Flashcards in Hem & Onc - Pathology (Macrocytic anemia) Deck (17):
How is macrocytic anemia defined? What are the divisions of macrocytic anemia?
Anemia with MCV > 100 fL; Megaloblastic and Non-megaloblastic
What are the defining characteristics of megaloblastic anemia?
(1) Impaired DNA synthesis --> maturation of nucleus delayed relative to maturation of cytoplasma (2) Abnormal cell division --> pancytopenia
What are examples of megaloblastic anemia?
(1) Folate deficiency (2) Vitamin B12 (Cobalamin) deficiency (3) Orotic aciduria
What are etiologies of folate deficiency?
(1) Malnutrition (e.g., alcoholics) (2) Malabsorption (3) Antifolates (e.g., methotrexate, trimethoprim, phenytoin) (4) Increased requirement (e.g., hemolytic anemia, pregnancy)
What is a key physical finding in folate deficiency? What about in blood smears? What about in labs?
Glossitis; Hypersegmented neutrophils; Decreased folate, increased homocysteine but normal methylmalonic acid
What are etiologies of B12 deficiency?
(1) Insufficient intake (e.g., strict vegans) (2) Malabsorption (e.g., Crohn's disease) (3) Pernicious anemia (4) Diphyllobothrium latum (fish tapeworm) (5) Proton pump inhibitors
What is a key physical finding in B12 deficiency? What about in blood smears? What about in labs?
Glossitis, neurologic symptoms (TBD); Hypersegmented neutrophils; Decreased B12, increased homocysteine AND increased methylmalonic acid
What is the kind of neurologic deficit seen in B12 deficiency, and why? More specifically, what neurologic symptoms manifest?
Subacute combined degeneration (due to involvement of B12 in fatty acid pathways & myelin synthesis); (1) Peripheral neuropathy with sensorimotor dysfunction (2) Posterior columns (vibration/proprioception) (3) Lateral corticospinal (spasticity) (4) Dementia
How can you differentiate B12 deficiency from folate deficiency?
(1) Increased levels of methylmalonic acid (normal in folate deficiency) (2) Neurologic symptoms (absent in folate deficiency)
What is orotic aciduria, and what causes it? What is its mode of inheritance?
Inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) because of defect in UMP synthase. Autosomal recessive.
How does orotic aciduria present? What are key physical, blood smear, and lab findings?
Presents in children as megaloblastic anemia that cannot be cured by folate or B12 with failure to thrive; PHYSICAL - glossitis, SMEAR - hypersegmented neutrophils, LABS - orotic acid in urine
What used as treatment for orotic aciduria, and why?
Uridine monophosphate to bypass mutated enzyme
What is nonmegaloblastic macrocytic anemia?
Macrocytic (MCV > 100 fL) in which DNA synthesis is unimpaired
What are causes of nonmegaloblastic macrocytic anemia?
(1) Liver disease (2) Alcoholism (3) Reticulocytosis (4) Drugs (5-FU, Zidovudine, hydroxyurea)
What are the findings associated with nonmegaloblastic macrocytic anemia?
Macrocytosis and bone marrow suppression can occur in the absence of folate/B12 deficiency
What distinguishes folate deficiency from B12 deficiency?
No neurologic symptoms (distinguishes from B12 deficiency)