Commonly Indicated

Common indications to measure serum potassium concentration include prolonged anorexia, vomiting, diarrhea, muscle weakness, bradycardia, supraventricular arrhythmias, oliguria, anuria, and polyuria. Serum potassium concentrations should be measured if hypoadrenocorticism, acute or chronic renal failure, diabetic ketoacidosis, prolonged vomiting, urethral obstruction, uroabdomen, or postobstructive diuresis are suspected, or if prolonged use of diuretics (e.g., furosemide, thiazides, spironolactone) or angiotensin-converting enzyme inhibitors (e.g., enalapril) has occurred.

Analysis

Serum potassium concentrations are measured in serum, plasma, or urine by dry reagent methods, ion-specific potentiometry, and flame photometry (rarely used now). Different methods provide comparable results. Measured potassium concentrations obtained with the new “point-of-care” instruments do not always correlate well with results determined by traditional analyzers. Point-of-care units that measure potassium in whole blood typically give results approximately 0.5 mEq/L less than those obtained with other instruments.

Artifacts

Serum potassium concentrations exceed plasma concentrations because potassium is released from platelets during clotting. This difference is most pronounced when thrombocytosis occurs. Hemolysis causes hyperkalemia if red blood cells (RBCs) have a high potassium content. Most dog and cat RBCs contain little potassium; however, RBCs in some breeds (e.g., neonates, Akitas, English springer spaniels) have a higher potassium content (i.e., ≥20 mEq/L), and hemolysis may cause hyperkalemia. In animals with white blood cell (WBC) counts greater than 100,000/µl, enough WBCs may lyse and release potassium during clotting that serum potassium is artifactually increased. These are causes of pseudohyperkalemia, because they only occur in vitro. Using lithium heparin tubes for collection plus prompt separation of plasma from cells prevents these problems. Samples contaminated by drawing them through improperly cleared intravenous (IV) catheters may yield falsely increased or decreased potassium concentrations, depending on the fluid being administered. When obtaining blood from an IV catheter, one should remove and discard enough blood to clear the catheter before collecting the sample. Using ethylenediaminetetraacetic acid (EDTA) or potassium oxalate as an anticoagulant may markedly alter measured values. Large amounts of bilirubin may slightly increase potassium concentrations measured with ion-selective electrodes.

Drugs That May Alter Serum Potassium Concentration

Hypokalemia may be caused by administration of furosemide, thiazides, acetazolamide, laxatives, mineralocorticoids (e.g., fludrocortisone, desoxycorticosterone pivalate), insulin, sodium bicarbonate, amphotericin B, large doses of sodium penicillin G given IV, chronic administration of ammonium chloride, potassium-free fluids, and glucose-containing crystalloid solutions. Peritoneal dialysis can be responsible if potassium-free dialysate is used long term.

Hyperkalemia may be caused by excessive potassium chloride (either IV or oral), heparin solutions containing chlorbutol, massive digitalis overdose, and potassium penicillin G given IV. It may also be caused by trimethoprim, angiotensin-converting enzyme inhibitors (e.g., enalapril), blood transfusions (if from a dog with high intracellular potassium), potassium-sparing diuretics (e.g., spironolactone, amiloride), mannitol infusions causing acute hypertonicity, nonspecific beta blockers, and nonsteroidal anti-inflammatory drugs (if they cause renal failure).

Causes of Hypokalemia

The three possible mechanisms for hypokalemia are (1) decreased intake, (2) translocation of potassium from extracellular to intracellular fluid, and (3) loss via the kidneys or gastrointestinal tract (Box 6-1 and Figure 6-1). Dilution of serum potassium concentration by giving potassium-free fluids, especially those containing glucose, may contribute to hypokalemia. Decreased intake may aggravate hypokalemia caused by increased loss or translocation, but it is unlikely to cause hypokalemia by itself. Hypokalemia often results from a combination of decreased intake plus urinary or gastrointestinal losses (e.g., administering potassium-free fluids to anorexic animals).

FIGURE 6-1 Algorithm for clinical approach to hypokalemia. GI, Gastrointestinal; IV, intravenous; pu-pd, polyuria-polydipsia.

(Modified from DiBartola SP: Fluid therapy in small animal practice, Philadelphia, 1992, WB Saunders, p 98.)

Translocation of potassium from extracellular to intracellular fluid may occur with bicarbonate administration or insulin-mediated glucose uptake by cells. Both situations typically are iatrogenic (e.g., aggressive treatment for diabetic ketoacidosis). Total parenteral nutrition may do likewise if sufficient potassium is not present in the solution. Hypothermia may cause potassium to enter cells (this effect is reversed when hypothermia is corrected). Hypokalemic periodic paralysis in young Burmese cats causes potassium to move intracellularly and is characterized by recurrent episodes of limb muscle weakness and neck ventroflexion, increased creatine kinase activity, and hypokalemia.

Excessive gastrointestinal (e.g., vomiting, diarrhea) and urinary (e.g., polyuria) losses commonly cause hypokalemia. Vomiting gastric contents causes loss of potassium and chloride. The resulting hypochloremia and metabolic alkalosis causes additional urinary loss of potassium and hydrogen ions. Aldosterone secretion due to dehydration from any cause results in sodium retention but further potassium excretion. Loop diuretics (e.g., furosemide) cause renal potassium wasting. Hypokalemia occurs in approximately 20% to 30% of cats and 10% of dogs with chronic renal failure.

Hypokalemic nephropathy characterized by tubulointerstitial nephritis may develop in cats fed high-protein diets with inadequate potassium, especially with diets that also contain urinary acidifiers.

Hypokalemia commonly occurs during the postobstructive diuresis after relief of feline urethral obstruction. Hypokalemia may occur in canine hyperadrenocorticism because of mineralocorticoid effects of endogenous steroids and is more common with adrenal tumors than in pituitary-dependent disease.

The most common causes of moderate to severe hypokalemia (i.e., <2.5 to 3.0 mEq/L) are vomiting of gastric contents, urinary losses (e.g., postobstructive diuresis, polyuric chronic renal failure), use of loop diuretics (especially in anorexic animals), aggressive insulin and sodium bicarbonate therapy (e.g., treatment of diabetic ketoacidosis), and inappropriate fluid therapy in anorexic animals. Causes of hypokalemia can usually be ascertained from history and physical examination. Additional laboratory tests are rarely needed.

Causes of Hyperkalemia

The three mechanisms for hyperkalemia are (1) increased potassium intake, (2) translocation of potassium from intracellular to extracellular fluid, and (3) decreased urinary potassium excretion (most common) (Box 6-2 and Figure 6-2). Increased intake is seldom the cause, unless potassium administration is greatly excessive or concurrent renal or adrenal impairment exists.

FIGURE 6-2 Algorithm for clinical approach to hyperkalemia. GI, Gastrointestinal; Tco₂, total carbon dioxide; WBC, white blood cell.

(Modified from DiBartola SP: Fluid therapy in small animal practice, Philadelphia, 1992, WB Saunders, p 107.)

Translocation of potassium from cells to extracellular fluid may occur with acute inorganic acidosis, massive tissue damage (e.g., acute tumor lysis) or potassium retention (caused by acute renal failure), insulin deficiency, and acute hypertonicity. Acute acidosis due to inorganic acids (e.g., NH₄Cl, HCl) but not organic acids (e.g., lactic acid, keto acids) may cause potassium to shift out of cells (uncommon). The effect of inorganic metabolic acidosis on serum potassium concentration varies, usually raising potassium 0.17 to 1.67 (mean, 0.75) mEq/L per 0.1-unit decrement in pH; however, this rule of thumb is not reliable. Respiratory acidosis has minimal effect on potassium. Acute tumor lysis syndrome rarely occurs after radiation or chemotherapy for lymphoma. Other causes of massive tissue damage include reperfusion injury and crush injury (rare). Insulin deficiency and hyperosmolality may cause hyperkalemia in diabetic ketoacidosis. Acute hypertonicity (e.g., mannitol infusion, hyperglycemia) may cause water and potassium to exit cells and enter the extracellular space, causing hyperkalemia (uncommon).

Decreased excretion is the most important mechanism; hyperkalemia seldom occurs if renal function is normal. The most common causes of decreased urinary potassium excretion are urethral obstruction, ruptured bladder (or ureter), anuric or oliguric renal failure, and hypoadrenocorticism. Hyperkalemia may occur within 48 hours of feline urethral obstruction, but it does not usually occur for at least 48 hours after urinary bladder rupture. Hyperkalemia seldom occurs in chronic renal failure and then usually only in oliguric patients. Hyperkalemia, hyponatremia, and Na/K ratios less than 27 : 1 are often (but not always) found in animals with hypoadrenocorticism or renal failure. An adrenocorticotropic hormone (ACTH) stimulation test (see Chapter 8) is necessary to diagnose hypoadrenocorticism, because identical electrolyte abnormalities can occur because of oliguric renal failure, whipworms, salmonellosis, and pleural or peritoneal effusions.

Very rarely, hyporeninemic hypoaldosteronism impairs urinary potassium excretion, causing hyperkalemia in patients with diabetes or renal failure. This disease is diagnosed by measuring aldosterone (not cortisol) concentrations before and after ACTH administration. Hyperkalemic periodic paralysis is another rare cause of hyperkalemia that has been reported in only one dog.

The most important causes of serious hyperkalemia (i.e., > 6.0 mEq/L) are oliguric and anuric acute renal failure (e.g., ethylene glycol ingestion), urethral obstruction in male cats, and hypoadrenocorticism. Pseudohyperkalemia should be eliminated first. If serum potassium concentration is greater than 7.0 mEq/L and the patient is asymptomatic (e.g., normal electrocardiogram and physical examination), serum potassium concentration should be rechecked using lithium heparin plasma. After artifact has been eliminated, history should be examined for iatrogenic causes. If hyperkalemia might be iatrogenic, the drug in question should be discontinued and serum potassium rechecked in 1 to 2 days. Diagnostic evaluation should continue in case another disease is present, however. Hyperkalemia is usually an indication for evaluation of some or all of the following: serum creatinine, blood urea nitrogen (BUN), urinalysis, and a resting serum cortisol concentration (see Chapter 8).

Seldom Indicated

Fractional excretion of potassium (FE_K) helps distinguish renal from nonrenal potassium loss. FE_K is calculated as follows:

where

Abnormalities

FE_K should be less than or equal to 6% if the animal has nonrenal sources of potassium loss (e.g., gastrointestinal loss). Values greater than 20% in hypokalemic patients with normal renal function indicate excessive renal potassium losses.

Commonly Indicated

Serum sodium determination is useful in systemic diseases characterized by vomiting, diarrhea, polydipsia and polyuria, muscle weakness, abnormal behavior, abnormal mentation, seizures, edema, pleural or peritoneal effusion, or dehydration. Serum sodium should be determined whenever adrenal, renal, hepatic, or cardiac failure has been diagnosed; in cases of prolonged fluid or diuretic therapy; or in patients that are not drinking water. Results obtained by using point-of-care instruments usually correlate well with results obtained by traditional instruments.

Analysis

Serum sodium is measured in serum, plasma, or urine by ion-specific potentiometry and dry reagent methods.

Artifacts

Historically, when flame photometry or indirect potentiometry was used and hyponatremia plus normal plasma osmolality was found, this was called pseudohyponatremia and was caused by hyperlipidemia or severe hyperproteinemia. Excessive lipid and protein in serum caused the machine to inaccurately determine the concentration. Pseudohyponatremia rarely occurs when ion-specific electrodes are used. Hyperviscosity caused by hyperproteinemia can lead to “short samples” (and artifactual hyponatremia) with certain aspiration techniques. Samples drawn through improperly cleared IV catheters may yield falsely increased or decreased sodium concentrations, depending on the fluid being administered. When obtaining blood from an IV catheter, one should remove and discard enough blood to clear the catheter before collecting the sample. Sodium salts of various anticoagulants (e.g., oxalate, fluoride, citrate) increase measured values.

Drugs That May Alter Serum Sodium Concentration

Hyponatremia may develop because of thiazides, furosemide, spironolactone, or trimethoprim combined with a diuretic. Drug-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH) is reported in people (e.g., with vincristine), but not dogs or cats. Hypernatremia may develop because of desoxycorticosterone acetate or pivalate, fludrocortisone, sodium bicarbonate, lactulose, inappropriate therapy with physiologic or hypertonic saline solutions, or sodium phosphate enemas.

Abnormal Serum Sodium Concentrations

Serum sodium concentration is the amount of sodium relative to the volume of water in the blood; it does not reflect total body sodium content. Hyponatremic and hypernatremic patients may have decreased, normal, or increased total body sodium. Hypernatremia almost always causes hyperosmolality, whereas hyponatremia usually implies hypo-osmolality.

Causes of Hyponatremia

Accurate evaluation of hyponatremia requires measuring plasma osmolality. Most hyponatremic patients are hypoosmolar, but hyperglycemia (i.e., diabetes mellitus) or mannitol administration (Box 6-3) may cause hyponatremia with hyperosmolality. The next step in evaluating hyponatremia is to estimate hydration status. History may indicate fluid loss. Physical examination allows some evaluation of a patient’s hydration status (e.g., skin turgor, moistness of mucous membranes, capillary refill time, pulse rate and character, appearance of jugular veins, presence or absence of ascites).

Dehydrated hyponatremic patients have lost water and sodium, but more sodium than water. Nonrenal or renal routes may result in loss of sodium-rich fluid. Nonrenal losses may be gastrointestinal (e.g., vomiting, diarrhea), third space (e.g., pancreatitis, peritonitis, uroabdomen, pleural effusion), or cutaneous (e.g., burns). Gastrointestinal fluid losses may lead to hyponatremia if the loss of sodium is greater than the loss of water or if subsequent replacement of the lost fluids by drinking water dilutes the remaining sodium. Hypoadrenocorticism, diuretics, diabetes mellitus, or renal disease may cause renal fluid and salt loss. Once again, drinking water replaces water but not sodium, causing hyponatremia. Hyponatremia also has been associated with chronic hemorrhage and hemoabdomen in dogs.

Overhydrated hyponatremic patients (e.g., ascites, edema) may have increased total body sodium. Impaired water excretion causes fluid retention, which dilutes serum sodium. Clinical signs of hypervolemia may not be visible, because the retained water may be intracellular or interstitial. Hypervolemic hyponatremia primarily occurs in congestive heart failure, severe hepatic disease, nephrotic syndrome, and advanced renal failure.

Normovolemic hyponatremia may be caused by primary (i.e., psychogenic) polydipsia, fluid therapy (e.g., 5% dextrose or 0.45% saline), SIADH (rare), drugs with antidiuretic effects, and myxedema coma from hypothyroidism (rare). Primary polydipsia (see Chapter 7) usually occurs in large breeds of dogs. These dogs have severe polydipsia, polyuria, severe hyposthenuria, mild hyponatremia, and mild plasma hypo-osmolality. SIADH refers to excessive antidiuretic hormone (ADH) release despite lack of normal stimuli; it can be caused by malignancy, pulmonary disease, or central nervous system (CNS) disorders. Diagnosis of SIADH requires eliminating adrenal, renal, cardiac, and hepatic disease and finding inappropriately high urine osmolality (> 100 mOsm/kg) despite serum hypo-osmolality. Drugs that stimulate ADH release or potentiate its renal effects may lead to hyponatremia with normovolemia.

The most common causes of moderate to marked hyponatremia (i.e., Na <135 mEq/L) in dogs and cats include vomiting, hypoadrenocorticism, and advanced congestive heart failure (with or without concomitant diuretic therapy). History or physical examination usually reveals the cause, but a resting serum cortisol should be measured (see Chapter 8) if the clinician suspects hypoadrenocorticism. If the cause is still unknown, plasma osmolality measurements are recommended.