Anemia due to Hemolysis Flashcards
Define hemolysis
decrease in red cell survival or increase in turnover beyond standard norms
intravascular hemolysis.
turnover within the vascular space, red cells undergoing this will release hemoglobin into the circulation –> dissociates into dimer alpha/beta –> binds to haptoglobin –> removed by liver. If haptoglobin is overwhelmed, hemoglobin will have the iron oxidized to methemoglobin. Dissociation of globin releases metheme which binds albumin or hemopexin –> converted to bilirubin.
extravascular hemolysis.
through ingestion and clearance by macrophages of the reiculoendothelial (RE) system. Red cell ingested by macrophage heme separated from globin, iron removed and stored in ferritin and porphyrin ring converted to bilirubin which is released from cell. Bilirubin converted to water-soluble compound with addition of glucuronic acid. After ecretion into biliary tract/small bowel, glucuronic acid is removed and bilibuin is converted to urobilinogen (this cycles between gut and liver or is excreted by kidney into urine
Describe the biochemical pathways of breakdown of hemoglobin and the relevant clinical lab tests for hemolysis
The CBC will determine whether anemia is present or not, the mean size of the red cells and whether the size varies significantly. In most cases, the short red cell life –> ↑reticulocyte count and index. ↑bilirubin (if hemolysis is brisk enough to overcome the bilirubin processing system of the liver –> ↑unconjugated fraction. ↓serum haptoglobin levels. ↑metheme or methemalbumin
Describe the major constituents of the RBC membrane and cytoskeleton.
major constituents of the RBC membrane and cytoskeleton ******
Identify the major defects in hereditary spherocytosis.
The basic pathophysiology is that spectrin, ankyrin or band 3 defects weaken the cytoskeleton and destabilize the lipid bilayer. Loss of membrane and formation of the spherocyte leads to decreased deformability and entrapment in the spleen. Conditioning in the red pulp leads to further loss of red cell membrane and, ultimately, removal by the macrophage
Relate the major defects in hereditary spherocytosis to the clinical findings of the disorder.
Clinically, patients present with a variable degree of anemia as well as jaundice and splenomegaly. One third have hyperbilirubinemia as neonates. Most inherit the condition as autosomal dominant, although inheritance is sometimes autosomal recessive. Treatment includes supportive care for chronic anemia and intermittent complications and splenectomy, which usually resolves the clinical manifestations.
Relate the major defects in hereditary spherocytosis to the laboratory findings of the disorder.
Hereditary pyropoikilocytosis is a severe form of congenital hemolytic anemia. It is clinically similar to, and now considered a subtype of, homozygous hereditary elliptocytosis. Hereditary pyropoikilocytosis is an autosomal recessive disorder that produces a molecular defect in spectrin and a partial spectrin deficiency. It manifests as a severe hemolytic anemia with thermal instability of the red blood cells.
Interpret an osmotic fragility test for diagnosis of hereditary spherocytosis.
Osmotic fragility test is a formal laboratory test used in the diagnosis of HS. The test measures the in vitro lysis of RBCs suspended in solutions of decreasing osmolarity. Normal RBCs swell in hypotonic solutions and burst when a critical cellular volume is reached. Spherocytes lyse in solutions of higher osmolarity than normal RBCs. Spherocytes are also more sensitive to a decrease in osmolarity. When graphed, compared to normal RBCs, if spherocytes are present, then the curve will be shifted to the left
Explain when splenectomy is indicated for treatment of hereditary spherocytosis
- The basic pathophysiology is that spectrin, ankyrin or band 3 defects weaken the cytoskeleton and destabilize the lipid bilayer. Loss of membrane and formation of the spherocyte leads to decreased deformability and entrapment in the spleen. Thus, if the spleen is taken out - no more entrapment.
- The pathophysiology of many hemolytic disorders, including hereditary spherocytosis, involves destruction by the spleen, so management of chronic severe anemia sometimes includes splenectomy as a specific strategy. After splenectomy, spherocytes are present on the peripheral blood smear, but RBC survival is relatively normal.
- Splenectomy is not indicated for children under 5 because their immune system is not fully developed
Describe the major energy and antioxidant pathways in the RBC: Embden-Meyerhof pathway
energy is generated through the breakdown of glucose in RBCs due to the absence of mitochondria. Metabolism of glucose to lactate and pyruvate provides ATP necessary to maintain the plasma membrane and cytoskeleton, and energize metabolic pumps to control intracellular sodium, potassium and calcium.
ATP generation is critical for RBC survival
Describe the major energy and antioxidant pathways in the RBC: Rapoport-Leubering pathway
produces 2,3-diphosphoglycerate which stabilizes the deoxy form of hemoglobin and maximizes transport of O2to tissues
Describe the major energy and antioxidant pathways in the RBC: Hexose monophosphate shunt
produces pyridine nucleotide which reduces glutathione and provides protection from oxidant stress.
Describe the major energy and antioxidant pathways in the RBC: methemoglobin reductase pathway
maintains the iron in hemoglobin in the ferrous state required for reversible oxygen binding by hemoglobin
explain how G6PD deficiency and pyruvate kinase deficiency affect these pathways, leading to hemolysis. Describe the inheritance patterns and discuss the clinical and laboratory findings in patients with these syndromes: G6PD deficiency
-Inheritance: sex-linked recessive (female carriers, male affected).
-G6PD is an enzyme in the hexose monophosphate shunt (phosphocluconate or pentose pathway) which protection against oxidant stress. Loss of enzyme activity in the red cell results in inability to restore reduced glutathione.
-Clinically, G6PD deficiency presents as intermittent episodes of acute hemolytic anemia and hyperbilirubinemia associated with oxidant stress (infection, drugs, ingestion of specific foods—fava beans). May be characterized as a chronic hemolytic anemia punctuated by episodes of acute exacerbation anemia.
Cause of neonate hyperbilirubinemia
No specific morphologic features are associated with G6PD deficiency. Although occasionally, the smear will show microspherocytosis and “blister” or “bite” cells.
