Month: August 2014

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OUWB Acid base question

The e-mail:

Hi Dr. Topf,

We were going through the acid-base study guide and Prince Harry has us all out of sorts. His scenario is this: 

Your first mistake. It is Prince William not Harry. Know your Royals. (Though I do not think royal genealogy is a board eligible topic.)

7.42 | 32 | 76
Na – 148
Cl – 98
K – 5.8
HCO3 – 28 

For the primary acid-base disturbance, I would think it is respiratory alkalosis because the pH is elevated, the PCO2 is decreased, and the HCO3 is elevated.  

You are correct

Then for the second acid base disturbance, I thought it would be metabolic alkalosis. His PCO2 is 32, which is down about 10. So, his bicarb should go down either 2 if acute or 4 if chronic, to either 22 or 20. Instead it is 28 which means he has excess HCO3 (base) and so has an additional alkalosis. 

Correct again

I tried doing the anion gap (22) and the bicarb before (38) but my understanding is that a bicarb before of 38 would also be metabolic alkalosis.  

Yes

In the answers, it says that if you have an AG with alkalosis or a primary acid-base disorder, that it would be an acidosis.  

If you have time, can you help me understand why his primary disorder is metabolic alkalosis, and how to apply the anion gap and bicarb before formulas to this case?  

Thanks for your time. 

Best regards,

This refers to this question in the handout:
There is an error in the ABG. Using the Henderson Hasselbalch equation it is obvious that this ABG is impossible, as pointed out by +MedCalc on twitter:

@kidney_boy Threw @medcalc at it. Don’t know how HCO3 could be 28 as Henderson (The Law) says it should be 21. pic.twitter.com/ilqD1l3Qec
— MedCalc (@MedCalc) August 23, 2014

So the actual pH should be 7.51. But that doesn’t change the rest of the answer or the calculations.
To get this problem right, it breaks one of the rules I established and uses another rule that was not discussed. This is failure on my part and I will fix this.
The rule that it breaks is the rule that compensation is always in the same direction as the primary disorder. Obviously with a pCO2 of 32 and bicarbonate of 28 the two independent Henderson-Hasselbalch variables are moving in discordant directions.
This is a great guideline, it just isn’t always true. In cases where patients have two primary disorders the pCO2 and bicarbonate can move in opposite directions. This is not the typical finding but when it occurs it is simple to interpret:
If the pCO2 falls it is respiratory alkalosis and if it rises it is respiratory acidosis. If the bicarbonate falls it is metabolic acidosis and if it rises it is metabolic alkalosis. So in the case of Prince William, his bicarb is up and pCO2 is down so he has both a metabolic and respiratory alkalosis. The reason I do not include this is that it is an additional complexity that if you follow the algorithm that I taught you will get the right answer without knowing this exception. I choose to streamline the teaching rather than teach this shortcut.
The rule that was not discussed is in regards to the anion gap. In my booklet I never discuss that the presence of an anion gap regardless of the pH or serum bicarbonate always indicates a metabolic acidosis. The hierarchy of acid interpretation that I showed in the booklet should include that right at the top and has been updated to reflect that:
So Prince William is rocking an anion gap of 22, this means he has an anion gap metabolic acidosis. If you use the bicarbonate before formula you see that his bicarbonate was 38 excluding his anion gap metabolic acidosis indicating a truly wicked metabolic alkalosis.
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OUWB School of Medicine Materials 2014

The Potassium and Metabolic Alkalosis lecture:

The Acid Base Lecture

  • Keynote (480 MB)
  • PDF (51 MB)
  • Extra lecture only about non-anion gap metabolic acidosis


The Potassium lecture (on your own)


The Sodium and Water Handout


The Electrolyte and Acid Base Companion


Acid Base Workshop
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Sodium is hard

Of all the concepts in fluids and electrolytes by far the most difficult is sodium, water and volume regulation. I think the problems stem from multiple angles, one of which is the confusion between total body sodium (reflected in volume status) and sodium concentration (the primary determinant of osmolality). When writing the sodium chapters I kept thinking about that exchange on Dagobah:

I lead a TBL exercise for second year medical students last week tackling this difficult subject and they ran in to all of the problems that befuddle students when they first try to grock this. On Friday I received this e-mail (only medical students include bibliography in their e-mails):

Good Afternoon Dr. Topf, 

I am a student at OUWB and you ran our TBL this past week. I’ve been struggling with this material and I was previewing for lectures next week. I apologize for emailing over the weekend, but I am confused over a concept that we went over in TBL – that is, the impetus for release/action of the RAAS system and ADH. 

From our discussion and our physiology class prior in the week, I am understanding that ADH primarily regulates osmolarity and that aldosterone primarily regulates blood volume. However, it seems that as I go over review books, I’m being told that ADH, “…also responds to low blood volume, which takes precedence over osmolarity,” (First Aid), and from our physiology text book (Costanzo), it indicates that ADH has 3 functions including: 

1. increasing H2O permeability of principal cells (which the text indicates is the primary function)
2. increasing activity of the Na+/K+/2Cl- cotransporter
3. increases urea permeability 

Upon my own research, a neuroscience text book source (from the University of Texas) indicates that there are angiotensin II receptors located in the subfornical organ which, upon binding of angiotensin II, cause a release of ADH from the posterior pituitary. I feel like I’m getting different information on what ADH’s role is a response to. 

In the case of isotonic volume loss (eg. hemorrhage, diarrhea), you would get activation of the RAAS system as a response to low blood volume/BP. My confusion rests in – does ADH get released as a result solely of the volume loss (not in response to a change in osmolarity) via the angiotensin II – subfornical organ – posterior pituitary pathway? (implying its importance and precedence in preserving blood volume over osmolarity?) 

OR is the production of aldosterone in this situation which leads to increased Na+ absorption, which in turn increases blood osmolarity leading to ADH release the mechanism for ADH release in relation to preservation of blood volume?

Thank you kindly in advance.

Best,

[Name withheld]

Sources: Physiology 4th ed. Linda S Costanzo pg. 291
First Aid for the USMLE Step-1 2013 Tao Le, Vikas Bhushan pg. 485
http://neuroscience.uth.tmc.edu/s4/chapter02.html Patrick Dougherty, Ph.D

Here was my reply

[Name withheld],

The goal of medical physiology is to build a model of how the body works so that the student can predict how the body will respond to various inputs. The more advanced the model the more situations the model will accurately predict the outcomes. Of course the down side of the more complex model is it becomes more and more difficult to remember and keep accessible for use.

Every concept in physiology that is taught should be taught as a step in building an accurate model. Any student that tries to memorize the avalanche of physiology facts without fitting them into a model will be lost. Additionally, students that confuse the model for reality will be disappointed because no model can adequately describe the wonderful complexity of the human body. The sweet spot is adopting a model that is accurate enough to describe the clinical scenarios you encounter in medicine without being so complex to confuse the user

This is especially appropriate for renal physiology.

Short answer is you have it right.:
RAAS is for volume (BP and perfusion) regulation and ADH is for osmoregulation.

Additionally the statement that ADH also responds to volume is also correct and essential in understanding why heart failure and volume depletion leads to hyponatremia. In both CHF and hyponatremia the perfusion is compromised so much that ADH is released (not because of high osmolality but because of the low perfusion signal for ADH). This ADH concentrates the urine and lowers urine output. Then even modest amounts of water will exceed intake and sodium is diluted.

The additional statement that it takes precedence over osmolality is critical. When there is simultaneous low osmolality (suppresses ADH) and low blood pressure (stimulates ADH), the volume stimulus wins. In the hierarchy of need, maintaining perfusion takes precedence over osmoregulation.

a page from the best book I ever wrote

Regarding Costanzo’s three functions:

  1. Increase water permeability. Yes this is the primary and most important function of ADH with regard to osmoregulation.
  2. Increase activity of the NaK2Cl this is likely true because the NaK2Cl is the pump needed to maintain the concentrated medullary interstitium that drives the reabsorption of water in the collecting ducts in response to ADH. Having ADH stimulate this receptor helps maintain that concentrated interstitium so it doesn’t get diluted by the reabsorbed water. However I would recommend you ignore this fact. This complicates the model of osmoregulation and will lead you down false roads.

    If you believe this is an important function of ADH you will assume that SIADH, a condition of unregulated over production of ADH will cause sodium accumulation (due to stimulation fo NaK2Cl pump) when in reality the most important aspect of SIADH to understand is that SIADH is a sodium neutral state (sodium in = sodium out) and only causes hyponatremia due to the over reabsorption of water (due to the ADH)

  3. Increased urea permeability. I have no idea if this is important and why it might be important. It likely is also important in maintaining the concentrated medullary interstitium. That is one of the strangest tissues in the body and ADH induced water reabsorption dilutes it so my guess is that many of the subtler renal affects of ADH are designed to maintain and restore this briny Superfund site in the middle of the kidney. Ignore the italics, that is only to impress other nephrologists that read this far.

In regards to the neuroscience textbook indicting AT2 receptors as a critical signal for ADH release. This is likely the trigger for the volume dependent release of ADH we discussed above. But again this is a fact that can be safely ignored because if you focus on AT2’s role in ADH release you may falsely assume that ACE inhibitors (and angiotensin receptor blockers and renin blockers) will block these receptors, decrease ADH and cause a diabetes insipidus picture. This does not happen. Keep it simple.

AT2 is for volume 
ADH is for osmolality 
don’t conflate the two

Your final question is about isotonic volume loss, the answer is: you are clearly describing a perfusion related release of ADH. Do not use an overly complex Rube Goldberg system of increasing osmolality to release ADH.

I also would recommend my book. You can download the whole thing for free (PDF). It is long and Adobe Acrobat did a shitty job of rendering much of the text but it is excellent and it is free.

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Recipe for IV Fluids

Normal Saline

1 tsp salt = 2,300mg sodium = 100 mmol sodium

1 gallon = 3.78 liters
1 liter of NS has 154 mmol of sodium
1 gallon need 582 mmol of sodium (154 * 3.78)
582/100 = approx 6 tsp of sodium

3% Saline

1 tsp salt = 2,300mg sodium = 100 mmol sodium

1 gallon = 3.78 liters
1 liter of 3% has 513 mmol of sodium
1 gallon need 1,939 mmol of sodium (513 * 3.78)
1,939/100 = approx 20 tsp of sodium

D5W

1 tsp sugar = 4.2 g sugar

1 gallon = 3.78 liters
1 liter of D5W has 50 g of sugar (glucose)
1 gallon needs 189 g of sugar (50 * 3.78)
189/4.2 = approx 45 tsp of sugar or 15 tablespoons
Anyone want to check my math?

IV fluid taste testing at McLaren Macomb Hospital

@kidney_boy Your math is correct, of course depending on the size of a table spoon http://t.co/OvkVzDoWMJ. In netherlands 1tsp = 10g NaCl
— Martijn vd Hoogen (@MWF_vd_Hoogen) August 13, 2014

@kidney_boy would be good to say glucose instead of “sugar”
— Lewis (@Lewis_Lab) August 14, 2014

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Just saw a heart failure patient in follow-up

We had a patient, who had been healthy until he ran into some a-fib. He then began a months long descent into the depths of decompensated heart failure. His dry weight prior to decompensation was 208. On admission to the hospital he was 262.

It took over a month of acute and sub-acute care, a failed cardioversion, a pacer, and a cardiac ablation, but he ultimately emerged from his heart failure. He is now back to his dry weight. He went from 208 to 262 pounds to 208 pounds’  That is 54 pounds of water weight. My understanding of heart failure is this excess fluid is almost entirely extracellular.

Think about how much water and sodium that is:

  • 54 pounds = 24.5 kg of 24 liters of water
    • Total body water of an average adult is 42 liters
    • Extracellular volume is a third of that, or 14 liters
    • at 208 pounds his total body water is only 47 liters
  • 24.5 kg of water with a sodium concentration of 140 = 3,430 mmol of sodium. 
    • For comparison the total body sodium for a 70 kg man is around 2,200 mmol
Incredible.
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Addendum to Hypokalemia

I can’t post to Vimeo until next week. So google docs once again.

The hypokalemima section did not cover vomiting, so I added this addendum.

Part 3 is uploading right now so the final pots with all three parts and the keynote and PDF will be available tonight.

Addendum to Part 2

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August is aPLA2R month

For decades we have known that membranous nephropathy was an antibody induced glomerulonephritis, we just didn’t know what the antigen was. Then, in 2009, Beck et al. rocked nephrology by discovering the antigen, Phospholipase A2 antibodies were detracted in 70% of patients with membranous nephropathy and no patients with either secondary membranous, other proteinuric glomerulonephritis or normal controls. Since then there has been a steady stream of positive trials showing tight association with aPLA2R antibodies and disease activity in idiopathic membranous nephropathy.

Panel H illus­ trates the domain structure of PLA2R, which is composed of an N­-terminal cysteine­rich domain (Cys­R), a fibronectin type II domain (FNII), eight CTLDs, a transmembrane domain (TM), and a short intracellular C-­terminal tail (IC). The blocking fragment used in the experiments consists of CTLDs 4, 5, and 6 of a recombinant rabbit PLA2R.

This month both CJSAN’s eJC and #NephJC will be going deep with studies that examine the state of the art in aPLA2R research.

This month CJASN’s online journal club is doing an interesting article looking at aPLA2R status at the beginning and end of therapy and its ability to predict long-term outcomes. It is a unique study with multiple titers of aPLA2r over the course of time matched with 5 years of follow-up. Though it is not the biggest trial of aPLA2R in some ways it is the best and it is an important step in understanding how to use this new tool in the management of membranous nephropathy.

Every month eJC has a sponsor, this month that sponsor is my home institution St John Hospital and Medical Center in Detroit. My fellow and I reviewed most of the key studies in aPLA2r and provided a helpful summary of this study. Check out our background post at Medium and then participate in the forum.

#NephJC will be shortly announcing its article for discussion and then have a twitter discussion on August 12th at 9pm EDT.