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17.6: Glossary- The Autonomic Nervous System - Biology

17.6: Glossary- The Autonomic Nervous System - Biology


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acetylcholine (ACh): neurotransmitter that binds at a motor end-plate to trigger depolarization

adrenal medulla: interior portion of the adrenal (or suprarenal) gland that releases epinephrine and norepinephrine into the bloodstream as hormones

adrenergic: synapse where norepinephrine is released, which binds to α- or β-adrenergic receptors

afferent branch: component of a reflex arc that represents the input from a sensory neuron, for either a special or general sense

agonist: any exogenous substance that binds to a receptor and produces a similar effect to the endogenous ligand

alpha (α)-adrenergic receptor: one of the receptors to which epinephrine and norepinephrine bind, which comes in three subtypes: α1, α2, and α3

antagonist: any exogenous substance that binds to a receptor and produces an opposing effect to the endogenous ligand

anticholinergic drugs: drugs that interrupt or reduce the function of the parasympathetic system

autonomic tone: tendency of an organ system to be governed by one division of the autonomic nervous system over the other, such as heart rate being lowered by parasympathetic input at rest

baroreceptor: mechanoreceptor that senses the stretch of blood vessels to indicate changes in blood pressure

beta (β)-adrenergic receptor: one of the receptors to which epinephrine and norepinephrine bind, which comes in two subtypes: β1 and β2

cardiac accelerator nerves: preganglionic sympathetic fibers that cause the heart rate to increase when the cardiovascular center in the medulla initiates a signal

cardiovascular center: region in the medulla that controls the cardiovascular system through cardiac accelerator nerves and vasomotor nerves, which are components of the sympathetic division of the autonomic nervous system

celiac ganglion: one of the collateral ganglia of the sympathetic system that projects to the digestive system

central neuron: specifically referring to the cell body of a neuron in the autonomic system that is located in the central nervous system, specifically the lateral horn of the spinal cord or a brain stem nucleus

cholinergic: synapse at which acetylcholine is released and binds to the nicotinic or muscarinic receptor

chromaffin cells: neuroendocrine cells of the adrenal medulla that release epinephrine and norepinephrine into the bloodstream as part of sympathetic system activity

ciliary ganglion: one of the terminal ganglia of the parasympathetic system, located in the posterior orbit, axons from which project to the iris

collateral ganglia: ganglia outside of the sympathetic chain that are targets of sympathetic preganglionic fibers, which are the celiac, inferior mesenteric, and superior mesenteric ganglia

craniosacral system: alternate name for the parasympathetic division of the autonomic nervous system that is based on the anatomical location of central neurons in brain-stem nuclei and the lateral horn of the sacral spinal cord; also referred to as craniosacral outflow

dorsal longitudinal fasciculus: major output pathway of the hypothalamus that descends through the gray matter of the brain stem and into the spinal cord

dorsal nucleus of the vagus nerve: location of parasympathetic neurons that project through the vagus nerve to terminal ganglia in the thoracic and abdominal cavities

Eddinger–Westphal nucleus: location of parasympathetic neurons that project to the ciliary ganglion

efferent branch: component of a reflex arc that represents the output, with the target being an effector, such as muscle or glandular tissue

endogenous chemical: substance produced and released within the body to interact with a receptor protein

endogenous: describes substance made in the human body

epinephrine: signaling molecule released from the adrenal medulla into the bloodstream as part of the sympathetic response

exogenous chemical: substance from a source outside the body, whether it be another organism such as a plant or from the synthetic processes of a laboratory, that binds to a transmembrane receptor protein

exogenous: describes substance made outside of the human body

fight-or-flight response: set of responses induced by sympathetic activity that lead to either fleeing a threat or standing up to it, which in the modern world is often associated with anxious feelings

G protein–coupled receptor: membrane protein complex that consists of a receptor protein that binds to a signaling molecule—a G protein—that is activated by that binding and in turn activates an effector protein (enzyme) that creates a second-messenger molecule in the cytoplasm of the target cell

ganglionic neuron: specifically refers to the cell body of a neuron in the autonomic system that is located in a ganglion

gray rami communicantes: (singular = ramus communicans) unmyelinated structures that provide a short connection from a sympathetic chain ganglion to the spinal nerve that contains the postganglionic sympathetic fiber

greater splanchnic nerve: nerve that contains fibers of the central sympathetic neurons that do not synapse in the chain ganglia but project onto the celiac ganglion

inferior mesenteric ganglion: one of the collateral ganglia of the sympathetic system that projects to the digestive system

intramural ganglia: terminal ganglia of the parasympathetic system that are found within the walls of the target effector

lesser splanchnic nerve: nerve that contains fibers of the central sympathetic neurons that do not synapse in the chain ganglia but project onto the inferior mesenteric ganglion

ligand-gated cation channel: ion channel, such as the nicotinic receptor, that is specific to positively charged ions and opens when a molecule such as a neurotransmitter binds to it

limbic lobe: structures arranged around the edges of the cerebrum that are involved in memory and emotion

long reflex: reflex arc that includes the central nervous system

medial forebrain bundle: fiber pathway that extends anteriorly into the basal forebrain, passes through the hypothalamus, and extends into the brain stem and spinal cord

mesenteric plexus: nervous tissue within the wall of the digestive tract that contains neurons that are the targets of autonomic preganglionic fibers and that project to the smooth muscle and glandular tissues in the digestive organ

muscarinic receptor: type of acetylcholine receptor protein that is characterized by also binding to muscarine and is a metabotropic receptor

mydriasis: dilation of the pupil; typically the result of disease, trauma, or drugs

nicotinic receptor: type of acetylcholine receptor protein that is characterized by also binding to nicotine and is an ionotropic receptor

norepinephrine: signaling molecule released as a neurotransmitter by most postganglionic sympathetic fibers as part of the sympathetic response, or as a hormone into the bloodstream from the adrenal medulla

nucleus ambiguus: brain-stem nucleus that contains neurons that project through the vagus nerve to terminal ganglia in the thoracic cavity; specifically associated with the heart

parasympathetic division: division of the autonomic nervous system responsible for restful and digestive functions

parasympathomimetic drugs: drugs that enhance or mimic the function of the parasympathetic system

paravertebral ganglia: autonomic ganglia superior to the sympathetic chain ganglia

postganglionic fiber: axon from a ganglionic neuron in the autonomic nervous system that projects to and synapses with the target effector; sometimes referred to as a postganglionic neuron

preganglionic fiber: axon from a central neuron in the autonomic nervous system that projects to and synapses with a ganglionic neuron; sometimes referred to as a preganglionic neuron

prevertebral ganglia: autonomic ganglia that are anterior to the vertebral column and functionally related to the sympathetic chain ganglia

referred pain: the conscious perception of visceral sensation projected to a different region of the body, such as the left shoulder and arm pain as a sign for a heart attack

reflex arc: circuit of a reflex that involves a sensory input and motor output, or an afferent branch and an efferent branch, and an integrating center to connect the two branches

rest and digest: set of functions associated with the parasympathetic system that lead to restful actions and digestion

short reflex: reflex arc that does not include any components of the central nervous system

somatic reflex: reflex involving skeletal muscle as the effector, under the control of the somatic nervous system

superior cervical ganglion: one of the paravertebral ganglia of the sympathetic system that projects to the head

superior mesenteric ganglion: one of the collateral ganglia of the sympathetic system that projects to the digestive system

sympathetic chain ganglia: series of ganglia adjacent to the vertebral column that receive input from central sympathetic neurons

sympathetic division: division of the autonomic nervous system associated with the fight-or-flight response

sympatholytic drug: drug that interrupts, or “lyses,” the function of the sympathetic system

sympathomimetic drug: drug that enhances or mimics the function of the sympathetic system

target effector: organ, tissue, or gland that will respond to the control of an autonomic or somatic or endocrine signal

terminal ganglia: ganglia of the parasympathetic division of the autonomic system, which are located near or within the target effector, the latter also known as intramural ganglia

thoracolumbar system: alternate name for the sympathetic division of the autonomic nervous system that is based on the anatomical location of central neurons in the lateral horn of the thoracic and upper lumbar spinal cord

varicosity: structure of some autonomic connections that is not a typical synaptic end bulb, but a string of swellings along the length of a fiber that makes a network of connections with the target effector

vasomotor nerves: preganglionic sympathetic fibers that cause the constriction of blood vessels in response to signals from the cardiovascular center

visceral reflex: reflex involving an internal organ as the effector, under the control of the autonomic nervous system

white rami communicantes: (singular = ramus communicans) myelinated structures that provide a short connection from a sympathetic chain ganglion to the spinal nerve that contains the preganglionic sympathetic fiber


Short answer
External stimuli can drive autonomic responses.

Background
The autonomic nervous system is a visceral sensory and motor system. The viscera are the internal organs. Virtually all visceral reflexes are mediated by local circuits in the brain stem or spinal cord (Fig. 1). It is one of two major subdivisions of the nervous system the other being the somatic (or voluntary) nervous system. The main distinction between the two is that the latter is involved in voluntary and conscious actions (e.g., movement, perception and cognition), while the autonomic nervous system is engaged in involuntary processes, such as regulating heart rate, breathing and bowel function (Fig. 1).

Fig. 1. Autonomic nervous system. Source: Austin Community College

Although by far most stimuli driving autonomous responses come from within (think muscle movements driving bowel movements, increased heart rates during physical exercise), outside stimuli do directly impinge on the autonomous system.

For example, the cilliary muscle in the iris is under the control of light coming into the retina. The pupillary light reflex test is based on this principle, and is routinely used to diagnose damage to the visual system. Also, production of saliva is controlled by external stimuli (smell and taste of food and see the striking example below from @anongoodnurse). And technically, the entire digestive tract can be considered to be outside the body, as it is continuous with the skin and lining of the mouth. Hence, the mechanical stimuli impinging on the intestines by a moving bolus of food that drives the waves of peristaltic movements can, arguably, be considered to be caused by external stimuli too. Lastly, the fight-flight-fright response involving the hypothalamic-pituitary-adrenal gland (HPA) axis is often initiated by external stimuli (loud sudden noises etc.).

The most important characteristic of the autonomic nervous system, as said, is that the autonomous responses are not voluntarily controlled. While you can decide to look or track a visual stimulus, you cannot decide to move the bolus of food back up to your stomach, or voluntarily constrict your pupil. The way the input is received may not be the best way to distinguish it from the voluntary nervous system.

Didactic answer
If you are left with questions, the first place to go to is your professor.


Autonomic Imbalance and Disease

The autonomic nervous system (ANS) connects the central nervous system (CNS brain and spinal cord) with the major peripheral organs and organ systems (targets in parenthesis): circulatory (heart, blood vessels), digestive (gastrointestinal tract glands and sphincters, kidney, liver, salivary glands), endocrine (adrenal glands), integumentary (sweat glands), reproductive (uterus, genitals), respiratory (bronchiole smooth muscles), urinary (sphincters), and visual (pupil dilator and ciliary muscles). The ANS is usually discussed as having two major branches𠅊 sympathetic branch, associated with energy mobilization, and a parasympathetic branch, associated with vegetative and restorative functions.

Modern conceptions of organism function that are based on complexity theory hold that organism stability, adaptability, and health are maintained through a dynamic relationship among system elements in this case, the sympathetic and parasympathetic branches of the ANS (Thayer & Lane, 2000). That is, patterns of organized variability, rather than static levels, are preserved in the face of constantly changing environmental demands. In contrast to homeostasis, this conception posits that the system has multiple points of stability, necessitating a dynamic organization of resources to match specific situational demands. These demands can be conceived in terms of energy regulation, with local energy minima serving as points of relative stability. For example, in healthy individuals, average heart rate is greater during the day, when energy demands are higher, than at night, when energy demands are lower. The system has a local energy minimum (attractor) for daytime and another for nighttime. Because the system operates �r from equilibrium,” it constantly searches for local energy minima to reduce the energy requirements of the organism. Consequentially, optimal system functioning is achieved via lability and variability in its component processes, whereas rigid regularity is associated with mortality, morbidity, and ill health (e.g., Peng et al., 1994).

Another corollary of this view is that autonomic imbalance, in which one branch of the ANS dominates over the other, is associated with a lack of dynamic flexibility and health. A large body of empirical evidence suggests that autonomic imbalance is associated with various pathological conditions. The broad label of 𠇊NS dysfunction” is associated with a host of complex and heterogeneous disorders and diseases with distinct etiologies, such as diabetic autonomic neuropathy, hyperhidrosis, orthostatic intolerance/postural tachycardia syndrome, pure autonomic failure, and vasovagal syncope. More generally, autonomic dysfunction is present in conjunction with neurodegenerative diseases such as Alzheimer's disease, multiple system atrophy, and Parkinson's disease neurodevelopmental disorders such as autism spectrum disorders autoimmune diseases such as multiple sclerosis mental disorders such as generalized anxiety, major depression, and schizophrenia and following ischemic stroke or myocardial infarction. In particular, when the sympathetic branch is hyperactive and the parasympathetic branch is hypoactive over an extended duration, energy demands on the system become excessive and ultimately cannot be met, resulting in premature aging, disease, and ultimately death.


Electrodiagnostic assessment of the autonomic nervous system: A consensus statement endorsed by the American Autonomic Society, American Academy of Neurology, and the International Federation of Clinical Neurophysiology

Evaluation of disorders of the autonomic nervous system is both an art and a science, calling upon the physician's most astute clinical skills as well as knowledge of autonomic neurology and physiology. Over the last three decades, the development of noninvasive clinical tests that assess the function of autonomic nerves, the validation and standardization of these tests, and the growth of a large body of literature characterizing test results in patients with autonomic disorders have equipped clinical practice further with a valuable set of objective tools to assist diagnosis and prognosis. This review, based on current evidence, outlines an international expert consensus set of recommendations to guide clinical electrodiagnostic autonomic testing. Grading and localization of autonomic deficits incorporates scores from sympathetic cardiovascular adrenergic, parasympathetic cardiovagal, and sudomotor testing, as no single test alone is sufficient to diagnose the degree or distribution of autonomic failure. The composite autonomic severity score (CASS) is a useful score of autonomic failure that is normalized for age and gender. Valid indications for autonomic testing include generalized autonomic failure, regional or selective system syndromes of autonomic impairment, peripheral autonomic neuropathy and ganglionopathy, small fiber neuropathy, orthostatic hypotension, orthostatic intolerance, syncope, neurodegenerative disorders, autonomic hyperactivity, and anhidrosis.

Keywords: Autonomic Autonomic nervous system diseases Denervation Diabetic autonomic neuropathy Hypotension Orthostatic Tilt table test Valsalva Maneuver.

Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


16.6 Nervous System

As you read this, your nervous system is performing several functions simultaneously. The visual system is processing what is seen on the page the motor system controls your eye movements and the turn of the pages (or click of the mouse) the prefrontal cortex maintains attention. Even fundamental functions, like breathing and regulation of body temperature, are controlled by the nervous system. The nervous system is one of two systems that exert control over all the organ systems of the body the other is the endocrine system. The nervous system’s control is much more specific and rapid than the hormonal system. It communicates signals through cells and the tiny gaps between them rather than through the circulatory system as in the endocrine system. It uses a combination of chemical and electrochemical signals, rather than purely chemical signals used by the endocrine system to cover long distances quickly. The nervous system acquires information from sensory organs, processes it and then may initiate a response either through motor function, leading to movement, or in a change in the organism’s physiological state.

Nervous systems throughout the animal kingdom vary in structure and complexity. Some organisms, like sea sponges, lack a true nervous system. Others, like jellyfish, lack a true brain and instead have a system of separate but connected nerve cells (neurons) called a “nerve net.” Flatworms have both a central nervous system (CNS), made up of a ganglion (clusters of connected neurons) and two nerve cords, and a peripheral nervous system (PNS) containing a system of nerves that extend throughout the body. The insect nervous system is more complex but also fairly decentralized. It contains a brain, ventral nerve cord, and ganglia. These ganglia can control movements and behaviors without input from the brain.

Compared to invertebrates, vertebrate nervous systems are more complex, centralized, and specialized. While there is great diversity among different vertebrate nervous systems, they all share a basic structure: a CNS that contains a brain and spinal cord and a PNS made up of peripheral sensory and motor nerves. One interesting difference between the nervous systems of invertebrates and vertebrates is that the nerve cords of many invertebrates are located ventrally (toward the stomach) whereas the vertebrate spinal cords are located dorsally (toward the back). There is debate among evolutionary biologists as to whether these different nervous system plans evolved separately or whether the invertebrate body plan arrangement somehow “flipped” during the evolution of vertebrates.

The nervous system is made up of neurons , specialized cells that can receive and transmit chemical or electrical signals, and glia , cells that provide support functions for the neurons. There is great diversity in the types of neurons and glia that are present in different parts of the nervous system.

Neurons and Glial Cells

The nervous system of the common laboratory fly, Drosophila melanogaster, contains around 100,000 neurons, the same number as a lobster. This number compares to 75 million in the mouse and 300 million in the octopus. A human brain contains around 86 billion neurons. Despite these very different numbers, the nervous systems of these animals control many of the same behaviors—from basic reflexes to more complicated behaviors like finding food and courting mates. The ability of neurons to communicate with each other as well as with other types of cells underlies all of these behaviors.

Most neurons share the same cellular components. But neurons are also highly specialized—different types of neurons have different sizes and shapes that relate to their functional roles.

Like other cells, each neuron has a cell body (or soma) that contains a nucleus, smooth and rough endoplasmic reticulum, Golgi apparatus, mitochondria, and other cellular components. Neurons also contain unique structures for receiving and sending the electrical signals that make communication between neurons possible (Figure 16.19). Dendrites are tree-like structures that extend away from the cell body to receive messages from other neurons at specialized junctions called synapses . Although some neurons do not have any dendrites, most have one or many dendrites.

The bilayer lipid membrane that surrounds a neuron is impermeable to ions. To enter or exit the neuron, ions must pass through ion channels that span the membrane. Some ion channels need to be activated to open and allow ions to pass into or out of the cell. These ion channels are sensitive to the environment and can change their shape accordingly. Ion channels that change their structure in response to voltage changes are called voltage-gated ion channels. The difference in total charge between the inside and outside of the cell is called the membrane potential.

A neuron at rest is negatively charged: the inside of a cell is approximately 70 millivolts more negative than the outside (–70 mV). This voltage is called the resting membrane potential it is caused by differences in the concentrations of ions inside and outside the cell and the selective permeability created by ion channels. Sodium-potassium pumps in the membrane produce the different ion concentrations inside and outside of the cell by bringing in two K + ions and removing three Na + ions. The actions of this pump are costly: one molecule of ATP is used up for each turn. Up to 50 percent of a neuron’s ATP is used in maintaining its membrane resting potential. Potassium ions (K + ), which are higher inside the cell, move fairly freely out of the neuron through potassium channels this loss of positive charge produces a net negative charge inside the cell. Sodium ions (Na + ), which are low inside, have a driving force to enter but move less freely. Their channels are voltage dependent and will open when a slight change in the membrane potential triggers them.

A neuron can receive input from other neurons and, if this input is strong enough, send the signal to downstream neurons. Transmission of a signal between neurons is generally carried by a chemical, called a neurotransmitter, which diffuses from the axon of one neuron to the dendrite of a second neuron. When neurotransmitter molecules bind to receptors located on a neuron’s dendrites, the neurotransmitter opens ion channels in the dendrite’s plasma membrane. This opening allows sodium ions to enter the neuron and results in depolarization of the membrane—a decrease in the voltage across the neuron membrane. Once a signal is received by the dendrite, it then travels passively to the cell body. A large enough signal from neurotransmitters will reach the axon. If it is strong enough (that is, if the threshold of excitation , a depolarization to around –60mV is reached), then depolarization creates a positive feedback loop: as more Na + ions enter the cell, the axon becomes further depolarized, opening even more sodium channels at further distances from the cell body. This will cause voltage dependent Na + channels further down the axon to open and more positive ions to enter the cell. In the axon, this “signal” will become a self-propagating brief reversal of the resting membrane potential called an action potential .

An action potential is an all-or-nothing event it either happens or it does not. The threshold of excitation must be reached for the neuron to “fire” an action potential. As sodium ions rush into the cell, depolarization actually reverses the charge across the membrane form -70mv to +30mV. This change in the membrane potential causes voltage-gated K + channels to open, and K + begins to leave the cell, repolarizing it. At the same time, Na + channels inactivate so no more Na + enters the cell. K + ions continue to leave the cell and the membrane potential returns to the resting potential. At the resting potential, the K + channels close and Na + channels reset. The depolarization of the membrane proceeds in a wave down the length of the axon. It travels in only one direction because the sodium channels have been inactivated and unavailable until the membrane potential is near the resting potential again at this point they are reset to closed and can be opened again.

An axon is a tube-like structure that propagates the signal from the cell body to specialized endings called axon terminals. These terminals in turn then synapse with other neurons, muscle, or target organs. When the action potential reaches the axon terminal, this causes the release of neurotransmitter onto the dendrite of another neuron. Neurotransmitters released at axon terminals allow signals to be communicated to these other cells, and the process begins again. Neurons usually have one or two axons, but some neurons do not contain any axons.

Some axons are covered with a special structure called a myelin sheath , which acts as an insulator to keep the electrical signal from dissipating as it travels down the axon. This insulation is important, as the axon from a human motor neuron can be as long as a meter (3.2 ft)—from the base of the spine to the toes. The myelin sheath is produced by glial cells. Along the axon there are periodic gaps in the myelin sheath. These gaps are called nodes of Ranvier and are sites where the signal is “recharged” as it travels along the axon.

It is important to note that a single neuron does not act alone—neuronal communication depends on the connections that neurons make with one another (as well as with other cells, like muscle cells). Dendrites from a single neuron may receive synaptic contact from many other neurons. For example, dendrites from a Purkinje cell in the cerebellum are thought to receive contact from as many as 200,000 other neurons.

Everyday Connection

Neurogenesis

At one time, scientists believed that people were born with all the neurons they would ever have. Research performed during the last few decades indicates that neurogenesis, the birth of new neurons, continues into adulthood. Neurogenesis was first discovered in songbirds that produce new neurons while learning songs. For mammals, new neurons also play an important role in learning: about 1,000 new neurons develop in the hippocampus (a brain structure involved in learning and memory) each day. While most of the new neurons will die, researchers found that an increase in the number of surviving new neurons in the hippocampus correlated with how well rats learned a new task. Interestingly, both exercise and some antidepressant medications also promote neurogenesis in the hippocampus. Stress has the opposite effect. While neurogenesis is quite limited compared to regeneration in other tissues, research in this area may lead to new treatments for disorders such as Alzheimer’s, stroke, and epilepsy.

How do scientists identify new neurons? A researcher can inject a compound called bromodeoxyuridine (BrdU) into the brain of an animal. While all cells will be exposed to BrdU, BrdU will only be incorporated into the DNA of newly generated cells that are in S phase. A technique called immunohistochemistry can be used to attach a fluorescent label to the incorporated BrdU, and a researcher can use fluorescent microscopy to visualize the presence of BrdU, and thus new neurons, in brain tissue (Figure 16.20).

Concepts in Action

Visit this link interactive lab to see more information about neurogenesis, including an interactive laboratory simulation and a video that explains how BrdU labels new cells.

While glial cells are often thought of as the supporting cast of the nervous system, the number of glial cells in the brain actually outnumbers the number of neurons by a factor of 10. Neurons would be unable to function without the vital roles that are fulfilled by these glial cells. Glia guide developing neurons to their destinations, buffer ions and chemicals that would otherwise harm neurons, and provide myelin sheaths around axons. When glia do not function properly, the result can be disastrous—most brain tumors are caused by mutations in glia.

How Neurons Communicate

All functions performed by the nervous system—from a simple motor reflex to more advanced functions like making a memory or a decision—require neurons to communicate with one another. Neurons communicate between the axon of one neuron and the dendrites, and sometimes the cell body, of another neuron across the gap between them, known as the synaptic cleft . When an action potential reaches the end of an axon it stimulates the release of neurotransmitter molecules into the synaptic cleft between the synaptic knob of the axon and the post-synaptic membrane of the dendrite or soma of the next cell. The neurotransmitter is released through exocytosis of vesicles containing the neurotransmitter molecules. The neurotransmitter diffuses across the synaptic cleft and binds to receptors in the post-synaptic membrane. These receptor molecules are chemically regulated ion channels and will open, allowing sodium to enter the cell. If sufficient neurotransmitter has been released an action potential may be initiated in the next cell, but this is not guaranteed. If insufficient neurotransmitter is released the nerve signal will die at this point. There are a number of different neurotransmitters that are specific to neuron types that have specific functions.

The Central Nervous System

The central nervous system (CNS) is made up of the brain and spinal cord and is covered with three layers of protective coverings called meninges (“meninges” is derived from the Greek and means “membranes”) (Figure 16.21). The outermost layer is the dura mater, the middle layer is the web-like arachnoid mater, and the inner layer is the pia mater, which directly contacts and covers the brain and spinal cord. The space between the arachnoid and pia maters is filled with cerebrospinal fluid (CSF) . The brain floats in CSF, which acts as a cushion and shock absorber.

The Brain

The brain is the part of the central nervous system that is contained in the cranial cavity of the skull. It includes the cerebral cortex, limbic system, basal ganglia, thalamus, hypothalamus, cerebellum, brainstem, and retinas. The outermost part of the brain is a thick piece of nervous system tissue called the cerebral cortex . The cerebral cortex, limbic system, and basal ganglia make up the two cerebral hemispheres. A thick fiber bundle called the corpus callosum (corpus = “body” callosum = “tough”) connects the two hemispheres. Although there are some brain functions that are localized more to one hemisphere than the other, the functions of the two hemispheres are largely redundant. In fact, sometimes (very rarely) an entire hemisphere is removed to treat severe epilepsy. While patients do suffer some deficits following the surgery, they can have surprisingly few problems, especially when the surgery is performed on children who have very immature nervous systems.

In other surgeries to treat severe epilepsy, the corpus callosum is cut instead of removing an entire hemisphere. This causes a condition called split-brain, which gives insights into unique functions of the two hemispheres. For example, when an object is presented to patients’ left visual field, they may be unable to verbally name the object (and may claim to not have seen an object at all). This is because the visual input from the left visual field crosses and enters the right hemisphere and cannot then signal to the speech center, which generally is found in the left side of the brain. Remarkably, if a split-brain patient is asked to pick up a specific object out of a group of objects with the left hand, the patient will be able to do so but will still be unable to verbally identify it.

Concepts in Action

Visit the following website to learn more about split-brain patients and to play a game where you can model split-brain experiments yourself.

Each hemisphere contains regions called lobes that are involved in different functions. Each hemisphere of the mammalian cerebral cortex can be broken down into four functionally and spatially defined lobes: frontal, parietal, temporal, and occipital (Figure 16.22).

The frontal lobe is located at the front of the brain, over the eyes. This lobe contains the olfactory bulb, which processes smells. The frontal lobe also contains the motor cortex, which is important for planning and implementing movement. Areas within the motor cortex map to different muscle groups. Neurons in the frontal lobe also control cognitive functions like maintaining attention, speech, and decision-making. Studies of humans who have damaged their frontal lobes show that parts of this area are involved in personality, socialization, and assessing risk. The parietal lobe is located at the top of the brain. Neurons in the parietal lobe are involved in speech and also reading. Two of the parietal lobe’s main functions are processing somatosensation—touch sensations like pressure, pain, heat, cold—and processing proprioception—the sense of how parts of the body are oriented in space. The parietal lobe contains a somatosensory map of the body similar to the motor cortex. The occipital lobe is located at the back of the brain. It is primarily involved in vision—seeing, recognizing, and identifying the visual world. The temporal lobe is located at the base of the brain and is primarily involved in processing and interpreting sounds. It also contains the hippocampus (named from the Greek for “seahorse,” which it resembles in shape) a structure that processes memory formation. The role of the hippocampus in memory was partially determined by studying one famous epileptic patient, HM, who had both sides of his hippocampus removed in an attempt to cure his epilepsy. His seizures went away, but he could no longer form new memories (although he could remember some facts from before his surgery and could learn new motor tasks).

Interconnected brain areas called the basal ganglia play important roles in movement control and posture. The basal ganglia also regulate motivation.

The thalamus acts as a gateway to and from the cortex. It receives sensory and motor inputs from the body and also receives feedback from the cortex. This feedback mechanism can modulate conscious awareness of sensory and motor inputs depending on the attention and arousal state of the animal. The thalamus helps regulate consciousness, arousal, and sleep states.

Below the thalamus is the hypothalamus . The hypothalamus controls the endocrine system by sending signals to the pituitary gland. Among other functions, the hypothalamus is the body’s thermostat—it makes sure the body temperature is kept at appropriate levels. Neurons within the hypothalamus also regulate circadian rhythms, sometimes called sleep cycles.

The limbic system is a connected set of structures that regulates emotion, as well as behaviors related to fear and motivation. It plays a role in memory formation and includes parts of the thalamus and hypothalamus as well as the hippocampus. One important structure within the limbic system is a temporal lobe structure called the amygdala . The two amygdala (one on each side) are important both for the sensation of fear and for recognizing fearful faces.

The cerebellum (cerebellum = “little brain”) sits at the base of the brain on top of the brainstem. The cerebellum controls balance and aids in coordinating movement and learning new motor tasks. The cerebellum of birds is large compared to other vertebrates because of the coordination required by flight.

The brainstem connects the rest of the brain with the spinal cord and regulates some of the most important and basic functions of the nervous system including breathing, swallowing, digestion, sleeping, walking, and sensory and motor information integration.

Spinal cord

Connecting to the brainstem and extending down the body through the spinal column is the spinal cord. The spinal cord is a thick bundle of nerve tissue that carries information about the body to the brain and from the brain to the body. The spinal cord is contained within the meninges and the bones of the vertebral column but is able to communicate signals to and from the body through its connections with spinal nerves (part of the peripheral nervous system). A cross-section of the spinal cord looks like a white oval containing a gray butterfly-shape (Figure 16.23). Axons make up the “white matter” and neuron and glia cell bodies (and interneurons) make up the “gray matter.” Axons and cell bodies in the dorsa spinal cord convey mostly sensory information from the body to the brain. Axons and cell bodies in the spinal cord primarily transmit signals controlling movement from the brain to the body.

The spinal cord also controls motor reflexes. These reflexes are quick, unconscious movements—like automatically removing a hand from a hot object. Reflexes are so fast because they involve local synaptic connections. For example, the knee reflex that a doctor tests during a routine physical is controlled by a single synapse between a sensory neuron and a motor neuron. While a reflex may only require the involvement of one or two synapses, synapses with interneurons in the spinal column transmit information to the brain to convey what happened (the knee jerked, or the hand was hot).

The Peripheral Nervous System

The peripheral nervous system (PNS) is the connection between the central nervous system and the rest of the body. The PNS can be broken down into the autonomic nervous system , which controls bodily functions without conscious control, and the sensory-somatic nervous system , which transmits sensory information from the skin, muscles, and sensory organs to the CNS and sends motor commands from the CNS to the muscles.

The autonomic nervous system serves as the relay between the CNS and the internal organs. It controls the lungs, the heart, smooth muscle, and exocrine and endocrine glands. The autonomic nervous system controls these organs largely without conscious control it can continuously monitor the conditions of these different systems and implement changes as needed. Signaling to the target tissue usually involves two synapses: a preganglionic neuron (originating in the CNS) synapses to a neuron in a ganglion that, in turn, synapses on the target organ (Figure 16.24). There are two divisions of the autonomic nervous system that often have opposing effects: the sympathetic nervous system and the parasympathetic nervous system.

The sympathetic nervous system is responsible for the immediate responses an animal makes when it encounters a dangerous situation. One way to remember this is to think of the “fight-or-flight” response a person feels when encountering a snake (“snake” and “sympathetic” both begin with “s”). Examples of functions controlled by the sympathetic nervous system include an accelerated heart rate and inhibited digestion. These functions help prepare an organism’s body for the physical strain required to escape a potentially dangerous situation or to fend off a predator.

While the sympathetic nervous system is activated in stressful situations, the parasympathetic nervous system allows an animal to “rest and digest.” One way to remember this is to think that during a restful situation like a picnic, the parasympathetic nervous system is in control (“picnic” and “parasympathetic” both start with “p”). Parasympathetic preganglionic neurons have cell bodies located in the brainstem and in the sacral (toward the bottom) spinal cord (Figure 16.25). The parasympathetic nervous system resets organ function after the sympathetic nervous system is activated including slowing of heart rate, lowered blood pressure, and stimulation of digestion.

The sensory-somatic nervous system is made up of cranial and spinal nerves and contains both sensory and motor neurons. Sensory neurons transmit sensory information from the skin, skeletal muscle, and sensory organs to the CNS. Motor neurons transmit messages about desired movement from the CNS to the muscles to make them contract. Without its sensory-somatic nervous system, an animal would be unable to process any information about its environment (what it sees, feels, hears, and so on) and could not control motor movements. Unlike the autonomic nervous system, which usually has two synapses between the CNS and the target organ, sensory and motor neurons usually have only one synapse—one ending of the neuron is at the organ and the other directly contacts a CNS neuron.


Chapter 15 The Autonomic Nervous System

Make certain that you can define, and use in context, each of the terms listed below, and that you understand the significance of each of the concepts.

  1. Compare the structural and functional characteristics of the somatic and autonomic nervous systems.
    1. comparison of somatic and autonomic nervous systems
      1. somatic nervous systems
      2. autonomic sensory neurons
        1. interoceptors
        1. anatomy of autonomic motor pathways
          1. preganglionic neurons
          2. thoracolumbar division
          3. thoracolumbar outflow
          4. craniosacral division
          5. craniosacral outflow
          6. autonomic ganglia (no specifics on each individual ganglia)
            1. sympathetic ganglia
            2. sympathetic trunk ganglia (or vertebral chain ganglia or paravertebral ganglia)
            3. prevertebral ganglia (or collateral ganglia)
            4. parasympathetic ganglia
            5. terminal ganglia (or intramural ganglia)
            1. structure of the sympathetic division
              1. white ramus (plural is rami)&mdashwhite rami communicantes
              2. gray ramus (plural is rami)&mdashgray rami communicantes
              3. Horner&rsquos syndrome
              1. cranial parasympathetic outflow
              2. sacral parasympathetic outflow
              3. pelvic splachnic nerves
              1. myenteric plexus
              2. submucosal plexus
              1. ANS neurotransmitters and receptors
                1. cholinergic neurons
                  1. acetylcholine (ACh)
                  1. nicotinic receptors
                  2. muscarinic receptors
                  3. acetylcholinesterase (AChE)
                  1. norepinephrine (NE) or noradrenalin
                  1. alpha (1 and 2) receptors and beta (1, 2, and 3) receptors
                  1. physiological effects of the ANS
                    1. autonomic tone
                    2. sympathetic responses
                      1. fight-or-flight response
                      1. rest-and-digest
                      1. autonomic reflexes
                        1. receptor
                        2. sensory neuron
                        3. integrating centre
                        4. motor neuron
                        5. effector

                        Complete the &ldquoChapter Review and Resource Summary&rdquo at the end of the chapter.

                        Work through the &ldquoCritical Thinking Questions&rdquo for this chapter in WileyPLUS and ORION.


                        Contents

                        The autonomic nervous system is divided into the sympathetic nervous system and parasympathetic nervous system. The sympathetic division emerges from the spinal cord in the thoracic and lumbar areas, terminating around L2-3. The parasympathetic division has craniosacral “outflow”, meaning that the neurons begin at the cranial nerves (specifically the oculomotor nerve, facial nerve, glossopharyngeal nerve and vagus nerve) and sacral (S2-S4) spinal cord.

                        The autonomic nervous system is unique in that it requires a sequential two-neuron efferent pathway the preganglionic neuron must first synapse onto a postganglionic neuron before innervating the target organ. The preganglionic, or first, neuron will begin at the “outflow” and will synapse at the postganglionic, or second, neuron's cell body. The postganglionic neuron will then synapse at the target organ.

                        Sympathetic division Edit

                        The sympathetic nervous system consists of cells with bodies in the lateral grey column from T1 to L2/3. These cell bodies are "GVE" (general visceral efferent) neurons and are the preganglionic neurons. There are several locations upon which preganglionic neurons can synapse for their postganglionic neurons:

                          (3) of the sympathetic chain (these run on either side of the vertebral bodies)
                        1. (3) (12) and rostral lumbar ganglia (2 or 3)
                    3. caudal lumbar ganglia and sacral ganglia
                      • (celiac ganglion, aorticorenal ganglion, superior mesenteric ganglion, inferior mesenteric ganglion) of the adrenal medulla (this is the one exception to the two-neuron pathway rule: the synapse is directly efferent onto the target cell bodies)
                  2. These ganglia provide the postganglionic neurons from which innervation of target organs follows. Examples of splanchnic (visceral) nerves are:

                    • Cervical cardiac nerves and thoracic visceral nerves, which synapse in the sympathetic chain (greater, lesser, least), which synapse in the prevertebral ganglia , which synapse in the prevertebral ganglia , which synapse in the inferior hypogastric plexus

                    These all contain afferent (sensory) nerves as well, known as GVA (general visceral afferent) neurons.

                    Parasympathetic division Edit

                    The parasympathetic nervous system consists of cells with bodies in one of two locations: the brainstem (Cranial Nerves III, VII, IX, X) or the sacral spinal cord (S2, S3, S4). These are the preganglionic neurons, which synapse with postganglionic neurons in these locations:

                      of the head: Ciliary (Cranial nerve III), Submandibular (Cranial nerve VII), Pterygopalatine (Cranial nerve VII), and Otic (Cranial nerve IX)
                2. In or near the wall of an organ innervated by the Vagus (Cranial nerve X) or Sacral nerves (S2, S3, S4)
                3. These ganglia provide the postganglionic neurons from which innervations of target organs follows. Examples are:

                  • The postganglionic parasympathetic splanchnic (visceral) nerves
                  • The vagus nerve, which passes through the thorax and abdominal regions innervating, among other organs, the heart, lungs, liver and stomach

                  Sensory neurons Edit

                  The sensory arm is composed of primary visceral sensory neurons found in the peripheral nervous system (PNS), in cranial sensory ganglia: the geniculate, petrosal and nodose ganglia, appended respectively to cranial nerves VII, IX and X. These sensory neurons monitor the levels of carbon dioxide, oxygen and sugar in the blood, arterial pressure and the chemical composition of the stomach and gut content. They also convey the sense of taste and smell, which, unlike most functions of the ANS, is a conscious perception. Blood oxygen and carbon dioxide are in fact directly sensed by the carotid body, a small collection of chemosensors at the bifurcation of the carotid artery, innervated by the petrosal (IXth) ganglion. Primary sensory neurons project (synapse) onto “second order” visceral sensory neurons located in the medulla oblongata, forming the nucleus of the solitary tract (nTS), that integrates all visceral information. The nTS also receives input from a nearby chemosensory center, the area postrema, that detects toxins in the blood and the cerebrospinal fluid and is essential for chemically induced vomiting or conditional taste aversion (the memory that ensures that an animal that has been poisoned by a food never touches it again). All this visceral sensory information constantly and unconsciously modulates the activity of the motor neurons of the ANS.

                  Innervation Edit

                  Autonomic nerves travel to organs throughout the body. Most organs receive parasympathetic supply by the vagus nerve and sympathetic supply by splanchnic nerves. The sensory part of the latter reaches the spinal column at certain spinal segments. Pain in any internal organ is perceived as referred pain, more specifically as pain from the dermatome corresponding to the spinal segment. [11]

                    and posterior vagal trunks
                • PS: vagus nerves
                • S: greater splanchnic nerves
                • PS: posterior vagal trunks
                • S: greater splanchnic nerves
                • S: greater splanchnic nerves
                • PS: vagus nerve
                • S: celiac plexus
                • right phrenic nerve
                • PS: vagus nerves and pelvic splanchnic nerves
                • S: lesser and least splanchnic nerves
                  , T11, T12 (proximal colon) , L2, L3, (distal colon)
              • PS: vagus nerves
              • S: thoracic splanchnic nerves
              • nerves to superior mesenteric plexus
              • PS: vagus nerve
              • S: thoracic and lumbar splanchnic nerves

              Motor neurons Edit

              Motor neurons of the autonomic nervous system are found in ‘’autonomic ganglia’’. Those of the parasympathetic branch are located close to the target organ whilst the ganglia of the sympathetic branch are located close to the spinal cord.

              The sympathetic ganglia here, are found in two chains: the pre-vertebral and pre-aortic chains. The activity of autonomic ganglionic neurons is modulated by “preganglionic neurons” located in the central nervous system. Preganglionic sympathetic neurons are located in the spinal cord, at the thorax and upper lumbar levels. Preganglionic parasympathetic neurons are found in the medulla oblongata where they form visceral motor nuclei the dorsal motor nucleus of the vagus nerve the nucleus ambiguus, the salivatory nuclei, and in the sacral region of the spinal cord.

              Sympathetic and parasympathetic divisions typically function in opposition to each other. But this opposition is better termed complementary in nature rather than antagonistic. For an analogy, one may think of the sympathetic division as the accelerator and the parasympathetic division as the brake. The sympathetic division typically functions in actions requiring quick responses. The parasympathetic division functions with actions that do not require immediate reaction. The sympathetic system is often considered the "fight or flight" system, while the parasympathetic system is often considered the "rest and digest" or "feed and breed" system.

              However, many instances of sympathetic and parasympathetic activity cannot be ascribed to "fight" or "rest" situations. For example, standing up from a reclining or sitting position would entail an unsustainable drop in blood pressure if not for a compensatory increase in the arterial sympathetic tonus. Another example is the constant, second-to-second, modulation of heart rate by sympathetic and parasympathetic influences, as a function of the respiratory cycles. In general, these two systems should be seen as permanently modulating vital functions, in usually antagonistic fashion, to achieve homeostasis. Higher organisms maintain their integrity via homeostasis which relies on negative feedback regulation which, in turn, typically depends on the autonomic nervous system. [14] Some typical actions of the sympathetic and parasympathetic nervous systems are listed below. [15]

              Target organ/system Parasympathetic Sympathetic
              Digestive system Increase peristalsis and amount of secretion by digestive glands Decrease activity of digestive system
              Liver No effect Causes glucose to be released to blood
              Lungs Constricts bronchioles Dilates bronchioles
              Urinary bladder/ Urethra Relaxes sphincter Constricts sphincter
              Kidneys No effects Decrease urine output
              Heart Decreases rate Increase rate
              Blood vessels No effect on most blood vessels Constricts blood vessels in viscera increase BP
              Salivary and Lacrimal glands Stimulates increases production of saliva and tears Inhibits result in dry mouth and dry eyes
              Eye (iris) Stimulates constrictor muscles constrict pupils Stimulate dilator muscle dilates pupils
              Eye (ciliary muscles) Stimulates to increase bulging of lens for close vision Inhibits decrease bulging of lens prepares for distant vision
              Adrenal Medulla No effect Stimulate medulla cells to secrete epinephrine and norepinephrine
              Sweat gland of skin No effect Stimulate to produce perspiration

              Sympathetic nervous system Edit

              Promotes a fight-or-flight response, corresponds with arousal and energy generation, and inhibits digestion

              • Diverts blood flow away from the gastro-intestinal (GI) tract and skin via vasoconstriction
              • Blood flow to skeletal muscles and the lungs is enhanced (by as much as 1200% in the case of skeletal muscles)
              • Dilates bronchioles of the lung through circulating epinephrine, which allows for greater alveolar oxygen exchange
              • Increases heart rate and the contractility of cardiac cells (myocytes), thereby providing a mechanism for enhanced blood flow to skeletal muscles
              • Dilates pupils and relaxes the ciliary muscle to the lens, allowing more light to enter the eye and enhances far vision
              • Provides vasodilation for the coronary vessels of the heart
              • Constricts all the intestinal sphincters and the urinary sphincter
              • Inhibits peristalsis
              • Stimulates orgasm

              Parasympathetic nervous system Edit

              The parasympathetic nervous system has been said to promote a "rest and digest" response, promotes calming of the nerves return to regular function, and enhancing digestion. Functions of nerves within the parasympathetic nervous system include: [ citation needed ]

              • Dilating blood vessels leading to the GI tract, increasing the blood flow.
              • Constricting the bronchiolar diameter when the need for oxygen has diminished
              • Dedicated cardiac branches of the vagus and thoracic spinal accessory nerves impart parasympathetic control of the heart (myocardium)
              • Constriction of the pupil and contraction of the ciliary muscles, facilitating accommodation and allowing for closer vision
              • Stimulating salivary gland secretion, and accelerates peristalsis, mediating digestion of food and, indirectly, the absorption of nutrients
              • Sexual. Nerves of the peripheral nervous system are involved in the erection of genital tissues via the pelvic splanchnic nerves 2–4. They are also responsible for stimulating sexual arousal.

              Enteric nervous system Edit

              The enteric nervous system is the intrinsic nervous system of the gastrointestinal system. It has been described as "the Second Brain of the Human Body". [16] Its functions include:

              • Sensing chemical and mechanical changes in the gut
              • Regulating secretions in the gut
              • Controlling peristalsis and some other movements

              Neurotransmitters Edit

              At the effector organs, sympathetic ganglionic neurons release noradrenaline (norepinephrine), along with other cotransmitters such as ATP, to act on adrenergic receptors, with the exception of the sweat glands and the adrenal medulla:

                is the preganglionic neurotransmitter for both divisions of the ANS, as well as the postganglionic neurotransmitter of parasympathetic neurons. Nerves that release acetylcholine are said to be cholinergic. In the parasympathetic system, ganglionic neurons use acetylcholine as a neurotransmitter to stimulate muscarinic receptors.
          7. At the adrenal medulla, there is no postsynaptic neuron. Instead the presynaptic neuron releases acetylcholine to act on nicotinic receptors. Stimulation of the adrenal medulla releases adrenaline (epinephrine) into the bloodstream, which acts on adrenoceptors, thereby indirectly mediating or mimicking sympathetic activity.
          8. The specialised system of the autonomic nervous system was recognised by Galen. In 1665, Willis used the terminology, and in 1900, Langley used the term, defining the two divisions as the sympathetic and parasympathetic nervous systems. [17]

            Caffeine is a bioactive ingredient found in commonly consumed beverages such as coffee, tea, and sodas. Short-term physiological effects of caffeine include increased blood pressure and sympathetic nerve outflow. Habitual consumption of caffeine may inhibit physiological short-term effects. Consumption of caffeinated espresso increases parasympathetic activity in habitual caffeine consumers however, decaffeinated espresso inhibits parasympathetic activity in habitual caffeine consumers. It is possible that other bioactive ingredients in decaffeinated espresso may also contribute to the inhibition of parasympathetic activity in habitual caffeine consumers. [18]

            Caffeine is capable of increasing work capacity while individuals perform strenuous tasks. In one study, caffeine provoked a greater maximum heart rate while a strenuous task was being performed compared to a placebo. This tendency is likely due to caffeine's ability to increase sympathetic nerve outflow. Furthermore, this study found that recovery after intense exercise was slower when caffeine was consumed prior to exercise. This finding is indicative of caffeine's tendency to inhibit parasympathetic activity in non-habitual consumers. The caffeine-stimulated increase in nerve activity is likely to evoke other physiological effects as the body attempts to maintain homeostasis. [19]

            The effects of caffeine on parasympathetic activity may vary depending on the position of the individual when autonomic responses are measured. One study found that the seated position inhibited autonomic activity after caffeine consumption (75 mg) however, parasympathetic activity increased in the supine position. This finding may explain why some habitual caffeine consumers (75 mg or less) do not experience short-term effects of caffeine if their routine requires many hours in a seated position. It is important to note that the data supporting increased parasympathetic activity in the supine position was derived from an experiment involving participants between the ages of 25 and 30 who were considered healthy and sedentary. Caffeine may influence autonomic activity differently for individuals who are more active or elderly. [20]


            Aging has various effects on the sympathetic nervous system. Research has demonstrated that with increased age that baroreceptors of the heart decrease and become less sensitive there is a compensatory increase in cardiovascular SNS activity and a reduction in PNS activity. However, both sympathetic and parasympathetic nervous activity to the iris decreases with aging, which is consistent with the general decline of peripheral somatic nerve function.[6] Research has also shown that baseline levels of noradrenaline levels increase with age resulting in an elevated basal SNS activation, while the reactivity becomes reduced with aging.[7] This increase in activation plays a role, among other disease processes, in both age-related hypertension and heart failure.[8]

            Horner syndrome is a complication born from interruption of the sympathetic innervation to the eye and adnexa at varying levels, most commonly of the neck, resulting in increased parasympathetic input. It presents with the classic triad of ipsilateral ptosis, pupillary miosis, and facial anhidrosis. It can be a complication of neck surgeries that damage the sympathetic input.[9] There are even reports after minimally invasive thyroidectomy.[10]ਏor more information on Horner syndrome, please refer to our accompanying article.[11]

            Hyperhidrosis, otherwise known as excessive sweating, is a common indication for minimally invasive thoracic sympathectomy. Hyperhidrosis is excessive sweating beyond the organism’s physiological need to sweat to have a temperature within an adequate range. Removing the sympathetic input to the part of the body affected by hyperhidrosis is an acceptable and well-tolerated treatment.[12] Thorascoposic sympathectomy can also be useful to treat severe Raynaud syndrome, defined as episodic vascular spasms and digital ischemia secondary to cold or emotional stimuli.[13]


            DESIGN AND COURSE CONTENT

            Regulation of Autonomic Nervous System Activity

            The efferent nervous activity of the ANS is largely regulated by autonomic reflexes. In many of these reflexes, sensory information is transmitted to homeostatic control centers, in particular, those located in the hypothalamus and brainstem. Much of the sensory input from the thoracic and abdominal viscera is transmitted to the brainstem by afferent fibers of cranial nerve X, the vagus nerve. Other cranial nerves also contribute sensory input to the hypothalamus and the brainstem. This input is integrated and a response is carried out by the transmission of nerve signals that modify the activity of preganglionic autonomic neurons. Many important variables in the body are monitored and regulated in the hypothalamus and the brainstem including heart rate, blood pressure, gastrointestinal peristalsis and glandular secretion, body temperature, hunger, thirst, plasma volume, and plasma osmolarity.

            An example of this type of autonomic reflex is the baroreceptor reflex. Baroreceptors located in some of the major systemic arteries are sensory receptors that monitor blood pressure. If blood pressure decreases, the number of sensory impulses transmitted from the baroreceptors to the vasomotor center in the brainstem also decreases. As a result of this change in baroreceptor stimulation and sensory input to the brainstem, ANS activity to the heart and blood vessels is adjusted to increase heart rate and vascular resistance so that blood pressure increases to its normal value.

            These neural control centers in the hypothalamus and the brainstem may also be influenced by higher brain areas. Specifically, the cerebral cortex and the limbic system influence ANS activities associated with emotional responses by way of hypothalamic-brainstem pathways. For example, blushing during an embarrassing moment, a response most likely originating in the frontal association cortex, involves vasodilation of blood vessels to the face. Other emotional responses influenced by these higher brain areas include fainting, breaking out in a cold sweat, and a racing heart rate.

            Some autonomic reflexes may be processed at the level of the spinal cord. These include the micturition reflex (urination) and the defecation reflex. Although these reflexes are subject to influence from higher nervous centers, they may occur without input from the brain.

            Efferent Pathways of the Autonomic Nervous System

            The efferent pathways of the ANS consist of 2 neurons that transmit impulses from the CNS to the effector tissue. The preganglionic neuron originates in the CNS with its cell body in the lateral horn of the gray matter of the spinal cord or in the brainstem. The axon of this neuron travels to an autonomic ganglion located outside the CNS, where it synapses with a postganglionic neuron. This neuron innervates the effector tissue.

            Synapses between the autonomic postganglionic neuron and effector tissue—the neuroeffector junction𠅍iffer greatly from neuron-to-neuron synapses. The postganglionic fibers in the ANS do not terminate in a single swelling like the synaptic knob, nor do they synapse directly with the cells of a tissue. Instead, where the axons of these fibers enter a given tissue, they contain multiple swellings called varicosities. When the neuron is stimulated, these varicosities release neurotransmitters along a significant length of the axon and, therefore, over a large surface area of the effector tissue. The neurotransmitter diffuses through the interstitial fluid to wherever its receptors are located in the tissue. This diffuse release of the neurotransmitter affects many tissue cells simultaneously. Furthermore, cardiac muscle and most smooth muscle have gap junctions between cells. These specialized intercellular communications allow for the spread of electrical activity from one cell to the next. As a result, the discharge of a single autonomic nerve fiber to an effector tissue may alter the activity of the entire tissue.

            Divisions of the Autonomic Nervous System

            The ANS is composed of 2 anatomically and functionally distinct divisions, the sympathetic system and the parasympathetic system. Both systems are tonically active. In other words, they provide some degree of nervous input to a given tissue at all times. Therefore, the frequency of discharge of neurons in both systems can either increase or decrease. As a result, tissue activity may be either enhanced or inhibited. This characteristic of the ANS improves its ability to more precisely regulate a tissue's function. Without tonic activity, nervous input to a tissue could only increase.

            Many tissues are innervated by both systems. Because the sympathetic system and the parasympathetic system typically have opposing effects on a given tissue, increasing the activity of one system while simultaneously decreasing the activity of the other results in very rapid and precise control of a tissue's function. Several distinguishing features of these 2 divisions of the ANS are summarized in Table ​ Table1 1 .

            Table 1

            Distinguishing Features of the Sympathetic and Parasympathetic Systems

            Each system is dominant under certain conditions. The sympathetic system predominates during emergency 𠇏ight-or-flight” reactions and during exercise. The overall effect of the sympathetic system under these conditions is to prepare the body for strenuous physical activity. More specifically, sympathetic nervous activity will increase the flow of blood that is well-oxygenated and rich in nutrients to the tissues that need it, in particular, the working skeletal muscles. The parasympathetic system predominates during quiet, resting conditions. The overall effect of the parasympathetic system under these conditions is to conserve and store energy and to regulate basic body functions such as digestion and urination.

            Sympathetic Division

            The preganglionic neurons of the sympathetic system arise from the thoracic and lumbar regions of the spinal cord (segments T1 through L2). Most of these preganglionic axons are short and synapse with postganglionic neurons within ganglia found in the sympathetic ganglion chains. These ganglion chains, which run parallel immediately along either side of the spinal cord, each consist of 22 ganglia. The preganglionic neuron may exit the spinal cord and synapse with a postganglionic neuron in a ganglion at the same spinal cord level from which it arises. The preganglionic neuron may also travel more rostrally or caudally (upward or downward) in the ganglion chain to synapse with postganglionic neurons in ganglia at other levels. In fact, a single preganglionic neuron may synapse with several postganglionic neurons in many different ganglia. Overall, the ratio of preganglionic fibers to postganglionic fibers is about 1:20. The long postganglionic neurons originating in the ganglion chain then travel outward and terminate on the effector tissues. This divergence of the preganglionic neuron results in coordinated sympathetic stimulation to tissues throughout the body. The concurrent stimulation of many organs and tissues in the body is referred to as a mass sympathetic discharge.

            Other preganglionic neurons exit the spinal cord and pass through the ganglion chain without synapsing with a postganglionic neuron. Instead, the axons of these neurons travel more peripherally and synapse with postganglionic neurons in one of the sympathetic collateral ganglia. These ganglia are located about halfway between the CNS and the effector tissue.

            Finally, the preganglionic neuron may travel to the adrenal medulla and synapse directly with this glandular tissue. The cells of the adrenal medulla have the same embryonic origin as neural tissue and, in fact, function as modified postganglionic neurons. Instead of the release of neurotransmitter directly at the synapse with an effector tissue, the secretory products of the adrenal medulla are picked up by the blood and travel throughout the body to all of the effector tissues of the sympathetic system.

            An important feature of this system, which is quite distinct from the parasympathetic system, is that the postganglionic neurons of the sympathetic system travel within each of the 31 pairs of spinal nerves. Interestingly, 8% of the fibers that constitute a spinal nerve are sympathetic fibers. This allows for the distribution of sympathetic nerve fibers to the effectors of the skin including blood vessels and sweat glands. In fact, most innervated blood vessels in the entire body, primarily arterioles and veins, receive only sympathetic nerve fibers. Therefore, vascular smooth muscle tone and sweating are regulated by the sympathetic system only. In addition, the sympathetic system innervates structures of the head (eye, salivary glands, mucus membranes of the nasal cavity), thoracic viscera (heart, lungs) and viscera of the abdominal and pelvic cavities (eg, stomach, intestines, pancreas, spleen, adrenal medulla, urinary bladder).

            Parasympathetic Division

            The preganglionic neurons of the parasympathetic system arise from several nuclei of the brainstem and from the sacral region of the spinal cord (segments S2-S4). The axons of the preganglionic neurons are quite long compared to those of the sympathetic system and synapse with postganglionic neurons within terminal ganglia which are close to or embedded within the effector tissues. The axons of the postganglionic neurons, which are very short, then provide input to the cells of that effector tissue.

            The preganglionic neurons that arise from the brainstem exit the CNS through the cranial nerves. The occulomotor nerve (III) innervates the eyes the facial nerve (VII) innervates the lacrimal gland, the salivary glands and the mucus membranes of the nasal cavity the glossopharyngeal nerve (IX) innervates the parotid (salivary) gland and the vagus nerve (X) innervates the viscera of the thorax and the abdomen (eg, heart, lungs, stomach, pancreas, small intestine, upper half of the large intestine, and liver). The physiological significance of this nerve in terms of the influence of the parasympathetic system is clearly illustrated by its widespread distribution and the fact that 75% of all parasympathetic fibers are in the vagus nerve. The preganglionic neurons that arise from the sacral region of the spinal cord exit the CNS and join together to form the pelvic nerves. These nerves innervate the viscera of the pelvic cavity (eg, lower half of the large intestine and organs of the renal and reproductive systems).

            Because the terminal ganglia are located within the innervated tissue, there is typically little divergence in the parasympathetic system compared to the sympathetic system. In many organs, there is a 1:1 ratio of preganglionic fibers to postganglionic fibers. Therefore, the effects of the parasympathetic system tend to be more discrete and localized, with only specific tissues being stimulated at any given moment, compared to the sympathetic system where a more diffuse discharge is possible.

            Neurotransmitters of the Autonomic Nervous System

            The 2 most common neurotransmitters released by neurons of the ANS are acetylcholine and norepinephrine. Neurotransmitters are synthesized in the axon varicosities and stored in vesicles for subsequent release. Several distinguishing features of these neurotransmitters are summarized in Table ​ Table2. 2 . Nerve fibers that release acetylcholine are referred to as cholinergic fibers. These include all preganglionic fibers of the ANS, both sympathetic and parasympathetic systems all postganglionic fibers of the parasympathetic system and sympathetic postganglionic fibers innervating sweat glands. Nerve fibers that release norepinephrine are referred to as adrenergic fibers. Most sympathetic postganglionic fibers release norepinephrine.

            Table 2

            Distinguishing Features of Neurotransmitters of the Autonomic Nervous System

            As previously mentioned, the cells of the adrenal medulla are considered modified sympathetic postganglionic neurons. Instead of a neurotransmitter, these cells release hormones into the blood. Approximately 20% of the hormonal output of the adrenal medulla is norepinephrine. The remaining 80% is epinephrine. Unlike true postganglionic neurons in the sympathetic system, the adrenal medulla contains an enzyme that methylates norepinephrine to form epinephrine. The synthesis of epinephrine, also known as adrenaline, is enhanced under conditions of stress. These 2 hormones released by the adrenal medulla are collectively referred to as the catecholamines.

            Termination of Neurotransmitter Activity

            For any substance to serve effectively as a neurotransmitter, it must be rapidly inactivated or removed from the synapse or, in this case, the neuroeffector junction. This is necessary in order to allow new signals to get through and influence effector tissue function.

            The primary mechanism used by cholinergic synapses is enzymatic degradation. Acetylcholinesterase hydrolyzes acetylcholine to its component choline and acetate. It is one of the fastest acting enzymes in the body and acetylcholine removal occurs in less than 1 msec. The most important mechanism for the removal of norepinephrine from the neuroeffector junction is the reuptake of this neurotransmitter into the sympathetic nerve that released it. Norepinephrine may then be metabolized intraneuronally by monoamine oxidase (MAO). The circulating catecholamines, epinephrine and norepinephrine, are inactivated by catechol-O-methyltransferase (COMT) in the liver.

            Receptors for Autonomic Neurotransmitters

            As discussed in the previous section, all of the effects of the ANS in tissues and organs throughout the body, including smooth muscle contraction or relaxation, alteration of myocardial activity, and increased or decreased glandular secretion, are carried out by only 3 substances, acetylcholine, norepinephrine, and epinephrine. Furthermore, each of these substances may stimulate activity in some tissues and inhibit activity in others. How can this wide variety of effects on many different tissues be carried out by so few neurotransmitters or hormones? The effect caused by any of these substances is determined by the receptor distribution in a particular tissue and the biochemical properties of the cells in that tissue, specifically, the second messenger and enzyme systems present within the cell.

            The neurotransmitters of the ANS and the circulating catecholamines bind to specific receptors on the cell membranes of the effector tissue. All adrenergic receptors and muscarinic receptors are coupled to G proteins which are also embedded within the plasma membrane. Receptor stimulation causes activation of the G protein and the formation of an intracellular chemical, the second messenger. (The neurotransmitter molecule, which cannot enter the cell itself, is the first messenger.) The function of the intracellular second messenger molecules is to elicit tissue-specific biochemical events within the cell which alter the cell's activity. In this way, a given neurotransmitter may stimulate the same type of receptor on 2 different types of tissue and cause 2 different responses due to the presence of different biochemical pathways within each tissue.

            Acetylcholine binds to 2 types of cholinergic receptors. Nicotinic receptors are found on the cell bodies of all postganglionic neurons, both sympathetic and parasympathetic, in the ganglia of the ANS. Acetylcholine released from the preganglionic neurons binds to these nicotinic receptors and causes a rapid increase in the cellular permeability to Na + ions and Ca ++ ions. The resulting influx of these 2 cations causes depolarization and excitation of the postganglionic neurons the ANS pathways.

            Muscarinic receptors are found on the cell membranes of the effector tissues and are linked to G proteins and second messenger systems which carry out the intracellular effects. Acetylcholine released from all parasympathetic postganglionic neurons and some sympathetic postganglionic neurons traveling to sweat glands binds to these receptors. Muscarinic receptors may be either inhibitory or excitatory, depending on the tissue upon which they are found. For example, muscarinic receptor stimulation in the myocardium is inhibitory and decreases heart rate while stimulation of these receptors in the lungs is excitatory, causing contraction of airway smooth muscle and bronchoconstriction.

            There are 2 classes of adrenergic receptors for norepinephrine and epinephrine, alpha (α) and beta (β). Furthermore, there are at least 2 subtypes of receptors in each class: α1, α2, β1 and β2. All of these receptors are linked to G proteins and second messenger systems which carry out the intracellular effects.

            Alpha receptors are the more abundant of the adrenergic receptors. Of the 2 subtypes, α1 receptors are more widely distributed on the effector tissues. Alpha one receptor stimulation leads to an increase in intracellular calcium. As a result, these receptors tend to be excitatory. For example, stimulation of α1 receptors causes contraction of vascular smooth muscle resulting in vasoconstriction and increased glandular secretion by way of exocytosis.

            Pharmacy Application: Alpha One Adrenergic Receptor Antagonists.

            Hypertension, or a chronic elevation in blood pressure, is a major risk factor for coronary artery disease, congestive heart failure, stroke, kidney failure, and retinopathy. An important cause of hypertension is excessive vascular smooth muscle tone or vasoconstriction. Prazosin, an α1-adrenergic receptor antagonist, is very effective in the management of hypertension. Because α1-receptor stimulation causes vasoconstriction, drugs that block these receptors result in vasodilation and a decrease in blood pressure.

            Compared to α1 receptors, α2 receptors have only moderate distribution on the effector tissues. Alpha 2 receptor stimulation causes a decrease in cAMP and, therefore, inhibitory effects such as smooth muscle relaxation and decreased glandular secretion. However, α2 receptors have important presynaptic effects. Where α1 receptors are found on the effector tissue cells at the neuroeffector junction, the α2 receptors are found on the varicosities of the postganglionic neuron. Norepinephrine released from this neuron binds to not only the α1 receptors on the effector tissue to cause some physiological effect it also binds to the α2 receptors on the neuron itself. Alpha 2 receptor stimulation results in “presynaptic inhibition” or in a decrease in the release of norepinephrine. In this way, norepinephrine inhibits its own release from the sympathetic postganglionic neuron and controls its own activity. Both α1 and α2 receptors have equal affinity for norepinephrine released directly from sympathetic neurons as well as circulating epinephrine released from the adrenal medulla.

            Stimulation of each type of β receptor leads to an increase in intracellular cAMP. Whether this results in an excitatory or an inhibitory response depends upon the specific cell type. As with α receptors, β receptors are also unevenly distributed with β2 receptors, the more common subtype on the effector tissues. Beta 2 receptors tend to be inhibitory. For example, β2 receptor stimulation causes relaxation of vascular smooth muscle and airway smooth muscle resulting in vasodilation and bronchodilation, respectively. Beta 2 receptors have a significantly greater affinity for epinephrine than for norepinephrine. Furthermore, terminations of sympathetic pathways are not found near these receptors. Therefore, β2 receptors are stimulated only indirectly by circulating epinephrine instead of by direct sympathetic nervous activity.

            Beta 1 receptors are the primary adrenergic receptor on the heart (a small percentage of the adrenergic receptors on the myocardium are β2). Both subtypes of β receptors on the heart are excitatory and stimulation leads to an increase in cardiac activity. Beta 1 receptors are also found on certain cells in the kidney. Epinephrine and norepinephrine have equal affinity for β1 receptors.

            Beta three (β3) receptors are found primarily in adipose tissue. Stimulation of these receptors, which have a stronger affinity for norepinephrine, causes lipolysis.

            Pharmacy Application: Sympathomimetic Drugs.

            Sympathomimetic drugs are those that produce effects in a tissue resembling those caused from stimulation by the sympathetic nervous system. An important use for these drugs is in the treatment of bronchial asthma which is characterized by bronchospasm. As discussed, bronchodilation occurs following β2-adrenergic receptor stimulation. Non-selective β receptor agonists, such as epinephrine and isoproterenol, are capable of causing bronchodilation. However, a potential problem with these drugs is that they stimulate all β-receptors including β1 receptors on the heart. Therefore, in patients with bronchospasm, an undesirable side effect of treatment with these non-selective agents is an increase in heart rate. Instead, β2-selective drugs, such as albuterol, are chosen for this therapy. They are equally effective in causing bronchodilation with a much lower risk of adverse cardiovascular effects.

            Functions of the Autonomic Nervous System

            The 2 divisions of the ANS are dominant under different conditions. As stated previously, the sympathetic system is activated during emergency 𠇏ight-or-flight” reactions and during exercise. The parasympathetic system is predominant during quiet conditions (“rest and digest”). As such, the physiological effects caused by each system are quite predictable. In other words, all of the changes in organ and tissue function induced by the sympathetic system work together to support strenuous physical activity and the changes induced by the parasympathetic system are appropriate for when the body is resting. Several of the specific effects elicited by sympathetic and parasympathetic stimulation of various organs and tissues are summarized in Table ​ Table3 3 .

            Table 3

            Effects of Autonomic Nerve Activity on Some Effector Tissue

            The 𠇏ight-or-flight” reaction elicited by the sympathetic system is essentially a whole body response. Changes in organ and tissue function throughout the body are coordinated so that there is an increase in the delivery of well-oxygenated, nutrient-rich blood to the working skeletal muscles. Both heart rate and myocardial contractility are increased so that the heart pumps more blood per minute. Sympathetic stimulation of vascular smooth muscle causes widespread vasoconstriction, particularly in the organs of the gastrointestinal system and in the kidneys. This vasoconstriction serves to “redirect” or redistribute the blood away from these metabolically inactive tissues and toward the contracting muscles. Bronchodilation in the lungs facilitates the movement of air in and out of the lungs so that the uptake of oxygen from the atmosphere and the elimination of carbon dioxide from the body are maximized. An enhanced rate of glycogenolysis (breakdown of glycogen into its component glucose molecules) and gluconeogenesis (formation of new glucose from noncarbohydrate sources) in the liver increases the concentration of glucose molecules in the blood. This is necessary for the brain as glucose is the only nutrient molecule that it can utilize to form metabolic energy. An enhanced rate of lipolysis in adipose tissue increases the concentration of fatty acid molecules in the blood. Skeletal muscles then utilize these fatty acids to form metabolic energy for contraction. Generalized sweating elicited by the sympathetic system enables the individual to thermoregulate during these conditions of increased physical activity and heat production. Finally, the eye is adjusted such that the pupil dilates letting more light in toward the retina (mydriasis) and the lens adapts for distance vision.

            The parasympathetic system decreases heart rate which helps to conserve energy under resting conditions. Salivary secretion is enhanced to facilitate the swallowing of food. Gastric motility and secretion are stimulated to begin the processing of ingested food. Intestinal motility and secretion are also stimulated to continue the processing and to facilitate the absorption of these nutrients. Both exocrine and endocrine secretion from the pancreas is promoted. Enzymes released from the exocrine glands of the pancreas contribute to the chemical breakdown of the food in the intestine and insulin released from the pancreatic islets promotes the storage of nutrient molecules within the tissues once they are absorbed into the body. Another bodily maintenance type of function caused by the parasympathetic system is contraction of the urinary bladder which results in urination. Finally, the eye is adjusted such that the pupil contracts (miosis) and the lens adapts for near vision.

            Pharmacy application: cholinomimetic drugs.

            Cholinomimetic drugs are those that produce effects in a tissue resembling those caused from stimulation by the parasympathetic nervous system. These drugs have many important uses including the treatment of gastrointestinal and urinary tract disorders that involve depressed smooth muscle activity without obstruction. For example, postoperative ileus is characterized by a loss of tone or paralysis of the stomach or bowel following surgical manipulation. Urinary retention may also occur postoperatively or it may be secondary to spinal cord injury or disease (neurogenic bladder). Normally, parasympathetic stimulation of the smooth muscle in each of these organ systems causes contraction to maintain gastrointestinal motility as well as urination. There are 2 different approaches in the pharmacotherapy of these disorders. One type of agent would be a muscarinic receptor agonist which would mimic the effect of the parasympathetic neurotransmitter, acetylcholine, and stimulate smooth muscle contraction. One of the more commonly used agents in this category is bethanechol which can be given subcutaneously. Another approach is to increase the concentration and, therefore, activity of endogenously produced acetylcholine in the neuroeffector junction. Administration of an acetylcholinesterase inhibitor prevents the degradation and removal of neuronally-released acetylcholine. In this case, neostigmine is the most widely used agent. Neostigmine may be given intramuscularly, subcutaneously, or orally.

            Pharmacy application: muscarinic receptor antagonists.

            Inspection of the retina during an ophthalmoscopic examination is greatly facilitated by mydriasis, or the dilation of the pupil. Parasympathetic stimulation of the circular muscle layer in the iris causes contraction and a decrease in the diameter of the pupil. Administration of a muscarinic receptor antagonist, such as atropine or scopolamine, prevents this smooth muscle contraction. As a result, sympathetic stimulation of the radial muscle layer is unopposed. This causes an increase in the diameter of the pupil. These agents are given in the form of eye drops which act locally and limit the possibility of systemic side effects.

            Adrenal Medulla

            A mass sympathetic discharge, which typically occurs during the 𠇏ight-or-flight” response and during exercise, involves the simultaneous stimulation of organs and tissues throughout the body. Included among these tissues are the adrenal medullae which release epinephrine and norepinephrine into the blood. In large part, the indirect effects of these catecholamines are similar to and, therefore, reinforce those of direct sympathetic stimulation. However, there are some important differences in the effects of the circulating catecholamines and those of norepinephrine released from sympathetic nerves.

            The duration of activity of the catecholamines is significantly longer than that of neuronally released norepinephrine. Therefore, the effects on the tissues are more prolonged. This difference has to do with the mechanism of inactivation of these substances. Norepinephrine is immediately removed from the neuroeffector synapse by way of reuptake into the postganglionic neuron. This rapid removal limits the duration of the effect of this neurotransmitter. In contrast, there are no enzymes in the blood to degrade the catecholamines. Instead, the catecholamines are inactivated by COMT in the liver. As one might expect, the hepatic clearance of these hormones from the blood would require several passes through the circulation. Therefore, the catecholamines are available to cause their effects for a comparatively longer period of time (up to 1-2 minutes as opposed to milliseconds).

            Because they travel in the blood, organs and tissues throughout the body are exposed to the catecholamines. Therefore, they are capable of stimulating tissues that are not directly innervated by sympathetic nerve fibers: airway smooth muscle, hepatocytes, and adipose tissue, in particular. As a result, the catecholamines have a much wider breadth of activity compared to norepinephrine released from sympathetic nerves.

            The third important feature that distinguishes the catecholamines from neuronally released norepinephrine involves epinephrine's affinity for β2 receptors. Norepinephrine has a very limited affinity for these receptors. Therefore, circulating epinephrine causes effects that differ from those of direct sympathetic innervation including a greater stimulatory effect on the heart and relaxation of smooth muscle (vascular, bronchial, gastrointestinal, and genitourinary).

            Epinephrine and norepinephrine have equal affinity for β1 receptors, the predominant adrenergic receptor on the heart. However, the human heart also contains a small percentage of β2 receptors which, like β1 receptors are excitatory. Therefore, epinephrine is capable of stimulating a greater number of receptors and of causing a greater stimulatory effect on the myocardium.

            Beta two adrenergic receptors are also found on smooth muscle in several organ systems. These receptors tend to be inhibitory and cause relaxation of the smooth muscle. Vascular smooth muscle in skeletal muscle contains both α1 and β2 receptors. Norepinephrine, which stimulates only the excitatory α1 receptors, causes strong vasoconstriction. However, epinephrine, which stimulates both types of receptors, causes only weak vasoconstriction. The vasodilation resulting from β2 receptor stimulation opposes and, therefore, weakens the vasoconstriction resulting from α1 receptor stimulation. Given that skeletal muscle may account for 40% of an adult's body weight, the potential difference in vasoconstriction, blood pressure, and the distribution of blood flow could be quite significant.

            Another noteworthy example of the relaxation of smooth muscle by way of β2 receptor stimulation involves the airways. Bronchodilation, or the opening of the airways, facilitates airflow in the lungs. Any direct sympathetic innervation to the lungs is irrelevant in this respect, as only circulating epinephrine is capable of stimulating these receptors on airway smooth muscle.

            Application of the ANS to Pharmacy

            In addition to the “Pharmacy Application” sections found throughout the discussion, further application of the lecture material to the practice of pharmacy is provided by required case studies. The case studies are then discussed in recitation sections. These exercises serve to separate students who have simply memorized aspects of the ANS from students who have a more thorough understanding of this system. Successful completion of the case studies requires higher level critical-thinking and problem-solving skills.

            Case #1: Insecticide Poisoning

            CD is a 44-year-old woman who had spent much of the day working in her garden. A blustery wind caused her to unintentionally inhale the insecticide that she was spraying throughout the garden. When she began wheezing severely, she was taken to the emergency room. The attending physician observed other symptoms including constricted pupils and a slowed heart rate. CD was treated with the intravenous administration of atropine sulfate.

            Insecticides contain organophosphates which inhibit acetylcholinesterase. What is the function of acetylcholinesterase?

            Which types of autonomic receptors are excessively stimulated as a result of this inhibition?

            Which division of the ANS has been primarily affected, the sympathetic or the parasympathetic?

            Under what conditions does this division of the ANS normally predominate?

            Explain how the insecticide resulted in her presenting symptoms.

            What effects may the insecticide have on the gastrointestinal system? Explain.

            What effect may the insecticide have on generalized sweating in this patient? Localized sweating? Explain.

            If exposed to high enough doses, what effect might the insecticide have on the patient's skeletal muscles?

            Would the administration of a β-adrenergic receptor antagonist be useful in the treatment of this patient? Why or why not?

            Would the administration of a β-adrenergic receptor agonist be useful in the treatment of this patient? Why or why not?

            Why is atropine an appropriate treatment?

            The “nerve gas,” sarin, is a potent, irreversible organophosphate. What is the likely cause of death resulting from exposure to this extremely toxic agent?

            Case Study #2: Pheochromocytoma

            AF is a 55-year-old woman who had been experiencing heart palpitations, a throbbing headache, sweating, pain in the abdomen, nausea and vomiting. Because these symptoms had failed to subside, she went to see her primary care physician. A urinalysis revealed the presence of catecholamines and their metabolites, including vanillylmandelic acid (VMA). A subsequent CT scan confirmed the presence of a tumor in the adrenal medulla. Surgery to remove the tumor was scheduled.

            What are the catecholamines? Which is the predominant compound?

            Describe the relationship of the adrenal medulla to the autonomic nervous system. Under what conditions are the catecholamines typically released?

            How are catecholamines normally eliminated from the blood?

            Is heart rate slower or faster than average in this patient? Why? What autonomic receptors are involved with this change in heart rate?

            Is blood pressure likely to be lower or higher than average in this patient? Why? What autonomic receptors are involved with this change in blood pressure?

            Describe the mechanism of excessive sweating in the patient. What autonomic receptors are involved with this sweating?

            Would you expect the patient's pupils to be constricted or dilated when her other symptoms are at a peak? What is the clinical term used to describe this condition?

            How does the duration of activity of the circulating catecholamines compare to that of neuronally released norepinephrine? Explain.

            How does the breadth of activity of the circulating catecholamines compare to that of neuronally released norepinephrine? Explain.

            In order to prepare the patient for surgery, what types of autonomic nervous system medications may be used to stabilize her blood pressure within the normal range?


            Key Terms

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              • Authors: J. Gordon Betts, Kelly A. Young, James A. Wise, Eddie Johnson, Brandon Poe, Dean H. Kruse, Oksana Korol, Jody E. Johnson, Mark Womble, Peter DeSaix
              • Publisher/website: OpenStax
              • Book title: Anatomy and Physiology
              • Publication date: Apr 25, 2013
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              © Sep 11, 2020 OpenStax. Textbook content produced by OpenStax is licensed under a Creative Commons Attribution License 4.0 license. The OpenStax name, OpenStax logo, OpenStax book covers, OpenStax CNX name, and OpenStax CNX logo are not subject to the Creative Commons license and may not be reproduced without the prior and express written consent of Rice University.


              Watch the video: Organization and Physiology of Autonomic Nervous System by Parmar (July 2022).


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