Intervertebral Disc

There are 23 IVDs in the spinal column, starting from the C2-3 interspace to the L5-S1 interspace. These discs constitute approximately 25% of the total height of the spinal column. The discs vary in thickness from the thinnest in the thoracic region to the thickest in the lumbar region. The IVD is a vital component of the joint system present at each spinal level. This system allows for the range of motion permitted at each segment. Each IVD works in conjunction with the paired dorsal zygapophyseal joints to form a three-joint complex. The functions of the individual components of this complex are intimately related, as are their effects on one another during the degenerative process.

The IVD has three main components. The central nucleus pulposus (NP) is surrounded by concentric layers of lamellae forming the surrounding annulus fibrosus (AF) ( Fig. 11-1 ). These structures are flanked rostrally and caudally by bony and cartilaginous end plates, which serve as a transitional zone between the discs and the adjacent vertebral bodies.

Axial and lateral views of the intervertebral disc (IVD). A, The IVD is composed of a central nucleus pulposus surrounded circumferentially by the anulus fibrosus. B, The anulus fibrosus is composed of multiple concentric lamellae made up of fibers oriented in alternating directions to create maximal tension resistance.

(Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography © 2011–2015. All rights reserved.)

Nucleus Pulposus

The central core of the IVD is composed of the nucleus pulposus. The nucleus pulposus is derived from a remnant of the notochord originating from the endoderm, unlike the remaining components of the IVD, which are derived from the mesoderm. The NP is a soft deformable gel-like structure composed mainly of water, proteoglycans, and type II collagen. Water contributes to 70% to 90% of the total weight, whereas proteoglycans contribute 50% of its dry weight. The NP also consists of multiple other types of collagen, most prominently type II, but it also includes types VI and XI. Unlike the outer annulus, this component of the IVD is nearly devoid of type I collagen. Aggrecans, a type of proteoglycan known as leucine-rich repeat proteins, are bound centrally to side chains of chondroitin and keratin sulfate. They form aggregates by binding to hyaluronan and collagen fibrils that result in extensive cross-linking of molecules within the NP to form its structure and support. The negatively charged side chains of the aggrecans help to create a hydrophilic environment favorable for water absorption, which creates the reversibly deformable properties of the nucleus. This is essential to the load bearing function of the nucleus within the spinal column. Elastin fibers are also found in the NP. These fibers are observed to be situated in both a radial distribution from the center to the periphery in the NP, as well as in a vertical orientation, anchoring the NP to the end plates. This orientation contributes to maintaining the structure of the NP within the AF, restoring the NP to its original form following load bearing, as well as playing a role in load transmission to surrounding AF.

Annulus Fibrosus

Surrounding the nucleus is a concentrically organized structure that occupies the majority of the disc space. The annulus fibrosus is composed primarily of bundles of collagen fibers that are arranged in concentric lamellae, separated into the inner and outer segments. Approximately 15 to 25 lamellae compose each annulus. The collagen fiber bundles within the lamellae are generally oriented at 30 degrees from the horizontal axis, although the fiber angles can vary from 20 to 55 degrees. Collagen fibrils in adjacent lamellae run in opposite directions, allowing for greater tensile strength during stretching. Collagen fibers also interact with matrix proteins to create much of the tensile strength and stiff structural integrity of the annulus.

The inner and outer annuluses have very different compositions, which dictates their unique properties. The outer AF is tougher and less flexible, and 70% of its dry weight is composed primarily of densely packed type I collagen fibers. The cells in the outer annulus are more ellipsoidal in shape and are fibroblast-like in nature. At the periphery of the outer annulus, fibrillar bundles known as Sharpey fibers extend superiorly and inferiorly to anchor the disc into the periosteal fibrils of the adjacent vertebral bodies. The inner annulus is softer, less dense, and contains a greater fibrocartilaginous component, composed primarily of type II collagen fibers. Type II fibers have a less structured cellular morphology with more widely spaced cells than type I collagen. Type II collagen also maintains 50% to 100% greater water content than type I collagen. Unlike the outer annulus, the inner annulus possesses a higher ratio of type II to type I collagen, with approximately 70% type II collagen. The inner annulus serves as a transitional zone between the dense fibrous region at the periphery of the disc and the gelatinous inner nucleus. In addition to the increasing concentration of type II collagen, proteoglycan concentration also increases from 10% to 30% from the outer to the inner annulus.

Cartilage End Plate

The superior and inferior surfaces of the IVD are flanked by end plates, which contain an osseous component and a cartilaginous component. The osseous end plates primarily consist of a thin sheet of bone that blends into the cortex of the adjacent vertebral body. The cartilage end plates (CEPs) are composed of thin layers of hyaline cartilage, which serves as the interface between the bony end plate and the disc. The primary role of the CEP is to provide support for the disc to prevent expulsion of disc material into the vertebral bodies as well as a scaffold for the passage of nutrients to the disc from the adjacent vertebral body. The composition of the CEP is similar to that of the adjacent disc; it is primarily composed of proteoglycans, type II collagen, and water. The collagen fibrils within the CEP merge with fibers in the inner AF. The thickness of the end plate ranges from 0.5 to 1.5 mm and is thinnest at the center adjacent to the NP. Numerous perforations exist throughout the end plates where calcium is absent. These perforations allow for the passage of vascular channels that traverse from the adjacent vertebral body into the disc. These channels regress as the disc ages and eventually become nonexistent past the second decade of life. The CEP serves as a stiff but porous barrier, which allows for the diffusion of nutrients and fluid movement into and out of the disc and prevents protrusion of the soft malleable disc material into the vertebral body. Such protrusions, known as Schmorl nodes, are from weaknesses in the end plates possibly due to dysregulation of the end plate composition, as those areas have been shown to have significantly decreased proteoglycan concentration.

Vascular Supply

The IVD is generally considered to be an avascular tissue structure, but this is a dynamic description. In infancy, the native disc has a direct vascular supply to the outer AF from segmental branches of the spinal artery as well as through vascular “buds” that extend from the vertebral bodies through the porous channels in the CEP. These channels are overtaken by scarring or collapse, secondary to continued weight bearing, past the second decade of life and become occluded and eventually nonexistent. Without a direct vascular supply, nutrient exchange to the central NP occurs primarily through diffusion from blood vessels that surround the periphery of the annulus. This process is hindered by its distance, which can be nearly 8 mm, as well as by the impermeable barrier created by the collagen fibers connecting the CEP and the inner annulus. Most nutrients are therefore provided by small molecule diffusion through the CEP.

Innervation

Innervation for the IVD derives from two main sources: the sinuvertebral nerve and the sympathetic trunk via the multiple gray rami communicantes ( Fig. 11-2 ). The sinuvertebral nerve is formed from a branch of the ventral primary ramus and the gray ramus communicans, which branches from the sympathetic trunk. The sinuvertebral nerve enters the spinal canal caudal to the pedicle through the intervertebral foramen and branches into a larger superior division and a lesser inferior division. The superior division travels laterally to the posterior longitudinal ligament in the ventral aspect of the spinal canal, supplying sensation to the dorsal and dorsolateral annulus, as well as the posterior longitudinal ligament. The inferior trunk passes medially and caudally. The lateral and ventral portions of the AF are supplied by multiple gray rami communicantes from the nearby sympathetic trunk. The sympathetic trunk runs in parallel, ventral and lateral to the vertebral column, comprising nerve root contributions from the thoracic and upper two segments of the lumbar spinal cord. The sympathetic trunk provides a number of gray rami communicantes, which help supply the annulus. At least one, but often more, rami communicantes travel around the vertebral body deep to the psoas muscle to join with each ventral primary ramus. Rami communicantes also traverse the psoas to join with the ventral primary ramus. In addition, “paradiscal” rami run along the surface of the IVD in the perianular connective tissue. Innervation of the end plate extends from intraosseous nerves that branch from the ventral primary rami and the basivertebral nerve, a branch of the sinuvertebral nerve, which enters the end plate dorsally.

Innervation of the intervertebral disc. The sinuvertebral nerve is formed from branches off the ventral primary ramus and the gray ramus communicans. The nerve enters the spinal canal caudal to the pedicle through the intervertebral foramen and branches into a larger superior division and a lesser inferior division. This nerve provides sensation to the dorsal and dorsolateral anulus, as well as the posterior longitudinal ligament.

(Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography © 2011–2015. All rights reserved.)

Innervation of the disc interspace is restricted to the outer annulus. A quantitative analysis of nerve density in multiple IVDs showed innervation extends to a depth of four to seven lamellae ventrally and no more than three lamellae dorsally. This is indeed very shallow, given that a usual AF contains an average of 15 to 25 lamellae. Unlike the annulus, innervation of the end plate is densest near the center, adjacent to the NP. Innervation of the end plates originates from the intraosseous nerves that penetrate the caudal portion of the vertebral body ventrally and dorsally and travel to the center of the end plate.

Extracellular Matrix

The main purpose of the IVD is to absorb axial loads and redistribute them across the entire disc. The capacity for load redistribution is determined, in part, by the molecular structure of the disc. The extracellular matrix of the intervertebral disc provides the necessary properties of the disc to handle its primary purpose of load bearing. The matrix is composed primarily of proteoglycans and collagen. Proteoglycan concentration is highest in the nucleus, constituting up to 50% of the cells. Aggrecans, a type of proteoglycans known as leucine-rich repeat proteins, are the predominant type of proteoglycans in the NP. Aggrecans are large proteoglycans that are bound centrally to chains of chondroitin and keratin sulfate. Early in life, they are rich in chondroitin sulfate chains, but these side chains are gradually replaced by keratin sulfate as the disc matures. At their N-terminus, aggrecans attach to hyaluronic acid. At their C-terminus, they can attach to various molecules in the extracellular matrix, including collagen fibrils, which result in extensive cross-linking of molecules within the nucleus. These aggregates along with their side chains possess negative charges on the surface, which create a hydrophilic environment allowing the NP to retain its hydrated state. The percentages of proteoglycan aggregates are highest in infancy and decrease with age. Aggrecans are also broken down during aging and are replaced by nonaggregated proteoglycans, which are less able to absorb water than their aggregated counterparts.

Collagen is the other major component of the IVD. Type I collagen predominates in the outer annulus, whereas the percentage of type II collagen increases toward the inner annulus and NP. The AF is composed of a mix of type I and type II collagen, which provides its necessary tensile strength. In addition to type I and II collagen, multiple other collagen types, including types VI and XI, are also present in smaller amounts. These collagens play a role in interlinking the collagen fibrils contributing to the overall strong fibrillar collagen network. The different compositions across the disc create a dynamic structure that is able to bear and distribute loads across the entire structure.

Metabolic Balance

The extracellular matrix of a healthy intervertebral disc is a dynamic environment, which is maintained at equilibrium due to a fine balance between anabolism and catabolism in order to maintain structure and integrity. Many factors contribute to this balance, including vascular supply, cellular metabolism, mechanical stimulus, and cellular mediators. The mature NP is nearly absent of direct vascular supply, and therefore diffusion and glycolysis are the primary sources of nutrient metabolism. Several growth factors, including insulin-like growth factor (IGF), bone morphogenetic protein (BMP), and transforming growth factor-β (TGF-β), contribute to the anabolism within the IVD. IGF and TGF-β have been shown to play a role in stimulating prostaglandin synthesis. BMP-2 also has been shown to stimulate prostaglandin synthesis, as well as promote cell proliferation and expression of type II collagen and aggrecans. These growth factors work against catabolic factors that lead to the breakdown of matrix products. Multiple forms of a zinc-dependent family of enzymes called matrix metalloproteinases (MMPs) are responsible for the degradation of several types of collagen and noncollagenous matrix proteins, including proteoglycans and glycoproteins. MMPs are a vital component of the disc’s natural biologic balance between synthesis and breakdown of the extracellular matrix, but they have been shown to be up-regulated in diseased discs. The activity of MMPs is tempered by the expression of countering enzymes known as tissue inhibitors of metalloproteinases (TIMPs). TIMPs inhibit the activity of MMPs to create a proper balance between tissue construction and degradation.

Dysregulation of this system occurs in degenerative disc disease. Compressive forces on the IVD can also influence the balance between anabolic and catabolic activity. Moderate compressive forces have been shown to stimulate anabolic activity and formation of extracellular matrix proteins. Persistent high load pressures can inhibit matrix synthesis and stimulate MMP activity shifting toward catabolic activity.

Disc Nutrition

The nutrient supply to the IVD changes with age and can be influenced by mechanical factors. Only a direct vascular supply exists in the immature disc, which originates from the adjacent vertebral body and passes through porous channels in the CEP. These channels decrease with age and are nearly nonexistent past the second decade as a result of calcification. In addition to the reduction in direct vascular supply, during the early stages of disc growth, the increase in disc height hinders direct blood supply to the deeper regions of the disc. Nutritional supply, as well as removal of metabolic waste products for the majority of the life of the disc, is restricted to diffusion or convection transport. Smaller molecules such as glucose and oxygen are able to effectively diffuse through the disc aided by brownian movements as a result of concentration gradients. This occurs either through the AF circumferentially or through the end plates from the vertebral bodies. The end plates act as a selectively permeable barrier to certain solutes. Calcification of the end plates that occurs with aging can hinder nutrient supply through this pathway. Convection transport, as a result of bulk fluid flow, is the alternative method of solute transport and is likely the preferential method for the transport of larger molecules. Cycling of mechanical loading between activity and rest can mobilize nearly 22% of the total disc volume. Therefore, the diurnal loading cycle can account for a substantial amount of metabolite transfer and is a necessary element of IVD metabolism.

Despite these mechanisms of nutrient supply, the disc lives in a relatively hypoxic environment. The periphery of the disc receives the greatest nutrient supply. This is evident in the increased cell density at the periphery of the AF. In the center of the disc, glucose and oxygen levels are lower, due to restrictions in solute diffusion, resulting in increased lactic acid concentration and a more acidic environment, which can hinder proper maintenance of the cell matrix. As a result of the natural course of aging and degeneration, further inhibition of nutrient supply pathways can occur, which results in even greater accelerated degeneration within the disc matrix. External factors such as smoking, which can hinder vascular supply, or accelerated calcification of the end plates, can compound this effect.

Biomechanics

The three components of the IVD work in conjunction to enable its load absorption properties. The disc is able to perform this task secondary to its viscoelastic properties, secondary to the high concentrations of proteoglycans in the NP. Proteoglycan aggregates facilitate the retention of water, thus allowing it to function essentially as a fluid under static conditions. The NP absorbs weight-bearing compressive loads by conforming its shape to redistribute the load radially to the adjacent AF through hydrostatic forces. Bulk fluid flow from the disc also contributes to its viscoelastic properties. In addition to its utilization for nutrient transport, fluid flow out of the disc allows absorption of compressive forces. When the spine is at rest, the axial-loading forces are removed, decreasing hydrostatic pressure. Water is therefore reabsorbed and the disc returns to its natural conformation. These mechanisms allow the NP to be the first component to absorb the compressive load, followed by redistribution of load radially to the annulus, capitalizing on the structure of the AF to contain tensile stresses. The alternating lamellar structure of the outer AF, composed of dense type I collagen fibrils, is optimally designed to resist these tensile strains. This mechanism allows the AF to share in compressive load bearing without being exposed to direct compressive forces. This is not to say that no direct compressive force is applied to the annulus, but rather that different regions of the AF exhibit varying degrees of load sharing, depending on the posture of the spine when the load is applied.

Load sharing is also performed by the dorsal zygapophyseal joints of the three-joint complex. Aging of the IVD, leading to loss of disc height, can transfer additional load-bearing responsibilities to the joints, and vice versa. The interplay between the IVD and the zygapophyseal joints constitutes the interaction of the three-joint complex, which is a key part of the degenerative process. Despite the interaction between the individual components, studies have shown that degeneration of the disc occurs before that of the joints, indicating the importance of the role of the disc in this system.