J J M MEDICAL COLLEGE, DAVANGERE.DEPT OF ANESTHESIA<br />PHYSIOLOGY OF AUTONOMIC NERVOUS SYSTEM<br />CHAIRPERSONPRESENTED ...
INTRODUCTION<br />Much of the action of the body in maintaining, cardiovascular, gastrointestinal and thermal homeostasis ...
HISTORY<br />GALEN - spoke of sympathy & consent of body & was probably 1st to describe Paravertebral nerve trunks.<br />...
JACOB WINSLOWcoined term ‘SYMPATHETIC’<br />ROBERT WHYTTrecognized that adequate stimulation is necessary for visceral s...
XAVIER BICHAT divided nervous system into 2 partsLa vie organique- Visceral nervous system.La vie animal- Somatic nervous...
BROWN-SEQUARD noted that sympathetic stimulation constricts blood vessels. <br />WALTER GASKELL described white communic...
JOHN LANGLEY i) Mapped 3 distinct divisions in system.ii) Coined term ‘AUTONOMIC’ & declared thatit was largely independe...
JJ ABELsynthetized Epinephrine<br />SIR HENRY DALE isolated Choline.<br />8<br />
DEFINITION<br />It is vegetative, visceral or involuntary nervous system consisting of nerves, ganglia & plexuses that inn...
PURPOSE OF AUTONOMIC NERVOUS SYSTEM <br />A major goal of anesthetic administration is maintaining optimum homeostasis in ...
FUNCTIONAL ANATOMY <br />Nervous System<br />Central Nervous System<br />Peripheral Nervous System<br />Somatic<br />Auton...
Difference between <br />12<br />
13<br />
14<br />
CENTRAL AUTONOMIC ORGANIZATION<br />Cerebral cortex is the highest level of ANS integration. <br />The principal ANS organ...
SYMPATHETIC NERVOUS SYSTEM<br />SNS originates from spinal cord in the thoraco-lumbar region. <br />Efferent SNS originate...
    Unpaired distal plexus,
    Terminal or collateral ganglia near the target organ. </li></ul>16<br />
The 22 paired ganglia lie along either side of the vertebral column. <br />Sympathetic trunks connect these ganglia to eac...
Sympathetic response is not confined to segments from which stimulus originates. This allows for a more dramatic response,...
Paired sympathetic chain ganglia<br />Superior <br />Middle and <br />Cervico-Thoracic ganglion (stellate ganglion formed ...
Unpaired pre-vertebral ganglia<br />Reside in the abdomen and pelvis anterior to the vertebral column.<br />Celiac ganglio...
Terminal/Collateral ganglia<br />Small, few in no. & near their target organs.<br />E.g Adrenal medulla<br />21<br />
PARASYMPATHETIC NERVOUS SYSTEM<br />Arises from Cranial n. III, VII, IX, X as well as from Sacral segments S2-4.<br />Gang...
Fibres arising in the Edinger-Westphal nucleus of the Occulomotor nerve course in the mid- brain to synapse in the ciliary...
In Medulla, the facial nerve gives off parasympathetic fibres to the chorda tympani and greater superficial petrosal nerve...
Glossopharyngeal nerve synapses in the Otic ganglion.<br />These post ganglionicfibres innervate the parotid, salivary and...
The Vagus n. transmits fully ¾  of the traffic of the PNS. <br />It supplies heart, tracheobronchial tree, liver, spleen, ...
The Sacral segments emerges from S2-S4.<br />Innervates organs of the pelvis and lower abdomen<br />Preganglionic cell bod...
28<br />
Difference between <br />29<br />
ENTERIC NERVOUS SYSTEM <br />ENS is the system of neurons and their supporting cells are found in the walls of GIT, includ...
It contains<br />Myenteric /Auerbach plexus<br />Submucous /Meissner plexus.<br />Acetylcholine is principle excitatory tr...
FUNCTIONS OF ANS <br />Sympathetic <br />“Fight or flight”<br />“E” division<br />Exercise, excitement, emergency, and emb...
Antagonistic Control<br />Most internal organs are innervated by both branches of the ANS which exhibit antagonistic contr...
Exception to the dual innervation rule:<br />Sweat glands and blood vessel smooth muscle are only innervated by symp and r...
AUTONOMIC INNERVATION <br />Heart:<br />The heart is well supplied by SNS and PNS. These nerves affect cardiac pumping is ...
The PNS fibres are distributed mainly to SA and AV node and to a lesser extent to the atria. <br />The main effect of Vaga...
SNS has the same supraventricular distribution as the PNS but with strongest representation, to the ventricles. SNS effere...
Peripheral circulation :<br />SNS nerves are imp regulators of the peripheral circulation stimulation produces both     v...
Lungs :<br />Lungs are innervated by both SNS and PNS.<br />Postganglionic SNS fibres from upper thoracic ganglia (stellat...
Both SNS and the vagus nerve provide active bronchomotor control. <br />SNS stimulation produces bronchodilatation and pul...
ANS Neurotransmitters<br />Predominant SNS neurotransmitter-nor epinephrine.<br />Predominant PNS neurotransmitter-Ach.<br...
Synthesis & Metabolism of ACH<br />42<br />
Catecholamines<br />A catecholamine is any compound having a catechol nucleus (a benzene ring with 2 adjacent OH group) an...
44<br />
Regulation :<br />Increased SNS activity as in chronic stress stimulates the synthesis of tyrosine hydroxylase & dopamine ...
Inactivation :<br />Catcholamine are removed from the synaptic cleft by 3 mechanism. <br />These are<br />(a) reuptake int...
Uptake 1 is an active energy requiring temperature dependent process that can be inhibited. <br />Extraneuronal uptake (up...
RECEPTORS<br />48<br />
Cholinergic receptors <br />49<br />
Nicotinic receptors<br />Pentamers of 5 types of glycoprotein subunits: α (a1-a10), β (b2-b5), γ, δ & ε.<br />Each subunit...
51<br />
Muscarinic receptors<br />These are 7 transmembrane domain, G-protein coupled receptors.<br />M1, M3,& M5<br />52<br />
Muscarinic receptors<br />M2 & M4<br />53<br />
54<br />
55<br />
56<br />
Adrenergic Receptors<br />57<br />
α1 Adrenergic receptor<br />G protein-coupled receptor (GPCR) associated with the Gqheterotrimeric G-protein . <br />It co...
α2 Adrenergic receptor<br />G protein-coupled receptor (GPCR) associated with the Giheterotrimeric G-protein . <br />It co...
β Adrenergic receptor<br />It is a G-protein coupled receptor associated with the Gs heterotrimeric G-protein.<br />They a...
61<br />
62<br />
 RECEPTORS IN CARDIOVASCULAR SYSTEM<br />Coronary arteries :<br />Sympathetic nerves cause coronary vasoconstriction whic...
Myocardium :<br />Myocardial postsynaptic α1 receptors mediate perhaps as much as 30-50% of the basal ionotrophic tone of ...
α-PERIPHERAL VESSELS<br />Activation of presynaptic 2 vascular receptor inhibit NE release, produces vasodilatation. <br ...
-RECEPTORS IN CNS<br />There is a close association between α and β for BP and HR control. <br />Cerebral and Spinal cord...
-RECEPTORS IN THE KIDNEY<br />The greatest density of adrenergic receptors innervation is present in the thick ascending ...
-receptors in CVS<br />1 and 2 receptors are present in myocardium & are functionally coupled to adenylcyclase. <br />P...
β-Peripheral vessels<br />Post synaptic vascular  receptors are virtually all of the 2 subtype. <br />The 2 receptors a...
-receptors in the kidney <br />Kidney contains both 1 and 2 receptors 1 being predominant. <br />Renin release from JG...
DOPAMINERGIC RECEPTORS <br />71<br />
Peripheral vessels<br />Greatest numbers of DA1-postsynaptic receptors are found on vascular smooth muscle cells of the ki...
73<br />
Central nervous system<br />Dopamine receptors have been identified in the hypothalamus where they are involved in prolact...
GIT, Kidney & Mesentery<br />Dopamine receptors are  found in the smooth muscle of esophagus, stomach, small intestine  e...
FUNCTIONAL RESPONSE MEDIATED BY ANS<br />76<br />
77<br />
78<br />
79<br />
80<br />
81<br />
82<br />
AUTONOMIC REFLEXES DURING ANAESTHESIA AND SURGERY<br />83<br />
OCULO-CARDIAC REFLEX (TRIGEMINO-VAGAL REFLEX)<br />Bernard Aschner & Guiseppe first described this reflex in 1908. <br />8...
CAROTID SINUS REFLEX<br />85<br />
NASOCARDIAC REFLEX<br />86<br />
PHARYNGEAL REFLEX<br />87<br />
LARYNGEAL REFLEX  (THE KRATSCHMER REFLEX)<br />Sensitivity of this reflex is reduced by age, CNS depressant drugs & Anaest...
TRACHEAL REFLEX : (VAGO-VAGAL REFLEX)<br />First described by Brace & Reid.<br />89<br />
ABDOMINAL REFLEX <br />Peritoneal, mesenteric reflex, & celiac plexus reflex have same effects.<br />90<br />
AUTONOMIC DYSFUNCTION<br />91<br />
TESTS OF AUTONOMIC SYSTEM FUNCTION<br />These tests measure how the various systems in the body, controlled by autonomic n...
Indications for ANS testing<br />Syncope<br />Central autonomic degeneration ex. Parkinsons<br />Pure autonomic failure<br...
Parasympathetic function tests<br />HR response with valsalvamanoeuver<br />Valsalvamanoeuver: valsalva ratio is an index ...
BP and HR are measured throughout the manoeuver for 60 seconds after temination of the manoeuver<br />An average of 2 tria...
VR=Max HR/Min HR. a normal VR indicates an intact baroreceptor mediated increase and decrease in HR. a decreased VR reflec...
HR variability with respiration (respiratory sinus arrhythmia)<br />Respiratory sinus arrhythmia is recorded with patient ...
E/I Ratio: sum of longest RR intervals divided by sum of shortest RR intervals. Normal value is a mean difference of >15 B...
The 30:15 ratio (HR response to standing)<br />With patient in supine position baseline HR is measured<br />Patient is ask...
100<br />
Sympathetic function tests<br />Blood pressure response to sustained hand grip<br />Sustained hand grip causes reflex incr...
Blood pressure response to standing<br />The patient moves from resting supine to standing position.<br />The standing Sys...
Head Up Tilt Table Test<br />This test determines BP & HR response to an orthostatic challenge as a measure of sympathetic...
Patient is slowly tilted upright to an angle of 60-80°.<br />Patient is asked to report any symptoms.<br />Patient is retu...
105<br />
Other tests used are-<br />Sympathetic Cholinergic Sweat Function<br />Quantitative Sudomotor Axon Reflex Test.<br />Silas...
DISEASES ASSOCIATED WITH PROGRESSIVE NEUROLOGICAL IMPAIRMENT OF AUTONOMIC NERVOUS SYSTEM<br />107<br />
They can be primary, familial or due to secondary systemic disease or idiopathic. <br />Primary :<br />1.	Idiopathic Ortho...
Secondary to systemic diseases:<br />Aging<br />Diabetes Mellitus<br />Chronic Alcoholism <br />Chronic Renal Failure<br /...
Ageing<br />Approximately 20% of people over 65 years of age have postural hypotension. <br />Half of these patients are s...
Diabetes Mellitus<br />Diabetic autonomic neuropathy is a well known clinical entity. It may result from neuronal degenera...
For those scheduled for surgery there are several implications that are important to anaesthesiologist.<br />Esophageal  d...
Autonomic changes in Spinal Cord Transection<br />It can cause various degrees of autonomic dysfunction depending on site,...
First, a transient state of decreased excitability occurs, known as Spinal Shock. It may last for days to weeks. <br />In ...
The phenomenon of Autonomic dysreflexia can occur with stimulation below the lesion.<br />Bladder & bowel distension can e...
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Physiology of ANS

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Physiology of ANS

  1. 1. J J M MEDICAL COLLEGE, DAVANGERE.DEPT OF ANESTHESIA<br />PHYSIOLOGY OF AUTONOMIC NERVOUS SYSTEM<br />CHAIRPERSONPRESENTED BY<br />Dr RAMAPPA M.D Dr PRITAM<br /> PROFESSOR Post Graduate<br />DATE: 20-08-2010<br />1<br />
  2. 2. INTRODUCTION<br />Much of the action of the body in maintaining, cardiovascular, gastrointestinal and thermal homeostasis occurs through the autonomic nervous system (ANS). <br />The ANS is our primary defense against challenges to that homeostasis. It provides involuntary control and organization of both maintenance and stress responses.<br />2<br />
  3. 3. HISTORY<br />GALEN - spoke of sympathy & consent of body & was probably 1st to describe Paravertebral nerve trunks.<br />THOMAS WILLIS  notion of <br /> involuntary movements<br />3<br />
  4. 4. JACOB WINSLOWcoined term ‘SYMPATHETIC’<br />ROBERT WHYTTrecognized that adequate stimulation is necessary for visceral sensation & that all sympathy must be referred to brain<br />4<br />
  5. 5. XAVIER BICHAT divided nervous system into 2 partsLa vie organique- Visceral nervous system.La vie animal- Somatic nervous system<br /> CLAUDE BERNARD<br />i) Theory of chemical synapse transmission.<br />ii) Described fundamental role of ANS in maintaining Homeostasis (la fixite du milieu interior)<br />5<br />
  6. 6. BROWN-SEQUARD noted that sympathetic stimulation constricts blood vessels. <br />WALTER GASKELL described white communicantirami & recognized that the system contained 2 antagonist set of nerve fibers.<br />6<br />
  7. 7. JOHN LANGLEY i) Mapped 3 distinct divisions in system.ii) Coined term ‘AUTONOMIC’ & declared thatit was largely independent from brain.<br />SHERRINGTON<br /> initiated systemic study of reflexes & described Characteristics of reflex function.<br />7<br />
  8. 8. JJ ABELsynthetized Epinephrine<br />SIR HENRY DALE isolated Choline.<br />8<br />
  9. 9. DEFINITION<br />It is vegetative, visceral or involuntary nervous system consisting of nerves, ganglia & plexuses that innervate all viscera & tissue except striated muscle.<br />It is primarily peripheral efferent system.<br />Autonomic - self governing<br />9<br />
  10. 10. PURPOSE OF AUTONOMIC NERVOUS SYSTEM <br />A major goal of anesthetic administration is maintaining optimum homeostasis in the patient.<br />The intelligent administration of anesthetic care to patients requires knowledge of ANS pharmacology in order to achieve desirable interactions of anesthetics with the involuntary control system and to avoid responses or interactions with deleterious effects. <br />10<br />
  11. 11. FUNCTIONAL ANATOMY <br />Nervous System<br />Central Nervous System<br />Peripheral Nervous System<br />Somatic<br />Autonomic<br />Enteric Nervous System<br />Sympathetic<br />Parasympathetic <br />11<br />
  12. 12. Difference between <br />12<br />
  13. 13. 13<br />
  14. 14. 14<br />
  15. 15. CENTRAL AUTONOMIC ORGANIZATION<br />Cerebral cortex is the highest level of ANS integration. <br />The principal ANS organization is the Hypothalamus. <br />SNS functions are controlled by nuclei in the postero-lateral hypothalamus. <br />PNS functions are governed by nuclei in the midline and some anterior nuclei of the hypothalamus. <br />The anterior hypothalamus is involved in regulation of Temperature. <br />The supra-optic hypothalamic nuclei regulates water metabolism.<br />15<br />
  16. 16. SYMPATHETIC NERVOUS SYSTEM<br />SNS originates from spinal cord in the thoraco-lumbar region. <br />Efferent SNS originates in the intermedio-lateral gray column of T1-12 and L1-L3 segments of spinal cord. <br />Nerve fibers, extend to three types of ganglia,<br /><ul><li> Paired sympathetic chains,
  17. 17. Unpaired distal plexus,
  18. 18. Terminal or collateral ganglia near the target organ. </li></ul>16<br />
  19. 19. The 22 paired ganglia lie along either side of the vertebral column. <br />Sympathetic trunks connect these ganglia to each other and gray ramicommunicans connect the ganglia to the spinal nerves.<br />SNS ganglion are almost always located closer to spinal cord than to organ they innervate.<br />17<br />
  20. 20. Sympathetic response is not confined to segments from which stimulus originates. This allows for a more dramatic response, with diffuse discharge of the SNS <br />After entering the Paravertebral ganglia of lateral sympathetic chain, the Pre-ganglionicfibres follows 1 of the 3 courses.<br />Synapses with post ganglionicfibres in ganglia at the level of exit.<br />Course upwards or downwards in the trunk of SNS chain to synapse in ganglion at other level.<br />Track for variable distance through the sympathetic chain and exist without synapsing to terminate in an outlying, unpaired, SNS collateral ganglion.<br />18<br />
  21. 21. Paired sympathetic chain ganglia<br />Superior <br />Middle and <br />Cervico-Thoracic ganglion (stellate ganglion formed by fusion of inferior cervical and thoracic ganglia). <br />The sympathetic distribution to the head and neck enable and mediate <br />vasomotor, <br />pupillodilator, <br />secretory and <br />pilomotor functions.<br />SNS post ganglionic neurons outnumber the pre ganglionic no. in an average ratio of 20:1 to 30:1. <br />19<br />
  22. 22. Unpaired pre-vertebral ganglia<br />Reside in the abdomen and pelvis anterior to the vertebral column.<br />Celiac ganglion  innervated by T5-T12  innervates the liver, spleen, kidney, pancreas and small bowel and proximal colon (many preganglionic fibers from T5 to T12 may pass through the paired paravertebral ganglia to form the splanchnic nerves).<br />Superior mesenteric ganglion  innervates the distal colon.<br />Inferior mesenteric ganglion  innervates the rectum, bladder and genitals.<br />20<br />
  23. 23. Terminal/Collateral ganglia<br />Small, few in no. & near their target organs.<br />E.g Adrenal medulla<br />21<br />
  24. 24. PARASYMPATHETIC NERVOUS SYSTEM<br />Arises from Cranial n. III, VII, IX, X as well as from Sacral segments S2-4.<br />Ganglia occur proximal to or within the innervated organ. This location of ganglia makes the PNS more targeted and less robust than SNS.<br />Pre ganglion fibres originate in 3 areas of the CNS. <br />Mid brain, <br />Medulla oblongata and <br />Sacral part of spinal cord<br />22<br />
  25. 25. Fibres arising in the Edinger-Westphal nucleus of the Occulomotor nerve course in the mid- brain to synapse in the ciliary ganglion. <br />This pathway innervate the smooth muscle of iris and the ciliary muscle.<br />23<br />
  26. 26. In Medulla, the facial nerve gives off parasympathetic fibres to the chorda tympani and greater superficial petrosal nerve<br />These subsequently synapse in the ganglia of the submaxillary or sublingual glands and the pterygopalatine ganglion respectively<br />24<br />
  27. 27. Glossopharyngeal nerve synapses in the Otic ganglion.<br />These post ganglionicfibres innervate the parotid, salivary and lacrimal glands.<br />25<br />
  28. 28. The Vagus n. transmits fully ¾ of the traffic of the PNS. <br />It supplies heart, tracheobronchial tree, liver, spleen, kidney and all GIT except distal colon. <br />Most vagalfibres synapse at small ganglia on and about thoracic and abdominal viscera PNS may synapse with a 1:1 ratio of nerve to effector cells, the vagal innervations of the Auerbach plexus may connect 1 nerve fibre to 8,000 cells.<br />26<br />
  29. 29. The Sacral segments emerges from S2-S4.<br />Innervates organs of the pelvis and lower abdomen<br />Preganglionic cell bodies<br />Located in visceral motor region of spinal gray matter<br />Form splanchnic nerves<br />27<br />
  30. 30. 28<br />
  31. 31. Difference between <br />29<br />
  32. 32. ENTERIC NERVOUS SYSTEM <br />ENS is the system of neurons and their supporting cells are found in the walls of GIT, including neurons within the pancreas and gall bladder.<br />It is derived from the neuroblasts of the neural crest that migrate to GIT along the Vagus nerve. <br />ENS having extraordinary degree of local autonomy.<br />Digestion and peristalsis, occurs after spinal cord transaction or during spinal anaesthesia, although sphincter function may be impaired.<br />30<br />
  33. 33. It contains<br />Myenteric /Auerbach plexus<br />Submucous /Meissner plexus.<br />Acetylcholine is principle excitatory trigger of non-specific portion of ENS. It causes muscle contraction. <br />Role of cholinergic neurons are  Excitation of external muscles, activation of motor neurons augmenting secretion of water & electrolytes & stimulation of gastric cells.<br />Nicotinic antagonist causes abolition of enteric reflexes while cholinergic overload or over-reversal of muscle relaxant causes hyper-reactive enteric reflexes.<br />31<br />
  34. 34. FUNCTIONS OF ANS <br />Sympathetic <br />“Fight or flight”<br />“E” division<br />Exercise, excitement, emergency, and embarrassment<br />Parasympathetic<br />“Rest and digest”<br />“D” division<br />Digestion, defecation, and diuresis<br />32<br />
  35. 35. Antagonistic Control<br />Most internal organs are innervated by both branches of the ANS which exhibit antagonistic control<br />A great example is heart rate. An increase in sympathetic stimulation causes HR to increase whereas an increase in parasympathetic stimulation causes HR to decrease<br />33<br />
  36. 36. Exception to the dual innervation rule:<br />Sweat glands and blood vessel smooth muscle are only innervated by symp and rely strictly on up-down control.<br />Exception to the antagonism rule:<br />Symp and parasymp work cooperatively to achieve male sexual function. Parasymp is responsible for erection while symp is responsible to ejaculation. There’s similar ANS cooperation in the female sexual response.<br />34<br />
  37. 37. AUTONOMIC INNERVATION <br />Heart:<br />The heart is well supplied by SNS and PNS. These nerves affect cardiac pumping is 3 ways -<br />By changing the rate (Chronotropism)<br />By changing the strength of contraction (Inotropism)<br />Modulating coronary blood flow.<br />The PNS cardiac vagalfibres approaches the stellate ganglion and then join the efferent cardiac SNS fibres. <br />35<br />
  38. 38. The PNS fibres are distributed mainly to SA and AV node and to a lesser extent to the atria. <br />The main effect of Vagal cardiac stimulation to the heart is chronotrophic.<br />Vagal stimulation decreases the rate of SA node discharge and decreases the excitability of the AV junction fibers.<br />36<br />
  39. 39. SNS has the same supraventricular distribution as the PNS but with strongest representation, to the ventricles. SNS efferents to the myocardium funnel through the paired stellate ganglion. <br />Right stellate stimulation decreases systolic duration and increases the heart rate. <br />Left stellate ganglion stimulation increases mean arterial pressure & left ventricular contractility without causing a substantial change in the heart rate.<br />The dominant effect of ANS on myocardial contractility is mediated primarily through SNS.<br />37<br />
  40. 40. Peripheral circulation :<br />SNS nerves are imp regulators of the peripheral circulation stimulation produces both vasodilatation & vasoconstriction with vasoconstriction effect being predominant. <br />Blood vessels in the skin, kidney, spleen and mesentery have a extensive SNS distribution where as those in the heart, brain and muscle have less SNS innervation. <br />Basal vasomotor tone is maintained by impulses from the lateral portion of the vasomotor center in the medulla oblongata that continuously transmits impulses through SNS maintaining partial arteriolar and venular constriction. <br />38<br />
  41. 41. Lungs :<br />Lungs are innervated by both SNS and PNS.<br />Postganglionic SNS fibres from upper thoracic ganglia (stellate) pass to the lungs to innervate the smooth muscles of the bronchi and pulmonary blood vessels.<br />PNS innervation of these structures is from the vagus nerve. <br />39<br />
  42. 42. Both SNS and the vagus nerve provide active bronchomotor control. <br />SNS stimulation produces bronchodilatation and pulmonary vasoconstriction.<br />Vagal stimulation produces bronchoconstriction & may increase secretion of bronchial glands. <br />40<br />
  43. 43. ANS Neurotransmitters<br />Predominant SNS neurotransmitter-nor epinephrine.<br />Predominant PNS neurotransmitter-Ach.<br />41<br />
  44. 44. Synthesis & Metabolism of ACH<br />42<br />
  45. 45. Catecholamines<br />A catecholamine is any compound having a catechol nucleus (a benzene ring with 2 adjacent OH group) and an amine containing side. <br />Endogenous catecholamines in humans are dopamine, NE and EPI. <br />Dopamine is a neurotransmitter in CNS and primarily involved in co-ordinating motor activity in the brain. It is a precursor of NE. NE is synthesized and stored in the nerve endings of postganglionic SNS neurons. <br />Catecholamines are often referred to as adrenergic drugs because their effector action is mediated through receptors specific for the SNS.<br />43<br />
  46. 46. 44<br />
  47. 47. Regulation :<br />Increased SNS activity as in chronic stress stimulates the synthesis of tyrosine hydroxylase & dopamine hydroxylase. <br />Glucocorticoid from the adrenal cortex pass through the adrenal medulla and stimulate increase in phenylethanolamine N methyl transferase that methylates NE to EPI. <br />The release of NE is dependent upon depolarization of the nerve and an increase calcium ion permeability. NE inhibits its own release by stimulating presynaptic prejunctional alpha 2 receptors. <br />45<br />
  48. 48. Inactivation :<br />Catcholamine are removed from the synaptic cleft by 3 mechanism. <br />These are<br />(a) reuptake into the presynaptic terminals, <br />(b) extraneuronal uptake, and <br />(c) diffusion. <br />Termination of NE at the effector site is almost entirely by reuptake of NE into the terminals of presynaptic neurons (uptake 1) and this is stored in the vesicle for reuse. <br />A small amount is deaminated in the cytoplasm of the neuron by MAO to form dihydroxylmandelic acid. <br />46<br />
  49. 49. Uptake 1 is an active energy requiring temperature dependent process that can be inhibited. <br />Extraneuronal uptake (uptake 2) is a minor pathway for inactivation of NE and NE that is taken up by the extraneuronal tissue is metabolized by MAO and COMT to form VMA. <br />The importance of uptake 1 & uptake 2 is diminished when sympathomimetics are given exogenously, uptake 3 is the predominant pathway for catecholamines given exogenously and is clinically important. The uptake 3 is slow metabolism. <br />47<br />
  50. 50. RECEPTORS<br />48<br />
  51. 51. Cholinergic receptors <br />49<br />
  52. 52. Nicotinic receptors<br />Pentamers of 5 types of glycoprotein subunits: α (a1-a10), β (b2-b5), γ, δ & ε.<br />Each subunit has 4 hydrophobic helical membrane-spanning domains labeled M1-M4. The M2 regions, which contain rings of negatively charged a.a & leucine residues, form the pore walls & provide hydrophilic environment for ions.<br />50<br />
  53. 53. 51<br />
  54. 54. Muscarinic receptors<br />These are 7 transmembrane domain, G-protein coupled receptors.<br />M1, M3,& M5<br />52<br />
  55. 55. Muscarinic receptors<br />M2 & M4<br />53<br />
  56. 56. 54<br />
  57. 57. 55<br />
  58. 58. 56<br />
  59. 59. Adrenergic Receptors<br />57<br />
  60. 60. α1 Adrenergic receptor<br />G protein-coupled receptor (GPCR) associated with the Gqheterotrimeric G-protein . <br />It consists of 3 highly homologous subtypes, including α1A, α1B, and α1Dadrenergic<br />58<br />
  61. 61. α2 Adrenergic receptor<br />G protein-coupled receptor (GPCR) associated with the Giheterotrimeric G-protein . <br />It consists of 3 highly homologous subtypes, including α2A, α2B, and α2C adrenergic<br />59<br />
  62. 62. β Adrenergic receptor<br />It is a G-protein coupled receptor associated with the Gs heterotrimeric G-protein.<br />They are further divided into β1,β2 & β3.<br />60<br />
  63. 63. 61<br />
  64. 64. 62<br />
  65. 65.  RECEPTORS IN CARDIOVASCULAR SYSTEM<br />Coronary arteries :<br />Sympathetic nerves cause coronary vasoconstriction which is mediated by postsynaptic 2 receptors. <br />Larger epicardial arteries posses mainly 1 receptors (1 agonists have got little influence on coronary resistance). <br />63<br />
  66. 66. Myocardium :<br />Myocardial postsynaptic α1 receptors mediate perhaps as much as 30-50% of the basal ionotrophic tone of the normal heart. <br />The increase in density of myocardial α1 adrenoreceptors shows a relative increase in failure and myocardial ischaemia, thus enhancing of myocardial α1 receptor numbers and sensitivity<br />Intracellular mobilization of cytosolic calcium by the activated α1 myocardial receptor during ischemia appears to contribute to arrhythmias. The 1 receptor also increases the sensitivity of contractile elements to calcium.<br />64<br />
  67. 67. α-PERIPHERAL VESSELS<br />Activation of presynaptic 2 vascular receptor inhibit NE release, produces vasodilatation. <br />Whereas postsynaptic 1 and 2 vascular receptors subserve vasoconstriction. <br />Postsynaptic α1 and 2 receptors co-exist in both the arterial and venous sides of the circulation with relative distribution of 2 receptors being greater on the venous side. <br />Nor epinephrine is the most potent venoconstrictor of all the catecholamine<br />65<br />
  68. 68. -RECEPTORS IN CNS<br />There is a close association between α and β for BP and HR control. <br />Cerebral and Spinal cord presynpatic2 receptors also involved in inhibition of presynpatic NE release. <br />Central neuraxial injection of 2 agonists such as clonidine act at these sites to produce analgesia, sedation and CVS depression<br />66<br />
  69. 69. -RECEPTORS IN THE KIDNEY<br />The greatest density of adrenergic receptors innervation is present in the thick ascending loop of Henle followed by DCT and proximal tubule. Both α1 and 2 are found but 2 is dominating, a1 receptor predominantes in the renal vasculature and elicits vasoconstriction which modulates renal blood flow. <br />Tubular α1 receptors enhance sodium and water reabsorption leading to anti-natriuresis where as tubular 2 receptors promotes sodium and water excretion.<br />67<br />
  70. 70. -receptors in CVS<br />1 and 2 receptors are present in myocardium & are functionally coupled to adenylcyclase. <br />Post synaptic 1 receptors are distributed predominantly to myocardium in SA node and ventricular conduction system. <br />2 receptors have the same distribution but are presynaptic. Activation of 2 presynaptic receptors accelerates the release of NE into the synaptic cleft. <br />The effect of NE on ionotropism in the normal heart is mediated entirely through the postsynaptic 1 receptors whereas the ionotropic effects of EPI are mediated through both the 1 and 2 receptors. <br />2 receptors may also mediate the chronotrophic response to EPI because selective 1 antagonists are less effective in suppressing induced tachycardias than the non selective 1 antagonist propranolol.<br />68<br />
  71. 71. β-Peripheral vessels<br />Post synaptic vascular  receptors are virtually all of the 2 subtype. <br />The 2 receptors are located in the smooth muscle of the blood vessels of the skin, muscle, mesentry and bronchi. <br />Stimulation of post synaptic 2 receptors produces vasodilatation and bronchial relaxation. <br />69<br />
  72. 72. -receptors in the kidney <br />Kidney contains both 1 and 2 receptors 1 being predominant. <br />Renin release from JG apparatus is enhanced by  stimulation. <br />1 receptor evokes renin release from the kidneys. <br />Renal 2 receptors also appear to regulate renal blood flow at vascular level. <br />70<br />
  73. 73. DOPAMINERGIC RECEPTORS <br />71<br />
  74. 74. Peripheral vessels<br />Greatest numbers of DA1-postsynaptic receptors are found on vascular smooth muscle cells of the kidney and mesentery. <br />The vascular receptors are like the 2 receptors linked to adenyl-cyclase and mediate smooth muscle relaxation. <br />Activation of these receptors produces vasodilatation increasing blood flow to the organs. Concurrent activation of vascular presynaptic DA2 receptors also inhibits NE release at the presynaptic 2 receptors. <br />Higher doses of dopamine can mediate vasoconstriction via the postsynaptic 1 and 2 receptors. <br />72<br />
  75. 75. 73<br />
  76. 76. Central nervous system<br />Dopamine receptors have been identified in the hypothalamus where they are involved in prolactin release.<br />They are also found in basal ganglia where they coordinate motor function.<br />Central action of dopamine is to stimulate the CTZ of medulla producing nausea and vomiting. <br />74<br />
  77. 77. GIT, Kidney & Mesentery<br />Dopamine receptors are found in the smooth muscle of esophagus, stomach, small intestine  enhance secretion, production & decrease intestinal motility.<br />DA1 receptors are located on renal tubules which inhibits sodium reabsorption with subsequent natriuresis and diuresis. It reduces afterload via dilatation of the renal and mesenteric arterial beds.<br />The natriuresis may be the result of combined renal vasodilatation, improved cardiac output and tubular action of DA1 receptors. <br />JG cells also contain DA2 receptors which increases renin release when activated. This action modulates the diuresis produced by DA1 activation of tubules. <br />75<br />
  78. 78. FUNCTIONAL RESPONSE MEDIATED BY ANS<br />76<br />
  79. 79. 77<br />
  80. 80. 78<br />
  81. 81. 79<br />
  82. 82. 80<br />
  83. 83. 81<br />
  84. 84. 82<br />
  85. 85. AUTONOMIC REFLEXES DURING ANAESTHESIA AND SURGERY<br />83<br />
  86. 86. OCULO-CARDIAC REFLEX (TRIGEMINO-VAGAL REFLEX)<br />Bernard Aschner & Guiseppe first described this reflex in 1908. <br />84<br />
  87. 87. CAROTID SINUS REFLEX<br />85<br />
  88. 88. NASOCARDIAC REFLEX<br />86<br />
  89. 89. PHARYNGEAL REFLEX<br />87<br />
  90. 90. LARYNGEAL REFLEX (THE KRATSCHMER REFLEX)<br />Sensitivity of this reflex is reduced by age, CNS depressant drugs & Anaesthetics.<br />88<br />
  91. 91. TRACHEAL REFLEX : (VAGO-VAGAL REFLEX)<br />First described by Brace & Reid.<br />89<br />
  92. 92. ABDOMINAL REFLEX <br />Peritoneal, mesenteric reflex, & celiac plexus reflex have same effects.<br />90<br />
  93. 93. AUTONOMIC DYSFUNCTION<br />91<br />
  94. 94. TESTS OF AUTONOMIC SYSTEM FUNCTION<br />These tests measure how the various systems in the body, controlled by autonomic nerves, respond to stimulation. The data collected during testing will indicate functioning of ANS. <br />These tests help to identify patients with autonomic neuropathy and is predictive of mortality and morbidity.<br /> Early autonomic dysfunction is defined as a single abnormal or two borderline-abnormal results on the tests involving changes in heart rate. <br />Definite involvement comes when two of the tests of changes in heart rate are abnormal. Severe dysfunction is defined as abnormalities in the blood pressure assessments.<br />Tests are done to monitor BP, blood flow, heart rate, skin temperature and sweating.<br />92<br />
  95. 95. Indications for ANS testing<br />Syncope<br />Central autonomic degeneration ex. Parkinsons<br />Pure autonomic failure<br />Postural tachycardia syndrome<br />Autonomic and small fiber peripheral neuropathies ex.- diabetic neuropathy<br />Sympathetically mediated pain<br />Evaluating response to therapy<br />Differentiating benign symptoms from autonomic disorders<br />93<br />
  96. 96. Parasympathetic function tests<br />HR response with valsalvamanoeuver<br />Valsalvamanoeuver: valsalva ratio is an index of HR response to BP changes that occur during valsalvamanoeuver resulting from mechanical and cardiovascular effects.<br />Measure baseline HR and BP 3 minutes before this test<br />Patient takes a deep inhalation, a complete exhalation, inhales again and then blows into a mouthpiece for 15 seconds<br />Expiratory pressure is maintained at 40 mm Hg. This pressure can be measured by having the patient to exhale through a mouth piece attached to a transducer<br />94<br />
  97. 97. BP and HR are measured throughout the manoeuver for 60 seconds after temination of the manoeuver<br />An average of 2 trials are taken for analysis<br />Caution while performing the test in elderly with pulmonary disease who may not be able to perform the test satisfactorily<br />As intraocular pressure is known to rise, the test must not be performed in those with recent retinal surgery<br />VR values are aggregated. There is a decrease with age.<br />95<br />
  98. 98. VR=Max HR/Min HR. a normal VR indicates an intact baroreceptor mediated increase and decrease in HR. a decreased VR reflects baroreceptor and cardiovagal dysfunction. Normal value is a ratio of >1.21<br />96<br />
  99. 99. HR variability with respiration (respiratory sinus arrhythmia)<br />Respiratory sinus arrhythmia is recorded with patient supine & breathing at fixed rate of 6 breaths/min with slow inhalation & exhalation. This provides close to maximum HR variability. <br />Timed breathing is done by coaching verbally or with electronic visual guidance.<br />6-8 cycles are recorded with one or two trials being performed.<br />Timed breathing potentiates normal sinus arrhythmia that occurs during the normal respiratory cycles<br />HR variability with respiration decreases with increasing age<br />Reduced HR variability with respiration is seen in autonomic peripheral neuropathies and central autonomic degenerations.<br />Other factors which can influence this test are poor respiratory efforts, hypercapnia, salicylatespostioning, obesity<br />97<br />
  100. 100. E/I Ratio: sum of longest RR intervals divided by sum of shortest RR intervals. Normal value is a mean difference of >15 BPM.<br />98<br />
  101. 101. The 30:15 ratio (HR response to standing)<br />With patient in supine position baseline HR is measured<br />Patient is asked to quickly stand up<br />HR variability is measured for at least 1 min of active standing<br />A normal ratio is greater than unity and reflects intact vagally mediated HR changes.<br />An abnormal ratio indicates parasympathetic cardiovagal dysfunction<br />Misinterpretations of this test can occur in hypovolemia, medical deconditioning, and hypothyroidism.<br />99<br />
  102. 102. 100<br />
  103. 103. Sympathetic function tests<br />Blood pressure response to sustained hand grip<br />Sustained hand grip causes reflex increase in heart rate & cardiac output without changing systemic vascular resistance.<br />Diastolic BP thus normally increases.<br />BP is measured every min for 5 min.<br />The initial diastolic BP is substracted from the diastolic BP just before release.<br />The normal value is difference of >16mm Hg.<br />101<br />
  104. 104. Blood pressure response to standing<br />The patient moves from resting supine to standing position.<br />The standing Systolic BP is substracted from the supine Systolic BP.<br />The normal value is difference of <10mm Hg.<br />102<br />
  105. 105. Head Up Tilt Table Test<br />This test determines BP & HR response to an orthostatic challenge as a measure of sympathetic function.<br />Used to access orthostatic intolerance caused by sympathetic nervous system dysfunction & to detect any predisposition to vasovagal syncope.<br />Patient lies supine on a tilt table & a belt is placed around the waist to secure them in case of syncope.<br />BP & ECG are monitored throughout the tests & recorded.<br />Baseline BP is recorded for atleast 3 min.<br />103<br />
  106. 106. Patient is slowly tilted upright to an angle of 60-80°.<br />Patient is asked to report any symptoms.<br />Patient is returned to horizontal supine position.<br />HR & BP are monitored in supine position until it returns to baseline.<br />IV Isoproterenol, a pharmacological measure to potentiate orthostatic challenge to the tilt table test, is frequently used.<br />A normal tilt table test is one in which there are no symptoms & a modest fall in BP.<br />104<br />
  107. 107. 105<br />
  108. 108. Other tests used are-<br />Sympathetic Cholinergic Sweat Function<br />Quantitative Sudomotor Axon Reflex Test.<br />Silastic Imprint Test.<br />Thermoregulatory Sweat Test.<br />Microneurography.<br />106<br />
  109. 109. DISEASES ASSOCIATED WITH PROGRESSIVE NEUROLOGICAL IMPAIRMENT OF AUTONOMIC NERVOUS SYSTEM<br />107<br />
  110. 110. They can be primary, familial or due to secondary systemic disease or idiopathic. <br />Primary :<br />1. Idiopathic Orthostatic Hypotension<br />2. Shy-Drager type of Orthostatic Hypotension <br />Familial :<br />1. Riley-Day Syndrome (Autonomic neuropathy in infants and children)<br />2. Lesch-Nyhan Syndrome<br />3. Gill Familial dysautonomia<br />108<br />
  111. 111. Secondary to systemic diseases:<br />Aging<br />Diabetes Mellitus<br />Chronic Alcoholism <br />Chronic Renal Failure<br />Hypertension<br />Rheumatoid Arthritis <br />Carcinomatosis<br />Chaga's disease <br />Tetanus<br />Spinal cord injury – Transection<br />Acute <br />Chronic<br />Neurological diseases<br />TabesDorsalis<br />Syringomyelia<br />Amyloidosis<br />109<br />
  112. 112. Ageing<br />Approximately 20% of people over 65 years of age have postural hypotension. <br />Half of these patients are symptomatic i.e they experience dizziness, faintness or loss of consciousness. <br />It is well known that the reflex regulation of heart rate which is mediated primarily by parasympathetic mechanisms declines progressively with age. <br />There will be a selective or earlier impairment of parasympathetic function with aging with a minimal or a more gradual involvement of the sympathetic nervous system<br />110<br />
  113. 113. Diabetes Mellitus<br />Diabetic autonomic neuropathy is a well known clinical entity. It may result from neuronal degeneration or metabolically related neuronal dysfunction. <br />The afferent central or efferent reflex pathways each can be involved. <br />It has been suggested that the Vagal neuropathy occurs earlier in the course of DM than the sympathetic neuropathy. <br />The most sensitive test of cardiac parasympathetic impairment is that of determining RSA during forceful breathing. Intolerance to upright posture is often evident. The presence of symptomatic postural hypotension is associated with a poor prognosis. These patients are prone to sudden cardiac death.<br />111<br />
  114. 114. For those scheduled for surgery there are several implications that are important to anaesthesiologist.<br />Esophageal dysfunction and gastric hypotonia increase the risk of regurgitation and aspiration.<br />Bradycardia, hypotension and cardiopulmonary arrest have been reported.<br />Abnormal blood pressure falls with induction and highest requirement for intraoperative pressor agents to maintain stable haemodynamics.<br />ANS dysfunction may also interfere with control of ventilation, making diabetics more susceptible to respiratory depressant effects of drugs.<br />Painless myocardial infarction and unexplained cardio respiratory arrest have been reported.<br />112<br />
  115. 115. Autonomic changes in Spinal Cord Transection<br />It can cause various degrees of autonomic dysfunction depending on site, extent & timing of the lesion.<br />Many autonomic reflexes are inhibited by Supraspinal feedback that is lost after spinal cord transaction.<br />In Paraplegic patient, small stimuli can cause exaggerated sympathetic discharges.<br />The only intact efferent component of baroreflex pathways in Quadriplegic patients is Vagus. <br />There are fundamental differences between acute & chronic spinal cord transaction.<br />113<br />
  116. 116. First, a transient state of decreased excitability occurs, known as Spinal Shock. It may last for days to weeks. <br />In these patients, the periphery is generally atonic & peripheral blood vessels are dilated.<br />In case of recent High Thoracic lesion, basal supine blood pressure is usually low & accompanied by plasma catecholamine levels that are approx 35% of normal.<br />In case of recent Low spinal injuries, compensatory tachycardia is exhibited from intact part of ANS.<br />In cases of chronic High spinal lesion, patient may fail to respond to hypovolemia with increased heart rate & may exhibit bradycardia. Renin-angiotensin-aldosterone system compensates for maintenance of blood pressure in these patients. <br />114<br />
  117. 117. The phenomenon of Autonomic dysreflexia can occur with stimulation below the lesion.<br />Bladder & bowel distension can elicit Mass Reflex.<br />Dramatic rise in blood pressure.<br />Marked reduction in flow to periphery.<br />Flushing & sweating in areas above the lesion.<br />In addition there may be contraction of bladder & bowel, skeletal muscle spasm & penile erection.<br />115<br />
  118. 118. PREVENTION AND TREATMENT OF ADVERSE AUTONOMIC REFLEXES<br />Atropine commonly used for both prevention and treatment.<br />Topical anaesthesia can eliminate the reflex.<br />Intravenous lidocaine is more effective than topical anaesthesia.<br />Cessation of applied stimulus immediately.<br />Vasopressors injected if there is persistent hypotensive response.<br />Depth of anaesthesia should be increased. Most of the intrathoracic and intraabdominal reflexes are observed during surgery when anaesthesia is to light or relaxation is inadequate.<br />116<br />
  119. 119. REFERENCES<br />Miller`s Anaesthesia- 7th ed.<br />Barash Clinical Anesthesia- 6th ed.<br />Stoelting`s Principles of Anesthesiology-3rd ed.<br />Collin`s Anesthesiology<br />Ganong`s Review of Medical Physiology-23rd ed.<br />K.D Tripathi`s Essentials of Medical Pharmacology 5th ed. <br />ISACON 2009.<br />117<br />
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