Anemia de Células Falciformes | Parte 1 | Fisiopatología
Understanding Sickle Cell Disease
Structure of Hemoglobin
- Hemoglobin A, the primary adult hemoglobin, is a tetramer composed of two alpha and two beta globin chains, each linked to a heme group capable of reversible oxygen binding.
Sickle Cell Disease Overview
- Sickle cell disease encompasses all combinations of sickle cell variants in one allele and another variant in the HBB gene on the other allele, leading to clinical sickle cell anemia.
- The focus is on cases where both alleles have the sickle cell variant (HbSS), which is the most common and severe form.
Genetic Basis
- This condition is a monogenic disorder caused by a point mutation in the HBB gene that results in an amino acid substitution at position six from hydrophilic glutamic acid to hydrophobic valine.
- The mutated hemoglobin is referred to as hemoglobin S (HbS), inherited in an autosomal recessive pattern.
Inheritance Patterns
- For manifestation of the disease, individuals must be homozygous (two affected alleles) or compound heterozygous. Parents are typically carriers with a 25% chance for offspring to inherit the condition.
- Heterozygous individuals exhibit sickle cell trait (benign carrier state), possessing about 40% HbS without vaso-occlusive crises or hemolysis.
Physiological Implications
- Carriers have normal life expectancy but face slightly increased risks for certain health issues while having evolutionary advantages against malaria due to reduced severity from Plasmodium falciparum infections.
Pathophysiology: Polymerization of HbS
- HbS polymerization occurs under low oxygen conditions, exposing hydrophobic sequences that lead to chain aggregation and formation of long fibers within red blood cells.
Consequences of Polymerization
- This process increases cellular rigidity and distorts erythrocyte shape into a sickle form, resulting in premature destruction and complications.
Vaso-Occlusion Events
- Vaso-occlusion leads to painful crises due to increased plasma viscosity from chronic hemolysis and reduced erythrocyte deformability affecting blood flow through small vessels.
Endothelial Dysfunction