Milk-Alkali Syndrome: A Century-old Cause of Hypercalcemia Requires the Addition of Venous Blood Gas in Hypercalcemia Workup.

The Milk-Alkali syndrome (MAS) is identified by the triad of high serum levels of calcium, metabolic alkalosis, and acute kidney injury, usually caused by consuming excessive amounts of calcium and absorbable alkali. If not treated promptly, the syndrome can result in rapid hypercalcemia, acute renal failure, and metastatic calcification. Notably, an increasing number of cases of MAS have been observed, potentially due to the rampant use of calcium-based over-the-counter supplements for the prevention and treatment of osteoporosis in postmenopausal women. Herein, we report a case of severe hypercalcemia due to prolonged intake of calcium carbonate supplements in the absence of any alkali. The case report highlights the importance of including venous blood gas (VBG) analysis as a part of the workup for hypercalcemia, as metabolic alkalosis can help clinch the diagnosis of MAS in the setting of severe hypercalcemia. How to cite this article: Sahu U, Trivedi T, Gupta R. Milk-Alkali Syndrome: A Century-old Cause of Hypercalcemia Requires the Addition of Venous Blood Gas in Hypercalcemia Workup. J Assoc Physicians India 2023;71(9):104-105.

Metabolic Alkalosis Pathogenesis, Diagnosis, and Treatment: Core Curriculum 2022.

Metabolic alkalosis is a widespread acid-base disturbance, especially in hospitalized patients. It is characterized by the primary elevation of serum bicarbonate and arterial pH, along with a compensatory increase in Pco2 consequent to adaptive hypoventilation. The pathogenesis of metabolic alkalosis involves either a loss of fixed acid or a net accumulation of bicarbonate within the extracellular fluid. The loss of acid may be via the gastrointestinal tract or the kidney, whereas the sources of excess alkali may be via oral or parenteral alkali intake. Severe metabolic alkalosis in critically ill patients-arterial blood pH of 7.55 or higher-is associated with significantly increased mortality rate. The kidney is equipped with sophisticated mechanisms to avert the generation or the persistence (maintenance) of metabolic alkalosis by enhancing bicarbonate excretion. These mechanisms include increased filtration as well as decreased absorption and enhanced secretion of bicarbonate by specialized transporters in specific nephron segments. Factors that interfere with these mechanisms will impair the ability of the kidney to eliminate excess bicarbonate, therefore promoting the generation or impairing the correction of metabolic alkalosis. These factors include volume contraction, low glomerular filtration rate, potassium deficiency, hypochloremia, aldosterone excess, and elevated arterial carbon dioxide. Major clinical states are associated with metabolic alkalosis, including vomiting, aldosterone or cortisol excess, licorice ingestion, chloruretic diuretics, excess calcium alkali ingestion, and genetic diseases such as Bartter syndrome, Gitelman syndrome, and cystic fibrosis. In this installment in the AJKD Core Curriculum in Nephrology, we will review the pathogenesis of metabolic alkalosis; appraise the precipitating events; and discuss clinical presentations, diagnoses, and treatments of metabolic alkalosis.

Intradialytic acid-base changes and organic anion production during high versus low bicarbonate hemodialysis.

The use of high dialysate bicarbonate for hemodialysis in end-stage renal disease is associated with increased mortality, but potential physiological mediators are poorly understood. Alkalinization due to high dialysate bicarbonate may stimulate organic acid generation, which could lead to poor outcomes. Using measurements of ß-hydroxybutyrate (BHB) and lactate, we quantified organic anion (OA) balance in two single-arm studies comparing high and low bicarbonate prescriptions. In study 1 (n = 10), patients became alkalemic using 37 meq/L dialysate bicarbonate; in contrast, with the use of 27 meq/L dialysate, net bicarbonate loss occurred and blood bicarbonate decreased. Total OA losses were not higher with 37 meq/L dialysate bicarbonate (50.9 vs. 49.1 meq using 27 meq/L, P = 0.66); serum BHB increased in both treatments similarly (P = 0.27); and blood lactate was only slightly higher with the use of 37 meq/L dialysate (P = 0.048), differing by 0.2 meq/L at the end of hemodialysis. In study 2 (n = 7), patients achieved steady state on two bicarbonate prescriptions: they were significantly more acidemic when dialyzed against a 30 meq/L bicarbonate dialysate compared with 35 meq/L and, as in study 1, became alkalemic when dialyzed against the higher bicarbonate dialysate. OA losses were similar to those in study 1 and again did not differ between treatments (38.9 vs. 43.5 meq, P = 0.42). Finally, free fatty acid levels increased throughout hemodialysis and correlated with the change in serum BHB (r = 0.81, P < 0.001), implicating upregulation of lipolysis as the mechanism for increased ketone production. In conclusion, lowering dialysate bicarbonate does not meaningfully reduce organic acid generation during hemodialysis or modify organic anion losses into dialysate.

Man versus machine? Acquired long QT syndrome in a patient with anorexia nervosa.

Computer-generated Bazett-corrected QT (QTcB) algorithms are common in clinical practice and can rapidly identify repolarization abnormalities, but accuracy is variable. This report highlights marked rate-corrected QT (QTc) interval prolongation not detected by the computer algorithm. A 26-year-old woman with anorexia nervosa was admitted with severe hypokalemia and ventricular ectopy. Computer-generated QTcB was 485 ms, while manual adjudication yielded a QTcB of 657 ms and a Fridericia-corrected QT (QTcF) interval of 626 ms using digital calipers. Computer-generated QTc intervals may aid in clinical decision-making. However, accuracy is variable, particularly in the setting of ectopy, and requires manual verification.

Liquorice, Liddle, Bartter or Gitelman-how to differentiate?

Hypokalaemia with alkalosis can suggest excess aldosterone. Aldosterone stimulates the collecting duct mineralocorticoid receptor (MR) to upregulate the epithelial sodium channel (ENaC) and stimulate electrogenic sodium reabsorption, with secretion of potassium and protons. Gitelman, Bartter and Liddle syndrome, and liquorice ingestion all cause hypokalaemic alkalosis. This mini-review outlines the pathophysiology of these conditions as well as how to differentiate them.

Induced Alkalosis and Gastrointestinal Symptoms After Sodium Citrate Ingestion: a Dose-Response Investigation.

Sodium citrate induces alkalosis and can provide a performance benefit in high-intensity exercise. Previous investigations have been inconsistent in the ingestion protocols used, in particular the dose and timing of ingestion before the onset of exercise. The primary aim of the current study was to quantify blood pH, blood bicarbonate concentration and gastrointestinal symptoms after ingestion of three doses of sodium citrate (500 mg⋅kg-1, 700 mg⋅kg-1 and 900 mg⋅kg-1). Thirteen participants completed four experimental sessions, each consisting of a different dose of sodium citrate or a taste-matched placebo solution. Blood pH and blood bicarbonate concentration were measured at 30-min intervals via analysis of capillary blood samples. Gastrointestinal symptoms were also monitored at 30-min intervals. Statistical significance was accepted at a level of p < .05. Both measures of alkalosis were significantly greater after ingestion of sodium citrate compared with placebo (p < .001). No significant differences in alkalosis were found between the three sodium citrate doses (p > .05). Peak alkalosis following sodium citrate ingestion ranged from 180 to 212 min after ingestion. Gastrointestinal symptoms were significantly higher after sodium citrate ingestion compared with placebo (p < .001), while the 900 mg.kg-1 dose elicited significantly greater gastrointestinal distress than 500 mg⋅kg-1 (p = .004). It is recommended that a dose of 500 mg⋅kg-1 of sodium citrate should be ingested at least 3 hr before exercise, to achieve peak alkalosis and to minimize gastrointestinal symptoms before and during exercise.