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Lymphoedema 1: components and function of the lymphatic system.

Lymphoedema is an incurable and debilitating condition which has a negative impact on the quality of life of the sufferer and his/her family. Information with regards to diagnosis and treatment is often scarce and conflicting in nature. The following series of articles should enable nurses to recognize the condition, provide basic information to a patient and instigate treatment though referral. The first article describes the anatomy, physiology and functions of the lymphatic system. The focus is on the parts of the lymphatic system which are specific to the condition of lymphoedema and aims to place subsequent articles in context. The following articles describe the different types of lymphoedema and the four main elements of treatment that are central to the management of the condition.

Humans↗

Intraoperative radiotherapy for the abdominal lymphatic system in patients with esophageal carcinoma.

We applied intraoperative radiotherapy (IORT) to the esophageal carcinoma in an attempt to prevent abdominal lymph node recurrence, and retrospectively studied patterns of failure and controllability of abdominal lymph nodes in patients treated with or without IORT. Between July 1986 and October 1997, 81 patients with radically resected esophageal carcinoma, aged 42-76 years (mean 61), were divided into two groups, the IORT group (39 patients) and the non-IORT group (42 patients). All patients except two, who received transhiatal esophagectomy for superficial carcinoma, underwent subtotal esophagectomy with thoracic and abdominal with/without cervical lymphadenectomy. Fourteen patients underwent only surgical resection, and the remaining 67 patients received radiotherapy to the mediastinum post-operatively (40-50 Gy/20-25 Fr/4-5 W) in 37 and preoperatively (44 Gy/40 Fr/4 W) in 30 patients. Preoperative irradiation was performed as a neoadjuvant chemoradiotherapy consisting of two courses of cisplatin (each patient received 80-100 mg, mean 60 mg m(-2), day 1, bolus injection) and 5-fluorouracil (each patient received 500-1000 mg day(-1), mean 400 mg m(-2), days 1-4, continuous infusion). The target volume of IORT encompassed the upper abdominal lymph node area including lymph node groups of right/left cardia, left gastric artery, celiac artery and abdominal para-aorta. A single dose of high-energy electrons (9-12 MeV) of 20-23 Gy, prescribed to the 90% isodose curve, was delivered. Treatment for the abdominal lymphatic system was classified into four categories: surgery alone in 30 patients, surgery with chemotherapy in 12, surgery with IORT in 15, surgery with chemotherapy and IORT in 24. There were no complications related to IORT. Forty patients (49%) had recurring carcinoma: in the lymph nodes (36%), in distant organs (27%) and locally (6%). The incidence of lymph node metastasis was 29% in the neck, 32% in the mediastinum, and 27% in the abdomen. Abdominal lymph node recurrence in the IORT group was less frequent than in the non-IORT group (p=0.048). In particular, 24 patients treated with a combination of surgery, chemotherapy and IORT had no recurrence in the abdominal lymphatic system. The overall median survival was 46 months, the survival at 1, 3, and 5 years being 85%, 52%, and 44% respectively. However, there was no difference in survival between the IORT group and the non-IORT group. The IORT for the abdominal lymphatic system was feasible for reduction of the rate of abdominal lymphatic recurrence without survival benefit in this study. This retrospective finding should be confirmed by a prospective randomized study.

Adult↗

Congenital malformations of the cervicothoracic lymphatic system: embryology and pathogenesis.

Familiarity with the embryology of the lymphatic system is helpful in understanding the pathogenesis and radiologic appearance of lymphangiomas of the cervicothoracic region. By considering anatomic location and radiologic appearance, one can predict the type of lymphangioma present, the primordial lymph sac from which the malformation arose, and when it formed in embryonic life. Cystic hygromas are composed of large, dilated lymphatic spaces. They form when a primordial lymph sac fails to reestablish communication with the central venous system from which it arose. These lesions may also result from an aberrant bud arising from a primordial lymph sac. Cavernous and capillary lymphangiomas are composed of smaller lymphatic channels. They form from abnormally sequestered buds of the developing lymphatic mesenchyme responsible for the fine meshwork of terminal branches in the periphery of the embryo. Their growth may be inhibited by the relatively tougher tissues in the periphery (eg, skin and muscle) compared with the relatively loose fatty connective tissue in which cystic hygromas form. Not only can all types of lymphangioma occur in one lesion, but lymphatic and vascular malformations may also coexist.

Humans↗

Lymphatic system of the rat pancreas.

Light and electron microscopy combined with morphometric analysis were used to investigate the distribution, extent and structure of lymphatic vessels in the head, body and tail of the rat pancreas. Serial sections 3-4 microns in thickness were cut from tissue fixed by perfusion. Alternate sections were processed for light microscopy. Intervening sections were left uncovered to be re-embedded and sectioned for electron microscopy as needed. Vessels with valves were tentatively identified as lymphatics using the light microscope, with final identification being made on adjacent sections by electron microscopy. The ultrastructure of the pancreatic lymphatic vessels was typical of lymphatics generally. Interlobular lymphatic vessels were present throughout the pancreas and were found to be associated primarily with blood vessels lying in connective tissue septa. Intralobular lymphatics were also seen but were comparatively rare. Only about 19% of the wall of the lymphatic system of the pancreas was in close relationship to acinar cells--none was closely related to the endocrine islets. The mean volume density of the system was 0.0012 microns3/microns3 and the profile density of lymphatics was 3.24/mm2. Special attention was paid to the areas of contact between adjacent endothelial cells. Open gaps of more than 30 nm in width were rare. Dilatations and associated cytoplasmic processes, suggestive of a type of intercellular transport, were seen in addition to the intracellular cytoplasmic vesicular system. The findings are consistent with the view that the lymphatic system of the pancreas does not have a specific role in the transport of pancreatic secretions other than the removal of macromolecules that may escape to the interstitium in small amounts under normal circumstances. The fine structure of the endothelial wall suggests that the mechanism of lymph formation in the pancreas is more comparable to that in other encapsulated organs such as the kidney and liver than to that in the dermis or diaphragm where fluid appears to enter lymphatics primarily by way of gaps between adjacent cells.

Animals↗

Microscopic and ultrastructural study of the lymphatic system in the human parotid gland.

The localization and fine structure of the lymphatic system vessels are examined in the human parotid gland. A network of lymphatic capillaries extends in the intralobular connective septa around the striated ducts. These lymphatics converge in collectors frequently bordering the excretory ducts. On the contrary, no lymphatics are present next to the intercalated ducts and adhenomers. Ultrastructurally, the lymphatic capillaries are characterized by a very thin endothelial wall and by slightly complicated intercellular adhesions. Open junctions are also present. The presence of numerous lymphatic capillaries bordering the striated ducts and their blood microvasculature is discussed in relation to the functional activities of the striated ducts in the modification of the saliva.

Humans↗

Morphology of the intrarenal lymphatic system. Capsular and hilar communications.

Recent functional evidence has indicated that ureteric obstruction for three or more days in dogs causes a diversion of renal lymph from the hilar to the capsular system. The present study was concerned with the structural correlate of this functional evidence, having special reference to communications between the two systems. Within three days of ureteric occlusion the capsular lymphatic system became dilated. On histological examination two types of tributaries were found. One (termed a perforating lymphatic) served as a primary pathway for superficial cortical lymph from the subcapsular plexus, and penetrated the capsule either alone or in company with a small vein. The other (termed a communicating lymphatic) was closely associated with the occasional penetrating interlobular blood vessel which traversed the capsule to ramify in the perirenal tissue. Approximately 60% of the penetrating arteries in eight dog kidneys had associated communicating lymphatics. On the renal surface the perforating and communicating lymphatics formed the primary collecting vessels of the capsular system. Within the renal substance the communicating lymphatics were directly continuous with lymphatics which surrounded the interlobular blood vessels and which have been shown to drain into the hilar network. Thus the communicating lymphatics formed direct connections between the hilar and capsular systems. It was concluded that these communications, although dilated by hydronephrosis, existed under control conditions. Functionally they are probably of importance only under special circumstances when intrarenal lymph may be diverted from one to the other system.

Animals↗

The endolymphatic sac receives antigenetic information from the organs of the mucosa-associated lymphatic system.

The endolymphatic sac holds the entire arrangement of immunocompetent cells and functions as an immunological potent control organ for the inner ear. The evidence of secretory immunoglobulin A and other features of lymphocyte subtypes characterizes the endolymphatic sac as an organ of the mucosa-associated lymphatic system (MALT). In this system a permanent recirculation of sensitized memory lymphocytes from one organ to the other has been demonstrated experimentally as serving to dispose memory lymphocytes after renewed antigenetic stimulus. The aim of this study was to prove the possible recirculation of antigen-sensitized lymphocytes to the endolymphatic sac after antigenic stimulus of another part of the mucosa-associated lymphatic system. The results are evidence that the endolymphatic sac is provided with immunocompetent cells which derive from the lymphatic tissue of the nasopharynx. While the origin of immunocompetent cells in the endolymphatic sac still remains uncertain, this study underlines the role of lympho-epithelial tissue of the nasopharynx as a possible cell source for the endolymphatic sac. The results might explain the altered or disturbed function of the endolymphatic sac as a possible cause of certain inner ear diseases.

Animals↗

Lymphatic system or hydro-oncotic forces. Which is more significant in drainage of pleural fluid?

Artificial pleural fluids, containing plasma protein from 0.1 to 9.0 g per 100 ml, indocyanine green (ICG) and para-aminohippurate (PAH), were injected into the pleural cavity of dogs. The concentration of these two indicators were measured at a regular time interval, and the lymphatic and non-lymphatic flows and PAH clearance were calculated by Stewart's and Takashina's equations. When the protein concentration in the pleural fluid was less than 4 g per 100 ml, the pleural fluid volume decreased at a rate of 0.20 ml/kg/hour. The decrease was due to pleural fluid drainage by the lymphatic flow, because the inward and outward non-lymphatic flows due to hydro-oncotic forces balanced each other and the net non-lymphatic flow was essentially zero. When the protein concentration was 6 g per 100 ml or more, the decrease of pleural fluid was remarkably attenuated, because of an increase of the inward non-lymphatic flow due to an increase of protein concentration in the pleural fluid. Even in these situations, the lymphatic flow was kept at the rate of 0.20 ml/kg/hour, similarly with the former conditions. From these results, it may be concluded that the lymphatic system is a principal factor, and that factors governed by hydro-oncotic elements have additive effect to that of the lymphatic system in the regulation of pleural fluid dynamics.

Animals↗

[Effect of hematopoietic stem cell transplantation in malignant hematologic disease of lymphatic system].

The study was aimed to investigate the effect of hematopoietic stem cells transplantation (HSCT) in treatment for hematologic malignancies of lymphatic system. Through observing 8 patients with non-Hodgkin's lymphoma (NHL) and 3 patients with lymphoblastic leukemia, who received auto or allo-HSCT after chemotherapy, the hematopoietic reconstitution, complication and survival time were evaluated. The results showed that 11 patients (7 patients after auto-PBSCT, 4 patients after allo-PBSCT) all achieved hematopoietic reconstitution and complete remission (CR). Within three years following-up, 5 patients with NHL were survival, but one case of NHL died at the 2 months after auto-PBSCT, one patient suicided. From 4 cases received allo-PBSCT, one patient with NHL (NK cell) was died at 79 days later, one patient with chronic lymphoblastic leukemia was surviving, another 2 cases of acute lymphoblastic leukemia were dead at 17 months and 54 days respectively after allo-PBSCT. In conclusion HSCT is an effective treatment for hematologic malignancies of lymphatic system, but the replase would occur in some patients received auto-PBSCT. The others by allo-PBSCT might die of severe complication of transplantation.

Adolescent↗

Lymphatic system of mice born from mothers treated with ampicillin or cloxacillin during gestation.

Ampicillin, an antibiotic, widely used for combating bacterial infections exerts great influence on cells of the immune system of mouse and man. We have studied the effect of ampicillin and cloxacillin treatment of mice in the final week of pregnancy on the development of the lymphatic system of their offsprings. The mice born from antibiotic or saline treated mothers were examined 30 days after delivery. The examination of relative organ weight, cellularity and histopathological picture of lymphatic system (thymus, spleen and lymph nodes) and some other organs was performed. In the group of mice from ampicillin treated mothers we have found decreased relative weight of thymus and spleen and increased weight of lymph nodes with increased cellularity in thymus and lymph nodes. In the group of mice from cloxacillin treated mothers increased cellularity of thymus and lymph nodes was found. The histopathological study of lymphatic organs structure did not reveal any specific changes but the symptoms of focal degeneration and fat necrosis were found in livers of mice born from ampicillin treated mothers. Moreover, in mice born from antibiotic treated mothers the significant lymphocytosis in the peripheral blood was assessed. It was accompanied by an increase of granulocyte number in offsprings from ampicillin treated mothers and increase of monocyte number in those of cloxacillin treated. In conclusion, it could be suggested that ampicillin treatment during pregnancy would exert some effect on the development of lymphopoietic system of fetuses.

Ampicillin↗

A study of the topography of the lymphatic system of the Australian brushtail possum (Trichosurus vulpecula).

The superficial and deep lymphatic systems of the Australian brushtail possum (Trichosurus vulpecula) are described. In common with other marsupials studied to date and in contrast with most eutherians, there were no popliteal lymph nodes and efferent drainage from the inguinal lymph centre passed directly to the deep axillary group of lymph nodes via an inguinoaxillary trunk. Efferent vessels from the tonsil passed directly to the deep cervical lymph node, which was drained by the tracheal trunk. The mandibular and parotid lymph nodes drained independently to the superficial cervical lymph node. All subcutaneous lymph drainage passed either through the superficial cervical or the axillary lymph centres before entering the venous system, an arrangement which is also found in kangaroos. The significance of the patterns of lesion distributions in possums with naturally occurring tuberculosis caused by Mycobacterium bovis is discussed.

Abdomen↗

The role of the lymphatic system in drainage of cerebrospinal fluid and aqueous humour.

1. The jugular lymphatic trunks were cannulated in anaesthetized rabbits and cats. Over 6-8 hr, the mean lymph flow was 2.3 microliters min-1 in the rabbit (one side only) and 5.0 microliters min-1 in the cat (sum of both sides). 2. After a single injection of radio-iodinated albumin into a lateral cerebral ventricle without significant rise in pressure, a mean of 14.4% of the radioactivity was recovered in deep cervical lymph of one side in the rabbit and of 12.9% in that of both sides in the cat. 3. During slow infusion of [125I]albumin and fluorescent dextran of 150,000 mol. wt. into a lateral ventricle of the cat at 20 microliters min-1, radioactivity and fluorescence reached plateaus in deep cervical lymph at 47.4 and 50.0% of their concentrations in cisternal c.s.f. respectively. 4. No significant radioactivity, other than from blood, was detected in superficial cervical lymph after intraventricular injection of radio-iodinated albumin in the cat. 5. No significant radioactivity, other than from blood, was detected in deep cervical lymph of the rabbit or in deep and superficial cervical lymph of the cat within 6 hr after injection of radio-iodinated albumin into the aqueous humour or orbital fat. 6. Gradients of radioactivity in tissues within the orbit suggested that there is a small flow of c.s.f., 0.05-0.15 microliters min-1 in the rabbit, passing centrifugally along the subarachnoid space of the optic nerve, through the posterior part of the globe and into the orbital tissue. Also a small proportion of aqueous humour, 1-2% or more, drains through the anterior sclera into the surrounding tissue. 7. A substantial quantity of cerebrospinal fluid drains into the deep cervical lymphatic system of the rabbit, 30% or more, and of the cat, 10-15% or more. The small component of aqueous humour drainage passing through the wall of the glove does not enter cervical lymph within 6 hr, if at all.

Animals↗

[The lymphatic system and its functioning in sheep].

Cannulation of the afferent and efferent lymph ducts of a lymph node in large domestic species have greatly facilitated the study of the immune system functions in mammals, both in physiological conditions and during immune responses to various pathogens. Summarizing the numerous studies undertaken in the ovine species, this review first presents a description of the structure and composition of the lymph nodes, vessels as well as the lymph fluid they transport. The functioning and the role of each of these immune compartments are also discussed. The characteristics and mechanisms of lymphocyte recirculation between the blood and the lymphatic system are treated in an other chapter. The last part is dedicated to analyzing the modifications observed in the ovine lymphatic system after antigenic stimulation.

Animals↗

Drug delivery to the lymphatic system.

The specialized structure and function of the lymphatics has stimulated considerable interest in both site-specific drug delivery to the lymph and lymphoid tissue, and delivery to the systemic circulation via lymphatic transport mechanisms. In this review, drug access to the lymphatic system from the vasculature or interstitium after parenteral administration, and from the gastrointestinal tract after enteral administration, is discussed. Macromolecular and lipophilic prodrug approaches to lymphatic delivery and the use of microparticulate systems such as microspheres, liposomes, and colloidal carbon are also examined and discussed.

Animals↗

CLS 2210, hyaluronidase and the cardiac lymphatic system.

Earlier studies have shown that hyaluronidase exerts a potent influence upon the lymphatic system of the myocardium and that it reduces the size of myocardial infarcts after coronary occlusion. In this study we compared, in mongrel dogs, the effect of intravenous hyaluronidase or CLS 2210 upon the cardiac lymphatic vessels. We observed that in CLS 2210-treated animals the number of visualized cardiac lymphatic vessels was significantly higher than in the hyaluronidase-treated control group. We have previously demonstrated a cardioprotective effect of hyaluronidase in the treatment of acute myocardial infarction. The present experimental data indicate that intravenous CLS 2210 may have a definite role in the management of acute coronary occlusion. Further studies are needed to confirm these preliminary findings.

Animals↗

[Effect of vibration on the functioning of the lymphatic system in the small intestine in rat].

The production rate and flow of the lymph in mesenteric lymph vessels under normal conditions and after horizontal vibration of 5 Hz frequency and 20 mm amplitude were measured by means of intravital, intravenous injection of trypan blue water solution. The investigations were carried out on 66 Wistar rats of both sexes. It was found, that 3 and 7-hour vibration and everyday 7-hour vibration applied during a week result in the acceleration of lymph flow, whereas 3- and 4-week vibrations result in reduction of production and flow of the lymph. In all cases the lymph flow speed becomes normal after one day break. The results obtained show that low frequency vibration causes reversible functional changes in small intestine lymphatic system. These changes more probably result from hemodynamic disturbances. The applied vibration parameters did not cause any perceptible morphological changes in the lymphatic system.

Animals↗

Peripheral vascular and lymphatic systems.

This article discusses normal anatomy and physiology of the peripheral vascular and lymphatic systems. Physical examination techniques are described and monitoring principles are illustrated by a case study.

Blood Pressure↗