Physiology of the Autonomic Nervous system (ANS)

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Physiology of the Autonomic Nervous system (ANS)

• Dr. Taha Sadig Ahmed

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A.1. The autonomic nervous system

• is regulated by the Hypothalamus
• It regulates activities of
• (1) Visceral muscles which are involuntary
  , and include
• cardiac muscle , and
• smooth moscle in arterioles and the
  gastro-intesinal tract (GIT) .
• (2) Glands ( e.g. , sweat glands and GIT glands )
• It consists of 2 subdivisions

Figure 11-2
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A.2 The autonomic nervous system pathways

• The autonomic division consists of two efferent
  neurons in series

Effector, postganglionic, neurons for the
autonomic nervous system (ANS) are different from
the neurons we have previously discussed. The
synapse between the ANS neuron and the target
cell is called the neuroeffector junction.
Fig. 11-4
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The efferent autonomic system consists of 2
effector neurons arranged in series

• Preganglionic nerves arise from the spinal cord
• Postganglionic nerves arise from ganglia .

The synapse between the ANS neuron and the target
cell is called the neuroeffector junction.
Fig. 11-4
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Higher control of autonomic function

• Sympathetic functions regulated by posterior
  hypothalamus
• Parasympathetic functions regulated by anterior
  hypothalamus

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The ANS has 2 subdivisions
sympathetic and parasympathetic
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Effect of sympathetic stimulation

• Sympathetic part of ANS is active during fear,
  anxiety, sever pain preparing the body for fight
  or flight
• Promoting mechanisms which increase energy
  metabolism

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Effect of parasympathetic stimulation

• Parasympathetic system activities is related to
  relaxed state
• Vegetative function
• Feeding
• Resting
• Part of the sexual function

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• Pathways of the Autonomic Nervous System
• Each of the 2 divisions of the ANS system sends
  neurons to each of the organs shown (except the
  adrenal, which receives input from only the
  Sympathetic division only .
• One division of the ANS will excite the organ
  while the other will inhibit it.
• Nerves of the Sympathetic system exit the spinal
  cord in the thoracic and lumbar regions of the
  spinal cord. Therefore , the Sympathetic is
  called Thoraco-lumbar Outflow
• Nerves of the Parasympathetic system exit at the
  brain stem and sacral region of the spinal cord.
  Therefore , the Parasympathetic division is
  called Cranio-sacral Outflow
• The preganglionic neurons of both divisions
  synapse in ganglia .
• From ganglia a second Postganglionic nerve
  arises and travels to the effector (target) organ
  .

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Sympathetic (Thoracolumbar) System

• The preganglionic neurons are located in the CNS.
• The postganglionic neurons (located in the
  sympathetic ganglia) are distant from their
  target tissues .
• There is greater divergence . The ratio
  (pre/post) being 1/10
• This divergence implies diffuse
• ( generalized )adrenergic actions .

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Parasympathetic (Craniosacral ) system

• The preganglionic neurons are located in the CNS.
• The postganglionic neurons (located in
  parasympathetic ganglia) are either close to or
  embedded in their targets tissues . The
  neurotransmitter between the preganglionic and
  the postganglionic neuron is Ach. The receptors
  on the postganglionic neurons are of the
  cholinergic nicotinic type.
• The neurotransmitter secreted by the
  postganglionic neuron is Ach. The receptors on
  the target are of the muscarinic cholinergic
  type.
• There is little divergence. The ratio (pre/post)
  1/3.
• The limited divergence results in more specific
  cholinergic actions.

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Effect of sympathetic parasympathetic
stimulation
Organ sympathetic parasympathetic
The eyes Pupil Ciliary muscle Dilatation of pupil ( mydriasis) Relaxation (far Vision) Constriction of pupil ( miosis ) Constricted (near vision
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Glands Nasal Lacrimal Parotid Submandibular Gastric Pancreatic Slight secretion Copious secretion
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Sweat Gland Sweating Sweating on palm of hands
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Blood vessels Constriction Little or no effect
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The heart SA node Myocardium Increased heart rate Increased strength of contraction Decreased heart rate Decrease force of contraction
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Effect of sympathetic parasympathetic
stimulation
Organ sympathetic parasympathetic
The eyes Pupil Ciliary muscle Dilatation of pupil Relaxation (far Vision) Constriction of pupil Constricted (near vision
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Sweat Glands Sweating
Other Glands
Nasal Lacrimal Salivary ( e.g , Parotid , Submandibular, sublingual ) Gastric Pancreatic Slight secretion , frequently rich in enzymes Copious secretion ( large quantity )
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Blood vessels Vasoconstriction ( except in sweat glands , and especially in skeletal muscle blood vessels , where the sympathetic system causes vasodilation dilation mediated by both cholinergic receptors and beta receptors ) Little or no effect ( negligible . The skin has no significant parasympathetic supply )
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Coronary Blood vessels ( actually , they are mainly influenced by changes in their local environment , rather than by extrinsic nerves ) Dilatation (dilation) Dilatation
Blood vessels to skeletal muscles Dilatation ( mediated by both cholinergic and beta-adrenergic receptors ) No significant effect on vascular caliber
Bronchiolar smooth muscles Relaxation ( beta 2 receptors ) Constriction
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GIT Digestive and Excretory Functions
Digestive secretions from salivary and other GIT Glands ( i.e., GIT secretions) Small amount of secretion Increased secretion ( copious secretions )
GIT motility ( movement ) Decreased , because longitudinal muscles in walls of organs are relaxed ? decreased peristaltic and segmentation movemets Increased contraction of longitudinal muscles ? increased peristaltic and mixing movemets ? more mixing of food with digestive enzymes ? digestion promoted
GIT Sphincters ( circular muscles guarding exits ),including internal anal sphincter Constriction ( therefore , emptying prevented or delayed ) Relaxation ( this , combined with increased wall motility , promotes emptying )
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Genito-urinary Systems
Ureters Relaxation Contractions increased
Erection of penis or clitoris Promoted
Ejaculation Promoted
Bladder wall Internal urinary sphincter Relaxation Contraction Contraction Relaxation Therefore , urine excretion promoted
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Metabolic and Other Functions
Adrenal medulla Secretion of epinephrine ( 80 ) and norepinephrine (20)
Blood glucose level Increased ( increased glycogenolysis in skeletal muscle )
Blood lipids Increased levels ( increased lipolysis in fat cells )
Blood coagulability Increased
Metabolic rate Increased
Mental alertness and vigilance ( may reach level of anxiety ) Increased
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It should be noted that

• Under physiological conditions , nearly all
  sympathetic and parasympathetic activities are
  opposite ( contradictory ) to each other
  however , the two systems cooperate ( may act
  in unison/accord ) in
• (1) salivary secretion ( sympathetic ? scanty
  secretion rich in enzymes , parasympathetic ?
  Watery , copious secretion ) ,
• (2) Emotional stress parasympathetic ?
  increased tear and nasal secretions , sympathetic
  ? increased heart-rate , BP , etc
• (3) Sexual intercourse parasympathetic ?
  erection of the penis or clitoris , sympathetic ?
  ejaculation or orgasm

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Autonomic Neurotransmitter

• All preg. Fibres (sympathetic and
  parasympathetic ) secrete acetylcholine at the
  ganglia .
• All postganglionic parasympathetic fibers secrete
  acetylcholine at target organs .
• Most postganglionic sympathetic fibers secrete
  norepinephrine at target organs .
• Postganglionic sympathetic fibers to sweat gland
  blood vessels of skeletal muscles release
  acetylcholine
• All epinephrine in the bloodstream comes from the
  adrenal medulla . Postganglionic sympathetic
  nerves can not synthesize epinephrine from its
  precursor which is norepinephrine .

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Actions of Norepinephrine and Epinephrine
Adrenergic( Alpha and Beta ) Receptors

• Norepinephrine acts on both alpha and beta
  receptors , but it acts much better on alpha than
  beta receptors .
• Epinephrine excites both a ß equally .

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Distribution of Adrenergic Receptors

• a is found in
• Iris
• Blood vessels , especially arterioles
• GIT
• ß is found in
• Heart
• Bronchioles
• Skeletal muscle
• GIT

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Noteworthy Effects of Alpha or Beta Receptor
Stimulation by Norepinephrine or by Epinephrine
Alpha (a) receptors Beta (ß) receptors
(1) Vasoconstriction ( ? raised BP) (2) Pupillary dilatation (1)Vasodilatation (ß2) (2) Increased HR (ß1) (3) Increased myocardial strength (ß1) 2 and 3 above lead to increased CO and consequently lead to increased BP (4) Bronchiolar relaxation (ß2) (5) Intestinal wall relaxation (ß2) (6) Bladder wall relaxation (ß2)
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The Heart
SA node (pacemaker ) Ventricular myocardium Increased heart rate ( HR) ( Beta 1 receptors ) Increased contractility ( force of contraction) (1) The inceased in both HR and contractility lead to ? increased cardiac output ( CO). (2) The increased CO and increased peripheral resistance ( which results from arteriolar vasoconstriction ) together lead to ? increased blood pressure ( BP) . Decreased heart rate There is no significant cholinergic supply to the myocardium . Therefore , the effect of parasympathetic stimulation is decreased HR , but it has no significant effect on contractility .
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Coronary Blood vessels Dilatation Dilatation
Blood vessels to skeletal muscles Dilatation (cholinergic) None
Bronchial muscles Relaxation Constriction
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GIT Salivary glands Pancreas Stomach Decreased secretion Increased secretion
Intestinal secretion motility Sphincters Decreased Constriction Increased Relaxation
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Ureters urinary bladder Detrusor muscle Internal sphincter Relaxation Constriction Constriction Relaxation
Male sex organs Ejaculation Erection
Adrenal medulla Secretion of adrenaline noradrenalin None
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Blood Coagulation Glucose Lipids Increased None
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Basal metabolism Increased None
Mental activity Increased None
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Skeletal muscle Increased glycogenolysis None
Fat cells Lipolysis None
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Figure 11-3
Figure 11-2
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Adrenal Medulla
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Neurotransmitters of ANS (cont.)

• All preganglionic fibers ( sympathetic and
  parasympathetic) secrete Acetylcholine at the
  ganglia
• All postganglionic parasympathetic fibers secrete
  Acetylcholine

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Neurotransmitters of ANS (cont.)
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Neurotransmitters of ANS (cont.)

• Most postganglionic sympathetic fibers secrete
  norepinephrine
• Postganglionic sympathetic fibers to sweat gland
  blood vessels of skeletal muscles release
  acetylcholine

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Adrenergic receptors

• Noradrenaline mainly excite a (and ß to a lesser
  extent)
• Adrenaline excite both a ß equally

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Alpha receptors (a) Beta receptors (ß)
-Vasoconstriction -Iris dilatation -Intestinal sphincter contraction -Bladder sphincter contraction -Vasodilatation (ß2) -Increased myocardial strength (ß1) -Intestinal relaxation(ß2) -Bladder wall relaxation (ß2)
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Adrenergic receptors

• a is found in
• Iris
• Blood vessels
• GIT
• ß is found in
• Heart
• Skeletal muscle
• GIT

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Cholinergic receptors

• Divided into
• Nicotinic ( in all ganglia )
• Muscarinic ( in effector tissues )

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Adrenergic receptors blockers

• a blockers
• Prazosin (a 1)
• Yohimbine (a 2)
• ß blockers
• Propranolol ( both ß1 ß2)
• Atenolol (ß 1)

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Drugs that you should know

• Epinephrine ( adrenaline ) .
• Salbutamol ( ventolin ) .
• Propranolo ( inderal ) .
• Atenolol ( tenormin ) .
• Atropine .

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Cholinergic receptors

• Muscarinic receptors are found on all effector
  cells stimulated by postganglionic
  parasympathetic
• And postganglionic cholinergic sympathetic
• Nicotinic receptors are found in the synapses
  between pre- postganglionic (both sympath.
  parasympath.)

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Cholinergic receptors

• Drugs acting on cholinergic receptorsHexamethoni
  um (block both types)Atropine (block muscarinic
  receptors)

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Sympathetic (Thoracolumbar)

1. The neurotransmitter between the preganglionic
   and the postganglionic neuron is Ach. The
   receptors on the postganglionic neurons are of
   the cholinergic nicotinic type.
2. The neurotransmitter secreted by the
   postganglionic neuron is NorEpinephrine (NE). The
   receptors on the target are adrenergic receptors
   (alpha or beta).
3. There is a great divergence. The ratio (pre/post)
   1/10.
4. The divergence implies diffuse adrenergic actions

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Parasympathetic (Craniosacral)

1. The neurotransmitter between the preganglionic
   and the postganglionic neuron is Ach. The
   receptors on the postganglionic neurons are of
   the cholinergic nicotinic type.
2. The neurotransmitter secreted by the
   postganglionic neuron is Ach. The receptors on
   the target are of the muscarinic cholinergic
   type.
3. There is little divergence. The ratio (pre/post)
   1/3.
4. The limited divergence results in more specific
   cholinergic actions.

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Comparison between beta 1 and beta 2 adrenergic
receptors
Beta 1 receptors BETA 2 RECEPTORS
Bind equally norepinephrine and epinephrine Bind preferentially ( more ) epinephrine than norepinephrine
Usually have excitatory effects ( e.g., increased HR). Usually have inhibitory effect ( e.g., relax skin arterioles (?and arterioles in skeletal muscle)? arteriolar vasodilation in the skin (? contribute , beside the postganglionic cholinergic sympathetic fibers in skeletal muscle , to vasodilation in skeletal muscle during exercise ) .
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Comparison between alpha 1 and alpha 2 adrenergic
receptors
Alpha1 Alpha2
Excitatory ( e.g., arteriolar vasoconstriction ) Inhibitory ( e.g., inhibited peristalsis in small intestine )
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It should be noted that

• Under physiological conditions , nearly all
  sympathetic and parasympathetic activities are
  opposite ( contradictory ) to each other
  however , the two systems cooperate ( may act
  in unison/accord ) in
• (1) salivary secretion ( sympathetic ? scanty
  secretion rich in enzymes , parasympathetic --.
  Watery , copious secretion ) ,
• (2) Emotional stress parasympathetic ?
  increased tear and nasal secretions , sympathetic
  ? increased heart-rate , BP , etc
• (3) Sexual intercourse parasympathetic ?
  erection of the penis or clitoris , sympathetic ?
  ejaculation or orgasm

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Applied Neurophysioloy (1)

• Epinephrine
• Stimulates both beta1 and beta2 receptors
• Useful in Tt of Asthma
• Contraindcated ( C/I ) in Hypertension or Heart
  disease . Why ?
• Salbutamol (ventolin )
• Stimlates mainly beta 2 receptors
• Used in Tt of Bronchial asthma
• Safer than epinephrine . Why ?

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Applied Neurophysioloy (2)

• Propranolol ( Inderal )
• Blocks beta1 beta2
• Used in Tt of hypertension
• Should not be given to a patient with Bronchial
  Asthma . Why ?
• Atenolol ( Tenormin )
• Blocks only beta 1
• Used in Tt of hypertension
• Safer than Inderal . Why ?
• Atropine
• Blocks muscarinic receptors ( of Ach )
• Used in Tt of colic
• Better use Hyoscine ( Buscopan ) especially if
  the patient has heart disease or glaucoma . Why ?

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Agonists and Antagonists of Cholinergic Receptors
Receptor Agonists Antagonists Other
Cholinergic Acetylcholine AChE inhibitors neostigmine, parathion Inhibit Ach release Botulinum toxin
Muscarinic Muscarine Atropine, scopolamine
Nicotinic Nicotine a-bungarotoxin (muscle only) Tetraethylammonium (TEA)
(ganglia only), curare
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Agonists and Antagonists of Adrenergic Receptors
Receptor Agonists Antagonists Other
Adrenergic Norepinephrine epinephrine Stimulate NE release ephedrine, amphetamines Prevent NE uptake cocaine
Alpha (a) Phenylephrine alpha blockers
Beta (b) Isoproterenol beta-blockers propranolol (b1 and b2) Metoprolol (b1 only) beta-blockers propranolol (b1 and b2) Metoprolol (b1 only)
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Dont Stop , Please !