(09) Clin Corr: Malignant Hyerpthermia Flashcards
What went wrong after giving the anesthesia?
- increased end tidal CO2 (110 mmHG)
- Hyperthermia (107)
- Tachycardia HR 108 bpm (vs 32-48)
- premature ventricular contractions
- Blood pH at 6.7, PaCO2 137 mmHg, PaO2 110 mmHg
- Hypertension
- High hemoconcentration
What did they treat the ventricular tachycardia with?
- magnesium sulfate and lidocaine
Voltage potential propagates into the T-tubule
Activates _____ (_____)
Activates \_\_\_\_\_ (\_\_\_\_\_) in the sarcoplasmic reticulum (SR)
_____ release into the cytoplasm
Ca2+ unbinds calsequestrin and binds to _____, uncovering myosin crossbridge binding sites on _____
Concentric contraction initiated
SERCA Ca2+-ATPase actively pumps Ca2+ back into the SR
Ca2+ is no longer bound to troponin C, the
troponin complex goes back to blocking binding
sites on actin.
- dihydropyridine receptors, DHPR
- ryanodine receptors, RYR
- Ca2+
- Troponin C
Mutation of what gene leads to Malignant Hyperthermia? (in what)?
What does this cause in humans?
MH in humans has also been associated with mutations in _____.
- gene encoding the skeletal muscle ryanodine receptor (RYR1)
- pigs, humans, dogs, horses
- central core disease, multi-mini core disease
- DHPR
• MH crisis results from uncontrolled muscle _____ release
• In vitro contracture test:
– Increased sensitivity to
_____ and _____
• SR calcium channels form MH pigs:
– Increased ______
release
– Enhanced activation by
______, ______
– Enhanced t-tubule
______
– Reduces inhibition by high
concentrations of _____ and
_____
- Ca2+
- caffeine, halothane
- calcium-induced-calcium
- caffeine, halothane
- depolarization
- calcium,
What type of disease is malignant hyperthermia?
List the types of anesthesia?
- How many RYR1 mutations have been identified in humans?
What domain are RYR1 found in in pigs? dogs? horses?
- autosomal dominant pharmacogenetic disease
- halothane > isoflurane > sevoflurane > desflurane
- > 80
- 1, 1, 2
What is particular is the fuck up in malignant hyperthermia?
What results due to this?
- abnormally induced or prolonged open state of RYR
- increased intracellular Ca2+
- sustained muscle cell activation and contraction
- increased aerobic and anaerobic metabolism
look at this for a spell
What induces the ventricular fibrillation?
Another thing I forgot to mention….
- Markedly increased ________ ventilation during ______ ventilation.
- hyperkalemia (high K)
- minute, spontaneous
(Clinical Findings During General Anesthesia)
Muscle rigidity-
- Initially _______ muscle spasm, contraction of _____
- Generalized muscle ______
- Protraction of the _________ and _______ of the globe
- _______ (brown, coffee-colored urine)
- masseter
- rigidity
- third eyelied, retraction
- myoglobinuria
(Laboratory Findings During General Anesthesia)
List them (there are 7)
-reminder PRAMHHH
- poor oxygenation depsite mechanical ventilation
- respiratory acidosis
- acidemia
- metabolic (lactic) acidosis
- hypertension
- hemoconcentration
- hyperproteinemia
(Laboratory Findings During general anesthesia) PART 2
List them (CHARE)
- hyperglycemia
- azotemia (increased blood urea nitrogen and creatinine)
- rhabdomyolysis
- Electrolyte abnormalties (high K, Phosphate, low chloride, low or high natremia, calcium)
- coagulopathy
What is used as treatement for malignant hyperthemry?
- Dantrolene (only specific treatment), abolishes excitation-contraction coupling, decreases intracellular calcium (by actin on ryanodine receptor)
- Supportive care (fluids, acid/base, hyperkalemia)
What is the combo that she talks about?
(Polysaccaride Storage Myopathy) LOOK AT TITLE
- A common inherited _____ in horses
- A dmoinant mutation in _____
- Unregulated _____ activity
- Accumulation of excess ____ and _____
- What percentage of horses are hetero and homo?
Phenotype?
- what can it cause?
- glycogenolysis
- GYS1
- glycogen synthas
- glycogen - abnormal, less branched polysaccharide
- 6%, 94% (quarter horses)
- varies widely
- exertional rhabdomyolysis, recumbency resulting in euthanasia
What are some environmental factors that affect phenotypic expression of polysaccharide storage myopathy?
- decreased consumption of starch (helps) - consistent daily exercise (these reduce exertional rhabdomylosis 75%)
- Allelic heterogeneity
- modifying genes
What was her hypothesis about the phenotypic variation?
- phenotypic variation in PSSM may be due in large part to presence of modifying genes
What are the three steps of identifying a modifying gene?
- genetic assocation (identifying a candidate gene)
- exercise trial (demonstrate clinical significance)
- retrospective analysis
Where is the GYS1 locus?
- ECA10
What was her hypothesis about the combo?
What did she notice when fed fat vs starch?
How did they meausre this?
- RYR1 mutation results in a more sever clinical phenotype in this family
- The affected horses fared much better on a high fat diet than on a high starch diet.
- creatinine kinase in the blood
- Horses with both GYS1 and RYR1 were more likely to have _____ rhabdomyolysis
- non-exertional
- What is the prevalence of RYR1 mutation in quarter horse and related?
- 0.5 to 1%
