Macrocytic anemia Flashcards
Anemia with an MCV > 100um3…
Macrocytic anemia
What are the 2 most common causes of macrocytic anemia?
Folate deficiency
Vitamin B12 deficiency
What must be removed from serum methyltetrahydrofolate (THF) in order for it to participate in DNA synthesis?
Methyl group must be transferred to Vitamin B12
Where is the methy group transferred to from methyltetrahydrofolate to allow THF to participate in DNA synthesis?
Vitamin B12
Where does Vitamin B12 transfer the methyl group to produce methionine?
Homocysteine
What leads to megaloblastic anemia?
Impaired division and enlargement of RBC precursors
Hypersegmented neutrophils occur with macrocytic anemia. What causes there to be produced?
Impaired division of granulocytic precursors
What are some causes of macrocytic anemia without megaloblastic change?
Alcoholism
Liver disease
Drugs (5-FU)
Where does the absorption of folate occur?
Jejunum
What are some common causes of folate deficiency?
Poor diet
Increased demand
Folate antagonists
Macrocytic anemia can be caused by a poor diet. Who are the two most common groups of people who present with a folate deficiency due to poor diet?
Alcoholics
Elderly
What are some causes of increased demand for folate, causing a folate deficiency?
Pregnancy
Cancer
Hemolytic anemia
What is a common drug that is a folate antagonist causing a folate deficiency?
Methotrexate—inhibits dihydrofolate reductase
What changes are seen with RBCs with folate deficiency?
Macrocytic RBCs
What changes are seen with neutrophils with folate deficiency?
Hypersegmented neutrophils (> 5 lobes)
With respect to folate levels and serum homocysteine, what are the laboratory values seen with a folate deficiency?
Serum folate—decreased
Homocystein—increased
What is a normal finding seen with folate deficiency with helps differentiated it from a different cause macrocytic anemia?
Methylmalonic acid
What is bound to vitamin B12 to allow it to be carried to through the stomach?
R-binder
What cause the detachment of R-binder from vitamin B12?
Pancreatic proteases
Where does the detachment of R-binder from vitamin B12 occur?
Duodenum
What binds vitamin B12 in the small bowel allowing absorption of B12 by the ileum?
Intrinsic factor
What cells produce intrinsic factor, which binds vitamin B12 to allow absorption in the ileum?
Gastric parietal cells
What is the most common cause of vitamin B12 deficiency?
Pernicious anemia
Autoimmune disorder involving destruction of parietal cells, which leads to intrinsic factor deficiency?
Pernicious anemia
Besides pernicious anemia, what are some other causes of vitamin B12 deficiency?
Pancreatic insufficiency
Damage to terminal ileum
Dietary deficiency (RARE, except in vegans)
What are the two most common causes of damage to the terminal ileum, which causes a vitamin B12 deficiency?
Crohn disease Diphyllobothrium latum (tapeworm)
What are changes that occur to RBCs with vitamin B12 deficiency?
Macrocytic RBCs
What changes occur to neutrophils with vitamin B12 deficiency?
Hypersegmented neutrophils
Why is poor proprioception and vibratory sensation, along with spastic paresis seen with vitamin B12 deficiency?
Vitamin B12 is cofactor for the conversion of methylmalonic acid to succinyl CoA
With Vitamin B12 deficient→ there is an increased level of methylmalonic acid impairing the spinal cord myelinization
With respect to serum Vitamin B12, serum homocysteine, and Methylmalonic acid, what are the laboratory results seen with a vitamin B12 deficiency?
Serum Vitamin B12→ decreased
Serum homocysteine→ Increased
Methylmalonic acid→ increased
What laboratory finding allows differentiation between a folate deficiency and a Vitamin B12 deficiency?
Methylmalonic acid levels
Normal with folate deficiency
Elevated with vitamin B12 deficiency
