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Functional micro-anatomy of the peripheral nerve trunks
Functional Micro-anatomy oJ the Peripheral Nerve Trunks--K. Kuczynski
FUNCTIONAL MICRO-ANATOMY OF T H E PERIPHERAL
NERVE
TRUNKS
K. KUCZYNSI
The structural unit of the nervous system is the neurone, i.e. the nerve cell with its processes (Fig. 1). The cell body (perikaryon) and the dendrites contain Nissl substance but the axon does not. This substance contains ribose nucleic acid (RNA) which is concerned with the protein synthesis and may be transformed into a more active form of R N A during so-called "chromatolysis" (Ducker, 1969) during the process of repair following injury. The nerve cell is one of the most active in the body. After axonal injury the cell shows a great increase in its metabolism which reaches a peak in two to three weeks. During regeneration and maturation of the repaired nerve there is another metabolic peak when new connections with the end organs are being established (Ducker, 1972). It is calculated that during successful repair the nerve
AXON~ . ~
_~DENDRITES
TERMINAL ~
NODEof RANVIER--
~
AXONHILLOCK I~_CELLULARSHEATH {myelin-block) i__
ENDPkAI~
I
MUSCLE
Fig. 1 Diagrammatic view of a neurone. The Hand--Vol. 6
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Functional Micro-anatomy of the Peripheral Nerve Trunks--K. Kuczynski FLOW OFAXOPLASM IN AXON
MICROTUBULE
-
MITOCHONDRION
Fig. 2 Suggested bidirectional axoplasmic flow. cell replaces up to 100 times the protein and organic material in the perikaryon (Hyden, 1960). In more proximal lesions of the peripheral nerves the duration of the increased metabolic activity for repair is much greater than in more distal lesions where the loss of cell mass is smaller. The axoplasm, surrounded by the cell membrane called axolemma, is in the form of a viscous fluid in which a bi-directional flow takes place. At least two varieties of proximo-distal transport of materials are thought to occur: (a) slow (about 1 mm a day) which is associated apparently with the peristalsis of the membrane of the nerve fibre (Weiss, 1961) and (b) fast transport (about 10 cm a day) which may be provided by the microtubules (Fig. 2) of the axon (Ochs, 1969; Mayor, 1972) in response to a sudden demand. Recently it has been shown (Watson, 1968; Kristensson, 1971) that there is also a transport from the periphery to the cell body which may be relevant to the theory that the nerve cell is normally influenced by substances from the peripheral field of innervation. All these forms of axonal transport depend on supply of oxygen and may be blocked by ischaemia (Kristensson, 1971). At the nodes of Ranvier the axons may give rise to the branches, i.e. collaterals (Fig. I). This is why a motor cell may innervate 200 or more muscle fibres when only a relatively gross movement is required as in the large muscles of the limb. On the other hand when fine gradations are necessary as in the muscles of the eyeball the number of muscle fibres innervated by each motor nerve cell is small; the number of muscle fibres in a motor unit at the extremity of the limb is probably small (Romanes, 1951). Such branching in motor axons occurs close to the muscle. NERVE
FIBRES
There are two varieties of the nerve fibres distinguished by the relative amount of myelin present in the cellular sheath. Those which have no compact myelin sheath are called non-myelinated (Fig. 3) while those with a myelin layer are known as myelinated fibres (Fig. 4). Most of the peripheral nerves contain a mixture of both varieties. Both types of fibres are surrounded by a chain of 2
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Functional Micro-anatomy o/ the Peripheral Nerve Trunks--K, Kuczynski
~ " x ~
AXON
~ --
MESAXON
PLASMAMEMBRANE OF SCHWANN CELL
- - ~ ........I..~.~,~ ~
--
. . . . . . . . .
.z-z~'~ 3 L,
protein lipid protein
3 &4 fuse
Fig. 3 Diagram to show the arrangement of the unmyelinated nerve fibres in relation to the Schwann cell and the mode of formation of the mesoaxon. 2XTRACELLULARIONS / \
MYELIN SHEATH
Fig. 4 Details of a myelinated nerve fibre. Schwann cells arranged end to end. In the case of non-myelinated fibres, one Schwann cell may a c c o m m o d a t e parts of m a n y axons, while in the myelinated variety each axon is associated with only one Schwann cell at any one level. In the latter case (Fig. 5 and 6), the m e m b r a n e of the Schwann cell is wrapped spirally around the axon thus producing a sheath of alternating layers of lipid and protein, the myelin sheath. Figure 4 shows in greater detail the organisation of the myelinated fibre. The Schwann cells, separated from the endoneurial tube by a basement m e m brane, lie end to end meeting at the node of Ranvier where their finger-like processes interdigitate. There is a space between these processes which allows the extracellular ions to reach the axon, while the internodal part of the axon is insulated f r o m these ions by the cellular sheath (Schwann cell and myelin sheath). This is important in saltatory propagation of the impulse from node to node. In some areas the laminae of the myelin sheath are separated by a relatively large amount of the cytoplasm of the Schwann cell which passes obliquely through the myelin between the inner and outer cytoplasmic layers of the cellular The Hand--Vol. 6
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Functional Micro-anatomy of the Peripheral Nerve T r u n k s - - K . Kuczynski
Fig. 5 The stages in formation of the myelin sheath (the Schwann cell being gradually wrapped around the axon).
Fig. 6 The flattened out Schwann cell and the areas of different thickness of its cytoplasm (including two Schmidt-Lantermann incisures). The arrow shows the direction of the spiral movement. sheath. These are called Schmidt-Lantermann incisures and m a y be related to the nutrition and function of the nerve fibre (Robertson, 1958; Krishnan, 1972). It has been suggested that they m a y prevent abnormal distortion and fracture of myelin under stresses applied to the nerve trunk (Glees, 1943). Their position may not be constant, but they m a y move to and fro along the fibre sheath, separating the lamellae of the myelin as they do so. The complex sheath composed of the myelin (in myelinated fibres), the Schwann cell and the endoneurial tube prevents the spread of nerve impulses f r o m a fibre to the adjacent ones. Such a spread m a y occur after injury to the fibres at the so-called "artificial synapse" (Granit, 1944; Sutherland, 1968; Murray, 1972). 4
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Functional Micro-anatomy of the Peripheral Nerve Trunks--K. Kuczynski PERIPHERAL NERVE TRUNKS
T h e peripheral nerve t r u n k s in the body wall and limbs are composed of motor, sensory and sympathetic nerve fibres enclosed in three connective tissue coats. On functional grounds the fibres are considered as either efferent or afferent. The efferent fibres are of three varieties: (1) large ~ fibres to the extrafusal muscle fibres, (2) small y fibres to the muscle spindles which alter their contraction and control their sensitivity and (3) postganglionic sympathetic fibres (vasomotor, pilomotor and sudomotor). The afferent fibres consist of the peripheral processes of the sensory nerve cells of the spinal ganglia which are distributed to the sensory endings. Muscular and cutaneous branches of a peripheral nerve trunk may contain several different types of fibres. Nerves to the muscles carry not only efferent fibres ( ~ , 7 and vasomotor) but also sensory fibres to the muscles and often also to the adjacent tendons, bones and joints. Cutaneous nerves are not exclusively sensory to the skin and the subcutaneous tissue but also contain efferent sympathetic fibres. In some cases (e.g. the digital nerve) sensory fibres to the joints, ligaments and bones m a y also be present. The nerve fibres in the peripheral trunk are not distributed in a uniform fashion throughout the cross-section of the trunk but are collected into separate bundles called funiculi, invested with a cellular connective tissue sheath of perineurium. Usually these funiculi contain motor, sensory and sympathetic fibres but this is not always so. Each funiculus repeatedly divides and its branches unite with those of other funiculi to form a plexus along the length of the nerve (Fig. 7). This results in rapid changes in the funicular pattern and in variation in size and content of the funiculi at different levels. According to Sunderland (1968) the m a x i m u m length of a constant pattern does not exceed 1.5 cm. The funicular redistribution of the nerve fibres resulting f r o m their plexiform arrangement may lead to the blending of two originally distinct groups of fibres. In some cases an individual bundle m a y retain its position for a considerable distance while fibres f r o m other funiculi are added progressively. N e a r the root of the limb there is widespread intermingling and dispersion of the fibres. In practice, the safe distance to which a branch can be stripped f r o m the nerve trunk depends on how far proximally it retains its independence in the funicular pattern. This is variable and can be studied in the tables provided by Sunderland (1968).
Fig. 7 The exchange of fibres in the funicular plexus and difference in the pattern of two cross-sections. The Hand--Vol. 6
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Functional Micro-anatomy o/ the Peripheral Nerve Trunks--K. Kuczynski
When an end-to-end repair is made between the nerve stumps even after a small resection, a large n u m b e r of regenerating axons m a y be lost in the connective tissue between the funiculi of the distal stump as in most instances two newly obtained cross-sections do not have matching funicular patterns, and even if they do, may not be correctly oriented. Thus some regenerating axons may enter wrong endoneurial tubes, e.g. efferent into afferent and vice versa and even if this does not happen, the efferent of one variety m a y grow into the tubes of the efferent of another type (,~, 7 and sympathetic). The same applies to the sensory fibres connected to different endings (e.g. muscle spindles and skin endorgans). To avoid this confusion a ]unicular suture is advocated. This may prevent or reduce escape of the growing axon buds into the interfunicular connective tissue of the distal stump, but the exact matching of the funiculi is difficult. Attempts are being made to determine the functional variety of the funicular fibres (Hakstian, 1968; Vandeput, 1969) in the two cut ends before suturing them together. In some regions the fibres representing individual branches are still well localised and in these cases a funicular suture can be performed with some confidence. The funiculi of the posterior interosseous and superficial radial branches in the trunk of the radial nerve and the dorsal branch of the ulnar nerve in the forearm m a y serve as an example. At the wrist the deep branch of the ulnar nerve can be isolated from the superficial branch and each separately sutured. In some cases where the bundle in the nerve trunk is not considered to be of great functional importance (e.g. superficial radial) it could be mobilised, excised and excluded from the suture of the radial nerve trunk. The same applies to the funiculus of the posterior cutaneous nerve of the f o r e a r m of the radial trunk in the spiral groove. The maps of the funicular patterns at different levels are given by Sunderland (1968). It should be r e m e m b e r e d however that the funicular pattern is subject to such a wide range of variation that its precise arrangement can be only established at the time of the operation. In other regions, funicular suture or exclusion is more difficult as for example in the median nerve where the intraneural interchange between funieuli is quite extensive. In cases of division of the median nerve in the upper part of the forearm when recovery of opposition is less likely because of the failure of the motor nerve fibres to reach the thenar muscles, it m a y be useful to transfer the muscular branch of the ulnar nerve to the third lumbrical to the distal end of the isolated and divided recurrent branch of the median nerve (Schultz and Aiache, 1972).
THE CONNECTIVE TISSUE OF THE P E R I P H E R A L N E R V E T R U N K
This is made up of three layers. E p i n e u r i u m consists of areolar connective tissue which separates the funiculi and is condensed on the surface of the nerve trunk to form an investing layer (Fig. 8). This layer is only loosely attached to the surrounding structures and thus the nerve enjoys considerable mobility except in those areas where the branches are given off and where the nutrient arteries enter the trunk. There are some longitudinal elastic fibres in epineurium which apparently maintain the tortuous course of the peripheral nerve trunks. This m a y help to prevent stretching during movements at the joints. Sunderland (1968) believes that the main cushion against compression is provided by the loose padding of the epineurium and that those nerve trunks which contain numerous small funiculi have more epineurial tissue and are therefore less vulnerable to compression than those which have only one single funiculus (e.g. ulnar nerve at the elbow). 6
The Hand--Vol. 6
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Functional Micro-anatomy of the Peripheral Nerve Trunks--K. Kuczynski ~ Plr',IFI ll~ll Ifvl
PER
UNI~ NEF
UM
I
Fig. 8 Cross-section of a peripheral nerve trunk (not to scale). Inset shows a simplified view of a myelinated nerve fibre. P e r i n e u r i u m invests each funiculus of nerve fibres. It is a relatively thin but dense multilayered sheath of fibrous tissue containing a compact network of collagen and elastic fibres (Fig. 8). These fibres are arranged into 6-12 concentric laminae separated by clefts lined by mesothelial cells (perineurial spaces). According to Gamble (1964) part of the bulk of the perineurium is made up of basement membranes, covering the cellular layers. The outer layer of perineurium merges without sharp distinction with the interfunicular tissue of the epineurium, while the inner layer forms a membrane composed of one or two layers of flattened cells, which is called perilemma. Elasticity of the perineurium apparently is responsible for the wavy course of the funiculi inside the perineurium, a feature by which the perineurium protects the nerve fibres during stretching (Sunderland, 1968). The perineurium maintains the intrafunicular pressure; the intrafunicular tissue prolapses when the perineurial sheath is opened. Solutions of dyes diffuse freely through epineurial tissue but do not enter the funiculi as the perineurium is considered to be a diffusion barrier. There is also some evidence suggesting that the intrafunicular contents communicate with the subarachnoid space via mesothelial clefts in the perineurium (Shantheveerappa, 1966). Perineurium is also considered to be resistant to infection; if it is intact a nerve can traverse a grossly infected area without being involved (Sunderland, 1968). E n d o n e u r i u m is the connective tissue inside the funiculus. Fine septa come off the inner aspect of the perilemma and separate the funiculus into smaller groups of the nerve fibres. There is also delicate areolar tissue between the individual fibres. Immediately outside each nerve fibre the collagen is organised to form a thin limiting membrane which is called an endoneurial tube. It contains the Schwann cell, the myelin sheath in myelinated fibres, and the axon. Between The H a n d - - V o l . 6
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Functional Micro-anatomy o/ the Peripheral Nerve Trunks--K. Kuczynski
the Schwann cell and the endoneurial tube, closely associated with its inner layer, lies the basement membrane of the Schwann cell (Figs. 4 and 8). The endoneurial tubes play an important role during the regeneration affording the budding axons a preformed route to the periphery. There is some evidence that endoneurium resists elongation, but the tensile strength and elasticity of the nerve trunks apparently depends largely on the tough perineurium (Sunderland, 1968). There is a considerable literature (for review see Sunderland, 1968; Haftek, 1970) relating to the protection of the nerve fibres provided by the connective tissue of the nerve trunk, but it is still controversial. Compression stresses are supposed to be resisted by the padding around and between the funiculi, but it is probable that the denser perineurium with its intrafunicular pressure would have some significance. Some authorities claim that nerves can be stretched to a considerable degree without ill effects, while others maintain that stretching a nerve trunk by more than 5-6% of its mobilised length gives rise to serious consequences. This is why Sunderland (1968) advises that this small percentage should not be exceeded. Millesi (1972) investigating the effects of stretching nerves, advocates the insertion of multiple funicular grafts to avoid any tensile insult when dealing with large nerve gaps. The mechanical effects of compression, traction and friction on the nerve trunks are not yet clearly understood. Further research is required and this should take account of differences in the experimental conditions (in situ versus on the work-bench), the species and age of the experimental subject and the functional as well as the structural changes (Ocboa, J., 1972; Lundborg, G., 1973). VASCULAR SUPPLY With the exception of the median and sciatic arteries, the blood vessels of the peripheral nerve trunks consist of numerous small nutrient vessels providing a very good blood supply. Arteriae nervorum enter the nerve and do not leave it, terminating intraneurally. The number and size of these small arteries are variable from subject to subject and even on the two sides of the same individual. In some regions a nerve may not receive a nutrient artery for a considerable distance, the circulation being maintained by the intraneural vessels (e.g. median nerve between the axilla and elbow). The nutrient arteries divide into anastomotic branches at some distance from the nerve trunk (Fig. 9) and it is important to ligate these vessels
'
CAPILLARY MESHWORK EPINEURIU PERINEURIUM
Fig. 9
8
NERVE FIBRES
The arrangement of the blood supply of the peripheral nerve trunk. Modified from Bateman's " T r a u m a to nerves in limbs". The Hand--Vol. 6
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Functional Micro-anatomy of the Peripheral Nerve Trunks--K. Kuczynski
a s far f r o m the nerve as possible in o r d e r to preserve their anastomosis. F r o m t h e n u t r i e n t a r t e r i e s a n i n t r a n e u r a l v a s c u l a r n e t is f o r m e d w h i c h e x t e n d s the l e n g t h of t h e nerve. T h e r e are f o u r l o n g i t u d i n a l systems r e c o g n i s e d in this f r a m e w o r k : (1) s u r f a c e chains, (2) i n t e r f u n i c u l a r chains, (3) p e r i n e u r a l c h a n n e l s a n d (4) i n t r a f u n i c u l a r c a p i l l a r y net. E x t e n s i v e a n a s t o m o s e s b e t w e e n t h e n u t r i e n t arteries, the s u r f a c e e p i n e u r i a l vessels a n d the i n t r a n e u r a l chains usually e n s u r e a s a t i s f a c t o r y c o l l a t e r a l c i r c u l a t i o n even if one or m o r e of t h e n u t r i e n t a r t e r i e s are i n t e r r u p t e d . V a r i a t i o n s in the a n a t o m i c a l a r r a n g e m e n t of the n u t r i e n t vessels m e n t i o n e d a b o v e o c c u r only p r o x i m a l l y to the final c a p i l l a r y mesh w h i c h on the w h o l e is the s a m e f o r all nerves. T h e v e n o u s system c o r r e s p o n d s to the a r t e r i a l a r r a n g e m e n t . L y m p h a t i c vessels a r e l i m i t e d to the e p i n e u r i a l tissues a n d do n o t c o m m u n i ~zate with the p e r i n e u r i a l a n d e n d o n e u r i a l spaces, the p e r i n e u r i u m p r o v i d i n g a n effective b a r r i e r b e t w e e n the e x t r a f u n i c u l a r l y m p h a t i c vessels a n d the i n t r a f u n i c u l a r spaces. N e r v i n e r v o r u m s u p p l y v a s o m o t o r s y m p a t h e t i c fibres to t h e b l o o d vessels of t h e n e r v e t r u n k a n d s e n s o r y fibres to its c o n n e c t i v e tissue ( H r o m a d a , 1963).
I a m g r a t e f u l to P r o f e s s o r G. J. R o m a n e s f o r r e a d i n g the m a n u s c r i p t a n d for his v a l u a b l e c o m m e n t s ; to Mrs. A n n M c N e i l l for t h e line drawings. REFERENCES
BATEMAN, J. E. (1962) Trauma to nerves in limbs, W. B. Saunders Co., Philadelphia and London. DUCKER, T. B., KEMPE, L. G. and HAYES, G. J. (1969) The Metabolic Background for Peripheral Nerve Surgery. Journal of Neurosurgery, 30, 270-280. DUCKER, T. B. (1972) Metabolic Factors in Surgery of Peripheral Nerves. The Surgical Clinics of North America, Vol. 52, 1109-1122. GAMBLE, H. J. and EAMES, R. A. (1964) An electron microscope study of the connective tissues of human peripheral nerve. Journal of Anatomy (London) 98, 655-663. GLEES, P. (1943) Observations on the Structure of the Connective Tissue Sheaths of Cutaneous Nerves. Journal of Anatomy, 77, 153-159. GRANIT, R., LEKSELL, L. and SKOGLUND, C. R. (1944) Fibre Interaction in Injured or Compressed Region of Nerve. Brain, 67, 125-140. HAFTEK, J. (1970) Stretch Injury of Peripheral Nerve. Acute Effects of Stretching on Rabbit Nerve. Journal of Bone and Joint Surgery, 52-B, 354-365. HAKSTIAN, R. W. (1968) Funicular Orientation by Direct Stimulation: An Aid to Peripheral Nerve Repair, Journal of Bone and Joint Surgery, 50-A, 1178-1186. HROMADA, J. (1963) On The Nerve Supply of The Connective Tissue of Some Peripheral Nervous System Components. Acta Anatomica, 55, 343-351. HYDEN, H. (1960) The neuron. In The Cell, Eds. Brachet, T. and Mirsky, A. E., New York and London. Academic Press, Vol. IV, Pt. 1, 292. KRISHNAN, N. and SINGER, M. (1973) Penetration of Perioxidase into Peripheral Nerve Fibres. American Journal of Anatomy, 136, 1-14. KRISTENSSON, K., OLSSON, Y. and SJOSTRAND, J. (1971) Axonal uptake and retrograde transport of exogenous proteins in the hypoglossal nerve. Brain Research, 32, 399.406. LUNDBORG, G. and RYDEVIK, B. (1973) Effects of Stretching The Tibial Nerve Of The Rabbit. A preliminary study of the Intraneural Circulation and the Barrier Function of the Perineurium. Journal of Bone and Joint Surgery, 55-B, 390-401. The Hand--Vol. 6
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Functional Micro-anatomy of the Peripheral Nerve Trunks--K. Kuczynski MAYOR, D., TOMLINSON, D. R., BANKS, P. and MRAZ, P. (1972) Microtubules and the intra-axonal transport of noradrenaline storage (dense cored) vesicles. Journal of Anatomy, 111, 344--345, P. MILLESI, H., MEISSL, G. and BERGER, A. (1972) The Interfascicular Nerve-Grafting of the Median and Ulnar Nerves. Journal of Bone and Joint Surgery, 54-A, 727-750. MURRAY, J. G. (1972) Repair process of nerves. In Scientific Basis of Surgery. Ed. Irvine, W. T., Churchill Livingstone, Edinburgh and London, 333 348. OCHOA, J., FOWLER, T. J. and GILLIATT, R. W. (1972) Anatomical changes in peripheral nerves compressed by a pneumatic tourniquet. Journal of Anatomy, 113, 433455. OCHS, S., SABRI, M. I. and JOHNSON, J. (1969) Fast Transport System of Materials in Mammalian Nerve Fibres. Science, 163, 686-687. ROBERTSON, J. D. (1958) The ultrastructure of Schmidt-Lantermann clefts and related shearing defects of the myelin sheath. Journal of Biophysical and Biochemical Cytology, 4, 3946. ROMANES, G. J. (1951) The Motor Cell Columns of the Lumbo-Sacral Spinal Cord of the Cat. Journal of Comparative Neurology, 94, 313 363. SCHULTZ, R. J. and AIACHE, A. (1972) An Operation to Restore Opposition of the Thumb by Nerve Transfer. Archives of Surgery, 105, 777-779. SUNDERLAND, S. (1968) Nerves and nerve injuries. E. & S. Livingstone Ltd., Edinburgh and London. SHANTHAVEERAPPA, T. R. and BOURNE, G. M. (1966) Perineural Epithelium: A New Concept of its Role in the Integrity of the Peripheral Nervous System. Science, 154, 1464-1467. VANDEPUT, J., TANNER, J. C. and HUYPENS, L. (1969) Electro-physiological Orientation of the Cut Ends in Primary Peripheral Nerve Repair. Plastic and Reconstructive Surgery, 44, 378-382. WATSON, W. E. (1968) Centripetal passage of labelled molecules along mammalian motor axons. Journal of Physiology (London) 196, 122 P, 123 P. WEISS, P. A. (1961) The Concept of Peripheral Neuronal Growth and Proximo-Distal Substance Convection. In Regional Neurochemistry, Ed. Kety, S. S. and Elkes, J. Pergamon Press, London, 220-242.
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FUNCTIONAL MICRO-ANATOMY OF T H E PERIPHERAL
NERVE
TRUNKS
K. KUCZYNSI
The structural unit of the nervous system is the neurone, i.e. the nerve cell with its processes (Fig. 1). The cell body (perikaryon) and the dendrites contain Nissl substance but the axon does not. This substance contains ribose nucleic acid (RNA) which is concerned with the protein synthesis and may be transformed into a more active form of R N A during so-called "chromatolysis" (Ducker, 1969) during the process of repair following injury. The nerve cell is one of the most active in the body. After axonal injury the cell shows a great increase in its metabolism which reaches a peak in two to three weeks. During regeneration and maturation of the repaired nerve there is another metabolic peak when new connections with the end organs are being established (Ducker, 1972). It is calculated that during successful repair the nerve
AXON~ . ~
_~DENDRITES
TERMINAL ~
NODEof RANVIER--
~
AXONHILLOCK I~_CELLULARSHEATH {myelin-block) i__
ENDPkAI~
I
MUSCLE
Fig. 1 Diagrammatic view of a neurone. The Hand--Vol. 6
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Functional Micro-anatomy of the Peripheral Nerve Trunks--K. Kuczynski FLOW OFAXOPLASM IN AXON
MICROTUBULE
-
MITOCHONDRION
Fig. 2 Suggested bidirectional axoplasmic flow. cell replaces up to 100 times the protein and organic material in the perikaryon (Hyden, 1960). In more proximal lesions of the peripheral nerves the duration of the increased metabolic activity for repair is much greater than in more distal lesions where the loss of cell mass is smaller. The axoplasm, surrounded by the cell membrane called axolemma, is in the form of a viscous fluid in which a bi-directional flow takes place. At least two varieties of proximo-distal transport of materials are thought to occur: (a) slow (about 1 mm a day) which is associated apparently with the peristalsis of the membrane of the nerve fibre (Weiss, 1961) and (b) fast transport (about 10 cm a day) which may be provided by the microtubules (Fig. 2) of the axon (Ochs, 1969; Mayor, 1972) in response to a sudden demand. Recently it has been shown (Watson, 1968; Kristensson, 1971) that there is also a transport from the periphery to the cell body which may be relevant to the theory that the nerve cell is normally influenced by substances from the peripheral field of innervation. All these forms of axonal transport depend on supply of oxygen and may be blocked by ischaemia (Kristensson, 1971). At the nodes of Ranvier the axons may give rise to the branches, i.e. collaterals (Fig. I). This is why a motor cell may innervate 200 or more muscle fibres when only a relatively gross movement is required as in the large muscles of the limb. On the other hand when fine gradations are necessary as in the muscles of the eyeball the number of muscle fibres innervated by each motor nerve cell is small; the number of muscle fibres in a motor unit at the extremity of the limb is probably small (Romanes, 1951). Such branching in motor axons occurs close to the muscle. NERVE
FIBRES
There are two varieties of the nerve fibres distinguished by the relative amount of myelin present in the cellular sheath. Those which have no compact myelin sheath are called non-myelinated (Fig. 3) while those with a myelin layer are known as myelinated fibres (Fig. 4). Most of the peripheral nerves contain a mixture of both varieties. Both types of fibres are surrounded by a chain of 2
The Hand--Vol. 6
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Functional Micro-anatomy o/ the Peripheral Nerve Trunks--K, Kuczynski
~ " x ~
AXON
~ --
MESAXON
PLASMAMEMBRANE OF SCHWANN CELL
- - ~ ........I..~.~,~ ~
--
. . . . . . . . .
.z-z~'~ 3 L,
protein lipid protein
3 &4 fuse
Fig. 3 Diagram to show the arrangement of the unmyelinated nerve fibres in relation to the Schwann cell and the mode of formation of the mesoaxon. 2XTRACELLULARIONS / \
MYELIN SHEATH
Fig. 4 Details of a myelinated nerve fibre. Schwann cells arranged end to end. In the case of non-myelinated fibres, one Schwann cell may a c c o m m o d a t e parts of m a n y axons, while in the myelinated variety each axon is associated with only one Schwann cell at any one level. In the latter case (Fig. 5 and 6), the m e m b r a n e of the Schwann cell is wrapped spirally around the axon thus producing a sheath of alternating layers of lipid and protein, the myelin sheath. Figure 4 shows in greater detail the organisation of the myelinated fibre. The Schwann cells, separated from the endoneurial tube by a basement m e m brane, lie end to end meeting at the node of Ranvier where their finger-like processes interdigitate. There is a space between these processes which allows the extracellular ions to reach the axon, while the internodal part of the axon is insulated f r o m these ions by the cellular sheath (Schwann cell and myelin sheath). This is important in saltatory propagation of the impulse from node to node. In some areas the laminae of the myelin sheath are separated by a relatively large amount of the cytoplasm of the Schwann cell which passes obliquely through the myelin between the inner and outer cytoplasmic layers of the cellular The Hand--Vol. 6
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Functional Micro-anatomy of the Peripheral Nerve T r u n k s - - K . Kuczynski
Fig. 5 The stages in formation of the myelin sheath (the Schwann cell being gradually wrapped around the axon).
Fig. 6 The flattened out Schwann cell and the areas of different thickness of its cytoplasm (including two Schmidt-Lantermann incisures). The arrow shows the direction of the spiral movement. sheath. These are called Schmidt-Lantermann incisures and m a y be related to the nutrition and function of the nerve fibre (Robertson, 1958; Krishnan, 1972). It has been suggested that they m a y prevent abnormal distortion and fracture of myelin under stresses applied to the nerve trunk (Glees, 1943). Their position may not be constant, but they m a y move to and fro along the fibre sheath, separating the lamellae of the myelin as they do so. The complex sheath composed of the myelin (in myelinated fibres), the Schwann cell and the endoneurial tube prevents the spread of nerve impulses f r o m a fibre to the adjacent ones. Such a spread m a y occur after injury to the fibres at the so-called "artificial synapse" (Granit, 1944; Sutherland, 1968; Murray, 1972). 4
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Functional Micro-anatomy of the Peripheral Nerve Trunks--K. Kuczynski PERIPHERAL NERVE TRUNKS
T h e peripheral nerve t r u n k s in the body wall and limbs are composed of motor, sensory and sympathetic nerve fibres enclosed in three connective tissue coats. On functional grounds the fibres are considered as either efferent or afferent. The efferent fibres are of three varieties: (1) large ~ fibres to the extrafusal muscle fibres, (2) small y fibres to the muscle spindles which alter their contraction and control their sensitivity and (3) postganglionic sympathetic fibres (vasomotor, pilomotor and sudomotor). The afferent fibres consist of the peripheral processes of the sensory nerve cells of the spinal ganglia which are distributed to the sensory endings. Muscular and cutaneous branches of a peripheral nerve trunk may contain several different types of fibres. Nerves to the muscles carry not only efferent fibres ( ~ , 7 and vasomotor) but also sensory fibres to the muscles and often also to the adjacent tendons, bones and joints. Cutaneous nerves are not exclusively sensory to the skin and the subcutaneous tissue but also contain efferent sympathetic fibres. In some cases (e.g. the digital nerve) sensory fibres to the joints, ligaments and bones m a y also be present. The nerve fibres in the peripheral trunk are not distributed in a uniform fashion throughout the cross-section of the trunk but are collected into separate bundles called funiculi, invested with a cellular connective tissue sheath of perineurium. Usually these funiculi contain motor, sensory and sympathetic fibres but this is not always so. Each funiculus repeatedly divides and its branches unite with those of other funiculi to form a plexus along the length of the nerve (Fig. 7). This results in rapid changes in the funicular pattern and in variation in size and content of the funiculi at different levels. According to Sunderland (1968) the m a x i m u m length of a constant pattern does not exceed 1.5 cm. The funicular redistribution of the nerve fibres resulting f r o m their plexiform arrangement may lead to the blending of two originally distinct groups of fibres. In some cases an individual bundle m a y retain its position for a considerable distance while fibres f r o m other funiculi are added progressively. N e a r the root of the limb there is widespread intermingling and dispersion of the fibres. In practice, the safe distance to which a branch can be stripped f r o m the nerve trunk depends on how far proximally it retains its independence in the funicular pattern. This is variable and can be studied in the tables provided by Sunderland (1968).
Fig. 7 The exchange of fibres in the funicular plexus and difference in the pattern of two cross-sections. The Hand--Vol. 6
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Functional Micro-anatomy o/ the Peripheral Nerve Trunks--K. Kuczynski
When an end-to-end repair is made between the nerve stumps even after a small resection, a large n u m b e r of regenerating axons m a y be lost in the connective tissue between the funiculi of the distal stump as in most instances two newly obtained cross-sections do not have matching funicular patterns, and even if they do, may not be correctly oriented. Thus some regenerating axons may enter wrong endoneurial tubes, e.g. efferent into afferent and vice versa and even if this does not happen, the efferent of one variety m a y grow into the tubes of the efferent of another type (,~, 7 and sympathetic). The same applies to the sensory fibres connected to different endings (e.g. muscle spindles and skin endorgans). To avoid this confusion a ]unicular suture is advocated. This may prevent or reduce escape of the growing axon buds into the interfunicular connective tissue of the distal stump, but the exact matching of the funiculi is difficult. Attempts are being made to determine the functional variety of the funicular fibres (Hakstian, 1968; Vandeput, 1969) in the two cut ends before suturing them together. In some regions the fibres representing individual branches are still well localised and in these cases a funicular suture can be performed with some confidence. The funiculi of the posterior interosseous and superficial radial branches in the trunk of the radial nerve and the dorsal branch of the ulnar nerve in the forearm m a y serve as an example. At the wrist the deep branch of the ulnar nerve can be isolated from the superficial branch and each separately sutured. In some cases where the bundle in the nerve trunk is not considered to be of great functional importance (e.g. superficial radial) it could be mobilised, excised and excluded from the suture of the radial nerve trunk. The same applies to the funiculus of the posterior cutaneous nerve of the f o r e a r m of the radial trunk in the spiral groove. The maps of the funicular patterns at different levels are given by Sunderland (1968). It should be r e m e m b e r e d however that the funicular pattern is subject to such a wide range of variation that its precise arrangement can be only established at the time of the operation. In other regions, funicular suture or exclusion is more difficult as for example in the median nerve where the intraneural interchange between funieuli is quite extensive. In cases of division of the median nerve in the upper part of the forearm when recovery of opposition is less likely because of the failure of the motor nerve fibres to reach the thenar muscles, it m a y be useful to transfer the muscular branch of the ulnar nerve to the third lumbrical to the distal end of the isolated and divided recurrent branch of the median nerve (Schultz and Aiache, 1972).
THE CONNECTIVE TISSUE OF THE P E R I P H E R A L N E R V E T R U N K
This is made up of three layers. E p i n e u r i u m consists of areolar connective tissue which separates the funiculi and is condensed on the surface of the nerve trunk to form an investing layer (Fig. 8). This layer is only loosely attached to the surrounding structures and thus the nerve enjoys considerable mobility except in those areas where the branches are given off and where the nutrient arteries enter the trunk. There are some longitudinal elastic fibres in epineurium which apparently maintain the tortuous course of the peripheral nerve trunks. This m a y help to prevent stretching during movements at the joints. Sunderland (1968) believes that the main cushion against compression is provided by the loose padding of the epineurium and that those nerve trunks which contain numerous small funiculi have more epineurial tissue and are therefore less vulnerable to compression than those which have only one single funiculus (e.g. ulnar nerve at the elbow). 6
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Functional Micro-anatomy of the Peripheral Nerve Trunks--K. Kuczynski ~ Plr',IFI ll~ll Ifvl
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Fig. 8 Cross-section of a peripheral nerve trunk (not to scale). Inset shows a simplified view of a myelinated nerve fibre. P e r i n e u r i u m invests each funiculus of nerve fibres. It is a relatively thin but dense multilayered sheath of fibrous tissue containing a compact network of collagen and elastic fibres (Fig. 8). These fibres are arranged into 6-12 concentric laminae separated by clefts lined by mesothelial cells (perineurial spaces). According to Gamble (1964) part of the bulk of the perineurium is made up of basement membranes, covering the cellular layers. The outer layer of perineurium merges without sharp distinction with the interfunicular tissue of the epineurium, while the inner layer forms a membrane composed of one or two layers of flattened cells, which is called perilemma. Elasticity of the perineurium apparently is responsible for the wavy course of the funiculi inside the perineurium, a feature by which the perineurium protects the nerve fibres during stretching (Sunderland, 1968). The perineurium maintains the intrafunicular pressure; the intrafunicular tissue prolapses when the perineurial sheath is opened. Solutions of dyes diffuse freely through epineurial tissue but do not enter the funiculi as the perineurium is considered to be a diffusion barrier. There is also some evidence suggesting that the intrafunicular contents communicate with the subarachnoid space via mesothelial clefts in the perineurium (Shantheveerappa, 1966). Perineurium is also considered to be resistant to infection; if it is intact a nerve can traverse a grossly infected area without being involved (Sunderland, 1968). E n d o n e u r i u m is the connective tissue inside the funiculus. Fine septa come off the inner aspect of the perilemma and separate the funiculus into smaller groups of the nerve fibres. There is also delicate areolar tissue between the individual fibres. Immediately outside each nerve fibre the collagen is organised to form a thin limiting membrane which is called an endoneurial tube. It contains the Schwann cell, the myelin sheath in myelinated fibres, and the axon. Between The H a n d - - V o l . 6
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Functional Micro-anatomy o/ the Peripheral Nerve Trunks--K. Kuczynski
the Schwann cell and the endoneurial tube, closely associated with its inner layer, lies the basement membrane of the Schwann cell (Figs. 4 and 8). The endoneurial tubes play an important role during the regeneration affording the budding axons a preformed route to the periphery. There is some evidence that endoneurium resists elongation, but the tensile strength and elasticity of the nerve trunks apparently depends largely on the tough perineurium (Sunderland, 1968). There is a considerable literature (for review see Sunderland, 1968; Haftek, 1970) relating to the protection of the nerve fibres provided by the connective tissue of the nerve trunk, but it is still controversial. Compression stresses are supposed to be resisted by the padding around and between the funiculi, but it is probable that the denser perineurium with its intrafunicular pressure would have some significance. Some authorities claim that nerves can be stretched to a considerable degree without ill effects, while others maintain that stretching a nerve trunk by more than 5-6% of its mobilised length gives rise to serious consequences. This is why Sunderland (1968) advises that this small percentage should not be exceeded. Millesi (1972) investigating the effects of stretching nerves, advocates the insertion of multiple funicular grafts to avoid any tensile insult when dealing with large nerve gaps. The mechanical effects of compression, traction and friction on the nerve trunks are not yet clearly understood. Further research is required and this should take account of differences in the experimental conditions (in situ versus on the work-bench), the species and age of the experimental subject and the functional as well as the structural changes (Ocboa, J., 1972; Lundborg, G., 1973). VASCULAR SUPPLY With the exception of the median and sciatic arteries, the blood vessels of the peripheral nerve trunks consist of numerous small nutrient vessels providing a very good blood supply. Arteriae nervorum enter the nerve and do not leave it, terminating intraneurally. The number and size of these small arteries are variable from subject to subject and even on the two sides of the same individual. In some regions a nerve may not receive a nutrient artery for a considerable distance, the circulation being maintained by the intraneural vessels (e.g. median nerve between the axilla and elbow). The nutrient arteries divide into anastomotic branches at some distance from the nerve trunk (Fig. 9) and it is important to ligate these vessels
'
CAPILLARY MESHWORK EPINEURIU PERINEURIUM
Fig. 9
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NERVE FIBRES
The arrangement of the blood supply of the peripheral nerve trunk. Modified from Bateman's " T r a u m a to nerves in limbs". The Hand--Vol. 6
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Functional Micro-anatomy of the Peripheral Nerve Trunks--K. Kuczynski
a s far f r o m the nerve as possible in o r d e r to preserve their anastomosis. F r o m t h e n u t r i e n t a r t e r i e s a n i n t r a n e u r a l v a s c u l a r n e t is f o r m e d w h i c h e x t e n d s the l e n g t h of t h e nerve. T h e r e are f o u r l o n g i t u d i n a l systems r e c o g n i s e d in this f r a m e w o r k : (1) s u r f a c e chains, (2) i n t e r f u n i c u l a r chains, (3) p e r i n e u r a l c h a n n e l s a n d (4) i n t r a f u n i c u l a r c a p i l l a r y net. E x t e n s i v e a n a s t o m o s e s b e t w e e n t h e n u t r i e n t arteries, the s u r f a c e e p i n e u r i a l vessels a n d the i n t r a n e u r a l chains usually e n s u r e a s a t i s f a c t o r y c o l l a t e r a l c i r c u l a t i o n even if one or m o r e of t h e n u t r i e n t a r t e r i e s are i n t e r r u p t e d . V a r i a t i o n s in the a n a t o m i c a l a r r a n g e m e n t of the n u t r i e n t vessels m e n t i o n e d a b o v e o c c u r only p r o x i m a l l y to the final c a p i l l a r y mesh w h i c h on the w h o l e is the s a m e f o r all nerves. T h e v e n o u s system c o r r e s p o n d s to the a r t e r i a l a r r a n g e m e n t . L y m p h a t i c vessels a r e l i m i t e d to the e p i n e u r i a l tissues a n d do n o t c o m m u n i ~zate with the p e r i n e u r i a l a n d e n d o n e u r i a l spaces, the p e r i n e u r i u m p r o v i d i n g a n effective b a r r i e r b e t w e e n the e x t r a f u n i c u l a r l y m p h a t i c vessels a n d the i n t r a f u n i c u l a r spaces. N e r v i n e r v o r u m s u p p l y v a s o m o t o r s y m p a t h e t i c fibres to t h e b l o o d vessels of t h e n e r v e t r u n k a n d s e n s o r y fibres to its c o n n e c t i v e tissue ( H r o m a d a , 1963).
I a m g r a t e f u l to P r o f e s s o r G. J. R o m a n e s f o r r e a d i n g the m a n u s c r i p t a n d for his v a l u a b l e c o m m e n t s ; to Mrs. A n n M c N e i l l for t h e line drawings. REFERENCES
BATEMAN, J. E. (1962) Trauma to nerves in limbs, W. B. Saunders Co., Philadelphia and London. DUCKER, T. B., KEMPE, L. G. and HAYES, G. J. (1969) The Metabolic Background for Peripheral Nerve Surgery. Journal of Neurosurgery, 30, 270-280. DUCKER, T. B. (1972) Metabolic Factors in Surgery of Peripheral Nerves. The Surgical Clinics of North America, Vol. 52, 1109-1122. GAMBLE, H. J. and EAMES, R. A. (1964) An electron microscope study of the connective tissues of human peripheral nerve. Journal of Anatomy (London) 98, 655-663. GLEES, P. (1943) Observations on the Structure of the Connective Tissue Sheaths of Cutaneous Nerves. Journal of Anatomy, 77, 153-159. GRANIT, R., LEKSELL, L. and SKOGLUND, C. R. (1944) Fibre Interaction in Injured or Compressed Region of Nerve. Brain, 67, 125-140. HAFTEK, J. (1970) Stretch Injury of Peripheral Nerve. Acute Effects of Stretching on Rabbit Nerve. Journal of Bone and Joint Surgery, 52-B, 354-365. HAKSTIAN, R. W. (1968) Funicular Orientation by Direct Stimulation: An Aid to Peripheral Nerve Repair, Journal of Bone and Joint Surgery, 50-A, 1178-1186. HROMADA, J. (1963) On The Nerve Supply of The Connective Tissue of Some Peripheral Nervous System Components. Acta Anatomica, 55, 343-351. HYDEN, H. (1960) The neuron. In The Cell, Eds. Brachet, T. and Mirsky, A. E., New York and London. Academic Press, Vol. IV, Pt. 1, 292. KRISHNAN, N. and SINGER, M. (1973) Penetration of Perioxidase into Peripheral Nerve Fibres. American Journal of Anatomy, 136, 1-14. KRISTENSSON, K., OLSSON, Y. and SJOSTRAND, J. (1971) Axonal uptake and retrograde transport of exogenous proteins in the hypoglossal nerve. Brain Research, 32, 399.406. LUNDBORG, G. and RYDEVIK, B. (1973) Effects of Stretching The Tibial Nerve Of The Rabbit. A preliminary study of the Intraneural Circulation and the Barrier Function of the Perineurium. Journal of Bone and Joint Surgery, 55-B, 390-401. The Hand--Vol. 6
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Functional Micro-anatomy of the Peripheral Nerve Trunks--K. Kuczynski MAYOR, D., TOMLINSON, D. R., BANKS, P. and MRAZ, P. (1972) Microtubules and the intra-axonal transport of noradrenaline storage (dense cored) vesicles. Journal of Anatomy, 111, 344--345, P. MILLESI, H., MEISSL, G. and BERGER, A. (1972) The Interfascicular Nerve-Grafting of the Median and Ulnar Nerves. Journal of Bone and Joint Surgery, 54-A, 727-750. MURRAY, J. G. (1972) Repair process of nerves. In Scientific Basis of Surgery. Ed. Irvine, W. T., Churchill Livingstone, Edinburgh and London, 333 348. OCHOA, J., FOWLER, T. J. and GILLIATT, R. W. (1972) Anatomical changes in peripheral nerves compressed by a pneumatic tourniquet. Journal of Anatomy, 113, 433455. OCHS, S., SABRI, M. I. and JOHNSON, J. (1969) Fast Transport System of Materials in Mammalian Nerve Fibres. Science, 163, 686-687. ROBERTSON, J. D. (1958) The ultrastructure of Schmidt-Lantermann clefts and related shearing defects of the myelin sheath. Journal of Biophysical and Biochemical Cytology, 4, 3946. ROMANES, G. J. (1951) The Motor Cell Columns of the Lumbo-Sacral Spinal Cord of the Cat. Journal of Comparative Neurology, 94, 313 363. SCHULTZ, R. J. and AIACHE, A. (1972) An Operation to Restore Opposition of the Thumb by Nerve Transfer. Archives of Surgery, 105, 777-779. SUNDERLAND, S. (1968) Nerves and nerve injuries. E. & S. Livingstone Ltd., Edinburgh and London. SHANTHAVEERAPPA, T. R. and BOURNE, G. M. (1966) Perineural Epithelium: A New Concept of its Role in the Integrity of the Peripheral Nervous System. Science, 154, 1464-1467. VANDEPUT, J., TANNER, J. C. and HUYPENS, L. (1969) Electro-physiological Orientation of the Cut Ends in Primary Peripheral Nerve Repair. Plastic and Reconstructive Surgery, 44, 378-382. WATSON, W. E. (1968) Centripetal passage of labelled molecules along mammalian motor axons. Journal of Physiology (London) 196, 122 P, 123 P. WEISS, P. A. (1961) The Concept of Peripheral Neuronal Growth and Proximo-Distal Substance Convection. In Regional Neurochemistry, Ed. Kety, S. S. and Elkes, J. Pergamon Press, London, 220-242.
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