Sickle Cell Disease Pathophysiology

Definition and Causes

• Sickle cell disease (SCD) is a genetic disorder that affects hemoglobin, a protein in red blood cells.
• It is caused by a mutation in the HBB gene that codes for hemoglobin subunit beta.
• The mutation leads to the production of abnormal hemoglobin, called sickle hemoglobin (HbS).

Pathophysiology

• HbS is prone to polymerization, causing red blood cells to become rigid and sickle-shaped.
• Sickled cells can get stuck in small blood vessels, leading to vaso-occlusion and ischemia.
• Repeated episodes of vaso-occlusion can cause chronic organ damage and organ failure.

Symptoms and Complications

• Anemia: sickled cells have a shorter lifespan, leading to chronic anemia.
• Pain episodes: vaso-occlusion can cause recurring pain in the hands, feet, and joints.
• Infections: people with SCD are more prone to infections, especially pneumonia and osteomyelitis.
• Organ damage: repeated vaso-occlusion can lead to damage in organs such as the kidneys, liver, and spleen.
• Stroke: SCD increases the risk of stroke due to blood vessel blockage.

Diagnosis

• Screening tests: newborn screening tests can detect HbS.
• Diagnostic tests: hemoglobin electrophoresis, sickle solubility test, and genetic testing can confirm the diagnosis.

Management and Treatment

• Pain management: medications such as acetaminophen and opioids can help manage pain.
• Hydroxyurea: a medication that can help reduce the frequency of pain episodes and prevent complications.
• Blood transfusions: can help increase oxygen delivery to tissues and organs.
• Bone marrow transplant: a potential cure for SCD, but it carries risks and is not always available.

Complications and Prognosis

• Increased risk of mortality: SCD can lead to premature death, especially in resource-poor countries.
• Quality of life: SCD can significantly impact quality of life due to recurring pain episodes and chronic organ damage.
• Pregnancy complications: women with SCD are at higher risk of pregnancy-related complications.

Definition and Causes

• Genetic disorder that affects hemoglobin in red blood cells
• Caused by mutation in the HBB gene, coding for hemoglobin subunit beta
• Leads to production of abnormal hemoglobin, called sickle hemoglobin (HbS)

Pathophysiology

• HbS prone to polymerization, causing red blood cells to become rigid and sickle-shaped
• Sickled cells can get stuck in small blood vessels, leading to vaso-occlusion and ischemia
• Repeated vaso-occlusion causes chronic organ damage and organ failure

Symptoms and Complications

• Anemia due to shorter lifespan of sickled cells
• Recurring pain episodes in hands, feet, and joints due to vaso-occlusion
• Increased risk of infections, especially pneumonia and osteomyelitis
• Organ damage, including kidneys, liver, and spleen, due to repeated vaso-occlusion
• Increased risk of stroke due to blood vessel blockage

Diagnosis

• Newborn screening tests detect HbS
• Hemoglobin electrophoresis, sickle solubility test, and genetic testing confirm diagnosis

Management and Treatment

• Pain management with medications like acetaminophen and opioids
• Hydroxyurea reduces frequency of pain episodes and prevents complications
• Blood transfusions increase oxygen delivery to tissues and organs
• Bone marrow transplant is a potential cure, but carries risks and is not always available

Complications and Prognosis

• Increased risk of premature death, especially in resource-poor countries
• Significant impact on quality of life due to recurring pain episodes and chronic organ damage
• Higher risk of pregnancy-related complications in women with SCD