Image Based Question-70267

Correct Answer » B Explanation

Ans:B. Intravascular hemolysis.

The patient in question is suffering from Sickle cell anemia.Extravascular hemolysis is seen in this condition.

Image shows:Sickle cell anemia—peripheral blood smear. A, Low magnification shows sickle cells, anisocytosis, poikilocytosis, and target cells. B, Higher magnification shows an irreversibly sickled cell in the center.

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SICKLE CELL DISEASE

• Normal adult red cells contain mainly HbA(α2β2), along with small amounts of HbA2(αδ2) and fetal hemoglobin HbF(α2γ2)

• Sickle cell disease is caused by a point mutation(missense mutation) at the 6th codon of β globin chain leading to substitution of glutamine by valine.

• Sickle cell disease is inherited as Autosomal recessive.

• Sickle cell anemia is the clinical manifestation of homozygous genes

• Sickle cell trait (heterozygotes) gives protection against falciparum malaria

• In sickle cell trait 40% is HbS and rest is HbA.

• Sickle cell anaemia is commonly seen in black

PATHOGENESIS OF SICKLE CELL DISEASE

• Sickle cell disease causes extravascular hemolysis.

• Sticky patch in sickle cell disease results from replacement of a polar residue (Glutamate) with a non polar residue (Valine) at the 6th position of the beta chain.

• RFLP results from a single base change in Sickle cell disease.

• Decreased Solubility is the cause of sickling of RBC in sickle cell disease.

• Deoxygenated HbS undergo aggregation and polymerization, producing a distorted sickle or holly-leaf shaped RBC which block microcirculation.

• Initial sickling is reversible on oxygenation, but after repeated aggregation, sickling is irreversible.

• There is a positive correlation between HBS and polymerization of HBS in Sickle cell anemia.

• HbF inhibit polymerization of HbS; hence infants are asymptomatic until 6 months

• In hereditary persistence of HbF – the disease is less severe

• HbC (lysine is substituted for glutamate in the 6th amino acid residue of β globin) has greater tendency to form aggregates than HbS – but disease is milder in HbSC

• Factors precipitating sickling

• Dehydration (↑MCHC)

• Hypoxia

• Acidosis (↓ pH)

• Increased transit time of red cells through microvascular beds

• Infections

CLINICAL FEATURES OF SICKLE CELL DISEASE

• Vaso-occlusive crisis or Pain crisis (hall mark) – most common clinical manifestation

• Bones (especially the back and long bones) and the chest are commonly affected

• Plugging of small vessels in bones – dactylitis (hand and foot syndrome)

• Avascular necrosis of femoral head, Osteomyelitis due to Salmonella.

• Reccurent infections is the most common cause of death in Sickle cell anemia.

• Acute chest syndrome

• Chest pain, tachypnea, fever, cough, and arterial oxygen desaturation

• Pulmonary infarction and pneumonia are the most frequent underlying conditions

• Extramedullary hematopoiesis prominent cheek bones and crew-hair cut appearance of skull

• Occlusion of vertebral arteries – fish mouth deformity of vertebrae

• Sequestration crisis – massive sequestration of sickled red cells leads to rapid splenic enlargement,hypovolemia and shock.

• In chronic disease due to repetititve infarction, there is progressive shrinkage of spleen following repeated episodes of sequestration crisis – autosplenectomy

• Children are more prone for Pneumococcus pneumoniae and H influenzae septicemia and meningitis with capsulated organisms like pneumococci

• Aplastic crisis – transient cessation of marrow erythropoiesis due to an acute infection with parvovirus B19.

• Unlike other crisis reticulocyte count is low

• Stroke is especially common in children and less common in adults

• Priapism may result in permanent impotence

• Increased break down of hemoglobin can cause pigment gallstones and hyperbilirubinemia.

• Renal papillary necrosis leads to hyposthenuria (inability to concentrate urine) and gross hematuria (less common in sickle cell disease)

• Leg ulcers, delayed puberty, pulmonary hypertension, retinopathy

• Granulocytosis is common

• PAH,Cardiomegaly

• Pulmonary hypertension.

• ‘Sea-Fan’ retina is seen.

• Decreased Osmotic Fragility

• Sickle cell anemia is a non-metabolic cause of abdominal pain.

• Female gender: less severe manifestations since HbF is high.

DIAGNOSIS OF SICKLE CELL DISEASE

• Peripheral blood: sickled cells, target cells, Howell-Jolly bodies, Anemia (extravascular hemolysis), reticulocytosis

• ↓ESR (raised in other anemias)

• Metabisulfite and sodium dithionite which consumes oxygen in a sample of blood, precipitates sickling if HbS is present – useful screening test

• Definite diagnosis by – Hemoglobin electrophoresis (which reveal 60% HbS),HbA2 is normal; HbF in varying concentrations: HbA absent

• Alkali denaturation method – to determine concentration of HbF (HbF is relatively resistant to denaturation by strong alkali)

• Quantitative estimation of HbF – Kleihauer test.

• Polymerase chain reaction with allele-specific oligonucleotide hybridization, Southern blot analysis ,DNA sequencing can be used to detect the point mutation in the beta globin gene that causes sickle cell anemia.

• Gandy gamma bodies are seen in sickle-cell anaemia .

• Vertebra plana ,Bone infarct , Marrow hyperplasia,’H’ shaped vertebra are the radiological features of Sickle cell anemia.