Hypoproteinemic alkalosis.

Hypoproteinemia by itself causes a nonrespiratory ("metabolic") alkalosis. On the average, a decrease in plasma albumin concentration of 1 g/dl produces an increase in "standard" bicarbonate of 3.4 mM/liter, and an apparent base excess of +3.7 meq/liter; it also reduces the value of the normal anion gap by about 3 meq/liter. Concentration of plasma protein should be measured as part of the analysis of acid-base status. Interpretation of acid-base data requires special consideration in "primary hypoproteinemic alkalosis."

Ventilatory response to carbon dioxide in humans.

Testing ventilatory responses to CO2 is fraught with difficulties in interpretation and, at present, it can hardly be considered suitable for routine evaluation of patients with pulmonary disease. In spite of the seventy years' work since Haldane's introduction of the CO2 response curve, much remains to be learned about the various components of the regulatory system, and for testing chemosensitivity to CO2 in patients with pulmonary disease, methods more direct than measuring pulmonary ventilation are needed for evaluation of the output of the regulatory system.

Acid-base effects of altering plasma protein concentration in human blood in vitro.

We altered the concentration of plasma proteins in human blood in vitro by adding solutions with [Na+], [K+], and [Cl-] resembling those in normal blood plasma, either protein-free or with a high concentration of human albumin. After equilibrating the samples with a gas containing 5% CO2-12% O2-83% N2 at 37 degrees C, we measured pH, PCO2, and PO2; in separated plasma, we determined the concentrations of total plasma proteins and albumin and of the completely dissociated electrolytes (strong cations Na+, K+, Mg2+ and anions Cl-, citrate3-). With PCO2 nearly constant (mean = 35.5 Torr; coefficient of variation = 0.02), lowering plasma protein concentration produced a metabolic alkalosis, whereas increasing plasma albumin concentration gave rise to a metabolic acidosis. These acid-base disturbances occurred independently of a minor variation in the balance between the sums of strong cations and anions. We quantified the dependence of several acid-base variables in plasma on albumin (or total protein) concentration. Normal plasma proteins are weak nonvolatile acids. Although their concentration is not regulated as part of acid-base homeostasis, hypoproteinemia and hyperalbuminemia per se produce alkalosis and acidosis, respectively.

Effect of chest wall vibration on breathlessness in normal subjects.

This study evaluated the effect of chest wall vibration (115 Hz) on breathlessness. Breathlessness was induced in normal subjects by a combination of hypercapnia and an inspiratory resistive load; both minute ventilation and end-tidal CO2 were kept constant. Cross-modality matching was used to rate breathlessness. Ratings during intercostal vibration were expressed as a percentage of ratings during the control condition (either deltoid vibration or no vibration). To evaluate their potential contribution to any changes in breathlessness, we assessed several aspects of ventilation, including chest wall configuration, functional residual capacity (FRC), and the ventilatory response to steady-state hypercapnia. Intercostal vibration reduced breathlessness ratings by 6.5 +/- 5.7% compared with deltoid vibration (P less than 0.05) and by 7.0 +/- 8.3% compared with no vibration (P less than 0.05). The reduction in breathlessness was accompanied by either no change or negligible change in minute ventilation, tidal volume, frequency, duty cycle, compartmental ventilation, FRC, and the steady-state hypercapnic response. We conclude that chest wall vibration reduces breathlessness and speculate that it may do so through stimulation of receptors in the chest wall.

Endogenous opioids and ventilatory responses to hypercapnia in normal humans.

Though administration of opioid peptides depresses ventilation and ventilatory responsiveness, the role of endogenous opioid peptides in modulating ventilatory responsiveness is not clear. We studied the interaction of endogenous opioids and ventilatory responses in 12 adult male volunteers by relating hypercapnic responsiveness to plasma levels of immunoactive beta-endorphin and by administering the opiate antagonist naloxone. Ventilatory responsiveness to hypercapnia was not altered by pretreatment with naloxone, and this by itself suggests that endogenous opioids have no role in modulating this response. However, there was an inverse relationship between basal levels of immunoactive beta-endorphin in plasma and ventilatory responsiveness to CO2. Furthermore, plasma beta-endorphin levels rose after short-term hypercapnia but only when subjects had been pretreated with naloxone. We conclude that measurement of plasma endorphin levels suggests relationships between endogenous opioid peptides and ventilatory responses to CO2 that are not apparent in studies limited to assessing the effect of naloxone.

Hydrochloric acid in the correction of metabolic alkalosis.

Intravenous infusion of hydrochloric acid was used as a safe, effective, and quantitative method for correction of metabolic alkalosis in two patients. The first shows the risks of intravenously administered ammonium chloride, the currently available alternative to hydrochloric acid therapy. The second shows the efficacy of intravenously administered hydrochloric acid. While breathing spontaneously throughout the period of severe alkalosis, this patient showed compensatory hypoventilation with conspicuous increase in arterial carbon dioxide pressure. Normal spontaneous ventilation returned with correction of the metabolic alkalosis.

Endogenous opioids and ventilatory adaptation to prolonged hypoxia in goats.

To investigate whether endogenous opioid peptides mediate time-dependent changes in ventilatory control during prolonged hypoxia, we studied four adult goats at rest during 14 days at simulated high altitude in a hypobaric chamber (PB approximately 450 Torr). Arterial PCO2 fell during the first several hours of hypoxia, remained stable over the next 7 days, and then rose slightly (but without statistical significance) by day 14. Ventilatory responsiveness to CO2 increased during the first week of hypoxia. By day 14, while still greater than control, the ventilatory response to CO2 was less than that observed on day 7. Immunoactive beta-endorphin levels in plasma and CSF did not change during the 14-day period. Administration of naloxone on day 14 did not restore the ventilatory response to CO2 to the level observed during the first week of acclimatization. We conclude that in adult goats, time-dependent changes in ventilatory response to CO2 during acclimatization to prolonged hypoxia are not primarily attributable to alterations in endogenous opioid peptide activity.

Naloxone does not affect ventilatory responses to hypoxia and hypercapnia in rats.

Ventilatory responses (tidal volume, respiratory frequency, and minute ventilation) to steady-state hypoxia and steady-state hypercapnia were measured plethysmographically in awake unrestrained adult rats, before and after subcutaneous injection of placebo (saline) naloxone in doses up to 5.0 mg/kg. Naloxone did not alter the ventilatory responses to hypoxia or hypercapnia.

General and regional hemodynamics in hypertension in chronic renal disease.

Cardiac output, total peripheral vascular resistance, renal, extrarenal, forearm muscle and skin hemodynamics and an indicator of the splanchic vascular resistance were estimated in 20 subjects with chronic renal disease without signs of chronic renal failure and without anemia. The data were compared with a group of subjects with essential hypertension. The high blood pressure of chronic renal disease of mild or moderate severity was maintained in the first place by a high cardiac output, this being due to a rise of the stroke volume, while the heart rate was only slightly increased. The total peripheral vascular resistance was within the normal range in most of the subjects. The vascular resistance in the skin was slightly raised, that in the splanchnic area and muscle unchanged in renal hypertension. The possible pathogenic mechanisms are considered.

Stewart's quantitative acid-base chemistry: applications in biology and medicine.

We review P.A. Stewart's quantitative approach to acid-base chemistry, starting with its historical context. We outline its implications for cellular and membrane processes in acid-base physiology; discuss its contributions to the understanding and analysis of acid-base phenomena; show how it can be applied in clinical problems; and propose a classification of clinical acid-base disturbances based on this general approach.

Acid-base disorders in critical care medicine.

In critically ill patients, nonrespiratory (metabolic) alkalosis is the most common acid-base disturbance; it is caused by hypochloremia and/or by hypoproteinemia. Information on the concentration of plasma proteins should be included when evaluating acid-base status.

Serum proteins and acid-base equilibria: a follow-up.

A mathematic model that described the acid-base behavior of blood plasma has been revised to incorporate pK values of individual histidine residues on human serum albumin determined by nuclear magnetic resonance spectroscopy. With the insights derived from the model a method for evaluation of the strong ion difference has been developed. Thus if pH, PCO2, and the concentrations of serum albumin and phosphate are measured, all independent variables, which physically determine "acid-base balance" in plasma, can be quantified. New ways to evaluate "unidentified anions" in metabolic acidosis can be explored with this approach.