FLUID BALANCE The placenta, the fetal and maternal kidenys, fetal skin, fetal membranes, and the fetal lung and intestine all play roles on maintaining the volume and composition of fetal fluids. During the first half of pregnancy, the amniotic fluid is consiered an extension of the fetal extracellular fluid space. The fetal skin is freely permeable to water and sodium early in gestation, and through midgestation, abortion can be induced by injection of hypertonic saline into the amniotic fluid. Removal of amniotic fluid at mid-pregnancy results in death of the fetus; however, removal near term still allows fetal survival. Late in gestation, amniotic fluid is a composite of secretions from lungs and kidneys. Urea, creatinine, and uric acid concentrations increase steadily towards the end of gestation; concentrations at term are much higher than in fetal plasma. The primary source for formation of amniotic fluid is the fetal kidney, while the primary source of disposal is the fetal digestive tract. Failure of fetal swallowing often leads to hydramnios, compromising fetal viability. Fluid Changes During Growth Both the water and chloride content of the body decrease with increasing growth and development. These changes are a consequence of decreasing extracellular fluid and increasing fat and protein. The brain of the newborn contains about 11% of the total bodywater, while that of the adult contains only 2%. The chloride content of the newborn is also proportionately higher than that of the adult. Muscle contains more extracellular wwater and less intracellular water earlier in development, and altricial species have these same differences when compared to precocial species. Heart muscle, by contrast, matures earlier and shows none of the changes seen in striated muscle. Bone water content decreases, while sodium content increases, during growth. The decrease in extracellular water during developmentresults from two processes: 1) the decreasing proportion of body weight accounted for by tissues high in extracellular water, and 2) the decrease in the percentage of extracellular water in skeletal muscle. In summary, the primary changes in fluid balance during maturation include decreases in total body water, extracellular water, and chloride, with a concomitant increase in potassium, protein, and fat content. Disturbances in the volume and composition of body fluids are far more common in the perinatal period than at any other age. Renal Function The regulation of extracellular fluid osmolality and volume is an important function of the renal system. Even with highly varied fluid intakes, the volume and composition of body fluids remains almost constant. The ability of the body to conserve water is related to the effective osmotic pressure of the extracellular fluid. Sodium plays an important role in the level and regulation of extracellular fluid effective osmotic pressure (osmoregulation) and volume (volume regulation). Osmoregulation is accomplished through the regulation of the ratio of sodium to water, while volume regulation occurs through control of sodium and water quantities. Plasma regulation is closely controlled by adjusting water intake and excretion. These adjustments are controlled by the hypothalamus which regulates the secretion of both antidiuretic hormone (ADH) and the thirst mechanism. If water intake exceeds water excretion, ADH secretion is inhibited and water excretion is enhanced. Conversely, if water loss exceeds intake, then ADH secretion is stimulated and the thirst mechanism stimulates water intake. Administratration of excess sodium tends to expand extracellular fluid volume which stimulates renal excretion of sodium to normalize volume. Similarly, sodium is conserved by the kidney in response to decreases in extracellular fluid volume. Changes in extracellular fluid volume are detected by pressure receptors in the heart atria, carotid sinuses, aortic arch, and afferent arterioles of the glomeruli. In the kidney, these receptors are found in the juxtaglomerular cells of the afferent arterioles and the macula densa cells of the distal tubules. These receptors stimulate the renin-angiotensin-aldosterone system in response to decreased extracellular fluid volume. Renin is a proteolytic enzyme which catalyzes the conversion of angiotensinogen (an inactive globulin) to angiotensin I (also inactive). Angiotensin I is then converted to angiotensin II (active form) by angiotensin converting enzyme. Angiotensin II directly enhances sodium reabsorption and water conservation, while indirectly causing the adrenal cortex to secrete aldosterone, which also enhances water reabsorption. Another improtant function of the kidney is to regulate ion concentrations in the extracellular fluid of the body. Although sodium reabsorption is affected by aldosterone, aldosterone is not considered a regulator of sodium concentration in the extracellular fluid. Regulation of potassium concentration of the extracellular fluid is accomplished by increasing reabsorption or excretion in the distal nephron. This occurs by release of aldosterone in response to an increase in plasma potassium concentration. Aldosterone increases transport of potassium into tubular cells, enhances sodium reabsorption, and increases luminal permeability to potassium, all of which enhance potassium movement from the tubular cells to the lumen for excretion in the urine. Renal regulation of acid-base balance is regulated through excretion or reabsorption of strong ions. Changes in strong ion concentration cause changes in the concentrations of bicarbonate and H+ across the renal tubule. The renal regulation of strong ion difference is slow in comparison to the respiratory control of pCO2. The kidneys regulate plasma strong ion difference by balancing sodium and chloride excretion rates. The response to acidosis is increased chloride excretion, which raises strong ion difference and results in the excretion of excess H+ and reabsorption of bicarbonate. Likewise, increased sodium or decreased chloride concentrations produce an above normal strong ion difference indicative of alkalosis. The renal response is to decrease excretion rates of chloride, decreasing strong ion difference, resulting in a secretion of excess bicarbonate and reabsorption of H+ following the chloride. Most neonatal mammals are more susceptible to fluid and electrolyte disorders than are adult animals. Newborns of most species have a limited capacity to excrete a water or electrolyte load, a limited capacity to produce a concentrated urine or to react to antidiuretic hormones or aldosterone, and a limited glomerular filtration rate. The capacity of newborn infants to excrete a water load is only about 10% of that of adults, although mature function is reached by one month of age. The ability to produce a concentrated urine does not appear until nearly 3 months of age, while the glomerular filtration rate is limited until nearly 18 months of age. These limitations are especially important in association with neonatal diarrhea. Neonatal limitations in renal clearance and reabsorption quickly lead to dehydration. Species differences complicate estimates of fluid and electrolyte replacement in newborns. Neonatal calves, for example, are unique in that their renal system is highly developed at birth. By 2-3 days postpartum, their renal function is similar to that of adult cattle. Neonatal calves are able to produce a highly concentrated urine during dehydration as early as 2 days of age. Calves may lose as much as 5% of their body weight during starvation and up to 15% by 96 hours. Urine output during this period may decrease as much as 90%, whereas urine osmolalaity may increase by up to 400%. In contrast, human infants need approximately 2.5 L of water to produce 1000 mOsm urinary solute, while a neonatal calf or adult human requires less than 1 L of water to produce such a response. Calves also have a unique ability to dilute urine and excrete large volume loads similar to adults.. Calves given large volumes of milk water or hypotonic electrolyte solutions respond by increasing urine output up to 10-fold. This diuretic response occurs very quickly; calves produced peak urine output by 60-90 minutes after loading, with 70-100% of the volume being excreted within 4 hours. Calves can easily handle a volume load of 50% of their body weight during the first day of life, while neonatal rats given 4.5% of their body weight show no difference in urine output after 5 hours. This rapid response in calves is due to their mature glomerular filtration rate and ability to dilute urine up to ~35 mOsm/L after volume loading. The diuretic response in calves is closer to adult humans or dogs than to adult cows, whose response is slower in onset, slower to peak urine output, and longer in duration than the calf.