04/06/2023
Nutrition supply to intervertebral discs 📌
👉 Maintaining an optimal nutrient-metabolite milieu for the survival and function of disc cells is a particular problem for intervertebral discs, which comprise the largest avascular tissue in the body. https://pubmed.ncbi.nlm.nih.gov/21944584/
👉 Although the cells of the outer annulus fibrosus receive their nutrients (and eliminate their metabolites) from capillaries in the soft tissues surrounding the disc, the only contact with the blood supply for most of the remaining cells within the disc is via capillaries that arise in the vertebral bodies, pe*****te the subchondral plate through the bone marrow spaces, and terminate in loops adjacent to the cartilaginous endplate (Figure 1a). https://pubmed.ncbi.nlm.nih.gov/2922637/
👉 Nutrients move mainly by diffusion (from the capillaries through the cartilaginous endplate and dense disc matrix to the cells of the disc; metabolites move in the opposite direction. The resulting concentration gradients are therefore determined by the difference between the rates of nutrient supply and consumption by the cells (Figure 1b). https://pubmed.ncbi.nlm.nih.gov/7127960/
👉 Consequently, the concentrations of glucose, oxygen and other nutrients are lowest in the center of the disc. The metabolism of cells in the nucleus is very sensitive to changes in pH. They are maximally active in pH ranges of 6.9–7.2, but below 6.8 their activity falls steeply. Below 6.3 their activity is only about 15% maximum. https://pubmed.ncbi.nlm.nih.gov/1411761/
👉 Therefore, factors that negatively affect nutrient concentration also limit the number of cells that can be maintained in this avascular tissue. https://pubmed.ncbi.nlm.nih.gov/23311982/, https://pubmed.ncbi.nlm.nih.gov/11725234/
👉 The balance between nutrient supply and nutrient consumption is precarious, and if either parameter is disturbed, the concentration of nutrients and the pH level (as a consequence of metabolite accumulation) in the discs can decrease to levels that adversely affect cellular activity and even cell viability. https://pubmed.ncbi.nlm.nih.gov/2138156/, https://pubmed.ncbi.nlm.nih.gov/24503692/, https://pubmed.ncbi.nlm.nih.gov/23283636/, https://pubmed.ncbi.nlm.nih.gov/11172169/
👉 A decrease in nutrients and oxygen supply to the disc due to loss of end plate permeability as a consequence of….
1⃣ impaired vertebral blood supply, (i.e. through atherosclerosis of the arteries that feed the lumbar spine associated with disc degeneration)
2⃣ impaired endplate blood supply (i.e. through endplate sclerosis, Modic changes, Schmorl’s nodes, etc.)
3⃣ increased cellular demand (i.e. resulting from a higher cell density or a rise in the rate of nutrient consumption per cell, making it difficult for the disc to maintain its matrix and cell turnover)
leads to degeneration and cellular apoptosis. https://pubmed.ncbi.nlm.nih.gov/18211591/
👉 With maturation, proteoglycans and aggrecan molecules are degraded, resulting in loss of glycosaminoglycans and decreased osmotic pressure. This affects the load-bearing function of the disc, resulting in loss of disc height and bulging of nuclear contents posteriorly through the thinning or torn annulus and the relatively weak posterior longitudinal ligament. https://pubmed.ncbi.nlm.nih.gov/23537454/, https://pubmed.ncbi.nlm.nih.gov/28546769/
Figure: https://www.nature.com/articles/nrrheum.2014.91
Pathways of nutrient supply in a normal intervertebral disc.
a | Cells of the avascular disc nucleus pulposus and inner annulus fibrosus are supplied by vertebral blood vessels. Capillaries pe*****te the subchondral plate through marrow spaces and terminate in loops at the junction of the subchondral plate and cartilaginous endplate. Nutrients (e.g. oxygen and glucose) diffuse from the capillary bed through the cartilaginous endplate under gradients arising from metabolic demands of disc cells, while metabolic wastes (e.g. lactic acid) diffuse in the reverse direction. Cells of the outer annulus fibrosus are supplied by capillaries from blood vessels in the surrounding soft tissues that pe*****te a few millimetres into the disc.
b | The centre of the disc has the lowest levels of nutrients and highest concentration of metabolites.
c | Schematic showing normalized concentration gradients of glucose, oxygen and lactic acid across the nucleus, endplate–endplate. Nutrient concentrations must remain above the critical levels to maintain cell viability and activity.
