CASE FILES: BIOCHEMISTRY
A N SW E R S TO C A SE 21: R H A B D O M Y O L Y SIS
29-year-old marathon runner with acute episode of generalized myal-
gias, weakness, fatigue, and dark-colored urine with urine myoglobin/hemoglobin,
hyperkalemia, and significantly increased CPK isoenzyme.
Most likely diagnosis: Rhabdomyolysis (skeletal muscle cell lysis)
after strenuous exercise.
Treatment: Aggressive intravenous hydration to help clear the excess
myoglobin from the serum, and correction of electrolyte abnormalities
and treatment of kidney failure if present.
Biochemical basis for elevated lactate: Nicotinamide adenine
dinucleotide (NADH) levels increase because of the relative lack
of oxygen for muscle, adenosine diphosphate (ADP) and adenosine
monophosphate (AMP) concentrations rise in the cytoplasm, leading to
an increased flux of glucose through the glycolytic pathway in the
muscle, causing pyruvate levels to increase. Pyruvate is reduced by
NADH to lactate in a reaction catalyzed by lactate dehydrogenase.
Lactate is transported out of the muscle cell to the blood.
C L IN IC A L C O R R E L A T IO N
Skeletal muscle has a need for oxygen and fuel (glucose and fatty acids). Short
exertion allows for replenishment of these important substrates; however, long,
grueling demands on muscle, such as running a marathon, can lead to relative
deprivation of oxygen (because of either overexertion or dehydration and
insufficient blood flow to the muscles). This lack of oxygen leads to the con-
version to the glycolytic pathway versus the tricarboxylic acid (TCA) pathway
for adenosine triphosphate (ATP) production. Marathon running has been
shown to effect increases in the blood and urinary concentrations of a number
of biochemical parameters that result from exertional muscle damage (rhab-
domyolysis) and hemolysis. These include increases in serum myoglobin,
CPK, as well as an increase in the anionic gap leading to a metabolic acidosis.
In the case of marathon runners, this is usually caused by an increase in the
serum lactate concentration. Other causes of rhabdomyolysis include cocaine
intoxication, hyperthermia, convulsions, or toxins.