Histology of Peripheral Nerves.

• Steven Deschner, MD































I.


INTRODUCTION


II.


MORPHOLOGIC ORGANIZATION OF PERIPHERAL NERVOUS SYSTEM


III.


NERVE FIBERS


Classification of Nerve Fibers: Axon Diameter, Myelination, Conduction Velocity


IV.


AXONS


V.


SCHWANN CELLS


VI.


MYELINATED AXONS


VII.


UNMYELINATED AXONS


Connective Tissue Sheaths of Peripheral Nerves


Epineurium


Perineuriunn


Endoneurium


Blood Supply to the Nerves (Vasa Nervorum)


VIII.


TRANSITION ZONE


Histologic Techniques for Peripheral Nerves


        INTRODUCTION


Knowledge of histology is vital to understanding cell function and the composition of the tissue layers and planes, as well as being relevant to clinical practice of regional anesthesia. The primary objective of this chapter is to provide a basic understanding of the structure, classification, and organization of peripheral nerves.


        MORPHOLOGIC ORGANIZATION OF PERIPHERAL NERVOUS SYSTEM


The peripheral nervous system consists of sensory afferent (centripetal) nerve fibers connecting receptors to the central nervous system (CNS) and motor efferent (centrifugal) nerve fibers connecting the CNS to muscle or glands. The system includes somatic and autonomic nerves, as well as their associated Schwann cells and connective tissue sheaths. All lie peripheral to the pial covering of the CNS, through which the central and peripheral nerve fibers are continuous.1


        The connection between the CNS and the peripheral structures derived from the somites and neural crest is formed by axon growth from the dorsal root ganglia into the alar píate of the neural tube and by axon outgrowth from neurons in the basal píate. These distally growing motor axons join the peripherally growing sensory axons of the dorsal root ganglia to form nerves innervating the somite at the same level, Figure 4-1. Nerves formed in this fashion at spinal level are the spinal nerves; those formed at the posterior fossa and supratentorial levels are the cranial nerves. Both types are composed of sensory and motor axons. Motor axons from the CNS innervate the muscles and autonomic ganglia, whereas sensory axons innervate receptors in the skin, muscle, bone, and viscerae. As the embryo develops and cells forming bone, muscles, skin, and internal organs migrate to their adult locations, these neural processes will follow suit in order to establish the peripheral nerves’ innervation pattern. Fibers innervating tissue derived from somites (muscles and skin) are described as somatic; fibers innervating endodermal or other mesodermal derivatives (internal organs) are called visceral.



Figure 4-1. Anatomy ofthe peripheral nerve. Shown arethecell body, axon with its myelin sheath, nodes of Ranvier, synaptic termináis, and the direction ofthe transmission.


        Axons are guided to their targets by apical growth cones. The growth cone, which is thought to move by means of filopodia, is believed to guide the axon to its destination by sensing molecular markers that designate the correct route. This activity of the growth cone is called path finding. Once the growth cone reaches its target, it halts and forms a synapse. Numerous mechanisms have been proposed to explain the ability of neurons to establish correct connections with each other and with end organs.2


         


Clinical Pearls



MOTOR AXONS


  The motor axons can arise from either the somatic or autonomic system. Somatic motor neurons innervate skeletal muscle.


  Alpha motor neurons innervate the extrafusal fibers. Smaller γ motor neurons innervate the intrafusal fibers. The perikarya of these neurons are located in specific brainstem nuclei or the ventral horn of the spinal cord.


  Autonomic motor neurons innervate cardiac muscle, smooth muscle, or glands. The autonomic motor neurons can be either sympathetic and parasympathetic.


  Peripheral nerves transmit both preganglionic and post-ganglionic sympathetic fibers. Preganglionic fibers arise from neurons in the intermediolateral column of the spinal cord between the Ti and L2 level. The fibers travel along peripheral nerves to synapse on paravertebral or preaortic ganglia. From the ganglia, postganglionic fibers travel to cardiac muscle, smooth muscle, or glands.


  In the parasympathetic system, only preganglionic fibers are transmitted on peripheral nerves. The fibers arise from nuclei within the brainstem or sacral spinal cord. They travel along peripheral nerves to synapse on intramural ganglia in the wall of target organs.


SENSORYAXONS


  Sensory axons are either somatic or visceral. The perikarya of all sensory neurons are located in the dorsal root ganglia or sensory ganglia of the cranial nerves.


  Somatic sensory neurons transmit proprioceptive information from skeletal muscle and joints or they transmit information about touch, temperature, or pain from receptors in the body wall.


  Visceral sensory neurons transmit information about pressure or chemicals adjacent to the wall of viscerae. The axons of these neurons travel along the autonomic motor fibers, pass through the gray rami communicans, and enter the dorsal root of the spinal nerves.


        Similarly to the organization of the CNS tracts, both myelinated and unmyelinated fibers occur peripherally too.34 A myelinated nerve fiber is surrounded by the plasma membrane of Schwann cell (lemmocyte). The plasma membrane spirals around the axon arranging the membranes in concentric layers. The structure is called a myelin sheath. In the myelinated nerve fiber a single axon is enclosed by a series of Schwann cells arranged along its length. The region where two adjacent Schwann cells abut and the myelin is interrupted is referred to as a node of Ranvier (Figure 4-2). Individual axons, generally less than 1.0 pm in diameter, that indent the surface of the Schwann cell and become embedded in separate troughs are known as unmyelinated nerve fibers. Each Schwann cell can sheathe many axons in this way. However, a single Schwann cell does not sheathe the entire length of a group of axons. Instead the sheath is formed by a chain of Schwann cells, the axons being passed on from cell to cell. Thus all axons in the peripheral nervous system are invaginated into Schwann cell surfaces, but myelin sheaths only form around larger axons, which represent only a small portion of peripheral nerve fibers.13


        Nerve trunks and their principal branches (Figures 4-3 and 4-4) consist of parallel bundles of nerve fibers (nerve fascicles, fasciculi). The size, number, and pattern of fasciculi vary in different nerves and at different levels along their paths. The axon-associated surface glycoprotein neurofascin is implicated in axonal growth and fasciculation as revealed by antibody perturbation experiments. We will examine the basic organization of the peripheral nerves using the sural nerve as an example. The sural nerve includes 9-21 fascicles and comprises 4600-9600 myelinated nerve fibers and 19,000-45,000 unmyelinated axons5,6 depending, on age of the nerve.


        Peripheral nerves have three separate connective tissue sheathes.3 On the outside of each peripheral nerve there is a dense irregular connective tissue sheath, the epineurium. Perineurium surrounds each fascicle of nerve fibers. Individual nerve fibers are embedded in a loose, delicate connective tissue (endoneurium), filling the space bounded by the perineurium. The connective tissue sheaths support nerve fibers and their associated blood and lymphatic vessels (see Figure 4-3).


        Both central and peripheral fibers present challenges for light microscopists because of the small size of unmyelinated fibers (Figure 4-5) and a disruption of sheaths of myelinated fibers that commonly occurs due to treatment with lipid solvents prior to sectioning. Various methods have been devised to overcome these problems. It is electron microscopy, however, that has added to our knowledge perhaps more than any method.


        NERVE FIBERS


As axons course through body tissues, they are associated with Schwann cells. The axon with its associated Schwann cells forms a nerve fiber. A nerve fiber is the basic structural and functional unit of peripheral nerves (Figure 4-6).



Figure 4-2. Nodes of Ranvier.



Figure 4-3. Connective tissue sheaths and fascicles of the human ulnar nerve as seen on light microscopy (Hematoxylin-eosin × 400).



Figure 4-4. Myelinated and unmyelinated nerve fibers bundled in a fascicle by perineurial membrane. Light microscopic image of rat sciatic nerve in cross section (Hematoxylin-eosin × 400).



Figure 4-5. Organization of the nerve shown in longitudinal section (Bodian × 400).



Figure 4-6. Schematic diagram of an axon with its accompanying connective tissue sheaths.


        Fresh myelinated fibers appear as homogeneous, glisteningtubes. In stained preparations (Figure 4-7) appearance of various constituents of the nerve fiber differs according to the technique applied (Table 4-1). Motor nerve fibers of the skeletal muscles are thick and heavily myelinated; those of visceral smooth muscle are thin, lightly myelinated, or without myelin. Tactile fibers are medium-sized and moderately myelinated, whereas pain and taste fibers are thinner, with less myelin or none at all. In comparison, olfactory nerve filaments are always unmyelinated.1,3



Figure 4-7. Exaggerated Schwann cells shown in cross section (x400).



Table 4-1.


Histological Techniques for Peripheral Nerves








































































































Technique


Application


General


    


    Hematoxylin and eosin


    Myelin and axons


    Hematoxylin van Giesen


    Myelin, black; collagen, red


    Reticulin stains


    Basement membrane of Schwann cells


    Toluidine blue


    Mast cells; general stain for semithin resin sections


 


Stains for Myelin


    


    Luxol-fast blue


    Myelin, blue


    Osmium


    Myelin, black


    Loyez


    Myelin, black


    Periodic acid Virgule Schiff (PAS)


    Myelin, bright pink


    Marchi


    Normal myelin, unstained


    Oil red O (frozen sections)


    Normal myelin, pink


 


Stains for Axons


    


    Palmgren or Bodian (silver stains)


    Axons, black


    Semithin resin sections


    


    Toluidine blue and carbol fuchsin


    Myelin, black; axons, unstained; Schwann cells and other cells, pink/blue;


    Toluidine blue


    Myelin, black; axons, unstained; Schwann cells, blue;


 


Immunocytochemistry


    


    S-100 protein


    Schwann cells


    Leu-7


    Schwann cells


    Epithelial membrane antigen


    Perineurium


    Neurofilament proteins


    Axons


 


Teased Fibers


    


    Osmium


    Myelin; nodes of Ranvier; de- and remyelination


    Enzyme histochemistry Mitochondrial enzymes


    Schwann cell; axoplasm


    Acid phosphatase


    Lysosomes


    Lipid histochemistry Sudan black B


    Myelin, black


    Oil red O


    Myelin, red


 


Electron Microscopy


    Ultrastructural characteristics

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

Dec 9, 2016 | Posted by in ANESTHESIA | Comments Off on Histology of Peripheral Nerves.

Full access? Get Clinical Tree

Get Clinical Tree app for offline access