Megaloblastic Anemia Flashcards
Macrocytic anemia definition
anemia with macrocytes present (> 100 fL MCV)
megaloblastic anemia is one type of _ anemia
macrocytic
megaloblast
large and abnormal precursor cell in the bone marrow exhibiting asynchrony
Asynchrony in macrocytic anemia
results from defective nucleus maturation
Due to impaired DNA synthesis
Thymidine triphophate (TPP) synthesis is inhibted causing
- nuclear fragment
- cell destruction
- impaired cell division
in macrocytic anemia, RNA is not affected
The cytoplasm matures normally
Normal MCHC
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
ineffective granulopoiesis
- increase WBC precursors in BM
- giant metamyelocytes die in BM
- Decrease in mature WBC released to PB
ineffective thrombopoiesis
- Increased megakaryocytes in BM that are abnormal
- impaired thrombopoiesis
- decrease in platelets in peripheral blood = thrombocytopenia
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 ^
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).
USA daily diet of Vitamin B12
5-30 um
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
How do we get vitamin B12?
Vitamin B12 in diet binds to Intrinsic factor (IF)
IF
glycoprotein secreted by parietal cells (stomach)
Complexed B12+IF travels to ielum, where B12 is absorbed
B12 enter PB in portal vein
In portal vein, B12 attaches to Transcobalamin II (or similar carrier proteins)
Transcobalamin II (TC II) - main transport protein of cobalamin to tissues
TC II takes B12 to the bone marrow, liver or other tissues
stored for 2-7years
Transcobolamin II
main transport protein of covalamin to the tissues
Diet - B12 defiency
strict vegans
Impaired absorption - B12 Deficiency
Lack of intrinsic factor –> Pernicious anemia
Ileum resection
Pernicious anemia
lack of intrinsic factor
Microorganism competition - Vitamin B 12 deficiency
Diphyllobothrium latum
Drug - Vitamin B 12 deficiency
Colchine
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
- diet/ inadequate intake
- increased requirement
- pregnancy, infancy, brest feeding - Impaired absorption
- tropical sprue infection
- celiac disease - 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
