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Adaptation to respiratory acidosis in the turtle bladder.

The effect of in vivo respiratory acidosis for 4 and 48 hr was examined in the turtle bladder by placing turtles in hypercapnic chambers. Blood pH was significantly lowered and pCO2 was significantly elevated over control values both 4 and 48 hr, while blood bicarbonate was only increased after 48 hr. In vitro rates for H+ secretion determined by the reverse short-circuit current were significantly greater in bladders from 48 hr of respiratory acidosis than those of controls (27.3 +/- 2.7 vs 20.6 +/- 1.7 microA, P less than 0.05). In vitro rates for HCO3- secretion determined by pH stat were not altered. Fluorescence microscopy was used to study cell morphology. The number of carbonic anhydrase cells (corrected for the total number of cells) as determined by four different fluorescence stains (6-carboxyfluorescein, rhodamine 123, acridine orange, and 3,3'-diethyloxacarbocyaninine iodide) was increased both after 4 and 48 hr of respiratory acidosis. However, the number of HCO3(-)-secreting (beta subtype) carbonic anhydrase cells, determined by a probe for the anion exchanger, NBD-taurine, was not increased. In vitro 1% CO2 for 4 hr also resulted in an increase in H+ secretion and in the number of 6-carboxyfluorescein-positive cells, both of which could be blocked with SITS pretreatment. We conclude that CO2 changes the mucosal cells more toward the carbonic anhydrase phenotype, and that if NBD-taurine accurately identifies the beta cells, that the adaptation produces or recruits more alpha-carbonic anhydrase cells.

Acidosis, Respiratory↗

Helium-oxygen mixtures in intubated patients with status asthmaticus and respiratory acidosis.

Seven patients with status asthmaticus intubated for respiratory failure who had elevated airway pressures and persistent respiratory acidosis were successfully ventilated using a mixture of 60 percent helium and 40 percent oxygen. All patients experienced a rapid reduction in airway pressures, CO2 retention, and resolution of acidosis while breathing a helium-oxygen mixture. There were no untoward effects. Helium-oxygen mixtures improve ventilation by reducing the Reynolds number and reducing density dependent resistance. Helium's beneficial effects are due to its high kinematic viscosity, high binary diffusion coefficient for CO2, and high diffusivity. Helium-oxygen mixtures should be considered for use in mechanically ventilated asthmatics with respiratory acidosis who fail conventional therapy.

Acidosis, Respiratory↗

One year period prevalence study of respiratory acidosis in acute exacerbations of COPD: implications for the provision of non-invasive ventilation and oxygen administration.

BACKGROUND: Non-invasive ventilation (NIV) reduces mortality and intubation rates in patients with chronic obstructive pulmonary disease (COPD) admitted to hospital with respiratory acidosis. This study aimed to determine the prevalence of respiratory acidosis in patients admitted with COPD, to draw inferences about oxygen therapy, and to determine the need for NIV services for acute COPD in typical UK hospitals. METHODS: This one year prospective prevalence study identified patients with COPD aged 45-79 years inclusive who were admitted to Leeds General Infirmary, St James's University, and Killingbeck Hospitals, Leeds between 1 March 1997 and 28 February 1998. The prevalence of respiratory acidosis and the relationship with oxygenation are described. Other outcomes included intensive care use and in hospital mortality. From this data population prevalence estimates were determined for respiratory acidosis, from which the need for NIV in a typical district general hospital was modelled. RESULTS: 983 patients were admitted, 11 of whom required immediate intubation. 20% of the remaining 972 had a respiratory acidosis. Acidosis was associated with subsequent admission to the intensive care unit (ICU): pH<7.25, OR 6.10 (95% confidence interval (CI) 1.19 to 31.11); pH 7.25-7.30, OR 8.73 (95% CI 2.11 to 36.06). pH was inversely correlated with arterial oxygen tension (PaO(2)) in the 47% of patients who were hypercapnic, with a PaO(2) of >10 kPa being associated with acidosis in most hypercapnic patients. 80% remained acidotic after initial treatment, giving an age/sex specific prevalence for England and Wales of 75 (95% CI 61 to 90)/100 000/year for men aged 45-79 years and 57 (95% CI 46 to 69)/100 000/year for women. Modelling the need for NIV for all COPD patients indicates that a typical UK hospital will admit 90 patients per year with acidosis of which 72 will require NIV. CONCLUSIONS: In patients with acute COPD the PaO(2) should be maintained at 7.3-10 kPa (SaO(2) 85-92%) to avoid the dangers of hypoxia and acidosis. If all COPD patients with a respiratory acidosis (pH<7.35) after initial treatment are offered NIV, a typical UK hospital will treat 72 patients per year.

Acidosis, Respiratory↗

Effect of metabolic or respiratory acidosis on rabbit renal medullary proton-ATPase.

Distal urinary acidification is thought to be mediated by an H+-ATPase sensitive to N-ethylmaleimide and dicyclohexyl-carbodiimide. We have studied the effect of chronic metabolic acidosis (NH4Cl for 3 days) or respiratory acidosis (inhalation of 10% CO2 for 2 days) on the H+-ATPase of plasma membranes prepared from the medulla. The enzymatic assay for the H+-ATPase was performed in the presence of ouabain and oligomycin and in the absence of Ca. H+-transport activity was assessed by the quenching of acridine orange in the presence of ATP. The 15-25% sucrose gradient fraction was enriched 40-fold in enzymatic activity over the homogenate, and 8-fold in enzymatic activity and 4-fold in H+-transport activity over the fluffy fraction (38,000 X g). Metabolic acidosis (pH less than 7.31) or chronic hypercapnia (PCO2 greater than 66 mmHg; 1 mmHg = 133.3 Pa) was induced for 2-3 days. Both groups showed the same enrichment factor in enzymatic and H+-transport assays as the control rabbits. Enzymatic and H+-transport activities, however, were not different between animals with respiratory acidosis and controls. Kinetic studies failed to disclose an increase in Vmax (673 vs. 702 mumol/(mg protein.min] or a decrease in Km (0.43 vs. 0.48 mM) in chronic hypercapnia as compared with controls. Metabolic acidosis also failed to increase H+-ATPase activity. These data demonstrate that the H+-ATPase of renal medulla does not display the expected increase in activity during acidosis. The role of this H+-ATPase in the adaptation to acidosis remains to be determined.

Acidosis↗

Effect of respiratory acidosis on ventricular shunt flow and hemodynamics in dogs with ventricular septal defect.

The effects of respiratory acidosis on ventricular shunt flow and hemodynamics were studied in 20 anesthetized dogs with a ventricular septal defect and a normal pulmonary vascular bed. The interventricular shunt flow was measured directly by using a specially designed electromagnetic flow probe. Respiratory acidosis was produced by hypoventilation and tachypnea with constant minute volume. Hypoxemia was also induced by hypoventilation, but not by tachypnea with constant minute volume. Systemic vascular resistance was increased in severe hypoventilation at 100 and 50 ml of tidal volume, and tachypnea at 100 ml of tidal volume. However the increase of pulmonary vascular resistance was observed in only severe hypoventilation: arterial pH 6.9, PaO2 24 mmHg, and PaCO2 88 mmHg. Left to right ventricular shunt flow and pulmonary blood flow were increased significantly with no change of systemic blood flow in both conditions of respiratory acidosis. The diastolic fraction of shunt flow was increased significantly. These findings indicate that the increase of left to right shunt flow in respiratory acidosis might be one of the risk factors of congestive heart failure for the patients with ventricular septal defect.

Acidosis, Respiratory↗

Dialysis-induced respiratory acidosis.

The inability to increase alveolar ventilation can lead to CO2 retention and acute respiratory acidosis in patients with ventilatory limitation. In this case, a young woman receiving maximum ventilatory support was unable to excrete excess CO2, associated with increasing dianeal concentrations of peritoneal dialysis. Since the patient's lung disease had necessitated a large amount of ventilatory support, the patient was unable to increase VE appropriately to handle excess CO2. Peritoneal dialysate was an additional source of carbohydrates. Peritoneal dialysate is an additional carbohydrate source that may result in hypercapnia and respiratory acidosis in patients with respiratory compromise. To our knowledge, this is the first case report in an adult which demonstrates that peritoneal dialysis with high glucose loads produced an acute respiratory acidosis that was reversed by decreasing the glucose concentrations in the dialysate. Excess CO2 production should be considered with respiratory disorders associated with dialysis.

Acidosis, Respiratory↗

Effects of acute respiratory acidosis on water and electrolyte transport in the human ileum.

Animal experiments have shown that acute respiratory acidosis stimulates water, Na and Cl absorption and HCO3 secretion in the ileum. The aim of this study was to investigate whether the human ileum also responds to changes in systemic acid-base balance. Seven healthy volunteers (mean age 24, range 21-29 years) underwent segmental ileal perfusion using a multi-lumen tube assembly with a proximal occluding balloon. A 30 cm test segment was perfused under steady state conditions with a plasma-like electrolyte solution containing PEG as a non-absorbable volume marker. After a control period, respiratory acidosis (blood pCO2 56.2 mmHg, pH 7.29 and [HCO3] 26.4 mmol l-1) was induced by CO2-breathing over a period of 50 min. Acute respiratory acidosis stimulated net HCO3 secretion in patients secreting HCO3 and reduced absorption in patients exhibiting net HCO3 absorption. These changes were immediate and appeared to be at least partly reversible. Net water, Na, K and Cl movement were not affected. The data suggest that HCO3 transport in the human ileum responds to acute respiratory acidosis.

Acid-Base Equilibrium↗

Adrenergic mechanisms and the pulmonary vascular response to respiratory acidosis.

The role of sympathetic mechanisms in mediating the pulmonary vasoconstrictor response to respiratory acidosis was studied in intact dogs. Arterial oxygen tension and ventilation were maintained at resting levels and the response was studied during a constant level of alpha- and beta-adrenergic blockade. There were significant increases in the pulmonary vascular resistance (PVR) and pulmonary perfusion pressure and no change in pulmonary blood flow (Q) when the dogs breathed 5% CO2 for 10 min. The alpha-adrenergic blocking agent, phenoxybenzamine, did not significantly alter the pulmonary vascular response, while the beta-adrenergic blocking agent, propranolol, enhanced the response. Phenoxybenzamine significantly reduced the resting pulmonary perfusion pressure from control values, while propranolol did not alter it. Both propranolol and phenoxybenzamine produced comparable decreases in the resting Q from control values. The resting PVR increased to a greater extent with propranolol than with phenoxybenzamine. These results indicate that adrenergic mechanisms do not play a role in mediating rise in PVR induced by respiratory acidosis. The finding that the pulmonary vasoconstrictor response to respiratory acidosis is enhanced during beta-adrenergic blockade suggests that vasoconstrictor alpha-receptors may be unmasked during beta-adrenergic blockade. Finally, the studies suggest that both alpha- and beta-receptors contribute to maintaining the resting PVR.

Acidosis, Respiratory↗

Severe pectus excavatum associated with cor pulmonale and chronic respiratory acidosis in a young woman.

Pectus excavatum has never been reported to cause hypercapnic respiratory failure. In this report, we describe the first such case in a young woman with severe pectus excavatum who presented with chronic respiratory acidosis, pulmonary hypertension, and chronic cor pulmonale. An extensive diagnostic workup failed to uncover any other cause of respiratory acidosis, which led us to conclude that the severe chest wall deformity and the resulting severe restrictive defect were responsible for the development of chronic respiratory acidosis and cor pulmonale.

Acidosis, Respiratory↗

Glucocorticoids and the renal Na-H antiporter: role in respiratory acidosis.

We examined the role of glucocorticoids in the activity of the renal brush border Na-H antiporter under baseline conditions (5% CO2 gassing) and during respiratory acidosis (10% CO2 gassing) in cultured monolayers of a proximal tubule suspension (primary cultures of the proximal tubule). Primary cultures of the proximal tubule showed an adaptive increase in renal brush border Na-H antiporter activity in response to respiratory acidosis in presence but not in the absence of physiologic concentrations of hydrocortisone in the medium. The effect of hydrocortisone to increase the activity of the renal brush border Na-H antiporter in respiratory acidosis could also be elicited by dexamethasone. Deletion of hydrocortisone from the medium also impaired the baseline activity of the Na-H antiporter. The effect of hydrocortisone to increase the activity of the Na-H antiporter under baseline conditions and during respiratory acidosis was elicited by physiologic concentrations of the hormone and 100-fold increase in concentration did not further increase the activity of the Na-H antiporter. These results demonstrate that the presence of physiologic concentrations of glucocorticoids are necessary for the baseline activity of the renal brush border Na-H antiporter and its adaptive increase in response to respiratory acidosis.

Acidosis, Respiratory↗

Effect of respiratory acidosis on hypoxic newborn myocardium.

We studied the effect of respiratory acidosis (pH = 6.8) on mechanical function, tissue adenosine triphosphate (ATP), and effluent creatine kinase (CK) in isolated arterially perfused hypoxic newborn and adult rabbit hearts. In the oxygenated muscle, acidosis reduced tension (T) and maximal tension first derivative [+ dT/dt (max)] in the adult more than in the newborn. In the adult hypoxic and reoxygenated hearts, acidosis during hypoxia (not reoxygenation) improved the recovery of T, + dT/dt (max) and tissue adenosine triphosphate (ATP) and reduced CK release and the rise in the resting tension. In the newborn heart, respiratory acidosis during hypoxia had no beneficial effects on recovery of mechanical function, tissue ATP and CK release. The buffering capacity and sarcolemmal H-Na exchange rate are both higher in the newborn heart than in the adult heart. This suggests that acidosis reduces the rise in intracellular Na and Ca, that is observed during hypoxia and reoxygenation, in the adult more than in the newborn and this may explain the beneficial effect of acidosis in the adult and not in the newborn.

Acidosis, Respiratory↗

The effect of propranolol and phentolamine on serum gastrin concentration in response to respiratory acidosis in normal man.

Serum gastrin concentration and basal acid secretion were studied in normal subjects under the influence of respiratory acidosis induced by CO2 rebreathing. During the intragastric instillation of 100 ml/h 0.5 M bicarbonate a significant increase of gastrinaemia from 133 to 158 pg/ml (p less than 0.01) occurred in ten subjects during respiratory acidosis (pCO2 62 torr, pH 7.25). Under the intragastric instillation of 100 ml/h 0.1 N HCl the rise of gastrin concentration in response to CO2 rebreathing (pCO2 68 torr, pH 7.20) was not significant. The relationship between the decrease of pH and the increase of the gastrin concentration was shifted in the direction of a greater systemic acidosis compared to the results performed in the presence of a neutral intragastric pH. 50 mug/kg propranolol intravenously produced a decrease of gastrin concentrations from 145 to 127 pg/ml (p less than 0.01) and a total suppression of hypergastrinaemia in response to CO2 rebreathing, suggesting activation of beta-cell receptors in respiratory acidosis. The infusion of phentolamine in a dose of 0.6 to 1.8 mg/min. resulted in a rise of gastrin concentration from 140 to 165 pg/ml (p less than 0.01) which was not further elevated during respiratory acidosis. The basal acid secretion showed a significant rise in response to CO2 rebreathing, which was abolished by the administration of propranolol.

Acidosis, Respiratory↗