Hematology · USMLE Step 1 and Step 2

Megaloblastic Anemia - B12 song

Megaloblastic Anemia - B12 Deficiency, as a song. Hear the short teaser here. The full song is on YouTube and Spotify.

Megaloblastic Anemia - B12

Full song on YouTube ↗Spotify ↗

Key points in this song10

B12 deficiency causes megaloblastic anemia due to impaired DNA synthesis, resulting in large, hypersegmented neutrophils (≥5 lobes) and macro-ovalocytes on peripheral smear.
The most common cause in the US is pernicious anemia — autoimmune destruction of gastric parietal cells leads to loss of intrinsic factor, preventing B12 absorption in the terminal ileum.
Unlike folate deficiency, B12 deficiency causes subacute combined degeneration of the spinal cord — demyelination of the dorsal columns (loss of vibration and proprioception) and lateral corticospinal tracts (upper motor neuron signs).
Serum B12 levels may be normal in early deficiency; elevated methylmalonic acid (MMA) and homocysteine are the most sensitive markers confirming true B12 deficiency.
Folate deficiency raises homocysteine but does NOT raise methylmalonic acid — this distinguishes the two causes of megaloblastic anemia.
Anti-intrinsic factor antibodies are highly specific for pernicious anemia; anti-parietal cell antibodies are sensitive but not specific.
Risk groups include strict vegans, patients post-gastrectomy, terminal ileum resection (Crohn's disease), and long-term metformin or proton pump inhibitor users.
The Schilling test historically differentiated pernicious anemia from other B12 malabsorption causes by correcting absorption with exogenous intrinsic factor.
Treatment is intramuscular cyanocobalamin, especially when absorption is impaired; neurological symptoms may be irreversible if treatment is delayed.
B12 deficiency causes a megaloblastic, macrocytic anemia with elevated MCV, low reticulocyte count, and can present with glossitis and neuropsychiatric symptoms including dementia.