Overview
This lecture explains sickle cell anemia, covering its genetic basis, pathophysiology, symptoms, and management strategies.
Definition and Genetics
- Sickle cell anemia is a type of anemia caused by abnormally shaped (crescent/sickle) red blood cells.
- It is an autosomal recessive disorder; both gene copies must be abnormal for symptoms to appear.
- Carriers have one normal and one abnormal gene copy but do not show disease symptoms.
- Affected children inherit one abnormal gene from each carrier parent.
- Autosomal means the defect is on chromosome pairs 1-22, not the sex (X or Y) chromosomes.
Pathophysiology and Triggers
- Sickle cell disease affects the beta chain of hemoglobin in red blood cells.
- Triggers for sickling include dehydration, acidosis (low blood pH), and low oxygen saturation (<60%).
- Sickled red blood cells are fragile, die early (shorter lifespan than the usual 120 days), and cause anemia.
- Cell breakdown increases bilirubin, leading to jaundice, first seen in the eyes (sclera).
Complications
- Sickled cells can clump in blood vessels (vaso-occlusive crisis), blocking blood flow (stasis) and leading to tissue ischemia and pain.
- Ischemia causes a switch to anaerobic metabolism, producing lactic acid, which irritates nerves and causes extreme pain.
- Symptoms start after 6 months of age, once fetal hemoglobin (which lacks beta chains) is replaced by adult hemoglobin.
Clinical Manifestations (5S of Sickle Cell)
- Swelling: Painful swelling of hands and feet (hand-foot syndrome) due to ischemia.
- Splenomegaly: Enlarged spleen, which may get damaged and increase infection risk.
- Short-lived RBCs: Lead to chronic anemia.
- Sclera Jaundice: Yellowing of the eyes from increased bilirubin.
- Sequestration: Spleen sequesters damaged cells, causing severe hypovolemia.
Management
- Prevent triggers: avoid dehydration, acidosis, and low oxygen.
- Management includes hydration (IV/oral fluids), oxygen therapy, and pain control (acetaminophen, morphine; use naloxone for overdose).
- Use hydroxyurea to increase fetal hemoglobin, which resists sickling.
- Hypertransfusion with packed red blood cells (not whole blood) may be needed after correcting dehydration, acidosis, and oxygenation.
Key Terms & Definitions
- Autosomal recessive — A genetic disorder requiring two abnormal gene copies to show disease.
- Hemoglobin beta chain — Protein part of adult hemoglobin; abnormal in sickle cell disease.
- Vaso-occlusive crisis — Blood vessel blockage by sickled cells, causing pain and tissue damage.
- Ischemia — Reduced blood flow to tissues, leading to lack of oxygen.
- Splenomegaly — Enlarged spleen.
- Jaundice — Yellowing of skin or eyes from high bilirubin.
- Sequestration — Spleen trapping many red blood cells, decreasing blood volume.
- Hydroxyurea — Medication that increases fetal hemoglobin to reduce sickling.
Action Items / Next Steps
- Review mechanisms of autosomal recessive inheritance.
- Study the triggers and management for sickle cell crises.
- Read about fetal versus adult hemoglobin structures and their roles in sickle cell anemia.