Lecture 21 Macrocytic Anemias Flashcards
Macrocytic Anemias
- megaloblastic
- B12 deficiency
- folate deficiency
- non-megaloblastic
- alcoholism
- liver disease
- hypothyroidism
- myelodysplastic syndromes
- hemolytic anemias
- congenital dyserythropoietic anemia (CDA)
- aplastic anemia
Megaloblastic Anemia
- anemia resulting from impaired red cell DNA synthesis
- affects mostly nucleus
Megaloblastic Changes
- cells larger than normal
- cytoplasm often more immature than normal
- nucleus:
- nuclei larger than normal
- chromatin is very fine and does not clump
- nucleoli retained and more visible in later stages
- asynchronous development:
- nuclear development lags behind cytoplasm which leads to large cells
- cells die in BM and anemia results
B12 Biochem
- belongs in family of vitamins called cobalamins (Cbl)
- corrin nucleus containing cobalt and four pyrrole rings
- no other organic cmpd containing Co in nature
- also involved in produc’n of succinyl-CoA
- deficiency leads to increase in methylmalonic acid (incr. in urinary measurement indicator of B12 deficiency)
B12-Folate Interaction
B12 and Folate interact with each other to convert homocysteine to methionine produce normal DNA
Vit B12 dietary sources
- meat
- liver
- kidney
- fish
- oysters
- clams
- eggs
- cheese
- milk
- not found in vegetables and fruit
Folate dietary sources
- green leafy vegetables
- cauliflower
- broccoli
- brussel sprouts
- liver
- kidney
- whole grain cereals
- yeast
- fruit
- dairy products
Pernicious Anemia
- a type of megaloblastic anemia due to a lack of intrinsic factor
- causes:
1. mucosal damage from mechanical, thermal, or chemical agents
2. endocrine disorders (thyroid, adrenal, or pancreatic)
3. genetic disorders (northern European)
4. autoimmune disorders (involved in most cases of pernicious anemia)
5. total of partial gastrectomy (removal of stomach causing decr. intrinsic factor)
B12 Nutritional Reqs
- nutritional deficiency of b12 not commonly seen except in strict vegetarians
- competition for dietary vit B12 from bacterial overgrowth can cause deficiency
- achlorhydria (reduced of absent HCl) causes improper absorption
- disease causing malabsorption (Crohn’s, colitis)
- fish tapeworm, H. pylori
- malabsorption main cause of vit B12 deficiency
Folate Deficiency
- Insufficient dietary intake:
- folate is heat-labile, easily destroyed in overcooked vegetables - Alcoholic cirrhosis:
- alcohol interferes with folate metabolism - Pregnancy:
- fetal development requires incr. folate - Folate antagonists:
- chemotherapy drugs - Folate malabsorption:
i) tropical sprue: from infectious agent causing intestinal atrophy
ii) gluten sensitive enteropathy
a. adult non-tropical sprue
b. childhood celiac disease
Clinical Findings in Megaloblastic Anemias
- fever due to neutropenia
- loss of appetite
- glossitis (sore tongue)
- neurological symptoms from degeneration of myelin and peripheral nerves
Lab Findings in Megaloblastic Anemias
- ineffective hematopoiesis
- pancytopenia
Schilling Test
- differentiate the 3 causes of megaloblastic anemia:
1) dietary deficiency
2) intrinsic factor deficiency
3) malabsorption - part 1: if normal IF is present -> dietary deficiency
- part 2: if corrected, pernicious anemia is diagnosis
if not corrected, malabsorption is the problem
Congenital Dyserythropoietic Anemia (CDA)
- rare inherited disorder causing abnormal nuclear development in erythroblasts only
- WBCs and platelets not affected
- 3 types: CDA Type I, II, III
Non-megaloblastic Macrocytosis
i) Liver Disease
- incr plasma lipids cause macrocytosis w/ target cells and acanthocytes
ii) Alcoholism
- liver disease (cirrhosis) also cause incr. lipids
iii) Hypothyroidism:
- thyroid malfunction leads to increased plasma lipids
iv) Myelodysplastic syndromes:
- stem cell defect causing oval macros
v) Hemolytic conditions:
- incr retics from hemolytic conditions can cause macros
