Assignment # 1 :
Use ‘text-matching software’ in the FLO assignment tool before final assignment submission. The textmatching score value should be kept less than 35% similarity. There is no need to worry about a high
matching score if it is mainly due to the reference list.
Answer the sub-questions separately. A line break is necessary between answers to each sub-question.
1) The immediate cause of the hyperthermia was likely the general anaesthesia. Specific agents in
general anaesthesia can result in the development of malignant hyperthermia. Malignant
hyperthermia results in a change in the skeletal muscle tissues, causing the skeletal tissues to
contract involuntarily. This excessive contraction can result in shivering, which can generate heat
and elevate Mrs Binns body temperature.
2) No, as administering NSAIDS did not assist in reducing Mrs Binns core temperature. Therefore, it
is unlikely that an infection was the cause, as NSAIDS disrupt the production of prostaglandin E2 by
inhibiting cyclooxygenase’s action, which in turn will suppress a fever, which are caused by an
infection.
3) The likely agents are suxamethonium and isoflurane.
4) The likely agents suggest that Mrs Binns is experiencing malignant hyperthermia, in which case, a
defect in the ryanodine receptor is expected.1 Traditionally, ryanodine receptors function as
intracellular Ca2+ release channels.1 The rapid release of Ca2+ from the endo/sarcoplasmic (ER/SR)
reticulum is facilitated by the ryanodine receptors in order to incite cellular functions dependent on
Ca2+. Particularly, skeletal and cardiac muscle cell function relies heavily on the correct function of
the ryanodine receptors.1
5) The ryanodine receptor can trigger malignant hyperthermia through mutations of a particular
variant, RyR1, a variant of ryanodine receptor that is skeletal muscle tissue specific.1 Activation of
RyR1 can be triggered through a “volatile halogenated anaesthetic”, leading to a sudden increase in
core temperature. In this case, RyR1 rapidly releases Ca2+, resulting in repeated muscular
contractions. ATP is then hydrolysed, by the SERCA enzyme in order to pump Ca2+ to the ER/SR2.
However, this process is considered to be inefficient, and ATP is expended for no other purpose
than to lower intracellular Ca2+.2 This consumption in ATP results in excessive heat generation.2
6) The first line medication for malignant hyperthermia is Dantrolene.
7) Dantrolene alleviates malignant hyperthermia by acting as an antagonist towards ryanodine
receptors in the sarcoplasmic reticulum, which in turn inhibits the flow of Ca2+ required in order for
muscles to contract.3 This action occurs intracellularly in the skeletal muscle in order to relieve the
effects of the excitation-contraction coupling interaction noticed in sarcomeres between myosin and
actin.3 Despite this effect however, the specific mechanism of action of Dantrolene appears to be
unknown.4
References:
1. Santulli G, Lewis D, Georges A, Marks AR, Frank J. Ryanodine Receptor Structure and Function
in Health and Disease. Subcell Biochem. 2018 Feb 21;87:329-352
2. Rosenberg H, Pollock N, Schiemann A, Bulger T, Stowell K. Malignant hyperthermia: A Review.
Orphanet J Rare Dis. 2015;10(1).
3. Shi Y, Wang Y, Wei H. Dantrolene : From malignant hyperthermia to alzheimer’s disease. CNS
Neurol Disord Drug Targets. 2020;18(9):668–76.
4. Choi RH, Koenig X, Launikonis BS. Dantrolene requires Mg2+ to arrest malignant hyperthermia.
PNAS Nexus. 2017;114(18):4811–5.