Fluid, Electrolyte, Acid–Base, and Renal-Developmental Physiology and Disorders

Published on 03/06/2015 by admin

Filed under Neonatal - Perinatal Medicine

Last modified 03/06/2015

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 3581 times

Chapter 9

Fluid, Electrolyte, Acid–Base, and Renal-Developmental Physiology and Disorders

During fetal life the placenta is responsible for fetal water and electrolyte homeostasis. The principal function of the fetal kidney is the continuous excretion of water and electrolytes into the amniotic cavity, which is essential for maintenance of amniotic fluid volume. Normal amniotic fluid volume is essential for normal lung development. After birth the kidneys assume responsibility for maintenance of appropriate total body water and electrolyte homeostasis ( Fig. 9-1).

Urine is made by the fetus in increasing amounts as gestation advances. In fact, fetal urine output is quite high—in the range of 25% of body weight per day, approximately 750 to 1000 mL per day near term. Fetal urine, along with pulmonary secretions, is an important contributor to amniotic fluid. The process is dynamic, with amniotic fluid being produced continuously, then swallowed and reabsorbed from the gastrointestinal tract ( Fig. 9-2). Fetal oliguria may produce oligohydramnios. Obstruction in the gastrointestinal tract or neurologic impairment of swallowing may result in polyhydramnios.

The first definitive nephrons form at 8 weeks of gestation. Renal function adequate to sustain extrauterine life develops by approximately 23 weeks of gestation. Nephrogenesis is complete at 36 weeks.

By 22 weeks’ gestation 95% of fetal kidneys are detectable.

Fetal renal blood flow (RBF) increases steadily from approximately 4% at 17 to 18 weeks of gestation to 6% at term. Adult kidneys receive between 20% and 25% of cardiac output. The low RBF in the fetus is due to high renovascular resistance caused by increased activity of the renin-angiotensis-aldosterone and sympathetic nervous systems.

RBF increases sharply after birth at term to between 8% and 10% of cardiac output. Adult levels of RBF are not achieved until approximately 2 years of age.

Fetal GFR slowly increases during fetal life until approximately 36 weeks, when nephrogenesis is complete. Thereafter little increase occurs until birth, at which time there is a dramatic increase in GFR. The increase in GFR with birth is less dramatic in preterm infants ( Fig. 9-3).

See Table 9-1.

The answer to this question is complicated. In fact, it is the change in serum [Cr]—not a single value—after birth that is relevant. At birth serum [Cr] is largely a function of maternal serum [Cr]. The subsequent change varies with gestational age. In infants younger than 30 weeks’ gestation, serum [Cr] either does not change or it increases 30% to 40% before declining to the birth level during the first 5 to 8 days of age, then subsequently declines before reaching a steady state by 7 to 10 weeks of age. The duration of the plateau is inversely related to gestational age; the rate of decline is directly related to gestational age. In infants at 30 weeks’ gestation or older, serum [Cr] declines from birth to reach a steady value at 3 to 6 weeks of age. The rate of decline is directly related to gestational age.

The volume of urine in the postnatal period is determined by water and sodium intake, GFR, the ability to maintain a concentration gradient in the renal medullary interstitium, and the presence or absence of antidiuretic hormone (ADH).

12. What are the important differences in the regulation of sodium ion (Na+) and potassium ion (K+) balance?

image The vast majority of total body Na+ is extracellular, whereas the vast majority of total body K+ is intracellular.

image Serum [Na+] is solely a function of total body water and sodium balance. Serum [K+] is a function of internal (the distribution of K+ across cell membranes) and total body (or external) potassium balance. Urinary Na+ excretion is a function of the amount of Na+ filtered (which depends on the GFR and serum [Na+]) and the amount of Na+ which is reabsorbed along the renal tubules. The amount of K+ filtered has little effect on urinary potassium because 5% to 10% of the filtered K+ is delivered to the distal nephron regardless of serum [K+] or total body potassium balance. Urinary K+ excretion, then, is a function of the amount of potassium secreted or reabsorbed in the distal nephron.

Potassium uptake by cells is stimulated by the following:

Potassium movement from the intracellular to extracellular space is stimulated by the following:

Term infants conserve sodium effectively after the first few hours of life (after contraction of the extracellular fluid space). Preterm infants conserve sodium less effectively for the following reasons:

No. Their ability to excrete a sodium load is limited by their low GFR.

Concentrating ability is limited in infants for several reasons. Protein intake by the infant is used to make new cells during this period of rapid growth, and relatively little nitrogen is diverted to urea. Urea is an important component of the tonicity of the medullary interstitium and the osmolality of urine. Additional factors include (1) the relatively short loops of Henle in the neonatal nephrons that limit the surface area available for equilibration with the interstitium and (2) a high level of prostaglandins that can increase medullary blood flow and “wash out” the medullary concentration gradient. The maximum urine concentration in the preterm infant is approximately 600 mOsm/L, in the full term infant is 800 mOsm/L, and in the adult is 1500 mOsm/L.

Not primarily. Preterm infants are capable of diluting their urine to 75 mOmol/L, compared with that of full-term infants and adults of 50 mOsm/L. The capacity of the newborn to excrete a free water load is limited by their lower GFR.

Data in animals suggest that potassium secretion by the immature distal nephron is limited by the following:

Fluid and Electrolyte Management

Ninety-seven percent of infants pass urine in the first 24 hours of life and 100% by 48 hours. During the first 2 days of life, infants urinate two to six times per day ( Table 9-2).

TABLE 9-2

TIME OF FIRST VOID IN 500 INFANTS ∗

image

∗In 395 term infants, 80 preterm infants, and 25 postterm infants.

Adapted from Clark DA. Time of first void and first stool in 500 newborns. Pediatrics 1977;60:457.

This decrease in weight is the result of catabolism secondary to low caloric intake and a physiologic decrease in the extracellular water (ECW) volume that is independent of caloric intake. Most premature babies manifest a natriuretic diuresis in the first few days of life, which results in negative net total body water and sodium balance and, therefore, a decrease in extracellular fluid (ECF) volume.

21. Why is the reduction in ECW volume in preterm infants considered physiologic?

The clinician should use what the attending physician requests. After the first day of life, however, it is important to understand that it is the absolute fluid and electrolyte intake (milliliters or millimoles per day) relative to that in the previous 8 to 24 hours that is relevant. In other words, should the absolute fluid or electrolyte intake be more or less than it was previously? The answer depends on what fluid and electrolyte balances resulted from the previous intakes and on what water and electrolyte losses are anticipated. There is no magic amount of water per kg/day that is appropriate for all infants, even infants at the same weight, gestational age, postnatal age, and in the same environment. If the infant loses more water (and therefore weight) than you judge to be appropriate and you anticipate that water losses will remain approximately the same, the absolute amount of water (milliliters per day) given should be increased. However, if the current weight is used to calculate fluid requirements, the absolute amount of water administered may be only slightly more or even less than the amount given the day before. For example, an 860-g infant loses 110 g (approximately 13% of birth weight) in the first day of life after receiving 100 mL/kg/day (86 mL/day). You decide this rate of weight loss is too great and increase water intake by 20% to 120 mL/kg/day. Based on the current weight of 750 gm, however, this is only 90 mL/day, which is barely more than that given the previous day. If water losses remain the same, weight loss will be only slightly less over the next 24 hours despite an increase in water intake per kilogram current body weight.

The most important determinants of IWL are gestational age, postnatal age, antenatal steroids, and environment. IWL decreases with increasing gestational and postnatal age ( Fig. 9-5), exposure to antenatal steroids, and increasing ambient humidity.

The concentration of dextrose in the intravenous solution is an irrelevant number. The relevant variable is the dextrose administration rate. Neonates normally produce 4 to 8 mg/kg/min of glucose endogenously. Administration at this rate usually maintains serum glucose concentration in the normal range and conserves glycogen stores. Once the rate of water administration is determined, a dextrose concentration is selected that provides somewhere between 4 and 8 mg/kg/min. In some infants higher glucose infusion rates may be necessary, occasionally exceeding even 12 to 14 mg/kg/min in some circumstances to maintain appropriate blood glucose levels.

image

Yes.

image

No. Although plasma blood glucose concentrations are approximately 10% to 18% higher than whole blood concentrations (because the water content of plasma is higher than that of blood cells), most POC analyzers are calibrated to plasma and therefore provide plasma glucose concentrations. However, POC analyzers have limited accuracy, with a tendency to read falsely lower than the actual plasma glucose concentration. Variation from the actual plasma glucose concentration may be as much as 10 to 20 mg/dL, with the greatest variation at low glucose concentrations. Because of limitations with rapid POC testing methods, any abnormal plasma glucose concentration must be confirmed by laboratory testing.

In the absence of unusual Na+ losses (e.g., loss of gastrointestinal or cerebrospinal fluid), no Na+ should be given. Under these conditions the kidney is the principal route of Na+ loss. During the first day of life, urine Na+ excretion is low (0.5 to 2 mEq/kg/day). With the onset of the postnatal diuresis (when the rate of net water loss often exceeds net Na+ loss), the serum sodium [Na+] level often rises. Therefore it is usually best to withhold Na+ initially, especially in extremely premature infants, in whom IWL is quite high and quite variable, therefore placing these infants at particular risk for developing significant hypernatremia in the first few days of life.

The main route of potassium loss is in the urine. Urine potassium losses are low initially because GFR and urine output are relatively low after birth. Moreover, serum potassium concentration ([K+]) may rise in extremely premature infants even in the absence of exogenous potassium. Therefore potassium should be withheld until it can be ascertained that renal function is normal and, in extremely premature babies, the serum [K+] is normal and not increasing.

Not necessarily. Serum [Na] is the concentration, not the amount, of sodium in the ECF space. If it is abnormally low, the amount of sodium in the ECF space is “insufficient” for the amount of water in the ECF space. Thus serum [Na] may be low because there is too little extracellular sodium, too much ECW, or both. The most common cause of hyponatremia in neonates in the first 1 or 2 days of life is excessive fluid administration. In such situations free water intake should be restricted. 789101112131415161718192021222324252627282930313233343536

image KEY POINTS: FLUIDS AND ELECTROLYTES

Nonoliguric Hyperkalemia in Premature Infants

Hyperkalemia is defined as a serum potassium concentration that is equal to or greater than 6.7 mEq/L from a nonhemolyzed whole blood sample.

Hyperkalemia is caused by perturbations in internal or external K+ balance:

and/or

Nonoliguric hyperkalemia is a rise in the serum potassium concentration equal to or greater than 6.7 mEq/L in the absence of a falling or low urine output.

Nonoliguric hyperkalemia may develop in the first 24 to 36 hours of life even in the absence of potassium intake. In fact, most infants who develop nonoliguric hyperkalemia are in negative potassium balance. Therefore nonoliguric hyperkalemia is caused by a shift of potassium from the intracellular fluid to the extracellular space. Although the mechanisms responsible for this shift are unknown, infants with nonoliguric hyperkalemia are believed to have lower levels of Na+/K+ ATPase. It is noteworthy that serum [K+] increases after birth in nearly all extremely preterm infants, even those who do not develop hyperkalemia. The etiology of this shift is unknown, but it is only clinically significant in very preterm infants.

When originally reported in the literature in the early 1980s, the prevalence of nonoliguric hyperkalemia ranged from 25% to 50% of infants below 1000 g birth weight or younger than 28 weeks’ gestational age. However, it is much less common now, even in infants younger than 25 weeks’ gestational age. This is probably the result of the increased prevalence of antenatal steroid therapy and more aggressive nutrition, which have been shown to reduce the risk of nonoliguric hyperkalemia.

Hyperkalemia increases the ratio of extracellular [K+] to intracellular [K+], depolarizing cells with excitable membranes, most importantly myocardial cells. This may causes bradyarythmias. These are uncommon with serum [K+]s lower than 7 to 8 mmol/L. If serum [K+] continues to rise, asystole may occur. However, asystole is uncommon with serum [K+]s lower than 8 to 9 mmol/L.

There is no consensus regarding this issue. Treatment may be considered if serum [K+] is equal to or greater than 7 meq/L or there are electrocardiographic changes resulting from hyperkalemia. It is important to know that nonoliguric hyperkalemia normally resolves without treatment with the onset of physiologic natriuretic diuresis.

Nonoliguric hyperkalemia is managed in the following ways:

image By antagonizing the arrythmagenic effect of hyperkalemia

image By stimulating cellular uptake of potassium

image By increasing renal potassium secretion

image Peritoneal dialysis is rarely required except with hyperkalemia caused by renal failure.

Use of this method to treat hyperkalemia is no longer considered safe and effective.

Insulin therapy has been shown as more effective in lowering serum [K+] in extremely premature infants with nonoliguric hyperkalemia in a randomized controlled trial. Moreover, cation exchange resins have been associated with intestinal injury.

image KEY POINTS: HYPERKALEMIA

1. Nonoliguric hyperkalemia (potassium >6.7 mEq/L in plasma from a nonhemolyzed whole blood specimen) still occurs in extremely premature infants, but the current prevalence is less than originally reported (15% to 50%). This probably results from the increased prevalence of antenatal steroid exposure. Therefore the clinician should be particularly vigilant in checking for nonoliguric hyperkalemia in extremely preterm infants whose mothers have not received antenatal steroids before their birth.

2. Other causes of hyperkalemia of which to be cognizant are oliguric acute renal failure and drugs that inhibit K excretion (e.g., spironolactone and enalapril).

3. Hyperkalemia may be a life-threatening emergency. In this circumstance inhalation treatment with albuterol is most rapidly effective.

373839404142434445

Acid–Base Balance

Hydrogen ion concentration ([H+]) is measured potentiometrically using a complicated system that employs two electrodes (usually Ag/AgCl) designed such that the potential between them is sensitive to the [H+] in the intervening medium. [H+] is expressed as pH, which equals the negative logarithm of [H+] (−log[H+]). Because pH is defined as the negative log [H+], pH decreases as [H+] increases and increases when [H+] decreases.

Note: Unfortunately, as a result of expressing pH as −log[H+], the proportional change in [H+] is masked. To understand logarithm, think of “power.” Thus 103 = 1000 and log (1000) = 3. When the pH changes by 0.3 units (e.g., from 7.4 to 7.1), the hydrogen ion concentration nearly doubles from 40 to 79 nanoMol/L.

The partial pressure of oxygen is measured amperometrically by the Clark electrode. The reduction reaction of interest is: 4e− + O2 + 2H2O = 4OH−. Current flows in linear proportion to the activity of dissolved oxygen.

The partial pressure of carbon dioxide (CO2) is measured using an electrode with a semipermeable membrane that allows only CO2 to diffuse into the electrode compartment, where it is converted to carbonic acid. The hydrogen ions produced by this reaction are then measured as previously described. The semipermeable membrane ensures that this measurement is completely independent of blood pH.

Plasma bicarbonate concentration image is not measured; it is calculated from the Henderson–Hasselbalch equation:

image

The concentration of carbonic acid ([H2CO3]) is not measured, but it is proportional to the dissolved carbon dioxide (CO2), with which it is in equilibrium. Dissolved carbon dioxide equals the product of the solubility coefficient of carbon dioxide in plasma at 37° C (0.031) and the partial pressure of carbon dioxide (pCO2), which is measured. Therefore the image can be calculated from the measured pH and measured pCO2 as follows:

image

The equation uses pK′ (the apparent pK), to account for the equilibrium between dissolved CO2 and image. The pK′ for H2CO3 dissociation in adult human plasma is 6.1.

The blood buffer bases of human adults are plasma image, plasma proteins, image in red blood cells, and hemoglobin (Hgb). The effect of these buffers is to establish and stabilize a pH of blood at approximately 7.4.

When measured, buffer base is the number of millimoles of strong base or strong acid needed to titrate 1 L of blood (Hgb = 15 g/dL) to pH = 7.4 at 37° C while pCO2 is held at 40 mmHg (at which point the addition of base or acid has restored the total blood buffers to normal values). Base excess (BE) in the blood (actual BE) is the difference between what actually is measured in the test sample and the sum of these values.

In clinical practice it is the BE in the extended extracellular space (red blood cells + plasma + interstitial fluid [ISF]) that is of interest. The concentration of buffer base in the ISF is lower than whole blood, primarily because ISF contains no Hgb. Therefore the algorithm used in blood gas autoanalyzers to calculate ECF BE uses a model of the blood volume diluted with ISF. There are minor variations in the algorithm used to calculate ECF BE, but the most common one is as follows:

image

The normal total of extracellular buffers for infants is 3 to 4 mEq/L lower, so infants normally have a base deficit in this range.

This has been subject of some debate for some time. However, BE is easier to interpret than serum image because it is less dependent on pCO2. When an increase in [H+] is not due to an increase in respiratory acid (i.e., carbonic acid produced from the combination of CO2 and H2O), the added H+ is bound by the buffer anions and base excess falls in direct proportion to the added H+. However, when an increase in [H+] is due to an increase in CO2, serum image increases (because it is in equilibrium with CO2) and the other buffer anions decrease in direct proportion; thus BE remains unchanged. Therefore at a pH of 7.4, what serum image is normal depends on the measured pCO2 ( Table 9-3).

The serum image in preterm infants is normally 17 ± 1.2 mEq/L, with two standard deviations encompassing values as low as 14.5 mEq/L. During the first week of life, term infants have a serum image of 20 ± 2.8 mEq/L. During the first year of life, the serum image is still only approximately 22 ± 1.9 mEq/L, compared with 23 ± 1 mEq/L and 26 ± 1 mEq/L in older children and adults.

These differences in normal serum bicarbonate levels with maturation result from the increased capacity of the mature kidney to conserve bicarbonate and to excrete [H+]. These factors also impair the capacity of the newborn to excrete acid loads. This is the result of immaturity of carbonic anhydrase in the renal tubules and the intercalated cells of the collecting duct.

Titratable acid is a term to describe acids such as phosphoric acid and sulfuric acid, which are involved in acid excretion. It excludes ammonium (NH4+) as a source of acid and is part of the calculation for net acid excretion. The titratable acid excretion rate in term infants younger than 1 month old is about one half of adult values, and the ammonium excretion rate about two thirds that of older children and adults. Preterm infants have even lower rates. After 1 month of age the net acid excretion rate in term infants is similar to that in older children and adults when expressed per 1.73 m2. Preterm infants also increase their rates of titratable acid and ammonium excretion with maturation, but these rates still remain lower than in term infants, even up to the age of 4 months. After 1 month of age the amount of ammonia excreted also depends on diet (ammonia production is increased in infants fed cow’s milk compared with that of infants fed breast milk).

During the first 3 weeks of life a premature infant can reduce the urine pH only to 6 ± 0.1. After 1 month, the urine pH can be reduced to 5.2 ± 0.4.

It is not useful. The oxygen saturation reported with the blood gas is calculated from the measured pO2 using an algorithm based on the adult oxygen–Hbg desaturation curve.

Acid–base measurements are made in the blood, but they are the same in the ISF space. Because image is calculated from pH and pCO2, it represents the plasma concentration of image. As calculated by blood gas autoanalyzers, the reported BE reflects the difference between the normal and actual buffer base concentrations. However, intracellular acid–base status cannot be measured in clinical practice. Because CO2 diffuses across cell membranes much more rapidly than image, it is possible for rapid changes in pCO2 to change the acid–base profile of the two compartments in different directions and at different rates. When attempting to treat acid-base disorders, the clinician must consider the possible consequences, such as worsening intracellular acidosis in the face of alkalinization of the ECF with infusions of bicarbonate.

Strictly speaking, acidemia and alkalemia refer to the actual pH of the blood relative to a pH of 7.4. A lower pH indicates acidemia; a higher pH indicates alkalemia. Acidosis and alkalosis refer to the respiratory and metabolic components of acid–base status compared with normal:

After a known amount of solute is introduced into a solution, the concentration is measured, and the apparent volume in which the solute is distributed is calculated. This volume is called the volume of distribution, and it is used to estimate how much solute is needed to change the measured concentration of that solute. For simple single compartments and inert solutes, the calculation measures the true volume. For multicompartment systems and unstable solutes, the solute may be distributed unevenly (i.e., either concentrated in or excluded from various compartments), metabolized, or otherwise eliminated. In these systems the calculated volume is different from the true volume in which the solute is distributed. Because of its interaction with a number of buffer systems, both intracellular and extracellular, and its elimination as CO2 through the lungs, the volume of distribution of bicarbonate is larger than the ECF space. For metabolic acidosis in neonates the dosage should be based on the following formula if blood gases and pH measurements are available: image(mEq) = 0.3 × weight (kg) × base deficit (mEq/L). The usual dosage is 1 to 2 mEq/kg/dose.

The anion gap is the difference in the serum between the concentrations of cations and anions. It its calculated as follows:

image

The [K+] may be excluded from the calculation because wide variation in serum potassium is lethal. With [K+] in the equation the normal anion gap is approximately 12, and without [K+] in the equation it is approximately 8.

If there is an increase in unmeasured cations, the anion gap will be increased. If there is an increase in unmeasured anions, the anion gap will be decreased.

Buy Membership for Neonatal and Perinatal Medicine Category to continue reading. Learn more here

Related posts:

Pulmonology Orthopedics Hematology and Transfusion Medicine Care of the Term Infant Obstetric Issues, Labor, and Delivery Infection and Immunity