Chapter 2. Embryology

A thorough understanding of the underlying anatomy is fundamental to a logical approach to the techniques used in regional anesthesia. An appreciation for the embryologic development of tissues and structures can significantly add to the understanding of functional anatomy as it relates to regional anesthesia. In this chapter I emphasize the embryologic development of the brain, spinal cord, peripheral and autonomic nervous systems, as well as the musculoskeletal system as it pertains to regional anesthesia. Many excellent comprehensive texts on embryology are available. For this chapter, I have relied heavily on information from primary texts and refer the reader to them for a complete discussion of all embryologic development. The first two, Langman's Medical Embryology1 and Basic Concepts in Embryology,2 are valuable for their ease of readability, clarity of figures, and clinical correlations. Human Embryology and Developmental Biology3 is a good contemporary, comprehensive explanation of the molecular genetics of embryologic development. The Developing Human: Clinically Oriented Embryology4 is the time-tested standard text of embryology.

The prenatal period is divided into two major periods: the embryonic period, from fertilization through 2 months, and the fetal period, from the third month through birth.

Embryonic Period

The embryonic period is the time when all tissue is formed and, particularly during the second month, when all organs are formed. The fetal period is a time of organ growth.2 Embryologic development begins with fertilization, the process by which the male and female gametes unite to give rise to a zygote. Approximately 3 days after fertilization cells of the compacted embryo divide to form a morula, which is composed of an inner and outer cell mass. The inner cell mass gives rise to the tissues of the embryoblast, and the outer cell mass forms the trophoblast, which later contributes to the placenta. After a period of cell division, during which time the morula enters the uterine cavity, the blastocoele forms, and the embryo is known as a blastocyst (Figure 2–1).

By the eighth day of development the blastocyst is partially embedded in the endometrium. At this time the trophoblast differentiates into an inner and an outer layer. Lacunae develop in the outer layer, maternal sinusoids are eroded, and by the end of the second week a primitive uteroplacental circulation begins to develop.

The inner cell mass, or embryoblast, differentiates into two layers, the epiblast and the hypoblast, which together form the bilaminar germ disk.

The most characteristic event occurring during the third week of gestation is gastrulation. This is the process that establishes all three germ layers: endoderm, ectoderm, and mesoderm in the embryo (Figure 2–2). Gastrulation begins with the formation of the primitive streak on the surface of the epiblast portion of the bilaminar germ disk. Cells migrate toward the primitive streak, detach from the epiblast, and slip beneath it. This inward movement is known as invagination. Once the cells have invaginated, some displace the hypoblast, creating the new embryonic endoderm. Other cells come to lie between the epiblast and the newly created endoderm to form the mesoderm. Cells remaining in the epiblast then form the ectoderm. Through the process of gastrulation, the epiblast therefore, becomes the source of all the germ layers in the embryo.1 Developments during the first 3 weeks of the embryonic period therefore produce an embryo with: one germ layer (week 1), two germ layers (week 2) and three germ layers with a recognizable three-dimensional body form (week 32 (Figure 2–3).

In general terms the ectoderm germ layer gives rise to organs and structures that allow us to maintain contact with the outside world.4 It gives rise to the central and peripheral nervous systems; the sensory epithelium of the eye, ear and nose; the epidermis and its appendages; hair and nails, mammary glands; the hypophysis, subcutaneous glands; and the enamel of the teeth.

The mesoderm gives rise to supporting structures of the body, such as cartilage, bone, and connective tissue; striated and smooth muscle; the heart, blood, lymph vessels, and cells; the kidneys, gonads, and serous membranes lining the body cavities, spleen, and the cortex of the adrenal gland.

The endoderm produces the epithelial lining of the gastrointestinal and respiratory tracts, as well as the epithelial lining of the bladder and urethra, tympanic cavity, antrum, and auditory tube. It also engenders the parenchyma of the tonsils, thyroid, parathyroid thymus, liver, and pancreas.

As the embryo forms, it rapidly develops along several axes,2 the first of which is the craniocaudal axis. It is established while the embryo is still a flat disk or sheet of cells. This axis runs from the future head to future tail of the body form. The dorsoventral axis is the next to be established. This occurs as the body folds and defines the future front and back sides of the body form.

Establishment of the body axes takes place prior to and during the period of gastrulation. Cells at the posterior margin of the embryonic disk signal the craniocaudal axis. The dorsoventral orientation of tissue is controlled by a complex interaction of proteins and growth factors.

This early orientation of cells in the body is a result of the expression of Hox genes. There are four Hox gene complexes in vertebrates: Hoxa, b, c, and d. Each consists of a group of between 9 and 11 genes arranged sequentially along a particular chromosome. A cascade of genes producing signaling factors also orchestrates left–right asymmetry, which is established early in development. As a result of complex interactions, for example, the heart and spleen lie on the left side of the body and the main lobe of the liver lies on the right.

Regions of the epiblast that migrate and ingress through the primitive streak have been mapped and their ultimate fates determined. Mesoderm cells that ingress through the cranial region of the primitive node become the notochord, those migrating at the lateral edges of the primitive node and from the cranial end of the primitive streak become the paraxial mesoderm. Cells migrating through the midstreak region become the intermediate mesoderm, and those migrating through the caudal part of the streak form the lateral plate mesoderm. This orientation of the mesoderm is important in understanding limb development.

The embryonic disc, initially flat and almost round, gradually becomes elongated, with a broad cephalic and a narrow caudal end. Expansion of the embryonic disk occurs mainly in the cephalic region. This growth in elongation is caused by continuous migration of cells from the primitive streak region in a cephalad direction. Invagination and migration forward and laterally of surface cells in the primitive streak continue until the end of the fourth week. Germ cell layers in the cephalic region begin their specific differentiation by the middle of the third week, whereas those in the caudal part differentiate beginning by the end of the fourth week. This causes the embryo to develop in a cephalocaudal direction (Figure 2–4).

At the beginning of the third week of development the ectodermal germ layer has the shape of the disk. The ectoderm gives rise to two subdivisions: neuroectoderm, which forms all neural tissue, and the epidermal covering of the body.2 Appearance of the notochord and prechordal mesoderm induces the overlying ectoderm to thicken and form the neural plate (Figure 2–5). Cells of the neural plate make up the neuroectoderm, and their induction represents the initial event in the process of neurulation. By the end of the third week the lateral edges of the neural plate become elevated to form neural folds, and the depressed midregion forms the neural groove. Gradually, the neural folds approach each other in the midline where they fuse, resulting in formation of the neural tube. Neurulation is then complete, and the central nervous system is represented by a closed tubular structure with a narrow caudal portion, the spinal cord, and a much broader cephalic portion characterized by a number of dilations, the brain vesicles. As the neural folds elevate and fuse, cells at the lateral border begin to dissociate from their neighbors. This cell population, called the neural crest, will undergo a transition as they leave the neuroectoderm to enter the underlying mesoderm.

During the body-folding process, the endoderm is formed into an epithelial tube, which runs the length of the body. The derivatives of the endoderm tube are all epithelial tissues (Figure 2–6).

Initially cells of the mesoderm germ layer form a thin sheet of tissue on each side of the midline.1 These cells proliferate and form a thick end plate of tissue known as paraxial mesoderm (Figure 2–7). More laterally the mesoderm remains thin and is known as the lateral plate. This lateral plate divides into two layers: a somatic, or parietal, mesoderm layer and a splanchnic, or visceral, mesoderm layer. Together these layers form the intraembryonic cavity. Intermediate mesoderm connects the paraxial and lateral plate mesoderm.

By the beginning of the third week, paraxial mesoderm is organized into segments. These segments are known as somitomeres. They first appear in the cephalic region of the embryo, and their formation proceeds in a craniocaudal direction. In the head region, somitomeres transition, in association with segmentation of the neural plate, into neuromeres. From the occipital region caudally, somitomeres further organize into somites. Somites give rise to the myotome (ultimately muscle tissue), sclerotome (ultimately cartilage and bone), and dermatome (ultimately subcutaneous tissue of the skin). Collectively, these are all supporting tissues of the body (Figure 2–8).

Signaling for this somite differentiation arises from surrounding structures, including the notochord, neural tube, epidermis, and lateral plate mesoderm. By the beginning of the fourth week cells forming the ventral and media walls of the somite lose their compact organization and shift their position to surround the notochord (the dense cord of mesoderm that induces neuroectoderm). These cells, collectively known as the sclerotome, form a loosely woven tissue called the mesenchyme. They will surround the spinal cord and notochord to form the vertebral column. Cells at the dorsolateral portion of the somite also migrate as precursors of limb and body wall structures. Following migration of these muscle cells and cells of the sclerotome, cells at the dorsomedial portion of the somite proliferate and migrate down the ventral side of the remaining dorsal epithelium of the somite to form a new layer, the myotome. The remaining dorsal epithelium forms the dermatome, and together these layers constitute the dermomyotome. Each segmentally arranged myotome contributes to muscles of the back, whereas the dermatomes disperse to form the dermis and subcutaneous tissue of the skin. Each myotome and dermatome retains its innervation from the segment of origin, no matter where the cells migrate to. Therefore, each somite forms its own sclerotome, the cartilage and bone component; its own myotome, providing the segmental muscle component; and its own dermatome, the segmental skin component. Each myotome and dermatome also has its owns segmental nerve component (Figure 2–9).

During the second month, the external appearance of the embryo is changed greatly by the enormous size of the head and formation of the limbs, face, ears, nose, and eyes.1 By the beginning of the fifth week, fore- and hindlimbs appear as paddle-shaped buds (Figure 2–10). The forelimbs are located dorsal to the pericardial swelling at the level of the fourth cervical to first thoracic somites, which explains their innervation by the brachial plexus. Hindlimb buds appear slightly later just caudal to the attachment of the umbilical stock at the level of the lumbar and uppers sacral somites. With further growth the terminal portions of the buds flatten, and a circular constriction separates them from the proximal, more cylindrical segment. Soon four radial grooves separating five slightly thicker areas appear on the distal portion of the buds. This development foreshadows formation of the digits. These grooves, known as rays, appear in the hand region first, and shortly afterward, in the foot because the upper limb is slightly more advanced in development than the lower limb. While fingers and toes are being formed, a second constriction divides the proximal portion of the buds into two segments, and the three parts characteristic of the adult extremities can be recognized.

Fetal Period

The period from the beginning of the ninth week to the end of the intrauterine life is known as the fetal period.1 It is characterized by maturation of tissues and organs and rapid growth of the body growth in length. This is particularly striking during the third, fourth, and fifth months, and increasing weight are most striking during the last 2 months of gestation. During the third month the face becomes more human-looking, and the limbs reach their relative length in comparison with the rest of the body, although the lower limbs are still a little shorter and less well developed than the upper extremities. Primary ossification centers are present in the long bones and the skull by the twelfth week.

Skeletal System: Limb Growth & Development

The skeletal system develops from paraxial and lateral plate mesoderm as well as neural crest tissue.1

The somites (as previously described) differentiate into a ventromedial component called the sclerotome and a dorsolateral component called the dermomyotome. This organization of cells forms a loosely woven tissue called the mesenchyme. The mesenchyme migrates and differentiates into fibroblasts, chondroblasts, and osteoblasts.

At the end of the fourth week of development limb buds become visible as out-pocketings of the ventrolateral body wall.1 Initially they consist of a mesenchymal core derived from the somatic layer of lateral plate mesoderm that will form the bones and connective tissue of the limb, covered by a layer of ectoderm. Ectoderm at the distal border of the limb thickens and forms a specialized inducing tissue known as the apical ectodermal ridge (AER). The AER exerts an inductive influence on the adjacent mesenchyme, causing it to remain as a population of undifferentiated, rapidly proliferating cells called the progress zone. As the limb grows, cells farther from the influence of the AER begin to differentiate into cartilage and muscle. In this manner of development of the limb proceeds proximodistally. In 6-week-old embryos, the terminal portion of the limb buds become flattened to form hand and footplates and are separated from the proximal segment by a circular constriction. Later a second constriction divides the proximal portions into two segments, and the main parts of the extremities can be recognized.1 Fingers and toes are formed when programmed cell death in the AER separates this ridge into five parts. Further formation of the digits depends on their continued outgrowth under the influence of the five remaining segments of ridge ectoderm. This results in condensation of the mesenchyme to form cartilaginous digital rays. Development of the upper and lower limbs is similar except that morphogenesis of the lower limb is approximately 1–2 days behind that of the upper limb.

During the seventh week of gestation a key event occurs that is critical in understanding the final orientation and innervation of the limbs. The limbs rotate in opposite directions. The upper limb rotates 90 degrees laterally so that the extensor muscles lie on the lateral and posterior surface and the thumbs lie laterally. The lower limb rotates approximately 90 degrees medially, placing the extensor muscles on the anterior surface and the great toe medially.1 This explains why homologous joints of the upper and lower extremities (knees and elbows) point in opposite directions. This limb rotation results in:2

1. The final orientation of the limbs

2. The final location and orientation of muscle groups (because the muscles are connected to the limb bones prior to rotation)

3. The patterns of sensory innervation of the skin (also because nerve fibers are connected with the dermis layer of the skin prior to rotation and are pulled along)

While the external shape is being established, mesenchyme in the buds begins to condense, and by the sixth week of development the first hyaline cartilage models can be recognized. Ossification of the bones of the extremities begins by the end of the embryonic period. Primary ossification centers are present in all long bones of the limbs by the twelfth week of development.

Molecular Regulation of Limb Development

Positioning of the limbs along the craniocaudal axis in the flank regions of the embryo is regulated by the Hox genes expressed along this axis.1 Once positioning along this axis is determined, growth must also be regulated along the proximodistal, anteroposterior, and dorsoventral axes. Patterning of the anteroposterior axis of the limb is regulated by the zone of polarizing activity (ZPA), a cluster of cells at the posterior border of the limb near the flank. These cells produce retinoic acid, which initiates expression of sonic hedgehog (Shh), a secreted factor that regulates development along this axis.1 This regulation results in digits appearing in the proper order, with the thumb on the radial (anterior) side. As the limb grows, the ZPA moves distally to remain in proximity to the posterior border of the AER. The dorsoventral axis is patterned in a similar fashion by the dorsal ectoderm of the limb.

Although patterning genes for the limb axes have been predetermined, it is the Hox genes that regulate the types and shapes of the bones of the limbs. These Hox genes are nested in overlapping patterns of expression that somehow regulate patterning.1 As a result, variations in their combinations create patterns of expression that may account for differences in fore and hind limb structures.

Vertebral Column

During the fourth week of development, cells of the sclerotome shift their position to surround both the spinal cord and the notochord.1 During further development, the caudal portion of each sclerotome segment proliferates extensively and condenses. This proliferation is so extensive that it proceeds into the subjacent intersegmental tissue and binds the caudal half of one sclerotome to the cephalic half of the adjacent sclerotome. By incorporation of this intersegmental tissue into the precartilaginous vertebral body, the body of the vertebrae becomes intersegmental (Figure 2–11). Hox genes also control this patterning. Mesenchymal cells between cephalic and caudal parts of the original sclerotome form the intervertebral disk. Although the notochord regresses entirely in the region of the vertebral bodies, it persists and enlarges in the region of the intervertebral disk. Here it contributes to the nucleus pulposus, which is later surrounded by circular fibers of the anulus fibrosus. Together these structures form the intervertebral disk.1

Muscular & Peripheral Nervous Systems

With the exception of some smooth muscle tissue, the muscular system develops from the mesoderm germ layer.1 Skeletal muscle is derived from paraxial mesoderm, which forms somites from the occipital to sacral regions and somitomeres in the head. The somites and somitomeres form the musculature of the axial skeleton body wall, limbs, and head. From the occipital region caudally, somites form and differentiate into this sclerotome, dermatome, and two muscle forming regions. One of these is in the dorsolateral region of the somite and provides progenitor cells (myoblasts) for the limb and body wall musculature. The other region lies dorsomedially, migrates ventrally to cells that form the dermatome, and forms the myotome. Patterns of muscle formation are under the influence of the surrounding connective tissue in to which myoblasts migrate. In the head region, this connective tissue is derived from neural crest cells. In cervical and occipital regions muscles differentiate from somitic mesoderm, whereas in the body wall and limbs they originate from the somatic mesoderm. By the end of the fifth week prospective muscle cells are collected into two parts: a small dorsal portion, the epimere, and a larger ventral part called the hypomere.1 Nerves innervating segmental muscles are also divided into a dorsal primary ramus for the epimere and a ventral primary ramus for the hypomere. These nerves remain with their original muscle segment throughout its migration. Myoblasts of the epimere form extensor muscles of the vertebral column, and those of the hypomere is give rise to the muscles of the limbs and body wall. The first indication of limb musculature is observed in the seventh week of development as a condensation of mesenchyme near the base of the limb buds. This mesenchyme is derived from dorsolateral cells of the somites that migrate into the limb bud to form the muscles. This connective tissue dictates the pattern of muscle formation and is derived from somatic mesoderm, which also gives rise to the bones of the limb.1

With elongation of the limb buds the muscles tissue splits into flexor and extensor components. The upper limb bud lies opposite the lower five cervical and upper two thoracic segments. The lower limb buds lie opposite the lower four lumbar and upper two sacral segments. As soon as the buds form, ventral primary rami from the appropriate spinal nerves penetrate into the mesenchyme (Figure 2–12). At first, each ventral ramus enters with isolated dorsal and ventral branches, but soon these branches unite to form large dorsal and ventral nerves. Thus, in the upper extremity, the radial nerve supplies all the extensor musculature and is formed by a combination of dorsal segmental branches. The ulnar and median nerves, which supply all the flexor muscles, are formed by a combination of the ventral branches1 (Figure 2–13). Immediately after the nerves have entered the limb buds they establish contact with the differentiating mesoderm condensations. This early contact is a prerequisite for their complete functional differentiation. Spinal nerves therefore play an important role in differentiation and motor innervation of the limb musculature, as well as providing sensory innervation for the dermatomes. Although the original dermatomal pattern changes with growth of the extremities, an orderly sequence can still be recognized in the adult.

Central Nervous System

The central nervous system (CNS) originates in the ectoderm and appears as the neural plate at the middle of the third week1 (Figure 2–14). After the edges of the plate fold, the neural folds approach each other in the midline to fuse, forming the neural tube. The CNS then forms as a tubular structure with a broad cephalic portion (the brain) and a long caudal portion (the spinal cord). A basal plate, containing the motor neurons, and an alar plate, containing the sensory neurons, characterize the spinal cord, which forms the caudal end of the CNS.

The walls of the recently closed neural tube consist of neuroepithelial cells. These cells give rise to another type of cell, the neuroblasts, which are primitive nerve cells. They form a mantle layer around the neuroepithelial layer. This mantle layer later forms the gray matter of the spinal cord. The outermost layer of the spinal cord, called the marginal layer, contains nerve fibers emerging from neuroblasts in the mantle layer. As a result of myelination, this layer takes on a white appearance and is called the white matter of the spinal cord.1 As a result of continuous addition of neuroblasts to the mantle layer, each side of the neural tube shows ventral and dorsal thickening. The ventral thickening—the basal plates—contains ventral motor horn cells. The dorsal thickening—the alar plates—forms the sensory areas. A group of neurons accumulate between these two areas, forming a small intermediate horn, which contains neurons of the sympathetic portion of the autonomic nervous system and is present only at thoracic and upper lumbar levels of the spinal cord1 (Figure 2–15).

Spinal Nerves

Motor nerve fibers begin to appear in the fourth week, arising from nerve cells in the basal plates of the spinal cord.4 They collect into bundles known as a ventral nerve roots. Likewise dorsal nerve roots form as collections of fibers originating from cells in dorsal root ganglia. Central processes from these ganglia form processes that grow into the spinal cord opposite the dorsal horns, and distal processes join the ventral nerve roots to form a spinal nerve. Spinal nerves divide into dorsal and ventral primary rami. Dorsal rami innervate dorsal axial musculature, vertebral joints, and the skin of the back. Ventral primary rami innervate the limbs and ventral body wall and form the major nerve plexuses.1

In the third month of development, the spinal cord extends the entire length of the embryo, and spinal nerves pass through the intervertebral foramina at their level of origin. With increasing age, the vertebral column and dura lengthen more rapidly than the neural tube, resulting in the terminal end of the spinal cord gradually shifting to a higher level. At birth, this level is at the third lumbar vertebra. In the adult the spinal cord terminates at the level of L2 to L3, whereas the dural sac and subarachnoid space extends to S2. As a result of this disproportionate growth, spinal nerves run obliquely from their segment of origin in the spinal cord to the corresponding level of the vertebral column. Below L2 to L3 a thread-like extension of the pia mater forms the filum terminale, which is attached to the periosteum of the first coccygeal vertebra and marks the tract of regression of the spinal cord.1

The Brain

The brain consists originally of three vesicles: the rhombencephalon (hindbrain), mesencephalon (midbrain), and prosencephalon (forebrain). The rhombencephalon will ultimately form the medulla oblongata, pons, and cerebellum. The mesencephalon resembles the spinal cord with its basal and alar plates. It will contain the anterior and posterior colliculi, forming the relay stations for visual and auditory reflex centers. The prosencephalon will ultimately give rise to the thalamus and hypothalamus as well as the cerebral hemispheres.1

Autonomic Nervous System

Functionally the autonomic nervous system can be divided into two parts: a sympathetic portion in the thoracolumbar region, and a parasympathetic portion in the cephalic and sacral regions. Both components of the autonomic nervous system consist of two tiers of neurons: pre- and postganglionic (Figure 2–16).

Sympathetic Nervous System

Preganglionic neurons of the sympathetic nervous system arise from the intermediate horn of the gray matter in the spinal cord.3 At levels from T1 to L2 their myelinated axons grow from the cord through the ventral roots, paralleling the motor axons that supply the skeletal musculature. Shortly after the dorsal and ventral roots of the spinal nerve join, the preganglionic sympathetic axons, derived from the neuroepithelium of the neural tube, leave the spinal nerve via a white communicating ramus. They soon enter one of a series of sympathetic ganglia to synapse with neural crest-derived postganglionic neurons. The sympathetic ganglia, the bulk of which are organized as two chains running ventrolateral to the vertebral bodies, are laid down by neural crest cells that migrate from the closing neural tube along a special pathway. Once the migrating sympathetic neuroblasts have reached the site at which the sympathetic chain ganglia form, they spread both cranially and caudally until the extent of the chains approximates that seen in the adult. Some of the sympathetic neuroblasts migrate farther ventrally than the level of the chain ganglion to form a variety of other collateral ganglia. The adrenal medulla can be broadly viewed as a highly modified sympathetic ganglion. The outgrowing preganglionic sympathetic neurons either terminate within the chain ganglia or pass through on their way to more distant sympathetic ganglia to form synapses with the cell bodies of the second-order, or postganglionic, sympathetic neuroblasts. Axons of some postganglionic neuroblasts, which are unmyelinated, leave the chain ganglion as a parallel group and reenter the nearest spinal nerve through the gray communicating ramus. Once in the spinal nerve, these axons continue to grow until they reach their peripheral targets.

During the fifth week of development cells originating in the neural crest of the thoracic region migrate on each side of the spinal cord toward the region immediately behind the dorsal aorta.1 Here they form a bilateral chain of segmentally arranged sympathetic ganglia interconnected by longitudinal nerve fibers. Together they form the sympathetic chains on each side of the vertebral column. From their position in the thorax neuroblasts migrate toward the cervical and lumbosacral regions, extending the sympathetic chains to their full length. Some sympathetic neuroblasts migrate in front of the aorta to form preaortic ganglia such as the celiac and mesenteric ganglia. Other sympathetic cells migrate to the heart, lungs, and gastrointestinal tract, where they give rise to sympathetic organ plexuses. Once the sympathetic chains have been established, nerve fibers originating in the intermediate horn of the thoracolumbar segments of the spinal cord penetrate the ganglia of the chain. They are known as preganglionic fibers, have a myelin sheath, and stimulate sympathetic ganglion cells. Passing from spinal nerves to the sympathetic ganglia, they form the white communicating rami. Axons of the sympathetic ganglion cells, the postganglionic fibers, have no myelin sheath. They either pass to other levels of the sympathetic chain or extend to the heart, lungs, and intestinal tract. Other fibers, the gray communicating rami, which are found at all levels of the spinal cord, pass from the sympathetic chain to spinal nerves and from there to peripheral blood vessels, hair, and sweat glands.

Parasympathetic Nervous System

Neurons in the brainstem and the sacral region of the spinal cord give rise to preganglionic parasympathetic fibers.1 Although also organized on a preganglionic and postganglionic basis, the parasympathetic nervous system has a distribution quite different from that of the sympathetic system. Like those of the sympathetic nervous system preganglionic parasympathetic neurons originate in the intermediate column of the CNS. However, the levels of origin of these neuroblasts are the mid- and hindbrain and in the second to fourth sacral segments of the developing spinal cord. Axons from these preganglionic neuroblasts grow long distances before they meet the neural crest-derived postganglionic neurons. These are typically embedded in small, scattered ganglia or plexuses in the walls of the organs they innervate.

Functional Analysis of the Brachial Plexus

The separation of the trunks of the brachial plexus into anterior and posterior divisions places the nerves into relation with muscles formed from primitive anterior and posterior mesoderm masses during the development of the limbs. Once these relationships are established they are never reversed, and the same fundamental correlation exists in the adult.5,6 The anterior divisions of the trunks unite to form the lateral and medial chords of the brachial plexus and the posterior divisions joined to form the single posterior cord. Thus, all branches of the lateral and medial chords carry nerve bundles derived from the anterior divisions of the trunks, and the branches of the posterior cord conduct exclusively fibers from the posterior divisions. The discrete compartments of the upper extremity contain muscle groups of similar and related functions as well as the blood vessels and nerves that supply them. This concept is emphasized in the word preaxial to designate the component and structures anterior to the bone and fascial plane or axis of the limb and the word postaxial to designate structures behind the bony and facial axis. With the limb in the anatomical position, those parts anterior to the bony axis are all in a continuous plane down the front of the limb, with the ventral axial line extending along the anterior surface of the arm and forearm. The postaxial parts are positioned continuously down the back of the limb.

The branches of the lateral and medial chords are all preaxial and innervate the preaxial muscles of the limb, whereas the posterior cord branches are postaxial and innervate the postaxial musculature. The radial nerve, being the only postaxial nerve below the shoulder, supplies all the postaxial muscles in the remainder of the limb. The median, musculocutaneous, and ulnar nerves share preaxial innervation.

The musculocutaneous nerve is muscular in the arm and cutaneous in the forearm, and it is the sole preaxial muscular nerve in the arm. The preaxial median and ulnar nerves are nerves of passage in the arm, but in the forearm and hand each contributes to innervation, the median nerve more heavily in the forearm, the ulnar nerve more heavily in the hand.

In the shoulder region, many of the supra- and infraclavicular branches of the brachial plexus arise from recognizable pre- and postaxial cords or divisions. Their origins have the same significance as the major anterior and posterior divisions of the trunks. An example of this is the clavicle and the scapula. The clavicle is an anterior and the scapula a posterior bone. An exception to this designation involves the scapula because its coracoid process has a phylogenetic history as a separate bone and fuses with the scapula. Therefore, all muscles arising from the scapula, exclusive of the coracoid process (pectoralis minor, coracobrachialis, and short head of biceps), belong to a postaxial group at the shoulder, and those from the clavicle and coracoid belong to a preaxial group. The nerve–muscle correlation is maintained in that all muscles of scapular origin are supplied by postaxial branches of the brachial plexus, and all muscles derived from the clavicle and coracoid are supplied by preaxial branches.

Functional Analysis of the Lumbosacral Plexus

The innervation of the lower extremity follows the same pattern of pre- and postaxial orientation as described for the upper extremity. The primordial dermatomal pattern has disappeared, but an orderly sequence of dermatomes can still be recognized. Most of the original ventral surface of the lower limb lies on the back of the adult limb. The ventral axial line extends along the medial side of the thigh and knee to the posteromedial aspect of the leg to the heel.

As previously described this results from the medial rotation of the lower limb at the end of the embryonic period. The lumbar plexuses are formed by the ventral rami of the first three lumbar nerves and part of the fourth lumbar nerve. The primary preaxial components are the genitofemoral nerve, which derives from L1 and L2, and obturator and accessory obturator nerves, which are derived from L2 and L3, respectively. The primary postaxial components are the lateral femoral cutaneous nerve, derived from L2 and L3, and the femoral nerve, derived from L2 through L4. The sacral plexus combines the ventral rami of part of L4 and L5 and S1 through S3, as well as part of S4. All these nerves, except S4, divide into anterior and posterior branches. Like the brachial plexus the anterior branches form preaxial nerves related to preaxial muscle masses in skin areas, and the posterior branches form similarly related postaxial nerves. The principal nerve of the sacral plexus is the sciatic, which is composed of a preaxial nerve (the tibial nerve) and a postaxial nerve (the common peroneal), which is enclosed within a single sheath.

In summary, regional anesthesia may be considered as a practice of applied anatomy. Successful neuraxial and peripheral nerve blockade alike require a logical approach to the anatomic principles. A knowledge of the embryologic development of tissues and neural structures can significantly add to the understanding of functional anatomy as it relates to regional anesthesia.