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Megaloblastic Anemia
Lecture 9/24
33
Medical
Professional
09/27/2013

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Term
Define Vitiligo
Definition
Loss of pigmentation
Term
What is the most readily available test to differentiate a B12 deficiency from Folic Acid Deficiency?
Definition
Serum Methylmalonic Acid
Term
What are the common causes of Macrocytic Anemia? (11)
Definition
DNA synthesis issues: Increased Reticulocytes (from bleeding/RBC destruction), Bone marrow failure, Liver disease, Drugs (methotrexate and hydroxyurea), and Alcohol
Term
Megaloblastic Anemias are associated with what, and a blood smear is characterized by what? (12)
Definition
Impaired DNA synthesis; Blood smear shows MacroOVALocyces, High MCV (100-140), Howell Jolly Bodies, and Hypersegmented Neutrophils (>5 lobes)
Term
Image 13 of macrocytic anemia findings
Definition
13
Term
Pathogenesis of Megaloblastic Anemia
Definition
It is a Biochemical defect in DNA synthesis resulting in 1) Delayed nuclear devo, impaired cell division, and unbalanced cell growth, 2) Orderly cytoplasmic maturation, 3) Ineffective erythropoiesis, 4) Intramedullary cell death (RBCs die in marrow)
Term
What are the Bone marrow findings in Megaloblastic Anemia?
Definition
Increased Immature precursors with delicate, open granular chromatin as well as Giant Metamyelocytes
Term
Images of Megaloblastic RBC precursors 17-20
Definition
17-20
Term
What disorder is often described as the Prototype of Megaloblastic Anemias?
Definition
Pernicious Anemia (PA)
Term
PA is a chronic gastritis mediated autoimmune disorder that prevents the release of what?
Definition
Intrinsic Factor from Parietal Cells
Term
How long can Cobalamin stores last?
Definition
3-4 years
Term
What is the function of Cobalamin?
Definition
It is a Coenzyme that transfers a Methyl group to Homocystiene to form Methionine
Term
Metabolic Reactions involving B12 (see 26)
Definition
26
Term
What does Cobalamin combine with in the stomach?
Definition
IF (Intrinsic Factor) AND R factor
Term
What happens once the R-IF-Cobalamin complex reaches the 2nd portion of the duodenum?
Definition
Cobalamin is cleaved from R factors by pancreatic proteases and Free Cobalamin binds remaining IF
Term
What happens when IF-Cobalamin reaches the Ileum?
Definition
The complex is cleaved and absorption of Cobalamin occurs as Transcobalamin (another complex released in portal veinous system)
Term
What is the role of TransCobalamin II? TransCobalamin III?
Definition
TCII Transports protein carrying Cobalamin to peripheral tissues; TCIII carries Cobalamin to the liver where it is excreted into the bile and channeled through the enterohepatic cycle
Term
When will TC III levels be high?
Definition
Myeloproliferative Disorders
Term
*What is Pernicious Anemia associated with?
Definition
Chronic Immunologically mediated Gastritis
Term
*What is the clinical presentation of PA?
Definition
Lemon Yellow complexion with Loss of Position and Vibratory Sense
Term
What are the Neurological Aspects of PA and what term describes them?
Definition
Myelin Degeneration of the Dorsal and Lateral spinal cord columns, Dorsal root Ganglia, and Peripheral nerves; Termed *Subacute Combined Degeneration*
Term
Image of Subacute Combined Degeneration on 37
Definition
37
Term
Laboratory Features of PA including: IF release, Oral absorption of B12, RBC life, Indirect Bilirubin and LDH, Serum B12, Serum/Urinary Homocysteine, Serum/Urinary Methylmalonic acid
Definition
Decreased gastric IF release, Low oral B12 absorption, Decreased RBC survival, Increased serum Indirect Bilirubin and LDH, Low Serum B12, Increased Serum/Urinary Homocysteiene and Methylmalonic acid
Term
What differentiates PA (cobalamin deficiency) from Folate deficiency?
Definition
the increased Serum/Urinary Methylmalonic acid
Term
B12 deficiency is best treated with what?
Definition
IntraMuscular B12 given for life
Term
Is transfusion necessary for B12 deficiency treatment? What other compound needs to be carefully monitored as RBC's are restored when treating PA?
Definition
Rare to have to use Transfusions; Potassium may drop upon RBC replenishment, so it is important to monitor to avoid sudden death
Term
What is the role of Folic Acid?
Definition
It is a catalytic acceptor-donor of one-carbon units (such as methylation of deoxyuridylate > Thymidylate)
Term
Folic Acid is acquired through green leafy vegies and is often deficient in diets with what cooking methods?
Definition
Starchy Fried foods and Long Boiling of Veggies
Term
What is the RDA (recommended Daily Allowance) of Folic acid and how long can stores last?
Definition
400mcg/day; stores last weeks-months
Term
What are some common causes of Folic Acid Deficiency?
Definition
Dietary deficiency among Alcohol Abusers, Impaired Absorption, Excessive Losses (hemodialysis), and situation with increased requirements like Pregnancy/Growth periods
Term
What are the three Major Drugs that cause Impaired Folate Metabolism?
Definition
Ethanol, Dilantin, and Methotrexate
Term
What is the most helpful Test for Differentiating Megaloblastic Anemia caused by Folate vs Cobalamin Deficiency?
Definition
Serum and Urinary Methylmalonate (high in B12 but not Folate deficiency)
Term
Why should therapy for Folate deficiency not only give Folate but B12?
Definition
If there IS a B12 deficiency, Neurological Deterioration can occur if B12 is not administered
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