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D Serum Osmolality
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Serum osmolality (normally 285 295 mosm/kg) can be calculated from the following formula: Osmolality = 2(Na mEq/L) + Glucose mg/dL BUN mg/dL -------------------------------- + -----------------------28 18 (1 mosm of glucose equals 180 mg/L and 1 mosm of urea nitrogen equals 28 mg/L) Solute concentration is usually expressed in terms of osmolality The number of particles in solution (ie, osmolytes; either molecules or ions) determines the number of milliosmoles Each particle has a unit value of 1, so if a substance ionizes, each ion contributes the same amount as a nonionizable molecule More importantly, permeability of the particle across the cell membrane determines whether it acts as a physiologically active osmolyte Tonicity refers to osmolytes that are impermeable to the cell wall Since osmolytes do not equilibrate on either side of the cell wall, it is tonicity that leads to osmosis, fluid shifts, stimulation of thirst, and secretion of antidiuretic hormone (ADH) Substances that easily permeate cell membranes (eg, urea, ethanol) are not effective osmolytes and therefore do not cause shifting of fluid in body fluid compartments For example, glucose in solution is nonionizable Therefore, 1 mmol of glucose has an osmole concentration of 1 mosm/kg H2O One millimole of NaCl, however, forms two ions in water (one Na+ and one Cl ) and has an osmole concentration of roughly 2 mosm/kg H2O Osmoles per kilogram of water is osmolality; osmoles per liter of solution is osmolarity At the solute concentration of body fluids, the two measurements correspond so closely that they are interchangeable A discrepancy between actual and calculated osmolality suggests the accumulation of unmeasured osmoles (osmolar gap)
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B Serum Electrolytes
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Table 21 2 shows the normal values for serum electrolytes The cause of electrolyte disorders may be determined by reviewing the history and underlying disease and the medications the patient is taking
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C Evaluation of Urine
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Urinalysis provides information about underlying renal disorders An electrolyte concentration in urine is a useful indicator of renal handling of water and the electrolyte, ie, whether the kidney loses or preserves the electrolyte
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Table 21 1 Total body water (as percentage of body weight) in relation to age and sex
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Age 18 40 41 60 Over 60 60% 60 50% 50% Male 50% 50 40% 40% Female
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Initial Evaluation
The initial approach to its investigation is the determination of serum osmolality (Figure 21 1) Although most cases of hyponatremia result from water imbalance, not sodium imbalance, measurement of urine sodium helps distinguish renal from nonrenal causes of hyponatremia Urine sodium exceeding 20 mEq/L is consistent with renal salt wasting (diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), mineralocorticoid deficiency, saltlosing nephropathy) Urine sodium less than 10 mEq/L or fractional excretion of sodium less than 1% (unless diuretics have been given) implies avid sodium retention by the kidney to compensate for extrarenal fluid losses from vomiting, diarrhea, sweating, or third-spacing, as with ascites
Assessment of ECF volume and serum osmolality are essential to determine etiology Hyponatremia usually reflects excessive water retention relative to sodium rather than sodium deficiency Hospitalized patients treated with hypotonic fluid are at increased risk for the development of hyponatremia Treatment strategy should be based not only on pathophysiology but also on the severity and speed of development
General Considerations
Hyponatremia (defined as a serum sodium concentration less than 130 mEq/L) is the most common electrolyte abnormality observed in a general hospitalized population, seen in approximately 20% of patients
Table 21 2 Normal values and mass conversion factors1
Normal Plasma Values Na+ K+ Cl
Mass Conversion 23 mg = 1 mEq 39 mg = 1 mEq 35 mg = 1 mEq 61 mg = 1 mEq 40 mg = 1 mmol 31 mg = 1 mmol 24 mg = 1 mmol
135 145 mEq/L 35 5 mEq/L 98 107 mEq/L 22 28 mEq/L 85 105 mg/dL 25 45 mg/dL 16 3 mg/dL 280 295 mosm/kg
HCO3 Ca Phosphorus Mg Osmolality
Isotonic and hypertonic hyponatremia should be initially ruled out by determining serum osmolality, blood lipids, and blood glucose Isotonic hyponatremia can be seen with hyperlipidemia and hyperproteinemia Because of marked increases, lipids (chylomicrons; triglycerides, which make the blood visibly lipemic; and very occasionally cholesterol, which may not make the blood visibly lipemic) and proteins (> 10 g/dL, eg, intravenous immunoglobulin therapy) occupy a disproportionately large portion of the plasma volume Plasma osmolality remains normal because its measurement is unaffected by the lipids or proteins A decreased volume of water results, so that the sodium concentration in total plasma volume is decreased Because the sodium concentration in the plasma water is actually normal, hyperlipidemia and hyperproteinemia cause so-called pseudohyponatremia Most laboratories measure serum electrolytes using ion-specific electrodes and thus avoid misdiagnosis unless dilution of samples is needed before direct measurement Hypertonic hyponatremia is most commonly seen with hyperglycemia When blood glucose becomes acutely elevated, water is drawn from the cells into the extracellular space, diluting the serum sodium The plasma sodium level falls 2 mEq/L for every 100 mg/dL rise when the glucose concentration is between 200 and 400 mg/dL If the glucose concentration is above 400 mg/dL, the plasma sodium concentration falls 4 mEq/L for every 100 mg/dL rise in glucose This dilutional or translocational hyponatremia is not pseudohyponatremia, since the sodium concentration does indeed fall Infusion of hypertonic solutions containing osmotically active osmoles (eg, mannitol) may also cause hypertonic hyponatremia by drawing water to the extracellular space
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