Lymphatic Structure and Function in Health and Disease

Felicity N.E. Gavins, J. Steve Alexander

• Publisher: Academic Press
• Year: 2019
• ISBN:
  9780128156469
• Topic: Sciences biologiques
• Subtopic: Neurosciences

Lymphatic Structure and Function in Health and Disease serves as a resource book on what has been learned about lymphatic structure, function and anatomy within different organ systems. This is the first book to bring together lymphatic medicine as a whole, with in-depth analysis of specific aspects of lymphatics in different vascular pathologies. This book is a useful tool for scientists, practicing clinicians and residents, in particular, those in vascular biology, neurology, cardiology and general medicine. Chapters discuss topics such as ontogeny and phylogeny of lymphatics, lymphatic pumping, CNS lymphatics, lymphatics in transplant and lymphatic reconstruction.

• Brings together lymphatic medicine as a whole, with an in-depth analysis of the specific basic science aspects of lymphatic structure and function
• Covers the clinical aspects of lymphatics in different vascular pathologies
• Co-published with the International Society of Neurovascular Diseases
• Discusses lymphatic structure and function in all of the major organ systems

Chapter 1

Introduction/overview

Felicity N.E. Gavins^a,b; J. Steve Alexander^a    a Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, LA, United States
^b Brunel University London, Kingston Ln, London, Uxbridge, United Kingdom

Abstract

The lymphatic system consists of the vascular network of tissues and organs (the lymph nodes, thymus, spleen, tonsils, and appendix) that drain interstitial fluid (lymph) from the peripheral tissue back to the blood circulation. The lymphatic system forms part of the well-described vascular system but is not a circulatory system as it is a group of one-way conduits. This incredibly complex network of vessels not only collects lymph, which is an astounding feat at the level of physics, but also plays a crucial role in our immune system; it is the least well characterized and often maligned and marginalized vascular system reflecting the great difficulty in visualizing lymphatics outside of the confines of a fat-meal consumption, which necessitated the identification of many molecular markers that distinguish lymphatic endothelial cells from the blood vascular endothelium. Consequently, there has been more recently an explosion of research into the lymphatic system with the annual number of publications on lymphatics climbing from 2093 in 1990 to 5519 in 2015. The literature is proceeding so quickly that we thought that this area of study deserved at this point a summary of how lymphatics and lymphatic endothelial cells contribute to the functioning of several different organ systems and to health and disease.

Keywords

Circulatory system; Congenital vascular malformations; Lymphadenopathy; Lymphatic system; Vascular system

The lymphatic system consists of the vascular network of tissues and organs (the lymph nodes, thymus, spleen, tonsils, and appendix) that drain interstitial fluid (lymph) from the peripheral tissue back to the blood circulation. The lymphatic system forms part of the well-described vascular system but is not a circulatory system as it is a group of one-way conduits. This incredibly complex network of vessels not only collects lymph, which is an astounding feat at the level of physics, but also plays a crucial role in our immune system; it is the least well characterized and often maligned and marginalized vascular system reflecting the great difficulty in visualizing lymphatics outside of the confines of a fat-meal consumption, which necessitated the identification of many molecular markers that distinguish lymphatic endothelial cells from the blood vascular endothelium. Consequently, there has been more recently an explosion of research into the lymphatic system with the annual number of publications on lymphatics climbing from 2093 in 1990 to 5519 in 2015. The literature is proceeding so quickly that we thought that this area of study deserved at this point a summary of how lymphatics and lymphatic endothelial cells contribute to the functioning of several different organ systems and to health and disease.

This text is therefore devoted to the evaluation of how the lymphatic organization and supply in several organ systems may contribute to how these organs function and how their disturbances in structure, patterning, or function may lead to organ stress. The multifaceted roles that lymphatics play in health and disease include contributions gathered from leading experts around the world who are actively working in the rapidly expanding field of lymphatic research.

The lymphatic system was first described by Hippocrates of Kos (c.460–377 BC), and as such, B.B. Lee and H. Suami have focused on the evolution and the embryonic development of the lymphatic system in Chapter 2. This team also brings together the recent advance in the field of lymphangiogenesis, highlighting both the physiological and pathological roles played by lymphatic development.

As mentioned earlier, the lymphatic system plays a key role in the immune system. In Chapter 3, M. Stephens and Pierre-Yves von der Weid focus on the role that lymphatic vessels and lymphatic contractions play in edema resolution and immune cell trafficking, especially in the context of the intestine and inflammatory processes associated with the gastrointestinal tract. Stephens and von der Weid discuss the implications and significance of lymph node swelling (lymphadenopathy), which occurs in inflammation, infection, and diseases. Finally, this chapter discusses the dysfunction of lymphatic vessel function in a variety of pathologies (often associated with chronic inflammation) such as rheumatoid arthritis and osteoarthritis, elephantiasis, inflammatory bowel diseases, metabolic syndrome and diabetes, and cancer, coupled with discussions regarding the consequences of targeting lymphatic pump for therapeutic benefits.

Next, we move to the hydrodynamic regulation of lymphatic vessel transport and the impact that aging has on these events (Chapter 4). In this chapter, A.A. Gashev and D.C. Zawieja discuss the concepts of intrinsic and extrinsic lymph pumps, along with the job that they play in modulating lymphatic vessel contractility. They will discuss the novel regulatory function of histamine as an endothelium-derived relaxing factor (EDRF). Additionally, while the important role that the aging process plays in and the impact it has on the vascular system (termed vascular aging) are recognized, very little is known with respect to lymphatic system and aging-associated changes in the active lymph pumps. As such, A.A. Gashev and D.C. Zawieja will discuss these issues in detail, bringing together their own work and that of the scientific community.

The brain is responsible for 25% of the body’s metabolism, even though it only encompasses 2% of the body’s total mass. As with the rest of the body, metabolism leads to the generation of waste products that need to be cleared, and it is particularly important when it comes to the brain that this clearance mechanism is efficient and effective. Therefore, Chapter 5 concentrates on the lymphatic system in the context of the central nervous system (CNS). J.W. Yun et al. discuss the three different brain lymphatic clearance pathways that are currently described, that is, (i) the perivascular pathway, (ii) the glymphatic pathway, and (iii) the meningeal pathway. These different pathways and the role that they play in diseases and conditions of the CNS, such as Alzheimer’s disease (AD), multiple sclerosis (MS), and cerebral ischemia (stroke), are reviewed at length. As discussed in the previous chapter (Chapter 4), aging is a significant contributing factor to peripheral immune responses; additionally, it also plays a considerable role in central immune responses, incorporating both the glymphatic system and brain lymphatic vasculature. Chapter 5 will deliberate aging in the context of the CNS and the lymphatic system and how the CNS lymphatics can be exploited for drug discovery programs to identify new therapeutic targets for the treatment of neurovascular and neurodegenerative disorders.

Moving on from the CNS, in the next chapter (Chapter 6), B.B. Lee and M. Amore weigh up the defective development of peripheral lymphatic system (termed lymphatic malformation (LM)), which is one of the various forms of congenital vascular malformations (CVMs) but only affects the lymphatic circulation. It is known that LMs can present clinically as a solitary/independent lesion or coexist with other CVMs, often as a hemolymphatic malformation (HLM). Not only do the authors discuss LMs in detail, but also they provide clinical and management options for patients with, for example, Klippel-Trenaunay syndrome.

In Chapter 7, the lymphatics of the heart are reviewed by J.S. Alexander and J.W. Yun. The heart is a dynamic organ in terms of its mechanical propulsion of the blood flow, and as such. Its lymphatic system has long remained enigmatic. J.S. Alexander and J.W. Yun discuss the origins and development of cardiac lymphatics, patterning, and functioning, placing particular emphasis on the roles that the cardiac lymphatics may play in clinical conditions ranging from surgically induced lymphatic distress, to myocardial infarction, to heart transplantation.

In the final chapter of our book (Chapter 8), A. Mohr et al. focus on the concept of the surgical approach of lymphatic reconstruction, which is commonly used for patients with destructed or obstructed lymphatic vessels who are suffering from secondary lymphedema. A main advantage of this surgical approach is that it allows for additional treatment options for the condition of secondary lymphedema especially if patients are resistant to conservative therapy. However, as with every intervention, there are pros and cons, which A. Mohr et al. discuss in detail in this chapter, along with the history of surgical approaches for lymphatic reconstruction.

We hope this volume serves as a starting point for readers both scientifically and medically minded alike at the level of students to more advanced readers. Here, we have begun to consider how this often nearly invisible, parallel sister to the circulatory system supports the blood vasculature, accomplishing so many diverse functions that are only recognized when lymphatic dysfunction occurs. The recognition that lymphatics may contribute to many clinical conditions opens vast new vistas for the development of therapies that exploit new findings, mechanisms, and reagents acting on the lymphatic vasculature.

Finally, we would like to thank Kristi and Melanie at Elsevier for their patience, encouragement, and support. In addition, we thank all the authors and reviewers without whom this book would not have been possible.

Chapter 2

Ontogeny and phylogeny of lymphatics: Embryological aspect

B.B. Lee^a; H. Suami^{b a} Vascular Surgery, George Washington University Hospital, Washington, DC, United States
^b Australian Lymphoedema Education, Research and Treatment, Macquarie University, Sydney, Australia

Abstract

The lymphatic system was first described by Hippocrates in 460–377 BC and further confirmed as one of the two major circulatory systems together with the blood vascular system by Gasparo Aselli in 1627. Despite these findings, this major circulatory system has been largely neglected for three centuries primarily due to limited knowledge, being often an invisible auxiliary to the blood vascular system and as such being considered less important. However, our understanding of the lymphatic system has significantly advanced over the last two decades with many landmark discoveries in lymphatic research, especially in the areas of cellular and molecular biology of lymphatic endothelial cells (LECs).

This chapter will discuss the lymphatic system in detail, along with recent advances in our understanding of the embryonic development of the lymphatic vasculature, including the molecular mechanisms to mediate lymphangiogenesis. These advances have brought to light the molecular control of physiological and pathological lymphangiogenesis and subsequently changed the paradigm to re-evaluate the lymphatic system's essential role in the human circulatory system.

Keywords

Lymphangiogenesis; Centrifugal model; Centripetal model; Lymphangioblast; Lymphatic endothelial cells (LECs); Lymphatic/LEC competence; Lymphatic commitment; Lymphatic endothelial cell specification; Vascular coalescence and maturation

Historical background

The lymphatic system was first described by Hippocrate...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• Contributors
• About the Editors
• Chapter 1: Introduction/overview
• Chapter 2: Ontogeny and phylogeny of lymphatics: Embryological aspect
• Chapter 3: Lymphatic pumping and pathological consequences of its dysfunction
• Chapter 4: Hydrodynamic regulation of lymphatic vessel transport function and the impact of aging
• Chapter 5: CNS lymphatics in health and disease
• Chapter 6: Defective development of the peripheral lymphatic system: Lymphatic malformations
• Chapter 7: Cardiac lymphatics and cardiac lymph flow in health and disease
• Chapter 8: Lymphatic reconstruction
• Index