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Intestine, Kidney, Bone and Dialysis: Determinants of ECF Ca Content

Intestine, Kidney, Bone and Dialysis: Determinants of ECF Ca Content. Reference: Bushinsky DA. Contribution of intestine, bone, kidney, and dialysis to extracellular fluid calcium content. Clin J Am Soc Nephrol. 2010;5:S12–S22. Introduction.

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Intestine, Kidney, Bone and Dialysis: Determinants of ECF Ca Content

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  1. Intestine, Kidney, Bone and Dialysis: Determinants of ECF Ca Content Reference: Bushinsky DA. Contribution of intestine, bone, kidney, and dialysis to extracellular fluid calcium content. Clin J Am Soc Nephrol. 2010;5:S12–S22.

  2. Introduction • The concept of calcium (Ca) balance, net calcium intake and output from the body over a period of time, overlooks the phenomenon of Ca redistribution which is often observed as soft tissue and/or vascular calcification in patients with chronic kidney disease (CKD), especially those on dialysis. • Extracellular fluid (ECF), more specifically the plasma water, facilitate channels to connect gastrointestinal tract, kidney and bone. • The daily Ca fluxes between these organs often exceed the total ECF Ca. In order to maintain optimal cellular functions, the ECF Ca concentration must be relatively constant.

  3. Introduction • Intestinal Ca absorption, bone resorption and Ca influx from dialysis procedures often contributes to the net Ca input to the ECF. • Hence, this Ca deposits at extraosseous sites such as soft tissue or vessels. • Various hormones and other factors like the amount of unmineralized collagen; influence the level of blood Ca level, especially the biologically active ionized Ca concentration to provide optimal cellular function. • Also, the blood Ca concentration increases only when the Ca movement into the ECF from intestine and/or bone exceeds the rate of Ca deposition at the other ECF sites. • Hence blood Ca concentration is not an informative tool to determine the Ca movement in and out of the ECF.

  4. Ca Content in the ECF • At a constant ECF volume, the difference between continual input and output of Ca in ECF determines the change in ECF Ca content (see Equation 1). The change in ECF content will be positive when Ca input exceeds Ca output and vice versa. • When considering ECF Ca content, in addition to the plasma water, other ECF compartments like interstitial, transcellular, bone and connective tissue fluids should also be considered. • But the equilibrium of Ca between these ECF compartments, especially bone fluids, is not well understood. • There is a vast difference in the consequences of Ca deposition in bone and in soft tissues such as the vasculation.

  5. Calcium Input • The kidney reabsorbs only filtered Ca. • Thus, bone mineral resorption and intestinal Ca absorption contributes to net Ca input into the ECF in people with normal renal function (see Fig 1). Calcium absorption occurs in all segments of small intestine via paracellular diffusion and active transport. 1,25-dihydroxycholecalciferol [1,25(OH)2D3] regulates the active transport. 1,25(OH)2D3 appears to stimulate active transport of Ca in all segments of small intestine and duodenum, jejunum and ileum demonstrates absorption as well as secretion of Ca. • But absolute net Ca transport in the colon is limited. AlfaCa reflects the overall net Ca absorption and reabsorption of any Ca secreted into the intestine (see Equation 2). • Consumption of extremely low Ca diet, little Ca intake, loss of secreted intestinal Ca in feces may demonstrate negative αCa. • During dialysis procedure the dialysis bath Ca concentration may exceed that of blood ionized and Ca can enter the ECF through this procedure.

  6. Calcium Output • Any combination of the bone formation, renal Ca excretion or sweat may contribute to Ca output from ECF in patients with normal renal function. • Ca loss in the milk of lactating women is also large. • Ca loss from ECF into the dialysate has also been appreciated in patients who are on dialysis; having residual renal function with some loss of urinary Ca. • The net efflux of Ca from bone mineral is denoted by JBCa (see Equation 3) and consists of the combination of a net cellular Ca flux and net physiochemical Ca flux. Efflux of Ca from bone into the ECF is represented by a positive JBCa and influx of Ca from the ECF into the bone yields negative JBCa. • The bone mineral contains a major proportion of body Ca. Similarly, during dialysis procedure, efflux of Ca from dialysate into the ECF yields positive JDialysisCa and vice versa.

  7. Calcium Concentration Regulation • Caion regulation is essential for maintaining cellular metabolic processes (see Table 1). The ECF transports a large quantity of Ca between gastrointestinal tract (GIT), kidney and bone.

  8. Sites Gastrointestinal Tract • GIT is the only route for net Ca influx in patients who are not on dialysis but intestine is a poor site for control of Caion. • 1,25(OH)2D3, synthesized de novo in response to parathyroid hormone (PTH) or decrease in phosphorus; fibroblast growth factor-23 (FGF-23) or ionized Ca, regulates the component of Ca absorption.

  9. Sites Kidney • Large effects on Caion are appreciated with small changes in renal tubular reabsorption. • But it is evident from two clinical examples, CKD and pseudohypoparathyroidism, that solely kidney cannot control these levels. • Caion is well-regulated even in later stages of CKD and during dialysis. • Similarly, renal absorption of Ca seems to be normal or slightly impaired during hypocalcemia of pseudohypoparathyroidism where ECFCa level is maintained below normal.

  10. Sites Bone • Results of experiments with cultured bone have shown that movement of Ca from ECF onto an early phase of resident mineral is a consequence of increase in Caion. • Thus the bone mineral lessens or “buffer” the changes in Caion. • Hormonal alterations in cell-mediated bone resorption and formation also mediate Ca regulation.

  11. Time • Rapid alterations in Caion occur with physicochemical • response of the bone mineral. • These changes subsequently affect renal tubular reabsorption and cell-mediated bone resorption as a consequence of filtered Ca load alteration and PTH changes. Gastrointestinal Ca absorption and cellmediated bone formation and resorption are finally altered by changes in the levels of 1,25(OH)2D3.

  12. Clinical Situations • For a 70-kg normal adult who ingests a diet adequate in Ca during the course of a day, there is no appreciable net bone formation or resorption. • Ca input from GIT is balanced by Ca output through urinary excretion and sweat. • Hence, no net change in ECF Ca content.

  13. The regulatory parameters change in different clinical situations. • In CKD patients who are on dialysis, Ca flux is a function of diffusion and convection. • While 0.75-mM and 1.75-nM Ca bath suggests Ca output and Ca input to ECF from dialysis procedure respectively, the net Ca flux is relatively little with 1.25-mM Ca bath. • Dialysate Ca concentration is crucial because higher dialysate Ca concentration increase Caion and suppress PTH and vice versa. • Further, the Ca out from ECF during dialysis is directly related to the number of liters of ultrafiltration times the ECFCa. • It was also observed that the intestinal Ca absorption of 19% in patients on dialysis increases to 25% on administration of activated vitamin D. • However, such increase with dietary Ca intake and activated vitamin D administration were not evident in patients who were not on dialysis.

  14. Model of ΔECFCa during a 1-Week Period • In patients on dialysis, data on movement of Ca between the intestine, bone and kidney are almost not available. • Hence, to model ΔECFCa for these patients several assumptions were made and the ΔECFCa was plotted as a function of Ca intake on the basis of these assumptions (see Fig. 2). • This analysis suggested that positive ΔECFCa is obtained in patients who consume >37.5 mmol of elemental Ca which increases further with addition of activated vitamin D. • Hence, this Ca is deposited in either osseous or extraosseous sites like soft tissue; which is often seen in patients on dialysis. • Coronary calcification is often associated with cardiovascular deaths in many dialysis patients.

  15. However, no vascular calcification occurs without Ca to complex with phosphate. • Hence, a nephrologist must be aware of the amount of Ca absorbed (especially in patients receiving activated vitamin D) and the potential site of Ca deposition, prior to advising addition dietary Ca in the form of phosphate binders to the patients.

  16. Comprehensive Basketin Anemia Management

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