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PubMed2000

Endothelium-independent and -dependent vasodilation in alkalotic and acidotic piglet lungs.

Although significant pulmonary hypertension can occur in patients treated with either hypocapnic alkalosis or "permissive" hypercapnic acidosis, the effects of sustained alkalosis or acidosis on subsequent vasodilator responses have not been established. This study measured the effects of 60-100 min of sustained alkalosis or acidosis on endothelium-independent and -dependent vasodilation with inhaled nitric oxide (iNO) and acetylcholine (ACh) in isolated lungs from 1-week-old piglets. After stabilization, lungs were divided into control (pH 7.40, PaCO(2) 40 torr, n = 5), alkalotic (pH 7.60, PaCO(2) 25 torr, n = 6), or acidotic (pH 7.25, PaCO(2) 65 torr, n = 5) groups and ventilated with 21% O(2) for 40 min. Acute hypoxic pulmonary vasoconstriction (HPV) was then induced with 4-6% O(2). After a stable pressor response had occurred (approximately 20 min), pulmonary artery dose-response relationships to increasing concentrations of iNO were measured. The iNO was then stopped and after a stable hypoxic pressure had again been reestablished (approximately 20 min), dose-responses to increasing concentrations of ACh were measured. Hypoxic pulmonary vascular resistance (PVR) was similar in all groups. Pulmonary artery pressure dose-response relationships to iNO and ACh were blunted in the alkalosis group, suggesting that both endothelium-independent and -dependent vasodilation were reduced during sustained hypocapnic alkalosis. In contrast, sustained acidosis did not alter subsequent vasodilator responses. Future studies must elucidate the mechanisms underlying blunted pulmonary vasodilation during sustained alkalosis and examine the consequences of sustained alkalosis therapy on subsequent vasodilator responses in clinical practice.

Acetylcholine↗
PubMed1995

Hypocapnia-induced ventilation/perfusion mismatch: a direct CO2 or pH-mediated effect?

The purpose of this study was to determine whether the increased ventilation/perfusion (VA/Q) mismatch caused by hypocapnic hyperventilation in dogs (J. Appl. Physiol. 1993; 74:1306-1314) is a direct CO2 or a pH-mediated effect. From an initial state of hyperventilated respiratory alkalosis (FIO2 = 0.21, VT = 18 ml/kg, RR = 35), we studied the changes in VA/Q distributions, respiratory gas exchange, and hemodynamics when the acid-base status of the dogs was manipulated by combinations of acid or alkali infusion with or without CO2 inhalation. In this manner, we studied respiratory alkalosis (high pH, low PCO2), normalized acid-base status (normal pH, normal PCO2), metabolic acidosis (low pH, normal PCO2), metabolic alkalosis (high pH, normal PCO2), and a mixed respiratory alkalosis and metabolic acidosis (normal pH, low PCO2). Gas exchange was evaluated using the multiple inert gas elimination technique. PaO2 was reduced and VA/Q heterogeneity was increased in all conditions defined by a high pH, independent of the PCO2 (respiratory alkalosis and metabolic alkalosis). In contrast, PaO2 and VA/Q heterogeneity was unchanged in conditions defined by either a normal or low pH (normalized acid-base status, mixed respiratory alkalosis and metabolic acidosis, and metabolic acidosis). Therefore, we conclude that hypocapnia-induced VA/Q mismatch in hyperventilated dogs is pH-mediated and is not a function of PCO2 per se.

Acid-Base Equilibrium↗
PubMed1981

Effect of PH on muscle glycolysis during exercise.

1. Five males were studied on three occasions, after oral administration of CaCO3 (control), NH4Cl (acidosis) and NaHCO3 (alkalosis), in a dose of 0.3 g/kg, taken over a 3 h period at rest. The subjects then exercised on a cycle ergometer for 20 min at 33% maximal oxygen uptake (VO2 max.), followed by 20 min at 66% and at 95% VO2 max. until exhaustion. 2. Endurance at 95% VO2 max. was longest with alkalosis (5.44 +/- 1.05 min), shortest with acidosis (3.13 +/- 0.97 min) and intermediate in the control study (4.56 +/- 1.31 min); venous blood pH at exhaustion was 7.33 +/- 0.02 (mean +/- 1 SEM), 7.13 +/- 0.02 and 7.26 +/- 0.02 respectively. 3. Concentrations of plasma lactate at exhaustion were 7.10 +/- 0.8 mmol/1 4.0 +/- 0.5 and 7.9 +/- 0.9 mmol/l in the control, acidosis and alkalosis studies respectively. 4. Muscle lactate increased most from rest to exhaustion with alkalosis to 17.1 +/- 2.5 mumol/g and least with acidosis to 12.2 +/- 1.4 mumol/g. Muscle glycogen depletion was comparable in control and alkalosis studies. 5. The lower plasma lactate concentration during exercise in acidosis compared with control and alkalosis appears to be due to an inhibition of muscle glycolysis combined with a reduction in lactate efflux from muscle.

Acidosis↗
PubMed1980

Effect of changes in blood flow, norepinephrine, and pH on oxygen uptake by resting skeletal muscle.

The purpose of this study was to examine the effects of norepinephrine infusion alone and during alkalosis on oxygen uptake in the dog gastrocnemius-plantaris muscle group under conditions of constant muscle blood flow. The animals were not cold acclimatized. Blood flow was pump controlled, alkalosis was produced by hyperventilation, and norepinephrine was infused intravenously at a rate of 1--1.5 micrograms/kg per minute. Alkalosis had no effect either alone or in combination with changes in blood flow. Similarly, changing blood flow from a low (0.10 +/- 0.02 mL/g muscle per minute (mean +/- SE)) to a high (0.34 +/- 0.04 mL/g muscle per minute) rate did not alter resting oxygen uptake. Norepinphrine caused an average increase of about 30% in resting muscle oxygen uptake which was sustained for the 15-min sampling period during a low flow-norepinephrine infusion and during the low and high blood flow-norepinephrine-alkalosis sampling periods. Norepinephrine infusion during the period of high muscle blood flow without alkalosis resulted in a transient increase followed by a decrease in muscle oxygen uptake. The data demonstrated that infusion of norepinephrine increased skeletal muscle oxygen uptake in "non-cold-acclimatized" dogs at low constant muscle blood flow. Further, without alkalosis, the norepinephrine effect at high flow was transient.

Alkalosis↗
PubMed1993

Acid-base regulation of hepatic glutamine metabolism and ureagenesis: study with 15N.

The metabolism of (5-15N)glutamine and (2-15N) glutamine has been studied by isolated hepatocytes obtained from either control, chronically acidotic, or alkalotic rats. The main goal was to elucidate the mechanism(s) by which altered acid-base state affects hepatic ureagenesis from glutamine. Isolated hepatocytes were incubated in Krebs buffer (pH 7.4) supplemented with 0.1 mM ornithine plus either 1 mM (5-15N)glutamine or (2-15N)glutamine. To elucidate the role of glutamine cycling in net ammonia metabolism, a separate series of experiments were performed with 1 mM unlabeled glutamine plus 1 mM (15N)H4Cl. Net glutamine utilization was significantly lower in hepatocytes obtained from chronically acidotic rats compared with control or alkalotic rats. The sum of the rates of 15NH3 and (15N)urea production from (5-15N)glutamine was decreased in acidosis compared with alkalosis. After incubations of 50 min, approximately 75, 65, or 90% of the N in carbamoyl-phosphate was derived from the 5-N of glutamine in control, acidosis, or alkalosis respectively. In experiments with (2-15N)glutamine, the production of singly and doubly labeled (15N)urea as well as (15N)aspartate and (15N)H3 was significantly smaller in acidosis compared with alkalosis. Furthermore, a correlation was observed between production rates of (15N)aspartate and (15N)urea, suggesting that alterations in urea production may depend on aspartate formed from glutamine. However, the production of (15N)alanine was higher in acidosis compared with alkalosis with apparent correlation between the production of (15N)alanine and 2-oxoglutaramate, a product of the glutamine aminotransferase pathway. In addition, the rate of glutamine recycling was significantly higher in acidosis compared with control or alkalosis, indicating that both flux through glutamine aminotransferase and flux through glutamine synthetase were elevated in acidosis compared with alkalosis. These data suggest that decreased formation of aspartate from glutamine may limit ureagenesis in chronic metabolic acidosis. The formation of aspartate may depend on the availability of oxaloacetate rather than diminished flux through transaminase reaction. The enhancement of alanine production and glutamine synthesis may provide an alternate route of N disposal in cases of diminished urea formation.

Acid-Base Equilibrium↗
PubMed1993

[The mechanisms of disorders of carbohydrate metabolism in changes to the acid-base balance].

Experiments on white rats found that both chronic acidosis and chronic alkalosis cause fasting hyperglycemia and decreases glucose tolerance. In hypophysectomized animals, alkalosis causes similar effects and acidosis leads to hypoglycemia. Acute acidosis stimulates insulin and corticotropin secretions acute alkalosis reduces blood insulin and corticotropin levels and increases glucagon concentration. Chronic acidosis and alkalosis decrease insulin secretion and stimulates corticotropin secretion. Glucagon levels remain increased in chronic alkalosis. It has been concluded that primary cause of diabetogenic action of chronic acidosis is glucocorticoid hyperfunction and exhausting stimulation of B cells with glucose. Alkalosis causes a direct inhibitory action on B cells and activates A cells of Langerhans' islets.

Acid-Base Imbalance↗
PubMed1999

Clinical assessment of acid-base status. Strong ion difference theory.

The traditional approach to evaluating acid-base balance uses the Henderson-Hasselbalch equation to categorize four primary acid-base disturbances: respiratory acidosis (increased PCO2), respiratory alkalosis (decreased PCO2), metabolic acidosis (decreased extracellular base excess), or metabolic alkalosis (increased extracellular base excess). The anion gap is calculated to detect the presence of unidentified anions in plasma. This approach works well clinically and is recommended for use whenever serum total protein, albumin, and phosphate concentrations are approximately normal; however, when their concentrations are markedly abnormal, the Henderson-Hasselbalch equation frequently provides erroneous conclusions as to the cause of an acid-base disturbance. Moreover, the Henderson-Hasselbalch approach is more descriptive than mechanistic. The new approach to evaluating acid-base balance uses the simplified strong ion model to categorize eight primary acid-base disturbances: respiratory acidosis (increased PCO2), respiratory alkalosis (decreased PCO2), strong ion acidosis (decreased [SID+]) or strong ion alkalosis (increased [SID+]), nonvolatile buffer ion acidosis (increased [ATOT]) or nonvolatile buffer ion alkalosis (decreased [ATOT]), and temperature acidosis (increased body temperature) or temperature alkalosis (decreased body temperature). The strong ion gap is calculated to detect the presence of unidentified anions in plasma. This simplified strong ion approach works well clinically and is recommended for use whenever serum total protein, albumin, and phosphate concentrations are markedly abnormal. The simplified strong ion approach is mechanistic and is therefore well suited for describing the cause of any acid-base disturbance. The new approach should therefore be valuable in a clinical setting and in research studies investigating acid-base balance. The presence of unmeasured strong ions in plasma or serum (such as lactate, ketoacids, and uremic anions) is best detected by calculating the SIG. The AG, actual bicarbonate concentration, and standard bicarbonate concentration all ignore the effects that changes in plasma protein and phosphate concentration have on plasma pH, thereby inevitably leading to inaccuracies in estimating the unmeasured strong ion concentration in plasma.

Acid-Base Equilibrium↗
PubMed1990

Effects of blood gas/pH abnormalities on the cardiovascular actions of verapamil in rats.

1. The effects of hypoxaemia, hyperoxaemia, alkalosis, acidosis, hypocarbia with alkalosis or hypercarbia with acidosis on the blood pressure and pulse rate responses to verapamil were studied in chloralose-anaesthetized rats. 2. At a fixed stroke volume (10 mL/kg) and rate (80 strokes/min; except for the hypocarbic group at 160 strokes/min), hypoxaemia, hyperoxaemia, hypercarbia with acidosis, or hypocarbia with alkalosis was induced by artificial ventilation with gas mixtures containing 17% O2, 28% O2, 23% O2, with 5% CO2, or 17% O2, without CO2 respectively. Acidosis or alkalosis was produced by intravenous infusion of 1 mol/L HCl or 1 mol/L NaHCO3 respectively, in animals artificially ventilated with room air. 3. Changes in individual blood gas/pH parameters had no significant effect on blood pressure except for acidosis which caused a significant decrease. Effects on pulse rate were significant increases in the alkalosis and hypercarbia groups, decrease in the acidosis group, while in other conditions no significant changes were recorded. 4. In the controls, intravenous injections of verapamil 20-320 micrograms/kg caused dose-dependent increases in mean blood pressure, while effects on pulse rate were not marked. 5. The hypotensive responses to verapamil were significantly alleviated or enhanced in the presence of alkalosis or acidosis respectively. Verapamil also caused greater falls in pulse rate during acidosis. Effects of Po2 changes were not statistically significant. The influence of PCO2 changes remained unclear. 6. The present findings suggest that changes in blood pH may play a more important role than Po2 alterations in affecting the cardiovascular responses to verapamil in the presence of blood gas abnormalities.

Acid-Base Imbalance↗
PubMed1986

Renal tissue citrate: independence from citrate utilization, reabsorption, and pH.

During alkalosis in vivo, renal tissue [citrate] [( citrate]t) increases and citrate reabsorption (Tcit) and utilization (Qcit) simultaneously decrease. The decrease in Qcit is interpreted to cause the increased [citrate]t, which in turn decreases Tcit X Renal citrate handling and [citrate]t could be regulated by other mechanisms, since alkalosis changes [substrate] and [H+] in extracellular (ECF) and intracellular (ICF) fluid. Also, since high plasma [citrate] decreases ionized [Ca2+] (Cai), it is not possible to determine in vivo whether there is a maximum for Tcit or Qcit and whether change in extracellular fluid (delta ECF) pH affects these maxima. We perfused the substrate-limited isolated rat kidney for either 110 (n = 36) or 50 min (n = 44) at pH 7.2, 7.4, or 7.6; pH was changed by varying [HCO3-]; Cai was held constant at approximately 2.5 meq/liter. When citrate was the only substrate available in a Krebs-Ringer-HCO3 perfusate containing 6% substrate-free albumin, both Qcit and Tcit had maximal rates: Qcit much greater than Tcit; at pH 7.6, Qcit and Tcit were significantly reduced below their values at pH 7.2 or 7.4. In contrast to in vivo observations, [citrate]t was not significantly increased at high ECF pH. To test whether [citrate]t in the perfused kidney can increase in alkalosis, 11 additional perfusions were done in the presence of glucose plus lactate plus malate but without added citrate: [citrate]t = 0.6 mumol X g-1 at pH 7.6 and 0.3 mumol X g-1 at pH 7.2 (P less than 0.01); no citrate was detectable in the perfusate, and urinary citrate excretion was negligible. Thus, in the isolated rat kidney, an increase in [citrate]t occurred in alkalosis and was derived from precursors and not from citrate in the ECF. Overall, when only citrate was available to the isolated kidney during alkalosis, a significant rise in [citrate]t did not occur, although Vmax for Tcit and Qcit decreased. These effects of alkalosis on Tcit are consistent with observations in brush-border vesicles, where divalent citrate is the preferential substrate for luminal Na+-coupled transport; by contrast, high ECF pH and [HCO-3] apparently decrease Qcit by a direct effect on the utilization of citrate.

Absorption↗
PubMedDate not supplied

Acute and chronic changes in intra- and extracellular potassium and responses to neuromuscular blocking agents.

The effects of acutely induced metabolic and respiratory alkalosis with reduction of serum potassium concentration as well as chronic total body potassium depletion induced by furosemide treatment were evaluated and correlated with alteration of neuromuscular blockade induced by d-tubocurarine, pancuronium, and succinylcholine in 12 mongrel dogs. Acute respiratory and metabolic alkalosis significantly reduced serum potassium by about 26%, while chronic furosemide treatment (1 mg/kg IV daily for 14 +/- 4 days) significantly reduced both serum potassium concentration (4.16 +/- 0.31 to 3.27 +/- 0.14 mEq/L) and skeletal muscle potassium content (80.9 +/- 5.6 to 58.7 +/- 4.1 mEq/kg). Succinylcholine neuromuscular blockages was essentially unchanged by acute respiratory or metabolic alkalosis or by chronic furosemide treatment, except for more rapid onset of blockade when 0.1 mg/kg succinylcholine was administered during metabolic alkalosis. Acute respiratory alkalosis shortened the duration of neuromuscular blockade induced by d-tubocurarine and pancuronium while acute metabolic alkalosis shortened the duration of pancuronium only and had no effect on d-tubocurarine. Chronic furosemide treatment had no effect on either d-tubocurarine or pancuronium neuromuscular blockage. Potassium concentration gradients between the intracellular and the extracellular compartments may be more important than cellular potassium depletion per se in affecting responses to neuromuscular blocking agents such as succinylcholine, d-tubocurarine, or pancuronium. Serum alkalemia and hypokalemia antagonize the duration of the neuromuscular blocking action of d-tubocurarine and pancuronium but not that of succinylcholine.

Animals↗
PubMed2006

Extracellular pH changes activate the p38-MAPK signalling pathway in the amphibian heart.

We investigated the activation of the p38-MAPK signalling pathway during extracellular pH changes in the isolated perfused amphibian heart. Extracellular alkalosis (pH 8.5 or 9.5) maximally activated p38-MAPK within 2 min (4.17- and 3.20-fold, respectively) and this effect was reversible since the kinase phosphorylation levels decreased upon reperfusing the heart with normal Tris-Tyrode's buffer. Extracellular acidosis also activated p38-MAPK moderately, but persistently (1.65-fold, at 1 min and 1.91-fold, at 60 min). The alkalosis-induced p38-MAPK activation depended upon the Na(+)/H(+) exchanger (NHE) and Na(+)/K(+)-ATPase, because it was abolished when the NHE inhibitors amiloride and HOE642 and the Na(+)/K(+)-ATPase inhibitor, ouabain, were used. Our studies also showed that extracellular alkalosis (pH 8.5) induced MAPKAPK2 phosphorylation (2.59-fold, 2 min) and HSP27 phosphorylation (5.33-fold, 2 min) in a p38-MAPK-dependent manner, as it was inhibited with 1 micromol l(-1) SB203580. Furthermore, immunohistochemical studies of the phosphorylated forms of p38-MAPK and HSP27 revealed that these proteins were localised in the perinuclear region and dispersedly in the cytoplasm of ventricular cells during alkalosis. Finally, alkalosis induced the increase of HSP70 protein levels (1.52-fold, 5 min), but independently of p38-MAPK activation. These data indicate that the p38-MAPK signalling pathway is activated by extracellular pH changes and in the case of alkalosis this activation may have a protective role.

Animals↗
PubMed1997

Hypomagnesemic hypokalemia and hypocalcemia: clinical and laboratory characteristics.

Clinically important electrolyte disturbances such as hypokalemia and hypocalcemia have been well described in patients with hypomagnesemia of various causes. We undertook the present study to describe in detail the clinical characteristics as well as the acid base and electrolyte abnormalities in an effort to better understand the conditions that favor the appearance of this syndrome of hypomagnesemic hypokalemia and hypocalcemia, and the underlying pathogenetic mechanisms. A total of 35 adult patients (23 male, 12 female), aged 21-79 years, who exhibited profound hypomagnesemia, hypokalemia, and hypocalcemia on their admission were studied. The most common causes of the syndrome were alcoholism and cisplatin administration. All but 2 patients with diarrhea had inappropriate magnesiuria. Despite hypokalemia and hypocalcemia all patients exhibited renal potassium and calcium wasting. Eight alcoholic patients with alcohol withdrawal syndrome or acute intoxication had pure respiratory alkalosis, while 6 patients with severe hypokalemia presented with metabolic alkalosis. Three chronic alcoholic patients exhibited metabolic alkalosis coexisting with respiratory alkalosis, while 1 alcoholic patient had the syndrome of alcoholic ketoacidosis. Hyponatremia was evident in only 2 patients with clinical and laboratory evidence of extracellular volume depletion. Hypophosphatemia was observed in 12 patients mainly due to inappropriate phosphaturia. Finally, hyperphosphatemia was found in 2 alcoholic patients with severe respiratory alkalosis. In conclusion, patients with hypomagnesemic hypokalemia and hypocalcemia exhibit multiple interrelated acid base and electrolyte abnormalities and mainly hypokalemia due to inappropriate kaliuresis, hypophosphatemia or rarely hyperphosphatemia, respiratory and metabolic alkalosis, as well as mixed acid base disorders.

Acid-Base Imbalance↗
PubMed1987

Alkalemia-associated morbidity and mortality in medical and surgical patients.

The difference in death rate among medical and surgical inpatients having alkalemia is incompletely defined. This prospective study was done to identify the incidence, mortality, and clinical factors that resulted in a poor outcome in both groups of patients. We screened a total of 10,811 consecutive arterial blood gas values; in 4,427 (40.9%) the pH was greater than 7.44, and in 2,577 (23.8%) the pH was greater than 7.48. The study group consisted of 409 patients (213 medical, 196 surgical) whose pH value was greater than 7.48; 253 of these patients (61.9%) had pure respiratory alkalosis, 120 (29.3%) had mixed respiratory and metabolic alkalosis, 27 (6.6%) had a mixed acid base disorder, and nine (2.2%) had pure metabolic alkalosis. Overall group mortality was 27.9% and increased as pH values rose, reaching 48.5% when the pH was greater than 7.60. The overall mortality among medical patients (36.6%) exceeded that among the surgical patients (12.4%) (P less than .05), an observation that applied over a wide range of pH values. Patients having mixed respiratory and metabolic alkalosis had a significantly poorer outcome (44.2% mortality) than the alkalemic group as a whole (27.9% mortality) (P less than .05). Alkalemia-associated illnesses are common in hospitalized patients and are associated with high mortality in both medical and surgical patients, though the death rate is higher among medical patients. Mixed respiratory and metabolic alkalosis appears to be associated with a particularly poor prognosis.

Alkalosis↗
PubMed2006

[A man with a classic serious milk-alkali syndrome and a carcinoma of the stomach].

A 42-year-old man was transferred to the Emergency Department after his friends had found him unresponsive and confused in his room. He had been experiencing upper abdominal complaints for a period of several months. He had taken large amounts of a calcium carbonate/magnesium subcarbonate preparation (Rennie) and had consumed at least 3 litres of dairy products per day. His behaviour was reported as being more and more abnormal during the previous few weeks. On admission he was confused and agitated and had involuntary movements of his limbs. Laboratory investigation indicated a triple acid base disorder, i.e. metabolic alkalosis, respiratory alkalosis and high anion gap metabolic acidosis, with severe dehydration. The metabolic alkalosis was caused by the intake of large amounts of dairy and antacids: milk-alkali syndrome. The metabolic acidosis was the result of hypovolaemia and pre-renal renal failure and the respiratory alkalosis was caused by hyperventilation due to the organic psychosyndrome. The patient was treated with volume expansion by isotonic saline and the administration of potassium and he was sedated with low-dose midazolam, which led to a full respiratory compensation of the metabolic alkalosis. A few days following admission, both the plasma calcium concentration and renal function returned to normal; the acid-base disorder completely normalized and the organic psychosyndrome disappeared. On gastroduodenoscopy a gastric ulcer was found; biopsies revealed a signet ring cell adenocarcinoma of the stomach.

Acidosis↗
PubMed1985

Simple acid-base disorders.

This article reviews normal acid-base regulation, related laboratory tests, and the potential disorders if the body's ability to compensate is disrupted. Acid derived from the oxidation of proteins and through tissue metabolism must be excreted or neutralized daily by the kidneys and lungs to maintain a proper acid-base balance. Acid-base homeostasis is normally maintained by chemical buffering, changes in renal hydrogen-ion excretion, and alterations in the rate and volume of alveolar ventilation. Metabolic disorders are characterized by disturbances in bicarbonate (HCO3-) concentration, and respiratory disorders develop with primary alterations in the partial pressure of carbon dioxide (Pco2). Metabolic acidosis is characterized by low pH, low serum HCO3- concentrations, and a compensatory decrease in Pco2 with hyperventilation. Bicarbonate administration can correct this disorder, and equations for calculating the necessary amount of HCO3- are presented. Metabolic alkalosis is characterized by a primary increase in HCO3-, compensatory hypoventilation, and an increase in Pco2 (hypercapnia). The drug therapy for this disorder is directed at either saline-responsive alkalosis or saline-resistant alkalosis. Formulas for estimating the volume requirements of patients and appropriate doses of acidifying agents are presented. Respiratory acidosis and alkalosis are also discussed. The initial therapy for the hypercapnia associated with respiratory acidosis requires reversing the underlying pulmonary disease with steroids, bronchodilators, or antibiotics. The increased Pco2 in this conditions must be lowered slowly to avoid precipitating cardiac arrhythmias and seizures. The correction of respiratory alkalosis requires elevating the Pco2 and again treating the underlying disease. Pharmacists should be knowledgeable about acid-base regulation and the disorders that frequently occur with disease because drugs are capable of inducing or exacerbating these disorders and are often key elements in therapy.

Acid-Base Equilibrium↗
PubMed1976

The interstitial pH of the working gastrocnemius muscle of the dog.

In isolated gastrocnemius muscles from 19 dogs the interstitial H+ activity ([H+]int) was measured with bulb-type buffer-filled glass minielectrodes. The muscles were working isotonically and perfused with blood. In addition arterial and venous pH, venous O2 saturation, muscle temperature, and blood flow were meausred continuously at rest, during 12 min of sustained exercise, and in the recovery period. Lactate (LA-) release and O2 consumption were calculated by the Fick principle. The experiments were performed under normal acid-base conditions and during artificially induced metabolic acidosis and alkalosis. 1. In normal acid-base balance [H+]int at rest was 54 +/- 3.3 neq/l (= pH 7.24), while venous H+ ([H+]ven) was 45 +/- 4.7 neq/l (= pH 7.34) A[H+] gradient was always observed between interstitial fluid and venous blood. 2. Immediately after onset of exercise [H+]int decreased transiently. After about 15 s [H+]int increased rapidly up to values of 105 +/- 7 neq/l (= pH 6.98). In the recovery period [H+]int diminished and reached control values after about 20-30 min. [H+]ven increased up to 74.4 +/- 8.4 neq/l (= pH 7.13). Maximal gradients between [H+]int and [H+]ven were 36 neq/l (= pH 0.2). 3. During repeated exercise the decrease in [H+]int at the onset of exercise was more extensive, while the subsequent increase was lowered. These changes correspond to a smaller LA- release. 4. During metabolic alkalosis at the onset of exercise [h+]int decreased less, during metabolic acidosis more than under normal acid-base conditions. Thereafter during metabolic alkalosis maximal values of 95.4 +/ 2 neq/l (= pH 7.03), during metabolic acidosis of 180 +/- 8.6 neq/l (= pH 6.74) were reached. This led to [H+] gradients between interstitial fluid and venous blood which were much higher in metabolic acidosis than in normal acid-base balance or in metabolic alkalosis. In metabolic acidosis [H+]int decreased very sle rapidly than during metabolic alkalosis or during normal acid-base conditions. It is concluded that the H+ activity measured is that within the interstitial space. Exercise hyperemia is not caused by changes of [H+]int. Mechanisms are discussed which may explain H+ gradients between interstitial fluid and venous blood and rapid changes of [H+]int at the onset of exercise.

Acidosis↗
PubMed1991

Influence of pH changes on the actions of verapamil on cardiac excitation-contraction coupling.

Langendorff preparations of Sprague-Dawley rat hearts were perfused with calcium-free Krebs solution of pH 7.48 (control), 7.26 (acidosis) or 7.69 (alkalosis) containing either adrenaline or potassium. The responses of the force of contraction, coronary perfusion pressure and heart rate to graded doses of calcium preceded by a single dose of verapamil were measured. Contractile responsiveness to calcium was reduced during acidosis in both adrenaline- and potassium-stimulated hearts but was increased or reduced during alkalosis with adrenaline- or potassium stimulation, respectively. The efficacy of verapamil as a calcium antagonist increased during acidosis or alkalosis in both adrenaline- and potassium-stimulated hearts. In conclusion, acidosis or alkalosis inhibits potassium-stimulated contractions of the heart and enhances the effects of verapamil on potassium- and adrenaline-mediated contractions. Acidosis inhibits and alkalosis enhances adrenaline-stimulated contractions.

Acidosis↗
PubMed2001

Compulsory hyperventilation and hypocapnia of patients with Leigh syndrome associated with SURF1 gene mutations as a cause of low serum bicarbonates.

Experimental data show that elevation of intracellular pH leads to severe lesions of brain cells. Acidification of intracellular fluid by accumulation of lactate may compensate the effect of respiratory alkalosis. Increased serum pH, and low PCO2, associated with hyperlactataemia (sometimes incorrectly called 'acidosis') have been reported in children with Leigh syndrome (LS). The aim of the study was to determine whether respiratory alkalosis is characteristic of patients with LS due to SURF1 mutations. All venous blood gas data (88 samples) of 18 spontaneously breathing LS patients with recently established SURF1 mutations, hospitalized during 1986-2000, were retrospectively reviewed. The data of an affected boy who survived on a respirator for more than 3 months (79 daily samples) were analysed separately. In spontaneously breathing patients, the data indicated that the patients had compensated or partially compensated respiratory alkalosis (pH 7.388+/-0.060, Pco2 29.2+/-5.7 mmHg, HCO3- 17.4+/-3.0 mmol/L, BE -6.7+/-3.2 mmol/L). Bicarbonate excretion was detected in urine of two examined LS cases in spite of decreased serum HCO3-. In the affected child maintained on a respirator, simple manipulation of the inspired CO2 tension to establish a normal pressure of 35-45 mmHg automatically caused an increase of serum HCO3- concentration to a normal value of 26.3+/-2.9 mmol/L (and BE to +2.2+/-3.1 mmol/L), in spite of cytochrome oxidase (COX) deficiency due to a confirmed SURF1 mutation. We suggest that respiratory alkalosis (hypocapnia) of Leigh syndrome patients with SURF1 mutations results from compulsory hyperventilation and speculate that hypocapnia may contribute to Leigh-like brain damage in the SURF1-deficient patients as well as in other patients presenting with Leigh-like syndrome. The supposition that accumulation of lactate may protect the brain of LS patients from alkalosis-related damage requires further study. Avoidance of any factors stimulating hyperventilation of LS patients and caution when attempting to correct low plasma bicarbonate are suggested.

Alkalosis, Respiratory↗