Notes on the Sympathetic Nervous System

Introduction to Sympathetic Nervous System

The sympathetic nervous system (SNS) is a major division of the autonomic nervous system, functioning primarily to prepare the body for perceived threats or challenging situations, commonly referred to as the "fight-or-flight" response. Its activation results in widespread physiological adjustments designed to optimize immediate survival and performance.

Key components include:

• Preganglionic neurons: Originating in the spinal cord.

• Postganglionic neurons: Synapsing with preganglionic neurons in ganglia and extending to target organs.

• Neurotransmitters: Primarily acetylcholine at ganglia and norepinephrine at most target organs.

Regulation of Glucose Release

The sympathetic nervous system exerts a profound influence on metabolic processes, particularly glucose homeostasis. During periods of stress, physical exertion, or perceived danger, the SNS stimulates the rapid release of stored glucose into the bloodstream.

This crucial energy mobilization involves:

• Hepatic Glycogenolysis: The breakdown of glycogen, the stored form of glucose, in the liver. This process is primarily mediated by epinephrine acting on hepatocytes' $\beta_2$ adrenergic receptors and glucagon, leading to a rapid elevation in blood glucose.

• Hepatic Gluconeogenesis: The synthesis of new glucose from non-carbohydrate precursors (e.g., lactate, amino acids, glycerol) in the liver. This pathway ensures a sustained supply of glucose, particularly during prolonged stress or fasting.

• Adrenal Medulla Stimulation: Preganglionic sympathetic fibers stimulate chromaffin cells in the adrenal medulla to release epinephrine (approximately 80%) and norepinephrine (approximately 20%) directly into the bloodstream. These catecholamines act systemically to enhance glucose mobilization.

• Pancreatic Effects: The SNS can inhibit insulin secretion from pancreatic $\beta$ cells via $\alpha<em>2$ adrenergic receptors, and stimulate glucagon secretion from pancreatic $\alpha$ cells via $\beta</em>2$ adrenergic receptors, both actions contributing to hyperglycemia.

This immediate surge in blood glucose provides essential fuel for skeletal muscles, the heart, and the brain, enabling sustained physical and cognitive activity during stressful scenarios.

Role in Body Temperature Regulation

The sympathetic nervous system is a crucial regulator of core body temperature, orchestrating both heat dissipation and heat conservation mechanisms.

Heat Dissipation (when body is too hot):

• Sweating: Postganglionic sympathetic fibers (unusual in that they release acetylcholine, not norepinephrine, at the sweat glands) stimulate eccrine sweat glands to secrete sweat onto the skin surface. Evaporation of this sweat is the primary mechanism for cooling the body.

• Cutaneous Vasodilation: Sympathetic cholinergic fibers can indirectly cause vasodilation in cutaneous blood vessels by inhibiting tonic sympathetic vasoconstrictor tone, thereby increasing blood flow to the skin. This facilitates conductive and convective heat loss to the environment. Recent evidence also points to sympathetic vasodilator fibers releasing nitric oxide and vasoactive intestinal peptide.

Heat Conservation (when body is too cold):

• Cutaneous Vasoconstriction: Sympathetic adrenergic fibers release norepinephrine, acting on $\alpha_1$ adrenergic receptors on vascular smooth muscle to cause constriction of cutaneous blood vessels. This reduces blood flow to the skin, minimizing heat loss to the environment.

• Piloerection: Stimulation of arrector pili muscles (by sympathetic postganglionic fibers releasing norepinephrine) causes hairs to stand erect, trapping a layer of insulating air near the skin surface, though this mechanism is more pronounced in animals.

• Shivering Thermogenesis: The hypothalamus, in response to cold, initiates shivering via somatic motor neurons, a rapid, involuntary muscle contraction that generates heat.

• Non-shivering Thermogenesis: In infants and some adults, the SNS stimulates brown adipose tissue (BAT) metabolism via $\beta_3$ adrenergic receptors, which uncouples oxidative phosphorylation to generate heat directly.

Neural Pathways and Myelination

Signal transmission speed within the sympathetic nervous system is heavily dependent on neuronal structure and myelination status.

• Preganglionic Sympathetic Fibers: These originate from the intermediolateral cell column of the spinal cord (T1-L2/L3). They are typically myelinated (Type B fibers), allowing for relatively rapid conduction from the spinal cord to the ganglia. These fibers release acetylcholine at the ganglia, acting on nicotinic acetylcholine receptors.

• Postganglionic Sympathetic Fibers: These neurons originate in the sympathetic ganglia and project to target organs. They are predominantly unmyelinated (Type C fibers), which are thinner and have slower conduction velocities compared to myelinated fibers. This slower conduction is physiologically appropriate for the widespread, sustained, and diffuse responses often characteristic of the sympathetic system. Most postganglionic fibers release norepinephrine at their target effector cells, acting on adrenergic receptors ($\alpha$ or $\beta$ subtypes).

• Unmyelinated Neurons: These are characterized by their small diameter and lack of a myelin sheath. While conducting impulses more slowly, they are crucial for nuanced or diffuse responses, such as innervating deeper dermal layers (e.g., hair follicles, some vasoconstrictor fibers) or mediating more prolonged effects, consistent with their role in postganglionic sympathetic innervation of target organs.

• Myelinated Fibers: The myelin sheath, composed of Schwann cells in the PNS, acts as an electrical insulator. Myelination facilitates saltatory conduction, where action potentials 'jump' between nodes of Ranvier, dramatically increasing conduction velocity. This rapid signaling is essential for the preganglionic segment to quickly activate the sympathetic ganglia.

Clusters of Sympathetic Neurons

The sympathetic nervous system features organized clusters of neurons known as ganglia, which serve as relay stations between preganglionic and postganglionic neurons. These ganglia allow for divergence and widespread innervation.

There are two primary types of sympathetic ganglia:

• Paravertebral (Sympathetic Chain) Ganglia: These are a paired chain of 21-23 ganglia located on either side of the vertebral column, extending from the cervical to the sacral region. They are segmentally organized and interconnected, allowing preganglionic fibers to either synapse at their entry level, ascend or descend to synapse at different levels, or pass through to reach collateral ganglia. They primarily innervate structures in the head, neck, thoracic cavity, and limbs (e.g., sweat glands, blood vessels, cardiac muscle, lungs, iris).

• Prevertebral (Collateral) Ganglia: These unpaired ganglia are located anterior to the vertebral column, typically in the abdominal cavity, associated with major abdominal arteries. Examples include:

  • Celiac Ganglion: Innervates the stomach, spleen, liver, gallbladder, duodenum, pancreas, and adrenal medulla.

  • Superior Mesenteric Ganglion: Innervates the small intestine and proximal colon.

  • Inferior Mesenteric Ganglion: Innervates the distal colon, rectum, urinary bladder, and reproductive organs.

These ganglia are vital for:

• Divergence: A single preganglionic neuron can synapse with multiple postganglionic neurons in various ganglia, amplifying the sympathetic response to affect numerous targets simultaneously.

• Convergent Input: Conversely, a postganglionic neuron can receive input from several preganglionic neurons.

• Target Innervation: Postganglionic neurons, characterized by their tiny, highly arborized (branched) axons, extend from these ganglia to directly innervate vast arrays of effector tissues, ensuring broad and efficient control over bodily functions.

Neuronal Organization in Sympathetic Nervous System

The sympathetic nervous system exhibits a distinct thoracolumbar outflow, meaning its preganglionic neurons originate exclusively from the thoracic (T1-T12) and upper lumbar (L1-L3) segments of the spinal cord.

Within these segments:

• The intermediolateral cell columns (IML), located in the lateral horns of the grey matter, house the cell bodies of the preganglionic sympathetic neurons.

• Axons from these neurons exit the spinal cord via the ventral roots, enter the spinal nerves, and then branch off as white rami communicantes to enter the sympathetic chain ganglia.

Once in the ganglia, preganglionic fibers can:

• Synapse immediately with a postganglionic neuron at the same level.

• Ascend or descend within the sympathetic chain to synapse at a different segmental level.

• Pass through the chain without synapsing to reach a prevertebral (collateral) ganglion.

Postganglionic neurons then project to their target organs, influencing diverse functions:

• Cardiovascular System: Increasing heart rate and contractility (via $\beta<em>1$ receptors), and modulating blood pressure via widespread vasoconstriction ($\alpha</em>1$ receptors) or vasodilation ($\beta_2$ receptors in skeletal muscle).

• Respiratory System: Causing bronchodilation (via $\beta_2$ receptors) to increase airflow.

• Gastrointestinal System: Inhibiting motility and secretion, and promoting sphincter constriction ($\alpha<em>1$ and $\alpha</em>2$ receptors).

• Urinary System: Relaxing the detrusor muscle and constricting the internal urethral sphincter, promoting urine retention.

• Ocular System: Causing pupillary dilation (mydriasis) and relaxation of the ciliary muscle for far vision.

Sympathetic nerves also play a critical role in regulating large vessels, such as those associated with the aortic arch and carotid sinuses, which house baroreceptors. Sympathetic output adjusts the sensitivity of these baroreceptors and directly influences total peripheral resistance and cardiac output, thereby precisely contributing to blood pressure homeostasis through reflex mechanisms.

Summary of Neuronal Structure

In summary, the sympathetic nervous system is characterized by a sophisticated and highly integrated neuronal organization, fundamental for orchestrating acute and adaptive physiological responses across the body. Its intricate structure involves:

• A thoracolumbar outflow from the spinal cord, utilizing distinct preganglionic (myelinated cholinergic) and postganglionic (unmyelinated adrenergic) neurons.

• Anatomically distributed ganglia (paravertebral and prevertebral) that allow for divergence and widespread innervation.

• Comprehensive distribution to nearly all organs and tissues, enabling systemic adjustments to internal and external stressors.

• Fine-tuned responsive actions, such as rapid glucose mobilization, precise thermoregulation (sweating, vasoconstriction), and cardiovascular adjustments (heart rate, blood pressure, blood flow redistribution).

• Coordinated innervation patterns that are indispensable for maintaining overall body homeostasis and executing a rapid, integrated response to physical and psychological challenges.

This complex architecture ensures that the body can quickly and effectively adapt to and manage various physiological demands and stressors.