Clinical Neuroscience Week 7 - Autonomic Nervous System

• The autonomic nervous system (ANS) is a component of the peripheral nervous system that regulates homeostasis, including circulation, respiration, digestion, metabolism, body temperature, and reproduction.
• The ANS carries out its functions through structures in the brainstem, with the hypothalamus playing a key role in synapsing with various parts of the peripheral nervous system.
• The autonomic system is a two-order neuron system, consisting of pre- and post-ganglionic components.

Divisions of the Autonomic Nervous System

• Sympathetic: Primarily involved in the "fight or flight" response, mobilizing energy.
• Parasympathetic: Primarily involved in "rest and digest" functions, conserving energy.
• Enteric: Coordinates digestive reflexes within the gastrointestinal (GI) tract.

Receptors in the Autonomic Nervous System

• Mechanoreceptors: Detect pressure and stretch, important for blood pressure regulation in the heart and aorta.
• Chemoreceptors: Detect different concentrations in the bloodstream, helping to maintain oxygen levels and blood glucose.
• Nociceptors: Respond to life-threatening stimuli such as ischemia or tissue death.
• Thermoreceptors: Respond to temperature changes, ensuring body temperature does not fluctuate too much.
• Neurotransmitter Receptors: Including Acetylcholine (Nicotinic and Muscarinic) and Adrenergic receptors.

Neurotransmission in the Autonomic Nervous System

• Acetylcholine (ACh) is the neurotransmitter in the pre-ganglionic fiber of the sympathetic nervous system.
• Acetylcholine is the pre- and post-ganglionic neurotransmitter in the parasympathetic nervous system.
• Parasympathetic fibers have longer pre-ganglionic fibers and shorter post-ganglionic fibers.
• Norepinephrine (NE) is the neurotransmitter within the post-ganglionic fiber (sympathetic).
• Key receptors include Nicotinic, Muscarinic, Alpha, and Beta receptors.

Subcomponents of the Autonomic Nervous System & CNS Involvement

• Parasympathetic (brainstem origin): Releases ACh, constricting airways, decreasing heart rate, and increasing GI activity, acts on muscarinic receptors, with longer pre-ganglionic and shorter post-ganglionic fibers.
• Sympathetic (thoracolumbar spinal cord): Releases ACh in preganglionic fibers and norepinephrine in post-ganglionic fibers into target organ.
• Actions of the sympathetic nervous system include constriction of venules and veins in skeletal muscle (alpha receptors), constriction of skin vascular smooth muscle (alpha receptors), increased heart rate and contractility, and dilation of blood vessels to the heart (Beta 1 receptors).
• The sympathetic nervous system releases ACh to act on adrenal gland, which releases epinephrine and norepinephrine (Beta 1 receptors), and targets the lungs to dilate airways (Beta 2 receptors), featuring short pre-ganglionic fibers and long post-ganglionic fibers.
• Parasympathetic (sacral spinal cord): Releases ACh, targeting pelvic organs and influencing functions like emptying the rectum and bladder, and sexual erection, composed of muscarinic receptors.

Receptor Significance

• Cholinergic drugs: Cause pupillary constriction, salivation, bronchial constriction/secretion, slowed heart rate, increased gastric secretion/colic diarrhea, and bladder voiding.
• Anticholinergic drugs: Cause pupillary dilation, dry mouth, bronchial relaxation, accelerated heart rate, reduced gastric secretion/constipation, and urine retention.

Maintaining Blood Supply

• The sympathetic nervous system helps constrict blood vessels, and a decrease in sympathetic activity allows for vasodilation.
• The sympathetic chain, also known as "thoracolumbar outflow," is where many sympathetic events take place.
• Due to its concentrated area, there are extensions within the lumbar region that help innervate the head, neck, genital and urinary system.
• Sympathetic features are only present within the thoracic and lumbar (thoracic spine and L1 and L2) spinal cord segments, because these areas contain the lateral horns that target organs.

Expected Sympathetic Nervous System Responses

• Eyelid: Keeps eyes open.
• Pupils: Dilates eyes.
• Vascular supply: Constricts.
• Lacrimal/salivary: Thickens saliva.
• Trachea: Dilates.
• Heart: Vessels dilate, increasing contraction rate/force.
• Stomach: Slows down digestion.
• Liver: Increases glucose release.
• Adrenal glands: Releases cortisol.
• GI tract: Decreases peristalsis.
• Bladder: Decreases emptying.
• Reproductive organs: Decreases activity/stimulation.

Parasympathetic Nervous System ("Rest and Digest")

• Main purpose is to conserve energy and secondarily store energy.
• Ganglia (cell bodies) are located close to the respective organ.
• Fibers originate from the brainstem and sacral levels.
• Cranial Nerves 3, 7, 9, and 10 are mainly included.
• Eye (Cranial nerve 3): pupil constricts to reduce light.
• Salivary & lacrimal glands (cranial 7 & 9): Increases secretion.
• Trachea: increases secretions.
• Heart: heart rate slows down.
• Stomach: increases secretion levels.
• Liver: reduces levels of glucose release.
• Intestine: Increases peristalsis.
• Bladder: Empties or increases ability to empty.
• External genitals: Increases in function.

Neurotransmitters in PNS & CNS

• Parasympathetic (brainstem origin) - Releases acetylcholine at both preganglionic and postganglionic synapses, constricts airways, decreases heart rate, increases GI activity.
• Receptors on target organs are muscarinic, while all receptors on post-ganglionic neurons are nicotinic.
• Parasympathetic (sacral spinal cord): - Releases ACh at both synapses, empties rectum and bladder, sexual erection
• Receptors are muscarinic, and all receptors on post-ganglionic neurons are nicotinic.
• Cholinergic drugs mimic acetylcholine, while anticholinergic drugs prevent its release.

Enteric System

• Intrinsic nerve supply to the GI tract, relatively independent.
• Runs entire GI tract, including pancreas and gallbladder.
• Gut-brain axis: Relationship between gut microbiome and brain.
• Alpha-synuclein protein misfolding in enteric nervous system may spread to brain via vagus nerve in Parkinson’s.
• Microbiome can regulate motor deficits and neuroinflammation in Parkinson’s.

Orthostatic Hypotension

• Definition: Decrease of at least 20 mmHg systolic, 10 mmHg diastolic, or heart rate increase of 20 bpm within 3 minutes of moving from supine to sitting.
• Mechanism: Gravity-induced blood pooling in lower limbs, compromising venous return and cardiac output.
• Symptoms: Dizziness, lightheadedness, feeling faint.
• Causes: Decreased blood volume due to bleeding, drugs causing vasodilation, diuretics, dehydration, spinal cord disorders interrupting signaling.
• Treatment: Lie patient down (Trendelenburg position), encourage activity (ankle pumps, walking), increase fluid intake for dehydration.

Autonomic/Sympathetic Storming

• Definition: Dysregulation biasing towards sympathetic output, common in severe TBI patients.
• Mechanism: Disconnect between inhibitory brain centers and sympathetic system in diencephalon (hypothalamus, brainstem, spinal cord).
• Symptoms: Increased heart rate, blood pressure, respiratory rate.
• Treatment: Supportive measures (quiet room, temporary medication).

Autonomic Dysreflexia

• Definition: Imbalance between parasympathetic and sympathetic systems due to spinal cord lesion at or above T6.
• Mechanism: Noxious stimuli below lesion trigger sympathetic response.
• Causes: Bowel or bladder obstruction, kinked catheter, constipation.
• Symptoms: Increased blood pressure, decreased heart rate, flushing, headache, sweating.
• Treatment: Elevate patient, find source of noxious stimuli (check catheter), call for assistance.