SPINAL CORD

The spinal cord lies within the vertebral column, in the upper two-thirds of the vertebral canal, and is continuous rostrally with the medulla oblongata of the brain stem (Ch. 43). For the most part, the spinal cord receives afferent input from, and controls the functions of, the trunk and limbs. Afferent and efferent connections between the periphery and the spinal cord travel in 31 pairs of segmentally arranged spinal nerves that attach to the cord as a linear series of dorsal and ventral rootlets. Adjacent groups of rootlets unite to form dorsal and ventral roots that combine to form the spinal nerves proper (Fig. 15.4). The dorsal and ventral roots are functionally distinct. Dorsal roots carry primary afferent nerve fibres from neuronal cell bodies located in dorsal root ganglia, whereas ventral roots carry efferent fibres from neuronal cell bodies located in the spinal grey matter.

Fig. 15.4 Transverse section through the spinal cord illustrating the disposition of grey and white matter and the attachment of dorsal and ventral spinal nerve roots.

Internally, the spinal cord consists of a central core of grey matter surrounded by white matter. The grey matter is configured in a characteristic H, or butterfly, shape that has projections known as dorsal and ventral horns (Fig. 15.5). In general, neurones situated in the dorsal horn are primarily concerned with sensory functions whilst those in the ventral horn are mostly associated with motor activities. At certain levels of the spinal cord a small lateral horn is additionally present, marking the location of the cell bodies of preganglionic sympathetic neurones. The central canal, a vestigial component of the ventricular system, lies at the centre of the spinal grey matter and runs the length of the cord. The white matter of the spinal cord consists of ascending and descending tracts that link spinal cord segments to one another and the spinal cord to the brain.

Fig. 15.5 Transverse section through the spinal cord at lumbar level. The section has been stained for nerve fibres, leaving the grey matter relatively unstained. (Figure enhanced by B Crossman.)

BRAIN

The brain (encephalon) lies within the cranium (Ch. 26). The brain receives information from, and controls the activities of, the trunk and limbs mainly through connections with the spinal cord. It also possesses 12 pairs of cranial nerves through which it communicates mostly with structures of the head and neck. The brain is divided into major regions on the basis of ontogenetic growth and phylogenetic principles (Fig. 15.6, Fig. 15.7, Fig. 15.8). Ascending in sequence from the spinal cord, the principal divisions are the rhombencephalon or hindbrain, the mesencephalon or midbrain, and the prosencephalon or forebrain.

Fig. 15.6 Nomenclature and arrangement of the major divisions of the brain. A, The major features of the basic brain plan, including their relationships to the major special sensory organs of the head. B, The corresponding regions in the adult brain, seen in sagittal section. C, the organization of the ventricular system in the brain.

Fig. 15.7 Base of the brain, showing major divisions and cranial nerves.

(Figure enhanced by B Crossman, from a photograph by Kevin Fitzpatrick on behalf of GKT School of Medicine, London.)

Fig. 15.8 Sagittal section of the brain. (Figure enhanced by B Crossman.)

The rhombencephalon is subdivided into the myelencephalon or medulla oblongata, metencephalon or pons, and the cerebellum. The medulla oblongata, pons and midbrain are collectively referred to as the brain stem which lies upon the basal portions of the occipital and sphenoid bones (clivus). The medulla oblongata is the most caudal part of the brain stem and is continuous with the spinal cord below the level of the foramen magnum. The pons lies rostral to the medulla and is distinguished by a mass of transverse nerve fibres which connect it to the cerebellum. The midbrain is a short segment of brain stem, rostral to the pons. The cerebellum consists of paired hemispheres united by a median vermis and lies within the posterior cranial fossa, dorsal to the pons, medulla and caudal midbrain, with all of which it has numerous fibre connections.

The prosencephalon is subdivided into the diencephalon and the telencephalon. The diencephalon equates mostly to the thalamus and hypothalamus, but also includes the smaller epithalamus and subthalamus. The telencephalon is mainly composed of the two cerebral hemispheres or cerebrum. The diencephalon is almost completely embedded in the cerebrum and is therefore largely hidden from the exterior. The human cerebrum constitutes the major part of the brain. It occupies the anterior and middle cranial fossae and is directly related to the cranial vault. It consists of two cerebral hemispheres. The surface of each hemisphere is convoluted into a complex pattern of ridges (gyri) and furrows (sulci). Internally, each hemisphere has an outer layer of grey matter, the cerebral cortex, beneath which lies a thick mass of white matter (Fig. 15.9). One of the most important components of the cerebral white matter, the internal capsule (see Fig. 15.11), contains nerve fibres which pass to and from the cerebral cortex and lower levels of the neuraxis. Several large nuclei of grey matter, usually referred to as the basal ganglia, are partly embedded in the subcortical white matter. Connections between corresponding areas of the two sides of the brain cross the midline within commissures. By far the largest commissure is the corpus callosum, which links corresponding regions of the two cerebral hemispheres.

Fig. 15.9 Section through the cerebral hemisphere and brain stem showing the disposition of grey and white matter, the basal ganglia and the internal capsule.

(Photograph by Kevin Fitzpatrick on behalf of GKT School of Medicine, London.)

Fig. 15.11 Corticospinal and corticobulbar tracts.

During prenatal development, the walls of the neural tube thicken greatly, but never completely obliterate the central lumen. Although the latter remains in the spinal cord as the narrow central canal, it becomes greatly expanded in the brain to form a series of interconnected cavities called the ventricular system (Ch. 16). In two regions, the fore- and hindbrains, parts of the roof of the neural tube do not generate nerve cells but become thin, folded sheets of highly vascular secretory tissue, the choroid plexuses. These secrete cerebrospinal fluid which fills the ventricles. The cavity of the rhombencephalon becomes expanded to form the fourth ventricle, which lies dorsal to the pons and upper half of the medulla. Caudally, the fourth ventricle is continuous with a canal in the caudal medulla and, through this, with the central canal of the spinal cord. The fourth ventricle is continuous with the subarachnoid space through three openings in its roof (the foramina of Luschka and of Magendie). At its rostral extent, the fourth ventricle is continuous with a narrow channel, the cerebral aqueduct, which passes through the midbrain. The rostral end of the cerebral aqueduct opens out into the third ventricle, a narrow, slit-like, midline cavity which is bounded laterally by the diencephalon. At the rostral end of the third ventricle, a small aperture on each side leads into the large lateral ventricle which is located within each cerebral hemisphere (see Fig. 15.6C).

OVERVIEW OF ASCENDING SENSORY PATHWAYS

Sensory modalities are conventionally described as being either special senses or general senses. The special senses are olfaction, vision, taste, hearing and vestibular function. Afferent information is encoded by highly specialized sense organs and transmitted to the brain in cranial nerves I, II, VII, VIII and IX (Ch. 25).

The general senses include touch, pressure, vibration, pain, thermal sensation and proprioception (perception of posture and movement). Stimuli from the external and internal environments activate a diverse range of receptors in the skin, viscera, muscles, tendons and joints (Ch. 3). Afferent impulses from the trunk and limbs are conveyed to the spinal cord in spinal nerves whilst those from the head are carried to the brain in cranial nerves. The detailed anatomy of the complex pathways by which the various general senses impinge upon conscious levels is better understood by reference to certain common organizational principles. Whilst undoubtedly oversimplified and subject to exceptions, this schema is helpful in emphasizing the essential similarities that exist between the ascending sensory systems.

In essence, ascending sensory projections related to the general senses consist of a sequence of three neurones that extends from peripheral receptor to contralateral cerebral cortex (Fig. 15.10). These are often referred to as either primary, secondary and tertiary neurones or first-, second- and third-order neurones. Primary afferents have peripherally located sensory endings and cell bodies that lie in dorsal root ganglia or the sensory ganglia associated with certain of the cranial nerves. Their axons enter the CNS through spinal or trigeminal nerves and terminate by synapsing on the cell bodies of ipsilateral second-order neurones: the precise location of this termination depends upon the modality.

Fig. 15.10 Organization of general sensory pathways showing first-order, second-order and third-order neurones.

Primary afferent fibres carrying pain, temperature and coarse touch/pressure information from the trunk and limbs terminate in the dorsal horn of the spinal grey matter, near their point of entry into the spinal cord. Homologous fibres from the head terminate in the trigeminal sensory nucleus of the brain stem. The cell bodies of second-order neurones are located in either the dorsal horn or the trigeminal sensory nucleus. Their axons decussate and ascend to the ventral posterior nucleus of the contralateral thalamus as the spinothalamic or the trigeminothalamic tract, respectively; they synapse on the cell bodies of third-order neurones in the thalamus. Axons of third-order neurones pass through the internal capsule to reach the cerebral cortex, terminating in the postcentral gyrus of the parietal lobe, which is also known as the primary somatosensory cortex.

Primary afferent fibres carrying proprioceptive information and fine (discriminative) touch from the trunk and limbs ascend ipsilaterally in the spinal cord as the dorsal columns (fasciculus gracilis and fasciculus cuneatus): they end by synapsing on second-order neurones in the dorsal column nuclei (nucleus gracilis and nucleus cuneatus) of the medulla. Axons of second-order neurones decussate in the medulla and then ascend as the medial lemniscus to the ventral posterior nucleus of the contralateral thalamus, where they synapse on the cell bodies of third-order neurones. Axons of third-order neurones pass through the internal capsule to reach the cerebral cortex, terminating in the primary somatosensory cortex. A similar homologous projection exists for afferents derived from the head.

OVERVIEW OF DESCENDING MOTOR PATHWAYS

Corticofugal fibres descend through the internal capsule and pass into the brain stem, where some of them (corticobulbar fibres) terminate. Corticobulbar fibres control the activity of brain stem neurones, including motor neurones within the cranial nerve nuclei. Current neuroanatomical nomenclature does not include a generally accepted term that denotes projections from the cerebral cortex to the brain stem as a whole. Such a term is, however, required in order to draw clinical comparison between the corticospinal system, coursing through the pyramids, and the functionally homologous fibres that terminate in the brain stem. The term ‘corticonuclear’ is sometimes used, but this implies specific innervation of cranial nerve nuclei and ignores the fact that numerous cortical efferents project to other sites, such as the reticular formation. The term ‘corticobulbar’ is also sometimes used but this, strictly speaking, refers to projections to the ‘bulb’, an archaic term for the medulla oblongata. In this text, ‘corticobulbar’ is used to denote cortical projections to the brain stem as a whole.

Corticospinal fibres (pyramidal tract) originate from widespread regions of the cerebral cortex, including the primary motor cortex of the frontal lobe where the opposite half of the body is represented in a detailed somatotopic fashion. They descend throughout the length of the brain stem; the majority cross to the contralateral side in the decussation of the pyramids in the medulla, subsequently continuing caudally as the lateral corticospinal tract of the spinal cord which terminates in association with interneurones and motor neurones of the spinal grey matter (Fig. 15.11). The principal function of the corticospinal and corticobulbar tracts is the control of fine, fractionated movements, particularly of those parts of the body where delicate muscular control is required. These tracts are particularly important in speech (corticobulbar tract) and movement of the hand (corticospinal tract).

The concept of upper and lower motor neurones is fundamental to the clinical description of the effects of lesions of the motor system. The signs and symptoms of upper and lower motor neurone lesions are very different and are indicative of the anatomical site of the lesion. ‘Lower motor neurones’ are the alpha motor neurones that innervate the extrafusal muscle fibres of skeletal muscle. In theory, the term ‘upper motor neurones’ refers collectively to all the descending pathways that impinge upon the activity of lower motor neurones. In common parlance, however, the term is often equated with the corticospinal tract. The terms upper and lower motor neurone lesion are used clinically to distinguish, for example, between the effects of a stroke in the internal capsule (a typical upper motor neurone lesion) and those of motor neurone disease (a typical lower motor neurone lesion).

Lower motor neurone lesions cause paralysis or paresis of specific muscles because they have lost their direct innervation. There is also loss or reduction of tendon reflex activity and reduced muscle tone. Spontaneous muscular contractions (fasciculation) occur and affected muscles atrophy over time. Upper motor neurone lesions cause paralysis or paresis of movements as a result of loss of higher control. There is increased tendon reflex activity and increased muscle tone but no muscle atrophy occurs. A positive plantar (Babinski) reflex is present. The combination of paralysis, increased tendon reflex activity and hypertonia is referred to as spasticity.

The pathophysiology underlying the symptoms of upper motor neurone lesions is complex. This is because many descending pathways other than the corticospinal tract exist and they also influence lower motor neurone activity. These pathways include corticofugal projections to the brain stem (e.g. corticoreticular and corticopontine) that traverse the internal capsule and numerous pathways that originate within the brain stem itself (e.g. reticulospinal, vestibulospinal). Clearly, these pathways may be compromised to varying extents, depending upon the site of a lesion. Their involvement is believed to be important in the pathophysiological mechanisms that underlie the generation of spasticity. Pure corticospinal tract lesions, which are exceedingly rare in man because corticospinal tract fibres lie in close relationship to other pathways throughout most of their course, are believed specifically to cause deficits in delicate, fractionated movements and to induce the positive plantar reflex.

Two other major systems that contribute to the control of movement are the basal ganglia and the cerebellum. The basal ganglia are a group of large subcortical nuclei, the major components being the caudate nucleus, putamen and globus pallidus (Fig. 15.9; Ch. 22). These structures have important connections with the cerebral cortex, certain nuclei of the thalamus and subthalamus and with the brain stem. They appear to be involved in the selection of appropriate movements and the suppression of inappropriate ones. Disorders of the basal ganglia cause either too little movement (akinesia) or abnormal involuntary movements (dyskinesias) as well as tremor and abnormalities of muscle tone. The basal ganglia are sometimes described as being part of the so-called ‘extrapyramidal (motor) system’. This term is used to distinguish between the effects of basal ganglia disease and those of damage to the ‘pyramidal’ (corticospinal) system. However, the progressive elucidation of the anatomy of the basal ganglia and of the pathophysiology of motor disorders has revealed the close functional interrelationship between the two ‘systems’, and has rendered the terms that distinguish them largely obsolete (Brodal 1981). The cerebellum (Ch. 20) has rich connections with the brain stem, particularly the reticular and vestibular nuclei, and with the thalamus. It is concerned with the coordination of movement: cerebellar disorders cause ataxia, intention tremor and hypotonia.

SPINAL NERVES

Spinal nerves are the means by which the CNS receives information from, and controls the activities of, the trunk and limbs. Spinal nerves are considered in detail elsewhere on a regional basis (Sections 5, 6, 8 and 9).

In brief, there are 31 pairs of spinal nerves (8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal) which contain a mixture of sensory and motor fibres. They originate from the spinal cord as continuous series of dorsal and ventral nerve rootlets. Adjacent groups of rootlets fuse to form dorsal and ventral roots which then merge to form the spinal nerves proper. The dorsal roots of spinal nerves contain afferent nerve fibres from cell bodies located in dorsal root ganglia. These cells give off both centrally and peripherally directed processes and do not have synapses on their cell bodies. The ventral roots of spinal nerves contain efferent fibres from cell bodies located in the spinal grey matter. They include motor neurones innervating skeletal muscle and preganglionic autonomic neurones.

Spinal nerves exit from the vertebral canal via their corresponding intervertebral foramina. They then divide to form a large ventral (anterior) ramus and a smaller dorsal (posterior) ramus. In general terms, the ventral ramus innervates the limbs together with the muscles and skin of the anterior part of the trunk. The dorsal ramus innervates the post-vertebral muscles and the skin of the back. The nerve fibres within the ventral rami serving the upper and lower limbs are redistributed within brachial and lumbosacral plexuses, respectively.

CRANIAL NERVES

Cranial nerves are the means by which the brain receives information from, and controls the activities of, the head and neck and to a lesser extent the thoracic and abdominal viscera. The component fibres, their route of exit from the cranial cavity, their subsequent peripheral course and the distribution and functions of the cranial nerves, are considered in detail elsewhere on a regional basis (Sections 4, 7, 8). Their origins, destinations and connections within the CNS are considered in this section.

Briefly, there are 12 pairs of cranial nerves. They are individually named and numbered (Roman numerals) in a rostrocaudal sequence (Table 15.1). Unlike spinal nerves, only some cranial nerves are mixed in function, carrying both sensory and motor fibres. Others are purely sensory or purely motor. The first cranial nerve (I; olfactory) has an ancient lineage and is derived from the forerunner of the cerebral hemisphere. It retains this unique position through the connections of the olfactory bulb, and is the only sensory cranial nerve that projects directly to the cerebral cortex rather than indirectly via the thalamus. The areas of cerebral cortex receiving olfactory input have a primitive cellular organization and are an integral part of the limbic system, which is concerned with the emotional aspects of behaviour (Ch. 23). The second cranial nerve (II; optic) consists of the axons of second order visual neurones and these terminate in the thalamus. The other ten pairs of cranial nerves attach to the brain stem and most of their component fibres originate from, or terminate in, the cranial nerve nuclei of the brain stem (Ch. 19).

The sensory fibres in individual spinal and cranial nerves have characteristic, but often overlapping, peripheral distributions. As far as the innervation of the body surface is concerned, the area that is supplied by a particular spinal or cranial nerve is referred to as a dermatome. There is marked overlap between dermatomes of adjacent spinal nerves, particularly for the segments least affected by development of the limbs, i.e. the second thoracic to the first lumbar. In some regions, e.g. the upper anterior thoracic wall, the cutaneous nerves that supply adjoining areas are not from consecutive spinal nerves and the overlap is minimal. Maps of dermatome distribution are useful in clinical neurology to identify the location of pathology in patients with peripheral sensory deficits. Dermatome maps are somewhat inconsistently reported by different authors, reflecting the fact that the maps are composite constructs that have been compiled to a large extent by clinical observations on patients with cranial or spinal nerve pathology (Fig. 15.12). Detailed dermatome maps are described on a regional basis (Chs 42, 45, 79). The motor axons of individual spinal and cranial nerves tend to innervate anatomically and functionally related groups of skeletal muscles, that are referred to as myotomes.

Fig. 15.12 Dermatome maps, illustrating the variation reported by different authors. A, Dermatome map based on Keegan JJ, Garrett FD 1948 The segmental distribution of the cutaneous nerves in the limbs of man. Anat Rec 102: 409–439. Mainly used in literature in the USA. B, Dermatome map based on Moffat DB 1993 Lecture Notes on Anatomy, 2nd edn. Oxford: Blackwell Scientific. Mainly used in literature in the UK.

SYMPATHETIC NERVOUS SYSTEM

The sympathetic trunks are two ganglionated nerve cords that extend on either side of the vertebral column from the cranial base to the coccyx (Ch. 55). The ganglia are joined to spinal nerves by short connecting nerves called white and grey rami communicantes. Preganglionic axons join the trunk through the white rami communicantes while postganglionic axons leave the trunk in the grey rami. In the neck each sympathetic trunk lies posterior to the carotid sheath and anterior to the transverse processes of the cervical vertebrae. In the thorax the trunks are anterior to the heads of the ribs, in the abdomen they lie anterolateral to the bodies of the lumbar vertebrae, and in the pelvis they are anterior to the sacrum and medial to the anterior sacral foramina. Anterior to the coccyx the two trunks meet in a single, median, terminal ganglion. Cervical sympathetic ganglia are usually reduced to three by fusion. The internal carotid nerve, a continuation of the sympathetic trunk, issues from the cranial pole of the superior ganglion and accompanies the internal carotid artery through its canal into the cranial cavity. There are from 10 to 12 (usually 11) thoracic ganglia, 4 lumbar ganglia and 4 or 5 ganglia in the sacral region.

The cell bodies of preganglionic sympathetic neurones are located in the lateral horn of the spinal grey matter of all thoracic segments and the upper two or three lumbar segments (Fig. 15.14). Their axons are myelinated with diameters of 1.5–4 μm. They leave the cord in the corresponding ventral nerve roots and pass into the spinal nerves, but soon leave in white rami communicantes to join the sympathetic trunk (Fig. 15.15). Neurones like those in the lateral grey column exist at other levels of the cord above and below the thoracolumbar outflow and small numbers of their fibres leave in other ventral roots. Preganglionic sympathetic neurones release acetylcholine as their principal neurotransmitter.

Fig. 15.14 Transverse section through the thoracic spinal cord showing the lateral horn where preganglionic sympathetic neurones are located. (Figure enhanced by B Crossman.)

Fig. 15.15 Relationship between spinal nerves and the sympathetic trunk.

On reaching the sympathetic trunk, preganglionic fibres behave in one of several ways (Fig. 15.15). They may synapse with neurones in the nearest ganglion, or traverse the nearest ganglion and ascend or descend in the sympathetic chain to end in another ganglion. A preganglionic fibre may terminate in a single ganglion or, through collateral branches, synapse with neurones in several ganglia. Preganglionic fibres may traverse the nearest ganglion, ascend or descend and, without synapsing, emerge in one of the medially directed branches of the sympathetic trunk to synapse in the ganglia of autonomic plexuses (mainly situated in the midline, e.g. around the coeliac and mesenteric arteries). More than one preganglionic fibre may synapse with a single postganglionic neurone. Uniquely, the suprarenal gland is innervated directly by preganglionic sympathetic neurones that traverse the sympathetic trunk and coeliac ganglion without synapse.

The somata of sympathetic postganglionic neurones are located mostly in ganglia of the sympathetic trunk or ganglia in more peripheral plexuses. The axons of postganglionic neurones are, therefore, generally longer than those of preganglionic neurones, an exception being some of those that innervate pelvic viscera. The axons of ganglionic cells are unmyelinated. They are distributed to target organs in various ways. Those from a ganglion of the sympathetic trunk may return to the spinal nerve of preganglionic origin through a grey ramus communicans, which usually joins the nerve just proximal to the white ramus, and are then distributed through ventral and dorsal spinal rami to blood vessels, sweat glands, hairs, etc., in their zone of supply. Segmental areas vary in extent and overlap considerably. The extent of innervation of different effector systems, e.g. vasomotor, sudomotor, etc., by a particular nerve may not be the same. Alternatively, postganglionic fibres may pass in a medial branch of a ganglion direct to particular viscera, or innervate adjacent blood vessels, or pass along them externally to their peripheral distribution. They may ascend or descend before leaving the sympathetic trunk as described above. Many fibres are distributed along arteries and ducts as plexuses to distant effectors.

The principal neurotransmitter released by postganglionic sympathetic neurones is noradrenaline. The sympathetic system has a much wider distribution than the parasympathetic. It innervates all sweat glands, the arrector pili muscles, the muscular walls of many blood vessels, the heart, lungs and respiratory tree, the abdominopelvic viscera, the oesophagus, the muscles of the iris, and the non-striated muscle of the urogenital tract, eyelids and elsewhere.

Postganglionic sympathetic fibres that return to the spinal nerves are vasoconstrictor to blood vessels, secretomotor to sweat glands and motor to the arrector pili muscles within their dermatomes. Those that accompany the motor nerves to voluntary muscles are probably only dilatatory. Most, if not all, peripheral nerves contain postganglionic sympathetic fibres. Those reaching the viscera are concerned with general vasoconstriction, bronchial and bronchiolar dilatation, modification of glandular secretion, pupillary dilatation, inhibition of alimentary muscle contraction, etc. A single preganglionic fibre probably synapses with the postganglionic neurones in only one effector system, which means that effects such as sudomotor and vasomotor actions can be separate.

PARASYMPATHETIC NERVOUS SYSTEM

Preganglionic parasympathetic neurone cell bodies are located in certain cranial nerve nuclei of the brain stem (see Fig. 19.1) and in the grey matter of the second to fourth sacral segments of the spinal cord. Efferent fibres, which are myelinated, emerge from the CNS only in cranial nerves III, VII, IX and X and in the second to fourth sacral spinal nerves. Preganglionic parasympathetic neurones are cholinergic.

The cell bodies of postganglionic parasympathetic neurones are mostly sited distant from the CNS, either in discrete ganglia located near the structures innervated, or dispersed in the walls of viscera. In the cranial part of the parasympathetic system there are four small peripheral ganglia, ciliary, pterygopalatine, submandibular and otic, that are all described on a regional basis in Section 4. These are solely efferent parasympathetic ganglia, unlike the trigeminal, facial, glossopharyngeal and vagal ganglia, all of which are concerned exclusively with afferent impulses and contain the cell bodies of sensory neurones. The cranial parasympathetic ganglia are also traversed by afferent fibres, postganglionic sympathetic fibres, and, in the case of the otic ganglion, even by branchial efferent fibres; none of these fibres synapse in the ganglia. Postganglionic parasympathetic fibres are usually unmyelinated and shorter than their counterparts in the sympathetic system, because the ganglia in which the parasympathetic fibres synapse are in or near the viscera they supply. Postganglionic parasympathetic neurones are cholinergic.

ENTERIC NERVOUS SYSTEM AND INTRINSIC NEURONES

Many peripheral autonomic ganglia contain neurones derived from the neural crest during embryonic development that are anatomically distinct from classical sympathetic and parasympathetic neurones. Connections between these intrinsic neurones allow them to sustain and modulate visceral activities by local reflex mechanisms. The enteric nervous system consists of many millions of neurones and enteric glial cells grouped into ganglionated plexuses lying in the wall of the gastrointestinal tract: ganglia containing neuronal cell bodies and glia are connected by bundles of axons to form myenteric and submucous plexi that extend from the oesophagus to the anal sphincter (Chs 3 and 60). This intrinsic circuitry mediates numerous reflex functions including the contractions of the muscular coats of the alimentary tract, secretion of gastric acid, intestinal transport of water and electrolytes and the regulation of mucosal blood flow. Although complex interactions occur between the enteric and sympathetic and parasympathetic nervous systems, the enteric nervous system is capable of sustaining local reflex activity independent of the CNS.

Since intrinsic neurones survive after section of the extrinsic sympathetic and parasympathetic nerves, organs that are transplanted are not truly denervated. Separation from their autonomic input often has no obvious impact on the non-striated muscle or glands innervated by autonomic fibres: contraction may be unaffected and no structural changes ensue. This has been variously attributed to the continued activity of local plexuses or to the intrinsic activity of visceral muscle. In some important instances, however, denervation does result in cessation of activity, e.g. in sweat glands, pilomotor muscle, orbital non-striated muscle and the suprarenal medulla.

VISCERAL AFFERENT PATHWAYS

General visceral afferent fibres from the viscera and blood vessels accompany their efferent counterparts, and are the peripheral processes of unipolar cell bodies located in some cranial nerve and dorsal root ganglia. They are contained in the vagus, glossopharyngeal, and possibly other cranial nerves; the second to fourth sacral spinal nerves, distributed with the pelvic splanchnic nerves; and in thoracic and upper lumbar spinal nerves, distributed through rami communicantes and alongside the efferent sympathetic innervation of viscera and blood vessels.

The cell bodies of vagal general visceral afferent fibres are in the superior and inferior vagal ganglia. Their peripheral processes are distributed to terminals in the pharyngeal and oesophageal walls where, acting synergistically with glossopharyngeal visceral afferents in the pharynx, they are concerned with swallowing reflexes. Vagal afferents are also believed to innervate the thyroid and parathyroid glands. In the heart, vagal afferents innervate the walls of the great vessels, the aortic bodies and pressor receptors, where they are stimulated by raised intravascular pressure. In the lungs they are distributed via the pulmonary plexuses. They supply bronchial mucosa, where they are probably involved in cough reflexes; bronchial muscle, where they encircle myocytes and end in tendrils, which are sometimes regarded as muscle spindles and which are believed to be stimulated by change in the length of myocytes; interalveolar connective tissue, where their knob-like endings, together with terminals on myocytes, may evoke Hering–Breuer reflexes; the adventitia of pulmonary arteries, where they may be pressor receptors; and the intima of pulmonary veins, where they may be chemoreceptors. Vagal visceral afferent fibres also end in the gastric and intestinal walls, digestive glands, and the kidneys. Fibres ending in the gut and its ducts respond to stretch or contraction. Gastric impulses may evoke sensations of hunger and nausea.

The cell bodies of glossopharyngeal general visceral afferents are in the glossopharyngeal ganglia. Their peripheral processes innervate the posterior lingual region, the tonsils and pharynx, but they do not innervate taste buds. They also innervate the carotid sinus and the carotid body, which contain receptors sensitive to tension and changes in chemical composition of the blood. Impulses from these receptors are essential to circulatory and respiratory reflexes.

Visceral afferents that enter the spinal cord through spinal nerve roots terminate in the spinal grey matter. The central processes of vagal and glossopharyngeal afferent fibres end in the vagal nucleus or the nucleus solitarius of the medulla. Visceral afferents establish connections within the CNS that mediate autonomic reflexes. In addition, afferent impulses probably mediate visceral sensations such as hunger, nausea, sexual excitement, vesical distension, etc. Visceral pain fibres may follow these routes. Although viscera are insensitive to cutting, crushing or burning, excessive tension in smooth muscle and some pathological conditions produce visceral pain. In visceral disease, vague pain may be felt near the viscus itself (visceral pain) or in a cutaneous area or other tissue whose somatic afferents enter spinal segments receiving afferents from the viscus, a phenomenon known as referred pain. If inflammation spreads from a diseased viscus to the adjacent parietal serosa (e.g. the peritoneum), somatic afferents will be stimulated, causing local somatic pain, which is commonly spasmodic. Referred pain is often associated with local cutaneous tenderness.

Afferent fibres in pelvic splanchnic nerves innervate pelvic viscera and the distal part of the colon. Vesical receptors are widespread: those in muscle strata are associated with thickly myelinated fibres and are believed to be stretch receptors, possibly activated by contraction. Pain fibres from the bladder and proximal urethra traverse both the pelvic splanchnic nerves and the inferior hypogastric plexus, hypogastric nerves, superior hypogastric plexus and lumbar splanchnic nerves to reach their cell bodies in ganglia on the lower thoracic and upper lumbar dorsal spinal roots: the significance of this dual sensory pathway is uncertain. Lesions of the cauda equina abolish pain from vesical overdistension, but hypogastric section is ineffective. Pain fibres from the uterus traverse the hypogastric plexus and lumbar splanchnic nerves to reach somata in the lowest thoracic and upper lumbar spinal ganglia, and hypogastric division may relieve dysmenorrhoea. Afferents from the uterine cervix traverse the pelvic splanchnic nerves to reach their somata in the upper sacral spinal ganglia: stretching the cervix uteri causes pain but cauterization and biopsy excisions do not.

In general, afferent fibres that accompany pre- and postganglionic sympathetic fibres have a segmental arrangement and end in spinal cord segments from which preganglionic fibres innervate the region or viscus concerned. General visceral afferents entering thoracic and upper lumbar spinal segments are largely concerned with pain. Nociceptive impulses from the pharynx, oesophagus, stomach, intestines, kidneys, ureter, gallbladder and bile ducts seem to be carried in sympathetic pathways. Cardiac nociceptive impulses enter the spinal cord in the first to fifth thoracic spinal nerves, mainly via the middle and inferior cardiac nerves, but some fibres pass directly to the spinal nerves. It is said that there are no general visceral afferents in the superior cardiac nerves. Peripherally, the fibres pass through the cardiac plexuses and along the coronary arteries. Myocardial anoxia may evoke symptoms of angina pectoris in which pain is typically presternal, and is also referred to much of the left chest, and radiates to the left shoulder, the medial aspect of the left arm, along the left side of the neck to the jaw and occiput, and down to the epigastrium. Cardiac afferents carried in vagal cardiac branches are concerned with the reflex depression of cardiac activity. Ureteric pain fibres, also running with sympathetic fibres, are presumably involved in the agonizing renal colic that follows obstruction by calculi. Afferent fibres from the testis and ovary run through the corresponding plexuses to somata in the tenth and eleventh thoracic dorsal root ganglia.

Certain primary afferent nerve fibres, that have their cell bodies in cranial and dorsal root ganglia, also have an efferent function (so-called sensory–motor nerves). The importance of sensory–motor nerve regulation in many organs, such as the gut, lungs, heart and blood vessels, is now recognized. While most such nerves are, presumably, purely sensory, certain of them have been termed sensory–motor because they release transmitters from their peripheral endings during the axon reflex and have a motor rather than a sensory role. The primary substances released in this way are substance P, calcitonin gene-related peptide (CGRP) and ATP. These act on target cells to produce several biological actions which include vasodilatation, increased venular permeability, changes in smooth muscle contractility, degranulation of mast cells and a variety of effects on leukocytes and fibroblasts, a process collectively known as ‘neurogenic inflammation’. The local release of such substances may play a trophic role in the maintenance of tissue integrity and repair in response to injury.

PARAGANGLIA

Paraganglia are extrasuprarenal aggregations of chromaffin tissue, distributed near to or within the autonomic nervous system (Fig. 15.16). Cells like those in paraganglia also occur in the sympathetic ganglia of various viscera and in a variety of retroperitoneal and mediastinal sites. All are derived from the neural crest, and all synthesize and store catecholamines. Their functions differ with location: some cells act as interneurones, others as sources of neuroendocrine secretion. Paraganglionic catecholamine release occurs mainly in response to chemical rather than to neural stimuli, e.g. in the suprarenal medulla. Extrasuprarenal chromaffin tissue is prominent in the fetus, and acts as the main source of catecholamines while the suprarenal medulla is immature. Although many paraganglia degenerate soon after birth, others persist into adulthood, often as microscopic paraganglia.

Fig. 15.16 The principal aggregations of ‘classic’ chromaffin tissue in the human neonate. The aggregates in stippled blue lie deep to overlying structures.

Paraganglia are well-vascularized and their secretory cells are usually close to one or more fenestrated capillaries. Most have a sympathetic innervation and act as endocrine organs, e.g. suprarenal medullary chromaffin cells. Others are associated with the parasympathetic system, and their secretions probably have activities on local nerve endings, e.g. the carotid body. Paraganglia produce regulatory peptides, particularly enkephalins, and store them as cytoplasmic granules until stimulated to release them. Their secretions may exert a local paracrine action on nearby cells, in addition to having remote endocrine effects.