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Interstitial Fluid and the Interstitium: Formation and Function

Linda Crampton is an experienced teacher with a first-class honors degree in biology. She writes about the scientific basis of disease.

Dense connective tissue may contain fluid-filled spaces between the collagen fibres.

Dense connective tissue may contain fluid-filled spaces between the collagen fibres.

A Potentially Significant Discovery

Although scientists have been studying the human body for a long time, there is still much that is unknown about our anatomy and physiology. A relatively recent discovery may be very important in adding to our knowledge. According to researchers, the technique used to prepare tissue samples for examination under a microscope has prevented us from seeing a component of the body. This component consists of connected, fluid-filled spaces extending through the body's dense connective tissue. The connected spaces may have many functions and might be involved in the spread of cancer.

The fluid in the connective tissue spaces is called interstitial fluid. Interstitial fluid is important because it bathes cells, supplying them with essential substances and removing harmful ones. A space containing the fluid is known as an interstitial space. The connected spaces form the interstitium. The recent research suggests that the interstitium is far more widespread in the body than many people realize.

The illustration above shows a view of dense connective tissue as it might exist in real life. Instead of being filled with collagen fibres in a compact arrangement, as is generally believed, the tissue may actually contain interstitial spaces between the fibres. These spaces are thought to collapse and lose their fluid as a tissue sample is prepared for examination under a microscope.

Cells in tissues are often (but not always) joined to their neighbours. The junctions are omitted in the video picture above.

Distribution of Fluid in the Body

Fluid in the body is classified according to its location. Extracellular and interstitial fluid are sometimes confused. Technically, interstitial fluid is a type of extracellular fluid.

Intracellular fluid is located within cells. Cells contain structures as well as fluid.

Extracellular fluid is located outside cells. It's generally said to include:

  • plasma within blood vessels
  • lymph within lymph vessels
  • transcellular fluids (cerebrospinal fluid in the brain and spinal cord, synovial fluid in joints, pleural fluid in the lungs, fluid in the digestive and urinary tracts, etc.)
  • interstitial fluid bathing the cells

Transcellular fluids are bordered on either side by a layer of epithelium (a thin tissue that lines canals and compartments in the body).

Interstitial fluid leaves the bloodstream and bathes the cells. It's also known as tissue fluid. Excess tissue fluid drains into lymph vessels.

The tissue space, interstitial space, or interstitium is located between the blood and lymph vessels and the cells. It contains both interstitial fluid and molecules that make up the extracellular matrix or ECM. The ECM provides mechanical, adhesive, and biochemical support for cells.

As can be seen from the information above, the existence of interstitial fluid is not a new discovery. What is new is the idea that it’s more widespread in the body than we realized and is present in additional places to the ones described above.

A highly simplified illustration of the human circulatory system

A highly simplified illustration of the human circulatory system

Arteries carry blood away from the heart and are traditionally coloured red in illustrations. Veins carry blood back to the heart and are traditionally coloured blue. The picture above doesn't show all of the blood vessels in our body. In addition, the capillary networks between arteries and veins are more extensive than the ones shown in the picture.

Blood Vessel Facts

Interstitial fluid comes from the plasma in the capillaries. Blood contains red blood cells, white blood cells, and platelets as well as liquid plasma. It leaves the heart in the aorta. This vessel then branches into multiple arteries. The arteries divide into narrower arterioles, which in turn divide into tiny capillaries within the tissues. Some capillaries are so narrow that red blood cells must squeeze through them in single file.

Some of the plasma leaves the capillaries and enters the spaces around cells, forming interstitial fluid. The fluid contains materials that cells need, such as nutrients. The cells absorb the nutrients and also release waste into the interstitial fluid.

When capillaries leave the tissues, they join to form larger venules. Venules then join to form larger veins. The blood finally drains into the vena cava, which returns blood to the heart.

Hydrostatic and Osmotic Pressure

Two forces control the direction of fluid movement between the capillary and the tissue spaces. One of these is hydrostatic pressure and the other is osmotic pressure.

Hydrostatic Pressure

In biology, hydrostatic pressure is sometimes defined as the pressure of a fluid in an enclosed space. In the capillaries, the enclosed space is the interior of a capillary. Hydrostatic pressure is determined by blood pressure, which is created by the heartbeat. Hydrostatic pressure is greater at the end of a capillary nearest to the pumping chamber of the heart and lower at the other end.

Concentration Gradient

The membranes surrounding and inside cells are semipermeable. They allow some substances to move through them but block others. Substances move across a semipermeable membrane according to their concentration gradient—that is, from a region where they are more concentrated to one where they are less concentrated. Water molecules follow this rule. The movement of water through membranes is so important that special terminology is used to describe it.

Osmotic Pressure

Osmotic pressure can be defined as the ability of a solution to absorb water through a semipermeable membrane. Like other substances, water molecules move from where they are most concentrated to where they are least concentrated. A solution with a low concentration of water molecules has a high attraction for water and is said to have a high osmotic pressure

A more detailed description of fluid movement out of and into a capillary

A more detailed description of fluid movement out of and into a capillary

Capillary-Tissue Fluid Exchange

In the capillaries, the effects of hydrostatic and osmotic pressure may partially or completely cancel each other out. The pressure that is greater wins the "competition" in controlling the direction of water movement through the capillary wall. Hydrostatic pressure decreases during the blood's journey through the capillaries while osmotic pressure stays the same.

At the end of the capillary closest to the artery, the hydrostatic pressure in the blood is higher than the bood's osmotic pressure. The higher hydrostatic pressure "wins" the competition, so fluid moves predominantly out of the capillary. Hydrostatic pressure drives water and dissolved chemicals out of the bloodstream and into the tissue spaces. In this way, interstitial fluid is formed. The process is known as filtration.

In the middle of the capillary, the hydrostatic and osmotic pressures are equal. Neither predominates in moving water out of or into the capillary. A net movement of substances still occurs due to another factor, however. Substances move through the capillary wall according to their concentration gradients. This happens everywhere in the capillary but is often overshadowed by pressure forces.

At the venule end of the capillary, hydrostatic pressure in the blood is lower than the blood's osmotic pressure. Now osmotic pressure wins the competition. Fluid predominately leaves the interstitial space and enters the capillary. This process is known as reabsorption.

Some substances in blood don't move through the capillary wall whatever the effect of pressure. Colloidal proteins are large particles that stay in blood and are thought to make a major contribution to its osmotic pressure. This is why the osmotic pressure of blood is sometimes known as colloidal osmotic pressure, as in the illustration above.

The Lymphatic System

The amount of fluid that leaves the capillaries and enters the tissue spaces is larger than the amount that returns to the capillaries. Excess fluid in the interstitium is collected by the lymphatic system. This system consists of branching vessels, like the circulatory system. The vessels contain lymph instead of blood, however. In addition, the lymphatic system is a one-way system. Small, blind-ended lymph vessels are found in tissue spaces. These lead to wider vessels. Eventually, the lymph drains into a blood vessel.

The walls of the lymph vessels are permeable to fluid and dissolved substances. Lymph is quite similar in composition to blood plasma. Unlike blood, it contains no red blood cells or platelets, but it does contain white blood cells.

The transport of fluid through lymph vessels before it returns to blood vessels offers some advantages. Lymph nodes are enlarged areas in lymph vessels. They remove pathogens (microbes that cause disease), cancer cells, and other harmful particles. They are an important part of the immune system.

Composition and Functions of Interstitial Fluid

Interstitial fluid is a solution of water containing solutes (dissolved substances). It's often said that capillaries supply cells with nutrients and remove wastes from them. The interstitial fluid plays a more direct role in this process, however, since it forms a liquid connection between capillaries and cells. Major components of the interstitial fluid include the following substances:

  • sugars: simple carbohydrates, such as glucose
  • salts: ions and ionic compounds
  • amino acids: the building blocks of proteins
  • fatty acids: important building blocks of fats
  • coenzymes: molecules that help enzymes do their job
  • signaling molecules, which pass messages from one cell to another

Interstitial fluid gives the cells chemicals that they need in order to survive, including nutrients and oxygen. It also transports signaling molecules between cells. As their name suggests, signaling molecules transport signals to other cells, triggering specific behaviours. Wastes, including carbon dioxide and urea, are transported away from cells by the interstitial fluid.

Dense Connective Tissue

An intriguing study may have discovered more about the interstitium, at least as it exists in dense connective tissue. The study was performed by a group of researchers from various U.S. institutions.

Dense connective tissue provides strength where it's needed in the body. The tissue contains fibres of a protein called collagen. In the traditional view of the tissue, these fibres are positioned in a compact arrangement. The tissue is found in many places in the body, including the lining of the digestive tract, urinary tract, and lungs, around the blood vessels, under the skin, in tendons and ligaments, and surrounding the muscles.

Based on their new observations, the researchers say that dense connective tissue actually contains interstitial spaces as well as collagen fibres. They say that the traditional method of examining pieces of body tissue collapses the fluid spaces in the tissue and causes loss of the fluid. The tissue undergoes a special process before it's examined under a microscope. It's subjected to many stresses, including the addition of a preservative, dehydration, and staining. These steps often produce a beautiful specimen to observe, but the image may not be a completely accurate view of the living tissue.

Dense connective tissue as viewed under a compound microscope

Dense connective tissue as viewed under a compound microscope

Magnification Endoscopy

The recent discoveries of interstitial spaces were made by using a relatively new method of examining magnified tissue. The method involved the use of an endoscope. An endoscope is a thin tube with an attached light and a camera. Doctors use it to examine tubular structures in living patients. The endoscope used by the researchers was an advanced type, however. It was able to provide a magnified view of living tissues inside patients.

The impressive technique used by the researchers is known as probe-based confocal laser endomicroscopy. At the start of this process, a fluorescent dye is administered to the patient. A low-powered laser beam is then directed at the relevant area of tissue. As a result, fluorescent light travels from the tissue to the imaging device, creating a magnified picture. The doctor in the video below says that the magnification is so great that items at the subcellular level can be seen.

The Recent Discoveries

The recent discoveries began when doctors were examining the bile ducts of a cancer patient with a magnifying endoscope. They wanted to see if the cancer had spread. As they investigated, they discovered some interconnected spaces in the patient's submucosal tissue that nobody had noticed or described before.

The doctors took samples of the tissue to examine under a traditional microscope. When they examined the prepared slide, they saw that the spaces that they had previously observed had disappeared. They did see very thin spaces in the tissue, however. Other researchers have noticed these thin spaces in human tissue viewed under a microscope as well. Until now, the spaces have been classified as tears in the tissue. They may in fact be collapsed interstitial spaces.

In their study, the researchers used probe-based confocal laser endomicroscopy to examine tissue in twelve patients. The pancreas and bile ducts were removed from the patients as part of a cancer treatment. Just before the removal, however, the bile ducts were examined by endomicroscopy. The researchers later examined other body tissues using the same technique. They found interstitial spaces in all of the tissues.

As a result of their discoveries, the researchers say that spaces containing interstitial fluid are present in dense connective tissue and exist in more areas of the body than was previously realized. They also say that the interstitial spaces are connected to one another.

A New Definition of Interstitium

The latest discoveries about interstitial fluid are not entirely new, but they provide novel and perhaps important details. Although the word "interstitium" was in use before the discoveries, the information about its nature may have been incomplete. Additional scientists have said that an interstitial space containing fluid may be connected to many other fluid-filled spaces. The research described in this article has provided more detail with respect to this idea. The scientists involved in the latest studies have found interstitium in unexpected places and have made new observations about its presence. The scientists say that the interstitium is so widespread that it should be classified as an organ.

Intriguing and Perhaps Important Information

The recent discoveries are exciting and seem to be respected by other scientists. Some scientists feel that calling the interstitium an organ is premature, however. It will be interesting to see whether other research teams can detect the fluid-filled spaces in connective tissue.

The results of single research projects are often respected in science if they are well designed. A discovery is more likely to be accurate if it's replicated by other scientists, however. Researchers may make mistakes in their procedure, be unaware of a vital requirement for accuracy, or inadvertently use equipment or techniques that produce misleading results. These risks are reduced—though not eliminated—when multiple teams of researchers explore a topic.

The discovery of connected and fluid-filled interstitial spaces could be very important with respect to understanding the human body and disease. The researchers suspect that a widespread interstitium could help cancer to spread through the body, for example. I hope more information is obtained by both the original researchers and by others. Whether or not the interstitium is officially classified as an organ and whether or not it's as widespread as the researchers believe, it's probably a very important component of the body.


  • Information about interstitial fluid from Physiological Reviews (published by the American Physiological Society)
  • Body fluids and fluid compartments from and Rice University
  • A Review of Probe-Based Confocal Laser Endomicroscopy for Pancreaticobiliary Disease from Clinical Endoscopy
  • A newfound "organ" from EurekAlert (An American Association for the Advancement of Science publication)
  • Structure and Distribution of an Unrecognized Interstitum in Human Tissues from Nature Scientific Reports

This content is accurate and true to the best of the author’s knowledge and is not meant to substitute for formal and individualized advice from a qualified professional.

Questions & Answers

Question: How does interstitial fluid form?

Answer: Interstitial fluid is formed by the liquid that escapes from blood vessels, enters the tissues, and bathes the cells. The factors that control the direction of fluid flow between the blood vessels and the tissues are described in the article.

Question: Why is it important to remove interstitial fluid from tissues?

Answer: It would probably be better to ask why excess interstitial fluid must be removed. The fluid has important functions and must be present. An excessive amount of the fluid could cause problems, though. For example, it could put pressure on body structures, damaging them. The large amount of fluid might also interfere with the passage of materials into and out of cells.

© 2018 Linda Crampton


Linda Crampton (author) from British Columbia, Canada on May 28, 2018:

Thanks for the visit, Peggy. I always appreciate your comments.

Peggy Woods from Houston, Texas on May 28, 2018:

The new probe-based confocal laser endomicroscopy information is most interesting. Getting to see cancer at earlier stages should help bring about earlier and hopefully more successful treatments.

Learning about the interstitium was also interesting. Your research into topics is always informative.

Linda Crampton (author) from British Columbia, Canada on April 18, 2018:

I agree, Manatita. If we find a new body component, it's probably useful to at least some extent. The article was based on interstitial fluid, but lymph is an interesting liquid to investigate, too. Thanks for the visit.

manatita44 from london on April 17, 2018:

All bodily components should be useful to some extent. Fascinating research into interstitial fluids and their spaces in between.

Dr Morse, the holistic practitioner, says that blood and lymph or rather the stagnation of, can lead to major problems in the body. Is your research connected with lymph or is it just extracellular fluid as you say?

Linda Crampton (author) from British Columbia, Canada on April 11, 2018:

Hi, Bede. I think the magnifying endoscope is a very exciting device. It might lead to some wonderful advances in medicine. Thanks for the visit.

Bede from Minnesota on April 11, 2018:

I probably learned of some of these amazing realities about the human body years ago… but, how much more I appreciate it now: “I am fearfully and wonderfully made.” The movement of the blood into smaller and smaller capillaries and then eventually going back to the heart is very impressive. To me, it is reminiscent of the water cycle found in nature.

The new discovery with the magnifying endoscope is also exciting. Let’s hope it will open fresh horizons for medical treatment. Thanks for the interesting article.

Linda Crampton (author) from British Columbia, Canada on April 09, 2018:

Thank you for such a lovely comment, Jackie! I appreciate it very much.

Jackie Lynnley from the beautiful south on April 09, 2018:

Well you are the best Linda when teaching us all these unbelievably interesting things. It is like getting it hot off the press with you! We can always be sure it is worth our time reading.

Another great article!

Linda Crampton (author) from British Columbia, Canada on April 09, 2018:

Hi, Mary. It's exciting that scientists are learning more about the human body. I hope the discoveries lead to new treatments for disease.

Linda Crampton (author) from British Columbia, Canada on April 09, 2018:

I appreciate your kindness, Devika. I think that biology topics related to health are important. There seems to be a lot more to discover about the human body.

Linda Crampton (author) from British Columbia, Canada on April 09, 2018:

Thanks, Larry. I never get tired of learning about human biology! I think it's a fascinating topic.

Linda Crampton (author) from British Columbia, Canada on April 09, 2018:

Hi, Bill. I appreciate your visit and comment!

Linda Crampton (author) from British Columbia, Canada on April 09, 2018:

Thank you very much, Flourish. The news is certainly exciting. I'm interested in seeing what else is discovered about the interstitium.

Linda Crampton (author) from British Columbia, Canada on April 09, 2018:

Thanks for the comment and for sharing the interesting information, Chris. I enjoy learning about your profession!

Mary Norton from Ontario, Canada on April 09, 2018:

This is one discovery I follow now as it gives us more knowledge of the complexity of our bodies. It is amazing that in spite of the advances we have had in this field, there are still things we are discovering. I am sure that the implications of this discovery will be studied more and we will definitely benefit from it.

Bill Holland from Olympia, WA on April 09, 2018:

It was all news to me, Linda! I had heard of some of the words, but had no clue what they meant. My education continues at the School of Linda!

Devika Primić from Dubrovnik, Croatia on April 09, 2018:

A fascinating hub! You write valuable information on many different health issues. It is always of ones benefit to know more about health issues and you know how to do that for your readers. I hope you get many more comments. Thank you for another well-informed hub.

Larry W Fish from Raleigh on April 09, 2018:

Wow, what an interesting read, Linda. I never get tired of reading your articles of illnesses and the human body. You have taught me so much that I did not know. Keep up the interesting reading.

FlourishAnyway from USA on April 09, 2018:

You always do such a thorough job introducing and explaining a topic. I had read an article heralding this as a new organ in plain sight but it was lacking in explanatory detail, unlike yours, and obviously they may have missed some important points since they were already referring to it as an organ.

Chris Mills from Traverse City, MI on April 09, 2018:

Excellent information, Linda. Once again you have touched on my profession. We who practice histology are the ones who remove the interstitial fluid by processing the tissue through varying grades of alcohol including three at 100 percent. The goal is to remove all water so it can be replaced by liquid paraffin. This enables us to cut thin sections of the tissue to go onto the glass slide.