[Congenital chylothorax in the newborn. Contribution of a case with study of fatty acid composition of the diet and chyle and review of the literature].
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Phosphatidylinositol (PI), mainly stearoyl-arachidonyl PI, occurs as a minor phospholipid constituent in both chyle and plasma lipoproteins. The kinetics and the pathway by which plasma and chyle PI is metabolized have not been investigated. The role of lipoprotein PI in the supply of arachidonic acid (20:4) and inositol lipid components to different tissues is thus unknown. In this study we examined the fate of chyle PI in vivo and its hydrolysis by lipoprotein lipase (LPL), hepatic lipase (HL), and postheparin plasma in vitro. Chyle and chylomicrons were labeled in the PI portion by feeding [3H]myo-inositol and in the phosphatidylcholine (PC) portion by feeding [14C]choline in a linoleate-rich fat meal (Intralipid) to mesenteric duct-cannulated rats. After intravenous injection of doubly labeled chyle into normal rats, [3H]PI disappeared from plasma at a slower rate than [14C]PC; after 60 min 41.6 +/- 2.7% 3H and 24.3 +/- 1.8% 14C (means +/- SEM, n = 4, P < 0.01) remained in plasma lipids. About 15% of both isotopes were in liver lipids after 60 min. Previous injection of a blocking antiserum against rat HL did not significantly influence the serum and liver radioactivity after 60 min. Radioactive PI was rapidly transferred to high density lipoproteins (HDL) during the metabolism of chylomicrons. Analysis of 3H and 14C in different molecular species of PI and PC in chyle and in serum indicated that there was no significant difference in disappearance rates between various species, stearoyl-arachidonyl PI thus disappearing at the same rate as total [3H]PI. Both lipoprotein lipase (LPL) and HL catalyzed formation of lyso-PI in vitro, the rate being increased by the addition of serum. About 60% of the lyso-PI formation catalyzed by postheparin plasma in 60 min could be blocked by antiserum to HL, which almost completely blocked the hydrolysis occurring after the first 10 min. The study thus shows that both LPL and HL hydrolyze chylomicron PI in vitro. LPL and HL may, however, be of limited importance for the clearance of chyle PI in vivo, most of the chylomicron PI being transferred to HDL, and thereafter eliminated from plasma at a slow rate mainly by other mechanisms.
Insulin-like growth factors (IGFs) are bound by several IGF-binding proteins (IGFBPs) that appear to regulate IGF transportation, receptor binding and action. In adult human serum, most of IGFs are bound in a 150 kDa complex which could not cross the capillary wall. We measured IGF-I and IGFBPs in chyle by radioimmunoassay and western ligand blot. The concentration of IGF-I in chyle was only 15% of the corresponding serum level and most of IGF-I was found in 50 kDa complex. The IGFBPs profile in chyle, especially IGFBP-3, was different from that of serum. The concentration of IGFBP-3 in chyle was much less than in serum and the size of glycosylated IGFBP-3 was different from that of serum. However, the size and relative amount of IGFBP-1 and -2 in chyle were similar to serum. This finding indicates that IGF-I and IGFBPs in chyle to a large extent originate in the vascular system and only the 50 kDa complex can cross the capillary barrier.
The effects on platelet aggregation of native rat chyle chylomicrons, chylomicron remnants, and chylomicrons that had been preincubated with rat or human EDTA-plasma, serum, whole blood, or pure human prothrombin were examined. The native chyle chylomicrons did not induce platelet aggregation but decreased ADP- and thrombin-induced platelet aggregation and [14C]serotonin release. Chylomicron remnants also failed to induce platelet aggregation, but they potentiated the aggregation and the [14C]serotonin release induced by ADP and thrombin. Aggregation, after a lag phase of 15 to 20 minutes, was seen when platelets were incubated with chylomicrons that had been preincubated with plasma and then isolated as the top layer after a single centrifugation at d = 1.006. This aggregation was inhibited in a dose-dependent manner by an antiserum against prothrombin that also inhibited thrombin-induced platelet aggregation. After washing by centrifugation the plasma-preincubated chylomicrons did not induce platelet aggregation, but this effect could be restored by adding a small amount of prothrombin, which did not cause aggregation when added alone or together with native chyle chylomicrons. Addition of 2% (vol/vol) plasma, however, induced aggregation when added together with either native chyle chylomicrons or washed preincubated chylomicrons, but not when added alone. Binding of 125I-labeled prothrombin to native chyle chylomicrons was demonstrated by gradient ultracentrifugation. During incubation of washed plasma-preincubated chylomicrons with 125I-prothrombin and platelets, a significant conversion of 125I-prothrombin to 125I-prethrombin and 125I-thrombin occurred, as demonstrated by autoradiography after separation on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The interaction between chylomicrons and prothrombin, and possibly other coagulation proteins, thus enhances prothrombin activation in the presence of platelets.
PHYSIOLOGY: Chylothorax corresponds to the intrathoracic presence of chyle. Chyle is a lymph of intestinal origin containing the product of digested fat. This lymph joins the blood circulation through the thoracic duct. The thoracic duct receives a part of the lymphatic drainage from the viscera below the diaphragm, from the diaphragm and from the sterno-costal wall. PHYSIOPATHOLOGY: Intrapleural chyle issue is explained by an acquired or spontaneous lesion of the thoracic duct or of one of its collaterals in the thorax. The iatrogenic or spontaneous lesions of the collaterals suggest that the latter are incontinent and have lost their valve capacity, and hence provoke a reflux of chyle from the thoracic duct. The anatomy of the chylothorax (occasionally pathological) can be specified by a pedal lymphography. FROM A THERAPEUTIC POINT OF VIEW: Treatment, essentially medical, can be completed by surgery. The medical treatment is based on re-nutrition and a diet excluding fat, supplemented by medium chain triglycerides. Surgery consists in pleural symphysis and/or suture of the damaged collaterals, or ligature of the thoracic duct. The indications depend on the severity of the chyle leakage and the type of original lesion. The indications therefore depend on the etiology and clinical evolution of each case. These different treatments, isolated or combined, lead to the regression of the effusion in nearly all cases.
Age and local changes of the lymphatic bed have been studied in the jejunum and ileum preparations obtained from 100 rabbits. The architectonics of the bed is stated to undergo some age and local changes. In fetuses and two-week-old rabbits, chyle sinuses are narrow and all flow into the capillaries of the tela submucosa. In one-month-old animals, the mucosal capillary network is developing and the chyle sinuses flow into it. In six--ten-month-old rabbits, intestinal bed is already formed, the chyle sinuses are wide. Aged changes are represented by a considerably rarefied networks, decrease in the chyle sinuses caliber, deformation of the sinus, capillary and vessel walls. In the jejunum, unlike the ileum, the chyle sinuses are of larger size and have more complex architectonics in the capillary networks of the mucosa and tela submucosa.
The stereochemistry of fat digestion and absorption was investigated in rats with thoracic duct fistulas, after feeding synthetic triacylglycerol or alkyldiacylglycerol. After feeding 1,2-dilauroyl-3-oleoyl-sn-glycerol, dilauroyloleoylglycerol and lauroyldioleoylglycerol were the most abundant chyle triacylglycerols. Positional analysis of the fatty acid distribution and the absence of optical activity indicated that the following structures dominated: rac-1,2-dilauroyl-3-oleoylglycerol and rac-1,3-dioleoyl-2-lauroylglycerol. Therefore, the triacylglycerol resynthesized from 2-lauroylglycerol (pre-cursor to 60% of chyle triacylglycerol) and other precursors was essentially racemic. Chyle phospholipids contained largely endogenous fatty acids, and the proportion of lauric acid was very low. A racemic mixture of 1,2-di[3H] oleoyl-3-tetradecyl-sn-glycerol and 1-tetradecyl-2,3-di[12C] oleoyl-sn-glycerol was absorbed to a lower degree than triacylglycerol. The appearace of oleic acid with different labels in chyle and intestinal lipids did not differ, indicating the absence of stereospecificity in fat digestion. Possible explanations for the low absorption are discussed.
1. Chyle lipids, labelled with (14)C, are taken up and oxidized by the isolated perfused rat heart. 2. In recirculatory perfusions, when chyle lipids are the sole exogenous energy source, about 24% of the total oxygen uptake is accounted for by their oxidation. This proportion is not changed by starvation of the rats for 48hr. and falls when an external work load is imposed on the left ventricle. 3. With albumin in the perfusion medium, the rate of (14)CO(2) output is reduced by half and there is a rise in the proportion of (14)C-labelled free fatty acids in the medium. 4. Clearing-factor lipase appears in the perfusion medium when chyle lipids are perfused through the heart. In the absence of albumin, the activity of the medium enzyme is low and only a small proportion of the (14)CO(2) output can be accounted for by the oxidation of free fatty acids released by it. In the presence of albumin, the enzyme is more active in the medium. 5. When a substantial proportion of the total clearing-factor lipase is removed from the heart by a prior perfusion with heparin, (14)C-labelled chyle lipid perfused subsequently is oxidized at only half the normal rate.
Of 300 congenital malformations of the lymphatics of the small intestine investigated, 120 were operated upon. Intestinal lymphography shows no injection of the cisterna chyli and histology proves that the mesenteric lymph nodes are abnormal. The induced hyperlipidemia test permits a biochemical diagnosis. Modifications of the flow of the chyle secondary to the hypoplasia of the cisterna chyli were studied: (1) in the abdominal cavity, (2) in the extraperitoneal region and the lower limb, (3) in the thorax, especially the chyle drainage channels from the diaphragm towards the cervical region. Our investigations have established that the following diseases are produced by malformation of the lymphatics of the small intestine: protein losing enteropathy, chyloperitoneum, chyluria, lymphedema with chyle reflux, chylothorax, chylopericardium, chyle reflux in the pulmonary lymphatics, hypoproteinemia and food allergies. A better understanding of the pathophysiology of the malformations of the intestinal lymphatics permits a more rational treatment of the diseases produced by this anomaly.
Most of the cholesterol in intestinal chyle and chylomicrons is derived from plasma. Our aim was to determine how much plasma low density (LDL) and high density (HDL) lipoproteins contribute to the cholesterol in chyle and chylomicrons, and to examine how plasma cholesterol becomes associated with lymph chylomicrons. Intravenous injection of radioiodinated plasma lipoproteins into two chyluric patients showed that 82% of the HDL plasma pool transferred daily to intestinal chyle, corresponding to 58% of lymph cholesterol; LDL contributed 18% of its plasma pool, corresponding to 18% of lymph cholesterol. When plasma HDL radiolabeled in both the protein and cholesteryl ester moieties was injected, the isotope ratios of plasma HDL and lymph lipoproteins were identical; 85% of the HDL cholesteryl esters transferred to triglyceride-rich lipoproteins, while the apolipoproteins remained largely (70%) in the higher density lipoproteins of the chyle. Incubations of similarly labeled plasma HDL showed preferential transfer of cholesteryl esters to artificial chylomicrons mediated by a factor present in lipoprotein-free plasma. Thus, a sizable portion of plasma HDL enters intestinal lymphatics probably as intact HDL, and then transfers part of their cholesteryl esters to chylomicrons, possibly mediated by transfer proteins. Reverse cholesterol transport may therefore include an extravascular loop via lymph chylomicrons and chylomicron remnants to the liver.
A large part of the circulating apolipoprotein A-I (apoA-I) is produced by the intestine. Yet the plasma levels of apoA-I are retained or even increased in rats with thoracic duct drainage (Johansson, B. and Nilsson, A, (1981) FEBS Lett. 130, 305-308 and Franzén, J. et al. (1987) Biochim. Biophys. Acta 918, 11-15). In this study we examined the effects of biliary drainage and of combined biliary and lymphatic drainage on the plasma apoA-I levels, and also the effects of lymphatic drainage on the output of biliary lipids in the rat. 63 h of biliary drainage caused a 40% decrease of the serum apoA-I concentration. In contrast the concentration in rats with combined thoracic duct and biliary drainage was 153% of that in control rats. The biliary secretion of bile acids, phosphatidylcholine and cholesterol declined to a lower level in rats with combined thoracic duct and biliary drainage, but increased at the later time intervals to the same levels as in rats with bile fistulas only. Intravenous chyle infusion 3-36 h after commencing the biliary drainage did not prevent the decrease in biliary lipid output. The study thus provided no evidence that the reduced hepatic inflow of apoB-containing lipoproteins during biliary drainage is of importance for the reduced biliary lipid output. The loss of all the chyle lipoproteins leads, however, to an even more pronounced decrease in the biliary lipid secretion. The drainage of all the chyle constituents also leads to an increased apoA-I synthesis that more than compensates for the apoA-I loss in chyle, whereas biliary drainage only lowers the plasma apoA-I levels.
A large pericardial effusion was discovered in an asymptomatic 12-year-old boy admitted for an elective orthopedic procedure. On physical examination, heart rate was 96 and blood pressure was 130/70 without paradox. The neck veins were not distended, but heart tones were distant. Chest roentgenogram (CXR) showed an enlarged cardiac silhouette. Echocardiogram showed a massive pericardial effusion compressing the right atrium, with depressed ventricular contractility. Pericardiocentesis yielded 450 mL of chylous fluid. A percutaneous pericardial drain was placed and drained another 400 mL of chyle. Pericardial fluid reaccumulated even though the patient was on a low-fat diet, and 1 week after admission left thoracotomy was performed with partial pericardiectomy and pericardial window. There was 1 L of chyle in the pericardial sac; frozen section of the pericardium showed lymphangiectasia. Chest tube drainage diminished rapidly and the patient was discharged. Follow-up CXR at 1 week showed fluid in both pleural spaces requiring bilateral tube thoracostomies again draining chyle. Even with total parenteral nutrition (TPN), 500 mL/d of chyle drained from the pleural tubes. Right thoracotomy with ligation of the thoracic duct was performed after 1 week of TPN. Pleural drainage abruptly dropped, and there has been no reaccumulation in either the pleural spaces or pericardium at 6-month follow-up. This case dramatically supports early thoracic duct ligation and partial pericardiectomy as the treatment of choice for primary massive chylopericardium.
Chyle is lymph fluid of intestinal origin containing fat digestion products. Chylothorax is produced by leaks from the thoracic duct or from one of its collaterals subsequent to valve incompetence. These leaks may be due to trauma (post-surgical chylothorax, the most frequent) or to spontaneous rupture of a lymph vessel distended by chyle reflux, the thoracic duct itself being pathological. When the thoracic duct is interrupted (obstruction, agenesis), chylothorax may occur from leakage due to reflux within substitution collateral pathways diverting the flow of chyle into the venoux confluents of the neck. Medical treatment is always attempted first: evacuation of chylothorax by drainage and fat-free diet or parenteral nutrition. Recently, treatment with octreotide has been found to be beneficial. Surgery consists in thoracic duct ligation or suture of leaking collaterals. In difficult cases, when the chyle leakage cannot be identified, pleurodesis is the only option.
A triacylglycerol analogue, rac-1,2-di-O-oleoyl-3-S-oleoyl-3-thioglycerol, was fed to rats and chyle acylglycerols were analyzed. Triacylglycerol was the dominating chyle lipid but X-triacyl-1-thioglycerol constituted approx. 6% of total chyle lipids. Its identity was verified by ultraviolet and mass spectra and its stereochemical structure by ORD and CD. The proportions of triacyl-1-thio-sn-glycerol/triacyl-3-thio-sn-glycerol were 63/37 and 78/22 in two experiments. Possible reasons for this stereospecificity are discussed. The study shows that the stereochemical configuration of lipids isolated from biological material can be assessed by ORD and CD.
Ligation of the thoracic duct has previously been recommended for adults with traumatic chylothorax when average daily chyle loss exceeds 1,500 mL/day over five days since such cases are usually refractory to medical management. We describe a case of traumatic chylothorax where chyle output exceeded 2 L/day for a week despite cessation of oral intake and institution of intravenous hyperalimentation. The chylothorax rapidly resolved when mechanical ventilation with positive end-expiratory pressure was begun for treatment of an acute respiratory distress syndrome. The artificial ventilation may have promoted tamponade of the injured lymphatic duct thereby accounting for the abrupt decrease in chyle flow the occurred.
We report the development of chylous ascites in a neonate as an uncommon complication during continuous peritoneal dialysis. Cloudy dialysis fluid containing many white blood cells might confuse the diagnosis of chylous ascites with infective peritonitis and result in inappropriate use of antibiotics. Resolution may be critical, since chyle removal during dialysis may result in profound immunosuppression and malnutrition due to lymphocyte and fat losses. After 4 weeks on a modified diet, the chyle leak resolved. The patient returned to breast milk and continues nighttime continuous-cycle peritoneal dialysis without further chyle leak.
BACKGROUND: Chylothorax complicating pulmonary resection (CCPR) is infrequent and surgical treatment is for the most part avoided. The purpose of this study is to analyze the clinical and therapeutic characteristics of this complication. METHODS: From March 1981 to June 2001, 26 cases of CCPR (24 men and 2 women; mean age 57 years) were treated in two departments of thoracic surgery. Twenty-five cases complicated lung resection for lung cancer (lobectomy n = 14, bilobectomy n = 3, pneumonectomy n = 8) and 1 case followed lobectomy for a benign lesion. Medical history, location, and characteristics of the chylothorax, lymphography, and clinical evolution after medical or surgical therapy were studied. RESULTS: Medical history was never predictive of CCPR. Chylothorax was right sided in 18 cases and left sided in 8 cases. The total amount of chyle ranged from 1.9 L to 27.9 L per patient with a mean of 7.9 L (pneumonectomy 12.3 L and lobectomy 6.3 L). In 15 patients (pneumonectomy n = 2 and lobectomy n = 13) mean quantity of daily chyle was 0.3 L. All these patients recovered with conservative therapy except for 2 patients who underwent drainage and talc slurry (n = 1) and video-assisted lysis of adhesions (n = 1). In the remaining 11 patients (pneumonectomy n = 6 and lobectomy n = 5) mean quantity of daily chyle was 1 L. The chylous leak was seen at lymphography (n = 4), during reoperation (n = 2), or at lymphography and reoperation (n = 3). The location was clearly identified at the level of thoracic duct tributaries in all cases. In 4 postlobectomy cases (4 of 7), surgery was not performed because of the therapeutic usefulness of lymphography. Reoperation was necessary in 6 cases (postpneumonectomy n = 5, postlobectomy n = 1) and consisted of duct ligation (n = 2), leak/suture (n = 3), and fibrin glue (n = 1). CONCLUSIONS: CCPR is rare and appears to respond well to medical treatment owing to the fact that the thoracic duct is generally patent as the leak is due to injury of its tributaries. When surgery is considered, lymphography may help to select cases in which conservative medical therapy should be continued. However, in a small number of cases, usually after pneumonectomy, surgery remains mandatory.
Chylothorax is defined as an accumulation of chyle in the pleural space caused by disruption of the thoracic duct or one of its major divisions. Chyle has a high content of triglycerides. The odorless fluid is turbid and milky due to the presence of fat containing particles, the chylomicrons. The etiology of chylothorax can be divided into four major categories: tumor, trauma, idiopathic and miscellaneous. Although chylothorax is uncommon, it is a serious and potentially hazardous disorder. Loss of chyle leads to metabolic disturbances, malnutrition and immunodeficiency. Treatment consists of treatment of the underlying disease, conservative treatment (medium chain triglyceride diet, parenteral nutrition) or surgical intervention. Appropriate timing of surgical intervention is essential. Since the ligation of the thoracic duct can be performed during thoracoscopy, this minimal interventional technique is the procedure of choice when conservative treatment fails.