Metabolic Acid-base Status Research Articles

Metabolic acid-base status and the role of carotid chemoreceptors in hyperoxic breathing.

There is controversy as to how much the peripheral chemoreceptors may contribute to pulmonary ventilation during hyperoxia under normocapnic and hypercapnic conditions. Whereas cutting the carotid sinus nerves (CSN) is reported to considerably depress ventilation in cats (Katsaros, 1968, Berkenbosch et al., 1979), we did not find any significant effect of cutting or cooling the CSN in rabbits (Kiwull et al., 1972). It has to be questioned, whether the metabolic acid-base status under otherwise normal blood-gas conditions could be responsible for these discrepancies. To exclude feedback effects of spontaneous breathing, this study was carried out with artificial ventilation.

The effect of varying arterial oxygen tension on neonatal acid-base balance.

Acute severe hypoxia, when the arterial partial pressure of O2 (PaO2) is sufficiently reduced, causes a shift from aerobic to anaerobic metabolism and can be fatal to neonates. The ability of the neonate to accommodate this shift, and prevent acidosis, could play a role in its ability to tolerate hypoxia. This study examines the effect of varying degrees of acute hypoxia on acid-base homeostasis in the neonate using a model of right to left shunting where PaO2 is decreased and, if severe, arterial partial pressure of CO2 is increased. Three-d-old swine were anesthetized, intubated, and mechanically ventilated. Ventilation with a gas mixture of medical air and 95% N2:5% CO2 resulted in four groups: 1) normoxia (n = 5); 2) mild hypoxia (n = 4); 3) moderate hypoxia (n = 3); and 4) severe hypoxia (n = 5), with PaO2 of 10.7, 8.0, 5.3, and 2.7 kPa (80, 60, 40, and 20 mm Hg), respectively. Acid-base status was evaluated via changes in arterial blood partial pressure of CO2, pH, HCO3-, and base excess at 0, 30, 60, and 120 min. Only the severe hypoxia group had significantly elevated (p less than 0.0001) arterial partial pressure of CO2 compared to the other groups at 60 and 120 min [8.7 +/- 0.5 and 8.0 +/- 0.5 kPa (65.5 +/- 3.7 and 60.0 +/- 3.7 mm Hg), respectively]. Base excess was unaltered in the normoxic and mild and moderate hypoxic groups, indicating no change in metabolic acid-base status. The severe hypoxic group had progressively decreased HCO3-, base excess, and pH at 60 and 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of metabolic acid-base changes on the ventilatory changes at the end of heavy exercise

The purpose of this study was to determine the effect of altered metabolic acid-base status on the changes in ventilation in the transition from heavy exercise above anaerobic threshold to rest. Seven subjects ingested, in a randomized and blind manner, either NaHCO3 or CaCO3 (placebo) at a dose of 300 mg.kg-1 body mass and ran on a treadmill for five minutes (90% VO2max and above anaerobic threshold) on ten different occasions. Changes in minute ventilation in the exercise transitions were studied by starting and stopping the treadmill abruptly with a remote switch. The fast increase in ventilation at the start of exercise was not accompanied by a corresponding fast drop in ventilation at the end of exercise (P less than or equal to 0.001) and the effects of chemicals on these changes were not significantly different (P greater than 0.05). A single-component exponential model, without a time delay, was used to determine the time constants of off-transitional decay in ventilation for the two chemicals in each subject. Parametric and non-parametric statistical tests revealed that the time constants were not as significantly different as the venous pH measurements which were significantly higher with NaHCO3 (P less than or equal to 0.001). The results indicate that the absence of fast change in ventilation at the end of heavy exercise is not due to lactic acidosis and the consequent slow ventilatory changes in the off-transition of heavy exercise are at least partly mediated by non-humoral factors such as a central neural reverberatory mechanism.

Characterization of acid-base disturbances and effects on calcium and phosphorus balances of dietary fixed ions in pregnant or lactating does.

Effects of fixed cation-anion balance on acid-base status and calcium and phosphorus balances were examined. Pregnant and lactating goats were fed a diet of alfalfa hay, concentrate and minerals to vary the cation-anion balance [meq sodium (Na) + meq potassium (K)-meq chloride (Cl)]/100 g diet dry matter (DM) over the range found in ruminant feeds. Small but significant effects on ruminal pH, fermentation and dilution rate were observed. Metabolic acid-base status of pregnant and lactating goats was normal when (Na + K - Cl) balance was 40 to 50 meq/100 g DM. The other treatments drastically altered plasma electrolyte concentrations, causing metabolic acid-base disturbances and profound changes in calcium and phosphorus metabolism. Subclinical hypernatremic, hypochloremic metabolic alkalosis was induced by a dietary fixed cation excess (Na + K - Cl) of greater than 85 meq/100 g DM (typical of buffered, alfalfa diets) and caused hypocalciuria, diminished calcium and phosphorus absorption, and possibly diminished dietary calcium absorption and resorption of calcium from bone. Subclinical hyperchloremic, hyponatremic metabolic acidosis from a diminished dietary fixed cation-anion balance (Na + K - Cl) of less than 10 meq/100 g DM (typical of nonbuffered corn silage or grain diets) caused hypercalciuria, enhanced calcium and phosphorus absorption and apparently enhanced calcium resorption from bone. Apparent effects on absorption and resorption depended on calcium and phosphorus intakes. Alterations in goats performance were not demonstrable. Dietary excesses of fixed cations over anions (meq Na + K - Cl/100 g diet DM greater than 50) cause metabolic alkalosis in ruminants, whereas fixed anion excesses (meq Na + K - Cl/100 g diet DM less than 40) cause metabolic acidosis. Content of electrolytes in diets should be reported in all nutrition trials with ruminants for assessment of metabolic acid-base status.

Effects of dietary electrolyte balance on growth and metabolic acid-base status of chicks

Three experiments were conducted to evaluate the performance, and physiological and metabolic effects of dietary electrolyte balance in broiler chicks. Increasing the electrolyte balance (Na+K−Cl) from 200 to 350 meq/kg improved gain and feed consumption of chicks fed high protein (28.6%) diets, but depressed gain and feed consumption of chicks fed low protein (14.3%) diets. Increasing Cl in high Na and K diets also depressed growth in both high and low protein diets. The growth responses were primarily the result of changes in feed consumption. The electrolyte balance x protein interaction on growth was less pronounced when feed intake was equalized. High Cl diets depressed blood pH, HCO 3, and base excess. Feeding high versus low electrolyte balance diets increased plasma uric acid concentration and decreased kidney asparaginase activity. The effect of dietary electrolytes on acid-base status and asparaginase activity were independent of crude protein level. Amino acid supplementation of the low protein diet did not alleviate the growth depressing effect of increased electrolyte balance. Further, either the addition of a mixture of K and Na or addition of isomolar levels of K or Na alone depressed growth of chicks fed low protein diets. The results confirmed our previous observation that the electrolyte balance which provides for optimum growth is dependent upon the dietary crude protein content. Moreover, acid-base status, kidney asparaginase activity and plasma uric acid concentrations were greatly affected by alterations in dietary electrolytes, but these changes were not correlated with the growth response.

Nutritional balance studies in very-low-birth-weight infants: role of whey formula.

Although the optimal type and amount of protein for feeding very-low-birth-weight (VLBW) infants is not well defined, a protein composition with a whey protein to casein ratio of 60/40 is generally considered desirable. This study used the metabolic balance technique to compare nitrogen retention rates in 19 VLBW (less than 1,530 g) infants fed either an experimental whey protein-predominant formula (WPF) containing ultra filtered whey protein or a conventional casein-predominant formula (CPF) containing approximately 20% more protein and more minerals. Blood chemistries and anthropometric measurements were assessed serially. Although infants fed CPF received and retained more protein than infants fed WPF, nitrogen retentions were 73.1 and 74.5% of intake, respectively, and not different between the two feeding groups. The data suggest that proteins from either WPF or CPF are adequately utilized by VLBW infants. Although WPF permitted nitrogen retention rates similar to fetal accretion rates, CPF more nearly met estimated nitrogen requirements of the low-birth-weight infant. Infants fed WPF showed a more favorable course with respect to their metabolic acid-base status, characterized by normal buffer base concentrations and less predisposition to metabolic acidosis. We conclude that whey-predominant protein is preferable to casein-predominant protein in the diet of VLBW neonates because it may lessen the risk of metabolic acidosis and its potential adverse effects.

Changes in Renal Handling of Platinum in Cisplatinum-Treated Rats Following Induction of Metabolic Acidosis or Alkalosis

Manipulations of metabolic acid-base status were used in an attempt to modify the renal handling and toxicity of the anticancer drug cisplatinum. Rats were orally pretreated with either tap water (TW), ammonium chloride (AC), or sodium bicarbonate (SB) for 3 days prior to intraperitoneal administration of a high cisplatinum dose (7.5 mg/kg b.w.). Urine was collected daily for 4 days between drug dosing and killing of the animals. AC-pretreated rats did not exhibit the characteristic cisplatinum-induced diuresis and were unable to maintain an acid urinary pH following drug administration. AC rats had a significantly lower, and SB rats a significantly higher, urinary excretion of platinum than did TW rats. Platinum excretion was found to be correlated with urinary pH (r = 0.88) and not urinary volume (r = 0.30). The renal concentration of platinum was greater in AC animals than in SB or TW animals, but no significant difference was observed in liver or plasma concentrations between the groups. Both pretreated groups had equal percent of free vs bound platinum. Proteinuria was more severe in AC-pretreated rats, but histologic evidence of renal tubular damage was present in all the three groups. It is concluded that metabolic acidosis can seriously impair the renal handling of high dose cisplatinum but that metabolic alkalosis offers no evident advantages over nonpretreatment.

Respiratory responses to ACTH and dexamethasone in unanesthetized goats

The effect of dexamethasone and adrenocorticotropin (ACTH) treatment (12 and 36 hr) on hypercapnic respiratory drive was studied in three unanesthetized goats with carotid loops. Minute ventilation, respiratory frequency, fractions of expired 0; and CO;, and arterial pH, CO 2 tension and bicarbonate concentration were measured while each animal breathed room air, 2.5% CO 2 and 5% CO 2 in air. Oxygen consumption, respiratory dead space and alveolar ventilation were calculated. With maintenance of unchanged metabolic acid-base status, the hormone treatments uniformly increased respiratory excitability without altering respiratory sensitivity. No changes in oxygen consumption were associated with the observed increase in respiratory responsiveness. The similarity of respiratory response changes occurring during ACTH and dexamethasone treatment suggests that glucocorticoids are the operative agents and that the induced effect occurs within the first twelve hours after treatment initiation.

Muscular exercise, 2,3-DPG and oxy-hemoglobin affinity.

This study was concerned with the effects of prolonged muscular work in healthy subjects on erythrocyte 2,3-diphosphoglycerate as a mediator of acute changes in the affinity of hemoglobin for oxygen. The experimental procedures were designed to elicit marked variation among exercise conditionsin factors which are known or hypothesized to effect oxy-hemoglobin dissociation in vivo, ·... namely respiratory and metabolic acid-base status, temperature, adequacy of systemic O2 transport and length of time to exhaustion. In contrast to a previous report, the only systematic effect of exercise under present conditions was a decline below resting levels in red cell 2,3-DPG which occurred at the mid-point of each work test. Neither the magnitude nor direction of change in 2,3-DPG was related to the physiologic intensity of exercise. Present findings are consistent with the contention that time is a critical determinant of any contribution the generation of erythrocyte 2,3-DPG may make to oxy-hemoglobin affinity, regardless of the apparent intensity of demand for increased O2 delivery.

Estimation of Arterial pH and pCO 2 from Central Venous Samples

any papers over the last few years have disagreed about the value of venous blood-gas and pH measurements [7, 13, 15, 18, 201. Some have gone so far as to say that “central venous blood gas analysis may substitute for arterial puncture in assessing the metabolic acid-base status of the patient” [13], while others state that “reliance upon venous blood samples for analysis of blood gas parameters can no longer be justified in the care of the acutely ill patient” [15]. We thus set out to define the limitations of central venous blood gases. We also wanted to determine if, in addition to arterial values, central venous blood gases could help in the management of a complicated case.