PhysioloPhysiologygyofof

Autonomic Autonomic Nervous Nervous System System

Dr. Ahmed Al-Dr. Ahmed Al-SehliSehli

AUTONOMIC AUTONOMIC NRVOUS SYSTEMNRVOUS SYSTEM

DefinitionDefinition :: It is the system for involuntary It is the system for involuntary subconscious functions , it controls the subconscious functions , it controls the internal environment to maintain homeostasis internal environment to maintain homeostasis . .

DIVISION OF NERVOUS SYSTEM :DIVISION OF NERVOUS SYSTEM :1- Central nervous system :1- Central nervous system :a) Braina) Brain b) Spinal cordb) Spinal cord2- Peripheral nervous system : 2- Peripheral nervous system : a) Cranial nervesa) Cranial nerves Autonomic Autonomic

(involuntary) (involuntary) Somatic (voluntary)Somatic (voluntary)

b) Spinal nervesb) Spinal nerves Autonomic Autonomic SomaticSomatic

Somatic N .S Somatic N .S (voluntary)(voluntary)

Autonomic N .S Autonomic N .S (involuntary)(involuntary)

1) Innervate skeletal 1) Innervate skeletal musclesmuscles

11 ) )Supply smooth muscles, Supply smooth muscles, Cardiac and GlandsCardiac and Glands

2) One neurone between 2) One neurone between C.N.S and effector C.N.S and effector organorgan

22 ) )Has 2 neurons connected Has 2 neurons connected by synapse between C.N.S & by synapse between C.N.S & organorgan

3) Efferent arises from 3) Efferent arises from ventral horn cell.ventral horn cell.

33 ) )Efferent preganglionic Efferent preganglionic arises from lateral horn cellsarises from lateral horn cells. .

4) Chemical transmitter 4) Chemical transmitter Acetyl cholineAcetyl choline

44 ) )Either acetyl cholin or Either acetyl cholin or norepinephrinenorepinephrine..

A.N.S differs from Somatic A.N.S differs from Somatic N.S in :-In A.N.S there is :N.S in :-In A.N.S there is :

1-1- Autonomic gangliaAutonomic ganglia

2-2- Connector neurone is Connector neurone is outside CNSoutside CNS

3-3- It regulates smooth It regulates smooth muscles muscles

Q: Discuss and differentiate Q: Discuss and differentiate the two divisions of the two divisions of A.N.S ?A.N.S ?

A.N.SA.N.S

SympatheticSympathetic ParasympatheticParasympathetic

1- ORIGIN: Thoraco-Lumber Cranio - sacral1- ORIGIN: Thoraco-Lumber Cranio - sacral (Tl - T12 , LI,2,3)(Tl - T12 , LI,2,3) 3,7,9,10 S2 , 3 , 3,7,9,10 S2 , 3 ,

44

1- ORIGIN: Thoraco-Lumber Cranio - sacral1- ORIGIN: Thoraco-Lumber Cranio - sacral (Tl - T12 , LI,2,3)(Tl - T12 , LI,2,3) 3,7,9,10, s2,3,4, 3,7,9,10, s2,3,4, 2-FUNCTION: Stress2-FUNCTION: Stress muscular exercisemuscular exercise - Digestion and sleep, - Digestion and sleep,

fear Empting fight micturation flight defication

- Catabolic - Anabolic(energy lost from the body) (energy

preserved)4- DISTRIBUTION: widspread Localised5- DISCHARGE : as one unit (most actions) To each system at the same time) separetly

RELATIONSHIP RELATIONSHIP BETWEEN SYMP BETWEEN SYMP

ATHETC AND ATHETC AND PARASYMPATHETICPARASYMPATHETIC

1- RECIPROCAL :1- RECIPROCAL : once once sympathetic is stimulated, sympathetic is stimulated, parasympaethetic isparasympaethetic is

inhibited and vise - versainhibited and vise - versa

2- COMPLEMENTAL :2- COMPLEMENTAL : e.g e.g micturation and defication reflex. micturation and defication reflex. sympathetic for FILLING and sympathetic for FILLING and parasympathetic for EVACUATION parasympathetic for EVACUATION

N.BN.B both sympathetic and both sympathetic and parasympathetic together help parasympathetic together help acurate control over an organ's acurate control over an organ's activity.activity.

AUTONOMIC AUTONOMIC GANGLIAGANGLIA

DEFINITION :DEFINITION : It is the site of It is the site of physiological contact between pre and physiological contact between pre and postpostganglionic fibers .ganglionic fibers .

TYPES:TYPES:a) lateral (sympathetic)a) lateral (sympathetic)b) collateral (mixed) or pure sympatheticb) collateral (mixed) or pure sympatheticc) terminal ( parasympathetic )c) terminal ( parasympathetic )

LateralLateral ( paravertebral) 23 ganglia( paravertebral) 23 ganglia:: 3 = cervical 3 = cervical sympathetic sympathetic

chainchain12 = thoracic 12 = thoracic 4 = lumber 4 = lumber

44 = = sacralsacral

CollateralCollateral:: Around large .B.V Around large .B.V

as:as:

- Caeliac ganglion- Caeliac ganglion

- Superior mesentric ganglion- Superior mesentric ganglion

- Inferior mesentric ganglion- Inferior mesentric ganglion

TerminalTerminal (in the wall of organ, (in the wall of organ, no post-ganglionic as vagus or no post-ganglionic as vagus or may be present very short may be present very short post-ganglionic fiberpost-ganglionic fiber

Pathway of pre-Pathway of pre-ganglionic sympathetic ganglionic sympathetic

fibersfibers::

1- May synapse in first sympathetic chain ganglion, it enters.

2- Synapsing in other sympathetic chain ganglia up or down.

3- Synapse in collateral ganglia.

4- Synapse in substance of adrenal medulla itself.

FunctionFunction : :1) Distributing center: Sympathetic 1) Distributing center: Sympathetic ParasympatheticParasympathetic

1 : 32 1:9 or 1:2 ??

2) Relay station between pre and post ganglionic fiber

Localization : To diagnose site of relay, by Nicotine test: (Langlay's test) painting the ganglia with large doses of nicotine to block the site of relay, after that if it gives no post - ganglionic response = relay

Cervical Division of sympathetic

DESTRIBUTION OF DESTRIBUTION OF SYMPATHETIC NERVOUS SYMPATHETIC NERVOUS

SYSTEMSYSTEM

1) CERVICAL DIVISION:1) CERVICAL DIVISION:

OriginOrigin :: It arises from lateral horn cell of Ti and T2 It arises from lateral horn cell of Ti and T2

and end in superior cervical ganglionand end in superior cervical ganglion

I) EYE :I) EYE :

a) dilatorpupilllary muscels = pupillary a) dilatorpupilllary muscels = pupillary dilatation dilatation

= Mydriasis= Mydriasis b) Tarsal m.=elevation of eye lid = widening ofb) Tarsal m.=elevation of eye lid = widening of eye superior eye superior inferiorinferior

c) Muller's m. = Exophthalamos = Protrusion ofc) Muller's m. = Exophthalamos = Protrusion of eye ball in animalseye ball in animals

d) Blood vessels of eye = V.Cd) Blood vessels of eye = V.C

e) relaxation of the ciliary muscle for e) relaxation of the ciliary muscle for visionvision

II) SALIVARY GLANDS :II) SALIVARY GLANDS : a) Secretion of small amount of a) Secretion of small amount of

saliva, rich in organic matters saliva, rich in organic matters (enzymes) (enzymes) i.e viscus saliva .i.e viscus saliva .

b) Squeezing around acinin of b) Squeezing around acinin of salivary glands salivary glands push saliva push saliva outsideoutside

III) SKIN :III) SKIN : a) Erector pilae m = erection of a) Erector pilae m = erection of

hairshairs b) Vaso-conistriction of blood b) Vaso-conistriction of blood

vessels = pallor vessels = pallor c) Sweat :Secretion = mental sweat.c) Sweat :Secretion = mental sweat. IV) Cerebral blood vesselsIV) Cerebral blood vessels == vaso-conistriction vaso-conistriction

HORNER'S SYNDROMEHORNER'S SYNDROME

It IsIt Is CerviaclCerviacl SympathectomySympathectomy : : characterized bycharacterized by : :

1-1-PTOSIS PTOSIS :: drop of upper eyelid drop of upper eyelid ..

2- 2- MIOSISMIOSIS : : pupillarypupillary constrictionconstriction . .

3- 3- ANHYDROSIS ANHYDROSIS :: dryness of skindryness of skin

4-4-EmrophthalamosEmrophthalamos

5- 5- Flushing of the faceFlushing of the face

ALL THESE EFFECTS ARE AT SAME SIDE OFALL THESE EFFECTS ARE AT SAME SIDE OF

LESHONLESHON

2) CARDIQ-PULMONARY DIVISION :2) CARDIQ-PULMONARY DIVISION : Segments and end in 3Segments and end in 3rdrd cervical and upper cervical and upper

4 thoracic ganglia 4 thoracic ganglia

I)I) HEARTHEART : : increase all cardiac prosperities as: increase all cardiac prosperities as:- positive inotropic effects = ↑ contractility- positive inotropic effects = ↑ contractility- positive chronotropic effect = ↑ Heart rate.- positive chronotropic effect = ↑ Heart rate. - = ↑ Conductivity- = ↑ Conductivity - = ↑ Excitability- = ↑ Excitability

II) CORONARY BLOOD VESSELSII) CORONARY BLOOD VESSELS vasodilatation vasodilatation III) LUNG :III) LUNG : a) bronco-dilatation . a) bronco-dilatation .

b) inhibits bronchial glands secretion ofb) inhibits bronchial glands secretion of mucousmucous

IV) IV) PULMONARY BLOOD VESSELSPULMONARY BLOOD VESSELS:: vasoconstriction. vasoconstriction.

33 - -SPLANCHIC DIVISION:SPLANCHIC DIVISION:To Abdomen and pelvisTo Abdomen and pelvis

A) Greater Splanchic Nerve : it supplies the A) Greater Splanchic Nerve : it supplies the abdomen e.g :abdomen e.g :

)From T)From T55–T–T99, relay in caeliac ganglion), relay in caeliac ganglion)

a) wall of G.I.T → relaxation of its walls = retention ↓ a) wall of G.I.T → relaxation of its walls = retention ↓ motility.motility.

b) sphincters → its contraction e.g pyloric sphincter of b) sphincters → its contraction e.g pyloric sphincter of stomachstomach

c) liver → glycogenolysis = glycogen converted to c) liver → glycogenolysis = glycogen converted to glucose .glucose .

d) adrenal medulla → release of epinephrin and nor d) adrenal medulla → release of epinephrin and nor epinephrine .epinephrine .

e) spleen → contraction & release of RBCs in case of e) spleen → contraction & release of RBCs in case of heamorrhageheamorrhage

f) adipose tissues → lipolysis .f) adipose tissues → lipolysis .

g) inhibite the intestinal juice secretion g) inhibite the intestinal juice secretion

h) relaxation of gall bladder and contraction ofh) relaxation of gall bladder and contraction of

its sphincter. its sphincter.

N.BN.B Stimulation of greater splanchic nerve causes two peaks Stimulation of greater splanchic nerve causes two peaks rise in blood pressure :rise in blood pressure :

a) First rise due to V.C of visceral blood vessela) First rise due to V.C of visceral blood vessel

b) Second peak due to release of catecholaminb) Second peak due to release of catecholamin

into blood.into blood.

ADRENAL ADRENAL MEDULLAMEDULLA::

Supplied by pre-ganglionic Supplied by pre-ganglionic sympathetic fibers (greater sympathetic fibers (greater splanchnic nerve). splanchnic nerve).

The circulating catecholamin The circulating catecholamin have same effects of direct have same effects of direct sympathetic stimulation, but sympathetic stimulation, but more prolonged , So body more prolonged , So body organs can be stimulated by 2 organs can be stimulated by 2 ways, Nervous (direct) & ways, Nervous (direct) & Hormonal (indirect), Also Hormonal (indirect), Also catecholamines can stimulate catecholamines can stimulate sites not supplied by direct sites not supplied by direct sympathetic nerves .sympathetic nerves .

N.B N.B adrenal meddulla is modified by adrenal meddulla is modified by sympethetic ganglion because :sympethetic ganglion because :

1- No post-ganglionic fibers1- No post-ganglionic fibers

2- Causes release of 80% epinephrin. 20% 2- Causes release of 80% epinephrin. 20% nor epinephrin. nor epinephrin.

N.BN.B Selective secretion of adrenal medulla:Selective secretion of adrenal medulla:

a) More epinephrine in unexpected a) More epinephrine in unexpected stresses as haemorrhaegestresses as haemorrhaege

b) More nor-epinephrine in familiar stresses b) More nor-epinephrine in familiar stresses as hypoxiaas hypoxia

B) Lesser splanchnic B) Lesser splanchnic nervenerve::

From LI - L3, relays in inferior mesentric From LI - L3, relays in inferior mesentric ganglion It supplies the pelvis e.gganglion It supplies the pelvis e.g :- :-

a) Rectum → retention of stool (+) of internal a) Rectum → retention of stool (+) of internal anal sphincteranal sphincter

b) Urinary bladder → retention of urine by b) Urinary bladder → retention of urine by relaxation of its wall and contraction of relaxation of its wall and contraction of internal uretheral sphincterinternal uretheral sphincter..

c) Sex organs → ejaculationc) Sex organs → ejaculation . .

External genitaliaExternal genitalia::

In males :In males : Inhibition of erection (v.c of Inhibition of erection (v.c of erectile tissue)-Ejaculation of semen erectile tissue)-Ejaculation of semen (contraction of vas deferens, prostate and (contraction of vas deferens, prostate and ejaculatory ductejaculatory duct((

In females:In females: Contraction or relaxation of Contraction or relaxation of female genital organ according to the stage female genital organ according to the stage of menstrual cycle and level of hormones in of menstrual cycle and level of hormones in blood. N.B Small splanchnic nerve (from blood. N.B Small splanchnic nerve (from T10 T10 –– T12, relayes in caeliac and superior T12, relayes in caeliac and superior mesentric ganglionmesentric ganglion((

44- - SOMATIC DIVISION :SOMATIC DIVISION : (Orbelli phenomenon(Orbelli phenomenon((

It is sympethetic supply of limbs, It is sympethetic supply of limbs, upper limbs (T4- Ts) lower limbs upper limbs (T4- Ts) lower limbs (T10T12), both relay in sympathetic (T10T12), both relay in sympathetic chain = Sympethetic stimulation chain = Sympethetic stimulation delays fatigue of muscle due to delays fatigue of muscle due to vasodilatation of skeletal blood vasodilatation of skeletal blood vesselsvessels

ORGANS SUPPLIED ORGANS SUPPLIED BY SYMPATHETIC BY SYMPATHETIC

ONLYONLY: :

1- Ventricles (vagal 1- Ventricles (vagal escape).escape).

2- Skin structures2- Skin structures

3- Skeletal B.V.3- Skeletal B.V.

4- Dilator pupillary 4- Dilator pupillary muscles .muscles .

5- Adrenal medulla 5- Adrenal medulla

ORGANS SUPPLIED ORGANS SUPPLIED BY BY

PARASYMPATHETICPARASYMPATHETIC 1- Constrictor pupillary 1- Constrictor pupillary

muscle .muscle .

22- - Oesophagus .Oesophagus .

3- Gastric glands .3- Gastric glands .

4- Erectile tissue .4- Erectile tissue .

N.BN.B Sympethetic → causes Sympethetic → causes V.C of all blood vessels, V.C of all blood vessels, except except

1. Coronaries.1. Coronaries.

2. Skeletal blood vessels.2. Skeletal blood vessels.

DISTRIBUTION DISTRIBUTION OF OF

PARASYMPATHETPARASYMPATHETICICI- CRANIAL DIVISIONI- CRANIAL DIVISION: :

A) Oculomotor nerve ( III N )A) Oculomotor nerve ( III N )::

It arises from occulomotor nucleus It arises from occulomotor nucleus , relays in ciliary ganglion, relays in ciliary ganglion

FUNCTIONFUNCTION : responsible for : responsible for near visions near visions

During fixation of eyes to near During fixation of eyes to near object, III nerve causes :object, III nerve causes :

1) Contraction of ciliary muscle → 1) Contraction of ciliary muscle → Increases convexity of the eye Increases convexity of the eye lens .lens .

2) Contraction of medical rectus 2) Contraction of medical rectus muscle → medial convergence of muscle → medial convergence of both eyes together. both eyes together.

3) Contraction of constrictor 3) Contraction of constrictor pupillae muscle → papillary pupillae muscle → papillary constriction constriction

B) Fascial Nerve (VII B) Fascial Nerve (VII NN):):

It arises from superior salivary nucleus, It arises from superior salivary nucleus, relays in sphenopalatine ganglion.relays in sphenopalatine ganglion.

FUNCTIONFUNCTION : : secretion of tears and secretion of tears and saliva which is watery, poor in saliva which is watery, poor in enzymes and big in amount .enzymes and big in amount .

C) Glossopharyngeal Nerve C) Glossopharyngeal Nerve (IX N):(IX N):

It arises from inferior salivary nucleus It arises from inferior salivary nucleus 9 relays in optic ganglion .9 relays in optic ganglion .

FUNCTIONFUNCTION : : secretion of saliva secretion of saliva

D) Vagus Nerve (XN)D) Vagus Nerve (XN)::

75%75% of parasympathetic fibers of the body of parasympathetic fibers of the body are the vagus nerve. It arises from are the vagus nerve. It arises from dorsal nucleus, relays in terminal dorsal nucleus, relays in terminal gangliaganglia..

FUNCTIONFUNCTION: : 1- Inhibition (supression) of heart rate and1- Inhibition (supression) of heart rate and contractility. contractility.

22 - -Broncho-constriction and inhibition ofBroncho-constriction and inhibition of inspirartory center and secretion ofinspirartory center and secretion of

mucous from bronchial glandsmucous from bronchial glands..

33 - -Stimulation (excitation) of G.I.T motilityStimulation (excitation) of G.I.T motility and secretionsand secretions. .

EFFECT OF EFFECT OF VAGUS NERVEVAGUS NERVE

1-) ON HEART1-) ON HEART* Inhibits all cardiac roperties, but it does * Inhibits all cardiac roperties, but it does

not supply the ventricles (vagus escape).not supply the ventricles (vagus escape).* Tonic (continuous) effect on the heart , * Tonic (continuous) effect on the heart ,

which is more marked in athelets.which is more marked in athelets.* Coronary vaso-constriction (V.C ) .* Coronary vaso-constriction (V.C ) .2) ON LUNGS: 2) ON LUNGS:

Mentioned before . Mentioned before . 3)3) ON G.I.T: ON G.I.T:* Evacuation of food (stimulation of G.I.T . * Evacuation of food (stimulation of G.I.T .

motility ).motility ).* Evacuation of gall bladder.* Evacuation of gall bladder.* Stimulates secretion of: gastric juice , * Stimulates secretion of: gastric juice ,

bile , pancreatic juice and mucus bile , pancreatic juice and mucus (Brunner's glands)(Brunner's glands)

* Increased hepatic blood flow.* Increased hepatic blood flow.N.BN.B Vagus nerve has no post-ganglionic Vagus nerve has no post-ganglionic

fibers fibers

WHY IT'S CALLED WHY IT'S CALLED VAGUSVAGUS? ?

Because it hasBecause it has-: -:

11 - -Afferent & efferentAfferent & efferent

22 - -Stimulatory & Stimulatory & inhibitoryinhibitory

33 - -Widely distributedWidely distributed

II- II- SACRAL DIVISION OFSACRAL DIVISION OF PARAS YMPATHETIC PARAS YMPATHETIC

) ) nerve erigentisnerve erigentis ( (It is 82 ,3,4 and called pelvic It is 82 ,3,4 and called pelvic nerve and relays in hypogastric ganglianerve and relays in hypogastric ganglia..

FUNCTIONFUNCTION : :

11 - -It supplies urinary bladder → causes It supplies urinary bladder → causes micturationmicturation

22 - -distal 2/3 of large intestine and rectum → distal 2/3 of large intestine and rectum → causes causes defecationdefecation 3- Male and female sex organs → erection 3- Male and female sex organs → erection

by vasodilatation of blood vessels of penis by vasodilatation of blood vessels of penis (♂) or clitoris (♀) (♂) or clitoris (♀)

MICTURATIONMICTURATION::

Pelvic nerve causes Pelvic nerve causes contraction of wall of contraction of wall of urinary bladder and urinary bladder and relaxation of internal relaxation of internal uretheral sphincter uretheral sphincter → → passage of urine passage of urine

DEFECATIONDEFECATION: :

pelvic nerve causes contraction of pelvic nerve causes contraction of wall of rectum and relaxation of wall of rectum and relaxation of internal anal sphincter → passage of internal anal sphincter → passage of stoolstool

N.BN.B External uretheral or anal External uretheral or anal sphincters are not under autonomic sphincters are not under autonomic control but under somatic control control but under somatic control via pudendal nerve .via pudendal nerve .

N.BN.B Internal sphincter is more Internal sphincter is more important than external sphincter important than external sphincter because it is smooth muscle i.e because it is smooth muscle i.e fatigue resistant, while external fatigue resistant, while external sphincter is skeletal muscle i.e sphincter is skeletal muscle i.e fatigable .fatigable .

CHEMICAL CHEMICAL TRANSMITTERSTRANSMITTERS

DEFINITION :DEFINITION : it is the substance which transmits the it is the substance which transmits the

nerve impulse from pre - synaptic to post - nerve impulse from pre - synaptic to post - synaptic membrane .synaptic membrane .

MECHANISM :MECHANISM : Arrival of nerve impulse to Arrival of nerve impulse to Pre-synaptic membrane → causes Ca+ uptake Pre-synaptic membrane → causes Ca+ uptake

by acetyl choline vesiclesby acetyl choline vesicles→ → causes swelling and rupture of vesiclescauses swelling and rupture of vesicles→ → causes release of acetyle choline which can causes release of acetyle choline which can cross the synaptic cleftcross the synaptic cleft→ → formation of acetylcholin - receptor formation of acetylcholin - receptor

complexcomplex→ → Increase Na permeabilityIncrease Na permeability→ → Depolarisation Action potential This Causes Depolarisation Action potential This Causes

Propagation Propagation of Nerve Impulseof Nerve Impulse

TYPES OF NERVE TYPES OF NERVE ENDINGSENDINGS

ADRENERGICADRENERGIC CHOLINERGICCHOLINERGIC(nor adrenaline)(nor adrenaline) (ac . Choline(ac . Choline((

I ) Cholinergic neurotransmission :- ( six steps I ) Cholinergic neurotransmission :- ( six steps ))

1- Synthesis of acetyl choline :-( In cytoplasm) 1- Synthesis of acetyl choline :-( In cytoplasm) choline + acetyl CoA CAT Ach + choline + acetyl CoA CAT Ach +

CoA. CoA. ( choline - acetyl - transferase)( choline - acetyl - transferase) 2- Storage of acetyl choline in vesicles 2- Storage of acetyl choline in vesicles In the synaptic vesicles .In the synaptic vesicles . 3- Release of Acetyl choline :-3- Release of Acetyl choline :- CaCa++++ channels in the presynaptic channels in the presynaptic

membrane opens → Ac.ch. membrane opens → Ac.ch. Release by exocytosisRelease by exocytosis

4- Binding to receptors .4- Binding to receptors . 5- Degradation of Ac.ch.5- Degradation of Ac.ch. cholinecholine Ac.ch. choline + acetateAc.ch. choline + acetate esteraseesterase

6- Recycling of choline6- Recycling of choline Into the neurone for resynthesis of Ac .ch. Into the neurone for resynthesis of Ac .ch.

SITES OF RELEASE SITES OF RELEASE OF ACETYL OF ACETYL CHOLINECHOLINE

1- Autonomic ganglia (i.e all 1- Autonomic ganglia (i.e all preganglionic fibers)preganglionic fibers)

2- All parasympathetic post - 2- All parasympathetic post - ganglionic fibers .ganglionic fibers .

3- Some sympathetic post - 3- Some sympathetic post - gangljpnic as sweet glands and gangljpnic as sweet glands and

blood vessels of skeletal blood vessels of skeletal muscles.muscles.

4- M.E.P = motor end plate 4- M.E.P = motor end plate (i.e neuro - muscular junction) (i.e neuro - muscular junction)

5- Adrenal medulla (pre 5- Adrenal medulla (pre ganglionic )ganglionic )

6- C.N.S .6- C.N.S .

TYPES OF CHQLINERGIC TYPES OF CHQLINERGIC RECEPTORSRECEPTORS

MUSCARINICMUSCARINIC NICOTINICNICOTINIC

1-This name from muscarine, a 1-This name from muscarine, a substance which has a same substance which has a same action as ac.choline in these action as ac.choline in these sites:sites:

a) parasympathetic posta) parasympathetic postb) sympathetic )ganglionicb) sympathetic )ganglionic

1- Name from nicotine 1- Name from nicotine which in small dose has the which in small dose has the same action of ac.choline in same action of ac.choline in a) M.E.Pa) M.E.PB) autonomic gangliaB) autonomic gangliac) adrenal medullac) adrenal medullad) C.N.Sd) C.N.S

2- Blocked by atropine by 2- Blocked by atropine by comopetitive Inhibition, not comopetitive Inhibition, not blocked by cholinestrase, so they blocked by cholinestrase, so they have longer duration of action than have longer duration of action than ac.cholineac.choline

2-Blocked by large dose of 2-Blocked by large dose of nicotine )autonomic)or by nicotine )autonomic)or by curare ) in MEP )curare ) in MEP )

A)A) Muscarinic Muscarinic receptorsreceptors

Sites : In cardiac muscles, smooth Sites : In cardiac muscles, smooth muscle and exocrine glands . muscle and exocrine glands .

Subtypes : Ml , M2 , M3 and M4 .Subtypes : Ml , M2 , M3 and M4 . -Some sympathetic post-ganglionic as -Some sympathetic post-ganglionic as

sweet glands and blood vessels of sweet glands and blood vessels of skeletal muscles.skeletal muscles.

- M.E.P = motor end plate (i.e neuro - - M.E.P = motor end plate (i.e neuro - muscular junction)muscular junction)

- Adrenal medulla (pre ganglionic )- Adrenal medulla (pre ganglionic ) - C.N.S .- C.N.S . Ml : in autonomic ganglia, CNS and Ml : in autonomic ganglia, CNS and

gastric mucosa gastric mucosa M2 : in cardiac cells and smooth M2 : in cardiac cells and smooth

muscles . muscles . M3 : in smooth muscles and secretory M3 : in smooth muscles and secretory

glands . glands . M4 and M5 : unknown sites .M4 and M5 : unknown sites .

Functions of Functions of muscarinic muscarinic receptorsreceptors

It has prolonged reseponse, It has prolonged reseponse, lasts for seconds, either lasts for seconds, either exitation or inhibition :exitation or inhibition :

1- Cardiac inhibition ( slow heart 1- Cardiac inhibition ( slow heart rate.)rate.)

2- Broncho-constriction .2- Broncho-constriction .3- Salivary secretion3- Salivary secretion4- Increases G.I.T secretion and 4- Increases G.I.T secretion and

motility.motility.5- Pupillary constriction .5- Pupillary constriction .6- Contraction of ciliary muscle.6- Contraction of ciliary muscle.7- Contraction of urinary bladder 7- Contraction of urinary bladder

and rectum . and rectum .

B) Function of B) Function of Nicotinic Receptors Nicotinic Receptors

It has short timed receponse It has short timed receponse only exitatory :only exitatory :

1- Help ganglion transmission .1- Help ganglion transmission .

2- Secretion of epinephrine and 2- Secretion of epinephrine and nor-epinephrine from nor-epinephrine from Ad. Medulla.Ad. Medulla.

3- Stimulates N.M.J (MEP) to 3- Stimulates N.M.J (MEP) to produce skeletal muscle produce skeletal muscle contractioncontraction

FATE (REMOVAL) OF AC FATE (REMOVAL) OF AC CHOLINECHOLINE . .

By choline-estrase enzyme By choline-estrase enzyme

2 types2 types . .

True True pseudo (false) pseudo (false)

- present in nerve - present in nerve ––endings - present endings - present in plasma.in plasma.

- specific only for Acspecific only for Ac - non specific, - non specific, can act oncan act on

any ester any ester

- highly potent (strong)- highly potent (strong) - less potent. - less potent.

PARASYMPATHOPARASYMPATHOMIM ETIC DRUGSMIM ETIC DRUGS

Acts By Two Ways :Acts By Two Ways :

A) Direct :A) Direct : on tissues as on tissues as muscarine, nicotine in muscarine, nicotine in small dose and carbachol.small dose and carbachol.

B) Indirect :B) Indirect : anticholinesterases as anticholinesterases as DFP and EserineDFP and Eserine

(war gas) (war gas)

Anti Anti cholinesterases : cholinesterases :

Two typesTwo types: : a) Reversible :a) Reversible : short acting short acting

e.g Eserine : generalized e.g Eserine : generalized i.e. ↑ both muscarinic and i.e. ↑ both muscarinic and nicotinic actions. Prostigmine: nicotinic actions. Prostigmine: Nicotinic i.e ↑ skeletal Nicotinic i.e ↑ skeletal muscles MEP activity = used muscles MEP activity = used in treatment of myasthenia in treatment of myasthenia gravis .gravis .

b) Irreversible :b) Irreversible : long acting long acting drugs i.e toxic, called nerve drugs i.e toxic, called nerve gases, or insecticides as DFP gases, or insecticides as DFP which causes paralysis of which causes paralysis of motor functions → difficulty in motor functions → difficulty in breathing → deathbreathing → death

PARASYMATHOLYTPARASYMATHOLYTIC DRUGSIC DRUGS

Mechanism of action :Mechanism of action :1) Persistent depolarization1) Persistent depolarization2) Competitive inhibition as curare. 2) Competitive inhibition as curare.

Types : Types : A) ganglion blockersA) ganglion blockers -Nicotine in large doses - -Nicotine in large doses -

Hexamethonium Hexamethonium They cause paralysis of autonomic They cause paralysis of autonomic

ganglia by persistant ganglia by persistant depolarization .depolarization .

B) post - ganglionic blockersB) post - ganglionic blockers -Atropine-Atropine C) MEP blockersC) MEP blockers - Curare- Curare - Botulinum - Botulinum - Flexidil- Flexidil - Succinyl cholin - Succinyl cholin

. . ( persistent ( persistent depolarization) depolarization)

Curare :- acts by competitive Curare :- acts by competitive inhibition to Ac.ch . It can be inhibition to Ac.ch . It can be usedused

together with succinyl choline as together with succinyl choline as muscle relaxants muscle relaxants

ATROPINE (anti-muscarinic drug ):ATROPINE (anti-muscarinic drug ):ACTION :ACTION :a) ON THE EYES :- Mydriasis and a) ON THE EYES :- Mydriasis and

cycloplegia(loss of ability for cycloplegia(loss of ability for near vision)near vision)

b) ON SALIVARY GLANDS :- b) ON SALIVARY GLANDS :- Dryness of mouthDryness of mouth

c) ON G.I.T :- Decrease motility = c) ON G.I.T :- Decrease motility = antispasmodicantispasmodic

d) ON RESPIRATION : - Block d) ON RESPIRATION : - Block secretions in respiratory tract secretions in respiratory tract

e) ON C.V.S :- Tachycardia = ↑ e) ON C.V.S :- Tachycardia = ↑ heart rate .heart rate .

f) ON URINARY TRACT :- ↓ f) ON URINARY TRACT :- ↓ motility of urinary bladder .motility of urinary bladder .

Effect of injection of Effect of injection of Ac.ch. after Atropine Ac.ch. after Atropine

on A.B.Pon A.B.P Nicotinic receptors in adrenal Nicotinic receptors in adrenal

medulla unblocked rise in A.B.P medulla unblocked rise in A.B.P CLINICAL USES OF ATROPINECLINICAL USES OF ATROPINE1- Fundus examination → Mydriasis1- Fundus examination → Mydriasis2- Bronchial asthma → 2- Bronchial asthma →

Bronchodilatation .Bronchodilatation .3- Treatment of colic →↓ motility 3- Treatment of colic →↓ motility

of G.I.T .of G.I.T .4- pre anaethetic drugs to prevent 4- pre anaethetic drugs to prevent

cardiac arrest.cardiac arrest.5- Befor surgery → to block 5- Befor surgery → to block

respiratory secretionsrespiratory secretions

ADRENERGIC ADRENERGIC TRANSMISSIONTRANSMISSION

5 STEPS :5 STEPS : Hydroxylase enz. Hydroxylase enz.

1- Tyrosine 1- Tyrosine DOPA (In cytoplasm). DOPA (In cytoplasm). Dopa Dopa dopamine . dopamine . 2- Storage of nor epinephrine in vesicles :-2- Storage of nor epinephrine in vesicles :- OHOH

Dopamine Nor. epinephrine Dopamine Nor. epinephrine ( In synaptic ( In synaptic

vesicles .) vesicles .)

N.BN.B In adrenal medulla only: In adrenal medulla only: CHCH33

Nor - epinephrine Nor - epinephrine epinephrine .epinephrine .

3- Release of nor-epinephrine :- Into the 3- Release of nor-epinephrine :- Into the synapse.synapse.

4- Binding by receptors : either post-synaptic 4- Binding by receptors : either post-synaptic ( on the effector organ) or pre- synaptic ( on the effector organ) or pre- synaptic receptors ( on nerve endings.)receptors ( on nerve endings.)

5- Removal of nor- epinephrine ( Fate ) .5- Removal of nor- epinephrine ( Fate ) .

SITES OF RELEASE SITES OF RELEASE OF OF

CATECHOLAMINESCATECHOLAMINES 1- Adrenergic endings :- only nor - adrenaline .1- Adrenergic endings :- only nor - adrenaline .2- Adrenal medulla :- 2- Adrenal medulla :- causes release of : causes release of : 80% epinephrine80% epinephrine 20% nor-epinephrine20% nor-epinephrine

FATE OF CATECHOLAMINESFATE OF CATECHOLAMINES

1- Active reuptake = 80-90% back into ad. 1- Active reuptake = 80-90% back into ad. vesicles.vesicles.

(Na-k Atpase sys.)(Na-k Atpase sys.)2- Destruction = 7 % by2- Destruction = 7 % by MAO MAO

(oxidation)(oxidation) COMT COMT

(methylation)(methylation)3- Excretion as such = 3 %3- Excretion as such = 3 %

ADRENERGIC ADRENERGIC RECEPTORS RECEPTORS (ALQUISTE)(ALQUISTE)

211 2

αα1 : STIMULATORY 1 : STIMULATORY aa) V.C) V.C

b) stimulation of sphincters .b) stimulation of sphincters .

α2 :- INHIBITORY 0α2 :- INHIBITORY 0

a) relaxation of walls of G.I.Ta) relaxation of walls of G.I.T b) pre - synaptic inhibition of release of nor b) pre - synaptic inhibition of release of nor epinephrine (-ve feedback)epinephrine (-ve feedback)

βl :- STIMULATORY )+) βl :- STIMULATORY )+) a) heart +ve increase H.R & contractiona) heart +ve increase H.R & contraction

b) adipose tissue = lipolysisb) adipose tissue = lipolysisc) renin - angiotensin . system = ↑ ABP.c) renin - angiotensin . system = ↑ ABP.

β2 :-INHIBITORYO )–)β2 :-INHIBITORYO )–) relaxation of smooth muscles in :relaxation of smooth muscles in :

1- bronchi = bronchodilatation .1- bronchi = bronchodilatation .2- blood vessels = V.D in skeletal blood vessels 2- blood vessels = V.D in skeletal blood vessels & coronaries.& coronaries.

N.BN.B β1 receptors are stimulated β1 receptors are stimulated equally by epinephrine and nor-equally by epinephrine and nor-epinephrine B2 receptors epinephrine B2 receptors stimulated more by epinephrine stimulated more by epinephrine than N.Ethan N.E

β2 adrcnoreceptors : tow groups β2 adrcnoreceptors : tow groups α 1 & α2:α 1 & α2:

αl receptors have high affinity for αl receptors have high affinity for phenyl-ephrine present on phenyl-ephrine present on post.synapticpost.synaptic

membrane of effector organ . membrane of effector organ . α2 receptors have high affinity for α2 receptors have high affinity for

clonidine. present on Pre-synaptic clonidine. present on Pre-synaptic nervenerve

endings to control release of nor-endings to control release of nor-epinephrine (causes its inhibition). epinephrine (causes its inhibition).

N.BN.B β2 pre-synaptic receptors β2 pre-synaptic receptors stimulate NE release, both a 2 and stimulate NE release, both a 2 and β2β2

receptors are called pre - synoptic receptors are called pre - synoptic receptors.receptors.

RECEPTOR RECEPTOR STIMULANTSSTIMULANTS

α Receptors stimulated by : nor - α Receptors stimulated by : nor - adrenaline ]- adrenaline} adrenaline ]- adrenaline} isoproterenol isoproterenol

β Receptors stimulated by : β Receptors stimulated by : isoproterenol J. adrenalin]- nor - isoproterenol J. adrenalin]- nor - adrenaline adrenaline

N.BN.B nor - adrenaline, has a more nor - adrenaline, has a more pressor effect because it acts pressor effect because it acts mainly on α due to receptor mainly on α due to receptor sensitivity.sensitivity.

RECEPTOR BLOCKERS :RECEPTOR BLOCKERS :α Blockers : ergot alkaloids .α Blockers : ergot alkaloids .β Blockers : inderal .(Propranolol.) β Blockers : inderal .(Propranolol.)

N.B In G.I.T inhibition of the N.B In G.I.T inhibition of the wall is by α2 and may be β2 wall is by α2 and may be β2

receptors.receptors. While stimulation of sphincters While stimulation of sphincters

only by al receptors (not β1 ). only by al receptors (not β1 ). N.BN.B α is stimulatory except on G.I.T, it α is stimulatory except on G.I.T, it

is inhibitory is inhibitory While β is inhibitory except on While β is inhibitory except on

heart, it is stimulatory.heart, it is stimulatory.

COMPARISON COMPARISON BETWEEN α & BETWEEN α & ββ

RECEPTORSRECEPTORS

α α –– RECEPTOR RECEPTOR β - RECEPTORβ - RECEPTOR

11 - -papillary dilatationpapillary dilatation2- vasoconstriction2- vasoconstriction3- intestinal relaxation3- intestinal relaxation4- contraction of G.I.T 4- contraction of G.I.T

sphincterssphincters

5- pilomotor contraction5- pilomotor contraction6- contraction of spleen 6- contraction of spleen

capsulecapsule7- inhibition of insulin 7- inhibition of insulin

secretionsecretion8- contraction of internal 8- contraction of internal

uretheral sphincteruretheral sphincter9- salivary secretion9- salivary secretion10- ejaculation10- ejaculationstimulated by :stimulated by :N.EN.E , epinephrine and , epinephrine and

phenyl -ephrinephenyl -ephrineBlocked by: Blocked by: Ergot alkaloidsErgot alkaloids

11 - -far vision )ciliary muscle far vision )ciliary muscle relaxation)relaxation)2- vasodilatation2- vasodilatation3- intestinal relaxation3- intestinal relaxation4- gastric wall relaxation4- gastric wall relaxation5- increase heart rate5- increase heart rate6- increase heart contractility6- increase heart contractility7- stimulation of insulin 7- stimulation of insulin secretionsecretion8- Broncho-dilatation.8- Broncho-dilatation.9- glycogenolysis .9- glycogenolysis .10- Liplysis10- Liplysis11- Renin secretion.11- Renin secretion.stimulated by:stimulated by:Isoproterenol, adrenaline , Isoproterenol, adrenaline , N.adrenalinN.adrenalinBlocked by : Blocked by : Propranolol.Propranolol.

MECHANISM MECHANISM OF OF ACTION OF ACTION OF

ADRENERGIC ADRENERGIC RECEPTORSRECEPTORS

αl Increases intra-cellular C-αl Increases intra-cellular C-AMP.AMP.

α2 Inhibit adenyl cyclase α2 Inhibit adenyl cyclase enzyme, so it decreases cyclic enzyme, so it decreases cyclic AMP so interfering between AMP so interfering between the combination between the the combination between the transmitter and its receptor transmitter and its receptor

βl receptors stimulates adenyl βl receptors stimulates adenyl cyclase , increases cyclic AMP cyclase , increases cyclic AMP

β2 receptors → unknown β2 receptors → unknown mechanism but may also act mechanism but may also act by increasing C-AMPby increasing C-AMP

Sympathomimetic Sympathomimetic drugs (adrenergic drugs (adrenergic

Agonists )Agonists )Mechanism Of Action:Mechanism Of Action:1- stimulate release of 1- stimulate release of

catecholamines e.g Tyraminecatecholamines e.g Tyramine

↓ ↓

(indirect acting agonist )(indirect acting agonist )

2- inhibit reuptake e.g Cocaine2- inhibit reuptake e.g Cocaine

3- α stimulants 3- α stimulants

Direct acting agonistDirect acting agonist

4- β stimulants 4- β stimulants

SYMPATHOLYTIC SYMPATHOLYTIC DRUGSDRUGS

1- Inhibit synthesis and 1- Inhibit synthesis and storage e.g reserpine .storage e.g reserpine .

2- Inhibit release of 2- Inhibit release of catecholamines e.g catecholamines e.g guanithidine .guanithidine .

3- Recepor blockers a & B 3- Recepor blockers a & B receptorsreceptors

4- False transmiters e.g a 4- False transmiters e.g a methyl dopa( aldomet ).methyl dopa( aldomet ).

5- Ganglion blockers e.g 5- Ganglion blockers e.g hexamethonium and hexamethonium and arfonadarfonad

DIFFERENCE DIFFERENCE BETWEEN BETWEEN

EPINEPHRINEPINEPHRIN NOR - NOR - EPINEPHREEPINEPHRE

11 - -sites of releasesites of release2- receptor 2- receptor sensetivitysensetivity3- on heart3- on heart4- pressor effect 4- pressor effect )peripheral )peripheral resistance)resistance)5- metabolic5- metabolic6- systolic pressure6- systolic pressure7- diastolic 7- diastolic pressurepressure8- G.I.T motility8- G.I.T motility

- -adrenal medullaadrenal medulla- - α and β equalα and β equal- increase cardiac - increase cardiac output and heart output and heart raterate- decrease- decrease

-glycogenolysis, -glycogenolysis, lipolysislipolysis- increase- increase- decrease- decrease- decrease- decrease

adrenal medulla & adrenal medulla & adrenergic nerve adrenergic nerve endingending- mainly a & - mainly a & β β slightlyslightly- decrease both- decrease both- increase- increase- no effect- no effect- little effect- little effect- increase- increase- increase- increase- decrease- decrease

PHEOCHROMOCYTOMPHEOCHROMOCYTOMAA

Tumour of adrenal medulla Tumour of adrenal medulla resulting in attacks of resulting in attacks of hypertension in emergency states, hypertension in emergency states, discharge of sympathetic leading discharge of sympathetic leading to: to:

1- increased arterial pressure1- increased arterial pressure 2- increased blood flow to active 2- increased blood flow to active

musclesmuscles 3- increased blood glucose level3- increased blood glucose level 4- increased rate of blood 4- increased rate of blood

coagulation . coagulation . 5- increased mental activity5- increased mental activity 6- increased glycogenolysis in liver 6- increased glycogenolysis in liver

and muscles.and muscles. 7- increased rate of cellular 7- increased rate of cellular

metabolism.metabolism.

Control of A.N.S Control of A.N.S by Higher centersby Higher centers

1- Some autonomic reflexes as 1- Some autonomic reflexes as micturation, defecation and micturation, defecation and erection are under inhibitory erection are under inhibitory control of centers in C.N.S .control of centers in C.N.S .

2- Cardio-vascular, respiratory 2- Cardio-vascular, respiratory and digestive activity are under and digestive activity are under control of medulla within the control of medulla within the brain stem.brain stem.

3- Stimulation of anterior 3- Stimulation of anterior nucleus of hypothalamus is nucleus of hypothalamus is accompanied by accompanied by parasympathetic effects, while parasympathetic effects, while stimulation of posterior stimulation of posterior nucleus is accompanied by nucleus is accompanied by sympathetic effects.sympathetic effects.

1- Cardiovascular autonomic 1- Cardiovascular autonomic

reflexes :reflexes : High arterial pressure → baro-High arterial pressure → baro-

receptors → pressure fall back receptors → pressure fall back toward normal.toward normal.

2- Gastrointestinal autonomic 2- Gastrointestinal autonomic reflexes :reflexes :

a) Un-conditioned reflex e.g. a) Un-conditioned reflex e.g. presence of food in mouth causing presence of food in mouth causing salivary secretion .salivary secretion .

b) Defecation reflex.b) Defecation reflex. c) Micturation reflex.c) Micturation reflex. d) Sexual reflexes : Erection d) Sexual reflexes : Erection

(parasympathetic function, followed (parasympathetic function, followed

by ejaculation (sympathetic by ejaculation (sympathetic function)function)

N.BN.B biofeedback research biofeedback research demonstrate that the A.N.S is not demonstrate that the A.N.S is not autonomic, it can be voluntary.autonomic, it can be voluntary.

DISORDERS OF DISORDERS OF AUTONOMIC AUTONOMIC FUNCTIONSFUNCTIONS

SYMPATHETIC SYMPATHETIC QVERACTIVITY:QVERACTIVITY:

1- HYPERTENSION :1- HYPERTENSION : sympathetic increases sympathetic increases peripheral resistanceperipheral resistance

2- ANGINA PECTORIS :2- ANGINA PECTORIS : sympathetic increases sympathetic increases myocardial Omyocardial O22

3- Hyperthyroidism:3- Hyperthyroidism: Thyroid Thyroid hormone increases sensitivity hormone increases sensitivity or number of adrenergic or number of adrenergic receptors receptors

GENERALISED GENERALISED AUTONOMIC AUTONOMIC

INSUFFICIENCYINSUFFICIENCY

1- Male impotence (no erection)1- Male impotence (no erection)2- Anhydrosis2- Anhydrosis3- Orthostatic hypotention .3- Orthostatic hypotention .3- No pupillary control3- No pupillary control4- Urinary retention .4- Urinary retention .

N.BN.B all these may accompany all these may accompany diabetes mellitus diabetes mellitus

THE ENTERIC SYSTEM:-THE ENTERIC SYSTEM:- Neural plexuses within walls of the Neural plexuses within walls of the

oesophagus , stomach small oesophagus , stomach small intestine and colon , Functioning intestine and colon , Functioning independent of A.N.S so independent of A.N.S so sympathetic and parasympathetic sympathetic and parasympathetic innervation alters the intrinsic innervation alters the intrinsic activity of the enteric neural activity of the enteric neural network .network .