Chapter 3

### INTRODUCTION AND HISTORICAL BACKGROUND

"The lymph vessels, so unimpressive when they were first pointed out to me in 1908 under the microscope—but, I was soon to discover, so elusive or baffling to everyone who had studied them—have lost none of their tantalizing nature in all these years."

Otto F. Kampmeier1

The lymphatic system, which is composed of four components—lymphatic vessels, lymph fluid, lymph nodes or lymphoid aggregates, and lymphocytes or immunocytes—is a distinctive vasculature different from and yet similar to the blood vasculature. It is an integral component of the plasma–tissue fluid–lymph circulation (the "blood–lymph loop"), the key lipid "absorbent," and the center of the immunoregulatory network.2 Lymphology—or fashioned after current omes and omics terminology, "lymphatomics"—is the study of lymphatic system biology in health and disease.

Although there were scattered observations on lymphatic vessels and lymph dating back to the ancient Greeks, Gaspar Aselli of Padua is credited with the discovery of the system of chyliferous vessels of the mesentery, glistening after a fat meal in a living dog. His posthumous publication appeared in 1627, the same year that Harvey described the blood circulation.3,4 Because of the difficulties in accessing and visualizing the lymphatic vessels during life, their collapse after death, and the meager physiologic understanding of the circulation of lymph, it was only during the past century, especially the past half-century, that the International Society of Lymphology founded lymphology as a distinct discipline in 1966. It was then that the integrated function of the four components of the lymphatic system—no longer viewed as "lymph nodes held together by strings"—was fully recognized. The peripheral and central lymphatic channels and nodes could be visualized in the living human by oily contrast lymphography, and the lymphatic system's characteristic constellation of disorders of swelling, scarring, malnutrition, immunodysregulation, and disturbed angiogenesis gained attention.2,5,6 Yet for centuries, clinicians had already viewed the lymphatic system as the stage on which key events in development, progression, and containment of cancer and of infections such as tuberculosis take place.7,8 Recent advances in molecular lymphology (i.e., the discovery of lymphatic growth factors, endothelial receptors, transcription factors, genes, and highly specific immunohistochemical markers) and in clinical lymphology (refined tools for noninvasive dynamic lymphatic and soft tissue imaging, advanced microsurgical techniques, and putative therapeutic agents for lymphangio- and hemangiomodulation) are providing new opportunities for translational lymphology (i.e., taking these advances from "bench to bedside").9,10,11,12

### ANATOMY AND DEVELOPMENT

#### Macroscopic Anatomy

Lymphatic vessels generally accompany venous trunks throughout the body except in the central nervous system, hepatic sinusoid, and cortical bony skeleton, where peri(blood)vascular spaces serve the function of prelymphatic vessels 5,13,14,15 (Figure 3-1). Lymph from the lower torso, including the legs, pelvis, and viscera, is carried by the thoracic duct to ...

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