Bile salts and cholesterol in the pathogenesis of target cells in obstructive jaundice

Abstract

Free cholesterol is in rapid equilibrium between serum lipoproteins and red cells. The level of red cell cholesterol is influenced by bile salts, which shift the serum/cell partition of free cholesterol to the cell phase and which inhibit the cholesterol-esterifying mechanism. During incubation in normal serum possessing an active cholesterol-esterifying mechanism, red cells lose cholesterol and surface area and thereby become more spheroidal and less resistant to osmotic lysis. When exposed to serum from patients with obstructive jaundice or to normal serum with added bile salts, red cells accumulate cholesterol and increase their surface area, thereby acquiring a flattened shape and an increased resistance to osmotic lysis. The described gains and losses of red cell cholesterol and surface area do not involve metabolic injury and occur with no significant change in phospholipid content. The red cells of patients with obstructive jaundice are flat and osmotically resistant and have an increased cholesterol:phospholipid ratio. When transfused into normal subjects these "target cells" rapidly lose their osmotic resistance. Similarly, normal cells acquire osmotic resistance in the circulation of patients with obstructive jaundice. These reversible changes in shape occur with half-times of about 9 and 24 hr, respectively, and occur without impairing cell viability. These studies indicate that the red cell membrane accumulates cholesterol in obstructive jaundice as a consequence of the elevated levels of bile salts. The resulting increment in red cell surface area is responsible for the physical properties and appearance of target cells. These observations substantiate Murphy's findings in vitro indicating that cholesterol is an important determinant of red cell shape and that its content in the cell membrane may vary independently from the phospholipids. Presumably any process or disorder affecting cholesterol exchange in vivo is capable of critically modifying the shape and behavior of red cells.