Non-natriuretic doses of furosemide: potential use for decreasing the workload of the renal outer medulla with minimal magnesium wasting in the rat.

Background/aims: Since furosemide (FS) inhibits active Na(+) reabsorption by medullary thick ascending limb (mTAL) in the renal outer medulla, it may decrease its work during periods of low O2 supply to deep in the renal outer medulla. This study was designed to demonstrate that there may be a dose of FS would reduce its metabolic work while preventing the excessive loss of magnesium (Mg(2+)). Mg(2+) is important because the ATP needed to perform work must have bound Mg(2+) to it.

Response of the renal inner medulla to hypoxia: possible defense mechanisms.

Background/aims: Owing to the precarious blood supply to the renal medulla and the high metabolic requirement of the medullary thick ascending limb of Henle's loop, this nephron segment should be especially vulnerable when its supply of O(2) declines.

Methods: Rats were exposed to 8 or 21% O(2) at different time points up to 5 h, and samples were collected for urine flow rate, urine (U(osm)) and renal papillary (RP(osm)) osmolality, urinary excretion of Na(+), Cl(-), K(+) and Mg(2+), blood gases, erythropoietin and vasopressinase activity in plasma. Other groups of rats were pretreated with desmopressin acetate (dDAVP) or underwent bilateral nephrectomy (BNX) 1 h prior to the exposure.

Is there escape from renal actions of vasopressin in rats with a hyponatremia for greater than 48 hours?

Escape from the renal actions of vasopressin is said to occur in rats with chronic hyponatremia. Our objective was to provide specific evidence to test this hypothesis. Hence the osmolality in the excised renal papilla and in simultaneously voided urine (U(Osm)) was measured in rats with and without hyponatremia.

Importance of Residual Water Permeability on the Excretion of Water during Water Diuresis in Rats.

When the concentration of sodium (Na(+)) in arterial plasma (P(Na)) declines sufficiently to inhibit the release of vasopressin, water will be excreted promptly when the vast majority of aquaporin 2 water channels (AQP2) have been removed from luminal membranes of late distal nephron segments. In this setting, the volume of filtrate delivered distally sets the upper limit on the magnitude of the water diuresis. Since there is an unknown volume of water reabsorbed in the late distal nephron, our objective was to provide a quantitative assessment of this parameter.

Properties permitting the renal cortex to be the oxygen sensor for the release of erythropoietin: clinical implications.

The PO2 at this site where erythropoietin release is regulated should vary only when the hemoglobin concentration changes in capillary blood. The kidney cortex is an ideal location for this O2 sensor for four reasons. First, it extracts a small proportion of the oxygen that is delivered in each liter of blood; this makes the PO2 signal easier to recognize.

Physiology of acid-base balance: links with kidney stone prevention.

Two processes permit the urine pH and the medullary interstitial pH to remain in an "ideal range" to minimize the risk of forming kidney stones. First, a medullary shunt for NH(3) maintains the urine pH near 6.0 to minimize uric acid precipitation when distal H(+) secretion is high.

Studies to identify the basis for an alkaline urine pH in patients with calcium hydrogen phosphate kidney stones.

Background: Patients with CaHPO(4) kidney stones belong to a diagnostic category that has a high urine pH as its common feature. Our objective was to provide a new clinical approach to examine the basis for this high pH.

Methods: The study group consisted of 26 CaHPO(4) stone formers and 28 normal volunteers.

Control of potassium excretion: a Paleolithic perspective.

Purpose Of Review: Regulation of potassium (K) excretion was examined in an experimental setting that reflects the dietary conditions for humans in Paleolithic times (high, episodic intake of K with organic anions; low intake of NaCl), because this is when major control mechanisms were likely to have developed.

Recent Findings: The major control of K secretion in this setting is to regulate the number of luminal K channels in the cortical collecting duct. Following a KCl load, the K concentration in the medullary interstitial compartment rose; the likely source of this medullary K was its absorption by the H/K-ATPase in the inner medullary collecting duct.

Requirements for a high rate of potassium excretion in rats consuming a low electrolyte diet.

Control mechanisms for potassium (K(+)) excretion in humans developed in Palaeolithic times when diets were sodium poor and episodically K(+) rich. Nevertheless, our understanding of the regulation of K(+) excretion comes from experiments in rats with large sodium and K(+) intakes. Our objective was to identify how K(+) excretion was regulated when rats consumed a low NaCl diet to reflect Palaeolithic conditions.

Defining conditions that lead to the retention of water: the importance of the arterial sodium concentration.

Background: A water diuresis occurs when a large volume of water is ingested rapidly. Nevertheless, water conservation is required to provide a source of water for evaporative heat dissipation throughout the day. Therefore, the objective was to define conditions that permit the retention of ingested water.

Dogmas and controversies in the handling of nitrogenous wastes: excretion of nitrogenous wastes in human subjects.

Two major nitrogenous waste products, urea and ammonium (NH(4)(+)), are produced in humans when proteins are oxidized, and in this manuscript their excretions are examined from two perspectives. First, the specific physiology of each nitrogenous waste is reviewed and the current dogmas summarized. Second, their excretions are considered in the context of integrative physiology, i.

Facilitating an understanding of integrative physiology: emphasis on the composition of body fluid compartments.

As a teaching exercise, we used deductive reasoning and a quantitative analysis to convert a number of facts into a series of concepts to facilitate an understanding of integrative physiology and shed light on the composition of the different body fluid compartments. The starting point was the central need to regenerate ATP to perform biologic work. Because a large quantity of O2 must be delivered to cells at a sufficiently high concentration to aid its diffusion into mitochondria, approximately one third of the O2 in inspired air was extracted; this led to a P(CO2) in arterial blood of 40 mmHg (1 mmHg = 133.

Effect of fasting for two days on the excretion of ammonium in dogs with chronic metabolic acidosis.

Background: The source of glutamine for renal ammonium production is ultimately dietary protein in the fed state and body proteins in fasting.

Objective: Our objective was to determine if less NH(+)(4) would be excreted by fasted dogs with chronic metabolic acidosis resulting in conservation of lean body mass.

Methods: Acid-loaded fed and fasted dogs were given 10 mmol NH(4)Cl/kg for 5 days; the fasted group had food withheld on days 4 and 5.

Influence of hypernatraemia and urea excretion on the ability to excrete a maximally hypertonic urine in the rat.

Rats normally excrete 20-25 mmol of sodium (Na+) + potassium (K+) per kilogram per day. To minimize the need for a large water intake, they must excrete urine with a very high electrolyte concentration (tonicity). Our objective was to evaluate two potential factors that could influence the maximum urine tonicity, hypernatraemia and the rate of urea excretion.

Mechanisms used to dispose of progressively increasing alkali load in rats.

Our objective was to describe the process of alkali disposal in rats. Balance studies were performed while incremental loads of alkali were given to rats fed a low-alkali diet or their usual alkaline ash diet. Control groups received equimolar NaCl or KCl.

Hypercalcaemia and metabolic alkalosis with betel nut chewing: emphasis on its integrative pathophysiology.

Background: Events in the gastrointestinal tract that might contribute to a high absorption of calcium were simulated in vitro to evaluate why only a small proportion of individuals who ingest alkaline calcium salts develop hypercalcaemia, hypokalaemia and metabolic alkalosis.

Methods: A patient who chewed and swallowed around 40 betel nuts daily developed hypercalcaemia, metabolic alkalosis, hypokalaemia with renal potassium wasting, and renal insufficiency. The quantities of calcium and alkali per betel nut preparation were measured.

Studies on the pathophysiology of the low urine pH in patients with uric acid stones.

Background: A very low urine pH is the major risk factor for uric acid stone formation.

Methods: A subgroup of patients with a history of uric acid stones and a persistently low urine pH (<5.5 for at least 12 h/day) were selected for detailed study.