Cells containing hemoglobin S become sickle-shaped at low oxygen concentrations as a result of hemoglobin molecule binding. This binding usually takes place in cells in the veins, where oxygen saturation is about 66-73 % compared to the arteries, where oxygen saturation is 98-100 % (Dulbecco 1997). The polymerized hemoglobin makes the cells long and rigid (like a sickle), a stark contrast from their usual round, pliable nature.
These pointy cells can easily puncture other cells, causing major damage to other sickled cells already weakened by waves of hemoglobin polymerization and depolymerization. Sickled cells as a result have a siginificantly shorter life span of 16 days rather than the 120 days of normal red blood cells (SCDAA 2005).
The anemia aspect of sickle cell disease (having too low red blood cell concentration) is a result of the short life span of sickled red blood cells, not of a too slow production of them. In fact, the production of red blood cells in people with sickle cell disease can be five to ten times higher than that of unaffected people (Bridges 2002). People with sickle cell anemia usually have about half of the normal concentration of hemoglobin in their blood (Nelson and Cox 2005).
Anemia can have many negative effects on the body. Since fewer red blood cells are available to transport oxygen, tissues receive less oxygen and patients may experience weakness or dizziness. To help increase oxygen to the tissues, the blood vessels dilate (Guyton 1991). At the same time, lower concentrations of red blood cells make the viscosity of the blood much lower (Guyton 1991). Lower blood viscosity provides less resistance in blood vessels, which increases the amount of blood to the heart (Guyton 1991). This decreased resistance, along with dilated vessels, combine to create a large workload on the heart (Guyton 1991).
Increased workload on the heart can help blood pump through the body more quickly, delivering more oxygen to the tissues that need it (Guyton 1991). This workload can be a problem, however, when people with sickle cell anemia exercise, further increasing the workload on the heart. The heart is unable to pump harder because it is already near its maximum output and required amounts of oxygen cannot be transported to the tissues (Guyton 1991). This can result in tissue hypoxia (not enough oxygen to the tissues) or cardiac failure (Guyton 1991).
Vaso-occlusive crises, or pain crises, are one of the most severe symptoms of sickle cell anemia. Pain crises are severe pain “attacks” in the chest, back, and legs. The frequency and severity of these crises vary from patient to patient. Severe pain crises must be treated immediately because they can cause damage to the major organs, bones, and the central nervous system.
These crises are caused by reduced or cut off blood flow through small blood vessels. As mentioned above, sickled cells are not only oddly shaped but are also less pliable, causing sickled cells to get caught in small vessels because they cannot change their shape in tight spaces like normal cells do. Once one sickled cell gets stuck in a capillary, a buildup occurs, cutting off blood flow (and hence oxygen supply). Severe pain ensues.
Blood vessels occluded by sickled cells, which cause pain crises. Image source: NHLB http://www.nhlbi.nih.gov/health/dci/ Diseases/Sca/SCA_WhatIs.html
Instances of pain crises can, however, be reduced if certain conditions are avoided. Circumstances of low oxygen supply (at high altitudes, exercise) should be avoided because cells are less likely to sickle if oxygen concentration in the blood is high (Sickle Cell Society 2005). Reduced oxygen supply during illness or pregnancy can also cause pain crises (Sickle Cell Society 2005).
Often pain crises can be so severe that treatment at a hospital is necessary. In a hospital severe pain crises may be treated with opiates to relieve pain, intravenous fluids, antibiotics, oxygen, and in the most severe cases a blood transfusion (Sickle Cell Society, 2005).
The vaso-occlusion of pain crises also irritates and inflames endothelial cells lining the capillary beds. This inflammation can, in turn, cause further occlusions, creating a “vicious cycle of inflammation causing occlusion causing inflammation” (Hebbel et al. 2004). The onset of this cycle is possible either through occlusion or through inflammation (caused by infection, etc.) and if avoided can help prevent excessive organ and tissue damage (Hebbel et al. 2004).