NEET PG High-Yield: Sickle Cell Anaemia
Sickle cell anaemia is a classic example of a point mutation resulting in a structural hemoglobinopathy.
Genetics & Pathophysiology
- Molecular Basis: Substitution of Glutamic acid by Valine at the 6th position of the $\beta$-globin chain (GAG $\rightarrow$ GTG mutation).
- Inheritance: Autosomal Recessive.
- Mechanism: Under deoxygenated conditions, HbS polymerizes, causing RBCs to undergo “sickling,” leading to hemolysis and vaso-occlusion.
Key Clinical Features
| Feature | Details |
|---|---|
| Vaso-occlusive Crisis | Severe pain in bones, chest, or abdomen due to ischemia. |
| Splenic Sequestration | Sudden splenomegaly, severe anemia, and hypovolemic shock. |
| Infections | Functional asplenia increases risk for encapsulated organisms (e.g., S. pneumoniae). |
High-Yield NEET PG Pearls:
- Diagnosis: Hemoglobin electrophoresis is the diagnostic gold standard.
- Blood Smear: Sickle-shaped cells, Howell-Jolly bodies (due to functional asplenia).
- Treatment: Hydroxyurea is the cornerstone therapy (increases HbF levels).
- Malaria Protection: Heterozygotes (Sickle Cell Trait) have a selective survival advantage against Plasmodium falciparum malaria.