Sickling in ‘Hbs’ disease is primaily caused by
**Core Concept**
Sickling in 'HbS' disease is primarily caused by a specific molecular mechanism involving hemoglobin. The underlying principle is the **polymerization of deoxygenated hemoglobin S**, leading to the characteristic sickle shape of red blood cells. This occurs due to a point mutation in the **HBB** gene.
**Why the Correct Answer is Right**
The correct answer is related to the **deoxyhemoglobin** state, where the **valine** substitution at position 6 of the beta-globin chain (instead of **glutamic acid**) leads to hydrophobic interactions between hemoglobin molecules. This interaction causes the **polymerization of deoxygenated hemoglobin S**, resulting in the distortion of red blood cells into a sickle shape.
**Why Each Wrong Option is Incorrect**
**Option A:** Incorrect because it does not directly relate to the primary cause of sickling.
**Option B:** Incorrect as it is not the main factor.
**Option C:** Incorrect because it is not directly involved in the sickling process.
**Option D:** Incorrect as it is unrelated to the primary mechanism.
**Clinical Pearl / High-Yield Fact**
A key point to remember is that **deoxyhemoglobin** is more prone to polymerization, leading to sickling. This is crucial in understanding the pathophysiology of **sickle cell disease**.
**Correct Answer:** D. Low Oxygen Tension