CONTROL OF VISCERAL

FUNCTION.
PRESENTERS:
FACILITATOR: DR. MURIITHI M. W

5TH JUNE 2018

 What is visceral activity?
• Any organ activity that is controlled by the autonomic
nervous system. Systems controlled by the autonomic
nervous system include:
• Respiratory system: trachea, bronchi, lungs.
 Visceral Structures
• Viscus - hollow structures bound by
smooth muscle

• Organs under autonomic nervous control

• Secretory glands function

• Systems under automatic control

 VISCERAL ACTIVITY
• Can also be
– Involuntary/ automatic
– voluntary
• Can be
– Endocrine
– Paracrine
– Neuronal/ nervous
 Composition of afferent input
Purely autonomic - HR, PUPIL, BARO, CHEMO

Autonomic + Somatic - MICT. VOMIT. COUGH

( rate can be modified voluntarily)
Autonomic + Cortical - HUNGER, RAGE ,
SWALLOW
(Encephalized – experience & memory
modified)
Programmed - SWALLOWING, HICCUPS
Mechanisms of visceral activity control

Can be
Negative feedback(most common)

Positive feedback e.g release of cck, secretin

Feedforward e.g exercise, salivation,

lactation, gastric secretion, labour
COMPONENTS OF A CONTROLLED SYSTEM

• Sensor
• Afferent pathway
• Controller/ intergrator
• Efferent pathway
• Effector
• Controlled variable
LEVELS OR HIERACHY OF REGULATION
I. Spinal cord
Bladder reflexes, Anorectal function, ejaculation
II. Medulla Oblongata
i. CVS and RS (vital centre) Brainstem
ii. Vomiting, coughing, gagging, sneezing, swallowing
III. Midbrain-pupillary and accommodation reflexes

IV. Hypothalamus
Satiety, hunger, thirst, chemoregulation.
baroreceptor mechanism
V. Basal nuclei and cortex-modulation of brain stem
Spinal cord(defecation/voiding)
 Major visceral activities

• Respiratory system
• Cardiovascular system
• Gastrointestinal system
• Renal system
• Genitourinary system
• Other control systems like temperature
& instinctive behaviour
• Cardiovascular system: heart, blood vessels.
• Gastrointestinal system: salivary
glands,oesophagus,stomach,large intestine,small
intestine,appendix,rectum,liver,gall bladder.
• Reproductive system: testis,ovaries,fallopian tubes,uterus.
• The endocrine system: pineal gland, pituitary
gland,hypothalamus, thyroid and parathyroid glands,adrenal
glands,endocrine pancreas,kidneys,ovaries and testes.
• Lymphatic system: thymus,spleen,lymphatics.
• Urinary system: kidneys,ureters,bladder,urethra.
• Central nervous system: brain, spinal cord,nerves,organs of special
sensation e.g eyes,ears,tongue.
 Regulation of respiration.
• Control of respiration is both by neural and chemical control.
• The pattern of motor stimuli during breathing can be divided
into inspiratory and expiratory phases.
• Inspiration shows a sudden, ramped increase in motor
discharge to the inspiratory muscles (including pharyngeal
dilator muscles).
• Before the end of inspiration, there is a decline in motor
discharge.
• Expiration is usually silent, except at high minute ventilation
rates.
 Regulation of respiration.
• Controlled variables: Oxygen,carbondioxide,blood hydrogen
ion concerntrations.
• Sensors:Peripheral chemoreceptor bodies(carotid and aortic
bodies) are strongly stimulated by fall in the oxygen
concentration in the arterial blood below normal, and also by
a rise in the carbon dioxide and hydrogen ion concentration.
• Affarents: Signals are sent to respiratory centers via the vagus
nerve (from aortic bodies) and glossopharyngeal nerve (from
carotid bodies).
 Regulation of respiration.
• Controller:
• Four main centers in the brain regulate respiration:
– Inspiratory center (medulla).
– Expiratory center (medulla).
– Pneumotaxic center (pons).
– Apneustic center (pons).
• Respiratory centers in medulla.
– Dorsal respiratory group
• Most of the neurons in this group are located in the nucleus tracts solitarius,some
neurons are located in the reticular substance of the medulla.
• These neurons receive afferent fibers from vagus and glossopharyngeal nerves which
transmit sensory signals from peripheral chemoreceptors,baroreceptors and receptors in
the lungs.
• Discharges from this group of neurons to muscles of inspiration brings about the
inspiratory ramp.
• This group of neurons controls the rate of increase of the ramp signal and the point at
which the inspiratory rump ceases, controlling the rate of respiration.
– Ventral respiratory group.
• Found anterior and lateral to the dorsal respiratory group of neurons. Rostrally they are
found in nucleus ambugus,caudally in the nucleus retroambigus.
• They are quiet during normal respiration, quiet expiration is due to elastic recoil of lungs
and thoracic cage.
• When respiratory drive for increased pulmonary ventilation becomes greater than
normal, signals from the dorsal respiratory group of neurons spills over to this group and
this group contributes to the extra respiratory drive.
• They contribute to both inspiration and expiration.
• Respiratory centers in the pons.
– Pneumotaxic centre.
• Located in the nucleus parabrachialis in the upper pons.
• Transmits signals to the inspiratory centre.
• Switches off the inspiratory ramp, limiting inspiration, increasing
the rate of breathing.

– Apneustic centre
• Coordinates transition between inhalation and exhalation
• Sends stimulatory impulses to the inspiratory area – activates and
prolongs inhalation (long deep breaths)
• Overridden by Pneumotaxic control from the Apneustic area to
end inspiration
 Chemical control of respiration.
• Changes in concentration of blood levels of oxygen, carbon dioxide and
hydrogen ions affect respiratory activity.
• Carbon dioxide in CSF dissolves to form carbonic acid which dissociates into
hydrogen ions that excite the chemo sensitive area which sends signals to the
respiratory centre increasing respiration.
• Hering-Breuer inflation reflex.
– In the walls of the bronchi, bronchioles and throughout the lungs there
are stretch receptors which transmit signals through the vagus into the
dorsal group of neurons when the lungs get overstretched(> 1.5 liters per
breath).
– This feedback mechanism switches off the inspiratory ramp stopping
further inspiration and increases the rate of respiration.
• Cortical control of respiration.
– Cortex can override the brain stem and induce voluntary control of
breathing when chemoreceptors detect rising C02 levels and lower O2
levels.
– Voluntary hyper or hypoventilation.
• Effect of irritant receptors in the airways(pulmonary irritant receptors).
– Found in epithelium of trachea, bronchi and bronchioles.
– In response to certain irritant stimuli, coughing sneezing,
bronchoconstriction can occur.
 VP
• T1/2 of18mins and
inactivated in the liver
• Regulated by OVLT
receptors but the
threshold for thirst is
slightly higher
• Significant changes
occur even if osm
changes by 1%
 Role of thalamus in respiration.
• The mediodorsal nucleus of the thalamus
affects the activity of respiratory neurons.
 Regulation of gastrointestinal activity.
• The GIT has a nervous system of its own called the enteric nervous
system, in the gut lining from the oesophagus to the anus.
• Its made up of the myenteric plexus (Auerbach’s plexus) between
the muscular layers of the wall, and a submucosal plexus, the
meissner’s plexus.
• Myenteric plexus
– Controls gut movements.
– Stimulation of this plexus causes increased tonic contraction of
the gut wall, increased intensity of the contractions, increasing
velocity of contraction of the gut wall.
– Has inhibitory neurons to the pyloric sphincter and ileocecal
valve to prevent their closing during gastric emptying and
movement of material through the bowel. The neurotransmitter
is VIP.
• Submucosal plexus.
– Controls the function within the inner wall of the intestine.
– In response to food, signals generated within the
gastrointestinal epithelium, are integrated in this plexus to
control local intestinal secretion and absorption.
 Afferent sensory nerve fibers from the gut.

• Have their cell bodies in the enteric nervous

system, some in the anterior horn cells of the
spinal cord.
• They send signals to the brainstem and spinal
cord. The brain stem initiates vagal refles signals
to the GIT tract.
• Stimulated by
– Gut mucosa irritation
– Excessive gut distension
– Specific chemical substances in the gut.
 Neurotransmitters secreted by enteric neurons.

• Acetylcholine: Excitatory to GIT activity.

• Norepinephrine: Inhibitory to GIT activity.
• Epinephrine: Inhibitory to GIT activity.
• ATP
• Serotonin
• Dopamine
• CCK
• Substance P
• VIP: Inhibitory to GIT activity.
• Somatostatin
• Leu-encephalin
• Metencephalin
• Bombesin.
 Autonomic control of the gastrointestinal tract.

• Parasympathetic innervation.
– Craniosacral divisions.
– Cranial parasympathetic fibres are carried via the vagus nerves to the
oesophagus,stomach,pancreas,small intestine and proximal half of the
large intestine.
– Sacral parasympathetic fibres are carried via the 2nd ,3rd and 4th sacral
segments via the pelvic nerves to the distal half of the colon all the
way to the anus.
– Postganglionic neurons of the GIT parasympathetic nervous system are
located in the gut wall in the plexuses. Stimulation of these nerves
causes increase in the activity of the enteric nervous system.
• Sympathetic nervous system
– Originate in the spinal cord between the segments of T5-L2.
– 2nd order neurons are found in ganglia along the sympathetic chains
lateral to the spinal column.
– These ganglia include celiac and mesenteric ganglia.
– They inhibit activity of the gastroentistinal tract.
 Regulation of salivation
• Mainly controlled by the parasympathetic nervous signals
from superior and inferior salivatory nuclei of the medulla.
• These are excited/inhibited by taste and tactile stimuli in
the mouth and pharynx, and also by signals from higher
centres in the brain.
• Reflexes from the stomach and upper intestine cause
salivation.
• Sympathetic stimulation from superior cervical ganglia to
salivary glands increase salivation slightly. Parasympathetic
stimulation causes salivation to a great extent, and causes
vasodilation to blood vessels.
• Salivation is also affected by blood supply to the salivary
glands.
vomiting
 Gastric acid secretion.
• Cephalic phase: neurogenic signals originating in the
cerebral cortex and in the appetite centres of the
amygdala and hypothalamus,through the dorsal
nucleus of the vagus and through the vagus nerves to
the stomach,cause gastric acid secretion.
• Gastric phase: by vagovagal reflexes from stomach to
brain then to stomach,local enteric reflexes and by the
gastrin mechanism to cause gastric acid secretion.
• Intestinal phase: presence of food in the upper part of
the small intestine causes secretion of gastric juice.
 MEDULLARY LEVEL
REGULATION OF CVS
• Can be
– Neural(rapid pressure changes e.g postural
changes)
– Endocrine( delayed response)
– paracrine
• Regulation occurs at
– Local tissue level(autoregulation)
– Systemic/ general
• CONTROLLED VARIABLES
– Blood pressure
– Oxygen and nutrients to the tissues
– Carbon dioxide, H+, metabolites from tissues
– Temperature(thermoregulation)
 Receptors cvs
• Baroreceptors
– Stretch receptors in the tunica adventia
• High pressure baroreceptors
– Carotid sinus
– Aortic arch receptors
• Low pressure baroreceptors(cardiopulmonary
receptors)
– Rt and lt atrium(Type A and Type B) receptors
– Pulmonary vessels receptors
– Ventricular walls
 Baroreceptors cont
• More sensitive to pulsatile pressure than to
constant pressure
• Chronic hypo/hypertension “resets” the
baroreceptors
• Carotid sinus- linear relationship in response
between 70 and 150mmHg
 chemoreceptors
• Peripheral chemoreceptors mainly exert their
effect on resp system but their stimulation
also causes vasoconstriction
• Hypoxia produces hyperpnea and increases
catecholamine release
 Afferent pathway
• Carotid sinus
– Glossopharyngeal(carotid sinus nerve)
• Aortic arch
– Vagus(aortic depressor nerve)
• Neurotransmitter
– glutamate
Basic pathways; medullary bp control
Medullary control of heart rate by vagus
 Other afferents to the RVLM
• excitatory
– Limbic cortex that relay in the hypothalamus
– Mesencephalic periaquaductal gray
– Brainstem reticular formation
– Pain pathways
– Somatic afferent(somatosympathetic
reflex..exercise)
 Afferent cont..
• Inhibitory
– Cortex via hypothalamus
– Caudal medullary raphe
– Lung inflation afferents
 Efferent and effector
• ANS to smooth muscles(mainly arterioles) via
endothelial cells
• Ach binds to end cells and they is increased
intracellular calcium which activate NOS3 which
activates guanyly cyclase then relaxation smooth
muscle
• Expt capillaries and venules
• Noradrenegic expt muscles
• Cardiac receives both PS and S
 autoregulation
• Myogenic theory of autoregulation
• Metabolic theory of autoregulation
– Stagnation built-up of metabolites
– Metabolites have vasodilator effect e.g low O2,
Low pH, inreases CO2, hyperosmolarity, rise in
temp, hyperkalaemia a feature, lactate, histamine,
adenosine, NO(EDRF),bradykinin, CO
– vasoconstriction 5-HT from plts in
injured,histamine via H1, sub P, VIP, ET
 REGULATION OF RS
• Can be voluntary or involuntary
• Can be neuronally or chemically controlled
• The controlled variable is pO2, pCO2 and pH
HYPOTHALAMUS
 Role of hypothalamus in;
• Posterior pituitary(oxytocin/VP)
• Appetitive mechanisms
– Hunger and satiety
– thirst
• Relation to
– Autonomic function
– Cyclic phenomenon
VISCERAL FUNCTION OF HYPOTHALAMUS
FUNCTIONS CONT..
 HUNGER AND SATIETY
• Appetite depends on interaction btwn
– Satiety centre(ventromedial nucleus)
– Feeding centre(bed nucleus of forebrain bundle at
its junction with the pallidohypothalamic fibres)
• Leptin and more than 20 proteins/pptides
have been implicated in the regulation of
appetite
HUNGER AND SATIETY
 AFFERENT MECHANISMS HYPOTHESIS
• Lipostatic hypothesis
– Humoral signal(leptin) from adipose produced
proportional to fat, acts on hypoTh to inhib apt
• Gut peptide hypothesis
– Food in GIT stimulates hormones to inhib hypoTh
• Glucostatic hypothesis
• Thermostatic hypothesis
– Fall in temp below set pt stimulate apt and vice
versa
 LEPTIN (lipostatic hypothesis)
• 167aas, o/b gene(leptin) and
d/b gene(receptor)
• Acts on the hypoTh to
decrease food intake by
– Decrease th activity of
neuropepptide Y neurons
– Increase th activity of POMC
from neurons
• Leptin acts on arcuate
nuclei(can be destroyed by
gold thioglucose)
• Competes for CB1 receptor
wth cannabinoids
 GHRELIN
• 28 aas pptide wth n-
octanyl on serine 3
residues
• Antagonizes the action of
leptin
• Produced by stomach to
act on th arcuate nuclei
to stimulate appetite
• Stimulates GH release
 Other peptides
• Peptide YY3-26(PYY)
– From small intestines and colon to inhibit appetite
• GIT hormones
– CCK, secretin, somatostatin, gastrin, GRP
 THIRST
• Triggered by
– hypovolaemia
– hyperosm
– Psychological
• Osmoreceptors located in th
ant hypoTh in th
circumventricular organs
• subfornical organ and OVLT
have receptors for Angiotensin
II
• Baroreceptor reflex
mechanisms also involved in
triggering thirst in hypovoelemic
Thirst-osmolarity relationship
Other factors affecting water intake
• Prandial water drinking
– Psychological/ habit
– Increased plasma osmolarity
– GIT hormones acting on the hypothalamus
• Ant cerebral artery injuries,lesions in the ant
hypoTh, altered state of unconsciousness, high
protein diet, pharyngeal mucosa drying
• Pharyngeal gastrointestinal “metering” probably
involved in satisfaction of thirst
 CONTROL OF POST PITUITARY FXN
OXYTOCIN AND VASOPRESSIN
• Nonapptides neural hormones
with terminal disulphide ring
• Synthesized by magnocellular
neurons(Herring bodies
granules) in the paraventricular
and supra-optic nuclei
• Other species have lysine-VP
• Also found in gonads,
thymus,adrenal cortex,
suprachiasmatic N, brainstem
& spinal cord(T.boutons)
CHEMISTRY OF VP AND OXYTOCIN
• An AP in the magnocellular neurons triggers a
Ca2+ mediated exocytosis of both VP and oxytocin
 Physiologic action of VP
• Release is phasic bursting non-synchronous and
mantains a prolonged output increase in VP
• Causes water retention in excess of solute by
acting on collecting duct
• VIA Receptors
– G protein coupled to increase IC Ca2+ and mediates
vasoC.(at high levels because at low level causes a
decrease in CO by acting on th area postrema)
– Also found in the liver(glycogenolysis), brain&cord(NT)
 Receptors cont…
• V1B(also calledV3) is a G protein coupled to
increase IC Ca2+ found in the ant pituitary to
release ACTH.
• V2 receptor
– is a Gs protein coupled that triggers to increase
cAMP
– found on the principal cells of the collecting duct
– Facilitates insertion of aquaporin-2 into the apical
membrane
Relationship btwn osm/BP and VP
 oxytocin
• Acts via G protein coupled receptors on the
myometrium, breast myoepithelial cells and ovary
to trigger increase in I.C Ca2+ .
• Milk ejection reflex(neuroendocrine reflex)
– Many hormones cause breast growth and secretion but
ejection is entirely due to oxytocin
– Tactile/stretch receptors on the nipple trigger a high
frequency, synchronous discharge of Oxytocin
– Emotions and genital stimulation stimulate release but
alcohol inhib
 Other actions of oxytocin
• Stimulate uterine contraction. Inhibited by
progesterone(competitive inhib on oxytocin
receptors) and activated by estrogen
• Coitus stretch stimulate uterine contraction to
facilitate mvnt of sperm.
• circulating levels elevated at ejaculation ???
contraction of vas deferens smooth muscle??
DISORDERS OF VISCERAL
FUNCTION
Presenter:

Facilitator: Dr. M. W. Muriithi

 INTRODUCTION
Central regulation of visceral function involves
complex reflexes.
Those that regulate respiration and blood pressure
integrated in the medulla oblangata
Those that regulate control of pupillary responses to
light and accomodation integrated in the midbrain
Those that maintain chemical constancy and
temperature of the internal environment
integrated in the hypothalamus
• We look at disorders in terms of the affected integration
centre
• MEDULLA OBLANGATA
• The vital centres are the medullary areas for the autonomic
reflex control of the circulation, heart, and lungs.
• Lesions in the vasomotor area would result in defective
blood pressure control.
 Postural hypotension-this is a fall in systollic pressure
≥20mmhg or diastollic ≥10mmhg due to failure of
autoregulatory systems
 Regulation of Respiration

• Rhythmic discharge of neurons in the medulla and pons

produces automatic respiration; transection of the
brainstem below the medulla stops respiration

• Other medullary reflexes autonomic reflexes that will be

affected include:
• Swallowing
• Gag reflex
• Cough
• Vomiting
 HYPOTHALAMIC RELATED DISORDERS
• Daibetes insipidus
• Syndrome of inappropriate hypersecretion of antidiuretic
hormone (SIADH)
• Abnormalities in temperature regulation
• Hypogonadism
• Precocious puberty
• Obesity
• emaciation
• Bulimia
• anorexia
 Diabetes Insipidus
• Is the syndrome that results when there is a
vasopressin deficiency or when the kidneys
fail to respond to the hormone
• Its estimated that
• 30% neoplastic lesions ( primary or
metastatic)
• 30% post traumatic
• 30% idiopathic
• 10% vascular lesions, infections, systemic
dxs-sarcoidosis
 DIABETES INSIPIDUS

• Symptoms- polyuria and polydipsia

provided the thirst mechanism is intact.
• In patients whith incomplete deficiency
treatment with drugs that increase
vasopressin secretion such as clofibrate is
of value
• Chlopropamide increases the renal
response to vasopressin
 SIADH
This occurs in patients with cerebral disease
(cerebral salt wasting) and pulmonary disease
(pulmonary salt wasting)
Vasopressin is responsible for dilutional
hyponatremia and loss of salt in the urine
when the water retention is sufficient to
expand the ECF volume, reducing
aldosterone secretion
Rx: demeclocycline, an antibiotic that reduces
renal reponse to vasopressin.
 Temperature regulation
abnormalities

• Hypothermia

• Fever-central pyrexia secondary to

craniotomy in the hypothalamic
area

• Pontine haemorhage
 hypogonadism

• Kallmann’s syndrome-combination of
hypogonadism due to low levels of circulating
gonadotropins(hypogonadotropic
hypogonadism) with partial or complete loss
of sense of smell

• GnRH neurons develope in the nose then

migrate
 Precocious puberty

• Precocious puberty refers to the

appearance of physical and hormonal
signs of pubertal development at an
earlier age than is considered normal
• There are 2 types
a. central precocious puberty (CPP) –
True PP
b. precocious pseudopuberty.
 PRECOCIOUS PUBERTY
• Central precocious puberty, which is gonadotropin-
dependent, is the early maturation of the entire
hypothalamic-pituitary-gonadal (HPG) axis, with the
full spectrum of physical and hormonal changes of
puberty. True precocious puberty.
Gametogenesis may occur

• Precocious pseudopuberty is much more common

and refers to conditions in which increased
production of sex steroids is usually gonadotropin-
independent but could also be due to pituitary
adenomas
 Obesity/anorexia
• Body weight depends on the balance
between caloric intake and utilization of
calories.
• Obesity results when the former exceeds
the latter.
• Hypothalamic regulation of the appetite for
food depends primarily upon the
interaction of two areas:
a. Feeding centre (lateral)
b. Satiety centre (medial)
 Control of appetites
• Stimulation of the feeding center (hunger
center) evokes eating behaviour, destruction
causes severe fatal anorexia in otherwise
healthy animals

• Lesions in the satiety center cause

hyperphagia and if food supply is abundant
results in syndrome of hypothalamic
obesity. Also caused by Leptin deficiency.
• THANK YOU
CENTRAL REGULATION OF VISCERAL
FUNCTION
PRESENTER

MODERATOR
Dr. M. W. Muriithi (Lecturer)

5TH JUNE,2018 MMED

95
 SCOPE
• Medullar
– Cardiac
– Respiration
– Reflexes: Cough,Sneezing,gagging, swallowing &Vomiting
• Midbrain
– Light reflex
– Accommodation
• Hypothalamus
– Thirst & hunger
– Autonomic-catecholamines
– Endocrine
– Temperature
– Cycles
• Limbic
 HIERACHY OF VISCERAL INTEGRATION

• Simple Reflexes- regulated by Spinal cord

– Contraction of full bladder
• Complex Reflexes:
– Respiration & BP-Medulla oblongata
– Pupillary reflex to light & Accommodation-Midbrain
– Chemistry constancy & temp of internal environment-
Hypothalamus
– Hypothalamus fxn with limbic system to regulate emotional &
instinctive behaviour

97
 MEDULLA OBLONGATA
• Has VITAL CENTRES-Areas for autonomic reflex control of
circulation, heart & lungs
• Controls BP,HR & Respiration

a. CARDIAC CENTRE
• Source of afferents:
– Carotid sinus & body
– Aortic sinus & body
– Receptor cells in medulla

Cardiac Centre Motor responses

• graded and delicately adjusted
• include somatic as well as visceral components.

98
MEDULLARY CENTRES
SNS: Basic pathways involved in the medullary control of blood pressure. IML, intermediolateral gray column; NTS,
nucleus of the tractus solitarius; CVLM, IVLM, RVLM, caudal, intermediate, and rostral ventrolateral medulla;

RVLM
 b. Respiration Centres

Internal
Intercostals

External Intercostals
RESPIRATORY CENTRES
 c. SWALLOWING

1. oral phase : mix bolus, propelled into pharynx

2. pharyngeal phase: transfer of bolus past the larynx

Once the bolus reaches the tonsils, it triggers this phase .
• Completely automatic (there is no ability to consciously control this).
• Lasts one second.
• Several events are occurring in rapid secession:

• palate closes against the back wall of throat prevents food from coming up through nose
• vocal cords close. This shuts off access to the trachea.

• throat muscles constrict in a coordinated manner to help push the food downwards .
• larynx is pulled upwards and forwards , epiglottis tilts posteriorly, covering and protecting the
vocal cords and directing bolus to the sides

• upper esophageal sphincter relaxes. This allows the bolus to enter the esophagus.

• Central program generator in the medulla initiated by pharyngial contact and involves carefully
timed responses of the respiratory as well as the gastrointestinal system.
• 3. Esophageal phase.
Once the food bolus
enters the esophagus, it
is actively transported
down to the stomach
through LES
SWALLOW
 Swallowing…………..
• Controlled by a Central Program Generator in medulla
• Initiated by voluntary act of propelling what is in the mouth
towards back of pharynx

d.COUGHING
• Initiated by irritation of lining of trachea & extrapulmonary
bronchi
• Glottis closes; Strong contraction of respiratory muscles builds
up intrapulmonary pressure
• Glottis suddenly opens
• Explosive air

106
 Cough………………….cont
• Receptors in and under the
epithelium of the airways.
– larynx, trachea, pharynx, ,
extra pulmonary bronchi
– absent beyond the
respiratory bronchioles.
– rapidly adapting,
– thin myelinated fibers in the
vagus nerves,
– Irritant : directly stimulated
by tussive agents, dust or
other foreign particles
• Sensory (afferent) pathway
– The internal laryngeal nerve, in the larynx to the CNS via vagus
– Activation of C-fibre receptors in the airway releases sensory neuropeptides.
– These cause neurogenic inflammation and may activate the receptors

• The central connections

• Signals transmitted to the cough centres in the medulla, and then to the
cerebral cortex (via the vagus nerve).

• C-fibre receptors inhibit cough controlling the sensitivity of the cough reflex
and its pattern of response
COUGH
 e. SNEEZING
• Due to irritation of nasal epithelium
• Initiated by stimulation of pain fibres in trigeminal nerve

f. VOMITING
• Vomiting Centre-In reticular formation of medulla
• Vomiting afferents:
– Irritation of mucosa of upper GIT
– From diencephalon & limbic system
– From vestibular nuclei-mediate nausea & vomiting of motion sickness
• Starts with salivation & sensation of nausea
• Reverse peristalsis empties material from upper s/int into stomach
• Glottis closes (prevent aspiration of vomitus into trachea)
• Breath held in mid aspiration
• Muscles of abdominal wall contract (hence increased intraabdominal
pressure bcause chest is in a fixed position
• LES & Esophagus relax & gastric contents ejected
110
 Vomiting………………….

• Afferents
• Irritation of the mucosa of upper GIT--visceral afferent pathways in sympathetic nerves
and vagi.
• vestibular nuclei input mediate the nausea and vomiting of motion sickness.
• Chemoreceptor cells in the medulla when stimulated by certain circulating chemical
agents.
• diencephalon and limbic system for emetic responses to emotionally charged stimuli ie
"nauseating smells" and "sickening sights."

• "vomiting center" in reticular formation of medulla (various scattered groups of neurons)

that control different components of the vomiting act.
• The chemoreceptor trigger zone in which these cells are located is in the area postrema

Receptors
• 5-HT3 receptors (GIT)
• dopamine D2 receptors and 5-HT3 receptors in postrema and adjacent nucleus of the solitary
tract
 Vomiting : Afferents

Uremia
CuSO4
Efferent pathway
Steps to vomiting

• Coordinated and carefully timed somatic

as well as visceral components.
• salivation and sensation of nausea.
• Reverse peristalsis into stomach.
• glottis closes, preventing aspiration of
vomitus into trachea
• breath is held in mid inspiration.
• abdominal wall contracts, with chest
fixed , increasing intra-abdominal
pressure.
• LES and the esophagus relax, and
gastric contents are ejected.
114
MIDBRAIN:Accomodation
 MIDBRAIN: Light reflex
• Parasympathetic response
http://library.med.utah.edu/kw/hyperbrain/a
nim/reflex.html
• Pupillary response to light
 HYPOTHALAMUS

Master of Neuroendocrine system

117
HYPOTHALAMUS

118
 HYPOTHALAMUS
• Position:
– Anterior end of diencephalon; below
hypothalamic sulcus; in front of interpeduncular
nuclei
• Afferent & Efferent:
– Most unmyelinated
– Connxn to limbic system & Nuclei in mid
brain,tegmentum,pons & hindbrain
• Relation to pituitary:
– Neural connxn btn hypothalamus & post lobe
– Vascular connxn btn hypothalamus & ant lobe
119
 PITUITARY
• Post Pituitary:
– Produce oxytocin & Vasopressin (released into general circulation
from endings of SON & PVN)
– Embryonically arise frm evagination of floor of 3rd ventricle
– Hv many axons from supraoptic & PVN
• Ant & Intermediate lobes:
– Embryonically from Rathke’s pouch (evagination from roof of pharynx)
– Hypophysiotropic hormones secreted frm Arcuate & other neurons
• Nerves to pituitary:
– Sympathetic-to Ant Lobe (frm its capsule)
– Parasympathetic-via petrosal verves,f ew via hypothalamus
• Axons btn hypothalamus & post pituitary:
– hypothalamohypophyseal tract
• Vascular link btn hypothalamus & post pituitary:
– Portal-hypophyseal vessels
• Blood supply to pituitary: 120
Relation: hypothalamus:pituitary, Nuclei

121
 Factors affecting Hypothalamic function
Gender
• Several hypothalamic nuclei are sexually dimorphic, i.e. there are clear
differences in both structure and function between males and females.

• E.g. sexually dimorphic nucleus within the preoptic area, which is present
only in males.
• growth hormone secretion is sexually dimorphic: males are much larger
than females
• However most of the differences are subtle changes in the connectivity
and chemical sensitivity of particular sets of neurons.
Pre-pubertal stress determines respond to an acute stressor
• glucocorticoid receptors mediate negative feedback control of CRF synthesis

Effects of aging on the hypothalamus

• SON and PVN lose one-third of IGF-1R cells with normal aging.
• Worsened by caloric restriction

Sex steroids
• Developmental influence of androgens : 'Tomboyism' in girls might reflect the
effects of androgens on the fetal brain, But first 2-3 years is most important
determinant of gender identity

• ovarian steroids: Males and females respond differently to ovarian steroids, partly
because the distribution of estrogen-sensitive neurons in the hypothalamus is
sexually dimorphic, in neurons of anterior and mediobasal hypothalamus, notably:
• the preoptic area (where LHRH neurons are located)
• the periventricular nucleus (where somatostatin neurons are located)
• the ventromedial hypothalamus (which is important for sexual behavior).
 Connections of the Hypothalamus
Mostly unmyelinated

• The limbic forebrain (amygdala, septum, diagonal band of Broca, and the olfactory bulbs, the cerebral cortex)

• nuclei in the tegmentum, pons, and hindbrain

• the brainstem reticular formation and autonomic zones, Pineal

• hindbrain and the spinal cord. neurons that secrete oxytocin and vasopressin
• Relation to the Pituitary Gland
• hypothalamohypophysial tract.
• portal hypophysial vessels . Sympathetic fibers reach the anterior lobe from its capsule, and
parasympathetic fibers from the petrosal nerves

• intrahypothalamic system of dopamine- secreting neurons in arcuate nucleus and end on the median
eminence capillaries.

• Serotonin-secreting neurons project to the hypothalamus from the raphe nuclei.

• Norepinephrine and epinephrine secreting (ventral hypothalamus).
 HYPOTHALAMO-HYPOPHYSEAL VESSELS
• Arterial twigs from the carotid arteries and circle of Willis form a network
of fenestrated capillaries called the primary plexus on the ventral surface
of the hypothalamus

• Capillary loops also penetrate the median eminence.

• They drain into the sinusoidal portal hypophysial vessels that carry blood down
the pituitary stalk to the capillaries of the anterior pituitary.
• This system begins and ends in capillaries without going through the heart and is
therefore a true portal system.
• There is no other anterior hypophysial arterial supply except capsular vessels and
anastomotic connections from the capillaries of the posterior pituitary.

• The median eminence is generally defined as the portion of the ventral

hypothalamus from which the portal vessels arise. This region is "outside
the blood-brain barrier“
 Connections of the Hypothalamus
• The hypothalamus co-ordinates many hormonal and behavioural circadian
rhythms, complex patterns of neuroendocrine outputs, complex homeostatic
mechanisms, and many important behaviours, gastric reflexes, maternal behavior,
blood pressure, feeding, immune responses

The hypothalamus is responsive to:

• Light: daylength and photoperiod for regulating circadian and seasonal rhythms
• Olfactory stimuli, including pheromones
• Steroids, including gonadal steroids and corticosteroids
• Neurally transmitted information arising in particular from the heart, the
stomach, and the reproductive tract
• Autonomic inputs
• Blood-borne stimuli, including leptin, ghrelin, angiotensin insulin, pituitary
hormones, cytokines, plasma concentrations of glucose and osmolarity etc
• Stress
• Invading microorganisms by increasing body temperature
Pituitary connections
 HYPOTHALAMIC FUNCTIONS
• Autonomic functions-catecholamines (fight & flight)
• Sleep & wakefulness
• Circadian rhythm-cyclic phenomena. Synchronized to day-night
cycle on the environment
– Circadian rhythm entrained by suprachiasmatic nuclei (SCN) which
receive information about light-dark cycle via a neural pathway-
Retinohypothalamic fibres from optic chiasma to SCN
– No effect during usual day time; but
• just after dark it delays onset of sleep period
• Before dawn it accelerates onset of next sleep period
• Endocrine- “releasing” hormones to pituitary
• Hunger
• Thirst
• Temperature regulation
• With Limbic system to regulate emotional & instinctive system
129
130
Hypothalamus fxns cont…

131
 hypothalamic function ………………..
• Some are fairly clear-cut visceral reflexes,
• complex behavioral and emotional reactions;
• all involve a particular response to a particular stimulus.

1. RELATION TO AUTONOMIC FUNCTION

Sherrington called the hypothalamus "the head ganglion of the
autonomic system."
• Stimulation of its lateral nuclei, produces the mass sympathetic
discharge seen in animals exposed to stress (the flight or fight
reaction).
• separate hypothalamic areas control of epinephrine and
norepinephrine secretion
 2. RELATION TO SLEEP
• The basal forebrain sleep zone includes parts of the hypothalamus.

• Slow-wave sleep, diencephalic sleep zone is in the posterior

hypothalamus and the nearby thalamic nuclei. The stimulus frequency
must be about 8 Hz; faster stimuli produce arousal.
• Sleep center : anterior
• Wake centre : posterior

• Orexin/hypocretin system of lateral hypothalamus is the main excitatory

neuromodulatory system that controls monoaminergic and cholinergic
systems that regulate vigilance
• Lesions associated with irreversible sleep: Narcolepsy
 3. RELATION TO CYCLIC PHENOMENA
Most cells have 24 hours rhythmic fluctuations ie, they are circadian (L circa "about" +
dia "day").
Entrained, ie, synchronized to day-night light cycle in the environment (24 hours)
• In the liver these are influenced by the pattern of food intake,
• other cells : suprachiasmatic nuclei (SCN),
• Efferents from SCN initiate neural and humoral signals that entrain a wide
variety of well-known circadian rhythms.
• secretion of ACTH and other pituitary hormones,
• the sleep-wake cycle, activity patterns,
• SCN connects to Pineal: melatonin nocturnal peaks in secretion important
hormonal signal entraining other cells in body

• retinohypothalamic fibers from the optic chiasm information about the light-
dark cycle
 Mechanism of cyclic phenomena
• SCN genes activated diurnally
• protein products enter modify cell function and thus neuronal discharge.
• proteins are then modified and return to the nucleus, for negative feedback

• Two different peaks of circadian activity in the SCN. affect the sleep-wake cycle in
humans depending on the time of day when it is experienced.
• during the usual daytime it has no effect,
• just after dark it delays the onset of the sleep period,
• just before dawn it accelerates the onset of the next sleep period.

• Injections of melatonin have similar effects.

• In experimental animals, exposure to light turns on immediate-early genes in the

SCN but only at times during the circadian cycle when light is capable of influencing
entrainment.
 4. Endocrine Function
• Hypothalamus:
– Produce Releasing Hormones to AP .eg CRH, TRH, GnRH,
GRH, PRH
– To Post. Pituitary: Oxytocin & Vasopressin (ADH)

136
Ant pituitary

137
 5. HUNGER
Feeding & Satiety
• Boby weight depends on balance btn caloric intake &
utilization of calories

FEEDING CENTRE SATIETY CENTRE

Lateral Ventromedial
In bed nucleus of medial forebrain In ventromedial nucleus
bundle at its junction with
pallidohypothalamic fibres

Stimulation cause eating behaviour in Stimulation cause cessation of eating

conscious animals
Inhibition/destruction cause severe, Lesions cause hyperphagia (abudant
fatal anorexia in healthy animals (Loss food leading to hypothalamic obesity)
of appetite)

138
Hypothalamic obesity

139
142
 Factors regulating food intake
• Increase appetite:
– Melanin concentrating hormone(MCH)
– Neuropeptide Y
– Orexins A & B
– Cold weather
– Hunger contraction (of empty stomach)
• Decrease food intake:
– POMC eg. α-MSH
– CART(Cocaine and Amphetamine Regulated Transcript)
– Malonyl CoA
– CRH
– Warm weather

143
144
 AFFERENT MECHANISMS IN FOOD INTAKE
CONTROL
• Lipostatic hypothesis:
– Adipose tissue produce humoral signal proportionate to
amount of fat in hypothalamus to decrease food intake &
increase energy output
• Gut Peptide hypothesis:
– Food in GIT cause release of 1 or more polypeptides that act
on hypothalamus to inhibit food intake
• Glucostatic hypothesis:
– Increased glucose utilization in hypothalamus produce
sensation of satiety
• Thermostatic hypothesis:
– Fall of body temp below a given set point stimulate appetite
– Rise above a given setpoint inhibits appetite
145
 LEPTIN
• 167 AA
• Inhibit food intake (Lipostatic hypothesis focused)
• Functions of Leptin:
– Activates enzyme ptdyl-inositol-3-hydroxykinase in hypothalamic
cells
– Increase activity of SOCS3 (Suppressor of cytokine signaling-3) in
neuropeptide Y neurons. (SOCS3 suppress further leptin receptor
signalling hence a turn-off mechanism)
– Cause bone loss
– Increase activity of uncoupling proteins-hence a direct peripheral
increase in energy expenditure

GHRELIN
• Stimulate GH secretion hence increase food intake
146
LEPTIN

147
 6. THIRST
• Factors:
– Plasma Osmolality:
• Osmoreceptors-located in ant hypothalamus
• Hypertonicity
• Osmolality is a measure of the osmoles of solute per
kilogram of solvent (osmol/kg or Osm/kg).
– Decrease in ECF volume
• Hypovolemia Regulated by RAAS.
• Renin secretion increased by hypovolemia
– Psychologic & social factors
– Dryness of pharyngeal mucous membrane
148
Thirst

149
 Cortical Thirst centre?
• The positron emission tomography
(PET) image at top, taken after
subjects received an infusion of a
concentrated NaCl to stimulate thirst,
shows regions of activity in the left
side of the brain in thirsty subjects.

• This activity changed dramatically

after their thirst was quenched. In
particular, the yellow and orange
areas above indicate activity along
the cingulate cortex that was
extinguished later.
 Clinicals: Thirstlessness
• Diencephalon dmg • In rare cases, when an
aneurysm or other brain
• Psychoses injury has destroyed the
• Coma sensors in the
• hypothalamus that regulate
Habenular artery dss
blood sodium
• For reasons that aren’t concentration, people can
clear, age tends to lose their sense of thirst
dampen thirst message completely. They must be
from the brain. prescribed a fixed amount
of fluids daily to keep their
body safely hydrated.
 Regulation of ECF Composition & Volume
• Aim:
– Maintain tonicity:
• By Vasopressin-secreting & Thirst mechanism
– Maintain Volume:
• By RAAS
– Specific ion composition eg H+
• By Respiratory acidosis & alkalosis: increased arterial
PCO2 due to decreased ventilation causes respiratoty
acidosis

152
Maintaining Tonicity

153
RAAS

154
155
 Clinical Implications
Surgery
pain and hypovolemia
both stimulants thus dilutional hyponatremia.
SIADH
• cerebral disease ("cerebral salt wasting")
• pulmonary disease ("pulmonary salt wasting"):
interruption of inhibitory impulses in vagal afferents from
the stretch receptors in the atria and great veins.
• Paraneoplastic : cancers secrete vasopressin.

Patients treated with demeclocycline, an antibiotic that

reduces the renal response to vasopressin.
 Diabetes insipidus
Central (Nuclei ,tracts ,Pituitary)
hypophysiectomy (temporary coz of neovs)
• 30% neoplastic 30% are posttraumatic; 30% are idiopathic;
• 10% vascular lesions, infections, systemic diseases, mutations in
prepropressophysin gene.
polyuria and polydipsia: intact thirst mechanism is protective else fatal
dehydration
RX: clofibrate (release), Chlorpropamide (response) to vasopressin.

Nephrogenic diabetes insipidus).

• V2 receptor mutations is X-linked, because the V 2 gene is on the X
chromosome.
• autosomal gene for aquaporin-2
• There is no rise in urinary aquaporin-2 in nephrogenic diabetes.
• Synthetic Agonists & Antagonists

• 1-deamino-8-D-arginine vasopressin (desmopressin; DDAVP)

• very high antidiuretic activity with
• little pressor activity,
• treatment of vasopressin deficiency , bleeding disorders

• Antagonists selectively blocking pressor or antidiuretic activity of

vasopressin have also been synthesized.

Metabolism
• Circulating vasopressin is rapidly inactivated, principally in the liver and
kidneys.
• It has a biologic half-life of approximately 18 minutes in humans.
• Its effects on the kidney develop rapidly but are of short duration.
 Physiologic Effects of Oxytocin
• Stimulation of milk ejection (milk letdown): stimulates contraction of
myoepithelial cells, causing milk Ejection the ducts and cisterns.
• Stimulation of uterine smooth muscle contraction at birth:
– Sensitivity to oxytocin enhanced by estrogen and inhibited by progesterone
(direct action oxytocin receptors)
– increase in number of oxytocin receptors and their mRNA
– positive feedback :dilation of the cervix, descent , impulses in the afferent
nerves relayed to supraoptic and paraventricular nuclei, causing enhanced
labor.
– Locally produced oxytocin may also play a role.
• Facilitate sperm transport.
– uterine contractions.
– contraction of the smooth muscle of the vas deferens, propelling sperm
toward the urethra.
• Establishment of maternal behavior: During parturition, there is an increase in
concentration of oxytocin in cerebrospinal fluid, and oxytocin acting within the
brain plays a major role in establishing maternal behavior
MILK LETDOWN
Control of Oxytocin Secretion
• The most important stimulus
physical stimulation
• The act of nursing or suckling is
relayed within a few ms to the
brain via a spinal reflex arc. These
signals impinge on oxytocin-
secreting neurons, leading to
release of oxytocin.
• Acute stress.
• Both the production and response
modulated by circulating levels of
sex steroids.
• is inhibited by alcohol.
 Stimuli affecting vasopressin secretion
Secretion Increased
• Increased effective osmotic Secretion Decreased
pressure : 285 mosm/kg
• Decreased extracellular fluid • Decreased effective osmotic
volume pressure of plasma
• Pain, emotion, • Increased extracellular fluid
• "stress," volume
• exercise • Alcohol
• Nausea and vomiting  
• Standing  
• Clofibrate, carbamazepine
•   Angiotensin II      
CONTROL OF ANTERIOR PITUITARY SECRETION
 Hypophysiotropic Hormones
• Secreted into the bloodstream and act at a distance from their site of origin.
• Dont escape into the general circulation to any degree, but in high concentration in portal hypophysial
blood.
• There are six established hypothalamic releasing and inhibiting hormones
• CRH
• TRH : PreproTRH contains six copies of TRH
• GRH
• GIH (somatostatin): Periventricular
• GnRH : Medial preoptic
• PIH : Dopamine
• ? prolactin-releasing hormone (PRH)
? TRH, VIP, a 31-amino-acid polypeptide

• Preprohormones may contain other hormonally active peptides in addition to the hypophysiotropic
hormones.
• May act on more than one target hormone
• Source: median eminence of the hypothalamus.
• few nerve cell bodies,
• many nerve endings in
• close proximity to the capillary loops from which the portal vessels originate.
ACTION MECHANISM
• Serpentine G-coupled
– Brain , Retina, ANS
– GIT : Somatostatin , TRH
– Pancreas : GRH (tumors), Somatostatin

• CRH
– hCRH1 hCRH2 : 29 aa
– Binding protein
• Inactivates CRH
• Receptor internalization in Corticotropes
 Significance & Clinical Implications
• The manifestations of hypothalamic disease
• neurologic defects,
• endocrine changes,
• metabolic abnormalities such as hyperphagia and hyperthermia.

Kallmann's syndrome,
• hypogonadotropic hypogonadism
• hyposmia or anosmia
• KALIG1 gene, X linked , codes for adhesion molecule for normal
development of the olfactory nerve on which the GnRH neurons
migrate into the brain.
• GnRH neurons do not reach the hypothalamus and pubertal
maturation of the gonads fails to occur.
Summary
 7. TEMPERATURE REGULATION
• Balance production and loss to determines the body temperature
• Constancy needed for speed of reactions and enzyme systems
• Poikilothermic vs Homeothermicic vs hibernating mammals
• Normal range : 37O C with std deviations 0.2OC
ie 36.3 – 37 .1 OC on 95% confidence interval
Gain Loss
• SDA Conduction
• Skeletal muscle Convection
• Endocrine Catecholamines(short term) Radiation
• Thyroid(long-term)
• Brown fat electrical blanket thermogerin Vaporization : 0.6kcal/g
• Skin Hair Clothing Humidity
 Temperature-regulating mechanisms.
Mechanisms activated by cold Mechanisms activated by heat
Increase heat production Increase heat loss
• Shivering • Cutaneous vasodilation
• Hunger • Sweating
• Increased voluntary activity • Increased respiration
• Increased secretion of Decrease heat production
norepinephrine and • Anorexia
epinephrine • Apathy and inertia  
Decrease heat loss
• Cutaneous vasoconstriction
• Curling up
• Horripilation
Thermoregulation
 Central regulation
Receptors Hypothalamus center
• Skin : Ruffini, Krause • Posterior
• Spinal cord – Cold
– Thresholds
• Hypothalamus
• Vc 36.8oC ,
• Brain • shivering 35.5oC
• Cold more than heat – Lesion hypothermia
• Anterior
– Heat stimulates
– Thresholds 37oC
– Lesion Hypertharmia
TEMP RECEPTORS: Skin
 Factors affecting body temp
• Circadian range o.5 to 0.7O C
• Site : Extremeties, Rectal vs oral, Scrotal 32OC
• Endocrine : Catecholamines Ovulation Thyroid
• Activity : Sleep Exercise Emotional
• Age : children 0.5 less
• Constitutional : ? Genetic
• Pathology : thermostat reset
 Fever: Posterior hypothalamus
Pyrogens • Protective
• Endogenous (from – Pathogens range
neurons / WBC) IL-1β,IL-6 – Antibody production
TNF-α INF-α, INF-β, – Tumors
• Harmful
• Exogenous (Bacterial
– Brain damage heatstroke
endotoxin , LPS)
death
– Malignant hyperthermia
• Stimulate OVLT which mutations predisposing to
stimulates Preoptic area to hyperthermia
Produce PGE2 – Pyrin neutrophil protein
• PGE2 Receptors EP1234 on – Mevalonate-k
– TNF receptor 1
preoptic (posterior)
hypothalamus
 Four phases to a fever
• Prodomal: feels unwell but temperature is normal, pyrogens are acting to
reset hypothalamic set point.

• Chill: -cold and shivering , body temperature is increasing. The body

thermostat is set at higher, the blood is still at 37 degrees C. The
hypothalamus detects a difference and initiates heat generating
mechanism
• Flush: cutaneous vasodilation occurs, the skin becomes warm and flushed
and dry and the temperature is elevated to new set point until a new set
point is determined by removal of pyrogens e.g destruction of bacteria by
antibiotics
• Diaphoresis: hypothalamus set point drops detects the blood as being too
hot and initiates heat loss, patient flushed and feels hot, the temperature
is falling, sweating. Diaphoresis assists in evaporative heat loss. The fever
breaks, and the client becomes ‘Afebrile”.
176
THANK YOU FOR YOUR PATIENCE…

END !!!!!
177