Sickle cell anemia

Pathogenesis of sickle cell anemia (2)

1. 2 Mutated Beta-globin

2. Hemoglobin S

Genetics of sickle cell anemia

The anemia is inherited in an autosomal recessive pattern

Sickle cell anemia (3)

1. Homozygous

2. Both mutated alleles

3. No HbA Mostly HbS

Sickle cell trait (4)

1. Heterozygous

2. One normal and one mutated allele

3. About 60% HbA About 40% HbS

4. Asymptomatic

Reversible Sickling with Sickle Cell Disease

HbS polymerizes

Factors that Affect Sickling of Red Cells (4)(3)

1. Oxygen tension

2. Presence of other forms of hemoglobin prevent polymerization

3. Concentration of HbS in the red cell

• e.g. Dehydration promotes sickling

4. Sluggish blood flow

• Longer time in capillaries → sufficient time for cells to sickle in the microvasculature

• Occurs especially in the spleen and the bone marrow, and with inflammation

Major Consequences of Sickle Cell Disease (2)

1. Chronic hemolytic anemia (typically moderate to severe)

2. Episodic pain crises (vaso-occlusive crisis) associated with ischemic tissue damage

Chronic hemolytic anemia Development and lifespan (5)

1. Multiple cycles of sickling

2. Extensive membrane damage

3. Irreversibly sickled cells which are more fragile

4. Extravascular and intravascular hemolysis

5. Lifespan 20 days

Signs and Symptoms of Sickle Cell Disease (from intra- and extravascular hemolysis → anemia) (7)

1. Fatigue, pallor

2. Low hemoglobin levels

3. Low erythropoietin levels

4. Elevated number of reticulocytes in blood

5. Elevated bilirubin in blood

6. Jaundice

7. Gallstones

Episodic pain crises Development (3)

1. Develop spontaneously (unknown why) OR

2. Precipitating stimulus

   1. Infection, inflammation, dehydration

3. ‘sticky’ to endothelium = Micro-vascular occlusion

Signs and Symptoms of Sickle Cell Disease (from vaso-occlusive pain crisis) (3)

1. Tissue or organ ischemia, infarction

2. Sudden, severe pain

3. Recurrent ischemia → damage to many organs

What happens to the spleen in a child with sickle cell disease (4)

1. First develop splenomegaly

2. Numerous splenic infarctions secondary to vaso-occlusion

3. Spleen becomes scar tissue and small

4. Functionally asplenic → risk of infections