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Sante Medical College

Introduction to Autonomic nervous system


PC-I Dental and Medical students

Abebaye.Aragaw@aau.edu.et

05/30/2024 1
Autonomic nervous system (ANS)

By:Abebaye A 2
Objectives
• To describe general organization of the nervous system

• To discus the major anatomical and physiological difference


in the autonomic division
• Centers of the brain regulating ANS and Autonomic reflexes

• To describe the specific functions of the sympathetic and


parasympthatic nerve
• To prepare the student for further studies in pathophysiology,
pharmacology, and therapeutics
By:Abebaye A 3
Nervous system

Sensory
Integrating
And motor functions

Fig 1: Function of the nervous system


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Organization of the nervous system

By:Abebaye A Fig 2: NS organization 5


Cranial nerves: Somatic and autonomic, efferent and afferent
Directly originated from cerebrum,
not pass through the brainstem

By:Abebaye A 6
Fig 3: Cranial Nerves
The cranial nerves ….
• Third, seventh, ninth and 10th cranial nerves

– Are purely autonomic and parasympathetic

• Trochlear nerve(cn IV) is somatic nerve

– The efferent nerve innervates (superior oblique muscle)

– TRIGEMINAL (CN V) are both somatic and autonomic

• Efferent for mastication

• Afferents: take touch, pain, and temperature

– Abducens (CN VI) nerve is somatic and innervates lateral rectus


muscle
– Vestibulochoclear nerve
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• Afferent: somatic
Spinal nerves

 Sensory and motor


 Autonomic and somatic
 Sympathetic and
parasympathetic

Fig 4: Spinal Nerves

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Functional division of the NS
• Somatic and autonomic
• Somatic
– Innervates voluntary muscles
– Single neuron between CNS & effectors (direct projection)
– Effecter or the motor neurons in the CNS project directly onto
the effectors
– The cell body is located in CNS

By:Abebaye A 9
Functional division of the NS…
• Somatic …
– Connives sensations from eyes, the nose and other sensory
organs to the brain (mainly the cerebral cortex) where most of
the impulses reach into consciousness/awareness
– Condition speed is faster(myelin sheath) than ANS
– Causes somatic reflexes

By:Abebaye A 10
Somatic and autonomic reflexes

 Smooth muscles
 Cardiac muscle
 Glands
 Visceral organs Catecholamine Ach

Adrenergic receptors Nicotinic receptor

Fig 5: Somatic and autonomic reflexes


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Autonomic nervous system (ANS)

 Controls involuntary actions and maintains constancy of internal


environment (homeostasis)
 Innervates Smooth, Cardiac muscles and glands
 Controls autonomic responses
 Not under voluntary control
 Helps to adapt the changes in environment

By:Abebaye A 12
Autonomic nervous system (ANS) …
 Regulates body activities that are generally not under

conscious control
 Mobilizes energy during emotional experience

• When subjects are emotionally excited, changes are made


 HR, BP (functions of the ANS) elevated
• Emotional experiences received by the limbic structures
 The limbic structures control ANS

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Autonomic nervous system (ANS) con’t
 Conveys sensory impulses from the blood vessels, the heart and
all of the visceral organs through afferent nerves to parts of the
brain (mainly the medulla, pons and hypothalamus)
 Autonomic afferents
 Impulses often do not reach our consciousness but still induce
responses
 Impulse sent to effectors via autonomic efferent and autonomic
reflexes (unconscious) generated
– Changes body vegetative functions

By:Abebaye A 14
Autonomic reflexes
• Subconscious sensory signals from a visceral organ enter the autonomic
ganglia, brainstem or hypothalamus,
• Subconscious reflex responses directly back to the visceral organ to
control its activities

Fig 6: Autonomic reflexes

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Visceral/Autonomic reflex arc

Fig 6.1: Autonomic reflexes and the components


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Components in the Autonomic reflexes
• Reflexes mediated by ANS

– Receptor – distal end of sensory neuron (Dendrites) are in

the viscera

– Sensory neuron – nerve impulse to CNS

– Integrating center –hypothalamus and brainstem

– Motor neurons – leave CNS

– Effectors – smooth muscle, cardiac muscle and glands


– E.g Braroreceptor and chemoreceptor reflexes, medullary reflexes,
By:Abebaye A 17
hypothalamic reflexes, midbrain reflexes
Somatic and autonomic efferent nerve arrangement
CNS
Somatic
SOMATIC
ANS

Pre ( large & myelinated) Post ganglionic (C fiber &


ganglionic fibers unmyelinated) motor fibers
By:Abebaye A Fig 7: Motor nerve 18
Comparison between somatic and ANS
Table 1: Somatic versus autonomic nerve
Characteristics Somatic Autonomic
Function Controls voluntary muscle tone, Controls visceral activities, digestion
sensation from skin, bones and joints glandular secretion, sweating,
urination, defecation…
Sensory inputs Somatic sense Mainly from interoceptors
Control of motor Voluntary control from cerebral Involuntary control from
output cortex, with contribution from basal hypothalamus, limbic structure,
ganglia, cerebellum, and spinal cord brainstem , spinal cord
Motor neuron One neuron pathway, somatic motor Pre and post ganglionic fibers. The
pathway neurons extended from the CNS preganglionic form synapse with
and form synapse with the effectors adrenal medulla
Neurotransmitter Ach Ach and catecholamines
s
Effectors Skeletal muscles Smooth, cardiac muscles and glands
Response Contraction Contraction or relaxation, increase or
Always excitatory reduce secretion. Preganglionic is
always excitatory
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Comparisons of peripheral nervous system

NMJ
Thoracolum
bar (L1- L2)

Fig 6: Anatomical and functional comparison


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Functional division of ANS
= Ergotropic rxn
Another name of PNS Another name of SNS
Trophotrophic rxn

Mostly
antagonistic but
sometime agonist
responses

Fig 7: Sympathetic and parasympathetic responses

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Sympathetic division

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Sympathetic nervous system(SNS)
• Activated during stressor exposure
– Physical, physiological, psychological stressors
• Together with HPA axis, reacts to dangerous situations
• mobilize body’s resources under stress, to induce the fight-or-flight
response.
• Mediates activities generated during sudden exposure
• Tries to fulfill the demand of the body during this exposure

By:Abebaye A 23
Sympathetic nervous system(SNS)…
• Makes the body to consume more energy
• Has thoracolumbar origin in the spinal cord
• Has diffuse activation
• Strengthens body during defense
• Increases circulation to skeletal muscles

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Sympathetic nervous system (SNS)
• Highly branched and causes massive responses
• ‘E’ (exercise, excitement, exam, emergency, embarrassment) and ‘F’
(Fear, fight, flight) responses
• It diverts blood flow away from GIT “splanchnic vessels ”and skin
via vasoconstriction
• Chemical from this nerve blocked by atropine

By:Abebaye A 25
Sympathetic nervous system (SNS)
• Glycogenosis, gluconeogenesis and anti-insulin secretion
– Increases blood glucose level
• Increases blood flow to the skeletal muscle
• Facilitates relaxation of lens
• Mydriasis: More light to the retina
• Helps for dark adaptation

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Changes during fight flight responses

Fig 7.1: changes during fight or flight


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Distribution of Sympathetic neurons

Segmental level Area of distribution


1. T1,T2 Head & Neck
2. T3,T4 Thoracic viscera
3. T5 toT9 Upper limb
4. T10 to L2 Lower Limb
5. T6 toT12 Upper Abdominal Viscera
6. L1,L2 Lower Abdominal Viscera
7. T1toT12 Thoracic & abdominal Vessels
Sympathetic nervous system(SNS)…
• Mediates fight and flight responses
• HR, RR, temperature, sweating, reduced digestion processes
– Glucose released from the liver
– Urine output reduced
– Inflammatory substance released
• Cytokines, inflammation aggravated
– Reduced visceral blood flow (GIT), but increased to:-
• Brian, respiratory structures heart and exercise muscles

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Fight/flight responses : acute stress response
What changes are made
during this flight-way
response in the body?

Fig 8: Fight or flight responses during threaten exposure

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Major changes during fight or flight responses
• Cardiovascular system
– Increase heart rate, peripheral vasoconstriction, elevated BP,
coronary circulation increased , blood flow to brain, respiratory
structures and exercise muscle increased
–  blood flow to skin and other visceral organs
– Red cells increase (reserved blood leave into the circulation|)
– Fibrinogen and thrombosis

By:Abebaye A 31
Major changes during fight or flight
responses

• Respiratory system
– Elevated respiratory rate, bronchiodilation
• Digestive system
– Motility reduced
– Secretion reduced
– Sphincter constriction

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Major changes during fight/flight con’t
• Metabolism

– Increase blood fatty acid, glucose, digestion and appetite reduced

• Nervous system

– Pupil dilated, adrenal secretion, brain (hypothalamus) activities

increased
• Muscular system

– Activities elevated and flow increase to exercise muscle

• Endocrine system
– Adrenalin secretion, and glucocorticoid elevated
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Autonomic reflexes: Papillary dilation

Fig 10: Sympathetic effect on pupil


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The sympathetic responses dissipation

Called stress resistance stage of adapatation syndrome

The sympathetic responses during


fight or flight dissipate quickly

Fig 9: Dissipation of fight/flight responses

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Hypothalamus activated during fight/flight
Fight /flight Limbic structures
stimuli/stressors
Fig 11: hypothalamic response during
stressor exposure

Glucocorticoid
secreted and d/f
physiological
responses generated

By:Abebaye A 36
Unique feature b/n SNS and adrenal medulla
Psychosocial stressor exposure induced lateral and posterior hypothalamic
regions activation thoracic spinal cord, converging at the celiac ganglion

Body r
espons
es

Small amount of dopamine


, From N cells

also produced
This system prolongs the
stress responses:
Catecholaminogenesis
augmentation
The hormones contain organic
compound catechols (or
pyrocatechols) and single amines
Fig 12: SNS and adrenal
medulla
By:Abebaye A 37
Sympatho-adrenomedullary system (SAMS)

stress

Fig 13:Sympathoadrenal
By:Abebaye A response 38
During fight or flight
actions like shock, cold,
fatigue, emotional
condition like anger

Fig 14:Synthesis of monoamines

By:Abebaye A 39
Effects of adrenal medullary axis stimulation

• Increase BP, cardiac activities, stimulation of skeletal muscle,


blood fatty acid, glucose, release of endogenous opioids, thrombus
formation, the risk of angina pectoris attacks in persons, risk of
MI, cardiac fibrillation
• Decreases blood flow to kidney, GIT, skin
• Active copying system or alarming /massive response
– Sympathoadrenomedullary system (SAM)

By:Abebaye A 40
Effects of adrenal medullary axis stimulation
con’t
• Most norepinephrin (Nepi) is from the sympathetic nerve axon
terminal
• Nepi from the gland has the same effect except induces responses
20 to 30 second delay behind the Nepi from the nerve terminals
– Slow response and augmented the sympathetic effects during
prolonged stress responses

By:Abebaye A 41
Biochemical functions of catecholamine:Summary
1. Effect on carbohydrate metabolism: increase glycogenolysis ,
gluconeogenesis and decrease glycogenesis. promote the release of
glucose from liver and decrees its utilization by muscle;
Epinepherine inhibits insulin secretion but promote glucagon
secretion.
2. Effect on lipid metabolism: Both of them enhance the breakdown of
TAG in adipose tissue. Free fatty acid in the circulation
3. Effect on physiological function: increase cardiac output, blood
pressure and oxygen consumption. They cause smooth muscle
relaxation in bronchi(bronchodilation), GIT and blood vessels
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supplying skeletal muscle.
Norepinephrine Release and Recycling

Fig 15: Life cycle of NE

By:Abebaye A 43
Pheochromocytoma
• Chromaffin cells/extra-adrenal tissue tumor
(paragangliomas,abdominal tissue)
– Biochemical effects strongly enhanced
– Risks for cardiac arrhythmias, MI, fibrilation, fluter
– Urination volume reduced
– Elevated urine concentration
– Excess sweating and pallor skin
– Reduction of body weight

By:Abebaye A 44
Sympathetic motor nerve problems
• Horner’s Syndrome
– Disruption of the cervical sympathetic chain innervating
• Pupillary dilator muscle
• Eyelids elevator muscle
• Facial blood vessels
• Facial glands
– Pupil constrict
– Smooth muscles embedded in the upper eyelids not contract
– Upper eyelids drooped in the waking day (eye not opened)
– Blood vessels corresponding to the face and head dilated
– No sweat production (anhydrosis) from corresponding face
By:Abebaye A 45
Horner’s syndrome …

Dropping of
Eyelid (ptosis)

ipsilateral pupillary
constriction (miosis)

apparent sinking of
eyeball (enophthalmos)

Fig 16: Manifestations of Horner’s syndrome

By:Abebaye A 46
Sympathetic motor nerve problems…
• Guillain-Barre syndrome
– Sympathetic nerve damage by Aab (during viral infection)
– Mainly its myelin affected
• Loss of reflexes
– Hyperactivity of the lumbar sympathetic nerve
– Seosory and motor problems are common

By:Abebaye A 47
Sympathetic motor nerve problems…
• Guillain-Barre syndrome
– Treated by plasma exchange
• Plasma of patients with abnormal active antibodies
replaced by donated blood
– Urethral obstruction and urine retained
• Avoided by 1-adrenergic antagonist
• Post void residue reduced

By:Abebaye A 48
Parasympathetic division

By:Abebaye A 49
Parasympathetic nerve
• Rest and digest
• Constriction of the pupils (Miosis), Near vision (accommodation),
lacrimation
• Contraction effects: detrusor, ciliary (Miosis) and bronchiole muscle:
• Relaxation effect: Sphincters
• Antagonizes most effects of the sympathetic nerve
• The fibers contain few branches
• Activated by antigens
– Antigen enters the body, local activation of immune cells causes the release of
proinflammatory mediators, which are able to excite afferent nociceptive and afferent
vagal nerve fiber
– If afferent signals is strong, other outputs get strong
By:Abebaye A 50
• SNS and HPA axis activities
Parasympathetic nerve …
• Regulates digestion, urination, defecation, and sexual
arousal
• Slowing the heart rate and lowering the blood pressure
• Plays a vital role in maintaining both mental and physical
health
• Helping the body to calm down from stress reactions
• It is 'peace maker' allowing restoration processes

By:Abebaye A 51
Parasympathetic nerve …
• Involved in the following responses
– Salivation, Lacrimation, Urination, Digestion & Defecation
– Paradoxical fear: when there is no escape route or no way
to win causes massive activation of parasympathetic
division
• Loss of control over urination and defecation

By:Abebaye A 52
PNS : Craniosacral origin

Cranial
nerve

Innervates the pelvic cavity

Pelvic nerve

By:Abebaye A Fig 17: PSN origin53


Parasympathetic origin
• Craniosacral….
– From Brainstem :
• III, VII, IX and X in the brain stem.
• III, VII and IX control pupil and salivary gland secretion
• X carries fibres to the heart, lungs, stomach, upper intestine
and ureter
– From spinal cord
• S2-S4 and innervates distal colon, rectum, bladder and,
reproductive organ

By:Abebaye A 54
Comparison between autonomic and somatic nerves

Table 2: Autonomic and somatic nerves


Feature Autonomic and somatic nerves
Sympathetic parasympathetic Enteric Somatic
Function For actions For actions need Initiate food Relatively
requiring quick slow responses process before Slow
responses extrinsic action response
Responsible For changes For activities Changes during Skeletal
during fight or during rest & digest digestion muscle
flight contraction
Action Preparing the Restorative Initiates food Controlling
body for action, functions and the process in the somatic
catabolism relaxation of the GIT reflexes
body, anabolism

By:Abebaye A 55
Comparison between autonomic and somatic nerves
Table 3: Autonomic and somatic nerves
Feature Autonomic and somatic nerve
Sympathetic parasympathetic Enteric Somatic
Response Ergotropic response : Trophotropic response: Rapid response Always
arousal responses inhibition, slowing, from the GIT than excitatory
restoration the extrinsic neural
pathway
Energy Consume energy Conserve energy Increase energy Consume
availability
Pre to post 1:20 1:1 in many organs Very less diffused Less diffused
ganglionic Diffuse/ massive Discrete & localized,
fibers ratio discharge, widespread with only specific
innervation tissues being stimulated
at any given moment

By:Abebaye A 56
Comparison between autonomic and somatic nerves ..

Table 4: Autonomic and somatic nerves

Feature Autonomic and somatic nerves


Sympathetic parasympathetic Enteric Somatic
Pre to post Short cholinergic Long cholinergic Cholinergic fibers Single fiber
ganglionic preganglionic fibers; pregnaglinic fiber, b/n CNS and
fiber mostly long short post effectors
relation adrenergic ganglionic
ship postganglionic fibers cholinergic fibers
The Norepinephrine Acetylcholine Acetylcholine Acetylcholine
primary
NTs of the
postganglio
nic fibers

By:Abebaye A 57
Comparison between peripheral nervous system con’t
Table 5: Comparison of peripheral nerve
Feature Autonomic and somatic nerves
Sympathetic parasympathetic Enteric Somatic
Predomina Emergency(fight Resting and digest Digestive Skeletal
te during or flight processes muscle
responses) contraction
Tissue/ Many at the Discrete response Discrete Discrete
organs same time
stimulated Massive
responses

By:Abebaye A 58
Dual innervations organs and ANS effects
• Antagonistic :
– Sympathetic and parasympathetic fibers innervate the same cells, organs.
• Actions counteract to each other. E.g Heart rate.
• Mostly this ANS has antagonistic effects

• Complementary:
– Sympathetic and parasympathetic stimulation produces similar effects.
• Salivary secretion: both increase secretion

• Cooperative:
– Sympathetic and parasympathetic stimulation produce different effects that
work together to produce desired effect.
• Micturition, sexual act

– One depends on the other for the Aeffect


By:Abebaye 59
Single innervations organs
• Organs receive only sympathetic innervations:-
 Adrenal medulla
 Arrector pili muscle
 Sweat glands
 Most blood vessels
 Non-shivering thermogenesis (adipose tissue)

By:Abebaye A 60
Sympathetic and parasympathetic effects
Table 6: Sympathetic and parasympathetic effects

Organ Symp. Parasymp.


Heart  rate and force  rate and force
Airway smooth dilatation constriction
muscle
GI tract  motility, secretion  motility, secretion
Male sex organs Ejaculation Erection
Eye (pupil) Dilatation Constriction
Liver Glycogenolysis No effect
Adipose tissue Lipolysis No effect

By:Abebaye A 61
Sympathetic and parasympathetic effects con’t
Table 7: Sympathetic and parasympathetic effects
Organ SYMP. PARASYMP.
Spleen Contract and blood release ----
Sweat gland Stimulate (Ach) Constrict blood
vessels
Adrenal gland Release of catecholamine ------
(Ach)
Kidney Reduces urine output ------
Abdominal viscera Constrict sphincters ------
Cerebrum Constrict blood vessels ----
Lacrimal gland Less effect secretion

By:Abebaye A 62
Sympathetic and parasympathetic effects con’t
Table 8: Sympathetic and parasympathetic effects
Blood vessels SYMP. PARASYMP.
Skin Constricts ----
Skeletal muscle Dilatation (Ach) -------
Renal Constrict ------
Bronchiole Dilates ------
Abdominal viscera Constrict blood vessels ------
Glucose Glycogenolysis, no effect
gluconeogenesis
Lipid Lipolysis No effect

By:Abebaye A 63
Effect of Sympathetic stimulation
Structure Effects
Heart
Cardiac stimulation
 +ve Chronotropic Effect
 +ve Dromotropic Effect
 +ve Bathmotropic Effect
Blood Vessels  +ve Inotropic Effect

Vasoconstriction – Splanchnic
Cutaneous
Vasodilatation-skeletal blood vessels
Effect of Sympathetic stimulation…

System/organ Effects
Respiratory
Bronchodilatation

Tachypnea
GIT
Relaxation of smooth muscle
CNS Constriction of sphincters

Increased alertness

Loss of sleep
Genitourinary
Relaxation of detruser

Constriction of sphincters

Ejaculation in male
Autonomic nerve response: Summary

Fig 18:Sympathetic and parasympathetic responses


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Neurotransmitters and receptors in ANS

By:Abebaye A 67
Neurotransmitters and receptors in ANS

Fig 19: NTs and receptors in ANS


By:Abebaye A 68
Neurotransmitters in autonomic nervous system
Table 9: Neurotransmitters
Features Acetylcholine Norepinephrine Epinephrine
Site of All preganglionic neurons of Most sympathetic Adrenal medulla
release ANS, all postganglionic postganglionic neurons; (80% )
neurons of PNS; some adrenal medulla (20%)
sympathetic postganglionic
neurons to sweat glands,
piloeryctyl tissues, skeletal
muscle blood vessels
Receptors Nicotinic, muscarinic 1,2, 1 (adrenergic) 1,2, 1,2
(cholinergic) (adrenergic)
Activity Enzymatic degradation: Reuptake, diffusion out of Metabolic
Terminatio cholinesterase synaptic cleft,breackdown transformation by
n by monoamine oxidase catechol-O-
(within nerve terminal) methyl-transferase
within liver

By:Abebaye A 69
Receptors in the ANS

By:Abebaye A 70
Receptors in ANS
Table 10: Neurotransmitter receptors
Cholinergic receptors Adrenergic receptors
Nicotinic Muscranic 1 2 1 2 3
Location NMJ, All Smooth Presynaptic Heart Adipose
autonomic visceral muscle cells neurons and Bronchiol tissue
ganglia, structures Ca+2 level Aoutorecepto kidneys e smooth
EUS, and r muscles
adrenal combined on
medulla calmodulin
Ionotropic GPCR
Stimulated Nicotine muscarine catecholamin catecholamin catechola catechola catechola
by e e mine mine mine
Response Na+ Affect ion The complex Inhibits the Activates Relaxatio Lipolysis
channels conductan activates further (heart n of
open and ce kinases release of and bronchiol
always Activates Contraction Nepi kidneys) e muscles
excitatory enzymes

By:Abebaye A 71
Cholinergic receptor responses
= ionotropic =metabotropic

• Adrenal medulla

Fig 20: Cholinergic responses


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Autonomic receptors in the urogenital structures

Fig 21: Autonomic receptors in the urogenital structures


By:Abebaye A 73
Receptors in the effectors

Except sweat glands,


piloerectyle muscle,
and skeletal muscle blood
vessels

Ach= excitatory,
Adrenergic= +ve/-ve,
depends on the types of Rs
(-2 is inhibitory)

Fig 22 Effectors receptors


By:Abebaye A 74
Summary of receptor location and responses

By:Abebaye A 75
Autonomic control of higher brain centers
• Limbic structures
– Emotional stimulus affect ANS
– Right part of the brain (insular cortex) controls the SNS and
the left controls the PNS
• Hypothalamus (autonomic integrator center)
– Control medulla oblongata
• Pre-autonomic parvocellular neuron : directly project to
the preganglionic autonomic neurons in the:-
– Dorsal motor nucleus of the vagus
– Rostral ventrolatralBy:Abebaye
medulla A
oblongata 76
Hypothalamus…
• Hypothalamus …
– Anterior part of the hypothalamus
– Posterior part of the hypothalamus controls SNS

By:Abebaye A 77
Brain centers controlling the ANS con’t
• Medulla oblongata
– Contains cell bodies for ANS and controls the autonomic outflow

– Sympathetic and parasympathetic nerve cell bodies


• Cardiovascular autonomic center

– Medulla oblongata under the influence of the higher brain areas

and the sensory inputs


• Nucleus of solitary tract
– Receives sensory information from visceral structures via VII,IX

and X
– Sends message to brainstem autonomic preganglionic fibrs
By:Abebaye A 78
Brain centers controlling ANS con’t
• Other centers
– Locus coeruleus
– Central nucleus of the amygdala,
– Dorsal motor nucleus of the vagus
– Nucleus ambiguous
– Raphe nuclei
– Periaqueductal gray

By:Abebaye A 79
Brain centers controlling the ANS
Cerebral cortex

Medulla oblongata autonomic


centers

Amygdala,thalamus DMNX RVLM


Hypothalamus
(paraventricular
nucleus (PVN) Parasympathetic Sympathetic
nervous system nervous system

Sympathetic and
parasympathetic afferents

Fig 23: Autonomic control centers

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Center: summary
• Centers in the
– Spinal cord
– Brainstem
– Hypothalamus
– Cerebral cortex (limbic cortex)

By:Abebaye A 81
Stress response and ANS

By:Abebaye A 82
Stressors
• Stressors: conditions/factors that triggers stress responses
– Physical (extreme temperature), psychological, mechanical
– Infection, trauma, inflammation, necrotizing agents, losing,
conflicts, social defats
– Stressor events can be real or imagined.
– Affect neurological triggering mechanisms (e.g. locus ceruleus,
limbic nuclei, hypothalamic nuclei)
– Target-organs activated and coping behavior developed
• Stress responses
– Physiological or behavioral
By:Abebaye A 83
Stress response
• Response: changes in ANS and
endocrine system
– SNS and HPA axis
• Acute exposure: Increase muscle
activities, memory
• Chronic exposure to stressor
– Memory is impaired, immune
function is suppressed
– Inflamamtion

By:Abebaye A 84
Stress responses
• Def: Non-specific response for stressors
– First/acute stress response
• Fight/flight responses
• Increased in catecholamines
• Reduced urine output
• Release of inflammatory substances
• Release of glucose from liver

By:Abebaye A 85
Stress responses …
– Delayed stress response
• Stress occurs for long time
• HPA axis activated
• Workload induced stress
• Relationship induced stress
• When stress is excessive and persistent
• Example: Post-traumatic stress disorder (PTSD)

By:Abebaye A 86
Anxiety and depression: Summary
charac Anxiety Depression
Energy Results in excess energy/ Results in loss of energy. feeling
become very energetic. exhausted, lethargic, lacking drive or
Sweating, shaking, and feeling motivation
fidgety/ restless.
Behavior Over worry and think about Sense of hopelessness about the
bad thing will happen. future. B/s they believed the bad
thing is unavoidable/inevitable, the
future is bad
Thinking Produces racing brain effect Thinking is slow down. General
(repetitive thinking), higher sense of dread and despair about the
thinking about something, mind= future.
noisy and busy
Emotion Strong emotion= Worry, anger, Lack of emotion = deep-seated sense
concern, nervousness, irritability. of sadness and futility.
Mechanis Amygdala more activated. DA HPA axis more activated and excess
m and NE high, GABA reduced glucocorticoid. Monoamine (↑NE,
DA, serotonin
Treatment sedatives :benzodiazepam Serotonin reuptake inhibitor
Summary: anxiety and depression generally
Anxiety Depression (2 weeks)
Characteriz Excessive worry and fear about Low energy, loos of appetite,
ed by future, exaggerated concern about sadness, discouraged, hopeless,
something unmotivated, lack of interests

Nerve abnormality Mood abnormality


Treatment Benzodiazepam (↑GABA);  NE and Monoamines (serotonin)
glutamate reuptake inhibitors
Also called nerve disorder mood disorder. Major
depression, dysthymia, and
bipolar disorder,

Stress  anxiety  depression


Brain areas, NTS and mechanism of stress response

Locus ceruleus (LC-NE),


Hypothalamus …Glucoc
Adrenergic and
serotonergic projection
NE, Glucocorticoid, DA (acute stressor increase DA
secretion), Glutamate and GABA. But chronic
stressors reduce DA and contribute to depression

Hippocampus, Amygdala, PFC


Sensory systems
Areas involved in stress response

Efferents to the effector organs (visceral and somatic efferent carrying


arousal signals): multiaxial stress responses. The target organs may be
overloaded

Fig 23: Mechanisms of emotional responses

By:Abebaye A 89
Mechanism of stress and anxiety

Elevated
Amygdala Fear stimuli/perception

Conscious cognitive fear


Subcortical areas
Cortical areas

 Fear Autonomic & hormonal changes.


 Avoidance Hypothalamus NE/EP(acutely) and cortisol (later),
 Reduced eye contact physiological changes

VTA NAc Reduction of interest and other


behavioral changes

Fig 24: Effects of amygdala on emotional responses


Stress responses pathways

Stress integration
(threat perception or no
threat perception)

Events that may Sensory pathway


causes stress

Stress response from the brain to end organs


Skeletal muscles (one of the target organ during stress response)
Visceral structures via ANS (induces short last responses)

Fig 25: Mechanisms of emotional responses

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Cortical response to stress …
• Medial PFC
– Translates stress into adaptive behavior response through
targeting HPA axis and autonomic outputs
– Dorsal mPFC/prelimbic prefrontal cortex
• Inhibits SNS outflow into the peripheral part of the body
• Inhibits Cortisol secretion
– For acute stress response, not for chronic

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Cortical response to stress …

• Lateral Hypothalamus

– Projects gutamaterig and GABAergic projection to PVN

– Innerves pre-ganglionic autonomic neurons in the


parasympathetic dorsal motor nucleus of the vagus and
sympathetic intermediolateral colum
– NMDA

– signaling in the LH inhibits cardiovascular responses to


restraint
– stress through parasympathetic activation
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Physiological and biochemical changes during stress
• Increased HR, BP

• BGL (liver releases glucose)

• Bronchodilation

• Less GI processes (sympathetic nerve)

• Reduced urine output

• Fat breakdown

• Increase inflammation (if not excessive is good to reduced farther


infection)
• Increase arousal/focus

• Emotional response
By:Abebaye A 94
Physiological and biochemical changes during stress
• Reduced immunity

– Reduced would healing

– Reduced vaccine and other drug response (vaccination during exam has less
effect)

– Easily infected

• Brain function affected

– Decreased concentration, memory, hippocampus atrophy

• Mood change

– Anxiety

– Depression

– Sleep problems
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Physiological and biochemical changes during stress

Where changes
 Glands, immune organs,
 Heart, blood vessels, GIT
 Respiratory structures,
 Brain

Fig 26: Effects of sensory stimuli on emotional responses

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Cognitive versus affective interpretation
Event

Sensory reception via sensory pathways

Cognitive interpretation by Affective integration by the


Neocortex limbic system

Perception of threat No perception of threat

Triggering mechanisms No stress responses

Stress responses via 1. Via neural innervations of ANS and


hypothalamus somatic nervous system
2. Fight or flight responses
End organ 3. General adaptation syndrome
Fig 27: Information integration and perceived
By:Abebaye A
as threat causes stress response 97
Mechanism of responses from the target organs
• Three pathways by which responses are made from the organs
– Neuronal axes
• Neuronal innervation of the target organs
• Fast and short last responses
– Neuroendocrine axis
• To maintain stress responses for long time
• Neuro-endocrine hormones are produced
– Endocrine axis
• Hormones are produced
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Neuronal axes

• This axes activated first during stress responses


• The response is quick and overlap with endocrine system
• Following information integration and perceived as a threat by the
brain:
– Anterior hypothalamus activated PSN outflow
• This is mainly after the threat is over

• Some mind relaxing hormones (Endorphin, DA, ser) produced

– Posterior hypothalamus activated SNS outflow


• However, sympathetic outflow is dominated than PNS

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Neuroendocrine Axis
• Sympathoadrenal axis (SAA) : Adrenalin secretion
– Fight or flight responses
– The response is manly by SNS and adrenal medulla
– To fight against or flee away from the perceived threat
– The response is organized by dorsomedial amygdalar
complex
– Impulse is moved down to lateral and posterior hypothalamic
regions  thoracic spinal cord adrenal medulla
(pheochromoblasts-cells)
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Sympathoadrenal axis (SAA)…
Perceived stimuli as threat Amygdala

Activated during
delayed stress response Activated during
delayed stress response

Fig 28: Sympathoadrenomedulary (SAM) axis


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Neroendocrine axis and stress responses
Stressors

Fig 29: Physiological and biochemical changes during stress 102


By:Abebaye A
Sympathoadrenal axis (SAA) …
Dorsomedial amygdalar complex
Events (Perceived as threat)

Lateral and posterior hypothalamic


regions

Thoracic spinal cord: preganglionic fibers


for SNS

Adrenal medulla (pheochromoblasts-cells)

Stress responses (Adrenalin secreted,


other body activities changes)

Fig 30: Sympathoadrenal axis (SAA) pathway

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Endocrine Axes
• The most delayed and prolonged stress response and activated
by greater intensity stimulation
– The adrenal cortical axis.
– The somatotropic axis.
– The thyroid axis.
– The posterior pituitary axis

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Stress and endocrine Axes

CTR

ADH

Fig 31: Endocrine axis


The adrenal cortical axis
• Originated from septal–hippocampal complex (limbic structure)

• Impulse reach into the neurosecretory cells in the hypothalamus that release
corticotropin releasing factor (CRF)
– Getting into hypothalamohypophysial portal system
– Anterior pituitary cells produce ACTH
• Activate the synthesis and secretion of glucocorticoid
• Affect catecholamine synthesis again (affects tyrosine hydroxylase,
which is the “rate-limiting” step in catecholamine synthesis (very less
effect)
• Activates the zona glomerullosa and mineralocorticoid secretion (less
effect), more by Ang II K+
• Androgen also produced By:Abebaye A 106
Regulation of cortisol secretion
Increased by
NE
Glutamate
Serotonin
CTR
Reduced by
GABA
opioids
 blood glucose, FA and
aa
 lipid peroxidation
  electrolytes (Na+, K+, Proopio melanocortin producing cells
Ca++) and lymphocytes
 Neutrophils
Melanocyte stimulating hormone

Fig 32:Regulation of glucocorticoid and its effect


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Amygdala in the adrenal cortical axis

 GR: intracellular nuclear steroid receptor


 Hippocampal mineralocorticoid receptor (MR):
Hypothalamus

_ act as the initiation of stress response


_  But GR at hippocampus, PVN, anterior pituitary
terminates the stress response
+ Brainstem
Ventral cubiculum
PFC nuclei (LC: NE)

Glutamate from other


areas
Amygdala
Fig 33: Amygdala effect on adrenal cortical response
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Amygdala portion for emotion

Fig 34: Amygdla center By:Abebaye A 109


Thus, stress also increase NA secretion from
LC and correlated with NE in healthy subjects

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Effects of cortisol in healthy subjects

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Fig 35: Effects of Cortisol to the body
The General Adaptation Syndrome (GAS): Hans Selye

• Physiological changes in the body after exposed to stressful


events.

• The responses have stages called GAS


– The overall responses from the body for stress
– Body's short-and long-term reactions and adaptations to stress in
order to restore homeostasis

– Has three stages


• Alarming stage (call for alarms), first stage
– Rapid responses , fight-or-flight response

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The General Adaptation Syndrome (GAS):
Hans Selye…
• Resistant (second) stage

– Those increased responses during the alarming stage start to


decreased to the normal
– The body tries to re-established to the normal functions
– Body starts to recover
• Exhaustion stage
– Response for chronic stress with out relief
– Unable to restore the changes
– Stress resistance reduced
– No longer response to fight stress
– Resistance to stress is reduced By:Abebaye A 113
Phases of general adaptation syndrome

Fig 36: Stages of general adaptation syndrome


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io n
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