Homozygous sickle cell anaemia (HbSS, autosomal recessive) is the most common
variant
Occurs in African and East Meditarranean populations (mosquito)
Point mutation of the beta chain of hemoglobin leads to a substitution of glutamic
acid by valine (changing the structure and properties)
Abnormal hemoglobin polymerizes when deoxygenated, resulting in sickle shaped
erythrocytes (cause vascular occlusion and ischaemia)
Manifests in early childhood with symptoms associated with vascular occlusion
and hemolytic anaemia (infarctions of the spleen, kidneys, bone, CNS, progressive
loss of organ function and acute and chronic pain)
Acute, painful vaso-occlusive crises are provoked by conditions associated with
reduced oxygen tension
Neonatal screening
Hemoglobin quantification are used to diagnose the condition
,Cornerstones of treatment; management of the painful vaso-occlusive crises,
hemolytic anaemia, disease complications and prevention of infection
Allogenic bone marrow transplantation is the only curative treatment option
Polymerise - ANSWER✔✔ The joining together of lots of small molecules called
monomers to form a long-chain molecule called a polymer.
Epidemiology - ANSWER✔✔ Predominantly affects individuals of African and East
Mediterranean descent
Africa has the highest prevalence of the disease (30% heterozygote prevalence).
Sickle cell anemia is the most common form of corpuscular anemia worldwide.
Heterozygotes - ANSWER✔✔ One sickle allele and the other (usually) normal
Sickle cell trait
Point mutation in the B-globin gene (chromosome 11) - ANSWER✔✔ Point
mutation in the β-globin gene (chromosome 11)→ glutamic acid replaced with
valine → 2 α-globin and 2 mutated β-globin subunits create pathological
hemoglobin S (HbS).
,Hemoglobin C - ANSWER✔✔ Glutamic acid can also be replaced with a lysine,
creating hemoglobin C (HbC)
Hemoglobin composition normal - ANSWER✔✔ HbA: 95-98%
HbF - ANSWER✔✔ The body increases the production of fetal hemoglobin (HbF)
to compensate for low levels of HbA in sickle cell disease.
, A hemoglobin protein variant made up of two alpha chains and two gamma
chains that is the dominant type in fetal circulation and persists in newborn
circulation for approximately 6 months. It has a higher affinity for oxygen than
adult hemoglobin.
Pathomechanism - ANSWER✔✔ HbS polymerizes when deoxygenated, causing
deformation of erythrocytes ("sickling"). This can be triggered by any event
associated with reduced oxygen tension.
Pathomechanism hypoxia - ANSWER✔✔ In homozygotes, up to 100% of the
hemoglobin molecules are affected, leading to sickle cell formation under
minimally decreased oxygen tension.
In heterozygotes, sickling only occurs due to severe reduction in oxygen tension.
Events associated with reduced oxygen tension - ANSWER✔✔ Hypoxia
Infections, dehydration, acidosis, sudden changes in temperature, stress,
pregnancy
Pathomechanism of adherence - ANSWER✔✔ Sickle cells lack elasticity and
adhere to vascular endothelium, disrupting microcirculation and causing vascular
occlusion and subsequent tissue infarction.
Pathomechanism hemolysis - ANSWER✔✔ Extravascular hemolysis (the sickled
cells are phagocytosed by macrophages in the spleen.) and intravascular
hemolysis are common.
Hemolysis and the subsequent increased turnover of erythrocytes may increase
the demand for folate, causing folate deficiency.
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