Sickle Cell Anaemia (1) Year 4 Paediatrics Notes OmpathStudy

Sickle Cell Anaemia (1) Year 4 · Paediatrics Collection: 4TH YEAR ALL NOTES / PAEDS / PAEDS 4.3 / Munge / HAEMATOLOGY -- Slide 1 Sickle Cell Anaemia Dr Rose Munge Slide 2 Hemoglobin is a tetramer consisting of 2 pairs of globin chains. Abnormalities in these proteins are referred to as hemoglobinopathies.\n The most common and useful clinical classification of hemoglobinopathies is based on nomenclature associated with alteration of the involved globin chain. Slide 3 Sickle Cell Disease Hemoglobin S (HbS) is the result of a single base-pair change, thymine for adenine, at the 6th codon of the β-globin gene.\nThis change encodes valine instead of glutamine in the 6th residue in the β-globin molecule.\nSickle cell anemia (HbSS), homozygous HbSS, occurs when both β-globin alleles have the sickle cell mutation (βs).\nSickle cell disease refers not only to patients with sickle cell anemia, but also to compound heterozygotes where one β-globin allele includes the sickle cell mutation and the 2nd β-globin allele includes a gene mutation other than the sickle cell mutation, such as HbC, β-thalassemia, HbD, and HbOArab In sickle cell anemia, HbS is typically as high as 90% of the total hemoglobin, whereas in sickle cell disease, HbS is 50% of all hemoglobin. Slide 4 In red blood cells (RBCs), the hemoglobin molecule has a highly specified conformation allowing for the transport of oxygen in the body.\n Usually hemoglobin molecules do not interact with one another but the presence of HbS results in a conformational change in the Hb tetramer, and in the deoxygenated state, HbS molecules interact with each other, forming rigid polymers that give the RBC its characteristic “sickled” shape.\n The lung is the only organ capable of reversing the polymers, and any disease of the lung can be expected to compromise the degree of reversibility Slide 5 Intravascular sickling primarily occurs in the postcapillary venules and is a function of both mechanical obstruction by sickled erythrocytes, platelets, and leukocytes and increased adhesion between these elements and the vascular endothelium.\n Sickle cell disease is also an inflammatory disease based on nonspecific markers of inflammation, including, but not limited to, elevated baseline white blood cell (WBC) count and cytokines.\n Intraerythrocytic changes lead to a shortened RBC life span and hemolysis.\nHemolysis leads to multiple changes, including altered nitric oxide metabolism and oxidant stress that contribute to endothelial dysfunction. Slide 6 Clinical Manifestations Acute and chronic pain: The most common clinical manifestation of SCD is vaso-occlusive crisis; pain crises are the most distinguishing clinical feature of SCD Bone pain: Often seen in long bones of extremities primarly due to bone marrow infarction Anemia: Universally present, chronic, and hemolytic in nature Aplastic crisis: Serious complication due to infection with B19V Splenic sequestration: Characterized by the onset of life-threatening anemia with rapid enlargement of the spleen and high reticulocyte count Infection: Organisms that pose the greatest danger include encapsulated respiratory bacteria, particularly Streptococcus pneumonia; adult infections are predominately with gram-negative organisms, especially Salmonella Growth retardation, delayed sexual maturation, being underweight Hand-foot syndrome: This is a dactylitis presenting as bilateral painful and swollen hands and/or feet in children Acute chest syndrome: Young children present with chest pain, fever, cough, tachypnea, leukocytosis, and pulmonary infiltrates in the upper lobes; adults are usually afebrile, dyspneic with severe chest pain, with multilobar/lower lobe disease Slide 7 Pulmonary hypertension: Increasingly recognized as a serious complication of SCD Avascular necrosis of the femoral or humeral head: This is due to vascular occlusion CNS involvement: Most severe manifestation is stroke Ophthalmologic involvement: Ptosis, retinal vascular changes, proliferative retinitis Cardiac involvement: Dilation of both ventricles and the left atrium GI involvement: Cholelithiasis is common in children; liver may become involved GU involvement: Kidneys lose concentrating capacity; priapism is a well-recognized complication of SCD Dermatologic involvement: Leg ulcers are a chronic painful problem Slide 8 Laboratory Tests Hemoglobin electrophoresis CBC count with differential and reticulocyte count Serum electrolytes Hemoglobin solubility testing Peripheral blood smear Pulmonary function tests (transcutaneous O 2 saturation) Renal function (creatine, BUN, urinalysis) Hepatobiliary function tests, (ALT, fractionated bilirubin) CSF examination: Consider LP in febrile children who appear toxic and in those with neurologic findings (eg, neck stiffness, + Brudzinski/Kernig signs, focal deficits); consider CT scanning before performing LP Blood cultures ABGs Secretory phospholipase A2 (sPLA2) Slide 9 Imaging Studies Radiography: Chest x-rays s