The question: I am going through the real well made sodium and water guide you made and there is a concept I am having trouble with regarding ADH stimulation by decreased BP. In the text, one of the reasons that ADH release is triggered is:
Decrease in blood pressure: ADH is a potent vasoconstrictor. 10% drops in blood pressure are required to release ADH. This drop in pressure is usually due to a drop in the blood volume from volume loss but can also be due to heart failure or cirrhosis. ADH is relatively insensitive to changes in pressure, this is why it takes a full 10% drop in pressure to start to stimulate ADH.
I thought blood pressure goes up with heart failure as hypertension is a risk factor for heart failure. How do we get decreased blood pressure from heart failure?
The Answer: Hypertension can cause heart failure. Hypertension is a risk factor for hypertension. Heart failure can present with hypotension or hypertension. Regardless of the blood pressure, heart failure can cause poor perfusion, and stimulate ADH release, with or without a low blood pressure. Sometimes the heart pumps so poorly that blood backs up in the venous circulation, this venous congestion slows perfusion since the back pressure blocks flow, even though blood pressure it good.
So the important point is that heart failure, cirrhosis and volume depletion all stimulate ADH release through decreased perfusion/blood pressure predisposing to hyponatremia.
Lets do this number by numbers. This is an algorithm that will allow you to map out any acid-base question.
1. Primary disorder: pH is up (<7.4), pCO12 is down (< 40) and HCO3 is up (>24)The H-H variables are moving in discordant direction so this is an respiratory disorder, the pH is elevated so this is a respiratory alkalosis.
If you are really on the ball you will note that this breaks one of the fundamental guidelines of acid-base in that compensation is not in the same direction as the primary disorder (pCO2 and HCO3 almost always move in the same direction). This only happens when there are two primary disorders.
2. Is there a second primary acid-base disorder affecting compensation?Yes. In Respiratory alkalosis, for every 10 the pCO2 falls the bicarb falls 2 acutely and 4 chronically, so the target HCO3 is 22 for acute respiratory alkalosis and 20 for chronic respiratory alkalosis, well the bicarb did not drop at all, in fact it went up, so there is an additional primary metabolic alkalosis.
3. What is the anion Gap?148-(98+28)=22.So we did not talk about this, but the presence of an anion gap means there is an metabolic acidosis buried deep in the ABG.
4. Calculate the bicarb beforeBicarb before = HCO3 + (Anion gap -12)Bicarb before = 28 (22-12) = 38So without the anion gap the bicarb would be 38, revealing a pretty severe metabolic alkalosis, that is mostly hidden or covered up by the anion gap metabolic acidosis. The severity of the metabolic alkalosis by looking at the electrolytes without the anion gap.
Put it all together and you have: A respiratory alkalosis, likely from the respiratory stimulant effect of feverA metabolic alkalosis from vomiting and/or some antacids he may have taken to soothe his stomach. An anion gap metabolic acidosis from the sepsis.
Since the demise of TTKG I have had to retrain my brain to determine if hypokalemia is due to renal wasting or extra-renal potassium losses (as well as intracellular shift). The is not so important in the evaluation of hyperkalemia as persistent hyperkalemia is always due to decreased renal clearance of potassium.
There are two methods of looking at renal potassium wasting, the first is Fractional Excretion of Potassium. Super easy calculation.
The mean FEK+ in normal subjects was 8% (range 4-16%). FEK+ was positively correlated with serum potassium (r = 0.74, p < 0.0001) and inversely with serum creatinine (r = -0.51, p < 0.001). The mean FEK+ in patients with hypokalaemia of external origin was 2.8% (range 1.5-6.4%). On the contrary, the mean FEK+ in hypokalaemic patients in whom renal potassium loss was the main aetiologic factor for the pathogenesis of hypokalaemia was 15% (range 9.5-24%).
Even though the creatinine is measured in mg/dL and the potassium is measured in mEq/L the units don’t mess you up because the serum and urine creatinine units cancel each other out.
The other way to look at hypokalemia is urine potassium creatinine ratio. Just divide the urine potassium by the urine creatinine and if it is greater than 1.5 you have renal potassium wasting. But alas this only works if the urine creatinine is measured in mmol/L. I get urine creatinines in mg/dl, so to make this conversion you need to multiply urine creatinine by 88 to get micromol/L of creatinine and then divide it by 1000 to convert to mmol/L. In one step it looks like this:
I often get a call from a nurse saying something to the effect of, “Dr. Smith is ready to discharge this patient home as long as he is cleared by nephrology.”
I will tell you, that the pre-test probability that I will “clear” the patient for discharge is high. I want patients to go home and I feel that a lot of what we do in the hospital can be achieved as an outpatient. Send the patient home and I’ll see them in clinic. But one needs to be careful.
I didn’t discharge the patient, but received him when he was readmitted. The patient was admitted with bilateral pleural effusions and respiratory distress. Patient was diagnosed with COPD exacerbation and heart failure.
The patient was on furosemide 40 mg daily at home and this bumped to 80 mg IV twice a day on admission.
Nephrology was consulted to assist with diuretics and added some metolazone on day 2. That was a one time order and not repeated. Adding a thiazide, metolazone, to a loop diuretic part to increase diuresis is called sequential nephron blockade. One cause of diuretic resistance, is with chronic loop diuretic use, sodium resorption that occurs after the thick ascending limb can short circuit effective loop blockade. So by stacking diuretics that act distal to the loop increases the effectiveness of the loop diuretic.
The addition of a thiazide or K sparing diuretic to a loop diuretic is an example of sequential nephron blockade.
I would have been a bit nervous adding a thiazide in a patient who already had hyponatremia, but the following day the labs look okay.
The following day is the day of discharge. The morning potassium is replaced with a combination of oral and IV potassium as well as 2 grams of magnesium sulfate.
The nephrologist clears the patient for discharge as long as the potassium is normal. The potassium is almost normal and the patient is sent home. On a combination of furosemide and metolazone!
Three days later the patient collapsed at home and during resuscitation is found to have a cardiac arrhythmia and potassium of 1.6.
Know your diuretics. Respect the diuretics
Also keep in mind this propensity matched trial of metolazone in acute decompensated heart failure. They found a large fraction of the excess mortality found with metolazone could be explained by hypokalemia.
(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
