Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ACIDOSIS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 559 records · Page 31Linked to original sources

Effect of acidosis on contraction, intracellular pH and calcium in the rabbit mesenteric small artery.

The purpose of the present study was to determine the effect of various types of acidosis on vessel diameter, intracellular pH (pHi), and calcium concentration ([Ca2+]i) in a cannulated preparation of the mesenteric arteriole of the rabbit. The effect of acidosis on vessel contraction was also studied in the wire-mounted preparation. In the cannulated preparation, pre-contracted by noradrenaline, hypercapnia caused vasoconstriction and increases in [Ca2+]i. In the wire-mounted preparation pre-contracted by either noradrenaline or high KCl, hypercapnia caused a transient vasoconstriction. In contrast, in the cannulated preparation pre-contracted by high KCl, hypercapnia caused a transient vasorelaxation and decreases in [Ca2+]i. Intracellular acidosis, induced by a NH4Cl prepulse, caused vasoconstriction and increases in [Ca2+]i even in the cannulated preparation pre-contracted by high KCl. The decrease in pHi during hypercapnia was similar to that observed after NH4Cl withdrawal. These data suggest that: (1) the effect of acidosis on vascular tone and [Ca2+]i is different depending upon the type of preparation and the mode of pre-activation, and (2) [Ca2+]i may, at least partly, regulate vascular contraction and relaxation during acidosis.

Acidosis↗

Effects of serosal-side acidosis on cell pH (pHi) and membrane electrical properties in gastric mucosa.

Acute gastric mucosal injury and bleeding occur in the settings of both respiratory acidosis or metabolic acidosis secondary to systemic sepsis or shock. Respiratory acidosis, however, is more predictably associated with acute injury than metabolic acidosis. We hypothesized that the gastric surface epithelial cells are more susceptible to acute increases in PCO2 than to acute decreases in HCO3-, even for the same level of extracellular acidification. To evaluate this hypothesis, we used intracellular microelectrodes to measure pHi, cell membrane potential (Vc), as well as ion conductances of the apical (Ga) and basolateral (Gb) membranes and the paracellular pathway (Gs) in gastric mucosal cells during acute changes in serosal PCO2 or HCO3-. Necturus antral mucosae were mounted in Ussing chambers, perfused on both sides by Ringer solution (40 mmHg PCO2, 18 mM HCO3-, pH 7.3). Measurements were performed before and during increases in PCO2 (80 mmHg, pH 7.0) or decreases in HCO3- (7.2 mM, pH 6.8 or 2.4 mM, pH 6.4). Both forms of acidosis acidified pHi, depolarized membrane potentials, and decreased ion conductances across apical and basolateral membranes, but not the paracellular pathways. For the same level of extracellular acidification, increases in PCO2 were more effective than acute decreases in HCO3- in acidifying pHi and eliciting disturbances in voltage-generating and ion permeability properties of the cell membranes. These findings suggest that pH-buffering mechanisms in gastric surface cells respond less effectively to high PCO2 than low HCO3.

Acidosis↗

Differential effects of acidosis, high potassium concentrations, and metabolic inhibition on noradrenaline release and its presynaptic muscarinic regulation.

It was the aim of the present study to characterize the effect of single components of ischaemia, such as inhibition of aerobic and anaerobic energy production by combined anoxic and glucose-free perfusion (metabolic inhibition), high extracellular potassium concentrations (hyperkalaemia), and acidosis, on (1). the stimulated release of noradrenaline from the in situ perfused guinea-pig heart and (2). its presynaptic modulation by the muscarinic agonist carbachol. The release of endogenous noradrenaline from efferent cardiac sympathetic nerve endings was induced by electrical stimulation of the left stellate ganglion (1 min, 5 V, 12 Hz) and quantified in the coronary venous effluent by high-performance liquid chromatography. Under control conditions, two consecutive electrical stimulations (S1, S2) elicited a similar noradrenaline overflow (S2/S1: 0.98 plus minus 0.05). After 10 min of global myocardial ischaemia overflow of endogenous noradrenaline was significantly reduced (S2/S1: 0.18 plus minus 0.03; P< 0.05). When studied separately, metabolic inhibition, hyperkalaemia (16 mM), and acidosis (pH 6.0) each markedly attenuated stimulated noradrenaline overflow (S2/S1: 0.65 plus minus 0.05, 0.43 plus minus 0.14, and 0.37 plus minus 0.09, respectively; P< 0.05). The muscarinic agonist carbachol (10 microM) inhibited stimulated noradrenaline release under normoxic conditions (S2/S1: 0.41 plus minus 0.07; P< 0.05). However, after 10 min of global myocardial ischaemia the inhibitory effect of carbachol on noradrenaline overflow was completely lost. Single components of ischaemia had a differential effect on presynaptic muscarinic modulation. Whereas hyperkalaemia (8-16 mM) did not affect muscarinic inhibition of noradrenaline release, carbachol lost its inhibitory effect during acidosis and metabolic inhibition. In conclusion, hyperkalaemia, metabolic inhibition, and severe acidosis each contribute to reduced overflow of noradrenaline after 10 min of myocardial ischaemia. However, presynaptic muscarinic inhibition of noradrenaline release was not affected by hyperkalaemia, but was sensitive to metabolic inhibition and low degrees of acidosis.

Acidosis↗

Response of cortical oxygen and striatal extracellular dopamine to metabolic acidosis in newborn piglets.

This study determined the relationships of metabolic acidosis, cortical oxygen pressure, and striatal extracellular dopamine in the brain of newborn piglets. After a baseline period of 120 minutes, a 0.6 N HCl solution was infused intravenously to decrease the blood pH to about 7.0-7.05. The metabolic acidosis was then corrected by injecting sodium bicarbonate and measurements were continued for one hour. The results show that decreased blood pH to about 7.2-7.15 does not cause a statistically significant change in mean blood pressure, cortical oxygen pressure or striatal extracellular dopamine. Further decrease in pH caused significant decrease in both blood pressure and cortical oxygen pressure. By the end of the period of acidosis the cortical oxygen pressure decreased from the control value of 43 +/- 4 Torr to 22 +/- 8 Torr. Changes in the extracellular level of striatal dopamine were parallel to changes in cortical oxygen pressure. The extracellular dopamine increased to 1270% of the control on the end of HCl injection. Infusion of bicarbonate to correct the acidosis resulted in an increase of cortical oxygen and progressive decline of dopamine in the extracellular medium. It is suggested that the level of extracellular dopamine in the striatum of newborn piglets was not directly affected by decrease in pH but was dependent on changes in tissue oxygen pressure during metabolic acidosis.

Acidosis↗

Continuous monitoring of cerebrospinal fluid acid-base balance and oxygen metabolism in patients with severe head injury: pathophysiology and treatments for cerebral acidosis and ischemia.

INTRODUCTION: Continuous monitoring of cerebral acid-base balance and oxygen metabolism has been introduced in neurointensive care settings. The hypothesis of this study utilizing multimodal neuromonitoring modalities is that hyperventilation and hypothermia improve cerebral acidosis through prevention of cerebral ischemia aggravation in patients with severe head injury. PATIENTS AND METHODS: Continuous monitoring of cerebrospinal fluid (CSF) pH, PCO2, HCO3-, base excess (BE), PO2, SO2, temperature, lactate and pyruvate (La and Py) measurements were conducted in 8 patients with severe head injury. Temperature-corrected CSF parameters were correlated with those in the jugular blood including oxygen saturation (SjO2), regional oxygen saturation (rSO2), intracranial pressure (ICP) and cerebral perfusion pressure (CPP), jugular blood temperature (Tjb), and endtidal PCO2 (PetCO2). Therapeutic significance of hyperventilation and hypothermia was evaluated. RESULTS: 1) CSF acidosis was observed in all cases (minimum pH 6.59-7.17) due to increased CSF PCO2 and/or decreased CSF HCO3- and tended to associate with abnormal ICP and/or CPP or ischemic episodes indicated by CSF PO2 and SO2, rSO2, and/or SjO2 during monitoring. 2) It was more obvious in CSF than in jugular blood that increased PCO2, La and Py, and/or decreased HCO3- resulted in decreased BE and pH. 3) Decreased CSF PO2 and SO2 only correlated with severe CSF acidosis. 4) Hyperventilation: Decreased PetCO2 did not always closely correlate with CSF PCO2 decrease and CSFpH increase. 5) Hypothermia: There were negative correlations of Tjb with CSF pH and SO2 in all cases, though correlation coefficients were not always high. CONCLUSIONS: CSF acidosis caused by increased CSF PCO2, La and Py, and/or decreased HCO3- tended to associate with abnormal ICP and CPP, and desaturation indicated by CSF SO2, rSO2, and/or SjO2. Hypothermia rather than hyperventilation tends to improve cerebral acidosis and ischemia.

Acidosis↗

Role of protein kinase C in acidosis induced glial swelling--current understanding.

A major factor in secondary brain injury following cerebral trauma is accumulation of lactic acid resulting in glial swelling. Further, evidence obtained in this context demonstrates activation of protein kinase C (PKC) under these circumstances. Glial swelling from acidosis is attributable to activation of the Na+/H(+)-exchanger, mediating influx of Na(+)-ions in exchange for the extrusion of H+ ions. The antiporter is activated following phosphorylation by PKC. The current study was made to elucidate the role of PKC activation in acidosis-induced glial swelling. For that purpose, suspended C6 glioma cells were used to examine changes of the cell volume and intracellular pH (pHi). Acidosis was induced by administration of isotonic lactic acid. Stimulation of PKC by the phorbol-ester PMA was significantly enhancing glial swelling from severe acidosis (pH 6.2), whereas the decrease of pHi was somewhat attenuated. On the other side, inhibition of PKC by staurosporine did not affect cell swelling nor the decrease of pHi from acidosis. The results indicate that activation of PKC in cerebral trauma or ischemia may enhance glial swelling from lactacidosis.

Acidosis, Lactic↗

Biguanide-induced lactic acidosis in Finland.

Twenty-four patients with biguanide-induced lactic acidosis were reported to the Adverse Drug Reaction Register of the Finnish National Board of Health from 1974-1977. Of them, 23 had been treated with phenformin and one with metformin. The mean age of the patients was 71 years, and all but one were more than 65 years of age. The mortality rate was 63%. One patient had cirrhosis of the liver and one was already known tohave had impaired renal function. Fourteen of the patients had a normal serum creatinine concentration either before or after the development of lactic acidosis. Thus, in most patients it had not been possible to prevent development of lactic acidosis by observing the contraindications to biguanide therapy. Most patients had some form of co-existing cardiovascular disease. Tetracycline therapy was a probable precipitating factor in three cases. Based on the statistics of biguanide consumption in Finland, the annual incidence of biguanide-induced lactic acidosis in 1976 and 1977 was between 1/2000 and 1/3000 and that of fatal lactic acidosis was 1/4000.

Acidosis↗

Lactic acid permeation rate in working gastrocnemii of dogs during metabolic alkalosis and acidosis.

In isolated, blood perfused, supramaximally stimulated, isotonically working gastrocnemii of dogs lactic acid (LA) output and O2-consumption (V O2) were measured according to the Fick principle. Simultaneously concentration of muscle tissue was determined at rest and at different times during exercise. In one series of experiments metabolic alkalosis was induced by infusions of THAM of Na bicarbonate. As a result arterial pH increased to about 7.5 and standard [HCO3-1] to 31-35 mmol per 1. In another group of experiments metabolic acidosis was induced by HCl infusions. In these experiments pH decreased to 7.0-7.1 and standard [HO301] to 8-11 mmol per 1. During the first 3-4 min after the onset of exercise LA concentration of muscle tissue rose to 18-19 mumol per g wet weight in both series of experiments. During acidosis the highest average values for LA release from the muscle were about 1.1 mumoles per g per minute. During alkalosis LA permeation rate was nearly three times as high. As a consequence of increased rate of permeation, LA concentration of muscle tissue decreased more rapidly in alkalosis than in acidosis. In both series of experiments work per time and VO2 were practically equal during the first 5-6 min of exercise. Thereafter work per time and VO2 decreased more rapidly in acidosis than in alkalosis, a result which probably is due to higher LA concentration in muscle at this time in acidosis. It is concluded that LA permeation rate across muscle cell membrane is increased by high extracellular HCO3- concentration in combination with low H+ activity and vice versa.

Acidosis↗

Intra- and inter-nephron heterogeneity of ammoniagenesis in rats: effects of chronic metabolic acidosis and potassium depletion.

In order to determine intra- and inter-nephron heterogeneity of ammoniagenesis, ammoniagenic activity in microdissected nephron segments of control, acidotic and potassium (K)-depleted rats was examined. Intranephron distribution of ammoniagenic activity in control rats revealed the highest amount at the second segment of the proximal tubule (S2). Chronic metabolic acidosis induced ammoniagenesis markedly at the first segment of the proximal tubule (S1) by 235% and the thick ascending limb of Henle's loop by 198% and moderately at the S2 by 49%. K-depletion increased ammonia production significantly in the S1 by 298% and the S2 by 107%, which is a pattern quite similar to the result of chronic metabolic acidosis. Ammonia production in K-depletion was also increased in the cortical and medullary collecting tubule by 71% and 102%, respectively, probably due to increases in protein amounts (41% and 158%, respectively) there. To evaluate inter-nephron heterogeneity of ammoniagenesis, ammonia formation from glutamine in the S1 of superficial (SF) and juxtamedullary (JM) nephrons was examined. Although there was no difference in ammonia production between SF-S1 and JM-S1 in control rats, ammonia production in SF-S1 was significantly higher than that in JM-S1 in both metabolic acidosis and K-depletion. From these studies, we conclude: The increase of ammonia production in the proximal tubule was quite similar in both acidosis and K-depletion, suggesting that the main trigger of ammoniagenesis in both conditions might be a reduction of intracellular pH. SF-S1 was the nephron most reactive to acidosis and K-depletion. JM nephrons could be considered to be important not for ammonia production but for ammonia secretion.

Acidosis↗

Renal tubular acidosis (RTA): recognize the ammonium defect and pHorget the urine pH.

To maintain acid-base balance, the kidney must generate new bicarbonate by metabolizing glutamine and excreting ammonium (NH4+). During chronic metabolic acidosis, the kidney should respond by increasing the rate of excretion of NH4+ to 200-300 mmol/day. If the rate of excretion of NH4+ is much lower, the kidney is responsible for causing or perpetuating the chronic metabolic acidosis. Thus, the first step in the assessment of hyperchloraemic metabolic acidosis is to evaluate the rate of excretion of NH4+. It is important to recognize that the urine pH may be misleading when initially assessing the cause of this acidosis, as it does not necessarily reflect the rate of excretion of NH4+. If proximal renal tubular acidosis (RTA) is excluded, low NH4+ excretion disease may be broadly classified into problems of NH4+ production and problems of NH4+ transfer to the urine; the latter being due to either interstitial disease or disorders of hydrogen ion secretion. The measurement of the urine pH at this stage may identify which problem predominates. This approach returns the focus of the investigation of RTA from urine pH to urine NH4+.

Acid-Base Equilibrium↗

Cellular changes in the toad urinary bladder in response to metabolic acidosis.

The urinary bladder of Bufo marinus excretes H+ and NH+4, and the H+ excretion is increased when the animal is placed in metabolic acidosis. The mitochondria-rich (MR) cells mediate the H+ excretion by the bladder. The purpose of this study was to determine if there is a change in MR cells of the bladder during metabolic acidosis. Bladders from normal toads and from toads that had been placed in metabolic acidosis were used. The bladders were mounted between plastic chambers and H+ excretion measured. The bladder was then fixed and prepared for scanning (SEM) and transmission (TEM) electron micrograph studies. SEM's at low magnification were used to count the various cell types and the TEM's were used to confirm the different cell types. Fields were randomly selected and a total of 2500 cells counted in each group. The bladders from toads in metabolic acidosis had a consistently higher ratio of MR cells to granular cell than did the normal bladders. These results indicate that during metabolic acidosis there is an increased number of MR cells in the bladder, and this increased the bladder's capacity to excrete H+.

Acidosis↗

Effect of acute metabolic acidosis on transmembrane electrolyte gradients in individual renal tubule cells.

We studied the effect of acute metabolic acidosis on potassium, sodium and chloride gradients across the apical membrane of proximal and distal tubule cells by determining electrolyte concentrations in individual cells and in tubule fluid employing electron microprobe analysis. Cellular measurements were performed on freeze-dried cryosections of the renal cortex, analysis of tubule fluid electrolyte concentrations on freeze-dried microdroplets of micropuncture samples obtained from proximal and from early and late distal collection sites. Acidosis (NH4Cl i.v. and i.g.) induced a substantial rise in plasma potassium concentration without significant effects on cell potassium concentrations. Potassium concentrations along the surface distal tubule were also unaltered; thus the chemical driving force for potassium exit from cell to lumen was not affected by acidosis. In all but intercalated cells acidosis markedly increased cell phosphorus concentration and cell dry weight indicating cell shrinkage and thus diminution of cell potassium content. Because the increase in intracellular chloride concentration exceeded the increase in plasma chloride concentration, the chemical chloride gradient across the contraluminal membrane was markedly depressed by acidosis.

Acidosis↗

Metformin-associated lactic acidosis in Sweden 1977-1991.

Since the withdrawal of phenformin in 1978, the use of metformin has increased from 13,500 to 22,000 patient years/year. During the period 1977-91 a total of 18 cases of metformin-associated acidosis was reported, of which 16 had lactic acidosis. The incidence of reported acidosis and lactic acidosis decreased from 1.50 cases per 10,000 patient years in 1977-81 to 0.24 cases per 10,000 patient years 1987-91, probably due to lower doses doses and reduced usage in the very old. All the reports described patients with several other concomitant diseases, mainly cardiovascular and renal, when the acidosis was diagnosed. It is important continuously to re-evaluate metformin therapy and to stop treatment at the onset of impaired renal or cardiovascular function.

Acidosis, Lactic↗

The effect of metabolic acidosis on serum apolipoprotein A I and apolipoprotein B levels in children with chronic renal failure.

In this report serum apolipoprotein A I (Apo A I) and apolipoprotein B (Apo B) levels were determined in children with chronic renal disease (CRD) during metabolic acidosis, after the correction of metabolic acidosis and in healthy children to look for the effect of metabolic acidosis on Apo A I and B levels. It was found that Apo A I levels were significantly decreased during metabolic acidosis (p < 0.05) but Apo A I/Apo B ratios were not affected before and after the correction of acidosis in the CRD group (p > 0.05) although it was significantly different from those in the controls (p < 0.01).

Acidosis↗

The effect of foetal acidosis on bupivacaine levels in utero.

Amide local anaesthetics are weak bases with pK's of 7.80 or greater. Therefore, tissue acidosis may result in ionization and "trapping" of the basic local anaesthetics The following study was done in the pregnant ewe to determine if the highly protein-bound local anaesthetic bupivacaine demonstrates ion-trapping in the acidotic foetus. Six pregnant ewes of 135 days gestation were prepared surgically with catheters placed in maternal and foetal femoral arteries an veins. Bupivacaine was infused into the maternal femoral vein to maintain a constant concentration. After two hours of bupivacaine infusion the foetus was made acidotic by an infusion of lactic acid for 45 minutes. Then the acidosis was corrected by an infusion of bicarbonate for an additional 45 minutes. Maternal and foetal bupivacaine levels were measured at 15 minute intervals throughout the experiment. The bupivacaine levels in the foetus and the foetus-maternal ratio increased significantly during the period of foetal acidosis and declined to the control levels when the acidosis was corrected with bicarbonate. We conclude from this study that foetal acidosis results in ion-trapping of bupivacaine to a significant extent, despite protein binding in the maternal blood.

Acidosis↗

Genetic and long-term data on a patient with permanent isolated proximal renal tubular acidosis.

UNLABELLED: A 12-year-old girl presented with permanent isolated proximal renal tubular acidosis (pRTA), glaucoma, band keratopathy, mild cataract and short stature. Severe metabolic acidosis was caused by the impairment of bicarbonate reabsorption in the proximal tubules and alkali therapy improved her acidaemia. A homozygous G to A transition at nucleotide 1,678 in the basolateral kidney type Na+/HCO3- (kNBC) cotransporter gene SLC4A4, which is critical in HCO3- resorption in renal proximal tubules, was identified. Her height and height velocity (HV) were very low (-4.0 SD and -4.4 SD, respectively) before alkali treatment, but both improved after initiating alkali therapy at the age of 2 years and 3 months. The patient's body height and HV were 131.5 cm (-2.7 SD) and 4.0 cm (-2.0 SD), respectively at the age of 12 years. CONCLUSION: This case demonstrates that early administration of alkali therapy and sustained correction of acidosis, even if inadequate to correct the metabolic acidosis, can markedly improves growth in permanent isolated proximal renal tubular acidosis.

Acidosis, Renal Tubular↗

[Hypercapnia and mixed acidosis as the only sign of malignant hyperthermia (MH)?].

CASE REPORT: A 34-year-old male (190 cm/100 kg) was scheduled for surgery of the nasal septum. He had had uneventful anaesthesia for appendicectomy 14 years earlier: following 600 mg thiopentone, 180 mg suxamethonium and up to 2 vol.% halothane for 20 min had been used and no symptoms of malignant hyperthermia (MH) were recorded. Following oral premedication with 2 mg flunitrazepam at 7.00 a.m. anaesthesia was induced with a priming dose of atracurium at 8.45 a.m. followed by 0.2 mg fentanyl, 500 mg thiopentone, and 100 mg suxamethonium. Endotracheal intubation was accomplished easily, and the patient was ventilated manually in a semi-closed circle system until spontaneous ventilation resumed. Enflurane (1.5% for 5 min, 1.0% for 10 min, and 0.8% until the diagnosis of MH was suspected) was given in 33% O2/66% N2O. Seventy minutes after induction it was noted that the spontaneous respiratory rate and minute volume had risen continuously from 10/min and 6 l/min, respectively, to 20/min and 12 l/min. Attempts at deepening anaesthesia with repeated doses of fentanyl up to a total dose of 0.95 mg failed to reduce the hyperventilation. In spite of a high fresh gas flow of 6 l/min and assisted manual ventilation, the FIO2 started to fall from 0.34 to 0.28 at 10:20 a.m. The O2/N2O ratio was changed to 1:1, but the FIO2 remained at 0.3. MH was suspected, enflurane was discontinued, and an arterial blood gas analysis was done (Table 2). When marked acidosis and hypercarbia were found, dantrolene 2.5 mg/kg was given, the operation was terminated, and the patient's trachea was extubated and he was monitored closely in the intensive care unit for 24 h. Vital signs were stable (Table 3) and no further complications were observed. The patient did not mention pain or uneasiness postoperatively. About 6 months later, a muscle biopsy was done according to the European MH Protocol and the patient was found to be MHEh. DISCUSSION: In this case five main reasons for the hypercarbia and mixed acidosis must be considered (Table 1). Firstly, hypoventilation does not seem to be reasonable as the patient was ventilated with 8 to 12 l/min, which is within the range of 80-120 ml/kg.min. Secondly, we can exclude shock and hypoperfusion because the patient had a normal blood pressure and heart rate (within 65-90 beats/min), his fingertips and skin were well perfused, his body temperature was 37 degrees C, and there was no sign of muscle rigidity. Thirdly, a defect of the CO2 absorber as well as CO2 admixture to the N2O and O2 ventilation gases can cause hypercarbia. We use two absorbers in sequence of which one is changed every day, and found neither a change in colour of the indicator nor an abnormally raised temperature of the absorbers. A postoperative check of the ventilator showed no defect in the O2/N2O supply and a correctly functioning anaesthesia apparatus. A malfunction of both CO2 absorbers resulting in intraoperative hypercarbia could not explain a postoperative mixed acidosis lasting for more than 6 h. Anaesthesias performed at the same time using soda lime from the same canisters were totally uneventful. CONCLUSION: It is concluded that the hypercarbia and mixed acidosis were caused by hypermetabolism. A thorough postoperative examination by an internist did not reveal any thyroid, pulmonary, endocrine, or circulatory reason for our intra- and postoperative findings. Iatrogenic factors like superficial anaesthesia or systemic side effects of adrenaline admixture to local anaesthetics can cause hypermetabolism without striking clinical signs, but they do not cause mixed acidosis lasting longer than 6 h (Table 2). The most suitable explanation in this case is an abortive form of MH. Even patients who are MHS positive on muscle biopsy do not necessarily go through an MH crisis every time they have stress or undergo anaesthesia. The diagnosis of a fulminant MH crisis is a clinical one. Therefore, we are aware that there is no direct scientific ev

Acidosis↗

The value of the chloride: sodium ratio in differentiating the aetiology of metabolic acidosis.

OBJECTIVE: Stewart's physicochemical approach to acid-base balance defines the aetiology of a metabolic acidosis by quantifying anions of tissue acids (TA), which consist of unmeasured anions (UMA) and/or lactate. We hypothesised that an increase in TA during metabolic acidosis would lead to a compensatory fall in the plasma chloride (Cl) relative to sodium (Cl:Na ratio) in order to preserve electro-neutrality. Thus, the Cl:Na ratio could be used as a simple alternative to the anion gap in identifying raised TA. PATIENTS: Two hundred and eighty two consecutive patients who were admitted to our Paediatric Intensive Care were enrolled in the study. INTERVENTIONS: We obtained 540 samples (admission n = 282, 24 h n = 258) for analysis of blood chemistry, lactate and quantification of TA and UMA. Samples were subgrouped into those with metabolic acidosis (standard bicarbonate < 22 mmol/l) either with or without increased UMA (> 3 mEq/l). MEASUREMENTS AND RESULTS: Metabolic acidosis occurred in 46% of samples, of which 52.3% (120/230) had increased UMA. The dominant component of TA was UMA rather than lactate, and these two components did not always rise in tandem. Our hypothesis of relative hypochloraemia was supported by a lower Cl:Na ratio (P < 0.0001) but not a lower absolute Cl (P = 0.5) in the acidotic subgroup with raised UMA, and by the inverse relationship between TA and the Cl:Na ratio. (coefficient of determination (r2) = 0.37, P < 0.0001). The best discriminator for the presence of raised TA was the albumin-corrected anion gap (AGcorr), however, this could not track changes in TA with clinical accuracy. The Cl:Na ratio discriminated reasonably well, a ratio of < 0.75 identified TA (positive predictive value (PPV) 88%) with a likelihood ratio (LR) similar to the AG (7.8 vs7.4). Conversely, a high ratio (> 0.79) excluded TA (PPV 81%, LR 4.5). Base deficit (BD) and lactate performed poorly. CONCLUSION: In metabolic acidosis due to TA, plasma Cl concentration decreases relative to sodium. The Cl:Na ratio is a simple alternative to the AG for detecting TA in this setting.

Acidosis↗