MALIGNANT HYPERTHERMIA GUIDE QUESTIONS

1. What is the role of calcium in the development of malignant hyperthermia?

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RYR1 receptor for ryanodine

On the sarcoplasmic reticulum is where I mean
The receptor controls release of calcium stores
But with Malignant Hyperthermia it doesn't close its doors.
The calcium exposes binding sites on actin,
Then ATP and myosin form an attraction.
ATP hydrolis causes muscle contraction,
This is how your muscles are called to into action.
But too much calcium can be a bad thing.
When all of your muscles are contracting.
The SERCA pump and MYOSIN both use ATP
Causing hyperthermia from the use of energy.
The increased cellular Ca concentration stimulates metabolism both
directly, through activation of phosphorylase to increase glycolysis, and
indirectly, bec. Of an increased demand for ATP production. ATPases are
important components of myofilament relaxtion and the Ca sequestration
pumps of the sarcoplasmic reticulum and sarcolemma.
As ATPs depleted within the muscle cell,
Metabolism causes CO2 to rise as well.
Sympathetic stimulus increase the heart rate
With no intervention death with surely be your fate.
Increased metabolism = SNS Stimulation = tachycardia

2. Why is metabolic acidosis manifested by patients with malignant

hyperthermia?
- Cell demands ATP = Body compensates = breakdown of carbs, lipids,
proteins = end product is CO2 = CO2 causes anaerobic metabolism and
CO2 binds with H20 forming hydrogen ions and bicarbonates = Early lactic
acid formation/carbonic acid.
- Metabolism produces acidic products that lower the pH of the body fluids.
For example, carbon dioxide is a by-product of metabolism, and carbon
dioxide combines with water to form carbonic acid. Also, lactic acid is a
product of anaerobic metabolism, protein metabolism produces
phosphoric and sulfuric acids, and lipid metabolism produces fatty acids.
These acidic substances must continuously be eliminated from the body to
maintain pH homeostasis. Rapid elimination of acidic products of
metabolism results in alkalosis, and the failure to eliminate acidic products
of metabolism results in acidosis.
- Metabolic acidosis results from all conditions that decrease the pH of the
body fluids below 7.35, with the exception of conditions resulting from
altered function of the respiratory system. As hydrogen ions accumulate in
the body fluids, buffers first resist a decline in pH. If the buffers cannot
compensate for the increase in hydrogen ions, the respiratory center helps
regulate the body fluid pH. The reduced pH stimulates the respiratory
center, which causes hyperventilation. During hyperventilation, carbon
dioxide is eliminated at a greater rate. The elimination of carbon dioxide

also eliminates excess hydrogen ions and helps maintain the pH of the
body fluids within a normal range.
3. What is the electron transport system? What is its role in hyperthermia?
4. What is the mechanism for the development of hyperkalemia in this case?
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Acidosis decreases binding of calcium to albumin and tends to increase

serum ionized calcium levels. In addition, acidemia causes an extracellular
shift of potassium, but respiratory acidosis rarely causes clinically
significant hyperkalemia.
A frequently cited mechanism for these findings is that acidosis causes
potassium to move from cells to extracellular fluid (plasma) in exchange
for hydrogen ions
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 outside 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.
H ions in blood vessels = body compensates = K goes to extracellular
level in exchange for H ions.
Persistent muscle contraction, Breakdown of proteins = breakdown of
intracellular proteins = disintegration of cells = K goes out =
hyperkalemia

MH is a subclinical myopathy that allows large quantities of calcium to be released from the sarcoplasmic
reticulum (SR) of skeletal muscle and cause a hypermetabolic state after exposure to triggering agents. Altered
calcium channel gating kinetics in the SR is the underlying cause. The sustained elevation of calcium allows
excessive stimulation of aerobic and anaerobic glycolytic metabolism, which accounts for respiratory and
metabolic acidosis, rigidity, altered cell permeability, and hyperkalemia.