Lymphatic Drainage System

The lymphatic system consists of the lymphoid organs containing the cells of the immune system and the lymphatic vessels, which transport interstitial fluid (as lymph) back to the venous circulation. Lymphatic vessels are spread extensively throughout the body, draining and filtering lymph, facilitating homeostasis, and aiding in defense against circulating pathogens. Fluid flow is unidirectional, enabled by valves in the collecting lymphatic vessels. In vessels without valves, the muscle contraction of organs and adjacent blood vessels help in the fluid movement. To return to the venous circulation, the lymph is collected by the major lymphatic ducts: right lymphatic duct (collects from the right side of the head and neck, the right side of the thorax, and the right upper extremity) and the thoracic duct (collects from the rest of the body). Pathologic conditions involving the lymphatic system are associated with infections, lymphatic damage, or injury and malignancies.

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Overview

Immune system

  • The immune system provides defense (immunity) against invading pathogens, ranging from viruses to parasites, and its components are interconnected by blood and the lymphatic circulation.
  • 2 lines of defense (which overlap):
    • Innate immunity (which is nonspecific) involves the following cells:
      • Natural killer cells
      • Monocytes/macrophages
      • Dendritic cells
      • Neutrophils, basophils, eosinophils
      • Tissue mast cells
    • Adaptive immunity (based on specific antigen recognition) involves:
      • T and B lymphocytes (derived from lymphoid organs)
      • Antigen-presenting cells

Lymphatic system

The lymphatic system (lymph vessels, lymph fluid, and lymphoid organs) is part of the body’s immune system.

  • Lymphoid organs:
    • Primary: 
      • Locations where lymphocytes develop from progenitor cells (initial formation)
      • Include the bone marrow and thymus
    • Secondary: 
      • Sites where lymphocytes undergo activation, proliferation and additional maturation
      • Include the spleen, lymph nodes, and MALT (e.g., tonsils)
  • Lymphatic vessels and ducts:
    • A network, similar to the blood vessels, that extends throughout the human body
    • Connect lymphoid organs and transport interstitial fluid (lymph) 
    • Play crucial roles in immune response and fluid balance
Anatomy of the lymphatic system

Anatomy of the lymphatic system: includes the primary (bone marrow, thymus) and secondary lymphoid organs (spleen, lymph nodes, and MALT).
Lymphatic vessels convey lymph to the larger lymphatic vessels in the torso, transporting fluid back to the venous circulation.

Image: “Anatomy of the Lymphatic System” by OpenStax. License: CC BY 4.0

Lymph and Lymphatic Vessels

Structures

  • Lymph: 
    • Fluid that enters the lymphatic vessels 
    • Originates from extracellular fluid and contains products of tissue metabolism and catabolism, apoptotic cells, debris, and immune cells
  • Lymphatic capillaries:
    • Permeable, blind-ended vessels (endothelial cells are not tightly joined)
    • Carry lymph from the tissues to the lymph nodes via lymphatic vessels
    • Greater diameter (as wide as 100 μm) than blood capillaries
    • Endothelial cells overlap each other, forming minivalves that can easily open.
    • Interstitial proteins cannot enter the blood capillaries, but they can enter lymphatic capillaries. 
  • Lymphatic vessels (types):
    • Initial lymphatics:
      • No valves
      • No smooth muscles in the walls
      • Found in regions such as the intestines and skeletal muscles
      • Fluid enters through junctions of endothelial cells, and muscle contractions (of organs and blood vessels) encourage fluid flow.
      • Drain into the collecting lymphatics
    • Collecting lymphatics: 
      • With valves (the beaded appearance of lymphatic ducts and vessels reflects the presence of valves)
      • With smooth muscles in the walls
      • Muscle contractions in the lymphatic vessels move the fluid along the vessels.

Main functions

  • Lymph transport and immune surveillance:
    • Pathogens, tumor cells, and debris travel through the lymph.
    • Lymph is filtered, and the appropriate immune response is mounted in the lymph nodes.
  • Fluid homeostasis:
    • Increase in interstitial fluid volume and leaked protein molecules will cause fluid accumulation in tissue spaces (edema).
    • Lymph capillaries pick up excess or extravasated fluid (which forces the minivalves to open) and proteins, enabling return to circulation.
  • Fat transport:
    • Fats and fat-soluble vitamins from the digestive system are absorbed.
    • Special lymphatic capillaries in the small intestinal villi (lacteals) facilitate transport to the venous circulation. 
    • Lymph in lacteals: also called chyle (milky appearance due to fat content) 

Route of lymphatic drainage

  • Unidirectional
  • Lymphatic capillaries → lymphatic vessels (enter lymph nodes via afferent vessels and leave via efferent vessels) → lymphatic ducts
  • 1 major lymphatic duct on each side of the body: 
    • The right lymphatic duct drains from:
      • Right side of the body above the diaphragm (the right side of the head and neck, the right side of the thorax, and the right upper extremity)
      • Drains into the junction of the right subclavian and internal jugular vein
    • The thoracic duct (larger) drains from the rest (75%) of the body.
      • Drains lymph from both lower limbs, left upper limb, and left half of the head and neck
      • Starts at the cisterna chyli, lymph sac at level of L2 vertebra 
      • Ascends into the thorax, going through the aortic hiatus of the diaphragm
      • Continues upward into the posterior mediastinum on the right, and then shifts to the left at T5 vertebra
      • Drains into the convergence between the left subclavian and internal jugular veins

Lymphatic Drainage Associations

Lymphadenopathy is caused by several etiologies, and an approach for determining the etiology is based on the location(s) of and areas drained by the lymph node(s).

Table: Lymphatic drainage associations
Lymph node clusterAreas drainedAssociated diseases
Cervical lymph nodesHead and neck
  • Infections:
    • EBV
    • Cytomegalovirus infection
    • Toxoplasmosis
    • Tuberculosis
  • Kawasaki disease
  • Head and neck malignancy
Preauricular lymph nodes
  • Conjunctiva
  • Ear canal
  • Anterior and temporal scalp
Infections in areas drained
Postauricular lymph nodesParietotemporal scalpInfections (common in rubella)
Supraclavicular lymph nodes
  • Right:
    • Mediastinum
    • Lungs
  • Left: abdomen
  • Right: cancer in the mediastinum, lungs, or esophagus
  • Left: abdominal malignancy (Virchow’s node)
Axillary lymph nodes
  • Arm
  • Thoracic wall
  • Breast
  • Infections (such as cat-scratch disease)
  • Breast cancer
  • Metastasis (left axillary node, or “Irish node” in gastric cancer)
Epitrochlear lymph nodesMedial side of the arm below the elbow
  • Infections (tularemia, secondary syphilis)
  • Lymphoma
  • Sarcoidosis
Mediastinal lymph nodes
  • Trachea
  • Esophagus
  • Infections (tuberculosis)
  • Granulomatous disease
  • Lung cancer
Hilar lymph nodesLungs
Celiac lymph nodes
  • Liver
  • Stomach
  • Spleen
  • Pancreas
  • Upper duodenum
  • Mesenteric lymphadenitis
  • Typhoid fever
  • Ulcerative colitis
  • Metastasis
  • “Sister Mary Joseph nodule”: periumbilical nodule believed to be a malignant extension via lymphatic and hematogenous spread (GI and genitourinary cancers)
Superior mesenteric lymph nodes
  • Lower duodenum to ileum
  • Colon to splenic flexure
Inferior mesenteric lymph nodesColon from splenic flexure to upper rectum
Paraaortic (lumbar) lymph nodes
  • Ovaries/testes
  • Kidneys
  • Uterus
Iliac lymph nodes (external and internal)
  • External:
    • Cervix
    • Superior bladder
    • Uterus (also receive lymph from inguinal lymph nodes)
  • Internal:
    • Lower rectum to anal canal (above pectinate line)
    • Bladder
    • Vagina
    • Cervix
    • Prostate
  • Infections: STD
  • Malignancy and metastasis
Inguinal lymph nodes
  • Lower extremity
  • Genitalia
  • Buttock
  • Abdominal wall below umbilicus
  • Lower extremity infection
  • STDs (such as chancroid, lymphogranuloma venereum (LGV), genital herpes, syphilis)
  • Cancer
Popliteal lymph nodesLower legInfection (cellulitis)

Clinical Relevance

  • Lymphedema: interstitial fluid colloid osmotic pressure increases, resulting in lymphedema. The lymphatic drainage serves as the main route for the removal of interstitial fluid. Dysfunction of the lymphatic vessels results in the development of edema. Patients can present with peau d’orange skin changes and elephantiasis. Causes occur from congenital hypoplasia of lymphatics (Milroy disease), malignancy, obesity, or surgery.
  • Chylothorax: condition in which the thoracic duct is disrupted and chyle escapes into the pleural space. The condition is commonly caused by trauma (e.g., thoracic surgery) but also arises from tumors. Presentation includes dyspnea and a pleural effusion on chest radiograph. On thoracentesis, a milky pleural fluid with an elevated triglyceride level is noted. Evaluation is by lymphangiogram and a mediastinal CT scan.
  • Lymphangitis: inflammation of the lymphatic vessels, often caused by bacterial spread. The most common etiology is group A β-hemolytic streptococcus. The vessels are dilated and filled with exudate. On examination, red subcutaneous streaks representing inflamed lymphatics are seen. This is accompanied by painful and enlarged lymph nodes (lymphadenitis).

References

  1. Barrett, KE, Barman, SM, Brooks, HL, & Yuan JJ. (Eds.). (2019). Blood as a circulatory fluid and the dynamics of blood and lymph flow. Ganong’s Review of Medical Physiology, 26e. McGraw Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=2525&sectionid=204296997
  2. Ferrer, R. (2021). Evaluation of peripheral lymphadenopathy in adults. UpToDate. Retrieved July 11, 2021, from https://www.uptodate.com/contents/evaluation-of-peripheral-lymphadenopathy-in-adults
  3. Ilahi, M, St Lucia, K, & Ilahi, TB. (2020). Anatomy, thorax, thoracic duct. In: StatPearls. Treasure Island (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK513227/
  4. Paulsen, DF. (Ed.). (2010). Circulatory system. Histology & Cell Biology: Examination & Board Review, 5e. McGraw Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=563&sectionid=42045306
  5. Santambrogio, L. (2018). The lymphatic fluid. Int Rev Cell Mol Biol. 337, 111–133. https://pubmed.ncbi.nlm.nih.gov/29551158/

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