Page 323 - Concise Pathology for Exam Preparation ( PDFDrive )

308 SECTION II Diseases of Organ Systems

Q. Write briefly on the pathophysiology, clinical features and
laboratory diagnosis of sickle cell disease.
Ans. Sickle cell disease is a hereditary haemoglobinopathy, which is characterized by
point mutation-substitution of glutamic acid (CTG) by valine (CAG) at 6th position in
b-globin chain.

Pathophysiology (Flowchart 12.10)

Sickled Hb (Hbs)
Deoxygenation
Hbs polymers

Hbs fiber

Distortion of RBC and formation of a sickle cell
Repeated cycles of
oxygenation and
deoxygenation
Irreversibly sickled cells (ISCs)
• ISCs loose K , H O and gain Ca 2+
+
2
• Undergo dehydration and show increased
intracellular concentration of Hb
• Exhibit impaired deformability and
increased adhesiveness
ISCs undergo
• Intravascular haemolysis
• Extravascular haemolysis (in spleen)
FLOWCHART 12.10. Pathophysiology of sickle cell anaemia.

Factors Affecting Sickling

• Amount of HbS: Heterozygotes do not show sickling except under severe hypoxia.
• Interaction with other type of Hb: HbF inhibits polymerization of HbS and hence,
sickling (so, the disease manifests 5–6 months after birth). HbC and HbD promote
sickling (HbSC is the more severe form of disease).
• MCHC value: Any condition (like dehydration) that increases MCHC increases
sickling.
• pH: Fall in pH increases sickling.
• Oxygen concentration: Increased oxygen concentration increases sickling.

Clinical Features

• Severe anaemia and generalized impairment of growth and development due to
hypoxia.
• Vasoocclusive complications which include acute chest syndrome, dactylitis (hand-foot
syndrome) and stroke.
• Chronic hyperbilirubinaemia and cholelithiasis.
• Septicaemia and meningitis caused by Pneumococci and H. influenzae are common.
Patients are also predisposed to Salmonella osteomyelitis. Increased susceptibility to
infection is attributed to
• Impaired splenic function (autosplenectomy), which occurs as a result of hypoxic
tissue damage consequent to chronic stasis and congestion of red pulp.
• Defect in alternative complement pathway (opsonization defect).
• Other commonly encountered crises include aplastic crisis (sudden cessation of
marrow erythropoiesis triggered by parvovirus infection manifesting as anaemia without

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