Transcript Clinical Chemistry and the Pediatric Patient

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 46 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.
bone growth is rapid in the first few years of life
and at puberty.
Sexual maturation results in significant endocrine
changes, particularly of the hypothalamicpituitary-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.
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. 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>6.5mmol/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 -1phosphate 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.