Chylothorax is defined as the accumulation of chyle in the pleural space, which distinguishes it from the presence of pus (pyothorax) or air (pneumothorax).
Chylothorax develops when chyle, fluid containing a high concentration of chylomicrons and lymph, effuses from the thoracic duct-cisterna chyli system into the pleural space. Chylothorax is fairly uncommon in dogs and cats, is usually secondary to other conditions or diseases, and can be difficult to treat.
Chylous effusion classically has been described as a milky-white pleural fluid that fails to become clear upon centrifugation. Pseudochylous effusion is also milky white, resembles chylous effusion grossly, and typically is associated with chronic inflammatory thoracic disease. Pseudochylous effusions do not contain chylomicra, clear upon centrifugation, and contain cholesterol and protein-lecithin compounds, giving them a higher cholesterol content than serum.
Dietary lipids, including triglycerides, cholesterol and phospholipids, undergo four major processes of assimilation. The first stage, emulsification, breaks up the lipids into smaller droplets. Emulsification starts in the stomach and continues into the small intestine. Stomach activity breaks the lipid globules into smaller droplets which can pass easily into the duodenum. Once the lipids are in the small intestine, bile acids coat and decrease the surface tension of lipid droplets, which further reduces the size of the emulsified droplets. The second stage, hydrolysis, occurs in the jejunum. Pancreatic enzymes such as lipase, co-lipase, cholesterol esterase and phospholipase degrade lipids in the emulsified droplets into nonesterified fatty acids, monoglycerides, cholesterol and lysophospholipids. In the third stage, micelle formation, the products of hydrolysis combine with bile acids and phospholipids to form micelles, which are water-soluble. The fourth stage is absorption, during which the micelles diffuse across the apical membranes of enterocytes in the jejunum. The bile acids do not enter the enterocyte, but are reabsorbed in the ileum. Once inside the enterocytes, the lipids are re-esterified into triglycerides and phospholipids. The re-esterified lipids then combine with cholesterol, other lipids and proteins to form chylomicrons.
Chylomicrons are small, water-soluble structures with a core of hydrophobic, nonpolar lipids and an outer coat of polar lipids. The chylomicrons are then absorbed into intestinal lymphatics, which travel to the cisterna chyli. The thoracic duct carries the chylomicrons from the cisterna chyli into the venous circulation for distribution to tissues.
Chylous effusions may result from leakage of chyle from intact lymph vessels or thoracic duct perforation. Obstruction of lymphatic flow commonly causes lymphatic hypertension, dilation of lymphatics, and subsequent leakage of lymph. Chylothorax may be idiopathic in cats, but several causes have been implicated including hypertrophic cardiomyopathy, thoracic and mediastinal neoplasia (e.g. lymphoma), mediastinal fungal granulomas (e.g. cryptococcus), heartworm disease, congenital lymphatic defects, trauma, chronic vomiting or coughing,  or rupture of lymphatic vessels, diaphragmatic hernia, lung lobe torsion, and venous thrombi.
Rupture of the thoracic duct secondary to trauma was once thought to be the sole cause of chylothorax, but it has been shown that the thoracic duct remains intact in the majority of patients.
- Hypertrophic cardiomyopathy
- Heartworm disease
- Idiopathic chylothorax
- Mediastinal neoplasia (lymphoma, thymoma)
- Trauma and rupture of the thoracic duct
- Other causes of pleuritis
There does not seem to be a gender predisposition for the development of chylous effusion in cats. Age does seem to be a factor, as trauma-related, idiopathic, and congenital causes of chylothorax tend to occur in younger animal. Chylothorax associated with neoplasia and heart disease tend to occur in older animals. A breed predisposition seems to exist in cats, with purebred cats having an increased relative risk for development of chylothorax.
Diagnosis is made based on physical examination, clinical signs, thoracic radiographs, and pleural fluid analysis. The most common presenting signs in cats are dyspnea and coughing. Other clinical signs and historical findings include weight loss, anorexia, gagging, lethargy, gagging, regurgitation, vomiting, exercise intolerance, and salivation. Abnormal physical findings most commonly include dyspnoea, muffled heart sounds, increased bronchovesicular sounds, and tachycardia. Thoracic radiographs should be performed, depending on the clinical status of the animal, but thoracocentesis may be necessary to stabilize the animal. Supplemental oxygen and dorsoventral radiographs may be required depending on the degree of dyspnea. Radiographs typically reveal pleural effusion, which may be unilateral or bilateral. Ultrasonography and echocardiography may be useful in identifying an underlying cause of the effusion, such as cardiomyopathy or mediastinal neoplasia.
The complete blood count may reveal mature neutrophilia due to inflammation and lymphopenia from the loss of lymphocytes into the fluid. The serum chemistry profile may disclose hypoalbuminemia, hyponatremia, or hyperkalemia. Hypoalbuminemia results from protein deficiency and frequent removal of effusion. Hyponatremia may result from removing fluid containing electrolytes (therapeutic drainage of the chylous effusion). Hyperkalemia may be due to hypovolemia and/or renal secretion defects of potassium.
Pleural fluid analysis is required for the diagnosis of chylothorax. Grossly, chylous effusion is milky white or pink, depending on the degree of haemorrhage associated with the effusion (Figs. 1 & 2). Chylous effusions should not clot or have an odour, and should be free of particulate matter. Collecting the fluid into an EDTA tube allows for cell counts on the sample. A culture and sensitivity should be performed, although chyle is considered to be bacteriostatic. Initial microbial cultures on 32 cats in one study were negative for bacterial; however, secondary infections were reported after repeat thoracocentesis or surgery in 5 cats. The effusion should form a cream layer upon standing in the tube because chylomicra have a low density and rise to the surface.
Upon centrifugation, the sample should become white following centrifugation if red blood cells are present (although the presence of hemolyzed erythrocytes will result in a fluid that remains red or pink following centrifugation), and should remain opaque.
Laboratory analyses that may be performed on the fluid include determination of specific gravity, total protein concentration, total and differential cell counts, cholesterol and triglyceride concentrations, and ratio of cholesterol to triglyceride. In two studies of cats with chylothorax, effusion fluid had a mean specific gravity of 1.030 and 1.032, and mean total protein concentration of 5.0 and 5.32 g/dl. The mean white blood cell count of the effusion fluid was 11,919 cells/µl in one feline study. Typically, a predominance of small lymphocytes is considered characteristic of chylous effusion; however, increase in neutrophils and macrophages may be associated with chronicity. The increase in neutrophils may occur as a result of an irritant effect of the effusion on the pleural lining or due to repeated therapeutic drainage of the effusion with subsequent peripheral lymphopenia. Differential nucleated cell counts performed on effusion fluid of cats with chylothorax indicated that lymphocytes were the predominant cell in 19 of 26 specimens. The remaining 7 specimens had a predominance of segmented neutrophils.
Comparison of concurrent serum and pleural fluid cholesterol and triglyceride concentrations and cholesterol to triglyceride ratios of the effusion can be helpful in diagnosing chylous effusion and differentiating chylous from pseudochylous effusion. Chylous effusions are typically characterized by cholesterol concentrations that are decreased or within the reference interval and an elevated triglyceride concentration as compared to serum. In contrast, pseudochylous effusions usually have elevated cholesterol concentrations, while triglyceride concentrations are equal to or lower than those of serum. Triglyceride concentrations may be increased markedly in chylous effusion, as chylomicrons are composed largely of triglyceride. Cholesterol to triglyceride ratios in chylous effusion are typically less than 1. Fluid to serum triglyceride ratios greater than 2-3:1 are diagnostic for chylous effusion; ratios of 10-20:1 are commonly encountered.
An ether clearance test is a quick test that may confirm the fluid is chylous. The ether clearance test is performed as follows: Divide the effusion into two test tubes, and add two drops of 10% potassium hydroxide to each tube. Dilute the first tube with a volume of water equal to the sample as a control, and add an equal volume of ether to the second tube. Invert the tubes, and the chylomicrons in the sample should dissolve in the ether. The first tube should appear diluted, but second tube should become clear.
Treatment and Prognosis
Treatment of chylothorax is dependent on the cause of the effusion. Both medical and surgical therapy have been used. An underlying cause or primary disease process should be identified and corrected, if possible. Medical therapy consists of thoracocentesis, dietary management, and drug therapy. Thoracocentesis allows palliative drainage and clinical improvement of respiratory distress. Initial thoracocentesis may be performed with a needle, but chest tube placement may be required for daily drainage. Traditionally, it has been suggested that the animal be placed on a low-fat diet to decrease the amount of lipid absorbed via intestinal lymphatics; however, loss of fat-soluble vitamins, lipids, and protein-rich lymph fluid may contribute to a state of malnourishment in the animal. It has been shown recently that a low-fat diet does not decrease the flow volume of effusion. It was once thought that supplemental medium-chain triglycerides would provide additional dietary lipid and bypass the thoracic duct because they were absorbed directly into the portal circulation. However, it has been demonstrated recently that the medium-chain triglycerides do not bypass the thoracic duct. In cases of severe malnutrition, parenteral nutrition can bypass the gastrointestinal system and decrease lymphatic flow.
- Nutriceutical 'fat binders' such as chitin and chitosan may be beneficial to decrease the fat-induced chyle flow.
- Rutin (a benzopyrone compound extracted from the fruit of the Brazilian Fava D’Anta tree) administration may result in clinical improvement of cats with idiopathic chylothorax. Suggested mechanisms of action for rutin include reduced leakage of lymph from lymphatic vessels, increased protein removal by lymphatics, increased phagocytosis by stimulation of macrophages, increased recruitment of macrophages in tissues, and increased proteolysis and removal of protein from tissues. Rutin is a bioflavonoid and a derivative of vitamin C. It stimulates macrophage uptake of protein and processing of inflammatory cells, thus improving the absorption of the remaining fluid. Dose is 50mg/kg tin, which can be mixed with food.
- Octreotide (Sandostatin, Novartis) is a synthetic somatostatin is being trialled in cats as a SQ injection three times daily. It has been used routinely for acromegaly and certain forms of adenocarcinomas, primarily lung-associated, but its efficacy in treatment of feline chylothorax is at present unknown.
Surgical management typically is performed in cases where medical therapy has failed. Surgical options include ligation of the thoracic duct, pleurodesis, and pleuroperitoneal or pleurovenous shunts. Ligation of the thoracic duct has been shown to be beneficial in 20% to 60% of cats with idiopathic chylothorax. Positive contrast mesenteric lymphangiography is useful to determine lymphatic anatomy and post-ligation success. Chylous or non-chylous effusions may continue to accumulate after ligation of the thoracic duct. Pleurodesis is the formation of adhesions between the parietal and visceral pleural surfaces. Substances such as tetracycline and talc have been infused to create adhesions, but studies in veterinary medicine reveal questionable efficacy. Pleuroperitoneal or pleurovenous shunts may be beneficial, but are associated with complications such as infection, adhesions, and clogging of the implants.
Regardless of the cause, chylothorax has been associated with poor survival rates in cats. A common sequela to chylothorax is restrictive pleuritis, resulting in an inability to expand the lungs. Chyle is irritating to the pleural surface; chronic exposure to chyle may cause fibrin deposition and connective tissue formation on the pleura resulting in restrictive pleuritis. Although chylothorax is rare, it is usually a fatal disorder in cats. Additional studies are needed to determine causes of idiopathic chylothorax and develop viable treatment options.
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- Wikipedia - lymphangiectasia
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