Hyponatremia and hyperkalemia associated with chylous pleural and peritoneal effusion in a cat

Abstract

A 6-year-old, castrated male shorthair was evaluated for chylous effusion in the thorax and abdomen. An underlying disease process was not determined. The cat developed hyponatremia and hyperkalemia, which was attributed to the mechanical drainage of pleural fluid and to the decreased urinary excretion of potassium.

A 6-year-old, castrated male shorthair was referred to the Small Animal Clinic at the Western College of Veterinary Medicine (WCVM) for evaluation of chylous effusion in the thorax and abdomen. The cat was presented to the referring veterinarian with respiratory distress 10 d prior to its presentation to the WCVM. The referring veterinarian removed 225 mL of chylous-appearing fluid by thoracentesis, and 5 d later, another 225 mL of chylous-appearing fluid from the chest and 20 mL of milky peritoneal fluid by abdominocentesis. At that time, the cat tested negative for both feline leukemia and feline immunodeficiency viruses. One day prior to presentation to the WCVM, the cat stopped eating.

On admission to the WCVM, the physical examination revealed that the abdomen was mildly distended and that the cat was overweight. Rectal temperature, pulse rate, respiratory rate, and body weight (BW) were 38.7οC, 200/min, 48/min, and 8.5 kg, respectively. On thoracic auscultation, lung sounds were decreased ventrally while bronchovesicular sounds were increased dorsally. Cardiac rhythm was normal and a murmur was not detected. Thoracic radiographs revealed a large volume of pleural fluid. On thoracic ultrasonographic examination, the cardiac chamber dimensions, wall thickness, and valvular structures appeared normal in motion and morphology. Thoracentesis yielded 135 mL (80 mL from the left hemithorax and 55 mL from the right hemithorax) of pink-tinged, milky fluid. Thoracic radiographs were taken again and no abnormalities within the cranial mediastinum or of the heart were noted. A complete blood cell (CBC) count, serum biochemical profile, and urinalysis were performed. Hematologic abnormalities included a mild neutrophilia (15.130 × 10⁹/L; reference range, 3.6 to 11.5 × 10⁹/L) and lymphopenia (1.020 × 10⁹/L; reference range, 1.5 to 7.0 × 10⁹/L). Results from the serum biochemical panel and urinalysis were within normal limits. Serum and pleural fluid triglyceride (T) and cholesterol (C) levels were (T = 1.0 mmol/L and 8.30 mmol/L, respectively) and (C = 3.06 mmol/L and 2.0 mmol/L, respectively) with a C/T ratio < 1 (0.25). These findings were diagnostic for chyle (1,2,3,4,5). Cytological examination of the pleural fluid showed that it was consistent with a chylous effusion of long duration (51% neutrophils, 28% small mononuclear cells, and 21% macrophages) (1,2). Neoplastic cells were not seen, and the bacterial culture was negative. Results from cytological examination, C/T ratio, and culture of peritoneal fluid were similar to those for pleural fluid. An occult heartworm test was negative. To rule out occult neoplastic processes, abdominal radiographs and abdominal ultrasonography were taken. Abdominal radiographs did not reveal any abnormalities. Abdominal ultrasonography revealed a moderate amount of ascites. During the ultrasonographic examination, the cat exhibited respiratory distress, and a repeat thoracentesis yielded 225 mL of chyle. Due to the rapidity of fluid development, it was decided to insert a chest tube. The cat was placed on IV isotonic crystalloid fluid therapy (lactated Ringer's solution with 20 mEq KCl), 120 mL/kg BW, q24h, for diuresis. Initially, 2 chest tubes were placed (1 in each hemithorax) to allow for maximum chest drainage. Thoracic radiographs showed that the tube in the right hemithorax was improperly placed, so it was removed. A percutaneous endoscopic gastrostomy (PEG) tube was being placed for nutritional support and to prevent hepatic lipidosis. When bleeding into the abdomen occurred, the procedure was aborted. The bleeding was attributed to hepatic or splenic laceration caused by the attempted PEG tube placement. No further attempts were made to place a PEG tube. The cat was monitored in the intensive care unit for 14 h and made an uneventful recovery.

On day 2, the cat was force-fed (A/D Diet; Hill's Pet Nutrition, Topeka, Kansas, USA). The cat was also started on rutin (General Nutrition Centers, Pittsburgh, Pennsylvania, USA), 250 mg, PO, q8h. A repeat serum biochemical panel showed mild hyponatremia (146 mEq/L; reference range, 150 to 160 mEq/L). Thoracic radiographs revealed a persistent effusion. The right cranial lung lobe appeared atelectic and the cranial mediastinum was slightly widened. The echogenicity of the cranial mediastinum was consistent with fat on ultrasonographic evaluation. Cytological examination of ultrasonographically-guided fine needle aspirates of the cranial mediastinum showed a mixed inflammatory population of mostly nondegenerated neutrophils and small lymphocytes. Neoplastic cells were not seen. A total of 152 mL of chyle was drained from the chest. In the evening, the cat began to eat on his own and the IV fluids were decreased to 60 mL/kg BW, q24h. On day 3, the cat continued to eat on his own and IV fluids were discontinued. On day 4, 130 mL of chyle was removed from the chest. The cat was discharged to the referring veterinarian for intermittent drainage from the chest tube and continued conservative management. Blood for analysis of kidney function and electrolytes (submitted just prior to discharge from the WCVM) showed hyponatremia (146 mEq/L; reference range, 150 to 160 mEq/L) and hyperkalemia (6.4 mEq/L; reference range 4.0 to 5.8 mEq/L). The sodium to potassium (Na/K) ratio was 23 (reference > 26).

Over the next 10 d, the referring veterinarian removed a total of 600 mL of chyle from the cat's chest. Administration of rutin had been increased to 500 mg, PO, q8h. On day 15, a serum biochemical panel showed hyponatremia and hyperkalemia (Table 1). The serum bicarbonate level was normal (20 mmol/L; reference range, 13 to 25 mmol/L). The calculated serum osmolality (2[Na mmol/L] + BUN mmol/L + glucose mmol/L) was 278 mmol/L. To further evaluate the cause of the hyponatremia and hyperkalemia, an adrenocorticotrophic hormone (ACTH) stimulation test was performed and showed normal plasma cortisol levels [pre- and post- 174 and 237 nmol/L, respectively (reference range pre, 15 to 150 nmol/L; reference range post-, 130 to 450 nmol/L)]. The post ACTH stimulation serum aldosterone level was markedly elevated (> 3329 pmol/L; reference range 277 to 721 pmol/L) (6). Test results were not consistent with hypoadrenocorticism. Pleural fluid and urine electrolyte panels were also submitted (Table 1). Urinary fractional clearances (FC) of sodium and potassium (Table 1) were calculated (7). Over the next 5 d the cat became increasingly inappetant, and on day 20, an esophagostomy tube was placed. The cat died 3 d later after he had developed Horner's syndrome and an abscess around the esophagostomy tube. A necropsy was not authorized.

Table 1.

Chyle is the term to denote lymphatic fluid arising from the intestine (1). Causes of chylous effusion may include right-sided heart failure, mediastinal masses, cranial venal cava thrombi, granulomas, trauma, congenital thoracic duct (TD) anomalies, and diffuse lymphatic disease (thoracic/intestinal lymphangiectasia, lymphangiosarcoma) (1,2,3). In this case, the cat was diagnosed with idiopathic chylous effusion, because an underlying cause was not determined. The owner was made aware of the grave prognosis, as the presence of chylous abdominal effusion is most often associated with diffuse lymphatic disease or neoplasia, or both (8). Surgical exploration of the thorax is often considered when idiopathic chylothorax is diagnosed; however, due to the presence of chylous effusion in the abdomen, conservative management was chosen initially. Medical management of idiopathic chylothorax with intermittent thoracentesis, low-fat diet, and rutin therapy has been recommended (1,3,4). Intermittent thoracentesis is an important part of management, because of the potential for fibrosing pleuritis to develop, which is a negative prognostic indicator (1,2,4). Low-fat diets are often poorly palatable and may be inappropriate for animals that are already losing weight (4). In addition, there is little experimental or clinical evidence that feeding a low-fat diet alters lymph flow (3,4). Rutin is a benzopyrone compound that is used in human medicine for the treatment of lymphedema (4,9) and has been used experimentally in cats with chylothorax (4). It is thought to increase proteolysis by tissue macrophages. Once the excess protein is eliminated, the edematous fluid can be reabsorbed more readily (3,4). Although rutin has been associated with resolution of idiopathic chylothorax in some cats, true association is debatable, because some cats will experience spontaneous resolution (1,4).

The condition of hyponatremia and hyperkalemia has been associated with acute renal failure, pregnancy, external blood loss, gastrointestinal disease (usually whipworm infestations in dogs), pleural effusions in dogs, and hypoadrenocorticism. Hyponatremia with hyperkalemia in the face of normal adrenal gland function was recently reported in cats with peritoneal effusions (10). In another study, hyponatremia with hyperkalemia was reported in association with mechanical (chest tube) drainage of chylous pleural effusions in 4 dogs (5). To the author's knowledge, concurrent pleural and abdominal chylous effusions; and hyponatremia with hyperkalemia associated with mechanical drainage of chylous pleural effusion have not been reported previously in cats.

Hyponatremia usually results in serum hypoosmolality (11). Likely causes of hypoosmolar hyponatremia in this cat included hypoadrenocorticism, salt-losing nephropathy, third-space loss due to effusion, and third-space loss due to chylothorax with repeated pleural fluid drainage. The normal ACTH stimulation test and increased serum aldosterone level ruled out hypoadrenocorticism. The FC of sodium in the urine was low (Table 1), ruling out salt-losing nephropathy. Nonrenal losses of sodium may occur with third-space losses. Renal conservation of sodium results in a FC of sodium of < 1% (11). Hyponatremia due to third-space losses into effusions (without drainage) is thought to occur secondarily to sodium and water retention, and impairment of free water excretion (10). Body cavity effusion causes a decreased effective circulating volume (ECV), despite an increase in total extracellular fluid volume (ECFV) (10,12). This develops when fluid is lost within a cavity (third-space) and no longer contributes to the ECV, resulting in a relative hypovolemia.

Hypovolemia decreases glomerular filtration rate, enhances isosmotic reabsorption of sodium and water in the proximal tubules of the kidney, and decreases delivery of fluid to distal diluting sites (12). This impairs excretion of water. Hypovolemia also causes antidiuretic hormone (ADH) release, activation of the renin-angiotensin-aldosterone system (RAAS), and stimulation of the sympathetic nervous system. Activation of these systems also stimulates thirst, impairs free water excretion, and decreases renal tubular flow (10). In this cat, ADH secretion and RAAS stimulation were supported by the formation of concentrated urine (specific gravity = 1.042), an increased serum aldosterone level, and a decreased urinary sodium excretion (Table 1). Aldosterone increases sodium reabsorption in the cortical collecting duct of the kidney by opening luminal sodium channels. Although this theory may explain the hyponatremia in this cat with the presence of effusion without drainage, hyponatremia resulting from mechanical removal of pleural fluid is the most likely explanation (5,12). The cat presented with evidence of chronic effusion, based on the cytologic examination of the pleural fluid, and electrolyte abnormalities were not present prior to repeated drainage of the cat's chest, further supporting mechanical drainage as the primary cause of hyponatremia. Third-space loss into the effusion as the predominant cause, however, could not be ruled-out.

Hyperkalemia can be caused by increased intake, transcellular shifts, or by diminished urinary excretion (5,13). In this cat, increased intake was unlikely in the presence of normal renal function. A cause for transcellular shifts, such as metabolic acidosis, was not supported based on normal serum bicarbonate. The normal ACTH stimulation test did not support hypoadrenocorticism as the cause of diminished urinary excretion. Diminished urinary excretion of potassium can be caused by chylothorax with repeated drainage of pleural fluid or by third space loss into effusions without drainage, and it is thought to result from an acquired defect in renal secretion of potassium (5,13). A relative hypovolemia decreasing renal tubular flow is thought to cause insufficient potassium secretion.

Aldosterone is a mineralocorticoid produced and secreted by the cells of the zona glomerulosa of the adrenal cortex. Secretion is controlled mainly by the serum potassium concentration and stimulation by the RAAS. An increase in either results in increased aldosterone secretion (13). Aldosterone is important for sodium and potassium regulation and maintenance of a normal intravascular volume. Aldosterone acts at the distal convoluted tubule of the kidney, increasing production of Na⁺-K⁺-ATPase, increasing the number of sodium pumps within the nephron, and facilitating potassium excretion at the luminal membrane (10,12,13). Aldosterone is the most important hormone affecting urinary potassium excretion. An increase in distal tubular flow results in enhanced potassium secretion. A decrease in distal tubular flow from relative hypovolemia, especially in conjunction with hyponatremia, impairs potassium secretion. Potassium secretion is impaired because of poor sodium delivery (decreased electrochemical gradient) and potassium saturation of the luminal fluid (decreased concentration gradient), despite normal or increased concentrations of aldosterone (10,13). In this cat, hyperkalemia caused by inadequate urinary secretion of potassium was demonstrated by the inappropriately low FC of potassium in the urine (Table 1), despite an increased serum aldosterone level. When FC is evaluated, the evaluation does not necessarily correlate with the 24-hour urinary excretion of electrolytes; however, reference values have been reported (1,6,7,11,14).

This cat's condition of hyponatremia with hyperkalemia was attributed to third-space loss of sodium brought about by mechanical drainage of the pleural effusion and to decreased urinary excretion of potassium. This case emphasizes the necessity to carefully monitor electrolytes in patients with effusions that are being treated by thoracic drainage. CVJ