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Graphic by Candace Van Auken symobolizing three fluid spaces (within cell, within heart, and 'third space')

Understanding third-spacing

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One of the more difficult aspects of understanding a chronic illness is learning to juggle medical terms.

Recently, someone introduced me to a new one, third-spacing. As I learned more about it, I realized that third-spacing is a useful and powerful concept in trying to understand what happens to at least some of us during anaphylaxis or times when our mast cells are “leaking [patient slang for partial degranulation of mast cells, which can cause various histamine-driven woes, such as diarrhea].”

Before we can understand about third-spacing, we’ll want to consider first– and second–spacing. The basic idea is that there are essentially two places where fluids are found within our bodies: Inside our cells and outside our cells.

Intracellular means inside our cells, and extracellular means outside our cells.

This terminology may be easier to remember if you think about high school sports teams. The intramural teams were the ones that played within the school (for example, home room 1’s volleyball team against home room 2’s). The extramural teams were those athletes who actually got to play students from schools outside their own high school. So, “intra-” means “within” and “extra-” means “outside.”

Intracellular fluid is the “first space,” and extracellular fluid is the “second space.”

In a healthy person, the amount of fluid that is inside and outside our cells stays relatively constant. Small amounts of fluids and solutes [dissolved substances like electrolytes] move back and forth through a cell’s membranes to keep everything in balance. Homeostasis — that word from a long-ago high school biology class — is the technical term for this process of keeping things balanced.

So, normally, when you measure how much fluid a person drinks and compare it to how much urine (and sweat!) a person produces, the two are basically equal.

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All about extracellular fluid

Intracellular fluid makes sense, but what do we mean by extracellular fluid? There are three kinds of extracellular fluids:

Illustration by Candace Van Auken uses an annotated picture of two cells to explain the difference between intracellular fluid (inside cells) and interstitial fluid (between tissue cells).
  1. Interstitial fluid — the fluid which surrounds cells but which does not circulate. The word “interstitial” means pertaining to the small, narrow spaces between tissues.

  2. Plasma — the fluid which flows through our circulatory system along with our blood cells, also called intravascular fluid because it’s inside our vascular system.

  3. Transcellular fluid — which includes things like our digestive juices, our cerebrospinal fluid, and mucus.

Normally, our interstitial fluid makes up about ¾ of our extracellular fluid, and our plasma compromises about ¼. (The transcellular fluid, altogether, only amounts to one or two quarts.) So there’s a fair amount of fluid that belongs in “the spaces between our tissues.” The problem starts when that amount of fluid increases dramatically.

Okay, to summarize, we have some fluids inside our cells (intracellular), some in between our cells (interstitial), some inside our circulatory system (plasma), and little bits of fluid here and there (transcellular). And usually, the amounts of fluid in each “space” stay pretty much the same. Reference [Patlak, Joe, “Fluid Compartments,” Department of Physiology, University of Vermont. 1999].

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But sometimes something goes terribly wrong. Suppose a person is badly injured in a car accident or has anaphylaxis. Under certain conditions, the circulatory system can outright hemorrhage (as with a traumatic injury or burn) or can release much more fluid through the capillaries because of the effects of things like the mast cell mediators being released by degranulating mast cells. In those cases, “third-spacing” can occur. Reference [Morton PG, Fontaine D. Patient Management: Renal System. In: Morton PG, Fontaine D, Hudak CM, Gallo BM, eds. Critical Care Nursing: Lippincott Williams & Wilkins; 2004].

Graphic by Candace Van Auken listing the physiological effects of third-spacing: Blood pressure and urine produced decrease, while heart rate, thirst, and fatigue increase.

Third-spacing is the movement of fluid into interstitial areas, outside the circulatory system. When this fluid moves into the spaces between tissues and organs in the abdomen, we call it ascites or peritoneum. When this fluid moves into the alveoli and interstitial spaces of the lungs, we can that pulmonary edema. When this fluid moves in between the deeper layers of the skin or mucosa or viscera, we call it angioedema [which is the aspect of anaphylaxis that can cause swelling of your eyelids, face, lips, throat, wrists, abdomen, and so on].

And if this “third-spacing” happens aggressively, the circulatory system can lose a significant amount of fluid. The effects on our bodies of this loss of blood plasma can be similar to what happens when someone bleeds profusely — the person becomes hypovolemic, which means that there is a significant decrease in the volume of circulating blood. (And remember, when we’re having anaphylaxis, we can also lose bodily fluids through severe vomiting and diarrhea.) Reference [Nursing Diagnoses associated with Urine Testing.].

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What it all means

In practical terms third-spacing leads to symptoms like:

When we talk about the danger of cardiovascular collapse as a result of anaphylaxis, we’re not talking about the heart being directly affected by the attack — rather the cardiovascular system can’t function when too much plasma is lost to third-spacing. The heart is a fluid pump, and if there's too little fluid entering the heart, it can no longer function.

So in third-spacing, fluids that should be going around and around inside our bodies are instead puddled here and there in places where they are not needed and where our cardiovascular system cannot quickly put them back into circulation.

How do we treat someone who becomes hypovolemic [has decreased blood supply]? The Joint Council of Allergy, Asthma and Immunology’s “Algorithm for the treatment of acute anaphylaxis” recommends that, “Hypotension should be addressed by placement of the patient in a recumbent position, and if necessary, administration of vasopressors and infusions of large volumes of intravenous fluids/colloid to compensate for peripheral vasodilation and for intravascular fluid loss caused by third spacing.” Reference [Lieberman P, Kemp SF, et al. The Diagnosis and Management of Anaphylaxis: An Updated Practice Parameter. J Allergy Clin Immunol. 2005; 115(3):S483–S523].

In other words, lie down (before you fall down!) and get ready for transfusions of fluids and medications to try to stem the outflow of fluid from your circulatory system. Reference [Diehl-Oplinger L, Kaminski MF. Choosing the right fluid to counter hypovolemic shock. Nursing. 2004;34:52-4].

Third-spacing can help us to understand some of the most dangerous symptoms in anaphylaxis, and it can also explain why after an attack we may feature unflattering pools of fluids that seem to take forever to resolve. The circulatory system cannot just suck that fluid back up — it takes time for our lymphatic system to clean up that fluid and slowly put it back into circulation.

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An earlier version of this article appeared in the Fall 2006 issue of The Mastocytosis Chronicles, the quarterly newsletter of the Mastocytosis Society (TMS). My thanks to Ashley Young for first introducing me to the concept of third-spacing.

Page last updated: March 20, 2011

All information contained in this site is one layperson's interpretation of medical journal articles, textbooks, seminars, presentations, and other materials. Nothing that is stated here should carry more weight than the informed and considered opinions of your own highly trained and qualified medical caregivers. The author of this site is not a doctor and has absolutely no authority to prescribe or diagnose.

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