Biomedical subjects

M B Goldstein

Publications and source records attributed to M B Goldstein.

At least 73 records · Page 4Linked to original sources

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

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

Renal excretion of uric acid during prolonged fasting.

Serum and urine uric acid were evaluated during prolonged therapeutic fasting in 15 obese patients. With increasing ketonemia the serum uric acid rose from a control value of 5.9 +/- 0.4 to 12.5 +/- 1.0 mg/100 ml at 7 days and then decreased progressively to 7.7 +/- 1.3 mg/100 ml by 28 days despite sustained ketonemia. The uric acid clearance were 5.5 +/- 0.9, 1.8 +/- 0.2, and 4.4 +/- 1.5 ml/min at days 0, 7, and 25 of fasting. At the same times the creatinine clearances were 114 +/- 11, 80 +/- 6, and 64 +/- 6.3 ml/min. There was no evidence of a renal tubular abnormality as assessed by glycosuria, bicarbonaturia, or increased phosphaturia. Urate binding to plasma proteins remained unchanged. Acute studies of the renal handling of uric acid revealed a uricosuric response to the administration of sodium lactate or sodium bicarbonate by intravenous infusion and low-dose acetylsalicylic acid orally. This renal tubular response departs significantly from that observed during the overnight fasted state and could not be accounted for by extracellular fluid volume expansion or the induced acid-base changes.

Adolescent↗

PubMed1976

Perirenal lymphocyst formation in renal transplant recipients: diagnosis and pathogenesis.

Perirenal lymphocyst formation occurred in 7 of 46 consecutive renal allografts which had survived at least one month. This complication developed from one to four and one-half months post-transplantation, resulted in a specific spectrum of clinical signs and symptoms, and was best diagnosed by a combination of intravenous pyelography and ultrasonic examination of the transplanted kidney. The lymph fluid is of recipient origin and its collection appears to be related to use of a high-dose immunosuppressive regimen and to a conscious decision to avoid the use of postoperative surgical drains. Surgical intraperitoneal marsupialization of the lymphocyst emerges as the clear treatment of choice for peritransplant lymphocyst formation.

Adolescent↗

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↗

PubMed1976

Stimulation of ammonia production and excretion in the rabbit by inorganic phosphate. Study of control mechanisms.

The purpose of this study was to clarify the mechanism (s) responsible for regulation of ammonia production and excretion in the rabbit. The normally low ammonia excretion rate during acute metabolic acidosis was stimulated acutely and increased approximately ninefold after infusion of sodium phosphate, but remained low if sodium sulphate or Tris was substituted for phosphate. Ammonia production was increased significantly by phosphate in rabbit renal cortex slices and in isolated renal cortex mitochondria. In isolated mitochondria, mersalyl, an inhibitor of both the phosphate/hydroxyl and phosphate/dicarboxylate mitochondrial carriers, inhibited the phosphate-induced stimulation, indicating that phosphate must enter the mitochondrion for stimulation. A malate/phosphate exchange seemed to be involved since N-ethylmaleimide, an inhibitor of the phosphate/hydroxyl exchange, did not inhibit phosphate-stimulated ammonia production, whereas there was inhibition by 2-n-butylmalonate, a competitive inhibitor of the dicarboxylate carrier. Phosphate itself was not essential since malonate stimulated ammoniagenesis in the absence of added phosphate. Similarly, citrate stimulated ammoniagenesis in isolated mitochondria in the absence of inorganic phosphate provided that it induced L-malate exit on the citrate transporter associated with inhibition of citrate oxidation by fluoroacetate. Similar results were also seen in mitochondria from rat renal cortex. A fall in mitochondrial alpha-ketoglutarate level resulted in an increase in ammonia production. This could be achieved directly with malonate or indirectly via L-malate exit. Simultaneous measurements of glutamate showed that the rate of ammonia production was reciprocally related to the glutamate content. We conclude that phosphate-induced stimulation of ammoniagenesis in the rabbit kidney is mediated by removal of glutamate, the feedback inhibitor of phosphate-dependent glutaminase. Glutamate removal is linked to phosphate-induced dicarboxylate exit across the mitochondrial membrane.

Acidosis↗

PubMed1975

Hyperglycemia-induced hyponatremia: metabolic considerations in calculation of serum sodium depression.

Hyperglycemia is associated with a decrease in serum sodium concentration. Previous methods of estimating the degree of decrease have not considered the fact that glucose will enter certain cells despite relative insulin deficiency; thus, glucose will not contribute directly to the osmotic gradient responsible for water shifts into or out of these tissues. The expected decrease in serum sodium concentration is 1.35 meg/l for every 100mg/dl increase in blood glucose concentration - the metabolic correction factor. Although the numerical difference between this factor and that calculated by others is small, the metabolic implications could be critical. In the hyperglycemic state the water content of tissues not requiring insulin for glucose transport could increase, and where tissue swelling is physically restricted (for example, in the brain) this expansion could seriously affect organ function.

Adipose Tissue↗

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

Mechanism for the paradoxical aciduria following alkali administration to prolonged-fasted patients.

Rapidly induced systemic alkalinization due to either sodium-lactate or sodium-bicarbonate infusion in prolonged-fasted subjects with steady-state ketoacidosis was associated with a decrease in urine pH. This decrease in urine pH from 5.50 to 5.20 was the result of a significant decrease in urinary ammonium excretion from 8.40 to 6.35 mEg/hr and was not accompanied by an increase in net acid excretion (11.3 vs. 10.6 mEg/hr). The decreased ammonium excretion is attributed to the raised pH of the proximal tubular fluid resulting in a less favorable pH gradient for gaseous ammonia entry. This would decrease gaseous ammonia generated in the loop of Henle for collecting duct buffering of secreted hydrogen ions.

Acidosis↗

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↗

PubMed1972

The nature of the renal adaptation to chronic hypocapnia.

Metabolic balance studies were carried out in normal dogs to define the renal mechanisms responsible for the adaptation to, and recovery from, chronic hypocapnia. A chronic reduction in arterial CO(2) tension (Pa(CO2)) of some 15 mm Hg was achieved by means of chronic exposure of the animals to 9% oxygen in an environmental chamber. The development of hypocapnia was associated with a marked suppression of net acid excretion which, together with a slight accumulation of organic acids, produced a reduction in plasma bicarbonate concentration (8 mEq/liter) that led to nearly full protection of extracellular pH (DeltaH(+) = - 2.5 nmoles/liter). When Pa(CO2) was returned to control levels, an augmentation of acid excretion restored plasma composition to normal after a brief period of "posthypocapneic metabolic acidosis."The changes in renal acid excretion during both adaptation and recovery were accomplished in a fashion notably different from that previously observed in chronic hypercapnia, being linked to changes in cation rather than chloride excretion. Thus, in dogs ingesting a normal NaCl diet, suppression of hydrogen ion excretion during adaptation to hypocapnia was associated with an increased excretion of sodium rather than with a retention of chloride. The fact that this loss of sodium occurred without a concomitant loss of potassium strongly suggests that the hypocapneic state specifically depressed distal sodium reabsorption; if distal sodium reabsorption had not been depressed, a reduction in proximal sodium reabsorption or a diminution in distal hydrogen ion secretion (or both) should have produced an increase in potassium excretion. The interpretation that chronic hypocapnia diminished sodium reabsorption was supported by the finding that when renal sodium avidity was enhanced by restriction of sodium intake, acid retention was accomplished by a loss of potassium rather than of sodium. The accompanying reduction in plasma bicarbonate concentration was slightly less than that observed in dogs ingesting a normal NaCl diet, a finding probably accounted for by a slight difference in the availability of cation for excretion under the two experimental circumstances. These findings, taken together with the observation that augmented acid excretion during recovery from hypocapnia is linked to cation retention, suggest that an adequate intake of cation during both adaptation and recovery from chronic hypocapnia may be critical to the physiologic regulation of acid-base equilibrium.

Absorption↗

PubMed1971

The influence of graded degrees of chronic hypercapnia on the acute carbon dioxide titration curve.

Studies were carried out to determine the influence of the chronic level of arterial carbon dioxide tension upon the buffering response to acute changes in arterial carbon dioxide tension. After chronic adaptation to six levels of arterial CO(2) tension, ranging between 35 and 110 mm Hg, unanesthetized dogs underwent acute whole body CO(2) titrations. In each instance a linear relationship was observed between the plasma hydrogen ion concentration and the arterial carbon dioxide tension. Because of this linear relationship, it has been convenient to compare the acute buffering responses among dogs in terms of the slope, dH(+)/dPaco(2). With increasing chronic hypercapnia there was a decrease in this slope, i.e. an improvement in buffer capacity, which is expressed by the equation dH(+)/dPaco(2)=-0.005 (Paco(2))(chronic) + 0.95. In effect, the ability to defend pH during acute titration virtually doubled as chronic Paco(2) increased from 35 to 110 mm Hg. The change in slope, dH(+)/dPaco(2), was the consequence of the following two factors: the rise in plasma bicarbonate concentration which occurs with chronic hypercapnia of increasing severity, and the greater change in bicarbonate concentration which occurred during the acute CO(2) titration in the animals with more severe chronic hypercapnia. These findings demonstrate the importance of the acid-base status before acute titration in determining the character of the carbon dioxide titration curve. They also suggest that a quantitative definition of the interplay between acute and chronic hypercapnia in man should assist in the rational analysis of acid-base disorders in chronic pulmonary insufficiency.

Acid-Base Equilibrium↗

PubMed1968