Metabolic Bone Disease (eBook)
464 Seiten
Elsevier Science (Verlag)
978-1-4832-1631-7 (ISBN)
Metabolic Bone Disease, Volume I covers the approach to a variety of disorders of mineral metabolism. The book discusses bone metabolism and calcium regulation; kidney function in calcium and phosphate metabolism; as well as the role of alkaline phosphatase in metabolic bone disorders. The text also describes the diagnostic value of bone biopsies; the etiology, clinical aspects, therapy, and the main syndromes of vitamin D deficiency, rickets, and osteomalacia; and the pathogenesis and therapy of osteoporosis. The pathogenesis and treatment of nephrolothiasis are also encompassed. Orthopedic doctors, physicians, endocrinologists, and people involved in the research of metabolic bone diseases will find the book invaluable.
Kidney Function in Calcium and Phosphate Metabolism
OLAV L.M. BIJVOET
Publisher Summary
This chapter discusses the kidney function in calcium and phosphate metabolism. Production of urine is the most conspicuous expression of kidney function but not the most significant always. The amount of phosphate excreted per day is equal to the amount of phosphate adsorbed from the diet. The average diet contains about 1500 mg phosphate per day, and the average 24-hour renal excretion of phosphate is about 600 mg. Variations in intake and urinary output are closely related. The most common cause of a low phosphate excretion rate is a phosphate-poor diet—such as low protein or low calcium diets—or administration of aluminum hydroxyde gels, which bind phosphate in the gut. Phosphate reabsorption is decreased in primary and secondary hyperparathyroidism and increased in hypoparathyroidism. A chronic high phosphate intake produces a steady state with reduced tubular reabsorption of phosphate, reduced calcium excretion, normocalcemia or slight hypocalcemia, increased immunoreactive parathyroid hormone serum level, and parathyroid hyperplasia. Chronic renal failure with decreased glomerular filtration rate is associated with bone disease.
A. The Elements of Renal Phosphate Transport
B. Renal Phosphate Transport as a Whole
C. Measurement of Phosphate Reabsorption
Production of urine is the most conspicuous expression of kidney function but not always the most significant. In 1844 Ludwig first proposed the theory of glomerular filtration and selective tubular reabsorption to explain the formation of urine; according to Cushny’s “modern theory” formulated in 1917, some substances are passively filtered in the renal glomeruli and actively reabsorbed through the walls of the renal tubules together with water at a rate required to produce an “optimal” concentration in the fluid reabsorbed into the extracellular fluid. In this manner, optimal concentrations of important solutes are maintained in the blood. The level of concentration in the reabsorbed fluid would then characterize renal function in respect to a given substance. With some modifications, this theory still describes renal handling of calcium and phosphate. It will be shown that variations in renal function will, in the steady state, be reflected in variations in plasma calcium or phosphate concentration, whereas variations in the excretion rate merely reflect corresponding variations in the net input of these substances into the extracellular fluid from sites other than the kidney, for instance, bone or gut. It is clear that the role of the kidney in extracellular calcium and phosphate homeostasis must be considered in relation to the physiology of other organs. But in order to provide a sufficient background for the understanding of the function of the kidney as an organ, the sections on phosphate and calcium will begin with a discussion of the sites and nature of renal tubular transport mechanisms within the kidney and the quantitative relationships between the filtration, reabsorption, and excretion of calcium and phosphate.
Other functions of the kidney related to calcium metabolism but not discussed in this chapter are the inactivation by the kidney of circulating parathyroid hormone, calcitonin, or 25-hydroxycholecalciferol and the formation of metabolically active metabolites from 25-hydroxycholecalciferol.
I RENAL PHOSPHATE TRANSPORT
A The Elements of Renal Phosphate Transport
The glomeruli produce an ultrafiltrate of serum. As this ultrafiltrate passes along the renal tubules, its composition is altered because specific substances are subtracted by reabsorption and added by tubular secretion. Three processes, therefore, determine the final composition of urine: ultrafiltration, tubular reabsorption, and tubular secretion.
1 Glomerular Filtration
Micropuncture studies in amphibians and rats, although beset by many technical difficulties, should provide a direct comparison of the simultaneous concentrations of phosphate in serum and in the glomerular filtrate. The results of many such studies seem to indicate that these concentrations do not differ. Walser (1961a) has pointed out that the phosphate concentrations in glomerular filtrate and in serum can only be equal when about 13% of the serum phosphate is not filterable. One reason is that in measuring serum phosphate concentrations, the volume occupied by proteins is not taken into account. In addition, the presence of serum proteins on only one side of the ultrafiltering membrane will induce an electrochemical gradient across the membrane, and, as a result, the distribution of ions along the two sides of the membrane will be unequal (the Donnan equilibrium). He further reviewed existing in vitro ultrafiltration studies of serum phosphate and found that many were unreliable because factors, such as pH, pCO2, or temperature, had not been taken into account. However the best available controlled studies and his own studies in man show that, whatever the absolute value of the serum phosphate concentration, the ultrafiltrates of serum have approximately the same phosphate concentration as the serum itself. On this basis, he reasoned that on the average 13% of the serum phosphate is protein-bound and nonfilterable (Walser, 1961a) (Table I). Therefore, it just so happens that, despite considerable protein binding, the phosphate concentration in glomerular filtrate equals the serum phosphate concentration [PO4 (w/v)]. This is true for a wide range of serum phosphate concentrations. The filterable fraction of phosphate does apparently not change when phosphate is infused to raise its concentration in the blood to 10 mg per 100 ml. However, rapid and marked elevations of calcium and phosphate levels can result in formation of nonfilterable colloidal complexes of calcium phosphate (McLean and Hinricks, 1938). The filtration rate of phosphate in the kidney (filtered load, LPO4 weight/time) can, therefore, be calculated as the product of serum phosphate concentration and glomerular filtration rate [G.F.R. (volume/time)] [Eq. (1)]
TABLE I
Concentrations of Phosphate in Normal Human Plasmaa
Phosphate | Concentration (mg/100 ml) | % Total |
Free HPO42− | 1.55 | 43 |
Free H2PO4− | 0.34 | 10 |
Protein bound | 0.43 | 12 |
NaHPO4− | 1.02 | 29 |
CaHPO4 | 0.12 | 3 |
MgHPO4 | 0.10 | 3 |
Total | 3.56 | 100 |
aReproduced from Walser (1961a).
(1)
Henceforth in this chapter the amount filtered per unit time will be designated as filtered load (LPO4) and defined as [PO4] × G.F.R. Moreover, the serum phosphate concentration [PO4] can be considered as equal to the amount of phosphate filtered per unit volume of glomerular filtrate [Eq. (2)].
(2)
2 Tubular Reabsorption and Secretion
Renal tubular handling of phosphate is still not completely understood. In man and in mammals the rate of phosphate excretion [UPO4V (weight/time)] is always less than the filtration rate. There is, therefore, a net reabsorption of phosphate. The net reabsorption rate [TPO4 (weight/time)] is defined as the difference between filtered load and excretion rate and can only be measured indirectly [Eq. (3)].
(3)
The occurrence of net phosphate reabsorption does not, however, preclude secretion of phosphate somewhere along the renal tubules, provided the reabsorption rate exceeds the secretion rate. Micropuncture studies in rats and dogs as well as stop-flow studies in dogs suggest a localization of phosphate reabsorption in the first part of the proximal tubules (Strickler et al., 1964; Malvin et al., 1958; Agus...
Erscheint lt. Verlag | 22.10.2013 |
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Sprache | englisch |
Themenwelt | Sachbuch/Ratgeber ► Gesundheit / Leben / Psychologie ► Krankheiten / Heilverfahren |
Medizin / Pharmazie ► Medizinische Fachgebiete | |
ISBN-10 | 1-4832-1631-4 / 1483216314 |
ISBN-13 | 978-1-4832-1631-7 / 9781483216317 |
Informationen gemäß Produktsicherheitsverordnung (GPSR) | |
Haben Sie eine Frage zum Produkt? |
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