Basic Science of Disk Degeneration



Basic Science of Disk Degeneration


Jimmy J. Chan

Woojin Cho

Alok D. Sharan



Introduction

The spinal column is an intricate construct that is designed to withstand tremendous force load while maintaining great flexibility. The principal joints of the spinal column are the 23 intervertebral disks (IVDs) that exist between 24 vertebral bodies. IVDs are sometimes considered diarthrodial joints containing articular cartilage. The combined heights of all IVDs contribute to nearly one-third of the total length of the spinal column. The diameter of each disk is about 4 cm with the height dependent on the function and mechanical load demanded at each spinal level. Collectively, the IVDs allow for the transmission of axial loads between vertebrae as well as absorption of mechanical energy. The IVD allows for a wide range of spinal motion in extension, flexion, lateral bending, and torsion.


Anatomy of Intervertebral Disk

The IVDs are composed of three components: the nucleus pulposus, the annulus fibrosis, and the cartilage end plates (Fig. 39.1). The nucleus pulposus is the semigelatinous center of the disk that is surrounded by the thick cartilaginous annulus fibrosis. Both structures are continuous inferiorly and superiorly with the cartilaginous end plates. Each component has its distinct properties that help maintain the function and integrity of the IVDs.


Nucleus Pulposus

The first of the three components of IVDs is the nucleus pulposus, a gel-like structure in the center of the disk that absorbs compressive pressure and distributes hydraulic forces evenly while keeping the vertebrae separate from one another. The nucleus pulposus is a remnant of the embryologic notochord that is derived from endodermal cells. The notochordal cells persist until birth where they begin to gradually decrease in number. By adulthood, chondrocyte-like cells from the end plate or annulus fibrosis replace these notochordal cells and become the principal cells in the nucleus responsible for homeostasis. The nucleus pulposus is a heterogeneous structure composed of roughly 80% water and 20% dry content. The dry content is composed of a lattice of randomly organized type II collagen and radially oriented elastin fibers embedded in a predominately hydrophilic proteoglycan gel. The concentration of proteoglycan and collagen is highest in the center and decreases as it progresses outward toward the annulus. The major proteoglycan involved in tissue hydration of the disk is the highly anionic and hydrophilic aggrecan, which is derived from chondroitin sulfate and keratin sulfate. Aggrecan provides osmotic properties that draw water into the nucleus to directly modulate the water content and pressurize the disk to resist axial loading. When mechanical force is exerted on the spine, the nucleus pulposus, under hydrostatic compression, acts as a shock absorber to modify and distribute the hydraulic pressure evenly in all directions to prevent damage to the underlying vertebrae, even when the spine is flexed or extended. Consequently, any changes in proteoglycan content can alter the water content and hence the function of the IVDs. Factors such as aging can alter the proteoglycan content and affect the ability of the nucleus pulposus to resist axial loading. Applied stress or increased load on the spine can also diminish the amount of hydration and proteoglycan content. In addition to proteoglycan content, the transition zone, which marks the division between the outer nucleus and inner annulus, is important. Similar to the epiphyseal growth plate of bones, the transition zone is an area of maximum metabolic activity playing a vital role in the growth and remodeling of the nucleus. It is tightly regulated by chemical, hormonal, and mechanical signals. The function of this transition zone diminishes with aging.


Annulus Fibrosus

The annulus fibrosus surrounds the central nucleus pulposus and defines the size and shape of the IVD. It is composed of a series of up to 25 concentric rings or
lamellae made from collagen fibers that withstand tensile and shearing load. Each collagen layer is oriented 60 degrees, alternating to the left and right of the vertical axis in adjacent layers (Fig. 39.2). The collagen fibers are connected by elastin fibers that form the Sharpey fiber, which attach the annulus to the bone and allow the annulus to resist radial tension from axial loading and to return to its original arrangement following bending. The annulus fibrosus relies on the integrity of the nucleus to prevent the inward collapse of the lamellae. The outer annulus inserts into the anterior and posterior spinal ligaments and the adjacent vertebral bodies.






Figure 39.1 Intervertebral disk: Nucleus pulposus, annulus fibrosus, and vertebral end plate. (Courtesy of Jaypee Brothers Medical Publishers (P) Ltd.)

The annulus fibrosis is composed of 65% water and 35% dry content, of which 55% is collagen (type I, II, III, V, and VI), 20% proteoglycan, and 10% elastic fibers. Type I collagen provides strength to the annulus and is concentrated in the outer layers to withstand compressive forces. Type II collagen, on the other hand, is more elastic and flexible, so it allows for the compression and restoration of the tissue under strain. It is predominately found on the inner annulus. The collagen fibers provide tensile strength to the disk and anchor the tissue to the vertebral body. The inner annulus is attached to the end plates through Sharpey fibers with accompanying ellipsoid or more oval-like cells. Cells in the outer annulus tend to be more fibroblast-like, elongated, thin, and aligned parallel to the collagen fibers. There are specialized cells in the disk, in both the nucleus and annulus, which have long, thin cytoplasmic projections (>30 μM) composed of actin and vimentin filaments with unknown function.






Figure 39.2 Annulus fibrosus with alternating 60-degree collagen fibers. (Courtesy of Jaypee Brothers Medical Publishers (P) Ltd.)


Cartilage End Plate

The cartilage end plates, which lie between the vertebral body and the disk, contain and support the IVDs. The end plate is composed of two layers. The first layer, which lies adjacent to the bone, contains the calcified cartilage and is known as the bony end plate. The densely packed collagen provides a strong barrier to limit the nucleus pulposus from bulging into the adjacent vertebral body and to absorb hydrostatic pressure and compressive stresses from mechanical loads. The second layer is a thin layer known as the cartilaginous end plate, which lies on the interface of the disk and vertebral body (Fig. 39.3). It is composed of hyaline cartilage, type II collagen, glycosaminoglycans and water. The cartilaginous end plate functions as a semipermeable membrane involved in the transport of solutes between the vertebrae and disk. The diffusion is regulated by proteoglycans, and thus any changes to the proteoglycan content can also affect the functions of the end plate. The end plates are 1 mm in thickness with the thinnest section at the center, adjacent to the nucleus pulposus, and are able to transversely support the whole disk proper. The end plate is not attached directly to the bone of the vertebral bodies and the central nucleus pulposus. Instead, it is loosely cemented by a thin layer of calcium to the underlying bone of the vertebral body. It has direct connections with the disk via the lamellae of the inner annulus fibrosus.


Disks in Cervical, Thoracic, and Lumbar Regions

The cervical disks tend to have an elliptical cross-sectional area and are thicker anteriorly than posteriorly. The cervical spine has the greatest range of motion including flexion, extension, and lateral flexion. C1 and C2 have no IVD; instead, a biconvex articular cartilage surface is present that allows for maximal rotation around the odontoid process. In the cervical region, the transverse diameter of the vertebral bodies is larger than the IVDs, causing the edges of the vertebral bodies to nearly overlap.

In the thoracic region, the disks are less wedge shaped and more circular than the IVDs in the cervical and lumbar spine. Each disk is almost uniform in height and is thinner as compared to disks in other regions. The thoracic spine has extra articulations in the costovertebral
joints, which offers a fourfold enhancement of stability from axial loading forces. Consequently, the movement of the thoracic spine is also severely limited. Disks in the lower thoracic region are distinctly thicker than those in the upper region, allowing for greater mobility of the lower thoracic vertebral column and the ability to resist axial forces. The shape of the vertebral bodies defines the thoracic curvature.

The lumbar disks have the greatest height and are thicker anteriorly than posteriorly. Lumbar disks tend to have an elliptical cross-section. The maximal disk height is in the fifth disk, which contributes to the lumbosacral angle. The L4–L5 disk is the largest and therefore the most avascular IVD. The weight-bearing capacity is also greatest at the caudal end of the lumbar spine, as it is required to support the majority of the weight in the upper torso and upper limbs. Normal curvature of the lumbar column is a result of the uneven thickness of the IVDs and the shape of vertebral bodies.


Growth Factors

The IVD is constantly maintaining a homeostatic balance between the synthesis and breakdown of the extracellular matrix. Catabolic processes occur via degradative proteins like matrix metalloproteinases (MMPs) and ADAMTs (a disintegrin and metalloproteinases with thrombospondin motifs). This delicate balance of macromolecules determines the quality and strength of the matrix, and thus the mechanical functionality of the disk. Maintaining homeostasis is a key principle in preventing disk degeneration. Growth factors like bone morphogenetic protein-2 (BMP-2), osteogenic protein-1 (OP-1), insulin-like growth factor-1 (IGF-1), fibroblast growth factor (FGF), and interleukin-1 (IL-1) have been demonstrated to play an intricate role in the regulation of IVD homeostasis. Dysregulation in any of these factors may result in an imbalance of catabolic and anabolic processes that are associated with disk degeneration (Table 39.1).

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Nov 11, 2018 | Posted by in ORTHOPEDIC | Comments Off on Basic Science of Disk Degeneration

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