Human Physiology (MMED 2931)

Nervous system 4:

Autonomic nervous system

A/Prof Vladimir ZagorodnyukDiscipline of Human Physiology

College of Medicine and Public Healthvladimir.zagorodnyuk@flinders.edu.au

FMC, Room: 6E135Tel: 8204-5238

1. Sympathetic nervous system: neural pathways, transmitters and function

2. Parasympathetic nervous system: neuronal pathways, transmitters and function

3. Enteric Nervous System

4. Sensory innervation of visceral organs

5. Visceral reflexes and brain control of autonomic activities

Learning objectives

• Nervous system controls many body activities aimed at maintaining homeostasis (= stable, relatively constant body’s internal environment including body temperature, pH, blood pressure, energy supply, metabolic rate etc) which is essential for survival of our body cells

• Once the peripheral sensory system detected changes in internal or external environment that threatens homeostasis, the CNS makes adjustments by controlling function of visceral organs and tissues via its peripheral efferent division – ANS (= the visceral motor system)

• The ANS is responsible for regulating most of the bodily functions that cannot be controlled by conscious effort

The ANS has 3 divisions:- Sympathetic Nervous system- Parasympathetic Nervous system - Enteric Nervous System (ENS)

Autonomic Nervous System (ANS)

•Both the sympathetic and parasympathetic nervous systems have ongoing activity or tone. In some specific circumstances activity of one division can dominate the other

•For example, the sympathetic NS is far more active (“sympathetic dominance”) during body stress (“fight or flight response” – heart rate and blood pressure, metabolic rates and blood glucose levels, blood supply to skeletal muscle, sweating are all elevated while blood supply to the gut is shut down)

•The parasympathetic NS usually is associated with a “rest and digest” state (“parasympathetic dominance”), it slows down heart rate, facilitates digestion, growth, immune responses, energy storage etc

•The sympathetic and parasympathetic NS often (not all the time) act producing opposite effects on visceral organs. In some cases the effects are different, but not simply opposite

•Most functions associated with digestion of food in the gut are controlled mainly by the ENS (with important inputs from the parasympathetic and sympathetic NS)

Sympathetic NS, parasympathetic NS and ENS

• Most of visceral organs receive a dual “autonomic” motor output from the CNS –sympathetic and parasympathetic NS

• “Two neuron autonomic pathways”: preganglionic cell body is in the CNS and postganglionic in peripheral ganglia. Autonomic neurons have single preganglionic myelinated axon and single postganglionic unmyelinated axon. At the periphery, autonomic axons branch extensively

Motor outputs from the CNS

Autonomic synapses in the target organs: autonomic varicosities of postganglionic neurons

Silverthorn, 2019

• Anatomical pathways, transmitters and function

Purves et al, 2001

Sympathetic and parasympathetic division of the visceral motor system

Sympathetic and Parasympathetic neurotransmitters and receptors

Silverthorn, 2019

• The preganglionic sympathetic axons leave the middle region of the spinal cord to synapse onto the neurons in the sympathetic chain ganglia (=paravertebral ganglia, which are located close to and on either side of the spinal cord) or in other large prevertebral ganglia(celiac ganglion, superior mesenteric ganglion, inferior mesenteric ganglion)

• The postganglionic axons go to large number of visceral organs

Sympathetic NS: basic plan

Preganglionicfibre

Postganglionic fibre

Spinalcord

Ganglion Target

Spinalcord (T1-L2)

Acetylcholine (ACh) Noradrenaline (NA)

Examples of sympathetic control of visceral organ function:

•Tonic activity (usually active all the time)- tonic constriction of skin, muscle and gut bloodvessels (NA from sympathetic nerves acts via α1

receptors to cause constriction of arterioles)- tonic inhibition of gut motility via α and β receptors- tonic inhibition of bladder muscle via β3 receptors

•Phasic activity (sometimes active) - increased cardiac output during exercise: NA released

from sympathetic nerves acts on β1 receptors to increaseheart rate and force of contraction

- sweating (when you get hot, Ach (an exception to the general rule) acts on M3 muscarinic receptors to stimulate secretion bysweat glands

- lift “goose bumps” (when you get cold, also used Ach as atransmitter to contract arrector pili muscle within hair follicle)

- pupil dilation in the dark

Sympathetic NS: innervation and function

• The cells of the adrenal medulla are innervated by preganglionic sympathetic fibers and they release ACh

• The cells of the adrenal medulla are very similar to sympathetic ganglion cells but they do not have an axon. They have nicotinic receptors, just like ganglion cells

• Instead of releasing a neurotransmitter (onto a target organ they release predominantly adrenaline (epinephrine) as a hormone into the blood

Sympathetic innervation of adrenal gland

Silverthorn, 2019

Sympathetic NS: innervation of sweat glands

• Physiological role of sweat glands is to maintain body temperature and release waste products. Thermoregulatory center of the hypothalamus controls thermoregulation via sympathetic NS

• Two types of sweat glands: eccrine (90% of the total 4 million glands) and apocrine (under the arms and in the groin). Highest density of eccrine sweat glands is in palm and soles (up to 600 glands per cm2)

• Sweat glands are innervated exclusively by sympathetic postganglionic nerves (Ach will be released stimulating sweat production by the glands in hot environment and during physical exercise). This, in turn, will increase skin conduction since more water and electrolytes are released

• Galvanic skin potential (response) is a measurement of voltage difference between two external electrodes on the skin. Sympathetic nerve activation will lead to changes in the skin potential because of an increased skin conduction during sweating

• In your Practicals, you will study sweat secretion from the skin of your palm by recording changes in the skin potentials evoked by electrical stimulation of the median nerve of the wrist (contains sympathetic fibers innervating sweat glands in the glabrous skin of the palm)

• Sympathetic NS arousal (for example, during “fight or flight response) will also increase sweat production and evoke changes in skin potential (stress-induced “cold sweating”, it is used in lie detectors polygraph devices)

• Preganglionic axons leaving either:1) in the cranial nerves (CN) from the brainstem (CN III, VII, IX and X). For example, 10th cranial nerve =vagus nerve the longest cranial nerve; it innervates all thorasic and most abdominal visceral organs)2) or in the sacral region of the spinal cord (S2, S3 & S4)

• They go to very small ganglia which are within (intramural ganglia) or very close to the target (terminal ganglia) organs

Parasympathetic NS: basic plan

Brainstem orsacral spinalcord

ganglion target

Preganglionicfibre

Postganglionic fibre

Brainstem

Sacral spinal cord

Ach/NAch/M

https://teachmeanatomy.info/head/cranial-nerves/summary/

Cranial nerves

• Examples of parasympathetic control of visceral organ function:

• Tonic activity (usually active all the time)- decreased cardiac output: ACh from parasympathetic nerves acts on M receptors to decrease heart rate

- pupil constriction- tears production (protective lubrication of the cornea)

• Phasic activity (sometimes active)- stomach and gut motility: ACh from parasympathetic nerves acts on N receptors of some enteric neurons(ENS) to increase motility and secretions

- urination: ACh from postganglionic parasympatheticnerves acts on M receptors to contact bladder duringmicturition

- tears (crying)- increase airway resistance by constricting airways

vagus nerve

Parasympathetic NS: innervation and function

The distinction sympathetic versus parasympathetic is based on:-1) their anatomical origin from the

CNS-2) on the location of the peripheral

ganglia-3) on the transmitter substances

they utilise in postganglionicneurons

-4) on the different functions theycontrol

Purves et al, 2001

Summary:sympathetic versus parasympathetic nervous nervous system

• The ENS (inside the gut) controls all regions of the GI tract (from oesophagus to rectum). ENS has inputs from sympathetic and parasympathetic systems

• The enteric system is by far the largest part of the ANS in terms of number of neurons (~100 million neurons)

• The ENS has:- own sensory receptor systems (intrinsicafferent neurons)

- interneurons- motor neurons (excitatory & inhibitory)

ENS control all regions of the gut

ENS

Lower oesophageal sphincter

Oesophagus

Pyloric sphincter

Duodenum

Ascendingcolon

Ileocecalsphincter

Stomach

JejunumIleum

Descendingcolon

• ENS is organised in two plexuses (Myenteric and Submucous) with ganglia containing several classes of neurons which automatically control motor activity, secretion and local circulation

• This picture shows a network of ganglia in the large intestine. This is the myenteric plexus. Each ganglion contains up to 50-100 neurons. The myenteric plexus lies between the longitudinal and circular muscle in the gut, and contains mostly nerve cells that control the smooth muscle activity

• The submucosal plexus lies between the circular muscle and the mucosa (lining) of the gut. Its cells are sensory, or control secretion and blood flow

• There is extensive communication between ganglia in the ENS. The ENS functions as a semi-independent “little brain” controlling the gut function

Two enteric nerve plexus in the gut

0.5mm

Myenteric ganglion

Descending Inhibitory Reflex (DIR)

balloon distension

Ascending Excitatory Reflex (AER)

oral anal

Oral contraction Anal relaxation 5 s

10g

• “Low of intestine”: ascending excitation and descending inhibition in response to balloon distension. They are simple standing (non-propagating) reflexes

• Other motor pattern (complex reflex behaviour) that can be recorded in vitro (without CNS) - propulsive (peristaltic) movement

Guinea pig distal colon in vitro

Once artificial pellet is inserted in the oral end of the isolated distal colon, it propagates down the gut

oral anal

ENS: simple motor reflexes and motor patterns in vitro

At the ganglion

•Acetylcholine (Ach) acting on Nicotinic receptors (N type)

At the final target

A wide variety of different substances • Excitatory motor neurons:- Ach acting on muscarinic receptors (M-type)

on the gut smooth muscle- small peptides (“substance P, neurokinin A acting

on NK1 and NK2 receptors)

• Inhibitory motor neurons: - gas nitric oxide (NO)- ATP - peptides: vasoactive intestinal polypeptide (VIP)

Ganglia in the GI tract

ANS

ENS

ENS: neurotransmitters and receptors

Brain

Brainstem

Spinal cord

• Spinal sensory neurons (cell bodies in the dorsal root ganglia, DRG) - ~ 5-10% neurons in the DRG innervate visceral organs and tissues (rest of the neurons innervateskeletal muscle and skin)- Sensory axons run from visceral organs to the spinal cord (together with the sympathetic or parasympathetic efferent fibres)- Participate in physiological reflex behavior of the gut, but some (nociceptors) can give give rise to sensation of pain

• Vagal sensory neurons innervate thoracic and upper abdomen visceral organs (cell bodies in the nodose ganglion, NG)

- their sensory axons run in the vagus nerve from the visceral organs to the brain stem (together withthe vagal efferent preganglionic parasympatheticfibres)- Participate in physiological reflex behavior of the gut. Give rise to sensation of fulness, bloating and nausea

Extrinsic sensory innervation of visceral organs

Vago-vagal reflex:• Once food is swallowed, it distends upper

oesophagus and stimulates vagal mechanoreceptors (their cell bodies in nodose ganglion, NG, axons in the vagusnerve). They will excite neurons in the medulla (vagal sensory nucleus)

• Then, via interneurons, this excitation passed to the motor nucleus where vagal motor neurons are located

• They send their axons (parasympathetic efferents in the vagus nerve) back to the gut (LES and stomach) and excite enteric inhibitory motor neurons that results in LES and proximal stomach relaxation even before food is arrived in the stomach

Example of visceral reflexes in the gut

food

Vagalmotor neuron

Vagalsensoryneuron

Enteric inhibitorymotor neuron

Vagalsensory nucleus

Lower oesophageal sphincter (LES)

Pyloricsphincter

Ileocecalsphincter

Descendingcolon

• Medulla:- Contains cardiovascular and

digestive control centers which control sympathetic and parasympathetic preganglionic neurons

• Coordination of ANS activities is carried out in the brain, mostly in the hypothalamus and the medulla

• Hypothalamus:- It is a major ANS coordinating center- Its specific nuclei regulate many

homeostatic functions, such as temperature control, food intake, thirst and urine output

- It also integrates somatic and visceral responses in accordance with the body needs

- Hypothalamus is important link between ANS and endocrine system

Hypothalamus

Brain stem

Cerebral cortex

Thalamus(medial)

Basal nuclei(lateral to thalamus)

Cerebellum

Midbrain

Pons

Medulla

Spinal cord

Sherwood, 2006

Brain control of autonomic activities

• The Autonomic nervous system has 3 divisions:• Sympathetic:

- ganglia distant from target- final transmitter noradrenalin

• Parasympathetic:- ganglia near target- final transmitter acetylcholine

• Enteric nervous system: - ganglia in the target (gut)- complex ganglion-to-ganglion activity- range of final transmitters

• In all 3, acetylcholine is a neurotransmitter acting on N type receptor within the ganglia

• Major function of ANS (together with peripheral sensory system) is to maintain body homeostasis

• ENS is organised in two nerve plexus (myenteric and submucosal), it controls motor activity, secretion and local blood flow in the gut

• Coordination of ANS activities is carried out in the brain, mostly in the hypothalamus and the medulla

Summary