Electrolyte and acid-base disorders may result from many different diseases. Timely correction of fluid, electrolyte, and acid-base disturbances is often of more immediate benefit to patients than a specific diagnosis, although both are important. SERUM POTASSIUM CONCENTRATION 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 angiotensinconverting 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. Normal Values • Dogs and cats, 3.5 to 5.5 mEq/L (mEq/L are the same as mmol/L for univalent ions). Danger Values • Concentrations less than 2.5 mEq/L (muscle weakness) or greater than 7.5 mEq/L (cardiac conduction disturbances) are considered dangerous. Severely hyponatremic animals seem less able to compensate for hyperkalemia. 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 ionselective 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 f luids, 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 potassiumfree 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). 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 highprotein 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
BOX 6-1. CAUSES OF HYPOKALEMIA Pseudohypokalemia (infrequent and rarely causing significant change) Increased Loss (most common and important category) Gastrointestinal (FEk < 6%) Vomiting of gastric contents (common and important) Diarrhea (common and important) Urinary (FEk > 20%) Chronic renal failure in cats (common and important) Diet-induced hypokalemic nephropathy in cats (important) Postobstructive diuresis (common and important) Inappropriate fluid therapy (especially with inadequate potassium supplementation) (common and important) Diuresis caused by diabetes mellitus/ketoacidosis (common and important) Dialysis (uncommon) Drugs Loop diuretics (e.g., furosemide) (common and important) Thiazide diuretics (e.g., chlorothiazide, hydrochlorothiazide) Amphotericin B Penicillins (rare) Albuterol overdose (rare) Distal (type I) RTA (rare) Proximal (type II) RTA after NaHCO3 treatment (rare) Mineralocorticoid excess (rare) Hyperadrenocorticism (mild changes) Primary hyperaldosteronism (i.e., adenoma, hyperplasia) Translocation (Extracellular Fluid → Intracellular Fluid) Glucose-containing fluids ± insulin (common and important) Total parenteral nutrition solutions (uncommon, but important) Alkalemia (uncommon) Catecholamines (rare) Hypokalemic periodic paralysis (Burmese cats) (rare) Hypothermia (questionable) Decreased Intake (Unlikely to cause hypokalemia by itself unless diet is severely deficient) Administration of potassium-free fluids (e.g., 0.9% NaCl, 5% dextrose in water) FEk, Fractional excretion of potassium; RTA, renal tubular acidosis. Modified from DiBartola SP: Fluid therapy in small animal practice, ed 2, Philadelphia, 2000, WB Saunders, p 93.
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 administra-tion is greatly excessive or concurrent renal or adrenal impairment exists.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 defi-ciency, 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 meta-bolic 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 reperfu-sion injury and crush injury (rare). Insulin deficiency and hyperosmolality may cause hyperkalemia in diabetic ketoacidosis. Acute hypertonicity (e.g., mannitol infu-sion, hyperglycemia) may cause water and potassium to exit cells and enter the extracellular space, causing hyper-kalemia (uncommon).Decreased excretion is the most important mecha-nism; 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.
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).
URINARY FRACTIONAL EXCRETION OF POTASSIUM Seldom Indicated • Fractional excretion of potassium (FEK) helps distinguish renal from nonrenal potassium loss. FEK is calculated as follows: [( K U S U S K / )/( / )] Cr where Cr ×100 UK = urine concentration of potassium (mEq/L) SK = serum concentration of potassium (mEq/L) UCr = urine concentration of creatinine (mg/dl) SCr = serum concentration of creatinine (mg/dl) Normal Values • Dogs and cats, 6% to 20%. Abnormalities • FEK 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. SERUM SODIUM CONCENTRATION 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
X 6-2. CAUSES OF HYPERKALEMIA Pseudohyperkalemia Thrombocytosis (usually mild, but can produce marked changes) WBCs > 100,000/µl (rare cause, but can cause significant changes) Hemolysis in breeds or individuals with high RBC potassium concentration (e.g., Akitas, English springer spaniels, neonates, occasional other dogs) Decreased Urinary Excretion (most common) Urethral obstruction (common and important) Ruptured bladder/ureter (uncommon but important) Anuric or oliguric renal failure (common and important) Hypoadrenocorticism (uncommon but important) Selected gastrointestinal diseases (e.g., trichuriasis, salmonellosis, perforated duodenal ulcer) Chylothorax with repeated pleural fluid drainage (rare) Hyporeninemic hypoaldosteronism (with diabetes mellitus or renal failure) (rare) Drugs (angiotensin-converting enzyme inhibitors [e.g., enalapril],* potassium-sparing diuretics [e.g., spironolactone, amiloride, triamterene],* prostaglandin inhibitors,* heparin*)
Unlikely with normal renal/adrenal function, unless administration is greatly excessive (e.g., IV administration of fluids with high KCl concentrations, administration of large doses of potassium penicillin G) Translocation (Intracellular Fluid → Extracellular Fluid) Insulin deficiency (e.g., diabetic ketoacidosis) (uncommon and transient) Acute inorganic acidosis (e.g., HCl, NH4Cl) (rare) Massive tissue damage (e.g., acute tumor lysis syndrome [rare], reperfusion of extremities after aortic thromboembolism in cats with cardiomyopathy [rare], crush injuries [rare]) Hyperkalemic periodic paralysis (rare) Drugs (nonspecific beta blockers [e.g., propranolol*]) IV, Intravenous; RBC, red blood cell; WBC, white blood cell;. *Only likely to cause hyperkalemia in conjunction with other contributing factors (e.g., decreased renal function, concurrent administration of potassium supplements). Modified from DiBartola SP: Fluid therapy in small animal practice, ed 2, Philadelphia, 2000, WB Saunders, p 100.
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.Normal Values • Dogs, 140 to 150 mEq/L; cats, 150 to 160 mEq/L (mEq/L are the same as mmol/L).Danger Values • Clinical signs of hyponatremia and hypernatremia are more related to rapidity of onset than to magnitude of change and associated plasma hypo-osmolality or hyperosmolality. Neurologic signs (e.g., disorientation, ataxia, seizures, coma) may occur at serum
sodium concentrations less than 120 or greater than 170 mEq/L in dogs.Artifacts • Historically, when flame photometry or indi-rect 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 f luid 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
BOX 6-3. CAUSES OF HYPONATREMIA With Normal Plasma Osmolality (Pseudohyponatremia) (rare with current instruments) Hyperlipidemia Marked hyperproteinemia (rare) With High Plasma Osmolality Hyperglycemia (common) Mannitol infusion With Low Plasma Osmolality Overhydration (i.e., hypervolemia) Severe hepatic disease causing ascites (common) Congestive heart failure causing effusion (common) Nephrotic syndrome causing effusion (common) Advanced renal failure (primarily oliguric or anuric) Dehydration (i.e., Hypovolemia) Gastrointestinal loss (common) (i.e., vomiting or diarrhea) Third-space loss (i.e., pancreatitis, peritonitis, uroabdomen [common], chylothorax with repeated pleural fluid drainage) Cutaneous loss (i.e., burns) Hypoadrenocorticism (uncommon but important) Diuretic administration (including osmotic diuretics) Normal Hydration (i.e., Normovolemia) Inappropriate fluid therapy with 5% dextrose, 0.45% saline solution, or hypotonic fluids (important) Psychogenic polydipsia Syndrome of inappropriate antidiuretic hormone secretion (SIADH) (rare) Antidiuretic drugs (e.g., heparin solutions containing chlorbutol, vincristine, cyclophosphamide, nonsteroidal anti-inflammatory drugs) Myxedema coma of hypothyroidism (rare) Modified from DiBartola SP: Fluid therapy in small animal practice, ed 2, Philadelphia, 2000, WB Saunders, p 60.
BOX 6-4. CAUSES OF HYPERNATREMIA Loss of Free Water without Adequate Replacement (important) Normal insensible water loss without normal replacement Water unavailable or patient unable to drink Abnormal thirst mechanism Primary hypodipsia (e.g., miniature schnauzers) (rare) Central nervous system (CNS) neoplasia Increased insensible water loss without replacement High environmental temperature, fever, tachypnea/ panting Urinary loss of free water Diabetes insipidus (either central or nephrogenic) Loss of Hypotonic Fluids without Adequate Replacement of Water (important) Extrarenal Gastrointestinal (i.e., vomiting, diarrhea, small intestinal obstruction) Third-space loss (i.e., peritonitis, pancreatitis) Cutaneous (e.g., burns) Renal Diuresis (osmotic [e.g., diabetes mellitus, mannitol], chemical [e.g., drugs]) Renal failure, postobstructive diuresis Increased Intake of Sodium Hypertonic fluid administration (e.g., hypertonic saline, sodium bicarbonate, total parenteral nutrition solutions, sodium phosphate enema) Inappropriate maintenance fluid therapy with sodiumcontaining fluids (important) Salt poisoning Hyperaldosteronism (rare) Hyperadrenocorticism (mild changes) Modified from DiBartola SP: Fluid therapy in small animal practice, ed 2, Philadelphia, 2000, WB Saunders, p 53.
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. Causes of Hypernatremia • Hypernatremia is caused by loss of water, gain of sodium, or both (Box 6-4). It is rare for animals with normal thirst mechanisms and adequate access to water to become hypernatremic unless they are unable to ingest water. Free-water loss (i.e., loss of water without appreciable amounts of electrolytes) occurs in diabetes insipidus and insensible losses. Central diabetes insipidus (see Chapter 7) is due to lack of ADH production and release. Affected animals have severe polydipsia and polyuria, and hypernatremia is common. Nephrogenic diabetes insipidus is a category that includes many disorders characterized by renal urine concentration abnormalities (see Chapter 7). Insensible losses (i.e., normal respiratory tract losses)
occur in all animals; if the patient cannot or will not drink (e.g., hypodipsia caused by an abnormal CNS thirst mechanism in young female miniature schnauzers), hypernatremia results. Clinical signs include anorexia, lethargy, weakness, disorientation, ataxia, and seizures. Hypotonic water loss is loss of both water and electrolytes, but more water than sodium. Such losses may be renal or extrarenal (e.g., gastrointestinal, third space, cutaneous). Vomiting, diarrhea, and small intestinal obstruction may cause hypotonic gastrointestinal losses. Third-space losses include pancreatitis and peritonitis. Cutaneous losses are rarely important in dogs and cats. Renal losses may result from lack of ADH, osmotic or drug-induced diuresis, or renal disease that affects concentrating ability. NOTE: If a patient with hypotonic fluid losses replaces f luids by drinking water, it may become hyponatremic instead of hypernatremic, because it is diluting remaining sodium with water it drinks. Administration of excessive sodium (e.g., hypertonic saline, sodium bicarbonate, inappropriate fluid therapy) causes hypernatremia if the patient does not ingest adequate water. Hyperadrenocorticism, sodium phosphate enemas, and primary hyperaldosteronism (rare) may cause hypernatremia. Clinically significant hypernatremia (i.e., Na > 160 mEq/L in dogs and 170 mEq/L in cats) usually is due to a pure water deficit (e.g., unable or unwilling to drink), loss of hypotonic fluid (e.g., gastrointestinal or renal losses), or fluid therapy. History is usually adequate to determine the cause of hypernatremia. URINARY FRACTIONAL EXCRETION OF SODIUM Seldom Indicated • Determining fractional sodium excretion (FENa) may help differentiate prerenal from primary renal azotemia (seldom needed for this purpose), and renal from extrarenal sodium loss in dehydrated patients with hypernatremia or hyponatremia. FENa is calculated by using the equation: [( Na / U S U S Na where )/( Cr / Cr )] ×100 UNa = urine concentration of sodium (mEq/L) SNa = serum concentration of sodium (mEq/L) UCr = urine concentration of creatinine (mg/dl) SCr = serum concentration of creatinine (mg/dl) Normal Values • FENa should be less than 1% in normal dogs and cats. Abnormalities • FENa should be less than 1% in animals with prerenal azotemia; greater than 1% suggests primary renal azotemia. Prerenal azotemia with FENa greater than 1% may occur despite normal renal function if the animal is receiving diuretics (e.g., furosemide). In dehydrated patients, FENa values less than 1% suggest nonrenal losses
(e.g., gastrointestinal, third space); values greater than 1% suggest renal losses (e.g., hypoadrenocorticism, diuretic administration, renal disease). SERUM CHLORIDE CONCENTRATION Commonly Indicated • Serum chloride concentration commonly is measured in systemic diseases characterized by vomiting, diarrhea, dehydration, polyuria, and polydipsia or in patients likely to have metabolic acid-base abnormalities. Analysis • Serum chloride is measured in serum, plasma, or urine by dry reagent systems, colorimetric titration, spectrophotometry (i.e., autoanalyzers), ion-specific potentiometry, and coulometric and amperometric titration. Results obtained by using point-of-care instruments do not always correlate well with results obtained by traditional methods. Normal Values • Changes in water balance change chloride and sodium concentrations proportionately. Chloride concentration can also change primarily; therefore, evaluation of chloride concentration must be done in conjunction with evaluation of sodium concentration. Using this approach, chloride disorders can be divided into artifactual (sodium and chloride change proportionately) and corrected (changes in chloride are proportionately greater than changes in sodium) categories (Boxes 6-5 and 6-6). Changes in free water are responsible for the chloride changes in artifactual disorders. In corrected chloride disorders, chloride ion itself changes. Corrected chloride can be estimated as: [ − [ ] = − Cl corrected Cl measured ] [ − [ ] − = ×146 Cl corrected Cl measured ] /[ + ] Na measured for dog ( ×156 /[ + ] Na measured for cat ( ss) ss)
BOX 6-5. CAUSES OF HYPOCHLOREMIA Artifactual (Dilutional) Corrected Hypochloremia Pseudohypochloremia (lipemic samples using titrimetric methods) Excessive loss of chloride relative to sodium Vomiting of stomach contents (common and important) Therapy with thiazide or loop diuretics (common and important) Chronic respiratory acidosis Hyperadrenocorticism Exercise Therapy with solutions containing high sodium concentration relative to chloride Sodium bicarbonate Modified from DiBartola SP: Fluid therapy in small animal practice, ed 2, Philadelphia, 2000, WB Saunders, p 78.
where [Cl−] measured and [Na+] measured are the patient’s serum chloride and sodium concentrations, respectively. The values 146 and 156 reflect the mean value for serum sodium concentrations in dogs and cats. Normal [Cl−] corrected is approximately 107 to 113 mEq/L in dogs and 117 to 123 mEq/L in cats. These values may vary among laboratories and analyzers. Danger Values • Unknown. Metabolic alkalosis and decreased ionized calcium concentration probably cause muscle twitching or seizures in hypochloremic animals, whereas clinical signs associated with hyperchloremia are probably caused by hyperosmolality. Artifacts • Pseudohypochloremia results when chloride is measured in lipemic or markedly hyperproteinemic samples via techniques that are not ion-selective. Hyperviscosity may cause problems in machines that dilute samples before analysis. In lipemic samples, chloride concentration is underestimated by some titrimetric methods and overestimated by colorimetric methods. Halides (e.g., bromide, iodide) are measured as chloride, falsely increasing reported values (especially important in animals receiving potassium bromide as an anticonvulsant). Drugs That May Alter Serum Chloride Concentration • Administration of NH4Cl, KCl, physiologic saline solution (with or without KCl), hypertonic saline solution, or total parenteral nutrition solutions containing arginine HCl and lysine HCl may add excessive Cl to the body. Acetazolamide may cause renal chloride retention. Hypochloremia may be caused by excessive renal loss of chloride relative to sodium (e.g., furosemide, thiazides) BOX 6-6. CAUSES OF HYPERCHLOREMIA Artifactual (Concentration) Corrected Hyperchloremia Pseudohyperchloremia Lipemic samples using colorimetric methods Potassium bromide therapy (common and important) Excessive loss of sodium relative to chloride Small bowel diarrhea (common and important) Excessive gain of chloride relative to sodium Therapy with chloride salts (e.g., NH4Cl, KCl) Total parenteral nutrition Fluid therapy (e.g., 0.9% NaCl, hypertonic saline, KCl-supplemented fluids) Salt poisoning Renal chloride retention Renal failure Renal tubular acidosis Hypoadrenocorticism Diabetes mellitus Chronic respiratory alkalosis Drugs (e.g., spironolactone, acetazolamide) Modified from DiBartola SP: Fluid therapy in small animal practice, ed 2, Philadelphia, 2000, WB Saunders, p 79.
r excessive intake of sodium without chloride (e.g., NaHCO3). Causes of Hypochloremia • Many causes of hyponatremia also produce hypochloremia. If changes in sodium are proportional to changes in chloride (hypochloremia with normal corrected chloride or artifactual hypochloremia), it is usually easier to search for the cause of the hyponatremia. Corrected hypochloremia results from excessive loss of chloride relative to sodium or administration of fluids containing high sodium concentration relative to chloride (see Box 6-5). The most common causes of corrected hypochloremia are chronic vomiting of gastric contents and aggressive furosemide or thiazide therapy. Administration of sodium without chloride (e.g., NaHCO3) also may cause corrected hypochloremia. Hypochloremia caused by increased renal chloride excretion is a normal adaptation to chronic respiratory acidosis. Persistent hypochloremia is an indication to determine serum sodium, potassium, and total carbon dioxide (TCO2) concentrations (preferably by blood gas analysis). Causes of Hyperchloremia • Most causes of hypernatremia produce concurrent hyperchloremia. If changes in sodium are proportional to changes in chloride (hyperchloremia with normal corrected chloride concentration or “artifactual” hyperchloremia), it is usually easier to search for the cause of the hypernatremia. Corrected hyperchloremia results from excessive sodium loss relative to chloride, excessive chloride gain relative to sodium, or renal chloride retention (see Box 6-6). Small bowel diarrhea can cause hyperchloremic metabolic acidosis because of loss of bicarbonate-rich, chloride-poor fluid (i.e., excessive sodium loss). Salt poisoning or therapy with NH4Cl, KCl, cationic amino acids, hypertonic saline, or 0.9% NaCl with or without added KCl represent excessive chloride gain (e.g., physiologic saline solution has 154 mEq chloride/L but contains 174 mEq chloride/L if supplemented with 20 mEq KCl/L). The most common cause of hyperchloremia is hypotonic fluid loss leading to hyperchloremic (normal anion gap) metabolic acidosis. Persistent hyperchloremia is an indication for determining serum sodium, potassium, and TCO2 concentrations and blood gas analysis. OSMOLALITY AND OSMOLAL GAP Osmolality refers to the number of osmotically active particles in a solution. Tonicity describes the osmolality of a solution relative to plasma. A solution with the same osmolality as plasma is said to be isotonic, whereas one with greater osmolality than plasma is hypertonic. A solution with osmolality lower than that of plasma is hypotonic. Tonicity depends on the ability of these particles to exert oncotic pressure and whether or not the particles can rapidly cross a semipermeable membrane (e.g., a cell membrane). For example, urea does not cause hypertonicity (i.e., exert oncotic pressure), because it rapidly diffuses across cell membranes and equilibrates throughout the body. Sodium and glucose cannot rapidly cross membranes; therefore, they tend to stay on one side and cause
hypertonicity (i.e., exert oncotic pressure), attracting f luids. Everything that affects tonicity (e.g., sodium) also affects osmolality, but not everything that affects osmolality also affects tonicity (e.g., urea). Occasionally Indicated • Serum or plasma osmolality helps differentiate causes of hyponatremia, aids in early diagnosis of ethylene glycol intoxication, evaluates hydration status and renal concentrating ability during water deprivation testing, and sometimes helps evaluate patients with diabetic ketoacidosis and those being treated with mannitol for cerebral edema. Disadvantage • Special equipment (e.g., freezing point depression or vapor pressure osmometer) is required. Analysis • Osmolality is measured in serum, plasma, or urine by freezing point or vapor pressure osmometry (citrate anticoagulants cause artifactual increases). It is estimated (i.e., calculated) by various formulas. In the absence of excessive unmeasured osmoles (e.g., ethylene glycol), the osmolality: . 1 86 following formula closely estimates ( Osmolality mOsm kg Na / ([ + + K + ] [ ]) ( + ) = glucose 18 + / ) ( / . BUN 2 88 9 ) + where serum sodium and potassium are expressed in mEq/L and BUN and glucose in mg/dl. However, 2 × [Na] may be used as a quick estimate of osmolality. Tonicity may be estimated by the following formula: = Tonicity Plasma osmolality BUN −( / . ) 2 8 where tonicity and osmolality are expressed in mOsm/kg and BUN is expressed in mg/dl. Normal Values • Serum or plasma osmolality: dogs, 290 to 310 mOsm/kg; cats, 308 to 335 mOsm/kg. Urine osmolality values vary widely. Typical ranges are 50 to 2800 mOsm/kg (dogs) and 50 to 3000 mOsm/kg (cats). Danger Values • Signs caused by hypo-osmolality or hyperosmolality are related more to rapidity of change than magnitude of change. Neurologic signs (e.g., disorientation, ataxia, seizures, coma) may occur when serum or plasma osmolality is less than 250 mOsm/kg or tonicity is greater than 360 mOsm/kg. Osmolal gap is defined as measured serum osmolality − calculated serum osmolality. An increased gap is due to unmeasured osmoles (e.g., ethylene glycol metabolites), pseudohyponatremia (i.e., normal osmolality plus hyponatremia), or laboratory error. Vapor pressure osmometry does not detect volatile solutes (e.g., methanol). If measured osmolality is less than calculated osmolality, a laboratory error is probably responsible. Normal Values (Osmolal gap) • Dogs, 10 to 15 mOsm/ kg; cats, unknown. Danger Values (Osmolal gap) • An osmolal gap greater than 25 mOsm/kg indicates the presence of an unmeasured osmole, usually as a result of intoxication (e.g., ethylene glycol, methanol, ethanol).
Causes of Serum or Plasma Hypo-osmolality • See Causes of Hyponatremia. Causes of Serum or Plasma Hyperosmolality • Hyperosmolality is caused by hypernatremia, hyperglycemia, severe azotemia, glycerin, and intoxications (e.g., ethylene glycol, ethanol, methanol). The most common causes of serum osmolality greater than 360 mOsm/kg are diabetic ketoacidosis, azotemia, and hypernatremia. Citrate anticoagulants may cause increased readings. Hyperosmolality is an indication to measure serum sodium, potassium, urea nitrogen, and glucose concentrations plus calculate anion and osmolal gaps. Causes of Increased Osmolal Gap • Pseudohyponatremia, glycerin, ethylene glycol, methanol, ethanol, and possibly other intoxications can increase the osmolal gap. Mannitol or lactic acid might also be responsible. If pseudohyponatremia is ruled out, an increased osmolal gap mandates a search for recent exposure to these toxins. The increase in osmolal gap in dogs with ethylene glycol intoxication peaks at 6 hours, persists for at least 12 hours, but may be normal 24 hours after ingestion. If ethylene glycol intoxication is likely, urinalysis looking for calcium oxalate crystals, blood gas analysis, anion gap, and appropriate toxicologic analyses (see Chapter 17) are indicated. BLOOD GAS ANALYSIS Occasionally Indicated • Acid-base evaluation is useful in severely ill animals (e.g., severe dehydration, vomiting, diarrhea, oliguria and anuria, hyperkalemia, tachypnea). Blood gas analysis is also necessary to evaluate gas exchange and TCO2 alterations in patients with respiratory disorders (see Chapter 11). Urine pH does not necessarily reflect systemic pH and cannot substitute for blood gas analysis. Advantages • Blood gas analysis allows precise identification of the different acid-base disturbances and aids in evaluation of pulmonary function. Disadvantages • Equipment is expensive, and careful technique is required in obtaining and handling blood specimens to prevent artifacts. The need for rapid analysis may prohibit use of remote laboratories; however, pointof-care units (e.g., immediate response mobile analysis [IRMA]) allow immediate determinations and are often affordable for busy practices. Analysis • Blood gas analyzers are equipped with specific electrodes to measure pH, carbon dioxide partial pressure or tension (PCO2), and oxygen partial pressure or tension (PO2). The bicarbonate (HCO3−) is calculated. Arterial blood is required to evaluate PO2 for pulmonary function, but free-flowing jugular blood is acceptable for acid-base analysis. Pulmonary artery, jugular vein, and cephalic vein samples usually have similar values in normal dogs, whereas arterial blood has a slightly lower HCO3− (21 mEq/L versus 22 to 23 mEq/L for venous blood) and much lower PCO2 (37 mm Hg versus 42 to
43 mm Hg for venous blood). Abnormal cardiovascular function may change this relationship. For routine blood gas analyzers, a 3-ml syringe with a 25-gauge needle is used to collect 0.5 to 1.5 ml of blood. Heparin (1000 U/ml) is drawn into the syringe (coating the interior) and it and all air are expelled, leaving the needle hub filled with heparin (approximately 0.1 to 0.2 ml). For point-of-care units, as little as 0.125 ml blood is required. After the blood is collected, air bubbles must be dislodged and expelled. Inserting the needle into a rubber stopper or placing a tightly fitting cap over the syringe hub prevents exposure of the sample to room air. The syringe is rolled between the palms of the hands to mix the sample, and then submitted. Analysis should occur within 15 to 30 minutes of collection (if stored at 25° C) or within 2 hours if the sample is immersed in an ice-water bath. Handheld devices (e.g., IRMA) developed for use at the bedside (or cage) have been marketed as point-of-care units. These units can provide rapid blood gas data (as well as electrolytes and selected other determinations) on critically ill patients that can aid in decision making while waiting for routine laboratory results. There appears to be good correlation between results obtained with these small units and those coming from larger laboratory units. Normal Values • Normal blood gas values are shown in Table 6-1. Danger Values • pH less than 7.10 indicates lifethreatening acidosis, which may impair myocardial contractility; pH greater than 7.60 denotes severe alkalosis. Artifacts • PCO2 decreases, whereas pH and PO2 increase, if the sample is exposed to air. Air bubbles in the sample may produce the same artifacts, especially if they occupy greater than or equal to 10% of sample volume. PCO2 increases and pH decreases if analysis is delayed. Aerobic metabolism by WBCs may decrease PO2. Cooling the sample from 25° to 4° C slows these changes. Prolonged venous stasis during venipuncture increases PCO2 and decreases pH. Excessive heparin (>10% of the sample volume) decreases pH, PCO2, and HCO3−, whereas citrate, oxalate, or EDTA may decrease pH. Blood gas analyzers calculate HCO3− from pH and PCO2; TCO2 is measured on serum chemistry autoanalyzers but calculated on many blood gas analyzers. TCO2 usually is 1 to 2 mEq/L higher than HCO3−. Drugs That May Alter Blood Gas Results • Acetazolamide, NH4Cl, and CaCl2 may cause acidosis. Antacids, sodium bicarbonate, potassium citrate or gluconate, and
NORMAL BLOOD GAS VALUES PCO2 pH Dog venous 7.32-7.40 Dog arterial 7.36-7.44 Cat venous (mm Hg) HCO3− (mEq/L) PO2 (mm Hg) 33-50 36-44 7.28-7.41 Cat arterial 7.36-7.44 33-45 28-32 18-26 18-26 18-23 17-22 ≈100 ≈100
TABLE 6-2. RENAL AND RESPIRATORY COMPENSATIONS FOR PRIMARY ACID-BASE DISORDERS IN DOGS DISORDER Metabolic acidosis Metabolic alkalosis Acute respiratory acidosis Chronic respiratory acidosis Acute respiratory alkalosis PRIMARY CHANGE ↓ [HCO3−] ↑ [HCO3−] ↑ PCO2 ↑ PCO2 COMPENSATORY RESPONSE 0.7 mm Hg decrement in PCO2 for each 1-mEq/L decrement in [HCO3−] 0.7 mm Hg increment in PCO2 for each 1-mEq/L increment in [HCO3−] 1.5-mEq/L increment in [HCO3−] for each 10 mm Hg increment in PCO2 3.5-mEq/L increment in [HCO3−] for each 10 mm Hg increment in PCO2 ↓ PCO2 Chronic respiratory alkalosis ↓ PCO2 2.5-mEq/L decrement in [HCO3−] for each 10 mm Hg decrement in PCO2 5.5-mEq/L decrement in [HCO3−] for each 10 mm Hg decrement in PCO2 From DiBartola SP: Fluid therapy in small animal practice, ed 2, Philadelphia, 2000, WB Saunders, p 196. loop diuretics may cause alkalosis. Salicylates may cause metabolic acidosis, respiratory alkalosis, or both. Analysis of Blood Gas Results • The clinician should begin by evaluating the pH. If it is abnormal, an acid-base disturbance exists. If the pH is within the normal range, the clinician should check the PCO2 and HCO3−. If they are abnormal, a mixed acid-base disturbance is probably present. If the pH is low and the HCO3− is decreased, metabolic acidosis is present. If the pH is low and the PCO2 is increased, respiratory acidosis is present. If the pH is high and the HCO3− is increased, metabolic alkalosis is present. If the pH is high and the PCO2 is decreased, respiratory alkalosis is present. Next, the clinician should calculate the expected compensatory response (e.g., respiratory alkalosis is compensation for metabolic acidosis; metabolic alkalosis is compensation for respiratory acidosis) using the guidelines in Table 6-2. These guidelines are for dogs only. If a patient’s compensatory response is within the expected range (i.e., within 2 mm Hg or 2 mEq/L of the calculated values), the acid-base disturbance is simple. If the compensatory response falls outside of the expected range, more than one acid-base disorder (i.e., a mixed disorder) is probably present. After classifying the type of disturbance and whether it is simple or mixed, the clinician should determine whether the acid-base disturbance is compatible with the patient’s history and clinical findings. If the acid-base disturbance does not fit with the patient’s history, clinical BOX 6-7. CAUSES OF METABOLIC ACIDOSIS Increased Anion Gap (Normochloremic) Ethylene glycol intoxication (important) Diabetic ketoacidosis* (common and important) Uremic acidosis† (common and important) Lactic acidosis (common and important) Salicylate intoxication Other rare intoxications (e.g., paraldehyde, methanol) Normal Anion Gap (Hyperchloremic) Hypoadrenocorticism‡ (uncommon but important) Diarrhea Carbonic anhydrase inhibitors (e.g., acetazolamide) Dilutional acidosis (e.g., rapid administration of 0.9% saline) Ammonium chloride (infrequent) Cationic amino acids (e.g., lysine, arginine, histidine) (rare) Post-hypocapnic metabolic acidosis (rare) Renal tubular acidosis (RTA) (rare) *Patients with diabetic ketoacidosis may have some component of hyperchloremic metabolic acidosis in conjunction with increased anion gap acidosis. †The metabolic acidosis early in renal failure may be hyperchloremic and later convert to increased anion gap acidosis. ‡Patients with hypoadrenocorticism typically have hypochloremia caused by impaired water excretion (dilutional effect) and absence of aldosterone. Modified from DiBartola SP: Fluid therapy in small animal practice,
f indings, and other laboratory data, the blood gas analysis should be questioned. Metabolic Acidosis • Metabolic acidosis (i.e., decreased pH and HCO3−, with a compensatory decrease in PCO2) is caused by addition of acid, failure to excrete acid, loss of HCO3−, or a combination thereof (Box 6-7). Addition of acid may be iatrogenic (e.g., ethylene glycol, salicylates, NH4Cl, cationic amino acids) or spontaneous (i.e., lactic acidosis, ketoacidosis). Decreased acid excretion is due to renal dysfunction (e.g., renal failure, hypoadrenocorticism, type I renal tubular acidosis [RTA]). Loss of HCO3− is usually caused by small bowel diarrhea (i.e., diarrheic f luid has more HCO3− than plasma); renal losses of HCO3− (e.g., carbonic anhydrase inhibitors, type II RTA) are rare. Metabolic acidosis is usually caused by renal failure, diabetic ketoacidosis, lactic acidosis from poor perfusion, hypoadrenocorticism, and perhaps small bowel diarrhea. The anion gap sometimes helps differentiate these causes and is discussed later. Measurement of blood lactate concentrations may help determine the cause of the acidosis and may also be prognostic (i.e., increased blood lactate is associated with a poorer prognosis). See Chapter 14 for a brief discussion of blood lactate measurement. Respiratory Acidosis • Respiratory acidosis (i.e., decreased pH, increased PCO2, with a compensatory increase in HCO3−) is due to hypoventilation (which increases PCO2) and is synonymous with “primary
6-8. CAUSES OF RESPIRATORY ACIDOSISAirway ObstructionAspiration (e.g., foreign body, vomitus)Respiratory Center DepressionNeurologic disease (e.g., brainstem, high cervical spinal cord lesion)Drugs (e.g., narcotics, sedatives, barbiturates, inhalation anesthetics)ToxemiaCardiopulmonary Arrest (common)Neuromuscular DefectsMyasthenia gravis, tetanus, botulism, polyradiculoneuritis, polymyositis, tick paralysis, hypokalemic periodic paralysis in Burmese cats, hypokalemic myopathy in catsDrug-induced (i.e., succinylcholine, pancuronium, aminoglycosides administered with anesthetics, organophosphates)Restrictive DiseasesDiaphragmatic hernia, pneumothorax, pleural effusion, hemothorax, pyothorax, chest wall trauma, pulmonary fibrosisPulmonary Diseases (less common)Respiratory distress syndrome, pneumonia, severe pulmonary edema, diffuse metastatic disease, smoke inhalation, pulmonary thromboembolism, chronic obstructive pulmonary disease, pulmonary mechanical ventilation fibrosisInadequate VentilationModified from DiBartola SP: Fluid therapy in small animal practice, ed 2, Philadelphia, 2000, WB Saunders, p 246.
hypercapnia” (Box 6-8). Hypoventilation may be caused by airway obstruction, cardiopulmonary arrest, restrictive respiratory diseases (e.g., diaphragmatic hernia, pneumo-thorax, pleural effusion, hemothorax, chest wall trauma, pulmonary fibrosis, pyothorax), severe pulmonary dis-eases, and inadequate mechanical ventilation. Hypoven-tilation may also result from respiratory paralysis from neuromuscular disease (e.g., myasthenia gravis, tetanus, botulism, polyradiculoneuritis, tick paralysis), as well as by neuromuscular blocking drugs (e.g., succinylcholine, pancuronium, aminoglycosides combined with anesthet-ics). Airway obstruction, cardiac arrest, and respiratory paralysis usually cause respiratory acidosis. These patients are invariably hypoxemic if breathing room air. Breathing oxygen-enriched air (i.e., anesthesia) sometimes causes normal or increased PO2.Metabolic Alkalosis • Metabolic alkalosis (i.e., in-creased pH and HCO3−, with a compensatory increase in PCO2) is caused by loss of acid from or addition of alkali to the body (Box 6-9). Loss of acid usually is due to vomiting gastric fluid, but loss of Cl− via the kidneys (i.e., caused by furosemide) may be responsible. Metabolic alkalosis is usually due to vomiting of gastric contents (especially but not exclusively because of gastric outflow
BOX 6-9. CAUSES OF METABOLIC ALKALOSISVomiting of gastric contents (common and important)Diuretic therapy (e.g., loop diuretics, thiazides) (important)Oral administration of sodium bicarbonate or other organic anions (e.g., lactate, citrate, gluconate, acetate)Hyperadrenocorticism (infrequent)Post-hypercapnia (rare)Primary hyperaldosteronism (rare)Modified from DiBartola SP: Fluid therapy in small animal practice, ed 2, Philadelphia, 2000, WB Saunders, p 231.
obstruction) or administration of furosemide. Adding alkali may occur by administering NaHCO3, lactated Ringer’s solution, or potassium citrate. Normal kidneys eliminate administered alkali, however, and iatrogenic alkalosis seldom results unless renal dysfunction is present.Respiratory Alkalosis • Respiratory alkalosis (i.e., increased pH, decreased PCO2, with a compensatory decrease in HCO3−) is due to tachypnea (which decreases PCO2) and is synonymous with “primary hypocapnia” (Box 6-10). It may be the result of pulmonary disease, pulmonary thromboembolism, hypoxemia, direct stimu-lation of the medullary respiratory center (e.g., Gram-negative sepsis, hepatic disease, salicylates, xanthines, CNS disease, heat stroke), and excessive mechanical ven-tilation. Unexplained respiratory alkalosis may suggest Gram-negative sepsis or pain. Pulmonary edema may cause respiratory alkalosis, metabolic acidosis, or respira-tory acidosis. Respiratory alkalosis may occur during recovery from metabolic acidosis because hyperventila-tion (the compensation for metabolic acidosis) persists for 24 to 48 hours after correction of the acidosis. These patients are sometimes hypoxemic. Respiratory disease
BOX 6-10. CAUSES OF TACHYPNEA RESULTING IN RESPIRATORY ALKALOSISHypoxemia from Almost Any CauseRight-to-left shunting, decreased PIO2 (e.g., residence at high altitude), congestive heart failure, severe anemia, pul-monary diseaseCentral Nervous System (CNS) (direct stimulation of medullary respiratory center)Central neurologic disease, hepatic disease, Gram-negative sepsis, drugs (i.e., salicylate intoxication, xanthines such as aminophylline), heat stroke, fear, pain, fever, hyperthy-roidismMechanical VentilationModified from DiBartola SP: Fluid therapy in small animal practice, ed 2, Philadelphia, 2000, WB Saunders, p 247.PIO2, Partial pressure of inspired oxygen.
sometimes initially causes tachypnea and consequently hypocapnia, which can change to hypercapnia if the disease worsens. TOTAL CARBON DIOXIDE FOR ACID-BASE EVALUATION TCO2 is synonymous with HCO3− in samples handled aerobically. Frequently Indicated • In any severe systemic disease process, TCO2 helps determine if blood gas analysis is needed. Diseases in which TCO2 determinations and blood gas analysis are indicated include ethylene glycol or salicylate intoxication, severe diabetic ketoacidosis, and severe uremia. Advantage • Abnormal TCO2 may be an indication to obtain blood gas analysis. Disadvantages • One cannot accurately define metabolic and respiratory acid-base disorders using just TCO2. High TCO2 could be the result of either metabolic alkalosis or compensated respiratory acidosis. Low TCO2 could be the result of either metabolic acidosis or compensated respiratory alkalosis. Analysis • TCO2 is measured in serum or plasma by enzymatic and dry reagent methods. Serum or plasma analyzed within 15 to 20 minutes of collection is preferred. Samples may be stored in a capped syringe on ice at 4° C for up to 2 hours before analysis. Normal Values • Dogs and cats, 17 to 23 mEq/L. Danger Values • Less than 12 mEq/L (implies but does not confirm diagnosis of severe metabolic acidosis). Artifacts • TCO2 determined by dry reagent methods is not affected by hyperlipidemia. Falsely decreased TCO2 occurs if processing of the blood sample is delayed for several hours, if the blood collection tube is underfilled, and if heparin anticoagulant occupies greater than 10% of the sample volume. Drugs That May Alter TCO2 • Acetazolamide and NH4Cl cause metabolic acidosis, reducing TCO2. Furosemide, thiazides, and sodium bicarbonate cause metabolic alkalosis, increasing TCO2. Causes of Decreased TCO2 • TCO2 concentrations are decreased in metabolic acidosis (most common cause) and compensated respiratory alkalosis. A hyperventilating animal with decreased TCO2 usually has metabolic acidosis but could have chronic respiratory alkalosis. Blood gas analysis may be necessary to determine which is present. Severely decreased TCO2 in a patient with a recognized cause of metabolic acidosis (e.g., diabetic ketoacidosis) is usually assumed to represent metabolic acidosis. Blood gas analysis is necessary to confirm the presence of metabolic acidosis and assess the severity of the change in pH. TCO2 less than or equal to 12 mEq/L in a patient with
undiagnosed systemic disease is an indication for blood gas analysis. If blood gas analysis is unavailable, the clinician must correlate TCO2 with the clinical setting and decide if NaHCO3 therapy is indicated. This approach, however, can be dangerous because the actual pH is not known. Measuring serum electrolyte concentrations allows optimal fluid therapy (i.e., disturbances that affect acid-base balance often also cause electrolyte abnormalities). Causes of Increased TCO2 • TCO2 concentrations are increased in metabolic alkalosis (most common) and compensated respiratory acidosis (rare). Serum sodium, potassium, and chloride concentrations should be measured, because hypochloremia and hypokalemia are common in metabolic alkalosis. If these changes occur, they should be corrected (i.e., administration of 0.9% NaCl + KCl) and the underlying cause (e.g., pyloric obstruction) diagnosed. ANION GAP Infrequently Indicated • The anion gap sometimes helps differentiate causes of metabolic acidosis and may help clarify mixed acid-base disorders. Metabolic acidosis with a high anion gap usually comes from acids that do not contain chloride (e.g., lactic acid, keto acids, salicylic acid, metabolites of ethylene glycol, phosphates, sulfates). Metabolic acidosis characterized by a normal anion gap has an increased plasma chloride concentration and is called hyperchloremic acidosis. Advantage • Only a simple calculation from values already measured is required. Disadvantage • The anion gap is affected by several factors and can be difficult to interpret. Analysis • The anion gap is calculated as (Na+ + K+) − (Cl− + HCO3−) or Na+ − (Cl− + HCO3−), depending on the clinician or laboratory’s preference. The anion gap and its component values are expressed in mEq/L. If the patient is severely hypoalbuminemic, the anion gap may not reflect expected findings. For each 1 g/dl decrease in serum albumin, the anion gap decreases approximately 2.4 mEq/L. Normal Values • The normal anion gap calculated by (Na+ + K+) − (Cl− + HCO3−) is approximately 12 to 24 mEq/L in dogs and 13 to 27 mEq/L in cats. Danger Values • Greatly increased values may be the result of acute ethylene glycol intoxication and warrant a careful review of the patient’s history. There may be a correlation between increasing anion gap and mortality in seriously ill animals. Causes of Decreased Anion Gap • Hypoalbuminemia is probably the most common cause of a decreased anion gap; immunoglobulin G (IgG) multiple myeloma may also be responsible. The magnitude of increase in unmeasured cations (e.g., calcium, magnesium) necessary to
lower the anion gap would probably be fatal. Laboratory errors resulting in overestimation of TCO2 or Cl− or in underestimation of sodium may artifactually decrease the anion gap. A decreased anion gap is seldom clinically significant. Causes of Normochloremic (Increased Anion Gap) Acidosis • The most common causes of an increased anion gap in acidotic patients are lactic acidosis, diabetic ketoacidosis, uremic acidosis, ethylene glycol intoxication, and laboratory error. Causes of Hyperchloremic (Normal Anion Gap) Acidosis • Severe, acute small bowel diarrhea causes HCO3− loss and produces hyperchloremic (normal anion gap) acidosis. Carbonic anhydrase inhibitors (e.g., acetazolamide) inhibit proximal renal tubular reabsorption of HCO3− and produce self-limiting hyperchloremic metabolic acidosis. Acidosis resulting from administration of NH4Cl decreases HCO3−, but serum Cl− increases and the anion gap is unchanged. Infusion of cationic amino acids (e.g., lysine HCl, arginine HCl) during total parenteral nutrition may cause hyperchloremic metabolic acidosis, because H+ ions are released when urea is generated. Renal acid excretion decreases during chronic respiratory alkalosis, with consequent reduction in plasma HCO3− and increase in Cl−. When the stimulus for hyperventilation is removed and PCO2 increases, pH decreases because it requires 1 to 3 days for the kidneys to increase acid excretion and increase plasma HCO3−. This transient phenomenon is called post-hypocapnic metabolic acidosis and is associated with hyperchloremia. Dilutional acidosis occurs when extracellular volume is expanded via an alkali-free chloride-containing solution (e.g., 0.9% NaCl). The high Cl− of physiologic saline solution (i.e., 154 mEq/L) and the highly resorbable nature of Cl− in renal tubules contribute to decreased plasma HCO3− and hyperchloremia. RTA is a rare disorder characterized by hyperchloremic metabolic acidosis because of either decreased HCO3− reabsorption (type II RTA) or defective acid excretion (type I RTA). Other Causes of Increased Anion Gap • Severe dehydration may increase both serum albumin concentration and the anion gap. Alkalemia may increase the anion gap slightly. Excessive standing of serum, especially in uncapped containers, also may increase the anion gap (a common error in samples not analyzed until the next day).