Megaloblastic Anemia Flashcards by Alexandra Kristensen

Macrocytic anemia definition

anemia with macrocytes present (> 100 fL MCV)

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megaloblastic anemia is one type of _ anemia

macrocytic

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megaloblast

large and abnormal precursor cell in the bone marrow exhibiting asynchrony

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Asynchrony in macrocytic anemia

results from defective nucleus maturation

Due to impaired DNA synthesis

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Thymidine triphophate (TPP) synthesis is inhibted causing

nuclear fragment
cell destruction
impaired cell division

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in macrocytic anemia, RNA is not affected

The cytoplasm matures normally

Normal MCHC

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Ineffective erythropoiesis

Increased RBC precursors in BM
RBC precursor cells are fragile
RBC precursor cells die prematurely in BM
Decreased RBC release into PB
Decreased RBC in PB stimulates EPO production
EPO stimulates RBC maturation and production

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ineffective granulopoiesis

increase WBC precursors in BM
giant metamyelocytes die in BM
Decrease in mature WBC released to PB

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ineffective thrombopoiesis

Increased megakaryocytes in BM that are abnormal
impaired thrombopoiesis
decrease in platelets in peripheral blood = thrombocytopenia

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Causes of Impaired DNA syntehsis (TTP synthesis inhibition)

Vitamin B12 Deficiency
- aka “Pernicious Anemia” when due to lack of intrinsic factor

Folic Acid deficiency

Drugs that impair availability of either ^

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Vitamin B 12 - Cobalamin

Produced by microorganisms and fungi
present in foods of animal origin
(can be aproblem for strict vegans, since plants do not contribute B12 to diet).

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USA daily diet of Vitamin B12

5-30 um

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recomended dietary intake of B12

2 ug/day

increased in pregnancy/breastfeeding, infancy, edlerly

Requirement is low, and storage rate is high. It can take several years for vitamin B12 deficiency to develop

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How do we get vitamin B12?

Vitamin B12 in diet binds to Intrinsic factor (IF)

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glycoprotein secreted by parietal cells (stomach)

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Complexed B12+IF travels to ielum, where B12 is absorbed

B12 enter PB in portal vein

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In portal vein, B12 attaches to Transcobalamin II (or similar carrier proteins)

Transcobalamin II (TC II) - main transport protein of cobalamin to tissues

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TC II takes B12 to the bone marrow, liver or other tissues

stored for 2-7years

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Transcobolamin II

main transport protein of covalamin to the tissues

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Diet - B12 defiency

strict vegans

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Impaired absorption - B12 Deficiency

Lack of intrinsic factor –> Pernicious anemia
Ileum resection

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Pernicious anemia

lack of intrinsic factor

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Microorganism competition - Vitamin B 12 deficiency

Diphyllobothrium latum

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Drug - Vitamin B 12 deficiency

Colchine

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Zollinger - Ellison syndrome . B12 defiency

Hypersecretion of HCl

Increased requirement - B12 deficiency

pregnancy, infancy, elderly

Folic acid - Synthetic Folate - Natural

Water soluble vitamin (B9) - high concentration in green leafy vegetables, fruits, dairy, animal products - synthesizes by microorganisms in our intestines, but not absorble

B9 Heat liable? USA Daily diet Recomended

Destroyed by over cooking USA Daily diet - 400-600 ug Recomended (50-100 ug) - increased in pregnancy, infancy, lactation Primarily stored in the liver (80%)

Folic acid (folate) deficiency causes

1. diet/ inadequate intake 2. increased requirement - pregnancy, infancy, brest feeding 3. Impaired absorption - tropical sprue infection - celiac disease 4. Drug induction - methotrexate

B12 and Folate (B9) deficiency: Clinical manifestations

- Pallor, weakness, lightheadedness - Shortness of breath - Glossitis - Graual onset

glossitis

smooth sore tongue

Only B12 Deficiency

Peripheral nerves Neurological manifestations **4 P's** 1. Peripheral neuropathy 2. Pyramidal Tract signs 3. Posterior Spinal Column Degeneration 4. Psychosis (megaloblastic madness) Paresthesia Fever of unknown origin (FUO)

Paresthesia (B12 deficiency)

tingling / prickling feeling

Anemia: Macrocytic, normochromic Anemia

- Low hemoglobin - high MCV: 100-160 fL - Normal MCHC

Pancytopenia

- Low RBC count - Low WBC count - Low/Borderline PLT count

Anisocytosis (megaloblastic)

oval macrocytes

inclusions (megaloblastic)

howell jolly bodies cabot rings (rare)

Poikilocytosis Megaloblastic

teardrop cells

reticulocytopenia

for the level of compensation expected

Peripheral smear WBC in megaloblastic anemia

- Hypersegmented neutrophils - Necrobiotic neutrophils

Bone marrow in Megaloblastic anemia

Decreased myeloid : Erythroid ratio 1:3 - 1:1 Erythroid hyperplasia

ineffective erythropoiesis

megaloblasts

Serum B12 Test

Decrease in B12 deficiency

Serum folate

Decrease in Folate deficiency

Reticulocyte production index Test

Decrease, due to ineffective erythropoiesis

Serum bilirubin test

Increased indifrect bilirubin

Lactate dehydrogenase (LDH)

Increase, due to destruction of megaloblasts

Urinary urobilinogen test

increase, due to RBC destruction

Vitamin B12 deficiency Treatment

lifelong vitamin therapy - oral dose - intramuscular or subcutaneous dose Therapy is monitored by reticulocyte counts Transfusion only in severe cases

Folic acid deficiency

Oral dose for couple of weeks Prophylaxis recomended for pregnancy and dialysis patients

aplastic anemia

hypoproliferative, disorder wirh cellular depletion and reduced production of all blood cells, aka pancytopenia - cytopenia - pancytopenia

cytopenia

abnormalities or deficiencies in specific blood cell elements

pancytopenia

depression of each of the normal bone marrow elements

aplastic anemia - possible mechanisms

- Antibody directed to stem cell antigen - T lymphocytes suppress stem cell proliferation

Aplastic anemia

- >95% is aquired - <5% is congenital

Acquired Aplastic Anemia

**- Idiopathic = 40-70% ** - Secondary = 30-60%

Idiopathic/Primary anemia (Acquired Aplastic Anemia) MAJORITY OF CASES

- 40 - 70 % of cases - no clear cut cause - not a result of another condition

Secondary Acquired Aplastic Anemia

- 30-60% - External, chemical, physical or infectious agent initates mechanism

chemical agents - secondary acquired aplastic anemia

benzene arsenic many more

drugs - secondary acquired aplastic anemia

- Chloramphenicol - phenylbutazone

infections - secondary acquired aplastic anemia

Hepatitits Epstein Barr Virus Cytomegalovirus

miscellaneous secondary acquired aplastic anemia

Pregnancy Malnutritoin Immunologic dysfunction

Megaloblastic Anemia Flashcards

(62 cards)