Third spacing describes the abnormal accumulation of fluid in body compartments that are not involved in dynamic circulation. Body fluid is usually distributed across three main areas: the intracellular space, the intravascular space (inside blood vessels), and the interstitial space (surrounding cells). Third spacing occurs when fluid shifts out of the blood vessels and pools in a non-functional area, such as the peritoneal cavity (ascites) or the pleural space (pleural effusion). This abnormal shift effectively removes fluid from the circulation, which can dangerously decrease the total volume of blood. The trapped fluid is unavailable to maintain blood pressure or support organ function, leading to systemic issues like hypovolemia and impaired tissue perfusion.
How Fluid Movement Is Regulated
The movement of fluid between the intravascular space and the interstitial space is governed by Starling forces. These forces determine whether fluid filters out of the capillary into the tissues or is reabsorbed back into the vessel. The two primary forces involved are hydrostatic pressure and oncotic pressure.
Hydrostatic pressure is the “pushing” force exerted by the blood against the capillary walls. This force tends to push fluid out of the blood vessel and into the surrounding interstitial space. Conversely, oncotic pressure is the “pulling” force, created primarily by large plasma proteins, mainly albumin, which are too large to easily escape the capillary.
Albumin creates an osmotic gradient, attracting water back into the blood vessel. Under normal conditions, these forces are nearly balanced, with the lymphatic system managing slight net filtration into the interstitial space. Third spacing results from a significant disruption in this balance, caused by excessive hydrostatic pressure, weakened oncotic pressure, or damage to the capillary wall itself.
Causes Related to Vessel Leakage
One immediate cause of third spacing is the rapid leakage of fluid from the blood vessels due to the compromise of the capillary wall structure. This is often seen in acute, systemic inflammatory conditions where the endothelial cells lining the vessels separate, dramatically increasing permeability.
In severe trauma or major surgery, the body’s generalized inflammatory response releases chemical mediators that damage the normally tight junctions between endothelial cells. This “capillary leak” permits not only water but also large plasma proteins, like albumin, to escape rapidly into the interstitial space. The loss of protein further diminishes the intravascular oncotic pressure, accelerating the fluid shift out of circulation.
Sepsis, a life-threatening response to infection, is a prominent cause of this widespread vascular leakage. The systemic inflammation associated with sepsis causes significant degradation of the endothelial glycocalyx, a gel-like layer protecting the inner surface of the blood vessels. When this protective layer is stripped away, the vessel becomes pathologically leaky, leading to massive fluid and protein loss into the tissues.
Severe burns cause a localized, yet massive, form of third spacing due to direct thermal damage to the capillaries. The intense heat causes immediate and extensive destruction of the vessel walls in the affected area. Plasma proteins and fluid pour out of the damaged vessels and accumulate in the burned tissue, leading to profound localized edema and systemic hypovolemia.
Causes Related to Systemic Organ Failure
Chronic diseases and systemic organ failure cause third spacing by altering the fundamental components of Starling forces over time. These conditions typically affect the concentration of plasma proteins or the systemic pressure within the circulation, rather than through acute vessel damage.
Liver failure, especially cirrhosis, is a common cause because the liver is the primary site of albumin synthesis. When the liver is damaged, it cannot produce enough albumin, leading to a condition called hypoalbuminemia. This lack of circulating protein severely lowers the intravascular oncotic pressure, reducing the “pull” that keeps fluid inside the blood vessels. Fluid leaks into the third space, often manifesting as ascites in the abdomen.
Kidney diseases, such as nephrotic syndrome, cause third spacing by allowing plasma proteins to be lost from the body. Damaged glomeruli in the kidneys become overly permeable, allowing large amounts of albumin to be filtered out and excreted in the urine. This continuous loss of albumin results in a chronically low oncotic pressure, which drives fluid out of the capillaries and into the interstitial tissues.
Congestive Heart Failure (CHF) primarily causes third spacing by increasing the hydrostatic pressure within the capillaries. When the heart’s pumping action is inefficient, blood backs up into the venous system and subsequently into the capillaries. This venous congestion dramatically increases the capillary hydrostatic pressure, creating an excessive “push” that forces fluid out into the tissues, leading to generalized edema.
Severe malnutrition, particularly protein-calorie malnutrition, also contributes to third spacing through a lack of the necessary building blocks for plasma proteins. Insufficient dietary protein intake prevents the liver from synthesizing adequate amounts of albumin. This results in decreased oncotic pressure, allowing fluid to accumulate in the interstitial spaces and presenting as widespread edema.