Acidosis and Urinary Calcium Excretion: Insights from Genetic Disorders.

Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibition of calcium transport processes within the renal tubule. The mechanisms whereby acid alters the integrity and stability of bone have been examined extensively in the published literature. Here, after briefly reviewing this literature, we consider the effects of acid on calcium transport in the renal tubule and then discuss why not all gene defects that cause renal tubular acidosis are associated with hypercalciuria and nephrocalcinosis.

Sodium bicarbonate therapy in patients with metabolic acidosis.

Metabolic acidosis occurs when a relative accumulation of plasma anions in excess of cations reduces plasma pH. Replacement of sodium bicarbonate to patients with sodium bicarbonate loss due to diarrhea or renal proximal tubular acidosis is useful, but there is no definite evidence that sodium bicarbonate administration to patients with acute metabolic acidosis, including diabetic ketoacidosis, lactic acidosis, septic shock, intraoperative metabolic acidosis, or cardiac arrest, is beneficial regarding clinical outcomes or mortality rate. Patients with advanced chronic kidney disease usually show metabolic acidosis due to increased unmeasured anions and hyperchloremia. It has been suggested that metabolic acidosis might have a negative impact on progression of kidney dysfunction and that sodium bicarbonate administration might attenuate this effect, but further evaluation is required to validate such a renoprotective strategy. Sodium bicarbonate is the predominant buffer used in dialysis fluids and patients on maintenance dialysis are subjected to a load of sodium bicarbonate during the sessions, suffering a transient metabolic alkalosis of variable severity. Side effects associated with sodium bicarbonate therapy include hypercapnia, hypokalemia, ionized hypocalcemia, and QTc interval prolongation. The potential impact of regular sodium bicarbonate therapy on worsening vascular calcifications in patients with chronic kidney disease has been insufficiently investigated.

Metabolic acidosis in the critically ill: part 1. Classification and pathophysiology.

Metabolic acidaemia (pH < 7.35 not primarily related to hypoventilation) is common amongst the critically ill and it is essential that clinicians caring for such patients have an understanding of the common causes. The exclusive elimination routes of volatile (carbon dioxide), organic (lactic and ketone) and inorganic (phosphate and sulphate) acids mean compensation for a defect in any one is limited and requires separate provision during critical illness. We discuss the models available to diagnose metabolic acidosis including CO2/HCO3(-) and physical chemistry-derived (Stewart or Fencl-Stewart) approaches, but we propose that the base excess and anion gap, corrected for hypoalbuminaemia and iatrogenic hyperchloraemia, remain most appropriate for clinical usage. Finally we provide some tips for interpreting respiratory responses to metabolic acidosis and how to reach a working diagnosis, the consequences of which are considered in Part 2 of this review.

Clinical review: the meaning of acid-base abnormalities in the intensive care unit part I - epidemiology.

Acid-base abnormalities are common in critically ill patients. Our ability to describe acid-base disorders must be precise. Small differences in corrections for anion gap, different types of analytical processes, and the basic approach used to diagnose acid-base aberrations can lead to markedly different interpretations and treatment strategies for the same disorder. By applying a quantitive acid-base approach, clinicians are able to account for small changes in ion distribution that may have gone unrecognized with traditional techniques of acid-base analysis. Outcome prediction based on the quantitative approach remains controversial. This is in part due to use of various technologies to measure acid-base variables, administration of fluid or medication that can alter acid-base results, and lack of standardized nomenclature. Without controlling for these factors it is difficult to appreciate the full effect that acid-base disorders have on patient outcomes, ultimately making results of outcome studies hard to compare.

Mortality and the nature of metabolic acidosis in children with shock.

HYPOTHESIS: Mortality in children with shock is more closely related to the nature, rather than the magnitude (base deficit/excess), of a metabolic acidosis. OBJECTIVE: To examine the relationship between base excess (BE), hyperlactataemia, hyperchloraemia, 'unmeasured' strong anions, and mortality. DESIGN: Prospective observational study set in a multi-disciplinary Paediatric Intensive Care Unit (PICU). PATIENTS: Forty-six children, median age 6 months (1.5-14.4), median weight 5 kg (3.2-8.8), admitted to PICU with shock. INTERVENTIONS: Predicted mortality was calculated from the paediatric index of mortality (PIM) score. The pH, base excess, serum lactate, corrected chloride, and 'unmeasured' strong anions (Strong Ion Gap) were measured or calculated at admission and 24 h. MEASUREMENTS AND RESULTS: Observed mortality ( n=16) was 35%, with a standardised mortality ratio (SMR) of 1.03 (95% CI 0.71-1.35). There was no significant difference in admission pH or BE between survivors and nonsurvivors. There was no association between elevation of 'unmeasured' anions and mortality, although there was a trend towards hyperchloraemia in survivors ( P=0.08). Admission lactate was higher in nonsurvivors (median 11.6 vs 3.3 mmol/l; P=0.0003). Area under the mortality receiver operating characteristic curve for lactate was 0.83 (955 CI 0.70-0.95), compared to 0.71 (95% CI 0.53-0.88) for the PIM score. Admission lactate level >5 mmol/l had maximum diagnostic efficiency for mortality, with a likelihood ratio of 2.0. CONCLUSION: There is no association between the magnitude of metabolic acidosis, quantified by the base excess, and mortality in children with shock. Hyperlactataemia, but not elevation of 'unmeasured' anions, is predictive of a poor outcome.

[Activity of elastase and its inhibitors in tissues of aorta and blood serum in various types of acidosis]. / Aktyvnist' elastazy ta ïï inhibitoriv u tkanynakh aorty ta syrovatsi krovy pry riznykh vydakh atsydozou.

In modeling of different types of acidosis (hyperchloraemic, lactate and ketoacidosis in the starvation) at rats the elastase activity, contents of alpha-2 macroglobulin (alpha 2M) and alpha-1 proteinase inhibitor (alpha 1PI) in aorta tissues and blood serum were studied. The obtained results indicate that the degree of disturbance in system elastase-inhibitors depends on expressiveness of parameters changes in system of acid-base state regulation. In modeling of various types of acidosis coefficient inhibitors/elastase is reduced due to different parameters change in aorta, namely decrease of alpha 2M contents--in hyperchloraemic acidosis, increase of elastase activity--in lactat-acidosis, increase of elastase activity and decrease of alpha 2M contents--in ketoacidosis. In blood serum the similar coefficient is reduced due to increase of elastase activity and decrease of alpha 2M contents in hyperchloraemic acidosis and starvation, and, in turn, due to decrease of alpha 2M contents--in lactat-acidosis. The obtained data indicate that one of mechanisms of vascular wall damage in acidosis is disturbance of balance between elastase and its inhibitors in tissues of arteries.

Using an algorithm to interpret arterial blood gases.

The arterial blood gas (ABG) analysis, one of the most common tests ordered, provides clinicians with valuable information on a patient's oxygenation and acid-base balance. Interpreting ABG analysis results can be challenging, even for the most experienced practitioners, because it requires knowledge of the physiology and cause-and-effect relationship of the disturbances. Applying the principles and the ABG algorithm described in this article will provide nurses with a systematic way to interpret uncomplicated arterial blood gas results, including primary, mixed, and compensated acidbase disturbances.

Acid-base disorders in milk-fed calves with chronic indigestion.

Acid-base disorders were investigated in 50 calves with chronic indigestion and metabolic acidosis. In the calves that were unable to stand up, the acidosis was significantly more severe than in the calves that could stand up. The anion gap and four different components of the base excess were calculated by the method described by Fencl. The anion gap was high in more than half of the calves, and it was significantly associated with the base excess due to unidentified anions. However, in seven of the calves, the excess of unidentified anions would not have been detected without the calculations, which made it possible to measure the effect of sodium, chloride, plasma protein and unidentified anions on the acid-base balance. Twenty-four of the calves had a combination of hyperchloraemic and high anion gap metabolic acidosis. Changes in sodium and plasma protein concentrations had a minor impact on the calves' acid-base status.

Clinical, haematological and biochemical findings in milk-fed calves with chronic indigestion.

The principal clinical signs in 59 milk-fed calves with chronic indigestion were general malaise and depression, poor appetite, poor body condition, dehydration, a dull and scaly hair coat, alopecia and clay-like faeces. All the calves had metabolic acidosis, which was associated with an inability to stand up in more than half of them. There were significant differences in the severity of acidosis between the calves that could stand and those that could not. Other signs in some of the calves were dehydration, leucocytosis, and increased activities of liver enzymes.

Base deficit in the elderly: a marker of severe injury and death.

BACKGROUND: Base deficit has been used as a marker of significant injury and to predict resource utilization and mortality. The significance of base deficit in trauma patients 55 years and older has not been specifically evaluated. The purpose of this study was to determine the utility of base deficit in assessing older trauma patients versus a younger cohort. METHODS: Data were obtained from the trauma registry on trauma patients admitted to a Level I trauma center. Arterial blood gases were obtained within 1 hour of arrival, by protocol, in 2,631 patients, and of these, 274 patients were 55 years or older. Data are presented as means+/-SEM. Statistical analysis was done by paired t test, analysis of variance, and chi2 analysis. Significance was attributed to a p value < 0.05. RESULTS: Patients older than 55 years were significantly more likely to have sustained blunt trauma (86 vs. 69%; p < 0.001). Despite similar Injury Severity Scores and base deficit values, older patients had markedly greater mortality and intensive care unit lengths of stay. A base deficit of < or = -6 had positive predictive values for Injury Severity Scores > or = 16 for 76% of patients younger than 55 years and 78 % of patients 55 years and older. The negative predictive value of a normal base deficit for Injury Severity Scores < or = 16 was 60% for the younger cohort and only 40% for patients 55 years and older (p < 0.001; chi2). CONCLUSIONS: A base deficit of < or = -6 is a marker of severe injury and significant mortality in all trauma patients, but it is particularly ominous in patients 55 years and older. Patients older than 55 years may have significant injuries and mortality risk without manifesting a base deficit out of the normal range.

[Acidosis in severe acute asthma]. / Les acidoses au cours des asthmes aigus graves.

On admission to intensive care units, the acid-base profile in acute severe asthma appears to be more diverse than previously. Especially a mixed or less frequently metabolic acidosis is eventually observed, which is not always caused by elevated lactate. On the other hand, hyperlactatemia is actually rather common, not necessarily accompanied by acidosis. This finding is as a rule related to massive doses of beta 2 adrenergic agents given parenterally: subsequent elevated lactate is in no way a marker of cellular hypoxia and has no pejorative meaning in this event. Hypercapnia with severe respiratory acidosis implies less and less mechanical ventilation; however, when mandatory, it has to be carried out using permissive hypercapnia, giving more favorable outcome while lowering side-effects.

[Diagnosis, countermeasure and classification of acidosis].

Acidosis is the result of the net addition of hydrogen ion to the extracellular space or loss of bicarbonate from that space. Hydrogen ion may be added by the increased production of strong acids, an increase in CO2 concentration, or the addition of exogenous acids. The common approach to the differential diagnosis of metabolic acidosis is to divide the patients into two categories based on whether the anion gap in plasma is increased or not. Metabolic acidosis with normal anion gap (hyperchloremic) suggests that bicarbonate has been effectively replaced by chloride. In contrast, metabolic acidosis with an increased anion gap suggests addition to the body fluids of an acid other than hydrochloric acids or its equivalent.

[Water-electrolyte and acid-base imbalance. VI. Metabolic acidosis]. / Alteraciones hidroelectrolíticas y ácido-base. VI. Acidosis metabólica.

Metabolic acidosis results from a disequilibrium between production and excretion of acid. Loss of base from the body through the gastrointestinal tract or in the urine or an increase in metabolic acid production are the three major mechanisms from which metabolic acidosis is generated. Uncomplicated metabolic acidosis is manifested by an increase in blood acidity, hypobicarbonatemia, and hypocapnea. The magnitude of these changes defines the severity wf the acidosis. It is convenient to divide metabolic acidosis into two general categories (hyperchloremic and normochloremic), based on the observed anion gap, as this serves to narrow the differential diagnosis. The normal anion gap is that amount of plasma anion not measure by routine laboratory screening that accounts for the difference between the measured sodium cation (Na+) and anions (Cl +/- HCO3-). Metabolic acidosis; causes; diagnosis; clinical manifestations.

Glutaric aciduria type II: autopsy study of a case with electron-transferring flavoprotein dehydrogenase deficiency.

An autopsy study of glutaric aciduria type II in a 62-day-old Japanese boy is presented. The diagnosis was made by analysis of organic acids in the urine. Immunoblot analysis of liver homogenate confirmed the diagnosis, revealing absence of electron-transferring flavoprotein dehydrogenase. The major findings were fatty changes of variable degree in many organs and tissues, the most severe being found in cardiac myocytes, hepatocytes, renal tubular epithelium, and skeletal muscle fibers. Other pertinent findings included multicystic and dysplastic kidney, pulmonary alveolar proteinosis, and spongiosis and gliosis of the spinal cord. The thymus was markedly depleted, and lymphocytes in the lymph nodes were mainly B cells. Although some of these changes may have been secondary to the sepsis and immunosuppression complicating 2 months of intensive care, the abnormal organic acid metabolism with severe acidosis may have been a significant contributing factor.

Pathophysiology of type A hypoxic lactic acidosis in dogs.

Hypoxic lactic acidosis (HLA) was induced in dogs by ventilating them with a hypoxic gas mixture of 8% O2-92% N2. The animals were studied both in the control state and after development of HLA, where arterial lactate was above 5 mM, pH was below 7.2, bicarbonate was below 12 mM, and arterial PO2 was between 26 and 30 Torr. After hypoxia had been present for 90 min, most of the increase in arterial lactate vs. control was due to increased lactate production from gut and carcass in the presence of a decreased capacity of the liver to extract lactate. The capacity of the liver to extract lactate in the normoxic state was evaluated in another group of six dogs after infusion of L-lactic acid such that arterial pH, lactate, and bicarbonate were similar to hypoxic values. In these experiments it was found that the capacity of the liver to extract lactate was 14.8 +/- 1.7% of the delivered load vs. 4.9 +/- 1.3% observed in hypoxic animals. The decreased liver lactate extraction in HLA was probably secondary to both a decrease in liver oxygen uptake and a decrease in liver intracellular pH and was paralleled by an increase in liver tissue lactate levels. Cardiac output, in contrast to other forms of lactic acidosis, was increased by 40% vs. control and femoral artery flow by 35%, whereas liver blood flow was unchanged and renal blood flow decreased. Hypoxic lactic acidosis thus is the consequence of overproduction of lactate by both gut and carcass, in the presence of impaired utilization of lactate by the liver.(ABSTRACT TRUNCATED AT 250 WORDS)