First, Etiology
The most common anemia in liver disease is Laennec cirrhosis, biliary cirrhosis, hemochromatosis, post-hepatic cirrhosis, acute hepatitis, and hepatolenticular degeneration, which can also cause anemia in liver disease.
Second, Pathogenesis
The pathogenesis of anemia in liver disease has not been fully understood, but it has been proven to be related to the following factors:
1. Deficiency of hematopoietic factors:The liver is an important organ of the body's metabolism and plays an important role in maintaining the normal physiological function of the blood system. Including:
(1) Storage of hematopoietic raw materials: Folic acid, vitamin B12, iron preparations, and many proteins and lipids are stored and used in the liver.
(2) Synthesis of coagulation factors: Coagulation factors I, II, V, VII, IX, X, XII, XIII, and so on are all synthesized in the liver.
(3) Partial secretion of erythropoietin: The liver is the main site for the renal secretion of erythropoietin.
Therefore, when the above functions are impaired in liver disease, it can cause folic acid and vitamin B12 deficiency leading to megaloblastic anemia; coagulation mechanism disorders causing bleeding, leading to iron deficiency anemia.
2. Shortened erythrocyte lifespan:A shortened erythrocyte lifespan can be seen in liver diseases such as alcoholic liver disease, biliary cirrhosis, obstructive jaundice, infectious hepatitis, and so on. Even in the above diseases without anemia, a shortened erythrocyte lifespan may occur, and about 70% of liver disease patients have a shortened erythrocyte lifespan. The exact cause of the shortened erythrocyte lifespan in liver disease is still not fully understood. When patients and healthy people are cross-transfused, the lifespan of the patient's erythrocytes in the healthy body is significantly prolonged, and the lifespan of the healthy person's erythrocytes in the patient's body is also shortened. This suggests that the shortened erythrocyte lifespan is caused by extracellular hemolysins. Research has shown that the following factors are related to the shortened erythrocyte lifespan of patients:
(1) Spleen enlargement: Congestive splenomegaly in liver disease can be accompanied by splenic hyperfunction, causing excessive destruction of erythrocytes in the spleen. The method of using 51Cr-labeled erythrocytes to test has proved that the lifespan of erythrocytes in patients with splenomegaly is significantly shorter than that in patients without splenomegaly. Foreign experiments have shown that in patients with myeloproliferative diseases, for every 1kg increase in the weight of spleen enlargement, the daily destruction of erythrocytes in the spleen increases by 1% of blood cell volume.
(2) Abnormal erythrocyte metabolism: In patients with liver disease, the erythrocyte pentose phosphate pathway metabolism is low, resulting in reduced intracellular reduced glutathione production, easy oxidation of hemoglobin, and the formation of Heinz bodies, leading to the easy destruction of erythrocytes. The low pentose phosphate pathway metabolism may be related to the decrease of nicotinamide adenine dinucleotide phosphate (NADP) or other unknown reasons. In addition, patients often have hypophosphatemia, which leads to a decrease in intracellular ATP levels and reduced membrane deformability, which can cause hemolysis.
(3) Abnormal red blood cell membrane lipids: The red blood cell membrane is composed of a bilayer of lipids. The outer side of the membrane is mainly free cholesterol and two phospholipids, namely phosphatidylcholine and sphingomyelin. The inner side of the membrane is mainly phosphatidylserine and phosphatidylethanolamine. In patients with hepatitis, cirrhosis, and obstructive jaundice, the free cholesterol and phosphatidylcholine on the outer side of the red blood cell membrane are increased by 20% to 50% compared to normal, leading to an increase in the surface area of red blood cells and forming specific thin macrocytes and target cells, causing them to stay for too long in the sinusoids of the spleen and be easily engulfed and destroyed by mononuclear macrophages. In addition, the activity of sialidase in patients with bile duct obstruction increases, causing an increase in the secretion of sialic acid on the red blood cell surface, leading to a decrease in red blood cell vitality.
(4) Acanthocyte hemolytic anemia: The cholesterol on the red blood cell membrane of patients is significantly increased, while the phosphatidylcholine does not increase correspondingly, leading to a decrease in the deformability of red blood cells. When passing through the spleen, the cell membrane is engulfed by mononuclear macrophages in pieces, causing the surface area of red blood cells to continuously decrease and finally become acanthocytes. The mechanism of red blood cell membrane lipid changes is known to be related to the following factors:
① The ratio of cholesterol to phospholipid in low-density lipoprotein in blood: The mature red blood cells themselves cannot synthesize lipids and need to rely on lipoproteins in plasma for renewal. Abnormal lipoproteins in plasma change the lipid components on the red blood cell membrane. However, why some patients do not have an abnormal mechanism of plasma lipoprotein is still unclear.
② Decreased activity of phosphatidylcholine-cholesterol acyltransferase in plasma.
③ Bile retention in plasma.
④ Other factors: Alcoholic liver disease patients often produce alcohol-induced vitamin E deficiency, leading to a decrease in various unsaturated fatty acids on the red blood cell membrane, causing membrane deformation and decreased resistance to oxidants. In addition, portal hypertension and splenomegaly may also be a partial cause of hemolysis in liver disease.
3. Decreased bone marrow hematopoietic function:The plasma iron turnover rate, intracellular iron utilization rate, and intracellular iron turnover rate in most liver disease patients are normal or decreased, indicating a decrease in bone marrow hematopoietic function. However, there are also reports of increased cases, which may be related to whether the patient has complications. Alcoholic liver disease patients have a significantly suppressed red blood cell hematopoietic function. This is manifested by megaloblastic changes in the erythroblasts of the bone marrow, vacuoles in the cytoplasm of erythroblasts and granulocytes, and an increase in ring-shaped sideroblasts, indicating pathologic erythropoiesis. After giving up alcohol, the above phenomena disappear.
4. Increased plasma volume:The majority of chronic liver disease patients are complicated with anemia, and their plasma volume is about 15% higher than that of normal people. For some anemic patients, the red blood cell volume does not decrease, so blood dilution is also one of the causes of anemia in liver disease.
5. Hemorrhage:Hepatic cirrhosis complicated with hemorrhage is reported to be between 24% and 75% in different reports. The main bleeding site in alcoholic cirrhosis patients is the gastrointestinal tract, followed by hemorrhoids and uterine bleeding. Abnormal coagulation mechanism further aggravates hemorrhage. Hemorrhage is also one of the causes of anemia in liver disease patients.