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Title: Interactions between the gastrointestinal tract, kidney, and the liver in the regulation of body phosphate balance
Author: Lee, G. J.
ISNI:       0000 0004 5351 8030
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2014
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Inorganic phosphate (Pi) is an essential element that fuels vital processes in the body. To date, there is discord regarding the mechanisms of Pi regulation and the proportion of transport attributed to active (sodium-driven), paracellular, or uncharacterized transcellular pathways. The present studies address this by comparing Pi transport in different segments of the intestine using in vitro, in situ, and ex vivo techniques. Potential Pi signalling between the intestine, kidney, and liver was also investigated using intestinal perfusion and in vivo renal clearance surgeries. Regional differences in intestinal Pi transport were investigated using the in situ closed-loop, in vitro everted sleeve, and ex vivo intestinal perfusion techniques. These studies highlighted measured Pi transport discrepancies between methods, confirmed the jejunum as the site of highest Pi transport ability in the GI tract, and also revealed that the distal colon transported a significant amount of Pi both in vitro and in situ. An intestinal perfusion technique never applied to studies of Pi transport also exposed a concentrated amount of Pi transported directly across the rat intestinal epithelium. Renal Pi clearance surgeries investigated a proposed Pi sensing mechanism between the small intestine and the kidney in which a high duodenal Pi load triggered rapid phosphaturia. Present data show no phosphaturia after a physiological 10mM Pi duodenal instillation. In contrast with previously published data, a high Pi load into the duodenum increased plasma Pi and parathyroid hormone (PTH) levels resulting in correlated phosphaturia. The role of the liver in Pi transport was investigated by removing the liver following instillation of 1, 5, 10, and 15mM 32P coupled Pi buffer into the jejunum. Data show a steady increase of Pi accumulated in the liver, which correlated with increased Pi concentration instilled into the jejunum. Between 10 and 15mM however, the Pi in the liver reached saturation, suggesting that the liver may only store physiological concentrations of Pi. Sodium-dependency of Pi uptake by the liver was also not apparent until 15mM Pi, in contrast with sodium-dependent Pi transport by the intestine at all four concentrations. This finding suggests a separate mechanism of liver Pi transport at this supraphysiological Pi concentration.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available