Transcript Parasympathetic stimulation

Physiology of the Autonomic Nervous system
Dennis M. Peffley, Ph.D., J.D.
Professor of Biochemistry
Nervous System
Central Nervous System, (CNS)
Brain & Spinal Cord
Peripheral Nervous System. (PNS)
Efferent
Somatic
Voluntary Movement
(muscles)
Regulated by corticospinal
tracts of motor cortex and
spinal reflexes
Afferent
Autonomic
Involuntary activity of smooth muscle,
glands, cardiac tissue.
Under brain stem regulation
Sympathetic
Fight or Flight
Enteric
“Brain of
The Gut”
Parasympathetic
Rest & Digest
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.
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.
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
Physiologic Anatomy of the
Sympathetic System
The Sympathetic System is catabolic (burns energy)
Shown are:
1. One of the two paravetebral sympathetic chains
of ganglia interconnected with spinal nerves
2. Twp prevertebral ganglia (celiac and hypogastric
3. 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
Physiologic Anatomy of the
Sympathetic System
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
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
Physiologic Anatomy of the
Parasympathetic System
• Cervicosacral
• Cervical (CNs III, VII, IX, X)
• Sacral (S2-S4)
• Remember S2-S4 keep your peepee off the floor
(parasympathetic points)
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
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.
Organization of the Sympathetic and
Parasympathetic Divisions
•
•
•
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.
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.
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
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
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
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
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
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
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
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
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
Miosis (Pupil Constriction)
Bronchoconstriction
Stimulates digestion
Vasodilatation
Increase Blood Pressure
Mydriasis (Pupil Dilation)
Bronchodilation
Inhibits digestion
Vasoconstriction
Contracts urinary bladder
Relaxes urinary sphincter
Relaxes urinary bladder
Constricts urinary sphincter
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
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.
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.
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.
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.
•
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
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.
•
•
•
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.
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
Board (and biochemist) Favorite
Tyrosine hydroxylase is the
rate-limiting step in
catecholamine synthesis
Cholinergic Neurotransmission
Choline
acetyltransferase
Nerve stimulation
calcium influx
Removed by
acetylcholinesterase
Adrenergic Neurotransmission
Cholinergic Muscarinic Receptors
Adrenergic
Receptors
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.
Receptors
α1 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)
Stimulation of adenylate cyclase and increase in cAMP
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
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
Horner Syndrome
•
Symptom combination:
1.
2.
3.
•
•
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.