and arbitrary rationalizations. Research has become much more rigorous in the last 40 years.
I don’t find this data to be cempelling but I’m also sure this was the source of the myth in question. And Chat GPT4o was instrumental in finding it and finding it fast.
That said the discussion on Bluesky was absolutely delightful. Follow the original post to see the rich conversation that bubbled up.
Post script: I do not believe that the most common cause of hyperkalemia is the treatment of hypokalemia. I think we live in a world with so much angiotensin and aldosterone inhibition that mistreatment of hypokalemia is a tiny blip on the radar.
That seems uncommon these days (suspect MRAs, RASi, etc). If anything, most hypoK cases are tail-chasing quests that never fully correct. In that ‘87 paper, pt must have an underlying renal issue 2 switch 2 hyperK, did they? Like we discussed in the podcast, it’s never just the bananas!
Post-Post Script: the first reference, the review from 2017 in the NEJM by Kamel and Haperin, It doesn’t exist. The computer is pulling their book from 2016.
This came up on rounds today. I thought I covered this on the blog before but if I did, Google failed me. The answer is 7.7 mEq of Na and 7.7 mEq of HCO3 in every 650 mg tablet of baking soda.
This is just 650 mg divided by the molecular weight of NaHCO3, 84 mg/mmol.
I spend a lot of time talking about how incredible the kidney is but then sometimes you see kidneys that just don’t do anything. I was in the hospital and we had a patient develop acute on chronic kidney disease. Following a few days of anuria they started to make urine so we checked urine creatinine to see how well the kidney was recovering.
Not good, Bob.
The patient had among the lowest urine creatinines I had ever seen. Compare the urine creatinine of 14 to the serum creatinine of 10 and you see the laziest nephron ever. It is barely altering the composition of the urine at all.
The patient also had the highly unusual situation with urine Na greater than serum Na. I think I have only ever seen that in cases of severe hyponatremia due to SIADH.
This patient had a fractional excretion of Na of 70%. Amazing. Normally the kidney reabsorbs 99% of the filtered sodium, here 70% of the filtered sodium just flies by.
This helped our discussions on the patient’s renal prognosis. The urine they were making was a useless gasp of a dying organ.
The first newsletter of 2025 and 30th newsletter for MashUp MD, successfully focuses on various topics while avoiding discussion of the new Trump administration.
So I just pushed out the latest episode of Channel Your Enthusiasm. This one was recorded in November of 2022. (Yes, I am a little behind on the editing, but I have a new workflow and its name is Simon Topf. Things are going better.) During the recording Josh mentioned that we had just won the ASN Innovations in Education Award and Melanie pipes in we won the 2022 version of the contest because even then we knew that it was going to be awhile before the episode was published and we all assumed that there would be other, subsequent winners.
Nope
2022 was the last year of the ASN Innovations in Education Award.
The website says that they are skipping 2023 and to check back in 2024
oof
I asked about the contest on ASN Communities and got the following reply:
The Channelers had a discussion about the award, which you can hear here
The audio is from the podcast recording, most of which ended up being cut from the episode. The images are from our video application for the award. You can see that video with the original audio, here. In the video we discuss how the winners were announced. Edgar took a video which i now on You tube. Take a look:
Awards given by professional societies is one of the ways that an organization can demonstrates its values. And the ASN Innovations in Education Award told the world that nephrology valued education and educators. Unfortunately, we live in a world where promotion and tenure committees undervalue the work that goes into educational initiatives. During my most recent tangle with P&T they expressly said that when outlining what you do for the medical school, to not include teaching, as that is just table stakes and not that important. The ASN education award provided a bit of incentive to pursue big audacious educational projects.
Some of the discussion was about how slipshod the award recognition was in 2022. This was a change from previous years and we couldn’t figure out why. Now it is apparent that the organization had already walked away from Innovation Award.
This is a disappointment. I am sorry to see it go away.
To work around this I have been exporting slides as short movies and uploading them to my YouTube channel and then embedding them into a Bluesky post like this
Hyponatremia physiology in a minute, forty seconds. #IsHomeostasisAJokeToYouyoutu.be/Q93D_SjaOEY
Bluesky does not have bookmarks. The best work around is to reply to a post with an emoji of your choice. Many people use 📌. Then when you want to look at your book marks, just go to the search panel and enter “from:me 📌” Consider bookmarking the results so you can get back there quickly.
There is no reason you need to use the push pins, and you can use multiple emoji to get organize you bookmarks. If you want to look at other people’s bookmarks replace “me” with their username. Here are Swap’s pins: from:hswapnil.bsky.social 📌
I imported my posts from Twitter into Bluesky using BluueArk.app. It worked great. A lot of my posts did not dome, but a lot did and it makes my Bluesky profile feel more fleshed out.
The imported tweets came in to bluesky recently but they are still ordered chronologically with a date created tag. So this post from 2018 was imported just a few weeks ago.
So this has resulted in a few of people replying to years old tweets which is simultaneously confusing and delightful.
