Unlike most other inborn errors of metabolism, which require advanced and expensive diagnostic techniques and complex drug and dietary management (often not feasible in developing countries), the renal tubular acidoses may be detected and treated both easily and cheaply. Diagnostic confusion is possible as this series demonstrates due to the protean clinical manifestations. Three recent cases from Port Moresby General Hospital are described and appropriate investigations and treatment discussed.
Acidosis, Renal Tubular - diagnosis ; Acidosis, Renal Tubular - metabolism ; Child, Preschool ; Female ; Humans, Infant

To evaluate urinary acidification defect and its contribution to metabolic acidosis (MA) during hemorrhagic fever with renal syndrome (HFRS), we serially analyzed acid-base balance and urinary acidification indices in 10 HFRS patients. Data of the patients were compared with those of 8 normal volunteers (NC). MA was observed in 6 of 8 patients in the oliguric phase, 5 of 7 in the early diuretic phase, 8 of 10 in the late diuretic phase and 2 of 9 in the convalescent phase. HFRS patients with MA had a higher plasma anion gap in the oliguric and early diuretic phases than NC and a higher plasma Cl/Na ratio in the late diuretic phase than NC. As compared with acid-loaded NC, HFRS patients had a higher urine pH in the oliguric, early diuretic and late diuretic phases, a higher urine anion gap (UAG) in the oliguric and early diuretic phases and a lower urinary NH4+ excretory rate in the oliguric, early diuretic and late diuretic phases. Overt distal acidification defect was observed in 6 of 8 patients in the oliguric phase, 3 of 7 in the early diuretic phase, 5 of 10 in the late diuretic phase and none of 9 in the convalescent phase. None of the convalescent patients had latent acidification defect. In conclusion, urinary acidification defect is marked in the oliguric and diuretic phases of severe HFRS and may play a role in the development of a high anion gap (AG) metabolic acidosis in the earlier phase and hyperchloremic MA in the later phase, but rapidly recovers in the convalescent phase.
Acidosis, Renal Tubular/urine ; Acidosis, Renal Tubular/metabolism ; Hemorrhagic Fever with Renal Syndrome/urine ; Hemorrhagic Fever with Renal Syndrome/metabolism ; Human

Fumaric aciduria(fumarase deficiency) is a rare inborn error of metabolism resulted from a deficiency of fumarase, one of the constituent enzymes of the Krebs tricarboxylic acid cycle. Enzyme deficiency causes excessive urinary excretion of fumaric acid due to a defective conversion of fumaric acid to malic acid. It usually presents early in infancy with a severe encephalopathy including hypotonia, developmental retardation and frequent seizures. We report a case of suspected fumarase deficiency presenting with persistent mild metabolic acidosis associated with moderate hydrocephalus in a newborn infant.
Acidosis* ; Citric Acid Cycle ; Fumarate Hydratase* ; Humans ; Hydrocephalus ; Infant, Newborn* ; Metabolism ; Muscle Hypotonia ; Seizures

3-Methylcrotonyl-CoA carboxylase(MCC) is a biotin-dependent enzyme involved in the leucine metabolism. We describe a patient with MCC deficiency who manifested with Reye syndrome-like illness with status epilepticus, metabolic acidosis, hypoglycemia, hyperammonemia, elevated liver enzymes and neurologic impairments after a viral gastroenteritis and then suffered from Lennox-Gastaut syndrome. Urinary organic acid analysis revealed increased excretions of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine. This patient was managed with a leucine restriction diet and supplementation of biotin and carnitine, which was not so effective. He suffered from neurologic sequelae such as Lennox-Gastaut syndrome, motor and cognitive impairements.
Acidosis ; Biotin ; Carnitine ; Diet ; Gastroenteritis ; Humans ; Hyperammonemia ; Hypoglycemia ; Leucine ; Liver ; Metabolism ; Status Epilepticus

Mitochondrial diseases are classified into the three major categories, defects of fatty acid oxidation, defects of pyruvate metabolism, and defects of the respiratory chain, and all of these cause severe neurologic dysfunction in the newborn period. Defects of the mitochondrial respiratory chain present as recurrent apnea, seizures, congenital lactic acidosis, hypotonia, hepatic dysfunction and hypertrophic cardiomyopathy in the neonatal period. Laboratory findings of hyperlactataemia(>2.5mM), elevated lactate/pyruvate(L/P) ratio(>20) and ketone body ratio(>2) suggest the diagnosis of mitochondrial respiratory chain defects. We report a case of mitochondrial respiratory chain defect diagnosed in the neonatal period presenting with multiorgan failure consisting of severe metabolic acidosis, comatous mental state, respiratory distress, hepatic dysfunction, renal failure with lactic acidosis(24mM), increased L/P ratois (55.6) and ketonuria (increased ratio of 3-hydroxybutyrate/acetoacetate).
Acidosis ; Acidosis, Lactic ; Apnea ; Cardiomyopathy, Hypertrophic ; Diagnosis ; Electron Transport* ; Humans ; Infant, Newborn ; Ketosis ; Metabolism ; Mitochondrial Diseases ; Muscle Hypotonia ; Neurologic Manifestations ; Pyruvic Acid ; Renal Insufficiency ; Seizures

Primary hyperparathyroidism is a generalezed disorder of calcium, phosphorus and bone metabolism due to an increased secretion of parathyroid hormone. Single parathyroid adenoma is the most common cause of primary hyperparathyroidism. Because parathyroid hormone has been proposed as an important inhibitor of renal bicarbonate reabsorption of proximal tubule, proximal renal tubular acidosis is not rare in primary hyperparaphyroidism. After parathyroid resection, significant hypocalcemia and hypophosphatemia requiring prolonged medical management may develop, termed hungery bone syndrome. We experienced a case of primary hyperparathyroidism associated with proximal renal tubular acidosis, and severe hungry bone syndrome after resection of the adenoma of parathyroid gland.
Acidosis ; Acidosis, Renal Tubular ; Adenoma ; Calcium ; Hyperparathyroidism, Primary ; Hypocalcemia ; Hypophosphatemia ; Kidney Tubules, Proximal ; Metabolism ; Parathyroid Glands ; Parathyroid Hormone ; Parathyroid Neoplasms ; Phosphorus

To evaluate the nutritional status according to the degree of metabolic acidosis(MA) and determine that MA is a risk factor for malnutrition, we screened the laboratory data of 37 hemodialysis(HD) patients who were clinically stable for more than 6 months and taken bioelectrical impedence analysis(BIA) twice 6 months apart to check lean body mass (LBM). Mean age of patients was 49.1+/-15.0 years and sex ratio 1:2.4. Mean serum albumin level was 3.97+/-0.36g/dl and weekly Kt/V and normalized protein catabolic rate(nPCR) were 3.04+/-0.85 and 0.99+/-0.21g/kg/day. According to mean total CO2 content during the periods between BIA, the patients were divided to three groups[group 1(n=16):&18mEq/L, group 2(n=9):18< or =tCO2&21mEq/L, group 3(n=12):> or =21mEq/L). Group 1 had significantly higher body weight gain than group 2 and 3(1.82+/-1.62 vs. 0.77+/-3.13 and 1.35+/-3.85kg, P<0.05), and higher LBM gain(1.99+/-4.38 vs. 3.35+/-7.99kg, P<0.05), nPCR(1.05+/-0.20 vs. 0.91+/-0.13g/kg/day, P<0.05), intact parathyroid hormone(88.4+/-78.7 vs. 32.0+/-26.5pg/ml, P< 0.05), and phosphate(5.4+/-1.3 vs. 3.9+/-1.3mg/dl, P< 0.05) than group 3. There were no differences in age, serum albumin, BUN, creatinine and weekly Kt/V among three groups. Mean total CO2 level was inversely correlated with body weight gain and LBM gain. In conclusion, metabolic acidosis in stable HD patients may be the result of high protein intake and not related to decrease of body weight by protein catabolism.
Acidosis* ; Body Weight ; Creatinine ; Humans ; Malnutrition ; Metabolism ; Nutritional Status ; Renal Dialysis* ; Risk Factors ; Serum Albumin ; Sex Ratio

HCO3(-) reabsorption in the renal tubules plays a critically important role in maintaining the global acid-base balance. Loss of HCO3(-) causes metabolic acidosis. Proximal renal tubule is the major site for HCO3(-) reabsorption, accounting for more than 80% of total HCO3(-) reabsorption along the nephron. Over the past more than half centuries, tremendous progresses have been made on understanding the molecular mechanisms underlying the HCO3(-) reabsorption in proximal tubules. The transepithelial movement of HCO3(-) involves the coordinated operation of machineries on both the apical and the basolateral membranes of the epithelial cells. On the apical domain, Na(+)-H(+) exchanger NHE3 and the vacuolar H(+)-ATPase are two major pathways mediating the apical uptake of HCO3(-)-related species. Taken together, NHE3 and H(+)-ATPase are responsible for about 80% of HCO3(-) reabsorption in the proximal tubule. The remaining 20% is likely mediated by pathways yet to be characterized. On the basolateral membrane, NBCe1 represents the only major known pathway mediating the extrusion of HCO3(-) coupled with Na(+) into the interstitial space. In the present article, we provide a historical view about the studies on the mechanisms of HCO3(-) reabsorption since 1940s. Moreover, we summarize the latest progresses emerging over the past decade in the physiological as well as pathological roles of acid-base transporters underlying the HCO3(-) reabsorption in proximal tubules.
Acidosis ; physiopathology ; Animals ; Bicarbonates ; metabolism ; Humans ; Kidney Tubules, Proximal ; physiopathology ; Sodium-Hydrogen Exchangers ; physiology ; Vacuolar Proton-Translocating ATPases ; physiology

OBJECTIVE: To investigate the effects of acid-sensing ion channels (ASICs) on electrophysiological epileptic activities of mouse hippocampal pyramidal neurons in the extracellular acidotic condition. METHODS: We investigated effects of extracellular acidosis on epileptic activities induced by elevated extracellular K concentration or the application of an antagonist of GABA receptors in perfusate of mouse hippocampal slices under field potential recordings. We also tested the effects of extracellular acidosis on neuronal excitability under field potential recording and evaluated the changes in epileptic activities of the neurons in response to pharmacological inhibition of ASICs using a specific inhibitor of ASICs. RESULTS: Extracellular acidosis significantly suppressed epileptic activities of the hippocampal neurons by converting ictal-like epileptic activities to non-ictal-like epileptic activities in both high [K ]o and disinhibition models, and also suppressed the intrinsic excitability of the neurons. ASICs inhibitor did not antagonize the inhibitory effect of extracellular acidosis on ictal epileptic activities and intrinsic neuronal excitability, but exacerbated non-ictal epileptic activities of the neurons in extracellular acidotic condition in both high [K]o and disinhibition models. CONCLUSIONS ASICs can differentially modulate ictal-like and non-ictallike epileptic activities via its direct actions on excitatory neurons.
Acid Sensing Ion Channels ; metabolism ; Acidosis ; Animals ; Epilepsy ; physiopathology ; Hydrogen-Ion Concentration ; Mice ; Pyramidal Cells ; pathology ; physiology

The sudden onset of respiratory acidosis or alkalosis due to inadequate ventilation during general inhalation anesthesia may influence the action of neuromuscular blocking agents. In virtro animal studies by Funk et al.(1980) suggested that the neuromuscular blocking action of Org NC 45(NC) was minimally depressed above pH 7.68 and significantly potentiated under acidotic conditions(pH 7.05). They proposed that this was the result of an increase in NC metabolism by alkaline hydrolysis in the alkalotic state and greater molecular stability during acidosis. This study was performed to determine the effects of the neuromuscular blocking action of NC during respiratory acidosis and alkalosis. The patients were divided in to 3 groups: 1, ll & lll and experienced normocarbia, hypocarbia and hypercarbia, respectively. Hypocarbia was induced by hyperventilation and hypercarbia by adjustment of a rebreathing valve in the CO2 absorber in the semiclosed system. Simultaneously, arterial blood samples were collected from radial arteries for arterial blood gas analysis including pH and pCO2. Following the administration of succinylcholine(SCC) and the recovery of a 75% twitch height, ED95 of NC was given to the patient and the results were recorded by an evoked electromyograph (NMT, Datex). The results are follows: 1) The number of patients in groups l, ll and lll were 22, 13 and 8, respectively. The patients in each group were evenly distributed with respect to age, body weight and anesthesia. 2) The end-tidal CO2 tension in group l, ll and lll group was 38.86+/-4.62, 20.23+/-2.42 and 52.00+/-4.86mmHg, and the arterial pCO2(pH) was 37.36+/-5.71(7.461+/-0.054), 23.00+/-1.51(7.649+/-0.032) and 53.29+3.35 mmHg(7.314+/-0.026), resptectively. The end-tidal CO2 tension, arterial CO2 tension and pH in group ll and lll were significantly different from those of group l(p<0.05). 3) The onset time of SCC in group ll and lll was shorter than that in group l (p<0.05), but within 1 min in all groups. The duration of SCC in group lll(19.56+/-6.15min) was longer than that in group l (14.74+/-4.56min) (p<0.05). 4) Although there was no significant difference among the groups with respect to onset time and duration, the recovery index in group ll(10.29+/-2.21min) was significantly different from group l and lll(14.76+/-5.26 and 13.50+/-13.67 min, respectively) (p<0.05). After administration of NC in 5 min intervals, twitch tension was measured and the results were inserted into a regression equation which emphasized the delayed recovery in group lll(r=0.87). In conclusion, the recovery index in alkalosis shortened and the initial twitch tension in acidosis following NC administration was delayed compared to that in normocapnis and alkalosis. Patients with alkalosis may require more frequent doses of NC and continuous monitoring following repeated or continuous infusion in acidosis.
Acid-Base Equilibrium ; Acidosis ; Acidosis, Respiratory ; Alkalosis ; Anesthesia ; Anesthesia, Inhalation ; Animals ; Arterial Pressure ; Blood Gas Analysis ; Body Weight ; Humans ; Hydrogen-Ion Concentration ; Hydrolysis ; Hyperventilation ; Metabolism ; Neuromuscular Blockade* ; Neuromuscular Blocking Agents ; Radial Artery ; Vecuronium Bromide* ; Ventilation