Autonomic Nervous System: Anatomy

Overview

Definition

The ANS is responsible for controlling functions that do not require conscious thought.

• Controls unconscious Unconscious Those forces and content of the mind which are not ordinarily available to conscious awareness or to immediate recall. Psychotherapy, involuntary, and visceral body functions
• Trajectory: CNS → ganglion → target tissue

Components

• Afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology ( sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology) neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology that originate in visceral receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors and provide inputs to the CNS
• Efferent Efferent Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology (effector or motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology) neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology generally consist of a 2-neuron series:
  • Preganglionic (presynaptic) neuron with a cell body in the CNS
  • Postganglionic (postsynaptic) neuron with a cell body in the periphery that innervates target tissues
• Presynaptic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology of both the parasympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification (PNS) and sympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification (SNS) accomplish synaptic signal transmission using acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS ( ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS) as a neurotransmitter.
• Postsynaptic sympathetic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology primarily release norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS (NE), but typically engage in co-transmission, simultaneously releasing ATP and neuropeptide Y. The predominant neurotransmitter varies by target tissue and physiological context.
• Postsynaptic parasympathetic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology generally accomplish synaptic signal transmission using ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS as a neurotransmitter.
• Enteric nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification (ENS) neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology may have 3 or more neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology in their pathways and accomplish synaptic signal transmission using several neurotransmitters:
  • ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS
  • Nitric oxide Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from arginine by nitric oxide synthase. Nitric oxide is one of the endothelium-dependent relaxing factors released by the vascular endothelium and mediates vasodilation. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic gmp. Pulmonary Hypertension Drugs (NO)
  • Serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS ( 5-hydroxytryptamine 5-hydroxytryptamine A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS (5HT))
  • GABA GABA The most common inhibitory neurotransmitter in the central nervous system. Receptors and Neurotransmitters of the CNS
  • Substance P
  • VIP VIP A highly basic, 28 amino acid neuropeptide released from intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems and is neuroprotective. It binds special receptors. Gastrointestinal Neural and Hormonal Signaling ( vasoactive intestinal peptide Vasoactive intestinal peptide A highly basic, 28 amino acid neuropeptide released from intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems and is neuroprotective. It binds special receptors. Gastrointestinal Neural and Hormonal Signaling)

Divisions of the ANS

• Sympathetic system:
  • Activation leads to a state of overall elevated function
  • Responsible for the “fight-or-flight” response
  • Connections to most tissues of the body
  • Sympathetic dominance → ↑ HR, ↑ blood pressure, cessation of GI peristalsis Peristalsis A movement, caused by sequential muscle contraction, that pushes the contents of the intestines or other tubular organs in one direction. Gastrointestinal Motility, glycogenolysis Glycogenolysis The release of glucose from glycogen by glycogen phosphorylase (phosphorolysis). The released glucose-1-phosphate is then converted to glucose-6-phosphate by phosphoglucomutase before entering glycolysis. Glycogenolysis is stimulated by glucagon or epinephrine via the activation of phosphorylase kinase. Glycogen Metabolism
• Parasympathetic system:
  • Activation leads to a state of overall depressed function
  • Responsible for the “rest-and-digest” response
  • Parasympathetic dominance → ↓ HR, ↓ blood pressure, promotion of GI peristalsis Peristalsis A movement, caused by sequential muscle contraction, that pushes the contents of the intestines or other tubular organs in one direction. Gastrointestinal Motility, glycogenesis Glycogenesis Glycogen Metabolism
• ENS:
  • Involved in the regulation of digestive processes
  • Capable of functioning independently of the remainder of the nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification
  • Made up primarily of 2 complex bundles of nerves:
    • The myenteric (Auerbach) plexus
    • The submucosal (Meissner) plexus
  • Exception to the 2-neuron innervation rule of the ANS

Sympathetic Nervous System

The SNS is involved with many of the functions associated with the “fight-or-flight” response. Although this response is at the extreme end of the sympathetic physiology spectrum, it serves as a model to understand that the SNS enables our tissues to respond appropriately to varying degrees of physiologic stress.

Sympathetic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology

• Cell bodies of preganglionic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology are located in the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy:
  • Emerge from the thoracolumbar regions
  • Located in the intermediolateral columns ( lateral horns Lateral horns One of three central columns of the spinal cord. It is composed of gray matter and is located laterally in lamina vii. Spinal Cord: Anatomy)
  • Presynaptic fibers exit the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy through the anterior roots and enter the anterior rami of T1‒L2.
  • Anterior roots give off branches (white rami communicantes) to the sympathetic trunks. Sympathetic fibers may:
    • Travel (ascend or descend) in the sympathetic trunks to a paravertebral ganglion → synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission with postganglionic sympathetic fibers
    • Join the adjacent anterior spinal nerve rami via branches (gray rami communicantes) → synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission with postganglionic sympathetic fibers
    • Pass through the sympathetic trunk (without synapsing), becoming continuous with 1 of the splanchnic nerves to reach and ultimately synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission with the prevertebral ganglia
    • Pass through the celiac ganglion (without synapsing) and travel directly to their target organ (only applies to the adrenal gland) to synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission with chromaffin cells Chromaffin cells Cells that store epinephrine secretory vesicles. During times of stress, the nervous system signals the vesicles to secrete their hormonal content. Their name derives from their ability to stain a brownish color with chromic salts. Characteristically, they are located in the adrenal medulla and paraganglia of the sympathetic nervous system. Adrenal Hormones, which secrete epinephrine Epinephrine The active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. Sympathomimetic Drugs directly into the bloodstream (another exception to the 2-nerve rule of the ANS).
    • ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS is the neurotransmitter at all of the above synapses.
• Paravertebral ganglia form a string of nodules known as the sympathetic trunk:
  • Located adjacent to the spinal column Spinal column The human spine, or vertebral column, is the most important anatomical and functional axis of the human body. It consists of 7 cervical vertebrae, 12 thoracic vertebrae, and 5 lumbar vertebrae and is limited cranially by the skull and caudally by the sacrum. Vertebral Column: Anatomy
  • Site of synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission between preganglionic and postganglionic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology
  • Ganglia are generally organized as follows:
    • 3 cervical ganglia (superior, middle, and inferior)
    • 12 thoracic ganglia (inferior cervical ganglion and the 1st thoracic ganglion may fuse to form the “stellate” ganglion)
    • 4 lumbar ganglia
    • 5 sacral ganglia
• Distal to the paravertebral ganglia, all nerves become splanchnic nerves.
• Splanchnic nerves contain afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology and efferent Efferent Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology fibers that convey information between the CNS and visceral structures:
  • Cardiopulmonary splanchnic nerves carry postsynaptic fibers that innervate the thoracic viscera.
  • Abdominopelvic splanchnic nerves carry postsynaptic fibers that innervate the abdominal and pelvic viscera.
• The abdominal and pelvic viscera are innervated by abdominopelvic splanchnic nerves.
  • Recall, these nerves pass through the sympathetic trunks (without synapsing) to become splanchnic nerves.
  • Abdominopelvic splanchnic nerves include:
    • Greater splanchnic nerve
    • Lesser splanchnic nerve
    • Least splanchnic nerve
    • Lumbar splanchnic nerve
  • Presynaptic nerves ultimately synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission in the prevertebral ganglia.
  • Prevertebral ganglia lie close to their target organ and branches of the aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy.
  • Prevertebral ganglia include:
    • Celiac ganglion
    • Aorticorenal ganglion
    • Superior mesenteric ganglion
    • Inferior mesenteric ganglion
  • Splanchnic/ganglionic connections:
    • Greater splanchnic nerve → celiac ganglion
    • Lesser + least splanchnic nerves → aorticorenal ganglion
    • Least + lumbar splanchnic nerves → superior and inferior mesenteric ganglia
  • Ganglionic/visceral connections:
    • Celiac ganglion (innervates the foregut-derived organs) → distal esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy, stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy, proximal duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy, pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, biliary system, spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy, adrenal glands Adrenal Glands The adrenal glands are a pair of retroperitoneal endocrine glands located above the kidneys. The outer parenchyma is called the adrenal cortex and has 3 distinct zones, each with its own secretory products. Beneath the cortex lies the adrenal medulla, which secretes catecholamines involved in the fight-or-flight response. Adrenal Glands: Anatomy
    • Aorticorenal ganglion → aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy, kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy
    • Superior mesenteric ganglion (innervates the midgut-derived organs) → distal duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy, jejunum Jejunum The middle portion of the small intestine, between duodenum and ileum. It represents about 2/5 of the remaining portion of the small intestine below duodenum. Small Intestine: Anatomy, ileum Ileum The distal and narrowest portion of the small intestine, between the jejunum and the ileocecal valve of the large intestine. Small Intestine: Anatomy, cecum Cecum The blind sac or outpouching area of the large intestine that is below the entrance of the small intestine. It has a worm-like extension, the vermiform appendix. Colon, Cecum, and Appendix: Anatomy, appendix Appendix A worm-like blind tube extension from the cecum. Colon, Cecum, and Appendix: Anatomy, ascending colon Ascending colon The segment of large intestine between the cecum and the transverse colon. It passes cephalad from the cecum to the caudal surface of the right lobe of the liver where it bends sharply to the left, forming the right colic flexure. Colon, Cecum, and Appendix: Anatomy, proximal transverse colon Transverse colon The segment of large intestine between ascending colon and descending colon. It passes from the right colic flexure across the abdomen, then turns sharply at the left colonic flexure into the descending colon. Colon, Cecum, and Appendix: Anatomy
    • Inferior mesenteric ganglion (innervates the hindgut-derived organs) → distal transverse colon Transverse colon The segment of large intestine between ascending colon and descending colon. It passes from the right colic flexure across the abdomen, then turns sharply at the left colonic flexure into the descending colon. Colon, Cecum, and Appendix: Anatomy, descending colon Descending colon The segment of large intestine between transverse colon and the sigmoid colon. Colon, Cecum, and Appendix: Anatomy, sigmoid Sigmoid A segment of the colon between the rectum and the descending colon. Volvulus colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy, rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy, anal canal, bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess, external genitalia, gonads Gonads The gamete-producing glands, ovary or testis. Hormones: Overview and Types
• Postganglionic sympathetic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology then travel to their target tissues where they stimulate sympathetic activity specific to the target organ.
  • NE is released as a neurotransmitter at adrenergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors in most organs.
  • Adrenergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors include:
    • Alpha-adrenergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors:
      • Alpha-1 (α₁): 3 subtypes (α₁ₐ, α₁ᵦ, α₁ᵈ) – primarily mediating smooth muscle contraction Smooth muscle contraction Smooth muscle is primarily found in the walls of hollow structures and some visceral organs, including the walls of the vasculature, GI, respiratory, and genitourinary tracts. Smooth muscle contracts more slowly and is regulated differently than skeletal muscle. Smooth muscle can be stimulated by nerve impulses, hormones, metabolic factors (like pH, CO2 or O2 levels), its own intrinsic pacemaker ability, or even mechanical stretch. Smooth Muscle Contraction
      • Alpha-2 (α₂): 3 subtypes (α₂ₐ, α₂ᵦ, α₂ᶜ) – primarily inhibitory autoreceptors and heteroreceptors
    • Beta-adrenergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors:
      • Beta-1 (β₁): Primarily cardiac effects
      • Beta-2 (β₂): Primarily smooth muscle relaxation and metabolic effects
      • Beta-3 (β₃): Primarily metabolic effects in adipose tissue Adipose tissue Adipose tissue is a specialized type of connective tissue that has both structural and highly complex metabolic functions, including energy storage, glucose homeostasis, and a multitude of endocrine capabilities. There are three types of adipose tissue, white adipose tissue, brown adipose tissue, and beige or “brite” adipose tissue, which is a transitional form. Adipose Tissue: Histology
      • Beta-4 (β₄): Recently identified, primarily in cardiac tissue
  • Peptides may be released at the synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission in addition to NE:
    • Neuropeptide Y is released at the cardiac vessels to regulate coronary blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure.
    • Somatostatin Somatostatin A 14-amino acid peptide named for its ability to inhibit pituitary growth hormone release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of thyroid-stimulating hormone; prolactin; insulin; and glucagon besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, srif-28 with a 14-amino acid extension at the n-terminal. Gastrointestinal Secretions is released at the intestinal mucosa Intestinal Mucosa Lining of the intestines, consisting of an inner epithelium, a middle lamina propria, and an outer muscularis mucosae. In the small intestine, the mucosa is characterized by a series of folds and abundance of absorptive cells (enterocytes) with microvilli. Small Intestine: Anatomy to regulate GI motility GI Motility The primary functions of the GI tract are digestion and absorption, which require coordinated contractions of the smooth muscles present in the GI tract. Peristaltic waves, segmentation contractions, and the migrating motor complex are all important contraction patterns that help to mix contents, get them in contact with the intestinal walls, and propel material down the tract at appropriate times and in appropriate amounts. Gastrointestinal Motility.
  • ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS is released as a neurotransmitter at the sympathetic cholinergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors in:
    • Sweat glands Sweat glands Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. Soft Tissue Abscess
    • Piloerector muscles of the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions (stimulation causes “goosebumps”)
    • Precapillary resistance vessels Resistance vessels Arteries: Histology located in skeletal muscle beds
  • Cholinergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors in the SNS are of the muscarinic subtype.
  • Peptides may be released in addition to ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS at the synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission:
    • Vasoactive intestinal peptide Vasoactive intestinal peptide A highly basic, 28 amino acid neuropeptide released from intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems and is neuroprotective. It binds special receptors. Gastrointestinal Neural and Hormonal Signaling ( VIP VIP A highly basic, 28 amino acid neuropeptide released from intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems and is neuroprotective. It binds special receptors. Gastrointestinal Neural and Hormonal Signaling) is released in the skeletal muscle beds and acts as a potent vasodilator.
    • Calcitonin Calcitonin A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. Other Antiresorptive Drugs gene-related peptide ( CGRP CGRP A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator. Gastrointestinal Neural and Hormonal Signaling) is released in the intracranial and extracranial vessels and acts as a potent vasodilator.

Sympathetic functions

At its extreme, the SNS triggers the “fight-or-flight” response in reaction to physiologic stress.

• Primarily a vascular response
• Most vessels respond to sympathetic stimulation by vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure and redirect blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure vital to “fight-or-flight” from:
  • Abdominal visceral organs 
  • Pelvic visceral organs
• Notable exceptions:
  • Coronary vessels dilate to enhance myocardial perfusion and enhance cardiac performance.
  • Vessels of the skeletal muscle beds dilate to enhance muscular perfusion and enhance muscular performance.
  • Vessels of the external genitalia dilate to allow arousal and erection Erection The state of the penis when the erectile tissue becomes filled or swollen (tumid) with blood and causes the penis to become rigid and elevated. It is a complex process involving central nervous system; peripheral nervous systems; hormones; smooth muscles; and vascular functions. Penis: Anatomy.
• The vascular response of a given target tissue depends on:
  • The relative proportion of alpha to beta receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
  • The presence of peptides released with neurotransmission Neurotransmission The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across electrical synapses. Synapses and Neurotransmission at the synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission

In times of normal physiologic stress, the SNS is still constitutively active (but in balance with the PNS):

• There is tonic stimulation of blood vessels but not to the extent of extreme vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure:
  • SNS and PNS allow coordinated activities at the level of the alveolar-capillary interface in the lung to allow optimal O₂ exchange.
  • SNS and PNS allow coordinated activities at the level of the intestinal epithelium-capillary interface to allow optimal absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption.
• At times of rest, SNS-mediated vascular tonicity Tonicity Plasma tonicity refers to the concentration of only the osmotically active solutes in blood Renal Sodium and Water Regulation is at a minimum.

The SNS plays a complex role in immune regulation:

• Innervates primary and secondary lymphoid organs Lymphoid organs A system of organs and tissues that process and transport immune cells and lymph. Primary Lymphatic Organs ( bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis, thymus Thymus A single, unpaired primary lymphoid organ situated in the mediastinum, extending superiorly into the neck to the lower edge of the thyroid gland and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat. Lymphatic Drainage System: Anatomy, spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy, lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy)
• Forms direct neuro-immune synapses with immune cells
• Most immune cells express multiple adrenergic receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors subtypes
• Effects on immune function are context-dependent:
  • Acute sympathetic activation: pro-inflammatory (β-receptor-mediated)
  • Chronic sympathetic activation: immunosuppressive (α-receptor-mediated)
• Regulates lymphocyte trafficking, cytokine production, and antibody responses
• Critical in coordinating neuro-immune responses during stress, infection, and inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
• Dysregulation contributes to autoimmune and inflammatory disorders

Parasympathetic Nervous System

The PNS is involved with many of the functions associated with “rest and digest.” Although the “rest-and-digest” response is at the extreme end of the parasympathetic physiology spectrum, it serves as a model to understand that the PNS enables our tissues to recover appropriately from and/or balance varying degrees of physiologic stress.

Parasympathetic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology

• Parasympathetic fibers emerge from the craniosacral regions of the nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification.
• Cell bodies of the preganglionic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology are located in the cranial nerve (CN) nuclei (CN III, CN VII, CN IX, and CN X) and in the terminal portion of the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy (S2-S4):
  • CN X ( vagus nerve Vagus nerve The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). Pharynx: Anatomy, comprises the majority of the PNS) has multiple nuclei in the medulla:
    • Dorsal motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles of the vagus (DMV): primary source of efferent Efferent Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology parasympathetic output to thoracic and abdominal viscera
    • Nucleus ambiguus Nucleus ambiguus Brain Stem: Anatomy: contains preganglionic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology to the heart and laryngeal muscles Laryngeal muscles The striated muscle groups which move the larynx as a whole or its parts, such as altering tension of the vocal cords, or size of the slit (rima glottidis). Larynx: Anatomy
    • Nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles tractus solitarius (NTS): integration center for afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology information, organized into subnuclei with distinct functions:
      • Gustatory subnucleus: taste sensation
      • Cardiorespiratory subnuclei: process visceral afferents
      • Gelatinous subnucleus: pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways modulation
    • Spinal trigeminal nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles: processes somatosensory information from the ear, laryngeal mucosa, and meninges Meninges The brain and the spinal cord are enveloped by 3 overlapping layers of connective tissue called the meninges. The layers are, from the most external layer to the most internal layer, the dura mater, arachnoid mater, and pia mater. Between these layers are 3 potential spaces called the epidural, subdural, and subarachnoid spaces. Meninges: Anatomy
    • Area postrema: chemosensitive “vomiting center”
• Some preganglionic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission inside the cranial vault Cranial Vault Increased Intracranial Pressure (ICP) in 1 of the 4 pairs of intracranial sympathetic ganglia:
  • CN III → ciliary ganglion Ciliary Ganglion Pupil: Physiology and Abnormalities → innervates the:
    • Iris
    • Pupillary  ciliary muscles Ciliary Muscles Pupil: Physiology and Abnormalities
  • CN VII → pterygopalatine and submandibular ganglia → innervate the:
    • Lacrimal glands Lacrimal Glands Dacryocystitis
    • Nasal glands
    • Palatine glands
    • Pharyngeal glands
    • Sublingual glands Sublingual glands A salivary gland on each side of the mouth below the tongue. Gastrointestinal Secretions
    • Submandibular glands Submandibular glands One of two salivary glands in the neck, located in the space bound by the two bellies of the digastric muscle and the angle of the mandible. It discharges through the submandibular duct. The secretory units are predominantly serous although a few mucous alveoli, some with serous demilunes, occur. Gastrointestinal Secretions
  • CN IX → otic ganglion → innervates the parotid glands Parotid glands The largest of the three pairs of salivary glands. They lie on the sides of the face immediately below and in front of the ear. Gastrointestinal Secretions
• Some preganglionic neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology outside the cranial vault Cranial Vault Increased Intracranial Pressure (ICP) synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission in the terminal or intramural ganglia of the target organ(s):
  • CN X ( vagus nerve Vagus nerve The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). Pharynx: Anatomy) → terminal ganglia of the:
    • Thoracic viscera: heart, lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy, distal esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy, stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy, proximal duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy, pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, biliary system, spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy
    • Midgut Midgut Development of the Abdominal Organs viscera: distal duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy, jejunum Jejunum The middle portion of the small intestine, between duodenum and ileum. It represents about 2/5 of the remaining portion of the small intestine below duodenum. Small Intestine: Anatomy, ileum Ileum The distal and narrowest portion of the small intestine, between the jejunum and the ileocecal valve of the large intestine. Small Intestine: Anatomy, cecum Cecum The blind sac or outpouching area of the large intestine that is below the entrance of the small intestine. It has a worm-like extension, the vermiform appendix. Colon, Cecum, and Appendix: Anatomy, appendix Appendix A worm-like blind tube extension from the cecum. Colon, Cecum, and Appendix: Anatomy, ascending colon Ascending colon The segment of large intestine between the cecum and the transverse colon. It passes cephalad from the cecum to the caudal surface of the right lobe of the liver where it bends sharply to the left, forming the right colic flexure. Colon, Cecum, and Appendix: Anatomy, proximal transverse colon Transverse colon The segment of large intestine between ascending colon and descending colon. It passes from the right colic flexure across the abdomen, then turns sharply at the left colonic flexure into the descending colon. Colon, Cecum, and Appendix: Anatomy
    • Note: The distal transverse colon Transverse colon The segment of large intestine between ascending colon and descending colon. It passes from the right colic flexure across the abdomen, then turns sharply at the left colonic flexure into the descending colon. Colon, Cecum, and Appendix: Anatomy receives dual innervation, with parasympathetic supply transitioning from vagal to pelvic splanchnic sources.
  • Pelvic splanchnic nerves ( S2 S2 Heart Sounds– S4 S4 Heart Sounds) → terminal ganglia of the:
    • Hindgut Hindgut Development of the Abdominal Organs viscera: distal transverse colon Transverse colon The segment of large intestine between ascending colon and descending colon. It passes from the right colic flexure across the abdomen, then turns sharply at the left colonic flexure into the descending colon. Colon, Cecum, and Appendix: Anatomy, descending colon Descending colon The segment of large intestine between transverse colon and the sigmoid colon. Colon, Cecum, and Appendix: Anatomy, sigmoid Sigmoid A segment of the colon between the rectum and the descending colon. Volvulus colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy, rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy, and upper anal canal
    • Pelvic viscera: lower ureters Ureters One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the urinary bladder. Urinary Tract: Anatomy, bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess, urethra Urethra A tube that transports urine from the urinary bladder to the outside of the body in both the sexes. It also has a reproductive function in the male by providing a passage for sperm. Urinary Tract: Anatomy, uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy, cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy, external genitalia
• Afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology parasympathetic fibers comprise visceral afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology fibers that convey input to the vagus nerve Vagus nerve The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). Pharynx: Anatomy and pelvic splanchnic nerves:
  • From the carotid and aortic baroreceptors Baroreceptors Receptors in the vascular system, particularly the aorta and carotid sinus, which are sensitive to stretch of the vessel walls. Diabetes Insipidus
  • From the heart, lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy, and alimentary tract
  • From the pelvic organs and external genitalia
• The majority of parasympathetic nerves are sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology and innervate most major organs.
• Preganglionic and postganglionic PNS release ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS as a neurotransmitter onto the cholinergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors:
  • Muscarinic cholinergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors:
    • M₁: neural/CNS, gastric parietal cells Parietal cells Rounded or pyramidal cells of the gastric glands. They secrete hydrochloric acid and produce gastric intrinsic factor, a glycoprotein that binds vitamin B12. Stomach: Anatomy
    • M₂: cardiac tissue, smooth muscle, neural
    • M₃: exocrine glands Exocrine glands Glands of external secretion that release its secretions to the body’s cavities, organs, or surface, through a duct. Glandular Epithelium: Histology, smooth muscle, endothelium Endothelium A layer of epithelium that lines the heart, blood vessels (vascular endothelium), lymph vessels (lymphatic endothelium), and the serous cavities of the body. Arteries: Histology
    • M₄: CNS, primarily presynaptic autoreceptors
    • M₅: CNS, particularly in substantia nigra Substantia nigra The black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce dopamine, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored melanin is a by-product of dopamine synthesis. Basal Ganglia: Anatomy and hippocampus
    • All cholinergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors at the preganglionic/postganglionic synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission are of the muscarinic subtype.
    • Cholinergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors at the sweat glands Sweat glands Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. Soft Tissue Abscess are of the muscarinic subtype.
  • Nicotinic cholinergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors: Cholinergic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors at most other target organs are of the nicotinic subtype.
  • Peptides may be released in addition to ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS at the synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission:
    • Neuropeptide Y
    • VIP VIP A highly basic, 28 amino acid neuropeptide released from intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems and is neuroprotective. It binds special receptors. Gastrointestinal Neural and Hormonal Signaling
    • CGRP CGRP A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator. Gastrointestinal Neural and Hormonal Signaling

Parasympathetic functions

At its extreme, the PNS triggers the “rest-and-digest” response in reaction to a need for physiologic recovery and balances the actions of the SNS.

• Decreases contractility in the atrial and ventricular myocardium Myocardium The muscle tissue of the heart. It is composed of striated, involuntary muscle cells connected to form the contractile pump to generate blood flow. Heart: Anatomy
• Reduces cardiac conduction velocity to slow tachycardic rhythms and prevent arrhythmias
• Promotes salivation
• Promotes/increases GI peristalsis Peristalsis A movement, caused by sequential muscle contraction, that pushes the contents of the intestines or other tubular organs in one direction. Gastrointestinal Motility and secretory activity
• Contracts smooth muscle in the airways during inspiration Inspiration Ventilation: Mechanics of Breathing to maintain patency

The PNS plays a crucial role in immune regulation:

• Parasympathetic ganglia inflammatory cytokine receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors:
  • “Inflammatory reflex” – vagus nerve Vagus nerve The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). Pharynx: Anatomy detects peripheral inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation via cytokine receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
  • Cholinergic anti-inflammatory pathway – efferent Efferent Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology vagal signaling suppresses pro-inflammatory cytokine production
  • Vagal efferents synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission with splenic nerve, releasing norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS
  • Norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS stimulates acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS release from T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions expressing choline acetyltransferase
  • Acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS binds α7 nicotinic receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors on macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation, inhibiting TNF-α, IL-1β, and IL-6 production
  • Forms a neuro-immune circuit distinct from hypothalamic-pituitary-adrenal axis Hypothalamic-pituitary-adrenal axis Adrenal Hormones
  • Therapeutic target for inflammatory disorders including rheumatoid arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis and inflammatory bowel disease

Sympathetic vs Parasympathetic Nervous System

Enteric Nervous System

The enteric portion of the ANS is associated with functions of digestion Digestion Digestion refers to the process of the mechanical and chemical breakdown of food into smaller particles, which can then be absorbed and utilized by the body. Digestion and Absorption and regulation of the GI secretions and the smooth muscle.

Intramural nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification

• Located in the wall of the GI tract (plexus entericus)
• Approximately 500 million neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology with more than 20 distinct functional neuron types form sophisticated neural networks
• Involved in the regulation of digestive processes and is capable of functioning independently of the remainder of the nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification
  • Fully self-contained and capable of independent function via local reflex activity
  • Connected to, communicates with, and receives feedback from the SNS and PNS.
• Consists of 2 ganglion-rich plexuses:
  • Submucous plexus ( Meissner plexus Meissner plexus One of two ganglionated neural networks which together form the enteric nervous system. The submucous (Meissner’s) plexus is in the connective tissue of the submucosa. Its neurons innervate the epithelium, blood vessels, endocrine cells, other submucosal ganglia, and myenteric ganglia, and play an important role in regulating ion and water transport. Gastrointestinal Neural and Hormonal Signaling): found in the submucosa → regulates fluid and electrolyte movement across the intestinal mucosa Intestinal Mucosa Lining of the intestines, consisting of an inner epithelium, a middle lamina propria, and an outer muscularis mucosae. In the small intestine, the mucosa is characterized by a series of folds and abundance of absorptive cells (enterocytes) with microvilli. Small Intestine: Anatomy
  • Myenteric plexus Myenteric plexus One of two ganglionated neural networks which together form the enteric nervous system. The myenteric (Auerbach’s) plexus is located between the longitudinal and circular muscle layers of the gut. Its neurons project to the circular muscle, to other myenteric ganglia, to submucosal ganglia, or directly to the epithelium, and play an important role in regulating and patterning gut motility. Gastrointestinal Neural and Hormonal Signaling ( Auerbach plexus Auerbach plexus One of two ganglionated neural networks which together form the enteric nervous system. The myenteric (Auerbach’s) plexus is located between the longitudinal and circular muscle layers of the gut. Its neurons project to the circular muscle, to other myenteric ganglia, to submucosal ganglia, or directly to the epithelium, and play an important role in regulating and patterning gut motility. Gastrointestinal Neural and Hormonal Signaling): found in the muscularis propria between the longitudinal and circular layers of the smooth muscle in walls of the GI tract → coordinates smooth muscle contractions involved in peristalsis Peristalsis A movement, caused by sequential muscle contraction, that pushes the contents of the intestines or other tubular organs in one direction. Gastrointestinal Motility
  • Deep muscular plexus: located within the circular muscle layer
• ENS neuron types:
  • Intrinsic primary afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology (IPANs): sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology detecting mechanical, chemical, and thermal stimuli
  • Interneurons: form chains for ascending and descending signal propagation Propagation Propagation refers to how the electrical signal spreads to every myocyte in the heart. Cardiac Physiology
  • Motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology: excitatory and inhibitory control of smooth muscle, secretion Secretion Coagulation Studies, and blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure
  • Intestinofugal neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology: project outside the gut to prevertebral ganglia
  • Secretomotor/vasomotor neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology: regulate secretion Secretion Coagulation Studies and blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure
• Enteric glial cells Glial Cells The non-neuronal cells of the nervous system. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the blood-brain barrier and blood-retinal barrier, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear. Nervous System: Histology:
  • Outnumber enteric neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology 2:1
  • Functionally similar to CNS astrocytes Astrocytes A class of large neuroglial (macroglial) cells in the central nervous system – the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from ‘star’ cells) are irregularly shaped with many long processes, including those with ‘end feet’ which form the glial (limiting) membrane and directly and indirectly contribute to the blood-brain barrier. They regulate the extracellular ionic and chemical environment, and ‘reactive astrocytes’ (along with microglia) respond to injury. Nervous System: Histology
  • Regulate intestinal barrier function
  • Participate in neuro-immune interactions
  • Essential for ENS development and maintenance

Sympathetic innervation

• Prevertebral ganglia:
  • Celiac ganglia
  • Superior mesenteric ganglia
  • Inferior mesenteric ganglia
• Nerves:
  • Splanchnic nerve(s)
  • Hypogastric nerve(s)
  • Colonic nerve(s)
• Effects:
  • ↓ GI peristalsis Peristalsis A movement, caused by sequential muscle contraction, that pushes the contents of the intestines or other tubular organs in one direction. Gastrointestinal Motility and secretion Secretion Coagulation Studies
  • Constriction of GI sphincters

Parasympathetic innervation

• Nerves:
  • Vagus
  • Pelvic splanchnic nerves ( S2 S2 Heart Sounds– S4 S4 Heart Sounds)
  • Afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology nerves → conscious sensation of visceral function (e.g., hunger, distention, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics)
• Effects:
  • ↑ GI peristalsis Peristalsis A movement, caused by sequential muscle contraction, that pushes the contents of the intestines or other tubular organs in one direction. Gastrointestinal Motility and secretion Secretion Coagulation Studies
  • Relaxation of GI sphincters

Clinical Relevance

• Horner syndrome Horner syndrome Horner syndrome is a condition resulting from an interruption of the sympathetic innervation of the eyes. The syndrome is usually idiopathic but can be directly caused by head and neck trauma, cerebrovascular disease, or a tumor of the CNS. Horner Syndrome: a condition resulting from any pathology that causes damage to the sympathetic nerves of 1 side of the face, affecting the sympathetic output of the superior cervical ganglion. Horner syndrome Horner syndrome Horner syndrome is a condition resulting from an interruption of the sympathetic innervation of the eyes. The syndrome is usually idiopathic but can be directly caused by head and neck trauma, cerebrovascular disease, or a tumor of the CNS. Horner Syndrome results from a traumatic injury, a disease, or a hereditary mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations. A commonly examined scenario is where Horner syndrome Horner syndrome Horner syndrome is a condition resulting from an interruption of the sympathetic innervation of the eyes. The syndrome is usually idiopathic but can be directly caused by head and neck trauma, cerebrovascular disease, or a tumor of the CNS. Horner Syndrome can present in a Pancoast lung tumor Tumor Inflammation and its metastatic spread can invade the sympathetic chain. Symptoms include unilateral miosis Miosis Pupil: Physiology and Abnormalities and ptosis Ptosis Cranial Nerve Palsies, as well as anhidrosis of the affected side of the face.
• Cardiovascular autonomic neuropathy Neuropathy Leprosy (CAN): a serious complication of diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus characterized by damage to autonomic nerve fibers Nerve Fibers Slender processes of neurons, including the axons and their glial envelopes (myelin sheath). Nerve fibers conduct nerve impulses to and from the central nervous system. Nervous System: Histology innervating the heart and blood vessels. Clinical manifestations include resting tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, exercise intolerance, orthostatic hypotension Orthostatic hypotension A significant drop in blood pressure after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm hg decrease in systolic pressure or a 10-mm hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include dizziness, blurred vision, and syncope. Hypotension, and silent myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction. Diagnosis involves cardiovascular autonomic reflex tests (CARTs) and heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology variability analysis. Treatment focuses on glycemic control, lifestyle modifications, and symptom management.
• ANS dysfunction (dysautonomia): encompasses a spectrum of disorders affecting autonomic regulation. Causes range from primary forms like pure autonomic failure Pure autonomic failure A degenerative disease of the autonomic nervous system that is characterized by idiopathic orthostatic hypotension and a greatly reduced level of catecholamines. No other neurological deficits are present. Hypotension and multiple system atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation to secondary forms linked to metabolic (e.g., diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus), infectious (e.g., HIV HIV Anti-HIV Drugs, post-COVID), autoimmune, neurodegenerative, and paraneoplastic conditions. Symptoms may include orthostatic hypotension Orthostatic hypotension A significant drop in blood pressure after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm hg decrease in systolic pressure or a 10-mm hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include dizziness, blurred vision, and syncope. Hypotension, abnormal sweating, GI and urinary dysfunction, and sexual issues. Diagnosis involves autonomic function tests, tilt-table testing, and sudomotor and sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology assessments. Treatment includes lifestyle changes, medications, and neuromodulation therapies such as vagus nerve Vagus nerve The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). Pharynx: Anatomy stimulation, spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy stimulation, and deep brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification stimulation in selected cases.
• Gut-brain axis disorders: bidirectional communication Communication The exchange or transmission of ideas, attitudes, or beliefs between individuals or groups. Decision-making Capacity and Legal Competence network between the CNS and ENS, involving neural, immune, and endocrine pathways. Dysregulation is implicated in functional gastrointestinal disorders ( IBS IBS Irritable bowel syndrome (IBS) is a functional bowel disease characterized by chronic abdominal pain and altered bowel habits without an identifiable organic cause. The etiology and pathophysiology of this disease are not well understood, and there are many factors that may contribute. Irritable Bowel Syndrome, functional dyspepsia Dyspepsia Impaired digestion, especially after eating. Lactose Intolerance), neurodevelopmental disorders ( autism spectrum disorder Autism spectrum disorder Autism spectrum disorder (ASD) is a neurodevelopmental disorder marked by poor social skills, restricted interests/social interactions, and repetitive/stereotyped behaviors. The condition is termed a “spectrum” because of the wide variability in the severity of symptoms exhibited. Autism Spectrum Disorder), and neurodegenerative diseases (Parkinson). Therapeutic approaches include dietary interventions, probiotics, prebiotics, and neuromodulation.