The relationship between bone mineral and its ions in extracellular fluid

MacGregor, James (1962) The relationship between bone mineral and its ions in extracellular fluid. PhD thesis, University of Glasgow.

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It is generally believed that the mineral portion of the skeleton cannot have a thermodynamic solubility product because of the complex and variable nature of the bone salt. This opinion is examined in the light of our present understanding of bone salt composition and of previous investigations into bone salt solubility. A simple experimental technique is described for studying the relationship between powdered whole bone and the concentrations of the ions of bone salt in solutions. It is shown that in bicarbonate-free buffer, bone powder establishes an ionic equilibrium in terms of the product [Ca++]3[PO4]2 within 24 hours. For human bone, the pK of the mean of this product is 26.39. Studies with synthetic ultrafiltrate of plasma suggest that there is a direct relationship between the carbonate and phosphate concentrations in solutions in equilibrium with bone salt. In experiments using tris buffer with added bicarbonate, the bone salt yields constant calcium phosphate products within 72 hours, the pK of the mean being 26.30. It has not been possible to demonstrate any calcium carbonate ion product even when very high solid: solution ratios of about 500 gm bone per litre buffer are employed, but a direct relationship between the carbonate and phosphate concentrations in solution is apparent. Equilibration studies with bone powder in normal serum suggest that the equilibrium could be operative in vivo provided the recently proposed views of Walser are accepted. Walser maintains that only about 53% of the total serum inorganic phosphate is in the non-associated 'free' form. With this assumption our experiment indicate that the ion product [Ca++]3[PO4]2 in serum is not significantly different from that in synthetic media, the pK of the mean being 26.17. Accepting Walser's views, which are indirectly confirmed by our experiments, it is then shown that bone mineral by a purely physico-chemical process, can maintain the concentrations of calcium and phosphate found in normal human extracellular fluids in vivo, provided the pH at the phase boundry is about 7.1. This value is roughly mid-way between intracellular and extracellular pH. Brief studies with bone powder of children and several animal species suggest that there is a relationship between plasma phosphate levels in vivo, equilibrium phosphate concentrations with bone powder in vitro and the carbonate content of the bone. It is suggested that the high plasma phosphate concentrations in children may be due in part to the low carbonate content of young immature bone mineral. A series of equilibration studies with bone from different sites in the same skeletons has yielded evidence which is compatible with the view that bone mineral behaves essentially as a calcium phosphate salt with divalent carbonate ion substitution for trivalent phosphate ion at the surfaces of the apatitic crystals. The evidence obtained is in conflict with the two other principal theories, namely that bone salt is a stoichiometric-carbonate-apatite, and alternatively that it is a two-phase system of calcium phosphate and calcium carbonate. There are two principal biological implications of these studies. Firstly, calcium homeostasis can be explained in terms of a physico-chemical equilibrium state between the mineral of the skeleton and its ions in extracellular fluids. Secondly, slight variation in the pH of the bone environment lead primarily to changes in plasma calcium concentration, total inorganic phosphate concentration being a function of the bicarbonate concentration. It is suggested that parathyroid hormone controls plasma calcium concentration by an effect on cellular metabolism which results in variation in the pH of the tissue fluid at the surface of the bone crystals.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: E J Wayne
Keywords: Medicine
Date of Award: 1962
Depositing User: Enlighten Team
Unique ID: glathesis:1962-73750
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jun 2019 08:56
Last Modified: 14 Jun 2019 08:56

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