Muscle necrosis

Muscle biopsy is usually undertaken to confirm the provisional clinical diagnosis. Because the skin lesions normally precede those in muscle, biopsies of muscle taken early may show little abnormality. Inflammatory foci may be scanty or absent and muscle fiber diameters may be normal. However typical biopsies show discrete foci of inflammatory cells, with a predominance of B-lymphocytes (see Figure 18). These cells are situated in perimysial connective tissue rather than in the en-domysium and are often also perivascular in location. Muscle fiber necrosis occurs in JDM but muscle fibers do not appear to be the primary target of the disordered immune process. Rather, it is the micro vasculature of the muscle which appears to degenerate first and muscle necrosis is preceded by capillary necrosis, detectable at the ultrastructural level. 

In addition to marked perifascicular atrophy, infarctlike areas are sometimes seen, and are also consistent with a microangiopathy. Muscle fibers which appear normal morphologically may show loss of myofibrillar ATPase activity from the center of the fibers this is also characteristic of muscle subject to ischemia. Such changes may be reversible, but more prolonged ischemia undoubtedly causes irreversible muscle necrosis. 

ADM may evolve over several years, the extent of fiber atrophy provides an important indication of the chronicity of muscle degeneration. Acute muscle necrosis and phagocytosis give some indication as to how active the disease is at the time of biopsy. In most biopsies from ADM patients, the inflammatory cell foci are perivascular and perimysial rather than endomysial and are dominated by B-lymphocytes. The ratio of T4 lymphocytes (helper cells) to T8 lymphocytes (cytotoxic) generally indicates a predominance of the former. As in JDM, this is consistent with humoral mechanisms of cell damage, and vascular involvement is also apparent in the form of capillary endothelial cell abnormalities (tubular arrays) and duplication of basal lamina. Loss of myofibrillar ATPase from the central portions of fibers is a common prelude to muscle necrosis. 

The histopathological features of PM may be radically different from those of JDM and ADM. There is little, if any, evidence of involvement of the micro vasculature and the muscle necrosis which occurs appears to be the direct result of targeting of individual muscle fibers. In the dermatomyositis syndromes, antibody-dependent humoral mechanisms are predominant and B-lymphocytes are seen to be the most abundant cell type in almost all JDM cases and a substantial proportion of ADM cases. In contrast, most muscle biopsies from PM patients show evidence of inflammation in which TS (cytotoxic) lymphocytes predominate (Figure 20). Moreover, the distribution of inflammatory cell infiltrates tends to be different. Instead of the mainly perifascicular location of lymphocytes in JDM/ADM, there... 

Biopsy findings show disseminated muscle fiber atrophy which is confined to type 2 fibers, in many instances with type 2B (glycolytic) fibers most affected (Figure 23). Muscle necrosis is not seen, though at ultrastructural level focal myofibrillar disruption and myofilament loss may be evident. The muscle atrophy seems to be due to decreased protein synthesis, and at high doses, to increased catabolism. The reason for the selective effect on phasic, glycolytic fibers is not clear since, although steroids interfere with carbohydrate metabolism and oxidative capacity, there seems to be no overall effect on ATP levels. Nevertheless it has been... 

The major mineralocorticoid, aldosterone, is secreted by cells of the zona glomerulosa. Primary hyperaldosteronism (Conn s syndrome) is associated with potassium depletion which is, in mm, responsible for the observed neuromuscular abnormalities seen in the disorder. These are similar to those seen in hypokalemic periodic paralysis (PP), with episodic and severe exacerbations of fixed muscle weakness. Muscle biopsy shows occasional muscle necrosis and vacuoles often these feamres are accompanied by mbular aggregates as in hypokalemic PP. All these changes can be attributed to the hypokalemia and not to excess aldosterone production per se. 

The neuromuscular complications of diabetes mellitus are most often neuropathic in origin, with distal sensorimotor polyneuropathies being the most common. In addition, ischemic infarction of skeletal muscle may occur due to occlusive vascular disease, with small and medium-sized arterioles particularly affected. This occurs in poorly-controlled diabetes and affects thigh, muscles in most cases. In acute stages, muscle biopsy findings are those of widespread muscle necrosis, edema, and phagocytic cell infiltration. Muscle regeneration may be incomplete and increased fibrous connective tissue may replace lost muscle tissue. 

Harris, J.B., Cullen, M.J. (1991). Muscle necrosis caused by snake venoms and toxins. Electron Microsc, Rev. 3, 183-211. 

Sileo, L. and A. Gilman. 1975. Carbofuran-induced muscle necrosis in the earthworm. Jour. Invert. Pathol. 25 145-148. 

Histologic and skeletal abnormalities in all BaP-exposed groups depressed mitotic rates in retina and brain in groups exposed to 0.08 pg/L and higher muscle necrosis in all groups exposed to 0.2 pg/L and higher microphthalmia was observed in 17% of BaP-treated trout No DNA adducts detected in liver... 

Clinical chemistry prior to death for both men revealed metabolic acidosis, acute renal and hepatic failure, skeletal muscle necrosis, and damage to other organ systems. Autolysis of viscera prevented complete characterization of lesions associated with mortality from these... 

Musculoskeletal Effects. Both patients described by Letz et al. (1984) (see Section 2.2.3.1) had greatly elevated levels of serum creatinine phosphokinase after 1,2-dibromoethane exposure this enzyme increases in the event of skeletal muscle necrosis. There was no report of skeletal muscle being examined at necropsy or histologically in either individual. 

At the sites of Injection of oxime in the rabbits, various extents of hemorrhage and of purulent, indurative myositis and muscle necrosis were seen. The rabbits that received physiologic saline and five that received intramuscular injections of 2.15 M sodium chloride on 8 d in a satellite experiment had waxy degeneration of muscle at the site of injection. Five rabbits that received intramuscular injections of 2.15 M I on 8 d also had waxy degeneration of muscle at the site of injection. This was stated to be more extensive than that seen in the rabbits given equimolar sodium chloride. No other lesions in the rabbits that seem to be attributable to the oximes were described. 

C-reactive protein (CRP) is a protein produced by the liver during episodes of acute inflammation. CRP is not a specific test, however, and a positive CRP may indicate a number of things including inflammatory disease, malignancy, muscle necrosis (e.g. myocardial infarction) and trauma, as well as infection. A normal CRP is unlikely in the presence of a bacterial infection and a very high CRP (>100 mg/L) is more likely to occur in bacterial than viral infection. In this case, the patient s high CRP is consistent with a bacterial infection. CRP may be used to monitor a patient s response to therapy. 

A 38-year-old man developed acute oliguric renal failure after repeated glue sniffing for about 8 hours (34). He also had severe liver damage, mild muscle necrosis, and bone marrow depression. He made a complete recovery. 

Conventional anticonvulsant compounds have been reported to provide limited protection against nerve agent-induced seizures and muscle necrosis when given therapeutically (Lipp, 1972 Clinton et al, 1988). Sedation, tolerance, and abuse potential, however, limit prophylactic use of benzodiazepine compounds. 

Since the major energy sources are ATP and PCr, an increase of both compounds in muscles through administration of creatine appears to sustain ATP levels under stress conditions. This is supported by the findings that rats pretreated intravenously with PCr showed reduced muscle necrosis otherwise seen following DFP treatment. PCr did not attenuate the DFP-induced muscle fasciculations generating the necrosis (Clinton and Dettbam, 1987). 

Dettbam, W-D. (1984). Pesticide induced muscle necrosis mechanisms and prevention. Fundam. Appl. Toxicol. 4, SI8-26. 

Paraldehyde is now rarely used. It smells and tastes unpleasant and is partly excreted unchanged via the lungs (75% is metabolised t) 5 h) it is an irritant (avoid in peptic ulcer) and causes painful muscle necrosis when injected i.m. It dissolves plastic syringes. 

Quite frequently, and typically 1-4 days after resolution of symptoms of acute exposure, the intermediate syndrome may develop, characterised by a proximal flaccid limb paralysis which may reflect muscle necrosis. Even later, after a gap of 2-4 weeks, some exposed persons exhibit the delayed polyneuropathy, with sensory and motor impairment usually of the lower limbs. Claims of chronic effects (subtle cognitive defects, peripheral neuropathy) following recurrent, low-dose exposure, as with organophosphate used as sheep dip, continues to be the subject of investigation but, as yet, no conclusive proof. 

Aminocaproic acid used during cardiopulmonary bypass reduced mediastinal blood losses by about one-third, while transfusion requirements were unchanged (41). In one series of over 950 patients, not a single thromboembolic complication could be ascribed to aminocaproic acid. However, a few cases of muscle necrosis and rhabdomyolysis with renal insufficiency have been reported with aminocaproic acid (42,43). 

Korsan-Bengtsen K, Ysander L, Blohme G, Tibbhn E. Extensive muscle necrosis after long-term treatment tvith aminocaproic acid (EACA) in a case of hereditary periodic edema. Acta Med Scand 1969 185(4) 341-6. 

Acute renal tubular damage occurs in association with the liver damage, together with muscle necrosis and hyperkalemia. The muscle necrosis, as demonstrated at autopsy in fatal cases (82), can itself exacerbate the severe electrolyte derangement, particularly marked hyperkalemia, that occurs in liver failure. The measurement of serum concentrations of coagulation factors V (below 10%) and VIII (VIII/V ratio over 30) can have predictive value and can thus be helpful in selecting patients who require hver transplantation (SEDA-17, 99). 

Muscle necrosis and round cell infiltrates have been seen in histological studies of animal muscle recently injected with phenol, but not after a few months have passed (36). 

Ischemic AKI may be induced by intrarenal norepinephrine injection or by renal artery clamping. There are similarities between these two models of ischemic renal failure. In the norepinephrine model of renal failure, as in the arterial clamping model, there is the same degree of tubular injury except for a slightly greater frequency of tubular casts at 48 hours in ischemic model [32]. In both models, calcium channel-blockers, improve renal function [33, 34]. The major difference is that in the renal artery clamping model, morphology at 48 hours showed smooth muscle necrosis in half of the resistance vessels, but in less than 10% of those in norepinephrine-induced model. 

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