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Physiology

Reflexes: principles and propertiesJames Waterhouse

iain Campbell

AbstractThe body responds to changing circumstances and environmental threats

both consciously and subconsciously. The cognitive response to a physi

cal threat normally involves movement mediated by skeletal muscle.

There are a number of control mechanisms ‘hardwired’ into the nervous

system which enable muscle systems to respond in an integrated fash

ion without involving a conscious decision, although the subject is usu

ally conscious of what has happened. These include the stretch reflex,

the withdrawal reflex and the crossed extensor reflexes. Muscle spindles,

golgi tendon organs and cutaneous nociceptors provide the sensory

input to these reflexes, and muscle spindles also play a role in the con

trol of voluntary movement. The autonomic nervous system controls the

internal environment in response to environmental change. it consists

of the parasympathetic division, which controls basal and vegetative

mechanisms, and the sympathetic nervous system, which controls vis

ceral adaptive responses to any sort of environmental change or threat.

Keywords fight or flight; neurotransmitters; sympathetic and para

sympathetic nervous system; synapses; withdrawal and crossed extensor

reflexes

The concept of homeostasis – maintaining the constancy of the internal environment – is fundamental to physiology; for this constancy to be achieved, a sensor (to measure the vari-able being controlled), an effector (to change this variable) and some linking pathway are required. Homeostasis results when these components act together, forming negative feedback loops. Similar components are needed when adaptation to change is required – escaping from a noxious stimulus or predator for example – although they will be ‘wired together’ differently to implement change rather than to maintain a steady state. The activities of the various ‘excitable tissues’ – sense organs, neu-rones and muscles – are integrated so that various controlled processes can ensue. Many of these processes do not require cognition (‘thought’) but are automatic. They occur also on two

James Waterhouse, DPhil, DSc, is Professor of Biological Rhythms at the

Research Institute for Sport and Exercise Sciences, Liverpool John

Moore’s University.

Iain Campbell, MD, FRCA, is Consultant Anaesthetist at the University

Hospitals of South Manchester NHS Trust and Visiting Professor

of Human Physiology at Liverpool John Moore’s University. He

qualified from Guy’s Hospital Medical School, London, and trained in

anaesthesia in Zimbabwe, Southend, Montreal and Leeds.

ANAEsThEsiA AND iNTENsiVE CARE MEDiCiNE 9:5 21

levels: those involving the somatic nervous system, integrated at the level of the spinal cord but of which the subject is generally aware (walking, maintenance of posture); and those concerning the autonomic nervous system (digestion of food, cardiac and metabolic responses to a stressor), of which the subject is not normally aware. These latter reflexes are integrated at the level of the midbrain and medulla.

Somatic reflexes

The stretch reflex is the basis of posture and is responsible for maintaining a set length for the muscles that support the weight of the body, so preventing us from falling over as a result of the influence of gravity. This reflex can be observed when tap-ping the tendon of a muscle; the rapid stretch produced by the tap results in a reflex contraction of the muscle, seen most com-monly with the patellar tendon of the quadriceps femoris or the triceps tendon above the elbow. The sensor organ in the skeletal muscles is the muscle spindle, which detects stretching of the muscle; the effector organ is the voluntary striated muscle sup-plied by α-motor neurones from the ventral root of the spinal cord. These two components combine in a negative feedback loop which maintains muscle length and posture.

The muscle spindle is a complex structure consisting of up to ten muscle fibres enclosed in a connective tissue capsule. These are termed ‘intrafusal’ fibres, to distinguish them from the ‘extra-fusal’ fibres that make up the bulk of the muscle, and which produce the contractile force when the muscle shortens. They are connected to the tendons at each end of the muscle or to the sides of the extrafusal fibres.

There are two types of intrafusal fibre – nuclear bag and nuclear chain fibres (Figure 1). A muscle spindle consists of about two nuclear bag fibres and four or more nuclear chain fibres. Nuclear bag fibres have contractile ends and a non-contractile central dilated area containing several nuclei. The nuclear chain

Each spindle has a capsule and usually contains two nuclear bag fibres and four or more nuclear chain fibres. Reproduced from Ganong WF. Review ofMedical Physiology, 19th edn. Connecticut: Appleton and Lange, 1999. Bypermission of the McGraw-Hill companies.

β-efferent

γ-efferentTo extra-

fusal fibres

Plate endings

Trail ending

Annulospiral ending

II secondary afferent

Nuclear bag fibre

Nuclear chain fibre

Flower-spray ending

Ia primary afferent from nuclear bag fibre 2

Diagrammatic representation of the main componentsof mammalian muscle spindle

Figure 1

0 © 2008 Published by Elsevier ltd.

Physiology

fibres are smaller and their nuclei are laid out along the length of the fibre. As implied above, the muscle spindles are stretch receptors. They give rise to two types of large-diameter, afferent (sensory) fibre: group Ia afferents arise from annulospiral end-ings around the central section of both types of intrafusal fibre; group II afferents arise from ‘flower-spray’ endings around the ends of the nuclear chain fibres. Both types of afferent fibre pass into the dorsal root of the spinal cord, the cell bodies lying in the dorsal root ganglion, and form monosynaptic connections with the α-motor neurones supplying the extrafusal fibres of the same muscle. The fact that both the afferent and efferent fibres are of large diameter, coupled with the presence of only one synapse in the pathway, means that the stimulus response delay time is minimal, about 20 ms in the case of a simple ‘knee jerk’.

The spindles are arranged in parallel with the extrafusal fibres of the muscle and monitor its length. If the muscle is stretched, the spindles produce more afferent impulses and these cause the muscle to contract (as with a knee jerk), so opposing the ori-ginal stretch. By contrast, if the muscle length decreases then the spindle is unloaded and its rate of firing is reduced; the resultant reduced rate of firing of the α-motor neurones reduces muscle contraction and allows it to lengthen.

Even though this negative feedback mechanism would, in principle, act to preserve an individual’s posture, in practice it is too slow. One of the problems of the system as described so far (and this applies to feedback loops in general) is that it meas-ures the length of the muscle and so has static sensitivity only. As we begin to lose our balance the initial error in length of the muscle is small, and so the response the feedback loop produces is small – too small to be effective. This problem is overcome by the dynamic sensitivity of the spindles. Dynamic sensitivity responds to change rather than state, and the dynamic compon-ent of the reflex comes from the Ia afferents arising from around the nuclear bags of the nuclear bag fibres. These fibres are sensi-tive to the rate of lengthening of the muscle, although the precise mechanism is not yet clear. Sensory nerves originating from the nuclear chain fibres show only static responses. The result of this dynamic input is that, as soon as the muscle starts to lengthen, there is a burst of activity from the afferent (nuclear bag) nerves that leads to a sufficiently large muscle contraction.

In practice the basic stretch reflex is complicated in three main ways.• Reciprocal innervation – through a pathway involving two synapses, increased input from the Ia fibres causes inhibition of the antagonistic muscle. There is an obvious benefit in having re-flex changes to antagonistic muscles behaving inversely to each other.• Efferent fibres – the above mechanism is appropriate for maintaining posture, where the length of the muscles needs to be maintained at a set value, but a problem arises if movement, which requires a controlled contraction or relaxation, is required. Beta-efferent and γ-efferent fibres pass to the ends of both nuclear bag and nuclear chain fibres and form ‘plate endings’ and ‘trail endings’ (Figure 1). These efferent fibres are of two types and can stimulate either the dynamic or static response of the muscle spindle. Changes in sensitivity of the spindle are brought about by contraction of the intrafusal fibres that stretch the area under the sensory nerve endings. If the firing of these efferent fibres increases, the increased sensory input from the spindles causes a


reflex contraction of the extrafusal fibres by the normal pathway. Likewise, a decreased rate of firing of these efferents will lead to muscle relaxation. In practice, when a voluntary movement is initiated by the motor cortex, for example, there is a co-activa-tion of the α-motor neurones (which provide the contractile force via the extrafusal fibres) and β- and γ-fibres (which change the ‘set-point’ of the system – the length at which the muscle is con-trolled by the stretch reflex). This co-activation of α-, β- and γ-fibres enables a controlled contraction or relaxation to take place. As a further example of the value of both intrafusal and extrafusal fibres, there is a high ratio of intrafusal fibres to extrafusal fibres in finely controlled muscles, such as those controlling the eye; this enables the length of these muscles and changes in length to be controlled with great accuracy. As a result, both eyes can point in exactly the same direction, as required for stereoscopic vision. The activity of the α-motor neurones and their efferent fibres is affected by several other sources, including noxious stimuli to the skin and muscle effort elsewhere in the body. For example, clasping the hands tightly and trying to pull them apart will increase the tendon reflex due to the ‘irradiation’ of nervous activity down the spine.• Inverse stretch reflex – the Golgi tendon organs are, as their name suggests, found in the tendons; they have a network of knobbly endings that ramify through the tendon bundles and send afferent impulses to the spinal cord via group Ib afferents. These afferent fibres make connections with the inhibitory inter-neurones that terminate on α-motor neurones supplying the extrafusal fibres of the same muscle. They also connect with ex-citatory fibres innervating antagonists to the muscle. Their posi-tion means that they are in series with the muscle and act as sen-sors of the force exerted by the contracting muscle rather than its length. Although their threshold is low, so that they are activated during normal muscle contractions, their effect is evident only when the force exerted by the muscle becomes large. In such cases, they inhibit muscle contraction and the muscle suddenly relaxes – the inverse stretch reflex. The value of this reflex is to prevent the development of excessive forces during contraction.

Although the above changes are often described as ‘simple’ reflexes, this refers to the lack of requirement of any processing by the central nervous system (CNS). Even so, information does pass up the spinal cord into the CNS, and this input to the cer-ebellum is an important part of controlling fine movement. The reflexes interact in several ways and integrate activities between antagonistic muscles. Figure 2 summarizes the pathways and neuronal arrangements of these reflexes.

The withdrawal and crossed extensor reflex

The withdrawal reflex is pre-potent, that is, its operation over-rides that of the stretch and inverse stretch reflexes. It is poly-synaptic, involving activation of some muscles and inhibition of others. It is initiated by nociceptive stimuli, generally impinging upon the skin, that are potentially harmful to the animal. There is a flexion of the associated limb – of the leg when a person stands on something sharp, or of the arm when the hand touches some-thing that is hot, for example – and a relaxation (inhibition) of the antagonist muscles. The stronger the stimulus, the more marked the response and the wider the area of the body that is affected. To take the example of standing on a sharp object: if the stimulus


Physiology

is relatively mild, then the leg is withdrawn; as the stimulus gets stronger, flexion is faster and lasts longer (involving after-discharge and reverberating circuits, see below). Even stronger stimuli cause the whole weight of the body to be shifted onto the other foot, thus supporting the body; this requires the extensors of this limb to contract – the crossed extensor reflex – and there might also be reflex changes in the upper limbs, with extension of the ipsilateral upper limb (as if to push the person away from the stimulus) and flexion of the contralateral limb. This spread of activity up or down the spinal cord (as in the example above, or factors affecting the activity of the γ-efferent fibres) is described as the irradiation of the stimulus. Information reaches the CNS and consciousness, the individual registering the effects of pain.

Not surprisingly, the reflex involves the simultaneous activity of many neurones and neuronal circuits, some excitatory, others inhibitory. Details of which circuits are involved, and whether there is some degree of activation of abductor or adductor muscles in addition to those involved in flexion, depends upon the stimulus site. Moreover, whereas the stretch reflex generally lasts for a short period of time (before another postural adjust-ment is required), the flexor response will last for longer. This longer period of activation is achieved by the presence of many polysynaptic pathways, the result of which is that the stimulus affects the α-motor neurones and muscles on multiple occasions, having traversed many pathways of different length. Moreover,

+, excite; –, inhibitWidth of arrow compares importanceNumber in brackets shows number of sensors; poly, manyRoman numeral indicates sensory group

Ia(1)

II(1)

II(poly)

Ib(poly)

Ia(2)

–

–

+

+

+ +

+

α-motor neuronesAgonist

α-motor neuronesAntagonist

Spindles

β-efferentsγ-efferents

Golgi tendon organ

Length of muscle

Tension in muscle

Summary of stretch and inverse stretch reflexes

Figure 2


some of the neurones involved send excitatory impulses back to earlier parts of the pathway, so forming reverberating circuits. These circuits, as well as the multiple pathways, prolong the time during which activation of the α-motor neurones is present, a phenomenon known as after-discharge.

Figure 3 summarizes the above reflexes in terms of the recep-tors and effectors involved and the nature of the connecting neural pathway.

Autonomic reflexes

The autonomic nervous system (ANS) controls visceral function and so regulates our internal environment, in particular by con-trolling smooth (involuntary) muscle in the blood vessels and gastrointestinal tract. This is in contrast to the somatic nervous system discussed above, which controls (voluntary) skeletal muscle and thus the way we interact, usually consciously, with our external environment.

The ANS is composed of two divisions – the parasympathetic (PNS) and the sympathetic (SNS) nervous systems. There is also an enteric nervous system which controls many of the functions of the gastrointestinal tract, and which is strongly influenced by the input from both divisions of the ANS. The central components of the ANS are in the midbrain and medulla: they include the limbic system (emotion), the hypothalamus, parts of the brainstem and the spinal cord. Myelinated axons arise in the CNS and synapse in peripheral ganglia with cells whose axons innervate the organs they control. These post-ganglionic neurones are un-myelinated. The ANS also has afferent (sensory) neurones. They transmit not only sensory information from visceral structures but also chemi-cal and mechanical data from chemoreceptors (carotid body) and pressure receptors (carotid sinus, aortic arch).

–

–

+

+

a. Stretch reflexb. Inverse stretch reflexc. Withdrawal and crossed extensor reflexes

+ +

+

+

+

+

+

-– –

––

Agonist (homonymous) muscle

Antagonist muscle

Agonist muscle

Antagonist muscle

Flexor muscle

Antagonist (extensor) muscle

Contra-lateral extensor muscle

Contra-lateral flexor muscle

Receptor Spinal cord

Withdrawal reflex

Crossed extensor

reflex

Effector and effect

a. Spindle

b. Tendon organ

c. Pain receptor

Interneuron pool with

reverberating circuits

‘Wiring diagrams’ of the three spinal reflexes

Figure 3


Physiology

Autonomic reflexes enable our physiological systems to cope with a spectrum of challenges, and this is generally done sub-consciously. The reflexes control basic functions, such as the response to eating a meal or standing up. They respond also to physiological and environmental demands, such as exercise, injury, heat, cold, altitude, gravity (space travel) and extremes of pressure (when deep-sea diving). The numerous individual reflexes the ANS is involved in are too many and too complex to cover in detail here. The reader is referred to the relevant chapters elsewhere in this journal, in particular to those on cardiovascular, respiratory and gastrointestinal physiology (including vomiting and defecation), as well as micturition and those on integrated and environmental physiology (exercise, injury, extremes of barometric pressure and thermoregulation). This chapter will cover only the general principles of autonomic control.

Anatomy

The PNS consists of four cranial nerves (III – occulomotor, VII – facial, IX – glossopharyngeal and X – vagus) and the sacral nerves, S2–S4, which supply the pelvic viscera – bladder, lower colon, rectum and uterine cervix; these are termed the ‘cranial’ and ‘sacral outflows’, respectively. Generally speaking, the effects of parasympathetic activity are relatively discrete, limited to the organ system(s) supplied by any particular nerve, although a number of systems are supplied by the vagus; they include the heart, bronchial tree and gastrointestinal tract. The effects of vagal stimulation are therefore relatively widespread.

The parasympathetic pre-ganglionic fibres are small myelin-ated B axons; they synapse with post-ganglionic cells with (un-myelinated) C axons. The ganglia are situated on or near the structures they innervate (Figure 4). The cell bodies of vagal ‘ganglia’ lie as microscopic collections of cells within the walls of the viscera themselves; the post-ganglionic fibres therefore have very short axons.

The cell bodies of the sympathetic nerves are situated in the spinal cord, in the lateral horn of the grey matter, over the whole length of the cord, although they exit the spinal cord only between T1 and L3. They, too, are made up of relatively slow, myelinated B axons, which leave the spinal cord as part of the spinal nerves. They branch off from the spinal nerves and pass in white (myelinated) rami communicantes (Figure 4) to the sym-pathetic ganglionic chain situated on the sides of the thoracic vertebral bodies. Some synapse with post-ganglionic cells whose un-myelinated C fibres pass via the grey rami communicantes to their target organs. In line with their diffuse effects, one pre-ganglionic fibre may synapse with several post-ganglionic fibres. Post-ganglionic fibres usually travel to their target organs in close proximity to the blood vessels supplying the same organ.

Other pre-ganglionic fibres pass straight through the thoracic ganglia to synapse with ganglia in the periphery. The splanchnic nerves contain such fibres; they are part of the thoracic sym-pathetic outflow and synapse in ganglia lying on and around the major abdominal blood vessels – the coeliac ganglion as well as the superior and inferior mesenteric ganglia. Sympathetic nerves from T10–T12 supply branches to the ovarian and the superior and inferior hypogastric plexuses, where they mingle with fibres from the sacral parasympathetic outflow and innervate the uterus. The sympathetic nerves innervate predominantly the uterine body


and the parasympathetic, the cervix. The sympathetic nerves supplying the head leave the spinal cord with the upper tho-racic nerves but synapse with their post-ganglionic cells in the superior and middle cervical ganglia and in the stellate ganglion. The detailed anatomy of the ANS is described elsewhere (Anaes-thesia and intensive care medicine 2008 9:2: 39–41).

Parasympathetic activity varies over a wide spectrum; in con-trast, sympathetic activity tends to be an all-or-none phenom-enon. A sympathetic discharge results in stimulation of all the functions controlled by the SNS, including cardiac output, blood pressure, blood sugar and sweating. As the SNS is usually stimu-lated in response to a stress, there is a need for an immediate reaction in a widespread range of systems.

Neurotransmitters

The neurotransmitters differ between the two divisions of the ANS. The ganglionic transmitter in both instances is acetyl cho-line, but the main transmitter released by post-ganglionic sympa-thetic nerves is noradrenaline and the transmitter released by the post-ganglionic/post-synaptic terminals of the parasympathetic nerves is acetyl choline. There are exceptions, however; acetyl choline is released by some fibres innervating blood vessels in skeletal muscle in some species and the sympathetic fibres inner-vating sweat glands are also cholinergic.

Cholinergic and noradrenergic receptors are subdivided accord-ing to their reaction to certain drugs. Cholinergic fibres are either muscarinic or niocotinic. The receptors on post-ganglionic neu-rons are nicotinic, whereas the receptors on target organs are usually muscarinic. Likewise, there are two types of noradrenergic receptor, alpha (α) and beta (β); β-receptors respond to isoprena-line more than do α-receptors. Both types of receptor have sub-divisions – α1-receptors are found in post-synaptic nerve endings, whereas α2-receptors are found predominantly on the pre-synaptic terminals of the adrenergic fibres and inhibit further discharge of noradrenaline. Both types of α-receptor and β1-receptors respond about equally to adrenaline and noradrenaline, whereas β2- receptors respond more to adrenaline than noradrenaline.

Autonomic afferents

Sensory fibres from internal structures such as the viscera, as well as muscle and bone, travel with both sympathetic and parasym-pathetic nerves to reach the CNS, their cell bodies lying in either the dorsal roots or the homologous cranial nerve nuclei. The nerve fibres are largely small un-myelinated C fibres. There are no proprioceptors in viscera and few touch or temperature sense organs. There are pain receptors, although fewer than in somatic structures. Pain fibres from the lungs and bronchi and from the pelvis travel largely in parasympathetic nerves; pain fibres from the abdominal viscera and the heart follow sympathetic nervous pathways. Pain felt in viscera is often ‘referred’ to the correspond-ing somatic segments innervated by somatic nerves at the same spinal level from which the visceral pain arises. The commonest examples are cardiac pain going down the arm or into the neck, and shoulder tip pain arising from the diaphragm.

Visceral pain is poorly localized; it frequently induces nausea and sets up a reflex sympathetic discharge involving a tachycar-dia, increased blood pressure and sweating, although visceral

© 2008 Published by Elsevier ltd.

Physiology

Parasympathetic division Sympathetic division

Coeliac ganglion

Cardiac plexus

Carotid plexus

Inferior mesenteric ganglion

Midbrain and medulla

III OculomotorPupil

Thoracic

Lumbar

1

2

3

4

5

6

7

8

9

10

11

12

1

2

3

Heart

Larynx

Trachea

Bronchi

Oesophagus

Stomach

Mesenteric blood vessels

Liver

Adrenal glandsSmall intestine

Large intestine

Kidney

Bladder

Sexual organs

Lacrimal glandsSalivary glands

Mucus membranesNose, mouth

VII Facial

IX Glossopharyngeal

X Vagus Ganglia

Sacral outflow

Lumbar

Sacrum

Thoracic

Superior mesenteric ganglion

Cervical

Thoracic

ganglia

Functional anatomy of the autonomic nervous system

2

3

4

Figure 4

stimulation can produce vasovagal episodes associated with pro-found bradycardia, loss of cardiac output and loss of conscious-ness. Stimulation of parasympathetic receptors, traction on pelvic organs, cervical dilatation, elevation of a fractured zygoma or even prolonged suctioning of the pharynx can all result in bradycardia, or even, although usually transient, cardiac standstill.

General principles relating to autonomic reflexes

As outlined above, much of the anatomy and most of the effects of the PNS are relatively discrete: the oculomotor nerve (III) synapses in the ciliary ganglion and innervates the sphincter muscle of the iris and the ciliary muscle, stimulation constrict-ing the pupil; pre-ganglionic fibres carried by the facial nerve


(VII) synapse in both the pterygopalatine and submandibular ganglia to supply secretomotor fibres to the submandibular and sublingual glands as well as sending a branch to the lacrimal gland. They respond to food intake and to corneal/conjuncti-val stimulation. The PNS fibres in the glossopharyngeal nerves synapse in the otic ganglion and supply secretory fibres to the parotid gland. The glossopharyngeal nerve also carries afferent nerves from the carotid body and the carotid sinus. The vagus nerve supplies fibres to the heart (sino-atrial and atrioventricular nodes) and carries afferents from the baroreceptors in the aortic arch, as well as a motor nerve to the vocal cords and sensory fibres to the trachea and bronchi. Further, the vagus provides the motor supply to the whole of the digestive tract down to the mid-point of the colon, including the liver, gall bladder and pancreas.


Physiology

The vagus and glossopharyngeal nerves coordinate the swallow-ing reflex (Figure 4).

The PNS is a vegetative anabolic system that promotes basal processes. It controls the digestive and absorptive processes following the ingestion of food by increasing gastrointestinal motility and stimulating gastrointestinal secretions, including those of the gall-bladder and pancreas. It also facilitates child-birth and evacuation of the bladder and rectum. It slows the heart and produces bronchoconstriction and stimulates bronchial secretions, thereby increasing respiratory resistance.

Sympathetic stimulation produces the classic fight-or-flight reaction. It responds to pain, blood loss and stress – physical and emotional – by constricting peripheral blood vessels, direct-ing blood centrally and to the muscles (away from ‘non-essential’ tissues such as the gut and the skin), arousing the central nervous system and enabling the organism to cope with whatever threat has arisen. It stimulates adrenaline secretion from the adrenal


medulla, which essentially functions as a collection of post- ganglionic adrenergic neurones secreting adrenaline. It produces pupillary dilatation, inhibits gastrointestinal motility and mobi-lizes energy substrate (stimulating glycogenolysis, lipolysis and proteolysis), so releasing glucose, lactate, fatty acids, glycerol and amino acids into the circulation to provide the energy to cope with the threat. It regulates blood pressure in all circumstances and controls thermoregulatory mechanisms in response to heat and cold. The SNS also reacts to internal threats such as illness, with sweating, tachycardia and fever being typical responses to such disturbances as infection, myocardial infarction, pain and injury.

As stated earlier, the precise details of the autonomic reflexes controlling the function of the various organ systems, such as respiratory, cardiovascular and gastrointestinal systems, are covered in the relevant chapters elsewhere in this journal. The same applies to the integrated responses to, for example, injury, exercise and high altitude. ◆


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