Articles on Medical Diseases and Conditions

Category: Serum Electrolytes and Protein-Calorie Malnutrition

Serum Electrolytes and Protein-Calorie Malnutrition

  • Tests in Calcium Disorders: Hypercalcemia

    Symptoms referable to hypercalcemia itself are very nonspecific; they include vomiting, constipation, polydipsia and polyuria, and mental confusion. Coma may develop in severe cases. There may be renal stones or soft tissue calcification. Hypercalcemia is most often detected on routine multitest biochemical screening panels, either in asymptomatic persons or incidental to symptoms from some disease associated with hypercalcemia (see the box on this page). In asymptomatic persons, primary hyperparathyroidism (PHPT) accounts for about 60% of cases. In hospital admissions, however, malignancy is the etiology for 40%-50% of cases and PHPT accounts for about 15%.

    Regulation of Serum Calcium Levels

    Regulation of serum calcium levels is somewhat complex. The major control mechanism is parathyroid hormone (PTH). Normally, parathyroid secretion of PTH is regulated by a feedback mechanism involving the blood calcium level. A decreased serum calcium level induces increased secretion of PTH, whereas an acute increase of the

    Selected Etiologies of Hypercalcemia

    Relatively common

    Neoplasia (noncutaneous)
    Bone primary
    Myeloma
    Acute leukemia
    Nonbone solid tumors
    Breast
    Lung
    Squamous nonpulmonary
    Kidney
    Neoplasm secretion of parathyroid hormone-related protein (PTHrP, “ectopic PTH”)
    Primary hyperparathyroidism (PHPT)
    Thiazide diuretics
    Tertiary (renal) hyperparathyroidism
    Idiopathic
    Spurious (artifactual) hypercalcemia
    Dehydration
    Serum protein elevation
    Lab technical problem

    Relatively uncommon

    Neoplasia (less common tumors)
    Sarcoidosis
    Hyperthyroidism
    Immobilization (mostly seen in children and adolescents)
    Diuretic phase of acute renal tubular necrosis
    Vitamin D intoxication
    Milk-alkali syndrome
    Addison’s disease
    Lithium therapy
    Idiopathic hypercalcemia of infancy
    Acromegaly
    Theophylline toxicity

    serum calcium level decreases secretion of PTH. PTH has a direct action on bone, increasing bone resorption and release of bone calcium and phosphorus. In addition, PTH increases the activity of the activating enzyme cyclic adenosine monophosphate (AMP) in the proximal tubules of the kidney, which increases conversion of calcidiol (25-hydroxyvitamin D) to calcitriol (1,25-dihydroxy-vitamin D). Calcitriol has metabolic effects that help to increase serum calcium levels, such as increased renal reabsorption of calcium, increased GI tract absorption of calcium, and the drawing out of some calcium from bone. On the other hand, an increased calcitriol level also initiates a compensatory series of events that prevents the calcium-elevating system from overreacting. An increased calcitriol level inhibits renal tubule phosphate reabsorption, which results in loss of phosphorus into the urine. This leads to a decreased serum phosphate level, which, in turn, inhibits production of calcitriol. The actions of PTH, phosphate, and calcitriol produce a roughly reciprocal relationship between serum calcium and phosphate levels, with elevation of one corresponding to a decrease of the other. Both PTH (through cyclic AMP) and phosphate act on the same enzyme (25-OH-D 1 a-hydroxylase), which converts calcidiol to calcitriol.

    Besides PTH, a hormone called “calcitonin” has important, although subsidiary, effects on calcium metabolism. Calcitonin is produced in the thyroid gland, and secretion is at least partially regulated by serum calcium levels. Acute elevation of serum calcium leads to increased calcitonin secretion. Calcitonin inhibits bone resorption, which decreases withdrawal of calcium and phosphorus and produces a hypocalcemic and hypophosphatemic effect that opposes calcium-elevating mechanisms.

  • Serum Electrolyte Panels

    Many physicians order serum “electrolyte panels” or “profiles” that include sodium potassium, chloride, and bicarbonate (“CO2”; when “CO2” is included in a multitest electrolyte panel using serum, bicarbonate comprises most of what is being measured). In my experience, chloride and “CO2” are not cost effective as routine assays on electrolyte panels. If there is some necessity for serum chloride assay, as for calculation of the anion gap, it can be ordered when the need arises. Assay of serum bicarbonate is likewise questionable as a routine test. In most patients with abnormal serum bicarbonate values, there is acidosis or alkalosis that is evident or suspected from other clinical or laboratory findings (e.g., as severe emphysema or renal failure). In patients with acid-base problems, blood gas measurement or PCO2 measurement is more sensitive and informative than serum bicarbonate assay.

  • Serum Chloride

    Chloride is the most abundant extracellular anion. In general, chloride is affected by the same conditions that affect sodium (the most abundant extracellular cation) and in roughly the same degree. Thus, in the great majority of cases, serum chloride values change in the same direction as serum sodium values (except in a few conditions such as the hyperchloremic alkalosis of prolonged vomiting). For example, if the serum sodium concentration is low, one can usually predict that the chloride concentration will also be low (or at the lower edge of the reference range). To confirm this I did a study comparing sodium and chloride values in 649 consecutive patients. There were 37 discrepancies (5.7%) in the expected relationship between the sodium and chloride values. On repeat testing of the discrepant specimens, 21 of the 37 discrepancies were resolved, leaving only 16 (2.5%). Of these, 6 (1%) could be classified as minor in degree and 10 (1.5%) as significant. Thus, in 649 patients only 1.5% had a significant divergence between serum sodium and chloride values.

  • Clinical Symptoms of Electrolyte Imbalance

    Before I conclude the discussion of sodium and potassium, it might be useful to describe some of the clinical symptoms of electrolyte imbalance. Interestingly enough, they are very similar for low-sodium, low-potassium, and high-potassium states. They include muscle weakness, nausea, anorexia, and mental changes, which usually tend toward drowsiness and lethargy. The electrocardiogram (ECG) in hypokalemia is very characteristic, and with serum values less than 3.0 mEq/L usually shows depression of the ST segment and flattening or actual inversion of the T wave. In hyperkalemia the opposite happens: the T wave becomes high and peaked; this usually begins with serum potassium values more than 7.0 mEq/L (reference values being 4.0-5.5 mEq/L). Hypokalemia may be associated with digitalis toxicity with digitalis doses that ordinarily are nontoxic because potassium antagonizes the action of digitalis. Conversely, very high concentrations of potassium are toxic to the heart, so IV infusions should never administer more than 20.0 mEq/hour even with good renal function.

    There is disagreement in the medical literature regarding preoperative detection and treatment of hypokalemia. On one hand, various reports and textbooks state that clinically significant hypokalemia (variously defined as less than 2.8, 3.0, or 3.2 mEq/L) produces a substantial number of dangerous arrhythmias. On the other hand, several investigators did not find any significant difference in intraoperative arrhythmias, morbidity, or mortality between those patients with untreated hypokalemia and those who were normokalemic.

  • Hyperkalemia

    High potassium values are not uncommon in hospitalized patients, especially in the elderly. One study reported serum potassium levels more than 5 mEq/L in 15% of patients over age 70. However, hyperkalemia is found in relatively few diseases.

    Decreased renal potassium excretion. Renal failure is the most common cause of hyperkalemia, both in this category and including all causes of hyperkalemia.

    Pseudohyperkalemia. Dehydration can produce apparently high-normal or mildly elevated electrolyte values. Artifactual hemolysis of blood specimens may occur, which results in release of potassium from damaged RBCs, and the laboratory may not always mention that visible hemolysis was present. In one series of patients with hyperkalemia, 20% were found to be due to a hemolyzed specimen, and an additional 9% were eventually thought to be due to some technical error. Rarely, mild hyperkalemia may appear with very marked elevation of platelets.

    Exogenous potassium intake. Examples include excessive oral potassium supplements or parenteral therapy that either is intended to supplement potassium (e.g., potassium chloride) or contains medications (e.g., some forms of penicillin) that are supplied as a potassium salt or in a potassium-rich vehicle. Some over-the-countersalt substitutes contain a considerable amount of potassium.

    Endogenous potassium sources. Potassium can be liberated from tissue cells in muscle crush injuries, burns, and therapy of various malignancies (including the tumor lysis syndrome), or released from RBCs in severe hemolytic anemias. In some cases where liberated potassium reaches hyperkalemic levels, there may be a superimposed element of decreased renal function.

    Endocrinologic syndromes. As noted previously, hyperkalemia may be produced by dehydration in diabetic ketoacidosis. Hyperkalemia is found in about 50% of patients with Addison’s disease. In one series, hyporeninemic hypoaldosteronism was found in 10% of patients with hyperkalemia. Decreased renal excretion of potassium is present in most endocrinologic syndromes associated with hyperkalemia, with the exception of diabetic acidosis.

    Drug-induced hyperkalemia. Some medications supply exogenous potassium, as noted previously. A few, including beta-adrenergic blockers such as propranolol and pindolol, digoxin overdose, certain anesthetic agents at risk for the malignant hyperthermia syndrome such as succinylcholine, therapy with or diagnostic infusion of the amino acid arginine, hyperosmotic glucose solution, or insulin, affect potassium shifts between intracellular and extracellular location. In the case of insulin, deficiency rather than excess would predispose toward hyperkalemia. Most other medications that are associated with increase in serum potassium produce decreased renal excretion of potassium. These include certain potassium-sparing diuretics such as spronolactone and triamterene; several nonsteroidal anti-inflammatory agents such as indomethacin and ibuprofen; angiotensin-converting enzyme inhibitors such as captopril; heparin therapy, including low-dose protocols; and cyclosporine immunosuppressant therapy.

  • Hypokalemia

    Hypokalemia has been reported in about 5% of hospitalized patients. Abnormalities in potassium have many similarities to those of sodium. Some conditions with potassium abnormalities are also associated with sodium abnormalities and were discussed earlier. Several different mechanisms may be involved.

    Inadequate intake. Ordinarily, 90% of ingested potassium is absorbed, so that most diets are more than adequate. Inadequate intake is most often due to anorexia nervosa or to severe illness with anorexia, especially when combined with administration of potassium-free therapeutic fluids. Alcoholism is often associated with inadequate intake, and various malabsorption syndromes may prevent adequate absorption.

    Gastrointestinal tract loss. Severe prolonged diarrhea, including diarrhea due to laxative abuse, can eliminate substantial amounts of potassium. One uncommon but famous cause is large villous adenomas of the colon.

    Clinical Conditions Commonly Associated With Serum Potassium Abnormalities

    Hypokalemia

    Inadequate intake (cachexia or severe illness of any type)
    Intravenous infusion of potassium-free fluids
    Renal loss (diuretics; primary aldosteronism)
    GI loss (protracted vomiting; severe prolonged diarrhea; GI drainage)
    Severe trauma
    Treatment of diabetic acidosis without potassium supplements
    Treatment with large doses of adrenocorticotropic hormone; Cushing’s syndrome
    Cirrhosis; some cases of secondary aldosteronism

    Hyperkalemia

    Renal failure
    Dehydration
    Excessive parenteral administration of potassium
    Artifactual hemolysis of blood specimen
    Tumor lysis syndrome
    Hyporeninemic hypoaldosteronism
    Spironolactone therapy
    Addison’s disease and salt-losing congenital adrenal hyperplasia
    Thrombocythemia

    Protracted vomiting is another uncommon cause. Patients with ileal loop ureteral implant operations after total cystectomy frequently develop hypokalemia if not closely watched.

    Renal loss. Twenty percent to 30% (range, 10%-40%) of hypertensive patients receiving diuretic therapy, particularly with the chlorothiazides, are reported to be hypokalemic. Combined with other conditions requiring diuretics, this makes diuretic therapy the most frequent overall cause of hypokalemia. Renal tubular acidosis syndromes might also be mentioned. Finally, there is a component of renal loss associated with several primarily nonrenal hypokalemic disorders. These include the various endocrinopathies (discussed next), diabetic ketoacidosis, and administration of potassium-poor fluids. The kidney is apparently best able to conserve sodium and to excrete potassium (since one way to conserve sodium is to excrete potassium ions in exchange), so that when normal intake of potassium stops, it takes time for the kidney to adjust and to stop losing normal amounts of potassium ions. In the meantime, a deficit may be created. In addition, renal conservation mechanisms cannot completely eliminate potassium excretion, so that 5-10 mEq/day is lost regardless of total body deficit.

    Endocrinopathies. These conditions are discussed in detail elsewhere. Patients with primary aldosteronism (Conn’s syndrome) are hypokalemic in about 80% of cases. Patients with secondary aldosteronism (cirrhosis, malignant hypertension, renal artery stenosis, increased estrogen states, hyponatremia) are predisposed toward hypokalemia. Cirrhosis may coexist with other predisposing causes, such as poor diet or attempts at diuretic therapy. About 20%-25% of patients with Cushing’s syndrome have a mild hypokalemic alkalosis. Congenital adrenal hyperplasia (of the most common 11-b-hydroxylase type) is associated with hypokalemia. Hypokalemia may occur in Bartter’s syndrome or the very similar condition resulting from licorice abuse. Most of the conditions listed in this section, except for cirrhosis, are also associated with hypertension.

    Severe trauma. In a review of three studies of trauma patients, hypokalemia was much more common (50%-68% of patients) than hyperkalemia. Hypokalemia usually began within 1 hour after the trauma and usually ended within 24 hours.

    Diabetic ketoacidosis. Extracellular fluid (ECF) may lose potassium both from osmotic diuresis due to hyperglycemia and from shift of extracellular to intracellular potassium due to insulin therapy. Nevertheless, these changes are masked by dehydration, so that 90% of patients have normal or elevated serum potassium values when first seen in spite of substantial total body potassium deficits. These deficits produce overt hypokalemia if fluid therapy of diabetic acidosis does not contain sufficient potassium.

    Hypokalemic alkalosis. Hypokalemia has a close relationship to alkalosis. Increased plasma pH (alkalosis) results from decreased ECF hydrogen ion concentrations; the ECF deficit draws hydrogen from body cells, leading to decreased intracellular concentration and therefore less H+ available in renal tubule cells for exchange with urinary sodium. This means increased potassium excretion in exchange for urinary sodium and eventual hypokalemia. Besides being produced by alkalosis, hypokalemia can itself lead to alkalosis, or at least a tendency toward alkalosis. Hypokalemia results from depletion of intracellular potassium (the largest body store of potassium). Hydrogen ions diffuse into body cells to partially replace the intracellular cation deficit caused by potassium deficiency; this tends to deplete ECF hydrogen levels. In addition, more hydrogen is excreted into the urine in exchange for sodium since the potassium that normally would participate in this exchange is no longer available. Both mechanisms tend eventually to deplete extracellular fluid hydrogen. As noted in Chapter 24, in alkalosis due to hypokalemia an acid urine is produced, contrary to the usual situation in alkalosis. This incongruity is due to the intracellular acidosis that results from hypokalemia.

    Medication-induced hypokalemia. Certain non-diuretic medications may sometimes produce hypokalemia. Ticarcillin, carbenicillin, and amphotericin B may increase renal potassium loss. Theophylline, especially in toxic concentration, may decrease serum potassium to hypokalemic levels.

    In one group of hospitalized patients with serum potassium levels less than 2.0 mEq/L, apparent etiology was potassium-insufficient IV fluids in 17%, diuretic therapy in 16%, GI loss in 14%, acute leukemia receiving chemotherapy in 13%, dietary potassium deficiency in 6%, renal disease with urinary potassium loss in 6%, diabetic acidosis in 5%, and all other single causes less than 5% each.

    Urine potassium assay in hypokalemia

    Measurement of urine potassium may sometimes be useful in differentiating etiologies of hypokalemia. Those conditions associated with decreased urine potassium include the following:

    1. Loss from the GI tract (diarrhea, villous adenoma, ileal conduit). Vomiting, however, is associated with alkalosis, which may increase renal potassium excretion.
    2. Shift of extracellular potassium to intracellular location (insulin therapy). However, hyperglycemic osmotic diuresis may confuse the picture.
    3. Inadequate potassium intake, in the absence of conditions that increase urine potassium excretion.
    4. Potassium deficiency associated with renal excretion of potassium (e.g., diuretic induced) after the stimulus for potassium loss is removed and renal loss ceases.

    Besides the first three categories, the other etiologies for hypokalemia usually demonstrate normal or increased urine potassium levels while active potassium loss is occurring.

  • Serum Potassium Abnormalities

    The potassium level in serum is about 0.4-0.5 mEq/L higher than the potassium level in whole blood or plasma (literature range, 0.1-1.2 mEq/L). This is attributed at least in part to potassium released from platelets during clotting. Serum specimens may have artifactual potassium level increase additional to that of normal clotting in patients with very high white blood cell (WBC) counts or platelet counts. The sodium concentration is about the same in serum, plasma, and whole blood. Potassium values increase 10%-20% if the patient follows the common practice of opening and closing his or her hand after a tourniquet is applied to the arm before venipuncture. Potassium can be increased in patient specimens by RBC hemolysis, sometimes considerably increased, which, unfortunately, is most often a laboratory artifact produced during venipuncture or when processing the specimen after venipuncture. Therefore, a pink or red color of plasma or serum usually means very inaccurate potassium values.

  • Hypernatremia

    Hypernatremia is much less common than hyponatremia. It is usually produced by a severe water deficit that is considerably greater than the sodium deficit and is most often accompanied by dehydration (see the box on this page). The water deficit can be due to severe water deprivation, severe hypotonic fluid loss (renal or nonrenal) without replacement, or a combination of the two. The serum sodium concentration and serum osmolality are increased. Urine volume is low and urine specific gravity or osmolality are high in water deprivation or in dehydration due to nonrenal water loss. Urine volume is high and urine specific gravity or osmolality is low in dehydration due to water loss through the kidneys. Other laboratory test values may suggest dehydration, and clinical signs of dehydration may be present. Although the serum sodium level is increased, the total body sodium level may be normal or even decreased, the sodium deficit being overshadowed by the water deficit. Occasionally, hypernatremia is caused by excess intake of sodium, which is usually not intentional.

  • Laboratory Investigation of Hyponatremia

    When the serum sodium level is unexpectedly low, one must determine whether it is due to false (artifactual) hyponatremia, sodium depletion, hemodilution, the IADH syndrome, or the reset osmostat syndrome. The first step is to rule out artifactual causes. The serum sodium tests should be repeated and blood redrawn if necessary, avoiding areas receiving IV infusions. Then, other causes for artifact, such as hyperlipemia or myeloma protein (if a flame photometer is being used), should be excluded. Next, iatrogenic causes should be considered, including sodium-poor IV fluids (producing dilution) and diuretics (producing sodium depletion). If none of these possibilities is the cause, measurement of urine sodium excretion and serum or urine osmolality may be useful.

    Urine sodium. In hyponatremia, the kidney normally attempts to conserve sodium, so that the urine sodium level is low (<20 mEq/L, usually <10 mEq/L). If the patient has hyponatremia and is not receiving IV fluids containing sodium, and if the urine sodium concentration is normal or high (e.g., early morning random urine sodium >20 mEq/L), this suggests inappropriate sodium loss through the kidneys. Possible etiologies are (1) acute or chronic renal failure, such as diffuse, bilateral, renal tissue injury (blood urea nitrogen [BUN] and serum creatinine levels confirm or eliminate this possibility); (2) effect of diuretics or osmotic diuresis; (3) Addison’s disease; (4) IADH syndrome; and (5) the reset osmostat syndrome.

    A low urine sodium concentration is a normal response to a low serum sodium level and suggests (1) nonrenal sodium loss (sweating or GI tract loss), (2) the reset osmostat syndrome, and (3) ECF dilution. Presence of edema favors ECF dilutional etiology (e.g., cirrhosis, congestive heart failure, nephrotic syndrome). Measurement of certain relatively stable constituents of blood, such as hemoglobin and total protein, may provide useful information. However, one must have previous baseline values to assist interpretation. A significant decrease in hemoglobin and total protein levels possibly in other substances such as serum creatinine and uric acid suggests hemodilution. Similar changes in several blood constituents are more helpful than a change in only one, since any constituent could change due to disease that is independent of vascular fluid shifts. A significant increase in hemoglobin level and other blood constituents suggests nonrenal sodium loss with accompanying dehydration.

    The best way to determine hemodilution or hemoconcentration is by plasma volume measurement, most often by using albumin tagged with radioactive iodine. However, the diagnosis usually can be made in other ways.

    Serum and urine osmolality. Osmolality is the measurement of the number of osmotically active particles in a solution. It is determined by either the degree of induced freezing point change or measurement of vapor pressure in special equipment. Units are milliosmoles per liter of water. Therefore, osmolality depends not only on the quantity of solute particles but also on the amount of water in which they are dissolved. Sodium is by far the major constituent of serum osmolality. Plasma proteins have little osmotic activity and normally are essentially noncontributory to serum osmolality. Serum (or plasma) osmolality may be calculated from various formulas, such as:

    mOs m/L = 2Na + BG/20 + BUN/3

    where blood glucose (BG) and BUN are in mg/100 ml and Na (sodium) is in mEq/L. The adult reference range is 275-300 mOsm/L. The ratio of serum sodium concentration to serum osmolality (Na/Osm) is normally 0.43-0.50.

    Increased serum osmolality. Increased serum osmolality may be caused by loss of hypotonic (sodium-poor) water producing dehydration. Some etiologies include diabetes insipidus, fluid deprivation without replacing the daily insensible water loss of 0.5-1.0 L, and hypotonic fluid loss from skin, GI tract, or osmotic diuresis. It may also be caused by sodium overload, hyperglycemia (100 mg of glucose/100 ml increases osmolality about 5.5 mOsm/L), uremia (10 mg of urea/100 ml increases osmolality about 3.5 mOsm/L), unknown metabolic products, or various drugs or chemicals, especially ethyl alcohol. Ethanol is one of the more common causes for increased serum osmolality. Each 100 mg of ethanol/100 ml (equivalent to a serum concentration of 0.1%) raises serum osmolality about 22 mOsm/L. An “osmolal gap” (the difference between the calculated and the measured osmolality) of more than 10 mOsm/L provides a clue to the presence of unusual solutes. Osmolality is one of the criteria for diagnosis of hyperosmolar nonketotic acidosis and of the IADH syndrome (discussed previously). Renal dialysis units sometimes determine the osmolality of the dialysis bath solution to help verify that its electrolyte composition is within acceptable limits.

    Decreased serum osmolality. Serum osmolality is usually decreased (or borderline low) in true noncomplicated hyponatremia. Hyponatremia with definitely normal or elevated serum osmolality can be due to (1) artifactual hyponatremia, due to interference by hyperlipidemia or elevated protein with flame photometer methods; (2) the presence of abnormal quantities of normal hyperosmolar substances, such as glucose or urea; or (3) the presence of abnormal hyperosmolar substances, such as ethanol, methanol, lactic acid or other organic acids, or unknown metabolic products. In categories 2 and 3, measured osmolality is more than 10 mOsm/L above calculated osmolality (alcohol does not produce this osmolal gap when the vapor pressure technique is used). Most of the hyperosmolar substances listed here, with the exception of ethanol, are associated with metabolic acidosis and will usually produce an elevated anion gap.

    An appreciable minority of patients with hyponatremia (especially of mild degree) have serum osmolality results in the low-normal range, although theoretically the osmolality value should be decreased. Some of these patients may be dehydrated; others may have cardiac, renal, or hepatic disease. These diseases characteristically reduce the Na/Osm ratio, this being partially attributed to the effects of increased blood glucose, urea, or unknown metabolic substances. Especially in uremia, osmolality changes cannot always be accounted for by the effects of BUN alone. Patients in shock may have disproportionately elevated measured osmolality compared with calculated osmolality; again, this points toward circulating metabolic products. Besides elevating osmolality, these substances displace a certain amount of sodium from serum, thus lowering sodium levels.

    Urine osmolality. In patients with hyponatremia, urine osmolality is most helpful in diagnosis of the IADH syndrome (discussed previously). Otherwise, urine osmolality values parallel the amount of sodium excreted, except that osmolality values may be disproportionately increased when large quantities of hyperosmotic substances (glucose, urea, ethanol, etc.) are also being excreted, causing an increased urine osmolality gap.

    Summary of laboratory findings in hyponatremia

    1. When hyponatremia is secondary to exogenous hemodilution from excess sodium-deficient fluid (e.g., excess IV fluids or polydipsia), serum osmolality is low, urine osmolality is low, and the urine sodium level is low. There may be other laboratory evidence of hemodilution.

    2. When hyponatremia is secondary to endogenous hemodilution in cirrhosis, nephrotic syndrome, or congestive heart failure, serum osmolality is decreased and the urine sodium concentration is low. There may be other laboratory evidence to suggest hemodilution. The patient may have visible edema. The underlying condition (e.g., cirrhosis) may be evident.

    3. When hyponatremia is due to sodium loss not involving the kidney (skin or GI tract), serum osmolality is usually decreased (or low normal due to dehydration if there is water intake that is inadequate). The degree of dehydration would influence the serum osmolality value. The urine sodium concentration is low. There may be other laboratory and clinical evidence of dehydration.

    4. When hyponatremia is due to sodium loss through the kidneys (diuretics, renal failure, Addison’s disease), there is low serum osmolality and the urine sodium concentration is increased. Both BUN and serum creatinine levels are elevated in chronic renal disease (although they can be elevated from prerenal azotemia with normal kidneys).

    5. In IADH syndrome, serum osmolality is low, urine osmolality is normal or increased, and urine sodium concentration is normal or high. Serum AVP (ADH) level is elevated.

    6. In false hyponatremia due to marked serum protein or triglyceride elevation, serum sodium concentration is mildly decreased, serum osmolality is normal, and urine sodium concentration is normal.

    7. In hyponatremia secondary to marked hyperglycemia, serum osmolality is increased; this suggests the presence of hyperosmotic substances, of which glucose can be confirmed by a blood glucose measurement.

    The laboratory findings described earlier and summarized above apply to untreated classic cases. Diuretic or fluid therapy, or therapy with various other medications, may alter fluid and electrolyte dynamics and change the typical laboratory picture, or may even convert one type of hyponatremia into another. There is also a problem when two conditions coexist, for example, depletional hyponatremia from GI tract loss (which should produce dehydration and low urine sodium concentration) in a patient with poor renal function (whose kidneys cannot conserve sodium and who thus continues to excrete normal amounts of sodium into the urine despite dehydration).

    Certain other test results or clinical findings suggest certain diseases. Hyperkalemia with hyponatremia raises the possibility of renal failure or Addison’s disease. If the patient’s hyponatremia is at least moderate in degree and is asymptomatic, it may reflect chronic hyponatremia rather than acute. If the patient has the reset osmostat syndrome, water restriction does not correct the hyponatremia, whereas water restriction would correct the hyponatremia of the IADH syndrome. If the serum osmolality is well within reference range in a patient with hyponatremia, and the sodium assay was done using flame photometry, serum total protein measurement and examination of the serum for the creamy appearance of hypertriglyceridemia can point toward pseudohyponatremia. If ion selective electrodes were used to assay sodium, and serum osmolality is normal or elevated in hyponatremia, calculation of the osmolal gap can point toward the presence of unexpected hyperosmolal substances.

  • Disorders Simulating Inappropriate Antidiuretic Hormone

    Refractory dilutional syndrome is a moderately frequent condition in which many features of IADH are seen but the classic syndrome is not present. The dilutional hyponatremia of cirrhosis and congestive heart failure may sometimes be of this type, although usually other mechanisms can better account for hyponatremia, such as overuse of diuretics. However, in some cases, IADH syndrome seems to be contributory. These patients differ from those with the classic IADH syndrome in that edema is often present and the urine contains very little sodium. In other words, the main feature is water retention with dilutional hyponatremia. Treatment with sodium can be dangerous, and therapy consists of water restriction.

    Reset osmostat syndrome is another syndrome involving hyponatremia without any really good explanation, although, again, IADH syndrome may contribute in part. These persons have a chronic wasting illness such as carcinomatosis or chronic malnutrition or may simply be elderly and without known disease. Serum sodium levels are mildly or moderately decreased. As a rule, affected persons do not exhibit symptoms of hyponatremia and seem to have adjusted physiologically to the lower serum level. Treatment with salt does not raise the serum values. Apparently the only cure is to improve the patient’s state of nutrition, especially the body protein, which takes considerable time and effort. This condition has also been called the “tired cell syndrome.”