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 ).
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.
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.
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 .
| 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 (β 3 ) | A | ||
| Liver glycogenolysis | Increase | α 1 (β 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 |
Adrenergic Pharmacology
Endogenous Catecholamines
Table 6.2 summarizes the 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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