Thursday, September 29, 2011

Medical school humor

I am knee deep studying for my internal medicine recertification, so my sense of humor maybe a bit warped, but I found this to be a scream:

Monday, September 19, 2011

How the kidney works, a primer for non-medical folks--updated now with fewer errors

I recently have joined a Bartter and Gitelman group on Facebook. It is a collection of people from all over the English speaking world, each with a long standing chronic disease and all of them are on an diagnostic island where they have never met another person with the disease and are generally seeing docs who are just as unfamiliar with the disease as they are. A lot of them have questions on how the kidney works so this primer is for them
The Nephron

The functional unit of the kidney is the nephron. A functional unit is not a common term so let's spend a sentence or two talking about what that means. a functional unit is the smallest fraction of a system that still accomplishes all the tasks of the entire system. For example, the functional unit of a muscle is a single muscle cell, a myocyte. A muscle's, sole function is to receive a signal and respond by shrinking. They remain shrunk until the signal ends. A single myocyte can do that. Though a muscle contains thousands of myocytes one can think of it as one giant myocyte without losing much.

On the other end of the spectrum is the heart, the functional unit of a heart is the entire organ, it makes no sense to think about a heart without all four chambers and all the heart valves.

The kidney lies in-between these two extremes, the functional unit of the kidney is the nephron, a complex collection of blood vessels, tubes, nanopumps and filters. Each kidney is composed of a million nephrons but you can understand every function of the kidney and understand just about any type of kidney disease by understanding it's affect on a single nephron. You can think of the kidney as being a single giant nephron and not lose much.

The primary role of the kidney is to keep the extracellular fluid (all the water that lies outside of the cells) in an ideal and balanced state. They manufacture the cellular atmosphere in which our cells live. To do this they:
  • replace chemicals which are consumed
  • excrete the variety of foreign substances absorbed by our indiscriminate gastrointestinal tracts
  • excrete the byproducts of our metabolism (the ashes of our body fires)
The basic procedure that is used is can be thought of like cleaning out a closet, take everything out, then put back what is valuable and throw away the rest.

Here are the parts of the nephron that accomplish this:

The glomerulus
The glomerulus is a colander that filters the blood. The blood cells and proteins of the body play the role of the pasta while the water, salts, and small molecules play the role of the water and flow through the colander into the tubules of the nephron. The primary difference between a colander and the nephron is that the water that passes through the colander is discarded as waste. In the body if you were to waste everything that was filtered you would quickly perish.
The tubules
Following the glomerulus, the filtered water, salts and small molecules enter through the tubules. The primary role of the tubules is to reclaim all that is valuable and secrete additional waste that wasn't filtered by the glomerulus. The end of the tubules is the renal pelvis which acts as the grand central station where the millions of tubules, one for every nephron, coalesce.

The tubules are further divided into functional regions. Here are the basic regions:
Proximal tubule
The proximal tubule does big, dumb, bulk reabsorption. Way too much fluid is filtered by the glomerulus.
over 3 ozs (100 ml) per minute, this means that in 30 minutes all of the water in the blood stream would be filtered and in 7 hours all the water in the body would be gone. Clearly this does not happen and the reason it doesn't happen is that 99% of the filtered water is reabsorbed. This is the focus of the early nephron. Actually a way to look at the nephron is that as you move down the tubule from the glomerulus to the bladder less fluid is recovered and more fine tuning occurs.

The proximal tubule, reabsorbs two-thirds of the date, sodium, potassium and many other substances that are filtered. It recovers all of the amino acids, glucose and other carbohydrates needed for energy and building the body. There is some subtle forms of regulation that occurs in the proximal tubule but most control and fine tuning occurs downstream in other segments of the nephron. Many drugs are secreted in the tubule so it is a key site for cleaning the blood of substances that are found at lower concentrations or escape being filtered by the glomerulus for one reason or another.

Loop of Henle
After the proximal tubule, the nephron takes a strange shape. It stretches down deep into the center of the kidney, like a Texas wildcatter digging a deep well. The loop of Henle is the engine which powers both the dilution of urine and the concentration of urine. The control of what type of urine is made is executed at the last minute but the work that makes that happen occurs in the loop. Concentrating or diluting the urine is how the body conserves or wastes water. When you think of what type evolutionary changes were required for animals to leave the ocean, the ability to conserve water by making concentrated urine must have been one of the critical breakthroughs, concentrated urine can only occur if the loop of Henle is working properly.

A lot of sodium, and magnesium reabsorption occurs here. The common water pill furosemide (Lasix) acts on the loop of Henle. The defects in Bartter syndrome are here and act by limiting the reabsorption of sodium, chloride and potassium.

The other important aspect of the loop of Henle is that at the very tip of the loop, the deepest part of the well, the tissue fundamentally changes so that water can not flow through the cells. From this point to the toilet the tissues lining the tubules are impermeable to water, a characteristic found no where else in the body. The collecting tubules can allow water pass through its walls but only under strict control with the use of specific water channels.

Distal convoluted tubule
There is not much to understand about the distal convoluted tubule. It is the site where thiazide diuretics act and is where the mutations that cause Gitelman syndrome is expressed.

Collecting duct
The last segment of the tubules is called the collecting duct and it has three primary roles:
  • excrete excess acid
  • excrete dietary potassium
  • regulate the excretion of water
The potassium situation is unique and is handled unlike other electrolytes. A lot of potassium is filtered by the glomerulus, but that potassium is reabsorbed in the proximal tubule and loop of Henle. By the time the tubular fluid winds around to the collecting tubule, all of the filtered potassium has been reabsorbed. All of the potassium that is excreted by the kidney must be secreted by collecting tubule. As far as potassium is concerned the only part of the nephron that matters is the collecting tubule.

The big finish
After the collecting tubule there is the renal pelvis where all of the collecting tubules empty into a common chamber and then flows into the ureters, the long tubes that drain the kidney into the bladder where it is stored until voiding. After urine leaves the tubules it does not undergo any further chemical changes.

The perfect organ
The last bit that is important is the concept of balance. One of the perfect things about the kidney is that it keeps the body in balance. In patients that are not growing, all of the sodium that is consumed is excreted by the kidney. When I want to investigate whether a patient's blood pressure might be due to excessive salt in the diet, I do not try to get the patients to remember and report what they eat, I simply have them collect all of their urine for 24-hours and measure the amount of sodium in the urine. If they have 3 grams of sodium in the urine, then they are eating 3 grams of sodium. This can be done with any substance that is ingested and then excreted unchanged by the body. Examples of intake that can be assessed with a 24-hour urine collection include:

  • potassium
  • sodium
  • phosphorous
  • water
  • protein

- Posted using BlogPress from my iPad
- hat tip to Steve Rankin for fact checking

Reminder of a great case from the archives

Last year I had one of the most severe cases of hyponatremia I had ever seen. Last night I was flipping through iPhoto (looking for the drawings Margret Atwood did of my alter ego, Kidney Boy) and found this photo...

Just looking at the labs gives me chills. Here is the whole story.

Friday, September 16, 2011

Michelle Bachmann taking up the anti-vaccine crusade

Earlier this week Congressperson Bachmann took a crack at the HPV vaccine, saying that she heard from some person that her daughter had become a retard after getting vaccinated.
"There’s a woman who came up crying to me tonight after the debate," Bachmann said after the debate, where she had told Perry on stage that she was "offended" by his decision. "She said her daughter was given that vaccine. She told me her daughter suffered mental retardation as a result of that vaccine." The Telegraph
It's unfortunate that people who don't die of cervical cancer never realize it and unable to talk with presidential hopefuls. I dream of day when nephrology fellows won't get calls in the middle of the night to handle potassiums of 8 caused by cervical cancer associated bladder outlet obstruction.

Interesting infographic on the HPV vaccine and cervical cancer. Click here for a readable version.

Outpatient hyponatremia

Almost all of the hyponatremia I see is inpatient, but this week a woman was referred to my clinic with a sodium of 128. She has a sharp family doctor who ordered all the right tests. Here are the key pieces:
  • Plasma sodium 128
  • Plasma osmolality 277
  • Urine osmolality 180
  • Urine SpGrav 1.005
  • Urine sodium 14
She has a history of hypothyroidism but her TSH was over suppressed, no hint of hypothyroidism. She was not taking any diuretics. She was on an SSRI that could cause SIADH but the low urine osmolality and low specific gravity argue against excessive ADH activity.

The case hinges on the low urine osmolality. This is a rare case of ADH-independent hyponatremia. All of the major causes of hyponatremia (volume depletion, diuretics*, heart failure, SIADH, etc) are driven by ADH which prevents the kidney from clearing free water. The low urine osmolality indicates the kidney is not under the influence of ADH and doing what it needs to in order to correct the sodium, i.e. excreting excess water in the form of dilute urine.

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

She described her diet as a peanut butter and jelly sandwich for breakfast, some fruit and juice with some nuts for lunch and nothing for dinner. Her fluid intake was high (4-5 cups of coffee, a large water bottle of water, some juice, some soda, and a couple of additional glasses of water) but no where near enough for psychogenic polydipsia.

I suspect she has tea and toast syndrome. I am checking a 24-hour urine osmolality to gauge her daily osmolar load and then plan to have her increase the amount of protein and minerals in her diet while trying to taper her fluid intake.

More on tea and toast syndrome here
A well done case report on a healthy patient wih reset osmostat can be found here (pdf)

* if the diuretics are still active the urine osmolality could be low but once the drug wears off the urine osmolality will climb

Wednesday, September 14, 2011

New kid on the block: The Kidney Doctor

I first met Ajay Singh when he came to St John Hospital as part of a symposium on chronic kidney disease in 2004 or 2005. It was a great meeting and Singh gave two memorable lectures.

The first was a dismantling of the MDRD equation as an accurate measure of GFR. He was speaking against an equation that was way better than a simple creatinine but had some real problems, especially when used in patients without kidney disease. It was a inflammatory and a bit wonky for a conference directed to primary care doctors. Here we, the local nephrologists, were trying to get our doctors to recognize occult CKD by abandoning serum creatinine in favor of the superior eGFR and then the invited expert comes in and tells them how stupid this is.

His second lecture was the correction of anemia dog-and-pony show. He gave an amazing and persuasive presentation in favor of correcting of anemia in renal disease. Though the data was all retrospective and observational it was clear that Dr. Singh was personally a few steps past equipoise. At the time CHOIR was in full swing recruiting and retaining patients and my group was part of that process as a research site for CHOIR.

Five or so years later he returned to talk with our fellows and staff regarding anemia. This was after the publication of CHOIR, but I believe before the release of TREAT, though my memory is a bit hazy on the timing.

What I do remember is that he talked about the dangers of correcting anemia and the lack of data supporting its use. I remember being so angry. I felt that for the last half dozen years I had worked to convince my CKD patients that they needed to enroll in our anemia clinic, needed to come to our office for EPO shots and iron infusions, and that all this would make them feel better, protect their heart and prolong their life, all purported advantages of ESA therapy. And now Mr. Harvard returns and tells us that this is wrong, without ever apologizing, without even mentioning how he'd jumped the fence.

I stopped him mid-lecture and told him that the last time he'd been in Detroit he'd been telling us how important it was to treat anemia and now he had completely changed positions. Dr. Singh paused, looked at me, and gave the best answer possible. I can't remember his exact words, so I'm paraphrasing here,
"The data has changed. Now we know more and what I'm telling you is what is currently correct. In medicine, there is no room for intellectual loyalty. We must be loyal to our patients not our theories. The reason my position has changed is that I am following the data. Would you want me to do anything else?"
His answer completly satisfied me and it extuinguished my rage. I was better able to deal with my regret and embarrassment at having to abandon a long held belief and practice pattern at the feet of new data.

His new blog is off to a flying start with a productivity that hasn't been seen since Nate Hellman and quality that, to my eyes, no one can match.

Thanks Ajay, I'm looking forward to following your blog.

Saturday, September 10, 2011

HIPAA violations go mass production

Stanford let demographic information on 20,000 ER visits escape onto the web.

A billing contractor created a spreadsheet containing names, account numbers, diagnosis, and length of stay for every admission to the ER for 6 months. Somehow, this spreadsheet was uploaded as an attachment to a post asking for help making bar-charts (you can't make this up) to the tutoring website Student of Fortune. The information remained on the site freely available from September 2010 to August 2011.

Get all the details at the New York Times.

Maybe the next time we get alarmed about the threat to privacy from a case report or educational lecture we should think about the losers that are releasing medical data by the bucketful.

Thursday, September 8, 2011

Free e-book: Oh Doctor, The Places You Will Go...

Dr. James Chang of the personal finance blog, PoorMD, has written a parody of Dr Seuss' classic Oh, the Places You'll Go! It is a candid look at the journey people make in order to become doctors. I found it charming. Go download it. All of the illustrations were done on his iPad. Terrific.

Tuesday, September 6, 2011

Great image from wikipedia

This graph from wikipedia allows you to see how different substances concentration in blood varies. Who new that the lowest molar concentration of all was PTH?

Monday, September 5, 2011

Hyperkalemia or not

A patient came to the hospital with a swollen arm. The ED suspected a DVT and ordered a doppler ultrasound which confirmed their suspicion. The admission labs included a chem-7 which revealed a potassium of 7. Her creatinine was 1 and she wasn't taking an ACEi, ARB, aldactone, ketoconazole, or potassium supplements. The ER was surprised and repeated the study and checked an EKG:

Narrow QRS and unimpressive T-waves

The EKG gave no hint of hyperkalemia, though EKG changes are not a sensitive marker for hyperkalemia. The ED gave insulin, glucose and Kayexalate for the lab finding of hyperkalemia. We were consulted to determine the cause of the hyperkalemia. The patient's past medical history was significant for primary thrombocytosis and during the hospital stay her platelet count rose to over a million.

dats a lot o'platelets
We presumed that his hyperkalemia was actually pseudohyperkalemia due to the high platelet count. Platelets release potassium when they clot and the risk of pseudohyperkalemia rises as the platelet count approaches a million.

You remember this classic NEJM article from 1962. 
We then sent the patients blood to the ABG lab in a heparinized syringe rather than a red top and the potassium normalized. Platelets release potassium when they are activated. By measuring the potassium in whole blood rather than serum, the contribution of platelet activation is prevented. The ABG results are the electrolytes to the far left in the screen-grab below (click to enlarge).

- Posted using BlogPress from my iPad

Sunday, September 4, 2011

Great animated gifs from Dr. Strangelove

General 'Buck' Turgidson listening to Premier Kissoff
Mr. President, we are rapidly approaching a moment of truth both for ourselves as human beings and for the life of our nation. Now, truth is not always a pleasant thing. But it is necessary now to make a choice, to choose between two admittedly regrettable, but nevertheless distinguishable, postwar environments: one where you got twenty million people killed, and the other where you got a hundred and fifty million people killed. 
Peter Seller's best movie?

From If We Don't Remember Me.
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