Embryology of the Intervertebral Disc
Most of the spinal cord, the vertebrae, the cartilage end plates, and the annulus fibrosus develop from the mesoderm. The embryonic nucleus pulposus, in contrast, is derived from the endoderm, being a remnant of the notochord. The vertebral column develops in the human embryonic mesoderm at approximately four weeks’ gestation, requiring both the central notochord and the neural tube for its induction.
The centrum of each vertebrae forms from the fusion of the lower and the upper region of adjacent somites, with the intersegmental artery running horizontally between them. The developing vertebral body surrounds the notochord. The cells in the outer region of what will become the Intervertebral disc align into sheets, adjacent layers of which are orientated at alternative directions to the vertebral axis. They then synthesize collagen fibres in the same planes, leading to the highly organized lamellar structure typical of the normal annulus fibrosis (Fig 1.a).
The origin of the nucleus pulposus is less well understood, some authors attribute it to the notochord, while others believe the notochord rescinds and the nucleus is formed starting from the inner aspect of the annulus and moving inward.
At birth the cartilage end plates make up 50% of the intervertebral space (compared to 5% in the adult) and has large vascular channels running through them. The intervertebral disc also has some blood vessels running between the lamella of the annulus fibrosus, (Fig 1.b) where nerves are commonly found. Soon after birth the vascular channels of the cartilage end plate fill in with extracellular matrix such that no channels remain by the first decade of life, with similar reduction in the vessels of the annulus.
Thus the intervertebral disc in adulthood is often described as the largest avascular tissue in the body and certainly renders cells in the disc, in particular the central nucleus, a long way from the source of nutrients or clearance of metabolites.
Macroscopic Anatomy of the Intervertebral Disc
The central gelatinous nucleus pulposus is contained within the more collagenous annulus fibrosus laterally and the cartilage end plates inferiorly and superiorly. The annulus consists of concentric rings or lamellae, with collagen fibres in the outer lamellae continuing into the adjacent tissues, tying this fibrocartilaginous structure to the vertebral bodies at its rim, to the longitudinal ligaments anteriorly and posteriorly, and the hyaline cartilage end plates superiorly and inferiorly.
The cartilage end plates in turn lock into the osseous vertebral endplates via the calcified cartilage, with few, if any, collagen fibres crossing the boundary.
The adult intervertebral disc consists of a large amount of extracellular matrix interspersed by a small number of cells that make up approximately 1% of the total volume. The cells are believed to be made up of at least two phenotypically distinct populations. The cells are morphologically different.
Those in the annulus fibrosus and cartilage end plate are more elongated and fibroblast-like (Fig 2.a), compared with those of the nucleus pulposus, which are more rounded or oval and chondrocyte like, sometimes with a capsule around them (Fig 2.b).These apparent simplistic shapes belie the complexity that may be present, with the cells often having extensive, long, thin cell processes that are possibly involved in sensing mechanical strain (Fig 2.c)
Nucleus pulposus cells generally synthesize only type II collagen in the alginate beads, whereas annulus fibrosus cells produce both type I and type II collagen
Nerves and blood vessels are both present to a limited degree in the healthy adult disc, restricted to the outer few millimetres of the annulus fibrosus. A small number of mechanoreceptors are also present, most likely having the morphology of Golgi tendon organs, a few ruffini receptors and even fewer pacinian corpuscles.
The Intervertebral discs are cartilaginous, articulating structures between the vertebral bodies that allow movement (flexion, extension and rotation) in the otherwise rigid anterior portion of the vertebral column. They provide load support and are exposed to substantial mechanical demands in this role.
Like all cells, those of the disc require nutrition to sustain themselves and fulfil their functions, while their metabolic wastes must be removed. Nutrient transport to the disc cells is precarious because of the avascular nature of the tissue. Interruptions in the supply of nutrients are strongly linked to the development of disc degeneration.
Supply of Nutrients to the Disc cells
The Adult disc is virtually avascular, apart from a sparse penetration of capillaries and nerves in to the outermost regions of the annulus. Thus blood vessels at the margin of the disc are responsible for the supply of nutrients and the removal of wastes. The nucleus, inner annulus and part of the outer annulus are supplied from a capillary network that arises from the vertebral arteries and penetrates the subchondral plate to terminate in loops at the bone cartilage end plate junction.
Solute transport and Nutrient Gradient
Nutrients move from the capillaries that supply the disc, through the cartilage end plates and the dense matrix of the disc, to the cells. For small solutes such as glucose, lactic acid and oxygen transport is accomplished mainly by diffusion. Hence the movement of fluid in and out of the disc as a result of diurnal loading pattern has little direct influence on transport.
Gradients in the concentration thus arise depending on the balance between the rate of supply of glucose and oxygen from the blood supply to the cells and the rate of cellular consumption.
The centre of the disc will have the lowest concentrations of the nutrients glucose and oxygen, and the highest concentrations of lactic acid with the lowest pH.
Under conditions in which supply becomes compromised, such as calcification of the end plates or artherosclerosis of the vertebral arteries, nutrient supply may fall to a level in which cell viability can no longer be sustained and the cells in the centre of the disc may be the first to undergo apoptosis (die off), Thus its noteworthy that the first signs of disc degeneration are seen in the disc centre.
What causes Disc degeneration?
Heavy physical loading?
How do you know if someone is a witch?
What do you do with witches, you burn them
What burns.. wood burns
Therefore a witch must float !!!
They actually used to dunk suspected witches and if they floated they were burned at the stake. For centuries people believed that this is logical and must be correct.
So where does that leave us with respect to heavy loading and disc degeneration?
What about twin studies that show physical loading specific to occupation and sport play a relatively minor role in disc degeneration?
But more importantly what are we going to do without Schalk Burger.
Effective musculoskeletal healing should re-establish an organs structural properties. For the intervertebral disc this process is slow at best. Its intrinsic constituents have limited capacity, the disc is large, and it is vascularized only at the margins.
Consequently accumulation of tissue damage from normal wear and tear may outpace the body’s ability to heal, leading to a progressive cycle of biomechanical insufficiency and escalating tissue damage. Attempts to heal are focused in regions of peripheral vascularity, namely, the end plate and outer annulus.
The three primary factors that contribute to accelerated disc degeneration rates are:
Symptoms derived from a degenerated disc may be classified into two types
Painful discs are characterized by a confluence of
Pain impulses are conducted through myelinated A delta fibres and unmyelinated C fibres to the dorsal root ganglion and continue by way of the spinothalamic tract to the thalamus and the somatosensory cortex. In response to nociceptors in the disc, the somatosensory system may increase its sensitivity, resulting in a non-functional response. In other words, normally innocuous stimuli may generate an amplified response.
Disc Degeneration may influence the nervous system by stimulation of nocioreceptors in the annulus fibrosus, causing nociceptive pain that is often referred to as discogenic pain. The stimulation of the nociceptors may be of mechanical or inflammatory origin. In addition an ingrowth of vessels and nerve fibres into deeper layers of the annulus fibrosus have been observed in degenerated discs.
Neuropathic pain can be the result of mechanical compression, chemical or inflammatory processes. Mechanical compression of peripheral nerves and of spinal nerve root is known to cause functional changes that present clinically as sensory or motoric deficits. However nerve root compression alone has not been shown to induce pain.
On the other hand, relief from the sciatic pain that accompanies acute herniations of a disc usually occurs immediately after a discectomy, when the compression of the affected nerve root is eliminated.
Could this have something to do with the fact that the nucleus pulposus has been shown to reduce the conduction velocity at the spinal nerve root, induce degeneration of nerve fibres, increase discharge of nerve fibres, attract inflammatory cells, induce increased intraneural capillary permeability and influence intraneural blood flow. Pro-inflammatory factors have been demonstrated in disc herniation tissue and also in the cell culture of nucleus pulposus cells.
Disc Injury initiates the production of proinflammatory molecules. This is characterized by an early transient response to the initiating event, followed by a delayed phase that is concurrent with morphologic and biochemical features of chronic deterioration. TNF-? and IL-1 and IL-6 are the major proinflammatory mediators.
Disc degeneration is defined by changes in architecture and biochemical composition that invariably alter the internal mechanical environment of the disc. Annular fibres become disorganized and torn, the nucleus becomes less hydrated and the border between the annulus and nucleus become less distinct. These changes in disc organization and/or substance alter the constraints placed on adjacent vertebrae, leading to spinal hypermobility, abnormal kinetics and altered tissue-stress distributions.
Inflammation, innervation and hypermobility interact in ways that enhance and perpetuate the risk of discogenic pain. For instance, a central feature of inflammation is hyperalgesia, or peripheral nerve sensitisation. Inflammatory mediators such as prostaglandin E2 can directly alter the sensitivity of nociceptors. Elevated tissue levels of TNF-? induce IL-1, which is in turn a powerful inducer of nerve growth factor.
The abnormal tissue stress associated with hypermobility may provoke disc cells to secrete proinflammatory factors that potentiate both inflammatory and nociceptor sensitisation. Tensile stretch also can increase the production of nitric oxide by annulus cells. Nitric Oxide (induced by IL-1 and TNF-?) has been shown to induce apoptosis and inflammation, suppress proteoglycan synthesis and upregulate matrix metalloproteinase synthesis. Inflammatory mediators can lead to matrix degradation, which enhances hypermobility.
The aetiology of disc degeneration is uncertain, but is most probably a combination of:
Because sensitized nerves are a prerequisite for discogenic pain, animal model data suggest that pathological degeneration may be chronic, ineffective healing response consisting of