11 ooff 55

KKEEVVCCHHAANN,, HHAACCHHIIUU,, JJOODDIIEE TTHHEE AAUUTTOONNOOMMIICC NNEERRVVOOUUSS SSYYSSTTEEMM

There are 2 basic types of neurotransmission (both found in the Autonomic Nervous System): 1. FAST

ionotropic receptors (directly stimulated)

neurotransmitter (NT) binds to receptor found on the ion channel; direct opening/closing of channel

2. SLOW

metabotropic receptors

has a separate receptor sides

intervening G-protein link receptors initiating cellular enzymatic cascade involving 2nd messengers resulting in opening/closing of channels, hence, they are slower

NT binds with with G-protein, then 2nd

messenger then open ion channels

local anesthetics – inhibit sodium channels so no pain perception

2 Types of electrical responses in the postsynaptic membrane: 1. Excitatory Postsynaptic Potential (EPSP) 2. Inhibitory Postsynaptic Potential (IPSP)

The potentials are graded for both. They need to summate and the net output (either + or -) will be the response.

The autonomic nervous system generally refers to sympathetic and parasympathetic nervous systems including the enteric nervous system.

Functions 1. Maintains homeostatic conditions (blood pressure, fluid &

electrolytes, pain, and body temperature) 2. Coordinates body’s responses to stress, injury and exercise;

Note: stress response fight and flight response. 3. Assists the endocrine system in regulating reproduction (in

which both sympathetic and parasympathetic act synergistically)

Flow: Input Integrating Coordinating Circuits Output

Inputs: Visceral, humoral (hormones, NTs) and environmental (temperature, humidity)

Integrating coordinating unit: Hypothalamus and limbic system

Outputs: Autonomic, neuroendocrine and behavioral Major Efferent Systems 1. Somatic

Under voluntary control

α-motor neuron is located in the CNS (brainstem or spinal cord)

Effector cells: skeletal muscle cells

Neurotransmitter: Acetylcholine (ACh)

Direct innervations to the effector cells

In the neuromuscular junction, there’s 1:1 ratio by your active zones and NT

2. Autonomic Nervous System

Known as visceral motor system since it provides motor control on visceral organs

Not under voluntary control = involuntary

2 relay station: preganglionic and postganglionic neurons

ANS is a two-neuron chain system – 2 relay stations (1) Preganglionic neuron: both sympathetic and

parasympathetic o Located within the CNS; beside IML

(intermediolateral) column of the gray matter o Synapses outside the CNS o Myelinated o Fibers exits the CNS and synapse with the

postganglionic neuron (located outside the CNS) o Have the same neurotransmitter: Acetylcholine o Ach binds only to nicotinic receptors

(2) Postganglionic neuron: different when comparing sympathetic and parasympathetic o intervening ganglion outside of the CNS o Unmyelinated o Primary neurotransmitter is Ach o Ach binds to both muscarinic and nicotinic receptors Fast EPSP – due to the activity of the nicotinic

receptor; ensures transmission of synapse Slow EPSP – due to activity of muscarinic

receptors; ensures modulation of synapse o parasympathetic utilizes ACh as neurotransmitter

(muscarinic receptor) o sympathetic utilizes norepinephrine, epinephrine

(except sweat glands) as neurotransmitter (α and β receptors)

o Post ganglionic fibers innervate these: Smooth muscle cells Gland cells Cardiac muscles

In the sympathetic system, the autonomic ganglia lie along the vertebral column

Both postganglionic fibers of sympathetic and parasympathetic systems end in varicosities (in contrast to the endplate of the somatic nervous system)

Fig 1. Pre- and Postganglionic neurons of the ANS

II.. IINNTTRROODDUUCCTTIIOONN

IIII.. TTHHEE AAUUTTOONNOOMMIICC NNEERRVVOOUUSS SSYYSSTTEEMM ((AANNSS))

From 2015 trans: (NOT DISCUSSED)

The ANS is under CNS control.

Central components of ANS include hypothalamus and higher levels of limbic system.

Actions of sympathetic and parasympathetic nervous system are not always antagonistic. Sometimes both work in a coordinated way acting reciprocally and synergistically.

Not all visceral structures are innervated by both systems

Skin and most of the vessels in the body receives sympathetic innervations exclusively. Small fraction of blood vessels has parasympathetic innervations

The parasympathetic nervous system does not innervate the body wall but only structures in the head and in the thoracic, abdominal and pelvic cavities.

I. Introduction

II. Autonomic Nervous System

A. Sympathetic Nervous System

B. Parasympathetic Nervous System

III. Relationship between Sympathetic and Parasympathetic

IV. Control of ANS

OS 202a: Integration and Control Systems

AUTONOMIC NERVOUS SYSTEM October 10, 2011

1 Dr. Ma. Salome Vios

22 ooff 55

KKEEVVCCHHAANN,, HHAACCHHIIUU,, JJOODDIIEE TTHHEE AAUUTTOONNOOMMIICC NNEERRVVOOUUSS SSYYSSTTEEMM

Divisions of the ANS

Sympathetic – “Sympathetic ANS” o The sympathetic preganglionic neurons are located in the

thoracic and lumbar segments of spinal cord (thoracolumbar division of ANS)

o The postganglionic neurons are generally found in the paravertebral or the prevertebral ganglia, which are located at some distance from the target organs

o Effects are more generalized o “fight-flight” responses o Adrenergic ANS

Parasympathetic – “Parasympathetic ANS” o The parasympathetic preganglionic neurons are found in

the brainstem and in the sacral spinal cord-craniosacral division of ANS

o Parasympathetic postganglionic neurons are found in parasympathetic ganglia near or actually on the walls of target organs

o Cholinergic ANS

Enteric (too be elaborated in OS206) o Gut has an intrinsic autonomic nervous system o You can denervate the gut and the intestine can still move

(peristalsis) o Gut has a predominantly parasympathetic innervation o Enteric nervous system includes neurons and nerve fibers

in myenteric and submucosal plexus in the walls of GIT o Primarily for secretions and intestinal motility

Responsible for the “fight or flight” system

Active when excited or in emergency, threatening situations

Also active during vigorous physical activity, adjusting blood vessel constriction

Effects are more generalized since it diverges into different organs, i.e. 1:5 ratio of preganglionic fibers : postganglionic fibers

Function can be excitatory or inhibitory depending on the receptors to which the neurotransmitter (mostly adrenergic)

Also referred to as Thoracolumbar Division

The preganglionic fibers arise from T1-L2, thus “thoracolumbar”, and become the white rami communicantes as they come out of the spinal cord

Preganglionic sympathetic efferent fiber system includes: o Superior cervical ganglion Innervates the pupilary dilator, lacrimal and nasal

glands, submaxillary and sublingual glands and the parotid gland

o Middle cervical ganglion o Inferior sympathetic ganglion Innervates the lungs and heart

o Celiac ganglion Innervates the stomach, liver, pancreas and the spleen

o Adrenal medulla (direct innervation from the presynaptic fiber of the spinal cord) The adrenal gland is a modified sympathetic ganglion Chromaffin cells contain and release epinephrine when

sympathetically activated o Superior mesenteric ganglion Innervates the small intestine and the colon

o Inferior mesenteric ganglion Innervates the colon, kidney and bladder

Preganglionic neurons synapse at paravertebral ganglion found at sympathetic trunk: o Some fibers ascend the sympathetic trunk before

synapsing at paravertebral ganglion (innervates head structures)

o Other preganglionic fibers don’t synapse immediately, just pass through the sympathetic chain and prevertebral ganglion They synapse directly with adrenal medulla Innervates the chromaffin cells of the adrenal medulla,

releasing epinephrine enhancing the stress response o Some exit the paravertebral ganglion forming gray rami

communicantes (innervates organs in the chest)

The Adrenergic System (MEMORIZE! Konti lang naman daw) Table 1. The different adrenergic receptors -- see last page :)

Epinephrine (or Adrenaline) o Mimics action of sympathetic stimulation but with greater

potency o Stimulates both α1 and β2 receptors o Produced by the chromaffin cells of the adrenal medulla o Projections of epinephrine-containing neurons in the locus

ceruleus (in the pons just beneath the floor of the 4th ventricle; widespread regions of the brain and spinal cord) modulating behavior

o Stimulates other organs/cells with adrenergic receptors that do not have sympathetic nerve innervation: liver and fat cells, RBC, leucocytes, platelets

o Activated in stressful situations o “fight or flight” response Increase blood flow to tissues Increase heart rate and blood pressure Increase blood sugar levels

Widespread effects

Norepinephrine (or Noradrenaline) o Effects will depend on the type of receptor on the organ o Circulating adrenaline and noradrenaline have similar

effects but differ in the following aspects: Adrenaline has greater effect on stimulating B receptors Adrenaline has causes only weak constriction of the

blood vessels (kaya may adrenaline sa anethesia because we want to minimize bleeding but only to a smaller extent)

Adrenaline has 5-10x greater metabolic effect: can increase metabolic rate by 100% above normal

BB.. TTHHEE PPAARRAASSYYMMPPAATTHHEETTIICC NNEERRVVOOUUSS SSYYSSTTEEMM

also known as the Craniosacral division or Cholinergic system

Its preganglionic fibers enter the peripheral nervous system via the cranial (CN III, VII, IX, X) and sacral (S2-S4).

Its postganglionic fibers are nearer to the organs they innervate

Restorative function (protection, rest and recuperation of individual organs and bodily functions); waste elimination

Effects are more discrete or localized

Localized effect due to the 1:1 ratio of postganglionic: preganglionic fibers

Preganglionic fibers extend to terminal ganglia close to supplied organs

Long preganglionic fibers; short postganglionic fibers Functions of the Parasympathetic Nervous System

Activation results in conservation and restoration of body energy

DECREASE in heart rate will decrease the demand for energy

INCREASE in GIT activity will promote restoration of body

AA.. TTHHEE SSYYMMPPAATTHHEETTIICC NNEERRVVOOUUSS SSYYSSTTEEMM

From 2015 trans:

Each spinal nerve receives a gray ramus from a higher or lower ganglion; only 14 white rami as opposed to 31 gray rami

Have postganglionic fibers from C1 to S5, and thus more divergent

From 2015 trans:

Fibers don’t have active zones; they have evaginations instead, hence, movement of neurotransmitter is diffuse. The effect then will be more widespread. The importance of this is emphasized in the example: in the event of stress, you need to call the action of different visceral organs at the same time (diffuse!)

33 ooff 55

KKEEVVCCHHAANN,, HHAACCHHIIUU,, JJOODDIIEE TTHHEE AAUUTTOONNOOMMIICC NNEERRVVOOUUSS SSYYSSTTEEMM

energy

Effects are more localized and short acting The Cholinergic System

NOTE: All preganglionic neurons are cholinergic

NOTE: Postganglionic ACh receptors differ, nicotinic (fast, ionotropic) while muscarinic (slow, metabotropic)

All organs have muscarinic receptors that facilitate slow activation with longer effects

Anatomically refers to parasympathetic postganglionic neurons

Recall Exception 1: The anatomically sympathetic postganglionic neurons which innervate sweat glands (Recall that the sweat glands are under the sympathetic innervations but uses Ach)

Recall Exception 2: Anatomically sympathetic postganglionic neurons which innervate the blood vessels of the skeletal muscles that produce vasodilation

Table 2. The Cholinergic Receptors and their functional roles (MEMORIZE – konti lang naman daw) -- see last page :)

Sympathetic and parasympathetic activity may be + or – in some organs

Both are active on organs and the two systems may act reciprocally to each other

The parasympathetic and sympathetic divisions generally have antagonistic effects (sympathetic – pupil dilation, parasympathetic – pupil constriction) though not all the time

May have synergistic effects (e.g. erection by the parasympathetic; ejaculation by the sympathetic)

The tone of the peripheral arteriolar smooth muscles is predominantly sympathetic

Some organs or tissues may be under the primary control of one system (background tone) but it is the balance of activity that maintains homeostasis in the face of the changing environment

Predominant tones: o Systemic arterioles have a sympathetic tone o GIT: Parasympathetic tone o Heart: Parasympathetic tone

Why does the sympathetic nervous system have more widespread effects?

More divergence (one preganglionic neuron synapses with several postganglionic fibers) widespread and lasts longer o Ratio of postganglionic fiber/preganglionic fiber is 5:1 o In parasympathetic division, ratio is 1:1 more discrete

and localized effect

ACh: simple enzymatic degradation through acetylcholinesterase, hence, it is easily degraded

Noradrenaline/Epinephrine: more complex degradation through reuptake, MAO, COMT, hence, longer persistence

Colocalization of NT with other Transmitters

Controls final outflow of the ANS

According to mam: “hindi lang ACh at norepinephrine ang nag-aact, madami pang ibang NTs na involved”

For Cholinergic preganglionic: neurotensin, substance P, LHRH

For Cholinergic postganglionic: CGRP, vasoactive intestinal polypeptide (VIP)

For Noradrenergic postganglionic: neuropeptide Y, purinergic, galanin, dynorphin, Enkephalin

IIVV.. CCOONNTTRROOLL OOFF AANNSS

ANS receives visceral sensory information

Visceral afferents synapse on nucleus of solitary tract; fibers are sent to: o Interomediolateral (IML) cell column of spinal cord o Lateral medullary reticular formation (rostroventromedial)

Parabrachial nucleus in the brainstem sent to: o Amygdala o Periaqueductal gray o Dorsal motor nucleus

ANS also influenced by cerebrum, hypothalamus, and brainstem

Fig 2. Central Integration Diagram

The Baroreceptor Reflex

Stretched during changes in blood pressure

It follows the following steps: 1. Baroreceptors synapse with nucleus tractus solitarius

(affector) which secretes glutamate (excitatory) stimulates both the CVLM and nucleus ambiguous

2. Caudal ventrolateral medulla (CVLM) – secretes GABA (inhibitory) to the rostroventrolateral medulla

3. Stimulated nucleus ambiguous (dorsal motor nucleus of X) then out as vagal nerve to heart (inhibitory to the heart)

4. Rostral ventrolateral medulla is inhibited by CVM, hence less glutamate is secreted.

5. Decreased glutamate causes less stimulation to the intermediolateral cell column(IML) causing vasodilation

Simple Clinical Evaluation Tests of the ANS A. Responses of Blood Pressure and Heart Rate Changes in

Posture and Breathing

IIIIII.. RREELLAATTIIOONNSSHHIIPP BBEETTWWEEEENN SSYYMMPPAATTHHEETTIICC

AANNDD TTHHEE PPAARRAASSYYMMPPAATTHHEETTIICC DDIIVVIISSIIOONNSS

From 2015 trans:

In a normal individual what is the BP response when one changes position from recumbent to standing? Normal heart rate response?

Assumption of an upright posture causes blood to shift downwards, creating a decrease in stroke volume. The circulatory adjustment to orthostatic stress is rapid in healthy subjects. Mechanisms like cardiopulmonary reflexes, venoarteriolar reflexes, and vasopressin (AVP) and renin-angiotensin systems contribute to maintenance of postural normotension (Wieling & Van Lieshout, 1993).

What is the nerve innervation of the heart rate response to changes in posture?

Mechanoreceptors in the atria and ventricles innervated by vagal afferents exert tonic inhibitory influence on sympathetic outflow and AVP release (Shepherd & Shepherd, 1992).

From 2015 trans:

Sympathetic: Generalized while Parasympathetic: Localized

Sympathetic and Parasympathetic Denervation

Immediate loss of background tone

Increase intrinsic tone normal intrinsic tone

Denervation supersensitivity

Major anatomical difference of sympathetic and parasympathetic: preganglionic fibers of sympathetic arise from thoracic and lumbar cords (hence, thoracolumbar/adrenergic division), fibers of parasympathetic from III,VII,IX,X and S2-S4 (cholinergic division)

Postganglionic fibers of parasympathetic is short (nearly close to the organ it innervates) though its preganglionic fibers are long

Longer duration of sympathetic due to the catabolism of epinephrine in contrast to acetylcholine of the parasympathetic

44 ooff 55

KKEEVVCCHHAANN,, HHAACCHHIIUU,, JJOODDIIEE TTHHEE AAUUTTOONNOOMMIICC NNEERRVVOOUUSS SSYYSSTTEEMM

B. The Valsalva Maneuver

C. Cold Pressor Test

Vasoconstriction induces elevation of BP

Immersion of one hand in ice water elevates the BP by 15-20 mmHg systolic and 10-15 mmHg diastolic

D. Hand Grip Test

Sustained isometric contraction for 5 minutes increases BP by 15 mmHg

E. Other ANS Tests

Galvanic skin-resistance test: used for those with excessive sweating

Starch-iodine test: also for sweating

Pharmacologic tests: pupillary reflex

Cutaneous flare response

END KEVCHAN: “:D” JODIE: Shout out to my anatomates (Team China – Chan, Chiu, Ciro, Climacosa, Co), Team Taiwan extension – Aimee Dy (haha! May Team HK and SG na ba?), SGD mates, MDL mates, IDC211 research mates, BioDil people, Class 2016, and to all people of the world! One last push before the sem ends! Stay Fierce Since Harold forgot to make a greeting. Ito na lang :)

Fig 3. The Autonomic Nervous System – Sympathetic and Parasympathetic Divisions

From 2015 trans: Normal physiological response consists of 4 phases. 1. Initial pressure rise: On application of expiratory force, pressure rises inside the chest forcing blood out of the pulmonary circulation into the L atrium. This causes mild blood pressure rise. 2. Reduced venous return and compensation: Return of blood to the heart is impeded by the pressure inside the chest. The output of the heart is reduced and BP falls. This occurs from 5-14 seconds. The fall in BP reflexly causes blood vessels to constrict with some rise in pressure (15-20 seconds). This compensation can be quite marked with pressure returning to near or even above normal but the cardiac output and blood flow to the body remains low. During this time, the pulse rate increases. 3. Pressure release: The pressure on the chest is release, allowing pulmonary vessels and the aorta to re-expand causing further slight fall in pressure (20-23 sec) due to decreased left ventricular return and increased aortic volume respectively. Venous blood can once more enter the chest and heart, and cardiac output begins to increase. 4. Return of cardiac output: Blood return to the heart is enhanced by the effect of entry of blood which had been dammed back, causing a rapid increase in cardiac output and of blood pressure (24 sec on). The pressure usually rises above normal before returning to a normal level. With return of BP, the pulse rate returns to normal.

55 ooff 55

KKEEVVCCHHAANN,, HHAACCHHIIUU,, JJOODDIIEE TTHHEE AAUUTTOONNOOMMIICC NNEERRVVOOUUSS SSYYSSTTEEMM

The Adrenergic System (MEMORIZE! Konti lang naman daw) Table 1. The different adrenergic receptors/adrenoreceptors (see last page)

α1 α2 β1 β2 β3

Agonist NA≥Ad Ad≥NA NA≥Ad Ad>NA NA

2nd

Messenger IP3/DAG ↓cAMP ↑cAMP ↑cAMP ↑cAMP

Functional Role Contractile effect on smooth muscles of

blood vessels, urogenital sphincter

muscles

Presynaptic control (inhibitory) of NE,

ATP, ACh, from nerver terminals

Stimulatory effects of NE and E on

heart

Relaxant effects on smooth muscles in

GIT, airways, urogenital

Release of free fatty acid from adipose tissue

EXCEPTIONS:

Not all sympathetic innervations are adrenergic

Postganglionic neurons which innervate the blood vessels of the skeletal muscles that produce vasodilation and sweat glands are cholinergic

Table 2. The Cholinergic Receptors and their functional roles (MEMORIZE – konti lang naman daw) -- see last page :)

TYPE (Tissue) Nicotinic (Ganglionic

fast current NMJ) M1 (Ganglionic, slow

current) M2 (cardiac)

M3 (bronchial, small muscular and glandular)

Agonist ACh ACh ACh ACh

2nd mes- senger

None IP3/DAG ↓cAMP IP3/DAG

Functional role Fast excitation of post- ganglionic neurons in autonomic ganglia; Skeletal M.

K+

channels; Modulatory effects on the ANS

Opens K+ channels;

Effects of ACh on heart (pacemaker)

Ach-induced secretion from glandular tissues (eg. salivary gland); contraction

NOTE: NMJ- nicotinic muscular junction

Ionotropic (direct acting)

Hence, no secondary messenger

Table 3. Summary of Sympathetic and Parasympathetic Divisions

Sympathetic Parasympathetic

CNS origin Hypothalamus Hypothalamus

S-ANS brainstem centers PAG, Parabrachial, ventrolateral medulla PAG, Parabrachial, ventrolateral medulla

Preganglionic neurons IML – T1-L2 CHOLINERGIC

Brainstem preganglionic III, VII, IX, X (Edinger-Westphal, Superior and Inferior Salivary Nuclei, Nucleus Ambiguous, Dorsal Motor Nucleus of Vagus)

S2-S4 CHOLINERGIC

Postganglionic neurons Sympathetic Trunk Cervical, stellate ganglia

Prevertebral ganglia Celiac, superior mesenteric, inferior mesenteric

NORADRENERGIC except nerves to sweat gland (Ach) & nerves to blood vessels of skeletal muscle

Brainstem nuclei Ciliary, pterygopalatine, otic, submandibular, visceral

Sacral – inferior hypogastric plexus CHOLINERGIC