Sickle cell anaemia learning card

Sickle cell anaemia learning card Sickle cell syndrome Hereditary hemoglobinopathy 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 The joining together of lots of small molecules called monomers to form a long-chain molecule called a polymer. Epidemiology 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 One sickle allele and the other (usually) normal Sickle cell trait Homozygotes Carry 2 sickle cell alleles Sickle cell anaemia Point mutation in the B-globin gene (chromosome 11) 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 Glutamic acid can also be replaced with a lysine, creating hemoglobin C (HbC) Hemoglobin composition normal HbA: 95-98% HbS: 0% HbF: <2% Hemoglobin composition sickle cell trait HbA: 60% HbS: 40% HbF: <2% Hemoglobin composition sickle cell disease HbA: 0% HbS: 75-95% HbF: 5-25% HbF 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 HbS polymerizes when deoxygenated, causing deformation of erythrocytes ("sickling"). This can be triggered by any event associated with reduced oxygen tension. Pathomechanism hypoxia 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 Hypoxia Infections, dehydration, acidosis, sudden changes in temperature, stress, pregnancy Pathomechanism of adherence Sickle cells lack elasticity and adhere to vascular endothelium, disrupting microcirculation and causing vascular occlusion and subsequent tissue infarction. Pathomechanism hemolysis 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. Clinical features sickle cell trait Persons with sickle cell trait (carriers) have half the HbS in their RBC's Painless hematuria may be present (1-4%) Sickling may occur in renal medulla (area of reduced oxygen tension) Sickling of RBC's may occur under severe conditions of low oxygenation So person with sickle cell trait are advised of risks of extreme physical activity, severe pressure changes, and deep sea diving Often asymptomatic Painless gross hematuria due to renal papillary necrosis: often the only symptom Hyposthenuria: nocturia, enuresis Recurrent urinary tract infections Renal medullary carcinoma (A rare but aggressive type of non-clear cell renal cancer that almost exclusively occurs in young individuals with sickle cell trait. May also present with painless gross hematuria.) Very rarely, symptoms of sickle cell disease may occur as a result of severe oxygen deficiency.