5.3 Macrocytic Anemias Flashcards
Microcytic anemias can be thought of as one extra division of precursor cells leading to small cells. Explain the formation of macrocytic cells in this context.
Macrocytic anemia can be thought of as one less division of the precursor cells leading to large cells. This is caused most often by a lack of vit B12 or folate that inhibits the reproduction of DNA precursors needed for the new cell.
Explain the reactions needed between folate and B12 for the synthesis of DNA
Folate circulates as methyltetrahydrofolate
The methyl groups need to be transferred to Vit B12 before folate can participate in DNA synthesis
Vit B12 transfers the methyl to homocysteine producing methionine
What is the meaning and significance of the term “megaloblastic anemia”
Megaloblastic refers to the situation of low B12 or folate preventing the synthesis of DNA precursors and affecting the production of all cells that are rapidly dividing. (It is a type of macrocytic anemia.) This includes granulocytes that will then produce hypersegmented neutrophils, and megaloblastic changes in other rapidly dividing cells like intestinal epithelial cells
What are some other causes of macrocytic anemia without megaloblastic changes?
Alcoholism, Liver disease, Drugs
Which anemia has hypersegmented neutrophils and why?
Megaloblastic macrocytic anemia
Involves folate or Vit B12 and therefore megaloblastic features will be seen in the blood in other cells besides just RBC’s
How would a macrocytic anemia look different than a megaloblastic anemia?
Both would have enlarged RBC’s, but the megaloblastic would also have hypersegmented neutrophils and other changes seen in rapidly-dividing cells like enlargement of intestinal epithelial cells
Which enzyme is inhibited by Methotrexate?
Dihydrofolate reductase
Same enzyme inhibited by Trimethoprim
Patient is found to have SSx of megaloblastic anemia. What lab value would be helpful in determining whether this is a problem with Vit B12 or Folate?
If Vit B12 is the problem, methylmalonic acid levels will be elevated because B12 is needed to convert it to succinyl CoA
Therefore, methylmalonic acid levels will be normal in a patient with only a folic acid problem
Where do we get folate from?
Diet
Green vegetables and some fruits
Absorbed in the jejunum
How quickly does a folate deficiency develop once uptake has decreased?
Within months, body stores are considered minimal
What are causes of folate deficiency?
Poor diet: alcoholics and elderly
Increased demand: pregnancy, cancer, hemolytic anemia
Folate antagonism: methotrexate or others
What are the clinical and lab findings in folate deficiency?
Macrocytic RBC’s and hypersegmented neutrophils
Glossitis
Decreased serum folate
Increased serum homocysteine (remember methyl groups are transferred from THF to B12 to homocysteine to form Methionine)
Normal methylmalonic acid
Explain the absorption of Vit B12
B12 is complexed to animal-derived proteins
Salivary enzymes like amylase cleave this bond freeing B12 that is then bound to R-binder (from salivary gland)
B12+R-binder go through stomach together into SI
Pancreatic enzymes break bond in duedenum
B12 binds intrinsic factor from parietal cells of stomach
B12+intrinsic factor absorbed together in ileum
How long does it take to develop a B12 deficiency?
Years because of large hepatic stores
Describe the most common cause of B12 deficiency
Pernicious anemia
Autoimmune destruction of the parietal cells of stomach leading to a deficiency in intrinsic factor preventing absorption of B12
