Fluid movement in the body is highly regulated, but sometimes fluid shifts from its normal circulatory pathways into an area where it can no longer be used for blood flow. This phenomenon is termed “third spacing,” which is the accumulation of fluid in the interstitial spaces or body cavities, such as the abdomen (ascites) or the chest cavity (pleural effusion). When this happens, the fluid is effectively trapped and becomes functionally unavailable to the circulatory system. This often leads to a drop in overall blood volume and symptoms of dehydration despite the body containing excess fluid.
Understanding Fluid Movement and the Third Space
Fluid is constantly exchanged between the blood vessels (intravascular space) and the tissues (interstitial space) through the thin walls of the capillaries. This movement is controlled by a delicate equilibrium known as the Starling forces, which are comprised of two opposing types of pressure. Hydrostatic pressure is the physical pressure exerted by the blood volume against the capillary walls, acting to push fluid out of the vessel into the surrounding tissue. Oncotic pressure is a pulling force created primarily by large proteins, mainly albumin, that are too large to easily escape the capillary.
This oncotic pressure acts to draw fluid back into the vessel, balancing the outward push of hydrostatic pressure. In a healthy state, these forces ensure a net balance, with filtered fluid returned to circulation by the lymphatic system. Third spacing occurs when this balance is severely disrupted, causing excessive filtration of fluid out of the capillaries that the lymphatic system cannot handle. This disruption results from hydrostatic pressure becoming too high, oncotic pressure becoming too low, or the capillary walls becoming abnormally leaky.
Causes Related to Vessel Damage and Inflammation
A primary cause of third spacing is increased permeability of the capillary walls, allowing fluid and large proteins like albumin to leak into the interstitial space. This is often called “capillary leak syndrome” and is triggered by widespread inflammation. Severe systemic inflammatory responses, such as those seen in sepsis, extensive burns, or major trauma, release powerful chemical signals.
Inflammatory mediators, including specialized proteins called cytokines, act directly on the endothelial cells lining the capillaries. These chemical signals cause the junctions between the cells to widen, creating gaps in the vessel wall. When these gaps form, not only does water leak out, but albumin escapes as well. The loss of albumin reduces the oncotic pressure inside the vessel while simultaneously increasing the oncotic pressure in the interstitial space, pulling more fluid out of circulation.
The resulting rapid loss of volume from the blood vessels can lead to low blood pressure and hypovolemic shock. Major burns cause this effect locally by damaging vascular tissue, while sepsis causes a widespread, systemic capillary leak.
Causes Related to Systemic Pressure and Protein Changes
Other common causes of third spacing involve chronic conditions that disrupt Starling forces systemically without widespread inflammation.
Increased Hydrostatic Pressure
One major pathway is an increase in hydrostatic pressure, which is the pushing force inside the capillaries. Congestive Heart Failure (CHF) is a classic example, where the heart’s inability to pump blood forward effectively causes blood to back up into the venous system. This venous congestion elevates the pressure inside the veins and, subsequently, the capillaries, dramatically increasing the outward hydrostatic pressure. The sustained high pressure overwhelms the ability of the oncotic pressure to pull fluid back in, forcing large amounts of fluid out into the surrounding tissues, especially in the lower extremities. Kidney failure also contributes by causing the body to retain excessive salt and water, which increases total blood volume and capillary hydrostatic pressure.
Decreased Oncotic Pressure
A second major systemic pathway is a significant decrease in the oncotic pressure, the pulling force that keeps fluid within the vessels. This is primarily caused by hypoalbuminemia, a low concentration of the protein albumin in the blood. Advanced liver disease, such as cirrhosis, severely impairs the liver’s synthetic function, resulting in a dramatic drop in circulating albumin levels. With less albumin to exert the inward-pulling oncotic pressure, the remaining hydrostatic pressure becomes unopposed, leading to fluid leakage, often accumulating in the abdominal cavity as ascites.
Protein loss can also be due to conditions causing excessive excretion, such as nephrotic syndrome, a kidney disorder where the filtering units (glomeruli) are damaged. This damage allows large amounts of albumin to pass into the urine, steadily depleting the protein from the circulatory system. Severe, prolonged malnutrition also results in hypoalbuminemia because the body lacks the raw materials (amino acids) to manufacture new proteins.