Myoglobinuria is a group of disorders characterized by injury of muscle and excretion of myoglobin in the urine. (“Rhabdomyolysis” has been proposed as a more precise term, focusing attention upon muscle rather than urine, but this is the kind of “progress” that is achieved by changing a name. It is more difficult to say, somewhat pompous sounding, no more revealing or scientific, and has gained favor for reasons which are difficult to fathom.)
Myoglobin may be released from muscle whenever there is extensive and rapid destruction. Sometimes, the cause is evident, as in the crush injuries of World War II when individuals were pinned beneath the timbers of buildings destroyed in bombing raids. Similar pressure injuries may occur in comatose persons who lie on one side without moving for prolonged periods. This kind of injury is perhaps more apt to occur when there are other causes of metabolic depression; for instance, in coma after suicidal ingestion of barbiturates or carbon monoxide intoxication, or prolonged unconsciousness in the snow. A similar effect may be induced by arterial occlusion by tourniquet or embolism, or even by prolonged knee-chest posture under anesthesia.
In other patients, the cause is less discernible. In every series of patients with myoglobinuria, a disproportionate number are alcoholics, but why this should occur is not known. Sometimes there has been exposure to a known membrane toxin, such as the bite of the Malayan sea snake. Or there may be metabolic alterations that do not ordinarily cause this kind of trouble, such as diarrhea with hypokalemia, diabetic acidosis, or systemic infection with fever. In many attacks, however, not even these clues prevail.
The most common cause of myoglobinuria is probably unusually vigorous exercise by an otherwise normal person, Most cases have been reported by military physicians, and local designations include such titles as the “squat-jump syndrome.” Some cases are attributed to “march hemoglobinuria.” When large numbers of recruits perform these tortures, a certain number will have attacks of myalgia followed by pigmenturia. Why these individuals have attacks and others are spared is not clear, but this seems to be a “normal” variation.
In civilians cases have been caused by the excess muscular activity of an initiation rite into a club or fraternity, and isolated attacks have occurred after the vigorous muscular activity induced by succinylcholine before it achieves relaxation. Spontaneous convulsions and electroconvulsive therapy have been followed by myoglobinuria. If an individual is subject to repeated attacks, it may be suspected that there is some kind of undiscovered genetic defect, although the only ones recognized now are deficiencies of phosphorylase or phosphofructokinase.
Clinical Manifestations Of Myoglobinuria.
In attacks other than those caused by local crushing or arterial occlusion, the clinical picture is similar. Affected muscles are apt to be the ones subject to greatest physical strain (the legs in squat-thrusts, the arms after chinning or push-ups, the arms1 and legs after wrestling matches). The muscles ache, may be swollen, and are weak. Sometimes there is so much edema that local vascular abnormalities are suspected. There may be fever and considerable malaise. Symptoms persist for several days even though pigmenturia rarely lasts more than 48 hours. Recovery may be gradual. Cranial muscles are rarely involved, and although respiratory failure is uncommon it is a hazard. The most important threat to life is renal injury secondary to excretion of heme. There may be red cells or. myoglobin in the urine as well as casts. Oliguria is followed by azotemia and hyperkalemia. This may be treated by appropriate measures.
Diagnosis of Myoglobinuria.
The diagnosis of myoglobinuria can be made on clinical grounds and with relatively simple tests, but precise identification of the pigment depends upon biochemical analysis. The urine may appear red-brown because of hemoglobin, myoglobin, or porphyrins. The latter would not give a positive test with benzidine (or other heme-reacting reagents), and would not give a positive Watson-Schwartz test for porphobilinogen, Besides, the neurologic disorder of porphyria is neuropathy, not an acute myopathy.
If the urine gives a positive test for heme and contains no or few erythrocytes, the pigment is either myoglobin or hemoglobin. If it is hemoglobin, the serum would be pink (after a hemolytic reaction), whereas the color of the serum in myoglobinuria is normal. (This distinction depends upon the affinity of serum haptoglobin for hemoglobin and not for myoglobin. Hemoglobin is not excreted until haptoglobin is saturated by visible amounts of the pigment, whereas myoglobin is excreted at much lower concentrations.)
Furthermore, in attacks of myoglobinuria, the muscular weakness and myalgia are distinctive, and serum enzymes are greatly increased, whereas they are not in hemolysis. Positive identification of myoglobin can be achieved by several tests: absorption spectrophotometry is direct and simple, but in many laboratories the most convenient method is electrophoresis on starch gel or cellulose acetate. In the future, immunochemical methods are apt to gain favor.
If there is no renal injury, myoglobinuria is not threatening. The hazards of renal injury are not directly correlated to the amount of pigment excreted, and other factors are probably involved. Once an attack starts, it is useful to encourage excretion of dilute*urine, and some authorities still favor alkalinizing agents although it has not been clearly demonstrated ‘hat these treatments protect the kidneys.