Question

The surgery is postponed while Edward recovers, though while in hospital, he starts complaining of muscle weakness and soreness. Additionally, his urine is observably darker. Explain the underlying physiological changes leading to his presentation.

Answer 1

This patient is most likely to be suffering from rhabdomyolysis:

Clues to the diagnosis:

This patient is presenting with classic triad of rhabdomyolysis.

1. Muscle pain
2. Weakness
3. Dark-colored urine.

Pathophysiology of rhabdomyolysis is as follows:

1. In normal rest state, the muscle tissue is characterized by the following features:
   1. Low intracellular levels of Sodium (Na+)
   2. High intracellular levels of potassium (K+)
   3. Low intracellular levels of Calcium (Ca+)
2. To maintain these levels the muscle requires energy (ATP)
3. In rhabdomyolysis there is depletion of ATP and direct injury to the myocyte. This leads to :
   1. There is excess intracellular movement of
      1. Ca+ - High levels of Ca+ leads to
         1. Sustained muscle contraction. this further depletes the ATP levels
         2. Several Ca+ dependent proteases and phospholipases are released.
         3. This damages the cell membrane and the ions channels.
      2. Na+ - this leads to movement of water into the cell. This disrupts the integrity of the intracellular space.
   2. The overall effect is inflammation of the muscle and necrosis of the muscle.
   3. Also, the myoglobin component of the muscle is also released into the blood.
      1. Normally, haptoglobulin will bind to these free myoglobulin and prevent them from causing damage.
      2. In rhabdomyolysis there is excess release of myoglobulin. this overwhelms the haptoglobulin levels.
      3. The myoglobin precipitates in the glomerular filtrate.
      4. At a pH of 5.6 or less, ferrihemate is formed from myoglobulin. Ferrihemate causes release of oxygen free hydroxy radicals
      5. This causes renal
         1. tubular obstruction.
         2. Tubular ischemia and tubular injury
         3. Intrarenal vasocontriction
         4. Acute kidney injury
         5. Lipid peroxidation
      6. Excretion of myoglobin int he urine gives urine a dark color