Tuesday, March 21, 2017

The Curbsiders

I love podcasts. I listen to them on my commute and when I walk my dog twice a day.

Bo the Dog

In the last year I have become addicted to The Curbsiders, what I consider the best internal medicine podcast. These three guys get interesting experts and interview them on topics with a primary care angle. They do a good job of digging deep to get good engagement from them and though they are respectful they do ask challenging questions (though honestly, I thought I got all softballs, listen to the podcast on coronary calcium scores for some probing questions).

Most importantly they are entertaining. I don't need NephSAP audio digest. That stuff kills me. Never absorbed a sentence of it. The Curbsiders make listening to medical science fun.

Looks like they stopped doing these in 2013. Anyone miss them?

And this week they had me as a guest. I enjoyed the experience immensely, but in an hour of talking off the cuff I made some embarrassing mistakes:
  • In describing water reabsorption I said it occured in the cortical collecting duct rather than the medullary collecting duct.
  • In describing my cure for cramps I tell the story of Gitelman's and say it is like congenital loop diuretics rather than congenital thiazide diuretics
  • I mucked up the story about MRFIT and how it allowed a head to head comparison of HCTZ and chlorthalidone. I really oversold what happened.
          Here is how Carter et al described the MRFIT story:
it was observed that in the 9 clinics that predominately used HCTZ, mortality was 44% higher in the special intervention (SI) group compared with the usual care (UC) group.10 The opposite was true in the 6 clinics that predominately used chlorthalidone. The MRFIT Data Safety Monitoring Board changed the protocol near the end of the trial to exclusively use chlorthalidone. In the initial clinics that used HCTZ that had a 44% higher mortality in the SI group, the trend was reversed after the protocol was changed to chlorthalidone, and they then had a 28% lower risk (P=0.04 for comparison of coronary heart disease mortality at the 2 time periods).
Like sending out newsletters, in Podcasts (especially when you are the guest) once it is recorded, you own your words with no chance to edit them.

Give The Curbsiders a listen, I think you'll enjoy them.

Monday, March 13, 2017

NephMadness Twitter Participation

Here is a summary of the first four editions of #NephMadness

And here is where we stand today.

And on March 22: 600 participants is bonkers!

And on March 26: Closing in on 700 participants.

The release of the first round results caused another surge in Twitter use:
It has also driven AJKDblog traffic to highest level ever.

Medical Greek and Medical Latin

It all started with a simple tweet by @MDaware

Chris Carrol corrected him

And I piled on

As I was posting this I was thinking. Nephrology is Greek. What ever, no one will care. Yeah, right.

The reason I knew that nephrology is Greek goes back to the early days of the The Fluid and Electrolyte Companion. We were planning the book and Sarah Faubel and I wanted to have a lot of little icons for little interesting factoids for the book. Here is the key for what made the cut:

But in earlier versions we had a lot of other icons. And one of the ideas was to have an icon for medical Latin but quickly we found that most words we wanted to define were actually Greek. We created a Medical Greek Icon, but it didn't really work so we ended up using the light bulb. Here is an example of Medical Greek as found in the Book.

This is what the unused medical Latin icon looked like:

Tricks of the Trade: How to get rid of those red squiggly line

This came across my Tweet Stream:

We are honored to have the @ISNKidneyCare Social Media Task Force covering NephMadness. However the image needs some first-aid.

Up first is getting rid of those ugly black bars on the left and right.

Solution: Use ⌘⇧4 to get a selection cross hairs, drag across your target, release the mouse button, and presto.

Tricks of the Trade: screeen shots from joel topf on Vimeo.

Alternatively. Open the picture in Preview, select the target and press ⌘K to crop.

Tricks of the Trade: Cropping in Preview from joel topf on Vimeo.

The other problem are the names on this picture, everyone of them has the spelling squiglies under the names. Here the problem is that the screen shot was taken in editing mode The two solutions are to export the document to images or put the document in Show Mode and take the screen shot. Demo time:

Tricks of the trade getting red of squigglies from joel topf on Vimeo.

Tuesday, March 7, 2017

NephMadness 2017

NephMadness launched today for the fifth consecutive year. The fourth sequal to an original is a precarious place to be. Exhibit A: Fast and the Furious resorted to bringing in Dwayne Johnson. We looked into it and sadly, he was not available.

And do we even need to mention Rocky V?

So it was with this ominous precedent that we began the journey to NephMadness. In our fifth year we were able to get 31 completely fresh concepts, with the only repeat being antiPLA2r which showed up in the inaugural NephMadness in 2013.

The regions have a few more repeats as we revisited Dialysis, Nutrition, Genetics and Biomedical Research. The theme for the year is Old versus New. More on that in an upcoming editorial (just one of a number of posts that didn't quite get finished for the launch).

If you are not familiar with NephMadness, these two videos maybe helpful.

For the next month these are the essential tools:
Brackets (PDF)

AJKDblog website for all of the scouting reports so you can make the best pics possible.

NephMadness.com bracket entry site.

Now get to it!

Saturday, March 4, 2017

Talk to Medical Students about "Why Nephrology"

I was invited to talk to the Internal Medicine Interest Group at Wayne State Medical School. Here was the deck I used, but to be honest it was mostly a discussion. Much more two way communication and less top down.

What would you have added?

Friday, March 3, 2017

Social Media Manifesto

Sharing: The Currency Of Social Media

Many people say information is power. I don’t believe that. Information sharing is power. People are more than willing to share information not because they are being paid but because they get a feeling of satisfaction that somebody else found their information useful. — Vint Cerf, Chief Internet Evangelist, Google, Inventor of TCP/IP

In this quote, Cerf was describing the value of sharing in order to explain the phenomenal success of social media sites like Facebook and Twitter, but I found that it explained much of my own Internet behavior. I think the principle is so useful: People should optimize their online creative output in order to make the content more useful for others.
Facebook has a billion people on a single network. This is unprecedented in human history, and the incentive to be part of this network comes from friends, relatives, and acquaintances volunteering information to be shared. Everything people add is effectively controlled by a third, profit-motivated, party. One would think this would paralyze sharing, yet 293,000 statuses are updated and 136,000 photos are uploaded every minute. The biggest mystery surrounding Facebook is why so many donate their time, energy, and privacy to this endeavor. The reason is not magnanimous generosity, but rather that these hundreds of millions of people are getting satisfaction from sharing.
I am a teacher and blogger. I teach nephrology to medical students, residents, fellows, and an occasional attending physician. I share all of my teaching materials on my blog. When I share these materials, I share them in a way that makes them most useful for the reader. Handouts should not be limited to PDFs but should be available in their native, editable, word processing files. How is this more useful? If you are a student and want to get my lesson, grabbing the more versatile and lighter-weight PDF makes sense; however, if you are a teacher and want to adapt a figure, or a small segment of the handout, having access to the native files is critical. The greatest satisfaction I get as a networked teacher is when I get an e-mail or tweet from a colleague thanking me for making a handout or presentation.

What was so enlightening about the explanation from Cerf was seeing that sharing is not strictly generosity but is powered by self-interest: By increasing usefulness of the resource, I get more satisfaction.
PowerPoint presentations can be distributed multiple ways over the Internet: Presentations can be exported as PDFs, SlideShare presentations, PowerPoint shows, or as native .ppt or .pptx files. Some of those formats are Read Only: PDFs, SlideShare presentations, PowerPoint shows, in that they cannot be edited or remixed by the user. Native .ppt and .pptx files are Read/Write formats that allow the user to see the presentation and freely edit, copy, and reuse parts of it.
The NYU Division of Nephrology has weekly renal grand rounds done by the fellows. In the spirit of Internet sharing, they post every presentation on the division’s website. Every presentation is available only as a PDF. This form of sharing is strictly Read Only; providing the information solely as a PDF limits users from remixing your content. Posting a presentation as a PDF says to users:

“You can use my material, but only if you use all my information. The way I teach this subject is the only way to teach this subject and my information is eternal and infallible.”

However, the Internet is inherently a Read/Write culture. The optimal way to post those presentations is as native PowerPoint files (or Google Docs Presentations or Apple Keynote presentations) so future fellows can leverage previous work, adding new data, correcting mistakes, and reworking the old into the new. Make the materials you provide online flexible to make them more useful, because the source of your satisfaction is usefulness to others.
Medicine and medical education need to abandon the Read Only assumptions about teaching materials and embrace a Read/Write culture: Students can become participants in their own education, and authors of a personalized textbook. This is how I post presentations on my web site:
  • I first have a picture of one of the slides; this helps me fly through the growing list to find a specific presentation.
  • Then I have the title and links to the native format and the PDF. The PDF is useful for people who are looking for the Read Only experience and for people without the software needed to read the native file. It is important to provide both.
  • After that, I have a few bullet points about the scope of the presentation: when it was last updated, weaknesses that need to be fixed. In this case, it has links to a supplementary handout, again as both native file and PDF. Other useful metadata includes how long the presentation is, and the size of the files.
One of the foundations of academic tradition is the ethic to attribute everything. I have seen professors seethe in national meetings as their slides or figures are used without attribution. I want to stress that providing easy ways for people to adapt and remix material in no way relieves them of the ethical obligation of attribution. In fact, attribution is another way to increase the usefulness of the work. Credibility is a primary ingredient in the usefulness of medical material, so a thorough chain of references is seen in the best medical adaptations of source material.
Putting up electronic locks in hope of dissuading people from using material without attribution is a failed strategy. It punishes the lawful without stopping the ruthless. And — importantly — if your effort to lock down your materials means that it is less useful to your audience, you get less satisfaction from sharing.
The currency of social media is sharing. If you want to build an audience and add value to whichever social media realm you occupy, you need to provide content that others can share.
If you create content, you want that content to be in the form that is most shareable. We live in a remix culture. People see content and they want to take it, change it, make it their own, and reshare it. Operating in the social media realm of medical education requires doctors to adapt to the customs of the realm and that means disposing the handcuffs of academic ownership and embracing the reason we are all educators: the dissemination of knowledge.

This post was originally published at Wing of Zock
May 8, 2013

Wednesday, March 1, 2017

One of these days...

...I'm moving my blog from blogger to WordPress.


        •  5 Reasons to switch

        •  7 Reasons to switch

        •  How to switch from Blogger to WordPress

Wednesday, February 22, 2017

In Honor of Moving Mountains for Multiple Myeloma (MM4MM) a Review of Acetazolamide

I'm going to Mount Everest Basecamp next year to help raise money and awareness for multiple myeloma. Basecamp is at 18,500 feet. In honor of that altitude, here is a review of all the times I have blogged about acetazolamide.

Please take the hint and make a donation. 

It is for multiple myeloma. 

It is a 4 star charity.

Sunday, February 19, 2017

Public health or public shaming

This seems like a pretty innocent infographic. It is trying to communicate how Canada is doing in preventing and managing diabetes.

Here is the tweet

Here is the response I saw in my timeline

This seemed a stretch that this poster was stigmatizing people with diabetes.

This Storify has the entire twitter exchange that follows.

I am gong to highlight a few of the tweets from that exchange here.

One of the first criticisms leveled was that the poster did not distinguish between type 1 and type 2 diabetes. This is important because the advice they were tracking and grading were all techniques to prevent type 2 diabetes: healthy weight, diet and physical activity.
This is a constant tension in building infographics, "How do you balance precision and clarity?" Not specifying type 2 diabetes makes the poster less precise but since type 2 diabetes represents 96% of diabetes in the US (not sure the Canadian data) I agree with the decision to simplify the poster. Type 1 diabetes is small potatoes compared to the public health nightmare of type 2 diabetes. Additionally, because of the potential for diabetes to grow like an epidemic and because we have tools to curtail this epidemic it becomes a good target for public health messaging in a way that type one diabetes does not lend itself.

There was then the argument that the therapy is not that effective and that people who follow this advice often still end up with diabetes:

The problem here is that since people have some agency in their disease, others will blame them for getting diabetes. The patients will be shamed because they didn't act strongly enough to avoid the disease. By publicizing ways to avoid diabetes you are setting up people with diabetes to be blamed for their condition.

How effective are the items in the poster at preventing diabetes. They are about as effective as any therapy we have in medicine. DPP is the best program to prevent diabetes. See this RCT. What was the interventin in DPP?
The goals for the participants assigned to the intensive lifestyle intervention were to achieve and maintain a weight reduction of at least 7 percent of initial body weight through a healthy low-calorie, low-fat diet and to engage in physical activity of moderate intensity, such as brisk walking, for at least 150 minutes per week. A 16-lesson curriculum covering diet, exercise, and behavior modification was designed to help the participants achieve these goals. 
All three items that are being tracked in the infographic.

So what do you get for that intervention? The DPP trial showed

  • 58% reduction in the incidence of diabetes compared to placebo. 
  • 39% reduction in the incidence of diabetes compared to metformin. 
In 2014 1.4 million people developed type two diabetes. A 58% reduction in the incidence of diabetes means that over 800,000 people would not develop diabetes in a year.

800,000 people 

That compares pretty favorably to the total population of people with type 1 diabetes: 1.2 million.

The problem with arguing the fact that some people progress to disease despite therapy to prevent it is that none of our medications are 100% effective. If I advise patients to take their ARB because it will help their diabetes and then they develop ESRD anyways, did I invite ridicule on them because I gave them an effective therapy? Will people not provide comfort because if they had just tried harder with their ARB they would not have developed ESRD? I hope not. And that concern should not stop me from making it well known that there is an effective drug for diabetic nephropathy, it is also important to remember the treatment effect in IDNT and RENAAL were pretty modest.

Losartan reduced ESRD by 28%, but a quarter of the treated patients still ended up on dialysis by 4 years.

Irbesartan had a similar treatment effect and a similar proportion of patients end up on dialysis despite therapy.

We should not blame people for the diseases they develop but we should not use the fear of that blame to avoid measuring, publicizing, or developing public health initiatives, because it looks like it maybe working.

I gave Dr. Witteman an early version of this blog post and an opportunity to respond.

Thanks for the opportunity to respond to your post. I would like to note the following five points.

  1. Type 1 diabetes in Canada is estimated to represent about 9% of all cases of diabetes. That's more than twice your US estimate. Even if it's still a relatively small percentage, given the prevalence of all types of diabetes, that's a lot of people. I am one of those people, so this is personally relevant to me.
  2. I think it's important to note that CIHI is not, strictly speaking, a public health agency. Their role in Canada is more or less to collect, collate and report data on health system quality and population health. The infographic is not intended to motivate individuals. However, when they tweet it out as they did, they're deliberately seeking a public audience.
  3. There is some evidence that blame & shame methods can be not only ineffective as health behaviour change mechanisms, they may be counterproductive. In other words, they may make health-related behaviours worse, not better.
  4. A Canadian survey in 2011 conducted on behalf of the Canadian Diabetes Association revealed that 37% of people would hesitate to tell others they have type 2 diabetes. Stigma around diabetes, particularly type 2 diabetes, is a very real issue in Canada.
  5. The most concerning cases of type 2 diabetes in Canada occur among people in marginalized populations (Indigenous peoples, immigrants from specific populations known to be at higher risk of type 2 diabetes, people living in poverty, etc.) Promoting the idea that diabetes is completely their own fault may reduce public support for interventions that can help prevent diabetes in these communities, including programs that promote healthy eating and physical activity. Maintaining or increasing public support for such programs is an important consideration in a publicly-funded health system such as we have in Canada.
Thank you for reaching out and offering me the opportunity to engage with you on this issue. As noted in my original 13 tweets, I strongly agree with encouraging healthy eating and physical activity. I also agree with preventing type 2 diabetes and reducing the burden that diabetes can place on people. The problem is that infographics like this typically don't move the needle, and they can even be counterproductive and harmful. 
Holly Witteman, PhD

Friday, February 17, 2017

Adding a little Usain Bolt to SPRINT

The SPRINT trial was a home run. The study showed compelling data that lowering blood pressure dramatically below what we were previously targeting was both well tolerated and yielded huge benefits to patients.

Now there are some questions to the method of blood pressure assessment and how this can be compared to previous blood pressure trials, but I believe that the BP assessment used in SPRINT is more reproducible in offices than the standardized BP typically used in trials that no one howls about (you mean your MA does not follow a 12 step checklist when checking patients in?).

One of the important corollaries that I emphasize when I teach SPRINT is that the study enrolled a very specific patient and we don't know just how generalizable these findings are:
  • 50 years of age
  • Systolic blood pressure of 130 to 180 mm Hg
  • Increased risk of cardiovascular events defined by one or more of the following: 
    • Clinical or subclinical cardiovascular disease other than stroke
    • Chronic kidney disease, excluding polycystic kidney disease, with eGFR of 20 to 60
    • 10-year risk of cardiovascular disease of 15% or greater on the basis of the Framing- ham risk score
    • Age of 75 years or older
  • Patients with diabetes mellitus or prior stroke were excluded
After you accept the all of these concerns and limitations you are left with a study that reduced the risk of death by 27%. NNT for the primary outcome was 62. This is pretty darn good in medicine.
But when counseling a single patient, it is not very compelling. You have to expose 62 people to multiple drugs and the risks of over treatment in order to save one life. Those other 61 people, are all exposed with no benefit. This is just the nature of internal medicine. All we can do is give out a handful of pills in order to load the dice in patient's favor. No guarantees. Just better odds.

But what if I told you I had a way 
to reduce that NNT from 62 to 26?

Is that something you might be interested in?

Francis Wilson, is pushing the data. He has dissected the SPRINT database further and can select patients that benefit from the aggressive blood pressure reduction while excluding those that won't. He calls it an Uplift Model to Personalize Intensive Blood Pressure Control. This system allows him to reduce the NNT from 62 to 26. 

This is Wilson's entry in the NEJM SPRINT Data Analysis. The voting is open until February 28th, go check out the site and vote for the best one, or just vote for the nephrologist.

Friday, February 10, 2017

Busy Friday at St John

When the Chief Resident calls you up and asks for two lectures in one day I say "Yes sir!"

I did the World's Greatest Potassium Lecture at 8:00 AM.

Then I did Getting started in social media for doctors at noon.

Wednesday, February 8, 2017

Tricks of the trade: How to insert a tweetstream into a Keynote presentation

If you are doing a talk on social media there will be moment when you want to show a Twitter chat or Storify on a slide. This can be tricky to do quickly. Here is one technique that I use.

Inserting a Storify (or Tweet Stream) into a Keynote presentation from joel topf on Vimeo.

  1. Make sure Storify is using the Storify Template rather than the slideshow template.
  2. Enter the "Print" dialog box
  3. Set the magnification to 10%
  4. Save as a PDF 
  5. Insert the resulting PDF into Keynote
  6. Use Mask to remove the large whate space covering 90% of the page.
  7. Increase the width by ten-fold to bring the tweets back to actual size
  8. Drag the image so it is completely above the slide
  9. In animation set the picture to build in by "Move in"
  10. Edit the Build so it builds from bottom to top.
  11. Change the build in time to as long as you want 8-12 seconds depending on how much detail you want people to read.

Monday, January 30, 2017

We are fighting multiple myeloma one step up the mountain at a time

We are Moving Mountains for Multiple Myeloma (MM4MM)

Yes, I get that it makes no sense but neither does "Race for the Cure." But today in order to raise money to advance science we need to do dramatic feats of physical exertion. I am going to the bottom of Everest. Yes, going to the top of Everest would be cooler but no I'm not doing that. The bottom is the goal.

In the nine years that I have been maintaining this blog I have never asked for money. Today this changes. I am making "the ask." Please donate to the Multiple Myeloma Research Foundation in my name. Need to raise $10,000. I get 30,000 page visits a month. Let's knock this out.

The MMRF is a 501(c)(3) organization so your donation is fully tax deductible in the U.S.

The MMRF is a really cool, outcomes oriented, research foundation that has successfully brought drug after drug to market for multiple myeloma. I feel really good about raising money for them. They get 4 stars on the charity navigator.

Here is my full pitch letter:

Help me get to the bottom of Mount Everest!

I know everybody else dreams of the top, but I’m the kind of kid that when my dad asked me what I wanted to be when I grew up I told him “co-pilot.”

In the spirit of wanting to be a co-pilot, I am now aspiring to get to the bottom of Everest, AKA Basecamp, elevation 18,000 feet. Keep in mind that non-pressurized aircraft are limited to an altitude of 12,500 feet.

I am part of an expedition for the Multiple Myeloma Research Foundation. Why is a nephrologist working with the myeloma foundation? Well besides the obvious, I get to go to Mount fricking Everest, multiple myeloma plays a constant and recurring role in my job as a kidney doctor. One of the first symptoms of multiple myeloma can be foamy urine. The foam is from protein and these patients are often referred to me. My job puts me right at the beginning of the long journey of myeloma. I am the person that explains that those bubbles in the urine were actually serious, and that they have cancer. Unfortunately, the protein also can clog the kidney and many of these patients require dialysis during their treatment. So again I get to play a role in the lives of these patients.

There have been tremendous advances in myeloma therapy during my career. Outside of HIV, no other deadly disease that has seen such impressive improvement during my career. One of the reasons is the Multiple Myeloma Research Foundation. The MMRF is an amazing organization that has invigorated myeloma research and helped bring 10 myeloma drugs to market.

I am asking you to help me raise $10,000 for the MMRF. The whole Everest trip is funded by a grant from Takeda Oncology, so none of your donations will be buying my ramen, it all goes to the Multiple Myeloma Research Foundation (rated 4 stars by Charity Navigator for the last 11 years). Learn more about MMF here.

I’m asking you to make a donation.
Help me get to the bottom of Everest. 


Polycythemia and a Horseshoe kidney

This is a reported complication.

Nice review of polycythemia, with full text: Current applications of therapeutic phlebotomy

Mention of this complication in a textbook of hematology.

Patients with Horseshoe Kidneys have increased risk of renal cell carcinoma, so make sure you rule this out before just sending the patient for phlebotomy.

FERE: Fractional excretion of random electrolytes


  • 142 controls: 1.8% (range 0.5-4%)
  • 74 hypomagnesemic
    • Extra-Renal origin 1.4% (range 0.5-2.7%)
    • Renal origin 15% (range 4-48%)
  • Authors conclusion: >4% per cent is indicative of inappropriate renal magnesium loss


  • 312 normal subjects: 8% (range 4-16%)
  • 84 hypokalaemic patients
    • Extra-renal origin: 2.8% (range 1.5-6.4%)
    • Renal origin: 15% (range 9.5-24%)
  • Authors conclusion: >6.5% per cent is indicative of inappropriate renal potassium loss

Saturday, January 28, 2017

Renal Physiology You Tube Videos

I'm trying to collect some you tube videos for med students. Send me your favorites. No hour long lectures. Only looking for lessons that are shorter than 10 minutes.

This was good.

I like this one

I'm a Ruz fan.

Competerized 3-D model serves no purpose. Just confusing.

Again I feel the 3-D computer modeling serves to confuse more than educate.

Khan? Is there anything this guy doesn't know?

Friday, January 27, 2017

We live in the future

Yesterday, the consult team was evaluating a patient in the ICU and I asked to see the x-ray. A fourth year medical student started scrambling with his iPad to bring up the image. After about 15 seconds he apologized for how slow it was and then a few seconds later the image resolved.

And I just started laughing.

It was just over decade ago that we started daily rounds down in radiology to go over all of the films for our service. Well not all the films because a third of them were always missing, usually the missing ones were in the OR or still on the radiologists light box carousel.

This looks ancient. It was 1999.

I still remember that uncomfortable shame that came from having to tell my attending that I couldn't get the films. Rounding in the ICU was great because there was a satellite reading room attached to the unit so we could just duck into a room to see the images fresh from the developer. I remember being alone in the University ER when a dying man came in. The story sounded like an acute MI but I was worried about an aortic aneurysm and I was so busy putting in lines and starting pressors I couldn't get to radiology to take a peak at the mediastinum. Luckily a co-resident wandered by and was able to sprint to radiology to get the answer.

Fast forward to today and I have a kid apologising that his handheld wireless device, that is capable of displaying decades of lab results, all the notes and consults, is going to take anther few seconds to display the x-ray that was taken an hour ago.

We didn't get flying cars, but we did get a lot more than just 140 characters.

Thursday, January 19, 2017

Big anion gap. Big knowledge gap.

I just saw one of the biggest anion gap of my life and I don't know the cause. Worse yet, the patient had this occur a few months ago, also with no explanation. So I want to figure out what is going on before admission number three.

Patient presented to the ED obtunded and was unable to give a cohesive history. The admission labs:

So lets calculate the anion gap.
Add the bicarb to the chloride 
subtract that sum from the sodium
 and you get OMG!

I mean
This comes in below the gap of 70 I took care of in 2011 (presumed metformin-induced lactic acidosis) but edges out the more recent 51 from propylene glycol from 2015. So the way I like to tackle these mysterious anion gaps is to create a Gamblegram named after pediatrician James Gamble who invented the concept in 1939. The idea behind the Gamblegram (and behind the concept of the anion gap itself) is that the total number of anions must equal the total number of cations, otherwise if you touched blood, it would give you a shock. Then we graph out the cations and anions that we know, while leaving "unmeasured or unstated" cations and anions as a box. This patient looks something like this:

Looking at the numbers, the gap gets so large because not only is the bicarb so phenomenally low, but they have a pathologically low chloride and a sodium which is bumping up gainst the upper limit of normal. Additionally the potassium is a bit low, shrinking the other cations box.

We have an ABG done a few minutes after the chemistries were drawn:

    • pH 6.94
    • paO2 179
    • pCO2 6
    • HCO3 1

Then we hit that with Winter's formula: 1.5 * 1 = 1.5 plus 8±2 gives a target CO2 of 7.5 to 9.5, just a bit higher than the actual pCO2 of 6. So this patient has a metabolic acidosis with a slight respiratory alkalosis. But who can fault them for hyperventilating with a pH south of 7.

So with a massive metabolic acidosis and a ginormous anion gap, you should be itching to order a toxic alcohol screen. But first check for other causes of an anion gap metabolic acidosis:

  • Aspirin: less than 2.0 mg/dl (works especially well with the concurrent respiratory alkalosis)
  • Acetaminophen: less than 5 mcg/dL
  • Lactic acid: 9 mmol/L
  • Ketoacidosis: This hospital doesn't do real time serum ketones. So we didn't have data acetone, betahydroxybutyrate or acetoacetate levels. However the U/A showed ketones at 20 mg/dL 
So if we start to fill in the gap:
  • A normal gap is 12 mmol/L
  • Lactate is 9 mmol/L
  • The phosphorus is 7 mg/dL. Four of that is included in the normal gap, the extra 3mg/dl converts to 1 mmol/L
  • That comes to 22, leaving an unknown gap of 31. Some of this will presumably be filled by ketones, acetoacetate and betahydroxyburyrate. 
Next step is to look for an osmolar gap, because if you aren't thinking toxic alcohol you aren't wired to be a nephrologist, toxicologist or critical care doc. The serum osmolality is 342. Calculated osmolality:

I know that your shitty medical calculator does not include ethanol or if it does it divides it by 4.6 not the correct 3.7. For crap calculators see MedScape, GlobalRPh, (QxMD and UpToDate don't even include alcohol?!). Even Wikipedia gets this right. Get with the program, get MedCalcX or use MD+Calc.

So the osmolar gap is 342-321= 21. High but not very impressive, especially compared to the anion gap in the stratosphere.

The thing to understand about toxic alcohol's, anion and osmolar gap is that they move in opposite directions. Ethylene glycol (antifreeze) and methanol (fuel, incompetently distilled spirits) are both neutral alcohols. They are osmotically active so they contribute to the osmolar gap, but since they are not anions they do not contribute to the anion gap. So early after ingestion the osmolar gap is high but the anion gap remains low.

Then the toxins are metabolized (initially and most importantly by alcohol dehydrogenase) into toxic downstream metabolites. Many of these metabolites are acids that lose a proton, and thus become anions. So after metabolism the anion gap will climb as neutral alcohols are converted into anionic acids. Interestingly, the osmolar gap falls. Even though the metabolites are low molecular weight and osmotically active, they do not contribute to the osmolar gap, because the equation includes them in the calculated osmolarity. When you multiply the sodium by two, you are covering all anions in solution. Since the acids are anions they are covered by the calculated osmolality and don't contribute to the gap.

So our patient with the big anion gap and the modest osmolar gap could just be a late presentation of a toxic alcohol. Once that has happened and the osmolar gap has retunred to normal. Even if there is a large anion gap it is probably too late to intervene with fomepizole to block alcohol dehydrogenase. Once the osmolar gap has closed the toxin has moved downstream of the alcohol dehydrogenase.

But our patient still had an osmolar gap. So we gave fomepizole and dialyzed the patient. The next morning the osmolar gap had closed and the anion gap was nearly normal. We stopped the fomepizole and dialysis. On the third hospital day we got back the toxic alcohol screen. 

  • Acetone 31 mg/dl
  • Methanol: not detected
  • Ethylene glycol: not detected
  • Isopropanol 12 mg/dL
Isopropanol, is commnly called isopropyl alcohol, rubbing alcohol. It will increase the osmolar gap but is not converted to an acid and does not cause anion gap metabolic acidosis. Divide the level by its moleculatr weight, 60, and then multiply by ten to convert "per dl" to "per liter." So the level of 12 accounts for 2 of our abnormal osmolar gap of 21.

The Acetone is interesting. It is also not a charged molecule so will not account for the anion gap, but it is in equilibrium with two charged molecules that can generate an anion gap: acetoacetate and beta-hydroxybutyrate. 

I looked but could not find the expected ratio of acetone to the other two ketones in order to extrapolate from the acetone level to the concentration of the anions. I couldn't find a reference, but I found a number of documents that said acetone was a definite minority. So if we estimate that each ketones is at 2-3 times the concentration of acetone we have a 20-30 mmol/liter combined concentration of acetoacetate and betahydroxybutyrate. (Molecular weight of acetone is 58, so 31 mg/dl is 5.3 mmol/L). This essentially fills the unknown gap.

Could this just be alcoholic ketoacidosis? The patient had a triglyceride level of 600 mg/dL which is consistent with alcoholism? The serum glucose on admission was 57, also consistent with alcohol induced ketosis. 

I personally am not very satisfied, because I see drunks all the time (at work, not socially) and nion gaps this high are very unusual. I personally think there is some other ingestion stimulating the massive ketosis. Looking for ideas.

Notes: We have an oxoproline level cooking, but the negative acetaminophen level makes this less likely in my mind. No, we didn't send a D-lactic acid level.
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