A Practical Approach, Second Edition=Ronald D. Ho.pdf

1014 DEVELOPMENTAL REPRODUCTIVE TOXICOLOGY: A PRACTICAL APPROACH, SECOND EDITIONsimilar to carbonic anhydrase IV expression that was approximately one-fourth adult levels at 2weeks of age and surged during postnatal weeks 3 and 4. The ability to concentrate urine developedalong this same timeline.Sheep — Renal water and electrolyte reabsorbtion have been studied in fetal sheep. The percentageof water, sodium and chloride reabsorbed increased throughout the later stages of gestation.However, electrolyte reabsorbtion exceeded water reabsorbtion to a degree that resulted in hypotonicurine until the last 2 weeks of gestation, at which time hypertonic urine was produced (8).Guinea Pigs — The fractional reabsorption of water in guinea pigs is constant during postnatalmaturation and similar in adults (13).Acid-Base EquilibriumHumansGrowth rate and the composition of intake determine renal acid-base control in infants. Excretedphosphate levels prior to birth and for the first two days after birth are very low, resulting in lowtitratable acidity (8). The intake of the fetus is relatively constant and regulated by the placenta,which limits the renal ability to contribute to acid-base equilibrium (8). As newborn feeding begins,the acidity varies directly in relation to the amount of protein, sulfate, and phosphate in the diet,and inversely with the rate of body growth. Walker (8) reports disturbances in equilibrium can beproduced by changes in intake in the two to three week old child, where these same changes wouldnot affect a 2-month-old child.Comparative SpeciesStudies in animals have demonstrated the role of enzymes in establishing and maintaining acidbase equilibrium. Carbonic anhydrase is a zinc metalloenzyme that catalyzes the hydration of CO 2and the dehydration of carbonic acid. Carbonic anhydrase activity has been detected in rat proximalconvoluted tubules and inner medullary collecting duct, and rabbit outer medullary collecting duct(18). Inhibition of luminal carbonic anhydrase has been found to diminish renal acid excretion andreduce HCO3- reabsorption (H + excretion) in the proximal tubule, suggesting an important role forcarbonic anhydrase IV in maintaining acid-base equilibrium. The authors hypothesized that the lowlevels of carbonic anhydrase in the neonatal kidney may help to explain the difficulty in maintainingacid-base homeostasis.Rats — In the rat carbonic anhydrase IV mRNA is expressed in the 20-day rat fetal kidney andincreases dramatically by postnatal day 17 (18).Rabbits — In rabbits, the expression of carbonic anhydrase was one-fourth adult levels at 2 weekspostnatally and surged to adult levels during postnatal weeks 3 and 4 (18).Dogs — In a study using mongrel dogs, postnatal excretion of uric acid decreased from 83% atbirth to 51% at 90 days of age (33). A direct correlation was observed between uric acid and sodiumclearance during early development. This study indicates acid-base homeostasis develops postnatallyin dogs.Urine Volume ControlUrine volume control in response to water diuresis is demonstrable in the human infant on Day 3after birth, and this capacity increases over a period of weeks (8). The diuretic response in infants© 2006 by Taylor & Francis Group, LLC