Hugh J. Carroll

D-Lactic Acidosis: A Review of Clinical Presentation, Biochemical Features, and Pathophysiologic Mechanisms

This report describes a case of d-lactic acidosis observed by the authors and then reviews all case reports of d-lactic acidosis in the literature in order to define its clinical and biochemical features and pathogenetic mechanisms. The report also reviews the literature on metabolism of d-lactic acid in humans. The clinical presentation of d-lactic acidosis is characterized by episodes of encephalopathy and metabolic acidosis. The diagnosis should be considered in a patient who presents with metabolic acidosis and high serum anion gap, normal lactate level, negative Acetest, short bowel syndrome or other forms of malabsorption, and characteristic neurologic findings. Development of the syndrome requires the following conditions 1) carbohydrate malabsorption with increased delivery of nutrients to the colon, 2) colonic bacterial flora of a type that produces d-lactic acid, 3) ingestion of large amounts of carbohydrate, 4) diminished colonic motility, allowing time for nutrients in the colon to undergo bacterial fermentation, and 5) impaired d-lactate metabolism. In contrast to the initial assumption that d-lactic acid is not metabolized by humans, analysis of published data shows a substantial rate of metabolism of d-lactate by normal humans. Estimates based on these data suggest that impaired metabolism of d-lactate is almost a prerequisite for the development of the syndrome.

D-lactic acidosis in a man with the short-bowel syndrome.

WE have recently studied a patient who had short-bowel syndrome that presented with peculiar neurologic manifestations and severe metabolic acidosis. The anion gap was increased, but the identity o...

Metabolic utilization and renal handling of D-lactate in men.

This study was carried out to investigate the renal handling of d- and l-lactate and the extent of their metabolism in men. Ten healthy male subjects were given an intravenous (IV) infusion of a racemic mixture of d- and l-lactate. At an infusion rate of 1.0 to 1.3 meq/kg body weight of each isomer, d-lactate achieved a concentration in plasma of 1.7 to 3.0 meq/L, and l-lactate 2.8 to 4.2 meq/L. At these levels, fractional excretion of d-lactate ranged from 40% to 65%, while fractional excretion of l-lactate was always less than 5%. At a higher infusion rate, 1.8 to 2.0 meq/kg/h, plasma concentrations of d- and l-lactate reached 4.5 to 6.0 meq/L, and 4.0 to 6.7 meq/L, respectively. Fractional excretion of d-lactate then ranged from 61% to 100%, while that of l-lactate ranged from 9% to 30%. At plasma concentrations of d-lactate less than 3.0 meq/L, reabsorption of l-lactate was nearly complete, but when plasma d-lactate exceeded 3.0 meq/L, reabsorption of l-lactate was considerably impaired. Similarly, for a given concentration of plasma d-lactate, its reabsorption was more efficient when the plasma l-lactate concentration and fractional excretion of l-lactate were low than when they were high. At an infusion rate of d-lactate of 1.0 to 1.3 meq/L, about 90% of the infused lactate was metabolized, and at a higher infusion rate, still more than 75% of the infused lactate was metabolized.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperchloremic Acidosis During the Recovery Phase of Diabetic Ketosis

We have studied 35 patients to find the occurrence of hyperchloremic acidosis during the recovery phase of diabetic ketoacidosis. At admission the patients had typical normochloremic acidosis, with increased anion gap exactly balancing decreased serum bicarbonate. In contrast, in 18 patients with phenformin-induced lactic acidosis, the increase in anion gap at admission was much greater than the decrease in bicarbonate. The difference between lactic acidosis and ketoacidosis may be explained by a slower rate of excretion of lactate than of ketone anions. After the patients with ketoacidosis were treated, the acidosis became predominantly hyperchloremic with normal anion gap. Failure to normalize serum bicarbonate is attributed to excretion of ketone anions in the urine.

The Mechanism of Hyperchloremic Acidosis During the Recovery Phase of Diabetic Ketoacidosis

To determine the mechanism of hyperchloremic acidosis during recovery from diabetic ketoacidosis (DKA), serial measurements were made in eight patients of serum and urinary electrolytes and organic acids, and of urinary net acid. On admission, the average decrease in serum total CO2 was 17.5 mmol/L, corresponding to the excess anion gap, 18.5 meq/L, and the serum organic acids, 17.1 meq/L. With the treatment, the anion gap and organic acids decreased by 16.1 and 14.7 meq/L, respectively, but the serum CO2 increased only by 8.4 mmol/L; serum electrolyte balance was maintained by increase in chloride concentration. Fluid retention was insufficient to explain the disparity between the increase in CO2 and the decrease in organic acids. Renal loss of bicarbonate precursors during treatment was modest and was exceeded by renal bicarbonate production. The disparity between the increase in serum CO2 and the decrease in organic acids during treatment of DKA may be explained to a large extent by a difference in volume of distribution between bicarbonate and organic anions The renal loss of ketone anions before admission, however, is ultimately responsible for the persistence of substantial metabolic acidosis.

Cerebral Edema and Depression of Sensorium in Nonketotic Hyperosmolar Coma

The influence of body water and solute equilibria between extracellular fluid and cerebrospinal fluid (CSF), both before and during therapy, was studied in fifty-three patients who had hyper-glycemia (blood glucose 600 mg./100 ml.) in the absence of ketoacidosis. Particular attention was directed to both depression of sensorium and the possible production of cerebral edema. Before therapy, depression of sensorium was highly correlated with plasma osmolality (r =.84), but not with glucose concentration or pH of either CSF or plasma. Plasma and CSF were in osmotic equilibrium before therapy (389 mOsm/kg.) but glucose concentration was significantly higher in plasma while Na+ and Cl− were higher in CSF. During treatment with insulin and hypotonic NaCl infusion, the osmolalities of CSF and plasma fell at essentially identical rates. Plasma osmolality fell as a consequence of both a fall in glucose concentration and a gain in free water, but the fall in CSF osmolality was almost entirely due to a gain in water by the CSF. Insulin administration was stopped when plasma glucose was about 250 mg./100 ml., and in all patients there was no increase in CSF pressure or clinical evidence of cerebral edema. In patients with nonketotic coma, depression of sensorium is highly correlated with the plasma osmolality. During therapy with insulin and hypotonic NaCl infusion, it appears that cerebral edema does not occur if insulin is stopped before plasma glucose falls below 250 mg./100 ml.

Bartter's syndrome due to a defect in salt reabsorption in the distal convoluted tubule.

Bartters syndrome is generally attributed to a primary defect in salt reabsorption either in the ascending limb of Henles loop or in the proximal tubule. 2 siblings presented here have all the clinical and biochemical features of Bartters syndrome but seem to have defective salt reabsorption in the distal convoluted tubule. A surreptitious use of diuretics was ruled out. Free water clearance was reduced in both patients and also was low after the addition of furosemide when compared with controls. Urine osmolalities following overnight dehydration were 883 and 1,000 mosm/l. The reduced maximal free water clearance argues against a proximal defect, and the normal urine concentration against a Henles loop defect. Low free water clearance after furosemide suggests a defect in the distal convoluted tubule.

Hyperkalemia in diabetes mellitus

Potassium filtered at the glomerulus is almost completely reabsorbed before the distal tubule; it must therefore be secreted into the collecting duct. The rate of potassium secretion is determined by a number of factors, notably aldosterone, distal sodium delivery, and serum potassium. Normal serum potassium is maintained by the interplay of passive leak of potassium from the cells and its active return to the cells. Transmembrane potassium distribution is influenced largely by acid-base equilibrium and hormones including insulin and catecholamines. In the diabetic with ketoacidosis hyperkalemia, in the face of potassium depletion, is attributable to reduced renal function, acidosis, release of potassium from cells due to glycogenolysis, and lack of insulin. Chronic hyperkalemia in diabetics is most often attributable to hyporeninemic hypoaldosteronism but other conditions including urinary tract obstruction may also contribute. A variety of clinical situations (e.g., volume depletion) and drugs (e.g., nonsteroidal antiinflammatory agents, and heparin) may acutely provoke hyperkalemia in susceptible individuals.

Content and Distribution of Water and Electrolytes in Maintenance Hemodialysis

A group of patients whose dietary potassium was unrestricted and who received 12-18 h of Kiil dialysis twice weekly against a bath containing no potassium, had body potassium concentrations (total body potassium/intracellular volume) of 7.6% lower than normal. Despite marked hypokalemia at the end of dialysis, suprisingly few electrocardiographic changes were seen. Another group of subjects, dialyzed fro 5-6 h thrice weekly against a bath containing 1 mEq/liter of potassium in a Dow dialyzer, showed more marked electrocardiographic abnormalities despite smaller alterations in transmembrane potassium gradients. Rapidity of establishment of potassium gradients is important as well as magnitude. The following changes occur in a single dialysis: 100 mEq of cell potassium and 20 mEq of extracellular potassium leave the body; 100 mEq of extracellular sodium enter the cells and 415 mEq of extracellular sodium leave the body; 3.5 liters of water leave the extracellular fluid, 2.5 liters into the bath and 1 liter into the cells.

A Mechanism of Hypoxemia during Hemodialysis

The present study is an investigation of the role of acetate metabolism in dialysis-induced hypoxemia and of the relative roles of acetate metabolism, bicarbonate loss, and CO2 gas (g) loss