PROF. N.

SYABBALO
MB., ChB., PhD., FCCP., FRS., FIBA

Professor of Physiology & Medicine

CONTROL OF ANTERIOR PITUITARY
SECRETION
ANTERIOR PITUITARY HORMONES
The anterior pituitary secretes six hormones:
adrenocorticotropic hormone (corticotropin,
ACTH), thyroid stimulating hormone
(thyrotropin, TSH), growth hormone, follicle-
stimulating hormone (FSH), luteinizing hormone
(LH), and prolactin (PRL)
An additional polypeptide β-lipotropin (β-LPH), is
secreted with ACTH but its physiologic role is
unknown (see Table NS 17.1)
TABLE NS 1-1 Hormones secreted by the
anterior pituitary gland
Adrenocorticotropic hormone (corticotropin, ACTH)
Thyroid stimulating hormone (thyrotropin, TSH)
Growth hormone
Follicle- stimulating hormone (FSH)
Luteinizing hormone (LH)
Prolactin (PRL)
Polypeptide β-lipotropin (β-LPH)
CONTROL OF ANTERIOR PITUITARY
SECRETION
The action of the anterior pituitary hormones are
summarized in Table 17-9
The hypothalamus plays an important stimulatory
role in regulating the secretion of ACTH, β-LPH, TSH,
growth hormone, FSH, and LH
It also regulates prolactin secretion, but its effect is
predominantly inhibitory rather than stimulatory
NATURE OT HYPOTHALAMIC CONTROL
Anterior pituitary secretion is controlled by chemical agents
carried in the portal hypophysial vessels from the
hypothalamus to the anterior pituitary
These substances used to be called releasing and inhibiting
factors, but now they are commonly called
hypophysiotropic hormones
The latter term seems appropriate since they are secreted into
the bloodstream and act at a distance from their site of origin
Small amounts escape into the general circulation, but they
are at their highest concentration in the portal hypophysial
blood
HYPOPHYSIOTROPIC HORMONES
There are six established hypothalamic releasing and
inhibiting hormones (Figure 17-10)
These are: corticotropin-releasing hormone
(CRH); thyrotropin-releasing hormone (TRH);
growth hormone-releasing-hormone (GRH);
growth hormone-inhibiting hormone (GIH), now
generally called somatostatin, luteinizing
hormone-releasing hormone (LHRH), generally
known as gonadotropin-releasing hormone
(GnRH); and prolactin-inhibiting hormone (PIH)
TABLE NS 17-2 Hypothalamic
releasing and inhibiting hormones
Corticotropin-releasing hormone (CRH)
Thyrotropin-releasing hormone (TRH)
Growth hormone-releasing-hormone (GRH)
Growth hormone-inhibiting hormone (GIH), now
generally called somatostatin
Gonadotropin-releasing hormone (GnRH)
Prolactin-inhibiting hormone (PIH)
Prolactin-releasing hormone (PRH) ??
HYPOPHYSIOTROPIC HORMONES
In addition, hypothalamic extracts contain prolactin-
releasing activity, and a prolactin-releasing hormone
(PRH) has been postulated to exist
TRH, vasoactive intestinal peptide (VIP), and other
several polypeptides found in the hypothalamus stimulate
prolactin secretion, but it is uncertain whether one or
more of these peptides is the physiologic PRH
Recently, an orphan receptor was isolated from the
anterior pituitary, and the search for its ligand led to the
isolation of a 31-amino-acid polypeptide from the human
hypothalamus
HYPOPHYSIOTROPIC HORMONES
This polypeptide stimulated prolactin secretion by an
action on the anterior pituitary receptor, but additional
research is needed to determine if it is physiologic PRH
GnRH stimulates the secretion of FSH as well as that of
LH, and it seems unlikely that a separate FSH-releasing
hormone exists
The structure of the six established hypophysiotropic
hormones are shown in Figure 17-11
The structures of the genes and preprohormones for
TRH, GnRH,CRH, GRH and somatostatin are known
HYPOPHYSIOTROPIC HORMONES
Prepro TRH contains six copies of TRH
Several other preprohormones may contain other
hormonally active peptides in addition to the
hypophysiotropic hormone
The area from which the hypothalamic releasing and
inhibiting hormones are secreted is the median
eminence of the hypothalamus
This region contains few nerve cell bodies, but many
nerve endings that are in close proximity to the
capillary loops from which the portal vessels originate
HYPOPHYSIOTROPIC HORMONES
The location of the cell bodies of the neurons that
project to the external layer of the median eminence
and secrete the hypophysiotropic hormones are shown
in Figure 17-12
Figure 17-12, also shows the location of neurons
secreting oxytocin and vasopressin
The GnRH-secreting neurons are primarily in the
medial preoptic area
The somatostatin secreting neurons are in the
periventricular nuclei
HYPOPHYSIOTROPIC HORMONES
The TRH-secreting neurons and CRH-secreting neurons
are in the medial parts of the paraventricular nuclei
And the GRH-secreting (and dopamine-secreting)
neurons are in the arcuate nuclei
Most, if not all, of the hypophysiotropic hormones
affect the secretion of more than one anterior pituitary
hormone (Figure 17-10)
The FSH-stimulatory activity of GnRH has been
mentioned previously, and GnRH also stimulates the
secretion of LH
HYPOPHYSIOTROPIC HORMONES
TRH stimulates the secretion of TSH as well as
prolactin
Somatostatin inhibits the secretion of TSH as well as
growth hormone
Somatostatin does not normally inhibit the secretion
of other anterior pituitary hormones, but it inhibits
the abnormally elevated secretion of ACTH in patients
with Nelson’s syndrome
CRH stimulates the secretion of ACTH and β-LPH
HYPOPHYSIOTROPIC HORMONES
Hypophysiotropic hormones function as
neurotransmitters in other parts of the brain, the retina,
and the autonomic nervous system
In addition, somatostatin is found in the pancreatic islets,
GRH is secreted by pancreatic tumors, and somatostatin
and TRH are found in the gastrointestinal tract
Receptors for most of the hypophysiotropic hormones are
coupled G proteins
There are two human CRH receptors: hCRH-RI and
hCRH-RII
HYPOPHYSIOTROPIC HORMONES
The physiological role of hCRH-RII is unsettled, though it
is found in many parts of the brain
In addition, a CRH-binding protein in the peripheral
circulation inactivates CRH
It is also found in the cytoplasm of corticotropes in the
anterior pituitary, and in this location it might play a role in
receptor internalization
However, the exact physiologic role of this protein is
unknown
Other hypophysiotropic hormones do not have known
binding proteins
SIGNIFICANCE & CLINICAL IMPLICATION
Research delineating the multiple neuroendocrine
regulatory functions of the hypothalamus is important
because it helps explain how endocrine secretion is
matched to the demands of a changing environment
The nervous system receives information about changes
in the internal and external environment from the sense
organs
It brings about adjustments to these changes through
effector mechanisms that include not only somatic
movement but also changes in the rate at which
hormones are secreted
SIGNIFICANCE & CLINICAL IMPLICATION
The manifestations of hypothalamic disease are
neurologic defects, endocrine changes, and metabolic
abnormalities such as hyperphagia and hyperthermia
The relative frequencies of the signs and symptoms of
hypothalamic disease in one large series of cases are
shown in Table 17-2, and specific endocrines diseases are
discussed in subsequent lectures
The possibility of hypothalamic pathology should be kept
in mind in evaluating all patients with pituitary
dysfunction, especially those with isolated deficiencies of
single pituitary tropic hormones
TABLE 17-2 SYMPTOMS AND SIGNS OF 60
PATIENTS WITH HYPOTHALAMIC DISEASE
Endocrine and metabolic findings % of cases
Precocious puberty 40
Hypogonadism 32
Diabetes inspidus 35
Obesity 25
Abnormalities of temperature regulation 22
Emaciation 18
Bulimia 8
Anorexia 7
TABLE 17-2 SYMPTOMS AND SIGNS OF 60
PATIENTS WITH HYPOTHALAMIC DISEASE
Neurogical findings % of cases
Eye signs 78
Pyramidal and sensory deficits 75
Headache 65
Extrapyramidal signs 62
Vomiting 40
Psychic disturbances, rage attacks, etc 35
Somnolence 30
Convulsions 15
SIGNIFICANCE & CLINICAL IMPLICATION
A condition of considerable interest in this context is
Kallmann syndrome, the condition of
hypogonadism due to low levels of circulating
gonadotropins (hypogonadotropic hypogonadism)
with partial or complete loss of the sense of smell
(hyposmia or anosmia)
Embryologically, gonadotropin-releasing hormone
(GnRH) neurons develop in the nose and migrate up
the olfactory nerves and then through the brain to the
hypothalamus
SIGNIFICANCE & CLINICAL IMPLICATION
If this migration is prevented by congenital abnormalities in the
olfactory pathway, the GnRH neurons do not reach the
hypothalamus
The hypothalamus does not produce GnRH and pubertal
maturation of gonads does not occur
The syndrome is most common in men, and the cause in many
cases is mutation of the KALIGI gene
KALIGI gene is located on the X chromosome that codes for
adhesion molecule necessary for the normal development of the
olfactory nerve
However, the condition also occurs in women and can be due to
other genetic abnormalities
CLINICAL BOX NS 17-1
Kallman syndrome
Kallman syndrome is due to an isolated GnRH deficiency
It is associated with decreased or abscent sense of smell
(hyposomnia, anosmia), and sometimes with other bony
defects (cleft palate), retinal and cerebral abnormalities
(e.g. colour blindness)
In left untreated, the epiphyses fail to fuse, resulting in tall
structure with disproportionately long arms and legs
relatively to trunk height (eunuchoid habitus)
In many individuals, agenesis or hypoplasia of the
olfactory bulbs, results in anosmia or hyposmia
CLINICAL BOX NS 17-1
Kallman syndrome
It is often familial and is X-linked, resulting from a
mutation in the KAL 1 gene which encodes anosmin-1
(producing loss of smell)
One sex-linked form is due to an abnormality of a cell
adhesion molecule necessary for the migration of the
GnRH neuron from the nose through the brain to the
hypothalamus
Management is androgen replacement therapy with
testosterone (dermal, Sc, IM, implant or oral)
Fertility is possible
TEMPERATURE REGULATION
In the body, heat is produced by muscular exercise,
assimilation of food, and all vital processes that
contribute to the basal metabolic rate
It is lost from the body by radiation, conduction, and
evaporation of water in the respiratory passages and
on the skin
Small amount of heat are also lost removed in urine
and faeces
The balance between heat production and heat loss
determines the body temperature
TEMPERATURE REGULATION
Because the speed of chemical reactions varies with
temperature and because the enzyme systems of the
body have narrow temperature ranges in which their
function is optimal, normal body function depends on a
relatively constant body temperature
Invertebrates generally, cannot adjust their body
temperatures and so are at the mercy of the environment
In vertebrates, mechanisms for maintaining body
temperature by adjusting heat production and heat loss
have evolved
TEMPERATURE REGULATION
In reptiles, amphibians, and fish, the adjustments are
relatively rudimentary, and these species are called
“cold-blooded” (poikilothermic) because their body
temperature fluctuates over a considerable range
depending on environmental temperature
In birds and mammals, the “warm-blooded”
(homeothermic) animals, a group of reflex responses
that are primarily integrated in the hypothalamus
operate to maintain body temperature within a narrow
range in spite of wide fluctuations in environmental
temperature
TEMPERATURE REGULATION
The hibernating mammals are a partial exception
While awake they are homeothermic, but during
hibernation their body temperature falls
In homeothemic animals, the actual temperature at
which the body is maintained varies from species to
species and, to a lesser degree, from individual to
individual
In humans, the traditional normal value for the oral
temperature is 37 °C (98.6 F)
NORMAL BODY TEMPERATURE
But in one large series of normal young adults, the
morning oral temperature of 36.3-37.1 °C (97.3-98.8 F;
mean ± 1.96 standard deviation)
Various parts of the body are at different temperatures,
and the magnitude of the temperature differences
between the parts varies with environmental temperature
The extremities are generally cooler than the rest of the
body
The temperature in the scrotum is carefully regulated at
32 °C
NORMAL BODY TEMPERATURE
The rectal temperature is representative of the
temperature at the core of the body and varies least
with changes in environmental temperature
The oral temperature is normally 0.5 °C lower than the
rectal temperature, but it is affected by many factors,
including ingestion of hot or cold drinks, gum
chewing, smoking, and mouth breath (halitosis)
The normal human core temperature undergoes a
regular circadian fluctuation of ±0.5-0.7 °C
NORMAL BODY TEMPERATURE
In individuals who sleep at night and are awake during the
day (even when hospitalized at bed rest), it is lowest at
about 06:00 AM and highest in the evenings
It is lowest during sleep, is slightly higher in the awake but
relaxed state, and rises with activity
In women, an additional monthly cycle of temperature
variation is characterized by a rise in basal temperature at
the time of ovulation
Temperature regulation is less precise in young children
and they may normally have a temperature 0.5 °C, or so
above the established norm for adults
NORMAL BODY TEMPERATURE
During exercise, the heat produced by muscular
contraction accumulates in the body and the rectal
temperature normally rises as high as 40 °C (104 F)
This rise is due in part to the inability of the heat-
dissipating mechanisms to handle the greatly
increased amount of heat produced
But evidence suggest that during exercise in addition
there is an elevation of the body temperature at which
the heat-dissipating mechanisms are activated
NORMAL BODY TEMPERATURE
Body temperature also rises slightly during emotional
excitement, probably owing to unconscious tensing of
the muscles
It is chronically elevated as much as 0.5 °C when the
metabolic rate is high, as in hyperthyroidism, and
lowered when the metabolic rate is low, as in
hypothyroidism
Some apparently normal adults chronically have a
temperature above the normal range (constitutional
hyperthermia)
HEAT PRODUCTION
A variety of basic chemical reactions contribute to body
heat production at all times
Ingestion of food increases heat production, but the
major source of heat is the contraction of skeletal muscle
Heat production can be varied by endocrine mechanisms
in the absence of food intake or muscular exertion
Epinephrine and norepinephrine produce a rapid but
short-lived increase in heat production; thyroid
hormones produce a slowly developing but prolonged
increase
HEAT PRODUCTION
Furthermore, sympathetic discharge decreases during
fasting and is increased by feeding
A source of considerable heat, particularly in infants,
is brown fat
This fat has a high rate of metabolism and its
thermogenic function has been likened to that of an
electric blanket
TABLE 17-3
Body heat production and loss
Body heat is produced by:
Basic metabolic process
Food intake (specific dynamic action)
Muscular activity
Heat is lost by: Percentage lost at 21 °C
Radiation and conduction 70
Vaporization of sweat 27
Respiration 2
Urination and defecation 1
HEAT LOSS
The processes by which heat is lost from the body
when the environmental temperature is below body
temperature are listed in Table 17-3
Conduction is heat exchange between objects or
substances at different temperatures that are in
contact with one another
A basic characteristic of matter is that molecules are
in motion, with the amount of motion proportional to
the temperature
HEAT LOSS
These molecules collide with the molecules in cooler
objects, transferring thermal energy to them
The amount of energy transferred is proportional to
the temperature difference between the two objects in
contact (thermal gradient)
Conduction is aided by convection, the movement of
molecules away from the area of contact
HEAT LOSS
Thus, for example, an object in contact with air at a
different temperature changes the specific gravity of
the air and because warm air rises and cool air fall, a
new supply of air is brought into contact with the
object
Convention is greatly aided if the object moves about
in the medium or the medium moves past the object,
for example, if a subject swims through water or a fan
blows air through a room
HEAT LOSS
Radiation is the transfer of heat by electromagnetic
radiation from one object to another at a different
temperature with which it is not in contact
When an individual is in a cold environment, heat is
lost by conduction to the surrounding air and by
radiation to cool objects in vicinity
Conversely, of course, heat is transferred to an
individual and the heat load is increased by these
processes when the environmental temperature is
above body temperature
HEAT LOSS
Note that because of radiation, an individual can feel
chilly in a room with cold walls even though the room
is relatively warm
On a cold but sunny day, the heat of the sun reflected
off bright objects exert an appreciable warming effect
It is the heat reflected from the snow, for example,
that in part makes it possible to ski in fairly light
clothes even though the air temperature is below
freezing
HEAT LOSS
Because conduction occurs from the surface of one
object to the surface of another, the temperature of the
skin determines to a large extent the degree to which
body heat is lost or gained
The amount of heat reaching the skin from the deep
tissues can be varied by changing the blood flow to the
skin
When the cutaneous vessels are dilated, warm blood
wells into the skin, whereas in the maximally
vasoconstricted state, heat is held centrally in the body
HEAT LOSS
The rate at which heat is transferred from the deep
tissues to the skin is called the tissue conductance
Further, birds have a layer of feathers next to the skin,
and mammals have a significant layer of hair or fur
Heat is conducted from the skin to the air trapped in
this layer and from the trapped air to the exterior
HEAT LOSS
When the thickness of the trapped air is increased by
fluffing the feathers or erection of the hairs
(horripilation), heat transfer across the layer is
reduced and heat losses (or, in a hot environment,
heat gain) are decreased
“Goose pimples” are the result of horripilation in
humans, they are visible manifestation of cold-
induced contraction of the piloerector muscles
attached to the rather meager hair supply
HEAT LOSS
Humans usually supplement this layer of hair with one or
more layers of clothes
Heat is conducted from the skin to the layer of air trapped
by clothes, from the inside of clothes to the outside, and
from the outside of the clothes to the exterior
The magnitude of the heat transfer across the clothing, a
function of its texture and thickness, is the most
important determinant of how warm or cool the clothes
feel
But other factors, especially the size of the trapped layer of
warm air, are also important
HEAT LOSS
Dark clothes absorb radiated heat and light-colored
clothes reflect it back to the exterior
The other major process transferring heat from the
body in humans and other animals that sweat is
evaporation of water on the skin and mucous
membranes of the mouth and respiratory passages
Vaporization of 1 g of water removes about 0.6 kcal of
heat
HEAT LOSS
A certain amount of water is vaporized at all times
This insensible water loss amounts to 50 ml/h in
humans
When sweat secretion is increased, the degree to
which the sweat vaporizes depends on the humidity of
the environment
It is a common knowledge that one feels hotter on a
humid day
This is due in part to the decreased vaporization of
sweat
HEAT LOSS
But even under conditions in which vaporization of
sweat is complete, an individual in a humid environment
feels warmer than an individual in a dry environment
The reason for this difference is unknown, but it seems
related to the fact that in the humid environment sweat
spreads over a greater area of the skin before it
evaporates
During muscular exertion in a hot environment, sweat
secretion reaches values as high as 1600 ml/h, and in a
dry atmosphere, most of the sweat is vaporized
HEAT LOSS
Heat loss by vaporization of water therefore varies
from 30 to over 900 kcal/h
Some mammals lose heat by panting
This rapid, shallow breathing greatly increases the
amount of water vaporized in the mouth and
respiratory passages and therefore the amount of heat
loss
Because the breathing is shallow, it produces relatively
little changes in the composition of alveolar air
HEAT LOSS
The relative contribution of each of the processes that
transfer heat away from the body (Table 17-3) varies
with the environmental temperature
At 21 °C, vaporization is a minor component in
humans at rest
As the environmental temperature approaches body
temperature, radiation losses decline and vaporization
losses increase
TEMPERATURE-REGULATING
MECHANISM
The reflex and semireflex thermoregulatory responses
in the humans are listed in Table 17-4
They include autonomic, somatic, endocrine, and
behavioral changes
One group of responses increase heat loss and
decreases heat production; the other decreases heat
loss and increases heat production
In general, exposure to heat stimulates the former
group of responses and inhibit the latter, whereas
exposure to cold does the opposite
TEMPERATURE-REGULATING
MECHANISM
Curling up “in a ball” is a common reaction to cold in
animals and has a counterpart in the position some
people assume on climbing into a cold bed
Curling up decreases the body surface exposed to the
environment
Shivering is an involuntary response of the skeletal
muscles, but cold also causes a semiconscious general
increase in motor activity
Examples include foot stamping and dancing up and
down on a cold day
TEMPERATURE-REGULATING
MECHANISM
Increased catecholamine secretion is an important
endocrine response to cold
Mice unable to make norepinephrine and epinephrine
because their dopamine β-hydroxylase gene is knocked
out do not tolerate cold; they have deficient
vasoconstriction and are unable to increase
thermogenesis in brown adipose tissue though UCP 1
TSH secretion is increased by cold and decreased by heat
in laboratory animals, but the change in TSH secretion
produced by cold in adult human is small and of
questionable significance
TEMPERATURE-REGULATING
MECHANISM
It is common knowledge that activity is decreased in
hot weather – the “it’s too hot to move” reaction
Thermoregulatory adjustments involve local
responses as well as more general reflex responses
When cutaneous blood vessels are cooled they
become more sensitive to catecholamines and the
arterioles and venules constrict
This local effect of cold directs blood away from the
skin
TEMPERATURE-REGULATING
MECHANISM
Another heat-conserving mechanism that is important in
animals living in cold water is heat transfer from the
arterial to venous blood in the limbs
The deep veins (venae comitante) run alongside the
arteries supplying the limbs and heat is transferred from
the warm arterial blood going to the limbs to the cold
venous blood coming from the extremities
(countercurrent exchange)
This warms the venous blood going to the body
This limits the ability to maintain heat in the tips of the
extremities but conserves body heat
TABLE 17-4 Temperature-regulating
mechanisms
Mechanisms activated by cold
Shivering
Hunger
Increased voluntary activity
Increased secretion of norepinephrine and
epinephrine
Decreased heat loss
Curling up
Horripilation
TABLE 17-4 Temperature-regulating
mechanisms
Mechanisms activated by heat
Increase heat loss
Cutaneous vasodilation
Sweating
Increased respiration
Decreased heat production
Anorexia
Apathy and inertia
AFFERENTS
The hypothalamus is said to integrate body
temperature information from sensory receptors
(primarily cold receptors) in the skin, deep tissues,
spinal cord, extrahypothalamic portions of the brain,
and the hypothalamus itself
Each of these five inputs contribute about 20% of the
information that is integrated
There are threshold core temperature for each of the
main temperature regulating responses and when the
threshold is reached the response begins
AFFERENTS
The threshold is 37 °C for sweating and vasodilation,
36 °C for vasoconstriction, 36 °C for nonshivering
thermogenesis, and 35.5 °C for shivering
FEVER
Fever is perhaps the oldest most universally known
hallmark of disease
It occurs not only in mammals but also in birds,
reptiles, amphibia, and fish
When it occurs in homeothermic animals, the
thermoregulatory mechanism behaves as if they were
adjusted to maintain body temperature at a higher
than normal level, that is, “as if the thermostat had
been reset” to a new point above 37 °C
FEVER
The temperature receptors then signals that the actual
temperature is below the new set point, and the
temperature-raising mechanisms are activated
This usually produces chilly sensations due to
cutaneous vasoconstriction and occasionally enough
shivering to produce a shaking chill and rigors
However, the nature of the response depends on the
ambient temperature
FEVER
The temperature rise in experimental animals injected
with a pyrogen is due mostly to increased heat
production if they are in a cold environment and mostly
to decreased heat loss if the are in a warm environment
The pathogenesis of fever is summarized in Figure 17-15
Toxins from bacteria, such as endotoxins, act on
monocytes, macrophages, dendritic cells, and Kupffer
cells to produce cytokines that act as endogenous
pyrogens (EPs)
FEVER
There is good evidence that IL-1β, IL-6, IFN-β, IFN-γ,
and TNF-α can act independently to produce fever
These circulating cytokines are polypeptides and it is
unlikely that they penetrate the brain
Instead, evidence suggests that they act on the
organum vasculosum of the lamina terminalis (OVLT)
one of the circumventricular organs
This in turn activates the preoptic area of the
hypothalamus which result in fever
FEVER
Cytokines are also produced by cells in the central
nervous system (CNS) when these are stimulated by
infection, and these may act directly on the
thermoregulatory centers
The fever produced by cytokines is probably due to
local release of prostaglandins in the hypothalamus
Intrahypothalamic injection of prostaglandins
produces fever
FEVER
In addition, the antipyretics effect of aspirin is exerted
directly on the hypothalamus
Aspirin inhibits prostaglandin synthesis by preventing
activation of the cyclo-oxygenase pathway involved in
the production of prostaglandins from arachidonic acid
PGE2 is one of the prostaglandins that causes fever
It acts on four sub-type of prostaglandin receptors - EP1,
EP2, EP3, and EP4 - and knockout of the EP3 receptor
impairs the febrile response to PGE2, IL-1β, and
endotoxin, or bacterial lipopolysaccharide (LPS)
FEVER
The benefit of fever to the organism is uncertain
A benefit effect is assumed because fever has evolved
and persisted as a response to infections and other
diseases
Many microorganisms grow best within a relatively
narrow temperature range and a rise in temperature
inhibits their growth
In addition, antibodies production is increased when
body temperature is elevated
FEVER
Before the advent of antibiotics, fevers were artificially
induced for the treatment of neurosyphilis and proved to
be beneficial
Hyperthermia also benefited individuals infected with
anthrax, pneumococcal pneumonia, leprosy, and various
fungal, rickettsial, and viral diseases
However, very high temperatures are harmful
A rectal temperature above 41 °C (106 F) for prolonged
periods result in some permanent brain damage
When the temperature is over 43 °C, heat stroke develops
and death is common
FEVER
Rarely, body temperature may increase to potentially
fatal levels after poisoning with central nervous system
stimulants such as cocaine, amfetamines including
ectasy (MDMA), monoamine oxidase inhibitors, and
anaesthetic agents
Muscle tone is often increased and convulsions and
rhabdomyolysis are common
Cooling measures, sedation with diazepam 1o mg i.v.
and, in severe cases, i.v. dantrolene 1 mg/kg body
weight should be given
FEVER
In malignant hyperthermia, various mutations of
the gene coding for ryanodine receptor (RYR1 , 19q
13) lead to excessive Ca release during muscle
contraction triggered by stress
This in turn leads to contractures of the muscles,
increased muscle metabolism, and a great increase in
heat production in the muscle
The increased heat production causes a marked rise in
body temperature that is fatal if not treated
FEVER
Periodic fever also occur in humans with mutations
in the gene for pyrin, a protein found in neutrophils;
the gene for mevalonate kinase, an enzyme involved in
cholesterol synthesis; and the gene for type 1 TNF
receptor, which is involved in inflammatory responses
However, how any of these three mutant gene
products cause fever is unknown
HYPOTHERMIA
In hibernating mammals, body temperature drops to
low levels without causing any demonstrable ill effects
on subsequent arousal
This observation led to experiments on inducing
hypothermia
When the skin or the blood is cooled enough to lower
the body temperature in nonhibernating animals or in
humans, metabolic and physiologic processes slow
down
HYPOTHERMIA
Respiration and heart rate are very low, blood pressure is
low, and consciousness is lost
At rectal temperatures of about 28 °C, the ability to
spontaneously return the temperature to normal is lost,
but the individual continues to survive and, if warmed
with external heat, returns to a normal state
If care is taken to prevent the formation of ice crystals in
the tissues, the body temperature of experimental
animals can be lowered to subfreezing levels without
producing any detectable damage after the subsequent
rewarming
HYPOTHERMIA
Humans tolerate body temperatures of 21-24 °C (70-75 F)
without permanent ill effects, and induced hypothermia
has been used in surgery
On the other hand, accidental hypothermia occur due to
prolonged exposure to cold air or immersion in cold water,
exposure to extreme climate such as during hill walking,
or as developed in an immobilized old individual
It is a serious condition and requires careful monitoring
and prompt rewarming in a controlled manner while
treating associated hypoxia (by oxygen and ventilation if
necessary)
HYPOTHERMIA
Correction of electrolyte disturbances, and
cardiovascular abnormalities, particularly
dysrhythmias may be required.
Careful handling is essential to avoid precipitating the
latter
The method of rewarming is dependent not on the
absolute core temperature, but on the haemodynamic
stability and the presence or absence of an effective
cardiac support