Clinical Chemistry and the Pediatric Patient Main Reference Clinical Chemistry Bishop M. L

When an infant is born, adaptation from intrauterine life to extrauterine life is essential. Homeostasis in intrauterine life is maintained by maternal and placental means. Self-maintenance is needed to adapt to extrauterine life. Adaptation is complicated by prematurity or intrauterine growth retardation.

Respiration and Circulation At birth, the normal infant rapidly adapts by initiating active respiration. The stimuli for this process include clamping of the umbilicus, cutting off maternal delivery of oxygen, and the baby,s first breath. Initiation of breathing requires the normal expression of surfactant in the lungs. Surfactant is necessary for the normal expansion and contraction of alveoli and allows gaseous exchange to take place.

Growth A normal baby delivered at term weighs about 3.2 Kg. A baby weighing less than 2.5 Kg at term is regarded as small for gestational age, which is usually a result of intrauterine growth retardation(IGR). Premature babies have low birth weight and born before term. As feeding is initiated, weight gain is 6 g/Kg/d, an infant,s body weight will double in 4-6 months. Premature babies grow at a slower rate.

Organ Development Most organs are not fully developed at birth. Glomerular filtration rate(GFR) of the kidney and renal tubular function mature during the first year of life. liver function can take 2-3 months to fully mature. Motor function and visual acuity develop during the the first year of life.

A switch from fetal hemoglobin to adult Hb takes place A switch from fetal hemoglobin to adult Hb takes place. bone growth is rapid in the first few years of life and at puberty. Sexual maturation results in significant endocrine changes, particularly of the hypothalamic-pituitary-gonadal hormone pathway which leads to adult secondary sexual characteristics and eventually to the adult.

Problems of Prematurity and Immaturity Intrauterine development is programmed for a normal 38-40 week gestation. Many organs are not fully ready to deal with extrauterine life before this time. This organ immaturity results in many of the clinical problems that are associated with prematurity, which include respiratory distress(lung immaturity), electrolyte and water imbalance(kidney immaturity), and excessive jaundice(liver immaturity).

Regulation of Blood Gases and pH in Neonates and Infants Lungs and kidneys must be mature for maintenance of blood gas and pH homeostasis (regulation of acid and base metabolism). At about 24 weeks of gestation, the lungs express two distinct types of cells; type 1 and type 2 pneumocytes. Type 2 pneumocytes are responsible for the secretion of surfactant, which contains the phospholipids lecithin and sphingomyelin.

Surfactant is required for the lungs to expand and the transfer of blood gases following delivery. Oxygen crosses into the circulation and carbon dioxide is removed and expired. Immaturity of the surfactant system as a result of prematurity or IGR results in respiratory distress syndrome(RDS). In RDS, there is failure to excrete carbon dioxide then acidosis develops, as oxygen levels are low, additional oxygen is required for the baby.

The relative amounts of lecithin and sphingomyelin are critical for normal surfactant function. The measurement of amniotic fluid L/S ratio has been used for many years to predict fetal lung maturity. A ratio less than 1.5 is considered indicative of surfactant deficiency. The fetal fibronectin test is designed to determine the likelihood of premature delivery and risk of fetal maturity, this protein is found in maternal cervical fluid toward term.

Regulation of Electrolytes and Water: Renal Function from the 35th week of gestation, the fetal kidneys develop rapidly in preparation for extrauterine life. The kidneys, critical organs for the maintenance of electrolyte and water homeostasis, control the rate of salt and water loss and retention. At term, neither the glomerular nor the renal tubules function at the normal rate. The GFR is about 25% of the rate seen in older children and does not reach full potential until age 2 years.

Tubular function also develops at a similar rate Tubular function also develops at a similar rate. The maximal concentrating power of the kidney is only about 78% of that of the adult kidney at this time, the tubular response to antidiuretic hormone appears to be normal. The kidneys also primarily maintain water loss and retention. However, in the newborn period, insensible water loss through the skin is also an important cause of water and electrolyte imbalance.

Increased water loss also occurs via respiration In children with RDS Increased water loss also occurs via respiration In children with RDS. Up to one third of insensible water loss may occure through this route. Disorders Affecting Electrolytes and Water Balance: Both hypernatremia(Na>145mmol/L) and hyponatremia(Na<130mmol/L) can have dire outcomes, with high risk of seizures. This is a result of the shift of water out of or into brain cells, with concurrent shrinkage or expansion of these cells.

Causes of Hypernatremia: Excessive loss of water through overhead heater. Gastrointestinal fluid loss. Fluid deprivation. Renal loss of water/ nephrogenic diabetes insipidus. Administration of hypertonic fluids containing sodium.

Causes of Hyponatremia: Inappropriate antidiuretic hormone secretion due to trauma or infection. Administration of hypotonic fluids. Renal tubular acidosis. Salt-losing congenital adrenal hyperplasia (21-hydroxylase deficiency) Cystic fibrosis Diuretics Renal failure

clinical evaluation and measurement of other components, including hematocrit, serum albumin, creatinine and blood urea nitrogen can be used to confirm diagnosis. Treatment of electrolyte and water loss is directed at replacing the loss to regain normal Physiologic levels. Care must be taken to avoid too rapid replacement, particularly with hypertonic dehydration. Quick replacement may result in rapid expansion of neuronal cell volume ending in seizures.

Hyperkalemia: Serum K>6 Hyperkalemia: Serum K>6.5mmol/L Symptoms include muscle weakness and cardiac conduction defects that may lead to heart failure. Causes of Hyperkalemia: Dehydration Intravascular hemorrhage causing release from RBCs Trauma/tissue damage Acute renal failure salt-losing adrenal hyperplasia Exchange transfusion with stored blood Hemolyzed blood sample for assay

Causes of Hypokalemia: Inappropriate antidiuretic hormone secretion Diuretics, particularly furosemide Alkalosis Pyloric stenosis Renal tubular acidosis secondary to bicarbonate loss

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.

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.

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

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%.

Galactosemia 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.

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.