Pathology/pathogenesis of lumbar disc degeneration

INDEX

BASIC DISC ANATOMY &PHYSIOLOGY

NORMAL DISC AGING

DISC / VERTEBRAL COLUMNPATHOLOGICAL CHANGESIN DEGENERATIVE DISCDISEASES

THE VASCULAR BASIS FORDISC DEGENERATION

BASIC DISC ANATOMY & PHYSIOLOGY

The intervertebral discs may be thought of as soft tough pads that separate the bones(vertebrae) of the spine from one another. Their basis function is three-fold: 1) they act as aligament by holding the vertebrae of the spine together, 2) they act as a shock absorberwhich carries the downward weight of the body (axial load) while in an up right position,and 3) they act as pivot point, which allows the spine to bend and twist.

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Professor Yasser Metwallywww.yassermetwally.com

There are 23 discs in the human spine: 6 in the neck (cervical region), 12 in the middleback (thoracic region), and 5 in the lower back (lumbar region). We shall focus on thelumbar discs on this page.

Figure 1 Depicts a Front view(AP) of the lumbar spine. Herewe can see how the discs (blue)lie in between every vertebrae.Spinal nerves (yellow) haveemerged from between everytwo vertebrae and travel downthe lower limbs to innervate(give life to) the skin andmuscle. Note how the sciaticanerve is formed within thepelvis by branches from the lastthree lumbar spinal nerves. It isthis giant nerve that causes somuch trouble in many of uschronic pain sufferers.

The disc is made up of three basic structures: the nucleus pulposus, the annulus fibrosus,and the vertebral end-plates. Although their composition percentage differs, the latterthree structures are made of three basic components: proteoglycan (protein), collagen(cartilage), and water. We will learn all about these structures below.



Figure 2. Shows a cut-away posterior view ofthe lumbar spine. Now we can better visualizehow the sciatic nerve is formed and see justhow close the spinal nerve roots come to theintervertebral disc. Any herniation of theposterior disc may compress the spinal nerveroot and result in severe lower back pain andlower limb pain (sciatica).

Axial Disc Anatomy and physiology:

The Nucleus Pulposus is the water rich gelatinous center of the disc which is under veryhigh pressure when the human is up-right. It has two main functions, to bear or carry thedownward weight (axial load) of the body, and to act as a 'pivot point' from which allmovement of the lower trunk occurs. It's third function is to act as a ligament and bind thevertebrae together.

The annulus Fibrosus is a much more fibrous structure that the nucleus pulposus. It has ahigher collagen content and lower water content. Its job is to 'corral' the pressurizednucleus and keep it from exploding outward. It is made of 15 to 25 concentric sheets ofcollagen, (a cartilage like substance) called the Lamellae. The lamellae are arranged in aspecial configuration which makes them extremely strong and easily able to contain thatpressurized nucleus pulposus.

The spinal nerves roots and Spinal Nerves are extensions of the brain and spinal cord. Likesuper highways the spinal nerves and nerve roots are constantly carrying electric messagesto and from the brain. The nerve roots exit the spine through bony holes called theIntervertebral Foramen (IVF). As the nerve roots 'peal-off' from the cauda equina, onesensory nerve root and one motor nerve root, and head for their respective IVF. Noteworthy is the fact that our two nerve root pass very close to the back of the disc. Oncewithin the IVF the two nerve roots merge into one spinal nerve. The spinal nerves arecalled 'mixed nerves' for they contains both sensory nerve fiber (afferent) and motor nervefiber (efferent). After leaving the spine through the IVF, the nerve split into a posterior



division (Dorsal Ramus) and an anterior division (Ventral Ramus). The Dorsal Ramusconnect to the muscle and skin over the lower back and butt and the Facet Joint. TheVentral Ramus combine in the pelvis and form the giant Sciatic Nerve and Lateral FemoralCutaneous Nerve which connect to all the skin and muscle of the lower limbs.

The ventral ramus has a 'recurrent branch' that connects to the back of the disc, as well asthe sympathetic nervous system (Grey Ramus Communicans); this special nerve is calledthe Sinuvertebral nerve (SN) (see below). In the lumbar spine (below the L1 disc level)there is no spinal cord. Instead the nerve roots hang in an enclosed sac which is called theThecal Sac. The thecal sac, which protects the dangling nerve roots, is made up of twodistinct but tightly bound layers called the dura mater and arachnoid mater. A clear fluidcalled Cerebral Spinal Fluid is also found within the thecal sac. This fluid protects thenerve roots and also supplies nutrients. Note how the nerve roots, that collectively arecalled the Cauda Equina, are highly organized within the thecal sac.

Because of this arrangement, which always puts the lower level nerve root in front, it ispossible for a large compressive L4 disc herniation to irritate the S1 and/or L5 roots. Thismay explain why disc herniations do not always match their dermatomal distribution - i.e.,a disc herniation at L4 may clinically present as nerve root pain (radicular pain, sciatica)and dysfunction in the S1 and/or L5 distributions! The Epidural Space is the space betweenthe bony neural canal and the thecal sac, or the space 'outside' of the thecal sac. Unlike mydrawing this space is filled with blood vessels and fat. Note worthy is the fact that this is theregion where 'epidural steroid injections' are placed.

The Facet Joints zygapophyseal joints) of the spine are where the vertebrae articulate(join) with each other. Actually, the gap between the inferior and superior articularprocesses is the true facet joint (white region). Collectively the inferior and superiorarticular processes and the facet joint are called the zygapophyseal Joints or articularpillars. These joints help carry the axial load of the body and limit the range of motion ofthe spine. They also make up the back of the intervertebral foramen and may causestenosis if they hypertrophy in later life (lateral stenosis). The Ring Apophysis is the 'nakedbone' of the outer periphery of the vertebral bodies.

The very outer fibers of the disc (Sharpey's Fibers) anchor themselves into this region.Bone spurs (Osteophytes) may arise from the ring apophysis as the result of the later stagesof Degenerative Disc Disease (DDD) and/or Osteoarthritis (Spondylosis). Specifically,osteophytes arise from the prolonged 'pulling and tugging' of 'Sharpey's Fibers' at theiranchor points. The Posterior Longitudinal Ligament (PLL) is a strong ligamentous tissuewhich courses down the anterior aspect of the vertebral canal and is attached to the outerfibers of the annulus fibrosus. This highly innervated (supplied with pain carrying nervefiber) tissue is the last line-of-defense the posterior neural tissue has against the irritatingand inflammatory effects of nucleus pulposus.



Figure 3. TheSinuvertebralNerve

The Sinuvertebral Nerve

The Sinuvertebral Nerves (SN), is a mixed nerve as well. It carries both autonomic fiber(sympathetic) and sensory (afferent) fiber. The sensory portion, which has the capability tocarry the feeling of PAIN, arises from the outer 1/3 of the posterior annulus fibrosus(yellow balls, fig. 3) and Posterior Longitudinal Ligament. It then spilts and attaches toboth the dorsal ramus and the grey ramus communicans, although this nerves anatomyand course seems to be quite anomalous. Of importance is the fact that if irritated, thenerve ending within the disc have the potential to generate both back pain and/or lowerlimb pain (discogenic pain).

o Discogenic Sciatica (referred discogenic pain)

It is believed that the sinuvertebral nerve-endings are 'sensitive' to the irritating effects ofdegenerated nucleus pulposus, that may be leak into the outer region of the annulus from agrade three annular tear. Amazingly, the sinuvertebral nerve also innervates (connects to)the disc above and below! So, the sinuvertebral nerve of the L4 disc also innervates the L5and L3 disc. This may help explain why a L4 disc herniation/annular tear may clinicallypresent with some signs of L5 and/or L3 involvement as well. It also carries autonomicnerve fiber to the blood vessels (not shown in fig. 3) of the epidural space. Sympatheticnerves control how the blood vessels function (vasomotor & vasosensory). Although rare,



injury to these sympathetic nerves may cause RSD symptoms in the patients lower limbs;this usually would occur following surgery.

The exact pain-pathway (how pain travels from the disc to the spinal cord) of discogenicpain is another fascinating and controversial subject. It seems that the sensory pathwayfrom the sinuvertebral nerves into the spinal cord, does not take the 'expected' route inevery patient. Some research has demonstrated that pain-signals travel from the disc, re-enter the IVF (via sinuvertebral nerve) and Dorsal Root Ganglion at the same level. Other,more recent research has indicated that pain-signals travel from the disc, through thesinuvertebral nerve, through the Gray Rami Communicans, into the Sympathetic Trunk(ST), up the sympathetic chain to the L2 vertebral level, through the gray ramicommunicans, into the L2 dorsal rami, into the L2 IVF, and into the L2 Dorsal RootGanglion. The latter pain pathway is why some investigators believe that lower level discherniations may present as L2 dermatomal pain (groin region) in some patients!

Figure 4. A sagittal view (lateral view) of the 'motionsegment'; Two vertebrae which are 'sandwiching' theintervertebral disc.

The disc (which is made of a annulus fibrosis and the nucleus pulposus) is made up of threedistinct areas: 1) The nucleus pulposus (green, fig 4), which is a water rich (due toproteoglycan aggrecan & aggrecate molecules which trap and hold water within the disc)gel in the center of the disc; 2) The annulus fibrosis (blue, fig 4), which is the fibrous outerportions of the disc that is made up of type I collagen; and 3) The vertebral end-plates(yellow, fig 4), which are cartilaginous plates that attach the discs to the vertebrae andsupply food (nutrients) to the inner 2/3 of the annulus and entire nucleus pulposus.

To further increase the strength of the annulus fibrosus, individual sheets of collagen arelayered throughout the annulus. There sheets of collagen are called lamellae (black curvedlines within blue, fig 4). The very outer lamellae (Sharpey's fibers), unlike the innerlamellae, are anchored into the solid bony periphery (Ring Apophysis) of each vertebralbody. This is the region that 'osteophytes' or bone spurs typically like to form.



CT SCAN / MRI ANATOMY, CLINICAL CORRELATION

Figure 5. MR study of lumbar disc 5. Although this patient does have a moderate degree ofdisc degeneration (black disc) and a small non-compressive 4 millimeter central discherniation, he had a very large 'central canal' which nicely demonstrates the axial MRIanatomy. The nucleus pulposus is not visible on these images. One reason for this isbecause the disc has too much desiccation to distinguish between the annulus and nucleus,and the other reason is that this is a T1 Weighted image which will not differentiatebetween the high water content of the nucleus and the more arid annulus; however, on anormal, non-degenerated disc, you can easily see a nuclear region and an annular region onthe T2 Weighted image. The 'posterior neural structures' include the Traversing NerveRoots, the Thecal Sac (dura and arachnoid mater) and the exiting nerve roots that liewithin the IVF (pink zone) and not very visible on this particular image.



Figure 6. Demonstrates another axial view of a normal health L4 disc. Now we can see adistinct nuclear region and annular region. Note the Facet Joints (pink star on one of them)are imaged 'white' as well. Again this indicates a high fluid content; in this case it's thesynovial fluid of the facet joint that is cause the increased signal.

Figure 7. CT myelography of the lumbar region. BLUE: This is the 'Central Region' and islocated directly behind the disc and encompasses the anterior aspect of the thecal sac. Since



the PLL (posterior longitudinal ligament) is at its thickest in this region, the disc usuallyherniates slightly to the left or right of this central zone. PINK: This is the 'ParacentralRegion' or 'Lateral Recess' and is located just outside of the Central Region. Because thePLL is not as thick in this region, disc herniations are frequently found here; in fact, this isthe number one region for disc herniations to occur in. The Traversing Nerve Roots, whichare the neural structures found in this zone, are frequently contacted, deviated andcompressed in this zone. GREEN: This is the 'Intraforaminal Zone', also known as the'Subarticular Zone', and is located within the intervertebral foramen (IVF). It is fairly rarefor a disc to herniate into this region or beyond; in fact, only 5% to 10% of all discherniation occur here or farther out. When herniations do occur in this zone, they are oftenvery troublesome for the patient. This is because a super-delicate neural structure calledthe 'Dorsal Root Ganglion' (DRG) lives in this zone. Any compression of the DRG canresult in severe pain, sciatica ( radiculopathy) and nerve cell body (neuron) damage.YELLOW: This is the 'extraforaminal zone' and, as the name implies, is just outside(lateral to) of the IVF. Again, it is very rare for a disc to herniate into this region, but whenit does happen, it is often very troublesome for the patient and surgeon. A herniation in thiszone may also irritate the 'Sympathetic Nervous System' and cause RSD like symptoms inthe lower limb.



Figure 8. CT myelography.Normal structure at L5 vertebra

DISC PHYSIOLOGY

The normal human intervertebral disc, which is considered the largest avascular structurein the human body, is made up of two main components, proteoglycan and collagen (type Iand type II). The annulus is mostly made of collagen, which is a tough fibrous tissue similarto the cartilage that is found in the knee, and the nucleus is made mostly of proteoglycan.Proteoglycans, which are produced by disc cells that resemble chondrocytes, are extremelyimportant for disc function and are what 'trap' and hold water molecules (H20) within thetissue of the disc. In fact both the disc and annulus are comprised mainly of water, i.e., thenucleus is 80% water, and the annulus is 65% water. Proteoglycans are the building blocksof the aggrecan molecule which is the true 'water trap' of the disc. Aggrecans combinewithin the disc on strands of hyaluronan acid to form huge structures called 'Aggregates'.These super water-filled proteoglycan aggregates are what give the healthy young disc itsamazing strengths and pliability, in fact a well hydrated disc is often even stronger than thebony vertebral body.



Figure 9. Here we have the healthy discof a teenager (cadaver). The watercontent is extremely high as you can evensee by the 'glistening' appearance of thenucleus (which is the gray center of thewhite disc).

Disc Function

In order for a disc to function properly, it must have high water content; this is especiallytrue of the nucleus. A well hydrated (with water) disc is both strong and pliable. Thenucleus pulposus needs to be strong and well hydrated to do its job (axial load), for it is thisstructure that supports or carries the lion's share of the axial load (downward weight ofbody) of the body. With an undamaged annulus, strongly corralling a fully hydratednucleus, the disc can easily support even the heaviest of bodies! As the disc dehydrates(loses water) the disc loose ability to support the axial load of the body (loses hydrostaticpressure); this causes a weight bearing shift' from the nucleus, outward, onto the annulus,outer vertebral body, and zygapophyseal joints (facets). Now, we have an 'over-load' on theannulus (which may trigger other destructive biochemical reactions) which, if severeand/or is imposed upon a genetically inferior annulus, will result in pathologicaldegenerative disc disease (spondylosis).

Hydration also is important with respect to disc nutrition. As we have already mentioned,nutrients (which all living tissue needs in order to survive) must diffuse (soak) through thediscal tissue in order to reach the hungry disc cells. This diffusion process is much fasterand easier if the diffusing tissue has a high water content. We may use 'swimming' as ananalogy: It's easier to swim through the water, than through the sands of a desert. Thesands of the desert would be a dehydrated disc, and the water would be a hydrated disc. So,water and disc hydration are one of the key factors for a normally functioning spine andwell fed disc.



Proteoglycans, which are produced by disc cells that resemble chondrocytes, areextremely important for disc function and are what 'trap' and hold water molecules (H20)within the tissue of the disc. In fact both the disc and annulus are comprised mainly ofwater, i.e., the nucleus is 80% water, and the annulus is 65% water. Proteoglycans are thebuilding blocks of the aggrecan molecule which is the true 'water trap' of the disc.Aggrecans combine within the disc on strands of hyaluronan acid to form huge structurescalled 'Aggregates'. These super water-filled proteoglycan aggregates are what give thehealthy young disc its amazing strengths and pliability.

Water is held within the disc by tiny sponge-like molecules called proteoglycanaggrecans. These 'super sponges' have an amazing ability to attract and hold watermolecules, and can in fact hold over 500 times their own weight in water; this gives thenon-dehydrated disc the tremendous 'hydrostatic pressure' which is needed to bear theaxial load of the body.

o Disc hydration

Water is held within the disc by tiny sponge-like molecules called proteoglycan aggrecans.These 'super sponges' have an amazing ability to attract and hold water molecules, and canin fact hold over 500 times their own weight in water; this gives the non-dehydrated discthe tremendous 'hydrostatic pressure' which is needed to bear the axial load of the body.Amazingly, the aggrecans water absorption is so powerful that over night (non-axialloading) the height of the disc and the body will actually measurably increase due to thediscs engorgement with water. This phenomenon is called 'Diurnal Change' and is onlypresent in non-degenerated discs.

Disc cells, particularly the chondrocyte-like cells of the nucleus and inner annulus,manufacture proteoglycan aggrecan molecules. Like little factories, they create, replaceand rebuild aggrecan molecules. As long as the disc cells have food (glucose), buildingmaterial (amino acids) and oxygen all is well in disc-land. It is also important for them tohave a non-acidic working environment, which is taken care of, since wastes are diffusedout of the disc through the same way nutrients diffuse in. In the living disc up to 100aggrecans combine on a long piece of 'hyaluronan acid' to form giant proteoglycanaggregate molecules. It's these aggregates that are found within the disc in the real world.

The nucleus pulposus has a unique ability to bind water. Initially the water binding capacity of the nucleus wasattributed to fluid exchange governed by osmotic pressure. The cartilaginous end-plates were thought to act as asemipermeable membranes with the nucleus drawing water from the vertebral bodies. It is presently thought thatthe hydrodynamics of the disc depend upon the nucleus possessing the properties of a gel rather than uponosmosis. this gel contains some cartilaginous cells, fibroblasts, collagen framework and the ground substance whichis mostly mucopolysaccharides with varying amount of salt and water. The high imbibition pressure is producedby the mucopolysaccharides contained within the gel which can bind almost nine times its volume of water. Thewater content of the nucleus is not chemically bonded and can be expressed from the nucleus by prolongedmechanical pressure.



Box 1 Factors necessary for chondrocytes-like disc cells to manufacture proteoglycanaggrecan molecules

Glucose Building material (amino acid) Oxygen Non-acidic environment

Disc Nutrition

The intervertebral disc is the largest avascular structure in thehuman body. The reason for this is because it has no directblood supply like most other body tissue. Nutrients for the discare found within tiny capillary beds (black arrows, fig. 6) thatare located in the subchondral bone, just above the vertebralend-plates . This subchondral vascular network 'feeds' the disccells of the nucleus and inner annulus through the diffusionprocess. Figure (fig. 10) shows the 'disc feeding vascularsystem' . Note that the outer annulus has its own blood supplythat is embedded within the very outer annulus. For the outerannulus this is a much more efficient system and nutrients

don't have to diffuse very far to find their disc cells. The 'more direct' blood supply of theouter annulus is why tears of the outer 1/3 of the annulus will heal with the passage of time,which unfortunately is not true for tears of the rest of the disc.

Research has indicated that disc tears will not heal in the inner zones of the disc - probablybecause of the avascular nature of the inner two thirds of the disc. Note the nutrients (pinkballs, fig. 10)) diffuse directly into the tissue of the outer annulus, where as the nucleus andinner annulus has a much longer diffusion route that is might be blocked by the vertebralend-plates if calcified. Note how the nutrients (pink balls) are released from the bloodvessels (red, fig. 10) in the subchondral bone just under the vertebral end-plates. Thesenutrients must 'diffuse' or soak their way through the vertebral end-plates and into thedisc. This 'diffusion method' is how the cells of the disc get the nutrients oxygen, glucose,and amino acids which are required for normal disc function and repair. This poorblood/nutrient supply system to the disc is one of the main reasons that the disc ages anddegenerates so early in life.

Nutrients for the disc arefound within tiny capillarybeds that are located in thesubchondral bone, justabove the vertebral end-plates. This subchondralvascular network 'feeds' thedisc cells of the nucleus andinner annulus through thediffusion process.



Figure 10. Disc anatomy, discvascular system and disc nutrition

The 'diffusion feeding process' is enhanced somewhat by a phenomena called 'DiurnalChange'. Our discs have the ability to expand and compress over the course of a day. As westart the day our discs, like squeezing out a sponge, will compress and dehydrate because ofthe gravity and physical activity which place axial loads upon the discs. In fact a healthydisc will shrink down some 20%, which in turn decreases our height by 15 to 25mm. As wesleep and decompress our spines, our discs swell with water plus nutrients and expandback to their fully hydrated state. This tide-like movement of fluids in and out of the discwill help with the movement of nutrients into the avascular center of the disc.

Advanced Anatomy & Physiologyo The Nucleus Pulposus

The nucleus pulposus is a hydrated gelatinous structure located in the center of eachintervertebral disc that has the consistency of toothpaste. Its main make-up is water (80%).Its solid/dry component make-up are proteoglycan (65%), type II collagen fiber (17%) anda small amount of elastin fibers. Collectively the proteoglycans and the collagen are calledthe 'nuclear matrix'. The cells of the disc, which produce the water holding proteoglycanmolecules are very similar to chondrocytes seen in articular cartilage and are also heldwithin the matrix.



Proteoglycans are found in several structural forms within the disc but the most important'arrangement' is called a proteoglycan aggrecan. These aggrecans main function is to trapand hold water, which is what gives the nucleus its strength and resiliency. Like a 'supersponge', aggrecans can trap and hold over 500 times their weight in water!

The nucleus has two functions. The first is to bear most of the tremendous axial loadcoming from the weight of the body above and second to 'stand-up' the lamellae of theannulus - so that the annulus can reach its full weight baring potential. In order for properweight bearing the nucleus and the annulus must work hand in hand.

o The annulus Fibrosis

The annulus is the outer portion of the disc that surrounds the nucleus. It is made up of 15to 25 collagen sheets which are called the 'lamellae'. The lamellae are 'glued' together witha proteoglycans. These sheets encircle the disc and, in concert with the nucleus, give thedisc tremendous axial load strength.

Figure 11. A, The annulus Fibrosis. B, The 'Nucleus Pulposus' (pink), which is a water-richgel-like mass of proteoglycan material, has the duty to support the tremendous 'Axial-Load' (weight) of the body. This nucleus is 'corralled' by the stronger 'annulus Fibrosus'.The annulus is made out of concentric rings of a cartilage-like material called 'lamellae'. Itis this specially arranged collagen that gives the annulus the tremendous strength needed tohold that nucleus in place.



The posterior portion of the annulus if further strengthened by the 'posterior longitudinalligament'. This structure is the final barrier between the disc and the delicate spinal cord,and nerve roots.

The biochemical make up of the annulus is similar to that of the nucleus with differentproportions. The annulus is 65% water, with the collagen, both type I and II making up55% of the dry weight, and proteoglycans (mostly the larger aggregate type - 60%) makingup 20% of the dry weight. 10% of the annulus also contain 'elastic fiber' that are seen nearwhere the annulus attaches into the vertebral end-plate.

The lamellae are made up of both Type I (very strong type) and Type II collagen fiber. Thevery outer lamellae are almost all Type I. As we move inward toward the nucleus the moreType II is seen and less Type I. The very inner layers are very hard to distinguish from thenucleus. There is not a clear boundary between the nucleus and the annulus.

A simply amazing fact about the lamellae design is that the collagen fibers that make-upeach lamellae run parallel at a 65 degree angle to the sagittal plane. Even more amazing isthe fact that the each lamellae are flipped so that the 65 degree angle alternates betweenevery lamellae, one to the right then one to the left. This design greatly increases the shearstrength of the annulus and makes it stronger for cracks to develop through the layers ofthe annulus.

The function of the annulus is to help the nucleus support the axial weight from the body.The annulus does need some help from the nucleus in order to achieve its strongestconfiguration. It relies on the nucleus to push it outward which keeps the lamellae fromcollapsing inward. The nucleus must keep a very high hydrostatic pressure to achieve this.

Box 2. Function of the proteoglycan

1. Proteoglycan traps water. Water is held within the disc by tiny sponge-likemolecules called proteoglycan aggrecans. These 'super sponges' have an amazingability to attract and hold water molecules, and can in fact hold over 500 times theirown weight in water; this gives the non-dehydrated disc the tremendous 'hydrostaticpressure' which is needed to bear the axial load of the body.

2. The lamellae of the annulus fibrosus are glued together by proteoglycan

o The Vertebral End-Plates

Both the top and the bottom of each vertebrae (spinal bones) are capped with a thin ¾millimeter cartilaginous pad called the 'Vertebral End-Plate'. Despite their name, theseend-plates are not attached to the subchondral bone of the vertebrae but are insteadstrongly interwoven into the annulus of the disc. It is for this reason, as well as strongmorphological similarities, that the vertebral end-plates are considered part of the disc andnot part of the vertebral body.



Figure 12. The Vertebral End-Plates

The biochemical morphology of the end-plates is extremely similar to that of the disc:Water, proteoglycans, collagen and cartilage cells (chondrocytes). The concentrationscheme of these components also mirrors that of the disc: The center of the end-plate ismostly water and proteoglycan. As we move outward toward the periphery, more andmore collagen is seen with less and less proteoglycans. This similar biochemical makeupand distribution scheme helps the diffusion of nutrients between the subchondral bone ofthe vertebra and the depths of the disc.

The very outer rim of the vertebrae is not covered by the end-plate, which leaves a ring ofexposed bone on the periphery of the top and bottom of each vertebra. This exposedperipheral area is called the 'Ring Apophysis' and is often a site for the development ofspur formation associated with the degeneration process.

BIOMECHANICS OF DISC DEGENERATION

In the lumbar region, the compressing forces occur primarily in a vertical axis. Both the nucleusand annulus act to absorb these forces and redistribute them evenly in all direction. The nucleusbears all the vertical load and the annulus bears only the tangential load. The liquid property ofthe nucleus enables it to alter its shape freely under pressure. This shape altering property of thenucleus enable it to withstand stresses varying in duration and magnitude, transmitting someradially to the annulus and the rest over the entire cartilaginous end- plate.

With degeneration of the disc, the gel inhibition pressure of the nucleus is impaired, markedchange occurs in the transmission of forces occurring along the vertical axis of the spine. Thedesiccated nucleus is unable to redistribute much of the vertical load radically, causing theannulus and the facet joints to sustain much of this load.



NORMAL DISC AGING

Unlike other tissues of the body, the intervertebral disc under goes an early and oftensevere form of aging and degeneration . In most humans, this aging/degeneration process isslow and steady, but in some the process rapidly accelerates and may lead to catastrophicfailure of the disc; which in turn may lead to chronic pain and disability. This 'accelerated'form of aging/degeneration may be called Degenerative Disc Disease (DDD), although theterm is commonly and erroneously used to describe any form of disc degeneration.

Figure 13. The figures to the leftshow the difference between thenormal discs and degenerative discdisease. Note the differencebetween the 'normal discs' (whitestructures) and the 'degenerateddiscs' (right). This is an example ofmoderate to severe degenerativedisc disease. The discs have bothcollapsed and severely dehydrated.They have also an ugly browncolor from the glycation process.

Research has strongly linked degenerative disc disease to back pain, and sciatica, althoughnot in every case, for it is well known that degenerative disc disease, disc protrusion, andstenosis do occur in completely asymptomatic people, but for about 10% of the population,degenerative disc disease will result in permanent chronic pain and disability. Technicallyit's not the actual process of degenerative disc disease that results in pain; it's the evil 'end-phases' of the disease that have the potential to generate back pain. These end-phasesinclude annular tears (Internal Disc Disruption or IDD); disc protrusions; nerve in-growth; and the ultimate end-phase, stenosis.

The most common and striking feature of disc aging and degeneration is the loss of theproteoglycan molecule from the nucleus of the disc. Other findings of aging include aprogressive dehydration, a progressive thickening (via cross-linking, glycation and CMLformation), brown pigmentation formation and increased 'brittleness' of the tissues of thedisc.

The three main factors of disc aging:

There are three main factors that are involved in the aging process of the disc and both ofthese factors are amplified because of the already poor vascular supply of the disc: 1)Idiopathic blood vessel/nutrient loss and dehydration, 2.) Non-Enzymatic Glycation,Glycosylation, 3) Free radical oxidation



Figure 14. Here we have early disc aging. The tissue of the disc has turned brown,secondary to the glycation process, and the disc has become much 'drier. The disc seen inadolescents, for comparison sake, shows us what the disc of a teenage looks like. Note thewell demarcated, wet looking, nucleus (gray center) and no ugly brown tissue

1) Idiopathic blood vessel/nutrient loss and dehydration:

Short term result

For unknown reasons the nucleus of the disc losses much of its vital blood supply duringthe first decade of life (6). Without sufficient nutrients (which are contained in the blood)the cells of the disc begin to die and the disc (especially the nucleus) becomes depleted ofwater. The drop in water/proteoglycan content is one or the classic signs of disc aging.Because of this dehydration of the nucleus, there is ultimately a 'weight-bearing shift' thatoccurs from the nucleus onto the outer annulus, ring apophysis, and the zygapophysealjoints. This increase stress upon the preceding posterior structures may lead to furthermore severe forms of aging, i.e., degenerative disc disease.

Long result

Under the physiology section of the 'Disc Anatomy', we have learned how important discnutrition is in maintaining a normally functioning disc. As long as the cells of the discreceive an adequate nutrient supply (which is obtain from the diffusion of oxygen, glucose,and amino acids from capillary beds just above the end-plates, into the disc), they willmanufacture the proteoglycan molecule, which combines within the disc to form the largeraggrecan and aggregate molecules. It is these aggrecan molecules that trap and hold waterwithin the disc. A fully hydrated disc will have a very high hydrostatic pressure (osmoticpressure) which makes the nucleus pulposus (which is 80% water in a normal disc)incredibly strong and able support the lion's share of the axial load from the body. Thenutrients to inner annulus and nucleus have a long way to 'diffuse' in order to reach all thedisc cells. (pink balls, fig 6)

Without an adequate supply of nutrients, the cells of the disc will die. If the cells of the discfailed to get proper nutrients - such as oxygen, or glucose - or if the pH level of the disc rose(because waste is not being diffused out of the disc), disc cells would die and stop producing



the vital proteoglycan molecule; without proteoglycans, the disc losses its water content(dehydrates) and losses its hydrostatic pressure (osmotic pressure). This lost proteoglycancontent is the most striking feature of disc aging and degeneration. By adulthood over 50%of the cells of the disc are dead.

So what's killing the disc cells and resulting in thisloss of proteoglycan content?. It seems that the humandisc becomes 'nutritionally compromised' from themoment we begin to stand and walk. An idiopathic"obliteration" of portions of the nutrient-providingcapillary beds, which lie just above the vertebral end-

plates. (These capillary beds are the only source of nutrients for the cells of the innerannulus and nucleus) is frequently observed very early in life, amazingly, this 'auto-destruction' begins within the first two years of life, and worsens over the next 8 years andbetween the ages of 3 and 10 there is "a dramatic decrease of physiologic vessels in the end-plate and an abundance of areas with obliterated vessels. and a substantial increase in(disc) cell death." These findings suggest that the initial causation of disc aging anddegeneration is 'nutritional compromise', secondary to an idiopathic loss of the discal bloodsupply above the vertebral end-plates.

Other factors affecting disc nutrition via diffusion rates of nutrients through the vertebralend-plates include end-plate calcification, the effects of changes in blood flow patternssecondary to arterial stenosis, smoking, diabetes, and exposure to vibration.

Box 3. Pathophysiological / biochemical steps of disc degeneration

Obliteration of portions of the nutrient-providingcapillary beds, which lie just above the vertebral end-plates.

Death of the proteoglycan forming disc cells Progressive loss of the water trapping capacity of the

nucleus Loss of disc hydration Disc degeneration

The Vicious Cycle of Disc Aging

This progressive loss of proteoglycan and dehydration begins to 'snowball' out of control.Not only because of the progressive loss of nutrients, but also because of the fact thatdecreased hydrostatic pressure also slows the production of proteoglycan by the disc cell.Here's what this vicious cycle looks like.

As the nutrient supply within the disc drops (because of blood vessel obliteration and laterend-plate mineralization), the disc cells start to die. Because there are fewer available disccells around to make proteoglycan, there is a drop in the amount of circulating

An idiopathic "obliteration" ofportions of the nutrient-providingcapillary beds, which lie just abovethe vertebral end-plates is frequentlyobserved very early in life.



proteoglycan aggrecan molecules. This decrease in the aggrecan molecule, (which is whatholds water within the disc) results in both dehydration, and a decrease in hydrostaticpressure within the nucleus. The loss of hydrostatic pressure has two negative effects on thedisc: a) it will cause a further decrease in the amount of circulating proteoglycan aggrecanmolecules, for we know that disc cells need a constant hydrostatic pressure level of 3 atm tofunction normally. Any increase or decrease in hydrostatic pressure caused a reductionproteoglycan production, which in turn decreases hydrostatic pressure even more - hencethe vicious cycle. b) Now, these biochemical changes begin to change the biomechanics ofthe disc: With the decrease of hydrostatic pressure the nucleus, like a deflating beach-ball,can no longer carry the full axial-load (weight) of the body. A 'shift' in the axial-loaddistribution begins to occur, with the periphery of the disc (outer annulus, ring apophysis,and zygapophyseal joints) taking on more and more of the load and stress. Experimentally,the annulus of a degenerated disc shows a very high 'stress-load' on the annulus and notthe nucleus. We will later learn that this 'load-shift' can be greatly accelerated if thevolume of the nucleus is increased by trauma-induced structural damage to either the end-plate (compression fracture) and/or tearing of the inner annulus.

2.) Non-Enzymatic Glycation: Glycosylation

Glycation (Glycosylation , or non-enzymatic glycation) is a biochemical reaction whichoccurs when reduced sugars (like glucose) come in contact with proteins (like disc collagen)in an avascular environment. The more avascular the tissue, the more severe this reactionoccurs. Since the disc is the largest avascular tissue in the body, the glycation processthrives within its substance and results in a slow but steady transformation of disc collageninto a thicker and more brittle substance. Specifically, this reaction occurs between theprotein molecules within the collagen, and free floating glucose (reduced sugar). Thisreaction is called 'posttranslational protein modification' or Glycation. Here's how itworks: In the absents of oxygen, reduced sugars start to 'rub against' (bind) the proteinswithin the collagen. The proteins are transformed into what is called an 'AdvancedGlycation End-Product' or AGE. These converted discal collagen strands (AGEs) becomemuch more brittle and also much more 'sticky', i.e., they love to combine with theirglycated neighbors in a process called 'cross-linking'. This 'cross-linking' phenomenonmakes the disc thicker, more fibrous and more susceptible to the development ofdegenerative disc disease. It also stains the discal tissue a distinct shade of brown as notedin figure 15,16

3) Free radical oxidation

Finally, the unstable AGEs molecules are oxidize by free radicals into a much more stablestructure called a CML (N- Carboxymethyl -lysine). CML formation has been found to bean excellent indication of discal aging



Figure 15. Dessication of the nucleus pulposus associated with multiple annular tears (eg,radial, circumferential). Notice that the disc is bulging without actual herniation. Becauseof the existing disc degeneration, it is possible to differentiate between the nucleus pulposusand annulus fibrosus. 1. annulus fibrosis 2. Circumferential annular tears 3- Posteriorlongitudinal ligament 4. The desiccated nucleus pulposus

Table 1. Factors implicated in disc aging and disc degeneration

Factor Comment

Nutritional compromise willdeprive the disc cells of thecapability to formproteoglycan. Withoutproteoglycans aggrecan &aggrecate, the water trappingfunction of the nucleus is lost,the disc losses its water content(dehydrates) and losses itshydrostatic pressure (osmoticpressure)

Idiopathic loss of the discal blood supply above thevertebral end-plates

End-plate calcification Vascular risk factors resulting in arteriolosclerosis of tiny

capillary beds that are in the subchondral bone, just abovethe vertebral end-plates (subchondral vascular network)

Non-Enzymatic Glycation

Specifically, this reaction occurs between the protein moleculeswithin the collagen of the annulus, and free floating glucose(reduced sugar) in an avascular medium. This reaction is called'posttranslational protein modification or Glycation. The proteinsare transformed into what is called an 'Advanced Glycation End-Product' or unstable AGE.

Free radical oxidation

The unstable AGEs molecules is oxidize by free radical into amuch more stable structure called a CML (N- Carboxymethyl -lysine). CML formation has been found to be an excellentindication of discal aging



Figure 16. Dessication of the nucleus pulposusassociated with multiple annular tears (eg,radial, circumferential). Notice that the disc isbulging without actual herniation. Because of theexisting disc degeneration, it is possible todifferentiate between the nucleus pulposus andannulus fibrosus. Notice the existence ofarticular facet pathology and tegmental flavumhypertrophy.

1. annulus fibrosis

2. Circumferential annular tears with infiltrationby nuclear material

3,4 . The desiccated nucleus pulposus

DISC / VERTEBRAL COLUMN PATHOLOGICAL CHANGES IN DEGENERATIVEDISC DISEASES

Degenerative disc disease commonly induces pathological changes in both theintervertebral discs and the vertebral column, collectively these are called spondylosis.Table 2

Table 2. Disc/ vertebral column pathological changes in degenerative disc disease

Pathology Comment

Disc pathology Annular bulging, annular tears, nucleus pulposus herniation, vacuum disc,canal stenosis

Parsinterarticularisdefect

Stress fractures of one or both sides of the neural arch through therelatively weak pars.

Facetpathology

Facet Joint disease can be defined as osteophytosis and hypertrophy of thearticular process.. etc

MRI bonemarrow signalchanges

MRI bone marrow signal changes in the vertebral endplates of thedegenerated discs



Figure 17. A,Normal spine,B,spondylosis

Role of end plate degeneration in intradiscal changes among patients with low backpain

The end plate is the main route of diffusion. The nutrition provided by arterial flow isdelivered through the end plate (Roberts et al. 1989, Moore et al. 1992). A comparisonbetween end plate degeneration in MRI and intradiscal changes revealed in discographyshowed end plate degeneration to be associated more clearly with long-term disc damage,i.e. degeneration, than acute disc damage, i.e. annular rupture. The primary nutritionalpathway into the avascular disc is assumed to be from the subchondral vessels via the endplate (Roberts et al. 1989, Moore et al. 1992). If this route were disturbed because of acalcified endplate or occlusion of the subchondral vessels, internal disc disruption couldfollow (Roberts et al. 1989). End plate degeneration has been found to occur parallel toother disc degeneration events (Horner & Urban 2001). Histologic studies have revealedcoincidence of microfractures in the end plate and intradiscal tears and clefts (Moon et al.2000, Boos et al. 2002). It is therefore assumed that the degenerative process affecting theend plate, the NP and the AF is a temporal sequence of nutritional deficiency (Boos et al.2002).

No differences were found between the end plate degeneration categories and painprovocation, and the results were hence opposite to the previous findings (Weishaupt et al.2001), which showed end plate changes to be associated with low back pain. It is yetpossible that the irritation of a ruptured disc by contrast medium is such a dominant factorin producing pain that minor variables, such as possible end plate irritation, will bemasked, which might explain why no evident correlation between pain provocation andend plate changes was found. On the other hand, we only evaluated intradiscal pain, andthe possible end plate-originated symptoms may not be discogenic. Yet, the results showedthat a significant number of positive pain provocations were associated with no end platedegeneration, which also indicates the negative role of end-plate degeneration in producinglow back pain. Findings of concordant pain during discography in discs with annularruptures support the results of previous studies showing an association between intradiscalruptures and low back pain (Vanharanta et al. 1988, Moneta et al. 1994).



THE VASCULAR BASIS FOR DISC DEGENERATION

Arterial findings, diffusion and disc degeneration among people without low backpain

Atherosclerotic changes in the lumbar arteries have been shown to be associated withlumbar disc degeneration (Kauppila et al. 1997). There is moderate variation in thefindings on lumbar artery status between the disc levels. It has been demonstrated that thecorrelation of atherosclerotic changes with disc degeneration is stronger at the uppercompared to the lower levels of the lumbar spine (Kauppila 1994)

The well-being of a disc is greatly dependent on its cells (Maroudas 1988, Boos et al. 2002).The cell density of a disc is controlled by nutritional factors (Stairmand et al. 1991). Duringthe degenerative process, considerable alterations occur in the structure and biochemistryof the intervertebral disc.

Arterial findings, disc degeneration and low back pain

The major findings in the literature concerning the role of blood flow and discdegeneration can be summarised as follows.

In cadaveric studies, atherosclerotic manifestations in the abdominal aorta and the lumbararteries correlated with low back pain (Kauppila et al. 1997) and disc degeneration(Kauppila et al. 1994).

In a cross-sectional cohort study, calcification of the abdominal aorta was found tocorrelate with disc degeneration (Kauppila et al. 1997). In some follow-up studies, vasculardisease and LBP have been found to correlate (Penttinen 1994, Kauppila et al. 1997), andone post-mortem study also showed this association (Kauppila & Tallroth 1993).

In epidemiological studies, low back pain and arterial disease have been found to havesome common risk factors (Frymoyer & Gordon 1989, Battie et al. 1991). The nutrientsupply to the nucleus cells can be disturbed at several points. Factors that affect the bloodsupply to the vertebral body such as vascular risk factors, the metabolic syndrome (type 2diabetes, inulin resistance, hypertension, increased blood viscosity and atherosclerosis...etc) can all result in disturbances of the nutrient supply to the nucleus cells andsubsequent disc degeneration. Histologic and experimental studies have revealed theassociation between nutritional factors and disc degeneration (Horner & Urban 2001, Booset al. 2002). It has been shown anatomically that vascular buds penetrate the cartilaginousend plates on the vertebral side, but rarely communicate with the disc substance itself(Moore et al. 1992), and that the nutrition of discs occurs mainly via diffusion from theblood vessels into the surrounding structures (Holm et al. 1981, Horner H.A. & Urban J.2001). Thus, changes in the end plate and the vessels may cause a reduction in thispathway.



It has been found in an experimental study that the reduction in nutrition may causeintradiscal tears and reduce the regenerative ability of cells in discs. The mechanical stressis also more likely to cause tears in conditions of reduced nutrition(Boos et al. 2002). Theseremaining tears could be a source of intradiscal pain and thus explain the difference in thedegree of disc degeneration and lumbar artery occlusion between people with and withoutlow back pain.

Vascular changes causing insufficient blood supply in the abdominal aorta and the lumbararteries are more common in the LBP population. Atheromatous lesions in the abdominalaorta most commonly occur around the aortic bifurcation, where the orifices of the lumbararteries are also located (Rogoff S.M. & Lipchik E.O. 1970, Ross R 1988). Patients withchronic low back pain were more likely to have atheromatous plaques in the abdominalaorta than patients without back pain, as analysed by CT, and this association was mostdistinct in the youngest patients. Also, when sciatica patients were compared to anasymptomatic population, intervertebral disc degeneration and narrowing of the lumbararteries were significantly more pronounced in the sciatic population at almost every disclevel. In general, it can be concluded that the present study showed multiple evidence of anassociation between vascular changes and low back pain and disc degeneration.

CONCLUSION

1. The metabolic syndrome (truncal obesity, type 2 diabetes, inulin resistance,hypertension, increased blood viscosity and atherosclerosis ...etc) is a risk factor fordisc degeneration and back pain. Vascular risk factors can result in disturbances ofthe nutrient supply to the nucleus cells and subsequent disc degeneration. Discdegeneration is a vascular process rather than a mechanical one.

2. Cardiovascular/cerebrovascular risk factors are significantly and independentlyassociated with symptomatic lumbar disc herniation. These findings provide furtherconfirmation that atherosclerosis may be involved in spinal disc degeneration.Modification of risk factors, particularly smoking, may also prove to be beneficial.

3. Stenosis of lumbar arteries is significantly associated with decreased diffusion oflumbar discs and may thus play an important role as a mechanism of discdegeneration.

4. End plate degeneration is associated with disc degeneration, but not with discrupture. Nor is end plate degeneration associated with discogenic pain caused by CTdiscography.

5. Atheromatous lesions in the abdominal aorta are more common and more extensivein patients with chronic low back pain than in asymptomatic people. There was noassociation between atheromatous lesions in the abdominal aorta and discdegeneration among chronic low back pain patients.

6. Stenosis of lumbar arteries is associated with disc degeneration among sciaticapatients, and the grade of occlusion of lumbar arteries and the severity of discdegeneration are significantly higher among sciatica patients compared toasymptomatic subjects.

7. Stenosis of lumbar arteries was associated with back pain symptoms and physicalactivity among sciatica patients in three-year follow-up.



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Health & Medicine

Pathology/pathogenesis of lumbar disc degeneration