I create all of my presentations in Keynote. In the past I was able to present them in Keynote but due to construction and having to give lectures in 156 of North Foundation I had to convert the presentations to PowerPoint. And then hope that PowerPoint on the PC was mostly like PowerPoint on the one true computer, the Mac. It works surprisingly well, but this slide is an outlier.
Here is what it looks like in PowerPoint on my iMac
This is better, but how does this slide fit into the lecture? It is a summary slide after I have discussed two of the causes of the maintenance of metabolic alkalosis. Here is the slide that introduces the four mechanisms for maintaining metabolic alkalosis
Then the lecture describes kidney failure (the easiest to unsderstand)
After that I cover the mechanisms by which hypokalemia maintains metabolic alkalosis in 7 slides as seen here:
The I do the same for chloride (volume) deficiency in 7 slides:
After going through that I noted similarities between the mechanisms of hypokalemia and chloride deficiency, the summary slide is designed to highlight those. Looking at that slide now, it doesn’t do such a good job of that. Does this pair of slides work better?
Here is the revised powerpoint for you to download
(and a gif for the people who want to rename this hyperhydronemia)
Chug Water GIF
Patient came to the hospital with abdominal pain, nausea, and vomiting. Patient has alcohol use disorder. Last drink was about a day prior to admission.
After arrival to the ER the patient has a seizure.
gross james van der beek GIF
Besides the weirdly elevated anion gap, and the hypokalemia, the initial labs just show some AKI. I don’t have an ABG but I suspect combined metabolic alkalosis and lactic acidosis.
This can be demonstrated by looking at the Delta Ratio which compares the change in bicarb to the change in anion gap. The ratio should be 1. If it is less than 1, there is an additional non-anion gap metabolic acidosis, > 2 additional metabolic alkalosis
A delta ratio of 6 is crazy high.
Kate Mckinnon Snl GIF by Saturday Night Live
A related calculation, called the “bicarb before” can tell you the serum bicarb without the anion gap acidosis, so if the patient has two disorders it allows you to look at the metabolic alkalosis (or non-anion gap metabolic acidosis) without the anion gap metabolic acidosis.
The “bicarb before” comes to a mostly unbelieable serum bicarb of 60.
But the reason I was intrigued by the case are the next two labs that come 10 and 20 hours after the initial labs…The sodium drops to 125 despite getting 150 an hour of 0.9% NS and the patient making 3600 ml of urine.
Additionally the full force of the metbolic alkalosis is revealed with the bicarb shooting from 29 to 41. I suspect this is due to vomiting. The urine chloride < 20 is consistent with this. This is Cl responsive metabolic alkalosis. It will (eventually) respond to the NS.
The urine also has a massive anion gap, around 90. What is the unmeasured anion?
(BTW the answer is bicarbonate)
But what is driving down the sodium? The patient appears volume depleted, and the steadily improving serum creatinine points to a patient with pre-renal AKI.
In volume depletion hyponatremia, giving fluid improves the serum sodium, it doesn’t make it worse. Also these patients do not typically make 3600 ml of urine
In it is highly unusual to make that much urine and have the sodium fall, usually that kind of urine output is associated with arising sodium. A hint to what is happenning can be found in the electrolyte free water clearance (Clefw).
The high urine sodium and really high urine potassium makes the urine essentially isotonic to plasma. Even though the patient is making 3.6 liters, it is like taking ladles of soup from a big pot, no matter how many ladles you take out it doesn’t change how salty the soup is.
pot wo GIF
Because the electrolyte free water is close to zero, those 3.6 liters of urine are not afffecting the serum sodium at all. So why is the sodium falling? I suspect this is due to the patient drinking (unrecorded) water.
So what would you do if faced with a falling sodium in a volume depleted patient?
I chose Tolvaptan plus continued 0.9% NS at 150/hr. The following day, the labs look…better.
I think this patient had nausea induced ADH in addition to severe metabolic alkalosis and volume deficiency. I found it interesting.
What I loved about it is that the full lab interpretation required six different equations:
Anion Gap
the rare case of a relevant anion gap despite an increased serum bicarb
Gap Gap analysis
First the Delta Ratio
Then the Bicarbonate Before
Urine chloride in metabolic alkalosis
<20 mEq/L is chloride responsive
Urina anion gap
People think it is just for RTAs…not true
Electrolyte free water clearance
And I got great comments from Twitter. Some highlights:
Great thread! Given the magnitude of the metabolic alkalosis, did you ask the patient if they were chronically ingesting sodium bicarb (generally to treat alcohol-induced gastritis)? Most of my 50+ mEq/L bicarbs have been associated with this.
Wild case. Thanks 4 sharing. With the high Ca on admission and unexplained low sNa, I thought u were going 2 show us Normal serum Osm and a pseudohypoNa picture from light chains/myeloma. But yes it does look like a transient inappropriate ADH release, but even then 3L UOP is odd
— Juan Carlos Q Velez (@VelezNephHepato) July 30, 2021
This is one of my favorite lectures. It starts with Izzy getting fired on Grey’s Anatomy to the metabolic consequences of crack cocaine in dialysis patients to the imaginary monogenic diseases of Ethan Hawke and Denzel Washington. Metabolic alkalosis is a topic that is rarely taught at all. This lecture goes deep tying metabolic alkalosis to potassium handling (as does the kidney). The lecture covers a lot of useful kidney physiology. In addition to metabolic alkalosis it covers some of the salt wasting nephropathies and monogenic causes of hypertension.
A few years ago I was talking one of my mentors at Kidney Week, John Asplin. He mentioned
that he taught an integrated lecture on metabolic alkalosis and hypokalemia. I thought this was an inspired idea.
Teaching separate classes on both subjects results in a lot of overlap because the renal mechanisms for both disease are the same, this means that many of the diseases that cause one, also cause the other.
Additionally hypokalemia can cause metabolic alkalosis and metabolic alkalosis can cause hypokalemia, so it makes sense to teach both of these conditions in an integrated lecture.
Lastly, teaching each electrolyte individually in isolation from each other is a missed opportunity. One can only appreciate the beauty of electrolyte physiology when one understands how each electrolyte fits together and how abnormalities in one is associated and affects all of the other electrolytes.
Unfortunately, I botched the lecture. I gave this lecture for the first time for the Oakland University Beaumont Medical School this past August. I knew it didn’t go too well, but this week I received the class feedback. Overall my statistical evaluations were excellent but when I read the comments the students were jackals. They savaged this lecture.
Timing was on my side, I was scheduled to give this lecture the day after I received feedback. I’m not done tweaking it but what I did for my Tuesday lecture was add more connective tissue between the concepts, and fill in with some additional summary slides.
Right now, I’m using it as a lecture to follow-up my potassium lecture, but at OU the students didn’t have any baseline potassium knowledge. In order for this lecture to work the students must already understand the basics of potassium, especially the central role that renal potassium handling has in potassium homeostasis. Hopefully I will be able to negotiate another hour into the GU schedule for this lecture.
My next plans for this lecture is to cut out a lot of the opening slides. The purpose of those slides is to quickly move from introducing potassium and hypokalemia to getting to the truth that hypokalemia is almost solely a disease of increased renal losses.
I want to add a slide about disease opposites:
Pseodohypoaldosteronism type 1 and Liddle syndrome
Godon’s syndrome and gittleman’s syndrome
Adrenal insufficiency and AME
I want to add some slides on how hypokalemia causes (specifically, maintanes) metabolic alkalosis and then how metabolic alkalosis causes hypokalemia.
42 year old African American woman presents with muscle weakness and palpitations. Her blood pressure is 180/110. Her hypertension has been documented since age 16.
Her sister has a history of hypokalemia and hypertension. Three of her six kids, all of which are younger than 20 have hypertension.
What is the primary acid-base disturbance. pH is elevated, so its an alkalosis. The pH, pCO2 and HCO3 are all going up (same direction) so it is a metabolic condition. Metabolic alkalosis.
Step two
Is compensation appropriate. To find the target pCO2 add two thirds of the delta bicarb to a normal pCO2 of 40 mmHg.
Her bicarb is 42, and the delta (42 – normal bicarb of 24) = 18. Two thirds of 18 is 12. 40 + 12 = 52 mmHg.
Actual pCO2 is 51, so we are in the house, pCO2 is appropriate for a serum bicarbonate of 42, no second primary disorder affecting compensation.
Step three
What is the differential of hypokalemia, metabolic alkalosis and abnormal blood pressures?
Hypokalemnia and metabolic alkalosis is an important pattern. The first concept that medical students invariably want to lean on is the intracellular exchange of hydrogen and potassium. When there is hypokalemia, potassium flows from the cells. To maintain electroneutrality hydrogen goes into the cells. The certainly is operating in these cases, however a model that looks at changes in total body potassium is much richer.
The reason that metabolic alkalosis and hypokalemia can walk together is that they both are responces to hyperaldosteronism. The increased aldosteronism can be primary, secondary or unusual.
Secondary hyperaldosteronism. Patients with GI losses, diuretics or other causes of volume depletion will upregulate their aldosterone. Aldosterone will fight the volume depletion by reabsorbing sodium in the principle cells, flowing down its concentration gradient through the eNAC. Aldosterone increases the number and activity of the eNAC channels (it also increases the number and activity of the potassium channels and the Na-K-ATPase).
Volume deficiency
Renal artery stenosis decreases renal blood flow and induces a secondary hyperaldosteronism
Primary hyperaldosteronism. This is major cause of hypertension. Patients can have metabolic alkalosis and hypokalemia. If your patient has hypokalemia and alkalosis, definatly pursue primary hyperaldo, but do not rule out primary hyperaldo if you don’t have the electrolyte abnormality. Most patients with pimary hyperaldo do not have the typical electrolytes.
Unusual: one conditions to remember that cause metabolic alkalosis and hypokalemia:
Liddle syndrome. Patients have a mutation at 16p12 that encode the beta and gamma subunits of the eNAC. The eNAC is no longer sodium selective and is always open. The sodium reabsorption causes hypertension. The eNAC channel also increases potassium and hydrogen secretion.
The functional opposite of Liddle syndrome is Pseudohypoaldosteronism type 1. Here mutations to the alpha, beta or gamma subunits results in resistance to the effects of aldosterone. Patient have sodium wasting and hyperkalemia. There is an autosomal recessive and autosomal dominant form.
Licorice and SAME (Syndrome of Apparent Mineralocorticoid Excess) The structure of cortisol and aldosterone are almost identical and the mineralocorticoid receptors in the principle cells are unable to differentiate between these molecules. This means that cortisol can activate the mineralocorticoid receptors. This is made worse by the fact that cortisol typically is found at concentrations a 1000-fold higher than aldosterone. To prevent cortisol from acivating the mineralocorticoid receptors, cortisol is rapidly metabolised by 11-beta-hydoxysteroid dehydrogenase. If this enzyme is absent (SAME) or inhibited (licorice ingestion) you can get wildly up-regulated mineralocorticoid activity with simultaneous suppression of aldosterone.
Sodium is reabsorbed through the ENaC. Sodium moves down its concentration gradient.
The movement of sodium is electrogenic and results in a negative charge in the tubule.
Chloride in the tubule can be reabsorbed paracellularly. The more chloride that is reabsorbed the less potassium is secreted.
Potassium flows down an electrical and chemical gradient into the tubule.
Step four
The family history shows first degree relatives with a similar condition. This suggestes autosomal dominant transmission. This is consistant with Liddle syndrome.
Step five
Next steps in the diagnosis. Though the genetics are suggestive of autosomal dominant transmission, Liddle Syndrome is very uncommon while primary hyperaldosteronism is relatively common. A serum aldosterone level will separate these patients neatly. In Liddle Syndrome the aldosterone is suppressed, while in primary hyperaldosteronism it is up regulated. Genetic testing is available to confirm the diagnosis.
See these posts at the Renal Fellow Network for additional information.
