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Widmaier, EP. Vanders human physiology 14th Ed. New York: McGraw-Hill, 2016.
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Marc Imhotep Cray, M.D.
Topics Outline
Homeostasis
Neurotransmitters
Receptors
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Marc Imhotep Cray, M.D.
Learning Objectives
After this presentation the learner should be able:
To describe the two divisions of the ANS and the main functions and
effects of each division.
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Marc Imhotep Cray, M.D.
ANS vs. Endocrine System in
Homeostasis
Autonomic nervous system (ANS) is moment-to-moment
regulator of internal environment regulating specific functions
that occur without conscious control:
respiration
circulation
digestion
body temperature
metabolism
sweating, secretions of certain endocrine glands
Also see: Cray MI. Walter Cannon, Homeostasis and the Physiological Response
to Stress, A Web Interactive PowerPoint Presentation
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Marc Imhotep Cray, M.D.
Homeostasis (1)
The physiologic process of maintaining an
internal environment (ECF environment)
compatible w normal health
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Marc Imhotep Cray, M.D.
Homeostasis (2)
A dynamic steady state of constituents in internal
environment (ECF) that surrounds and exchanges
materials with cells
Wired Wireless
Neurotransmitters Hormones
Hormones
Short
Short Distance
Distance Long
Long Distance
Distance
COMPARATOR +
SENSOR
ERROR
stretch receptors, chemo-, SET EFFECTOR
baro-, osmo-, and thermo- SIGNAL
POINT
receptors etc.
-
Negative feedback:
Initiation of responses
CONTROLLED that counter deviations of
controlled variables
VARIABLE
(SEE NEXT SLIDE)
-
NEGATIVE
from their normal range
FEEDBACK
Important variable maintained
within a normal range Effector opposes stimulus
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Marc Imhotep Cray, M.D. Redrawn after: Kibble JD, Halsey CR, Homeostasis. In: Medical Physiology -The Big Picture; McGraw-Hill , 2009; 2.
Examples of Physiologic
Controlled Variables & Set Points
Controlled Variable Typical Set Point Value
(Arterial Blood Sample)
Arterial O2 partial pressure 100 mm Hg
Arterial CO2 partial pressure 40 mm Hg
Arterial blood pH pH 7.4
Glucose 90 mg/dL (5 mM)
Core body temperature 98.4F (37C)
Serum Na+ 140 mEq/L
Serum K+ 4.0 mEq/L
Serum Ca2+ 4.5 mEq/L
Mean arterial blood pressure 90 mm Hg
Glomerular filtration rate 120 mL /min
Adopted from: Kibble JD, Halsey CR, Homeostasis: In Medical Physiology :The Big Picture.
New York, NY: McGraw-Hill , 2009; 3.
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Marc Imhotep Cray, M.D.
Important Negative Feedback
Control Systems
Modified from Carroll RG. Elseviers Integrated Physiology. Mosby, Inc. 2007; Table 1-3, Pg. 5.
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Marc Imhotep Cray, M.D.
Example: Baroreceptor Reflex
control of blood pressure
COMPARATOR + EFFECTOR
SENSOR cardiac
SET N 95 contractility,
stretch receptors in mm Hg ERROR
Aortic arch and POINT vascular tone,
SIGNAL urinary fluid
Carotid sinus
excretion
CNS|
Medulla Oblongata
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Marc Imhotep Cray, M.D.
Baroreceptors (3)
From http://www.zuniv.net/physiology/book/chapter6.html
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Marc Imhotep Cray, M.D.
Mean Arterial Pressure Control and
Autonomic & Hormonal Feedback Loops
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Marc Imhotep Cray, M.D.
Organization of Nervous System
BRAIN & SPINAL CORD CENTRAL
NERVOUS
SYSTEM (CNS)
AFFERENT EFFERENT
PERIPHERAL
(Sensory) (Motor) NERVOUS
NERVES NERVES SYSTEM (PNS)
SMOOTH MUSCLE,
EFFECTOR SKELETAL
CARDIAC MUSCLES
ORGANS MUSCLES
AND GLANDS
VOLUNTARY
INVOLUNTARY
Monosynaptic
Pre & Post Ganglionic Fiber
Marc Imhotep Cray, M.D.
Peripheral Nervous System (PNS)
Peripheral nerves contain both motor and sensory neurons
Motor neurons:
somatic innervate skeletal muscles
autonomic innervate smooth muscle, cardiac muscle,
and glands (autonomic motor neurons)
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Marc Imhotep Cray, M.D.
Generic Neuron Anatomy
Basic structural unit of nervous system >>> neuron
http://en.wikipedia.org/wiki/Neuron
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Marc Imhotep Cray, M.D.
Autonomic (Visceral) Reflex
Functional unit of the ANS
Afferent fibers from periphery to CNS
CNS integration
Cortex
Thalamus
Hypothalamus
Medulla
Spinal cord
Efferent fibers from CNS to periphery
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Marc Imhotep Cray, M.D.
Sympathetic Nervous System Wiring
Dorsal root Intermediolateral cell column
ganglion (IML)
Sympathetic trunk
Gray ramus
White ramus
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Marc Imhotep Cray, M.D.
Neurotransmitters
Chemicals synthesized and stored in neurons
Liberated from axon terminus in response to
action potentials
Interact with specialized receptors
Evoke responses in innervated tissues
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Marc Imhotep Cray, M.D.
ANS Neurotransmitters
Class Chemical Synthesis Postsynaptic Signal Functions
Receptors Termination
Small molecule
Transmitters ANS
Acetylcholine Choline + acetyl Nicotinic Extracellular Movement
CoA, via enzyme (cation channel) hydrolysis by control
Choline Muscarinic Acetylcholinestrase Cognition
Acetyltransferase (G-protein
Catecholamines Dopamine From the amino coupled) Reuptake ANS
acid tyrosine via D1 (stimulatory Movement
the enzyme G- protein control
Tyrosine coupled) General
hydroxylase D2 (inhibitory affect
in the G-protein
catecholamine coupled)
pathway
Norepinephrine From dopamine & Adrenergic Reuptake or ANS
in the receptors breakdown via the Alertness
catecholamine enzymes General
pathway monoamine oxidase affect
and catecholO-
methyltransferase
Effector
Pre Post organ
Ganglion
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Marc Imhotep Cray, M.D.
Anatomic Divisions of ANS
Parasympathetic (PANS) (CN3,7,9,10) & (S2-S4)
Preganglionic axons originate in brain, and sacral spinal cord
Peripheral ganglia are near, often within* the effector organs
Ratio of postganglionic-to-preganglionic axons is small, resulting in
discrete responses
Sympathetic (SANS) T1-L2/L3
Preganglionic axons originate in the thoracic and lumbar cord
Peripheral ganglia are distant from the effector organs
Ratio of post-to-preganglionic axons is large, resulting in widely
distributed responses
Enteric Nervous System (ENS) (Discussed in GI)
Has been described as a "second brain" for several reasons:
operate autonomous of SANS & PANS
Vertebrate studies show when the vagus nerve is severed, ENS
continues to function
* Exceptions are the four paired parasympathetic ganglia of head and neck
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Marc Imhotep Cray, M.D.
Schematized Anatomic Comparison of
PANS & SANS (1) (click to expand)
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Marc Imhotep Cray, M.D.
Schematized Anatomic Comparison
of PANS & SANS (2)
Effectors: cardiac muscle, smooth mm, vascular endothelium,
exocrine glands, and presynaptic nerve terminals
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Marc Imhotep Cray, M.D.
Somatic Nervous System
(included for comparison)
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Marc Imhotep Cray, M.D.
Neurochemical Transmission in
Peripheral Nervous System (PNS)
Cholinergic nerves
Acetylcholine is neurotransmitter
Locations of Ach
Preganglionic neurons to all ganglia
Denotes ACh
Parasympathetic
Cranial or sacral cord
Pre Post
Ganglion Effector
organ
Sympathetic Denotes ACh
Sympathetic Parasympathetic
Responses Responses
heart rate increases slows heart rate
blood pressure protects retina from
increases excessive light (near
blood is shunted lowers blood pressure
from skin & viscera empties the bowel
to skeletal muscles and bladder
blood glucose increases
increase gastrointestinal
bronchioles dilate motility
pupils dilate promotes absorption
of nutrients
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Marc Imhotep Cray, M.D.
ACh Synthesis, Release, and Fate (1)
Synthesized from choline and acetyl-CoA
Released in response to neuronal depolarization
(action potential)
Calcium enters the nerve cell
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Marc Imhotep Cray, M.D.
ACh Synthesis, Release, and Fate (2)
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Marc Imhotep Cray, M.D.
Cholinergic Neuron Pharmacology
From Le T., Bhushan V. First Aid 2017. New York, NY: M-H. 2017. 42
Marc Imhotep Cray, M.D.
NE Synthesis, Release, and Fate (1)
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Marc Imhotep Cray, M.D.
NE Synthesis, Release, and Fate (2)
VMAT-Vesicular Monoamine
transporter
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Marc Imhotep Cray, M.D.
Adrenergic Neuron Pharmacology
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Marc Imhotep Cray, M.D. From Le T., Bhushan V. First Aid 2017. New York, NY: M-H. 2017.
Receptors*
Specialized proteins that are binding sites for
neurotransmitters and hormones
Postsynaptic cell membranes
(neurotransmitters)
Cell nucleus (steroid hormones)
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Marc Imhotep Cray, M.D.
GPCR structure & function (simplified)
G-Protein Coupled Receptor
* Remember there are four major classes of ligandreceptor interactions (more in Pharm.)
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Marc Imhotep Cray, M.D.
G-protein-linked 2nd messenger
mechanisms (1)
Sympathetic (Adrenergic-Noradrenergic-R)
Receptor G-Protein Class Major Function
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Marc Imhotep Cray, M.D.
G-protein-linked 2nd
messenger mechanisms (3)
Receptor G-Protein Class Major Function
Dopamine:
D1 Receptor - s - Relax Renal Vascular Smooth Muscle
D2 Receptor - i - Modulate Neurotransmitter release (especially in
Brain)
Vasopressin:
V1 Receptor - q - Increase Vasoconstriction
V2 Receptor - s - Increase Water Permeability and Water
Reabsorption in Collecting Tubule (V2 in 2 Kidneys)
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Marc Imhotep Cray, M.D.
Cholinergic Receptors
Activated by ACh and cholinergic drugs
Anatomic distribution
Postganglionic, parasympathetic neuroeffector
junctions
All autonomic ganglia, whether
parasympathetic or sympathetic
Somatic neuromuscular junctions
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Marc Imhotep Cray, M.D.
Schematic of Cholinergic Receptor
Locations
junctions (M1-M5)
Nicotinic
Distinction of two different subtypes
Na+/K+ channels
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Marc Imhotep Cray, M.D.
Schematic representation of
Cholinergic Receptor Subtype Locations
Parasympathetic
N1
Thoracic or lumbar Pre
Post
cord Ganglion Effector
organ
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Marc Imhotep Cray, M.D.
Adrenergic Receptors
Activated by NE, Epi, and adrenergic drugs
Anatomic distribution
Postganglionic, sympathetic, neuroeffector
junctions
Subtypes
Alpha-1, 2; Beta-1, 2, 3
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Marc Imhotep Cray, M.D.
Schematic representation of Adrenergic
Receptor Locations
Alpha or Beta
adrenergic receptors
Sympathetic
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Marc Imhotep Cray, M.D.
Functional Significance of ANS (1)
Organ system integration & Dual innervation
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Marc Imhotep Cray, M.D.
Functional Significance of ANS (2)
Dual innervation
Organ responses moderated by both
parasympathetic and sympathetic influences
Parasympathetic dominant at rest
Predominate tone
Balance of opposing neurologic influences
determines physiologic responses
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Marc Imhotep Cray, M.D.
Alpha-1 Adrenergic Receptor
Vascular smooth muscle contraction
Arterioles, veins
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Marc Imhotep Cray, M.D.
Alpha-2 Adrenergic Receptor
postsynaptic 2-adrenoceptors (located in bld
vessels) cause constriction
Modulation of NE release
Presynaptic receptors on axon terminus
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Marc Imhotep Cray, M.D.
Beta-1 Adrenergic Receptor
To myocardium (renal-renin and fat cell also)
Agonists
Increase HR, contractility, and impulse
conduction speed
May be arrhythmogenic
Antagonists
Decrease HR, contractility, and impulse
conduction speed
Used clinically as antiarrhythmics
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Marc Imhotep Cray, M.D.
Beta-2 Adrenergic Receptor
Vascular smooth muscle in skeletal muscle
Agonists evoke active vasodilation, increased
blood flow
Bronchial smooth muscle
Agonists evoke bronchodilation, decreased
airway resistance
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Marc Imhotep Cray, M.D.
Muscarinic Cholinergic Receptor
(mAChR)
Myocardium
Agonists decrease HR, contractility and AV conduction
velocity
Antagonists used clinically to increase HR & facilitate AV
conduction such as in heart block
Iris sphincter muscle
Agonists evoke pupillary constriction (miosis)
Gastrointestinal tract
Agonists increase peristalsis and relax sphincter
Urinary bladder
Agonists evoke urination
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Marc Imhotep Cray, M.D.
Effect of ANS on Organ Systems (1)
Sympathetic (NE)
Receptor Function Distribution
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Marc Imhotep Cray, M.D.
Effect of ANS on Organ Systems (2)
Sympathetic (NE)
Receptor Function Distribution|Organ
GI (intestinal relaxation)
Bladder (bladder relaxation)
Liver (to liberate glucose via
glycogenolysis)
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Marc Imhotep Cray, M.D.
Effect of ANS on Organ Systems (3)
Parasympathetic (Ach)
Receptor Function Distribution|Organ
Bladder (constriction)
GI (intestinal contraction)
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Marc Imhotep Cray, M.D.
Exception
Sympathetic innervation of adrenal medulla is direct from
spinal cord and uses ACh as neurotransmitter
Adrenal gland functions as a special form of ganglion that secretes
Epi & NE in a 4 to 1 ratio directly into the bloodstream
Important note:
Agonists
Mimic physiologic activation
Antagonists
Block actions of neurotransmitters or agonists
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Marc Imhotep Cray, M.D.
Signaling Mechanisms and Pharmacology of
ANS Receptor Subtypes- SANS
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Marc Imhotep Cray, M.D.
Signaling Mechanisms and Pharmacology of
ANS Receptor Subtypes- PANS
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Marc Imhotep Cray, M.D.
PNS summary schematic
Le T., Bhushan V. First Aid 2017. New York, NY: M-H. 2017.
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Marc Imhotep Cray, M.D.
Summary: Take Home Points (1)
ANS functions involve a variety of effector tissues, including:
cardiac muscle, smooth mm, vascular endothelium, exocrine
glands, and presynaptic nerve terminals
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Marc Imhotep Cray, M.D.
Summary: Take Home Points (2)
By using drugs that mimic or block actions of chemical transmitters and /
or their receptor mechanisms, we can selectively modify autonomic
functions
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Marc Imhotep Cray, M.D.
THE END
Articles
Laurie Kelly McCorry. Physiology of the Autonomic Nervous System
Am J Pharm Educ. 2007 August 15; 71(4): 78.
Goldstein DS, Robertson D, Straus SE, et al. Dysautonomias: clinical disorders of the
autonomic nervous system. Ann Intern Med 2002;137(9):75363.
Cannon, WB, Organization for Physiological Homeostasis. PDF Physiological Rev July
1, 1929 9:399-431
PowerPoint Presentation:
Cray MI. Walter Cannon, Homeostasis and the Physiological Response to Stress.
A Web Interactive PowerPoint Presentation , 2014
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Marc Imhotep Cray, M.D.