Sickle Cell Disease
- Group of inherited, autosomal recessive disorders
- Characterized by presence of an abnormal form of Hgb in RBC
- Genetic disorder usually identified during routine neonatal screening
- Incurable and often fatal by middle age
Etiology and pathophysiology
- Abnormal hemoglobin, HgbS, causes the RBC to stiffen and elongate
- Erythrocytes take on a sickle shape in response to decrease O2 levels
- Substitution of valine for glutamic acid on the β-globin chain of hemoglobin
- Types of SCD
- Sickle cell anemia
- Most severe
- Homozygous for hemoglobin S (HgbSS)
- Sickle cell thalassemia
- Sickle cell HgbC disease
- Sickle cell trait (HgbAS)
- Sickle cell anemia
- Sickle cell hemoglobin aggregates and alters shape of RBC
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Normal red blood cells |
Sickled red blood cells |
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Normal hemoglobin |
Sickle cell hemoglobin forms long and inflexible chains |
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Normal RBCs are compact and flexible, enabling them to squeeze through small capillaries |
Sickled RBCs are stiff and angular, causing them to become stuck in small capillaries |
- Sickling episodes
- The major pathophysiologic event of this disease
- Triggered by low O2 tension in blood
- Infection is most common precipitating factor
- Initially, sickling is reversible with re-oxygenation
- Sickling episodes are most commonly triggered by low oxygen tension in the blood.
- Hypoxia or deoxygenation of the RBCs can be caused by viral or bacterial infection, high altitude, emotional or physical stress, surgery, and blood loss.
- Infection is the most common precipitating factor. Other events that can trigger or sustain a sickling episode include dehydration, increased hydrogen ion concentration (acidosis), increased plasma osmolality, decreased plasma volume, and low body temperature. A sickling episode can also occur without an obvious cause.
- Initially the sickling of cells is reversible with reoxygenation, but it eventually becomes irreversible because of cell membrane damage from recurrent sickling.
- Thus vaso-occlusive phenomena and hemolysis are the clinical hallmarks of sickle cell disease.
- The major pathophysiologic event of this disease
- Sickle cell crisis
- Severe, painful, acute exacerbation of sickling causes a vaso-occlusive crisis
- Severe capillary hypoxia eventually leads to tissue necrosis
- Life-threatening shock is a result of severe O2 depletion of the tissues and a reduction of the circulating fluid volume
