Clinical chemistry at the
extremes of age
AGEISM
• The function of some organs declines with age
– Gerontology is the study of the aging process.
– As the population ages, increase in chronic diseases such as cancer, arthritis, hypertension and
diabetes are expected.
• For example the glomerular filtration rate and creatinine clearance
decrease with age while plasma creatinine decreases a little
• Changes in normal function mean that the reference ranges
applicable for healthy adults may not be applicable to the elderly or
the young ones
• Some diseases are more prone in children such as inherited
diseases; down’s syndrome, neuroblastomas
– Elderly; DM, Paget’s disease of bone, osteoporosis
• There is need for age-related reference ranges for age-dependent
analytes
– Different patterns, presentation of diseases
– Greater likelihood of more than one illness
– Decline in normal function with age
Age-dependent analytes
Analyte Changes
Cholesterol Increases progressively during
adult life
Glucose Increases; glucose tolerance
decreases with age
ALP Increases with life stages
Urate Increases with age
Total Protein and Albumin Decreases; slight decreases
associated with poor protein
intake
Screening tests in the elderly
Analyte Changes
Plasma Potassium Hypokalemia due to diuretic and
purgative induced
Hyperkalemia due to potassium sparing
diuretic with poor renal function
Plasma Calcium Hypercalcaemia (hyperparathyroidism)
hypocalcaemia (oestemalacia)
Plasma creatinine Increased (renal impairment)
Plasma ALP Increased esp. in Paget’s disease and
malignancy
Plasma glucose Increased (DM)
Plasma TSH and fT4 Hypothyroidism and hyperthyroidism
Faecal occult blood Carcinoma of the larger bowel
Screening tests in childhood
• RR for certain analytes are
different in the newborn
Analyte Difference
from the adults and may Plasma Potassium Mean and upper
vary throughout childhood limit in newborns
and diet e.g calcium and Plasma Calcium Higher at birth;
normal adult
phosphate are affected by concentration by
the diet 72hrs
• Creatinine clearance must be Plasma Phosphate
ALP
Higher at birth, then
falls but remains
corrected for the surface higher than adult
concentrations
area in a child since it throughout
increases as the child grows childhood; rises at
puberty then falls to
– Children should be screened adult
for phenylketonuria and concentrations
congenital hypothyroidism
Childhood disorders
Neonatal hypoglycemia
• irritability, twitching and convulsions
• Asymptomatic hypoglycemia can be harmful esp. to CNS
• Can be transient but common in neonates with respiratory distress, severe
infection, brain damage or those who are small-for-dates
• Premature and small-for-dates babies are at higher risk for developing NH
because of low hepatic glycogen and more likely to have feeding problems
• Due to extensive physiological changes; sudden interruption of maternal
glucose supply at birth so glycogenolysis must go on for the entire period
until feeding becomes established
• Babies born to mothers with DM can have islet cell hyperplasia which
increase the risk of hypoglycemia developing in the immediate postnatal
period and cease thereafter
• Blood glucose tests should be performed every 4 hours for the first 48hrs
• Persistent hypoglycemia should prompt for search for metabolic and
endocrine causes
Childhood disorders
Neonatal hypocalcaemia and hypomagnesaemia
• The signs of hypocalcaemia include; irritability, twitching
and convulsions if glucose levels are normal
• Often accompanied by hypomagnesaemia
• Causes;
– High phosphate intake especially in “raw” cow milk
– Vitamin D deficiency
– Hypoparathyroidism
– DiGeorge Syndrome (genetic disease caused by deletion in
chromosome 22 causing immunodeficiency)
– Pseudohypoparathyroidism
– Blood transfusion (exchange transfusion)
– hypomagnesaemia
• A female baby was born at 38 weeks’ gestation by spontaneous vaginal
delivery to a primigravid woman. The baby appeared normal at birth but
was slow to feed and frequently vomited after feeds. On the third day
after birth, she was noticed to be jaundiced. On examination she had
enlarged liver and bilateral cataracts
Lab Results
Serum bilirubin; total 168 µmol/L (3-20)
Direct 45 µmol/L (<5.2)
AST 122 IU/L (10-50)
ALP 244 IU/L (30-150)
Urine Clinitest (reducing test for sugars) Positive
Comment on the results. What is the probable diagnosis and the
pathophysiology of your diagnosis.
• Direct bilirubin is conjugated bilirubin and presence in blood is pathological. AST
normal in neonates but ALP elevated typical of inflamed hepatocytes with patent
bile ducts “neonatal hepatitis” and also in other metabolic disorders. The
presence of cataracts and positive clinitest suggest galactosaemia . Confirmatory
test is galactose-1-phosphate-uridyl transferase activity and ultrasound to
distinguish between neonatal hepatitis and extrahepatic biliary atresia
Childhood disorders
Jaundice
• Most babies become mildly jaundiced shortly after birth called physiological
jaundice due to immaturity of the hepatic conjugating enzymes, normal postnatal
hemolysis and enterohepatic circulation of bilirubin (conversion of bilirubin
cannot occur until the gut becomes colonized with bacteria)
– Primarily unconjugated and its plasma levels rarely exceeds 100 µmol/L
– Not present at birth and does not persists beyond 14 days of life
– Made worse by dehydration, hypoxia, premature or trauma birth leading to cephalohaematoma
• High unconjugated bilirubin >350 µmol/L increases the risk to brain damage
(kernicterus)
Causes of Unconjugated hyperbilirubinemia in Causes of Conjugated
newborns hyperbilirubinemia in newborns
Increased heamolysis • Hemolytic conditions
• Rh blood and/or ABO blood incompatibility • Hepatic dysfunction e,g hepatitis,
• G6PD or pyruvate kinase deficiency syphilis
• Decreased conjugation • Metabolic disorders such as
• Crigler-Najjar syndrome galactosaemia, alpha1 antitrypsin
• Hypothyroidism deficiency
• Breast milk jaundice (interference of • Congenital abnormality
conjugation due to FFA)
Case 1
• An elderly woman presented with an exacerbation of
congestive heart failure. She was on digoxin and a
thiazide diuretic treatment. Lab results as follows;
Serum digoxin (12hr after previous dose); 2.5 ug/L
Serum Potassium; 3.0 mmol/L
Serum Urea; 11.2 mmo/L
Serum Creatinine; 160 umol/L
Comment on the results and history.
Questions?
• What
– Are the problems associated with collecting
blood/specimen from small children?
– the effects of drug treatment and
pharmacokinetics on children and elderly?
