Learning Outcomes - Week 7 - Autonomic Nervous System Flashcards
Describe the basic structural elements of the autonomic nervous system.
Like most parts of the nervous system, the autonomic nervous system consists of elements located within both the peripheral nervous system (PNS) and the central nervous system (CNS). In this lesson we will concentrate on the peripheral elements and touch on the CNS components towards the end.
As shown in the image on the right, in the autonomic nervous system the central nervous system is linked to its target tissue by a two neurone pathway.
The first neurone has its cell body in the CNS, an axon which projects into the PNS and synapses with the second neurone in a collection of neurones known as an autonomic ganglion. For this reason the first neurone is referred to as the preganglionic neurone and the second as the postganglionic neurone.
The postganglionic neurone has its cell body in the autonomic ganglion and axon terminals in close apposition to the peripheral tissue that it regulates. The site of functional interaction between the axon terminals of the postganglionic neurones and the peripheral tissue is known as the neuroeffector junction.
The autonomic nervous system is subdivided into two major divisions known as the sympathetic division and the parasympathetic division. These two divisions differ in terms of their specific functions, structure and neurochemistry. In the following sections we will review these three aspects for both the sympathetic and parasympathetic divisions.
Understand the consequences of increased activity in the sympathetic division of the autonomic nervous system.
The general function of the sympathetic division is to prepare the other systems of the body for activity. These functions are encapsulated by the phrase ‘fight or flight’ in that they either prepare the body to fight off a predator or take the more sensible option and run away.
This division of the autonomic nervous system is also responsible for preparing the body for activities such as exercise and is also involved in behavioural responses to things like stress and fear (see right).
The general characteristics of increased activity in the sympathetic division include increased heart rate, elevated blood pressure, release of metabolic fuels such as glucose, dilation of airways, pupils and blood vessels to muscles.
Collectively these responses elevate blood sugar levels, enhance the delivery of well oxygenated blood to skeletal muscles and potentiate visual awareness of the environment.
At the same time reproductive, digestive and urinary functions are attenuated because the last thing you want when you are being chased through the woods by a hungry bear is feeling like you need to stop to go to the toilet.
Appreciate the physiological consequences of increased activity in the parasympathetic division of the autonomic nervous system.
The overall functions of the parasympathetic division of the autonomic nervous system are to enable relaxation and recuperation. These functions are sometimes referred to as ‘rest and digest’.
Activity in the parasympathetic division results in decreased heart rate, increased motility and secretion of digestive enzymes in the digestive tract, a decrease in metabolic rate and stimulation of defecation and urination.
These responses are clearly appropriate for restoring metabolic energy stores and enabling rest and recovery.
Describe the structural features of both the preganglionic and postganglionic neurones of the sympathetic division of the autonomic nervous system.
Describe the sympathetic division and it’s structure (location in which horns at which vertebrae), relevant ganglia, and what it is sometimes referred to as.
Because of the proximity of the collateral and sympathetic chain ganglia to the spinal cord, sympathetic preganglionic neurones are…?
In the parasympathetic division however the terminal ganglia are…?
A. Sympathetic Division
The preganglionic neurones of the sympathetic division (known as sympathetic preganglionic neurones) are located in the lateral horns of the T1 to L2/3 segments of the spinal cord. For this reason the sympathetic division is sometimes referred to as the thoracolumbar division.
Sympathetic postganglionic neurones have their cell bodies in either the sympathetic chain ganglia or collateral ganglia, small diameter unmyelinated axons and axon terminals that form neuroeffector junctions with a variety of peripheral tissues.
…relatively short whilst sympathetic postganglionic neurones are comparatively long.
…actually within or close to the peripheral tissue they innervate so the parasympathetic preganglionic neurones are long whilst the postganglionic neurones are short.
Understand the structural features of preganglionic and postganglionic neurones of the parasympathetic division of the autonomic nervous system
Describe the parasympathetic division, location, horns location, what is it sometimes referred to as.
Preganglionic parasympathetic neurones have _______________ axons which leave the brain through _________ if they have their cell bodies in the brain stem, or through ___________ if they have their cell bodies in the _______________.
These neurones synapse with…?
B. Parasympathetic Division
The preganglionic neurones of the parasympathetic division are located in the brain stem or in the lateral horns of the S2-S4 segments of the spinal cord. For this reason the parasympathetic division is sometimes referred to as the craniosacral division.
Preganglionic parasympathetic neurones have unmyelinated axons which leave the brain through one of four cranial nerves (if they have their cell bodies in the brain stem) or through the ventral roots (if they have their cell bodies in the sacral spinal cord).
These neurones synapse with parasympathetic postganglionic neurones in terminal ganglia which are located very close to (or actually within) the peripheral tissue they innervate.
Parasympathetic postganglionic neurones have relatively short, small diameter myelinated or unmyelinated axons that form neuroeffector junctions with the adjacent tissues
Name the neurotransmitters and class of neurotransmitter receptor associated with preganglionic and postganglionic neurones of both the sympathetic and parasympathetic divisions of the autonomic nervous system.
SYMPATHETIC
Sympathetic preganglionic neurones utilise acetylcholine (ACh) as their neurotransmitter and the postsynaptic effects of this neurotransmitter are mediated by the nicotinic acetylcholine receptor. The nicotinic acetylcholine receptor is a ionotropic receptor which results in depolarisation of the postsynaptic membrane by opening of a non-selective cation channel. The resultant EPSP is often large enough to cause an action potential in the postganglionic neurone.
Sympathetic postganglionic neurones use noradrenaline (called norepinephrine by citizens of the US of A) as their principal neurotransmitter. The receptors for noradrenaline (known as adrenergic receptors) are located on the plasma membrane of the cells innervated by the postganglionic neurones. These features are summarised in the diagram below.
Know the subclass of adrenergic receptor located on cardiac muscle and bronchial smooth muscle and the physiological consequence of activation of these.
There are five different types of adrenergic receptor and whilst the regional variation in expression of these can be confusing for the student of physiology, they have turned out to be very useful clinically. Adrenergic receptors are all metabotropic receptors whose intracellular effects are produced by G-protein-mediated upregulation of a number of second messengers. The distribution of some adrenergic receptors as well as their effects are summarised in the table below.
Name the subclass of muscarinic receptors found on cardiac muscle cells and the smooth muscle cells of the digestive tract and the physiological consequence of activation of these.
What is also interesting to note about 1) the names of the two different types of Ach receptors and 2) what preganglionic neurones of both divisions of the ANS utilise in terms of receptors?
There are three major types of muscarinic Ach receptors and their distribution and effects are summarised in the table below.
Note that the names for the two different types of acetylcholine receptor is due to the fact that they were originally distinguished by two separate drugs. Nicotine (a toxin which can be isolated from tobacco) selectively activates nicotinic receptors whilst muscarine (a chemical present in poisonous mushroom, Amanita muscaria) selectively activates muscarinic receptors. It is important to realise that whilst these exogenous drugs can be used to distinguish between the two types of receptor, acetylcholine activates them both under physiological circumstances.
It is also interesting to note that the preganglionic neurones of the both the sympathetic and parasympathetic divisions utilise an ionotropic receptor (characterised by fast synaptic transmission and short duration of action) the postganglionic neurones employ metabotropic receptors (typically slow in onset but with a much longer duration of action).
Explain the concepts of dual innervation and autonomic tone with reference to at least one organ.
One feature of tissues that receive such dual innervation is that the autonomic neurones that innervate them are continuously active (i.e. there are always action potentials travelling along them). This gives rise to the concept that these tissues are subjected to a constant autonomic tone. Activity in these tissues can therefore be controlled by increasing or decreasing the level of sympathetic or parasympathetic tone.
Although this two level control system might seem a little over the top, it does permit very fine control over the activities of what include some of our most vital organs. This arrangement means in effect that the level of activity of any tissue subject to dual innervation is a balance between the opposite effects of the sympathetic and parasympathetic divisions. In fact this makes a lot of sense if you want to exert precise control over important physiological functions. If you only had an excitatory effect it would be a little like riding a bike without any brakes. You’d probably still be able to get around but weaving your way along George Street at 6 pm on a Friday evening might be a little exciting.
Understand the different between antagonistic and cooperative effects in relation to the functional organisation of the autonomic nervous system.
Whilst in most tissues that receive dual innervation the sympathetic and parasympathetic divisions exert antagonistic effects, there are some tissues where they act cooperatively to produce the same effect. Probably the best example of this is where the sympathetic and parasympathetic divisions work together to produce an erection. We will revisit this issue when we deal with the reproductive system in Medical Physiology 2 (LQB488)
Appreciate that some structures are innervated by only the sympathetic division of the autonomic nervous system
Despite the predominance of dual innervation (whether it be antagonistic or cooperative) there are tissues which receive innervation from only the sympathetic OR parasympathetic divisions of the nervous system. Some of these are highlighted in the table below.
Describe the structural and functional organisation of the adrenal medulla.
The adrenal medulla is a very special example of an gland innervated by the autonomic nervous system. You will hear more about the adrenal gland when you cover the endocrine system. It is a small endocrine gland that sits on top of each kidney and consists of a shell region (cortex) that secretes a large number of steroid hormones, surrounding a core region (medulla) that secretes adrenaline (epinephrine to our American friends) and noradrenaline (norepinephrine).
In many respects the cells of the adrenal medulla can be considered to be sympathetic postganglionic neurones in that they are innervated by sympathetic preganglionic neurones and secrete substances which act on adrenergic receptors.
The major difference between the adrenal medulla and sympathetic postganglionic neurones is that the chemicals secreted by the adrenal medulla are hormones that enter the blood stream and consequently can exert influence over cells throughout the body.
Sympathetic postganglionic neurones on the otherhand release noradrenaline into the narrow cleft of the neuroeffector junction and have a very specific and localised effect on a small number of cells.
The relationship between the sympathetic division of the autonomic nervous system and the adrenal medulla is summarised in the figure opposite.
The endocrine secretions of the adrenal medulla consist of approximately 80% adrenaline and 20% noradrenaline. The secretion of these hormones is enhanced by an increase in sympathetic tone so the local and highly specific effects of activation of the sympathetic division of the autonomic nervous system are reinforced further by the more widespread actions of the hormones.
Understand that the autonomic nervous system is controlled by autonomic reflexes and autonomic control centres.
So far in this consideration of the autonomic nervous system we have only examined the peripheral aspects. We should have by now a fairly good idea of what happens when the activity in symapathetic or parasympathetic preganglionic neurones is altered. The question that we need to address if our knowledge of this topic is to be complete is - what is it that regulates the activity of the preganglionic neurones?
The neuronal circuits responsible for this control are collectively known as the autonomic control systems and, perhaps not surprisingly, these are fairly complex and in many instances remain poorly understood. However what is clear is that there exist fairly simple reflex circuits which act at the level of the brainstem and spinal cord to carryout the more mundane roles of the autonomic nervous system as well as higher order circuits responsible for the regulation and coordination of more complex functions. We’ll consider each of these briefly in the subsequent sections.
A. Autonomic Reflexes
Like most reflexes, autonomic reflexes require a population of sensory neurones to monitor the state of play in the peripheral tissues and a population of efferent neurones to mediate the effects. In the case of autonomic reflexes of course the efferent pathway is mediated by the sympathetic or parasympathetic divisions. Two fairly simple autonomic reflexes will serve to illustrate this point:
B. Autonomic Control Centres
Whilst autonomic reflexes do a very good job of producing rapid and appropriate responses in specific peripheral tissues (the eye and bladder in the examples above) clearly homeostasis requires the involvement of more complex neural systems to integrate the diverse functions that the autonomic nervous system can regulate. One important fact that has come to light in the last decade is that in both the sympathetic and parasympathetic divisions there are very specific pools of preganglionic neurones that make highly ordered synaptic contacts with postganglionic neurones innervating particular peripheral tissues. This idea is illustrated in the figure opposite.
In this example, separate populations of sympathetic neurones innervate the blood vessels of the heart (red) and the skin (blue).
As a result of this highly ordered arrangement, regulation of activity of the preganglionic neurones going to the heart or those going to the skin will permit independent control of blood flow to these particular tissues.
Clearly then all the central control systems need to do is modify the activity of the appropriate population of preganglionic neurones (in the appropriate direction) to produce the desired result.
It is becoming increasingly evident that throughout the brainstem and forebrain there are neural circuits that are able to selectively modify activity in specific populations of preganglionic neurones and thereby coordinate some of the more complex interactions in peripheral tissues.
These so-called higher order autonomic control centres will be considered when the specific system they regulate are covered. The important thing to realise at this juncture is that they mediate their effects by switching on or off the appropriate population of preganglionic neurones.
Describe the structural and functional aspects of the pupillary and voiding reflex.
Pupillary Reflex
The pupillary reflex is the fairly well known change in the diameter of the pupil of the eye in response to varying environmental lighting conditions. If someone shines a bright light into your eye the pupil constricts reflexly. In this case the sensory neurones are in your retina. The axons of these sensory neurones project out of the eye along the optic nerve and synapse in the brainstem. These sensory neurones excite a population of efferent neurones which in turn synapse on preganglionic parasympathetic neurones whose axons exit the brainstem via the IIIrd cranial nerve and synapse with the parasympathetic postganglionic neurones very close to the eye. The parasympathetic postganglionic neurones in turn cause contraction of the constrictor muscles of the iris which constricts the pupil.
Voiding Reflex
Another familiar autonomic reflex controls the contractions of the bladder as it begins to approach full capacity. The distension of the bladder by urine is detected by sensory neurones in its walls. These sensory neurones synapse with parasympathetic preganglionic neurones in the sacral segments of the spinal cord which cause reflex contraction of the smooth muscle in the wall of the bladder and the bladder empties. Fortunately in most healthy adults the reflex can be consciously inhibited until it is socially acceptable for bladder emptying to take place.
Explain what is meant by the terms muscarinic receptor agonist and antagonist and be able to name at least one example of each.
In an earlier module we considered the neurochemistry of the peripheral components of the autonomic nervous system. What was clear from that analysis was that the neurotransmitters used by the postganglionic neurones of the sympathetic and parasympathetic divisions of the autonomic nervous system were different. This has been useful because it has allowed the development of drugs to modify the action of one or the other division to produce clinically beneficial outcomes.
Drugs which mimic the actions of the sympathetic nervous system are called sympathomimetics whilst those that mimic the action of the parasympathetic division are called parasympathomimetics.
Not surprisingly, most sympathomimetics are adrenergic receptor agonists (i.e. they have the same effect as noradrenaline when they combine with adrenergic receptors) and most parasympathomimetics are muscarinic receptor agonists.
In addition to drugs which mimic the actions of the sympathetic and parasympathetic divisions of the autonomic nervous system there are also those that block them. These are known as parasympathetic or sympathetic blockers (or more correctly antagonists). These drugs block the actions of acetylcholine at muscarinic receptors and noradrenaline at adrenergic receptors respectively.
Given the large number of physiological processes that the autonomic nervous system regulates, it is not surprising that sympathomimetic and parasympathomimetic drugs (as well as the antagonists) have found widespread applications in modern medicine. Because of the dual innervation of many organs, antagonists can be used to reduce the effects of one division of the autonomic nervous system or agonists can be used to enhance the effects of the other division
Explain the difference between adrenergic receptor agonists and antagonists and be able to name at least one example of each.
Finally, the fact that there are 5 different types of adrenergic receptor and 3 different types of muscarinic receptor and that these are expressed by different peripheral tissues has been very useful.
This complex neurochemistry has allowed pharmaceutical companies to design drugs that are reasonable specific for a particular receptor and can therefore be used to target particular tissues with a reasonable amount of specificity. This allows more effective treatment outcomes with the drugs and of course less side-effects.
The table below summarises some of the drugs which modify autonomic nervous system and their clinical applications
Name the neurotransmitters and class of neurotransmitter receptor associated with preganglionic and postganglionic neurones of both the sympathetic and parasympathetic divisions of the autonomic nervous system.
PARASYMPATHETIC
The preganglionic neurones of the parasympathetic division have exactly the same neurochemistry as those of the sympathetic division. They utilise ACh as their neurotransmitter and it exerts its effects on the postganglionic neurone by binding to nicotinic acetylcholine receptors which open ion channels. The postganglionic neurones of the parasympathetic also utilise ACh as their neurotransmitter but the effectors cells express muscarinic acetylcholine receptors which are functionally distinct from the nicotinic receptors. Like adrenergic receptors, muscarinic ACh receptors are metabotropic and thus mediate their effects by an intracellular second messenger system. These features are summarised in the diagram below.
