IUHS Student-2-Student USMLE Step 1 Recall
Hematology
Microcytic/Hypochromic Anemia
Anemia of Chronic Disease
microcytic, hypochromic
...the
serum iron and percentage of saturation are decreased in anemia of chronic disease...in anemia of chronic disease,
iron is present, but is restricted to and increased within macrophages...it is
decreased in amount within marrow erythroid precursors...serum ferritin is increased
with anemia of chronic desease...The iron and iron binding capacity are both low.
The amount of storage iron in macrophages is increased.Underlying chronic inflammatory or neoplastic diseases increase the secretion of cytokines such as interleukin-1, tumor necrosis factor, and interferon-gamma. These cytokines depress erythropoiesis.
associated with Hep C infection or other chronic diseases
...Iron Deficiency Anemia
approximately 80% of the functional iron is found in hemoglobin; myoglobin and iron-containing enzymes such as catalse and the cytopchomres contain the rest...
the storage pool represented by hemosiderin and ferritin contains approximately 15-20% of total body iron...
all storage of iron is in the form of either ferritin or hemosiderin
...ferritin is essentially a protein-iron complex that can be found in all tissues but particularly in liver, spleen, bone marrow, and skeletal muscles...i
n the liver, most of the ferritin is stored within the parenchymal cells; in other tissues, such as spleen and bone marrow, it is mainly in the mononuclear phagocytic cells...the iron within the hepatocytes is derived from plasma transferrin, whereas the storage of iron in the mononuclear phagocytic cells, including in the kupffer cells, is obtained largely from the breakdown of red blood cells...within cells, ferritin is located both in the cell sap and in lysosomes, in which the protein shells of the ferritin are degraded and iron is aggregated into hemosiderin granules...
iron is transported in the plasma by an iron-binding glycoprotein called transferrin
, which is synthesized in the liver...the major function of plasma transferrin is to deliver iron to the cells, including erythroid precursors, where iron is required for hemoglobin synthesis...immature red cells posssess high affinity receptors for transferrin, and iron is transported into erythroblasts by receptors-mediated endocytosis...most active site for absorption of iron is the upper parts of the small intestine, such as the duodenum
...iron is more readily absorbed in the duodenum in the ferrous state (Fe+++)...heme iron is in the ferrous state (Fe++) and can be absorbed directly...once inside the duodenal epithelial cells, heme is enzymatically degraded to release the heme iron...in contast, nonheme iron is in the ferric (Fe+++) state and must first be reduced to the ferrous form before it can be absorbed...vitamin C is the most impotant factor in reducing ferric iron to the ferrous state...dietary lack, impaired absorption, increased requirement, or chronic blood loss
...impaired absorption is encountered in sprue, other causes of intestinal steatorrhea, and chronic diarrhea...gastrectomy impaires iron absorption by decreasing hydrochloric acids and transit time through the duodenum...
iron deficiency in adult men and post-menopausal women in the western world should be considered to be caused by gastrointestinal blood loss until proven otherwise
...to prematurely ascribe an iron lack in such individuals to any of the other possible origins is to run the risk of missing an occult gastrointestinal cancer or other bleeding lesion...
uncommonly, esophageal webs may appear, to complete the triad of major findings in
Plummer-Vinson syndrome: (1) microcytic hypochromic anemia, (2) atrophic glossitis, and (3) esophageal webs...hemoglobin and hematocrit are depressed
, usually to moderate levels, and are associated with hypochromia, microcytosis, and some poikocytosis (different shapes)...the
serum iron and serum ferritin are low, and the total plasma iron-binding capacity (reflecting transferrin concentration) is high...low serum iron with increased iron-binding capacity results in a reduction of transferrin saturation levels to below 15%...the level of transferrin receptors is inversely related to available serum iron
...with iron deficiency, the level of cell-bound transferrin receptors and their soluble forms circulate in the blood is elevated...iron deficiency is the most likely cause of anemia due to a GI bleed
...the level of transferrin receptors in the serum has been found to be an excellent test for the diagnosis of iron deficiency...
patients tend to chew ice to sooth sores in mouth
...Thalassemia Syndromes
characterized by a lack of or decreased synthesis of either the alpha or beta globin chain of HbA...beta thalassemia is characterized by deficient synthesis of the beta chain, whereas alpha thalassemia is characterized by deficient synthesis of the alpha chain...the hematologic consequences of diminished synthesis of one globin chain derive not only from the low intracellular hemoglobin but also from the relative excess of the other chain...
the abnormality common to all beta-thalassemias is a total lack of or a reduction in the synthesis of structuraly normal beta-globin chains with unimpaired synthesis of alpha chains...
beta globin genes are located on chromosome 11, whereas alpha are located on 16...
beta thalassemia can be classified as beta (0) thalassemia or beta (+) thalassemia...
beta (0) is associated with a total absence of beta-globin chains
in the homozygous state...beta (+) is associated with reduced (but detectable)
beta globin synthesis in the homozygous state...in beta-thalassemia, the G-T sequence is mutated to A-T such that correct RNA splicing does not occur...
lack of adequate HbA formation, so that the overall concentration of hemoglobin in the cells is lower and the cells are hypochromic...
there is an imbalance of alpha and beta chain synthesis...since synthesis of alpha globin chains continues unimpaired, most of the chains produced cannot find complementary beta chains to bind...the free alpha chains form highly unstable aggregates that precipitate within the normoblasts in the form of insoluble inclusions...
marked anemia produced by ineffective erythropoiesis and hemolysis...
erythropoietin secretion is stimulated, which leads to severe erythroid hyperplasia in the bone marrow and often at extramedullary sites....
massive erythropoiesis within the bones invades the bony cortex, impairs bone growth, and produces other skeletal abnormalities...
also, iron overload and hemochromatosis...
beta thalassemia major
homozygous individuals with beta+/beta+ genes or beta^0/beta^0....have a severe form of beta thalassemia...
beta thalassemia minor
heterozygotes...beta+/beta or beta^0/beta...usually leads to enough normal beta globin chain synthesis so that the affected individulas are usually asymptomatic with only a mild anemia...
brief, unless supported by transfusions, children suffer from growth retardation and die at an early age from the profound effects of anemia...
blood transfusion not only improve the anemia but also suppress secondary features related to excessive erythropoiesis...
the clinical manifestations can be deduced largely from the hematologic and morphologic changes....
in those who survive long enough, the face becomes overlarge and somewhat distorted...
hepatosplenomegaly
is usually present...cardiac disease resulting from iron overload and secondary hemochromatosis is an important cause of death even in patients who can otherwise be supported by blood transfusions
...to reduce the amount of iron overload, most patients also receive iron chelators (desferoxamine)...bone marrow transplantation from an HLA-identical sibling is currently the only therapy that offers a cure...
decreased Hemoglobin A, increased Hemoglobin A2, and increased Hemoglobin F...
Sideroblastic Anemia
associated with ring sideroblasts
in bone marrow...may be either pyridoxine (vit B6) responsive or pyridoxine unresponsive; the latter is a form of myelodysplastic syndrome (refractory anemia with ring sideroblasts)...
peripheral blood may show dimorphic RBC population...
Lab: increased serum iron, ferritin, FEP, and % saturation of TIBC with
decreased TIBC...alcoholics can get sideroblastic anemia...alcohol uncouples oxidative phosphorylation...