Macrocytic Synthesis Of Pernicious Anemia (PA)

Introduction Pernicious anemia (PA) is a type of macrocytic normochromic anemia. It is a slow-developing disorder with the underlying cause of Vitamin B12 absorption and deficiency due to lack of intrinsic factor (IF). Vitamin B12 absorption is facilitated by IF, which binds B12 in the duodenum, forming the IF-vitamin-B12 complex, later recognized by receptors and absorbed in the jejunum (Anderson, et al., 445). A consequence of vitamin B-12 deficiency is altered DNA replication and erythropoiesis as well as the demyelination of neurons (Orton, 548), leading to the clinical manifestations of anemia, gastrointestinal symptoms, and neurodegeneration (Huether, 503).
Pathophysiology
The development of pernicious anemia (PA) is often the outcome
It is required for normal DNA synthesis and nuclear maturation during cell division. Erythrocytes are produced by differentiating pluripotent hematopoietic stem cells. Without B12, the growth and development of the erythrocytes occurs at different rates, with DNA synthesis lagging (Orton, 548). RNA and hemoglobin are produced normally; however, because the cell cycle is delayed, hemoglobin is overproduced, resulting in abnormally large, oval-shaped cells in decreased number and cellular lifespan (Huether, 503), which cause the systemic manifestations of
Vitamin B12 is a co-enzyme in the conversion of methylmelonyl CoA into succinyl CoA, an intermediate in the citric acid cycle. Without vitamin B12, methylmelonyl is instead converted into methylmalonic acid (MMA), which destabilizes myelin. In place of myelin, abnormal fatty acids are synthesized and incorporated into lipids, resulting in a fragile sheath or demyelination (Orton, 548). This leads to neuronal and neuropsychological complications due to neuron degenerative