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Physiology of Lymph Vessels: Structure, Function, Modelling, and Clinical Perspectives
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Physiology of Lymph Vessels: Structure, Function, Modelling, and Clinical Perspectives

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Physiology".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 11725

Special Issue Editor

Dr. Andrea Moriondo

E-Mail Website
Guest Editor
Department of Medicine and Technological Innovation (DIMIT), Università degli Studi dell’Insubria, 21100 Varese, Italy
Interests: lymphatic vessels physiology; lymph flow; lymph drainage; mechanisms of intrinsic lymphatic muscle contraction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lymphatic vessels provide a unique circulatory system offering interstitial and serosal liquids a drainage route back into the blood stream. This task is particularly difficult as the vessels face a net pressure gradient acting against the intended direction of lymph from the periphery to the blood venous district. Furthermore, the hydraulic pressure of the tissue can be subatmosferic. Therefore, lymphatic vessels exploit two different pumping mechanisms, which rely on external compression and/or distention forces exerted by the surrounding tissues, or by intrinsic, spontaneous contractile activity of the lymphatic musculature of the wall comprising lymphatic vessels. Parietal and intraluminal lymphatic valves cooperate with these two pumping mechanisms to attain lymph drainage and transport. Since the first discovery of lacteals in 1622 by Aselli, later published in 1627 after his death, the knowledge of lymphatic vessels’ physiology has lagged behind the wealth of data regarding blood circulation, despite lymphatics being a prominent actor in maintaining the fluid volume homeostasis in tissues and serosal cavities. This Special Issue will highlight the most relevant and latest findings on lymphatic physiology, anatomy and histology, as well as on new, with a particular focus on eventual new data coming from basic research and comparative research among different species.

Dr. Andrea Moriondo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • lymphatic vessel
  • oedema
  • lymphatic muscle
  • spontaneous contractions
  • functional imaging
  • translational medicine
  • intrinsic pumping
  • extrinsic pumping
  • fluid homeostasis
  • numerical modelling

Published Papers (6 papers)

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Research

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26 pages, 17844 KiB  
Article
Fluid Osmolarity Modulates the Rate of Spontaneous Contraction of Lymphatic Vessels and Lymph Flow by Means of a Cooperation between TRPV and VRAC Channels
by Eleonora Solari, Cristiana Marcozzi, Daniela Negrini and Andrea Moriondo
Biology 2023, 12(7), 1039; https://doi.org/10.3390/biology12071039 - 23 Jul 2023
Cited by 1 | Viewed by 1073
Abstract
Lymphatic vessels are capable of sustaining lymph formation and propulsion via an intrinsic mechanism based on the spontaneous contraction of the lymphatic muscle in the wall of lymphatic collectors. Exposure to a hyper- or hypo-osmolar environment can deeply affect the intrinsic contraction rate [...] Read more.
Lymphatic vessels are capable of sustaining lymph formation and propulsion via an intrinsic mechanism based on the spontaneous contraction of the lymphatic muscle in the wall of lymphatic collectors. Exposure to a hyper- or hypo-osmolar environment can deeply affect the intrinsic contraction rate and therefore alter lymph flow. In this work, we aimed at defining the putative receptors underlying such a response. Functional experiments were conducted in ex vivo rat diaphragmatic specimens containing spontaneously contracting lymphatic vessels that were exposed to either hyper- or hypo-osmolar solutions. Lymphatics were challenged with blockers to TRPV4, TRPV1, and VRAC channels, known to respond to changes in osmolarity and/or cell swelling and expressed by lymphatic vessels. Results show that the normal response to a hyperosmolar environment is a steady decrease in the contraction rate and lymph flow and can be prevented by blocking TRPV1 channels with capsazepine. The response to a hyposmolar environment consists of an early phase of an increase in the contraction rate, followed by a decrease. The early phase is abolished by blocking VRACs with DCPIB, while blocking TRPV4 mainly resulted in a delay of the early response. Overall, our data suggest that the cooperation of the three channels can shape the response of lymphatic vessels in terms of contraction frequency and lymph flow, with a prominent role of TRPV1 and VRACs. Full article
(This article belongs to the Special Issue Physiology of Lymph Vessels: Structure, Function, Modelling, and Clinical Perspectives)
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27 pages, 9853 KiB  
Article
Solute Transport across the Lymphatic Vasculature in a Soft Skin Tissue
by Dingding Han, Ziyang Huang, Ehsan Rahimi and Arezoo M. Ardekani
Biology 2023, 12(7), 942; https://doi.org/10.3390/biology12070942 - 30 Jun 2023
Cited by 1 | Viewed by 1503
Abstract
Convective transport of drug solutes in biological tissues is regulated by the interstitial fluid pressure, which plays a crucial role in drug absorption into the lymphatic system through the subcutaneous (SC) injection. In this paper, an approximate continuum poroelasticity model is developed to [...] Read more.
Convective transport of drug solutes in biological tissues is regulated by the interstitial fluid pressure, which plays a crucial role in drug absorption into the lymphatic system through the subcutaneous (SC) injection. In this paper, an approximate continuum poroelasticity model is developed to simulate the pressure evolution in the soft porous tissue during an SC injection. This poroelastic model mimics the deformation of the tissue by introducing the time variation of the interstitial fluid pressure. The advantage of this method lies in its computational time efficiency and simplicity, and it can accurately model the relaxation of pressure. The interstitial fluid pressure obtained using the proposed model is validated against both the analytical and the numerical solution of the poroelastic tissue model. The decreasing elasticity elongates the relaxation time of pressure, and the sensitivity of pressure relaxation to elasticity decreases with the hydraulic permeability, while the increasing porosity and permeability due to deformation alleviate the high pressure. An improved Kedem–Katchalsky model is developed to study solute transport across the lymphatic vessel network, including convection and diffusion in the multi-layered poroelastic tissue with a hybrid discrete-continuum vessel network embedded inside. At last, the effect of different structures of the lymphatic vessel network, such as fractal trees and Voronoi structure, on the lymphatic uptake is investigated. In this paper, we provide a novel and time-efficient computational model for solute transport across the lymphatic vasculature connecting the microscopic properties of the lymphatic vessel membrane to the macroscopic drug absorption. Full article
(This article belongs to the Special Issue Physiology of Lymph Vessels: Structure, Function, Modelling, and Clinical Perspectives)
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11 pages, 1112 KiB  
Article
Adjustable Compression Wraps (ACW) vs. Compression Bandaging (CB) in the Acute Phase of Breast Cancer-Related Arm Lymphedema Management—A Prospective Randomized Study
by Katarzyna Ochalek, Joanna Kurpiewska and Tomasz Gradalski
Biology 2023, 12(4), 534; https://doi.org/10.3390/biology12040534 - 31 Mar 2023
Viewed by 2251
Abstract
The objective of this study is to compare the effectiveness, comfort and possibilities of the self-application of adjustable compression wraps (ACW) with compression bandaging (CB) in the acute phase of treatment in advanced upper-limb lymphedema. In total, 36 patients who fulfilled the admission [...] Read more.
The objective of this study is to compare the effectiveness, comfort and possibilities of the self-application of adjustable compression wraps (ACW) with compression bandaging (CB) in the acute phase of treatment in advanced upper-limb lymphedema. In total, 36 patients who fulfilled the admission criteria were randomly assigned into ACW-Group (18 patients), or CB-Group (18 patients). Treatment in both groups lasted for two weeks. In the first, all patients were educated in applying adjustable compression wraps (ACW-Group) or self-bandaging (CB-Group) and treated by experienced physiotherapists. In the second week, the use of ACW and CB was continued by the patients themselves at home. In both groups, a clinically significant reduction in the affected limb volume was found after the first week (p < 0.001). A further decrease in the affected limb volume within the second week was noted only in the CB-Group (p = 0.02). A parallel trend was found in the percentage reduction in the excess volume after one and two weeks of compression therapy. Within two weeks, both groups achieved a significant improvement in decreasing lymphedema-related symptoms, but women from the ACW-Group reported complications related to carrying out compression more frequently (p = 0.002). ACW can reduce lymphedema and disease-related symptoms, but based on the results it is difficult to recommend this method as an alternative option in the acute phase of CPT among women with advanced arm lymphedema. Full article
(This article belongs to the Special Issue Physiology of Lymph Vessels: Structure, Function, Modelling, and Clinical Perspectives)
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20 pages, 4237 KiB  
Article
An Enhanced 3D Model of Intravascular Lymphatic Valves to Assess Leaflet Apposition and Transvalvular Differences in Wall Distensibility
by Christopher D. Bertram and Michael J. Davis
Biology 2023, 12(3), 379; https://doi.org/10.3390/biology12030379 - 27 Feb 2023
Cited by 2 | Viewed by 1139
Abstract
Lymphatic valves operate in a fluid-dynamically viscous environment that has little in common with that of cardiac valves, and accordingly have a different, axially lengthened, shape. A previously developed 3D fluid/structure interaction model of a lymphatic valve was extended to allow the simulation [...] Read more.
Lymphatic valves operate in a fluid-dynamically viscous environment that has little in common with that of cardiac valves, and accordingly have a different, axially lengthened, shape. A previously developed 3D fluid/structure interaction model of a lymphatic valve was extended to allow the simulation of stages of valve closure after the leaflets come together. This required that the numerical leaflet be prevented from passing into space occupied by the similar other leaflet. The resulting large deflections of the leaflet and lesser deflections of the rest of the valve were mapped as functions of the transvalvular pressure. In a second new development, the model was reconstructed to allow the vessel wall to have different material properties on either side of where the valve leaflet inserts into the wall. As part of this, a new pre-processing scheme was devised which allows easier construction of models with modified valve dimensions, and techniques for successfully interfacing the CAD software to the FE software are described. A two-fold change in wall properties either side of the leaflet made relatively little difference to valve operation apart from affecting the degree of sinus distension during valve closure. However, the numerically permitted strains were modest (<14%), and did not allow examination of the large-scale highly nonlinear elastic properties exhibited by real lymphatic vessels. A small series of murine popliteal, mesenteric, and inguinal-axillary lymphatic vessel segments containing a valve were experimentally investigated ex vivo. The pressure–diameter curves measured just upstream and just downstream of the valve were parameterised by computing the difference in tubular distensibility at three values of transmural pressure. In the popliteal and mesenteric segments, it was found that the distensibility was usually greater just downstream, i.e., in the sinus region, than upstream, at low and intermediate transmural pressure. However, there was wide variation in the extent of difference, and possible reasons for this are discussed. Full article
(This article belongs to the Special Issue Physiology of Lymph Vessels: Structure, Function, Modelling, and Clinical Perspectives)
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Review

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18 pages, 5137 KiB  
Review
Secondary Lymphedema: Clinical Interdisciplinary Tricks to Overcome an Intriguing Disease
by Sylvain Mukenge, Daniela Negrini and Ottavio Alfieri
Biology 2023, 12(5), 646; https://doi.org/10.3390/biology12050646 - 24 Apr 2023
Cited by 2 | Viewed by 3673
Abstract
Secondary lymphedema is a complex pathology which is very impairing to the patient, consisting of fluid accumulation in the tissue, accompanied by alteration of the interstitial fibrous tissue matrix, deposition of cellular debris and local inflammation. It develops mostly in limbs and/or external [...] Read more.
Secondary lymphedema is a complex pathology which is very impairing to the patient, consisting of fluid accumulation in the tissue, accompanied by alteration of the interstitial fibrous tissue matrix, deposition of cellular debris and local inflammation. It develops mostly in limbs and/or external genitals because of demolishing oncological surgery with excision of local lymph nodes, or it may depend upon inflammatory or infective diseases, trauma, or congenital vascular malformation. Its treatment foresees various approaches, from simple postural attitude to physical therapy, to minimally invasive lymphatic microsurgery. This review focuses on the different types of evolving peripheral lymphedema and describes potential solutions to single objective symptoms. Particular attention is paid to the newest lymphatic microsurgical approaches, such as lymphatic grafting and lympho-venous shunt application, to successfully heal, in the long term, serious cases of secondary lymphedema of limbs or external genitals. The presented data also emphasize the potential role of minimally invasive microsurgery in enhancing the development of newly formed lymphatic meshes, focusing on the need for further accurate research in the development of microsurgical approaches to the lymphatic vascular system. Full article
(This article belongs to the Special Issue Physiology of Lymph Vessels: Structure, Function, Modelling, and Clinical Perspectives)
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15 pages, 3841 KiB  
Review
Morphological, Mechanical and Hydrodynamic Aspects of Diaphragmatic Lymphatics
by Daniela Negrini
Biology 2022, 11(12), 1803; https://doi.org/10.3390/biology11121803 - 12 Dec 2022
Cited by 4 | Viewed by 1325
Abstract
The diaphragmatic lymphatic vascular network has unique anatomical characteristics. Studying the morphology and distribution of the lymphatic network in the mouse diaphragm by fluorescence-immunohistochemistry using LYVE-1 (a lymphatic endothelial marker) revealed LYVE1+ structures on both sides of the diaphragm—both in its the [...] Read more.
The diaphragmatic lymphatic vascular network has unique anatomical characteristics. Studying the morphology and distribution of the lymphatic network in the mouse diaphragm by fluorescence-immunohistochemistry using LYVE-1 (a lymphatic endothelial marker) revealed LYVE1+ structures on both sides of the diaphragm—both in its the muscular and tendinous portion, but with different vessel density and configurations. On the pleural side, most LYVE1+ configurations are vessel-like with scanty stomata, while the peritoneal side is characterized by abundant LYVE1+ flattened lacy-ladder shaped structures with several stomata-like pores, particularly in the muscular portion. Such a complex, three-dimensional organization is enriched, at the peripheral rim of the muscular diaphragm, with spontaneously contracting lymphatic vessel segments able to prompt contractile waves to adjacent collecting lymphatics. This review aims at describing how the external tissue forces developing in the diaphragm, along with cyclic cardiogenic and respiratory swings, interplay with the spontaneous contraction of lymphatic vessel segments at the peripheral diaphragmatic rim to simultaneously set and modulate lymph flow from the pleural and peritoneal cavities. These details may provide useful in understanding the role of diaphragmatic lymphatics not only in physiological but, more so, in pathophysiological circumstances such as in dialysis, metastasis or infection. Full article
(This article belongs to the Special Issue Physiology of Lymph Vessels: Structure, Function, Modelling, and Clinical Perspectives)
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