Pathophysiology
1) family of hemoglobinopathies with deformation of deoxygenated erythrocytes into a sickle shape 2) homozygous individuals are severely affected, with sickled hemoglobin (HbS) making up 80-95% of hemoglobin 3) sickled cells obstruct the small blood vessels, creating the many sequelae of the disease 4) heterozygous state has a protective effect against malaria, especially in children
Signs and Symptoms
1) presents 8-10 weeks after birth (patient is protected by residual fetal hemoglobin) 2) typical disease course is marked by episodic “sickle crisis” with greatly increased severity of symptoms 3) severe pain in abdomen, chest (acute chest syndrome), and bones 4) swollen hands and feet (hand-foot syndrome) 5) skin ulceration (especially on ankles) 6) cardiomegaly 7) cholecystitis (due to pigment stones) 8) osteomyelitis (especially Salmonella typhimurium) 9) blindness 10) stroke 11) priapism
Characteristic Test Findings
Laboratory – 1) chronic hemolytic anemia Radiology – 2) bilateral lung infiltrates
Histology/Gross Pathology
1) RBCs with classic sickle morphology 2) erythrocyte ghosts (complete lack of hemoglobin) with sickle shape 3) splenic infarcts with fibrosis and atrophy 4) Howell-Jolly bodies 5) infarcts in femoral head 6) renal infarcts
Associated Conditions
increased incidence of 1) aplastic crisis with severe anemia secondary to infection (especially parvovirus B19) 2) sequestration crisis with anemia (especially in infants and young children) 3) life-threatening infections with encapsulated bacteria (especially Streptococcus pneumoniae) 4) Mycoplasma pneumoniae infections
Biochemistry
1) caused by point mutation (glutamic acid replaced by valine in the beta-globin chain) 2) causes HbS to aggregate at a low oxygen tension with contraction of RBC around it 3) overall effect is to make cells less deformable and more likely to act as obstruction point 4) increased adhesion to endothelium
Inheritance/Epidemiology
1) autosomal recessive 2) defect is on chromosome 11p) 3) sickle cell disease is homozygous for HbS gene 4) sickle cell trait is heterozygous for HbS gene (10% of American blacks; does not affect life span and no treatment is needed) 5) sickle cell disease affects 50,000 people in the USA (almost entirely in black population) 6) also affects populations in India, Middle East, and Mediterranean
Treatment
1) hydroxyurea (increases amount of protective fetal hemoglobin) 2) clotrimazole (blocks RBC adhesion) 3) vigorous hydration 4) narcotics 5) vaccination against pneumococci and Haemophilus 6) antibiotic prophylaxis for invasive procedures 7) bone marrow transplantation (best in children)
Tips for USMLE
if acute chest syndrome or hand-foot syndrome is mentioned, think sickle cell disease
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