Higher Urine pH Research Articles

The syndrome of renal tubular acidosis and nerve deafness. Discordant manifestations in dizygotic twin brothers

The syndrome of renal tubular acidosis (RTA) and nerve deafness is a distinct nosological entity that is inherited as an autosomal recessive trait. We studied a pair of dizygotic twin brothers both with nerve deafness but only one with RTA. Distal RTA was diagnosed in twin A because of inappropriately high urinary pH (6.9) and low net acid excretion (40.0 muEq/min per 1.73 m2) in the presence of hyperchloraemic metablic acidosis, and fractional bicarbonate excretion of 1.6% at a normal serum bicarbonate concentration. The urine minus blood PCO2 differences (U-B PCO2) during a neutral sodium phosphate load and in alkaline urine induced by bicarbonate supplementation were: 11 and 0 mm Hg, respectively. Twin A developed nephrocalcinosis and, after a 9.5-year follow-up period, was 5.3 cm taller than his brother. Twin B remained asymptomatic. Periodic determinations of blood pH and serum bicarbonate were normal and urine pH decreased to 4.6 in the face of ammonium chloride-induced metabolic acidosis. The U-B PCO2 assessed in alkaline urine was 33.5 mm Hg. Audiograms demonstrated bilateral nerve deafness in both brothers. The presence of deafness without RTA has not been previously reported in this syndrome. This report also shows that a primary distal acidification defect is responsible for the RTA observed in this syndrome.

Solubility of Uric Acid and Supersaturation of Monosodium Urate: Why is Uric Acid So Highly Soluble in Urine?

The solubility of uric acid and the stability of supersaturation of monosodium urate (NaU) were studied in buffer solutions containing 150mM sodium in the physiological urinary pH range at 37C. The solubility of uric acid increased with the rise in pH, and the total dissolved urate (undissociated uric acid + urate anion) concentration did not change during seven-day incubation in the pH range below 6.6. In this pH range, the calculated concentration of undissociated uric acid was constant (about six mg./dl.). Consequently, the increasing solubility of uric acid with the rise in pH depended solely on the increase of urate anion. As much as 220mg./dL of uric acid could be dissolved for 24hours at pH 7.0. But following seven-day incubation the total dissolved urate concentration decreased to 16mg./dl. due to NaU crystallization. The stability of NaU supersaturation depended not only on the concentration of sodium and urate anion but also on time and pH. When monopotassium urate crystals were incubated for seven days, the total dissolved urate concentration decreased according to NaU crystallization; the higher the pH, the more marked the decrease. However, at least some 80mg./dl. of total dissolved urate was stable up to pH 8.2 within 24hours. These findings can well explain why NaU crystals are seldom formed in the normal urine. Urinary stasis and/or pathological high urinary pH may cause NaU crystallization. (J. Urol, 142: 1095–1098, 1989)

EXTERNAL NET ACID BALANCE (NAB) IN INFANTS WITH CHRONIC DIARRHEA CONSEQUENT TO ACQUIRED GLUCOSE INTOLERANCE (AGI)

A close relationship exists between the presence of a watery and acidic diarrhea and the development of metabolic acidosis in AGI infants. With the objective to identify possible mechanisms of acidosis, 12 malnourished infants, 2 to 17 months old were studied during 3 to 4 days, by the NAB technique, divided in : Group 1 - infants with diarrhea, glucose in stools, and acidosis; Group 2 - infants who tolerated formula feedings well and free of acidosis. Endogenous acid production (AP) was significantly higher in group 1: 3.69 ± 1.92 vs 0.45 - 1.70 mEq/kg/day (p < .002). Urinary excretion of sulfate was similar in both groups and organic acids (OA) were higher in group 1 (p < .05). Absorbed undetermined anions (UA) were significantly different between the groups, positive in group 2, representing base gained : 1.65 ± 1.80 mEq/kg and negative in group 1, representing produced and gained acid: -022 ± 1.85 mEq/kg (p < .05). Urinary net acid excretion (NAE) was similar in both groups, observing group 1 who had inappropriated high urinary pH and bicarbonaturia. We concluded that the metabolic acidosis was conditioned largely by the overproduction of intestinal OA as well as urinary excretion of AO as salts. Impairment in NAE was the factor responsible for maintaining systemic acidosis in group 1.

An in vitro model of nephrocalcinosis using rabbit inner medullary collecting tubular cell culture

In order to investigate the pathogenesis of medullary nephrocalcinosis, rabbit inner medullary collecting duct cells were grown in media containing different Ca++, PTH and pH levels. It was found that high Ca++ (7.8mM) only reduced growth slightly and that crystalline deposits were found under the cells. This suggests that high Ca++ is not severely toxic to the cells but can lead to deposition of calcium beneath the basement membrane. PTH did not effect cell growth even in the presence of high Ca++ implying that it has an indirect effect on tubular cells in medullary nephrocalcinosis associated with hyperparathyroidism. In renal tubular acidosis these cells are subjected to a persistently high urinary pH and low interstitial pH. Raising the pH reduced the cell growth in normal Ca++ medium whereas lowering the pH increased cell growth in vitro. Our results show that nephrocalcinosis is not due to the direct effect of raised pericellular Ca++ or PTH alone and that persistently alkaline tubular fluid may play a role.

Quadriplégie hypokaliémique et coma au cours d'une acidose tubulaire rénale

A case is reported of acute episode of severe hypokalaemia (K + = 1.1 mmol · 1 −1) associated with hyperchloraemic acidosis and simultaneous high urine pH (pH = 7) in a 24 year old woman with type I distal tubular acidosis and nephrocalcinosis. The flaccid paralysis involved the trunk, neck, facial and pharyngeal muscles. She was in areflexic quadriplegia, coma and respiratory failure requiring endotracheal intubation and positive pressure ventilation. There were no cardiac disturbances, presumably because of the chronic potassium depletion, the patient's youth and healthy myocardium. Despite the usually recommended maximal potassium infusion rate (0.25 mmol · kg −1 · h −1), there was a transient worsening of her neuromuscular status. Only 12 h later, the first movements were noticed. In order to prevent such a deterioration, a more rapid potassium infusion could have been used. However, in our case, the occurrence of hypokalaemic extrasystoles was reduced and the patient was still intubated and ventilated. It was therefore decided not to run the risk of myocardial inexcitability carried out with supramaximal infusion rates and to keep the usual protocol. Besides, several pitfalls have to be avoided during the treatment of the numerous metabolic disorders coexisting with severe hypokalaemia, such as metabolic acidosis and hyperglycaemia.

Familial Aggregation of Renal Calcium Stone Disease

The question of a familial predisposition towards stone formation in primary nephrolithiasis has not been explored completely. In a sample of 214 calcium stone patients, and 428 age and sex-matched controls we observed a higher frequency of stones among the first degree relatives of stone patients compared to the relatives of controls.A family history of renal stones was more common among the female (45 per cent) than among the male patients (31 per cent). There was no relationship between family history of renal stones, and abnormal calcium and oxalate excretion rates. A significant association between a family history and a higher urinary pH was observed among the female calcium stone patients. A genetic defect in urinary acidification with variable expressivity might be associated with a high frequency of stone formation. Moreover, uric acid excretion was higher in male stone patients with a family history of stones. Finally, the parents and siblings of the renal stone patients were affected more by calculi than were the corresponding relatives of their spouses.

Pathophysiology of Stone Formation

Urinary stone disease is a multifactorial disorder arising essentially from an abnormal combination of a number of urinary risk factors. In the case of calcium urolithiasis the main risk factors are a low urine volume, a high urinary pH, increased excretions of calcium, oxalate and uric acid and a low net level of inhibitory activity against the crystallization of calcium salts. The last mentioned, in turn, is dependent on the balance between the macromolecular inhibitors, including glycosaminoglycans, ribonucleic acid and acidic glycoproteins, and the promoters of crystallization such as Tamm-Horsfall mucoprotein. There is currently some debate as to whether or not an immunological factor might also be involved in the renal tubules, which results in crystals becoming bound to the renal epithelium.

Pathophysiology of stone formation.

Urinary stone disease is a multifactorial disorder arising essentially from an abnormal combination of a number of urinary risk factors. In the case of calcium urolithiasis the main risk factors are a low urine volume, a high urinary pH, increased excretions of calcium, oxalate and uric acid and a low net level of inhibitory activity against the crystallization of calcium salts. The last mentioned, in turn, is dependent on the balance between the macromolecular inhibitors, including glycosaminoglycans, ribonucleic acid and acidic glycoproteins, and the promoters of crystallization such as Tamm-Horsfall mucoprotein. There is currently some debate as to whether or not an immunological factor might also be involved in the renal tubules, which results in crystals becoming bound to the renal epithelium.

Graphic Display of Urinary Risk Factors For Renal Stone Formation

From the analysis of various urinary constituents and the estimation of urinary saturation of stone-forming salts, it is now possible to identify risk factors responsible for or contributing to stone formation. Metabolic factors included calcium, oxalate, uric acid, citrate and pH. Environmental factors were total volume, sodium, sulfate, phosphate and magnesium. Physicochemical factors represented saturation of calcium oxalate, brushite, monosodium urate, struvite and uric acid.A scheme for graphic display of risk factors was developed to allow ready visual recognition of important risk factors presumed to cause stone formation. This graphic display had diagnostic use as well as practical value in following response to treatment. For example, a low urinary pH and high urinary concentration of undissociated uric acid could be discerned readily in cases of uric acid lithiasis, as were high urinary pH and exaggerated urinary supersaturation of struvite in cases of infection lithiasis. In a patient with absorptive hypercalciuria and hypocitraturia treatment with thiazide and potassium citrate could be shown to abolish high risks (hypercalciuria, hypocitraturia and relative supersaturation of calcium oxalate) displayed before treatment.

SELECTED PHYSIOLOGICAL EFFECTS RESULTING FROM ADDITION OF SODIUM BICARBONATE TO DIETS FOR YEARLING HORSES

Sodium bicarbonate or a commercial vitamin-mineral mixture was included at the 1% level (air-dry weight) in the diets of 16 yearling horses over a 140-day period in a 2 × 2 factorial design. Feed additives resulted in a pH range from 5.78 to 7.87 in the concentrate portion of the diets. Feces, urine and venous blood were collected 24 h after feeding the concentrate. Average daily gain, respiration rate, venous pCO2 and pO2, as well as serum K, Cl, Ca, P, urea N and protein levels were unaffected by treatment. Horses receiving the vitamin-mineral supplement had higher serum Na and lower serum glucose concentrations than horses not receiving the supplement. Horses receiving sodium bicarbonate had a higher urine pH, lower fecal pH, higher packed cell volume, lower blood pH and lower serum glucose concentrations at 24 h after a meal than horses not receiving the buffer. Key words: Horse, sodium bicarbonate, dietary supplements, hematology

H+ transport by the aldosterone-deficient rat distal nephron

AbstractH+ transport by the aldosterone-deficient rat distal nephron. The effect of aldosterone on distal nephron acidification was investigated by comparing isolated perfused kidneys from adrenalectomized rats treated for 3 to 5 days with dexamethasone alone (10 µg/day i.p.) and from rats given in addition a physiologic dose of d-aldosterone (10 µg/day in oil s.c). The maximal pH gradient between urine and perfusate, determined at a perfusate pH of 6.7 with glucose as the sole substrate, did not differ significantly between the aldosterone deplete and replete groups (1.27 ± 0.12 vs. 1.35 ± 0.12). H+ secretory capacity of the distal nephron was determined by perfusing kidneys at pH 6.8 and providing saturating quantities of urinary buffer in the form of creatinine. Under these experimental conditions kidneys from aldosterone deplete rats had a higher urine pH and lower excretion rate of titratable acid indicative of a defect in H+ secretion. Acid secretion below a pH of 6.0 (T.A.-pH 6.0), an index of H+ secretion by the distal nephron, was also significantly lower in the aldosterone deplete kidneys. Thus, aldosterone depletion decreased the H+ secretory capacity of the distal nephron, but had no clear effect on the force of the pump as reflected by the maximal pH gradient. Amiloride (10-5 M) was added to the perfusate of kidneys undergoing the H+ secretory capacity protocol to distinguish between sodium-linked and sodium-independent effects of aldosterone. The difference in T.A. pH 6.0 between aldosterone deplete and replete kidneys was reduced by approximately 70% in the presence of amiloride. This indicates that a substantial portion of the aldosterone-dependent component of distal nephron H+ secretion is mediated by a sodium-dependent mechanism.Transport d'H+ par le néphron distal de rats déficients en aldostérone. L'effet de l'aldostérone sur l'acidification du néphron distal a été étudié en comparant des reins perfusés isolés provenant de rats surrénalecomisés traités pendant 3 à 5 jours avec de la dexaméthasone seule (10 µg/jour i.p.) et de rats recevant en plus une dose physiologique de d'aldostérone (10 µg/j dans de l'huile s.c.). Le gradient maximum de pH entre l'urine et le perfusat, déterminé avec un perfusat de pH 6,7 avec du glucose comme seul substrat, ne différait pas significativement entre les groupes recevant ou ne recevant pas d'aldostérone (1,27 ± 0,12 contre 1,35 ± 0,12). La capacité sécrétoire d'H+ du néphron distal a été déterminée en perfusant les reins à pH 6,8 et en apportant des quantités saturantes de tampons urinaires sous forme de créatinine. Dans ces conditions expérimentales, les reins de rats déplétés en aldostérone avaient un pH urinaire plus élevé et un débit d'excrétion d'acidité titrable plus faible, indiquant un défaut de sécrétion d'H+. La sécrétion acide pour un pH inférieur à 6,0 (T.A.-pH 6,0), index de sécrétion d'H+ par le néphron distal était également significativement plus faible dans les reins déplétés en aldostérone. Ainsi la déplétion en aldostérone diminuait la capacité sécrétoire en H+ du néphron distal, mais n'avait pas d'effet clair sur la force de la pompe, comme le reflétait le gradient de pH maximal. De l'amiloride (10-5 M) a été ajouté au perfusat des reins subissant le protocole de capacité sécrétoire d'H+, afin de distinguer entre les effets de l'aldostérone reliés au sodium ou indépendants du sodium. La différence de T.A. pH 6,0 entre les reins déplétés ou réplétés en aldosterone était réduite d'environ 70% en présence d'amiloride. Ceci indique qu'une portion substantielle du constituant dépendant de l'aldostérone de la sécrétion H+ dans le néphron distal est médiée par un mécanisme dépendant du sodium.

Hydrogen ion secretion by the rat distal nephron: adaptation to chronic alkali and acid ingestion.

Isolated rat kidneys perfused at a low bicarbonate concentration were subjected to increased rates of buffer excretion, provided as creatinine, in order to examine the maximal hydrogen ion secretory capacity of the distal nephron. Preliminary experiments with kidneys from normal rats indicated that the quantity of hydrogen ion that titrated creatinine from urine pH to a pH of 6.0, designated TA-pH 6.0, provided an index of net hydrogen ion secretion by a functional segment of the distal nephron. With this technique the response of distal nephron hydrogen ion transport to ingestion of both acid and alkali loads was examined. Perfused kidneys from rats with chronic metabolic acidosis, produced by drinking 1.5% NH4Cl for 3-5 days, excreted urine with a lower pH and higher total titratable acid and TA-pH 6.0 than appropriate controls. Perfused kidneys from rats that ingested NaHCO3 for 7 days exhibited a higher urine pH and lower rates of total titratable acid and TA-pH 6.0 than controls. By contrast, kidneys from rats acutely tube-fed NaHCO3 3 h prior to study showed no change in urinary acidification parameters. Thus, chronic ingestion of an acid load stimulates, and chronic ingestion of an alkali load inhibits, the intrinsic hydrogen ion secretory capacity of the rat kidney at a distal nephron site. This intrinsic adaptation of the hydrogen ion transport mechanism is not secondary to changes in aldosterone because rats that ingested NaHCO3 chronically had higher plasma aldosterone levels than controls.

Distal nephron function in patients receiving chronic lithium therapy

Renal tubular function was studied in 14 patients chronically treated with lithium for affective disorders. Patients were separated into two groups according to the duration of lithium therapy: long-term (35 +/- 7.0 months) and short-term (4.8 +/- 0.8 months). At comparable urine lithium concentrations, patients on long-term therapy had a lower maximal urine osmolality (Umax) and free water reabsorption (TcH2O) than did patients on short-term therapy. The latter group achieved a Umax above 800 mOsm kg H2O. In contrast, both groups of patients failed to increase the urine-blood (U-B) Pco2 gradient normally during acute sodium bicarbonate loading. This low U-B Pco2 was observed at comparable urine bicarbonate concentrations between both groups of patients and controls, and thus was associated with a higher urine pH in patients. These findings indicate that the inability of these patients to achieve a normal U-B Pco2 in a maximally alkaline urine was the result of decreased distal hydrogen ion secretion rather than inability to raise urine bicarbonate concentrations as a result of a concentrating defect. Bicarbonate reabsorptive capacity was normal in our lithium-treated subjects. Both groups of patients achieved a normal U-B Pco2 gradient in response to sodium phosphate loading. They also were able to achieve a minimal urine pH and a maximal acid excretion similar to those of controls in response to a 3-day ammonium chloride loading test. Our data demonstrate that chronic lithium therapy is associated with a mild distal acidification defect disclosed only by the finding of a low U-B Pco2 gradient during sodium bicarbonate loading. This peculiar defect can be found in short-term lithium-treated patients in whom the concentrating capacity is relatively well preserved.

A Preliminary Study of the Possible Application of Gastrocystoplasty in Selected Cases of Feline Urolithiasis

SUMMARY A correlation between high urinary pH and the occurrence of struvite crystals in the urinary tract of the cat has been noted by several authors. Gastrocystoplasty was investigated as a means to lower urine pH. Two gastrocystoplasty techniques were investigated in 10 cats. The results indicate that the successful transplantation of gastric fundic mucosa into the urinary bladder leads to a reduction in the urine pH. The survival of gastric parietal cells within the transplanted tissue suggests that they may be responsible for acidifying the urine. This preliminary investigation aimed to determine whether gastrocystoplasty might provide an alternative surgical procedure in cases of feline urolithiasis. The results indicated that there was justification for mounting further studies and experiments with a view to exploring the clinical applications.

Ambulatory evaluation of nephrolithiasis: Classification, clinical presentation and diagnostic criteria

Using the ambulatory protocol previously described, 241 patients with nephrolithiasis were evaluated. They could be categorized into 10 groups from the results obtained. Absorptive hypercalciuria type I (87 per cent male) comprised 24.5 per cent and was characterized by normocalcemia, normal fasting urinary calcium (< 0.11 mg/100 nil glomerular filtration), an exaggerated urinary calcium following an oral calcium load (>0.20 mg/mg creatinine), normal urinary cyclic adenosine monophosphate (AMP) (< 5.4 nmol/100 ml glomerular filtration) and serum parathyroid hormone (PTH), and hypercalciuria (>200 mg/day during a calcium- and sodium-restricted diet). Absorptive hypercalciuria type II (58 per cent male) accounted for 29.8 per cent; its biochemical features were the same as those for absorptive hypercalciuria type I, except for normocalciuria during a restricted diet and low urine volume (1.42 ± 0.55 SD liter/day). Renal hypercalciuria (56 per cent male), disclosed in 8.3 per cent, was represented by normocalcemia and high values for fasting urinary calcium (0.160 ± 0.054 mg/100 ml glomerular filtration), urinary cyclic AMP (6.80 ± 2.10nmol/100 ml glomerular filtration) and serum PTH. Primary hyperparathyroidism (57 per cent female), accounted for 5.8 per cent, typically included hypercalcemia, hypophosphatemia, hypercalciuria and high urinary cyclic AMP. Hyperuricosuric calcium urolithiasis (100 per cent male) comprised 8.7 per cent, and was characterized by hyperuricosuria (776 ± 164 mg/day) and urinary pH exceeding pK for uric acid (5.91 ± 0.33). In enteric hyperoxaluria (60 per cent female), encountered in 2.1 per cent of cases, urinary oxalate was increased (6.29 ± 13.2 mg/day). Noncalcium-containing stones were found in 2.1 per cent of the patients with uric acid lithiasis (100 per cent male) and in another 2.1 per cent of the patients with infection lithiasis (60 per cent female). These conditions were typified by low urinary pH (5.29 ± 0.12) and high urinary pH (6.69 ± 1.16), respectively. Renal tubular acidosis was found in one patient (male, 0.4 per cent). In 10.8 per cent of the patients (81 per cent male), no metabolic abnormality could be found, although urine volume was low (1.41 ± 0.51 liter/day). Hypercalciuria could not be differentiated between absorptive hypercalciuria and renal hypercalciuria in 5.4 per cent of the patients. Thus, this ambulatory protocol disclosed a physiologic disturbance in nearly 90 per cent of the cases and provided a definitive diagnosis in 95 per cent of the patients.

Central, renal and adrenal effects of lithium in man

The effect of lithium on thirst and plasma vasopressin concentration was tested in seven subjects with affective psychiatric disorders. Mean ad libitum fluid intake was liberal but no different before (3,293 ml/day) and three to four weeks after treatment with lithium (3,443 ml/day). After fluid deprivation, plasma vasopressin was 1.5 ± 0.39 pg/ml before and 3.72 ± 0.55 pg/ml after treatment with lithium (p < 0.02) as plasma osmolalities and body weights were comparable. Urinary osmolalities were no different (735 versus 759 mOsm/kg) and did riot increase with exogenous vasopressin. With a water load, plasma vasopressin decreased 1.58 to 0.79 pg/ml (p < 0.05) before and from 2.68 to 0.91 pg/ml (p < 0.025) after treatment with lithium. The water load excreted in 4 hours was less during lithium therapy (66 versus 85 per cent, p < 0.05). Lithium therapy had no effect on plasma renin activity (PRA) or aldosterone. On standing, PRA increased from 2.27 to 5.28 ng/ml/hour (p < 0.05) before and from 2.19 to 7.59 ng/ ml/hour (p < 0.05) after lithium therapy. At the same time plasma aldosterone increased from 121 to 365 pg/ml (p < 0.05) before and from 76 to 436 pg/ml (p < 0.05) after treatment with lithium. Lithium had no effect on indices of proximal tubular function (HCO 3 −, HPO 4 =, glucose, amino acid and uric acid excretion). A lower titratable acid excretion (21 ± 5 versus 32 ± 4 μeq/min, p < 0.05) and higher urine pH (5.40 versus 5.02, p < 0.05) was observed after NH 4Cl ingestion during lithium therapy as compared to control. In conclusion, three to four weeks of lithium therapy neither stimulates thirst nor suppresses vasopressin release; some of the polyuria in patients with affective disorders may be due to their liberal fluid intakes. Lithium does not alter base line or standing PRA, aldosterone or proximal tubular function. Lithium does, however, induce an incomplete renal tubular acidosis.

Bacteroides fragilis meningitis in a neonate successfully treated with metronidazole

after one year (Table II). In the PM group the total number of recurrences and of recurrences per patient was significantly less in either sex than in the EC group (Table II). The first recurrence in six of nine (all boys) in the PM group was due to PM. In the EC group, seven of eight recurrences were due to EC. DISCUSSION This study revealed a number of characteristics of initial UTI due to Proteus mirabilis. Most patients were male, relatively young, and had fewer clinical findings, fewer abnormalities of urine or urinary tract structure, and a relatively benign course. The predominance of PM infection among boys (58%) in our series is comparable to that in previous observations (59%), ~ but varies with that in other reports of 2% 3 to 32% 5 . The basis for the male predilection to PM infection is not known. Age seems to influence sex distribution. In the study showing a very low incidence (2%) among boys, ~ the mean age was much higher (9 years) than in our group (2.7 years). The relative paucity of symptoms in patients with PM infection may also be related in part to age, since many were too young to verbalize complaints. The observation of a less acid, or even alkaline, urinary pH has been previously described? Structural abnormalities were less common among the patients with PM infection than in the EC group and than in a prior series 2 of males patients with Proteus infection. The recurrence rate (31%) in the male patients with PM infection may be compared with the 36% reported in a previous study, ~ which included some patients with EC and with urinary tract abnormalities. The number of recurrences per patient and their relative rarity after one year suggest a favorable outlook. The frequency of stone formation associated with PM infection seems to be variable. During the initial episode it may be low as in this series (a single patient) or totally absent, as in a previous study. ~ Its prevalence, however, may be higher with persistent and/or chronic infection.' It may be concluded that Proteus mirabilis, the most prevalent pathogen in boys in this series, predominantly involves younger patients and is associated with fewer clinical signs and urinary findings, higher urinary pH, a relatively benign course, and a low incidence of structural abnormalities of the urinary tract. REFERENCES

Red Blood Cell Carbonic Anhydrase Activity in Children with Distal Renal Tubular Acidosis

Red blood cell carbonic anhydrase activity was studied in three children with distal renal tubular acidosis, the parents of one of the patients, and in control subjects. Although each patient had distal renal tubular acidosis as defined by an inappropriately high urine pH in the face of a systemic metabolic acidosis, hyperchloremia and a low (U-B)pCO2, they differed in that two had deafness. The deafness was inherited as an autosomal recessive mode in one and by an autosomal dominant gene in the other. Red blood cell carbonic anhydrase activity was determined in hemoglobin-free hemolysate by the esterolytic action of the enzyme on the substrate p-nitrophenyl acetate. The two isoenzymes, B and C, of carbonic anhydrase were identified using polyacrylamide disc gel electrophoresis. The red blood cell carbonic anhydrase activity of nine control children aged 2-10 years was 3.8 (3.2-5.0) units/g Hb. The values obtained from the three patients were 3.0, 3.7, and 4.36 units/g Hb. These did not differ from those of the control subjects. No abnormalities were found in the ratios of the B and C peaks or in their electrophoretic mobility.

Some unusual features of gouty arthritis in females

Gouty arthritis in females is relatively infrequent, although the sex ratio may be somewhat altered in different races. A positive family history is relatively prevalent among females whose onset of gout is premenopausal. In those patients with a postmenopausal onset, the incidence of diuretic-associated gout is high. The bimodal distribution of serum urate might be related to some variance of genetic transmission in female gout. Hypertension and coronary heart disease are common coexisting conditions, as is true of gouty arthritis in males. Chronic urinary tract infection dating from previous pregnancies is a frequent complication. The relative prevalence of proteinuria and diminished renal function leads to increased hyperuricemia, with a tendency to a low urinary uric acid output. This explains in part the higher incidence of extensive tophaceous deposition but lower incidence of renal calculi. Diuretics are associated with a higher urine pH, likewise, they reduce the urinary uric acid excretion. This also may contribute to the lower incidence of renal calculi. There may be some statistical support for the low fertility rate among the gouty females. Only two females became pregnant after the onset of gouty arthritis. All other pregnancies occurred before the onset of arthritis. Even then, abnormal pregnancies were relatively frequent. Some hormonal malfunction among the gouty females cannot be discounted. Both renal calculi and tophi are frequent in female gout associated with blood dyscrasias. They may manifest early, preceding the first attack of acute gouty arthritis. In both the male and female secondary gout, the primary underlying disease governs the uric acid metabolism and the clinical symptomatology of gout. The predominant role in pathogenesis is the excessive rate of uric acid production, and its disposal is governed by the different stages of the underlying disease and the treatment. Thus, secondary gout in females appears to be somewhat different from primary gout in females, but not different from secondary gout in males.

Renal tubular acidosis: practical guides to diagnosis and treatment.

The syndrome of renal tubular acidosis in some one of its various forms should be suspected when an infant or child has failure to thrive, metabolic acidosis, constipation, diarrhea, vomiting, anorexia, polyuria, or dehydration in infancy. Confirmatory biochemical findings include an inappropriately high urinary pH, inadequate acid excretion and/or abnormal tubular reabsorption of filtered bicarbonate. Growth can be normal when there is sustained correction of the metabolic acidosis through appropriate alkaline therapy.