The following are answers to the questions specifically asked in the PBL:

1. Exercise-induced rhabdomyolysis

2. Medical reasons for the onset of rhabdomyolysis in physically fit individuals, especially at the ambient temperature for this case, are relatively unknown. Rhabdomyolysis typically is accompanied by exertional heat stroke.

The term "rhabdomyolysis" medically defines an injury to skeletal muscle cells that is so severe that the cellular contents leak into the circulation. Exertional rhabdomyolysis is an exceptionally common event. Indeed it is probably experienced in a mild form by everyone who has undergone some form of exercise training during their youth when it is expressed simply by stiff and tender muscles.

The threat of acute exertional rhabdomyolysis is often unappreciated and not understood by physicians who initially provide care for these patients. Although the patient may collapse and appear to recover quickly, in some of these cases potentially fatal metabolic acidosis, hyperkalemia, sisseminated intravascular coagulation and acute respiratory distress syndrome may appear during the following 24 hours.

There is strong experimental and clinical evidence that training induces a degree of resistance to the development of exertional rhabdomyolysis as well as exertional heat stroke.

Exertional rhabdomyolysis is most commonly seen in intelligent, education persons who are able to arrange their work schedule to permit considerable time for running. Data indicates that none of these individuals perform particularly hard, physically strenuous work during the day and, for this reason, seem to have enough energy to run several miles each day or several days of each work. In contrast, exertional rhabdomyolysis seldom occurs in blue collar people such as carpenters, plumbers, dockworkers, farmers, or other manual laborers.

Two common and related factors in almost every clinical case of exertional rhabdomyolysis are dehydration and ambient temperature above 75°F. Other factors that have been associated with exertional rhabdomyolysis are eccentric muscular activity, genetic predisposition (such as sickle cell train and malignant hyperthermia), metabolic defects associated with skeletal muscle, existing bacterial or viral infections, and nutritional supplement and drug usage. However, exertional rhabdomyolysis is often unaccompanied by any of the above risk factors.

3. Chewing and the initial phases of swallowing require skeletal muscle activity. Because the effects of exertional rhabdomyolysis are wide spread, skeletal muscles of the jaw, throat and upper 1/3 of the esophagus would be affected.

4. Severe cases of exertional rhabdomyolysis, such as that seen in this patient, causes the following:

• Skeletal muscle cell destruction.
  
  
• Breakdown of sodium-calcium and sodium-potassium homeostasis in the skeletal muscle cells, resulting in inward flow of fluid, sodium and calcium and an outward flow of potassium with regards to skeletal muscle cells. The high intracellular levels of calcium result in the activation of calcium-activated enzymes, resulting in the disruption of the cellular membrane.
  
  
• Exertional rhabdomyolysis is also associated with an increased level of myoglobin, creatine kinase (CK) and other muscle cell cytosolic compounds resulting from cellular destruction.
  • Myoglobin will enter the urine when plasma concentrations exceeds 15mg/l, producing a dark reddish-brown colored urine.
  • A rise in serum myoglobin level precedes an increase in serum CK. CK plays an important role in the metabolism by catalyzing the reversible transfer of the terminal phosphate group of ATP to creatine to form phosphocreatine.
  • With the rupture of muscle cell membranes the leakage of cellular contents is not limited to myoglobin and serum CK. Other protein and non-protein cellular components are also released into the circulation. Common clinical findings include
    • Hyperkalemia
    • Hypocalcemia
    • Hyperphosphatema
    • Release of cellular enzymes and urea into the bloodstream from damaged skeletal muscle cells
      
      
• Major system complications include
  • Elevated heart rate and the possibilities of cardiac arrhythmia and/or cardiac arrest due to altered serum levels of potassium and calcium
  • Elevated respiratory rate in an effort to counteract metabolic acidosis as a result of cellular damage and release of acidic cellular contents into the circulatory system.
  • Development of renal failure. In order to counteract the possibility of renal failure in patients with exertional rhabdomyolysis it is essential to maintain an adequate circulating blood volume, typically through the IV administration of significant amounts of normal saline, often accompanied with IV mannitol and sodium bicarbonate. (The presence of acidic urine enhances the effects of myoglobin toxicity in the kidney. Therefore, sodium bicarbonate is administered to counteract this effect upon the kidney by myoglobin.)
  • Although the exact cause of renal failure due to high circulating levels of myoglobin is unknown, some of the associated theories include (but are not limited to)
    • Vasoconstriction and accompanying renal ischemia due to renal vasoconstriction
    • Damage to the peritubular vasculature and associated endothelium, resulting in a "back leak" of renal filtrate.
    • Associated patient shock, resulting in reduced renal blood flow.
    • Tubular obstruction by precipitation of pigmented casts in the renal filtrate.
    • Tubular injury due to the direct toxicity of myoglobin.