Influence of chronic respiratory acid-base disorders on acute CO2 titration curve

We have recently shown that background presence of chronic metabolic acid-base disorder markedly alters in vivo acute CO2 titration curve. These studies were carried out to assess the influence of chronic respiratory acid-base disorders on response to acute hypercapnia and to explore whether the chronic level of plasma pH is the factor responsible for alterations in the CO2 titration curve. We compared whole-body responses to acute hypercapnia of dogs with preexisting chronic respiratory alkalosis (n = 8) with that of normal animals (n = 4) and animals with chronic respiratory acidosis (n = 13). Chronic respiratory alkalosis and acidosis, as well as the acute CO2 titrations, were produced in unanesthetized dogs within a large environmental chamber. For comparison with our data on chronic metabolic acidosis and alkalosis, plasma bicarbonate levels, which are secondarily altered in chronic respiratory acid-base disorders, were used as an index of chronic acid-base status of the animals. Results indicate that, as with chronic metabolic acid-base disorders, a larger increment in plasma bicarbonate occurs during acute hypercapnia when steady-state plasma bicarbonate is low (respiratory alkalosis) than when it is high (respiratory acidosis). Yet, in further analogy with the metabolic studies, plasma hydrogen ion concentration is better defended at higher plasma bicarbonate levels in accordance with mathematical relationships defined by the Henderson-Hasselbalch equation. Combined results demonstrate that the influence of chronic acid-base status on whole-body response to acute hypercapnia is independent of initial plasma pH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Non-invasive mechanical ventilation for acute respiratory failure.

The value of mechanical ventilation using intermittent positive pressure ventilation delivered non-invasively by nasal mask was assessed in six patients with life threatening exacerbations of chronic respiratory disease. Median (range) arterial oxygen and carbon dioxide tensions were 4.4 (3.5-7.2) kPa and 8.7 (5.5-10.9) kPa respectively, with four patients breathing air and two controlled concentrations of oxygen. The arterial oxygen tension increased with mechanical ventilation to a median (range) of 8.7 (8.0-12.6) kPa and the carbon dioxide tension fell to 8.2 (6.5-9.2) kPa. Four patients discharged after a median of 10 (8-17) days in hospital were well five to 22 months later. One died at four days of worsening sputum retention and another after five weeks using the ventilator for 12-16 hours each day while awaiting heart-lung transplantation. This technique of mechanical ventilation avoids endotracheal intubation and can be used intermittently. Hypercapnic respiratory failure can be relieved in patients with either restrictive or obstructive lung disease in whom controlled oxygen treatment results in unacceptable hypercapnia. Respiratory assistance can be tailored to individual need and undertaken without conventional intensive care facilities.     

Effects of acute acid-base changes on rat renal pyruvate dehydrogenase. Renal pyruvate dehydrogenase during acid-base alterations

Glutamine, the principal source of urinary ammonia, can be fully oxidized or converted to glucose by the kidney. To be oxidized, the carbon skeleton of glutamine must enter the TCA cycle as acetyl CoA formed by pyruvate dehydrogenase (PDH). The purpose of this study was to measure kidney PDH activity (active and total) following acute acid-base changes in vivo. PDHa activity was elevated after acute metabolic alkalosis and acidosis and unchanged by respiratory acidosis. Kidney ADP/ATP, CoA/acetyl CoA and calculated mitochondrial NAD+/NADH ratios were also determined and revealed an increase in kidney ADP/ATP with alkalosis but no changes during metabolic and respiratory acidosis.     

Oxygen as a driving gas for nebulisers: safe or dangerous?

Changes in blood gas tensions occurring when 100% oxygen or air was used as the driving gas for nebulised salbutamol were studied in 23 patients with severe airways obstruction. The patients fell into three groups: nine had chronic bronchitis and emphysema with carbon dioxide retention, seven had emphysema and chronic bronchitis without carbon dioxide retention, and seven had severe asthma (no carbon dioxide retention). When oxygen was used as the driving gas patients who retained carbon dioxide showed a mean rise of 1.03 kPa (7.7 mm Hg) in their pressure of carbon dioxide (Pco2) after 15 minutes (p less than 0.001) but the Pco2 returned to baseline values within 20 minutes of stopping the nebuliser. The other two groups showed no rise in Pco2 with oxygen. When air was used as the driving gas none of the groups became significantly more hypoxic. Although it is safe to use oxygen as the driving gas for nebulisers in patients with obstructive airways disease with normal Pco2, caution should be exercised in those who already have carbon dioxide retention.     

The effect of acid-base changes on vasopressin-stimulated water flow in toad urinary bladder

Water flow was measured gravimetrically in the presence and absence of vasopressin across the toad urinary bladder. Four groups of toads in different states of acid-base balance were used; a normal group, a group in NH₄Cl induced metabolic acidosis, respiratory acidosis, and a group in NaHCO₃ induced metabolic alkalosis. Vasopressin induced water flow was significantly reduced during metabolic acidosis and respiratory acidosis. Metabolic alkalosis had no effect on the hydro-osmotic response to vasopressin. Dibutyryl cyclic-AMP-stimulated water flow on the other hand was not affected by either a metabolic or respiratory acidosis. Treatment with indomethacin was able to reverse the observed reduction in the vasopressin-stimulated water flow response in the toad bladder during metabolic and respiratory acidosis. We conclude that the vasopressin stimulated water flow is altered during acidosis and evidence suggests that prostaglandins may be involved in the observed reduction in vasopressin-stimulated water flow.     

Criteria of fitness for anaesthesia in patients with chronic obstructive lung disease.

Twelve patients with severe chronic obstructive lung disease undergoing 15 operations were assessed with preoperative lung function tests and blood gas estimations. Their operative and postoperative course was followed. There were no deaths or serious complications. Patients fell into three groups: those with low respiratory capacity but normal blood gases, who required no special respiratory treatment apart from physiotherapy and antibiotics; those with hypoxaemia but normal arterial carbon dioxide pressure, who needed more prolonged oxygen treatment after operation; and those with hypoxaemia and hypercapnia, who needed postoperative ventilatory support. While forced expiratory volume in one second (FEV) is a good screening test in preoperative assessment it should be supplemented by arterial blood gas estimations in patients with an FEV of less than 1 litre.     

Mixed acid-base disorders, hydroelectrolyte imbalance and lactate production in hypercapnic respiratory failure: the role of noninvasive ventilation

Background

Hypercapnic Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with comorbidities and multidrug therapy is complicated by mixed acid-base, hydro-electrolyte and lactate disorders. Aim of this study was to determine the relationships of these disorders with the requirement for and duration of noninvasive ventilation (NIV) when treating hypercapnic respiratory failure.

Methods

Sixty-seven consecutive patients who were hospitalized for hypercapnic COPD exacerbation had their clinical condition, respiratory function, blood chemistry, arterial blood gases, blood lactate and volemic state assessed. Heart and respiratory rates, pH, PaO₂ and PaCO₂ and blood lactate were checked at the 1st, 2nd, 6th and 24th hours after starting NIV.

Results

Nine patients were transferred to the intensive care unit. NIV was performed in 11/17 (64.7%) mixed respiratory acidosis–metabolic alkalosis, 10/36 (27.8%) respiratory acidosis and 3/5 (60%) mixed respiratory-metabolic acidosis patients (p = 0.026), with durations of 45.1±9.8, 36.2±8.9 and 53.3±4.1 hours, respectively (p = 0.016). The duration of ventilation was associated with higher blood lactate (p<0.001), lower pH (p = 0.016), lower serum sodium (p = 0.014) and lower chloride (p = 0.038). Hyponatremia without hypervolemic hypochloremia occurred in 11 respiratory acidosis patients. Hypovolemic hyponatremia with hypochloremia and hypokalemia occurred in 10 mixed respiratory acidosis–metabolic alkalosis patients, and euvolemic hypochloremia occurred in the other 7 patients with this mixed acid-base disorder.

Conclusions

Mixed acid-base and lactate disorders during hypercapnic COPD exacerbations predict the need for and longer duration of NIV. The combination of mixed acid-base disorders and hydro-electrolyte disturbances should be further investigated.     

Control of breathing in uremia: ventilatory response to CO2 after hemodialysis.

The mechanisms responsible for the transient respiratory alkalosis which follows clinical hemodialysis were evaluated by studying the ventilatory response to carbon dioxide in chronic uremic patients, and in unanesthetized normal and chronic uremic goats. A significant increase in sensitivity to CO2 was found in acidotic uremic patients immediately (within 30 min) following hemodialysis (P less than 0.01). Sensitivity to CO2 returned to the predialysis value within 24 h. Lung volume and maximal breathing capacity were unchanged. A similar increase in sensitivity to CO2 was seen in nonacidotic uremic goats following hemodialysis. In the goats, these changes in sensitivity could not be explained by changes in cerebrospinal fluid acid-base status. Adding sufficient urea to the dialysate to prevent a fall in plasma urea concentration, eliminated this increase in sensitivity to CO2 in both uremic patients and goats. These results suggests that the transient respiratory alkalosis following hemodialysis is due to an increase in the sensitivity of the ventilatory response to carbon dioxide and is a consequence of dialysis-induced osmotic disequilibrium.     

Effect of neuromediators on acid-base status]

A relationship between the state of adrenergic, cholinergic, and serotoninergic systems, on the one hand, and the acid-alkaline balance of the organism, on the other hand, was revealed in sharp and chronic experiments on dogs. A surplus of each of the mediators was accompanied by respiratory alkalosis, and its deficiency--by combined respiratory and metabolic acidosis.     

Brain glutamate metabolism during metabolic alkalosis and acidosis.

Glutamate modifies ventilation by altering neural excitability centrally. Metabolic acid-base perturbations may also alter cerebral glutamate metabolism locally and thus affect ventilation. Therefore, the effect of metabolic acid-base perturbations on central nervous system glutamate metabolism was studied in pentobarbital-anesthetized dogs under normal acid-base conditions and during isocapnic metabolic alkalosis and acidosis. Cerebrospinal fluid transfer rates of radiotracer [13N]ammonia and of [13N]glutamine synthesized de novo via the reaction glutamate+NH3-->glutamine in brain glia were measured during normal acid-base conditions and after 90 min of acute isocapnic metabolic alkalosis and acidosis. Cerebrospinal fluid [13N]ammonia and [13N]glutamine transfer rates decreased in metabolic acidosis. Maximal glial glutamine efflux rate jm equals 85.6 +/- 9.5 (SE) mumol.l-1 x min-1 in all animals. No difference in jm was observed in metabolic alkalosis or acidosis. Mean cerebral cortical glutamate concentration was significantly lower in acidosis [7.01 +/- 0.45 (SE) mumol/g brain tissue] and tended to be larger in alkalosis, compared with 7.97 +/- 0.89 mumol/g in normal acid-base conditions. There was a similar change in cerebral cortical gamma-aminobutyric acid concentration. Within the limits of the present method and measurements, the results suggest that acute metabolic acidosis but not alkalosis reduces glial glutamine efflux, corresponding to changes in cerebral cortical glutamate metabolism. These results suggest that glutamatergic mechanisms may contribute to central respiratory control in metabolic acidosis.     

Ventilatory response to chronic metabolic acidosis and alkalosis in the dog

Systematic data are not available with regard to the anticipated appropriate responses of arterial PCO2 to primary alterations in plasma bicarbonate concentration. In the present study, we attempted to rigorously characterize the ventilatory response to chronic metabolic acid-base disturbances of graded severity in the dog. Animals with metabolic acidosis produced by prolonged HCl feeding and metabolic alkalosis of three different modes of generation, i.e., diuretics (ethacrynic acid or chlorothiazide), gastric drainage, and administration of deoxycorticosterone acetate (alone or in conjunction with oral sodium bicarbonate), were examined. The results indicate the existence of a significant and highly predictable ventilatory response to chronic metabolic acid-base disturbances. Moreover, the magnitude of the ventilatory response appears to be uniform throughout a wide spectrum of chronic metabolic acid-base disorders extending from severe metabolic acidosis to severe metabolic alkalosis; on average, arterial PCO2 is expected to change by 0.74 Torr for a 1-meq/l chronic change in plasma bicarbonate concentration of metabolic origin. Furthermore, the data suggest that the ventilatory response to chronic metabolic alkalosis is independent of the particular mode of generation.     

Teaching acid/base physiology in the laboratory

Acid/base homeostasis is one of the most difficult subdisciplines of physiology for medical students to master. A different approach, where theory and practice are linked, might help students develop a deeper understanding of acid/base homeostasis. We therefore set out to develop a laboratory exercise in acid/base physiology that would provide students with unambiguous and reproducible data that clearly would illustrate the theory in practice. The laboratory exercise was developed to include both metabolic acidosis and respiratory alkalosis. Data were collected from 56 groups of medical students that had participated in this laboratory exercise. The acquired data showed very consistent and solid findings after the development of both metabolic acidosis and respiratory alkalosis. All results were consistent with the appropriate diagnosis of the acid/base disorder. Not one single group failed to obtain data that were compatible with the diagnosis; it was only the degree of acidosis/alkalosis and compensation that varied.     

Mechanisms of gas exchange response to lung volume reduction surgery in severe emphysema

Lung volume reduction surgery (LVRS) improves lung function, respiratory symptoms, and exercise tolerance in selected patients with chronic obstructive pulmonary disease, who have heterogeneous emphysema. However, the reported effects of LVRS on gas exchange are variable, even when lung function is improved. To clarify how LVRS affects gas exchange in chronic obstructive pulmonary disease, 23 patients were studied before LVRS, 14 of whom were again studied afterwards. We performed measurements of lung mechanics, pulmonary hemodynamics, and ventilation-perfusion (Va/Q) inequality using the multiple inert-gas elimination technique. LVRS improved arterial Po? (Pa(O?)) by a mean of 6 Torr (P = 0.04), with no significant effect on arterial Pco? (Pa(CO?)), but with great variability in both. Lung mechanical properties improved considerably more than did gas exchange. Post-LVRS Pa(O?) depended mostly on its pre-LVRS value, whereas improvement in Pa(O(2)) was explained mostly by improved Va/Q inequality, with lesser contributions from both increased ventilation and higher mixed venous Po(2). However, no index of lung mechanical properties correlated with Pa(O?). Conversely, post-LVRS Pa(CO?) bore no relationship to its pre-LVRS value, whereas changes in Pa(CO?) were tightly related (r2 = 0.96) to variables, reflecting decrease in static lung hyperinflation (intrinsic positive end-expiratory pressure and residual volume/total lung capacity) and increase in airflow potential (tidal volume and maximal inspiratory pressure), but not to Va/Q distribution changes. Individual gas exchange responses to LVRS vary greatly, but can be explained by changes in combinations of determining variables that are different for oxygen and carbon dioxide.     

Homeostatic Problems in General Surgery

For electrolyte problems that arise during surgical procedures, the surgeon must be versed in the physiologic function of the organs that play vital roles in homeostasis. Pulmonary and renal evaluation before operation can give forewarning of potential dangers. Hyperaldosteronism, a disease entity influencing electrolytic changes and causing other pathophysiological effects, should be understood by the surgeon. Not only should he understand the causes of dehydration, hyperhydration, metabolic and respiratory acidosis and metabolic and respiratory alkalosis, he should also be able to recognize their deleterious effects clinically, know how to make use of adequate laboratory procedures to substantiate a diagnosis and determine the effect of treatment.The effect of water deficit and water excess, and of deficits and excesses of such ions as sodium, potassium, calcium, carbon dioxide and bicarbonate on the renal, cardiac, pulmonary and neuromuscular systems must be considered.Tetany before or after operation challenges a surgeon''s diagnostic acuity. Relying on laboratory tests only, without correlating the results with history and clinical features, may lead to errors in the administration of electrolytic fluids.     

A functional analysis of the shift from gill- to lung-breathing during the evolution of land crabs (Crustacea, Decapoda)

The evolution of air-breathing in land crabs is associated with a progressive shift in the primary site of respiratory gas exchange from the diffusion-limited gills used for water-breathing, via a simple 'cutaneous' lung surface to the perfusion-limited, invaginated lung described in the mountain crab, Pseudothelphusa garmani. The reduced diffusion limitation over the lungs facilitates oxygen transfer from air to the tissues at lower ventilation rates but is associated with accumulation of carbon dioxide. A potential respiratory acidosis is buffered by the respiratory pigment haemocyanin and by elevation of haemolymph bicarbonate levels. These changes parallel those described in vertebrates but air-breathing crustaceans maintain relatively low carbon dioxide levels in the haemolymph, either by retaining an aquatic route for its elimination over the reduced gills or by blowing it off across the lung. Maintenance of low carbon dioxide levels may be associated with a limited capacity to buffer against an acidosis due to low levels of circulating haemocyanin (i.e. crustaceans lack red blood cells). This may ultimately limit their survival in air as an acidosis will reduce oxygen transport due to a marked Bohr effect on haemocyanin. The primary role of an invaginated lung may be to reduce rates of water loss in air.     

Relationship of CSF pH, O2, and CO2 responses in metabolic acidosis and alkalosis in humans

The effect of induced metabolic acidosis (48 h of NH4Cl ingestion, BE - 10.6 +/- 1.1) and alkalosis (43 h of NaHCO3- ingestion BE 8.8 +/- 1.6) on arterial and lumber CSF pH, Pco2, and HCO3- and ventilatory responses to CO2 and to hypoxia was assessed in five healthy men. In acidosis lumbar CSF pH rose 0.033 +/- 0.02 (P less than 0.05). In alkalosis CSF pH was unchanged. Ventilatory response lines to CO2 at high O2 were displaced to the left in acidosis (9.0 +/- 1.4 Torr) and to the right in alkalosis (4.5 +/- 1.5 Torr) with no change in slope. The ventilatory response to hypoxia (delta V40) was increased in acidosis (P less than 0.05) and it was decreased in four subjects in alkalosis (P, not significant). We conclude that the altered ventilatory drives of steady-state metabolic imbalance are mediated by peripheral chemoreceptors, and in acidosis the medullary respiratory chemoreceptor drive is decreased.     

Acid-base balance and plasma glutamine concentration in man

Plasma glutamine concentrations were measured in chronic metabolic acidosis and alkalosis in healthy male volunteers. Metabolic acidosis resulted in a significant drop in glutamine concentration while metabolic alkalosis significantly elevated glutamine levels. These changes in glutamine concentration correlated with both the bicarbonate and PCO2 levels. To determine whether bicarbonate or PCO2 levels influence the glutamine concentrations, respectively acidosis was induced by respiring 5% CO2. This resulted in a significant elevation in both PCO2 and glutamine while bicarbonate levels remained unchanged. The results demonstrate an effect of acid-base alterations upon plasma glutamine concentration mediated by PCO2.     

Air pollution and the lung: epidemiological approach

Epidemiological evidence has concurred with clinical and experimental evidence to correlate current levels of ambient air pollution, both indoors and outdoors, with respiratory effects. In this respect, the use of specific epidemiological methods has been crucial. Common outdoor pollutants are particulate matter, nitrogen dioxide, carbon monoxide, volatile organic compounds and ozone. Short-term effects of outdoor air pollution include changes in lung function, respiratory symptoms and mortality due to respiratory causes. Increase in the use of health care resources has also been associated with short-term effects of air pollution. Long-term effects of cumulated exposure to urban air pollution include lung growth impairment, chronic obstructive pulmonary disease (COPD), lung cancer, and probably the development of asthma and allergies. Lung cancer and COPD have been related to a shorter life expectancy. Common indoor pollutants are environmental tobacco smoke, particulate matter, nitrogen dioxide, carbon monoxide, volatile organic compounds and biological allergens. Concentrations of these pollutants can be many times higher indoors than outdoors. Indoor air pollution may increase the risk of irritation phenomena, allergic sensitisation, acute and chronic respiratory disorders and lung function impairment. Recent conservative estimates have shown that 1.5-2 million deaths per year worldwide could be attributed to indoor air pollution. Further epidemiological research is necessary to better evaluate the respiratory health effects of air pollution and to implement protective programmes for public health.     

Effects of acid-base imbalance on pulmonary angiotensin-converting enzyme in vivo

The effects of acid-base balance disturbances on pulmonary endothelial angiotensin-converting enzyme (ACE) were studied in anesthetized mechanically ventilated rabbits. Enzyme function was estimated from [3H]benzoyl-Phe-Ala-Pro ([3H]BPAP) utilization under first-order reaction conditions during a single transpulmonary passage and expressed as 1) substrate metabolism (M), 2) Amax/Km (Amax being equal to the product of enzyme mass and the constant of product formation), and 3) (Amax/Km)/100 ml blood flow. When respiratory acidosis/alkalosis was produced by altering respiratory rate at constant airway pressure, substrate (BPAP) utilization varied proportionally to arterial pH and inversely proportionally to arterial PCO2 (PaCO2) (P less than 0.05). Percent BPAP metabolism (%M) ranged from 92 +/- 3 (respiratory alkalosis) to 85 +/- 3 (normal), 82 +/- 3 (respiratory acidosis), and 78 +/- 2% (severe respiratory acidosis). Amax/Km similarly decreased from 899 +/- 129 to 825 +/- 143, 601 +/- 74, and 450 +/- 34 ml/min, respectively, and (Amax/Km)/100 ml blood flow was reduced from 176 +/- 26 to 131 +/- 22, 111 +/- 12, and 97 +/- 5, respectively. However, when respiratory acidosis/alkalosis was produced by altering both respiratory rate and airway pressure, no changes were observed in either %M, Amax/Km or (Amax/Km)/100 ml blood flow. Similarly metabolic alkalosis or acidosis did not alter M, Amax/Km or (Amax/Km)/100 ml blood flow. These results indicate that pulmonary endothelial ACE function can be affected by acid-base disturbances, probably indirectly through changes in perfused microvascular surface area.