Autonomic Nervous System





The autonomic nervous system (ANS) is essential for survival and responsible for the body’s involuntary activities such as cardiovascular, gastrointestinal, and thermoregulatory homeostasis. The ANS is divided into two major branches: the sympathetic nervous system (SNS), which controls the “fight or flight” responses, and the parasympathetic nervous system (PNS), which oversees the body’s maintenance functions including digestion. Both disease states and the stress of surgery can lead to changes in the ANS that can have potentially deleterious effects. Thus, a primary goal of anesthetic management is to modulate the body’s autonomic responses. Contemporary anesthesia providers have access to many pharmacologic drugs that can profoundly alter autonomic activity; thus, a thorough understanding of the anatomy and physiology of the ANS is essential.


Anatomy of the Autonomic Nervous System


The Sympathetic Nervous System


The preganglionic fibers of the SNS originate from the thoracolumbar region (T1 to L2 or L3) of the spinal cord ( Fig. 6.1 ). The cell bodies of these neurons lie in the spinal gray matter. The nerve fibers extend to paired ganglia, creating the sympathetic chains that lie immediately lateral to the vertebral column or extend to unpaired distal plexuses (e.g., the celiac and mesenteric plexuses). Preganglionic sympathetic fibers not only synapse at the ganglion of the level of their origin in the spinal cord but can also course up and down the paired ganglia. A sympathetic response, therefore, is not confined to the segment from which the stimulus originates, as discharge can be amplified and diffuse. The postganglionic neurons of the SNS then travel to the target organ. The sympathetic preganglionic fibers are relatively short because sympathetic ganglia are generally close to the central nervous system (CNS). In contrast, the postganglionic fibers run a long course before innervating effector organs ( Fig. 6.2 ).




Fig. 6.1


Schematic representation of the autonomic nervous system depicting the functional innervation of peripheral effector organs and the anatomic origin of peripheral autonomic nerves from the spinal cord. Although both paravertebral sympathetic ganglia chains are presented, the sympathetic innervation to the peripheral effector organs is shown only on the right side of the figure, whereas the parasympathetic innervation of peripheral effector organs is depicted on the left. The roman numerals on nerves originating in the tectal region of the brainstem refer to the cranial nerves that provide parasympathetic outflow to the effector organs of the head, neck, and trunk.

From Ruffolo R. Physiology and biochemistry of the peripheral autonomic nervous system. In Wingard L, Brody T, Larner J, et al, eds. Human Pharmacology: Molecular to Clinical. St. Louis: Mosby-Year Book; 1991:77.



Fig. 6.2


Schematic diagram of the peripheral autonomic nervous system. Preganglionic fibers and postganglionic fibers of the parasympathetic nervous system release acetylcholine (ACh) as the neurotransmitter. Postganglionic fibers of the sympathetic nervous system release norepinephrine (NE) as the neurotransmitter (exceptions are fibers to sweat glands, which release ACh).

From Lawson NW, Wallfisch HK. Cardiovascular pharmacology: a new look at the pressors. In Stoelting RK, Barash J, eds. Advances in Anesthesia. Chicago: Year Book Medical Publishers; 1986:195-270.


The neurotransmitter released at the terminal end of the preganglionic sympathetic neuron is acetylcholine (ACh), and the cholinergic receptor on the postganglionic neuron is a nicotinic receptor. Norepinephrine is the primary neurotransmitter released at the terminal end of the postganglionic neuron at the synapse with the target organ ( Fig. 6.3 ). Other classic neurotransmitters of the SNS include epinephrine and dopamine. Additionally, co-transmitters, such as adenosine triphosphate (ATP) and neuropeptide Y, modulate sympathetic activity. Norepinephrine and epinephrine bind postsynaptically to adrenergic receptors, which include the α 1 -, β 1 -, β 2 -, and β 3 -receptors. When norepinephrine binds to the α 2 -receptors, located presynaptically on the postganglionic sympathetic nerve terminal, subsequent norepinephrine release is decreased (negative feedback). Dopamine (D) binds to D 1 receptors postsynaptically or D 2 receptors presynaptically.




Fig. 6.3


Schematic depiction of the postganglionic sympathetic nerve ending. Release of the neurotransmitter norepinephrine (NE) from the nerve ending results in stimulation of postsynaptic receptors, which are classified as α 1 , β 1 , and β 2 . Stimulation of presynaptic α 2 -receptors results in inhibition of NE release from the nerve ending.

Adapted from Ram CVS, Kaplan NM. Alpha- and beta-receptor blocking drugs in the treatment of hypertension. In Harvey WP, ed. Current Problems in Cardiology. Chicago: Year Book Medical Publishers; 1970.


Sympathetic neurotransmitters are synthesized from tyrosine in the postganglionic sympathetic nerve ending ( Fig. 6.4 ). The rate-limiting step is the transformation of tyrosine to dihydroxyphenylalanine (DOPA), which is catalyzed by the enzyme tyrosine hydroxylase. DOPA is then converted to dopamine and, once inside the storage vesicle at the nerve terminal, is β-hydroxylated to norepinephrine. In the adrenal medulla, norepinephrine is methylated to epinephrine. The neurotransmitters are stored in vesicles until the postganglionic nerve is stimulated. Then the vesicles merge with the cell membrane and release their contents into the synapse ( Fig. 6.5 ). In general, only 1% of the total stored norepinephrine is released with each depolarization; thus, there is a tremendous functional reserve. The released norepinephrine binds to the pre- and postsynaptic adrenergic receptors. The postsynaptic receptors then activate secondary messenger systems in the postsynaptic cell via G protein–linked activity. Norepinephrine is then released from these receptors and mostly taken up at the presynaptic nerve terminal and transported to storage vesicles for reuse. Norepinephrine that escapes this reuptake process and makes its way into the circulation is metabolized by either the monoamine oxidase (MAO) or catechol- O -methyltransferase (COMT) enzyme in the blood, liver, or kidney.




Fig. 6.4


Biosynthesis of norepinephrine and epinephrine in sympathetic nerve terminal (and adrenal medulla). (A) Perspective view of molecules. (B) Enzymatic processes.

From Tollenaeré JP. Atlas of the Three-Dimensional Structure of Drugs. Amsterdam: Elsevier North-Holland; 1979, as modified by Vanhoutte PM. Adrenergic neuroeffector interaction in the blood vessel wall. Fed Proc. 1978;37:181.



Fig. 6.5


Release and reuptake of norepinephrine at sympathetic nerve terminals. Solid circle, Active carrier; aad, aromatic l -amino acid decarboxylase; DβH, dopamine β-hydroxylase; Dopa, l -dihydroxyphenyalanine; NE, norepinephrine; tyr hyd, tyrosine hydroxylase.

From Vanhoutte PM. Adrenergic neuroeffector interaction in the blood vessel wall. Fed Proc. 1978;37:181, as modified by Shepherd J, Vanhoutte P. Neurohumoral regulation. In Shepherd S, Vanhoutte P, eds. The Human Cardiovascular System: Facts and Concepts. New York: Raven Press; 1979:107.


The Parasympathetic Nervous System


The PNS arises from cranial nerves III, VII, IX, and X as well as from sacral segments S1-S4 (see Fig. 6.1 ). Unlike the ganglia of the SNS, the ganglia of the PNS are in close proximity to (or even within) their target organs (see Fig. 6.2 ). Like the SNS, the preganglionic nerve terminals release ACh into the synapse, and the postganglionic cell binds the ACh via nicotinic receptors. The postganglionic nerve terminal then releases ACh into the synapse it shares with the target organ cell. The ACh receptors of the target organ are muscarinic receptors. Like the adrenergic receptors, muscarinic receptors are coupled to G proteins and secondary messenger systems. ACh is rapidly inactivated within the synapse by the cholinesterase enzyme. The effects of stimulating adrenergic and cholinergic receptors throughout the body are listed in Table 6.1 .



Table 6.1

Responses Elicited in Effector Organs by Stimulation of Sympathetic and Parasympathetic Nerves

From Bylund DB. Introduction to the autonomic nervous system. In Wecker L, Crespo L, Dunaway G, et al, eds. Brody’s Human Pharmacology: Molecular to Clinical . 5th ed. Philadelphia: Mosby; 2010:102.









































































































































Effector Organ Adrenergic Response Receptor Involved Cholinergic Response Receptor Involved Dominant Response (A or C)
Heart
Rate of contraction
Force of contraction
Increase
Increase
β 1
β 1
Decrease
Decrease
M 2
M 2
C
C
Blood vessels
Arteries (most)
Skeletal muscle
Veins
Vasoconstriction
Vasodilation
Vasoconstriction
α 1
β 2
α 2
A
A
A
Bronchial tree Bronchodilation β 2 Bronchoconstriction M 3 C
Splenic capsule Contraction α 1 A
Uterus Contraction α 1 Variable A
Vas deferens Contraction α 1 A
Gastrointestinal tract Relaxation α 2 Contraction M 3 C
Eye
Radial muscle, iris
Circular muscle, iris
Ciliary muscle
Contraction (mydriasis)
Relaxation
α 1
β 2
Contraction (miosis)
Contraction (accommodation)
M 3
M 3
A
C
C
Kidney Renin secretion β 1 A
Urinary bladder
Detrusor
Trigone and sphincter
Relaxation
Contraction
β 2
α 1
Contraction
Relaxation
M 3
M 3
C
A,C
Ureter Contraction α 1 Relaxation A
Insulin release from pancreas Decrease α 2 A
Fat cells Lipolysis β 1 3 ) A
Liver glycogenolysis Increase α 1 3 ) A
Hair follicles, smooth muscle Contraction (piloerection) α 1 A
Nasal secretion Decrease α 1 Increase C
Salivary glands Increase secretion α 1 Increase secretion C
Sweat glands Increase secretion α 1 Increase secretion C

A, Adrenergic; C, cholinergic; M, muscarinic.




Adrenergic Pharmacology


Endogenous Catecholamines


Table 6.2 summarizes the pharmacologic effects and therapeutic doses of catecholamines.



Table 6.2

Pharmacologic Effects and Therapeutic Doses of Catecholamines
































































Catecholamine Mean Arterial Pressure Heart Rate Cardiac Output Systemic Vascular Resistance Renal Blood Flow Arrhythmogenicity Preparation (mg/250 mL) Intravenous Dose (µg /kg/min)
Dopamine + + +++ + +++ + 200 (800 μg/mL) 2-20
Norepinephrine +++ +++ −−− + 4 (16 μg/mL) 0.01-0.1
Epinephrine + ++ ++ ++ −− +++ 1 (4 μg/mL) 0.01-0.15
Isoproterenol +++ +++ −− +++ 1 (4 μg/mL) 0.03-0.15
Dobutamine + + +++ ++ 250 (1000 μg/mL) 2-20

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Oct 21, 2019 | Posted by in ANESTHESIA | Comments Off on Autonomic Nervous System
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