B12 deficiency: pathogenesis of symptoms

Clinical presentation of megaloblastic anemia

•Severe anemia

–Circulatory-hypoxic syndrome

–Anemic syndrome

•Hunter`s Glossitis: smooth tongue due to loss of papillae

•Funicular myelosis:

–Subacute combined degeneration of the cord in cobalamine deficiency. Abnormal gait,

–loss of balance,

–speech impairment

–loss of proprioceptive and vibratory senses

•Lemon-yellow skin

•Hyperpigmentation of the skin and abnormal pigmentation of hair due to increased melanin synthesis

•Mental changes, from irritability to psychosis

•Splenomegaly

Funicular myelosis

Diagnostics

•Hyperchromia, macrocytosis

•Megaloblastosis

•Single and multiple Howell-Jolly bodies (nuclear fragments in RBC)

•Cabot rings (remnants of mitotic spindles)

•Hypersegmented neutrophils

•Pancytopenia

•Hyperbilirubinemia (↑indirect bb due to hemolysis in the bone marrow)

•High LDH activity

•Low reticulocytes

•Low B12 and/or folates

•Bone marrow is hypercellular (”blue”) with erythroid hyperplasia – megaloblastic erythropoiesis

Peripheral blood smear in megaloblastic anemia

Treatment

•Life-long treatment with cobalamine (parenteral)

•Oral supplements of folic acid

•If B12-deficiency is not excluded treat with both supplements

Response to therapy with B12 – reticulocytosis within 7-10 days

Hemolytic anemia

•Hemolysis – premature destruction of erythrocytes.

•A hemolytic anemia will develop if bone marrow activity cannot compensate for the erythrocyte loss.