The Physiology of the Lymphatic System
The lymphatic system serves three essential physiological functions: maintaining tissue fluid homeostasis by returning interstitial fluid to the bloodstream, facilitating immune surveillance through trafficking of immune cells and antigens to lymph nodes, and absorbing dietary lipids and fat-soluble vitamins from the intestinal tract. 1, 2, 3
Core Physiological Functions
Fluid Homeostasis and Transport Mechanisms
The lymphatic system maintains tissue fluid balance by collecting excess interstitial fluid and returning it to the venous circulation, preventing tissue edema 2, 4, 3
Lymph transport occurs through both extrinsic pumps (compression by surrounding tissues) and intrinsic pumps (rhythmic contractions of lymphatic smooth muscle cells in collecting vessels) 4, 5
Initial lymphatic vessels (lymphatic capillaries) absorb fluid from the interstitium, while collecting lymphatic vessels actively propel lymph centrally through muscular contractions 5
Intraluminal valves in collecting lymphatic vessels ensure unidirectional lymph flow toward the central circulation, preventing backflow 4, 5
The intrinsic lymph pump is activated by increased lymph pressure and vessel wall stretch, while lymph flow and shear stress can either activate or inhibit pumping depending on magnitude and pattern 4
Immune Surveillance and Cell Trafficking
The lymphatic system connects peripheral tissues to draining lymph nodes, serving as the primary conduit for initiating adaptive immune responses 6
Immune cells, including lymphocytes and antigen-presenting cells, traffic through lymphatic vessels to reach lymph nodes for immune activation 2, 6
Lymphocytes express transferrin receptor 1 (TfR1) to import iron, which is essential for their proliferation and function during immune responses 1
The lymphatic system actively participates in pathogen clearance, restricts pathogen dissemination, and controls immunopathology during infections 6
Lipid Absorption
Specialized lymphatic vessels in the small intestine (lacteals) absorb dietary fats and fat-soluble vitamins A, D, E, and K from the gastrointestinal tract 2, 3
This absorbed lipid is transported as chylomicra through the lymphatic system before entering the bloodstream 4
Regulation of Lymphatic Function
Growth Factor Signaling
The VEGF-C/VEGFR-3 signaling system is the most important pathway regulating lymphatic vessel growth (lymphangiogenesis) 1
Increased tissue VEGF-C concentration through transgenic overexpression or viral gene delivery leads to lymphatic vessel overgrowth 1
Conversely, overexpression of soluble VEGFR-3 extracellular domain suppresses lymphatic vessel growth 1
Mechanical and Biochemical Modulation
Lymphatic contractile activity is modulated by neural, humoral, and physical factors including pressure, stretch, and flow patterns 4, 5
Lymphatic endothelial cells respond dynamically to infection and inflammation through vessel remodeling, including lymphangiogenesis (new vessel growth) and lymphangiectasia (vessel dilation) 6
Interstitial Space Dynamics
In normal tissues, the interstitial space between blood and lymphatic vessels facilitates transport of immune cells, oxygen, nutrients, and waste products toward the lymphatic system 1
Lymphatic drainage supports convective flow from blood to lymph vessels; when lymphatic drainage is impaired (as in tumors), transport occurs only by diffusion, which is significantly less effective 1
Compression of lymphatic vessels or lack of lymphatic vessel formation leads to increased interstitial fluid pressure and impaired tissue drainage 1
Clinical Relevance
Pathological Conditions
Inherited or acquired insufficiency of lymphatic vessel development results in various forms of lymphedema 1
In cancer, lymphangiogenesis contributes to disease progression by facilitating tumor cell dissemination to lymph nodes 1
Protein-losing enteropathy can cause hypoalbuminemia and decreased oncotic pressure, leading to fluid accumulation 7
Fontan circulation (congenital heart condition) can result in ascites due to decreased oncotic pressure from hypoalbuminemia secondary to protein-losing enteropathy 7