18 y/o female with hyperthermia
Case Based Learning - Case-based learning is an active learning strategy in which students read and discuss complex, real-life scenarios that call on their analytical thinking skills and decision-making.
You will work on this case in 8 groups of 7 students per group at tables in classroom 2.125. The group should discuss the case and the questions (10 min) and then each member of the group should pick one of the 7 questions to research during the during the next 30 minutes of the first session and submit their answer using this form. During the last 10 minutes of the first session, the 7 students who researched each question will form a new group (e.g., 7 students who worked on question 1) and take 10 minutes to discuss their individual answers and make plans for coming up with a group consensus answer to be presented during the second session for the case. During the second session, one or more students from each group will present the answer to their group’s question for 5 minutes followed by 2 minutes for questions from the class.
Pre-reading
Costanzo (sections on muscle)
Youtube (good video - you may want to kill the soundtrack)
Patient Presentation
18-year-old Stephanie Kuleba was a senior in high school, a cheerleader, and making plans to attend the University of Florida as a pre-med student. She had gone to an outpatient surgical center for cosmetic breast surgery to correct asymmetrical breasts. The surgeon was a board certified plastic surgeon with offices in Fort Lauderdale, Boca Raton and West Palm Beach. She was anesthetized with halothane. About an hour and 45 minutes after she went into the surgical suite, the surgeon came out to tell her mother that there had been an emergency and that paramedics had been called to take her to a nearby hospital. He reported that Stephanie had developed a heart rate of 120 beats per minute, muscle rigidity, and a fever of 112 F.
Learning Objectives:
- Contrast the signal transduction mechanisms of skeletal, smooth, and cardiac muscle.
- Diagram the sequence of events in excitation - contraction of skeletal muscle showing the intracellular compartments and molecules involved in muscle contraction and relaxation.
- Draw & label the structure of a sarcomere. Describe the location and function of the ryanodine receptor.
- Describe the signs and pathophysiology of malignant hyperthermia on basal metabolic rate (BMR), arterial blood gases, lactate, muscle breakdown (rhabdomyolysis) and renal function (urine chemistry).
- Explain the mechanisms that regulate human body temperature under normal conditions and during fever and hyperthermia. Explain why Stephanie’s body temperature increased to 112 F and the clinical interventions used to reduce high body temperatures.
- Describe the mechanisms of muscle cramping and tetany.
- Explain the etiology (genetic basis), epidemiology, and treatment (including rationale) of malignant hyperthermia.
History of Present Illness (HPI)
When Stephanie arrived at the emergency department of the hospital she was unconscious. Her mother reported that Stephanie had no known drug allergies and had no medical problems other than the asymmetrical breasts.
Stephanie was taken to the intensive care unit. An arterial catheter was placed as was a Foley catheter for urine collection.
Physical Exam
General – comatose, hyperthermic, rigid muscles
Vital signs
Oxygen saturation – 70% (normal = 95 - 100%)
Blood pressure 135/95 mm Hg (normal = 120/80 mmHg)
Pulse - 115 beats per minute (normal = 60 - 100 bpm)
Respiration 25 breaths per minute (normal = 8 - 115 bpm)
Weight - 115 lbs
Height - 5’4”
Body temperature – 112 Fahrenheit (44.4 C)
Laboratory Tests/Investigations
EKG – irregular heart rate with premature ventricular contractions (PVCs) and atrial fibrillation
Metabolism
Oxygen consumption = 500 ml/min (normal = 250)
Carbon dioxide production = 500 ml/min (normal = 200)
Enzymes
Creatinine kinase - 300 IU/L (normal = 25 - 90 IU/L)
Arterial Blood Gases
PO2 = 60 mm Hg (normal = 75 -110)
PCO2 = 60 mm Hg (normal = 40 mm Hg)
pH = 6.6 (normal = 7.35 - 7.45)
Blood Chemistry
Na = 140 mEq/L (normal = 136 - 145 mEq/L)
K = 8 mEq/L (normal = 4 mEq/L)
Cl = 110 mEq/L (normal = 95 -105)
HCO3- = 6 mEq/L (normal = 24 mEq/L)
Urine Chemistry
Color – reddish brown
pH – 4.2
Myoglobinuria
- Contrast the signal transduction mechanisms of skeletal, smooth, and cardiac muscle.
From Google Form:
They all have excitation, depolarization, and triggers the release of calcium but smooth muscle does not have any second messenger receptors so they cannot be influenced by hormones/second messengers/Gproteins etc.
Cardiac and smooth muscle undergo second-messenger based intracellular signaling while skeletal muscle undergoes depolarization-based transduction. All muscle cells utilize calcium as a mediator for contraction but in slightly different mechanisms. Smooth muscle can utilize GPCR Aq linked system as well as a calcium-based system similar to that of skeletal muscle where calcium is bound to calmodulin and then activates myosin-light-chain-kinase which undergoes a cyclical reaction with kinase phosphatase both of which effect myosin which then interacts with the crossbridging of actin-myosin.
Skeletal- The depolarization is propagated directly by the cell membrane to the T tubules. This leads to the release of the Ca2+ intracellularly from the sarcoplasmic reticulum which goes on to bind to troponin C and eventually lead to a contraction. It is based on a direct pathway from the neuron. Smooth- The ligand channels release intracellular Ca2+ from the sarcoplasmic reticulum after binding ligands (neurotransmitters or hormones). IP3 channels in the sarcoplasmic reticulum membrane also release Ca2+ after being opened by hormones and neurotransmitters. Voltage gated Ca2+ channels can be opened with subthreshold depolarization. Thus, smooth muscles cells unlike skeletal do NOT need a full action potential to BEGIN releasing Ca2+ which leads to a contraction. Cardiac- An action potential occurs in the cell membrane similarly to the skeletal muscle. However, unlike the action potential of the skeletal muscle, the inward current created by the Ca2+ flow through L-type Ca2+ channels creates a plateau in the action potential. The size of the plateau and the amount of Ca2+ stored in the SR dictate how much Ca2+ is released intracellularly which then bind to troponin C and lead to a contraction. Extra note: The receptors themselves can cause differences from muscle type to muscle type. For example, both smooth muscle and cardiac muscle contain Beta Adrenergic receptors which bind epinephrine. Cardiac muscle contains B1 receptors that activate adenylate cyclase increasing cAMP and leading to heart muscle contraction. In smooth muscle, the B2 receptors also activate adenylyl cyclase and also increase cAMP; however, the result is smooth muscle relaxation.
- Diagram the sequence of events in excitation - contraction of skeletal muscle showing the intracellular compartments and molecules involved in muscle contraction and relaxation.
From Google Form:
In order for muscle contraction to occur, three things must happen: calcium must be released from the sarcoplasmic reticulum and bind to troponin, ATP must bind to myosin, and myosin must move up the actin filament. The process of calcium release and subsequent binding occurs when an action potential from a neuromuscular junction travels down the sarcomere until it reaches the T-tubule. Here it opens up the voltage gated dihydropyridine which causes ryanodine to allow the release of calcium from the sarcoplasmic reticulum. Calcium binds to troponin which causes tropomyosin to shift away from the active site on actin, allowing myosin and actin to interact. The myosin head shifts via the binding of ATP, this reduces its affinity for actin, causing it to release and move up the actin chain. ATP undergoes hydrolysis from ATP to ADP + Pi in the myosin head, this "cocks" the head. The release of ADP + Pi allow the myosin head to change its conformation back to the original and be bound to the new site opened up by the shifting of tropomyosin.
- Draw & label the structure of a sarcomere. Describe the location and function of the ryanodine receptor.
- Describe the signs and pathophysiology of malignant hyperthermia on basal metabolic rate (BMR), arterial blood gases, lactate, muscle breakdown (rhabdomyolysis) and renal function (urine chemistry).
From Google Form:
An abnormality in the ryanodine receptor allows excessive Ca to leave the sarcoplasmic reticulum, binding to the troponin C, and maintaining persistent contraction. The basal metabolic rate is increased in efforts to provide ATP to the muscle. Cellular respiration produces ATP which provides energy for the muscle, and CO2 which begins to accumulate and is now in equilibrium with carbonic acid. This results in the decrease ph levels of the blood. Once the available oxygen is used, the muscle then switches to anaerobic respiration (lactate fermentation) producing ATP but also lactic acid (contributing to the low ph). Next, the body will begin to break down muscle (rhabdomyolysis), and creatine kinase in the blood is present during this time. Urine is a reddish brown color because the myoglobin from the muscle is excreted. Additionally, the persistent contraction of the muscle is generating too much heat, reaching the temperature of 112 degrees Fahrenheit.
An abnormality in the ryanodine receptor allows excessive Ca to leave the sarcoplasmic reticulum, binding to the troponin C, and maintaining persistent contraction. The basal metabolic rate is increased in efforts to provide ATP to the muscle. Cellular respiration produces ATP which provides energy for the muscle, and CO2 which begins to accumulate and is now in equilibrium with carbonic acid. This results in the decrease ph levels of the blood. Once the available oxygen is used, the muscle then switches to anaerobic respiration (lactate fermentation) producing ATP but also lactic acid (contributing to the low ph). Next, the body will begin to break down muscle (rhabdomyolysis), and creatine kinase in the blood is present during this time. Urine is a reddish brown color because the myoglobin from the muscle is excreted. Additionally, the persistent contraction of the muscle is generating too much heat, reaching the temperature of 112 degrees Fahrenheit.
Defects in the ryanodine receptor, which is then abnormally triggered by certain anesthetics such as halothane, causes consistent release of calcium from the sarcoplasmic reticulum into the myoplasm. This causes consistent muscle contraction, requiring large amounts of oxygen and ATP consumption and a greatly increased BMR. There is also an increased production of carbon dioxide in the muscle cells, leading to metabolic and respiratory acidosis. A switch to anaerobic metabolism leads to increased production of lactate, furthering metabolic acidosis. The very high temperature resulting from muscle contraction and ATP breakdown leads to rhabdomyolysis, and release of myoglobin, potassium, and creatinine kinase from muscle cells. High levels of myoglobin is released in urine, along with greater concentration of acid.
In malignant hyperthermia the basal metabolic rate is increased. Calcium is increased in the cell and this in turn causes increase in ATP consumption. When calcium is increased protease activation releasing intracellular creative kinase, myoglobin and other intracellular contents. The increase use of ATP consumption will move respiration to lactate respiration. The increase in lactate causes a decrease in the pH. The increase in muscle breakdown causes an increase in myoglobin that is excreted through the kidneys and able to be detected through urine chemistry.
BMR: Increase in intracellular calcium causes contractions which lead to a hypermetabolic state. Hypermetabolism causes increased carbon dioxide production and acidosis, which causes activation of sympathetic nervous system and increased heart rate. Arterial blood gases: The hypermetabolic state will cause cells to deplete all their ATP, which will increase membrane permeability, releasing arterial blood gasses Lactate: Is produced in high numbers due to prolonged, sustained contractions which deplete ATP and require cell to utilize anaerobic pyruvate-lactate pathway to create more energy. Muscle breakdown (rhabdomyolysis)- Muscle contraction causes cell to delete ATP stores. Membrane permeability is increased, causing ions and proteins to leave the cell. This causes destruction of the cell, and muscle breakdown by neutrophils. Muscle cell contents gets dumped into blood. Renal function- Kidneys filter the muscle cell contents, but become damaged when myoglobin reacts with Tamm-Horsfall protein in the kidney nephron, which form solid aggregates that obstruct normal flow of fluid. Iron released from heme generates oxidative oxygen species, which damage kidney cells. Low blood pressure constructs vessels and causes a lack of blood flow to kidneys, which can cause necrosis. Urine has high levels of myoglobin, potassium, and other muscle proteins/chemicals.
The abnormal ryanodine receptor interferes with the regulation of calcium in the muscle causing a build up of calcium inside the muscle cell, resulting in a massive metabolic reaction that is seen as muscle rigidity and fever. The sustained muscle contraction causes ATP depletion because of sustained cross-bridge cycling and calcium ATPase activity. The metabolic rate increase to provide ATP causes 1) an increase in oxidative phosphorylation, which increases oxygen consumption and carbon dioxide release (500ml/min in O2 consumption and CO2 production), 2) increase in glycolysis, which increases lactate production that leads to acidosis (HCO3-=6mEq/L in patient) in the absence of oxygen (PO2=60mmHg, PCO2=60, pH=6.6 in patient), 3) increase in heat production (112 degree F in patient). The ATP generated for the contraction come from Creatine Phosphate (fist source of energy, which is explained since the muscle is in a prolonged contraction), glycolysis , and oxidative phosphorylation (which produces the majority of the ATP and generates CO2). When homeostatic mechanisms cannot be sustained, membrane potentials cannot be maintained, and permeability of the cell membranes increase. This causes loss of phosphate and H+ as well as K+ and Mg++, and later myoglobin and creatine kinase. The myoglobinuria and reddish brown urine is indicative of muscle breakdown. Acidosis leads to sympathetic stimulation and the resulting increase in HR and blood pressure.
The clinical picture is often dramatic, with intense tachycardia, overproduction of CO2, muscular rigidity, respiratory and metabolic acidosis, hyperkalaemia and terminal haemodynamic collapse. The pathophysiology of the MH reaction involves inherited oversensitivity to triggering agents which, when used on MHS patients, can cause rapid accumulation of calcium in striated muscle myoplasm, resulting in muscle contracture followed by rhabdomyolysis and an intense heat producing reaction.
- Explain the mechanisms that regulate human body temperature under normal conditions and during fever and hyperthermia. Explain why Stephanie’s body temperature increased to 112 F and the clinical interventions used to reduce high body temperatures.
From Google Form:
Thermoregulation Summary • Preoptic Anterior Hypothalamus o Warm sensitive neurons ▪ Parasympathetic responses: Vasodilation, decrease thermogenesis, o Sympathetic response: Sweating • Posterior Hypothalamus o Cold sensitive neurons ▪ Sympathetic responses: Vasoconstriction, increased thermogenesis/shivering, ▪ Parasympathetic responses: Inhibition of sweating • Fever Summary o Phagocytic cells secrete cytokines upon being stimulated by exogenous/endogenous substances ▪ Interleukin-1 stimulates production of prostaglandin E2 ▪ PGE2 raises the set point in the hypothalamus • Stimulates cold sensitive neurons o Vasoconstriction, increased thermogenesis/shivering/chills Hyperthermia: Any elevation in body temperature that is above the normal accepted range Can be physiological (exercise) or pathological (malignant hyperthermia, hypermetabolism due to high levels of thyroid hormone or epinephrine) Can be due to a malfunction of the hypothalamic control centers Malignant Hyperthermia: The majority of MHS patients have mutations encoding for abnormal RYR1 or DHP receptors leading to unregulated release of calcium from the sarcoplasmic reticulum into the intracellular space. The accumulation of myoplasmic calcium causes sustained muscle contraction – generating heat. Accelerated levels of aerobic metabolism sustain the muscle for a time, but deplete oxygen and ATP. Reuptake of calcium by SERCA is uses ATP which also generates heat. Over time, sustained contraction (Hypermetabolism) generates more heat than the body is able to dissipate. Severe hyperthermia (up to 113ºF), which occurs minutes to hours following the initial onset of symptoms, leads to a marked increase in carbon dioxide production, and increased oxygen consumption that can cause widespread vital organ dysfunction. Severe hyperthermia is associated with the development of disseminated intravascular coagulation, a poor prognostic indicator and often terminal event Clinical Interventions Dantrolene: Postsynaptic muscle relaxant that lessens excitationcontraction coupling in muscle cells by antagonizing ryanodine receptors to inhibit Ca2+ ions release from sarcoplasmic reticulum. Noninvasive cooling techniques Evaporative cooling misting the patient’s body continuously to allow water to cool the skin through evaporation Ice water immersion place patient in an ice bath; administer benzodiazepines for shivering as needed Whole body or strategic ice packing –placing ice packs throughout the whole body or in select areas Invasive cooling techniques - Gastric lavage –using a nasogastric tube, water (or saline) with ice is instilled using a lavage bag - Peritoneal lavage – most effective, lavage is placed in a peritoneal catheter - Cold saline infusion together with a diuretic to prevent pulmonary edema and hyponatremia
- Describe the mechanisms of muscle cramping and tetany.
From Google Form:
Question 6 - Mechanism of Muscle Cramping and Tetany During muscle contraction, t-tubules carry the depolarization to the dihydropyridine receptor. This receptor activates a channel on the sarcoplasmic reticulum, Ryanodine. The voltage gated channel opens, releasing calcium. The calcium then binds to troponin C, causing a conformational change in tropomyosin. The conformational change allows the myosin head to bind with actin, forming a cross bridge. The myosin releases ADP and Pi to produce a pull that draws the actin centrally, a contraction. Relaxation of the muscle is obtained until the calcium bound to troponin is released and taken back to the sarcoplasmic reticulum by the SERCA channel. Muscle cramps and tetany are common disturbances in the muscle contraction and relaxation mechanism. These are sudden involuntary contraction of a skeletal muscle. Tetany occurs when a rapid stimuli from a motor neuron does not give the SERCA channel enough tome to reuptake calcium into the sarcoplasm, leaving the calcium bound to troponin C producing a continuous muscle contraction. The primary cause of tetany is hypocalcemia, which is a representation of low calcium levels in the extracellular fluid. This increases the permeability of sodium ion on the sarcoplasm, causing a progressive depolarization. In other words, the low calcium levels lower the threshold potential. If calcium levels decrease more than half its original state, action potentials can be spontaneously generated. All this occurs because calcium has a small affinity to the sodium voltage gated channel, meaning it can “plug” it during influx of sodium. Calcium can therefore act as a modulator for excitability. The second cause of tetany is the infection of Clostridium tetani; this gram-negative pathogen produces a strong toxin, tetanus toxin (TeTx), eventually causing a disease called tetanus. This toxin is distributed to motor neurons and prevents the release of inhibitory neurotransmitters, GABA and Glycine. These neurotransmitters serve as an inhibitory control of action potentials; this reduces inhibition, allowing for repeated stimulation of a muscle. Cramping is caused by dehydration. When a body is dehydrated, water and NaCl is lost from the extracellular fluid, this leads to swelling causing the calcium pump, Ryanodine, to “short circuit”. The high levels of calcium outside the sarcoplasmic reticulum allow calcium to maintain bound to troponin C, allowing contraction to persist. During dehydration, there is an increase of osmolality, which stimulates the secretion of ADH, antidiuretic hormone. This hormone will cause water retention in cells; this is done to maintain intravascular volume. If excessive water loss occurs and intravascular volume can’t be maintained the stimulation of renal sodium retention will occur. Sodium is a major solute in the extracellular fluid that determines the extracellular fluid (ECF) volume. The effective arterial blood volume is part of the extracellular fluid volume in the arteries; therefore all levels are proportional to each other. If sodium levels decrease during dehydration, ECF and EABV decrease as well. When the diminished level of EABV during dehydration is detected, the kidneys will halt sodium excretion by increasing sympathetic activity, decreasing atriopeptin and increasing renin-angiotensin aldosterone. The calcium parallels sodium reabsorption, therefore there is a decrease in calcium excretion as well. This lack of excretion signifies a high level of calcium in the cell, the calcium levels will not reach the low concentration needed to be picked up by SERCA efficiently and be removed from troponin C, meaning muscle relaxation will not occur, producing a muscle cramp.
7. Explain the etiology (genetic basis), epidemiology, and treatment (including rationale) of malignant hyperthermia.
From Google Form:
The genetic basis of malignant hyperthermia implicates the RYR1 gene. The RYR1 gene is responsible for the calcium release channel. A mutation of this gene causes malignant hyperthermia in some human families. The mutation consists of a substitution of a cysteine amino acid for an arginine 615. This is not observed in all human families with malignant hyperthermia. The epidemiology of malignant hyperthermia: it occurs in all ethnic groups in all parts of the world, most frequently in males than females with ration of 2:1. 45 - 52% of reported events occur in children under 19 years of age. The treatment protocol calls for administration of dantrolene. Dantrolene is thought to reduce muscle tone / metabolism by preventing an ongoing release of calcium from sarcoplasmic reticulum. In malignant hyperthermia intracellular calcium levels are elevated, dantrolene counteracts this.
SCW: The mode of inheritance of MHS is autosomal dominant with reduced penetrance and variable expressivity, although sporadic cases and recessive autosomal hereditary patterns have occasionally been seen.8 In recent years, a mutation in chromosome 19q13.1, linked to a mutation in the ryanodine receptor gene, was discovered to be linked to MHS
Dantrolene, which is a non-specific muscle relaxant. It probably acts by blocking the release of calcium from the sarcoplasmic reticulum of skeletal muscle cells.1 Before dantrolene was used in the treatment of an MH reaction, mortality was well above 50%.
The incidence of MH reaction during anaesthesia is estimated at from 1/15 000 in children, to 1/50 000 in adults.5 The acute MH syndrome is more prevalent in young individuals, with more than 50% of cases occurring before the age of 15.6 The MHS patient is normally in apparent good health, but suffers from subclinical myopathy which can be dramatically exposed when triggering agents are used during anaesthesia.
First discovered by Harrison to be of value in the therapy of MH crises in pigs,25 dantrolene was later confirmed as of value in a number of human MH episodes,26 and became the drug of choice in the prevention and treatment of acute MH crises. Dantrolene is a diphenylhydantoin analogue which is poorly soluble in water. Although the mechanism of action is still unclear, dantrolene appears to inhibit release of calcium from the sarcoplasmic reticulum to the myoplasm.25 Dantrolene is manufactured in a lyophilized formulation which also contains mannitol and sodium hydroxide. Each vial contains 20 mg dantrolene, 3 g mannitol and enough sodium hydroxide to raise the pH to 9.5. The lyophilized contents of each vial must be reconstituted with 60 ml sterile water. In an acute MH episode, a supply of at least 36 vials of dantrolene should be available for immediate use, which corresponds to a maximal dosage of 10 mg/kg in a 70 kg adult.21' 22 Dantrolene should be administered repeatedly in 2-3 mg/kg doses every 5-10 min, until symptoms are controlled.
Treatment
The attending physician’s diagnosis was malignant hyperthermia, probably triggered by halothane. Stephanie was intubated and hyperventilated with 100% oxygen. Dantrolene was administered in a 2.5mg/kg bolus and repeated at 2mg/kg every 5 minutes.
She was infused with cold IV normal saline and packed in ice bags in an attempt to lower her body temperature. Her acidosis was treated with IV sodium bicarbonate. Attempts were made to produce good urine output (maintain >2ml/kg/h urine output with conscientious fluid management; furosemide, mannitol).
Her arrhythmias were treated with procainamide and calcium chloride.
Patient Follow Up
Despite the aggressive intervention, Stephanie died 12 hours after admission.
Tutor Notes:
Malignant Hyperthermia is an inherited disorder and generally those who have it don't know they do until they are exposed to certain anesthesia. Additionally, there is no simple, straightforward test to diagnose the condition
The condition is reversible if recognized and acted upon - usually within 30 minutes of onset- with Dantrolene, the only known antidote,
The drug, which has a shelf life of about three years, isn't cheap. It costs about $2,200 for 36 vials, the dosage needed for a single treatment, said Rosenberg.
"It's like an insurance policy. You hope you never need it, but when you do, you do," he said. He said about 80 percent of hospitals have it.
Despite the risks, the number of cosmetic procedures has skyrocketed in recent years, particularly among those 18 and younger.
More than 333,000 adolescents 18 years or younger underwent plastic surgery and cosmetic procedures in 2005, according to the American Society of Plastic Surgeons. Breast augmentation was one of the most popular.
In 2007, there were 10,505 breast augmentation procedures performed on 18- and 19-year-olds; up from, 9,104 the year before. Another 1,700 teens between 13 and 19 underwent breast lift surgery.
And it's not just teenage girls undergoing breast surgery. Close to 14,000 males between the ages of 13 and 19 underwent gynecomastia, or breast reduction surgery, in 2006.
About one third of women will experience some degree of an inverted areola. As a woman gets older and wants to have children, corrective surgery is suggested in order to breast feed properly.
Triggering agents for MH are inhaled general anesthetic (GA) agents (i.e. halothane, desflurane and sevoflurane) and the muscle relaxant, succinycholine (SCH), used to intubate the airway.
Among those avoidable risks are MH, blood clots to the lungs, airway mishaps leading to lack of oxygen to the patient’s brain, postoperative nausea and vomiting (PONV), and postoperative cognitive disorder (POCD).
In susceptible individuals, these drugs can induce a drastic and uncontrolled increase in skeletal muscle oxidative metabolism which overwhelms the body's capacity to supply oxygen, remove carbon dioxide, and regulate body temperature, eventually leading to circulatory collapse and death if untreated.
Susceptibility to MH is often inherited as an autosomal dominant disorder, for which there are at least 6 genetic loci of interest,[1] most prominently the ryanodine receptor gene (RYR1). MH susceptibility is phenotypically and genetically related to central core disease (CCD), an autosomal dominant disorder characterized both by MH symptoms and myopathy. MH is usually unmasked by anesthesia, or when a family member develops the symptoms. There is no simple, straightforward test to diagnose the condition. When MH develops during a procedure, treatment with dantrolene sodium is usually initiated; dantrolene and the avoidance of anesthesia in susceptible people have markedly reduced the mortality from this condition.
Malignant hyperthermia is diagnosed on clinical grounds, but various investigations are generally performed. This includes blood tests, which may show a raised creatine kinase level, elevated potassium, increased phosphate (leading to decreased calcium) and - if determined - raised myoglobin; this is the result of damage to muscle cells. Metabolic acidosis and respiratory acidosis (raised acidity of the blood) may both occur. Severe rhabdomyolysis may lead to acute renal failure, so kidney function is generally measured on a frequent basis.[
Clinically, creatine kinase is assayed in blood tests as a marker of myocardial infarction (heart attack), rhabdomyolysis (severe muscle breakdown), muscular dystrophy and in acute renal failure.
MH is thought to be due to a reduction in the reuptake of calcium by the sarcoplasmic reticulum necessary for termination of muscle contraction. Consequently, muscle contraction is sustained, resulting in signs of hypermetabolism, including acidosis, tachycardia, hypercarbia, glycolysis, hypoxemia, and heat production (hyperthermia).
References:
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