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The interstitium is a contiguous fluid-filled space existing between a structural barrier, such as a cell wall or the skin, and internal structures, such as organs, including muscles and the circulatory system.[1][2] The fluid in this space is called interstitial fluid, comprises water and solutes, and drains into the lymph system.[2] The interstitial compartment is composed of connective and supporting tissues within the body – called the extracellular matrix – that are situated outside the blood and lymphatic vessels and the parenchyma of organs.[2][3]

Anatomical terminology


The non-fluid parts of the interstitium are predominantly collagen types I, III, and V, elastin, and glycosaminoglycans, such as hyaluronate and proteoglycans that are cross-linked to form a honeycomb-like reticulum.[3] Such structural components exist both for the general interstitium of the body,[2] and within individual organs, such as the heart and kidney.[4][5]


The interstitial fluid is a reservoir and transportation system for nutrients and solutes distributing among organs, cells, and capillaries, for signaling molecules communicating between cells, and for antigens and cytokines participating in immune regulation.[2] The composition and chemical properties of the interstitial fluid vary among organs and undergo changes in chemical composition during normal function, as well as during body growth, conditions of inflammation, and development of diseases,[2] as in heart failure[4] and chronic kidney disease.[5]

The total fluid volume of the interstitium during health is about 20% of body weight, but this space is dynamic and may change in volume and composition during immune responses and in conditions such as cancer, and specifically within the interstitium of tumors.[2] The amount of interstitial fluid varies from about 50% of the tissue weight in skin to about 10% in skeletal muscle.[2]


Preliminary research of the interstitium in people with lung diseases, heart disease, cancer, kidney disease, immune disorders, and periodontal disease indicates that the interstitial fluid and lymph system are sites where disease mechanisms may arise or develop.[2][4][5][6]

In 2018, the interstitium in bile duct submucosa was directly visualized in living human tissue with confocal laser endomicroscopy following fluorescein injection and shown to contain larger spaces than previously described, up to 60 micrometres in the living tissue; these spaces collapsed with the dehydration that follows upon tissue sampling and fixation so that the traditional histology showed an artifactual appearance of a densely collagenized layer.[7] Similar analyses were applied to the submucosae of all the visceral organs, the dermis, superficial fascia and perivascular adventitia confirming that these, too, were fluid filled spaces supported by a collagen bundle lattice, rather than the densely collagenized stroma of traditional histology. The fluid spaces were shown to communicate with draining lymph nodes though they did not have lining cells or structures of lymphatic channels; therefore they were interpreted as pre-lymphatic interstitial spaces.[7]

See alsoEdit


  1. ^ Bert JL; Pearce RH (1984). The interstitium and microvascular exchange. In: Handbook of Physiology. The Cardiovascular System. Microcirculation (sect. 2; pt. 1; chapt. 12; vol. IV ed.). Bethesda, MD: American Physiological Society. pp. 521–547. ISBN 0683072021.
  2. ^ a b c d e f g h i Wiig, H; Swartz, M. A (2012). "Interstitial fluid and lymph formation and transport: Physiological regulation and roles in inflammation and cancer". Physiological Reviews. 92 (3): 1005–60. doi:10.1152/physrev.00037.2011. PMID 22811424.
  3. ^ a b Scallan J; Huxley VH; Korthuis RJ (2010). The Interstitium. In: Capillary Fluid Exchange: Regulation, Functions, and Pathology. San Rafael, CA: Morgan & Claypool Life Sciences.
  4. ^ a b c Eckhouse SR; Spinale FG (2012). "Changes in the myocardial interstitium and contribution to the progression of heart failure". Heart Fail Clin. 8 (1): 7–20. doi:10.1016/j.hfc.2011.08.012. PMC 3227393. PMID 22108723.
  5. ^ a b c Zeisberg, M; Kalluri, R (2015). "Physiology of the Renal Interstitium". Clinical Journal of the American Society of Nephrology. 10 (10): 1831–1840. doi:10.2215/CJN.00640114. PMC 4594057. PMID 25813241.
  6. ^ Berggreen, E; Wiig, H (2014). "Lymphatic function and responses in periodontal disease". Experimental Cell Research. 325 (2): 130–7. doi:10.1016/j.yexcr.2013.12.006. PMID 24503053.
  7. ^ a b Benias, Petros C.; Wells, Rebecca G.; Sackey-Aboagye, Bridget; Klavan, Heather; Reidy, Jason; Buonocore, Darren; Miranda, Markus; Kornacki, Susan; Wayne, Michael (2018-03-27). "Structure and Distribution of an Unrecognized Interstitium in Human Tissues". Scientific Reports. 8 (1): 4947. doi:10.1038/s41598-018-23062-6. ISSN 2045-2322. PMC 5869738. PMID 29588511.