5b sickle cell anemia Year 4 Internal Medicine Notes

5b sickle cell anemia Year 4 · Internal Medicine Collection: 4TH YEAR ALL NOTES / IMED / IMED 4.2 / Mogere -- Slide 1 SICKLE CELL ANEMIA Dr Alex Mogere Consultant Physician Slide 2 Normal Hbs 750 structural hemoglobin variants are identified Hb A(α2β2)- main component(96%) HbA2 (α2δ2)- 2-3% of adult hemoglobin HbF(α2γ2)- gradually decreases after 2 yrs - in adults only traces\nIncreased levels of HbF are seen in SCA,Sickle beta-Thalasemia, leukemias ( Juvenile CML, Erythroleukemia), MPD, Normal Pregnancy Slide 3 Hemoglobinopathies The alpha chain contains 141 AAs, the beta chain 146 Aas Qualitative Disorders: Structural abnormalities in synthesis of Hb e.g: SCA, HbC, HbD etc… \nQuantitative Disorders: Decrease in globin synthesis of Hb eg: Thalessemias Slide 4 Hereditary Hbinopathy, x-terized by prdn of defective Hbns (Autosomal Recessive inheritance) SCA: Point mutations at 6th position of -globin chain: Glutamic acid is replaced with valine  Hb S, Glutamic acid in HbA, Lysine in Hb C Sickle cell Disease Slide 5 Epidemiology As of 2015, about 4.4 million people had SCD, and 43 m were estimated to have sickle cell trait.\nPrevalence of the disease was high among the people of sub-Saharan Africa, South Asia, the Middle East, and the Mediterranean.\nThe most common genotype was homozygous hemoglobin SS\n\nMahesh B. Borhade; Noah P. Kondamudi. Slide 6 Characteristic of sickle cells Normal RBCs 120 day life span Hb has normal O2 carrying capacity 12-14g/dl of Hb Sickled cells 30-40 day life span Hb has reduced O2 carrying capacity 6-9g/dL of Hb Slide 7 Heterozygous state for HbS (only 40% of Hb is HbS): Sickle cell trait (Asymptomatic carrier state) Homozygous state for HbS ( 80%Hb is HbS): Sickle cell anemia Double Heterozygous states\neg: Sickle -Thalassemia, Sickle-C-disease (SC), Sickle-D-disease (SD) Sickle cell Syndromes Slide 8 Sickle cell trait Inherit a mutated gene (HbS) only from one parent No symptoms/reduced symptoms Slide 10 Deoxygenated HbS molecules undergo \naggregation & polymerization\nReversible sickling: Initially sickling is \na reversible phenomenon \nWith oxygenation HbS depolymerizes & \ncell shape normalizes Repeated episodes of sickling  Irreversible sickling,brain damage Permanent sickling even when fully oxygenated SCA - Pathogenesis Slide 11 Sickle Cell Disease Deoxygenation Polymerization of Hb S Sickle cell O2 (or H20, pH) Slide 13 1. Amount of HbS & interaction with other Hb \nchains in the cells: \nHeterozygous state: Only with severe hypoxia \nHomozygous state: Full-blown SCA\nHbF: Inhibits polymerization of HbS. Hence \nnewborns do not manifest the disease until \nthey attain 5 to 6 months age\nHbC: Point mutation in -globin at 6th \nposition (substitution of lysine for glutamic acid)\n- Greater tendency to form aggregates with \ndeoxygenated HbS than HbA (HbSC disease) Factors influencing rate & degree of sickling Slide 14 2. Rate of HbS polymerization is strongly \ndependent upon Hb concentration per \ncell (MCHC): Eg:- Intracellular dehydration   MCHC \n  sickling \n- Sickle -thalassemia  reduces globin \nsynthesis MCHC milder disease 3. Decrease in pH:\nOxygen affinity of Hb sickling Ct.Factors influencing rate & degree of sickling Slide 15 4. Length of time RBC are exposed to low \noxygen tension:\nSickling of red cells is confined to\nmicrovascular beds where blood flow is \nsluggish Eg: Spleen & Bone marrow\nInflammation &red cell adhesion  longer red cell transit time  sickling Ct.Factors influencing rate & degree of sickling Slide 16 Natural protection from Malaria Patients with HbS are relatively protected against Falciparum malaria Plasmodium infects RBC & induces quicker sickling\nSickled RBC with parasite inside them are sequestered in spleen thus providing protection Slide 17 Chronic hemolysis, Hyperbilirubinemia, microvascular occlusion, infarction & thrombosis\nExpansion of bone marrow  bone resorption \n& secondary new bone formation  prominent \ncheekbones & changes in skull (Crew-cut \nappearance in X-ray)\nSpleen: Early phase: Splenomegaly\nMicro: Marked congestion with trapping of \nsickled red cells in splenic cords & sinuses Progressive shrinkage of spleen  autosplenectomy by adolescence or early childhood Sickle cell Anemia Morphology Slide 18 Peripheral smear: Sickle cells and target\ncells; Features of splenic atrophy (HowellJolly Bodies) Sickling Test: Mixing of blood sample with oxygen consuming reagent (Sodium metabisulfite) induces sickling of red cells\nif HbS is present Reticulocytosis & Hyperbilirubinema\nHb Electrophoresis: Predominance of HbS \n& 2-20 % HbF Sickle cell Anemia - Morphology Slide 19 Autosplenectomy Slide 20 Sickle cell crisis vaso-occlusive crisis (acute painful crisis),\naplastic crisis,\nsplenic sequestration crisis,\nhyperhemolytic crisis,\nhepatic crisis,\ndactylitis, and\nacute chest syndrome Slide 21 Vaso-occlusive crisis Pain can begin from any part of the body but frequently affects the extrem