MACROCYTIC NORMOCHROMIC ANEMIA

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AA

-Characterized by enlargement of all rapidly proliferating cells of the body including

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marrow cells

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-Abnormality:

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Nuclear cytoplasmic asynchrony (maturation arrest).

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Cytoplasm development is

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normal

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-Most common causes:

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Vitamin B12 deficiency
Folate deficiency

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1) MEGALOBLASTIC ANEMIA Laboratory Findings:

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-macroovalocytes
-hypersegmented neutrophils
-basophilic stippling, multiple Howell jolly bodies
-nucleated RBC’s with karyorrheexis
-Pancytopenia, leucopenia and thrombocytopenia
-Increased serum lactate dehydrogenase
-Increased serum muramidase -Increased endogenous CO

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-required in the demethylation of folate during DNA synthesis Reaction that involves Vit B12

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Vitamin B12

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*Isomerization of methylmalonyl CoA to succinyl CoA

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Vitamin B12

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causes high level of serum of methylmalonic acid (MMA) and its level is diagnostic

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Vitamin B12

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*Serves as a coenzyme (methylcobalamin form) in generation of Tetrahydrofuran (THF)

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Vitamin B12

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-is absorbed through the ileum with the aid of the intrinsic factor (IF) produced by parietal cells transported by transcobalamin (TC II) in the plasma

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Folate

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*The function is to transfer carbon units in the form of methyl groups from donors to receptors during metabolism of amino acid and nucleotides.

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Folate

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• Deficiency leads to impaired cell replication.

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Folate

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Related Causes of Vitamin B12 Deficiency
1.Inadequate intake
2.Impaired absorption
3. Malabsorption Syndrome
4. Lack of availability of Cobalamin

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Celiac and Ileal disease (Crohn’s disease/ regional enteritis)

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3. Malabsorption Syndrome

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tropical sprue, resection of small bowel

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3. Malabsorption Syndrome

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: deficiency of IF-B1 receptors

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Imerslund-Grasbeck syndrome

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: gastric hypersecretion

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Zollinger-Ellison syndrome

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Blind loop syndrome

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4. Lack of availability of Cobalamin

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Infection with Diphyllobothrium latum

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4. Lack of availability of Cobalamin

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Inability of gastric mucosa to secrete intrinsic factor resulting to Pernicious anemia.

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-Decrease/Deficiency of Vit B12

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also causes this deficiency

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-Neomycin and Ethanol

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May also be due to abnormal production of TC II.

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-Neomycin and Ethanol

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-Autoimmune type of Vit B12 deficiency anemia

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**PERNICIOUS ANEMIA

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**PERNICIOUS ANEMIA Autoantibodies involved:

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1. Anti-parietal cell antibodies
2. Anti-intrinsic factor antibodies
3. Pathologic CD4 T cells

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Anti-intrinsic factor antibodies Types:

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Blocking antibody Binding antibody

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: blocks the binding of cobalamin to IF

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Blocking antibody

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: binds to the cobalamin IF complex and prevents the complex rom binding to receptors in the ileum.

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Binding antibody

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- inappropriately recognize and initiate an autoimmune response resulting to chronic inflammatory infiltration follows, which extends into the wall of the stomach.

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Pathologic CD4 T cells

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PERNICIOUS ANEMIA S/S:

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-atrophic glossitis and atrophic gastritis -Achloridria -Episodic abdominal pain, constipation and diarrhea -anemia w/ combination of skin pallor and lemon yellow skin -Diffuse and irregular degeneration of CNS white matter

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*sensation of pins and needles in distal extremities

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-Diffuse and irregular degeneration of CNS white matter

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*emotional instability and change of personality

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-Diffuse and irregular degeneration of CNS white matter

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Diagnosis of Vitamin B12 Deficiency

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1. Serum Cobalamin Assay 2. Methylmalonic acid and Homocysteine Assay - 3. Deoxyuridine Supression Test 4. Schilling Test 5. Competitive Protein Binding Radioassay 6. Other tests: Fecalysis (bothriocephalus anemia)

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- Microbiological assay

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1. Serum Cobalamin Assay

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uses E. gracilis (requires Vit B12 for growth) to test the level of B12 in the serum of patients.

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1. Serum Cobalamin Assay

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1. Serum Cobalamin Assay NV.

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200-900 mg/dL

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-Deficiency of B12 will lead to excretion of increased amount of methylmalonate in urine

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2. Methylmalonic acid and Homocysteine Assay

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--measures ability of the BM to utilize deoxyuridine in DNA synthesis

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3. Deoxyuridine Supression Test

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- Measures the body’s ability to secrete viable IF and absorb orally administered Co-labeled B12

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4. Schilling Test

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- Method of choice for B12 and folate deficiency quantitation

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5. Competitive Protein Binding Radioassay

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6. Other tests

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Fecalysis (bothriocephalus anemia)

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-abnormal in both cobalamin and folate deficiency

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Deoxyuridine Supression Test