Thoracic Duct: Conditions Affecting function
Waldemar L. Olszewski in Lymph Stasis: Pathophysiology, Diagnosis and Treatment, 2019
Lymph vessels arise from veins, and in mammals the thoracic duct and azygos vein develop from a common primordial structure, the embryological system of supracardinal veins. Actual or potential communications between intrathoracic lymph vessels and veins persist and begin to function as shunts when flow in the thoracic duct becomes impaired. Thus when thoracic duct lymph is formed at an approximately normal rate in adults of 0.8 ml/min, simple ligation of the thoracic duct does not result in clinically significant sequelae. Under these circumstances the thoracic duct lymph is diverted into the venous system via channels which communicate with the right lymph duct and by the aforementioned lymphatic-venous shunts. The transport function of the thoracic duct fails at a normal rate of lymph production when flow in these collateral channels is impaired together with flow in the duct itself.
Internal Fistulas in the Rat
Waldemar L. Olszewski in CRC Handbook of Microsurgery, 2019
The animal receives 1 mℓ of Intra-lipid® (Vitrum, Stockholm) orally by means of a gastric tube 1 hr before the operation. After opening the abdomen by a midline incision a right nephrectomy is carried out. Using microsurgical instruments, the cannulation sites are carefully dissected under a Zeiss® OP-MI 6 operation microscope with a magnification of approximately 4 ×. Silastic® tubing (Dow Corning, internal diameter 0.30 mm, external diameter 0.64 mm) filled with heparin in saline (50 U/mℓ) is inserted first into the ureter and fixed with 8/0 nylon. The ureter is flushed with heparin/saline solution via the cannula until the bladder is filled. This is to prevent clotting in the early stage of the cannulation procedure. In the ensuing period a regular flow prevents clotting of the chyli. The mesenteric lymph duct is tied close to its outflow point into the thoracic duct with 8/0 nylon. Because the mesenteric lymph duct is very intimately connected to the mesenteric artery it is of great help to use atraumatic suture material (8/0 nylon connected to a BV 2 needle, Ethicon, Germany). Using this, it is not necessary to separate both structures; with a small needle it is rather easy to slip through the layer of connective tissue between the duct and the artery. A cut is made distally from this ligature. The cannula is inserted and fixed with the same suture material. Uniformly, immediately after cannulation, the milky fluid is seen entering the cannula. The intestines are brought back into the abdomen and the wound is closed. To help recover from anesthesia the animals are put for some time under an IR lamp.
Interstitium and Lymphatics
John H. Barker, Gary L. Anderson, Michael D. Menger in Clinically Applied Microcirculation Research, 2019
The main sites where lymph is returned to the blood are the unions of the thoracic duct, and of the right lymph duct, with the great veins in the neck. However, there are many other places where such communications exist. It is not certain to what extent they are normally patent, although it is well known that much more lymph is formed in the periphery than ever reaches the main lymph ducts.33 Such additional communications open when the intralymphatic pressures rise high enough — and thus help to prevent lymphedema.
Enhanced dissolution and bioavailability of revaprazan using self-nanoemulsifying drug delivery system
Published in Pharmaceutical Development and Technology, 2022
Yoon Tae Goo, Cheol-Ki Sa, Min Song Kim, Gi Hyeong Sin, Chang Hyun Kim, Hyeon Kyun Kim, Myung Joo Kang, Sangkil Lee, Young Wook Choi
Oral administration is a preferable route for drug delivery because of its convenience and safety. Orally administrated drugs are dissolved in the gastrointestinal (GI) fluid, transported into epithelial cells, and eventually passed into the bloodstream for systemic circulation. Following uptake by epithelial cells, only a small portion of the absorbed drugs can bind to lipoproteins and enter the lacteal ducts (Liao et al. 2019). Substances absorbed by the lacteal ducts enter the mesenteric lymph duct, pass through the cisterna chyli, and flow upward into the thoracic duct (Hsu and Itkin 2016). Thereafter, lymphatic fluid flows into the bloodstream at the junction of the subclavian vein and the internal jugular vein (Hsu and Itkin 2016). Unlike absorption through intestinal capillaries, lymphatic transport is not connected to the portal vein. Therefore, lymphatic transport improves oral bioavailability (BA) by evading the first-pass effect, thereby enhancing the total systemic BA (Caliph et al. 2000; Sanjula et al. 2009).
Mechanisms of oral absorption improvement for insoluble drugs by the combination of phospholipid complex and SNEDDS
Published in Drug Delivery, 2019
Yingpeng Tong, Qin Zhang, Wen Shi, Jianxin Wang
The intestinal lymphatic transport studies were conducted according to the established methods with some modifications (Chaudhary et al., 2015; Li et al., 2017). SD rats (male, 280–320 g) were fasted for 12 h with free access to water. 30 min before the experiment, each rat was fed with 1 mL of sesame oil to facilitate viewing of the mesenteric lymph duct due to its milky-white in appearance and adhesion to the mesenteric artery. At the beginning of the experiments, the rats were anesthetized by intraperitoneal injection of 200 mg kg−1 sodium pentobarbital, then shaved and disinfected on the right side of their necks and flanks. The jugular vein in the right neck was isolated and used to collect blood sample by cannulating with PE10 tubing. Then, the mesenteric lymph duct and duodenum in the right abdomen were exposed and cannulated with PE10 and PE50 tubing, respectively. The mesenteric lymph duct was fixed with instant cyanoacrylate adhesive. The PE50 tube inserted into the duodenum was adopted for administration and saline infusion. The body temperature of the rats was maintained by a heating pad set at 37 °C.
Targeting the intestinal lymphatic system: a versatile path for enhanced oral bioavailability of drugs
Published in Expert Opinion on Drug Delivery, 2018
Renuka Suresh Managuli, Sushil Yadaorao Raut, Meka Sreenivasa Reddy, Srinivas Mutalik
Intestinal lymphatic system (ILS) plays a major role in regulating tissue fluid homeostasis and transports fat and fatty acids and other nutrients from the intestine to blood [7]. ILS has been considered as an alternative pathway for increasing the bioavailability of such drugs which undergo extensive first pass metabolism. Most of the drugs are transported almost exclusively by the portal circulation as the blood flow rate in the portal vein is about 500 times greater than that of lymph flow in the intestine [8,9]. Therefore, unless selective uptake occurs in lymphatics, most of the drugs get metabolized before reaching to systemic circulation. For selective uptake by lymphatics, a compound has to be lipophilic with high partition coefficient and solubility in a triglyceride lipid [10,11]. A majority of the orally administered drugs get absorbed into the portal vein through the intestinal enterocytes and after metabolized in the liver, enter the systemic circulation. The metabolism of drug in liver before reaching to systemic circulation decreases the oral bioavailability of drug. However, when the drugs are highly lipophilic or are formulated into nano structures such as lipid/polymeric nanoparticles, they get access into ILS via lacteal and Peyer’s patches. Lymph from the small intestine that originates at lacteals and from Peyer’s patches flows via a network of lymphatic microvessels into a collecting (afferent) lymphatic vessel that transports lymph into mesenteric lymph nodes. Within the nodes, lymph passes through a series of medullary sinuses where exchange occurs with node resident immune cells as well as material entering the node from the blood. The post-nodal (efferent) lymph vessels thereafter drain lymph into the efferent superior mesenteric lymph duct and subsequently the cisterna chyli. The cisterna chyli is a lymph collecting reservoir that receives lymph from the caudal peripheral tissues, intestinal, hepatic and lumbar regions and is continued into the thoracic lymph duct (major lymphatic vessel). Thoracic lymph duct also collects lymph from the mediastinum and cranial parts of the body and empties lymph directly into the venous system at the junction of the left internal jugular and left subclavian veins [8,12]. This unique physiology potentially enables orally administered drugs to bypass the liver and thus avoids first pass metabolism of drugs and enhances the bioavailability. To understand the ILS in a better way, it is mandatory to know the structure of small intestine.