Physiology of the Gastrointestinal Lymphatics

  • Toshio OhhashiEmail author
  • Yoshiko Kawai


In this chapter, we focus on the physiology of gastrointestinal lymphatic system and then demonstrate with current inspired studies that (1) functional properties of the intestinal microcirculation are summarized as higher permeability of plasma protein, especially albumin through the venule walls, which contribute to the oncotic pressure-mediated much absorption of interstitial fluid into lymphatic capillaries, (2) the larger amount of lymph formation in the intestinal villi may be related to the presence of lacteal vessels in the tissues, (3) the mesenteric collecting lymphatics demonstrate marked heart-like spontaneous contractions working as transport of the larger amount of lymph to chylous cyst, (4) the sentinel lymph node (SLN) may be defined as the node subjected to higher lymph flow from physiological point of view, and (5) the higher lymph flow may be, in part, related to develop the suitable microenvironment of the SLN for metastasis of carcinoma cells, which is produced by the cell surface F1/F0 ATP synthase-dependent overexpression of intercellular adhesion molecule-1 on the marginal endothelial-like cells of SLN.


Albumin Starling’s law Spontaneous contraction Lipid absorption Lacteal vessel 


  1. 1.
    Yoffey JM, Courtice FC. Lymphatics, lymph and the lymph myeloid complex. London: Academic Press; 1970.Google Scholar
  2. 2.
    Guyton AC, Taylor AE, Granger HJ. Circulatory physiology II, dynamics and control of body fluids. Philadelphia: Saunders; 1975. p. 125–60.Google Scholar
  3. 3.
    Ohhashi T, Mizuno R, Ikomi F, Kawai Y. Current topics of physiology and pharmacology. Pharmacol Ther. 2005;105:165–88.CrossRefGoogle Scholar
  4. 4.
    Roitt I. Essential immunology. Oxford: Blackwell Scientific Publication; 1980.Google Scholar
  5. 5.
    Gowans JL, Knight EJ. The route of re-circulation of lymphocytes in the rat. Proc R Soc Lond B Biol Sci. 1964;159:257–82.CrossRefGoogle Scholar
  6. 6.
    Hall JG, Morris B. The origin of the cells in the efferent lymph from a single lymph node. J Exp Med. 1965;121:901–10.CrossRefGoogle Scholar
  7. 7.
    Ohhashi T, Kawai Y. Proposed new lymphology combined with lymphatic physiology, innate immunology, and oncology. J Physiol Sci. 2015;65:51–66.CrossRefGoogle Scholar
  8. 8.
    Hargens AR, Zweifach BW. Transport between blood and peripheral lymph in intestine. Microvasc Res. 1976;11:89–101.CrossRefGoogle Scholar
  9. 9.
    Landis EM, Pappenhimer JR. Exchange of substances through the capillary walls. In: Hamilton WF, Dow P, editors. Circulation, Handbook of physiology, vol. II. Washington, DC: American Physiological Society; 1963. p. 961–1034.Google Scholar
  10. 10.
    Wasserman K, Mayerson HS. Exchange of albumin between plasma and lymph. Am J Phys. 1951;165:15–26.CrossRefGoogle Scholar
  11. 11.
    Brace RA, Taylor AE, Guyton AC. Time course of lymph protein concentration in the dog. Microvasc Res. 1977;14:243–9.CrossRefGoogle Scholar
  12. 12.
    Adair TH, Moffatt DS, Paulsen A. Quantitation of changes in lymph protein concentration during lymph node transit. Am J Phys. 1982;243:H351–9.Google Scholar
  13. 13.
    Ono N, Mizuno R, Ohhashi T. Effective permeability of hydrophilic substances through walls of lymph vessels: roles of endothelial barrier. Am J Phys. 2005;289:H1676–82.Google Scholar
  14. 14.
    Adair TH, Guyton AC. Modification of lymph by lymph nodes. III. Effect of increased lymph hydrostatic pressure. Am J Phys. 1985;249:H777–82.Google Scholar
  15. 15.
    Quin JW, Shannon AD. The influence of the lymph node on the protein concentration of efferent lymph leaving the node. J Physiol Lond. 1977;264:307–21.CrossRefGoogle Scholar
  16. 16.
    Knox P, Pflug JJ. The effect of the canine popliteal node on the composition of lymph. J Physiol Lond. 1983;345:1–14.CrossRefGoogle Scholar
  17. 17.
    Borgstrom B, Lau Rell CB. Studies on lymph and lymph-protein during absorption of fat and saline. Acta Physiol Scand. 1953;29:264–80.CrossRefGoogle Scholar
  18. 18.
    Granger DN, Taylor AE. Effects of solute-coupled transport on lymph flow and oncotic pressures in cat ileum. Am J Phys. 1978;235:E429–36.Google Scholar
  19. 19.
    Granger DN, Perry MA, Kvietys PR, Taylor AE. Interstitium-to-blood movement of macromolecules in the absorbing small intestine. Am J Phys. 1981;241:G31–6.Google Scholar
  20. 20.
    Adamson RH, Zeng M, Adamson GN, Lenz JF, Curry FE. PAF- and bradykinin-induced hyperpermeability of rat venules is independent of actin-myosin contraction. Am J Phys. 2003;285:H406–17.Google Scholar
  21. 21.
    Moy AB, Van Engelenhoven J, Bodmer J, Kamath J, Keese C, et al. Histamine and thrombin modulate endothelial focal adhesion through centripetal and centrifugal forces. J Clin Invest. 1996;97:1020–7.CrossRefGoogle Scholar
  22. 22.
    Taylor AE, Townsley MI. Evaluating of the Starling fluid flux equation. NIPS. 1987;2:48–52.Google Scholar
  23. 23.
    Webb RC Jr, Starzl TE. The effect of blood vessel pulsations on lymph pressure in large lymphatics. Bull Johns Hopkins Hosp. 1953;93:401–7.PubMedGoogle Scholar
  24. 24.
    Kinmonth JB, Taylor GW. Spontaneous rhythmic contractility in human lymphatics. J Physiol Lond. 1956;133:3P.Google Scholar
  25. 25.
    Mawhinney HJ, Roddie IC. Spontaneous activity in isolated bovine mesenteric lymphatics. J Physiol Lond. 1973;229:339–48.CrossRefGoogle Scholar
  26. 26.
    Ohhashi T, Azuma T, Sakaguchi M. Active and passive mechanical characteristics of bovine mesenteric lymphatics. Am J Phys. 1980;239:H88–95.Google Scholar
  27. 27.
    Hall JG, Morris B, Woolley G. Intrinsic rhythmic propulsion of lymph in the unanaesthetized sheep. J Physiol Lond. 1965;180:336–49.CrossRefGoogle Scholar
  28. 28.
    Azuma T, Ohhashi T, Sakaguchi M. Electrical activity of lymphatic smooth muscles. Proc Soc Exp Biol Med. 1977;155:270–3.CrossRefGoogle Scholar
  29. 29.
    Ohhashi T, Azuma T, Sakaguchi M. Transmembrane potentials in bovine lymphatic smooth muscle. Proc Soc Exp Biol Med. 1978;159:350–2.CrossRefGoogle Scholar
  30. 30.
    Ohhashi T, Azuma T. Effect of potassium on membrane potential and tension development in bovine mesenteric lymphatics. Microvasc Res. 1982;23:93–8.CrossRefGoogle Scholar
  31. 31.
    Speden RN. Electrical activity of single smooth muscle cells of the mesenteric artery produced by splanchnic nerve stimulation in the Guinea pig. Nature. 1964;202:193–4.CrossRefGoogle Scholar
  32. 32.
    Ohhashi T, Fukushima S, Azuma T. Vasa vasorum within the media of bovine mesenteric lymphatics. Proc Soc Exp Biol Med. 1977;154:582–6.CrossRefGoogle Scholar
  33. 33.
    Ikomi F, Mizuno R, Nakaya K, Ohhashi T. Effects of vasoactive substances on oxygen tension in thoracic duct lymph. Jpn J Physiol. 2000;50(Suppl):S74.Google Scholar
  34. 34.
    Ohhashi T, Kobayashi S, Tsukahara S, Azuma T. Innervation of bovine mesenteric lymphatics: from histochemical point of view. Microvasc Res. 1982;24:377–85.CrossRefGoogle Scholar
  35. 35.
    Ohhashi T. Regulation of motility of small collecting lymphatics. In: Staub NC, Hargens AR, editors. Interstitial-lymphatic liquid and solute movement. Basel: Karger; 1987. p. 171–83.Google Scholar
  36. 36.
    Sakaguchi M, Ohhashi T, Azuma T. A photoelectric diameter gauge utilizing the image sensor. Pflügers Arch. 1979;378:263–8.CrossRefGoogle Scholar
  37. 37.
    Morton DL, Wen DR, Wang JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg. 1992;127:392–9.CrossRefGoogle Scholar
  38. 38.
    Kitagawa Y, Kitajima M. Gastrointestinal cancer and sentinel node navigation surgery. J Surg Oncol. 2002;79:188–93.CrossRefGoogle Scholar
  39. 39.
    Kawai Y, Ajima K, Nagai T, Kaidoh M, Ohhashi T. Real-time imaging of the lymphatic channels and sentinel lymph nodes of the stomach using contrast-enhanced ultrasonography with Sonazoid in a porcine model. Cancer Sci. 2011;102:2073–81.CrossRefGoogle Scholar
  40. 40.
    Hiratsuka S, Watanabe A, Aburatani H, et al. Tumor-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat Cell Biol. 2006;8:1369–75.CrossRefGoogle Scholar
  41. 41.
    Kawai Y, Yokoyama Y, Kaidoh M, Ohhashi T. Pivotal roles of shear stress in the microenvironmental changes that occur within sentinel lymph nodes. Cancer Sci. 2012;103:1245–52.CrossRefGoogle Scholar
  42. 42.
    Kawai Y, Kaidoh M, Yokoyama Y, Sano K, Ohhashi T. Chemokine CCL2 facilitates ICAM-1-mediated interactions of cancer cells and lymphatic endothelial cells in sentinel lymph nodes. Cancer Sci. 2009;100:419–28.CrossRefGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Innovation of Medical and Health Sciences ResearchSchool of Medicine, Shinshu UniversityMatsumotoJapan
  2. 2.Faculty of Medicine, Division of PhysiologyTohoku Medical and Pharmaceutical UniversitySendaiJapan

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