Megaloblastic Anaemia Presentation PDF

Megaloblastic anaemia Gavin Knight  Learning Objectives Upon completion of this session, you should be able to: 1) Define the term megaloblastic anaemia and describe its features. 2) Recognise the association between cobalamin & folate deficiency and megaloblastic change. 3) Associate coba...

Megaloblastic anaemia Gavin Knight  Learning Objectives Upon completion of this session, you should be able to: 1) Define the term megaloblastic anaemia and describe its features. 2) Recognise the association between cobalamin & folate deficiency and megaloblastic change. 3) Associate cobalamin and folate functions with the cell cycle. 4) Identify the common causes of both deficiencies.  MEGALOBLASTIC ANAEMIA The result of a nuclear maturation defect primarily due to ineffective erythropoiesis Leads to cell cycle arrest Approximately 95% of megaloblastic anaemias caused by cobalamin or folate deficiency Cobalamin deficiency tends to be due to a lack of intrinsic factor rather than inadequate diet Folate deficiency tends to be due to poor nutrition B12 absorption B12 must be liberated from foodstuff by pepsin and stomach acid B12 binds to haptocorrin In the upper duodenum, pancreatic trypsin releases B12 from haptocorrin Free B12 binds to Intrinsic Factor and is transported to the distal/terminal ileum Absorbed by the enterocyte via the multicomplex receptor Cubilin In the circulation 80% binds haptocorrin (TC2) and 20% transcobalamin (TC1) The transcobalamin:B12 complex is absorbed by target cells by the megalin/transcobalamin receptor Lysosomal degradation of the complex releases B12 into the cytoplasm while megalin/transcobalamin receptor returns to the membrane Folate absorption Folates are mainly absorbed in the duodenum and jejunum and require an acidic microenvironment Dietary polyglutamated folates are converted into monoglutamate by glutamate carboxypeptidase II Require: proton-coupled folate transporter (PCFT) - optimal pH 5.0–5.5 reduced folate carrier (RCF) - optimal pH 7.4 Once inside the enterocytes, folates are reduced and methylated to form 5- methyltetrahydrofolate (5MTHF) 5MTHF is removed to the circulation by MRP3 found on the basolateral membrane  COBALAMIN VERSES FOLATE DEFICIENCY Cobalamin-related deficiency Folate-related deficiency Dietary Dietary Reduced release from food Jejunal abnormalities Inadequate IF Drug induced Impaired release from malabsorption Haptocorrin Malabsorption of ileum Increased requirement Drug induced malabsorption Increased loss Inactivation by nitrous oxide Acquired defects of folate Inherited metabolic defect metabolism Inherited metabolic abnormalities NUCLEAR CYTOPLASMIC ASYNCHRONY Image from: http://media.mssm.edu/blood/morphology_tutorial_scigliano/1027.html MEGALOBLASTIC MORPHOLOGY Moore CA, Adil A. Macrocytic Anemia. [Updated 2020 Jul 15]. In: StatPearls https://imagebank.hematology.org/image/60047/hypersegmented-neutrophil? [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. [Figure, type=atlas Macrocytic anemia. Contributed by Ruozhi Xiao via SlideShare, “Anemia Overview,”] Available from: https://www.ncbi.nlm.nih.gov/books/NBK459295/figure/article-17535.image.f1/  Summary Cobalamin and folate deficiency are a cause of macrocytic anaemia The name ‘megaloblastic’ is a consequence of the appearance of BM derived progenitors Abnormal DNA synthesis is responsible for morphological findings A variety of conditions can lead to cobalamin and/or folate deficiency Deficiency of cobalamin can lead to irreversible neurological degeneration