Clinical Chemistry and the Pediatric Patient Part 2

Hyperkalemia and Hypokalemia The symptoms of hyperkalemia (serum potassium, >6.5 mEq/L) include muscle weakness and cardiac conduction defects that may lead to heart failure. In pediatrics, it is particularly important to recognize artificial hyperkalemia as a result of hemolysis and bad capillary blood collection. Because the situation regarding electrolyte and water homeostasis can change rapidly in small infants, it is important to monitor therapeutic intervention on a frequent basis. Increase plasma potassium; decreasing the resting membrane potential, increase excitability, muscle weakness

Hyperkalemia and Hypokalemia The availability of POCT devices that use small volumes of whole blood helps with management of these imbalances, with the only caution being that it is impossible to detect hemolysis and artificial hyperkalemia on a whole blood sample. The Abbott i-STAT System offers test results for the most commonly ordered tests in surgical and specialty care areas, including: blood gases, chemistries, lactate, electrolytes, hemoglobin and hematocrit, and coagulation (including PT/INR). 

Intraventricular Blood tests will reveal low blood levels of potassium and chloride in association with an increased blood pH and high blood bicarbonate level due to loss of stomach acid

DEVELOPMENT OF LIVER FUNCTION Physiologic Jaundice The most striking effect of an immature liver, even in a normal-term baby, is the failure to adequately metabolize bilirubin. Normally, the liver conjugates bilirubin to glucuronic acid using the enzyme bilirubin UDP-glucuronoyltransferase. Conjugated bilirubin can be readily excreted in bile or through the kidneys. At birth, this enzyme is too immature to complete the process and increased levels of unconjugated Bilirubin and physiologic jaundice results. Normally, it returns back to normal level in 10 days. Uridine 5'-diphospho-glucuronosyltransferase

DEVELOPMENT OF LIVER FUNCTION Physiologic Jaundice Excessive jaundice can lead to kernicterus and result in severe brain damage. The measurement of blood conjugated and unconjugated bilirubin has an important role in pediatrics. High uncojugated bilirubin levels can be reduced by phototherapy which causes bilirubin to be converted to a potentially less toxic and more readily excreted metabolite. Severe cases may require an exchange transfusion. Kernicterus is a bilirubin-induced brain dysfunction.

DEVELOPMENT OF LIVER FUNCTION Physiologic Jaundice At its most basic, phototherapy refers to the use of light to convert bilirubin molecules in the body into water soluble isomers that can be excreted by the body. 

DEVELOPMENT OF LIVER FUNCTION Energy Metabolism Important biochemical pathways in the liver: Catabolic Transamination, amino acid oxidation to make ketones and acetyl-CoA, fatty acid oxidation to make ketones, urea cycle to remove ammonia, bilirubin metabolism, detoxification Anabolic Albumin synthesis, clotting factor synthesis, lipoprotein synthesis, VLDL, gluconeogenesis, bile acid synthesis

DEVELOPMENT OF LIVER FUNCTION Energy Metabolism The liver plays an essential role in energy metabolism for the whole body. The primary sugars in newborns and infants come from the breakdown of disaccharide lactose in milk. Lactose is broken down to glucose and galactose, when it reaches hepatocytes, galactose is converted to glucose by a series of enzymatic reactions. Genetic deficiency of any of the reactions results in failure to convert galactose to glucose and essentially reduce the energy content of milk by 50%.

DEVELOPMENT OF LIVER FUNCTION Genetic Defects in Carbohydrate Metabolism The most common cause of failure to convert galactose to glucose results in galactosemia or deficiency of galactose-1-phosphate uridyltransferase, a serious genetic disease of the newborn. Galactose -1-phosphate accumulates inside liver cells and causes hepatocellular damage and rapid liver failure. Renal tubules and eyes are affected, glucose, amino acids and phosphate are lost in urine resulting in hypoglycemia, cataract is formed in the eyes. Galactosemia is fatal if undiscovered but it is treatable by dietary lactose restriction.

DEVELOPMENT OF LIVER FUNCTION Nitrogen Metabolism The liver plays a central role in nitrogen metabolism. It is involved with the metabolic interconversions of amino acids and the synthesis of nonessential amino acids. The liver synthesizes many body proteins, including most proteins found in the circulation, such as albumin, transferrin and clotting factors. The liver is also responsible for complete metabolism of the breakdown products of nitrogen turnover, such as ammonia and urea through the urea cycle and creatinine and uric acid from energy stores and nucleic acids, respectively.

DEVELOPMENT OF LIVER FUNCTION Nitrogen Metabolism Blood ammonia levels are higher in the newborn period than in later life, presumably due to immaturity of urea cycle enzymes. A blood ammonia level of 100 µmol/L in a newborn would be regarded as less significant than the same level in a 1-year-old. Persistently elevated ammonia levels should alert the investigator to possible liver damage and secondary failure of the urea cycle. The upper limit of the reference range is 35-65 μmol/L.

DEVELOPMENT OF LIVER FUNCTION Physiologic Hypoglycemia At birth, a term baby has sufficient liver glycogen stores to provide glucose as an energy source and maintain euglycemia. If delivery is stressful, this reserve of energy may become depleted prematurely. At this time, gluconeogenesis (conversion of alanine into glucose) becomes critical, this pathway is not always mature at birth and suboptimal operation results in what is termed Physiologic hypoglycemia which is corrected as the enzyme systems mature or by simple I.V. glucose infusion. Persistent hypoglycemia should alert physician to possible inborn error of metabolism such as galactosemia, disorders of gluconeogenesis or oxidative fatty acid metabolism.

CALCIUM AND BONE METABOLISM IN PEDIATRICS Normal bone growth, which parallels body growth, requires integration of calcium, phosphate, and magnesium metabolism with endocrine regulation from vitamin D, parathyroid hormone (PTH), and calcitonin. The active metabolite of vitamin D is 1,25-dihydroxy vitamin D. Hydroxylation of vitamin D from the diet takes place in the liver and in the kidneys and requires normal functioning of these organs.

CALCIUM AND BONE METABOLISM IN PEDIATRICS Vitamin D deficiency can result from inadequate nutritional intake of vitamin D coupled with inadequate sunlight exposure. Disorders that limit vitamin D absorption and conditions that impair the conversion of vitamin D into active metabolites including certain liver and kidney diseases. Deficiency results in impaired bone mineralization and leads to rickets in children. Vitamin D can help in preventing other diseases including several types of cancer, diabetes, multiple sclerosis, obesity, and hypertension.