Anemia of Chronic Renal Failure

1. Anemia of Chronic Renal Failure Etiology Metabolic Red Blood Cell Dysfunction Decreased Erythropoietin production Hemolytic Ureamic Syndrome Marrow Suppression ( ureamic inhibitors ) Hyperthyroidism

2. Metabolic Red Cell Dysfunction • ATP is high possibly due to a high serum phosphate • 2,3 DPG is increased in response to anemia and hyperphosphatemia • ATPase, Na-K pump are decreased in ureamia and resulting in shortening life span (more rigidity and cell shape changes), HMP decreased response renders excessively sensitive to Oxidant drugs and Chemicals (เช่น พวกกลูตาไธโอนจะลดการทำงานลง)

3. Glucose G-6-PD 6-Phosphoglycerate (HMS) Glucose-6-Phosphate NADP NADPH GSSG GSH Lactate (EMP)

4. Decreased Erythropoietin (EPO) Production • Glycoprotein MW 36,000 daltons. • Eschbach showed that the patient with renal failure even there was anemia but normal EPO level. However, it was lower than the anemia from other causes.

5. Hemolytic Ureamic Syndrome • Pathology of renal endothelial cell forming fibrin clot and platelet thrombi resulting in microangiopathic hemolytic anemia • Decreased platelet mass, mildly lower platelet count and MPV • Reduced platelet adhesion such as high molecular weight multimers of von Willebrandare reduced, GP Ib has been reported to be defective • Defective platelet activation and aggregation (reduced synthesis of thromboxane A2). Platelet functions defected due mainly to toxic substances e.g. Guanidinosuccinic acid, phenol.

6. Marrow suppression (Ureamic inhibitors) • Experiment found that serum from ureamic patient can suppress the growth of CFU-E and burst forming unit- erythroid ( BFU-E) • After hemodialysis or continuous ambulatory peritoneal dialysis can increase Hb level. Anyway, hemodyalysis may cause iron and folate deficiency.

7. Hyperthyroidism • Hyperparathyroidism is a complicated condition in renal failure • Increased PTH resulting in suppression of RBC production in BM

8. Anemia of endocrine disorder • Anemia of Pituitary deficiency • Anemia of thyroid dysfunction • Anemia of adrenal dysfunction • Anemia of gonadal dysfunction • Anemia of pregnancy • Anemia of parathyroid dysfunction

9. Anemia of pituitary deficiency • Hypophysectomy in animal causes severe erythroid hypoplasia and anemia (เพราะขาด GH) • It has been proposed that the pituitary gland produces a specific erythropoietic hormone • Growth hormone has been shown to be capable of stimulating red cell production in vitro • It has been claimed that hypothalamic injury may affect erythropoietin release, the rate of red cell production or both • Hypophyseal dysfunction is often associated with leukopenia and a normochromic, normocytic anemia (ขาด GH การผลิตลดลง) • The red cell life span is normal and relative marrow failure

10. Anemia of Thyroid dysfunction • Kocher reported that thyroidectomy is followed by a reduction in the red cell count • Anemia is normocytic, microcytic, macrocytic • Lack of thyroid hormone is complicating of iron, Vitamin B12, folic acid • T3, T4 potentiate the effect of erythropoietin on the formation of erythroid colonies • Many hypothyroid patients have a hypoplastic anemia ( Hb 8 – 9 g/dl) • Normochromic, normocytic anemia is the characteristic form of hypothyroidism

11. Anemia of Adrenal Dysfunction • Adrenalectomy in animal causes a mild anemia and respond to therapy with adrenal glucocorticoid or erythropoietin • Normochromic, normocytic anemia has been observed (เพราะขาดการกระตุ้น แต่ไม่มีปัจจัยอื่น) • The erythropoietic effect of ACTH or adrenal cortical hormone are unclear

12. Anemia of Gonadal Dysfunction • Androgens extensively utilized in the treatment of patients with various types of refractory anemia. It has been shown to stimulate red cell production by increasing the production of erythropoietin (ฮอร์โมนชายกระตุ้นอีโป้) • Castration of animal causes a decrease in the rate of red cell production until the Hb and red cell volume stabilized at levels the same as those of the normal female • Right now the recombinant human erythropoietin is used in place of androgens. Even now, androgens is used to reduce the cost of such therapy.

13. Anemia of Pregnancy • Anemia in pregnancy is thought due to changes in hormonal environment • In mice even progressive decrease in the Hct, the red cell volume, erythropoietin secretion and rate of red cell production increase during pregnancy. Placental lactogen may in part be responsible for the erythropoietic stimulation. • In human, anemia is aggravated by dietary restrictions resulting in iron deficiency sometimes folic acid deficiency • Anemia will be manifested about the 8 th wk progresses slowly until the 32-34 wk. This is so-called a dilution anemiathe red cell volume increases by 20 % while the plasma volume increases by 30 %.

14. Anemia of Parathyroid Dysfunction • Anemia in hyperparathyroidism will disappear after parathyroidectomy • Parathyroidectomy in renal disease results in some improvement in the anemia • One report says that parathyroid hormone can suppress normal red cell production but in fact these hormones may cause either renal calcification resulting in reduction of erythropoietin formation or marrow sclerosis resulting in reduction of erythroid proliferation