13.

Pathophysiology

Pernicious anemia
Pathologic CD4 Trecognize an autoimmune response against the H1/K1–
Production of antibodies against adenosine triphosphatase embedded in the
membrane of the parietal cells.

Parietal cells Chronic inflammatory infiltration

Intrinsic Factor

Loss of parietal cells

Antibodies block site for B12
attachment

Decreased H+ ions
Inhibit IF-B12 complex Decreased Intrinsic
factor
Achlorrhydria

Decreased B12

Decreased conversion of Homocysteine to Methionine

Decreased production of Methyl THF

Decreased thymidine availability

Uridine replaces thymidine in DNA replication

At any point where a thymidine nucleotide is

needed, there is essentially an empty space in the replicated
DNA sequence, which results in many single-strand breaks
When excisions at opposing DNA strand sites coincide,
double-strand breaks occur

Repeated DNA strand breaks

lead to fragmentation of the DNA strand

DNA is nonfunctional and DNA replication is incomplete

Cell division is halted, resulting in either cell lysis or

apoptosis

Ineffective hematopoieisis

Erythroid cells are larger with immature nuclei with nuclear

Pancytopenia cytoplasmic asynchrony
Macrocytosis