Red Blood Cell disorders Flashcards
What are the signs and symptoms of hypoxia/anemia?
dyspnea, fatigue, weakness
pale conjunctiva and skin
headache and lightheadedness
angina in people with pre-existing CAD
What is the pathogenesis of a microcytic anemia?
decreased hemoglobin (hemoglobin = iron + protoporphyrin+ globin) causes an “extra” division of the RBC progenitor cell to maintain hemoglobin concentration within the cell
What are the four types of microcytic anemias?
iron deficiency anemia, anemia of chronic disease, sideroblastic anemia and thalassemias
How does iron get into the body and how is it stored? What type of anemia will an iron deficiency cause? What other symptoms will be present in an iron deficiency anemia?
Enterocytes in the duodenum transport heme from food into the cell and transport iron across the basolateral membrane into the blood via ferroportin. In the blood, iron is transported via transferrin and is delivered to the liver and bone marrow macrophages for storage. Stored intracellular iron is bound to ferritin. Iron deficiency causes decreased hemoglobin and thus, a microcytic anemia. Other symptoms of iron deficiency anemia include pica and koilonychia
What is the pathogenesis of anemia of chronic disease? What type of anemia does it cause?
Chronic inflammation causes continuous production of acute phase reactants, including hepcidin. Hepcidin sequesters iron in storage and does not allow it to be transferred from macrophages to erythrocyte precursors. Hepcidin also decreases EPO production. Since there is less iron in the erythrocyte precursors, hemoglobin levels are decreased and thus a microcytic anemia results.
What is the pathogenesis of sideroblastic anemia? What type of anemia does it cause? What are the causes of sideroblastic anemia? What are the histological feature of sideroblastic anemia?
Decreased production of protoporphyrin causes decreased hemoglobin and therefore a microcytic anemia. Decreased protoporphyrin can be due to genetic defects in the enzyme ALAS (aminolevulinic acid synthase), a vitamin B6 deficiency (vitB6 is a cofactor for ALAS), lead poisoning (inhibits ferrochelatase) and alcoholism. Under the microscope, iron-filled mitochondria form a ring around the nucleus of erythroid precursors given them the name “ringed sideroblasts”. Iron gets trapped in the mitochondria because the last step in heme synthesis is the binding of iron to protophorphyrin and it takes place in the mitochondria. If there is no protoporphyrin, then iron just builds up in the mitochondria.
What is the pathogenesis of thalessemia? What type of anemia does it cause? What is the difference between alpha thalessemia and beta thalessemia?
Thalessemia is when there is decreased production of the globin polypeptide chain, leading to decreased hemoglobin levels and thus a microcytic anemia. Alpha thalessemias have a deletion in two or three of the four alpha genes (4 deletions are not compatible with life). In contrast beta thalessemias are due to a mutation in beta globin gene that leads to no production or underproduction of the beta chain.
What symptoms result when there is massive erythroid hyperplasia? What are some of the causes of massive erythroid hyperplasia?
1) expansion of hematopoesis into the skull (crew cut appearance on x-ray) and into the facial bones (chipmunk facies)
2) expansion of hematopoesis into the spleen and liver - hepatosplenomegaly
3) risk of aplastic crisis with parvovirus B19 infection
Causes: Beta thalassemia major, sickle cell disease
What is the pathogenesis of macrocytic anemia? What are the causes of macrocytic anemia? What is the difference between macrocytic and megaloblastic?
Macrocytic anemia results where there is a deficiency of DNA precursors so the erythrocyte precursor does not undergo the last cell division and is thus, slightly larger. Megaloblastic anemia is caused by a folate or vitamin B12 deficiency. Macrocytic anemia is caused by alcoholism, liver disease and drugs. Macrocytic anemia means only the RBCs are enlarged. Megaloblastic anemia means that many of the rapidly dividing cells in the body are enlarged (e.g. gut epithelial cells)
What are the signs and symptoms and lab findings of folate-deficiency?
macrocytic/megaloblastic anemia hypersegmented (greater than 5) neutrophils glossitis decreased serum folate increased serum homocysteine normal methylmalonic acid levels
What is pernicious anemia?
Autoimmune destruction of parietal cells in the stomach leads to intrinsic factor deficiency which leads to a vitamin B12 deficiency which leads to a macrocytic anemia
What are the signs, symptoms and lab findings of vitamin B12 deficiency?
macrocytic/megaloblastic anemia
hypersegmented (greater than 5) neutrophils
glossitis
subacute combined degeneration of spinal cord due to build up of methylmalonic acid in myelin (not seen in folate deficiency)
increased serum homocysteine
increased methylmalonic acid levels
What is the path of absorption of vitamin B12?
R-binder, an enzyme secreted by the salivary gland, binds to vitamin B12 in the mouth and carries is through the stomach. Once in the duodenum, pancreatic enzymes cleave R-binder from vitamin B12, freeing vitamin B12 to bind with intrinsic factor that was released from parietal cells in the stomach. The vitamin b12-intrinsic factor complex is absorbed in the ileum.
What are the two main etiologies of a normocytic anemia? What laboratory finding distinguishes between them?
Normocytic anemia is either due to over destruction or underproduction. Reticulocyte count distinguishes between over destruction or underproduction. If the corrected reticulocyte is elevated, there is a good marrow response suggesting peripheral destruction. If the corrected reticulocyte is not elevated, the bone marrow is probably underproducing RBCs.
What type of anemia will result from chronic blood loss?
Iron deficiency anemia -> microcytic anemia
