View source for Extracellular fluid

{{short description|Body fluid outside the cells of a multicellular organism}}
[[File:Cellular Fluid Content.jpg|thumb|250 px|The distribution of the [[Body water|total body water]] in [[mammals]] between the [[intracellular fluid|intracellular compartment]] and the extracellular compartment, which is, in turn, subdivided into [[interstitium|interstitial]] fluid and smaller components, such as the [[blood plasma]], the [[cerebrospinal fluid]] and [[lymph]]]]

In [[cell biology]], '''extracellular fluid''' ('''ECF''') denotes all [[body fluid]] outside the [[Cell (biology)|cells]] of any [[multicellular organism]]. [[Body water|Total body water]] in healthy adults is about 50–60% (range 45 to 75%) of total body weight;<ref>{{Cite journal |last1=Chumlea |first1=W. Cameron |last2=Guo |first2=Shumei S. |last3=Zeller |first3=Christine M. |last4=Reo |first4=Nicholas V. |last5=Siervogel |first5=Roger M. |date=1999-07-01 |title=Total body water data for white adults 18 to 64 years of age: The Fels Longitudinal Study |journal=Kidney International |volume=56 |issue=1 |pages=244–252 |doi=10.1046/j.1523-1755.1999.00532.x |pmid=10411699 |issn=0085-2538|doi-access=free }}</ref> women and the obese typically have a lower percentage than lean men.<ref name=":1">{{Cite web|url=http://www.anaesthesiamcq.com/FluidBook/fl2_1.php|title=Fluid Physiology: 2.1 Fluid Compartments|website=www.anaesthesiamcq.com|access-date=2019-11-28}}</ref> Extracellular fluid makes up about one-third of body fluid, the remaining two-thirds is [[intracellular fluid]] within cells.<ref>{{cite book| vauthors = Tortora G |title=Principles of anatomy and physiology| url = https://archive.org/details/principlesofan1987tort | url-access = registration |date=1987|publisher=Harper and Row|location=New York|isbn=978-0-06-350729-6|page=[https://archive.org/details/principlesofan1987tort/page/693 693]|edition=5th}}</ref> The main component of the extracellular fluid is the [[#Interstitial fluid|interstitial fluid]] that surrounds cells.

Extracellular fluid is the internal environment of all [[multicellular organism|multicellular animals]], and in those animals with a [[blood]] [[circulatory system]], a proportion of this fluid is [[blood plasma]].<ref>{{cite book|last1=Hillis|first1=David | name-list-style = vanc |title=Principles of life|date=2012|publisher=Sinauer Associates|location=Sunderland, MA|isbn=978-1-4292-5721-3|page=589}}</ref> Plasma and interstitial fluid are the two components that make up at least 97% of the ECF. [[Lymph]] makes up a small percentage of the interstitial fluid.<ref>{{cite book|last1=Pocock|first1=Gillian|last2=Richards|first2=Christopher D. | name-list-style = vanc |title=Human physiology : the basis of medicine|date=2006|publisher=Oxford University Press|location=Oxford|isbn=978-0-19-856878-0|page=548|edition=3rd}}</ref> The remaining small portion of the ECF includes the [[transcellular fluid]] (about 2.5%). The ECF can also be seen as having two components – plasma and lymph as a delivery system, and interstitial fluid for water and solute exchange with the cells.<ref name="pmid_19817339">{{cite journal | vauthors = Canavan A, Arant BS | title = Diagnosis and management of dehydration in children | journal = American Family Physician | volume = 80 | issue = 7 | pages = 692–696 | date = October 2009 | pmid = 19817339 | url = http://www.aafp.org/afp/2009/1001/p692.pdf }}</ref>

The extracellular fluid, in particular the interstitial fluid, constitutes the body's [[milieu intérieur|internal environment]] that bathes all of the [[Cell (biology)|cells]] in the body. The ECF composition is therefore crucial for their normal functions, and is maintained by a number of [[Homeostasis|homeostatic mechanisms]] involving [[negative feedback]]. Homeostasis regulates, among others, the [[pH#Living systems|pH]], [[sodium]], [[potassium]], and [[calcium]] concentrations in the ECF. The volume of body fluid, [[blood glucose]], [[oxygen]], and [[carbon dioxide]] levels are also tightly homeostatically maintained.

The volume of extracellular fluid in a young adult male of 70&nbsp;kg (154 lbs) is 20% of body weight – about fourteen liters. Eleven liters are interstitial fluid and the remaining three liters are plasma.<ref name="Hall">{{cite book|last1=Hall|first1=John| name-list-style = vanc |title=Guyton and Hall textbook of medical physiology|date=2011|publisher=Saunders/Elsevier|location=Philadelphia|isbn=978-1-4160-4574-8|pages=286–287|edition=12th}}</ref>

== Components ==
The main component of the extracellular fluid (ECF) is the interstitial fluid, or tissue fluid, which surrounds the cells in the body. The other major component of the ECF is the intravascular fluid of the [[circulatory system]] called [[blood plasma]].  The remaining small percentage of ECF includes the transcellular fluid. These constituents are often called "[[fluid compartments]]". The volume of extracellular fluid in a young adult male of 70&nbsp;kg, is 20% of body weight – about fourteen liters. {{cn|date=August 2025}}

===Interstitial fluid===
{{See also|Fluid compartments#Interstitial compartment|Lymph#Development}}

Interstitial fluid is essentially comparable to [[blood plasma|plasma]]. The interstitial fluid and plasma make up about 97% of the ECF, and a small percentage of this is [[lymph]]. {{cn|date=August 2025}}

Interstitial fluid is the body fluid between blood vessels and cells,<ref name="Wiig Swartz 2012 pp. 1005–1060">{{cite journal | last1=Wiig | first1=Helge | last2=Swartz | first2=Melody A. | s2cid=11394172 | title=Interstitial Fluid and Lymph Formation and Transport: Physiological Regulation and Roles in Inflammation and Cancer | journal=Physiological Reviews | publisher=American Physiological Society | volume=92 | issue=3 | year=2012 | issn=0031-9333 | pmid=22811424 | doi=10.1152/physrev.00037.2011 | pages=1005–1060}}</ref> containing nutrients from [[Capillary|capillaries]] by diffusion and holding waste products discharged by cells due to [[metabolism]].<ref>{{Cite web |date=2011-02-02 |title=Definition of interstitial fluid |url=https://www.cancer.gov/publications/dictionaries/cancer-terms/def/interstitial-fluid |access-date=2022-03-08 |website=www.cancer.gov |language=en}}</ref><ref name="Diabetes Community, Support, Education, Recipes & Resources 2019">{{cite web | title=Interstitial Fluid – What is the Role of Interstitial Fluid | website=Diabetes Community, Support, Education, Recipes & Resources | date=2019-07-22 | url=https://www.diabetes.co.uk/body/interstitial-fluid.html | access-date=2019-07-22}}</ref> 11 liters of the ECF are interstitial fluid and the remaining three liters are plasma.<ref name="Hall"/> Plasma and interstitial fluid are very similar because water, ions, and small solutes are continuously exchanged between them across the walls of capillaries, through pores and [[Intercellular cleft#Capillary intercellular clefts|capillary clefts]]. {{cn|date=August 2025}}

Interstitial fluid consists of a water solvent containing sugars, salts, fatty acids, amino acids, coenzymes, hormones, neurotransmitters, white blood cells and cell waste-products. This solution accounts for 26% of the water in the human body. The composition of interstitial fluid depends upon the exchanges between the cells in the biological tissue and the blood.<ref name=":0">Widmaier, Eric P., Hershel Raff, Kevin T. Strang, and Arthur J. Vander. "Body Fluid Compartments." ''Vander's Human Physiology: The Mechanisms of Body Function''. 14th ed. New York: McGraw-Hill, 2016. 400–401. Print.</ref> This means that tissue fluid has a different composition in different tissues and in different areas of the body. {{cn|date=August 2025}}

The plasma that filters through the blood capillaries into the interstitial fluid does not contain red blood cells or platelets as they are too large to pass through but can contain some white blood cells to help the immune system. {{cn|date=August 2025}}

Once the extracellular fluid collects into small vessels ([[Lymph capillary|lymph capillaries]]) it is considered to be lymph, and the vessels that carry it back to the blood are called the lymphatic vessels. The lymphatic system returns protein and excess interstitial fluid to the circulation. {{cn|date=August 2025}}

The ionic composition of the interstitial fluid and blood plasma vary due to the [[Gibbs–Donnan effect]]. This causes a slight difference in the concentration of cations and anions between the two fluid compartments. {{cn|date=August 2025}}

===Transcellular fluid===
{{See also|Fluid compartments#Transcellular compartment}}

Transcellular fluid is formed from the [[Cell physiology#Physiological processes|transport activities of cells]], and is the smallest component of extracellular fluid. These fluids are contained within [[epithelial]] lined spaces. Examples of this fluid are [[cerebrospinal fluid]], [[aqueous humor]] in the eye, [[serous fluid]] in the [[serous membranes]] lining [[Body cavity|body cavities]], [[perilymph]] and [[endolymph]] in the inner ear, and [[synovial fluid|joint fluid]].<ref name=":1" /><ref>{{Cite book|title=Physiology | edition = 5th |last=Constanzo|first=Linda S. | name-list-style = vanc |publisher=Elsevier Saunders|year=2014|isbn=9781455708475|pages=264}}</ref> Due to the varying locations of transcellular fluid, the composition changes dramatically. Some of the electrolytes present in the transcellular fluid are [[sodium]] ions, [[chloride ion]]s, and [[bicarbonate]] ions. {{cn|date=August 2025}}

== Function ==
[[File:Cell membrane detailed diagram en.svg|thumb|340px|Cell membrane details between extracellular and intracellular fluid]]
[[File:Sodium-potassium pump and diffusion.png|thumb|340px|Sodium–potassium pump and the diffusion between extracellular fluid and intracellular fluid]]
Extracellular fluid provides the medium for the exchange of substances between the ECF and the cells, and this can take place through dissolving, mixing and transporting in the fluid medium.<ref name="GT">{{cite book|last1=Tortora|first1=Gerard|name-list-style=vanc|title=Principles of anatomy and physiology|date=1987|publisher=Harper & Row|location=New York|isbn=978-0-06-046669-5|pages=[https://archive.org/details/principlesofanat05tort/page/61 61]–62|edition=5th ed. Harper international|url=https://archive.org/details/principlesofanat05tort|url-access=registration}}</ref> Substances in the ECF include dissolved gases, nutrients, and [[electrolyte]]s, all needed to maintain life.<ref>{{cite book|last1=Tortora|first1=Gerard|name-list-style=vanc|title=Principles of anatomy and physiology|date=1987|publisher=Harper & Row|location=New York|isbn=978-0-06-046669-5|page=[https://archive.org/details/principlesofanat05tort/page/17 17]|edition=5th ed. Harper international|url=https://archive.org/details/principlesofanat05tort|url-access=registration}}</ref> ECF also contains materials [[Secretion|secreted]] from cells in soluble form, but which quickly coalesce into fibers (e.g. [[collagen]], [[reticular connective tissue|reticular]], and [[elastic fibres]]) or precipitates out into a solid or semisolid form (e.g. [[proteoglycan]]s which form the bulk of [[cartilage]], and the components of [[bone]]). These and many other substances occur, especially in association with various proteoglycans, to form the [[extracellular matrix]], or the "filler" substance, between the cells throughout the body.<ref>{{Cite book|title=Fundamentals of Biochemistry: Life at the Molecular Level|last1=Voet|first1=Donald|last2=Voet|first2=Judith|last3=Pratt|first3=Charlotte | name-list-style = vanc |publisher=John Wiley & Sons|year=2016|isbn=978-1-118-91840-1|location=Hoboken, NJ|pages=235}}</ref> These substances occur in the extracellular space, and are therefore all bathed or soaked in ECF, without being part of it. {{cn|date=August 2025}}

== Oxygenation ==
One of the main roles of extracellular fluid is to facilitate the exchange of molecular oxygen from blood to tissue cells and for carbon dioxide, CO<sub>2</sub>, produced in cell mitochondria, back to the blood. Since carbon dioxide is about 20 times more soluble in water than oxygen, it can relatively easily diffuse in the aqueous fluid between cells and blood.<ref>{{Cite journal|last1=Arthurs|first1=G.J.|last2=Sudhakar|first2=M|date=December 2005|title=Carbon dioxide transport|url=https://linkinghub.elsevier.com/retrieve/pii/S1743181617305292|journal=Continuing Education in Anaesthesia, Critical Care & Pain|language=en|volume=5|issue=6|pages=207–210|doi=10.1093/bjaceaccp/mki050|doi-access=free|url-access=subscription}}</ref>

However, hydrophobic molecular oxygen has very poor water solubility and prefers hydrophobic lipid crystalline structures.<ref>{{Cite journal|last1=Bačič|first1=G.|last2=Walczak|first2=T.|last3=Demsar|first3=F.|last4=Swartz|first4=H. M.|date=October 1988|title=Electron spin resonance imaging of tissues with lipid-rich areas|url=http://doi.wiley.com/10.1002/mrm.1910080211|journal=Magnetic Resonance in Medicine|language=en|volume=8|issue=2|pages=209–219|doi=10.1002/mrm.1910080211|pmid=2850439|s2cid=41810978|url-access=subscription}}</ref><ref>{{Cite journal|last1=Windrem|first1=David A.|last2=Plachy|first2=William Z.|date=August 1980|title=The diffusion-solubility of oxygen in lipid bilayers|url=https://linkinghub.elsevier.com/retrieve/pii/0005273680904691|journal=Biochimica et Biophysica Acta (BBA) - Biomembranes|language=en|volume=600|issue=3|pages=655–665|doi=10.1016/0005-2736(80)90469-1|pmid=6250601|url-access=subscription}}</ref> As a result of this, plasma lipoproteins can carry significantly more O<sub>2</sub> than in the surrounding aqueous medium.<ref>{{Cite journal|last1=Petyaev|first1=I. M.|last2=Vuylsteke|first2=A.|last3=Bethune|first3=D. W.|last4=Hunt|first4=J. V.|date=1998-01-01|title=Plasma Oxygen during Cardiopulmonary Bypass: A Comparison of Blood Oxygen Levels with Oxygen Present in Plasma Lipid|url=https://portlandpress.com/clinsci/article/94/1/35/76833/Plasma-Oxygen-during-Cardiopulmonary-Bypass-A|journal=Clinical Science|language=en|volume=94|issue=1|pages=35–41|doi=10.1042/cs0940035|pmid=9505864|issn=0143-5221|url-access=subscription}}</ref><ref>{{Cite journal|last=Jackson|first=M. J.|date=1998-01-01|title=Plasma Oxygen during Cardiopulmonary Bypass|url=http://dx.doi.org/10.1042/cs0940001|journal=Clinical Science|volume=94|issue=1|pages=1|doi=10.1042/cs0940001|pmid=9505858|issn=0143-5221|url-access=subscription}}</ref>

If [[hemoglobin]] in erythrocytes is the main transporter of oxygen in the [[blood]], plasma lipoproteins may be its only carrier in the ECF. {{cn|date=August 2025}}

The oxygen-carrying capacity of lipoproteins, reduces in [[ageing]] and [[inflammation]]. This results in changes of ECF functions, reduction of [[Tissue (biology)|tissue]] O<sub>2</sub> supply and contributes to development of tissue [[Hypoxia (medical)|hypoxia]]. These changes in lipoproteins are caused by oxidative or inflammatory damage.<ref>{{Cite journal|last1=Petyaev|first1=Ivan M.|last2=Hunt|first2=James V.|date=April 1997|title=Micellar acceleration of oxygen-dependent reactions and its potential use in the study of human low density lipoprotein|url=https://linkinghub.elsevier.com/retrieve/pii/S0005276097000052|journal=Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism|language=en|volume=1345|issue=3|pages=293–305|doi=10.1016/S0005-2760(97)00005-2|pmid=9150249|url-access=subscription}}</ref>

==Regulation==
The internal environment is stabilised in the process of [[homeostasis]]. Complex homeostatic mechanisms operate to regulate and keep the composition of the ECF stable. Individual cells can also regulate their internal composition by various mechanisms.<ref name="Pocock">{{cite book|last1=Pocock|first1=Gillian|last2=Richards|first2=Christopher D.| name-list-style = vanc |title=Human physiology : the basis of medicine|date=2006|publisher=Oxford University Press|location=Oxford|isbn=978-0-19-856878-0|page=3|edition=3rd}}</ref>

[[File:Basis of Membrane Potential2-en.svg|thumb|350px|Differences in the concentrations of ions giving the membrane potential]]
There is a significant difference between the concentrations of [[sodium]] and [[potassium]] ions inside and outside the cell. The concentration of sodium ions is considerably higher in the extracellular fluid than in the intracellular fluid.<ref name="tortora">{{cite book|last1=Tortora|first1=Gerard|name-list-style=vanc|title=Principles of anatomy and physiology|date=1987|publisher=Harper & Row, International|location=New York|isbn=978-0-06-046669-5|pages=[https://archive.org/details/principlesofanat05tort/page/40 40], 49–50, 61, 268–274, 449–453, 456, 494–496, 530–552, 693–700|edition=5th|url=https://archive.org/details/principlesofanat05tort|url-access=registration}}</ref> The converse is true of the potassium ion concentrations inside and outside the cell. These differences cause all [[cell membrane]]s to be electrically charged, with the positive charge on the outside of the cells and the negative charge on the inside. In a resting neuron (not conducting an impulse) the [[membrane potential]] is known as the [[resting potential]], and between the two sides of the membrane is about −70 mV.<ref>{{cite book|last=Tortora|first=Gerald|name-list-style=vanc|title=Principles of Anatomy and Physiology|year=1987|isbn=978-0-06-046669-5|page=[https://archive.org/details/principlesofanat05tort/page/269 269]|publisher=Harper & Row |url=https://archive.org/details/principlesofanat05tort|url-access=registration}}</ref>

This potential is created by [[sodium–potassium pump]]s in the cell membrane, which pump sodium ions out of the cell, into the ECF,  in return for potassium ions which enter the cell from the ECF. The maintenance of this difference in the concentration of ions between the inside of the cell and the outside, is critical to keep normal cell volumes stable, and also to enable some cells to generate [[action potential]]s.<ref name="GJT">{{cite book|last1=Tortora|first1=Gerard| name-list-style = vanc |title=Principles of anatomy and physiology|date=2011|publisher=Wiley|location=Hoboken, NJ|isbn=978-0-470-64608-3|pages=73–74|edition=13th}}</ref>

In several cell types [[voltage-gated ion channel]]s in the cell membrane can be temporarily opened under specific circumstances for a few microseconds at a time. This allows a brief inflow of sodium ions into the cell (driven in by the sodium ion concentration gradient that exists between the outside and inside of the cell). This causes the cell membrane to temporarily depolarize (lose its electrical charge) forming the basis of action potentials. {{cn|date=August 2025}}

The sodium ions in the ECF also play an important role in the movement of water from one body compartment to the other. When tears are secreted, or saliva is formed, sodium ions are pumped from the ECF into the ducts in which these fluids are formed and collected. The water content of these solutions results from the fact that water follows the sodium ions (and accompanying [[anion]]s) osmotically.<ref>{{cite book| vauthors = Tortora G, Anagnostakos N |title=Principles of anatomy and physiology| url = https://archive.org/details/principlesofan1987tort | url-access = registration |date=1987|publisher=Harper and Row |location=New York |isbn=978-0-06-350729-6 |pages=[https://archive.org/details/principlesofan1987tort/page/34 34], 621, 693–694 |edition=5th }}</ref><ref>{{cite web |url=http://pcwww.liv.ac.uk/~petesmif/petesmif/salivary%20secretion/fluid%20secretion.htm |title=Data |website=pcwww.liv.ac.uk}}</ref> The same principle applies to the formation of many other [[body fluid]]s. {{cn|date=August 2025}}

Calcium ions have a great propensity to [[Calcium metabolism#Function|bind to proteins]].<ref name="stryer">{{cite book|title=Biochemistry.|last1=Stryer|first1=Lubert| name-list-style = vanc |publisher=W.H. Freeman and Co.|isbn=0-7167-2009-4|edition=4th|location=New York|date=1995|pages=255–256, 347–348, 697–698}}</ref> This changes the distribution of electrical charges on the protein, with the consequence that the [[Protein tertiary structure|3D (or tertiary) structure of the protein]] is altered.<ref name=macefield>{{cite journal | vauthors = Macefield G, Burke D | title = Paraesthesiae and tetany induced by voluntary hyperventilation. Increased excitability of human cutaneous and motor axons | journal = Brain | volume = 114 ( Pt 1B) | issue = 1 | pages = 527–540 | date = February 1991 | pmid = 2004255 | doi = 10.1093/brain/114.1.527 | doi-access = free }}</ref><ref>{{cite book |last1= Stryer |first1= Lubert | name-list-style = vanc | title= Biochemistry. |edition= 4th |location= New York |publisher= W.H. Freeman and Co.|date= 1995 |pages= 347, 348 |isbn= 978-0-7167-2009-6 }}</ref> The normal shape, and therefore function of very many of the extracellular proteins, as well as the extracellular portions of the cell membrane proteins, is dependent on a very precise ionized calcium concentration in the ECF. The proteins that are particularly sensitive to changes in the ECF ionized calcium concentration are several of the [[clotting factors]] in the blood plasma, which are functionless in the absence of calcium ions, but become fully functional on the addition of the correct concentration of calcium salts.<ref name=tortora /><ref name=stryer /> The [[Sodium channels|voltage gated sodium ion channels]] in the cell membranes of nerves and muscle have an even greater sensitivity to changes in the ECF ionized calcium concentration.<ref name=CMArmstrong1999>{{cite journal | vauthors = Armstrong CM, Cota G | title = Calcium block of Na+ channels and its effect on closing rate | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 7 | pages = 4154–4157 | date = March 1999 | pmid = 10097179 | pmc = 22436 | doi = 10.1073/pnas.96.7.4154 | bibcode = 1999PNAS...96.4154A | doi-access = free }}</ref> Relatively small decreases in the plasma ionized calcium levels ([[hypocalcemia]]) cause these channels to leak sodium into the nerve cells or axons, making them hyper-excitable, thus causing spontaneous muscle spasms ([[tetany]]) and [[paraesthesia]] (the sensation of "pins and needles") of the extremities and round the mouth.<ref name=macefield /><ref name="CMArmstrong1999"/><ref name=harrison>{{cite book | vauthors = Harrison TR | title =Principles of Internal Medicine | edition = 3rd | pages = 170, 571–579 | location = New York | publisher =  McGraw-Hill Book Company}}</ref> When the plasma ionized calcium rises above normal ([[hypercalcemia]]) more calcium is bound to these sodium channels having the opposite effect, causing lethargy, muscle weakness, anorexia, constipation and labile emotions.<ref name=harrison /><ref name="Waters">{{cite journal| vauthors = Waters M |title=Hypercalcemia|journal=InnovAiT|year=2009|volume=2|issue=12|pages=698–701|doi=10.1093/innovait/inp143}}</ref>

The tertiary structure of proteins is also affected by the [[pH]] of the bathing solution. In addition, the pH of the ECF affects the proportion of the total amount of calcium in the plasma which occurs in the free, or ionized form, as opposed to the fraction that is bound to protein and phosphate ions. A change in the pH of the ECF therefore alters the ionized calcium concentration of the ECF. Since the [[Homeostasis#Blood pH|pH of the ECF is directly dependent on the partial pressure of carbon dioxide]] in the ECF, [[hyperventilation]], which lowers the partial pressure of carbon dioxide in the ECF, produces symptoms that are almost indistinguishable from low plasma ionized calcium concentrations.<ref name=macefield />

The extracellular fluid is constantly "stirred" by the [[circulatory system]], which ensures that the [[Milieu intérieur|watery environment]] which bathes the body's cells is virtually identical throughout the body. This means that nutrients can be secreted into the ECF in one place (e.g. the gut, liver, or fat cells) and will, within about a minute, be evenly distributed throughout the body. Hormones are similarly rapidly and evenly spread to every cell in the body, regardless of where they are secreted into the blood. Oxygen taken up by the lungs from the alveolar air is also evenly distributed at the [[Respiratory system#Gas exchange|correct partial pressure]] to all the cells of the body. Waste products are also uniformly spread to the whole of the ECF, and are removed from this general circulation at specific points (or organs), once again ensuring that there is generally no localized accumulation of unwanted compounds or excesses of otherwise essential substances (e.g. sodium ions, or any of the other constituents of the ECF). The only significant exception to this general principle is the plasma in the [[vein]]s, where the concentrations of dissolved substances in individual veins differ, to varying degrees, from those in the rest of the ECF. However, this plasma is confined within the waterproof walls of the venous tubes, and therefore does not affect the interstitial fluid in which the body's cells live. When the blood from all the veins in the body mixes in the heart and lungs, the differing compositions cancel out (e.g. acidic blood from active muscles is neutralized by the alkaline blood [[Homeostasis#Blood pH|homeostatically]] produced by the kidneys). From the [[Atrium (heart)|left atrium]] onward, to every organ in the body, the normal, homeostatically regulated values of all of the ECF's components are therefore restored. {{cn|date=August 2025}}

==Interaction between the blood plasma, interstitial fluid and lymph==
{{Further |Starling equation |Microcirculation#Capillary exchange}}
[[File:Capillary microcirculation.svg|thumb|Formation of interstitial fluid from blood]]
[[File:Illu lymph capillary.png|thumb |Diagram showing the formation of lymph from interstitial fluid (labeled here as "tissue fluid"). The tissue fluid is entering the blind ends of [[lymph capillaries]] (shown as deep green arrows).]]
The arterial blood plasma, interstitial fluid and lymph interact at the level of the blood [[capillary|capillaries]]. The capillaries are [[Vascular permeability|permeable]] and water can move freely in and out. At the [[arteriole|arteriolar end]] of the capillary the blood pressure is greater than the [[Hydrostatics#Medicine|hydrostatic pressure]] in the tissues.<ref name="Guyton">{{cite book|last1=Hall|first1=John | name-list-style = vanc |title=Guyton and Hall textbook of medical physiology|date=2011|publisher=Saunders/Elsevier|location=Philadelphia|isbn=978-1-4160-4574-8|pages=177–181|edition=12th}}</ref><ref name=tortora /> Water will therefore seep out of the capillary into the interstitial fluid. The pores through which this water moves are large enough to allow all the smaller molecules (up to the size of small proteins such as [[insulin]]) to move freely through the capillary wall as well. This means that their concentrations across the capillary wall equalize, and therefore have no osmotic effect (because the osmotic pressure caused by these small molecules and ions – called the [[Crystalloid solution|crystalloid osmotic pressure]] to distinguish it from the osmotic effect of the larger molecules that cannot move across the capillary membrane – is the same on both sides of capillary wall).<ref name="Guyton" /><ref name=tortora />

The movement of water out of the capillary at the arteriolar end causes the concentration of the substances that cannot cross the capillary wall to increase as the blood moves to the [[Venule|venular]] end of the capillary. The most important substances that are confined to the capillary tube are [[Serum albumin|plasma albumin]], the [[Globulin|plasma globulins]] and [[fibrinogen]]. They, and particularly the plasma albumin, because of its molecular abundance in the plasma, are responsible for the so-called [[Oncotic pressure|"oncotic" or "colloid" osmotic pressure]] which draws water back into the capillary, especially at the venular end.<ref name="Guyton" />

The net effect of all of these processes is that water moves out of and back into the capillary, while the crystalloid substances in the capillary and interstitial fluids equilibrate. Since the capillary fluid is constantly and rapidly renewed by the flow of the blood, its composition dominates the equilibrium concentration that is achieved in the capillary bed. This ensures that the [[Milieu intérieur|watery environment]] of the body's cells is always close to their ideal environment (set by the body's [[Homeostasis|homeostats]]). {{cn|date=August 2025}}

A small proportion of the solution that leaks out of the capillaries is not drawn back into the capillary by the colloid osmotic forces. This amounts to between 2–4 liters per day for the body as a whole. This water is collected by the [[Lymphatic vessel|lymphatic system]] and is ultimately discharged into the left [[subclavian vein]], where it mixes with the venous blood coming from the left arm, on its way to the heart.<ref name=tortora /> The [[lymph]] flows through [[Lymph capillary|lymph capillaries]] to [[lymph node]]s where bacteria and tissue debris are removed from the lymph, while various types of [[white blood cell]]s (mainly [[lymphocyte]]s) are added to the fluid. In addition the lymph which drains the small intestine contains fat droplets called [[chylomicron]]s after the ingestion of a fatty meal.<ref name=stryer /> This lymph is called [[chyle]] which has a milky appearance, and imparts the name [[lacteal]]s (referring to the milky appearance of their contents) to the lymph vessels of the small intestine.<ref name=grays>{{cite book |last1=Williams |first1=Peter L |last2=Warwick |first2=Roger |last3=Dyson|first3=Mary |last4=Bannister |first4=Lawrence H. | name-list-style = vanc |title=Gray's Anatomy| pages=821 |location=Edinburgh|publisher=Churchill Livingstone | edition=37th |date=1989|isbn= 0443-041776 }}</ref>

Extracellular fluid may be mechanically guided in this circulation by the vesicles between other structures.  Collectively this forms the [[interstitium]], which may be considered a newly identified biological structure in the body.<ref>{{cite news|last1=Rettner|first1=Rachel| name-list-style = vanc |title=Meet Your Interstitium, a Newfound 'Organ'|url=https://www.scientificamerican.com/article/meet-your-interstitium-a-newfound-organ/|access-date=28 March 2018|work=[[Scientific American]]|date=27 March 2018}}</ref> However, there is some debate over whether the interstitium is an organ.<ref>{{Cite web|url=https://www.the-scientist.com/?articles.view/articleNo/52168/title/Is-the-Interstitium-Really-a-New-Organ-/|title=Is the Interstitium Really a New Organ? |website=The Scientist }}</ref>

==Electrolytic constituents==
Main [[cations]]:<ref name=ciba>{{cite book | vauthors = Diem K, Lentner C | chapter= Blood – Inorganic substances| title= in: Scientific Tables | edition= 7th |location=Basle, Switzerland |publisher=Ciba-Geigy Ltd. |date=1970 |pages=561–568}}</ref>
* [[Sodium]]  (Na<sup>+</sup>) 136–146 [[Molar concentration#Units|mM]]
* [[Potassium]] (K<sup>+</sup>) 3.8–5.0 mM
* [[Calcium]] (Ca<sup>2+</sup>)  1.0–1.4 mM

Main [[anions]]:<ref name=ciba />
* [[Chloride]] (Cl<sup>−</sup>)  103–112 mM
* [[Bicarbonate]] (HCO<sub>3</sub><sup>−</sup>)  22–28 mM
* [[Phosphate]] (HPO<sub>4</sub><sup>2−</sup>) 0.8–1.4 mM
<ref>Guyton & Hall ''Textbook of Medical Physiology'', p. 5.</ref>

== See also ==
* [[Effective circulating volume]] (ECV)
* [[Fluid compartments]]

== References ==
{{Reflist}}

== External links ==
* [http://www.britannica.com/EBchecked/topic/199041/extracellular-fluid Britannica.com]
* [http://www.biology-online.org/dictionary/Extracellular_fluid Biology-online.org]

{{Renal physiology}}
{{Water-electrolyte imbalance and acid-base imbalance}}
{{Authority control}}

[[Category:Body fluids]]
[[Category:Cell biology]]