Pathogenesis of Metabolic Acidosis in Preterm Infants

Objective: To determine how the balance between mineral base, and carbonic and organic acids is altered to cause metabolic acidosis in preterm infants. Study Design: Mineral balance and arterial blood measurements of 3 groups of preterm infants given 5 different Total Parenteral Nutrition (TPN) regimens were analyzed. Mineral base was measured as the difference between mineral cations and anions. Organic acid was measured as the difference between mineral base, bicarbonate and protein anion. Results: The degree of metabolic acidosis measured as base excess, was determined by deviation in both mineral base and organic acid from normal. Sodium minus chloride balance determined change in arterial blood mineral base. TPN containing more chloride than sodium caused mineral acidosis with low mineral base, whereas TPN containing more sodium than chloride caused mineral alkalosis with high mineral base. Lactic, organic and carbonic acidosis all increased mineral base. Arterial blood organic acid was determined by: 1. Glomerular filtration rate: Low rates after delivery caused high organic acid that fell as GFR improved. 2. TPN non metabolized organic acid content: Gluconate and sulphate caused organic acidosis by accumulating in blood and mineral acidosis by urine excretion resulting in mineral base loss. 3. Rate of protein catabolism: Increased protein catabolism from TPN providing only 25 kcal/g amino acids or from dexamethasone caused organic acidosis. Conclusion: Metabolic acidosis was caused by high organic acid, resulting from low glomerular filtration rates in the first 1-2 weeks, exacerbated by TPN containing gluconate or sulphate or only 25 kcal/g amino acids. Renal bicarbonate wasting could not account for metabolic acidosis. InTRODuCTIOn At present “renal bicarbonate wasting” provides the textbook explanation for otherwise unexplained metabolic acidosis in preterm infants. In blood, carbon dioxide is mainly in the form of bicarbonate kept in a constant ratio with 1/20th the amount of carbonic acid. The lungs eliminate large amounts of carbon dioxide, but insignificant amounts are excreted via the kidneys. So how could “renal bicarbonate wasting” be significant in the face of massive “pulmonary bicarbonate wasting”? Studies since 1970 have found low urine net hydrogen ion excretion after delivery in preterm compared to term infants [1], which then increases by 4 weeks following the time course of their metabolic acidosis [2]. Since then low renal hydrogen ion secretion in preterm babies has been assumed to cause “renal bicarbonate wasting”. However urine bicarbonate is determined by urine organic acid, mineral base and ammonium concentrations, not merely the rate of hydrogen ion secretion. In one of these groups of preterm infants [3], the development of metabolic acidosis was clearly shown to be due to chloride retention exceeding sodium retention for the first 14 days, but this has not become recognized as the cause. Reports of metabolic acidosis in infants given Total Parenteral Nutrition (TPN) [4, 5] also showed that the tendency to cause acidosis was related to how much more chloride than sodium TPN regimens contain, but once again this has not been recognized as the cause. The previous article describes how to measure mineral base, carbonic and organic acids in blood and the principles governing the balance between them [6]. This is the original acid base theory, based on the work of Lawrence Henderson, Donald van Slyke, Alfred Shohl and others up to 1928. It was validated by three prospective cohort studies of mineral balance and arterial blood gas measurements in preterm infants receiving TPN. This article demonstrates that the composition of parenteral fluids, renal function and the rate of protein catabolism affect mineral base and organic acids accounting for the acid base status of these infants. The following two arPathogenesis of Metabolic Acidosis in Preterm Infants www.ijnmr.net Christopher Geoffrey Alexander Aiken, Pathogenesis of Metabolic Acidosis In Preterm Infants Indian Journal of Neonatal Medicine and Research. 2013 April, Vol-1(1): 8-17 9