Rhabdomyolysis
Encyclopedia
Rhabdomyolysis icon is a condition in which damaged skeletal muscle
tissue (Greek: ῥαβδω rhabdo- striped μυς myo- muscle) breaks down (Greek: λύσις –lysis) rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin
, are harmful to the kidney
s and may lead to kidney failure. The severity of the symptoms, which may include muscle pains
, vomiting
and confusion
, depends on the extent of muscle damage and whether kidney failure develops. The muscle damage may be caused by physical factors (e.g. crush injury
, strenuous exercise), medications, drug abuse
, and infection
s. Some people have a hereditary muscle condition that increases the risk of rhabdomyolysis. The diagnosis is usually made with blood test
s and urinalysis
. The mainstay of treatment is generous quantities of intravenous fluids, but may include dialysis
or hemofiltration
in more severe cases.
Rhabdomyolysis and its complications are significant problems for those injured in disasters such as earthquakes and bombings. Relief efforts in areas struck by earthquakes often include medical teams with the skills and equipment to treat survivors with rhabdomyolysis. The disease was first described in the 20th century, and important discoveries as to its mechanism were made during the Blitz of London
in 1941. Horse
s may also suffer from rhabdomyolysis from a variety of causes.
s in the context of other problems. More severe rhabdomyolysis is characterized by muscle pain
, tenderness, weakness
and swelling
of the affected muscles. If the swelling is very rapid, as may happen after someone is released from under a collapsed building, the movement of fluid from the bloodstream into damaged muscle may cause low blood pressure
and shock. Other symptoms are nonspecific and result either from the consequences of muscle tissue breakdown or from the condition that originally led to the muscle breakdown. Release of the components of muscle tissue into the bloodstream causes disturbances in electrolyte
s, which can lead to nausea
, vomiting
, confusion
, coma
or abnormal heart rate and rhythm. The urine may be dark, often described as "tea-colored", due to the presence of myoglobin
. Damage to the kidneys may give rise to decreased
or absent urine production
, usually 12 to 24 hours after the initial muscle damage.
Swelling of the damaged muscle occasionally leads to compartment syndrome
—compression of surrounding tissues, such as nerves and blood vessel
s, in the same fascial compartment
—leading to the loss of blood supply and damage or loss of function in the part(s) of the body supplied by these structures. Symptoms of this complication include pain or reduced sensation in the affected limb. A second recognized complication is disseminated intravascular coagulation
(DIC), a severe disruption in blood clotting
that may lead to uncontrollable bleeding.
or any of the other causes of rhabdomyolysis listed above. Inherited muscle disorders and infections together cause the majority of rhabdomyolysis in children.
The following hereditary disorders of the muscle energy supply may cause recurrent and usually exertional rhabdomyolysis:
Damage to skeletal muscle may take various forms. Crush injuries and other physical causes damage muscle cells
directly or interfere with their blood supply, while non-physical causes interfere with muscle cell metabolism
. When damaged, muscle tissue rapidly fills with fluid from the bloodstream, including sodium ions
. The swelling itself may lead to destruction of muscle cells, but those cells that survive are subject to various disruptions that lead to rise in intracellular calcium ions; the accumulation of calcium in the sarcoplasmic reticulum leads to continuous muscle contraction
and depletion of ATP
, the main carrier of energy in the cell. ATP depletion can itself lead to uncontrolled calcium influx. The persistent contraction of the muscle cell leads to breakdown of intracellular proteins and disintegration of the cell.
Neutrophil granulocyte
s—the most abundant type of white blood cell
—enter the muscle tissue, producing an inflammatory
reaction and releasing reactive oxygen species
, particularly after crush injury. Crush syndrome may also cause reperfusion injury
when blood flow to decompressed muscle is suddenly restored.
The swollen, inflamed muscle may directly compress structures in the same fascial compartment
, causing compartment syndrome
. The swelling may also further compromise blood supply into the area. Finally, destroyed muscle cells release potassium ions, phosphate
ions, the heme
-containing protein myoglobin
, the enzyme
creatine kinase
and uric acid
(a breakdown product of purine
s from DNA
) into the blood. Activation of the coagulation system may precipitate disseminated intravascular coagulation
. High potassium levels
may lead to potentially fatal disruptions in heart rhythm
. Phosphate binds to calcium from the circulation, leading to low calcium levels in the blood.
Rhabdomyolysis may cause renal failure by several mechanisms. The most important problem is the accumulation of myoglobin in the kidney tubules. Normally, the blood protein haptoglobin
binds circulating myoglobin and other heme-containing substances, but in rhabdomyolysis the quantity of myoglobin exceeds the binding capacity of haptoglobin. Myoglobinuria
, the presence of myoglobin in the urine, occurs when the level in plasma
exceeds 0.5–1.5 mg/dl
; once plasma levels reach 100 mg/dl, the concentration in the urine becomes sufficient for it to be visibly discolored. About 200 grams of muscle needs to be destroyed for visible myoglobinuria to occur. As the kidneys reabsorb more water from the filtrate, myoglobin interacts with Tamm–Horsfall protein
in the nephron
to form casts (solid aggregates) that obstruct the normal flow of fluid; the condition is worsened further by high levels of uric acid and acidification of the filtrate, which increase cast formation. Iron released from the heme generates reactive oxygen species, damaging the kidney cells. In addition to the myoglobinuria, two other mechanisms contribute to renal impairment: low blood pressure leads to constriction of the blood vessels
and therefore a relative lack of blood flow to the kidney, and finally uric acid may form crystals in the tubules of the kidneys, causing obstruction. Together, these processes lead to acute tubular necrosis
, the destruction of the cells of tubules. Glomerular filtration rate falls and the kidney is unable to perform its normal excretory functions. This causes disruption of electrolyte regulation, leading to a further rise in potassium levels, and interferes with vitamin D
processing, further worsening the low calcium levels.
A diagnosis of rhabdomyolysis may be suspected in anyone who has suffered trauma, crush injury or prolonged immobilization, but it may also be identified at a later stage due to deteriorating kidney function (abnormally raised or increasing creatinine
and urea
levels, falling urine output) or reddish-brown discoloration of the urine.
(CK) in the blood. This enzyme is released by damaged muscle, and levels above 5 times the upper limit of normal (ULN) indicate rhabdomyolysis. Depending on the extent of the rhabdomyolysis, concentrations up to 100,000 U
/l are not unusual. CK concentrations rise steadily for 12 hours after the original muscle injury, remain elevated for 1–3 days and then fall gradually. Initial and peak CK levels have a linear relationship with the risk of acute renal failure: the higher the CK, the more likely it is that kidney damage will occur. There is no specific concentration of CK above which renal impairment definitely occurs; concentrations below 20,000 U/l are unlikely to be associated with a risk of renal impairment, unless there are other contributing risk factors. Mild rises without renal impairment are referred to as "hyperCKemia". Myoglobin has a short half-life, and is therefore less useful as a diagnostic test in the later stages. Its detection in blood or urine is associated with a higher risk of renal impairment. Despite this, use of urine myoglobin measurement is not supported by evidence as it lacks specificity
and the research studying its utility is of poor quality.
Elevated concentrations of the enzyme lactate dehydrogenase
(LDH) may be detected. Other markers of muscle damage, such as aldolase
, troponin
, carbonic anhydrase type 3
and fatty acid-binding protein
(FABP), are mainly used in chronic muscle diseases. The transaminase
s, enzymes abundant in both liver and muscle tissue, are also usually increased; this can lead to the condition being confused with acute liver injury, at least in the early stages. The incidence of actual acute liver injury is 25% in people with non-traumatic rhabdomyolysis; the mechanism for this is uncertain.
High potassium levels
tend to be a feature of severe rhabdomyolysis. Electrocardiography (ECG) may show whether the elevated potassium levels are affecting the conduction system of the heart, as suggested by the presence of T wave
changes or broadening of the QRS complex
. Low calcium
levels may be present in the initial stage due to binding of free calcium to damaged muscle cells.
Urinalysis
by urine test strip
may reveal a positive result for "blood", even though no red blood cell
s can be identified on microscopy
of the urine; this occurs because the reagent on the test strip reacts with myoglobin. The same phenomenon may happen in conditions that lead to hemolysis
, the destruction of red blood cells; in hemolysis the blood serum
is also visibly discolored, while in rhabdomyolysis it is normal. If kidney damage has occurred, microscopy of the urine also reveals urinary casts that appear pigmented and granular.
is a clinical diagnosis, i.e. no diagnostic test conclusively proves its presence or absence, but direct measurement of the pressure in a fascial compartment, and the difference between this pressure and the blood pressure, may be used to assess its severity. High pressures in the compartment and a small difference between compartment pressure and blood pressure indicate that the blood supply is likely to be insufficient, and that surgical intervention may be needed.
Disseminated intravascular coagulation
, another complication of rhabdomyolysis and other forms of critical illness, may be suspected on the basis of unexpected bleeding or abnormalities in hematological tests, such as a decreasing platelet
count or prolongation of the prothrombin time
. The diagnosis can be confirmed with standard blood tests for DIC, such as D-dimer
.
in the blood and high levels of acylcarnitine in blood and urine may indicate a lipid metabolism defect, but these abnormalities revert to normal during convalescence. Other tests may be used at that stage to demonstrate these disorders. Disorders of glycolysis
can be detected by various means, including the measurement of lactate
after exercise; a failure of the lactate to rise may be indicative of a disorder in glycolysis, while an exaggerated response is typical of mitochondrial disease
s. Electromyography
(EMG) may show particular patterns in specific muscle diseases; for instance, McArdle's disease
and phosphofructokinase deficiency
show a phenomenon called cramp-like contracture. There are genetic tests available for many of the hereditary muscle conditions that predispose to myoglobinuria and rhabdomyolysis.
Muscle biopsy
can be useful if an episode of rhabdomyolysis is thought to be the result of an underlying muscle disorder. A biopsy sample taken during an episode is often uninformative, as it will show only evidence of cell death
or may appear normal. Taking the sample is therefore delayed for several weeks or months. The histopathological
appearance on the biopsy indicates the nature of the underlying disorder. For instance, mitochondrial diseases are characterised by ragged red fibers. Biopsy sites may be identified by medical imaging
, such as magnetic resonance imaging
, as the muscles may not be uniformly affected.
(0.9% weight per volume sodium chloride
solution). In victims of crush syndrome it is recommended to administer intravenous fluids even before they are extracted from collapsed structures. This will ensure sufficient circulating volume to deal with the muscle cell swelling (which typically commences when blood supply is restored), and to prevent the deposition of myoglobin in the kidneys. Amounts of 6 to 12 liters over 24 hours are recommended. The rate of fluid administration may be altered to achieve a high urine output (200–300 ml/h in adults), unless there are other reasons why this might lead to complications, such as a history of heart failure.
While many sources recommend additional intravenous agents to reduce damage to the kidney, most of the evidence supporting this practice comes from animal studies, and is inconsistent and conflicting. The use of mannitol
, which acts by osmosis
to enhance urine production and may prevent myoglobin deposition in the kidney, has not been directly studied in clinical trial
s. The addition of bicarbonate
to the intravenous fluids may alleviate acidosis
(high acid level of the blood) and make the urine more alkaline to prevent cast formation in the kidneys, but there is limited evidence that it has benefits above saline alone, and it can worsen hypocalcemia by enhancing calcium and phosphate deposition in the tissues. If urine alkalinization is used, the pH of the urine is kept at 6.5 or above. Furosemide
, a loop diuretic
, is often used to ensure sufficient urine production, but evidence that this prevents renal failure is lacking.
or salbutamol
to redistribute potassium into cells, and infusions of bicarbonate solution.
Calcium levels initially tend to be low, but as the situation improves calcium is released from where it has precipitated with phosphate, and vitamin D production resumes, leading to hypercalcemia (abnormally high calcium levels). This "overshoot" occurs in 20–30% of those people who have developed kidney failure.
Kidney dysfunction typically develops 1–2 days after the initial muscle damage. If supportive treatment is inadequate to manage this, renal replacement therapy
(RRT) may be required. RRT removes excess potassium, acid and phosphate that accumulate when the kidneys are unable to function normally and is required until kidney function is regained.
Three main modalities of RRT are available: hemodialysis
, continuous hemofiltration
and peritoneal dialysis
. The former two require access to the bloodstream (a dialysis catheter
), while peritoneal dialysis is achieved by instilling fluid into the abdominal cavity and later draining it. Hemodialysis, which is normally done several times a week in chronic kidney disease, is often required on a daily basis in rhabdomyolysis. Its advantage over continuous hemofiltration is that one machine can be used multiple times a day, and that continuous administration of anticoagulant
drugs is not necessary. Hemofiltration is more effective at removing large molecules from the bloodstream, such as myoglobin, but this does not seem to confer any particular benefit. Peritoneal dialysis may be difficult to administer in someone with severe abdominal injury, and it may be less effective than the other modalities.
is treated with surgery to relieve the pressure inside the muscle compartment and reduce the risk of compression on blood vessels and nerves in that area. Fasciotomy
is the incision of the affected compartment. Often, multiple incisions are made and left open until the swelling has reduced. At that point, the incisions are closed, often requiring debridement
(removal of non-viable tissue) and skin grafting
in the process. The need for fasciotomy may be decreased if mannitol is used, as it can relieve muscle swelling directly.
Disseminated intravascular coagulation
generally resolves when the underlying causes are treated, but supportive measures are often required. For instance, if the platelet count drops
significantly and there is resultant bleeding, platelets may be administered.
of 20%. Admission to the intensive care unit is associated with a mortality of 22% in the absence of acute kidney injury, and 59% if renal impairment occurs. Most people who have sustained renal impairment due to rhabdomyolysis fully recover their renal function.
Crush injuries are common in major disasters, but especially so in earthquakes. The aftermath of the 1988 Spitak earthquake prompted the establishment, in 1995, of the Renal Disaster Relief Task Force, a working group of the International Society of Nephrology
(a worldwide body of kidney experts). Its volunteer doctors and nurses assisted for the first time in the 1999 İzmit earthquake
in Turkey
, where 462 people received dialysis, with positive results. Treatment units are generally established outside the immediate disaster area, as aftershock
s could potentially injure or kill staff and make equipment unusable.
The Bible may contain an early account of rhabdomyolysis. In , the Pentateuch says that the Jews demanded wholesome food while traveling in the desert; God sent quail in response to the complaints, and people ate large quantities of quail meat. A plague then broke out, killing numerous people. Rhabdomyolysis after consuming quail was described in more recent times and called coturnism
(after Coturnix
, the main quail genus). Migrating quail consume large amounts of hemlock
, a known cause of rhabdomyolysis.
In modern times, early reports from the 1908 Messina earthquake
and World War I on renal failure after injury were followed by studies by London physicians Eric Bywaters and Desmond Beall, working at the Royal Postgraduate Medical School
and the National Institute for Medical Research
, on four victims of The Blitz
in 1941. Myoglobin was demonstrated in the urine of victims by spectroscopy
, and it was noted that the kidneys of victims resembled those of patients who had hemoglobinuria
(hemoglobin rather than myoglobin being the cause of the kidney damage). In 1944 Bywaters demonstrated experimentally that the renal failure was mainly caused by myoglobin. Already during the war, teams of doctors traveled to bombed areas to provide medical support, chiefly with intravenous fluids, as dialysis was not yet available. The prognosis of acute renal failure improved markedly when dialysis was added to supportive treatment, which first happened during the 1950–1953 Korean War
.
and selenium
, poisoning associated with pasture or agricultural poisons such as organophosphate
s), while others predispose to exertional rhabdomyolysis (e.g. the hereditary condition equine polysaccharide storage myopathy
). 5–10% of thoroughbred
horses and some standardbred horses suffer from the condition equine exertional rhabdomyolysis
; no specific cause has been identified, but an underlying muscle calcium regulation disorder is suspected.
Rhabdomyolysis affecting horses may also occur in outbreaks; these have been reported in many European countries, and later in Canada, Australia, and the United States. It has been referred to as "atypical myopathy" or "myoglobinuria of unknown etiology". No single cause has yet been found, but various mechanisms have been proposed, and a seasonal pattern has been observed. Very high creatine kinase levels are detected, and mortality from this condition is 89%.
Skeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...
tissue (Greek: ῥαβδω rhabdo- striped μυς myo- muscle) breaks down (Greek: λύσις –lysis) rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin
Myoglobin
Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in almost all mammals. It is related to hemoglobin, which is the iron- and oxygen-binding protein in blood, specifically in the red blood cells. The only time myoglobin is found in the...
, are harmful to the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s and may lead to kidney failure. The severity of the symptoms, which may include muscle pains
Myalgia
Myalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
, vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
and confusion
Mental confusion
Confusion of a pathological degree usually refers to loss of orientation sometimes accompanied by disordered consciousness and often memory Confusion (from Latin confusĭo, -ōnis, noun of action from confundere "to pour together", also "to confuse") of a pathological degree usually refers to loss...
, depends on the extent of muscle damage and whether kidney failure develops. The muscle damage may be caused by physical factors (e.g. crush injury
Crush syndrome
Crush syndrome is a medical condition characterized by major shock and renal failure after a crushing injury to skeletal muscle...
, strenuous exercise), medications, drug abuse
Substance abuse
A substance-related disorder is an umbrella term used to describe several different conditions associated with several different substances .A substance related disorder is a condition in which an individual uses or abuses a...
, and infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s. Some people have a hereditary muscle condition that increases the risk of rhabdomyolysis. The diagnosis is usually made with blood test
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s and urinalysis
Urinalysis
A urinalysis , also known as Routine and Microscopy , is an array of tests performed on urine, and one of the most common methods of medical diagnosis...
. The mainstay of treatment is generous quantities of intravenous fluids, but may include dialysis
Dialysis
In medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
or hemofiltration
Hemofiltration
In medicine, hemofiltration, also haemofiltration, is a renal replacement therapy similar to hemodialysis which is used almost exclusively in the intensive care setting...
in more severe cases.
Rhabdomyolysis and its complications are significant problems for those injured in disasters such as earthquakes and bombings. Relief efforts in areas struck by earthquakes often include medical teams with the skills and equipment to treat survivors with rhabdomyolysis. The disease was first described in the 20th century, and important discoveries as to its mechanism were made during the Blitz of London
The Blitz
The Blitz was the sustained strategic bombing of Britain by Nazi Germany between 7 September 1940 and 10 May 1941, during the Second World War. The city of London was bombed by the Luftwaffe for 76 consecutive nights and many towns and cities across the country followed...
in 1941. Horse
Horse
The horse is one of two extant subspecies of Equus ferus, or the wild horse. It is a single-hooved mammal belonging to the taxonomic family Equidae. The horse has evolved over the past 45 to 55 million years from a small multi-toed creature into the large, single-toed animal of today...
s may also suffer from rhabdomyolysis from a variety of causes.
Signs and symptoms
The symptoms of rhabdomyolysis depend on the severity of the condition, and whether kidney failure develops. Milder forms of rhabdomyolysis may not cause any muscle symptoms, and the diagnosis is based on abnormal blood testBlood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s in the context of other problems. More severe rhabdomyolysis is characterized by muscle pain
Myalgia
Myalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
, tenderness, weakness
Muscle weakness
Muscle weakness or myasthenia is a lack of muscle strength. The causes are many and can be divided into conditions that have true or perceived muscle weakness...
and swelling
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
of the affected muscles. If the swelling is very rapid, as may happen after someone is released from under a collapsed building, the movement of fluid from the bloodstream into damaged muscle may cause low blood pressure
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
and shock. Other symptoms are nonspecific and result either from the consequences of muscle tissue breakdown or from the condition that originally led to the muscle breakdown. Release of the components of muscle tissue into the bloodstream causes disturbances in electrolyte
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....
s, which can lead to nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
, confusion
Mental confusion
Confusion of a pathological degree usually refers to loss of orientation sometimes accompanied by disordered consciousness and often memory Confusion (from Latin confusĭo, -ōnis, noun of action from confundere "to pour together", also "to confuse") of a pathological degree usually refers to loss...
, coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
or abnormal heart rate and rhythm. The urine may be dark, often described as "tea-colored", due to the presence of myoglobin
Myoglobin
Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in almost all mammals. It is related to hemoglobin, which is the iron- and oxygen-binding protein in blood, specifically in the red blood cells. The only time myoglobin is found in the...
. Damage to the kidneys may give rise to decreased
Oliguria
Oliguria is the low output of urine, It is clinically classified as an output below 300-500ml/day. The decreased output of urine may be a sign of dehydration, renal failure, hypovolemic shock, HHNS Hyperosmolar Hyperglycemic Nonketotic Syndrome, multiple organ dysfunction syndrome, urinary...
or absent urine production
Anuria
Anuria means nonpassage of urine, in practice is defined as passage of less than 50 milliliters of urine in a day. Anuria is often caused by failure in the function of kidneys. It may also occur because of some severe obstruction like kidney stones or tumours. It may occur with end stage renal...
, usually 12 to 24 hours after the initial muscle damage.
Swelling of the damaged muscle occasionally leads to compartment syndrome
Compartment syndrome
Compartment syndrome is a limb threatening and life threatening condition, defined as the compression of nerves, blood vessels, and muscle inside a closed space within the body . This leads to tissue death from lack of oxygenation due to the blood vessels being compressed by the raised pressure...
—compression of surrounding tissues, such as nerves and blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s, in the same fascial compartment
Fascial compartment
On the human body, the limbs can be divided into segments, such as the arm and the forearm of the upper limb, and the thigh and the leg of the lower limb.If these segments are cut transversely, it is apparent that they are divided into multiple sections...
—leading to the loss of blood supply and damage or loss of function in the part(s) of the body supplied by these structures. Symptoms of this complication include pain or reduced sensation in the affected limb. A second recognized complication is disseminated intravascular coagulation
Disseminated intravascular coagulation
Disseminated intravascular coagulation , also known as disseminated intravascular coagulopathy or consumptive coagulopathy, is a pathological activation of coagulation mechanisms that happens in response to a variety of diseases. DIC leads to the formation of small blood clots inside the blood...
(DIC), a severe disruption in blood clotting
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
that may lead to uncontrollable bleeding.
Causes
Any form of muscle damage of sufficient severity can cause rhabdomyolysis. Multiple causes can be present simultaneously in one person. Some people have an underlying muscle condition, usually hereditary in nature, that makes them more prone to rhabdomyolysis.Common and important causes
| Type | Causes |
|---|---|
| Exertion | Extreme physical exercise Physical exercise Physical exercise is any bodily activity that enhances or maintains physical fitness and overall health and wellness. It is performed for various reasons including strengthening muscles and the cardiovascular system, honing athletic skills, weight loss or maintenance, as well as for the purpose of... (particularly when poorly hydrated), delirium tremens Delirium tremens Delirium tremens is an acute episode of delirium that is usually caused by withdrawal from alcohol, first described in 1813... (alcohol withdrawal), tetanus Tetanus Tetanus is a medical condition characterized by a prolonged contraction of skeletal muscle fibers. The primary symptoms are caused by tetanospasmin, a neurotoxin produced by the Gram-positive, rod-shaped, obligate anaerobic bacterium Clostridium tetani... , prolonged seizure Seizure An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness... s or status epilepticus Status epilepticus Status epilepticus is a life-threatening condition in which the brain is in a state of persistent seizure. Definitions vary, but traditionally it is defined as one continuous unremitting seizure lasting longer than 5 minutes, or recurrent seizures without regaining consciousness between seizures... |
| Crush | Crush syndrome Crush syndrome Crush syndrome is a medical condition characterized by major shock and renal failure after a crushing injury to skeletal muscle... , blast injury Blast injury A blast injury is a complex type of physical trauma resulting from direct or indirect exposure to an explosion. Blast injuries occur with the detonation of high-order explosives as well as the deflagration of low order explosives... , car accident, physical torture Torture Torture is the act of inflicting severe pain as a means of punishment, revenge, forcing information or a confession, or simply as an act of cruelty. Throughout history, torture has often been used as a method of political re-education, interrogation, punishment, and coercion... or abuse Physical abuse Physical abuse is abuse involving contact intended to cause feelings of intimidation, injury, or other physical suffering or bodily harm.-Forms of physical abuse:*Striking*Punching*Belting*Pushing, pulling*Slapping*Whipping*Striking with an object... , or confinement in a fixed position such as after a stroke Stroke A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage... , due to alcohol intoxication or in prolonged surgery Surgery Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical... |
| Blood supply | Arterial thrombosis Thrombosis Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss... (blood clots forming locally) or embolism Embolism In medicine, an embolism is the event of lodging of an embolus into a narrow capillary vessel of an arterial bed which causes a blockage in a distant part of the body.Embolization is... (clots or other debris from elsewhere in the body), clamping of an artery Hemostat A hemostat , is a vital surgical tool used in almost any surgical procedure, usually to control bleeding. Therefore, it is not uncommon to see the initial incision lined with hemostats closing blood vessels awaiting ligation during the initial phases of surgery... during surgery |
| Metabolism | Hyperglycemic hyperosmolar state Nonketotic hyperosmolar coma Nonketotic hyperosmolar coma is a type of diabetic coma associated with a high mortality seen in diabetes mellitus type 2. The preferred term used by the American Diabetes Association is hyperosmolar nonketotic state . Other commonly used names are hyperosmolar hyperglycemic nonketotic coma or... ), hyper- Hypernatremia Hypernatremia or hypernatraemia is an electrolyte disturbance that is defined by an elevated sodium level in the blood. Hypernatremia is generally not caused by an excess of sodium, but rather by a relative deficit of free water in the body... and hyponatremia Hyponatremia Hyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular... (elevated or reduced blood sodium levels), hypokalemia Hypokalemia Hypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low... (low potassium levels), hypocalcemia (low calcium levels), hypophosphatemia Hypophosphatemia Hypophosphatemia is an electrolyte disturbance in which there is an abnormally low level of phosphate in the blood. The condition has many causes, but is most commonly seen when malnourished patients are given large amounts of carbohydrates, which creates a high phosphorus demand by cells,... (low phosphate levels), ketoacidosis Ketoacidosis Ketoacidosis is a metabolic state associated with high concentrations of ketone bodies, formed by the breakdown of fatty acids and the deamination of amino acids. The two common ketones produced in humans are acetoacetic acid and β-hydroxybutyrate.... (e.g. in diabetic ketoacidosis Diabetic ketoacidosis Diabetic ketoacidosis is a potentially life-threatening complication in patients with diabetes mellitus. It happens predominantly in those with type 1 diabetes, but it can occur in those with type 2 diabetes under certain circumstances... ) or hypothyroidism Hypothyroidism Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or... (abnormally low thyroid function) |
| Body temperature | Hyperthermia Hyperthermia Hyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate... (high body temperature) and heat illness Heat illness Heat illness or heat-related illness is a spectrum of disorders due to environmental heat exposure. It includes minor conditions such as heat cramps, heat syncope, and heat exhaustion as well as the more severe condition known as heat stroke.... , hypothermia Hypothermia Hypothermia is a condition in which core temperature drops below the required temperature for normal metabolism and body functions which is defined as . Body temperature is usually maintained near a constant level of through biologic homeostasis or thermoregulation... (very low body temperature) |
| Drugs and toxins | Many medications increase the risk of rhabdomyolysis. The most important ones are:
Poisons linked to rhabdomyolysis are heavy metals and venom Venom Venom is the general term referring to any variety of toxins used by certain types of animals that inject it into their victims by the means of a bite or a sting... from insects or snakes. Hemlock Conium Conium is a genus of two species of highly poisonous perennial herbaceous flowering plants in the family Apiaceae, native to Europe and the Mediterranean region as Conium maculatum, and to southern Africa as Conium chaerophylloides.... may cause rhabdomyolysis, either directly or after consuming quail Quail Quail is a collective name for several genera of mid-sized birds generally considered in the order Galliformes. Old World quail are found in the family Phasianidae, while New World quail are found in the family Odontophoridae... that have fed on it. Haff disease Haff disease Haff disease is the development of rhabdomyolysis within 24 hours of ingesting fish.-History:... is rhabdomyolysis after consuming fish; a toxic cause is suspected but has not been proven. Drugs of abuse, including: alcohol Ethanol Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a... , amphetamine Amphetamine Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,... , cocaine Cocaine Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic... , heroin, ketamine Ketamine Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist... , LSD and MDMA (ecstasy) |
| Infection | Coxsackie virus Coxsackie A virus Coxsackie A virus is a cytolytic coxsackie virus of the Picornaviridae family, an enterovirus .-Diseases:... , influenza A virus and influenza B virus, Epstein-Barr virus Epstein-Barr virus The Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis... , primary HIV infection Acute HIV infection Acute HIV infection or primary HIV infection is the second stage of HIV infection. It occurs after the incubation stage, before the latency stage and the potential AIDS succeeding the latency stage.... , Plasmodium falciparum Plasmodium falciparum Plasmodium falciparum is a protozoan parasite, one of the species of Plasmodium that cause malaria in humans. It is transmitted by the female Anopheles mosquito. Malaria caused by this species is the most dangerous form of malaria, with the highest rates of complications and mortality... (malaria Malaria Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases... ), herpes viruses Herpesviridae The Herpesviridae are a large family of DNA viruses that cause diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word herpein , referring to the latent, recurring infections typical of this group of viruses... , Legionella pneumophila Legionella pneumophila Legionella pneumophila is a thin, ærobic, pleomorphic, flagellated, non-spore forming, Gram-negative bacterium of the genus Legionella. L. pneumophila is the primary human pathogenic bacterium in this group and is the causative agent of legionellosis or Legionnaires' disease.-Characterization:L... and salmonella Salmonella Salmonella is a genus of rod-shaped, Gram-negative, non-spore-forming, predominantly motile enterobacteria with diameters around 0.7 to 1.5 µm, lengths from 2 to 5 µm, and flagella which grade in all directions . They are chemoorganotrophs, obtaining their energy from oxidation and reduction... |
| Inflammation | Autoimmune muscle damage: polymyositis Polymyositis Polymyositis is a type of chronic inflammation of the muscles related to dermatomyositis and inclusion body myositis.-Signs and symptoms:... , dermatomyositis Dermatomyositis Dermatomyositis is a connective-tissue disease related to polymyositis and Bramaticosis that is characterized by inflammation of the muscles and the skin.- Causes :... |
Genetic predisposition
Recurrent rhabdomyolysis may result from intrinsic muscle enzyme deficiencies, which are usually inherited and often appear during childhood. Many structural muscle diseases feature episodes of rhabdomyolysis that are triggered by exercise, general anesthesiaGeneral anaesthesia
General anaesthesia is a state of unconsciousness and loss of protective reflexes resulting from the administration of one or more general anaesthetic agents...
or any of the other causes of rhabdomyolysis listed above. Inherited muscle disorders and infections together cause the majority of rhabdomyolysis in children.
The following hereditary disorders of the muscle energy supply may cause recurrent and usually exertional rhabdomyolysis:
- GlycolysisGlycolysisGlycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...
and glycogenolysisGlycogenolysisGlycogenolysis is the conversion of glycogen polymers to glucose monomers. Glycogen is catabolized by removal of a glucose monomer through cleavage with inorganic phosphate to produce glucose-1-phosphate...
defects: McArdle's diseaseGlycogen storage disease type VGlycogen storage disease type V is a metabolic disorder, more specifically a glycogen storage disease, caused by a deficiency of myophosphorylase. Its incidence is reported as 1 in 100,000, approximately the same as glycogen storage disease type I....
, phosphofructokinase deficiencyPhosphofructokinase DeficiencyPhosphofructokinase deficiency, also known as Glycogen storage disease type VII or Tarui's disease, is metabolic disorder with autosomal recessive inheritance.It may affect humans as well as other mammals...
, glycogen storage diseases VIII, IX, XGlycogen storage disease type VIGlycogen storage disease type VI is a type of glycogen storage disease caused by a deficiency in liver glycogen phosphorylase or other components of the associated phosphorylase cascade system.It is also known as "Hers' disease", after Henri G...
and XIGlycogen storage disease type XIGlycogen storage disease type XI is a form of glycogen storage disease.It is also known as "Fanconi-Bickel syndrome", for Guido Fanconi and Horst Bickel.It is associated with GLUT2.... - Lipid metabolism defects: carnitine palmitoyltransferase ICarnitine palmitoyltransferase I deficiencyCarnitine palmitoyltransferase I deficiency is a rare metabolic disorder that prevents the body from converting certain fats called long-chain fatty acids into energy, particularly during periods without food....
and II deficiencyCarnitine palmitoyltransferase II deficiencyCarnitine palmitoyltransferase II deficiency is a metabolic disorder characterized by an enzymatic defect that prevents long-chain fatty acids from being transported into the mitochondria for utilization as an energy source....
, deficiency of subtypes of acyl CoA dehydrogenaseAcyl CoA dehydrogenaseAcyl-CoA dehydrogenases are a class of enzymes that function to catalyze the initial step in each cycle of fatty acid β -oxidation in the mitochondria of cells. Their action results in the introduction of a trans double-bond between C2 and C3 of the acyl-CoA thioester substrate...
(LCADLong-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiencyLong-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency, often shortened to LCHAD deficiency, is a rare autosomal recessive fatty acid oxidation disorder that prevents the body from converting certain fats into energy...
, SCADShort-chain acyl-coenzyme A dehydrogenase deficiencyShort-chain acyl-coenzyme A dehydrogenase deficiency , also called ACADS deficiency and SCAD deficiency, is an autosomal recessive fatty acid oxidation disorder which affects enzymes required to break down a certain group of fats called short chain fatty acids.-Characteristics:Some affected infants...
, MCADMedium-chain acyl-coenzyme A dehydrogenase deficiencyMedium-chain acyl-coenzyme A dehydrogenase deficiency is a fatty acid oxidation disorder associated with inborn errors of metabolism. It is due to defects in the enzyme complex known as medium-chain acyl dehydrogenase and reduced activity of this complex...
, VLCADVery long-chain acyl-coenzyme A dehydrogenase deficiencyVery long-chain acyl-coenzyme A dehydrogenase deficiency is a fatty acid oxidation disorder which prevents the body from converting certain fats to energy, particularly during periods without food....
, 3-hydroxyacyl-coenzyme A dehydrogenase deficiency3-hydroxyacyl-coenzyme A dehydrogenase deficiency3-hydroxyacyl-coenzyme A dehydrogenase deficiency is a rare condition that prevents the body from converting certain fats to energy, particularly during fasting. Normally, through a process called fatty acid oxidation, several enzymes work in a step-wise fashion to metabolize fats and convert them...
), thiolaseThiolaseThiolases also known as acetyl-Coenzyme A acetyltransferases are enzymes which converts two units of acetyl-CoA to acetoacetyl CoA in the mevalonate pathway....
deficiency - Mitochondrial myopathiesMitochondrial myopathyMitochondrial myopathy is a type of myopathy associated with mitochondrial disease. On biopsy, the muscle tissue of patients with this disease usually demonstrate "ragged red" muscle fibers...
: deficiency of succinate dehydrogenase, cytochrome c oxidaseCytochrome c oxidaseThe enzyme cytochrome c oxidase or Complex IV is a large transmembrane protein complex found in bacteria and the mitochondrion.It is the last enzyme in the respiratory electron transport chain of mitochondria located in the mitochondrial membrane...
and coenzyme Q10 - Others: glucose-6-phosphate dehydrogenase deficiencyGlucose-6-phosphate dehydrogenase deficiencyGlucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of glucose-6-phosphate dehydrogenase , a metabolic enzyme involved in the pentose phosphate pathway, especially important in red blood cell metabolism. G6PD deficiency is...
, myoadenylate deaminase deficiencyMyoadenylate deaminase deficiencyAdenosine monophosphate deaminase deficiency type 1 is also called myoadenylate deaminase deficiency. It a recessive genetic metabolic disorder that affects approximately 1–2% of populations of European descent. It appears to be considerably rarer in Asian populations...
and muscular dystrophiesMuscular dystrophyMuscular dystrophy is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.In the 1860s, descriptions of boys who...
Mechanism
Myocyte
A myocyte is the type of cell found in muscles. They arise from myoblasts.Each myocyte contains myofibrils, which are long, long chains of sarcomeres, the contractile units of the cell....
directly or interfere with their blood supply, while non-physical causes interfere with muscle cell metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
. When damaged, muscle tissue rapidly fills with fluid from the bloodstream, including sodium ions
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
. The swelling itself may lead to destruction of muscle cells, but those cells that survive are subject to various disruptions that lead to rise in intracellular calcium ions; the accumulation of calcium in the sarcoplasmic reticulum leads to continuous muscle contraction
Muscle contraction
Muscle fiber generates tension through the action of actin and myosin cross-bridge cycling. While under tension, the muscle may lengthen, shorten, or remain the same...
and depletion of ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
, the main carrier of energy in the cell. ATP depletion can itself lead to uncontrolled calcium influx. The persistent contraction of the muscle cell leads to breakdown of intracellular proteins and disintegration of the cell.
Neutrophil granulocyte
Neutrophil granulocyte
Neutrophil granulocytes are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system. They are generally referred to as either neutrophils or polymorphonuclear neutrophils , and are subdivided into segmented neutrophils and banded neutrophils...
s—the most abundant type of white blood cell
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
—enter the muscle tissue, producing an inflammatory
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
reaction and releasing reactive oxygen species
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
, particularly after crush injury. Crush syndrome may also cause reperfusion injury
Reperfusion injury
Reperfusion injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen. The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and...
when blood flow to decompressed muscle is suddenly restored.
The swollen, inflamed muscle may directly compress structures in the same fascial compartment
Fascial compartment
On the human body, the limbs can be divided into segments, such as the arm and the forearm of the upper limb, and the thigh and the leg of the lower limb.If these segments are cut transversely, it is apparent that they are divided into multiple sections...
, causing compartment syndrome
Compartment syndrome
Compartment syndrome is a limb threatening and life threatening condition, defined as the compression of nerves, blood vessels, and muscle inside a closed space within the body . This leads to tissue death from lack of oxygenation due to the blood vessels being compressed by the raised pressure...
. The swelling may also further compromise blood supply into the area. Finally, destroyed muscle cells release potassium ions, phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
ions, the heme
Heme
A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...
-containing protein myoglobin
Myoglobin
Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in almost all mammals. It is related to hemoglobin, which is the iron- and oxygen-binding protein in blood, specifically in the red blood cells. The only time myoglobin is found in the...
, the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
creatine kinase
Creatine kinase
Creatine kinase , also known as creatine phosphokinase or phospho-creatine kinase , is an enzyme expressed by various tissues and cell types. CK catalyses the conversion of creatine and consumes adenosine triphosphate to create phosphocreatine and adenosine diphosphate...
and uric acid
Uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
(a breakdown product of purine
Purine
A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....
s from DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
) into the blood. Activation of the coagulation system may precipitate disseminated intravascular coagulation
Disseminated intravascular coagulation
Disseminated intravascular coagulation , also known as disseminated intravascular coagulopathy or consumptive coagulopathy, is a pathological activation of coagulation mechanisms that happens in response to a variety of diseases. DIC leads to the formation of small blood clots inside the blood...
. High potassium levels
Hyperkalemia
Hyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated...
may lead to potentially fatal disruptions in heart rhythm
Cardiac dysrhythmia
Cardiac dysrhythmia is any of a large and heterogeneous group of conditions in which there is abnormal electrical activity in the heart. The heart beat may be too fast or too slow, and may be regular or irregular.Some arrhythmias are life-threatening medical emergencies that can result in cardiac...
. Phosphate binds to calcium from the circulation, leading to low calcium levels in the blood.
Rhabdomyolysis may cause renal failure by several mechanisms. The most important problem is the accumulation of myoglobin in the kidney tubules. Normally, the blood protein haptoglobin
Haptoglobin
Haptoglobin is a protein that in humans is encoded by the HP gene. In blood plasma, haptoglobin binds free hemoglobin released from erythrocytes with high affinity and thereby inhibits its oxidative activity. The haptoglobin-hemoglobin complex will then be removed by the reticuloendothelial system...
binds circulating myoglobin and other heme-containing substances, but in rhabdomyolysis the quantity of myoglobin exceeds the binding capacity of haptoglobin. Myoglobinuria
Myoglobinuria
Myoglobinuria is the presence of myoglobin in the urine, usually associated with rhabdomyolysis or muscle destruction. Myoglobin is present in muscle cells as a reserve of oxygen.-Causes:...
, the presence of myoglobin in the urine, occurs when the level in plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
exceeds 0.5–1.5 mg/dl
Gram per litre
A gram per liter or litre is a unit of measurement of mass concentration that shows how many grams of a certain substance are present in one litre of a usually liquid or gaseous mixture. It is not an SI unit because it contains the non-SI unit litre...
; once plasma levels reach 100 mg/dl, the concentration in the urine becomes sufficient for it to be visibly discolored. About 200 grams of muscle needs to be destroyed for visible myoglobinuria to occur. As the kidneys reabsorb more water from the filtrate, myoglobin interacts with Tamm–Horsfall protein
Tamm-Horsfall protein
The Tamm-Horsfall glycoprotein also known as uromodulin is a glycoprotein that in humans is encoded by the UMOD gene. Up to 150 mg/dl of uromodulin may be excreted in the urine, making it the most abundant protein in normal urine.- Gene :...
in the nephron
Nephron
The renal tubule is the portion of the nephron containing the tubular fluid filtered through the glomerulus. After passing through the renal tubule, the filtrate continues to the collecting duct system, which is not part of the nephron....
to form casts (solid aggregates) that obstruct the normal flow of fluid; the condition is worsened further by high levels of uric acid and acidification of the filtrate, which increase cast formation. Iron released from the heme generates reactive oxygen species, damaging the kidney cells. In addition to the myoglobinuria, two other mechanisms contribute to renal impairment: low blood pressure leads to constriction of the blood vessels
Vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...
and therefore a relative lack of blood flow to the kidney, and finally uric acid may form crystals in the tubules of the kidneys, causing obstruction. Together, these processes lead to acute tubular necrosis
Acute tubular necrosis
Acute tubular necrosis or is a medical condition involving the death of tubular cells that form the tubule that transports urine to the ureters while reabsorbing 99% of the water . Tubular cells continually replace themselves and if the cause of ATN is removed then recovery is likely...
, the destruction of the cells of tubules. Glomerular filtration rate falls and the kidney is unable to perform its normal excretory functions. This causes disruption of electrolyte regulation, leading to a further rise in potassium levels, and interferes with vitamin D
Vitamin D
Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
processing, further worsening the low calcium levels.
Diagnosis
Creatinine
Creatinine is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body...
and urea
Blood urea nitrogen
The blood urea nitrogen test is a measure of the amount of nitrogen in the blood in the form of urea, and a measurement of renal function. Urea is a by- product from metabolism of proteins by the liver and is removed from the blood by the kidneys.-Physiology:The liver produces urea in the urea...
levels, falling urine output) or reddish-brown discoloration of the urine.
General investigations
The most reliable test in the diagnosis of rhabdomyolysis is the level of creatine kinaseCreatine kinase
Creatine kinase , also known as creatine phosphokinase or phospho-creatine kinase , is an enzyme expressed by various tissues and cell types. CK catalyses the conversion of creatine and consumes adenosine triphosphate to create phosphocreatine and adenosine diphosphate...
(CK) in the blood. This enzyme is released by damaged muscle, and levels above 5 times the upper limit of normal (ULN) indicate rhabdomyolysis. Depending on the extent of the rhabdomyolysis, concentrations up to 100,000 U
Enzyme unit
The enzyme unit is a unit for the amount of a particular enzyme.One U is defined as the amount of the enzyme that catalyzes the conversion of 1 micro mole of substrate per minute...
/l are not unusual. CK concentrations rise steadily for 12 hours after the original muscle injury, remain elevated for 1–3 days and then fall gradually. Initial and peak CK levels have a linear relationship with the risk of acute renal failure: the higher the CK, the more likely it is that kidney damage will occur. There is no specific concentration of CK above which renal impairment definitely occurs; concentrations below 20,000 U/l are unlikely to be associated with a risk of renal impairment, unless there are other contributing risk factors. Mild rises without renal impairment are referred to as "hyperCKemia". Myoglobin has a short half-life, and is therefore less useful as a diagnostic test in the later stages. Its detection in blood or urine is associated with a higher risk of renal impairment. Despite this, use of urine myoglobin measurement is not supported by evidence as it lacks specificity
Sensitivity and specificity
Sensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...
and the research studying its utility is of poor quality.
Elevated concentrations of the enzyme lactate dehydrogenase
Lactate dehydrogenase
Lactate dehydrogenase is an enzyme present in a wide variety of organisms, including plants and animals.Lactate dehydrogenases exist in four distinct enzyme classes. Two of them are cytochrome c-dependent enzymes, each acting on either D-lactate or L-lactate...
(LDH) may be detected. Other markers of muscle damage, such as aldolase
Aldolase
Aldolase A is an enzyme that catalyses a reverse aldol reaction: The substrate, fructose 1,6-bisphosphate is broken down into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate . This reaction is a part of glycolysis. Three aldolase isozymes , encoded by three different genes, are...
, troponin
Troponin
400px|thumb|right|alt = Colored dice with checkered background|Ribbon representation of the human cardiac troponin core complex in the calcium-saturated form...
, carbonic anhydrase type 3
Carbonic anhydrase III, muscle specific
Carbonic anhydrase 3 is an enzyme that in humans is encoded by the CA3 gene.-Further reading:...
and fatty acid-binding protein
Heart-type fatty acid binding protein
Heart-type fatty acid binding protein also known as mammary-derived growth inhibitor is a protein that in humans is encoded by the FABP3 gene.- Function :...
(FABP), are mainly used in chronic muscle diseases. The transaminase
Transaminase
In biochemistry, a transaminase or an aminotransferase is an enzyme that catalyzes a type of reaction between an amino acid and an α-keto acid. To be specific, this reaction involves removing the amino group from the amino acid, leaving behind an α-keto acid, and transferring it to the...
s, enzymes abundant in both liver and muscle tissue, are also usually increased; this can lead to the condition being confused with acute liver injury, at least in the early stages. The incidence of actual acute liver injury is 25% in people with non-traumatic rhabdomyolysis; the mechanism for this is uncertain.
High potassium levels
Hyperkalemia
Hyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated...
tend to be a feature of severe rhabdomyolysis. Electrocardiography (ECG) may show whether the elevated potassium levels are affecting the conduction system of the heart, as suggested by the presence of T wave
T wave
In electrocardiography, the T wave represents the repolarization of the ventricles. The interval from the beginning of the QRS complex to the apex of the T wave is referred to as the absolute refractory period. The last half of the T wave is referred to as the relative refractory period...
changes or broadening of the QRS complex
QRS complex
The QRS complex is a name for the combination of three of the graphical deflections seen on a typical electrocardiogram . It is usually the central and most visually obvious part of the tracing. It corresponds to the depolarization of the right and left ventricles of the human heart...
. Low calcium
Calcium in biology
Calcium plays a pivotal role in the physiology and biochemistry of organisms and the cell. It plays an important role in signal transduction pathways, where it acts as a second messenger, in neurotransmitter release from neurons, contraction of all muscle cell types, and fertilization...
levels may be present in the initial stage due to binding of free calcium to damaged muscle cells.
Urinalysis
Urinalysis
A urinalysis , also known as Routine and Microscopy , is an array of tests performed on urine, and one of the most common methods of medical diagnosis...
by urine test strip
Urine test strip
A urine test strip or dipstick is a basic diagnostic instrument used to determine pathological changes in the urine in standard urinalysis. A standard urine test strip may comprise up to 10 different chemical pads or reagents which react when immersed in, and then removed from, a urine sample....
may reveal a positive result for "blood", even though no red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s can be identified on microscopy
Microscopy
Microscopy is the technical field of using microscopes to view samples and objects that cannot be seen with the unaided eye...
of the urine; this occurs because the reagent on the test strip reacts with myoglobin. The same phenomenon may happen in conditions that lead to hemolysis
Hemolysis
Hemolysis —from the Greek meaning "blood" and meaning a "loosing", "setting free" or "releasing"—is the rupturing of erythrocytes and the release of their contents into surrounding fluid...
, the destruction of red blood cells; in hemolysis the blood serum
Blood serum
In blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...
is also visibly discolored, while in rhabdomyolysis it is normal. If kidney damage has occurred, microscopy of the urine also reveals urinary casts that appear pigmented and granular.
Complications
Compartment syndromeCompartment syndrome
Compartment syndrome is a limb threatening and life threatening condition, defined as the compression of nerves, blood vessels, and muscle inside a closed space within the body . This leads to tissue death from lack of oxygenation due to the blood vessels being compressed by the raised pressure...
is a clinical diagnosis, i.e. no diagnostic test conclusively proves its presence or absence, but direct measurement of the pressure in a fascial compartment, and the difference between this pressure and the blood pressure, may be used to assess its severity. High pressures in the compartment and a small difference between compartment pressure and blood pressure indicate that the blood supply is likely to be insufficient, and that surgical intervention may be needed.
Disseminated intravascular coagulation
Disseminated intravascular coagulation
Disseminated intravascular coagulation , also known as disseminated intravascular coagulopathy or consumptive coagulopathy, is a pathological activation of coagulation mechanisms that happens in response to a variety of diseases. DIC leads to the formation of small blood clots inside the blood...
, another complication of rhabdomyolysis and other forms of critical illness, may be suspected on the basis of unexpected bleeding or abnormalities in hematological tests, such as a decreasing platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
count or prolongation of the prothrombin time
Prothrombin time
The prothrombin time and its derived measures of prothrombin ratio and international normalized ratio are measures of the extrinsic pathway of coagulation. This test is also called "ProTime INR" and "INR PT". They are used to determine the clotting tendency of blood, in the measure of warfarin...
. The diagnosis can be confirmed with standard blood tests for DIC, such as D-dimer
D-dimer
D-dimer is a fibrin degradation product , a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. It is so named because it contains two crosslinked D fragments of the fibrinogen protein....
.
Underlying disorders
If an underlying muscle disease is suspected, for instance if there is no obvious explanation or there have been multiple episodes, it may be necessary to perform further investigations. During an attack, low levels of carnitineCarnitine
Carnitine is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine. In living cells, it is required for the transport of fatty acids from the cytosol into the mitochondria during the breakdown of lipids for the generation of metabolic energy. It is widely...
in the blood and high levels of acylcarnitine in blood and urine may indicate a lipid metabolism defect, but these abnormalities revert to normal during convalescence. Other tests may be used at that stage to demonstrate these disorders. Disorders of glycolysis
Glycolysis
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...
can be detected by various means, including the measurement of lactate
Lactic acid
Lactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3...
after exercise; a failure of the lactate to rise may be indicative of a disorder in glycolysis, while an exaggerated response is typical of mitochondrial disease
Mitochondrial disease
Mitochondrial diseases are a group of disorders caused by dysfunctional mitochondria, the organelles that are the "powerhouses" of the cell. Mitochondria are found in every cell of the human body except red blood cells...
s. Electromyography
Electromyography
Electromyography is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph, to produce a record called an electromyogram. An electromyograph detects the electrical potential generated by muscle...
(EMG) may show particular patterns in specific muscle diseases; for instance, McArdle's disease
Glycogen storage disease type V
Glycogen storage disease type V is a metabolic disorder, more specifically a glycogen storage disease, caused by a deficiency of myophosphorylase. Its incidence is reported as 1 in 100,000, approximately the same as glycogen storage disease type I....
and phosphofructokinase deficiency
Phosphofructokinase Deficiency
Phosphofructokinase deficiency, also known as Glycogen storage disease type VII or Tarui's disease, is metabolic disorder with autosomal recessive inheritance.It may affect humans as well as other mammals...
show a phenomenon called cramp-like contracture. There are genetic tests available for many of the hereditary muscle conditions that predispose to myoglobinuria and rhabdomyolysis.
Muscle biopsy
Muscle biopsy
In medicine, a muscle biopsy is a procedure in which a piece of muscle tissue is removed from an organism and examined microscopically. A biopsy needle is usually inserted into a muscle, wherein a small amount of tissue remains. Alternatively, an "open biopsy" can be performed by obtaining the...
can be useful if an episode of rhabdomyolysis is thought to be the result of an underlying muscle disorder. A biopsy sample taken during an episode is often uninformative, as it will show only evidence of cell death
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
or may appear normal. Taking the sample is therefore delayed for several weeks or months. The histopathological
Histopathology
Histopathology refers to the microscopic examination of tissue in order to study the manifestations of disease...
appearance on the biopsy indicates the nature of the underlying disorder. For instance, mitochondrial diseases are characterised by ragged red fibers. Biopsy sites may be identified by medical imaging
Medical imaging
Medical imaging is the technique and process used to create images of the human body for clinical purposes or medical science...
, such as magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
, as the muscles may not be uniformly affected.
Treatment
The main goal of treatment is to treat shock and preserve kidney function. Initially this is done through the administration of generous amounts of intravenous fluids, usually isotonic salineSaline (medicine)
In medicine, saline is a general term referring to a sterile solution of sodium chloride in water but is only sterile when it is to be placed intravenously, otherwise, a saline solution is a salt water solution...
(0.9% weight per volume sodium chloride
Sodium chloride
Sodium chloride, also known as salt, common salt, table salt or halite, is an inorganic compound with the formula NaCl. Sodium chloride is the salt most responsible for the salinity of the ocean and of the extracellular fluid of many multicellular organisms...
solution). In victims of crush syndrome it is recommended to administer intravenous fluids even before they are extracted from collapsed structures. This will ensure sufficient circulating volume to deal with the muscle cell swelling (which typically commences when blood supply is restored), and to prevent the deposition of myoglobin in the kidneys. Amounts of 6 to 12 liters over 24 hours are recommended. The rate of fluid administration may be altered to achieve a high urine output (200–300 ml/h in adults), unless there are other reasons why this might lead to complications, such as a history of heart failure.
While many sources recommend additional intravenous agents to reduce damage to the kidney, most of the evidence supporting this practice comes from animal studies, and is inconsistent and conflicting. The use of mannitol
Mannitol
Mannitol is a white, crystalline organic compound with the formula . This polyol is used as an osmotic diuretic agent and a weak renal vasodilator...
, which acts by osmosis
Osmosis
Osmosis is the movement of solvent molecules through a selectively permeable membrane into a region of higher solute concentration, aiming to equalize the solute concentrations on the two sides...
to enhance urine production and may prevent myoglobin deposition in the kidney, has not been directly studied in clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s. The addition of bicarbonate
Bicarbonate
In inorganic chemistry, bicarbonate is an intermediate form in the deprotonation of carbonic acid...
to the intravenous fluids may alleviate acidosis
Acidosis
Acidosis is an increased acidity in the blood and other body tissue . If not further qualified, it usually refers to acidity of the blood plasma....
(high acid level of the blood) and make the urine more alkaline to prevent cast formation in the kidneys, but there is limited evidence that it has benefits above saline alone, and it can worsen hypocalcemia by enhancing calcium and phosphate deposition in the tissues. If urine alkalinization is used, the pH of the urine is kept at 6.5 or above. Furosemide
Furosemide
Furosemide or frusemide is a loop diuretic used in the treatment of congestive heart failure and edema. It is most commonly marketed by Sanofi-Aventis under the brand name Lasix...
, a loop diuretic
Loop diuretic
Loop diuretics are diuretics that act on the ascending loop of Henle in the kidney. They are primarily used in medicine to treat hypertension and edema often due to congestive heart failure or renal insufficiency...
, is often used to ensure sufficient urine production, but evidence that this prevents renal failure is lacking.
Electrolytes
In the initial stages, electrolyte levels are often abnormal and require correction. High potassium levels can be life-threatening, and respond to increased urine production and renal replacement therapy (see below). Temporary measures include the administration of calcium to protect against cardiac complications, insulinInsulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
or salbutamol
Salbutamol
Salbutamol or albuterol is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease. It is marketed as Ventolin among other brand names....
to redistribute potassium into cells, and infusions of bicarbonate solution.
Calcium levels initially tend to be low, but as the situation improves calcium is released from where it has precipitated with phosphate, and vitamin D production resumes, leading to hypercalcemia (abnormally high calcium levels). This "overshoot" occurs in 20–30% of those people who have developed kidney failure.
Acute renal impairment
Renal replacement therapy
Renal replacement therapy is a term used to encompass life-supporting treatments for renal failure.It includes:*hemodialysis,*peritoneal dialysis,*hemofiltration and*renal transplantation.These treatments will not cure chronic kidney disease...
(RRT) may be required. RRT removes excess potassium, acid and phosphate that accumulate when the kidneys are unable to function normally and is required until kidney function is regained.
Three main modalities of RRT are available: hemodialysis
Hemodialysis
In medicine, hemodialysis is a method for removing waste products such as creatinine and urea, as well as free water from the blood when the kidneys are in renal failure. Hemodialysis is one of three renal replacement therapies .Hemodialysis can be an outpatient or inpatient therapy...
, continuous hemofiltration
Hemofiltration
In medicine, hemofiltration, also haemofiltration, is a renal replacement therapy similar to hemodialysis which is used almost exclusively in the intensive care setting...
and peritoneal dialysis
Peritoneal dialysis
Peritoneal dialysis is a treatment for patients with severe chronic kidney disease. The process uses the patient's peritoneum in the abdomen as a membrane across which fluids and dissolved substances are exchanged from the blood...
. The former two require access to the bloodstream (a dialysis catheter
Dialysis catheter
A dialysis catheter is a catheter used for exchanging blood to and from the hemodialysis machine from the patient.The dialysis catheter contains two lumens:*Venous*ArterialThis is a confusing terminology for layperson, because both lumens are in the vein...
), while peritoneal dialysis is achieved by instilling fluid into the abdominal cavity and later draining it. Hemodialysis, which is normally done several times a week in chronic kidney disease, is often required on a daily basis in rhabdomyolysis. Its advantage over continuous hemofiltration is that one machine can be used multiple times a day, and that continuous administration of anticoagulant
Anticoagulant
An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...
drugs is not necessary. Hemofiltration is more effective at removing large molecules from the bloodstream, such as myoglobin, but this does not seem to confer any particular benefit. Peritoneal dialysis may be difficult to administer in someone with severe abdominal injury, and it may be less effective than the other modalities.
Other complications
Compartment syndromeCompartment syndrome
Compartment syndrome is a limb threatening and life threatening condition, defined as the compression of nerves, blood vessels, and muscle inside a closed space within the body . This leads to tissue death from lack of oxygenation due to the blood vessels being compressed by the raised pressure...
is treated with surgery to relieve the pressure inside the muscle compartment and reduce the risk of compression on blood vessels and nerves in that area. Fasciotomy
Fasciotomy
Fasciotomy or fasciectomy is a surgical procedure where the fascia is cut to relieve tension or pressure . Fasciotomy is a limb-saving procedure when used to treat acute compartment syndrome. It is also sometimes used to treat chronic compartment stress syndrome...
is the incision of the affected compartment. Often, multiple incisions are made and left open until the swelling has reduced. At that point, the incisions are closed, often requiring debridement
Debridement
Debridement is the medical removal of a patient's dead, damaged, or infected tissue to improve the healing potential of the remaining healthy tissue...
(removal of non-viable tissue) and skin grafting
Skin grafting
Skin grafting is a type of graft surgery involving the transplantation of skin. The transplanted tissue is called a skin graft.Skin grafting is often used to treat:*Extensive wounding or trauma*Burns...
in the process. The need for fasciotomy may be decreased if mannitol is used, as it can relieve muscle swelling directly.
Disseminated intravascular coagulation
Disseminated intravascular coagulation
Disseminated intravascular coagulation , also known as disseminated intravascular coagulopathy or consumptive coagulopathy, is a pathological activation of coagulation mechanisms that happens in response to a variety of diseases. DIC leads to the formation of small blood clots inside the blood...
generally resolves when the underlying causes are treated, but supportive measures are often required. For instance, if the platelet count drops
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
significantly and there is resultant bleeding, platelets may be administered.
Prognosis
The prognosis depends on the underlying cause and whether any complications occur. Rhabdomyolysis complicated by acute kidney impairment in patients with traumatic injury may have a mortality rateMortality rate
Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...
of 20%. Admission to the intensive care unit is associated with a mortality of 22% in the absence of acute kidney injury, and 59% if renal impairment occurs. Most people who have sustained renal impairment due to rhabdomyolysis fully recover their renal function.
Epidemiology
The exact incidence of rhabdomyolysis is difficult to establish, because different definitions have been used. In 1995, hospitals in the U.S. reported 26,000 cases of rhabdomyolysis. Up to 85% of people with major traumatic injuries will experience some degree of rhabdomyolysis. Of those with rhabdomyolysis, 10–50% develop acute kidney injury. The risk is higher in people with a history of illicit drug use, alcohol misuse or trauma when compared to muscle diseases, and it is particularly high if multiple contributing factors occur together. Rhabdomyolysis accounts for 7–10% of all cases of acute kidney injury in the U.S.Crush injuries are common in major disasters, but especially so in earthquakes. The aftermath of the 1988 Spitak earthquake prompted the establishment, in 1995, of the Renal Disaster Relief Task Force, a working group of the International Society of Nephrology
International Society of Nephrology
The International Society of Nephrology is an international body representing specialists in nephrology . Its headquarters are located in Brussels, Belgium....
(a worldwide body of kidney experts). Its volunteer doctors and nurses assisted for the first time in the 1999 İzmit earthquake
1999 Izmit earthquake
The 1999 İzmit earthquake was a 7.6 magnitude earthquake that struck northwestern Turkey on August 17, 1999, at about 3:02am local time. The event lasted for 37 seconds, killing around 17,000 people and leaving approximately half a million people homeless...
in Turkey
Turkey
Turkey , known officially as the Republic of Turkey , is a Eurasian country located in Western Asia and in East Thrace in Southeastern Europe...
, where 462 people received dialysis, with positive results. Treatment units are generally established outside the immediate disaster area, as aftershock
Aftershock
An aftershock is a smaller earthquake that occurs after a previous large earthquake, in the same area of the main shock. If an aftershock is larger than the main shock, the aftershock is redesignated as the main shock and the original main shock is redesignated as a foreshock...
s could potentially injure or kill staff and make equipment unusable.
History
Coturnism
Coturnism is an illness featuring muscle tenderness and rhabdomyolysis after consuming quail . The condition was certainly known by the 4th century BC to ancient Greek and subsequently Roman naturalists, physicians and theologians...
(after Coturnix
Coturnix
Coturnix is a genus of Old World quail in Phasianidae.- Species list :*Blue Quail, Coturnix adansonii*King Quail, Coturnix chinensis*Rain Quail, Coturnix coromandelica*Harlequin Quail, Coturnix delegorguei*Common Quail, Coturnix coturnix...
, the main quail genus). Migrating quail consume large amounts of hemlock
Conium
Conium is a genus of two species of highly poisonous perennial herbaceous flowering plants in the family Apiaceae, native to Europe and the Mediterranean region as Conium maculatum, and to southern Africa as Conium chaerophylloides....
, a known cause of rhabdomyolysis.
In modern times, early reports from the 1908 Messina earthquake
1908 Messina earthquake
The 1908 Messina earthquake and tsunami took some 100,000–200,000 lives on December 28, 1908 in Sicily and Calabria, southern Italy.-Quake:On December 28, 1908 from about 05:20 to 05:21 an earthquake of 7.2 on the moment magnitude scale occurred centered on the of city Messina, in Sicily. Reggio...
and World War I on renal failure after injury were followed by studies by London physicians Eric Bywaters and Desmond Beall, working at the Royal Postgraduate Medical School
Royal Postgraduate Medical School
The Royal Postgraduate Medical School was an independent medical school, based primarily at Hammersmith Hospital in west London. In 1988, the school merged with the Institute of Obstetrics & Gynaecology, and in 1997 became part of the Imperial College School of Medicine.-History:The medical school...
and the National Institute for Medical Research
National Institute for Medical Research
The National Institute for Medical Research, commonly abbreviated to NIMR, is a medical research facility situated in Mill Hill, on the outskirts of London, England. It is mainly funded by the Medical Research Council, or MRC, and is its largest establishment and the only one designated as an...
, on four victims of The Blitz
The Blitz
The Blitz was the sustained strategic bombing of Britain by Nazi Germany between 7 September 1940 and 10 May 1941, during the Second World War. The city of London was bombed by the Luftwaffe for 76 consecutive nights and many towns and cities across the country followed...
in 1941. Myoglobin was demonstrated in the urine of victims by spectroscopy
Spectroscopy
Spectroscopy is the study of the interaction between matter and radiated energy. Historically, spectroscopy originated through the study of visible light dispersed according to its wavelength, e.g., by a prism. Later the concept was expanded greatly to comprise any interaction with radiative...
, and it was noted that the kidneys of victims resembled those of patients who had hemoglobinuria
Hemoglobinuria
In medicine, hemoglobinuria or haemoglobinuria is a condition in which the oxygen transport protein hemoglobin is found in abnormally high concentrations in the urine. The condition is often associated with hemolytic anemia, in which red blood cells are destroyed, thereby increasing levels of free...
(hemoglobin rather than myoglobin being the cause of the kidney damage). In 1944 Bywaters demonstrated experimentally that the renal failure was mainly caused by myoglobin. Already during the war, teams of doctors traveled to bombed areas to provide medical support, chiefly with intravenous fluids, as dialysis was not yet available. The prognosis of acute renal failure improved markedly when dialysis was added to supportive treatment, which first happened during the 1950–1953 Korean War
Korean War
The Korean War was a conventional war between South Korea, supported by the United Nations, and North Korea, supported by the People's Republic of China , with military material aid from the Soviet Union...
.
In other animals
In animals, rhabdomyolysis mainly affects horses. Horses can develop a number of muscle disorders, many of which may progress to rhabdomyolysis. Of these, some cause isolated attacks of rhabdomyolysis (e.g. dietary deficiency in vitamin EVitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings...
and selenium
Selenium
Selenium is a chemical element with atomic number 34, chemical symbol Se, and an atomic mass of 78.96. It is a nonmetal, whose properties are intermediate between those of adjacent chalcogen elements sulfur and tellurium...
, poisoning associated with pasture or agricultural poisons such as organophosphate
Organophosphate
An organophosphate is the general name for esters of phosphoric acid. Phosphates are probably the most pervasive organophosphorus compounds. Many of the most important biochemicals are organophosphates, including DNA and RNA as well as many cofactors that are essential for life...
s), while others predispose to exertional rhabdomyolysis (e.g. the hereditary condition equine polysaccharide storage myopathy
Equine polysaccharide storage myopathy
EPSM or Equine Polysaccharide Storage Myopathy is a muscle disease most commonly associated with heavy horse breeds. Common heavy horse breeds in the United States include the Clydesdale, Shire, Belgian Draft or Belgian, Suffolk Punch and Percheron. EPSM may also occur in the American Quarter...
). 5–10% of thoroughbred
Thoroughbred
The Thoroughbred is a horse breed best known for its use in horse racing. Although the word thoroughbred is sometimes used to refer to any breed of purebred horse, it technically refers only to the Thoroughbred breed...
horses and some standardbred horses suffer from the condition equine exertional rhabdomyolysis
Equine Exertional Rhabdomyolysis
Equine exertional rhabdomyolysis is a syndrome that damages the muscle tissue in horses...
; no specific cause has been identified, but an underlying muscle calcium regulation disorder is suspected.
Rhabdomyolysis affecting horses may also occur in outbreaks; these have been reported in many European countries, and later in Canada, Australia, and the United States. It has been referred to as "atypical myopathy" or "myoglobinuria of unknown etiology". No single cause has yet been found, but various mechanisms have been proposed, and a seasonal pattern has been observed. Very high creatine kinase levels are detected, and mortality from this condition is 89%.