1. Physiology of the Autonomic Nervous system
Dennis M. Peffley, Ph.D., J.D.
Professor of Biochemistry

2. Central Nervous System, (CNS) Brain & Spinal Cord
Peripheral Nervous System. (PNS)
Efferent
Afferent
Somatic
Voluntary Movement
(muscles)
Regulated by corticospinal
tracts of motor cortex and
spinal reflexes
Autonomic
Involuntary activity of smooth muscle,
glands, cardiac tissue.
Under brain stem regulation
Enteric
“Brain of
The Gut”
Sympathetic
Fight or Flight
Parasympathetic
Rest & Digest

3. Autonomic Nervous System
The autonomic nervous system is responsible for maintaining the internal environment of the body (homeostasis)
Visceral functions
Controls arterial pressure, gastrointestinal secretion, urinary bladder emptying, sweating, body temperature, and other functions
Changes visceral functions rapidly and with a great degree of intensity – within 3 to 5 seconds the ANS can increase heart rate to twice that of normal;
the arterial pressure can be doubled within 10 to 15 seconds;
conversely blood pressure can be decreased low enough within 10 to 15 seconds resulting in fainting.

4. Autonomic Nervous System
The autonomic nervous system is divided into the sympathetic and parasympathetic systems.
Sympathetic division (stressful situations) - fight or flight
increasing heart rate, constricting blood vessels to the skin and viscera (thereby increasing blood flow to muscles), increasing pupil size and decreasing salivation
Parasympathetic (restful situations) - rest and digest
Effects of the parasympathetic nervous system include slowing heart rate, increasing gastric motility, and increasing salivation.

5. Organization of the Sympathetic and Parasympathetic Divisions
Within the autonomic nervous system, two neurons are required to reach a target organ, preganglionic neuron and a postganglionic neuron.
The preganglionic neuron originates in the central nervous system >> it forms synapse with the postganglionic neuron, the cell body of which is located in a ganglia or wall of target organ.
Boron & Boulpaep, Medical Physiology

6. Physiologic Anatomy of the Sympathetic System
The Sympathetic System is catabolic (burns energy)
Shown are:
One of the two paravetebral sympathetic chains of ganglia interconnected with spinal nerves
Twp prevertebral ganglia (celiac and hypogastric
Nerves extending from ganglia to different internal organs
The sympathetic nervous system is also called the thoracolumbar system because the ganglia are located lateral to the vertebral column in the thoracic and lumber regions (T1-L3)
Because the ganglia are fixed along the back, the postganglionic sympathetic fibers can be quite long
Within the sympathetic system the preganglionic axons form synapses with many postganglionic cells, therefore giving this system a widespread action

7. Physiologic Anatomy of the Sympathetic System

8. Physiologic Anatomy of the Sympathetic System
Sympathetic nerves differ from skeletal motor nerves in the following way
Each sympathetic pathway from the cord to the tissue consists of two neurons – a preganglionic neuron and a postganglionic neuron (only a single neuron is found in the skeletal motor pathway);
Cell body of each preganglionic body lies in the intermediolateral horn of the spinal cord

9. Physiologic Anatomy of the Parasympathetic System
The parasympathetic system is anabolic (tries to conserve energy)
The cell bodies of preganglionic parasympathetic neurons are located in specific nuclei of the medulla, pons, midbrain, and in the S2 through S4 level of the spinal cord.
brain >> with four cranial nerves: the oculomotor nerve (CN III), the facial nerve (CN VII), the glossopharyngeal nerve (CN IX), and the vagus nerve (CN X).
S2 –S4 >> the pelvic splanchnic nerves.
The parasympathetic system: cranosacral

10. Physiologic Anatomy of the Parasympathetic System
Cervicosacral
Cervical (CNs III, VII, IX, X)
Sacral (S2-S4)
Remember S2-S4 keep your pee-pee off the floor (parasympathetic points)

11. Preganglionic Parasympathetic Neurons
CN III, VII, and IX originate in three groups of nuclei:
(1): Edinger-Westphal nucleus >> subnucleus of the oculomotor complex in the mesencephalon. Parasympathetic neurons in this nucleus project to the eye via CN III and synapse onto postganglionic neurons in the ciliary ganglion
(2): the Superior salivatory nucleus >> in the rostral medulla.
Parasympathetic neurons in this nucleus project to the pterygopalatine via CN VII >> supply the lacrimal glands.
Another branch of the facial nerve carries preganglionic fibers to the submandibular ganglion >> supply submandibular and sublingual glands

12. Preganglionic Parasympathetic Neurons
CN III, VII, and IX originate in three groups of nuclei:
(3): the Inferior salivatory nucleus, and the rostral part of the nucleus ambiguus in the rostral medulla contain parasympathetic neurons that project via CN IX to the otic ganglion >> supply to the parotid gland
Cranial Nerve X: Cell bodies are found in the medulla within the nucleus ambiguus and the dorsal motor nucleus of the vagus >> supplies parasympathetic innervation to all the viscera of the thorax and abdomen, including the GI tract between the pharynx and distal end of the colon.

13. Organization of the Sympathetic and Parasympathetic Divisions
Postganglionic neurons (blue) have long projections to their targets. The right panel shows the parasympathetic division.
The cell bodies of parasympathetic preganglionic neurons (orange) are either in the brain (midbrain, pons medulla) or in the sacral spinal cord (S2-S4). Their axons project to ganglia very near (or even inside) the end organs.
Postganglionic neurons (green) therefore have short projections to their targets.
The left panel shows the sympathetic division. The cell bodies of sympathetic preganglionic neurons (red) are in the intermediolateral column of the thoracic and lumbar spinal cord (T1-L3). Their axons project to paravertebral ganglia (the sympathetic chain) and prevertebral ganglia.
THIS SLIDE HAS MAJOR PROBLEMS

14. Effects of Sympathetic and Parasympathetic Stimulation on Specific organs
Eyes
Two functions are controlled by the ANS
Pupillary opening
Focus of the lens
Sympathetic stimulation contracts meridional fibers of the iris that dilate the pupil
Parasympathetic stimulation contracts the circular muscle of the iris to constrict the pupil
Parasympathetics controlling the pupil reflex are stimulated when excess light enters the eyes; this reflex reduces pupillary opening
Sympathetics are stimulated during excitement and increase the pupillary opening.
Lens focusing is controlled almost entirely by the parasympathetic nervous system
Parasympathetic excitation contracts the ciliary muscle, which is a ring like structure encircling the outside of the lends; constriction of this muscle allows the lens to become more convex causing the eye to focus on objects near at hand

15. α1 stimulation: 1) Mydriasis 2) No cycloplegia Muscarinic stimulation:
1) Miosis
2) Accomodation (near vision)
Muscarinic antagonism
1) Mydriasis
2) Accomodation for far vision
leading to cycloplegia
(paralysis of accomodation)
α1 stimulation:
1) Mydriasis
2) No cycloplegia

17. Effects of Sympathetic and Parasympathetic Stimulation on Specific organs
Glands of the body
Nasal, salivary, and many gastrointestinal glands are strongly stimulated by the parasympathetic nervous system
This results in secretion of copious amounts of watery secretion
Sympathetic stimulation has a direct effect on alimentary gland cells resulting in formation of a concentrated secretion high in enzymes and mucous\
Sweat gland secrete large amounts of sweat with sympathetic stimulation – No effect with parasympathetic stimulation
However, sweat glands are stimulated primarily through centers in the hypothalamus that are considered to be parasympathetic centers – sweating may be called a parasympathetic function even though it is controlled by fibers anatomically distributed through the sympathetic nervous system
Apocrine glands secrete a thick, odoriferous secretion with sympathetic stimulation – no response to parasympathetic stimulation
Apocrine gland secretions function as a lubricant that allows easy sliding motion of the shoulder joint

18. Effects of Sympathetic and Parasympathetic Stimulation on Specific organs
Intramural Nerve Plexus of the GI System
The GI system has it own intrinsic set of nerves known as the intramural plexus or intestinal enteric nervous system – located in the walls of the gut
Parasympathetic stimulation generally increases overall degree of activity of the GI system by promoting peristalsis and relaxing sphincters
Strong stimulation of the sympathetic system inhibits peristalsis and increases the tone of the sphincters

19. Effects of Sympathetic and Parasympathetic Stimulation on Specific organs
Heart
Sympathetic stimulation increases overall heart activity –increases in both the rate and force of heart contraction
Parasympathetic stimulation causes opposite effects – decreased rate and force of heart contraction

20. Effects of Sympathetic and Parasympathetic Stimulation on Specific organs
Systemic Blood Vessels
Sympathetic simulation results in constriction of most systemic blood vessels, especially those of the abdominal viscera and skin of the limbs
Parasympathetic stimulation has almost no effects
except to dilate vessels in certain restricted areas such as the blush area of the face

21. Stimulation Effects of Sympathetic and Parasympathetic on Specific organs
Arterial Blood Pressure
Sympathetic stimulation
increases both propulsion by the heart and resistance to flow – causes a marked acute increase in arterial pressure (but very little change in long-term pressure (unless sympathetics stimulate the kidneys to retain salt and water simultaneously)
Parasympathetic stimulation (moderate stimulation) via the vagal nerves decreases pumping by the heart but has no effect on vascular peripheral resistance – results in only a slight decrease in arterial pressure
Strong vagal parasympathetic stimulation can almost stop the heart entirely for a few seconds and cause temporary loss of all or most arterial pressure
Clinical Relevance: See this in septic shock

22. Other Effects of the Sympathetics and Parasympathetics on Organ Systems
Endodermal structures are inhibited by sympathetic stimulation and excited by parasympathetic stimulation
Ducts of the liver
Gallbladder
Ureter
Urinary bladder
Bronchi
Metabolic effects
Sympathetic stimulation results in release of glucose from the liver, increased blood glucose concentration, increased glycogenolysis in liver and muscle, increase in skeletal muscle strength, increase in basal metabolic rate, and increased mental activity
Sexual Acts
Male
Parasympathetic (points) stimulation induces erection
Sympathetic (shoots) stimulation induces ejaculation
Female
Parasympathetic (protruding) stimulation induces engorgement and secretion
Sympathetic (screaming) induces contraction of smooth muscles
Metabolic effects: Sympathetic releases glucose from liver. Just think about all the downstream effects from this and you pretty much hit everything.

23. Parasympathetic versus Sympathetic
Parasympathetic "Rest & Digest"
Sympathetic "Fight or Flight"
Slows Heartbeat
Accelerates Heartbeat
Decrease Force of Contraction
Increase Force of Contraction
Decrease Blood Pressure
Increase Blood Pressure
Miosis (Pupil Constriction)
Mydriasis (Pupil Dilation)
Bronchoconstriction
Bronchodilation
Stimulates digestion
Inhibits digestion
Vasodilatation
Vasoconstriction
Contracts urinary bladder
Relaxes urinary bladder
Relaxes urinary sphincter
Constricts urinary sphincter

24. Function of the Adrenal Medullae
Sympathetic
Epinephrine and Norepinephrine into the circulating blood
distributed to all tissues of the body
Organ effects
direct sympathetic stimulation
longer effect (5x-10x longer) than direct sympathetic stimulation
Circulating effects
constriction of blood vessels
increased heart activity
decreased peristalsis
dilation of pupils
80% epinephrine and 20% norepinephrine
Epinephrine has almost the same effects as norepinephrine
Stimulates beta receptors to a greater extent and has a greater effect on cardiac stimulation than norepinephrine
Epinephrine causes only weak constriction of blood vessels in comparison to the effects of norepinephrine
Epinephrine is 5 to 10 times more effective in stimulating metabolism compared to norepinephrine

25. Visceral Afferents
Internal organs are densely innervated by visceral afferents. These receptors monitors either nociceptive (painful) input or sensitive to mechanical and chemical stimuli (stretch of the heart, blood vessels, and hollow viscera, and changes in PCO2, PO2, pH, blood glucose, temperature of skin and internal organs)
Most of the visceral nociceptive fibers travel with sympathetic nerves, while axons from physiological receptors travel with parasympathetic fibers.
The visceral afferent axons are mainly concentrated in the vagus nerve, which carries non-nociceptive afferent input from the viscera of thorax and abdomen to the CNS.
The cell bodies of vagal afferents are located in the nodose ganglion of medulla.

26. Visceral Afferents
The visceral pain input is mapped 'viscero-topically' at the level of the spinal cord because most visceral nociceptive fibers travel with the sympathetic fibers and enter the spinal cord along with a spinal nerve.
This mapping is also present in the brain stem, but not at the level of cerebral cortex.
Awareness of visceral pain is not localized to a specific organ but is instead referred to the dermatome that is innervated by the same spinal nerve.
For example, nociceptive input from the left ventricle of the heart is referred to the left T1 to T5 dermatomes and leads to discomfort in the left arm and left side of the chest.

27. The Enteric Division Is a Self-Contained Nervous System That Surrounds the Gastrointestinal Tract and Receives Sympathetic and Parasympathetic Input
The enteric nervous system (ENS) is a collection of nerve plexuses that surround the gastrointestinal (GI) tract, including the pancreas and biliary system
The ENS also receives input from the sympathetic and parasympathetic divisions of the autonomic nervous system (ANS)
The total number of neurons in the ENS exceeds that of the spinal chord
Schematic representation of the ENS. A, The submucosal (or Meissner's) plexus is located between the muscularis mucosae and the circular muscle of the muscularis externa. The myenteric (or Auerbach's) plexus is located between the circular and longitudinal layers of the muscularis externa. In addition to these two plexuses that have ganglia, three others'mucosal, deep muscular, and tertiary plexus'are also present. B, The ENS consists of sensory neurons, interneurons, and motor neurons. Some sensory signals travel centrally from the ENS. Both the parasympathetic and the sympathetic divisions of the ANS modulate the ENS. This figure illustrates some of the typical circuitry of ENS neurons.

28. Myenteric or Auerbach's plexus
The myenteric plexus lies between the external longitudinal and the deeper circular smooth-muscle layers.
It is involved in the control of motility
Submucosal (Meissner’s) plexus lies between the circular muscle and the most internal layer of smooth muscle, the muscularis mucosae. It is involved in the control of ion and fluid transport
The myenteric and submucosal plexuses receive preganglionic parasympathetic innervation from the vagus nerve (sacral nerves in case of the distal portion of the colon and rectum)
In this sense, The enteric division is homologous to a large complex parasympathetic terminal ganglion
The ENS functions normally without autonomic input.

29. Synaptic Physiology of the Autonomic Nervous System
The sympathetic and parasympathetic divisions have opposite effects on most visceral targets
Visceral targets receive both inhibitory and excitatory synapses
Antagonistic synapses arise from opposing divisions of the ANS – sympathetic and parasympathetic
During Exercise
Sympathetic division is excitatory
Parasympathetic division is inhibitory
Exceptions
Salivary glands are stimulated by both divisions
Some organs receive innervation from only one of these two divisions of the ANS –
sweat glands, piloerector muscles, and most peripheral blood vessels receive input only from the sympathetic division
Know the exceptions.

30. Synapses of the ANS are Specialized in Function
Many postganglionic autonomic neurons have bulbous expansions or varicosities that are distributed along their axons within the target organ
Synapses of autonomic neurons with their target organs. Many axons of postganglionic neurons make multiple points of contact (varicosities) with their targets. In this scanning electron micrograph of the axon of a postganglionic sympathetic neuron from a guinea pig grown in tissue culture, the arrows indicate varicosities.

31. You must know this table. All of it.
Sympathetic postganglionic is adrenergic (adrenaline i.e. will use norepinephrine, which is similar to epinephrine) and is so strong it does not need myelin.
Parasympathetic postganglionic is close to the target organ (except in cervical) so does not need myelination uses the Ach + Muscarinic singling.

32. Nicotinic Receptors
In both the sympathetic and parasympathetic divisions, synaptic transmission between preganglionic and postganglionic neurons (ganglionic transmission)is mediated by acetylcholine (Ach) acting on nicotinic receptors
Nicotinic receptors are ligand-gated channels (ionotropic receptors) with a pentameric structure
Boron & Boulpaep, Medical Physiology

33. Board (and biochemist) Favorite
Tyrosine hydroxylase is the rate-limiting step in catecholamine synthesis

34. Cholinergic Neurotransmission
Choline acetyltransferase
Nerve stimulation calcium influx
Removed by acetylcholinesterase

35. Adrenergic Neurotransmission

36. Cholinergic Muscarinic Receptors

37. Adrenergic Receptors

38. G-protein Coupled Secondary Messengers in Cholinergic Receptors:
M1 and M3
Gq coupled
↑ phospholipase C →↑ IP3, DAG, Ca2+ M2
Gi coupled
↓ adenylyl cyclase → ↓ cAMP
G-protein Coupled Secondary Messengers in Adrenergic Receptors: α1
Gq coupled
↑ phospholipase C →↑ IP3, DAG, Ca2+ α2
Gi coupled
↓ adenylyl cyclase → ↓ cAMP
β1β2D1
Gs coupled
↑ adenylyl cyclase → ↑ cAMP
*Nicotinic receptors (ionotropic) are (NOT) G-protein coupled. Thus, no second messenger is involved.

39. Receptors α1 receptors α2 receptors β1 receptors β2 receptors
vascular smooth muscle, on GI and bladder sphincters, and radial muscle of the eye
Excitation (contraction)
Gq, IP3
α2 receptors
Presynaptic nerve terminals, platelets, fat cells, walls of GI tract
Cause inhibition (dilatation) (smooth muscle)
inhibition of adenylate cyclase and decrease in cAMP
β1 receptors
Cardiac muscle - SA node, AV node, ventricular muscle of heart produce excitation
Increases heart rate, contractility, conduction velocity
Stimulation of adenylate cyclase and increase in cAMP
β2 receptors
vascular smooth muscle, bronchioles, walls of GI tract and bladder
Produce relaxation (dilation of vascular smooth muscle and bronchioles, relaxation of bladder wall)

40. CNS Control of the Viscera
Sympathetic Response:
increases in heart rate
cardiac contractility
Increases in blood pressure
Increased ventilation of the lungs
bronchial dilatation
sweating
piloerection
release of glucose into the blood
decreased GI activity
In response to fear, exercise, or other types of stress, the sympathetic division produces a massive and coordinated output to all end organs simultaneously (fight-or-flight), whereas parasympathetic output ceases

41. CNS Control of the Viscera
The hypothalamus is the most important brain region for coordinating autonomic output.
The hypothalamus projects to the parabrachial nucleus, medullary raphe, NTS (nucleus tractus solitarius), central gray matter, locus coeruleus, dorsal motor nucleus of the vagus, nucleus ambiguous, and intermediolateral cell column of the spinal cord.
The hypothalamus plays a dominant role in the integration of higher cortical and limbic systems with autonomic control.
feeding, thermoregulation, circadian rhythms, water balance, emotions, sexual drive, reproduction, motivation

42. Horner Syndrome Symptom combination:
unilateral ptosis (drooping eyelid)
miosis (small pupil)
anhidrosis (lack of sweating).
Sympathetic neurons innervate the smooth muscle that elevates the eyelid, the pupillary dilator muscle, and the sweat glands of the face.
Horner syndrome results from loss of the normal sympathetic innervation on one side of the face.
(1) the hypothalamus to the intermediolateral (IML) column in the spinal cord (first-order neuron). (2) A preganglionic sympathetic neuron with the cell body in the inter-mediolateral column gets a synapse from (1) and sends an axon to the superior cervical ganglion (SCG). (3) A postganglionic sympathetic neuron with the cell body in the SCG sends axons to pupillary dilator (smooth) muscles