Rhabdomyolysis

A.D. Van den Abbeele, M.D.

J. Anthony Parker, M.D.

April 9, 1985

Case Presentation:

A 63 year-old white male had a history of chronic schizophrenia, tardive dyskinesia and adult onset diabetes mellitus. He was admitted after he fell on his abdomen and was unable to get up. The physical examination revealed poor pulses as well as paralysis and anesthesia of the lower extremities.

Findings:

The laboratory results were as follows: CPK = 126,500 IU/L (nl 0-200), LDH = 3,740 IU/L (nl 60-200, SGOT = I, 080 IU/L (nl 8-40), SGPT = 293 IU/L (nl 13-41), lactic acidosis, elevated uric acid, elevated phosphorus, and myoglobinuria. These results were compatible with the diagnosis of rhabdomyolysis.

An aortography performed on the second day of admission demonstrated complete occlusion of the aorta below the renal arteries with well-developed collaterals and no intraluminal filling defects, suggestive of an old aortic occlusion.

Tc-99m PYP scintigraphy was performed on the third day of admission, and showed diffusely increased uptake in the lower abdomen and pelvic area as well as in the right calf (outlined areas). At that time the CPK level had decreased to 27,725 IU/L. The explanation for the clinical presentation was unclear but was probably related to a temporarily occlusion of an already compromised circulation. The anesthesia of the lower extremities rapidly resolved in the first days of the admission.

Discussion:

Rhabdomyolysis results from skeletal muscle injury with release of muscle cell contents into the plasma. These cell contents include enzymes such as creatinine kinase, glutamic oxalacetic transaminase, lactate dehydrogenase, and aldolase; the heme pigment myoglobin; electrolytes such as potassium and phosphates; and purines. It may or may not result in myoglobinuria, depending on the amount of myoglobin released into the plasma, the GFR and the urine concentration.

Rhabdomyolysis was first reported in 1881, in the German literature but the major clinical sequelae were described in 1941 by Bywaters (3), during the blitz of London, in patients with crush injuries. Rhabdomyolysis may occur after trauma, ischemia (including acute myocardial ischemia), excessive exertion (marathon runners), bacterial and viral sepsis, electrical burns, other injuries related to heat or cold, prolonged muscle compression as often seen in the unconscious state after alcohol or drug intoxication, seizures, hypokalemia and shock. It has also been reported in associated with metabolic disorders (phosphoglycerate kinase deficiency, and carnitine palmityl transferase deficiency) and exposure to various drugs and toxins (meperidine HCI).

Many theories have been advanced to explain soft tissue uptake of bone imaging agents, including binding of the radiopharmaceutical to soft tissue calcium deposits, iron deposits, denatured proteins, enzymes or immature collagen and deposition second to altered tissue perfusion or capillary permeability.

Buja, et al (6) performed electron microscopy on experimentally induced canine myocardial infarctions and concluded that Tc-phosphates do absorb onto several kinds of calcium, such as Ca hydroxyapatite, amorphous Ca phosphates, and Ca complexed with myofibrils and other macromolecules. Many tissues when infarcted, among them liver, spleen, gut, brain, muscle and fat, show hyperconcentration of Tc phosphates compounds. Other pathological entities with increased Tc phosphate affinity contain demonstrable calcium, such as nephrocalcinosis, tumoral calcinosis, milk-alkali syndrome, calcified nodules, and infiltrated calcium.

Dewanjee and Kahn (5) explain the uptake of Tc chelates in myocardial infarcts by the formation of polynuclear complexes with denatured macromolecules rather than the deposition of calcium in the mitochondria. Zimmer, et al. (7) advanced the hypothesis of binding of Technetium phosphates by enzymes such as alkaline phosphatase.

McRae et al (8) demonstrated increased soft tissue and renal deposition with intramuscular administration of iron gluconate in rats. The fact that renal concentration was increased as well may relate to the increased renal concentration also seen in hemosiderosis, thalassemia major, and to the splenic concentration seen in chronic sickle cell anemia, and glucose-6-phosphate dehydrogenase deficiency.

Any mechanism involving active in bony deposition, such as adsorption onto immature collagen, hyperemia and altered capillary permeability could play a role in soft tissue deposition of Tc-phosphates. No single mechanism has gained universal acceptance. Quite probably, several are involved and in some cases multiple mechanisms may be in operation simultaneously.

References:

1) Gabow PA, Kaehny WD, Kelleher SP. The spectrum of rhabdomyolysis. Medicine 1982; 61:141-152.

2) Haseman MK, Kriss JP. Selective, symmetric, skeletal muscle uptake of Tc-99m pyrophosphate in rhabdomyolysis. Clinical Nuclear Medicine 1985;180-183.

3) Bywaters EGL, Beall D. Crush injuries with impairment of renal function. British Medical Journal 1941;1:427.

4) Brill DR. Radionuclide imaging of non-neoplastic soft tissue disorders. Seminars in Nuclear Medicine 1981; 2(4):277-288.

5) Dewanjee MK, Kahn PC. Mechanism of localization of Tc-99m labeled pyrophosphate and tetracycline in infarcted myocardium. JNM 1976; 17(7):639- 646.

6) Buja LM, Tofe AJ, Kalkarni P al. Sites and mechanisms of localization of Tc- 99m phosphorus radiopharmaceuticals in acute myocardial infarcts and other tissues. J Clin Invest 1977; 60:724-740.

7) Zimmer AM, Isitman AT, Holmes RA. Enzymatic inhibition of diphosphonate: a proposed mechanism of tissue uptake. JNM 1975; 16:352-256.

8) McRae J, Hambright P, Valk P, et al. Chemistry of Tc-99m tracers. In vivo conversion of tagged (HEPD and pyrophosphate (bone seekers) into gluconate ( renal agent). Effects of Ca and Fe (II) on in vivo distribution. JNM 1976; 17:208-211.

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J. Anthony Parker, MD PhD, jap@nucmed.bih.harvard.edu