Extreme metabolic acidosis

A 42-year-old male patient, who suffered from insulin-dependent diabetes mellitus (IDDM) and intolerance of lactose, presented with extreme metabolic acidosis (lactic acidosis). On arrival, an arterial blood sample showed: pH 6.79, PO2 18.8 kPa, PCO2 0.9 kPa, base excess-33 mmol l-1, blood glucose 38 mmol l-1 and oesophageal temperature 30 degrees C. Apart from the uncontrolled hyperglycaemia, a fluid balance disorder elicited by diarrhoea and disturbed tissue perfusion were possible aetiological factors. The patient was treated with a low-dose insulin regimen and infusion of isotonic sodium bicarbonate with a satisfactory result.     

Hypophosphatemia and metabolic acidosis

The aim of the paper was to describe an unusual case of non lactic metabolic acidosis connected to hypophosphatemia and refractory to infusion of bicarbonate. A 37 year old man was admitted to Intensive Care Unit with a severe metabolic acidosis. On admission the arterial gas analysis showed non lactic metabolic acidosis (pH 7.17; base excess [BE] -20.3; lactic acid 0.8 mMol/L), with hypoxemia and critical hypocapnia. Despite therapy with bicarbonate the acidosis persisted. After 4 hours glucose phosphate was administered, although the phosphoremia was unknown. After phosphate supplementation an improvement of acidosis was observed. Our hypothesis is that in the kidney phosphate depletion caused impaired tubular reabsorption of bicarbonate, which led to a non lactic metabolic acidosis.     

The deleterious effect of metabolic acidosis on nutritional status of hemodialysis patients

One of the main causes of protein-energy malnutrition in patients on maintenance hemodialysis (MHD) is metabolic acidosis. The aim of this study was to evaluate the effect of metabolic acidosis on nutritional status in a group of MHD patients with adequately delivered dialysis treatment. Of 165 eligible anuric MHD outpatients with Kt/V ≥ 1 and no underlying inflammatory diseases, 47 subjects were enrolled. In order to evaluate the effect of different parameters on serum albumin, we measured the pre-dialysis serum albumin, blood pH, serum bicarbonate (HCO 3￣ ), Kt/V, normalized protein catabolic rate (nPCR) and body mass index (BMI) in these patients. The mean age of the study patients was 55 ± 13.8 years; there were 22 females and six diabetics. The average Kt/V was 1.22 ± 0.16, pH was 7.40 ± 0.15, serum HCO 3￣ was 23.18 ± 2.38 mEq/L, serum albumin was 4.03 ± 0.56 g/dL, nPCR was 1.00 ± 0.16 g/kg/day, post-dialysis body weight was 58.50 ± 11.50 kg and BMI was 23.47 ± 2.70 kg/m 2 . There was a statistically significant direct correlation between serum albumin and BMI (r = 0.415, P = 0.004), and between serum albumin and serum HCO 3 (r = 0.341, P = 0.019). On multiple regression analysis, the predictors of serum albumin were serum HCO3￣ and BMI (direct effect) and nPCR (inverse effect). In 17 patients on MHD with serum HCO3￣ <22 mEq/L, there was a significant inverse correlation between HCO 3 and nPCR (r = 0.492, P = 0.045), and these patients had significantly lower serum albumin compared with patients with serum HCO3￣ >22 mEq/L (P = 0.046). These data demonstrate that patients on MHD with metabolic acidosis had a lower serum albumin concentration despite adequate dialysis treatment. The inverse effect of nPCR on serum albumin concentration in acidotic MHD patients may be due to hypercatabolism in the setting of metabolic acidosis, leading to deleterious effects on the nutritional status of patients on MHD.     

Captopril-induced metabolic acidosis with hyperkalemia

Hyperreninemic hypoaldosteronism was diagnosed in a 34-year-old woman with hypertension who was receiving captopril therapy. Renal biopsy revealed an advanced stage of IgA nephropathy, and her creatinine clearance was 40 ml/min. Elevation of serum potassium from 4.7 to 5.8 mEq/l and development of hyperchloremic metabolic acidosis with laboratory findings of pH 7.285, HCO3- 13.5 mEq/l, Na 141, and Cl 114 mEq/l were observed after captopril therapy. When captopril was withdrawn, elevated serum potassium levels and metabolic acidosis returned to normal. Challenge with captopril resulted in a decrease in plasma aldosterone levels, an increase in plasma renin activity, and development of hyperkalemic, hyperchloremic metabolic acidosis which is corrected with mineralocorticoid replacement. This case study demonstrates that captopril can cause hyperreninemic hypoaldosteronism with the laboratory finding of hyperkalemic, hyperchloremic metabolic acidosis.     

Correction of metabolic acidosis and its effect on albumin in chronic hemodialysis patients

Serum albumin concentration has been strongly associated with risk of death in hemodialysis patients, with mortality increasing as albumin decreases. Metabolic acidosis stimulates protein catabolism and decreases protein synthesis. A study was undertaken to investigate the effect of increasing predialysis serum bicarbonate (HCO3) concentrations on the nutrition of hemodialysis patients as measured by albumin and total lymphocyte count (TLC). Metabolic acidosis was defined as a predialysis serum bicarbonate concentration of < or = 18 mEq/L. Thirty-six hemodialysis patients were enrolled in the study. Each had been stable on hemodialysis for > or = 3 months and each had a mean serum bicarbonate concentration of < or = 18 mEq/L on predialysis monthly laboratory values during the preceding 3 months. The subjects were randomized into 2 groups. The first group consisted of 18 control subjects who were dialyzed on a standard bicarbonate bath of 35 mEq/L. The second group consisted of 18 experimental patients who were dialyzed on a bicarbonate bath of 40 mEq/L. Subjects in the experimental group who had predialysis serum bicarbonate concentrations less than 22 mEq/L after 2 weeks on the higher bicarbonate bath were additionally supplemented with oral sodium bicarbonate at a dosage of 1 mEq/kg dry weight/d. Monthly predialysis laboratory values were checked for all subjects and included serum electrolytes, blood urea nitrogen, calcium, and albumin. TLCs were obtained at the initiation and at the conclusion of the study. Intact parathyroid hormone, blood pressures, and interdialytic weight gains were also followed. The study lasted 16 weeks; 32 subjects completed the study (16 in each group). There were no statistically significant differences between the two groups at the initiation of the study. The serum bicarbonate concentrations were significantly different between the two groups at the end of the study (control HCO3 17.3 +/- 3.2 mEq/L v experimental HCO3 20.2 +/- 2.9 mEq/L; P = 0.01). Serum albumin concentrations and TLCs were not statistically different (P > 0.05) between the two groups at the end of the study (control albumin 3.88 +/- 0.28 g/dL v experimental albumin 3.76 +/- 0.26 g/dL and control TLC 1,780.0 +/- 779.4/mm3 v experimental TLC 2,020.1 +/- 888.0/mm3). Potassium, intact parathyroid hormone, interdialytic weight gain, blood pressures, Kt/Vs, and protein catabolic rates did not differ. We found that the change in serum bicarbonate concentration was well-tolerated and was without any demonstrable side effects. We conclude that increasing the serum bicarbonate concentration by 3 mEq/L for 16 weeks has no effect on the indicators of nutrition that we measured (serum albumin and TLC).     

Bicarbonate therapy in severe metabolic acidosis

The utility of bicarbonate administration to patients with severe metabolic acidosis remains controversial. Chronic bicarbonate replacement is obviously indicated for patients who continue to lose bicarbonate in the ambulatory setting, particularly patients with renal tubular acidosis syndromes or diarrhea. In patients with acute lactic acidosis and ketoacidosis, lactate and ketone bodies can be converted back to bicarbonate if the clinical situation improves. For these patients, therapy must be individualized. In general, bicarbonate should be given at an arterial blood pH of < or =7.0. The amount given should be what is calculated to bring the pH up to 7.2. The urge to give bicarbonate to a patient with severe acidemia is apt to be all but irresistible. Intervention should be restrained, however, unless the clinical situation clearly suggests benefit. Here we discuss the pros and cons of bicarbonate therapy for patients with severe metabolic acidosis.     

Calcitriol metabolism during chronic metabolic acidosis

Chronic metabolic acidosis causes a profound disturbance in renal proximal tubule 1OHase activity through perturbation of the normal ionic and hormonal controls of the enzyme activity. A lack of enzyme stimulation in response to hypophosphatemia and a paradoxical response of increased 1OHase activity to increased extracellular phosphorus are the important extracellular markers of deranged P control of 1OHase activity during chronic metabolic acidosis. 1OHase activity is down-regulated during chronic metabolic acidosis by an increase in renal cortical tubule mitochondrial calcium content and a functional abnormality in calcium handling, a reduction in extramitochondrial buffering capacity. There is a defect in PTH regulation of 1OHase during chronic metabolic acidosis, despite PTH levels which are inappropriately normal in relation to ionized hypercalcemia. PTH-directed cAMP accumulation is likely normal as well. Metabolic clearance of calcitriol is increased during chronic metabolic acidosis. Thus, the hormonal stimulus to maintain calcium and phosphorus homeostasis, calcitriol, is so altered by chronic metabolic acidosis that it is easy to understand the profound clinical effects of the acidosis on the skeleton of growing children. Chronic metabolic acidosis has allowed a greater understanding of the complex regulatory physiology that underlies renal proximal tubular 1OHase activity and calcitriol metabolism.     

Unexpected metabolic acidosis during rectal surgery

A case is reported in which severe metabolic acidosis developed during rectal surgery in a patient who was normal in all other respects. The possible connection of pre-operative whole gut irrigation with the development of the acidosis is discussed.     

Should metabolic acidosis be alkalinized?]

At present, the administration of bicarbonate for metabolic acidosis has become controversial with regard to the indications and the modalities of treatment. Scientific evidence of the therapeutic value of bicarbonate is still lacking. In the opposite, there is a strong evidence of its adverse effects, such a paradoxical acidosis, sodium load and over all a worsening of haemodynamic status. Other therapeutic measures are limited. They include the administration of Carbicarb which does not increase the CO2 content, haemodialysis with bicarbonate and/or hyperventilation. As for every therapeutic action, the treatment must rely on an interpretation of the pathophysiological mechanism, resulting in the definition of therapeutic goals. The amendment of acidosis is not always a therapeutic priority. In ketoacidosis for instance, the depth of acidosis is mainly related to the degree of dehydration, the treatment of which results in a normalization of pH.     

Effect of vanadate in acute metabolic acidosis

Summary: The effect of vanadate on urinary excretion of acid and electrolyte in dogs with hydrochloric acid (HCI)-induced acute metabolic acidosis was studied. Vanadate caused no changes in systemic and renal haemodynamics, blood parameters and net acid excretion (NAE) in the control group. In the acute metabolic acidosis group, metabolic acidosis per se also had no effect on haemodymic parameters. Fractional excretion of bicarbonate was decreased, while NAE was markedly increased. Following vanadate treatment, acute acid-loaded animals showed an increase in mean arterial pressure (MAP), but a decreased glomerular filtration rate and effective renal plasma flow. These animals had reduced NAE compared to that seen with HCI alone. Thus, vanadate impaired the renal adaptive responses to acute metabolic acidosis. the decreased NAE induced by vanadate might be caused by its known inhibitory effect on hydrogen-potassium-adenosine triphosphatase (H-K-ATPase) and sodium-potassium-adenosine triphosphatase (Na-K-ATPase), and by renal vasoconstriction.     

Renal response to metabolic acidosis: role of mRNA stabilization

The renal response to metabolic acidosis is mediated, in part, by increased expression of the genes encoding key enzymes of glutamine catabolism and various ion transporters that contribute to the increased synthesis and excretion of ammonium ions and the net production and release of bicarbonate ions. The resulting adaptations facilitate the excretion of acid and partially restore systemic acid-base balance. Much of this response may be mediated by selective stabilization of the mRNAs that encode the responsive proteins. For example, the glutaminase mRNA contains a direct repeat of 8-nt AU sequences that function as a pH-response element (pHRE). This element is both necessary and sufficient to impart a pH-responsive stabilization to chimeric mRNAs. The pHRE also binds multiple RNA-binding proteins, including zeta-crystallin (zeta-cryst), AU-factor 1 (AUF1), and HuR. The onset of acidosis initiates an endoplasmic reticulum (ER)-stress response that leads to the formation of cytoplasmic stress granules. zeta-cryst is transiently recruited to the stress granules, and concurrently, HuR is translocated from the nucleus to the cytoplasm. On the basis of the cumulative data, a mechanism for the stabilization of selective mRNAs is proposed. This hypothesis suggests multiple experiments that should define better how cells in the kidney sense very slight changes in intracellular pH and mediate this essential adaptive response.     

The effect of induced metabolic acidosis on vitamin D3 metabolism in rachitic chicks

Summary The metabolism of vitamin D₃ was studied in 3-week-old, vitamin D deficient chicks, fed since hatching with a diet containing 3% ammonium chloride, 1% calcium, and 0.7% phosphorus. When kidney homogenates were incubated in vitro with [³H]25-(OH)D₃, the production of 1,25-(OH)₂D₃ was reduced by 40% in acidotic birds. During in vivo experiments, after injection of [³H]D₃ (1220 pM/bird), the level of 1,25-(OH)₂D₃ was also reduced in blood plasma, intestine, and tibiae in acidotic chicks as compared with the controls. As a large increase in plasma phosphate was found during acidosis, these results are discussed in relation to the possible role of phosphorus in the control of 1,25-(OH)₂D₃ synthesis.     

Acid-base disturbances in the intensive care unit: metabolic acidosis

This article will discuss metabolic acidosis and, to a lesser extent, metabolic alkalosis in the ICU setting. A classification and clinical approach will be the focus.     

The plasma potassium concentration in metabolic acidosis: a re-evaluation

The purpose of these investigations was to describe the mechanisms responsible for the change in the plasma [K] during the development and maintenance of hyperchloremic metabolic acidosis. Acute metabolic acidosis produced by HCI infusion resulted in a prompt rise in the plasma [K], whereas no change was observed during acute respiratory acidosis in the dog. After 3 to 5 days of acidosis due to NH4Cl feeding, dogs became hypokalemic; this fall in the plasma [K] was due largely to increased urine K excretion. Despite hypokalemia, aldosterone levels were not low, and the calculated transtubular [K] gradient was relatively high, suggesting renal aldosterone action. Thus, rather than anticipating hyperkalemia in patients with chronic metabolic acidosis due to a HCl load, the finding of hyperkalemia should suggest that the rate of urinary K excretion is lower than expected (ie, there are low aldosterone levels or failure of the kidney to respond to this hormone).