Hematology - Abnormal iron metabolic anemias, megaloblastic anemia
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- 2 causes of anemia associated with iron metabolism
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1. faulty heme production
(lack of Fe, defective iron production, or defective PORPHYRIN production)
2. faulty globin synthesis
(thalassemias) - Etiology of Iron deficiency anemia (IDA)
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1. poor diet
2. malabsorption
3. increased demand (pregnancy, etc)
4. blood loss (most common cause) - symptoms of decrease of hemoglobin in body
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weakness, fatigue, dizziness
shortness of breath
palpitations
skin pallor - symptoms of decrease of Fe-containing enzymes in tissues
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impaired neutrophil phagocytosis
impaired cell-mediated immunity
splenomegaly
inflammation
koilonychia
neurologic abnormalities - Stages of IDA
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1. iron depletion: Fe stores exhausted, normal peripheral blood values & morphology except for slight increase in RDW
2. Fe-deficient erythropoiesis: Fe levels drop, no sideroblasts in marrow
Increased: FEP, TIBC
Decreased: MCV
3. Fe deficiency anemia
decrease in Hb, microcytic hypochromic RBCs - peripheral blood smear features of IDA
- Microcytosis, hypochromia, anisocytosis, poikilocytosis
- changes in bone marrow in IDA
- erythroid hyperplasia in bone marrow, abnormal erythroblasts, decreased hemosiderin, decreased sideroblasts
- lab findins of IDA
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DECREASED: Hb, Hct, RBC count, Retic count, Serum Fe, ferritin, transferrin saturation
INCREASED: TIBC - What is hemachromatosis?
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condition of Fe overload characterized by high Fe absorption rate
note: NOT assoc. w/ anemia! - Etiology of Hemachromatosis
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1. PRIMARY idiopathic (inherited)
2. Chronic transfusion therapy - Pathophysiology of hemachromatosis
- excess Fe deposits accumulate & interfere w/ normal cellular function
- Lab findings of hemachromatosis
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DECREASED: normal or low TIBC
INCREASED: Serum Fe, serum ferritin, transferrin saturation - what is sideroblastic anemia?
- group of disorders characterized by abnormalities of HEME metabolism
- Pathophysiology of sideroblastic anemia
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1. Fe absorption is normal but UTILIZATION is impaired
2. Fe present but not incorporated into hemoglobin
3. Positive Fe balance, yet anemia still exists - Unique characterics of sideroblastic anemia
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1. ringed sideroblasts in bone marrow
2. dimorphic peripheral blood picture - classifications of sideroblastic anemia
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1. Idiopathic (primary) - idiopathic refractory anemia w/ dyserythropoiesis, abnormal Fe utilization, PRE-Leukemia
2. secondary -
disturbance in enzymes regulating heme synthesis (alcoholism, malignancies, etc) - visual characteristics of secondary sideroblastic anemia
- poikilocytosis, inclusions, basophilic stippling, dimorphism in peripheral blood
- lab findings in secondary sideroblastic anemia
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DECREASED: TIBC (can be normal too)
INCREASED: serum Fe, transferrin, FEP - what is anemia of chronic disease (AOD)/anemia of inflammation (AOI)
- anemia caused by a long term chronic disease, 2nd most common anemia in western world
- Pathophysiology of AOD/AOI
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caused by decrease of Fe flow to bone marrow (by blockage?)
erythropoietin not stimulated
shortened RBC survival: changes to rbc surfaces, hyperactive macrophages, intramedullary destruction
suppression of erythropoiesis:
release of IL-1 - Effect of IL-1 on body in situation of AOD
- IL-1 inhibits erythroid stem cell proliferation. Activates neutrophilic response w/ release of lactoferrin. Aids release of tissue necrosis factor (TNF)
- Clinical findings of AOI/AOD
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1. general symptoms of anemia
2. generally present in mild form - Lab findings of AOD/AOI
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Polychromasia, Anisocytosis (P b4 A)
DECREASED: serum Fe, TIBC, transferrin saturation, sideroblasts in marrow
INCREASED: serum ferritin - what is a megaloblastic anemia
- group of disorders which have characteristic of macrocytosis. Caused by impairment of DNA synthesis, resulting in abnormal erythrocyte, GRANULOCYTE, & MEGAKARYOCYTE maturation
- megaloblastic vs. non-megaloblastic macrocytosis
- nonmegaloblastic macrocytosis results if RBCs are released too early from marrow (acute blood loss, hemolysis, alcoholism)
- classification of megaloblastic anemia (3)
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1. due to folic acid deficiency
2. due to vitamin B12 deficiency
3. due to unresponsiveness to folic acid or B12 - Mechanism of megaloblastic transformation
- unbalanced growth of developing cells in bone marrow due to impaired DNA synthesis w/o assoc. impairment of RNA/protein synthesis. disparity between nucleus & cytoplasm called NUCLEAR-CYTOPLASMIC ASYNCHRONISM
- nutritional aspects of Folic Acid deficiency
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SOURCES: leafy veggies, liver, kidney, yeast, mushrooms, dairy, eggs
DAILY REQ: narrow margin between what is required and what is intaked
BODY STORES: depleted within months if no new source
INTESTINAL ABSORPTION: most in proximal jejunum - Etiology of folic acid deficiency
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1. inadequate dietary intake (folate is destroyed when heated during cooking)
2. increased requirements of Folic acid
3. impaired absorption
4. drug inhibition: alcoholism, oral contraceptives, anti-cancer drugs - Clinical features of folic acid deficiency
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1. general signs of anemia
2. glossitis
3. insidious onset
4. diarrhea/steatorrhea (fatty stool)
5. weight loss - visual findings of peripheral blood in folic acid deficiency
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MACROCYTIC, NORMOCHROMIC
hypersegmented neutrophils
large, hypogranular bands
decreased, enlarged platelets
oval macrocytes
poikilcytosis
Howell-jolly bodies, baso. stip., cabot rings
polychromatophilia, nucleated RBCs - lab findings in folic acid deficiency
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DECREASED: Hb, Hct, RBC count, retic count (RPI<2), pancytopenia
INCREASED: LDH, Bilirubin - Changes in bone marrow in folic acid deficiency
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hypercelluar
2. megaloblastic changes
a. loose, open chromatin in RBC precursors
b. Giant bands & metamyelocytes
c. giant megakaryocytes - Specific features of folic acid deficiency
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decreased serum and red cell folate
NORMAL B12 levels
treated w/ folic acid
INCREASED FIGLU (intermed. in glutaminic acid synthesis) - nutritional aspects of Vitamin B12 deficiency (sources, daily req., body stores, absorption)
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SOURCES: liver, meat, milk, eggs, fish
Daily requirements: 3-5ug, plenty in all but vegan diets
Body stores: enough for few years
absorption: occurs in ileum and requires INTRISIC FACTOR (IF) & TRANSCOBALAMIN II (TC II) - etiology of B12 deficiency
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1. impaired absorption:
several problems, main is Pernicious anemia
2. microorganism competition: tapeworms, bacteria in blind loop syndrome
3. defects in transport proteins:
hereditary deficiency of TCII
abnormal TC II
4. dietary deficiency - What is Pernicious anemia?
- megaloblastic anemia caused by absence of IF secondary to gastric atrophy. B12 can't be absorbed w/o it. most common B12 deficiency
- Clinical features of B12 deficiency
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1. same as folic acid deficiency
2. addition of NEUROLOGIC abnormalities:
parasthesias, gait abnormality, difficulty w/ fine motor coordination - Lab findings of B12 deficiency
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same as seen in folic acid deficiency and megaloblastic anemia in general.
SPECIFIC features: decreased serum B12
responsive to B12 therapy
increased methylmalonic acid - causes of megaloblastic anemia to be unresponsive to B12 or folate therapy
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1 antimetabolic drugs
2. Congenital deficiencies
a. hereditary orotic aciduria
b. Leysch-Nyhan syndrome
c. errors of folate metabolism
3. unexplained disorders
a. myelodysplastic syndrome (preleukemia)
b. erythroleukemia - causes of macrocytosis WITHOUT megaloblastic changes
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1. Alcoholism
2. liver disease
some overlap, lipids build up on RBC surface w/ no way to metabolise them
3. reticulocytosis - Characteristics of macrocytosis
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1. ROUND, not oval macrocytes
2. less pronounced macrocytes
3. no super segs
4. no pancytopenia
5. absence of megaloblastic anemia signs: jaundice, glossitis, neuropathy - Etiology of macrocytosis
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there is an increase in membrane lipids
there is a delay in blast maturation - chemsitry tests useful in differential Dx of macrocytosis
- LDH, bilirubin, serum B12, serum and red cell folate levels, gastric analysis, SCHILLING TEST, BONE MARROW EXAMINATION
- what is Schilling test?
- differentiates B12 deficiency resulting from malabsorption, dietary inadequacy, or lack of IF.