Tag: OUWB

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OUWB Non-anion gap question

Where does the chloride come from.

XXXXX and I had a question following the Acid-Base workshop. What is the origin of the increase in chloride ions in patients with NAGMA due to GI or renal causes?  

Thanks, 

 

So the key here is not to think of the body as static. As patients lose bicarb in the stool or in the urine, this will result in volume depletion which will be compensated for by renal retention of sodium and yes, chloride.

Great review of non-anion gap metabolic acidosis here:

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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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OUWB Question: Acid-Base

Hi Dr. Topf,
(I don’t have Twitter) I wanted to ask you about question 6 on the week 2 quiz:
“An unresponsive woman is brought to the emergency room. She has a history of a suicide attempt a few years earlier. The lab tests are: Serum Na 140 mmol/L Serum K 4.0 mmol/L Serum Cl 100 mmol/L Serum HCO3 14 mmol/L, BUN 17 mg/dl, creatinine 0.7 mg/dL, serum osmolality 323 mOsm/Kg, Blood glucose 72 mg/dl, Blood gases: pH 7.28 pCO2 27 mmHg. What would you expect the urine pH to be in this patient?”
Why is it that we would expect the urine pH to be acidic? Since blood pH is 7.28, I would imagine that urinating out HCO3- (explaining the low serum HCO3) would have caused the acidic blood pH, thus making urine pH basic?

 

Thanks for your help,

When answering multiple choice board-style question try to figure out what they are looking for. Let’s break this down.
“An unresponsive woman is brought to the emergency room. She has a history of a suicide attempt a few years earlier.

This is the “tell” of the stem. Acid base + suicide = ethylene glycol toxicity

The lab tests are: Serum Na 140 mmol/L Serum K 4.0 mmol/L Serum Cl 100 mmol/L Serum HCO3 14 mmol/L, BUN 17 mg/dl, creatinine 0.7 mg/dL , Blood glucose 72 mg/dl, 

They don’t tell you the anion gap. Calculate it.

Anion gap = Na – (Cl + HCO3)
Anion gap = 140 – (100+14)
Anion gap = 26 (normal 6-12)

High anion gap.

serum osmolality 323 mOsm/Kg

More of the tell. They won’t tell you the osmolality unless they want you to calculate the osmolar gap (or it is a hyponatremia question)

Osmolar gap= Measured osmolality – (Na x2 + glucose/18 + BUN/2.8 + ethanol/3.6)
Osmolar gap = 323 – (280 + 4 + 6 + 0)

Osmolar gap = 323 – 290
Osmolar gap is a massive 33 (Upper limit of normal is 10, over 20 starts to gain a lot specificity for toxic alcohol)
This confirms our earlier suspicions of ethylene glycol toxicity

Blood gases: pH 7.28 pCO2 27 mmHg. What would you expect the urine pH to be in this patient?”

The ABG confirms the metabolic acidosis.

Let’s do Winters formula (not really needed for this question, but you know…practice)
1.5 x 14 =21 + 8 =29, measured CO2 is within ±2 of predicted so an appropriately compensated metabolic acidosis.

Why is it that we would expect the urine pH to be acidic? Since blood pH is 7.28, I would imagine that urinating out HCO3- (explaining the low serum HCO3) would have caused the acidic blood pH, thus making urine pH basic?

So the bicarbonaturia you are talking about would happen if the cause of the metabolic acidosis is renal loss of bicarbonate (what we call renal tubular acidosis).

RTA should only be considered if you are dealing with an normal (or non-anion gap) metabolic acidosis. Since we have an anion gap metabolic acidosis and functioning kidneys the kidneys will be working as hard as possible to clear the exogenous acid. This means the urine is acidic.

The urine would also be acidic if the patient had a non-anion gap metabolic acidosis from diarrhea.

Hope this helps

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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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Question from OUWB M2 on SIADH

Another question from the e-mail

I am trying to understand why SIADH does not cause edema. I understand that in SIADH, there is an increase in Total Body Water, as the increased ADH causes increased water reabsorption. However, there is no change in total body sodium. This implies that the issue is a euvolemic hyponatremia. I would imagine that with total body water increase, there is increased ECF and therefore increased capillary hydrostatic pressure. How come this doesn’t result in edema?

This is a question I get every year.

The question comes from a student with clear thinking about SIADH. And it is true that careful and precise measurements of total body water will show that people with SIADH have excess total body water, so they are not truly “euvolemic.” But we use the term euvolemia here because they are in sodium balance. Their sodium intake equals their sodium excretion:

This is very different than patients with hypervolemic hyponatremia (heart failure and liver failure) where sodium intake is much greater than sodium excretion. With positive sodium balance (total body sodium increases everyday) heart failure patients develop progressive and clinically evident edema.

The other way to look at the increased water that patients have with SIADH is to quantify it. If a patient with SIADH drops their sodium from 140 to 120 they have dropped there sodium by 14%. This comes from an increase in total body water of 14%, so in a 70 kg young man (42 liters total body water), this represents a increase in total body water of 5.88 liters. Two thirds of this water would be intracellular, so only 2 liters would be extracellular. In heart failure, dogma states people gain 5 kilograms of body weight before they develop clinically evident edema. Since the edema is from excess sodium all of this fluid gain is extracellular. So the amount of water that needs to be retained to lower the sodium 20 points, is less than half the amount that is needed to cause clinically evident edema.

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Question from OUWB M2s on potassium excretion

Here is the question:

Regarding potassium secretion, I’m having a little trouble understanding one concept: increased flow rates with the collecting tubules results in increased potassium secretion. Say a person is on a loop diuretic and their flow rates are increased. I understand that increasing sodium delivery will result in more potassium secretion, but how does the flow rate affect it? 

I would’ve guessed high flow rates would decrease sodium re-absorption and therefore decrease potassium secretions.

My answer was just a figure from The Fluid and Electrolyte Acid Base Companion:
  The idea is that increased tubular flow has two interrelated explanations for why it increases potassium excretion. 
  1. The first is that when potassium excreted by either the ROMK or Big K channel, potassium in the tubule then will decrease the chemical gradient from in the cell to out of the cell. By increasing the tubular  flow potassium is quickly washed away, maintaining (or refreshing) the chemical gradient. 
  2. The second is that increased tubular flow is really synonymous with increased sodium delivery. This sodium is then sucked up by the eNaC allowing the generation of the electronegative tubule increasing the excretion of potassium.
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Question from the OUWB M2s

This question came via e-mail:

A couple of my classmates and I had a question regarding one of your slides (slide 39 on the Potassium, Metabolic Alkalosis presentation). We were unsure of the mechanisms that prevented bicarbonate excretion with hypokalemia, specifically decreased NaK2Cl activity in the loop of Henle and decreased NaCl resorption in the distal convoluted tubule. Could you please give us an explanation for these mechanisms?

So the reason you can’t remember a mechanism is I gave the old “just because” mechanism without much explanation.
The first step of why the the Na-K-2Cl transporter slows own in response to a low K is pretty sraight forward. Tubular potassium will fall as patients get hypokalemia. As the plasma potassium falls, less and potassium is filtered and then less potassium will be available to cycle the Na-K-2Cl pumps. The decreased activity in the loop of Henle results in more distal delivery of sodium and that drives move acid secretion and maintenance of the metabolic alkalosis.
The distal convoluted tubule is a bit more complex. Here is a diagram:
The hypokalemia stimulates the hydrogen-potassium exchanger. This generates intracellular acidosis, even though the patient has alkalosis. In order to correct the acidosis the cell slows sodium-chloride co transport so more sodium washes down stream and stimulates the hydrogen secretion, maintaining the alkalosis.
If you are looking for a deeper dive into metabolic alkalosis I recommend this review by Galla in JASN. 
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OUWB Resources 2016

Here is the PDF of today’s Acid-Base Workshop

There is a typo on slide 111 of the the acid-base lecture:

here is the correct table. Sorry.

8 AM Tuesday lecture

Potassium metabolic alkalosis and hypertension:

Introduction to potassium lecture:

Video 

part 1:

part 2:
Greatest Potassium Lecture Ever…part 2 from joel topf on Vimeo.

Part 3:
Greatest Potassium Lecture Ever…part 3 from joel topf on Vimeo.

Monday’s Lecture:

  • Introduction to Acid Base, deep dive into metabolic acidosis (keynote | PDF)

Wednesday’s lecture in Keynote format

When the medical students come in all excited to learn about sodium and water: https://t.co/6dFCfONZqf

— Joel Topf, MD FACP (@kidney_boy) August 9, 2016

The reading material for the TBL

TBL today: @kidney_boy‘s reaction when my team decided to raise the patient’s serum K conc. to 6mmol/L in 2 hr pic.twitter.com/A88vS76Hbz

— Noah Kline (@NoahKline) August 11, 2016

More links to be added shortly.

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#OUWB Renal question: The bad quiz question

Apparently there was a weekly quiz and one of the questions was as follows:

And I received an e-mail asking e to answer this question. Lets go through it item by item. The stem sets up a patient with diarrhea induced metabolic acidosis. This is a cause of non-anion gap metabolic acidosis due to GI loss of bicarbonate.
Choice A. This is wrong. The filtered load of bicarbonate is dependent solely on the plasma bicarbonate concentration. The lower bicarbonate concentration seen in all metabolic acidosis would cause decreased not increased filtered load.
Choice B. This is right. Ammonia is produced in the proximal tubule in response to metabolic acidosis and hypokalemia. This is why ammonium excretion is able to be up-regulated due to an acid load. Titratable acid is fixed and can’t accommodate an increased acid load. The ammonia production varies depending on metabolic need and chronic diarrhea would up-regualte ammonia production so it could be converted to ammonium in the medullary collecting duct to help clear the excess acid load.
Choice C. This is right. Hydrogen secretion is increased in the distal nephron in response to the metabolic acidosis. This is needed to replace the bicarbonate lost in the stool. Every hydrogen in secreted int eh distal nephron synthesizes a new bicarbonate molecule for the body.
Choice D. This is wrong. Diarrhea causes a non-anion gap or normal anion gap metabolic acidosis.
Choice E. This is right. Hydrogen secretion in the distal nephron is stoichiometrically equivalent to producing new bicarbonate, one cannot happen without the other.
Some of the social media action around this question:
What am I missing here? It looks like B, C and E should all be correct. #NephPearls pic.twitter.com/ztg94B4mR5

— Joel Topf (@kidney_boy) August 24, 2015

@kidney_boy @Nephro_Sparks @hswapnil Nothing. Questions fail. Perhaps author trying to write an “all are true except” question.

— Graham Abra, MD (@GrahamAbra) August 24, 2015

@S_brimble @kidney_boy C leads to E Both are D/T B

— د علي السهو (@alialsahow) August 24, 2015

@kidney_boy If the distal nephron still commences with the TALoH and ends with the papillary collecting duct, B-C-E are all right

— Fra Ian (@caioqualunque) August 24, 2015

@alialsahow @NephJC I agree with you, B, C and E are all correct.

— Joel Topf (@kidney_boy) August 24, 2015

@GrahamAbra @Nephro_Sparks @hswapnil and we wonder why students find nephrology so hard.

— Joel Topf (@kidney_boy) August 24, 2015