Autonomic Nervous System Flashcards
Describe the autonomic nervous system.
The autonomic nervous system (ANS) is a network of nerves and ganglia that provide involuntary
(i.e., unconscious) control of the physiological actions that maintain internal homeostasis and respond to stress. The ANS innervates structures within the cardiovascular, pulmonary, endocrine, exocrine, gastrointestinal (GI), genitourinary, skeletal muscle, and central nervous systems (CNS) and can influence metabolism and
thermal regulation.
The ANS consist of three components: sympathetic nervous systemic (SNS), parasympathetic nervous system (PNS), and enteric nervous system (ENS). The ENS governs the function of the GI tract, is the largest component of the ANS, and can function independent of the CNS. The SNS produces widespread effects, whereas the PNS tends to produce more localized, discrete effects. The SNS and PNS generally have opposing effects on most organs. At rest, the PNS predominates (i.e., rest-and-digest), whereas in stressful situations, the SNS predominates (i.e., fight-or-flight).
What is the origin of the terms sympathetic and parasympathetic?
The origin of the term sympathetic (nervous system) comes from the Greek word “sympathy,” which can be traced to the Greek physician and scientist, Claudius Galen (129–210 CE). Galen described the nervous system as the framework which facilitates a physiologic “sympathy,” coordinating synergistic interactions among various organ systems. Parasympathetic (nervous system) comes from the Greek word “para” + “sympathy,” where “para” denotes the meaning of “near, alongside, contrary, or against.”
Review the anatomy of the sympathetic nervous system.
Preganglionic sympathetic neurons originate from the intermediolateral columns in the spinal cord (T1–L2). These myelinated fibers exit via the ventral root of the spinal nerve, travel into the sympathetic chain, and synapse with three types of ganglia (Fig. 4.1):
1) Paravertebral sympathetic ganglia—A chain of paired ganglia located lateral to the vertebral column
(i.e., paravertebral), which runs from the skull to the coccyx forming the sympathetic trunk.
2) Prevertebral sympathetic ganglia—Unpaired ganglia that are located anterior to the vertebral column
(i.e., prevertebral).
3) Adrenal medulla—A modified ganglia located within the adrenal gland. Although other ganglia function as
relay stations with long postganglionic fibers that innervate specific organs, the adrenal medulla directly secretes catecholamines into the venous blood stream.
Preganglionic sympathetic neurons may ascend or descend the sympathetic chain multiple levels and a
single preganglionic fiber may synapse with multiple ganglia. On average, one preganglionic sympathetic fiber synapses with approximately 20 ganglia. Whereas most preganglionic sympathetic fibers that enter the sympathetic trunk ultimately synapse with paravertebral sympathetic ganglia, some will not and instead continue through the sympathetic trunk and synapse with other ganglia (e.g., prevertebral ganglia or adrenal medulla). Preganglionic sympathetic fibers release acetylcholine at their synapse to stimulate nicotinic cholinergic postganglionic neurons (or chromaffin cells of the adrenal medulla).
Postganglionic adrenergic neurons synapse at target organs and release norepinephrine
(NE, and epinephrine in the adrenal medulla), except in the case of sweat glands, where acetylcholine is released (Fig. 4.2).
List examples of specific sympathetic ganglia that are often used as a target for interventional pain management.
Stellate ganglia—Paired paravertebral sympathetic ganglia formed as a fusion of the inferior cervical ganglia and the first thoracic ganglia from the sympathetic trunk. They are located at the level of C7, anteromedial to the vertebral artery, and posterior to the carotid, internal jugular, and phrenic nerve. They provide most of the sympathetic innervation to the head, neck, and upper extremities. It is a common target for a nerve block to
treat complex pain disorders, such as complex regional pain syndrome of the upper extremity.
Celiac plexus—A collection of prevertebral sympathetic ganglia located anterior to the aorta in the
retroperitoneal space. It provides sensory and sympathetic outflow to the stomach, liver, spleen, pancreas, kidney, and GI tract up to the splenic flexure. It is a common target for a nerve block to treat complex abdominal pain disorders, such as pain from pancreatic cancer.
Describe the anatomy and function of the parasympathetic nervous system.
Preganglionic parasympathetic neurons originate from cranial nerves III, VII, IX, and X and sacral segments 2 to 4 (see Fig. 4.1). Of these, the vagus nerve accommodates approximately 75% of PNS traffic. Preganglionic parasympathetic neurons, as opposed to preganglionic sympathetic neurons, synapse with postganglionic neurons close to the target end-organ facilitating fine, discrete physiological effect. Both preganglionic and postganglionic parasympathetic neurons release acetylcholine; these cholinergic receptors are subclassified as either nicotinic
or muscarinic. The response to cholinergic stimulation is summarized in Table 4.1.
What are the adrenergic receptors and what is their response to agonism?
There are alpha-1 (α1), alpha-2 (α2), beta-1 (β1), and beta-2 (β2) adrenergic receptors. The α1, β1, and β2 receptors are postsynaptic and are stimulated by the neurotransmitter NE. The α2 receptors are presynaptic and are also stimulated by NE. Stimulation of α2 receptors inhibits the presynaptic release of NE, reducing overall sympathetic response. Molecular pharmacologists have further subdivided these receptors, but this is beyond the scope of this discussion. The response to receptor activation at different sites is described in Table 4.1.
What are catecholamines? Which occur naturally? Which are synthetic?
Catecholamines are monoamines that stimulate adrenergic nerve terminals. NE, epinephrine, and dopamine are naturally occurring catecholamines, whereas dobutamine and isoproterenol are synthetic catecholamines.
Review the synthesis of dopamine, norepinephrine, and epinephrine.
The amino acid tyrosine is actively transported into the adrenergic presynaptic nerve terminal cytoplasm, where
it is converted to dopamine by two enzymatic reactions: hydroxylation of tyrosine by tyrosine hydroxylase to L-DOPA and subsequent decarboxylation by aromatic L-amino acid decarboxylase to dopamine. Dopamine is transported into storage vesicles, where it is hydroxylated by dopamine β-hydroxylase to NE. Epinephrine is synthesized in
the adrenal medulla from NE, through methylation by phenylethanolamine N-methyltransferase.
How are catecholamines metabolized?
Although NE is primarily removed from the synaptic junction by reuptake into the presynaptic nerve terminal, a small amount enters the circulation and undergoes metabolism. Catecholamines are metabolized in the blood, liver, and kidney by the enzymes monoamine oxidase and catecholamine O–methyltransferase. The important metabolites of epinephrine and NE are metanephrine and normetanephrine, respectively.
Why is it important to know the metabolites of epinephrine and norepinephrine?
Because the half-life of catecholamines is ultrashort (t1/2 % 2 minutes), it is difficult to directly measure catecholamines when diagnosing catecholamine secreting tumors, such as a pheochromocytoma.
The catecholamine metabolites, metanephrine and normetanephrine, have a much longer half-life
(t1/2 % 1–2 hours) and are often measured to diagnose pheochromocytoma. Catecholamine metabolites can be measured directly from the plasma or from a 24-hour urine sample.
What enzyme metabolizes acetylcholine?
Acetylcholine (ACh) is rapidly metabolized to choline and acetate by acetylcholinesterase (AChE), an enzyme located within the junctional cleft.
What problems could result from acethylcholine accumulation in the junctional cleft?
Inhibition of AChE, such as with neuromuscular blocking reversal agents (e.g., neostigmine) will result in accumulation of ACh, causing the following side effects: bradycardia, salivation, lacrimation, urination, defecation, and emesis. In general, these side effects can be mitigated with anticholinergic agents, such as glycopyrrolate. However, excessive accumulation may result in cholinergic crisis, causing severe bradycardia, bronchoconstriction, blindness, and muscular paralysis in addition to the aforementioned. The latter more severe side effects may be seen with pesticides (e.g., organophosphates) or in chemical warfare (e.g., Sarin gas).
How should cholinergic crisis be treated?
Cholinergic crisis should be treated with atropine and intubation for respiratory support. Atropine will antagonize muscarinic receptors located within the cleft at parasympathetic innervated organs; however, it will not antagonize nicotinic receptors located within the neuromuscular junction. Paralysis caused by cholinergic crisis requires intubation and respiratory support, until the offending agents abates.
What are the indications for using β-adrenergic antagonists?
β-Adrenergic antagonists, commonly called β blockers, are antagonists at β1 and β2 receptors. β blockers are a common treatment for hypertension, angina, and dysrhythmias. Perioperative β blockade is essential in patients with coronary artery disease, and the use of these medications has been shown to reduce death after myocardial infarction.
Review the mechanism of action for β antagonists and their side effects.
β1 and β2 antagonism decreases the activation of adenylate cyclase, resulting in decreased production of cyclic adenosine monophosphate (cAMP). β blockers may be cardioselective (relatively selective β1-antagonist properties), or noncardioselective. β1-Blockade produces negative chronotropic and inotropic effects, decreasing heart rate, contractility, cardiac output, and myocardial oxygen requirement. β1-Blockers also inhibit renin secretion, thereby reducing fluid retention and angiotensin II. Because volatile anesthetics also depress myocardial contractility, intraoperative hypotension may result with perioperative β-blocker administration. Abrupt withdrawal of these medications is not recommended because receptor upregulation can lead to hypertension, tachycardia, and myocardial ischemia. Because of their benefits in ischemic heart disease, patients receiving β-blocker therapy should continue their usual regimen the day of surgery.
β blockers interfere with the translocation of potassium ions across the cellular membrane and can
cause hyperkalemia. β blockers may also decrease signs of hypoglycemia (i.e., tachycardia and tremor); thus it should be used with caution in diabetic insulin-dependent patients.
