THERMOREGULATION

DR. MALWEYI
FACILITATOR: DR. MWENDWA
 ● Introduction

LEARNING ● Normal body temperature

● Control of body
OBJECTIVES temperature
● Role of the hypothalamus
in thermoregulation
● Abnormalities of
temperature regulation
 BODY CORE TEMPERATURE VS SKIN
TEMPERATURE

CORE TEMPERATURE: SKIN TEMPERATURE:

This is the temperature of the deep In contrast, skin temperature rises and
tissues of the body. falls depending on the surrounding

Remains fairly constant; between important when we refer to the skin’s

+/-0.6°C, except during a febrile ability to lose heat to the surroundings.
illness

Centrally controlled by the brain

Rectal 0.5⁰C > oral 0.5⁰C > axilla

Skin temp: normally slightly above

atmospheric temp.

scrotum - carefully regulated at 32°C.

Core Temperature Variations
1. Regular circadian fluctuation of 0.5–0.7°C

● Lowest at about 6:00 AM and highest in the evenings .It is lowest during sleep, is
slightly higher in the awake but relaxed state, and rises with activity.

1. Monthly cycle of temperature variation

● Menstrual cycle: Follicular phase (which lasts from the first day of menstruation until
the day of ovulation), the average basal body temperature in women ranges from
36.45 to 36.7 °C .

● Ovulation: within 24 hours of ovulation, women experience an elevation of 0.15–0.45

°C due to the increased metabolic rate caused by sharply elevated levels of
progesterone

1. Young children

● Temperature regulation is less precise ; Normal variation of 0.5°C or so above that of

adults
4. Exercise,

● rectal temp 40°C (104°F).

● elevation of the body temperature at which the heat-dissipating mechanisms are
activated.

[Link] excitement

● unconscious tensing of muscles

[Link] rate

● Chronic elevation of 0.5°C when high, as in hyperthyroidism,

● Reduced when low, as in hypothyroidism

[Link] hyperthermia

● Some apparently normal adults chronically have a temperature above the normal
range
CONTROL OF
BODY
TEMPERATURE
KEY TERMS:
Thermoregulation: process of maintaining core body temperature
within the optimal physiologic range.

Set point: A crucial temperature level where all the temperature

control mechanisms continually attempt to bring the body
temperature back to it’s desired/ targeted level.

Heat Tolerance: Ability to tolerate heat stress without physiological

and work failures

Adaptation due to single sublethal heat exposure that allows the

organism to survive a subsequent exposure to lethal heat stress
Heat Strain & Stress

Both describe a state of positive heat storage in the body

heat strain - the magnitude of departure from resting Tc, i.e., difference between peak and
resting Tc

heat stress - the total heat load that the thermoregulatory system has to cope with to
maintain physiological homeostasis and is indicated by the peak Tc.

if Tc increased from 37 ◦C to 39.8 ◦C heat strain would be 2.8 ◦C and heat stress would be
39.8 ◦C.
Heat Transfer and Storage
Heat Storage = + M ± Ra ± Cv ± Cd − E

M = metabolic heat production,

Ra = radiative heat exchange,

Cv = convective heat exchange,

Cd = conductive heat exchange,

E = heat loss due to evaporation.

Insulator System of the Body
● The skin, the subcutaneous ● When no blood is flowing from
tissues, and especially the fat of the heated internal organs to
the subcutaneous tissues act the skin, the insulating
together as a heat insulator for properties of the normal male
the body. body are about equal to three
● The fat is important because it quarters the insulating
conducts heat only one third as properties of a usual suit of
readily as other tissues. clothes. In women, this
insulation is even better.
HEAT GAIN
Heat production is a principal by-product of metabolism.

Different factors determine the rate of heat production.

Basal rate of metabolism (BMR) of all the cells of the body: i.e, minimum energy/calories
required to perform biological reactions that can keep the body functioning at rest.

Extra rate of metabolism caused by muscle activity, including muscle contractions caused
by shivering

Extra metabolism caused by the effect of hormones i.e: thyroxine, growth hormone, leptin
and testosterone)
● Extra metabolism caused by the effect of epinephrine, norepinephrine, and
sympathetic stimulation on the cells
● Extra metabolism caused by increased chemical activity in the cells,
especially when the cell temperature increases
● Extra metabolism needed for digestion, absorption, and storage of food
(thermogenic effect of food).
Muscle activity
● Changes in muscle activity is the major control of heat
production for temperature regulation.
● Much of the energy from muscle activities becomes
heat due to the viscous friction between muscle and
tissue.
● The first muscle changes in response to a decrease in
core body temperature is skeletal muscle contraction
which may lead to shivering.
● Muscles are also used voluntarily to produce heat
such as foot stamping and hand rubbing.
Hormones and heat production (chemical
thermogenesis).
● Thyroid hormone: Is the single most ● Hypothyroidism reduces both
important determinant of basal metabolic rate and core body
metabolic rate ( BMR). temperature across mammalian
species, including humans
● Thyroid hormone increases the
oxygen consumption and heat
production of most of the body
tissues, except the brain, through
production of thyroxine and
conversion of T4 to T3. This is the
calorigenic effect. Hyperthyroidism is
associated with an increased BMR
and can cause hyperthermia
Epinephrine and Growth hormone
● An increase in either sympathetic 1. Increased rate of protein synthesis
stimulation or circulating
norepinephrine and epinephrine in 2. Increased mobilization of fatty acids
the blood can cause an immediate from adipose tissue
increase in the rate of cellular 3. Increased use of free fatty acids for
metabolism energy
4. Decreased rate of glucose utilization
throughout the body.
● For heat production: In tissues
● Growth hormone (GH) has several throughout the body, GH enhances
metabolic effects including: the conversion of fatty acids to
acetyl-coA and its subsequent
utilization for energy and in turn heat
production.
Leptin
● Leptin –Hormone is produced primarily in adipose tissue and exerts broad
spectrum of regulatory actions including metabolic programming
● deficiency is associated not only with hypothermia, but also with reduced
circulating thyroid hormone levels.
● Both conditions are ameliorated by leptin replacement.
Heat loss
● Most of the heat produced in the body is generated in the deep organs, especially the
liver, brain, and heart, and in the skeletal muscles during physical activity.
● This heat is then transferred from the deeper organs and tissues to the skin, where it
is lost to the air and other surroundings.
● The rate at which heat is lost is determined almost entirely by two factors:
● (1) how rapidly heat can be conducted from where it is produced in the body core to
the skin
● (2) how rapidly heat can then be transferred from the skin to the surroundings.
Mechanisms of heat loss
● Blood vessels are distributed
profusely beneath the skin.
Especially important is a continuous
venous plexus that is supplied by
inflow of blood from the skin
capillaries
● The rate of blood flow into the skin
venous plexus can vary
tremendously, from barely above
zero to as great as 30 percent of the
total cardiac output.
● In the most exposed areas of the
body—the hands, feet, and ears—
blood is also supplied to the plexus
directly from the small arteries
Central Regulation of Temperature
● Human endothermic property - the ability to produce heat endogenously (heat gain)
through the metabolic pathway
● Homeothermic property- the innate regulation of heat gain and loss to maintain
homeostasis of Tb
● Both endothermic and homeothermic functions are coordinated centrally through a
Tc set-point by a “thermostat” mechanism in the hypothalamus.

The hypothalamus:

● part of the limbic system

● serves as a common point of consolidation for efferent outputs
● preserves physiological homeostasis through autonomic regulation
Physiology of thermoregulation
The processing of thermoregulatory
information has three components:

• Afferent thermal sensing

• Central regulation

• Efferent responses

The above work together to maintain the

normal core body temperature
Afferent thermal sensing
Thermal gradations are discriminated by
at least three types of sensory receptors:
cold receptors, warmth receptors, and
pain receptors.

The pain receptors are stimulated only by

extreme degrees of heat or cold and,
therefore, are responsible, along with the
cold and warmth receptors, for “freezing
cold” and “burning hot” sensations.
SKIN THERMORECEPTORS
● Although the signals generated by ● Deep body temperature receptors
the temperature receptors of the are found mainly in the spinal cord,
hypothalamus are extremely in the abdominal viscera, and in or
powerful in controlling body around the great veins in the upper
temperature, receptors in other parts abdomen and thorax.
of the body play additional roles in ● These deep receptors function
temperature regulation. differently from the skin receptors
● This is especially true of temperature because they are exposed to the
receptors in the skin and in a few body core temperature rather than
specific deep tissues of the body. the body surface temperature. Yet,
● The skin has far more cold receptors like the skin temperature receptors,
than warmth receptors—in fact, 10 they detect mainly cold rather than
times as many in many parts of the warmth.
skin.
Warm receptors
Also known as the bulbs of Rufinni.

● Elliptical structures located in the

skin and discharge statically once
stimulated between 30 – 40C.
Maximum discharge is at 44C and
cease to discharge at 46C.
● Signals from warmth receptors are
conveyed by unmyelinated C fibres
to the hypothalamus.
● There are also warm receptors
located in the spinal cord and
intestinal wallss
Cold receptors
Also known as the bulbs of krause

Signals from cold receptors travel along

Aδ fibres and have a peak rate of
discharge of impulses at 25-30 0C
ROLE OF THE ANTERIOR HYPOTHALAMIC-
PREOPTIC AREA IN DETECTION OF
TEMPERATURE
● The anterior hypothalamic-preoptic area
contains large numbers of heat-
sensitive neurons, as well as about one
third as many cold-sensitive neurons.
● These neurons are believed to function
as temperature sensors for controlling
body temperature.
ROLE OF POSTERIOR HYPOTHALAMUS
● The temperature sensory signals from the anterior hypothalamic-preoptic area and
the signals from elsewhere in the body are combined and integrated to control the
heat- producing and heat-conserving reactions of the body in the posterior
hypothalamus
● The area of the hypothalamus that they stimulate is located bilaterally in the
posterior hypothalamus approximately at the level of the mammillary bodies.
● When the hypothalamic temperature centers detect that the body temperature is
either too high or too low, they institute appropriate temperature-decreasing or
temperature-increasing procedures.
Temperature decreasing mechanisms
[Link] of skin blood vessels:

● In almost all areas of the body, the skin blood vessels become intensely dilated. This
dilation is caused by inhibition of the sympathetic centers in the posterior
hypothalamus that cause vasoconstriction.
● Full vasodilation can increase the rate of heat transfer to the skin as much as 8 fold.

B. Sweating:

● There is a sharp increase in the rate of evaporative heat loss resulting from sweating
when the body core temperature rises above the critical level of 37.1°C (98.8°F).
● An additional 1°C increase in body temperature causes enough sweating to remove
10 times the basal rate of body heat production.
Temperature increasing mechanisms
A. Skin vasoconstriction throughout the body:
● This vasoconstriction is caused by stimulation of the posterior hypothalamic
sympathetic centers. Threshold is 36.5C
A. Piloerection:
● Piloerection means hairs “standing on end.”
● Sympathetic stimulation causes the arrector pili muscles attached to the hair
follicles to contract, which brings the hairs to an upright stance and produces
“goose bumps” on the skin at the base of the hairs.
A. Increase in thermogenesis (heat production):
● Heat production by the metabolic systems is increased by:
● Promoting shivering
● Sympathetic excitation of heat production, and
● Thyroxine secretion.
Thermogenesis mechanisms
1. Hypothalamic stimulation of shivering.
● The ‘primary motor center for shivering’;
● Located in the dorsomedial portion of the posterior hypothalamus, near the wall of
the third ventricle;
● Inhibited by signals from the heat center in the anterior hypothalamic-preoptic area
● Excited by cold signals from the skin and spinal cord(small temp drops)
● Shivering signals ->bilateral tracts in brain stem -> lateral columns of the spinal
cord ->anterior motor neurons.
● Signals are nonrhythmic and do not cause the actual muscle shaking.
● They instead increase the tone of the skeletal muscles by facilitating the activity of
the anterior motor neurons.
● When the tone rises above a certain critical level, shivering begins
2. Sympathetic “chemical” excitation of
heat production

● sympathetic stimulation or circulating

norepinephrine and epinephrine rapidly
increase cellular metabolism rate.
● This effect is called chemical
thermogenesis, or non-shivering
thermogenesis.
● A result of norepinephrine and
epinephrine’s ability to uncouple
oxidative phosphorylation. This
releases energy in form of heat,
without formation of adenosine
triphosphate .
1. Increased thyroxine output as a long-term cause of increased heat production.
● Cooling the anterior hypothalamic-preoptic area increases production of Thyrotropin-
releasing hormone (TRH)
● TRH ->TSH -> Thyroxine
● Thyroxine activates uncoupling protein and increases rate of cellular metabolism
(chemical thermogenesis) by:
A. Changing transcription rate of uncoupling protein 1 (UCP1).
B. Increasing metabolic cycling.
C. By direct actions on the sodium/potassium and calcium pump in skeletal muscle.
D. By central regulation
● This increase in metabolism does not occur immediately but requires several weeks’
exposure to cold to make the thyroid gland hypertrophy and reach its new level of
thyroxine secretion
Non–shivering thermogenesis in Infants
● Mechanism of heat production occurring in the first 6 months of life that is not
associated with muscle activity.
● Associated with brown adipose tissue (BAT) located suprarenally, axillary and around
the great vessels of the heart and vertebral arteries.
● This type of fat contains large number of mitochondria and multiple small fat
globules.
● BAT is responsive to thyroid hormone, epi and sympathetic nervous system.
● BAT) contains large numbers of proteins called uncoupling proteins.
● These proteins uncouple oxidation from phosphorylation, thus generating less ATP
● The major product of this inefficient metabolism is heat, which then contributes to
maintaining body temperature in infants.
CLINICAL APPLICATION OF
THERMOREGULATION
Thermoregulation in the
Perioperative
Period
Effects of anaesthesia on thermoregulation
● Under general anaesthesia, hypothermia can occur due to exposure to a cold
environment and anaesthesia induced impaired thermoregulation (causing
vasodilatation, inhibition of vasoconstriction and reduced metabolic rate by 20-
30%)
● The process of thermoregulation describes heat balance and basal metabolic rate
which is independent of thermoregulatory feedback
● Heat is lost or transferred from the body via conduction, convection(35%),
radiation(40%), evaporation(15%) and respiration(10%)
CONT..
Unintentional hypothermia occurring under anaesthesia can be divided into 3 phases :

1. Phase 1 (Redistribution phase) – occurs during the 1st hour, where core temperature
decreases by 1 to 2C and when there is no attempt to actively warm an anaesthetized
patient. Redistribution of heat occurs, from the warm ‘central’ compartments
(e.g.,abdomen, thorax) to the cooler peripheral tissues (e.g., arms, legs) from anaesthetic
induced vasodilation.

2. Phase 2 (Linear phase) – is a more gradual decline, occurring over the next 2 - 4hrs.
There is continuous heat loss to the environment. Heat lost exceeds metabolic heat
production. The rate of fall depends on the heat lost, produced and size of the patient.

3. Phase 3 (plateau phase) – steady state occurring after 3-4hrs. Heat loss equals
metabolic heat production. Core temperature stabilises and remains unchanged due to
peripheralvasoconstriction (triggered by a fall in core temperature) and this restricts
metabolic heat to the core.
Neuraxial anaesthesia
● Impairs autonomic and behavioural thermoregulation, just like general anaesthesia. In
the patient under spinal and epidural anaesthesia, all thermal input from the
anaesthetized region is blocked, and there is a decrease in the threshold triggering
vasoconstriction and shivering by 0.6C above the level of the block.
● Reduction in these thresholds is proportional to the number of segments blocked.
● Blocking the vasomotor nerves causes the vessels in the blocked dermatomes to
vasodilate, which accelerates heat loss. Patients tend to have a feeling of warmth post
neuraxial anaesthesia, even if they become hypothermic.
● Core temperature is also not commonly monitored during neuraxial anaesthesia, and
this can lead to a missed diagnosis of hypothermia.
Shivering
● Shivering in the perioperative or postoperative period is an autonomic response to
perioperative hypothermia, but it can also occur in the normothermic patient.
● The adverse effects of shivering include patient discomfort, disturbance to monitoring
techniques, stretching of the surgical incision leading to increased postoperative
surgical pain, an increase in intraocular and intracranial pressure.
● Shivering increases a patients’ metabolic rate and oxygen consumption. Shivering is
not only caused by hypothermia in the perioperative period, and it is therefore
important to exclude and treat other causes such as pain, stress and over-activity of
the sympathetic nervous system.
● The treatment of perioperative shivering can be divided into pharmacological and
nonpharmacological methods. Drugs used include pethidine 25mg, clonidine 75ug,
dexmedetomidine 5ug/kg (be aware of sedative effects) and ketamine 0.5mg/kg. The
non-pharmacological treatment includes actively warming a patient’s skin

.
EFFECTS OF PERIOPERATIVE HYPOTHERMIA
1. Shivering
2. Excessive sympathetic nervous system stimulation
3. Metabolic acidosis which can prolong the metabolism of neuromuscular blocking
agents and propofol.
4. Delayed recovery from anaesthesia
5. Impaired platelet activity
6. Prolongation of the coagulation time
7. Decreased clot formation time
8. Impaired immune function and delayed wound healing.
9. Increased breakdown and decreased synthesis of muscle protein
10. Surgical site infection due to impaired immune cell recruitment due to
vasoconstriction i.e macrophages
11. Myocardial infarction
How do we prevent redistributive
hypothermia
● Pre-operative warming if a patient’s temperature is <36C and keeping the patient
warm in the perioperative period between a temperature of 36.5C – 37.5C
● Airway heating and humidification: in the respiratory system, 10% of metabolic heat
produced is lost by evaporation.
● Warming intravenous (I.V.) fluids: the infusion of cold IV fluids can lead to significant
heat loss. Fluid warming leads to direct core warming and is recommended for all
intraoperative fluid infusions >500ml in adults. Rapid transfusion (>100ml/min) of
refrigerated blood (40C) and cold iv fluids can cause a sudden decrease in
temperature with serious consequences
THERAPEUTIC HYPOTHERMIA
The use of mild induced hypothermic temperature 32-34C as a way to
protect the brain after anoxic injury.

Induced hypothermia reduces metabolic demand from injured body tissues

Can be applied in conditions such as:

● Neonatal ischemic encephalopathy

● Cardiac arrest
● Ischemic stroke
● Traumatic brain injury
● Post resuscitation syndrome.
● Septic shock .
Hypothermia after Cardiac Arrest
The European resuscitation council and European society of Intensive Care Medicine
Guidelines of 2021, recommend targeted temperature monitoring for adults after out of
hospital cardiac arrest or in hospital cardiac arrest, with any initial rhythm, who are
unresponsive after return of spontaneous circulation (ROSC).

Targeted temperature is maintained at a constant temperature between 32C and 36C

for at least 24hrs.

Avoid fever (>37.70C) for at least 72hr after ROSC in patients who remain in a coma.

Proposed benefits of therapeutic hypothermia include reduction in cerebral metabolic

rate-for every 10C drop, a 6-10% drop in the cerebral metabolic rate of oxygen
consumption (CMRO2), reduced ischaemic-reperfusion injury, and improved brain
glucose metabolism to name a few
Cardiopulmonary bypass

Hypothermia during Cardiopulmonary

bypass is favoured due its effectiveness in
reducing oxygen demand and increasing
ischaemic tolerance of organ systems.

CPB can be performed under

hypothermia(25-320C) or normothermia
NEONATAL HIE
Therapeutic hypothermia is practised in
new-borns with moderate to severe
hypoxic ischeamic encephalopathy.

The recommended gestational age is

>36weeks. The core body temperature of
the neonate is kept between 33 -34 C for
72hrs, then rewarmed or 6-12hrs22

It has been proven to decrease mortality

and severe long-term
neurodevelopmentaldisabilities in infants
with moderate-to-severe HIE, without
increasing the incidence of disability in
survivors
CRYOSURGERY/CRYOABLATION
● Cryosurgery is the controlled application of cold to cause tissue damage. It can be

used to treat both benign and malignant skin conditions.

● With cryosurgery, the degree of tissue damage is controlled in order to destroy the

target lesion with minimal damage to normal surrounding tissue.

● Freezing causes intracellular and extracellular ice crystals to form, and the

subsequent vascular stasis causes tissue anoxia and necrosis.

● The most efficient technique employs a rapid freeze and slow thawing. Multiple

short freezes produce more damage than a long freeze.

Cryosurgery has been used to treat :

● Precancerous skin growths such as

actinic keratosis
● Early stage skin cancers( both basal
and squamous cell carcinoma)
● Precancerous conditions of the cervix
such as cervical intraepithelial
neoplasia.
● Small and localised kaposi sarcoma
lesions
● Early stage Prostate cancers that are
confined to prostate .
● Low grade cancerous and on
cancerous bone tumors.
HYPOTHERMIC ORGAN PRESERVATION
● Whole organ donated can be stored under hypothermic perfusion machines to
preserve their function before transplantation eg kidney
● The ex vivo perfusion of organs by hypothermic perfusion preservation (HPP) on a
machine prior to transplant, as opposed to static cold storage (SCS) on ice, offers the
prospect of making available more and better organs for transplantation
● Studies have shown that expanded criteria donor (ECD) kidneys preserved by SCS had
an overall increased risk of reduced graft viability. However, HPP was clearly
associated with a reduced incidence of delayed graft function (DGF), an overall
improved graft survival, and an increased rate of clinical use.
HYPERTHERMIA THERAPY IN CANCER.
● Hyperthermia (HT) as an adjuvant to radiation and chemotherapy:

● Heating the body activates the immune system, increasing interactions between

immune cells designed to alert the body when it is under attack and mobilizing

immune cells such as T and B cells to tissues where they are needed.

● Several recent studies have found that hypothermia coupled with chemotherapy

appears to be a safe and potentially more effective treatment for some noninvasive

forms of bladder cancer than chemotherapy alone .

PATHOPYSIOLOGY OF
THERMOREGULATION
CAN BE BROADLY DIVIDED INTO:
● FEVER
● HYPOTHERMIA
● HYPERTHERMIA
FEVER
Fеvеr is a type of hyреrthеrmiа defined by a regulated increase in the internal thermostat
setpoint.

Fеver is mediated by circulating pyrogenic cytokines including interleukins and interferon.

Pyrogens activate the vagus nerve, which triggers release of prostaglandin E2 in the
hурοthalamսs, thereby increasing the setpoint.

Mediated by exogenous and endogenous pyrogens

Exogenous pyrogens are substances,
Immune cells detect the presence of
which originate outside the body and
exogenous pyrogens and in turn produce
which are capable of inducing interleukins
inflammatory cytokines. Cytokines
Exogenous pyrogens are subdivided into : produced and released by phagocytes
include :
1. Microbial ( from bacteria , viruses ,
fungi or protozoa) 1. Interleukin-1, Interleukin-6,
2. Non-microbial pyrogens :Antigens Interleukin-18
from vaccines, Products of tissue 2. Tumor Necrosis Factor -alpha
decay (burns , mechanical trauma , 3. Gamma Interferon.
surgical operations, internal 4. GM-CSF(Granulocyte Macrophage
hemorrhage , allergic reactions, colony stimulating factor)
autoimmune processes. ) 5. Interferon alpha
3. Drugs : anticancer drugs s.a 6. Gp 130 receptor ligand
bleomycin , blood and blood related
products,
Causes of intraoperative fever include:

1. Acute transfusion reactions

2. Infections, including those that were present before ѕսrgerу
3. Adverse effects of certain medications (eg, neuroleptic malignant syndrome,
serotonergic syndrome)

Notably, fеvеr rarely occurs during general аոеѕthеsia because both volatile anesthetics
and opioids blunt the febrile response. Fеvеr is more likely to occur in the postoperative
period when the thermoregulatory effects of аnеsthesia dissipate
HYPERTHERMIA
In hyperthermia, the set-point is unaltered, and the body temperature becomes elevated in
an uncontrolled fashion due to exogenous heat exposure or endogenous heat production
that exceeds the body’s ability to lose heat

CAUSES OF HYPERTHERMIA:

● Exogenous; hot climate, heat-isolated cloth , high humidity, insufficient ventilation

● Endogenous disturbances of heat regulation: without pyrogen formation

● heat regulation center violation (cerebral trauma, encephalitis, cerebral edema)

● Fever caused by psychical diseases, nervous excitation, stresses

MINOR HEAT ILLNESSES
● Prickly heat rash : vesicular rash caused by obstruction of sweat gland pores.

● Heat edema : Swelling of the feet and ankle. Dependent edema due to vasodilatory

pooling hence body fluids move to feet and legs by gravity.

● Heat cramps: intermittent muscle cramps lasting 1-3min ,likely related to salt

deficiency (extracellular Na+) secondary to heavy sweating. Occurs in muscles that

are heavily used .

● Heat syncope: temporary loss of consciousness caused by shunting of blood from

brain to peripheries following prolonged peripheral vasodilatation.

MALIGNANT HYPERTHERMIA
A life threatening disorder

A rare genetic Autosomal Dominant trait with reduced penetrance involving skeletal
muscles

it is associated with gene mutations;

● RYR-1(Ryanodine receptor type 1) which encodes skeletal muscles isoform of the

calcium-release channel of sarcoplasmic reticulum.
● CACNA1S
● STAC3
TRIGGERS OF MH
● Drugs : Volatile gaseous inhalational anaesthetics: Sevoflurane , Desflurane ,

Isoflurane, Enflurane, Methoxyflurane , Halothane , cyclopropane , ether.

● Depolarising muscle relaxants : Succinylcholine

● Emotional stress

● Strenuous exercise exertion

Pathophysiology of malignant
hyperthermia
● The uncontrolled release of calcium from the skeletal muscle sarcoplasmic reticulum

leads to sustained muscle contraction.

● The sustained muscle contraction produces a depletion of adenosine triphosphate

(ATP) and dramatically increases oxygen consumption, carbon dioxide production,

and heat.

● The depletion of ATP stores leads to membrane integrity failure and cell content

leakages such as potassium, creatinine kinase, and myoglobin into the circulation
Symptoms of MH
● Tachycardia
● Tachypnea
● Hypoxemia
● Hypercarbia
● metabolic and respiratory acidosis
● hyperkalemia
● cardiac dysrhythmias
● hypotension
● skeletal muscle rigidity
● hyperthermia.
NEUROLEPTIC MALIGNANT SYNDROME
A rare life threatening , idiosyncratic reaction to neuroleptic medication like haloperidol,
chlorpromazine, fluphenazine, clozapine, olanzapine and others

It is characterized by:

● hotness of body
● muscular rigidity –lead pipe
● altered mental status
● autonomic dysfunction

onset 4-14 days of initial exposure to the drugs but it may also occur after years into
therapy.

Complications: rhabdomyolysis, Acute kidney injury, MI, acute resp failure, brain damage,
sepsis , DIC , hepatic failure and others
REFERENCES
● Clinical Methods: The History, Physical, and Laboratory
Examinations. 3rd edition.
● Guyton and hall textbook of medical physiology, 14th edition
● Ganong’s review of medical physiology 26th edition
● Uptodate: perioperative temperature management
● Sessler DI, Schroeder M, Merrifield B, et al. Optimal duration and
temperature of prewarming. Anesthesiology 1995; 82:674.
● Thermoregulation in the Perioperative Period, Dr. TT curtis, et al.