The term “sequestration” in medicine refers to the process of isolating, separating, or removing a substance or structure from its normal physiological environment. This concept is applied across various scales, from the molecular level to entire organs or large pieces of tissue. This separation typically prevents the sequestered item from functioning or interacting with the rest of the body as it normally would. The medical implications differ widely, depending on whether the process involves blood cells, solid tissue, or microscopic chemical components.
Blood Cell Pooling in Organs
A common and acutely serious application of sequestration involves the rapid pooling of blood cells within an organ, most notably seen in a Splenic Sequestration Crisis (SSC). This medical emergency frequently affects young children diagnosed with Sickle Cell Disease (SCD), where abnormal, crescent-shaped red blood cells become trapped in the spleen’s filtering mechanism. The blockage prevents blood from flowing out, causing the spleen to swell dramatically (splenomegaly).
The accumulation of red blood cells in the enlarged spleen effectively removes a large volume of blood from the general circulation. This sudden loss of circulating blood volume leads to severe anemia and a dangerous drop in blood pressure, which can progress to hypovolemic shock. A diagnosis of SSC is often made when a child with SCD experiences a sudden drop in hemoglobin (typically more than 2 g/dL) alongside a rapid increase in spleen size. Prompt treatment with blood transfusions is required to restore circulating blood volume and prevent a fatal outcome.
The same process can also occur with platelets, leading to thrombocytopenia (low platelet count). In some cases, the liver can also be affected, leading to hepatic sequestration. For patients who experience recurrent splenic sequestration crises, the spleen may need to be surgically removed to eliminate the risk of future life-threatening episodes.
Isolated Non-Functioning Tissue
Sequestration also describes the structural isolation of solid, non-functional tissue, where a segment is cut off from the main healthy architecture. A prime example is Pulmonary Sequestration, a rare congenital condition involving lung tissue that does not connect to the normal bronchial tree or airways. Instead of receiving blood from the pulmonary circulation, this isolated tissue receives its blood supply aberrantly from the systemic circulation, often directly from the aorta.
Because this tissue is disconnected from the respiratory system, it cannot participate in gas exchange. Pulmonary sequestration is broadly divided into intralobar (contained within the visceral pleura) and extralobar (having its own separate pleural sac). This sequestered tissue is often a source of recurrent infections or is discovered incidentally on imaging scans.
Another structural example is a sequestrum, a piece of dead bone tissue separated from the surrounding healthy bone. This separation occurs during necrosis, often as a complication of osteomyelitis (a severe bone infection). The infection causes inflammation that increases pressure within the bone, leading to a lack of blood supply and subsequent bone death. The body attempts to wall off this dead, infected fragment with new bone formation called involucrum. Since the sequestrum is avascular, antibiotics struggle to reach the site, making chronic osteomyelitis difficult to treat and often requiring surgical removal.
Molecular Isolation within the Body
At the microscopic level, sequestration refers to the binding or isolation of ions, molecules, or foreign substances within cells or tissues. This process is often a protective or regulatory mechanism utilized by the body, or it can be induced therapeutically. For instance, cells use internal compartments like the endoplasmic reticulum to sequester calcium ions, tightly controlling the concentration in the rest of the cell to regulate various signaling pathways.
In a clinical setting, molecular sequestration is deliberately achieved using specialized compounds called chelating agents. These agents are designed to tightly bind to toxic substances, such as heavy metals like lead or mercury, preventing them from interacting with biological systems. Once bound, the sequestered toxic metal is made inert and safely excreted through the kidneys.
Furthermore, phase separation involves the sequestration of cellular components, like specific proteins or RNA molecules, into dense, droplet-like structures called biomolecular condensates. This can temporarily isolate and inactivate a protein, such as a transcription factor, regulating gene expression or pausing a biochemical pathway until conditions are met for its release.