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Biomedical subjects

B J Stinebaugh

Publications and source records attributed to B J Stinebaugh.

At least 37 records · Page 2Linked to original sources
PubMed1978

Treatment of hypoparathyroid patients with chlorthalidone.

In an effort to maintain normal serum calcium levels without inducing hypercalciuria, we treated seven hypoparathyroid patients for up to 25 months with chlorthalidone, a thiazide-like sulfonamide diuretic, plus a salt-restricted diet, without added vitamin D. Mean 24-hour calcium excretion decreased from 179 to 88 mg (P less than 0.001), and mean serum calcium increased from 8.2 to 9.3 mg per deciliter (P less than 0.05). Diuretic therapy or moderate salt restriction alone was not as effective as combined therapy. Beneficial effects were sustained for as long as therapy was maintained. The rise in serum calcium, which involves the filterable and ionized fractions, cannot be due entirely to reduced excretion and may in part be explained by increased intestinal absorption. Oral chlorthalidone plus a low salt diet appears to be an effective alternative to vitamin D in the maintenance therapy of at least some patients with hypoparathyroidism.

Administration, Oral↗
PubMed1978

Disequilibrium pH and bicarbonate reabsorption: relevance to the pathogenesis of distal renal tubular acidosis.

An augmented renal capacity to reabsorb bicarbonate (RHCO3) has been noted in patients with distal renal tubular acidosis (dRTA), and construed as evidence that the basic defect in dRTA is abnormal distal tubular permeability. According to this interpretation, the absence of a disequilibrium pH due to a back-leak of H2C03 permits increased distal H+ secretion and results in an increased RHCO3. To test this assumption, we have evaluated the effect of acute elimination of the disequilibrium pH by carbonic anhydrase infusion. The results establish that this maneuver doses not cause a rise in RHCO3. Thus, the elevated value of RHC3 described in dRTA cannot be the consequence of increased back-diffusion of H2CO3 and is more likely due to coexisting extracellular volume depletion and/or postassium deficiency.

Acidosis, Renal Tubular↗
PubMed1978

Collecting duct hydrogen ion secretion in the rabbit: role of potassium.

The purpose of this study was to investigate distal nephron hydrogen ion secretion in the intact animal. The rabbit was chosen as the experimental model because it produces acid urine containing little ammonium. Upon replacement of the usual rabbit diet with milk, plus administration of an acid load (10 mEq/kg), the urine pH fell consistently from very alkaline values (PH greater than 7.4) to 4.8 +/- 0.2. Despite the ability to achieve high urine-to-blood hydrogen ion concentration gradients, the U-B PCO2, an index of collecting duct hydrogen ion secretion, was virtually zero. In these studies, the urine bicarbonate and buffer concentration were comparable to those observed in dog, rat, and man in which a high U-B PCO2 gradient was achieved. The rabbits studied had low plasma potassium concentrations (less than 3 mEq/L). Since potassium deficiency has been implicated in impaired urine acidification, potassium was administered, and it resulted in an increase in collecting duct hydrogen ion secretion as evidenced by a further fall in minimum urine pH during acidemia and a prompt rise in the U-B PCO2 during alkali administration. In summary, rabbits had a very low but not absent rate of collecting duct hydrogen ion secretion. Potassium administration increased the rate of hydrogen ion secretion in a segment of the collecting duct in which hydrogen ion secretion is reflected by an increase U-B PCO2.

Acidosis↗
PubMed1977

Lack of dependence of urine PCO2 upon reduction of glomerular filtration rate in alkalotic dogs.

1. The PCO2 gradient between alkaline urine and arterial blood (U-B PCO2) is thought to depend primarily on distal hydrogen ion secretion. However, other variables affecting the U-B PCO2 include the urine flow rate, the urinary bicarbonate and phosphate excretion rates and the glomerular filtration rate. 2. In order to evaluate the effects of acute changes in these factors on the U-B PCO2, bicarbonate-loaded dogs with maximal U-B PCO2 values were subjected to either acute unilateral elevations of ureteral pressure or hypotension caused by nitroprusside infusion. The results demonstrate that acute reduction in the glomerular filtration rate does not cause a decrease in the U-B PCO2 as long as the urinary concentrations of phosphate and bicarbonate do not decline. 3. Urinary concentrations of phosphate and bicarbonate appeared more important than their excretion rates in the maintenance of elevated U-B PCO2 values.

Alkalosis↗
PubMed1977

Mechanism by which neutral phosphate infusion elevates urine PCO2.

Currently, the ability to elevate the urine PCO2 above that of the arterial blood is employed as an estimate of distal hydrogen ion secretion. Therefore, it is important to establish the mechanisms by which various factors affect the urine CO2 tension. This paper examines the physiologic process by which phosphate elevates the urine PCO2 in the dog. The rise in urine PCO2 due to phosphate could be the result of either (1) a distal mechanism, by affecting the delayed dehydration of carbonic acid, or (2) an increase in the medullary PCO2. The phosphate-induced elevation of urine PCO2 was abolished by carbonic anhydrase infusion. This indicates that a distal mechanism is a major factor in the phosphate effect. Since acid phosphate infusion did not result in an elevated urine PCO2, it is unlikely that changes in the medullary PCO2 occur as a ry an increase in net acid excretion, indicating an increase in hydrogen ion secretion. The increased hydrogen ion secretion and rise in urine PCO2 were reproduced by infusion of the buffer, Tris-(hydroxymethyl)-aminomethane, but not by sodium sulfate administration. These findings suggest that the phosphate-induced rise in urine PCO2 is due to the buffer properties of phosphate rather than to its nonreabsorable anion characteristics.

Animals↗
PubMed1977

Effect of amphotercin B on urine acidification in rats: implications for the pathogenesis of distal renal tubular acidosis.

It has been proposed that distal renal tubular acidosis is a gradient-limited disorder an that the low urine Pco2 observed in this condition is caused by back diffusion of carbonic acid. This study was designed to examine this hypothesis using the amphotericin B model of gradient-limited distal renal tubular acidosis in rats. After induction of acute metabolic acidosis the minimum urine pH in 12 of 24 amphotericin B-treated rats exceeded 5.63 (mean 5.76 +/- 0.04), whereas it was 5.41 +/-0.04 in control rats. These animals with impaired urine acidification were presumed to have a gradient lesion and were studied in bicarbonate-loading experiments. The urine minus blood Pco2 gradient in these rats was 24.9 +/- 1.5 mm. Hg, a value similar to that of the control rats (26.7 +/- 2.1 mm. Hg). The presence of a normal urine minus blood Pco2 value in this experimentally induced gradient-limited type of acidification lesion indicates that a permeability defect for hydrogen ions was not associated with a similar defect for carbonic acid and that the urine minus blood Pco2 gradient is a valid index of distal nephron hydrogen ion secretion in amphotericin B-like gradient-type lesions.

Acidosis, Renal Tubular↗
PubMed1976

Lithium-induced impairment of urine acidification.

The purpose of this study was to clarify the means by which lithium induced a disorder of urine acidification. Rats infused with hydrochloric acid (1 mEq/kg) developed acute metabolic acidosis (blood Ph = 7.32; bicarbonate, 18 mEq/liter) with a urine pH of approximately 5.85. The addition of lithium chloride (4 mEq/kg i.p) caused an increase in the urine pH (6.38) and a further decrease in blood bicarbonate (11.0 mEq/liter). During bicarbonate loading, lithium caused the urine PCO2 to fall significantly (urine minus blood PCO2 decreased from 25.3 +/-2.8 To 14.4 +/- 2.3 mm Hg) These changes were not seen following equimolar i.p. administration of sodium chloride. Similarly, lithium administration depressed bicarbonate reabsorption by 11.1% (from 30.6 to 27.2muEq/ml of GFR) during alkali infusion, while saline caused only a 5% decrease (30.0 to 28.5muEq/ml of GFR). The combination of an increase in urine PCO2 in alkaline urine indicates that lithium produced a defect in distal nephron hydrogen ion secretion. The fall in bicarbonate reabsorption following lithium administration oculd be due to a mild hydrogen ion secretory defect located in the proximal tubule or a severe defect in the distal nephron.

Acid-Base Imbalance↗
PubMed1976

The effect of hyperventilation on distal nephron hydrogen ion secretion.

This study was designed to determine the effect of acute hyperventilation on distal nephron hydrogen ion secretion. The blood PCO2 declined and stabilized rapidly when bicarbonate loaded rats were hyperventilated. In contrast, the urine PCO2 declined slowly, resulting in an early increase in the urine minus blood (U-B) PCO2 which could not be obliterated by carbonic anhydrase infusion. Within approximately 50 min, the U-B PCO2 in the hyperventilated and carbonic anhydrase infused rats approached zero. Consequently, equilibrium between collecting duct urine and arterial blood PCO2 was then presumed to exist. This provided the basis for the subsequent studies on a series of rats. The U-B PCO2 decreased from a control of 22+/-1 mm Hg (mean+/-SEM) to 11+/-2 mm Hg (mean+/-SEM) with hypocapnia, and rose again to its control value when the blood PCO2 returned to prehyperventilation values. This decline in U-B PCO2 with acute hyperventilation could not be attributed to changes in urine flow, phosphate, or bicarbonate excretion, suggesting, therefore, a decrease in distal nephron (probably collecting duct) hydrogen ion secretion with acute hyperventilation. Possible pitfalls in the interpretation of the UB PCO2 are illustrated.

Acute Disease↗
PubMed1975

Renal tubular acidosis during therapy for diabetic ketoacidosis.

A young woman presented with typical diabetic ketoacidosis. Five hours after insulin had been given hyperchloremic metabolic acidosis developed. This could not be attributed to gastrointestinal loss of bacarbonate, ingestion of HCI or carbonic anhydrase inhibitor, or the administered fluids and electrolytes. The combination of hyperchloremic metabolic acidosis and a urine pH of 5.6 during acidemia prompted specific studies that established the presence of disorders of renal acidification. A transient defect of hydrogen ion secretion in the distal nephron was suggested by the decrease in urine-blood Pco-2 gradient after administration of sodium bicarbonate. Proximal renal tubular acidosis was indicated by the reduced bicarbonate threshold that persisted for approximately 7 weeks.

Acid-Base Equilibrium↗
PubMed1975

Taste thresholds for salt in fasting patients.

Since it has been controversial whether in man changes in taste sensitivity for salt occur in relation to changes in extracellular volume, as has been described in animals, we assessed saline acuity in human volunteers undergoing a predictable pattern of external sodium balance. Our results demonstrate that taste thresholds for salt did not vary despite oppositely directed changes in renal sodium excretion and sodium balance.

Animals↗
PubMed1974

Studies on the pathogenesis of type I (distal) renal tubular acidosis as revealed by the urinary PCO2 tensions.

This study was designed to investigate the pathogenesis of type I (distal) renal tubular acidosis. Urinary and blood Pco(2) tensions were determined when the pH of the urine was equal to or exceeded the corresponding blood pH. This provided an indication of net hydrogen ion secretion in the distal nephron. In 16 normal subjects, the Pco(2) of the urine exceeded blood values (U-B Pco(2)) by 32.7+/-3.1 mm Hg. In contrast, the urinary Pco(2) tensions in 10 patients with type I (distal) renal tubular acidosis were not significantly greater than blood values (U-B Pco(2) = 2.0+/-2.2 mm Hg). These results indicate that type I (distal) renal tubular acidosis is caused by failure of the cells of the distal nephron to secrete hydrogen ions rather than to gradient-limited hydrogen ion addition to the urine. This is suggested by the fact that urinary Pco(2) levels should be higher than blood Pco(2) levels when hydrogen ions are secreted into urine containing bicarbonate in the distal nephron and they were not in this study despite the presence of a favorable hydrogen ion gradient (tubular fluid pH exceeded blood pH).

Acidosis, Renal Tubular↗
PubMed1974

Effects of glucose on bicarbonate reabsorption in the dog kidney.

The effects of glucose on renal bicarbonate reabsorption were investigated in the dog. The infusion of small amounts of glucose calculated to slightly exceed the renal threshold for glucose absorption increased bicarbonate reabsorption in bicarbonate loaded dogs. Galactose in similar doses also increased the reabsorption of filtered bicarbonate. This effect is not due to insulin secretion since insulin alone did not alter bicarbonate reabsorption and the infusion of glucose into alloxan-diabetic dogs given a steady infusion of insulin also enhanced bicarbonate reabsorption. It is more likely that the increased tubular reabsorption of glucose, secondary to an increased filtered load, resulted in the increase in bicarbonate reabsorption since phlorizin reversibly inhibits the effect of glucose.

Analysis of Variance↗
PubMed1972

Glucose-induced alkalosis in fasting subjects. Relationship to renal bicarbonate reabsorption during fasting and refeeding.

This study documents the development of alkalosis in patients returning to caloric intake after a period of starvation and investigates the mechanisms responsible for this metabolic alteration. We studied the acid-base status, bicarbonate reabsorption, acid excretion, and sodium metabolism during fasting and glucose refeeding in 19 patients receiving sodium supplements. Metabolic alkalosis developed promptly in all of the subjects who terminated an 18 day fast with 300 g of glucose daily for 4 days. Tubular maximum reabsorptive capacity for bicarbonate and renal bicarbonate threshold determinations were performed at varying intervals in six and seven subjects, respectively, who had fasted for 3-18 days. The results demonstrated that bicarbonate reabsorptive capacity was normal or low during early fasting, markedly elevated during the 2nd wk; and moderately elevated during the 3rd wk of fasting. Glucose administration at all stages of fasting caused a further increase in bicarbonate threshold. Sodium balance during fasting with sodium supplements was found to follow a triphasic pattern, with the occurrence of a natriuresis during the 1st wk followed by a period of sodium retention after which neutral daily sodium balance was reestablished. Correlation of bicarbonate reabsorption with sodium homeostasis indicated a slight decrease in renal bicarbonate threshold during the natriuretic phase, a marked increase in bicarbonate reabsorption during the period of sodium retention, and a continued moderate elevation of threshold after sodium balance was reestablished. This relationship was interpreted to indicate that changes in bicarbonate reabsorption during fasting and refeeding may be secondary to alterations in the renal reabsorption of sodium.

Absorption↗