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Questions: Learning objectives

•  Parts & nuclei of hypothalamus
•  Functions of hypothalamus
The Hypothalamus •  Role of hypothalamus in:
–  Thermoregulation
–  Thirst mechanism
–  Control of feeding (Hunger & satiety)
–  Circadian rhythm

Hypothalamus Hypothalamus

Hypothalamus Hypothalamus location

•  Weight: 10g
•  Location:
–  On each side of third ventricle
–  Below thalamus (hypo-thalamus)
•  Hypothalamus, thalamus and subthalamus
forms diencephalon
•  Consists of large numbers of nucleus

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Hypothalamus essential for

homeostatic functions, visceral functions, Functional divisions
behavior, sleep-wakefulness, body rhythm
and reproductive functions

Zones of Hypothalamus Zones of Hypothalamus

Zones of Hypothalamus Regions of Hypothalamus

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Functional Zones of hypothalamus Functional Zones

Hypothalamus
Posterior Tuberal Anterior
Region Region Region

Region Anterior Tuberal Posterior

Lateral
Zone Zone Medial Lateral Medial Lateral Medial
Anterior
Posterior Nucleus Nucleus Nucleus
Medial
Zone

Nuclei of Hypothalamus Anterior Region of Hypothalamus

Nucleus Functions
Paraventricular Oxytocin hormone
Supraoptic ADH hormone
Preoptic Thermoregulation, Sleep
regulation, BP & HR
Anterior & Sexual behavior
periventricular
Suprachiasmatic Biological rhythm (circadian)
Lateral Thirst and hunger

Tuberal region of Hypothalamus Posterior region of Hypothalamus

Nucleus Functions
Nucleus Functions
Dorsomedial Emotion (rage)
Posterior Thermoregulation (shivering),
Venteromedial Satiety Increased blood pressure
Arcuate Dopamine, GnRH Mammillary Emotion, Feeding reflex
Lateral Thirst and hunger

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Functions of Hypothalamus
1.  Regulation of hormones release from
pituitary gland.
2.  Regulation of autonomic functions
3.  Regulation of thirst
4.  Control of feeding: feelings of hunger and
satiety

Functions of Hypothalamus
5.  Regulates circadian rhythms & sleep cycle.
6.  Regulation of sexual behaviours. 1. Regulating release of
7.  Involved with perception of pleasure, fear, hormones from pituitary gland
and rage.
8.  Controls mechanisms needed to maintain
normal body temperature.
9.  Regulation of homeostatic functions

Relation to the pituitary gland Relation to the pituitary gland

•  Vascular connections between the
hypothalamus and the anterior lobe.

Portal hypophysial
•  Neural connections between the
Hypothalamohypophysial hypothalamus and the posterior lobe of the
circulation
tract
pituitary gland.

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Regulation of Anterior Pituitary
Releasing and inhibiting
Hormones from Hypothalamus
Enter the Portal vessels of pituitary
Reach the anterior pituitary to
Control “trope” cell
ACTH, TSH, GH,FSH,LH &
Prolactin release from Pituitary
2. Regulation of autonomic
functions
3. Regulation of thirst
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Regulation of Posterior Pituitary
Hormone synthesis in supraoptic
& paraventricular nucleus
Hormone transported down the
axons (axoplasmic transport)
Secreted from Posterior
Pituitary (Oxytocin &Vasopressin)
Autonomic function &
Hypothalamus
•  Sherrington called the hypothalamus “the
head ganglion of the autonomic system.”
•  Stimulation of lateral areas, produces diffuse
sympathetic discharge.
•  Separate hypothalamic areas are for control
of epinephrine and norepinephrine
secretion.
Regulation of thirst
•  Drinking is regulated by plasma osmolality
and ECF volume.
•  Water intake is increased by:
1.  Increased Osmolality of the plasma
2.  Decreases in ECF volume (increase AgII)
3.  Psychological and other factors.
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Mechanism of osmo-receptor
Mechanism of thirst
activation
Hypertonicity of blood •  Hyperosmolality causes osmoreceptor membrane
Hypovolemia
depolarization via activation of nonselective
calcium-permeable cation channels.
é  Angiotensin II
éOsmolality, éNa+ é  Baroreceptor •  The channel opening may be due to mechanical
effect linked to cell membrane shrinkage
Osmo- •  Urea & glucose (in presence of insulin) are
receptor
ineffective osmoles because they cross cell
Ant. Hypo membrane
(Pre-optic nucleus)
Clin J Am Soc Nephrol. 2015 May 7; 10(5): 852–862

Hypovolemia and thirst Hypovolemia and thirst

éOsmolality •  Hemorrhage causes increased drinking
é AngII even if there is no change in the osmolality
of the plasma???
Osmo-
receptor •  Fluid loss from body (hemorrhage,
+ +
Lateral Supraoptic
vomiting, diarrhea) increases thirst???
Ant. Hypo
(Pre-optic nucleus) Hypotha Nucleus

é Thirst é ADH

Intake of liquids is increased during

Hypovolemia and thirst eating (prandial drinking)???
ê in ECF (êBP) 1.  The increase has been called a learned
Inhibition of baroreceptor or habit response.
Stimulates intra-renal
Baroreceptor (JG cell) 2.  Increase in plasma osmolality that occurs
Sympathetic stimulation as food is absorbed.
é Renin secretion 3.  Action of one or more gastrointestinal
Thirst stimulation hormones on the hypothalamus.
Increase AgII

Stimulates
Osmo-receptor

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Regulation of food intake

The hypothalamus contains:
•  Hunger centers (feeding center): Lateral
4. Control of Feeding
hypothalamic (LH) nuclei
•  Satiety centers: Ventromedial (VM) nuclei
•  Paraventricular and arcuate nuclei of the
hypothalamus also play a major role in
regulating food intake.

Control of feeding Discovery of feeding center

Venteromedial
Lat. Hypothal •  Indian Physiologist
Hypothal.
•  Discovery of feeding
center (1951).
Satiety Feeding
lin

center center •  Founder of modern

su
In

Neurophysiology in
India.
Glucose

Food intake

Hypothalamic Obesity

Causes:Destruction of satiety center

•  Craniopharyngioma
•  Pituitary macroadenoma
•  Treatment of above tumor (Surgery or, radiotherapy)
Hyperphagia is associated with
Hyperglycemia during diabetes mellitus ????

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Polyphagia in DM
Venteromedial
Hypothal. Lat. Hypothal
•  Hunger was due to a reduction in the utilization
Satiety Feeding of glucose by cell (satiety center) rather than to
lin

center center a reduction in its concentration in the blood

su
In

High glucose Cellular

In blood Hypoglycemia

Food intake

PVN Food Intake

éFood intake
êFood intake
(orexigenic)
(anorexigenic)
Role of paraventricular and
Arcuate
arcuate nuclei in feeding NPY POMC Nucleus

Insulin
Ghrelin Leptin
CCK
Neuropeptide Y (NPY) pro-opiomelanocortin (POMC)
Insulin Deficiency ????

Role of paraventricular and arcuate Role of paraventricular and arcuate

nuclei in feeding
Two groups of neurons in the arcuate nuclei
control appetite and energy expenditure:
•  Pro-opiomelanocortin (POMC) neurons that
produce α-melanocyte-stimulating hormone
(α-MSH)
•  Neurons that produce the OREXIGENIC
substances neuropeptide Y (NPY)
nuclei in feeding……
•  POMC neuron acts on paraventricular nuclei
and activates sympathetic system through
NTS.
•  The net effect is reduces food intake while
increasing energy expenditure.
•  Activation of NPY receptor on paraventricular
neurons results in stimulation of appetite.

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Peripheral factors in control of
feeding
•  Insulin, leptin and cholecystokinin (CCK) are
hormones inhibit NPY neurons and stimulate
adjacent POMC neurons, thereby reducing food
intake.
•  Ghrelin, a hormone secreted from the stomach,
activates NPY neurons and stimulates food intake.
Circadian rhythm
Example of circadian rhythm
•  Melatonin secretion by pineal gland
•  Sleep-Wake cycle (6-8h of sleep &16-18h
of wakefulness)
•  Body temperature
•  Certain hormone secretion (ACTH,
Cortisol)
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5. Regulates circadian
rhythms & the sleep cycle
Circadian rhythm
•  A circadian rhythm is a roughly 24 hour
cycle in the physiological processes of
living beings, including plants, animals.
•  In a strict sense, circadian rhythms are
endogenously generated.
•  They are modulated by external cues such
as sunlight and temperature.
Melatonin secretion
•  Melatonin secretion shows circadian
rhythm
•  Peak level at 3-4am
•  Fluctuation of melatonin depends on
sympathetic innervation of pineal gland
•  Pineal gland secretion increases during
darkness and decreases by light.
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Melatonin secretion: Circadian rhythm Melatonin secretion in pinealocyte

Sympathetic nerve
Pineal
GABA
Eye SCN PVN Gland
NE

Light β- receptor

Superior CAMP
Cervical
ganglia
Tryptophan Melatonin Blood

Pinealocyte
IML (T-L region) Preganglionic sympathetic

Melatonin secretion…….. Melatonin secretion…….

•  Light-dark input to retina is conveyed by •  Density of beta receptor increases during
sympathetic nerve to the pineal gland. night.

•  Sympathetic neurotransmitter (NE) stimulates •  Melatonin secretion is more during winters

and less during summers.
pinealocytes via adrenergic receptor (beta).
•  So, in addition to circadian rhythm,
•  Increase CAMP in pinealocyte stimulates N-
melatonin has an annual rhythm also.
acetyltransferase (NAT) enzyme

•  NAT converts tryptophan to melatonin.

Melatonin in Mood and Sleep disorders Sleep-Wake cycle: Circadian rhythm

•  Melatonin worsens depression symptoms Light Pineal

Gland Entrainment to
•  Mood disorders typically occurs in winter months Retina 24hour
are known as seasonal affective disorder (SAD) 12:00 5 am
RHT
•  SAD patients improves in response to phototherapy.
SCN Sleep-Wake
•  Melatonin is a sleep inducing substance 8 pm
cycle
10 am
•  It induces and improves sleep duration particularly
REM sleep duration. 3 pm
•  Melatonin has beneficial role in insomnia
Endogenous rhythm
(25-30 hour duration)

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Sleep-Wake cycle: Circadian rhythm…. Jet lag

•  Sleep wake cycle follow a 24hour (circadian)
rhythm due to light-dark input.
•  If external cues in the form of light and darkness
are removed, the sleep wake cycle lengthen to
25-30 hours.
•  The biological clock for sleep is located in SCN
•  SCN receive afferent input from retina via retino-
hypothalamic tract (RHT).
•  Endogenous rhythm is entrained by light dark
cycle to an exact 24hour via RHT
Jet Lag: Alterations to the body's circadian rhythms
resulting from rapid long-distance trans-meridian
(east–west or west–east) travel on high-speed aircraft
•  Light: Dark cycle is out of phase with the place from
where the journey has started.
•  It takes time for the body clock to entrain to new
light: dark cycle
•  Daytime tiredness and sleepiness are common
symptoms

6. Sexual Drive Regulation

•  The most anterior (medial preoptic area)
and most posterior portions of the
hypothalamus. 8. Thermoregulation
•  Medial preoptic region participates in the
control of masculine sexual behavior, such
as erection and ejaculation.
•  Ventral regions of the hypothalamus play
a major role in the control of feminine
sexual behaviors, such as lordosis.

Body Temperature Core and Shell temperature

•  Normal Body Temperature: 98.6°F(37°C)
–  Range: 97°F to 99°F
•  Rectal Temp: 0.5F to 1°F more than Oral
•  Rectal temp. reflects the internal body
temp. (Core Body Temp)
•  Core Body temp remain almost constant
•  Skin temp (Shell Temp): Variable

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Temperature Homeostasis
•  Keep the body temp within a very narrow
range of 97°F to 99°F
•  Temperatures above this: denature
enzymes and block metabolic pathways
•  Temperatures below this: slow down
metabolism and affect the brain.
Heat production (Thermogenesis)
Heat production rate in adult is 80 kcal/h at rest to 600
kcal/h during exercise. Body heat is produced by:
•  Activity of skeletal muscle
•  BMR (Basic metabolic rate) or, RMR
•  Specific Dynamic Action of food (SDA)
•  Chemical Thermogenesis: Epinephrine, NE, Thyroxine
•  Brown Fat (infant): Source of considerable heat
production
BMR
•  BMR: Amount of energy expended while at
rest in a neutrally temperate environment, in
the post-absorptive state (meaning that the
digestive system is inactive, which requires
about twelve hours of fasting)
•  BMR is due to essential activities of CNS,
heart, kidneys, and other organs.
•  Normal BMR is about 70-80 kcal/h
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Temperature Homeostasis..
•  Balance between heat production & heat
loss (Heat Balance)
•  Heat production is called thermogenesis
•  Heat loss is called as thermolysis
Basal Metabolic Rate (BMR)
The Minimum Energy Expenditure for the Body to
Exist. BMR is calculated after:
•  Fasting for at least 12 hours
•  A night of restful sleep
•  All psychic and physical factors eliminated
•  The room temperature between 68° and 80°F
•  No physical activity
•  No strenuous activity (in last1 hour)
Specific Dynamic Action of food (SDA)
•  Also known as Thermic effect of food (TEF) or
dietary induced thermogenesis (DIT)
•  It is the amount of energy expenditure above the
resting metabolic rate due to the cost of digestion
& absorption food for use and storage.
•  The energy used is converted into heat
•  There is 15% increase in heat production due to
SDA
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Heat Loss (Thermolysis) Cutaneous Heat Loss

•  Cutaneous heat loss
•  Pulmonary heat loss
•  Excretory heat loss

Cutaneous Heat Loss Pulmonary & Excretory Heat Loss

•  Radiation: 60% Pulmonary Heat Loss:
•  Conduction: –  Evaporation of water in expired air
–  To objects:3% –  Warming of inspiratory air
–  To air: 15% –  Panting
•  Convection: 15%
•  Evaporation: 22% Excretory Heat Loss:
–  Urine and stool

Thermal sensors
•  Thermal sensors are thermoreceptors
located in two areas in body:
Mechanisms of Thermoregulation –  Skin (free nerve ending)
•  Cold
•  Warm
–  Hypothalamus (Anterior: pre-optic area)

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Hypothalamic temperature regulating
neurons
•  Three categories of neurons:
o Sensory neurons: located in anterior
hypothalamus
o Heat loss neurons: located in anterior
hypothalamus
o Heat production neurons: located in
posterior hypothalamus
Set point Hypothalamus acts as a thermostat
The hypothalamic “set point” average is 98.6F
in hypothalamus
Thermoregulatory responses
Activated by Exposure to Heat
1.  Vasodilatation
2.  Sweating
3.  Anorexia
4.  Apathy
5.  Increase in Respiration
6.  Decrease TSH secretion
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Alteration in Body temperature
Thermoreceptor
Spinal cord tract
Hypothalamus
(integration center)
Compares prevailing thermal
condition with “set point”
Generate command signal
(Ant. & Post. Hypothalamus)
Alteration of heat gain or, loss
Thermoregulatory responses
Activated by Exposure to Cold
1.  Shivering
2.  Vasoconstriction
3.  Horripilation
4.  Curling up
5.  Increase voluntary activity
6.  Increase TSH secretion
7.  Increase Catecholamines
Heat Exchange in the Skin
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Thermoregulatory regulatory Central Peripheral

Thermo-receptor Thermo-receptor
responses
Exposure to Cold Exposure to Heat
Shivering Vasodilatation
Hypothalamus
Vasoconstriction Sweating Sympathetic Somatic
Horripilation Increase in Respiration nervous system nervous system
Curling up Anorexia
Increase voluntary activity Apathy Sweat Blood Brown Skeletal muscle
Increase TSH secretion Decrease TSH gland vessel fat
Increase Catecholamines secretion
Non-Shivering Shivering
thermogenesis (heat production)

9. Regulation of homeostatic
Thank you
functions

Homeostatic functions

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