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Factors influencing renal ammonium excretion in man, particularly in relation to urinary pH

Thomason, Margaret Jean; (1993) Factors influencing renal ammonium excretion in man, particularly in relation to urinary pH. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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The excretion of ammonium (NH4+) by the kidney is regulated by a variety of factors which fall into two main categories; those which affect renal ammoniagenesis and those which affect renal ammonia transport from the tubular cell to the urine. The aim of this work was to investigate, in man, the principal influences regulating these two control mechanisms, along with any consequent alteration in the relationship between NH4+ excretion rate and urinary pH. A linear relationship of log NH44+ excretion rate against urine pH, with a slope of approximately -0.3, was found in all studies of normal subjects experiencing spontaneous changes in urine pH, or submitted to minor acute systemic acid-base changes. This relationship was then compared to that found during chronic acidosis and chronic alkali loading, administration of glutamine substrate, administration of a mineralocorticoid and its suppression, water diuresis and osmotic diuresis, and administration of different pharmacological diuretics. It was discovered that, in all these circumstances, whether the NH4+ excretion rate increased, decreased or remained the same, the negative correlation with slope -0.3 persisted. Chronic acidosis increased NH4+ excretion rate more than could be explained simply by a low urine pH facilitating diffusion trapping, and conversely long term alkali loading reduced NH4+ excretion rate in relation to urine pH. An adaptive change in the ammonia- generating metabolic pathway may have been induced. Increasing the availability of glutamine substrate substantially enhanced the rate of NH4+ excretion in relation to urine pH, indicating that substrate transport into the renal proximal tubular cell may be a factor rate-limiting to ammoniagenesis. The administration or suppression of a mineralocorticoid, whilst the subject remained normokalaemic, produced no change in the relationship between NH4+ excretion rate and urinary pH, implying that potassium availability is the more important factor controlling renal NH4+ excretion. Both water and osmotic diuresis substantially augmented the rate of NH4+ excretion, possibly by enhancing the concentration gradient for NH4+ diffusion into the collecting duct. Osmotic diuresis gave rise to a greater increase in NH4+ excretion rate than did water diuresis. It is suggested that this was due to the production of a steep concentration gradient for NH4+ secretion into the proximal tubule. The administration of both thiazide and loop diuretics reduced the rate of urinary NH4+ excretion in relation to pH, an effect which may have been caused by the inhibition of potassium-linked mechanisms which can also transport NH4+. Administration of a potassium-sparing diuretic had no effect on NH4+ excretion rate. Overall the constancy of the negative slope in the relationship between NH4+ excretion rate and urine pH indicates that the mechanism of diffusion trapping is a consistent factor in renal ammonium excretion. Also important in determining the rate of excretion are ammoniagenesis in the proximal tubule and factors influencing ammonia movements in and out of the tubule.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Factors influencing renal ammonium excretion in man, particularly in relation to urinary pH
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Ammonium excretion
URI: https://discovery.ucl.ac.uk/id/eprint/10105859
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