RBC Disorders - Macrocytic Anemia

Question 1

Macrocytic Anemia

Answer 1

MCV>100
Megaloblastic: Folate deficiency, B12 deficiency, Orotic aciduria
Non-megaloblastic: Liver disease, Alcoholism, Diamond-Black anemia

Question 2

Megaloblastic Anemia

Answer 2

Impaired DNA synthesis –> maturation of nucleus of precursor cells in bone marrow delayed relative to maturation of cytoplasm

RBC macrocytosis, hyperhsegmented neutrophils, glossitis

Question 3

Folate Deficiency

Answer 3

Causes: malnutrition (e.g. alcoholics), malabsorption, drugs (e.g. methotrexate, trimethoprim, phenytoin), ^ requirement (e.g. hemolytic anemia, pregnancy)

Green veggies and fruit - absorbed in jejunum

Takes months to develop (smaller stores)

^homocysteine
normal methylmalonic acid

NO neuro symptoms (vs B12 deficiency)

Question 4

Vitamin B12 (cobalamin) Deficiency

Answer 4

Causes: insufficient intake (e.g. vegans), malabsorption (e.g. Chron's), Diphyllobothrium latum (fish tapeworm), gastrectomy 
pernicious anemia (autoimmune destruction of parietal cells in body of stomach --> intrinsic factor deficiency, so can't bind to B12 and be absorbed in ileum)

animal-derived proteins - absorbed in ileum

Takes years to develop - large hepatic stores

^homocysteine
^methylmalonic acid (B12 is cofactor for conversion of methylmalonic acid to succinyl CoA)

Neuro symptoms: subacute combined degeneration (due to involvement of B12 in FA pathways and myelin synthesis): spinocerebellar tract, lateral corticospinal tract, dorsal column dysfunctional

Diagnosed w Schilling test - 4 stages that determines if cause is dietary insufficiency or malabsorption

Question 5

Orotic Aciduria

Answer 5

Inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) bc of defect in UMP synthase.
Autosomal recessive.
Presents in kids as failure to thrive, developmental delay, megaloblastic anemia refractory to folate and B12.
No hyperammonemia (vs ornithine transcarbamylase deficiency - ^orotic acid w hyperammonemia)

Orotic acid in urine

Tx: UMP to bypass mutated enzyme

Question 6

Diamond-Blackfan Anemia

Answer 6

Rapid-onset anemia within 1st yr of life due to intrinsic defect in erythroid progenitor cells.

^ %HbF (but v total Hb)

Short stature, craniofacial abnormalities, upper extremity malformations (triphalangeal thumbs) in up to 50% of cases

Question 7

Nonmegaloblastic Anemia

Answer 7

Macrocytic anemia in which DNA synthesis is unimpaired

Causes: alcoholism, liver disease

RBC macrocytosis w/o hyperhsegmented neutrophils