An Analysis of Lipoproteins, Bile Acids, and Red Cell Membranes Associated with Target Cells and Spur Cells in Patients with Liver Disease

Abstract

A B S T R A C T MNlost p)atiellts witlh stable cirrhosis of the alcoholic have "target" red cells; however, a minoritv have "spur" cells and severe hemolytic anemia. These two syndromes were studied in 27 patients with target cells and 17 patients with spur cells, all of whom had advanced cirrhosis. The cholesterol and phospholipi(d content of red cell membranes effectively distinguished target cells from spur cells. Target cells alone were rich in lecithin, and both the cholesterol/phospholipid and cholesterol/lecithin mole ratios were greater in spur cells. The cholesterol/phospholipid mole ratio of both types of red cells correlated closely with the free cholesterol saturation of serum lipoproteins, as defined by the anmount of free clholesterol relative to phospholipid and protein in these lipoproteins. Lecithin: cholesterol acyltransferase (LCAT) activity was decreased in most patients with target cells and spur cells; however, the relationship between this activity and the lipid abnormiialities observed was weak. Serum bile acid levels also correlated poorly witlh serum and cell lipids. However, in patients with target cells the amount of cholic and (leoxycholic acids in serumi was approximately equal to the amount of chenodeoxycholic acid, whereas in patients with spur cells chenodeoxycholic acid (the precursor of lithocholic acid) pre(lominatedl.

Sodium Taurocholate Modifies the Bile Acid-Independent Fraction of Canalicular Bile Flow in the Rhesus Monkey

“…Bile acids are amphipathic and are capable of insertion into the lipid-water interphase as has been suggested for erythrocytes (29)(30)(31), thus resulting in altered membrane permeability to water, inorganic anions, and inert molecules such as inulin. Scanning electron microscopic studies from our laboratory demonstrated irregularities and outpouchings in the canalicular surface membranes Bile Flow (ml/24h) 300 FIGURE 8 Predicted differences in the diffusion permeability constant (K) during administration of7.0 ,umol/min taurocholic acid followed by 3.5 ,umol/min (solid lines) and 3.5 umol/min taurocholic acid followed by 7 of rats infused with bile acids, alterations which might occur through such a bile acid-canalicular membrane interaction and account for some of the differences in choleretic effect which we observed.…”

Modification of the erythrocyte membrane by a non-specific lipid transfer protein

“…Therefore, the protein can be useful to modify normal erythrocytes so as to mimic abnormal red cells, which are often acquired in patients with a liver disease. These hemolytic syndromes are associated with a disordered plasma lipoprotein metabolism, inducing red cell modifications [29][30][31][32][33][34][35][36]. 'Spur' cells are such abnormal erythrocytes, which are characterized by an increased content of cholesterol and PC, be it that the total amount of phospholipids is comparable to that in normal erythrocytes [23,29,33,36].…”

“…Elevated amounts of PC and cholesterol are also found in the so-called 'target' cells. These red cells are characterized by their targeted appearance, due to an increased surface area induced by an elevated lipid content [29,31,33,35]. The amount of cholesterol may range between 25% and 75% above normal in these cells, whereas the enhancement in phospholipid content is approx.…”

“…60%. Changes in phospholipid composition do not concern all phospholipids, but are usually confined to phosphatidylcholine [29,33]. Similar alterations in PC and cholesterol content can be induced in normal red cells by incubating them together with PC/cholesterol in the presence of nonspecific lipid transfer protein ( Fig.…”

Boston city hospital and the thorndike memorial laboratory: the birth of modern haematology

“…They demonstrated an increase in membrane lipid in normal red cells (which formed target cells) and in HS red cells (which became less spheroidal) in a bile salt environment in vitro and in patients with obstructive jaundice resulting in a decrease in osmotic fragility, perhaps enabling these red cells to survive longer in the splenic circulation (Cooper & Jandl, 1969a,b). Cooper also provided the first clear explanation of the lipid abnormalities leading to red cell defects in spur cells and target cells in patients with severe chronic liver disease (Cooper, 1969;Cooper et al, 1972). Aster and Jandl (1964) refined methods using Cr 51 -labelled platelets, and showed the survival and sequestration of platelets in normal subjects, in those with splenomegaly (where the splenic pool may harbour 50-90% of platelets) (Aster, 1966) and in patients with autoimmune thrombocytopenia (Aster & Keene, 1969).…”