RBC morphology offers visual clues about a patient’s health. When red cells change their characteristic smooth, biconcave disc shape, it signals poikilocytosis, often linked to systemic illness. The burr cell, technically known as an echinocyte, is a significant finding among abnormal red blood cell shapes. Its presence indicates a serious systemic failure or metabolic disturbance, prompting investigation into conditions affecting the kidneys, liver, or metabolism.
Morphology and Identification of Burr Cells
Burr cells are easily recognizable under a microscope due to their distinctive, spiky appearance, caused by multiple small projections (spicules) emanating from the cell surface. These spicules are typically short, blunt, and distributed uniformly across the entire cell circumference, giving the cell a serrated outline. They generally maintain a size and central pallor similar to a normal red blood cell. Observing these cells requires examining a stained peripheral blood smear at high magnification.
It is necessary to distinguish burr cells (echinocytes) from acanthocytes, often called spur cells, as they indicate different disease processes. Acanthocytes have fewer spicules that are long, pointed, and irregularly distributed on the cell surface, lacking the uniform appearance of burr cells. Acanthocyte formation is often tied to specific lipid metabolism disorders like abetalipoproteinemia or certain forms of severe liver disease.
Primary Conditions Indicated by Burr Cells
The presence of burr cells is a strong indicator of several systemic conditions. The most frequent association is with severe kidney dysfunction, known as uremia. In this condition, the kidneys fail to properly filter waste products from the blood, causing a buildup of toxins that directly alter the red blood cell membrane.
Another major association is with microangiopathic hemolytic anemia (MAHA), a group of disorders where small blood vessels are damaged, causing red cells to be mechanically fragmented. Although burr cells are a feature, they are often seen alongside fragmented red cells (schistocytes) in conditions like Thrombotic Thrombocytopenic Purpura (TTP) or Hemolytic Uremic Syndrome (HUS).
Severe liver disease, particularly alcoholic liver disease, is also a common cause of burr cell formation. The liver’s failure to regulate lipid metabolism leads to changes in the plasma environment, which subsequently changes the lipid composition of the red cell membrane. Metabolic disturbances, such as severe hypophosphatemia (low phosphate levels) or the hereditary condition Pyruvate Kinase Deficiency, can also cause echinocyte formation.
Cellular Mechanisms Leading to Burr Cell Formation
The deformation of a red blood cell into a burr cell is ultimately caused by changes that affect the outer layer of the cell’s membrane relative to the inner layer. This mechanism is known as the bilayer couple hypothesis, where expansion of the outer lipid leaflet causes the membrane to buckle outward, forming spicules. This alteration can be triggered by either a direct chemical interaction with the membrane lipids or an internal energy crisis within the cell.
ATP Depletion
One primary mechanism involves the depletion of adenosine triphosphate (ATP), the cell’s main energy source. When ATP levels drop, such as in severe systemic stress or specific enzyme deficiencies like Pyruvate Kinase Deficiency, the cell’s internal scaffolding stiffens and the membrane’s stability is compromised, leading to spicule formation.
Toxin and Lipid Interaction
The second significant mechanism is the interaction of metabolic waste products or abnormal lipids with the cell membrane. In uremia, accumulated toxins like indoxyl sulfate and p-cresol directly interact with the red cell membrane, triggering the characteristic shape change. Similarly, in liver disease, an imbalance of lipids in the blood can result in the incorporation of abnormal lipid components into the outer leaflet of the red cell membrane.