I am an avid recreational runner. I am just about to come up on my 2 year anniversary of being a pretty regular runner, see Operation: Marathon. So it was pretty disturbing to see these two abstracts getting press form the 2010 American College of Cardiology:
- Researchers have shown that long-term marathon runners, those who have completed at least 25 marathons over the past 25 years, have increased coronary calcium and calcified plaque volume.
- A second group did a study which suggested that marathon runners had increased aortic stiffness compared with individuals who exercised recreationally
I would really like to stress that both of these studies do not look at patient oriented endpoints but intermediate end-points. I would hesitate to turn anyone off of exercise, which I tell my patients is the closest thing we have to a fountain of youth, until we had data containing hard end-points.
To corroborate that, the first study looked at a number of other cardiovascular risk factors, and all of these pointed to improved cardiovascular risk profiles:
- lower heart rate
- lower body weight
- lower BMI
- Higher HDL-cholesterol levels
The press release is at this link
, but you will need to register to get to the meat.
Fluid and electrolyte deity, Robert Schrier, had an interesting editorial in Feburary’s Nature Reviews: Nephrology (yes, I’ve gotten a little behind in this blogging business).
Escape versus breakthrough refere to completely different and unrelated concepts related to aldosterone.
- Aldosterone breakthrough occurs following administration of an ACEi or ARB. ACEi block the conversion of angiotensin I to angiotensin II. The decrease in angiotensin II lowers aldosterone. Angiotensin receptor blockers prevent angiotensis II from from binding receptors through out the vasculature but including the adrenal gland where it prevents aldosterone release. At least that is the plan. In reality about 30-40% of patients given ACEi or ARBs have only a temporary decrease in aldosterone and then after a few weeks, aldosterone returns to pre-treatment levels.
- Aldosterone escape is a physiologic phenomenon that occurs with hyperaldosteronism. Aldosterone initially decreases urinary sodium increasing sodium retension contributing to hypertension. This does not result in edema because the sodium retention is short lived. After a short time urinary sodium returns to normal through a process called aldosterone escape. There are two processes that account for this:
- Pressure natriuresis. Increased blood pressure decreases distal sodium resorption. The exact mechanism of pressure natriuresis is unknown, it is thought to be mediated by hydrostatic forces. Increased blood pressure is transmitted to the peritubular capillaries, so the resorption of solutes must overcome an elevated hydrostatic pressure gradient. In the face of this increased gradient, sodium resorption falls.
- Decreased proximal sodium resorption. Volume expansion decreases proximal sodium reabsorption and increases sodium delivery to the distal nephron and overwelms the aldosterone induced sodium resorption.
The implications of aldosterone escape is that primary hyperaldosteronism does not cause edema. It also explains the delay in hypokalemia found with primary hyperaldosteronism. Aldosterone stimulates potassium excretion but hypokalemia is a late finding in primary hyperaldosteronism. The increased potassium excretion occurs with aldosterone escape when the increased sodium delivery (decreased proximal absorption, i.e. escape) occurs with the increased aldosterone levels.
The worst day in medical school. If you don’t match you get contacted that you need to scramble for a spot. ugghh. Scramble starts tomorrow at noon. Its high stake musical chairs. Hope everyone finds a seat.
Best day of med school just around the corner on March 18th at noon EDT.
Are any PBfluid readers fourth year med students? Where did you match? Leave a comment.
Are Calcium supplements good for you?
Maybe not. This article from 2008 shows increased cardiovascular events in woman randomized to calcium supplementation. I had my mom stop her calcium supplement.
women were included in the study if they had been postmenopausal for more than five years, were aged 55 or more, and had a life expectancy of more than five years. We excluded women who were receiving treatment for osteoporosis or taking calcium supplements; those with an other major ongoing disease including hepatic, renal, or thyroid dysfunction, malignancy, or metabolic bone disease; and those with serum 25-hydroxyvitamin D levels less than 25 nmol/l.
Patients were then randomized to a gram of elemental calcium, as calcium citrate as Citracal or matched placebo.
The results were surprising.
Its amazing the study reached clinical significance given the small size of the trial, only 1,400 patients.
A much larger study, The Women’s Health Initiative
randomized 36.282 patients to 500 mg of elemental calcium. They just missed significance for the composite outcome of Myocardial infarction/CHD death/CABG/PCI with a confidence interval of 0.99-1.19.
There might be some signal there.
I have been doing a monthly fluid and electrolyte conference for the residents at St. John. Today we did a case of hypernatremia initially due to hypercalcemia and then due to nephrogenic diabetes insipidus.
When I was a fellow I got an opportunity to write the chapter in Intensive Care in Nephrology on Disorders of Potassium Homeostasis.
Dr. Murray, the editor and my fellowship program director, told me that I couldn’t use review articles or text books as references. It was a golden experience. I systematically went through all of the pearls I had collected on potassium and drilled down to the original data.
The primary conclusion I had after months of exploring the stacks of The Crerar was that the wall of knowledge that I had assumed backed up all of our clinical practices was more like a chain link fence with isolated points of solidity but mostly holes. Science could provide a rough outline but too much of medicine is based on conjecture and reasoned guesses.
One of my finds was the near total lack of data showing cation-exchange resins to be effective. In the chapter I wrote:
…Two recent studies have questioned the effectiveness of SPS [sodium polysterene] resins, but until larger studies corroborate these findings, SPS resins remain part of the therapy for acute hyperkalemia. (106, 122, PDF) SPS and sorbitol usage have rarely been associated with intestinal necrosis; whether this is due to sorbital, the resin, or other factors is unclear. (123, 124, 125)
The key table from the Gruy-Kappal article showing the lack of effectiveness of SPS resins
This was actually the revised paragraph. The first draft was much stronger. I railed against the use of kayexylate given the lack demonstrated benefit and the emerging data on the dangers of this medication. I was ready to throw kayexalate on the hyperkalemic trash heep along with bicarbonate. My co-author, John Asplin calmed me down and had me moderated the section. He explained that despite the lack of data, SPS resins have a long history of use and explained that though I have the option of using dialysis, intensivists often find themselves in binds where dialysis is not available and they need an extra-renal method for potassium clearance.
I can appreciate Asplin’s wisdom now. In the last decade I have used SPS resins innumerable times in patients with and without ESRD, though my data is circumstantial I am believer in the effectiveness of this drug. I hope the latest publicity about the purported ineffectiveness of Kayexalate leads to well done large studies rather than a loss of this effective medicine.
1.050 is really high. Even the healthiest kidneys can’t concentrate urine past a specific gravity of 1.030. To get this high the urine must contain another substance.
In this patient’s case she had just undergone a heart catheterization. IV contrast is rapidly cleared by the kidney and increased the density of the sample. Proteinuria and glucosuria are other conditions which can cause an abnormally high urine specific gravity.
I am the Principle Investigator for a drug company sponsored trial. One of the things I do prior to randomizing patients is spend some time talking with each subject. Today, we enrolled a patient who told me how he helped produce the firs polio vaccine. His first job was at Park-Davis and when they began to mass produce the Salk live-Polio Vaccine he was transferred to that facility. Its cool that this man had, as a young man been part of drug production and now, near the end of his life he is again integral to drug research and development.
A few years ago I read Patenting the Sun by Jane S. Smith. It is an account of the scientific, political and beaurocratic dramas associated with this breakthrough. One of the most interesting aspects of the book was seeing how the egos of the scientific establishment worked against Salk at every turn.
The title of the book comes from an interview of Jonas Salk in which he was asked if he was going to patent the vaccine. He looked at the questioner with surprise and told him, “That would be like patenting the sun.”
What a great attitude and one that is so different than our world where doctors patent bicarbonate to prevent contrast nephropathy. Shameful.
Hypokalemia can induce rhabdomyolysis. The purported mechanism is that hypokalemia antagonizes one of the natural causes of exercise induced vasodilation. Normally, during exercise muscles release intracellular potassium causing local pockets of hyperkalemia which triggers vasodilation and increases perfusion to the active myocytes. Total body potassium depletion and hypokalemia decrease local hyperkalemia preventing the vasodilation which results in tissue hypoxia and rhabdomyolysis.
In The Fluid and Electrolyte Companion we illustrated it thusly:
I remember thinking how funny it was that we used bowling to represent exercise (though we did slide in those runners behind the bowler). Oh clipart, how much nerdtainment you have given me.
This past week-end one of my patients experienced this. He is a high school student who loves to fish. He has congenital type 2 RTA, so is predisposed to hypokalemia. The exercise that triggered his rhabdo: fishing. He presented to the ER following a day of fishing with complaints of muscle cramps and weakness. His potassium was reported as less than 2, with CPKs in the 800 range.
One of the unexpected consequences of the rhabdomyolysis was that his cramping continued after the potassium was corrected. In fact, it was actually much worse muscle spasm and tetany of the hands. Turns out, this second round of neuromuscular symptoms weren’t due to hypokalemia but rather rhabdomyolysis induced hypocalcemia. He had a normal total calcium and a low ionized calcium. The muscular symptoms responded to a gram of IV calcium gluconate.