Hyponatremia in Marathon Runners

Every once in a while one of the world's most physically fit persons
drops over and dies.  In fact four persons have died during
or shortly after running the Boston Marathon.



It has been href="http://content.nejm.org/cgi/content/short/352/15/1550">known
for a while that the cause, in at least some cases, is an abnormally
low concentration of sodium in the blood (hyponatremia.)



The reason is that some people, especially the slower runners, drink
too much water during the race.  But the exact mechanism
(pathophysiology) has not been fully understood.



Now, in a short piece on Medpage Today, at least part of it is
explained:



href="http://www.medpagetoday.com/Surgery/Urology/tb2/5534?pfc=101&spc=246">Marathon
Runners' Deaths Attributed to Antidiuretic Hormone

This
is documented in the following journal article from href="http://www.sciencedirect.com/science/journal/00029343">The
American Journal of Medicine.

Hyponatremia
in Marathon Runners due to Inappropriate Arginine Vasopressin Secretion

href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TDC-4NKGSSK-N&_user=10&_coverDate=05%2F31%2F2007&_rdoc=19&_fmt=summary&_orig=browse&_srch=doc-info%28%23toc%235195%232007%23998799994%23650628%23FLA%23display%23Volume%29&_cdi=5195&_sort=d&_docanchor=&_ct=32&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=05d6551065f6d44476250e17e6ff476d">Abstract



Purpose



Exercise-associated
hyponatremia (EAH), as defined by a blood sodium
concentration [Na+] less than 135 mmol/L, may lead to hypotonic
encephalopathy with fatal cerebral edema. Understanding the
pathogenetic role of antidiuresis may lead to improved strategies for
prevention and treatment.



Methods



Normonatremic
marathon runners were tested pre- and post-race for
creatine kinase, interleukin-6, cortisol, prolactin, and arginine
vasopressin. Similar testing also was carried out in runners with
encephalopathy caused by EAH, including 2 cases with fatal cerebral
edema.



Results



Normonatremic
runners (n = 33; 2001) with a mean 3% decrease in body
weight showed a 40-fold increase in interleukin-6 (66.6 ±
11.9
pg/mL from 1.6 ± 0.5 pg/mL, P = .001), which was
significantly
correlated with increases in creatine kinase (r = 0.88, P =
<.0001),
cortisol (r = 0.70, P = .0003), and prolactin (r = 0.67, P
<.007),
but not arginine vasopressin (r = 0.44, P = .07). Collapsed runners
with EAH (n = 22; 2004) showed a mean blood urea nitrogen less than 15
mg/dL with measurable plasma levels of arginine vasopressin
(>0.5
pg/mL) in 43% of cases. Two marathon runners with fatal cerebral edema
additionally showed less than maximally dilute urines (>100
mmol/kg/H2O) and urine [Na+] greater than 25 mEq/L.



Conclusions



Cases
of EAH fulfill the essential diagnostic criteria for the syndrome
of inappropriate antidiuretic hormone secretion (SIADH). Runners with
hypotonic encephalopathy at subsequent races were treated with
intravenous hypertonic (3%) saline on the basis of this paradigm, which
resulted in rapid clinical improvement without adverse effects. Release
of muscle-derived interleukin-6 may play a role in the nonosmotic
secretion of arginine vasopressin, thereby linking rhabdomyolysis to
the pathogenesis of EAH.

So it is not just the amount of water consumed that is important.
 The breakdown of muscle tissue ( face="Helvetica, Arial, sans-serif">rhabdomyolysis)
may play a role too.  



If a person has abnormally low sodium, one would expect the kidneys to
create urine that is as dilute as possible.  That would tend
to increase the amount of sodium relative to the amount of water.
 The fact that these runners did not have maximally dilute
urine indicates that something else is going on.  That
something else is the inappropriate secretion of antidiuretic hormone
(arginine vasopressin.)



This may not have any practical significance, as the href="http://arpa.allenpress.com/arpaonline/?request=get-document&doi=10.1043%2F1543-2165%282005%29129%3C227:SSOCMR%3E2.0.CO%3B2">guideline
for water consumption during a race remains: 400 and 800 mL/h, as
opposed to the previous “as much as possible”
advice.  Still, the finding does help us understand what is
going on, which is always nice.  



Besides, antidiuretic hormone is produced in the hypothalamus, and its
release is controlled by the hypothalamus.  The hypothalamus
is part of the brain.  It is interesting to see how the brain
seems to be at the center of so many unexpected things.