Tag: hyponatremia

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Another question from OUWB

Hi Dr. Topf 

First of all, apologies for sending this via email but I do not have a Twitter account (I know, its the 21st century, who doesn’t?). 

I had a quick question regarding a practice problem I was doing. Rather than summarize the question for you, I included a screenshot so that you have the primary source with the explanation provided. Below, I also included my explanation for my reasoning for choosing that option. Basically, I am confused as to why the bicarb would be decreased in this scenario.

So the stem describes acute trauma. Specifically crush injuries, so you should be thinking rhabdomyolysis where the body gets turned inside out. In my very first lecture we talked about the intracellular atmosphere versus the extracellular atmosphere:

So expect increased potassium and phosphorus.
The vital signs show a patient with circulatory insufficiency, i.e. shock. There are some initial labs drawn from the blood and urine right before resuscitation is initiated. The urine shows an osmolality of 800 mmol/kg H2O (highly concentrated, indicating a lot of ADH activity) and a urine sodium of 5 mEq/L (very low, indicating increased activity of the renin angiotensin aldosterone system).
The question then asks you to predict the serum labs. Cool question. The best testing strategy here is to cross off ones that make no sense. Here are the foils:
BUN. This should be elevated as the patient moves to a pre-renal physiology. This leads to an increased filtration fraction to maintain GFR in the face of decreased renal plasma flow. This causes an increase in the osmolality in the efferent arteriole and vasa recta. this increases osmotic reabsorption of fluid from the proximal tubule. BUN flows passively with the fluid, decreasing renal urea clearance and increasing serum BUN. So D is wrong. E is wrong.
Potassium (K+) ions. All the choices show that it rises as the rhabdomyolysis from the crush injury releases loads of intracellular potassium. No answers are eliminated here.
Sodium (Na+) ions. We have a mishmash of choices here. This is difficult to predict. The increased ADH released due to shock would tend to lower the sodium. Increased aldosterone and renin would tend to increase the sodium. Since both are happening together I would expect them to balance each other out resulting in no change in sodium concentration. This is especially true since the stem specifically says there has not been much urine output I would go with D, for no change in sodium concentration. NOTE: About activation of the RAAS as a cause of hypernatremia. Hypernatremia is commonly listed as a symptom of Cushing syndrome and hyperaldosteronism so it is possible to have hypernatremia from (at least the pathological) activation of the renin angiotensin aldosterone system) but this is very unusual as increased in sodium concentration stimulates thirst which dilutes the sodium back to normal.
THIS COLUMN IS MESSED UP. THIS IS AN ERROR BY THE QUESTION AUTHOR.
Hydrogen (H+) ions. All the choices show that it rises. In shock we expect an increase in hydrogen ions as patients move to anaerobic metabolism due to inadequate perfusion (the functional definition of shock). No answers are eliminated here.
 
Bicarbonate (HCO3-) ions. Bicarbonate is the primary buffer in the body. Increases in hydrogen ions will be buffered by bicarbonate and bicarbonate will be consumed.
So the right answer is bicarbonate will be decreased. This eliminates answer A.
This leaves us with B or C and the question hangs on what the sodium will do and the reality is the change in sodium is unknowable. Shit question. Sorry.
Here is what Kaplan claims to be true:
The forth bullet point is the one where the question fails. It is true that there is accumulation of plasma electrolytes in acute kidney injury. The problem is that these are electrolytes are measured as concentrations and there is also an accumulation of water (which is normally excreted by the kidney). This means that the effect on concentration is variable. Some, like hydrogen and potassium, reliably increase in AKI, but sodium is often decreased in AKI. Maybe the question writers were looking at an unconventional way measuring ions in the the plasma (as total amount rather than concentration).
The line in the answer that pre-renal azotemia is associated with hypernatremia is just wrong. You will encounter numerous patients with pre-renal disease that will have simultaneous hyponatremia. It is impossible to predict the serum sodium concentration from the volume status. This question reinforces the worst instincts of med students when it comes to predicting serum sodium. As I emphasized in the lecture, volume regulation and osmoregulation have two different regulatory systems and, though there is some cross talk, they are largely independent from each other.
The last paragraph tries to make the case that hyponatremia is more common in ATN while hypernatremia predominates in pre-azotemia. This is total fiction and does not exist. Though there can be more urinary sodium in ATN, if the patient is oliguric, it doesn’t matter how high the urine sodium concentration is, if the urine volume volume is close to zero there will not be much urinary sodium excretion.
Distinguishing between pre-renal azotemia and ATN is a constant problem in nephrology. Trust me you can’t make the determination by looking at the serum sodium. It aint that easy.
This question writer should never write another question about sodium.

 I posted this to twitter. The subsequent discussion was pretty interesting:

Kaplan Blows it on Hypernatremia and AKI

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OUWB Euvolemic Hyponatremia question

Hello Dr. Topf,

I hope you are enjoying your weekend. I had a question in regards to one of your lectures. I was wondering why there is a low level of Uric acid in euvolemic hyponatremia but not in hypervolemic or hypovolemic hyponatremia. Also, how is it that Na taken in equals Na excreted in euvolemic hyponatremia?

All the best,

 
So why is there a low level of uric acid with euvolemic hyponatremia? Let’s first look at what happens to uric acid in the other causes of hyponatremia, namely hypovolemic and hypervolemic. In both of these situations the kidney is experiencing decreased perfusion, either from absolute volume depletion (diuretics, diarrhea) or perceived volume depletion from pump failure (CHF) or fluid maldistribution (cirrhosis and nephrotic syndrome).
In these volume depleted states there is an increase in the filtration fraction, i.e. more of the plasma that enters the glomerulus is actually filtered. This is how the kidney compensates for a decrease in renal plasma flow while maintaining GFR, it increases the fraction of fluid that is filtered.
A consequence of this, is that the oncotic pressure in the blood leaving the glomerulus is higher because more of the fluid (but none of the protein) has gone down the glomerular drain leaving the plasma in the efferent arterioles with a higher oncotic pressure.
This plasma then enters the vasa recta where it surrounds on the proximal tubule. Here the increased oncotic pressure pulls more fluid back.
This is an ideal situation. The increased filtration fraction maintains GFR in the face of decreased renal plasma flow, and the increased filtration fraction results in enhanced reabsorption of fluid in the proximal tubule limiting fluid loss in situations where patients have decreased perfusion.
Uric acid handling is complex and not fully worked out.
It appears that there is both uric acid secretion and reabsorption in the proximal tubule.
Functionally, uric acid clearance tracks with renal perfusion:
  • Decreased uric acid clearance with decreased renal perfusion
  • Increased uric acid clearance with increased perfusion of the kidney

This is similar to what we see with urea. The following description of urea handling gives a model that will work for uric acid, though the truth of uric handling is much more complex.

The key with urea is that it’s handling in the proximal tubule tracks with total fluid reabsorption in the proximal tubule.
With volume depletion, increased filtration fraction causes increased oncotic pressure in the vasa-recta increasing urea reabsorption in the proximal tubule.
In volume overload, decreased angiotensin 2 decreases sodium reabsorption resulting in less fluid reabsorption and less passive reabsorption of urea  so increased urea loss in the urine and lower serum urea.
Now what happens in euvolemic hyponatremia.
Sodium in equals sodium out. This means that these patients do not have a primary volume abnormality as we see in the hypovolemic and hypervolemic patients. Because of this their sodium regulation volume regulation system is not stressed, they are at homeostasis with regards to body sodium. When you are in homeostasis, in order to stay in homeostasis you need to excrete all the sodium that comes in. In other words sodium in equals sodium out.
However these patients are not in water balance. they have a disease that forces their ADH to 11. They have a fixed ADH secretion and it is set at full blast. This minimizes urinary water excretion, but they are able to stay in sodium balance. So the net of this is they make only a little bit of urine but that small amount of urine carries all of their ingested sodium (sodium in = sodium out) so the sodium is excreted in a small volume at a high concentration.
Now the obvious problem here is that they are holding on to an excess of water. And that will increase their total body volume. This is subtle and doesn’t cause edema, or heart failure, or fluid overload in the lungs, but it is there. This fluid overload suppresses angiotensin 2 and decrease sodium resorption in the proximal tubule and hence decreases urea (and uric acid in our model) reabsorption.
And yes this does mean it is not exactly sodium in = sodium out, there will be a slight excess of sodium excretion.
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Two more OUWB questions

Hi Dr. Topf,

I had a question regarding the Macula Densa.  When reviewing your powerpoint on volume control, you have a slide that said there is only one osmoreceptor (Hypothalamus) because osmolarity across the body is the same at all times.  I’ve had some confusion regarding the Macula Densa, but from what I understand it is also an osmoreceptor (sensing Na+ in the tubule), which would make sense because the tubules are the only part of the body where osmolarity is different.

I thought that the Macula Densa would affect GFR and stimulate the release of renin from the Juxtaglomerular cells, but that would seem to affect volume (RAAS System maintains volume), so my question is why does the macula densa (which senses Na+) controlling volume and not Osmolarity?

Good question.

So the macula densa is a major part of a process called tubulo-glomerular feedback

As the name implies this is important for balancing GFR with tubular reabsorption.

If you had excess GFR and limited tubular reabsorption, people could literally pee them selves to death in minutes.

Think about the math, you have 3 liters of plasma and filter 125 ml of it every minute. so it would only take 24 minutes to completely filter all of the plasma. if you are not constantly reabsorbing 99% of the filtered fluid you could very rapidly become volume depleted and suffer from cardiovascular collapse.

Tubular glomerular feedback prevents that. At the end of the thick ascending limb of the loop of henle, there are chloride receptors as part of the juxtaglomerular apparatus. If there is too much filtration and not enough reabsorption, the excess chloride will bind these receptors and cause a release of intra-renal signals that decrease GFR by adjusting the dilation of the afferent and efferent arterioles.

So yes there are receptors that bind chloride and you can think of them responding to the various concentrations of chloride (like an osmoreceptor) but they are not involved in volume regulation or osmoregulation, but rather the safe running of the kidney to prevent a person from accidentally peeing themselves to death.

Hope this helps

Hello Dr. Topf,

I hope you are doing well. I had a few questions in regard to your last lecture at OUWB. I was wondering if you could explain the pathophysiology behind euvolemic hyponatremia caused by hypothyroidism and adrenal insufficiency. Also, in the case of SIADH, whay wouldn’t the person have hypervolemia if there is a constant reabsorption of water? Is there a pathophysiologic explaination for this as well? I could not find any answers online.


So the key here is to remember that volume is determined by total body sodium and that SIADH is generally Na in = Na out. So they are in sodium balance and will not be volume overloaded.

You are right that these patients will have excess water, but much of this water disappears into the intracellular compartment and the excess volume can not be picked up clinically (by exam or by conventional blood and radiology tests). Yes there is excess water.

We try to reserve terms like hypervolemia for excess total body sodium, and this is not found in SIADH.

Hope that is helpful.

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OUWB Sodium and Water Questions

For the sixth year I have had the privledge of teaching at OUWB. When I teach I get e-mail questions from the students. I respond to the students by e-mail but also post the questins and answers here so all the students get the advantages of the questions.

Caller one you are on the line…
“Long time listener; First time caller. Some of the M3s were telling us that last year, they were confused on this Team Based Learning exercise because they learned hyponatremic means low water/volume but originally they thought it meant low salt, and hypovolemic means low salt but they thought it meant low water/volume. 
 
Could you explain? A lot of us are confused now…”
The conflation of volume and osmolality is always confusing.
Hyponatremia means a low sodium concentration.
Hypovolemia means a low total body sodium (literally the total number of grams of sodium in the body). Hypovolemia does not say anything about the concentration of that sodium.
That low total body sodium may be at a high a high or low concentration depending on what the total body water is.
For example heart failure is a common cause of hyponatremia. These patients have edema and other evidence of volume overload. This is a combination of volume overload and hyponatremia. Increased total body sodium, but even great increase in total body water.
Patients with severe diarrhea also can develop hyponatremia. In this case they are volume depleted, decreased total body sodium.
And lastly, patients with SIADH, say from small cell lung cancer, are euvolemic and have a normal total body sodium*.
You can’t equate the two, just like saying that a bowl of soup is salty doesn’t explain how big the bowl is. If the soup is salty but you have only a spoonful, there is not much salt.
Hope this is helpful.
Next caller…
“Hi Dr. Topf,
 
I hope your day has been going well! I was reading over the TBL preparatory material for tomorrow and came across a point that was slightly confusing. 
 
Could you please clarify what exactly was meant by the following: 
 
“Clinicians often characterize hyponatremia by the volume status, hypovolemic hyponatremia versus hypervolemic hyponatremia. It should be clear that both of those two seemingly different causes of hyponatremia, share a single patho- physiologic explanation.”
 
I’ll hang up and take my answer off the line.”
 
Thanks for calling. Great question. This was covered in this slide from my second lecture:
The point of the slide and that both hypovolemic (on the left) and hypervolemic (on the right) cause hyponatremia by the same physiologic mechanism:
1. decreased perfusion (from heart failure in hypervolemic and volume depletion in hypovolemic)
2. Release of ADH (due to the low perfusion, not a high osmolality)
3. Decreased urine output
4. Water intake > urine output
Is that clear?
Next caller…
Hello Dr. Topf,
Please, call me @Kidney_Boy.
Hope you’re doing well. I really enjoyed your lectures today. I was studying for our upcoming class on Friday where we are going to be quizzed on a lot of the same information and I became a little confused. In the TBL article (pg 12) there is a figure and a paragraph that says glucose induced hyponatremia is a type of pseudo-hyponatremia. However it also defines pseudo-hyponatremia as a decreased serum sodium with a normal serum osmolality. 
 
Is the glucose induced factitious hyponatremia is a kind of pseudo-hyponatremia ? If so how can it be a pseudo-hyponatremia when the glucose causes an osmolality imbalance?
 
Thank you so much. 
This one is one me. The TBL document needs to be updated This is just a nomenclature issue.
There is some ambiguity on whether glucose induced hyponatremia can be called pseudohyponatremia, there is some support for it and I used to be in that camp (in fact I wrote a whole book about fluid electrolytes waving the glucose induced pseudohyponatremia flag) but most people limit the term pseudohyponatremia to just the high protein and high lipids causing the lab error (sometimes called a lab artifact), and separate out the high osmolar causes under a different category (factitious hyponatremia).
So I would study what I taught in lecture today. Understanding concepts is more important than knowing the specific names.
Obligatory blog post about the subject (see the segment after the Update):
Hope that helps.
That really clears things up for me! Thank you so much! 
That’s all we have time for. Until next time…
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I get some great letters, here is one of the best from a woman with SIADH

An e-mail I received last month:

I love your blog.  I have had SIADH for a zillion years.  I only found out what I had when I went with 5 girlfriends to a fancy spa hotel  in Tucson for a mini-vacation/ 4th of July Weekend in 1997 where the heat increased to an uncomfortable 117 degrees.

Healthcare workers in the hotel kept handing out bottles of water at each hotel exercise location with orders to “hydrate, hydrate, hydrate” and I stupidly followed their directions.  I drank myself into a 6 day coma.

The only time that sentence has been used for water, not alcohol.

Very non-traumatic for me. Very traumatic for my family. I woke up on day 6 saying, “I am STARVING!  Will someone go get me a taco?” which was very anxiety-relieving for all of them; they’d been sure I’d wake up cognitively impaired.  I wasn’t.  This “taco” sentence sounded JUST like me.  And I have continued to be not cognitively impaired despite interesting lab numbers.

My dad (who is a physician too) has SIADH as well, though his was diagnosed after mine.  I was mis-diagnosed for 9 years prior to my coma as having a “seizure disorder.”  The excellent care I received when my mental status went to heck in a handbasket was truly life-saving.  I remain a very grateful nephrology patient.  And I really do love your blog.

Thought you should know this.
She wrote back a few days later giving me permission to post her letter:
I am dying (well not literally dying) to start an SIADH group on Facebook.  We are so not connected to one another, and each of our nephrologists only have a handful of patients and of course the doctors can’t introduce us to eachother because of HIPAA. 
  • For those of us that have the Syndrome without lung cancer and so on and have to live our lives thirsty
  • and our summers avoiding the sun through our sunroofs (Demeclocycline)
  • and have to, if we’re female, find inventive ways to paint our nails to avoid Demeclocycline making our nailbeds ugly colors
  • and have to fear that Otsuka Pharmaceutical will convince the ONE manufacturer who makes Demeclocycline to stop making it and force us into buying Tolvaptan even though they never tested it in 3rd stage human trials on people that weren’t already cognitively impaired (I know because I volunteered for every single US trial), 
Well, we NEED each other.  We need tips on nail polish, tips on drinking our fluids out of 1 ounce shot glasses, tips on rolling ice cubes around our mouths during the days our sodium is tanking, and your website is a GREAT place for us to meet up!  
You have my non-dying thanks and permission to reprint/repost any or all of my statements!
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Outpatient hyponatremia

Almost all of the hyponatremia I see is inpatient, but this week a woman was referred to my clinic with a sodium of 128. She has a sharp family doctor who ordered all the right tests. Here are the key pieces:

  • Plasma sodium 128
  • Plasma osmolality 277
  • Urine osmolality 180
  • Urine SpGrav 1.005
  • Urine sodium 14
She has a history of hypothyroidism but her TSH was over suppressed, no hint of hypothyroidism. She was not taking any diuretics. She was on an SSRI that could cause SIADH but the low urine osmolality and low specific gravity argue against excessive ADH activity.
The case hinges on the low urine osmolality. This is a rare case of ADH-independent hyponatremia. All of the major causes of hyponatremia (volume depletion, diuretics*, heart failure, SIADH, etc) are driven by ADH which prevents the kidney from clearing free water. The low urine osmolality indicates the kidney is not under the influence of ADH and doing what it needs to in order to correct the sodium, i.e. excreting excess water in the form of dilute urine.

I believe there are only a few causes of ADH-independent hyponatremia, and only two occur with any regularity:
  • Psychogenic polydipsia
  • Tea and toast syndrome
  • Reset osmostat (rare)
When the kidney is making dilute urine and the patient has hyponatremia the problem is not in the quality of the urine, which is appropriate, but in the quantity of urine, which is inadequate.

She described her diet as a peanut butter and jelly sandwich for breakfast, some fruit and juice with some nuts for lunch and nothing for dinner. Her fluid intake was high (4-5 cups of coffee, a large water bottle of water, some juice, some soda, and a couple of additional glasses of water) but no where near enough for psychogenic polydipsia.
I suspect she has tea and toast syndrome. I am checking a 24-hour urine osmolality to gauge her daily osmolar load and then plan to have her increase the amount of protein and minerals in her diet while trying to taper her fluid intake.
More on tea and toast syndrome here
A well done case report on a healthy patient wih reset osmostat can be found here (pdf)
* if the diuretics are still active the urine osmolality could be low but once the drug wears off the urine osmolality will climb