tailieunhanh - Chapter 099. Disorders of Hemoglobin (Part 9)

Unstable hemoglobins occur sporadically, often by spontaneous new mutations. Heterozygotes are often symptomatic because a significant Heinz body burden can develop even when the unstable variant accounts for a portion of the total hemoglobin. Symptomatic unstable hemoglobins tend to be β-globin variants, because sporadic mutations affecting only one of the four α-globins would generate only 20–30% abnormal hemoglobin. Hemoglobins with Altered Oxygen Affinity High-affinity hemoglobins [., Hb Yakima (β99Asp - His )] bind oxygen more readily but deliver less O2 to tissues at normal capillary PO2 levels (Fig. 992). Mild tissue hypoxia ensues, stimulating RBC production and erythrocytosis (Table 99-3). . | Chapter 099. Disorders of Hemoglobin Part 9 Unstable hemoglobins occur sporadically often by spontaneous new mutations. Heterozygotes are often symptomatic because a significant Heinz body burden can develop even when the unstable variant accounts for a portion of the total hemoglobin. Symptomatic unstable hemoglobins tend to be 0-globin variants because sporadic mutations affecting only one of the four a-globins would generate only 20-30 abnormal hemoglobin. Hemoglobins with Altered Oxygen Affinity High-affinity hemoglobins . Hb Yakima 099Asp - His bind oxygen more readily but deliver less O2 to tissues at normal capillary PO2 levels Fig. 99- 2 . Mild tissue hypoxia ensues stimulating RBC production and erythrocytosis Table 99-3 . In extreme cases the hematocrits can rise to 60-65 increasing blood viscosity and producing typical symptoms headache somnolence or dizziness . Phlebotomy may be required. Typical mutations alter interactions within the heme pocket or disrupt the Bohr effect or salt-bond site. Mutations that impair the interaction of HbA with 2 3-BPG can increase O2 affinity because 2 3-BPG binding lowers O2 affinity. Low-affinity hemoglobins . Hb Kansas p102Asn - Lys bind sufficient oxygen in the lungs despite their lower oxygen affinity to achieve nearly full saturation. At capillary oxygen tensions they lose sufficient amounts of oxygen to maintain homeostasis at a low hematocrit Fig. 99-2 pseudoanemia . Capillary hemoglobin desaturation can also be sufficient to produce clinically apparent cyanosis. Despite these findings patients usually require no specific treatment. Methemoglobinemias Methemoglobin is generated by oxidation of the heme iron moieties to the ferric state causing a characteristic bluish-brown muddy color resembling cyanosis. Methemoglobin has such high oxygen affinity that virtually no oxygen is delivered. Levels 50-60 are often fatal. Congenital methemoglobinemia arises from globin mutations that stabilize iron in the ferric .