salicylates and Acidosis--Respiratory

Topics: Acidosis, Respiratory; Acute Disease; Age Factors; Animals; Central Nervous System; Hyperventilation; Oxidative Phosphorylation; Poisoning; Rabbits; Rats; Salicylates

We examined the effect of respiratory acidosis on the Na-HCO3 cotransporter activity in primary cultures of the proximal tubule of the rabbit exposed to 10% CO2 for 5 min, 2, 4, 24 and 48 hr. Cells exposed to 10% CO2 showed a significant increase in Na-HCO3 cotransporter activity (expressed as % of control levels, 5 min: 142 +/- 6, 2 hr: 144 +/- 13, 4 hr: 145 +/- 11, 24 hr: 150 +/- 15, 48 hr: 162 +/- 24). The increase in activity was reversible after 48 hr. The role of protein kinase C (PKC) on the stimulatory effect of respiratory acidosis on the cotransporter was examined in presence of PKC inhibitor calphostin C or in presence of PKC depletion. Both calphostin C and PKC depletion prevented the effect of 10% CO2 for 5 min or 4 hr to increase the activity of the cotransporter. 10% CO2 for 5 min or 4 hr increased total and particulate fraction PKC activity. To examine the role of phosphotyrosine kinase (PTK) on the increase in cotransporter activity we studied the effect of two different inhibitors, 2-hydroxy-5-(2,5-dihydroxylbenzyl) aminobenzoic acid (HAC) and methyl 2,5-dihydroxycinnamate (DHC) which inhibit phosphotyrosine kinase in basolateral membranes. Cells were pretreated either with vehicle or HAC or DHC and then exposed to 10% CO2 for 5 min or 4 hr. In cells treated with vehicle, 10% CO2 significantly increased cotransporter activity as compared to control cells exposed to 5% CO2. This stimulation by 10% CO2 was completely prevented by HAC or DHC at 5 min (5% CO2: 1.8 +/- 0.2, 10% CO2: 2.6 +/- 0.2, 10% CO2 + HAC: 1.6 +/- 0.2, 10% CO2: +DHC: 2.0 +/- 0.3 pH unit/min) and also at 4 hr. The protein synthesis inhibitors actinomycin D and cycloheximide appear to prevent the effect of 10% CO2 for 4 hr on the cotransporter. Our results show that early respiratory acidosis stimulates the Na-HCO3 cotransporter through PKC and PTK-dependent mechanisms and the late effect appears to be mediated through protein synthesis.

Topics: Acidosis, Respiratory; Adaptation, Physiological; Aminobenzoates; Animals; Carbon Dioxide; Carrier Proteins; Cells, Cultured; Cinnamates; Cycloheximide; Dactinomycin; Enzyme Inhibitors; Kidney Tubules, Proximal; meta-Aminobenzoates; Protein Kinase C; Protein Synthesis Inhibitors; Protein-Tyrosine Kinases; Rabbits; Salicylates; Sodium-Bicarbonate Symporters

Noncardiogenic pulmonary edema occurs in 35% of salicylate-intoxicated patients who are over 30 years old. Cigarette smoking, chronic salicylate ingestion, a component of metabolic acidosis, and the presence of neurological symptoms on admission are strong risk factors for the subsequent development of pulmonary edema in the appropriate age group. In the absence of these risk factors, salicylate-induced pulmonary edema is rare. The etiology is multifactorial, but it centers around altered vascular permeability in the lungs.

Topics: Acidosis; Acidosis, Respiratory; Adolescent; Adult; Aged; Capillary Permeability; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Lung; Male; Middle Aged; Pulmonary Edema; Radiography; Risk; Salicylates; Smoking

This study examined the acid-base disturbances in 67 adults with salicylate intoxication. On admission, 66 patients had an acid-base distrubance. In contract to previous suggestions, however, only 25% of the patients had simple respiratory alkalosis. Unlike salicylate intoxication in children, 33% of these adults with salicylate intoxication had ingested additional drugs. These additional drugs generally were CNS depressants and were important determinants of the variety of the acid-base disturbance. Those patients who ingested additional drugs had a significantly lower incidence of respiratory alkalosis (P less than .005) and a higher incidence of respiratory acidosis (P less than .005) and acidemia (P less than 0.25). The incidence of acidemia correlated with the presence of neurological symptoms.

Topics: Acid-Base Imbalance; Acidosis, Respiratory; Adolescent; Adult; Aged; Alkalosis, Respiratory; Humans; Middle Aged; Salicylates

Salicylate intoxication has been investigated in young baboons. The results of these studies are similar to these previously obtained in man. Acidosis appears to be of considerable importance in the pathogenesis of infantile salicylism as it enhances the passage of salicylate into the CSF. The CSF concentration of salicylate seems to be of major physiologic importance in this condition. Moreover, the serum concentration of free salicylate correlates more closely with the CSF concentration of salicylate than does the total serum concentration of salicylate.

Topics: Acid-Base Equilibrium; Acidosis, Respiratory; Alkalosis, Respiratory; Ammonium Chloride; Animals; Aspirin; Bicarbonates; Blood; Carbon Dioxide; Haplorhini; Hydrogen-Ion Concentration; Medulla Oblongata; Papio; Permeability; Protein Binding; Salicylates; Serum Albumin

Topics: Acid-Base Equilibrium; Acidosis; Acidosis, Respiratory; Alkalosis; Alkalosis, Respiratory; Animals; Bicarbonates; Brain; Calcium; Cerebrospinal Fluid; Humans; Hydrocephalus; Hydrogen-Ion Concentration; Hyperventilation; Intracranial Pressure; Magnesium; Potassium; Radioisotopes; Salicylates

Two carbonic anhydrase inhibitors, acetazolamide and benzolamide, are capable of increasing the toxicity of sodium salicylate in mice. Beginning at about 2 mg/kg, each of the inhibitors, in combination with a fixed (400 mg/kg) dose of salicylate, generates a dose-mortality curve that reaches a plateau at about 60% deaths at 6 to 8 mg/kg. This effect can be duplicated by 8 to 10% inspired CO2. It appears that the respiratory acidosis secondary to the inhibition of red cell carbonic anhydrase is responsible for the increased toxicity; earlier work by others shows that acidosis increases the concentration of salicylate in the brain. In the treatment of salicylate poisoning by carbonic anhydrase inhibitors, the goal is to alkalinize the urine and increase the excretion of salicylate. With the newer inhibitor, benzolamide, it is possible to dissociate the respiratory acidosis from the renal effect. Maximal alkalinization of the urine is possible with a dose (about 1 mg/kg) below that which generates a respiratory acidosis. With this dose, there is no increase in the early toxicity of salicylate.

Topics: Acetazolamide; Acidosis, Respiratory; Alkalies; Animals; Benzolamide; Carbon Dioxide; Hydrogen-Ion Concentration; Lethal Dose 50; Male; Mice; Mice, Inbred ICR; Salicylates; Thiadiazoles

Topics: Acidosis, Respiratory; Animals; Aspirin; Blood-Brain Barrier; Brain; Carbon Dioxide; Dogs; Humans; Hydrogen-Ion Concentration; Hyperventilation; Infant; Male; Oxygen; Respiratory Center; Salicylates

Topics: Acid-Base Equilibrium; Acidosis; Acidosis, Respiratory; Alkalosis; Alkalosis, Respiratory; Arteries; Asthma; Carbon Dioxide; Education, Medical; Female; Heart Arrest; Humans; Hydrogen-Ion Concentration; Infant; Keto Acids; Kidney Failure, Chronic; Male; Mathematics; Middle Aged; Pulmonary Edema; Respiratory Insufficiency; Salicylates; Teaching

Topics: Acidosis, Respiratory; Adolescent; Aged; Aspirin; Child, Preschool; Citrates; Female; Humans; Lactates; Malates; Male; Salicylates