The problems associated with SCD are not caused only by the sickle cells, but also by altered vascular wall function.
- Especially during infections, but also in case of fever, dehydration, pain, high altitude, cold environment, lack of oxygen, or stress, sickle cells can get stuck in the small blood vessels and clump together. The sickle cells then basically stick to the wall of the smaller blood vessels. Although these kinds of sickle cell crises can occur spontaneously, they are generally triggered by the circumstances listed above. Given that these vessels are very narrow, they clog up easily, which blocks blood flow. The area behind the obstruction will then not receive blood and consequently be deprived of oxygen. This results in damage to the cells in the surrounding tissue. As soon as the obstruction is dissolved and blood flow is restored, the blood can reach the tissue again, which is a process that is called reperfusion. The process where the tissue first suffers lack of oxygen during the obstruction and is then suddenly reoxygenated through reperfusion results in permanent adverse changes in the vascular wall.
The red blood cells do not live as long as normal, due to the presence of hemoglobin S, resulting in accelerated breakdown of red blood cells. This is also what causes the severe anemia in people with sickle cell disease. Their red blood cell count is low, which means they cannot bind and transport as much oxygen as needed. The body therefore absorbs less oxygen and, consequently, receives less fuel. This leads to a variety of symptoms, including tiredness.
- Nitric oxide (NO) is bound to the free hemoglobin in the bloodstream. SCD patients have more free hemoglobin because the red blood cells are continuously broken down and the resulting free hemoglobin stays in the bloodstream. This binding of NO to free hemoglobin makes that there is less functional NO available. Normally, NO relaxes the wall of blood vessels, widening them to allow more blood to flow through.
A shortage of NO can lead, among other things, to high blood pressure in the lungs, because the blood vessels in the lungs are unable to relax properly, leading to reduced blood flow through the lungs. This is called pulmonary hypertension. A shortage of NO also leads to excessive release of ornithine, which is a substance that causes the vascular wall to change, creating more smooth muscle tissue and boosting collagen synthesis. Other processes are also affected by NO shortage, causing extra complications in SCD patients.
