IVD Flashcards
(24 cards)
Explain how AXIAL COMPRESSIVE LOADS on the functional spine unit (FSU) are supported by stresses in the NP, AF and their interactions. Then relate this to the most important compositional and structural properties of each tissue.
Axial compressive loads are supported by:
- Hydraulic pressure in NP supported by longitudinal and circumferential tensile stresses and radial compressive stresses in AF.
- The osmotic swelling pressure (high [GAG]) and compressibility (high [H2O]) of the NP.
Structural properties:
- Circumferential lamellar structure of AF with collagen in the lamellae anchored in the vertebral bone.
- High resistance to fluid flow out of NP and AF, i.e. low permeability (NP high [GAG]) and AF high [collagen]).
- Hydraulic pressure in NP is contained/balanced by tensile strength and impermeability of the AF.
Explain how FLEXION/ EXTENTION BENDING MOMENTS on the FSU (functional spine unit) are supported in the NP, AF and their interactions. Then relate this to the most important compositional and structural properties of each tissue.
- Pressure in NP and shift towards side of angle opening –> creates radial bulging force & axial expansion force on the AF which is balanced by longitudinal and circumferential tension if AF.
- Incompressibility (high [H2O]) and low shear modulus (low [collagen] and high [H2)]) of NP.
- Circumferential lamellar structure of AF with collagen in the lamellae (high [collagen]) anchored in the vertebral bone.
Explain how AXIAL ROTATION MOMENTS on the FSU are supported in the NP, AF and their interactions. Then relate this to the most important structural properties of each tissue.
As the vertebrae twist, this shears the AF lamellae and is carried by stretching of the obliquely oriented collagen fibers in the AF (high [collagen]) anchored in the vertebral bone –> this creates a loss in disc height supported compression/pressurization of the NP which is similar to axial compression, i.e. osmotic swelling pressure (high [GAG]) and compressibility (high [H2O]).
In both IVD ageing and degeneration, there is degradation of the extracellularmatrix (ECM). However, what tissue morphology change and biological process additionally happen during degeneration?
Ageing: is mild degradation of the tissue matrix.
Degeneration: includes aberrant (‘afwijkend’), cell-mediated response to progressive structural failure.
Q1: What are the three major etiological causes in the pathophysiology of disc degeneration?
Q2: Describe the pathophysiological mechanism.
- Genetic predisposition/ hereditary; SNP, e.g. Coli-IX, weakening collagen network, leading to structural failure of AF, depressurizing NP.
- Mechanical loading; high frequency or mag loads causing cell death and inability to maintain healthy matrix.
- Cell nutrition; lack of nutrients causing cell death and as above, or low pH due to lactic acid buildup causing MMP activity but no PG synthesis.
As a treatment for DDD, regenerative therapies based on cells, molecular agents and TE discs are being developed. For two of these regenerative treatment strategies, explain how the three causes of IVD degeneration could be addressed. If they are not, explain how the cause might interact with the cause to make things better or worse.
- Cell; autologous cells would have same hereditary issues, thus allogenic or genetically modified cells should be used. Although pathogenetic spinal loading would continue, renewed tissue would alter mechanobiological signal transduction possibly making them less gegenerative. Addition of more cells would create more nutritional demand > possibly making nutrient & metabolite transport even more degenerative.
Molecular agents; cells would continue to produce genetically inferior (‘minder’) product, but this may be overcome by concentration increases. Although pathogenetic spinal loading would continue, renewed tissue would alter mechanobiological signal transduction possibly making them less degenerative. Stimulating the cells to be more metabolic active or to proliferate would create more nutritional demand > transport even more degenerative.
TE; allogenic or genetically modified cells should be used. Although pathogenetic spinal loading would continue, a new IVD would alter mechanobiology signal transduction possibly making them less degenerative. As most IVDs also replace the CEP/BEP and have more permeable NP and AF, nutritional supply would be resolved. However, care must be taken to make sure that perfusion of the CEP/BEP is quickly re-established upon TE IVD implantation.
Developmentally the IVD of humans is different to that in mice and rats. What is different? A. Source of germ layer. B. Adult NP cell phenotype. C. Cartilaginous endplate. D. Endplate vascularization. E. Apophyseal growth plate.
E
No physis (growthplate), instead CEP undergoes endochondral ossification for vertebral growth.
The AF is composed of collagen rich lamellae. Although interlamellar cross-bridges restrict interlamellar sliding, there is considerable sliding under load.
Elastin ensures return of lamellae to their original positions when unloaded, but what structural characteristics make this possible under different load directions?
A. The globular configuration of elastin.
B. The crisscross pattern of elastin fibers between lamellae.
C. Elastin in the cross-bridges.
D. A & B.
E. A, B & C.
E
Cells in the IVD are sensitive to their physicochemical environment.
What characteristics of the mechanical load are the cells sensitive to? Is increase better of worse?
A. Magnitude
B. Duration
C. Frequency
D. Tonicity
E. All of the above
E, an increase in all the characteristics is worse.
Except for: tonicity (is defined as the ability of a solution surrounding a cell to cause that cell to gain or lose water. Some loss in osmotic pressure, not complete decompression). Decrease is worse.
Cells in the IVD are sensitive to their physicochemical environment. Contract the sensitivity of the cells to each type? A. Magnitude > duration B. Duration > magnitude C. Frequency < magnitude D. Tonicity > all E. None of the above
B
Remember the good, the bad & the ugly:
- The good: normal loads, activity of daily living, healthy.
- The bad: increase in duration & increase in frequency, more detrimental than increase in magnitude.
- The ugly: traumatic decompression and static loading, promote disc degeneration.
What types of events cause the most severe degenerative changes to the IVD? A. Static loading B. NP decompression C. Hypoxia D. A & B E. None of the above
D: static loading & NP decompression
C: no, because low O2 is actually better
What characteristics of the chemical environment are IVD cells sensitive to?
Oxygen, glucose, & lactate.
Endplate: high O2 & glucose, low lactate.
NP: low O2 & glucose, high lactate.
Endplate: high O2 & glucose, low lactate.
What are typical levels of each at the center of the disc? (And how does this compare to well vascularized areas in the body?)
[glucose]= ? mM
[O2]= ? %
pH= ?
[glucose]= 0.5 mM (7.8 mM) [O2]= <2% (5-21%) pH= 6.2-7.2 (7.4)
To what chemical milieu factor or combination of factors is the IVD cell most sensitive to?
A. Oxygen tension
B. [glucose] > 5 umol/L
C. pH
B
- [Glucose] critical to maintain viable cells: > 0.05 umol/L.
- But low pH from lactic acid accumulation also compromises cell viability.
We are taller when we wake up from a night of sleep and shorter at the end of an active day. Why?
A. Viscoelasticity of the collagen in the AF
B. Fluid flow out of the disc
C. Poor posture
D. Muscle fatigue
How much is the loss in height for each disc?
B
10% change in height.
20% in volume.
Which of these are known to cause secondary OA? A. Collagen XI SNP B. Joint dysplasia C. Cartilage contusion D. A & B E. B & C
E: joint dysplasia & cartilage cintusion
Collagen XI SNP: primary
What is NOT a consequence of cartilage overloading? A. Softening B. Chondrocyte death C. Fissures D. Blistering E. Tidemark migration
E
What differentiates between IVD ageing and IVD degeneration?
A. Decreased [PG] in the NP
B. Structural damage to the AF
C. Increased glycation cross-linking of collagen
D. Increased collagen turnover
E. B and D
E: structural damage to AF and increased collagen turnover.
Ageing= biological process of matrix degradation.
Similarities IVD degeneration & ageing, but in IVDD; aberrant, cell-mediated response to progressive structural failure.
Degenerated IVD= structural failure + accelerated ageing.
DDD= IVDD + pain.
What is NOT a hallmark indicator of IVD degeneration?
A. Vertebral osteophytes
B. Increased [PG] in IAF
C. Decreased NP signal intensity of T2 MRI
D. Disc hernia
E. Irregular stress profile in AF
B
What is NOT a major factor in the etiology/pathogenesis of DDD?
A. Genetics
B. Autoimmune reaction
C. Mechanical stimulation
D. Cellular nutrition
For the other 3 give an example of a risk factor.
A. Genetics –> some genotypes have an odds ratio
B. Autoimmune reaction –> NO
C. Mechanical stimulation –> increase in duration and frequency (“the bad”)
D. Cellular stimulation –> disc degeneration associated w/ conditions induce decreased nutrient supply (e.g. abdominal aorta atherosclerosis, capillary blockage from thrombophilia and hypofibrinolytic disorders, smoking)
Structural failure of the AF, i.e. tearing, is an important pain mechanism in DDD. This mechanism is:
A. Chemical
B. Mechanical
C. Combined
C
Like most tissues, the IVD is also populated with stem cells. What is the distinguishing cell marker(s) for these cells? A. Tie2 B. CD34 C. GD2 D. CD45 E. A & C
B. IVD progenitor cell: CD34
IVD specific progenitor cells:
Tie2= tyrosine-protein kinase receptor
GD2= ganglioside
Why are cells difficult to use for IVD regeneration?
A. They can proliferate but not indefinitely
B. They dedifferentiate during proliferation
C. They are not truly multi-potent
D. They decrease in number with age and degeneration
D
TE IVDs have been implanted in animal models. the cells used in these TE IVDs have differed. Which cell strategy has worked the best so far? A. Only NP cells B. Only AF cells C. Only MSCs D. NP and AF cells
D
