{"id":1467,"date":"2024-03-12T16:23:47","date_gmt":"2024-03-12T20:23:47","guid":{"rendered":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/?post_type=chapter&p=1467"},"modified":"2025-10-17T19:31:06","modified_gmt":"2025-10-17T23:31:06","slug":"rhabdoymyolysis","status":"web-only","type":"chapter","link":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/chapter\/rhabdoymyolysis\/","title":{"raw":"Rhabdoymyolysis","rendered":"Rhabdoymyolysis"},"content":{"raw":"

Rhabdomyolysis<\/strong><\/h1>\r\nAs mentioned in the last section on Crush Syndrome<\/a>, the term rhabdomyolysis<\/strong> originates from the Greek words rhabdos<\/em> meaning rod, myo<\/em> meaning muscle and lusis<\/em> meaning loosening, dissolving, or dissolution.\u00a0 Rhabdomyolysis is depicted by skeletal muscle damage that leads to the leakage of cytoplasmic contents from ruptured skeletal muscle cells (myofibers\/myocytes).<\/strong>\u00a0 Leaked cellular components include proteins<\/strong> such as: myoglobin, myosin, actin, troponin, tropomyosin, and creatine kinase as well as cellular electrolytes (e.g., sodium, calcium, potassium and phosphate) that spill into the interstitial spaces.\u00a0 Many of these cellular components are then taken up by blood and lymph vessels giving rise to myoglobinemia,<\/strong> elevated serum creatine kinase levels and electrolyte imbalances.\u00a0 High levels of serum myoglobin result in renal tubular obstruction, causing tubular injury and renal ischemia giving rise to Acute Kidney Injury<\/strong> (AKI)<\/strong>, which can lead to renal failure if not treated (or prevented).\u00a0 In short, rhabdomyolysis, if not treated, can lead to acute kidney injury.\r\n\r\n \r\n

Pathogenesis - Rhabdomyolysis<\/strong><\/h3>\r\nSignificant damage to skeletal muscles that causes myofibers to rupture is termed rhabdomyolysis.\u00a0 Myofibers can be damaged by shear<\/strong> or blunt force, extreme temperatures, hypoxia, infection, toxins,<\/strong> various chemicals, free radicals,<\/strong> lack of ATP, pH imbalances,<\/strong> and electrolyte imbalances,<\/strong> as well as dehydration.<\/strong>\u00a0 As muscle cells die, their spilled contents fill interstitial spaces, creating a hypertonic environment that draws in more water from nearby blood vessels, increasing the swelling in the affected area.\u00a0 As noted above, leaked myofiber components include proteins<\/strong> (e.g., myoglobin, myosin, actin, troponin, tropomyosin, and creatine kinase) and cellular electrolytes<\/strong> (e.g., sodium, calcium, potassium and phosphate).\u00a0 Some components (e.g., K+<\/sup>, Ca++<\/sup>, and ATP) released by dead muscle cells, which induce the immune response.\u00a0 Macrophages<\/strong> and mast cells<\/strong> migrate to the area and release pro-inflammatory cytokines<\/strong> (e.g., histamine, prostaglandins, bradykinin) which stimulates vasodilation and increased capillary permeability.\u00a0 This effect on blood vessels leads to the leaking of plasma exudate,<\/strong> swelling, hyperemia<\/strong> (causing warmth and redness and influx of activated white blood cells and platelets).\r\n\r\nAt the same time, white blood cells (WBCs)<\/strong> such as macrophages, mast cells and neutrophils are involved in phagocytosing debris, any infecting agents, and\/or toxins, as well as stimulating the repair of tissue.\u00a0 If necrosis<\/strong> is significant and swelling continues to develop within a contained fascial compartment(s),<\/strong> this edema can lead to rising intracompartmental pressure and compartment syndrome.<\/strong>\r\n\r\nCompartment syndrome is detailed in the previous section, and if not treated, can lead to ischemia within the compartment, causing further death of muscle cells and other cells in the region (e.g., sensory and motor neurons).\u00a0 Compartment syndrome is depicted by the progressive development of the 5Ps of symptoms of acute muscle necrosis (severe pain, pallor, pulselessness, pallor, paresthesia and paralysis).\r\n\r\nPain<\/strong> is caused by the triggering of nociceptors by chemicals released from both damaged cells and activated WBCs, as well as by increases in swelling and pressure. \u00a0 Increased intracompartmental pressure leads to pinching off of blood vessels resulting in pulselessness, pallor, paresthesia (sensory dysfunction depicted by numbness, tingling or complete loss of feeling), partial\/full paralysis).\r\n\r\nIncreases in intracompartmental pressure pinch off blood vessels causing ischemia and hypoxia as well as pallor<\/strong> and pulselessness<\/strong> (particularly distal to the injury).\r\n\r\nReduced blood flow (and therefore oxygen and nutrients) within the compartment is detrimental to the functioning of cells that require a constant supply.\u00a0 Sensory neuron dysfunction gives rise to paresthesias<\/strong> such as tingling, numbness and eventual absences of sensation (e.g., as noted in 2-point discrimination tests).\u00a0 Motor neuron dysfunction gives rise to partial\/full temporary\/permanent flaccid paralysis<\/strong> of the muscle involved.\r\n\r\n \r\n\r\nRhabdomyolysis in addition to potentially causing muscle and neuron infarctions<\/strong> can also cause Acute Kidney Injury and renal failure.\u00a0 As myofibers die and burst, spilled myoglobin enters the bloodstream, leading to myoglobinemia.\u00a0 High levels of serum myoglobin can accumulate in renal glomeruli, causing damage and the release of nephrotoxic breakdown products, including the production of free radicals.\u00a0 The glomeruli become leaky and the ensuing damage to nephron tubules leads to the formation of obstructive urinary casts<\/strong> and renal vasoconstriction and hypoxia which increase the amount of renal injury.\u00a0 This is a serious condition as acute kidney injury potentially leads to oliguria, acidosis<\/strong> (due to failure to excrete excess H+<\/sup> ions), as well as uremia<\/strong> and uricemia<\/strong> (due to failure to excrete excess nitrogenous wastes, urea and uric acid respectively).\u00a0 Conditions of acidosis, elevated blood urea nitrogen levels and hyperuricemia<\/strong> can lead to cardiac arrest, loss of consciousness, and brain damage.\r\n\r\n \r\n\r\nRhabdomyolysis can also give rise to cardiac arrhythmias<\/strong> due to the electrolyte imbalances and acidosis.\r\n\r\n \r\n

Risk Factors - Rhabdomyolysis<\/strong><\/h3>\r\nRhabdomyolysis is caused by severe skeletal muscle damage that occurs in a short period of time.\u00a0 Instances that can cause significant acute skeletal muscle damage resulting in rhabdomyolysis include trauma, muscle compression, compartment syndrome, bone fracture, thromboemboli, burns, heat stroke, dehydration, some viral, bacterial and fungal infections, electrolyte imbalances, drug\/alcohol abuse, vigorous physical exertion, seizures, hyperthermia\/hypothermia, and inherited disorders.\r\n\r\n \r\n

Signs and Symptoms - Rhabdomyolysis<\/strong><\/h2>\r\nThe cellular damage within the affected muscle induces the inflammatory response<\/strong>, leading to pain, swelling, redness, warmth and possibly loss of function (depending on the extent of the injury).\r\n\r\nTypically individuals report myalgia (muscle pain), muscle weakness and may have noticed dark tea-coloured urine.\u00a0 Myoglobin is a heme pigment containing protein which gives rise to dark coloured urine (i.e., myoglobinuria)<\/strong> when myoglobinemia<\/strong> and damaged nephrons are present.\r\n\r\nThe affected muscle may appear swollen and signs of compartment syndrome may be present.\u00a0 When untreated compartment syndrome can lead to acute ischemic necrosis which can give rise to the 5Ps<\/strong> (pain, pulselessness distal to affected site, pallor, paresthesia, and paralysis) with a 6th P being pressure (or feeling fullness or swelling).\r\n\r\n \r\n\r\nElevated tonometer (or needle manometer) readings will be present if compartment syndrome has developed.\u00a0 See compartment syndrome section for more details.\r\n\r\n \r\n\r\nElevated serum creatine kinase, hyperkalemia, hyperphosphatemia, hyperuricemia, and hypoalbuminemia may occur with electrolyte disturbances leading to increases in swelling of the affected muscle as well as cardiac arrhythmias, nausea, vomiting, confusion, and coma.\r\n\r\n \r\n\r\nIf third-spacing<\/strong> is significant, hypovolemia will occur coupled with hypotension and reduced cardiac output.\u00a0 This condition can lead to hypovolemic shock<\/strong>, oliguria,<\/strong> and reflex tachycardia<\/strong>.\r\n\r\n \r\n\r\nShock<\/strong> is defined as insufficient blood flow that can lead to organ dysfunction and failure and is often accompanied by the following signs and symptoms:\u00a0 tachycardia, pallor, delayed capillary refill, nausea, vomiting, diaphoresis, anxiety, confusion, loss of consciousness and signs of organ-failure.\r\n\r\n \r\n

Diagnostic Tools - Rhabdomyolysis<\/strong><\/h3>\r\nBlood tests<\/strong> can be used to track the levels of serum creatine kinase, myoglobin, electrolytes (K+, Ca++, PO4), pH as well as blood urea nitrogen (BUN) levels, in addition to other factors (e.g., complete blood count, platelets) that can be used to rule out other issues.\r\n\r\n \r\n\r\nUrine tests<\/strong> will reveal the levels of myoglobin and other factors (proteinuria, hematuria) indicative of kidney function.\r\n\r\n \r\n\r\nBlood urea nitrogen (BUN)<\/strong> and serum creatinine tests<\/strong> can also provide information on kidney function.\r\n\r\n \r\n\r\nImaging<\/strong> can be used to assess the extent of damage, bleeding and\/or inflammation.\r\n\r\n \r\n\r\nElectrocardiography (ECG)<\/strong> readings will help to indicate whether cardiac conduction has been affected by any electrolyte imbalances that may have occurred (e.g., hyperkalemia, hyperphosphatemia and calcium imbalances).\r\n\r\n \r\n\r\nIntracompartmental pressure measurements<\/strong> using a tonometer or needle manometer will be taken if the individual is at risk of compartment syndrome.\r\n\r\n \r\n\r\nCausative factors that include genetic, autoimmune, and infection can be tested for using immunoassays,<\/strong> muscle biopsies,<\/strong> and PCR tests<\/strong>.\r\n\r\n \r\n

Treatment - Rhabdomyolysis<\/strong><\/h3>\r\n \r\n\r\nFluid resuscitation,<\/strong> possibly intravenous (IV) fluids with sodium bicarbonate buffer will be used to help correct electrolyte and blood pH levels as well as rehydrate (if dehydration has occurred, and may be a contributing factor to the rhabdomyolysis and\/or acute kidney injury that is occurring).\r\n\r\n \r\n\r\nDecompression therapy<\/strong> (e.g., fasciotomy) may be required if compartment syndrome has developed.\r\n\r\n \r\n\r\nHemodialysis<\/strong> may be used if there is a risk of acute kidney injury, to help remove excess myoglobin, H+, K+, PO4, urea and other excess electrolytes, metabolites, and waste products.\r\n\r\n \r\n\r\nPossibly lifestyle-related modifications<\/strong> may be required if lifestyle was a contributing factor (e.g., intense vigorous exercise, dehydration, drug\/alcohol abuse)\r\n\r\n \r\n

Potential Complication - Rhabdomyolysis<\/strong><\/h3>\r\nPotential Complications include:\r\n\r\nCompartment Syndrome<\/strong> can arise as a result of significant inflammation and accumulation of inflammatory exudate and\/or blood within a deep fascia compartment that is housing the affected muscle.\u00a0 The layer of deep fascia is composed of dense irregular connective tissue that does not expand readily, meaning that added fluid volume will increase intracompartmental pressure, leading to the pinching off of veins, capillaries and eventually arteries, causing ischemia.\u00a0 If not treated, compartment syndrome can lead to ischemic necrosis causing further muscle destruction, in addition to dysfunction and death of neurons and other cells within the compartment. Compartment syndrome can lead to renal failure<\/strong>, muscle infarction, neuron dysfunction, Volkmann\u2019s contractures, renal failure, cardiac arrhythmias, shock,<\/strong> organ-failure<\/strong>, and cardiac arrest.<\/strong>\u00a0 This is discussed in detail in the Compartment Syndrome section as well.\r\n\r\n \r\n\r\nDisseminated Intravascular Coagulation (DIC)<\/strong> can be triggered when severe damage to the body occurs that triggers a widespread immune response.\u00a0 The activation of platelets can become excessive leading to the formation of blood clots that block blood vessels throughout the body causing ischemia, hypoxia and potentially failure of multiple organs.\u00a0 This is coupled with the fact that the excessive clotting of platelets can leave a person susceptible to hemorrhaging as the number of available platelets and clotting factors diminishes.\u00a0 DIC can be a fatal condition if not prevented\/treated promptly.\r\n\r\n \r\n\r\n \r\n\r\nSummary\r\n