The Autonomic Nervous System
General Overview
Autonomic Nervous System (ANS) functions to maintain homeostasis ù i.e. maintain the environment necessary for cells to function properly.
Optimal Conditions
Body Temp 37oC
Mean Blood Pressure 90 mmHg
pH 7.4
Blood Plasma Osmolarity 300 mOsmol
Coordinates bodily functions needed for survival e.g. senses the need for food, water.
Autonomic reflexes regulate blood pressure, heart rate, respiration, water balance and body temperature
Also prepares body for life threatening conditions.
The ANS innervates heart, blood vessels, glands, viscera, smooth muscle.
Mant of these effector organs cannot be consciously controlled.
ANS often called the involuntary nervous system.
Central component hypothalamus, brain stem and spinal cord
Peripheral component ù nerves that innervate the various organs
Divided into:
(i) Sympathetic ù coordinates bodyùs response to stress
(ii) Parasympathetic Divisions ù coordinates bodyùs vegetative activities (housekeeping) e.g. digestion
An autonomic reflex adjusts the activity of a visceral effector organ. i.e. it results in the contraction of smooth or cardiac muscle or secretion by a gland.
The sensory arm of the autonomic reflex pathway is similar to the somatic reflex: sensory information is relayed to the spinal cord via sensory fibers originating in peripheral visceral receptors.
Visceral reflexes often operate at a subconscious level but some visceral afferent fibres do provide a sensory experience. e.g. visceral pain caused by excessive distention of hollow organs or ischemia.
The motor pathways differ between somatic and autonomic systems:
The motor (efferent) outflow of the ANS from the spinal consists of two neurons (unlike somatic nervous system where the motor (efferent) branch consists of only 1 motor neuron)
Autonomic motor pathways
consist of (Fig 13-2 p431)
a) preganglionic neurons with the cell bodies located
in the brain or
spinal cord. Their axons synapse on
the cell bodies of a second set of
neurons the:
b) postganglionic neurons that are located in all cases outside the central nervous system in collections of nerve cell bodies called autonomic ganglia. Their axons innervate the visceral effector organs.
Sympathetic and Parasympathetic divisions of the ANS differ anatomically and functionally (see Figure 11-5 and Table 11-4 for summary)
Sympathetic
Nervous System (Thoracolumbar Division)
Preganglionic cell bodies are concentrated in the intermediolateral cell column in the thoracic and upper lumbar segments of the spinal cord.
Axons pass to the paravertebral sympathetic ganglion chain where they synapse with cell bodies of the postganglionic neurons.
The preganglionic axon:
(i) may synapse on postganglionic cells in the paravertebral ganglion at this segmental level.
(ii) may enter the sympathetic chain and travel rostrally or caudally to a nearby or distant paravertebral ganglion
(iii) some preganglionic axons pass through the sympathetic chain and enter a splanchnic nerve
(iv) Preganglionic axons that enter a splanchnic nerve often travel to a prevertebral ganglion (e.g. mesenteric, celiac ganglia) and synapse with postganglionic neurons located in these distant ganglia.
(v) Some preganglionic axons in the splanchnic nerve innervate chromaffin cells of the adrenal medulla directly. The adrenal medulla is embryologically and functionally analogous to a sympathetic ganglion.
(vi) The axons of preganglionic neurons tend to be short, wheras axons of postganglionic neurons tend to be long.
(vii) Sympathetic preganglionic axons may synapse on many (average =20) postganglionic cells via collateral fibres. Result: a single signal from the CNS can affect a large number of target cells simultaneously.
(viii) This anatomical arrangement allows sympathetic reactions to be widespread, affecting the response of the organism as a whole as opposed to being restricted to individual organs.
(i) Preganglionic cell bodies of the parasympathetic division are located in the mid brain and medulla (Cranial nerve nuclei 3, 7, 9, 10), and the sacral region of the spinal cord. The major parasympathetic tract is part of the vagus nerve.
(ii). Most postganglionic parasympathetic cells are located near or in the walls of the visceral effector organs.
(iii) Some postsynaptic cells are located in cranial ganglia
(iv) In contrast to the sympathetic nervous system, parasympathetic preganglionic fibres tend to be long, wheras postganglionic fibres tend to be short.
(iv) This anatomical arrangement allows the innervation of the parasympathetic nervous system to be specifically directed to an individual organ.
The terminals of sympathetic nerves are specialized to ensure that the effect of the transmitter is widespread (diffuse synapse)
The sympathetic terminals branch extensively. Transmitter is released from varicosities located on the terminal branches.
The vesicles containing NE located in the varicosities show no preferred orientation towards the postsynaptic membrane.
Unlike the neuromuscular junction which has a very small synaptic cleft, the synaptic cleft at the neuroeffector junction is wide.
The Effects of Sympathetic Activation
on the Body
The sympathetic and parasympathetic systems are continually active and the basal rates of activity are known as sympathetic and parasympatheric tone respectively. The advantage of tone is that it allows for regulation in either direction.
Autonomic regulation is usually modulatory rather than initiatory. e.g. the heart pumps blood in the absence of sympathetic or parasympathetic input. The autonomic input serves to modulate the existing autogenic capacity of the heart.
General discharge of sympathetic nerves and the adrenal medulla can occur in response to life threatening or emergency situations. This Fight or Flight response is an extreme example of sympathetic action on the body that serves to prepare the individual to cope with the emergency.
The combination of changes seen in this reaction serve as a useful tool to remember some of the actions of sympathetic activation.
Fight or flight adaptive effects include
a) increased cardiac activity, increased blood pressure, dilation of skeletal muscle blood vessels - provides increased perfusion of vital organs and muscles
b) constriction of blood vessels in skin - limits bleeding from wounds
c) dilation of pupil - letting more light into the eye
d) inhibition of gut and urinary bladder contractions - inhibit defecation and urination
e) increase in blood glucose and free fatty acid levels - supply more energy
e) dilation of bronchial smooth muscle - easier flow of air
f) secretion of viscous saliva - possibly to avoid choking
g) sweating
h) lower threshold for reticular formation activation - reinforcing the alert state
i) liver produces glucose to provide energy for muscle contraction.
In contrast to the mass sympathetic activation seen during this mode of operation, under normal circumstances associated with day to day living the firing rate of some sympathetic pathways may increase wheras the firing rate of other sympathetic pathways may decrease.
One important function of the sympathetic nervous system is the maintenance of arteriole pressure.
Tonic sympathetic innervation to the smooth muscle in arteriole walls results in a moderate state of vasoconstriction at all times. This state of tonic contraction called vasomotor tone plays an important role in maintaining peripheral resistance and blood pressure.
Decreased sympathetic stimulation of
arterioles leads to vasodilation and a decrease in blood
pressure; increased sympathetic stimulation, vasoconstriction and
an increase in blood pressure.
The parasympathetic division controls periods of relaxation concerned primarily with conservation and restoration of energy.
Unlike the sympathetic division which is
organized for mass responses, the parasympathetic division is
organized mainly for discrete and localized discharge to
individual organs.
Parasympathetic activation results in
a) decreased cardiac acivity
b) secretion of watery saliva and stimulaton of GI secretions
c) contraction of urinary bladder
d) Increased insulin and glucagon secretion
e) bronchiole constriction
Most internal organs are innervated by both autonomic branches which exhibit antagonistic control.
e.g. heart is innervated by the parasympathetic division (vagus nerve) and the sympathetic division. Sympathetic stimulation increases heart rate, parasympathetic decreases heart rate
Acetylcholine (ACh) is the neurotransmitter at all autonomic ganglia (whether the ganglion is sympathetic or parasympathetic) ù (cholinergic innervation)
The innervation of the adrenal medulla (from sympathetic preganglionic fibres in splanchnic nerves) is also cholinergic.
Some autonomic ganglia also contain
neuropeptides that appear to act as neuromodulators, for example,
sympathetic preganglionic neurons may contain enkephaline,
substance P or somatostatin in addition to ACh.
At the synapse between sympathetic postganglionic fibres and the effector organ (often called the neuroeffector junction) the neurotransmitter is norepinephrine (NE) ù an adrenergic synapse.
There are some exceptions: e.g. the innervation of thermoregulatory sweat glands and blood vessels of skeletal muscles is anatomically sympathetic but postganglionic fibres release ACh instead of NE.
Acetylcholine is the transmitter at parasympathetic neuroeffector junctions.
Epinephrine released from the adrenal medulla, enters the blood stream where it exerts influences in many parts of the body.
1.
Norepinephrine (NE) mediates sympathetic actions via
activation of adrenergic receptors
2. Adrenergic receptors subdivided into a and b receptors (a is the most common sympathetic receptor)
a receptors further subdivided into a1 and a2
a. a 1 receptors located mainly on membrane of effector organs. e.g.
activation of a1 receptors in smooth muscle of arteriole walls by NE following sympathetic stimulation produces vasoconstriction resulting in an increase in peripheral vascular resistance (PVR) and arterial pressure.
b. a1 receptor antagonists - phentolamine.
antagonizing alpha one receptors would tend to decrease PVR and arterial pressure
c. a 2 receptors are located mainly on the presynaptic membrane of the adrenergic nerve terminal. They function to modulate NE release by a negative feedback mechanism.
d. a 2 receptor antagonist - yohimbine.
Antagonizing the a2 receptor would lead to an increase in release of NE due to a blockade of the negative feedback loop that serves to inhibit further NE release from the sympathetic terminal
4. b receptors further subdivided into b1 and b2.
a. b1 receptors located mainly in the heart. Activation of b1 receptors mediate sympathetic actions on the heart e.g. increase in both heart rate and force of contraction.
b b2 receptors located on a variety of effector organs including urinary bladder, stomach, uterus and bronchial smooth muscle.
c. b receptor antagonist - propranolol.
Many pharmacological agents produce their effects by preferentially acting on specific receptor subtypes located in tissues of one or more organ. So it is important to consider where specific agents are going to act when prescribing drugs for patients
e.g. b antagonist propranolol is often prescribed in the treatment of certain forms of cardiac arrhythmias because it prevents endogenously released adrenergic agents from acting on b1 receptors in the heart.
But, propranolol also acts on b2 receptors located on airway smooth muscle resulting in airway constriction thus it is not desirable to prescribe propranolol in patients with airway disease.
d. NE termination
Norepinephrine action at the target site is terminated by active uptake into the presynaptic terminal where it is either repackaged into vesicles or broken down by intracellular enzyms such as monoamine oxidase (MOA).
Some older antidepressants act by blocking MOA activity (MOA inhibitors). But they had side effects related to their actions on other systems of the body including cardiovascular problems, constipation, and sexual dysfunction.
More recent antidepressants include serotonin reuptake blockers (tricyclic antidepressants) which have fewer global effects (serotonin is primarilt a CNS neurotransmitter) and thus fewer side effects
Cocaine blocks NA reuptake into terminals into adrenergic nerve terminals thereby extending the actions of NE on its target organ.
1.
Acetylcholine (ACh)
mediates parasympathetic actions via activation of cholinergic
receptors.
2.
Cholinergic receptors further subdivided into nicotinic
and muscarinic receptors.
3. Nicotinic receptors are located on postganglionic cells in all autonomic ganglia.
4. Muscarinic receptors located mainly on membrane of effector organs e.g. activation of muscarinic receptors in heart by ACh mediates parasympathetic actions on the heart - decrease in heart rate and decreased force of contraction.
5. Muscarinic antagonist: Atropine, scopolamine
Different organs can have different sensitivities to muscarinic receptor antagonists. Salivary, bronchial and sweat secretion are particularly sensitive to these antagonists.
Muscarinic antagonists tend to induce similar side effects: dry mouth, decreased sweating, tachycardia, decreased respiratory secretions and constipation.
In fact, atropine is a major ingredient in antidiarrhoea preparations because it reduces GI secretions and and motility and inhibits contractions of the stomach and small and large bowel thus delaying transit through the digestive system.
Nicotinic antagonist: hexamethonium
These drugs are rarely used theraputically because of the severe side effects resulting from non-selective blockade of nicotinic receptors in both sympathetic and parasympathetic ganglia.
Receptors for NE and ACh also exists on presynaptic terminals.
Alpha 2 receptors are located on parasympathetic terminals at parasympathetic neuroeffector junctions. Activation of these receptors inhibits release of ACh.
Muscarinic receptors are located on sympathetic terminals at sympathetic neuroeffector junctions. Activation leads to inhibition of NE release.
Thus ù the effect of either sympathetic or parasympathetic actions are enhanced by inhibiting opposing actions at the target organ.
Autonomic Regulatory Systems maintain a constant internal environment for the optimal functioning of the various organs and their cells.
The autonomic regulatory system is a negative feedback system.
Examples:
Osmoreceptors that detect plasma osmolarity are located in different parts of the hypothalamus and regulate thirst and water volume,
Brain stem receptors involved in respiration are activated by chemoreceptors sensitive to oxygen, CO2 and H+.
Brain stem responses that control blood pressure are activated by stretch receptors that sense pressure changes.
Higher levels of Autonomic Functioning - Fig 11-2
Efferent (motor) neurons of the autonomic dvision are closely limked to homeostatic control centers in the hypothalamus, pons and medulla.
Autonomic functions controlled by the brain include: heart rate, blood pressure, temperature regulation and water balance.
Cerebral cortex and the limbic system can influence autonomic output via descending pathways.
Blushing, fainting at the sight of a needle and butterflies in the stomach are all examples of emotional influences on autonomic function.