Learn More About: Pathophysiology

Pathophysiology of Sickle Cell Disease

Jennifer L. Mathews, Ph.D.

Learning Objectives:

  1. Define intrinsic hemolytic anemia and how it relates to sickle cell disease.
  2. Describe the pathophysiology and genetics associated with sickle cell disease.
  3. Describe vaso-occlusive crisis, avascular necrosis, and acute chest syndrome.

Intrinsic Hemolytic Anemia

  • Inherited
  • Abnormal genes lead to abnormal erythrocytes
    • Fragile or malformed, do not function correctly
    • Destroyed more easily
  • Types
    • G6PD Deficiency
    • Sickle Cell Anemia
    • Thalassemias
    • Aplastic Anemia

Sickle-Cell Disease

Illustration shows how sickle cell hemoglobin forms long, unflexible chains.
Normal hemoglobin compared to sickle cell hemoglobin
  • Mutation in one of the 146 amino acid molecules in a beta-globin chain leads to production of abnormal hemoglobin (hemoglobin S, HbS)
  • Under hypoxic conditions, the beta chains link together
    • Form stiff rods that are sharp and spike-like
    • RBC becomes crescent-shaped
  • RBCs rupture easily and dam up small vessels
    • Can cause extreme pain and loss of circulation


A Vicious Cycle

Illustration shows how hypoxic conditions feed into cell sickling that feed into erythrocyte rupture that feeds into a decrease of the oxygen carrying capacity of blood before the cycle starts again.
A vicious cycle
  • Once the process starts, it progresses rapidly
  • Patients can decompensate quickly, within a few hours:
    • Dangerously low erythrocyte counts
    • Will lead to death if not treated promptly

Vaso-occlusive Crisis

  • Acute pain
  • Can occur without warning
  • Pain described as sharp, intense, stabbing, or throbbing
  • Pain often occurs in the:
    • Lower back
    • Legs
    • Arms
    • Abdomen
    • Chest
  • Can be brought on by triggers


Crisis Precipitation

The following may precipitate a vaso-occlusive crisis in a patient who has sickle-cell disease:

  • High altitudes
  • Rigorous exercise
  • Hypothermia

Triggers for Vaso-occlusive Crisis

  • Illness
  • Changes in temperature
  • Stress
  • Dehydration
  • High altitude


Avascular Necrosis

  • Caused by repeated disruptions in blood flow to the joint
  • Usually found in adolescents and adults, not children
  • Sickling in the bones of the hip, shoulder joints, knees, and ankles
  • Decreased oxygen flow results in severe damage
  • Symptoms:
    • Pain and problems with walking and joint movement


Acute Chest Syndrome

  • Caused by occlusion of blood vessels in the lungs
  • Lungs can be deprived of oxygen causing tissue damage
  • Often starts after a painful crisis
  • Symptoms:
    • Pain
    • Fever
    • Shortness of breath
    • Cough


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