I'm reading The Immortal Life of Henrietta Lacks

The Immortal Life of Henrietta Lacks is about the HeLa cells and the woman they came from. I've just started it but it is really interesting.

HeLa Cells from Radiolab on Vimeo.

One of the most striking parts of the story is hearing how Jim Crow laws and segregation affected medicine. Rebecca Skloot discusses sick black patients coming to a hospital and being turned away to go to a "Colored" hospital and then dying in the parking lot without ever receiving therapy. Hard for me to imagine.



The other interesting story was that of Alexis Carrel the winner of the  1912 Nobel Prize for medicine. His Nobel was for his work in creating a surgical technique for sewing blood vessels together. He is important in the HeLa story as he claimed to have created the first immortal tissue cell culture. This was embryonic chicken heart cells. The heart tissue long outlived the lifetime of the chicken and even outlived Carrel himself but the book states that Carrell faked his results by adding fresh embryonic cells periodically. The book also discredits him as a Nazi sympathizer and a eugenics proponent.

The book is good. I recommend it.

New Handout Tab.

Look up, just below General Jack Ripper and Group Commander Lionel Mandrake are two new tabs: Blog and Handouts. This fulfills a constant request I get from residents and medical students, how do I get a copy of your handouts. Clicking on Handouts will take you to an index with every handout in PDF and Pages format.

I plan on adding pages for presentations and the Fluid and Electrolyte Companion.

Enjoy.

ASN Renal Week day 3: My talk

I spoke on the openning day in one of the big rooms. This was my first talk at a national meeting (though I did do an oral presentation to a small room for the American Society of Hypertension but the room held only about 50 people. This felt like a thousand.

Here is the room before it began to fill:

and here is the talk. To see the real presentation, download and view the powerpoint. Slideshare squashes the animations so the slides don't build right.

Imaging in Acute Kidney Injury, how not to harm patients

View more presentations from Joel Topf.

Renal week day 4: The case for DDAVP in severe hyponatremia

Today I went to see Richard Stern talk about Therapeutic Considerations in the Hyponatremic Patient. It was an excellent talk. One of the concepts he introduced, at least to me, was the use of DDAVP in the patient with severe hyponatremia.

His argument was that the biggest threat to to these patients is the overly rapid correction of sodium due to the sudden suppression of endogenous ADH in the middle of therapy. This is exactly what I was worried about when I was treating that severe case of hyponatremia a couple of weeks ago. My solution up to now is to write an order for the nurse to call me if the patient's urine output rises over 100 mL an hour. Unfortunately this is an unusual call order and nurse compliance with it is questionable.

He proposes using DDAVP to essentially lock, or hold constant urinary losses. Then you use 3% saline and the increases in plasma sodium should be more predictable.

This maneuver has a high degree of difficulty but I think it solves an important problem. I'm going to try this on my next case of extreme hyponatremia.

Has anyone else used this technique?

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Chemical Party

What is there to say?

If you are going to ASN Renal Week, let's meet up

It would be fun to put a face on people interested in medical blogging. I am in Denver right now but I'm too stressed about my talk to meet until after noon on Thursday. If anyone is interested leave a comment, and I'll come up with a location for a casual meeting.

Lowest sodium I have ever seen

I'm not sure if it is really the lowest sodium but it definately was among the lowest.

I received a call regarding a consult for a patient with a sodium of 105.

The patient is a 60 year old caucasian woman who had been started on chlorthalidone 3 days prior to admission. Her physician had been wrestling with hypertension and changed her from 25 mg of hydrochorothiazide to 50 mg of chlorthalidone. (The internist was keeping up with her American Journal of Hypertension. Though 50 mg is a whole lotta chlorthalidone.)

Both figures are from Ernst Et al. Hypertension 2006

After one or two days of the new diuretic the patient started vomiting and developed diarrhea. The only thing she was able to keep down was water. When she came to the ER she hadn't eaten anything solid for two days.

She was admitted with hypovolemic hyponatremia. She was given a bolus of 500 mL of normal saline in the ER and the sodium went up to 108. Additionally her potassium was 2.7 and her magnesium and phosphorous were low. She was started on potassium chloride and sodium phosphate prior to being transferred to the ICU. When I called the nurse I was told the intensivist  planned on starting her on 3% saline.

I was immediately worried about overcorrecting her sodium and developing osmotic demyelination syndrome from 3% saline and aggressive correction of her potassium. Tom Berl had come and spoken to our fellow and had put the fear of potassium in me by discussing a case that was triggered by potassium repletion. From the case report:

This patient was at risk of overcorrection because she had two of the most common clinical settings in which such overcorrection occurs: thiazide use and hypovolemia.

Patients with hypovolemic hyponatremia send conflicting signals to the hypothalamus regarding ADH release. The volume deficiency stimulates ADH (if the body volume deficient, let's not lose any water via the kidneys) and low osmolality surpresses ADH (the body is too diluted so let's lose some water to bring the concentration up). In the case of this conflict, volume rules. As I tell my medical students,

Remember the ABC's, Airway, breathing and circulation. O for osmoregulation is way down in the alphabet.

The problem of rapid correction occurs when you correct the volume deficiency and all of the sudden the hypothalamus asks itself, why am I releasing any ADH with an osmolality of 260?

Then the kidney starts producing urine that you could probably bottle and sell as organically filtered water. Electrolyte free water clearance begins to approach the urine output and the sodium also starts to climb and climb fast.

To protect this patient I told the nurse to decrease the normal saline to 100 mL per hour and to call me if the urine output goes over 200 per hour. We also started checking the sodium every six hours and I ordered urine osmolality, sodium and potassium.

Her sodium started to rise slowly, the urine output increased but never resembled Niagra. After two days her sodium was in the 120s her urine still appeared volume depleted and volume status began to look wet. She developed wheezes and she had a few rales. We had to abandon the normal saline. We started tolvaptan. She received 30 mg once and then 15 mg the next day after she had a brisk response. After that her urine electrolytes resembled SIADH.

Once the sodium crossed 130 I stopped the tolvaptan, restricted her free water, and added a gram of sodium chloride twice a day. Her sodium stabilized around 130.

Around this time I sent a renin aldo ratio. I usually order these before I start a patient on aldactone, because after you start it you need to wash them out for weeks prior to checking for primary hyperaldosteronism. Our patient had difficult to treat hypertension and hypokalemia on admission, so I checked it. I just found out that it came back positive. The high aldosterone was after we had corrected her volume deficiency. I think it is primary, and this may explain why she had persistently low urine sodiums despite successful volume resuscitation.

We looked for a cause of the SIADH, but couldn't find anything. No narcotics, no pulmonary disease, no malignancy, normal TSH and cortisol, no anti-depressants. She had a normal non-contrast head CT scan on admission. I even ordered a contrasted CT scan of the chest to make sure she didn't have a cancer in there. Nothing. Idiopathic SIADH hiding behind, at least initially, volume depletion and in the background of primary hyperaldosteronism. Strange case.

Post transplant erythrocytosis

I have a 35 year old patient who recently received his second kidney transplant. He received his first transplant in his 20s in Albania after going into renal failure due to SSG (that's Some Sort of Glomerulonephritis, a typical diagnosis for a patient who emigrates to the US with a failing transplant and little medical history).

Soon after his transplant his hemoglobin began to rise. We initiated phlebotomy when his hemoglobin rose above 19.

His hemoglobin fell to 17.2 but then increasd up to 18.5.

I started 5 mg of enalepril and it fell to 16.9.

I increased the enalepril to 10 mg and it fell to 16.2 and continued to fall until it is now around 14.

Must see photo

Check out Joshua Schwimmer's photo of a foley bag.

Great shot, highly illustrative of vaptans effect on urine osmolality.

Best (only?) nephrology rap: The Kidney Kid

One of my friends from residency sent me this video. It's perfect.

My line favorite is:

There is multiple medical mysteries but I'm a renal super sleuth 

and my one diagnostic tool is the golden window of truth.

Check!

Celebrity interaction: How I "met" Margaret Atwood on Twitter

In September I recommended Oryx and Crake to @DrSnit, a person I follow on Twitter.

Link to tweet

Then to both of our surprise Margaret Atwood retweeted this. 

Link to tweet

This was cool because a famous author had noticed our exchange but in retrospect it seems to be standard social media marketing, track your mentions and regard your fans. But moments later it turned deeper, and dare I say, weirder:

Link to tweet

Now, I agree that Kidney boy does sound like a lame, super-hero side-kick, created by a large dialysis organization for an in-house comic book to give to pediatric patients. But I never imagined that a super-star writer would be creating my costume.

I remember thinking, "What is she talking about? She can't be serious."

Link to tweet

Five days later she was still thinking about this...

Link to tweet

Then a month after the initial exchange, Ms. Atwood delivered:

Link to tweet

And in full size:

Then a couple of days later:

Link to tweet

And finally last night:

Link to tweet

Full size

This has been wonderful and exciting. How cool is it to exchange with an author I love and respect. It demonstrates how small the world can be. Everyone go out and read Margaret Atwood. She does a great job of looking at where the world is going and extrapolating it forward into a unique, detailed and terrifying future. Start with Oryx and Crake, but I liked The Year of the Flood better.

Update

Ms. Atwood took her time but months after this exchange she tweeted the fully colored version:

Update 2. This incident ended up getting world-wide attention. Here is an article in The Guardian. Comics alliance cover it. And the artists from Periscope studios were even inspired to create their own versions of Kidney Boy and Dr. Snit.

Update 3. What happens to your traffic profile when you get a link from the front page of the World section of the Guardian?

Steve Jobs and the revisionist history of Randall Stross

A few weeks ago the Sunday New York Times had an op ed by Randall Stross regarding Steve Jobs. Stross suggested that Jobs' leaving Apple in 1985 was instrumental in him becoming the capable executive that he is today rather than "the worst personnel decision."

In 1993, Stross released a book, Steve Jobs and the Next Big Thing, chronicling the NeXT computer company and its struggles. The book is out of print but I found an old copy and read it a few years ago. The book is well researched and Stross provides ample evidence to to support his conclusion that Jobs was an immature brat, a terrible leader, a liar, and a poor manager. The picture he paints of Steve Jobs is the classic story of the entrepreneur conquring the world, becoming egocentric and then failing miserably when attempts to replicate his initial success. When I read the book, in 2007, I was in possetion of invaluable data not available to Stross in 1993. Jobs masterful turn around of Apple.

So everytime I read a chapter I had to accept the anecdotes Stross recounted while rejecting his thesis and attempt to fit the data to a different conclusion. It was a fun reading experience.

In another recent bit of news on Steve Jobs, take a look at John Scully's interview with Leander Kahney. Its a fascinating view of their relationship and what Steve meant to Apple.

No Dr. Topf, no EKG changes

On Monday night I was called by one of our fellows regarding a patient in the ED with a potassium of 8.5. They had already given insulin, glucose and kayexalate and the follow-up potassium was 8.1. This is not much improvemnt and less than you typically see. The patient was in acute renal failure with a creatinine of 3 and was anuric.

I asked if the patient had any EKG changes and according to the ER doc the patient had just a touch o'QRS widening. What do you think?

Peaked symmetric T's

Link for more on EKG changes in hyperkalemia

That night his CPK was 5,000. The next day it rose to 341,680.

Now dat's a spicy meatball!


- Initially posted using BlogPress from my iPhone

More on acetazolamide

A few weeks ago while on acetazolamide for altitude sickness prophylaxis the whole group noted tingling and paresthesias. What was curious is that the symptoms were most pronounced in the morning. The paresthesias were primarily on the hands and feet with a rare complaint of symptoms on the face.

I suspected that these symptoms are due to hyperventilation induced hypophosphatemia and the high carbohydrate breakfast (oatmeal) caused a bolus of insulin that further lowered the phosphorous. Does anyone know the etiology? Does hyperventilation cause hypophosphatemia if the increase in ventialtion is compensatory for metabolic acidosis?

FYI: the acetazolamide taste alteration makes carbonated beverages inedible.

Journal Club: dialysis time, not the critical factor in graft survival

One of the inherent truths in transplant is that the longer someone is on dialysis the worse the outcome after transplant. Patient with higher dialysis vintage prior to transplant are more likely to lose their graft and die following transplant. This was first shown by Cosio Et al. and subsequently verified by other researchers.

Cosio's primary figure showing dramatically increased mortality with increasing time on dialysis

Though Cosio et al. was the first (?) to find this association the most elegant data comes from Meier-kreiesche, Et al. who looked at graft survival when a paired sets of cadaveric kidneys is donated to recipients with differing duration of dialysis. By looking at paired kidneys they were able to neutralize any confounding factors from the donor. The primary analysis looked at kidneys that were split between one recipient with less than 6-months of dialysis and another with more than 2-years of dialysis. The end-point was graft survival:

They also calculated patient survival and they likewise found a significant splay based on time on dialysis:

Five- and ten-year unadjusted overall patient survival for paired kidneys was 89% and 76%, respectively, in the group on dialysis less than 6 months compared to 76% and 43%, respectively, in the group on dialysis for more than 2 years (P<0.001 each).

The obvious implication was that dialysis was bad for you. The longer you were on dialysis the more baggage you were carrying at the time of transplant and that baggage comes back to haunt the recipient with a shorter life and shorter kidney survival. From the conclusion:

...the longer patients wait on dialysis for a transplant the longer patients are exposed to the chronic effects of end-stage renal failure and dialysis. It is well documented that patients on dialysis have alterations in the concentration of a number of substances (e.g., homocysteine, advanced glycosylation end products, and lipoproteins) that may predispose these patients to both cardiovascular and renal allograft vascular damages. In addition, the poor nutrition, chronic in- flammatory state, altered immunologic function, and inade- quate clearance that often accompanies patients with ESRD on dialysis may predispose these patients to poorer toler- ance to the immunosuppressive agents after transplantation.

On our journal club last week we looked at a study by Schold, et al. that analyzed time on dialysis prior to transplant by dividing it into time prior to wait list and time after being listed. They found that all of the risk from prolonged dialysis comes from the time prior to being placed on the transplant wait list:

The data was more dramatic for graft loss than for mortality. The intersting part of this is trying to explain this discrepancy.  Why would time on dialysis prior to wait listing be any different that time on dialysis after wait listing? There is no biological difference so the authors conclude that the difference must be in a subtle, previously unmeasured difference in co-morbidity or access to care. The authors go on to pre-suppose that efforts to reduce patient exposure to dialysis may not yield the benefits one might expect if these other factors are not also corrected.

Acetazolamide was a smashing success

My camping club, Aggressive Deer Adventures had a great trip to Kings Canyon National Park. The group consisted of 7 men, all 40-something who lived at around 600 feet above sea level. The whole trip took place between eight thousand and twelve thousand feet.

Every one started on low dose acetazolamide (125 mg bid) 36 hours before we left home.

Not one of us developed anything more than a small headache on travel day. Complete success.

SIADH: Day 9

The patient had SIADH due to viral encephalitis. We started tolvaptan 30 mg and his SIDAH rapidly reversed with the sodium rising from 124 to 128 overnight and up to 136 in the following week. Along with his improved sodium the patients mental status improved. I attribute that more to improvement in the encephalitis than the normalized osmolality but the association is there.

I stopped the Tolvaptan after 8 days and the next morning here are his urine chemistries:



Urine sodium 20, urine osmolality was 614. Somehow, I got a urine chloride rather than the urine potassium I ordered. The sodium nudged up to 137 off the tolvaptan. It looks like the SIADH has resolved with the urine sodium falling from 148 prior to the drug to 70 after the first dose to 20 off the drug completely.
Also note that even though the urine osmolality (614) is greater than serum osmolality, the serum sodium can still rise. This is because the electrolyte free water is still positive, despite a negative solute free water.


- Posted using BlogPress from my iPhone and edited on my 15 inch MacBook with a big dent in the corner.

Altitude sickness and the role of acetazolamide

I am going to Kings Canyon National Park at the end of the month. I will leave Detroit, elevation 600 feet and will travel via planes, trains and automobiles to 9,000 feet for the first night. Then we will begin out hike and cross passes over 12,500 feet.

In the past, I have developed modest altitude sickness going from 600 to 8,000 feet. So, I am nervous about the same problem on this trip. Acetazolamide is supposed to ameliorate altitude sickness.

The body acclimates to decreased oxygen and is so effective that people can function at the top of Mt. Everest without supplemental oxygen. The partial pressure of oxygen at the summit is 43 mmHg which is equivalent to breathing 6% FiO2.

From NEJM 2009, 360: 140-9

The primary means of improving oxygenation is hyperventilation. Hypoxia stimulates ventilation. There is also an increased ventilatory response to carbon dioxide so that that the normal respiratory response to carbon dioxide is exaggerated so that one gets more ventilation at lower CO2 levels. The reason that increased ventilation improves oxygenation has to do with the effect carbon dioxide in the blood has on oxygen transfer in the alveoli. During respiration CO2 leaving the blood dilutes the incoming oxygen at the alveoli, increased respiration, lowers the pCO2 and hence minimizes this dilution.

Antagonizing the hyperventilatory response is respiratory alkalosis. Central chemoreceptors detect alkalosis in the CSF and slow respiration. This is one of the key factors preventing the essential hyperventilation.

Acetazolamide (Diamox) is a carbonic anhydrase inhibitor. Carbonic anhydrase catalyzes the reaction converting bicarbonate to carbon diaoxide and water:

This is the fundamental buffer reaction in the body and it is amazing to me that blocking this essential acid-base reaction is not lethal. Acetazolamide works in the proximal tubule by blocking the reabsorption of filtered bicarbonate.

Acetazolamide induces a proximal renal tubular acidosis (RTA 2). This results in metabolic acidosis. The metabolic acidosis stimulates compensatory hyperventilation. This metabolic acidosis antagonizes the respiratory alkalosis which normally occurs with hyperventilation.

Their maybe additional advantages of acetazolamide including decreased CSF production and antagonizing fluid retention.

Happy climbing.

SIADH: day two

I gave the patient from yesterday 30 mg of tolvaptan. The repeat sodium was 128, up from 124 and urine sodium was down to 70, from 148 and the potassium was 40, down from 48. Urine output rose to 3425 mL.

The electrolyte free water clearance went from negative 1,364 to positive 481 mL.

Tolvaptan FTW.

The SIADH is due to West Nile Virus induced encephalitis.

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Dense SIADH

Check out that urine sodium. The guys pissing normal saline. That's the highest urine sodium I have ever seen.






Urine sodium 148
Urine potassium 48
Serum sodium 124
Urine output 2350

Electrolyte free water clearance:
-1364 mL

Interpretation: with those urine electrolytes, when urinates 2,300 mL it is as if he actually drank nearly a liter and a half of tap water. And that is why fluid restriction fails in dense SIADH.

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New slang for the fractional excretion of urea: febun

Since the abbreviation for the fractional excretion of sodium is FENa, all the cool kids call it the fena (rhymes with Gina). So the fractional excretion of urea by extension is the FEUrea, which doesn't quite role off the tongue.

Last month on vacation, we had dinner with an old friend from medical school, now a hospitalist outside Atlanta, and she started talking about ordering febuns. I asked her what a febun was and she explained the fractional excretion of BUN. Ahhh.

My wife, who hated driving my car with the license plate FE UREA immediately declared febun both cute and the official title, at least in the Topf household.

Kidney Stone riddle: the answer

The commenters nailed it.

He had primary hyperparathyroidism and went for a parathyroidectomy. The recurrent laryngeal nerve was severed during the procedure and that left him unable to speak.

He suffered in silence for 6 months before going for a procedure which pushes the vocal cords on the paralyzed side medially. This allows the normal cord to meet the still paralyzed, but medially displaced cord and phonate.

Kidney Stone Riddle

I was at my great aunt's 90th birthday party on Tuesday and was chatting with a neighbor. He mentioned that after being treated for kidney stones he couldn't speak for 6 months.

My face screwed up as I tried to figure out what the hell he was talking about. His next sentence explained everything.

What happened?

Other hints: his stone were conventional calcium oxalate stones, and he had recurrent stones.

I'll leave the answer later today or tomorrow.

The iPad needs a content creation system

The iPad is screaming out for a system to make interactive content designed for that intimate touch based user interface.

Powerpoint is a computerization of the old-fashioned photographic slide. This metaphor is continued down to the presentations being called decks. The iPad needs a presentation software as slick and versatile as Powerpoint and Keynote are but is constantly aware that the audience is a single person rather than a room. With that knowledge of an audience of one the program should explode interactivity.

Audience response systems can be grafted on to slide decks but questions and interactivity should really be central to the iPad presentation experience. Change the presentation from a slide show to an exploration.

I don't think it was a coincidence that Steve Job reminded everyone of HyperCard during his interview with Walt Mossberg at the D conference. I don't think it was deliberate name dropping but rather he had been spending a lot of time thinking about the strengths and weaknesses of that technology because he is guiding and overseeing the development of a similar technology to be authored on Macintosh's and consumed on iPads.



This program should be akin to Garageband, iDVD and Keynote. Consumer grade software that allows an amateur to produce pro-level documents. Imagine using an interactive iPad program is the followng situations:

• Teachers could produce class room materials, such as course packs, lab manuals or study guides
• Restaurants could develop menus with wireless ordering
• Conferences could create on-the-fly lecture notes with interactive commenting

All of this could be done with Objective-C but the idea would be to expand the market of content creators from sophisticated programmers to the entire universe of knowledge workers. Done right this would create an explosion of iPad specific content. and hopefully relieve med students of the endless dreary morning reports and noon conferences.

Reading David Pogues review of Google App Inventor, it sounds like Google stumbled out of the gate. Let's see if this rumor is Apple's counter punch.