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424 Exam 1
Microcytic and Macrocytic Anemia
49
Medical
Undergraduate 4
02/09/2013

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Term
Categorize by the Wintrobe classification of the classic presentation and by pathophysiological classification of megaloblastic anemia.
Definition
High MCV, normal MCHC. Macrocytic, normochromic.
Term
Categorize by the Wintrobe classification of the classic presentation and by pathophysiological classification of myelodysplasic anemia.
Definition
High MCV, normal MCHC. Macrocytic, normochromic.
Term
Categorize by the Wintrobe classification of the classic presentation and by pathophysiological classification of liver disease associated anemia.
Definition
High MCV, normal MCHC. Macrocytic, normochromic.
Term
Categorize by the Wintrobe classification of the classic presentation and by pathophysiological classification of reticulocytosis.
Definition
High MCV, low MCHC. Macrocytic, hypochromic. (I would say hypochromic because their Hgb hasn't increased entirely yet.)
Term
CBC results of megaloblastic anemia.
Definition
Low RBC, low WBC, low platelets, low-no retix. Macro-ovalocytes and hypersegmented neutrophils.
Term
CBC results of myelodysplasia
Definition
Low RBC, low WBC, low platelets, some retix, poik, sideroblasts.
Term
CBC of liver disease associated anemia
Definition
Low RBC, ok WBC, ok platelets, some retix, acanthocytosis, target cells, maybe burr cells.
Term
CBC of reticulocytosis
Definition
Low RBC, ok WBC, ok platelets, lots of retix.
Term
The blood picture of megaloblastic anemia.
Definition
There is a lack of folate or B12, which causes overall pancytopenia from the inability to make DNA. In turn, there are less cellular divisions resulting in macrocytic cells. The Hgb production is untouched, so the cells are normochromic. Since there might be some older and ok cells, there is a large RDW...which is made even worse from different sizes of macro-ovalocytes. The pathognomonic findings are macro-ovalocytes and hypersegmented neutrophils. RBC inclusions may also be present, such as nucleated RBCS, howell-jolly bodies, and baso stip.
Term
The blood picture of myelodysplasia.
Definition
Myelodysplasia results from a mutated stem cell, which results in megaloblastoid development of RBC and pancytopenia. Because of the lack of cellular divisons, there is development of macrocytic cells, blasts, and abberant RBC morphology. Quite often you'll see multiple and fragmented nuclei, poik, and a dimorphic population as evidenced by a binodal RDW. A key characteristic finding is megaloblastOID development where the nucleus lags behind the cytoplasm. For example, a basophilic normoblast can have a super dark blue nucleus but a very pink cytoplasm. Will also see sideroblasts as well as retix.
Term
The blood picture of liver disease.
Definition
For the most part, the blood picture of liver disease isn't too extreme. You will see macrocytic (sometimes only microcytic) and normochromic RBC. There is an elevated RDW due to an increase in MCV. The morphology is the most wild aspect (since the liver is repsonsible for RBC membrane lipids) and you'll see acanthos, target cells, and possibly echinos and burr cells.
Term
The blood picture of reticulocytosis.
Definition
One word sums this up: polychromasia. The MCV will be increased since reticulocytes are larger than RBCs, but the Hgb is low resulting in hypochromic cells. RDW is increased.
Term
List and describe the mechanisms by which folate and B12 deficiency develop:
Definition
  • Dietary deficiency
  • Increased need (pregnancy and fast growth)
  • impaired absorption (GI problems, food intolerances, etc.)
  • Increased loss with renal dialysis
  • If B12: can get antibodies against the parietal cells that make intrinsic factor and against intrinsic factor itself
Term
Describe the etiology and pathogenesis of pernicious anemia
Definition
Autoantibodies attack parietal cells that make intrinsic factor, which destroys the ability to absorb B12. Can also make autoantibodies against intrinsic factor.
Term
Describe the expected results for LDH and bilirubin assays for megaloblastic anemia
Definition
Increased LDH, indirect bilirubin, and total bilirubin from hemolysis.
Term
The pathognomonic feature of megaloblastic anemia
Definition
hypersegmented neutrophils
Term
Describe the bone marrow appearance of megaloblastic anemia
Definition
The bone marrow will show erythroid hyperplasia and the nucleus will lag behind the cytoplasm.
Term
Describe in general terms the role of folate and B12 in DNA metabolism
Definition
Folate and B12 are responsible for making thymidine nucleotides. No T, no DNA.
Term
Define myelodysplasia
Definition
Myelodysplasia is a mutation in a stem cell that results in abnormal cell development and slowed divisions.
Term
Describe the epidemiologic groups affected by myelodysplasia
Definition
People 50+, people who've undergone chemotherapy
Term
Correlate the MCV and MCHC with RBC morphology
Definition
MCV: size. MCHC: color/hgb content.
Term
List and describe the pathogenesis of the four pathophysiological categories of anemia
Definition
  1. whole blood loss from the vascular system
  2. increased destruction of RBCs: may be due to extracellular causes like HTRs, malarial parasites, enzyme deficiencies, etc.
  3. Decreased RBC production: due to defected stem cell, deficiencies of materials, etc.
  4. Dilutional anemia: pregnancy, over hydration, whatever.
Term
Explain why jaundice and reticulocytosis may occur with hemolytic anemias
Definition
Jaundice and reticulocytosis may occur with hemolytic anemias because when RBCs lyse, they release bilirubin, which in turn can exceed the liver's capacity to conjugate and excrete it. This results in prehepatic jaundice. Reticulocytes might be elevated because the body is trying to fix the oxygen carrying capacity that was lost with the destroyed RBCs.
Term
Given results of bilirubin (total and fractionated), recognize the results consistent with prehepatic jaundice
Definition
Prehepatic jaundice signs: high total bili, high indirect, normal direct bili, yellowing of skin and sclera.
Term
Name three sites where hemolysis may occur leading to anemia
Definition
In blood vessels (intravascular), in bone marrow (intrmedullary), and in spleen.
Term
Correlate expected results of bilirubin assays, plasma and urinary Hgb, haptoglobin, LDH, stool and urinary urobilinogen, and RBC morphology with hemolysis and time since hemolysis began.
Definition

Umm, here's the order of the signs:

  1. Hgb high
  2. haptoglobin low
  3. urine positive for hgb
  4. plasma bili high
  5. retix high, high LDH
Term
Wintrobe and pathophysiological classification of iron deficiency anemia
Definition
Low MCV, low MCHC. Microcytic, hypochromic. Anemia of decreased production.
Term
Wintrobe classification and pathophysiological classification of anemia of chronic inflammation
Definition
Low MCV, low MCHC. Microcytic, hypochromic. Anemia of decreased production.
Term
Wintrobe classification and pathophysiological classification of sideroblastic/lead poisoning anemia.
Definition
Normal-low MCV, normal-low MCHC. Anemia of decreased production?
Term
Wintrobe classification and pathophysiological classification of thalassemia
Definition
Low MCV, Low MCHC. Microcytic, hypochromic. Anemia of decreased production.
Term
CBC of iron deficiency anemia
Definition
Low Hgb, low Hct, low MCV, low MCHC, low retix, high RDW, maybe thrombocytosis.
Term
CBC of ACI
Definition
Lowish Hgb, lowish Hct, normal RDW, RDW ok, low-no retix.
Term
CBC of sideroblastic/lead poisoning anemia
Definition
Low Hgb, ok-low Hct, ok RDW, baso stip, pappenheimer bodies, maybe high retix.
Term
CBC of thalassemia
Definition
Low Hgb, low Hct, high aniso, high poik, high RDW, super high retix, baso stip, target cells, shistos.
Term
Confirmatory follow up tests of iron deficiency
Definition
  1. serum iron levels=low
  2. ferritin=low
  3. TIBC=high
  4. fluorometry of protoporphyrin IX and ZPP (high)
Term
Confirmatory follow up tests for ACI
Definition
  1. normal-high ferritin
  2. serum Fe and Tf are low
  3. high hepcidin
  4. high lactoferrin
  5. low EPO
  6. low TIBC
  7. high ZPP
Term
Confirmatory follow up tests for lead poisoning
Definition
  1. serum lead levels are through the roof
  2. serum Fe is ok
  3. ferritin is normal
  4. TIBC is normal
  5. ZPP is through the roof
Term
Confirmatory testing for thalassemia
Definition
  1. serum Fe is normal or high
  2. TIBC is ok
  3. ferritin is ok
  4. high total and indirect bili
  5. high LDH
  6. high stool and urine urobilinogen
  7. DO AN ELECTROPHORESIS to see what Hgb banding patterns there are!
Term
Stages of Fe deficiency
Definition
  1. Storage depletion is marked by low ferritin.
  2. Transport depletion is marked by low ferritin, low serum Fe, and high TIBC.
  3. Functional depletion is marked by decreases in Hgb.
Term
Describe the etiology of ACI
Definition
  • Anemia of decreased production.
  • Associated with autoimmune diseases, chronic infections, malignancies, etc.
  • ACI paradox: there's plenty of iron but the body is sequestering it and reducing absorption.
  • Hepcidin, ferritin, and lactoferrin are acute phase proteins that cause the enterocytes and macrophages to lock up iron.
Term
Define sideroblastic anemia and list causes, the hallmark feature of the bone marrow, and the points where lead interferes with heme metabolism.
Definition
  • Sideroblastic anemia is an anemia of decreased production since heme synthesis is impaired by either heavy metals or drugs.
  • It is marked by sideroblasts in the bone marrow, RBCs with Fe deposites circling nuclei. 
  • Lead impairs the heme sythesis at the conversion of ALA to porphobilinogen and the incorporation of Fe into protoporphyrin IX by ferrochelatase.
Term
Differentiate the underlying cause of the thalassemias from conditions such as sickle cell anemia.
Definition
Thalassemia is a hemolytic anemia and also one of decreased production. It is different from sickle cell anemia because the globin chain is affected resulting in screwed up hemoglobin rather than having a strange form of genetically determine Hgb, like Hgb S or C.
Term
Describe the geographic/ethic groups affected by thalassemia.
Definition
People from the Mediterranean all the way to South Asia and their descendents.
Term
Describe the cause of hemolysis in thalassemia
Definition
  1. Intravascular rupturing from globin precipitation and increased osmotic fragility.
  2. Intramedullary hemolysis
  3. Splenic macrophage phagocytosis
Term
List three different types of mutations that can produce beta thalassemia
Definition
  1. point mutations causing a frameshift or a base pair substitution in either the promoter sequence or the exon causing RNA pol to not bind and undergo translation.
  2. chain terminator mutations causing non-functional globin fragments.
  3. splicing mutations that result in the wrong RNA sequence and a bad globin chain
Term
State the number of alpha globin genes and describe the five mutations of alpha thalassemia.
Definition
  • 4 alpha globin genes
  • Genotypes:
    • --a/aa is a silent carrier
    • --a/--a has the alpha thal trait
    • --/aa has the alpha thal trait
    • --/-a has hemoglobin H disease
    • --/-- would have hydrops fetalis and is fata.
Term

Define Hgb Barts and Hgb H including their globin chain composition

 

Definition
Hgb Barts is found in infants and it is made of 4 gamma chains. Hgb H is found in adults and it is made of 4 beta chains.
Term
Explain the rationale for the use of the reticulocyte hemoglobin in assessement of anemia treatment.
Definition
We test the RHC because it reflects the Fe in the bone marrow within one day, so it's useful to see if the body is able to incorporate Fe into new cells that it's making. We're pretty much asing "what amount of Hgb came out of the bone marrow yesterday?"
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