Sickle Cell Disease | Pathophysiology, Symptoms and Treatment

Summary

This video provides an in-depth explanation of sickle cell disease, a hereditary blood disorder characterized by sickle-shaped red blood cells. It covers the genetic basis, where the disease is inherited in an incomplete autosomal dominant fashion, and explains how a point mutation in the hemoglobin beta globin chain leads to the abnormal shape. The pathophysiology, including RBC sickling, hemolysis, and vaso-occlusion, as well as acute and chronic complications such as pain, anemia, and organ damage, are discussed. Diagnosis and treatment options, including hydroxyurea and bone marrow transplants, are also highlighted.

Takeaways

• 🧬 Sickle cell disease is a hereditary blood disorder characterized by sickle-shaped red blood cells.
• 🧬 It is inherited in an incomplete autosomal dominant fashion, where individuals with two copies of the affected allele are fully affected.
• 🧬 People with one affected allele have sickle trait, which offers some protection against malaria but causes less severe symptoms.
• 🧬 The disease is caused by a single point mutation in the hemoglobin beta-globin chain, substituting glutamic acid with valine at position six.
• 🔬 Sickle-shaped red blood cells can clog small blood vessels, leading to painful vaso-occlusion and increased risk of organ damage.
• 🔬 Red blood cells in sickle cell disease have a shorter lifespan (around 17 days) compared to normal red blood cells (120 days).
• 💉 Acute complications include severe anemia, infections, and pain caused by the sickling of red blood cells during stress conditions like hypoxia and dehydration.
• 🩺 Chronic complications include hemolytic anemia, chronic pain, delayed growth, and neurological, renal, and cardiovascular issues.
• 🧪 Sickle cell disease can be diagnosed through prenatal testing, newborn screening, and hemoglobin electrophoresis.
• 💊 Hydroxyurea is a common treatment that reduces pain episodes and prolongs survival, while bone marrow transplants offer a potential cure for patients under 16.

Q & A

What is sickle cell disease?

Sickle cell disease is a group of hereditary blood disorders characterized by sickle-shaped red blood cells.

How is sickle cell disease inherited?

Sickle cell disease is inherited in an incomplete autosomal dominant fashion. Individuals with two copies of the affected allele (homozygous) are fully affected, while those with one copy (heterozygous) are carriers and can be slightly affected.

What is the difference between individuals with sickle cell disease and those with sickle cell trait?

Individuals with sickle cell disease are homozygous for the hemoglobin S allele, while those with sickle cell trait are heterozygous and experience milder or no symptoms.

Why does the sickle cell mutation persist in certain populations?

The sickle cell mutation provides protection against malaria, which is why it persists in populations where malaria is prevalent.

What causes the abnormal shape of red blood cells in sickle cell disease?

A single point mutation on the hemoglobin beta globin chain changes glutamic acid to valine at position six, causing hemoglobin S. When deoxygenated, hemoglobin S is less soluble and aggregates, leading to red blood cell sickling.

What complications arise from sickle-shaped red blood cells?

Sickle-shaped red blood cells can get trapped in small blood vessels, leading to vascular occlusion, hemolysis, and inflammatory responses, which cause pain, anemia, and other complications.

How long do sickle-shaped red blood cells live compared to normal red blood cells?

Sickle-shaped red blood cells have a significantly reduced lifespan, living about 10 to 20 days compared to normal red blood cells, which live around 120 days.

What are some of the acute complications of sickle cell disease?

Acute complications include an increased risk of infections, severe anemia, and vaso-occlusive pain due to sickled red blood cells blocking blood vessels.

What are some chronic complications of sickle cell disease?

Chronic complications include chronic hemolytic anemia, pain, neurologic deficits, pulmonary issues, renal problems, osteoporosis, cardiomyopathy, delayed growth, and chronic leg ulcers.

What treatments are available for sickle cell disease?

Treatment options include hydroxyurea, which reduces pain episodes and hospitalizations, blood transfusions for severe anemia, and hematopoietic cell transplantation, which is considered a potential cure for individuals under 16 years old.