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.
