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[Severe hypokalemia with paralysis in a patient with distal renal tubular acidosis as an initial expression of Sjögren's syndrome].

In a 33-year-old woman with a recent flaccid paralysis of the arms and legs, laboratory tests demonstrated a severe hypokalemia with hyperchloremic metabolic acidosis and abnormally acidified urine. The urinary anion gap was positive in the presence of acidosis, thus establishing the diagnosis of distal renal tubular acidosis. The patient made a full recovery after potassium and alkali replacement. Further investigation revealed Sjögren's syndrome as the underlying cause.

Acid-Base Equilibrium↗

Adaptations in metabolic acidosis: a reinterpretation.

Hydrochloric-acid induced acidosis reduced urea excretion in the rat, with an equimolar increase in NH+4 excreation and no change in their sum. By contrast, in the guinea pig, where ammonium excretion is small, HC1 administration did not effect urea excretion. Ammonium administered as NH4HCO3 was excreted mainly in the form of urinary urea, whereas that administered as NH4C1 was mainly in the form of ammonium. Methionine sulphoximine did not impair the increased ammonium excretion induced by acidosis, but did lead to a marked decrease in plasma glutamine levels and an overall increase in total urinary urea and ammonium nitrogen excretion. A reinterpretation of some aspects of the adaptations to metabolic acidosis is made based on these findings.

Acidosis↗

Lactic acidosis and anti-retroviral drugs.

(1) Lactic acidosis is a serious, often fatal adverse reaction to nucleoside HIV reverse transcriptase inhibitors. (2) The presenting symptoms are non specific, and include gastrointestinal upset, fatigue, fever, and breathlessness. They appear gradually after several weeks or months of antiretroviral treatment. (3) Moderate hyperlactataemia, with few if any symptoms, is common in patients taking nucleoside inhibitors, and is not predictive of severe lactic acidosis. (4) Cases of lactic acidosis were reported in newborns whose mothers were given nucleoside inhibitors to reduce the risk of mother to child transmission of HIV. (5) In practice, hyperlactataemia should be suspected in patients taking antiretroviral drugs who present with unexplained symptoms, and especially breathlessness. Elevated lactataemia (especially above 5 mmol/l) requires rapid withdrawal of antiretroviral treatment.

Acidosis, Lactic↗

[Evaluation of the use of sodium bicarbonate in a group of children with diarrhea, 10 per cent dehydration and metabolic acidosis].

Considering the disparity of criteria regarding the use of sodium bicarbonate in the management of infants with diarrhea, dehydration and metabolic acidosis, a prospective study was done in 25 infants (13 managed without and 12 with bicarbonate) where it was demonstrated; a) The use of bicarbonate does not lead to a more rapid correction of the metabolic acidosis. b) Bicarbonate should not be used in patients with serum bicarbonate levels of 5 mEq/1. or over. c) Patients with dehydration and metabolic acidosis show hyperglycemia that returns to normal when the dehydration is corrected. This fact is of great interest because these children should not be considered nor managed as diabetics.

Acidosis↗

[Effect of PTH, phosphate, and metabolic acidosis on the progression of renal insufficiency in the azotemic rat].

In a previous study we have observed that NH4Cl-induced metabolic acidosis halted the progression of renal disease in azotemic rats with a high phosphate diet. We hypothesized that NH4Cl-induced metabolic acidosis may exert its protective effect by decreasing renal calcium content independent of serum levels of PTH and phosphate loading. To test this hypothesis we studied azotemic rats with very low phosphate diet or parathyroidectomy. Rats with low phosphate diet and parathyroidectomized rats developed renal failure after 5/6 nephrectomy, and in both groups the acid loading significantly decreased the progression of renal disease. Calcium renal content increased in both groups, even in rats with low phosphate diet, and this effect was also significantly decreased after an acid loading. Rats with acid loading developed greater hypertrophy of renal tissue than rats without acid loading. We conclude that NH4Cl-induced metabolic acidosis halted the progression of renal disease by decreasing calcium precipitation on renal tissue. Parathyroidectomy did not prevent progression of renal disease nor calcium precipitation, and a low phosphate diet in azotemic rats did not prevent increased calcium content on remnant renal tissue.

Acidosis↗

Fatal lactic acidosis and pancreatitis associated with ribavirin and didanosine therapy.

Pancreatitis and lactic acidosis are severe and life-threatening adverse events associated with nucleoside analogue antiretroviral therapy used to treat HIV infection. The drug from this class most commonly associated with these adverse events is stavudine, although zidovudine and didanosine have also been implicated. Ribavirin is a nucleoside analogue used in combination with interferon alfa to treat hepatitis C. Because of similar mechanisms of action, the combination of these 2 drugs could potentially increase such toxicity. A case of fatal lactic acidosis and pancreatitis is described in an HIV-infected patient coinfected wtih hepatitis C on a didanosine-containing antiretroviral regimen after treatment of hepatitis C was initiated with ribavirin and pegylated interferon alfa-2b. Extreme caution should be exercised when didanosine and ribavirin are used concomitantly because of the increased risk of mitochondrial toxicity and the syndrome of severe metabolic acidosis with elevated lactic acid levels.

Acidosis, Lactic↗

[The correction of metabolic acidosis by the instillation of 0.1N sodium hydroxide in an experimental model].

The critically ill patient, during the natural course of the disease often presents acid-base disturbances acidosis being the most common metabolic problem. Sodium bicarbonate has been used, for its correction but due to complications its use is restricted. In the present experimental study, mixed race dogs were artificially induced metabolic acidosis with in chloride acid. Arterial and venous blood gases were determined. Afterwards 0.1N sodium hydroxide was administered in the same amount statistically demonstrating modifications, in the pH values, as well as an excess of arterial and venous base which indicates the possibility of using this substance in humans to correct metabolic acidosis.

Acidosis↗

[Vitamin D3 overdosage due to rashly diagnosed rachitis in a child with distal tubular acidosis].

Metabolic acidoses are diseases causing many diagnostic and therapeutic problems. Compensated metabolic acidosis can be unrecognised for a long time. This refers especially to isolated renal tubular acidosis (RTA). Unrecognised RTA causes calcium and phosphorus balance disturbances with clinical signs of improper bone mineralization. It happens that some patients with mentioned problems are "treated" as rachitic and take high doses of vitamin D. As a result, serum calcium and phosphates as well as urine calcium increase, without the satisfied influence on bone mineralization. We present a case of a 3.5 months old baby, who was "treated" as ricket in vitamin D deficiency. This baby was "cured" with high doses of cholecalciferol (0.0875 mg/24h for 2 weeks, then 0.175 mg/24h for 3 weeks) because of craniotabes. This treatment was carried on without any metabolic tests and caused the following disturbances: 25(OH)D serum level - 102.7 ng/ml (normal 11-54), 1,25(OH)2D serum level - 39.5 pg/ml (normal 15-70), calcaemia 2.7-2.85 mmol/l, phosphataemia 2.1 mmol/l. In this time the considerable hipercalciuria (second morning urine sample Ca/cr ratio 2.06 mmol/mmol) occurred. The other laboratory test showed as follows: serum albumins 4.5 g/dl, alkaline phosphatase 188 U/l, acid phosphatase 10.7 U l, Cl- 114.9 mmol/l, Na 146 mmol/l, K 4.8 mmol/l, HCO3a 16.6-20.1 mmol/l and pCO2 3.63-3.85 kPa, serum anion gap 11 mEq/l; pH of morning urine 6.5-7. These results suggested the presence of distal RTA aside from symptoms of vitamin D overdosage. The high serum levels of calcium and phosphates, craniotabes, rather low serum alkaline phosphatase activity and presence of metabolic acidosis the symptoms after the normalisation of calcium and phosphorus balance suggested that the distal RTA had been prior to calcium disturbances.

Acidosis, Renal Tubular↗

Metformin-associated lactic acidosis and acute renal failure in a type 2 diabetic patient.

Metformin belongs to a class of drugs known as the biguanides that are widely used in the treatment of type 2 diabetes mellitus. Its association with lactic acidosis is well established, although rare. Metformin-associated lactic acidosis is recognized as a potentially lethal condition that can occur in patients with contraindications to the drug, such as renal dysfunction, liver diseases, alcoholism, and cardiopulmonary diseases. In these cases, the plasma concentration of metformin is not necessarily abnormally high. We describe a 75-year-old diabetic woman with acute renal failure and life-threatening lactic acidosis due to metformin intoxication. Clinical manifestations included vomiting, diarrhea, hypothermia, hypotension and transitory blindness. Her initial renal function was recovered after hemodialysis and she was discharged 3 months after admission.

Acidosis, Lactic↗

Protein synthesis and growth in uremic rats with and without chronic metabolic acidosis.

The effects of uremia-induced chronic acidosis on fractional protein synthesis rate (FSR), degradation (FDR) and protein tissue growth (FRG) in skeletal muscle were examined in young rats fed a 30% protein diet. This diet induced acidosis in UA rats, which was corrected by NaHCO3 supplementation in UB rats. Blood pH and plasma HCO3- were 7.22 +/- 0.01 and 15.2 +/- 0.8 mmol/l in UA rats vs. 7.41 +/- 0.01 and 25.8 +/- 0.9 in UB rats. Both UA and UB groups had similar renal function and food intake. Acidosis impaired weight gain (4.0 +/- 0.3 vs. 5.0 +/- 0.4 g/day, p < 0.05) and length gain (0.31 +/- 0.02 vs. 0.42 +/- 0.02 cm/day, p < 0.001). UA and UB rats showed similar muscle FSR (10.4 +/- 0.5 vs. 10.8 +/- 0.5%/day) and RNA content (6.3 +/- 0.2 vs. 6.2 +/- 0.2 micrograms/g protein). UA rats had lower FGR than UB rats (3.9 +/- 0.8 vs. 5.9 +/- 0.6%/day, p < 0.05). Therefore, muscle FDR was increased in UA rats (6.30 +/- 0.99 vs. 5.10 +/- 0.7%/day).

Acidosis↗

[Effect of chronic acidosis on protein metabolism].

In experiments on mongrel albino male rats, we studied the effects of 30 mmol/kg lactic acid, 30 mmol/kg NaHCO3, and 20 mmol/kg NH4Cl (intraventricular injections, daily for 7 days) on the contents of total protein, residual nitrogen, urea, and creatinine in the blood, as well as on the activities of aldolase and alanine aminotranspherase (ALT). We also studied the effects of the above agents on renal functions: glomerular filtration rate (GFR), diuresis, and excretion of ammonium, creatinine, and protein with urine. We have found that chronic, hyperchloremic, and lactic acidosis resulted both in a significant decrease in the levels of protein and residual nitrogen and in an increase in the concentration of the urea; these phenomena were accompanied by a considerable intensification of the urinary NH4+ excretion. In contrast, under conditions of chronic alkalosis we observed a drop in the level of urea in the blood with no changes in the concentrations of protein and residual nitrogen, as well as a dramatic depression of the urinary NH4+ excretion. In that case, the concentration of creatinine in the blood, GFR, diuresis, and excretion of creatinine and protein with urine did not correlate with the above-mentioned changes in protein metabolism. In all experiments, the activities of aldolase and ALT preserved their normal level giving evidence against damage to the liver. These results give evidence for spending a great number of amino acids on the renal ammoniogenesis at chronical acidosis; their saving at alkalosis; an impairment of the protein synthesis, and an increase in protein catabolism at acidosis to replenish the pool of amino acids, as well as for an activation of the urea synthesis to eliminate the excessive amount of NH4+ from the blood.

Acidosis↗

[Acidosis is associated with an intracellular accumulation of Ca2+. Its role in the modulation of myocardial contractility].

Myocardial acidosis, as during ischemia, profoundly modifies excitation-contraction mechanisms. The decreased myofilament sensitivity to Ca2+ reduces contractility regardless of an intracellular accumulation of Ca2+. To determine the source for this increase in Ca2+ we evaluated the effect of acidosis on diastolic [Ca2+] and mitochondrial [Ca2+]. We used single cardiac cells loaded with the fluorescent probes, indo-1 for Ca2+ and SNARF-1 for pH. Acidosis increases [Ca2+] both in cytosol and mitochondria. The cytosolic accumulation depends, most likely, on an active release from mitochondria. A competition among Ca2+ and H+ ions may, instead, explains the increase in mitochondrial [Ca2+].

Acidosis↗

[Lactate acidosis in the course of status asthmaticus--case report].

A case report of lactate acidosis in the course of status asthmaticus in a 34 year old female is presented. The lactate acidosis was due to increased anaerobic glycolysis in respiratory muscles caused by decreased oxygen recruitment and increased oxygen consumption by respiratory muscles. The authors discuss the clinical significance of lactate acidosis and proper treatment of status asthmaticus.

Acidosis, Lactic↗

Highly active antiretroviral therapy (HAART)-associated lactic acidosis: in vitro effects of combination of nucleoside analogues and protease inhibitors on mitochondrial function and lactic acid production.

Lactic acidosis is a rare but potentially life-threatening and poorly understood sequelae among HIV-infected patients on highly active antiretroviral therapy (HAART). Mitochondrial DNA depletion and inhibition of respiratory complexes have been hypothesized to be involved in HAART-associated lactic acidosis. Although mitochondrial toxicity and increased plasma lactates are associated with long-term exposure to nucleoside analogue reverse transcriptase inhibitors (NRTI), reports of lactic acidosis are now emerging among HIV-infected patients exposed to combination therapy that includes not only NRTI but also protease inhibitors (PI). We therefore investigated the effects of clinically relevant NRTI and PI combinations on mitochondrial membrane potential, uncoupling of mitochondrial respiration from oxidative phosphorylation and lactic acid production. Our study demonstrated that treatment of HepG2 cells with a combination of nucleoside analogues and PI, decreased mitochondrial membrane potential (delta psi m) within 24 hr, followed by increased lactic acid production after 9 days of treatment. However, loss of delta psi m and increased lactates were not associated with mitochondrial uncoupling or ATP production. Our findings suggested that not only NRTI but also PI are capable of increasing lactic acid production in vitro, and probably involve early biochemical changes in mitochondrial function such as loss of mitochondrial membrane potential.

Acidosis, Lactic↗

Severe lactic acidosis and thiamine deficiency during total parenteral nutrition--case report.

We encountered a case of total parenteral nutrition-associated lactic acidosis that did not respond to sodium bicarbonate or other conventional emergency treatments. He was characterized by minimal food intake before surgery, delayed gastric emptying after pylorus-preserving pancreatoduodenectomy due to pancreas head cancer and long-term total parenteral nutrition without food intake and vitamin supplements after surgery. After thiamine administration, the patient very quickly recovered with dramatic reestablishment of the acid-base balance. We emphasize the need to supplement total parenteral nutrition with thiamine-containing vitamins for the patients whose food intake does not meet nutritional requirements and to intravenously replenish using high-dose thiamine simultaneously with the manifestation of signs and symptoms of severe lactic acidosis with unknown cause. In conclusion, thiamine deficiency should be included in the differential diagnosis of lactic acidosis for the patients who received total parenteral nutrition without food intake and vitamin supplements.

Acidosis, Lactic↗

The role of endotoxins in induced ruminal acidosis in calves.

Experimentally induced ruminal acidosis was carried out in 4 calves to investigate the possibility of resorption of endotoxins from Gram negative bacteria originating from the gastro-intestinal tract. The ruminal acidosis was induced by overfeeding of oats and the effect was evaluated by clinical and blood biochemical changes. Blood samples were collected every 2 h for 60 h before and after experimental feeding. The animals showed signs of ruminal acidosis and also the clinical and blood biochemical changes were similar to those seen after experimental endotoxaemia. However, although being less dramatic the changes in many relevant parameters such as an increase in prostaglandin F metabolite levels, body temperature, endotoxins and a decrease in iron indicate that an endotoxaemic state had occurred. The results of the present study show that ruminal acidosis/stasis is linked to resorption of endotoxins from the gastro-intestinal tract causing endotoxaemia/endotoxicosis.

Acidosis↗

[Lactic acidosis in HIV-patients--diagnosis and treatment].

Lactic acidosis is a life-threatening complication of antiretroviral therapy with an incidence of about 1% per year. Its clinical onset is often abrupt, with uncharacteristic muscular, cardiac or hepatic symptoms. Lactic acidosis is caused by nucleoside analogue reverse transcriptase inhibitors (mainly didanosine, stavudine and zalcitabine), which are relatively strong inhibitors of gamma polymerase, the enzyme responsible for the replication of mitochondrial DNA. Zidovudine is also a mitochondrial toxin, but its toxicity probably reflects several mechanisms unrelated to mtDNA-depletion. When lactic acidosis is diagnosed, nucleoside analogues and other mitochondrial toxins, such as valproic acid and acetylsalicylic acid, must be discontinued immediately. Uridine should be supplemented, a cocktail consisting of vitamins, L-carnitine and coenzyme Q10, may be given.

Acid-Base Equilibrium↗

Renal tubular acidosis in children treated with trimethoprim-sulfamethoxazole during therapy for acute lymphoid leukemia.

The antibiotics trimethoprim (TMP) and sulfamethoxazole (SMZ), when used in combination, can cause metabolic acidosis, renal bicarbonate wasting, and growth failure. Retrospective review of repeated random serum chemistries from 10 children receiving TMP-SMZ and maintenance chemotherapy for acute lymphoid leukemia revealed low serum bicarbonate (P = .0002) and elevated serum chloride (P less than .0005) concentrations. These values normalized after all medications were discontinued. Prospective study of 8 children receiving TMP-SMZ and chemotherapy for acute lymphoid leukemia revealed lower serum bicarbonate concentrations and higher urine pH following a dose of TMP-SMZ than paired values obtained more than 3 days after a dose. Four children (50%) met serum bicarbonate and urinary pH criteria for the diagnosis of renal tubular acidosis soon after a dose of TMP-SMZ. The occurrence of TMP-SMZ-induced renal tubular acidosis has implications for the acid-base balance of children receiving TMP-SMZ on a long-term basis.

Acidosis, Renal Tubular↗