Hem & Onc - Pathology (Macrocytic anemia)

Question 1

How is macrocytic anemia defined? What are the divisions of macrocytic anemia?

Answer 1

Anemia with MCV > 100 fL; Megaloblastic and Non-megaloblastic

Question 2

What are the defining characteristics of megaloblastic anemia?

Answer 2

(1) Impaired DNA synthesis –> maturation of nucleus delayed relative to maturation of cytoplasma (2) Abnormal cell division –> pancytopenia

Question 3

What are examples of megaloblastic anemia?

Answer 3

(1) Folate deficiency (2) Vitamin B12 (Cobalamin) deficiency (3) Orotic aciduria

Question 4

What are etiologies of folate deficiency?

Answer 4

(1) Malnutrition (e.g., alcoholics) (2) Malabsorption (3) Antifolates (e.g., methotrexate, trimethoprim, phenytoin) (4) Increased requirement (e.g., hemolytic anemia, pregnancy)

Question 5

What is a key physical finding in folate deficiency? What about in blood smears? What about in labs?

Answer 5

Glossitis; Hypersegmented neutrophils; Decreased folate, increased homocysteine but normal methylmalonic acid

Question 6

What are etiologies of B12 deficiency?

Answer 6

(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

Question 7

What is a key physical finding in B12 deficiency? What about in blood smears? What about in labs?

Answer 7

Glossitis, neurologic symptoms (TBD); Hypersegmented neutrophils; Decreased B12, increased homocysteine AND increased methylmalonic acid

Question 8

What is the kind of neurologic deficit seen in B12 deficiency, and why? More specifically, what neurologic symptoms manifest?

Answer 8

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

Question 9

How can you differentiate B12 deficiency from folate deficiency?

Answer 9

(1) Increased levels of methylmalonic acid (normal in folate deficiency) (2) Neurologic symptoms (absent in folate deficiency)

Question 10

What is orotic aciduria, and what causes it? What is its mode of inheritance?

Answer 10

Inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) because of defect in UMP synthase. Autosomal recessive.

Question 11

How does orotic aciduria present? What are key physical, blood smear, and lab findings?

Answer 11

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

Question 12

What used as treatment for orotic aciduria, and why?

Answer 12

Uridine monophosphate to bypass mutated enzyme

Question 13

What is nonmegaloblastic macrocytic anemia?

Answer 13

Macrocytic (MCV > 100 fL) in which DNA synthesis is unimpaired

Question 14

What are causes of nonmegaloblastic macrocytic anemia?

Answer 14

(1) Liver disease (2) Alcoholism (3) Reticulocytosis (4) Drugs (5-FU, Zidovudine, hydroxyurea)

Question 15

What are the findings associated with nonmegaloblastic macrocytic anemia?

Answer 15

Macrocytosis and bone marrow suppression can occur in the absence of folate/B12 deficiency

Question 16

What distinguishes folate deficiency from B12 deficiency?

Answer 16

No neurologic symptoms (distinguishes from B12 deficiency)

Question 17

How is orotic aciduria distinguished from ornithin transcarbamylase deficiency?

Answer 17

No hyperammonemia (vs. ornithine transcarbamylase deficiency - increased orotic acid with hyperammonemia)