# Interstitium

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{{Short description|Fluid-filled space in organs}}
{{Use American English|date=May 2026}}
{{Use dmy dates|date=May 2026}}
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{{Infobox anatomy|Identifiers=|Details=|Name=Interstitium|Image=Intersticio (órgano).jpg|Caption=Three-dimensional schematic of the interstitium, a fluid-filled space supported by a network of collagen}}

In [anatomy](/source/anatomy), the '''interstitium''' is a contiguous fluid-filled space existing between a structural barrier, such as a [cell membrane](/source/cell_membrane) or the [skin](/source/skin), and internal structures, such as [organs](/source/organ_(anatomy)), including [muscle](/source/muscle)s and the [circulatory system](/source/circulatory_system).<ref name="bert">{{cite book|author1=Bert JL|author2=Pearce RH|title=The interstitium and microvascular exchange. In: Handbook of Physiology. The Cardiovascular System. Microcirculation|date=1984|publisher=American Physiological Society|location=Bethesda, MD|isbn=0-683-07202-1|pages=521–547|edition=sect. 2; pt. 1; chapt. 12; vol. IV}}</ref><ref name="wiig">{{cite journal|pmid=22811424|year=2012|last1=Wiig|first1=H|title=Interstitial fluid and lymph formation and transport: Physiological regulation and roles in inflammation and cancer|journal=Physiological Reviews|volume=92|issue=3|pages=1005–60|last2=Swartz|first2=M. A|doi=10.1152/physrev.00037.2011}}</ref> Fluid in this space &ndash; the [interstitial fluid](/source/interstitial_fluid) &ndash; is composed of [solute](/source/solute)s and water draining into the [lymphatic system](/source/lymphatic_system).<ref name="wiig" /> 

The interstitial compartment is composed of [connective tissue](/source/connective_tissue)s comprising an [extracellular matrix](/source/extracellular_matrix), which is situated outside the blood, [lymphatic vessels](/source/Lymphatic_vessel), and the [parenchyma](/source/parenchyma) of organs.<ref name=wiig/><ref name="scallan">{{cite book|author1=Scallan J|author2=Huxley VH|author3=Korthuis RJ|title=The Interstitium. In: Capillary Fluid Exchange: Regulation, Functions, and Pathology|date=2010|publisher=Morgan & Claypool Life Sciences|location=San Rafael, CA|url=https://www.ncbi.nlm.nih.gov/books/NBK53446/|access-date=2018-03-29|archive-date=2021-02-08|archive-url=https://web.archive.org/web/20210208191509/https://www.ncbi.nlm.nih.gov/books/NBK53446/|url-status=live}}</ref> The interstitium has a role in regulating solute concentration, protein transport, and [hydrostatic pressure](/source/hydrostatic_pressure), which may affect human pathology and [physiological responses](/source/physiology), such as [edema](/source/edema), [inflammation](/source/inflammation), and [shock](/source/Shock_(circulatory)).<ref name="stewart-2020a">{{Cite journal |last=Stewart |first=Randolph H. |date=2020-11-05 |title=A Modern View of the Interstitial Space in Health and Disease |journal=Frontiers in Veterinary Science |volume=7 |article-number=609583 |doi=10.3389/fvets.2020.609583 |doi-access=free |issn=2297-1769 |pmc=7674635 |pmid=33251275}}</ref>

==Structure==
The non-fluid parts of the interstitium are predominantly [collagen](/source/collagen) types I, III, and V; [elastin](/source/elastin); and [glycosaminoglycan](/source/glycosaminoglycan)s, such as [hyaluronan](/source/hyaluronan) and [proteoglycan](/source/proteoglycan)s, that are cross-linked to form a [honeycomb](/source/honeycomb)-like [reticulum](/source/Reticular_connective_tissue).<ref name=scallan/> Collagen bundles of the extracellular matrix form scaffolding with a high [tensile strength](/source/tensile_strength). [Interstitial cells](/source/List_of_interstitial_cells) (e.g., [fibroblast](/source/fibroblast)s, dendritic cells, [adipocyte](/source/adipocyte)s, [interstitial cells of Cajal](/source/Interstitial_cell_of_Cajal) and inflammatory cells, such as [macrophage](/source/macrophage)s and [mast cell](/source/mast_cell)s), serve a variety of structural and immune functions.<ref name="scallan" /><ref name="stewart-2020a" /> Fibroblasts synthesize the production of structural molecules as well as [enzyme](/source/enzyme)s that break down [polymer](/source/polymer)ic molecules.<ref name="scallan" /> Such structural components exist both for the general interstitium of the body,<ref name=wiig/> and within individual organs, such as the [myocardial](/source/myocardium) interstitium of the [heart](/source/heart),<ref name="heart">{{cite journal|author1=Eckhouse SR|author2=Spinale FG|title=Changes in the myocardial interstitium and contribution to the progression of heart failure|journal=Heart Fail Clin|date=2012|volume=8|issue=1|pages=7–20|doi=10.1016/j.hfc.2011.08.012|pmid=22108723|pmc=3227393}}</ref> the renal interstitium of the [kidney](/source/kidney)s,<ref name="kidney">{{cite journal|pmc=4594057|year=2015|last1=Zeisberg|first1=M|title=Physiology of the Renal Interstitium|journal=Clinical Journal of the American Society of Nephrology|volume=10|issue=10|pages=1831–1840|last2=Kalluri|first2=R|doi=10.2215/CJN.00640114|pmid=25813241}}</ref> and the [pulmonary](/source/pulmonary) interstitium of the [lung](/source/lung)s.

The interstitium in the [submucosa](/source/submucosa)e of [viscera](/source/viscera)l organs, the [dermis](/source/dermis), superficial [fascia](/source/fascia), and perivascular [adventitia](/source/adventitia) are fluid-filled spaces supported by a collagen bundle lattice. Blind end, highly permeable, lymphatic [capillaries](/source/capillary) extend into the interstitium. The fluid spaces communicate with draining [lymph nodes](/source/Lymph_node), although they do not have lining cells or structures of lymphatic channels.<ref name="benias">{{Cite journal|last1=Benias|first1=Petros C.|last2=Wells|first2=Rebecca G.|last3=Sackey-Aboagye|first3=Bridget|last4=Klavan|first4=Heather|last5=Reidy|first5=Jason|last6=Buonocore|first6=Darren|last7=Miranda|first7=Markus|last8=Kornacki|first8=Susan|last9=Wayne|first9=Michael|date=2018-03-27|title=Structure and Distribution of an Unrecognized Interstitium in Human Tissues|journal=Scientific Reports|language=En|volume=8|issue=1|pages=4947|doi=10.1038/s41598-018-23062-6|pmid=29588511|pmc=5869738|bibcode=2018NatSR...8.4947B |issn=2045-2322}}</ref> Interstitial fluid entering the lymphatic system becomes [lymph](/source/lymph), which is transported through lymphatic vessels until it empties into the [microcirculation](/source/microcirculation) and the [venous system](/source/Vein).<ref name="stewart-2020a" />

==Functions==
The interstitial fluid is a reservoir and transportation system for nutrients and solutes distributing among organs, cells, and [capillaries](/source/capillary), for [signaling molecule](/source/signaling_molecule)s communicating between cells, and for [antigen](/source/antigen)s and [cytokine](/source/cytokine)s participating in [immune regulation](/source/immune_system).<ref name=wiig/> The structure of the gel reticulum plays a role in the distribution of solutes across the interstitium, as the microstructure of the extracellular matrix in some parts excludes larger molecules (exclusion volume). The density of the collagen matrix fluctuates with the fluid volume of the interstitium. Increasing fluid volume is associated with a decrease in matrix fiber density, and a lower exclusion volume.<ref name="scallan" /><ref name="stewart-2020a" />

The total fluid volume of the interstitium during health represents about 20% of body weight, but the interstitial space is dynamic and may change in volume and composition during immune responses and in conditions such as [cancer](/source/cancer),  specifically within the interstitium of [tumor](/source/tumor)s.<ref name="wiig" /> The amount of interstitial fluid varies from about 50% of the tissue weight in [skin](/source/skin) to about 10% in [skeletal muscle](/source/skeletal_muscle).<ref name="wiig" /> Interstitial fluid pressure is variable, ranging from −1 to −4 mmHg in tissues like the skin, [intestine](/source/Gastrointestinal_tract) and lungs to 21 to 24 mmHg in the liver, kidney and myocardium. Generally, increasing interstitial volume is associated with increased interstitial pressure and microvascular filtration.<ref name="stewart-2020a" />

The [renal](/source/Kidney) interstitium facilitates solute and water transport between blood and urine in the vascular and tubular elements of the kidneys, and water reabsorption through changes in solute concentrations and [hydrostatic](/source/Hydrostatics) gradients.<ref>{{Cite book |last1=Moe |first1=Orson W. |chapter=Logic of the Kidney |date=2009 |title=Genetic Diseases of the Kidney|veditors= Lifton RP, Somlo S et al.|pages=39–73 |url=https://doi.org/10.1016/B978-0-12-449851-8.00003-6 |access-date=2024-04-22 |publisher=Academic Press|location=New York |doi=10.1016/b978-0-12-449851-8.00003-6 |isbn=978-0-12-449851-8 |last2=Giebisch |first2=Gerhard H. |author-link2=Gerhard Giebisch |last3=Seldin |first3=Donald W. |author-link3=Donald Seldin|url-access=subscription }}</ref><ref>{{Cite book |last1=Breshears |first1=Melanie A. |chapter=The Urinary System |date=2017 |pages=617–681.e1|publisher=Elsevier |doi=10.1016/b978-0-323-35775-3.00011-4 |pmc=7271189 |last2=Confer |first2=Anthony W.|title=Pathologic Basis of Veterinary Disease |isbn=978-0-323-35775-3 }}</ref> The myocardial interstitium participates in [ionic exchanges](/source/Ion_exchange) associated with the spread of electrical events.<ref>{{Cite book |last1=Haschek |first1=Wanda M. |chapter=Cardiovascular and Skeletal Muscle Systems |date=2010 |title=Fundamentals of Toxicologic Pathology |pages=319–376 |url=https://doi.org/10.1016/B978-0-12-370469-6.00012-X |access-date=2024-04-22 |publisher=Academic Press|location=New York |doi=10.1016/b978-0-12-370469-6.00012-x |last2=Rousseaux |first2=Colin G. |last3=Wallig |first3=Matthew A.|isbn=9780123704696 |url-access=subscription }}</ref> The pulmonary interstitium allows for fluctuations in lung volume between inspiration and expiration.<ref>{{Cite book |last1=Matthes |first1=Stephanie A. |title=Comparative Biology of the Normal Lung Extracellular Matrix - Chapter 20 |date=2015 |pages=387–402 |url=https://doi.org/10.1016/B978-0-12-404577-4.00020-5 |publisher=Elsevier|doi=10.1016/b978-0-12-404577-4.00020-5 |last2=Hadley |first2=Ryan |last3=Roman |first3=Jesse |last4=White |first4=Eric S.}}</ref>

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](/source/Human_body), conditions of [inflammation](/source/inflammation), and development of [disease](/source/disease)s,<ref name="wiig" /> as in [heart failure](/source/heart_failure)<ref name="heart" /> and [chronic kidney disease](/source/chronic_kidney_disease).<ref name="kidney" />

==Disease ==
In people with [lung diseases](/source/Respiratory_disease), heart disease, [cancer](/source/cancer), kidney disease, [immune disorder](/source/immune_disorder)s, and [periodontal disease](/source/periodontal_disease), the interstitial fluid and lymph system are sites where disease mechanisms may develop.<ref name=wiig/><ref name=heart/><ref name=kidney/><ref>{{cite journal|pmid=24503053|year=2014|last1=Berggreen|first1=E|title=Lymphatic function and responses in periodontal disease|journal=Experimental Cell Research|volume=325|issue=2|pages=130–7|last2=Wiig|first2=H|doi=10.1016/j.yexcr.2013.12.006}}</ref> Interstitial fluid flow is associated with the migration of cancer cells to [metastatic](/source/Metastasis) sites.<ref name="wiig" /><ref name="munson-2014">{{Cite journal |last1=Munson |first1=Jennifer |last2=Shieh |first2=Adrian |date=2014-08-01 |title=Interstitial fluid flow in cancer: implications for disease progression and treatment |journal=Cancer Management and Research |volume=6 |language=en |pages=317–328 |doi=10.2147/CMAR.S65444|doi-access=free |issn=1179-1322 |pmc=4144982 |pmid=25170280}}</ref> The [enhanced permeability and retention effect](/source/enhanced_permeability_and_retention_effect)s refers to increased interstitial flow causing a neutral or reversed pressure differential between blood vessels and healthy tissue, limiting the distribution of intravenous drugs to tumors, which under other circumstances display a high-pressure gradient at their periphery.<ref name="munson-2014" />

Changes in interstitial volume and pressure play critical roles in the onset of conditions like shock and inflammation.<ref name="scallan" /><ref name="stewart-2020a" /> During [hypovolemic shock](/source/hypovolemic_shock), digestive enzymes and inflammatory agents diffuse to the interstitial space, then drain into the [mesenteric](/source/Mesentery) lymphatic system and enter into circulation, contributing to [systemic inflammation](/source/systemic_inflammation).<ref name="stewart-2020a" /> Accumulating fluid in the interstitial space (interstitial edema) is caused by increased microvascular pressure and permeability, a positive feedback loop mechanism resulting in an associated in increasing the rate of microvascular filtration into the interstitial space.<ref name="stewart-2020a" /> Decreased lymphatic drainage due to blockage can compound these effects. Interstitial edema can prevent oxygen diffusion across tissue and in the brain, kidney and intestines lead to the onset of compartment syndrome.<ref name="stewart-2020a" />

==See also==
* [Extracellular matrix](/source/Extracellular_matrix)
* [Extracellular fluid](/source/Extracellular_fluid)

== References ==
{{reflist|30em}}

Category:Anatomy
Category:Extracellular matrix
Category:Matrices (biology)
Category:Tissues (biology)

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Adapted from the Wikipedia article [Interstitium](https://en.wikipedia.org/wiki/Interstitium) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Interstitium?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.