Tuesday, August 25, 2015

#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:




Monday, August 17, 2015

Big anion gap or biggest anion gap?

One night that I was on call, I received an interesting patient from the ED.

The patient was confused but walked into the ER and was able to give at least a partial history. They did some initial chemistries and called me with the following results:
This is the kind of lab that grabs your attention.

With that glucose the first thought should be, "Is this DKA?"

Yes.

Beta-hydroxybutyrate: 6 mmol/L

I try to account for the anion gap. So I look at all the anions I measure and see how well they explain the gap. And if I can't account for the majority of the gap I have difficulty sleeping. This patient's gap was 51, 12 is normal which leaves 39 to account for. Only 6 can be accounted for with beta-hydroxybutyrate.

"Is there a lactic acidosis?"

Yes.

Lactate:16

That still leaves 17 mmol/L of unexplained anions.

Next step, look for an osmolar gap.

Measured osmolality 348
Ethanol level 0

iTunes

Yes.


An osmolar gap of 32 is a profound osmolar gap. We ordered fomepizole and started hemodialysis for presumed toxic alcohol poisoning. 

The alcohol screen came back the next day:

ETHYLENE GLYCOL, SERUM = 0 mg/dL (Reference Range: 0.0-5.0 mg/dL)

PROPYLENE GLYCOL, SERUM = 8.1 mg/dL (Reference Range: 0.0-5.0 mg/dL)

Propylene glycol is normally due to the solvents used to dissolve IV drips. So usually we see problems in patients who have been in the ICU for awhile.
Arroliga AC


Propylene glycol is also found in antifreeze and hydraulic fluids. 

The molecular weight is 76, so the 8.1 mg/dl represents only about 1 mmol/L, however it may explain the severe lactic acidosis and by stimulating the production of D-lactate it may explain even more of the gap.
Kraut, JA
Dialysis removes the parent compound and metabolites. Whether patients need to receive fomepizole is less clear. Kraut and Kurtz suggest fomepizole would be beneficial, while others feel less strongly.



In this N=1 case, our patient did well without receiving fomepizole. 

Thursday, August 13, 2015

#OUWB Questions

This question came in after class from a couple of students.

If the urine sodium in volume depletion and the great edematous states (heart failure, liver failure, and nephrotic syndrome) is low how can the urine osmolality be high?
The osmolality of the urine is made up of electrolytes (sodium, potassium and chloride) and non-electrolytes. The non-electrolytes like urea and ammonia will make up the bulk of the osmolality in the small volume of urine that is seen in this clinical setting.



In the advanced electrolyte class (nephrology and critical are fellowship) we look at the electrolyte content of the urine and use it to look at hypo- and hypernatremia more sophistically. For the purpose of medical school, SHELF exams, and USMLE parts 1, 2, 3 you can safely just look at the osmolality of the urine. We are trying to build a model that is understandable and good enough to predict how patients will behave in health and illness. This works pretty good.

The next question also came from a couple of people in class.

In SIADH, you say that the patients are euvolemic, but then you say they retain water via ADH in the medullary collecting duct. How can both of these be true? Won't they become volume overloaded if they retain water.
This is a common question. The key to understanding this takes a bit of a leap of faith. First off, there is no slight-of-hand here. If you do careful water measurements as patients develop SIADH you can measure an increase in total body water. But critically, the increase in water is not progressive and it does not cause clinically significant volume overload. It does not cause pulmonary edema, it does not cause peripheral edema and it does not cause hypertension, all consequences of true volume overload from a positive sodium balance. 

One of the reasons that excessive water intake does not cause volume overload is that most of that water (two-thirds) disappears into the intracellular compartment. Just like no one complains of their rings not fitting after drinking a lot of water, having high ADH does not cause interstitial edema.

This image from the lecture needs to be front and center when you think about SIADH: water out of balance, sodium in balance:


The last question for now comes from an e-mail (jtopf@mac.com):

I had a question from the second half of the lecture about treating euvolemic hyponatremia in the case of adrenal insufficiency. I'm having a hard time understanding why urea and salt tablets would help to reverse the hyponatremia. If solute in = solute out and the kidneys are already in sodium balance, how would it increase the solute load in the case of salt tablets? Even if the urine output goes up, won't there still be non-physiological ADH release and concentration of the urine?
So the best way to think about salt and urea tablets is be visualizing this slide from this SIADH lecture:


In SIADH, the secretion of ADH is fixed and maximal. It's like somone is stepping on the gas and can't remove his foot.

Normally the ADH slides from minimal to maximal in order to balance water excretion with variable water intake:

The ADH slider is supposed to indicate that the ADH can slide from minimal activity, resulting in large volumes of urine, to maximal activity, resulting in minimal urine output. As the questioner correctly intuited, the osmolar load is fully excreted. In euvolemic hyponatremia, the slider is jammed to the right. If the urine osmolality (the denominator) is fixed the only way to adjust the urine volume will be to adjust the osmolar load (the numerator). Increasing the osmolar load with a high protein diet or salt tablets or urea pills will raise the numerator and hence increase the urine volume. It's just math. Yes, taking sodium tablets will just result increase the sodium excretion since these patients are in sodium balance, but this additional sodium excretion increases the urine output making it easier for the patient to have less water intake than excretion, the goal for the treatment of hyponatremia.

Wednesday, August 12, 2015

OUWB School of Medicine materials for 2015

Here is a link to the resources I used last year. They are largely unchanged. The water and solute lecture is available under the lecture tab. I will continue to edit this post with additional materials and links.
  • Solute and Water lecture (Keynote | PDF)
  • Acid-Base lecture (Keynote | PDF)
  • Metabolic alkalosis, potassium and monogenic hypertension (Keynote | PDF)

Tuesday, August 11, 2015

Diuretics, MedMastery, and Keurig

PBFluids has been quiet. Took awhile to just clear the cobwebs to get this post up.

One of the things that has kept me busy has been a project with a company called MedMastery. Franz Wiesbauer was a fan of my fluids book and reached out to me. We worked together to create a curriculum covering body water, diuretics, IV Fluids, sodium and potassium. The full course is about 1,000 slides. But the genius of MedMastery is how they edit and craft the course so it is broken up into an odd fifty 6-minute morsels. It is medical school for Generation Keurig.

MedMastery has opened up a few of the K-cups for promotion. 

Take a look at two of my diuretic lectures:









Some photos from the recording studio




Saturday, June 6, 2015

Reading about Art Levinson in Emperor of All Maladies

Art Levinson is the current Chairman of Apple. He was brought on to the board in 2000 during Job's second act and was present for the introduction of the iPod, iTunes and iPhone.

Art Levinson is always introduced as the former CEO of Genentech but I didn't know his story until I read the Herceptin story in Emperor of All Maladies. Turns out Levinson was trained by Nobel Michael Bishop of oncogene fame. In the late 80's Levinson was leading a group pursuing treatment for breast cancer by doggedly tracking a gene called HER-2.  Genentech's executives turned away from cancer research after some high profile failures in the 80's. This should have been the end of genentech's role in HER-2 except for the leadership of Levinson. He dodged the bureaucracy, pursued resources and lead a small team to continue work on HER-2. The group produced Herceptin, one of the most important breakthroughs in chemotherapy in the molecular era in, a jaw-dropping, 3 years.
Laureate


Reading that story I can see why Jobs would want him on the Apple board.

Monday, June 1, 2015

Who are "your people"?

As we were gearing up for NephMadness Mealnie Hoenig mentioned that she loved working with the Nephmadness crew because they were "her people." This resonated with me and has become my latest way of looking at the word. This particularly resonated with me when my college roommate introduced me to Public Broadcast Service.



Gene Kranz
There best song is "Go" which samples Gene Kranz dialog with his flight controllers during the Apollo 11 lunar lander landing. I love this because though I have heard the story of the Apollo mission a 100 times I had never thought of it from the perspective of the flight controllers.

This struck me as a great example of my people. While I never could imagine myself as Neil Armstrong, I could imagine me, and my ilk, being a flight controller in Houston. Which one would I be? flight SURGEON, of course.

Summary of the different flight controllers can be found here.

Transcript from the song:

Narrator (NASA Spokesman?)
This is Apollo Control 102 hours into the flight of Apollo 11.
It has grown quite quiet here at Mission Control

A few moments ago Flight Director Gene Krantz requested that everyone sitdown and get prepared for the events that were coming and he closed with the remark "Good luck to all of you." [Ed. not quite One small step for man; one giant leap for Mankind]

12 minutes now until ignition for powered descent. Everything still looking very good at this point

Gene Krantz
Okay all flight controllers, "Go" "No go" for powered descent.
Or if you prefer, the Ed Harris version

RETRO?
      Go!
FIDO?
      Go!
GUIDANCE?
      Go!
CONTROL?
      Go!
Deltcom? [can't quite tell, maybe INCO?]
      Go!
GNC?
      Go!
EECOM?
      Go!
SURGEON?
      Go!

CAPCOM we are go for powered descent [CAPCOM, capsule communicator, was an astronaut in Houston responsible for communicating with the mission astronauts. At the time of the landing it was Charlie Duke]

We are off to a good start.
Play it cool.

Okay all flight controllers, I'm going around the horn

RETRO?
      Go!
FIDO?
      Go!
GUIDANCE?
      Go!
CONTROL?
      Go!
Deltcom?
      Go!
GNC?
      Go!
EECOM?
      Go!
SURGEON?
      Go!



RETRO?
      Go!
FIDO?
      Go!
GUIDANCE?
      Go!
CONTROL?
      Go!
Deltcom?
      Go!
GNC?
      Go!
EECOM?
      Go!
SURGEON?
      Go!

CAPCOM we are go for landing

Kranz: okay everybody lets hang tight and look for landing radar

Aldrin: 75 feet down a half 
Aldrin: 1202 alarm 
60 seconds [This is the amount of fuel that is left before they must abort]
Transcript of Apollo 11 landing.
CAPCOM: we;re go on that flight
Aldrin: we are go on that alarm?
Aldrin: 40 feet down 2 and a half
GUIDANCE: If it doesn't reoccur we'll be go.
Aldrin: starting second
Armstrong: 1201 
Aldrin: 1201
CAPCOM: Roger 1201 alarm
CAPCOM: Okay, we are go

Aldrin: we've had shut down.
Armstrong: Houston...ah...Tranquility base here. The Eagle has Landed.

Kranz: Okay keep the chatter down in this room. [The greatest moment in the history NASA and Kranz is focused on keeping his team on task]

CAPCOM: T1 standby for T1

Kranz: Stay or no Stay all flight controllers [Apparently it was possible to land on the moon but have something go wrong requiring an immediate return to orbit, so this was a check to see if they could proceed to the lunar surface mission]

RETRO?
      Stay!
FIDO?
      Stay!
GUIDANCE?
      Stay!
CONTROL?
      Stay!
Deltcom?
      Stay!
GNC?
      Stay!
EECOM?
      Stay!
SURGEON?
      Stay!


RETRO?
      Go!
FIDO?
      Go!
GUIDANCE?
      Go!
CONTROL?
      Go!
Deltcom?
      Go!
GNC?
      Go!
EECOM?
      Go!
SURGEON?
      Go!

Wednesday, May 13, 2015

Goldfarb takes the ACP to the woodshed

David Goldfarb has written a sternly worded letter to the ACP in response to their clinical practice guideline, Dietary and pharmacologic management to prevent recurrent nephrolithiasis in adults. The guidelines took positions that seemed to make no sense when looked at as a whole. Due to insufficient evidence the guidelines recommend:

  • no need to determine stone composition prior to treating stones
  • no need to analyze blood chemistry before treating stones
  • no need to do 24-hour (or 48-hour) urine collections before treating stones
What makes those positions so absurd is that if increased fluid intake did not reduce stones the authors suggested a trial of allopurinol, thiazide diuretics or citrate (without guidance on how to dose, follow or how to choose among those therapies). These recommendations are based on research done on patients where the type of stone had been determined. Not following those enrollment criteria makes the conclusions irrelevant.

It is as if the ACP said not to measure blood pressure because there has never been a randomized controlled trial of patients where blood pressure was measured versus patients who do not measure blood pressure.

Goldfarb's letter added some other incredible details to the story I was unaware of including:
None of the authors of the paper have a single other co-authorship in PubMed relevant to kidney stones, other than the AHRQ review. I believe that none of the authors are nephrologists or urologists, none have a kidney stone clinic, none appear at, or present research at, kidney stone meetings, none have any experience regarding management of kidney stones
And this doozy, in response to a comment of the paper from the lead author:

As we point out in the guideline, we are aware that many physicians do select medications based on stone type, for example, allopurinol for uric acid stones, and we do not discourage that practice. 



Physicians who regularly treat stones or who played NephMadness (2014 edition) know that allopurinol is used to prevent calcium stones not uric acid stones which are best treated with alkalinization.

Read Goldfarb's letter. It is excellent.

Calcium Booklet

Minor updates.

PDF (7.6 mb)

Pages (8.7 mb)

I think this covers all the high points that residents need to know about calcium. Please send feedback of what is missing.

Saturday, May 2, 2015

One million

The blog turns 7 on May 30th. But tonight we flipped the odometer.
One million page views.




I bet we never see ten million.

PBFluids.com Established 2008

The push to one million. Blog post about Twitter (NephJC) and Twitter mention of an old post on MDRD and protein restriction. A PBFluids deep cut.

Friday, May 1, 2015

NephJC: one year in the can

The first NephJC chat was April 29th 2014, so the official birthday went unrecognized a couple of days ago. Such is the way of academic medicine.



Swapnil and I are delighted with the success of the endeavor which launched with humble beginnings on Medium aweek before the first chat with this manifesto:


Coincidental to the calendar turning over, NephJC is being recognized in two articles in the medical literature. The first is the first systematic review of microblogging journal clubs. It is an interesting and thought provoking article. NephJC takes a victory lap in Table 2:




NephJC is third in participants and total number of tweets and first in tweets and impressions per month. I found this paragraph particularly insightful:




Especially in light of Twitter's recent financial results.




The other entry in the medical literosphere was an article written by Swapnil and I as part of a special issue of International Psychiatry Review dedicated to social media and edited by the fabulous Margaret Chisolm. It was a unique opportunity to formalize our thoughts on NephJC and journal clubs in general.






It's been whirlwind first year and I'm looking to see what new boundaries NephJC can stretch in year two.

Sunday, April 26, 2015

Videos for patients and by patients

This is my go to video for helping patients make decisions on what modality to choose.


Last night I received the following Tweet:


I can't recommend the video enough. In this age where everything is sanitized and abstracted as much as possible this video is just authentic. It's as real as it gets. To me it brings to life all of the little things we ask dialysis patients to do, from waking up early, to restricting fluids, to spending 12 hours a week in a recliner hooked up to a machine with only one hand free. 

It is awesome. 

Everyone should watch it.
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