Renal hyperkalemia.
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Adaptation, Physiological↗
Biomedical subjects
A Sebastian
Publications and source records attributed to A Sebastian.
[Primary mediastinal seminoma (apropos of 2 cases)].
Two cases of primary mediastinal seminoma in patients aged 43 and 37 respectively are reported, with remarks on the pathogenesis, clinical features, diagnosis and treatment of the disease and a review of the literature. The favourable outcome in these two cases after 1 and 7 years respectively was remarkable. Emphasis is laid on the value of thoracotomy for the diagnosis and treatment.
Adult↗
Effects of dietary potassium depletion and mineralocorticoid excess on renal Cl-conservation in the dog.
Preexisting dietary K+ depletion (KD) in dogs exaggerates the renal acid excretory response to mineralocorticoid hormone (MCH) and attenuates the renal Cl- reabsorptive response without altering the Na+ reabsorptive response. The exaggerated acid excretory response has been postulated to be an electrophysiological consequence of a defect in renal Cl- reabsorption caused by KD. To investigate the specific effects of KD on renal Cl- transport in dogs, we assessed renal Cl- conservation during dietary Cl- restriction in KD adrenalectomized dogs maintained on physiological replacement doses of MCH. After a 16-day period of dietary K+ restriction and physiological MCH replacement, reduction of dietary NaCl from 5.0 to 0.25 mmol X kg-1 X 24 h-1 was attended by reduction in urinary Cl- excretion to values less than intake and to significantly lower values than in K+ -replete controls. In a subsequent experimental period of continued Cl- restriction and administration of DOC (15 mg/24 h, i.m.), urinary Cl- excretion decreased further in both groups to stable values, but the values were significantly greater in KD (2.7 +/- 0.4 vs. 1.1 +/- 0.1 meq/24 h, P less than 0.05) and the cumulative retention of urinary Cl- was significantly less (10.3 +/- 1.4 vs. 29.5 +/- 6.7 meq, P less than 0.05). These findings demonstrate that preexisting dietary KD accelerates chronic renal Cl- conservation in response to dietary Cl- restriction under conditions in which MCH supply is normal and fixed but that it impairs maximal renal Cl- -conserving ability in response to MCH excess.
Animals↗
[Type IV renal tubular acidosis: pathogenetic role of aldosterone deficiency and hyperkalemia].
Type IV renal tubular acidosis (RTA) is a syndrome of tubular dysfunction manifested clinically by persisting hyperkalemia and metabolic acidosis that occurs usually in patients with mild to moderate chronic glomerular insufficiency. The pathophysiologic characteristics include: reduced renal clearance of potassium; a reduced rate of renal bicarbonate reabsorption at normal plasma bicarbonate concentrations (the magnitude of which is insufficiently great to implicate the proximal tubule); an unimpaired ability to maintain a steep hydrogen ion concentration gradient between blood and urine during acidosis; and a reduced rate of renal net acid excretion despite highly acidic urine, due in part to reduced urinary excretion of ammonium, which in turn appears to be due in part to suppression of renal ammoniagenesis by hyperkalemia. Many patients with type IV RTA, but not all, have hyporeninemic hypoaldosteronism. The roles of mineralocorticoid deficiency and hyperkalemia in the pathogenesis of type IV RTA will be considered and the ameliorative effects of treatment with fludrocortisone, furosemide, and dietary potassium restriction reviewed.
Acidosis, Renal Tubular↗
Reduced glomerular filtration and enhanced bicarbonate reabsorption maintain metabolic alkalosis in humans.
The mechanism that sustains chloride-depletion metabolic alkalosis is presumed to be a stimulation of renal acidification, so that the elevated filtered bicarbonate load that attends hyperbicarbonatemia is completely reabsorbed. However, such enhancement of renal bicarbonate reabsorption is not necessary to maintain hyperbicarbonatemia if the filtered bicarbonate load is not increased owing to a concomitant reduction in glomerular filtration rate (GFR). To assess the relative contributions of enhanced renal bicarbonate reabsorption and reduced GFR in the maintenance of chloride-depletion alkalosis in humans, selective hydrochloric acid depletion was induced in five normal subjects. Plasma bicarbonate concentration increased by 27% (25.3 +/- 0.1 to 32.1 +/- 0.3 mEq/liter, P less than 0.005), whereas the rate of renal bicarbonate reabsorption increased by only 17% (2.7 +/- 0.1 to 3.2 +/- 0.2 mEq/min, P less than 0.05) owing to a 10% reduction in GFR (93.2 +/- 4.4 to 84.3 +/- 4.1 ml/min, P less than 0.01). Thus, in chloride-depletion metabolic alkalosis in humans, the increase in plasma bicarbonate concentration is not attended by a commensurate increase in filtered bicarbonate and rate of renal bicarbonate reabsorption. Both a reduction in GFR and an enhancement of renal bicarbonate reabsorption contribute to maintenance of the alkalotic state.
Absorption↗
Renal tubular acidosis induced by dietary chloride.
Previous studies have demonstrated that dietary intake of anions with high renal reabsorbability (Cl- greater than SO4=) can result in either exacerbation of chronic metabolic acidosis or correction of chronic metabolic alkalosis. These results, however, fail to predict the renal acid-base response to Cl- administration when systemic acid-base composition is initially normal, but accompanied by an extracellular fluid (ECF) volume-mediated renal avidity for Cl- reabsorption; that is, the renal options include HCl retention, KCl retention, and phosphaturia. Accordingly, the present metabolic balance studies evaluated the response to substitution of dietary Cl- (2.5 mEq/kg/day) for Pi in five dogs previously ECF-depleted with diuretics and maintained on a dietary K+ supplement, 5.0 mEq/kg daily as neutral Pi (electrolyte-free diet) during a steady-state control period. Dietary Cl- resulted in a decrease in arterial plasma [HCO3-] from 21.2 +/- 0.7 to 17.8 +/- 0.8 mEq/liter, (P less than 0.01) and increase in [H+] from 38.5 +/- 0.7 to 43.3 +/- 0.8 nEq/liter (P less than 0.001). Urine pH increased (P less than 0.01), the cumulative change in net acid excretion decreased (-79 mEq, P less than 0.05), and Cl- retention (39 mEq, P less than 0.05) occurred. No change in Na+, K+, or Pi excretion occurred. The renal acidosis was fully corrected when SO4= was substituted for dietary Cl- and redeveloped when Cl- was resubstituted . Superimposition of a large oral buffer load (creatinine) did not ameliorate Cl- -induced renal acidosis. The results indicate that dietary reabsorbable anions can result in renal acidosis when Cl- reabsorption is stimulated and suggest that anion reabsorbability characteristics and not anion buffer properties are responsible.
Acid-Base Equilibrium↗
Amelioration of hyperchloremic acidosis with furosemide therapy in patients with chronic renal insufficiency and type 4 renal tubular acidosis.
In hypoaldosteronemic patients with chronic renal insufficiency, administration of a mineralocorticoid steroid such as fludrocortisone can ameliorate hyperkalemia and metabolic acidosis, but this therapy is not always safe owing to the deleterious consequences of extracellular fluid volume expansion resulting from mineralocorticoid-induced sodium chloride retention. In the present study of 8 patients with renal hyperchloremic acidosis, mild hyperkalemia and chronic glomerular insufficiency, we evaluated the therapeutic effect of chronic administration of a natriuretic/chloruretic agent, furosemide, a renoactive drug that is known to increase renal acid excretion in experimental animals without increasing body content of sodium chloride. 4 patients had hyporeninemic hypoaldosteronism. During 8 days of treatment in 6 patients who received furosemide alone, metabolic acidosis was significantly ameliorated. Urinary net acid excretion increased, except in the 2 patients who had the most severe hypoaldosteronism. For the group as a whole, the cumulative change in net acid excretion correlated positively with the rate of aldosterone excretion (r = 0.94, p less than 0.01). Thus, the aciduric response to furosemide is attenuated by aldosterone deficiency. When furosemide was administered in combination with fludrocortisone (4 subjects), an amelioration of metabolic acidosis occurred that was greater than that observed in the group treated with furosemide alone. Combined therapy ameliorated acidosis in the patient with the most severe degree of hypoaldosteronism, the same patient in whom administration of furosemide without fludrocortisone was ineffective even after 6 months of treatment. The findings in this study indicate that chronic furosemide therapy, alone or in combination with fludrocortisone, is a safe and effective means of ameliorating metabolic acidosis in patients with chronic renal insufficiency, including those with hypoaldosteronism.
Acidosis↗
Amelioration of metabolic acidosis by dietary potassium restriction in hyperkalemic patients with chronic renal insufficiency.
Hyperkalemia has been implicated in the pathogenesis of metabolic acidosis in chronic renal insufficiency because acidosis is ameliorated after administration of medications that correct hyperkalemia: mineralocorticoids, diuretics, intestinal K+-binding agents. However, the acidosis-ameliorating effect of these medications may be a consequence not of their ability to correct hyperkalemia, but of their ability to directly stimulate renal or intestinal excretion of acid. To investigate the specific effect of correcting hyperkalemia, balance studies were performed wherein hyperkalemia was corrected solely by restriction of dietary K+ in three patients with moderate chronic renal insufficiency (Ccreat 36, 44, and 58 ml/min/1.73 m2, respectively). Reduction of K+ intake was effected by substitution of Na+ for K+ in the electrolyte supplement to a whole-food diet of low K+ content. This maneuver resulted in correction of hyperkalemia and sustained amelioration of metabolic acidosis in each patient. Net acid excretion increased only transiently, and not enough to fully account for the magnitude of the increment in plasma [HCO3-], suggesting that an extrarenal mechanism of HCO3- input to the systemic circulation was the major factor that ameliorated the systemic acidosis. Evidence of an extrarenal mechanism was obtained only during the phase of decreasing plasma [K+]. Subsequently, during sustained normokalemia, the increased plasma [HCO3-] was maintained as a consequence of a sustained increase in total renal H+ secretion, evidenced by complete reabsorption of the increased filtered load of HCO3- and no reduction in net acid excretion from control values. These results indicate that in some patients with moderate chronic renal insufficiency, metabolic acidosis is ameliorated when hyperkalemia is corrected by restriction of dietary K+ (Na+ substitution) without otherwise changing diet composition and without administration of medication. Amelioration of the acidosis is predominantly effected by extrarenal mechanisms, and is sustained by an increase in the set point at which plasma [HCO3-] is regulated by the kidney.
Acidosis, Renal Tubular↗
Effect of extracellular fluid volume depletion on renal regulation of acid-base and potassium equilibrium during prolonged mineral acid administration.
Previous studies of the renal and systemic acid-base response to prolonged administration of mineral acids in dogs have suggested that during the steady state of acidosis, the level at which plasma bicarbonate concentration is regulated by the kidney is dependent on the degree of augmentation of "distal delivery" of sodium imposed by the increased filtered load of administered mineral acid anion with filtered sodium, and on the degree of augmentation of "distal avidity" for sodium reabsorption imposed by ECF volume ( ECFV ) contraction secondary to renal sodium losses accompanying the administered mineral acid anion. This formulation, however, fails to predict the level at which plasma bicarbonate concentration would be regulated under conditions of preexisting ECFV depletion, which would simultaneously limit distal delivery of sodium salts and yet increase distal avidity for sodium reabsorption. Our studies assessed the renal and systemic acid-base responses to prolonged daily administration of 5.0 mEq/kg of H+ as HCl (groups 1 and 2) or H2SO4 (groups 3 and 4) in dogs with normal ECFV (groups 1 and 3) vs. preexisting ECFV depletion (groups 2 and 4) induced by administration of ethacrynic acid. In response to HCl administration, dogs with depleted ECFV developed more severe acidosis than ECFV -replete dogs (delta[HCO-3,]p, -5.0 +/- 0.6 mEq/L, group 2 vs. -2.7 +/- 0.5 mEq/L, group 1, p less than 0.02). The exacerbated metabolic acidosis in group 2 persisted in the steady state, even though the steady-state net systemic acid load was not greater than in group 1. No exacerbation of acidosis was observed in H2SO4-fed dogs with depleted ECFV . In response to either HCl or H2SO4, persistent hypokalemia caused by increased renal potassium clearance occurred in ECFV -replete dogs but not in ECFV -depleted dogs. Our results indicate that preexisting ECFV depletion results in impaired renal hydrogen ion secretion during prolonged HCl feeding, but not during H2SO4 feeding. These results suggest that during prolonged HCl loading under conditions of preexisting ECFV depletion, hypovolemia-mediated restriction of the normal augmentation of distal delivery of sodium salts overrides the effects of enhanced distal cation secretory capacity that attends hypovolemia-mediated augmentation of distal avidity for sodium reabsorption.
Acid-Base Equilibrium↗
Effect of diet on plasma acid-base composition in normal humans.
Steady-state plasma and urine acid-base composition was assessed in 19 studies of 16 normal subjects who ingested constant amounts of one of three diets that resulted in different rates of endogenous noncarbonic acid production (EAP) within the normal range. Renal net acid excretion (NAE) was used to quantify EAP since the two variables are positively correlated in normal subjects. A significant positive correlation was observed between plasma [H+] and plasma PCO2, and between plasma [HCO3-] and plasma PCO2, among the subjects. Multiple correlation analysis revealed a significant interrelationship among plasma [H+], plasma PCO2, and NAE (r = 0.71, P less than 0.001), and among plasma [HCO3-], plasma PCO2, and NAE (r = 0.77, P less than 0.001). The partial correlation coefficients indicated a significant positive correlation between plasma [H+] and NAE, and a significant negative correlation between plasma [HCO3-] and NAE, when plasma PCO2 was held constant. These findings indicate that two factors influence the level at which plasma [H+] is maintained in normal subjects: (1) the steady-state rate of endogenous noncarbonic acid production, and (2) the setpoint at which plasma PCO2 is regulated by the respiratory system. Plasma [HCO3-] is also co-determined by these two factors. In disease states, therefore, both factors must be known before a disturbance in acid-base homeostasis can be excluded.
Acid-Base Equilibrium↗
Chronic hyperkalemic renal tubular acidosis induced by KCl loading.
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Acid-Base Equilibrium↗
Metabolic alkalosis in models of primary and secondary hyperparathyroid states.
Hyperchloremic metabolic acidosis has been reported in clinical states of primary and secondary hyperparathyroidism (HPT). Acute administration of parathyroid hormone (PTH) decreases renal acidification in humans and dogs, but the renal and systemic acid-base effects of chronic HPT have not been extensively investigated. In chronically thyroparathyroidectomized (TPTX) dogs (group I), bPTH 1-5 U/kg twice daily resulted in sustained hypophosphatemia, hypercalcemia, and Cl- -resistant metabolic alkalosis that was of renal origin at least in part: delta [HCO3-]p + 4.1 +/- 0.8 meq/liter, P less than 0.01; delta [H+]p -4 +/- 1 neq/liter, P less than 0.001, days 10-12. The cumulative change (sigma delta) in net acid excretion (NAE) was +44 meq (day 9, P less than 0.05). Similarly, metabolic alkalosis of renal origin, at least in part, occurred when PTH was administered by chronic continuous intravenous infusion (group II). Since chronic administration of calcitriol in dogs results in metabolic alkalosis, plasma calcitriol concentration was measured and found not to be increased by chronic intravenous PTH administration. In intact dogs (group III), a continuous chronic intravenous infusion of the Ca2+ chelator, Na4EGTA (3.0 mmol/kg daily), substituted for an equimolar amount of prechelated EGTA (CaNa2EGTA), resulted in a model of hypocalcemic HPT and severe Cl- -resistant metabolic alkalosis: delta [HCO3-]p +9.1 +/- 1.9 meq/liter, P less than 0.05; delta [H+]p -5 +/- 1 neq/liter, P less than 0.01, days 6-8. NAE decreased significantly. Thus, whereas metabolic alkalosis induced by PTH administration could be accounted for by increased NAE (group I), EGTA-induced metabolic alkalosis was accounted for by an extrarenal mechanism of base input to extracellular fluid (group III). Neutralization of the extrarenal base input by chronic administration of HCl during the period of EGTA-induced HPT did not preclude the development of metabolic alkalosis (group V), suggesting that a renal component was present in EGTA-induced metabolic alkalosis as well as in models of primary HPT (groups I and II). During the steady state, in this group as in the groups administered PTH, the net endogenous load of acid to the systemic circulation requiring renal excretion was unchanged from control, as indicated by stable values of NAE not significantly different from control. Yet metabolic alkalosis persisted in the steady state.(ABSTRACT TRUNCATED AT 400 WORDS)
Acid-Base Equilibrium↗
Incidence of radiographically evident bone disease, nephrocalcinosis, and nephrolithiasis in various types of renal tubular acidosis.
The syndrome of renal tubular acidosis has been categorized into three physiologic types that have different clinical findings and prognostic and therapeutic implications. We reviewed radiographs of the skeleton and kidneys in 92 patients (56 children and 36 adults) with renal tubular acidosis in order to determine whether the radiologic findings could be related to the type of syndrome. Forty-four patients had Type 1 renal tubular acidosis, 18 had Type 2, and 30 had Type 4. Evidence of skeletal abnormalities was uncommon (17 per cent) and was confined to patients who had the Type 2 disorder or azotemia. The children with Type 2 and skeletal abnormalities had rickets; the adults had osteopenia without pseudofractures. Nephrocalcinosis was evident in approximately one fourth of the group (29 per cent) and was restricted to patients with the Type 1 syndrome. In patients with Type 4, osteopenia was evident in 12 per cent, all of whom were azotemic. Our observations indicate that the radiographic manifestations of renal tubular acidosis are influenced by the physiologic type of renal tubular acidosis.
Acidosis, Renal Tubular↗
Disorders of distal nephron function.
In this review, the distal nephron is considered to be that portion of the renal tubule commencing with the thick ascending limb of the loop of Henle and ending with the papillary collecting duct. The collecting duct, including its subdivisions in the cortex and medulla, originates from a different embryologic anlage than more proximal nephron segments, which may explain its morphologic and functional dissimilarities from the thick ascending limb and the distal convoluted tubule. This review summarizes selected aspects of the physiology of the distal nephron, with particular emphasis on the physiology of distal nephron transport of sodium, potassium, chloride and hydrogen ion. The pathophysiologic features of the following disorders of distal nephron function are reviewed: (1) pseudohypoaldosteronism, a heterogenous group of disorders in which the signs and symptoms are suggestive of aldosterone deficiency, but in which aldosterone levels are supernormal and administration of exogenous mineralocorticoid is not ameliorative; (2) pseudohyperaldosteronism (Liddle syndrome), a familial disorder in which the clinical manifestations closely resemble those resulting from an aldosterone-producing adenoma of the adrenal gland (primary aldosteronism), but in which the measured rate of aldosterone secretion and excretion is greatly subnormal; (3) Bartter syndrome and related syndromes of renal potassium wasting; (4) type 1 renal tubular acidosis (classic, distal); (5) type 4 renal tubular acidosis (hyperkalemic). Reference citations are generally to articles reporting recent advances in these areas and to review articles that contain comprehensive bibliographies.
Acidosis, Renal Tubular↗
On the mechanism of diminished urinary carbon dioxide tension caused by amiloride.
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Acidosis, Renal Tubular↗
Systemic and renal acid-base effects of chronic dietary potassium depletion in humans.
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Acid-Base Equilibrium↗
Renal and systemic acid-base effects of the chronic administration of hypercalcemia-producing agents: calcitriol, PTH, and intravenous calcium.
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Acid-Base Equilibrium↗