Iron Deficiency Anemia Study Guide PDF

Iron Deficiency Anaemia 07 October 2024 12:55         **Symptoms of Low Hb:** - Tiredness, - Breathlessness - Pallor - Cardiovascular symptpoms   **4 main causes of ID Anaemia:** - Blood loss - Inadequate intake - Malabsorption - Increased demand   **Iron Regulatio...

Iron Deficiency Anaemia 07 October 2024 12:55         **Symptoms of Low Hb:** - Tiredness, - Breathlessness - Pallor - Cardiovascular symptpoms   **4 main causes of ID Anaemia:** - Blood loss - Inadequate intake - Malabsorption - Increased demand   **Iron Regulation Cycle:**      - Dietary iron is absorbed by microvilli in SI (duodenum) - Enters blood stream & is transported by transferrin (protein) to bone marrow or liver: - Used in bone marrow for RBC production - Used in liver (or other tissues) to be stored as ferritin - Old RBCs are broken down by macrophages within reticuloendothelial system in liver and spleen.\ Iron is released from haemoglobin and is transported by transferrin to bone marrow or iron stores - Small about of iron is lost in urine, faeces, skin, nails, hair - Iron absorption is just sufficient to make up for iron loss - a tightly regulated delicate balance   **Dietary Iron Absorption and regulation:**   A close up of a map Description automatically generated   - Dietary iron intake is \~10-15 mg/day, only 1 mg absorbed - From haem and non-haem sources (meat or non-meat) - Occurs within duodenal enterocytes via haem receptors or Divalent Metal Transporter 1(DMT-1): - Meat sources enter via haem receptor - Non-haem iron is reduced by ferriductase from Fe^3+^ to Fe^2+^, enters via DMT-1 - Iron either enters stores as ferritin or enters portal circulation via ferroportin (transmembrane exporter) - Transferrin transports iron to bone marrow or other tissues with transferrin receptors (TFR-1) for storage **Iron Storage** - Stored as ferritin or haemosiderin - Ferritin: - Present in cell of liver, spleen & bone marrow. - Has an outer protein cell (apoferritin) which binds and stores iron in ferric-hydroxide-phosphate compound - ferritin - Iron accounts for 20% of its weight - Degradation of ferritin by phagolysosomes release iron from storage - Haemosiderin: - Protein-iron complex present in macrophages - Derived from partial lysosomal digestion of ferritin - Iron accounts for 37% of its body weight - Visible by perls stain:                     **Iron Regulation** - Self-regulated (regulated by iron status) **4 Key points/stages where iron levels are controlled:** - Iron import from the intestine into the enterocyte via DMT-1 - Iron export from the entroocyte into the circulation via ferroportin - Ferritin synthesis - TfR-1 (transferritin receptor 1) synthesis **Mechanisms of control:** - Gene regulation - Hormonal control   **Gene Regulation:** - Controlled by iron status: - Regulation of ferritin, TfR1 and DMT-1 genes - When iron levels are high: - Increased ferritin production - reduced TfR1 and DMT-1 - When iron levels are low: - Reduced ferritin production - Increased TfR1 and DMT-1 - Iron regulatory proteins (IRPs) control levels of ferritin. TfR1 and DMT-1 by binding to Iron Response Element (IRE) structures within untranslated regions of ferritin, TfR1 and DMT-1 mRNA - Upstream IRP/IRE binding reduces translation - Downstream IRP/IRE binding stabilises mRNA and increases translation - In iron deficiency, IRP/IRE binding is more effective - In iron overload, binding is reduced - Ferritin regulation: - The IRE is at the 5\' end of the mRNA strand - IRP binding reduces translation - When iron levels are low IRP binding is increased and less ferritin is produced - When iron levels are high IRP binding is reduced and more ferritin is produced - TFR1 and DMT-1 regulation: - The IRE is at the 3\' end of the strand - IRP binding stabilises mRNA and there is increased translation - When iron levels are low IRP binding is increased and more TFR1 and DMT-1 is produced - When iron levels are high, IRP binding is reduced and less TFR1 and DMT-1 is produced     *Khan academy AI chat - simplified & explained:*           **Hormonal Regulation - Hepcidin:** - Polypeptide hormone - Produced in liver - Production is controlled and regulated by iron status, inflammatory cytokines, erythropoiesis and hypoxia - Accelerates degradation of ferroportin (transmembrane iron exporter) - Increased hepcidin leads to: Reduced iron absorption in SI & Reduced release of iron from macrophages - Elevated iron levels: - Saturated transferrin stimulates liver sinusoidal cells to secrete Bone Morphogenetic Proteins (BMPs) - BMPs bind to receptors on hepatocyte cell membrane - Saturated transferrin also stabilises TfR2 - Signalling complex comprises BMPRs, TfR2, HJV and HFE which stimulates hepcidin synthesis via signalling proteins (SMADS) - Reduced iron levels: - Reduced presence of saturated transferrin and reduced synthesis of BMPs - TfR2 (stabilised at higher levels of saturated transferrin) is degraded and HFE binds to un-occupied TfR1 - Matriptase is stimulated and cleaves HJV from the cell membrane and histone deacetylase suppresses the hepcidin gene locus to suppress transcription - Haemochromatosis: Condition with mutation in HFE gene. Leads to reduced hepcidin production and excessive iron absorption - Other regulators of hepcidin: - Inflammatory processes/cytokines(IL-6) increase hepcidin production - Hypoxia suppresses hepcidin synthesis - Increased erythropoiesis suppresses hepcidin synthesis through secretion of erythroferrone (suppresses BMP mediated cell signalling)     **Laboratory findings**   - FBC: low Hb, low MCV, low MCH - Blood film: microcytic/hypochromic anaemia - Red Cell Distribution Width (RDW - measures variation of red cell size, \>variation=\>value):  - Ferritin: Low - Zinc Protoporphyrin (ZPP zinc is carried in RBCs instead of iron- ): Raised - Serum iron (not very useful, can indicate iron OD) - Total Iron Binding Capacity (TIBC - amount of iron bound to transferrin) - Decreased serum iron & increased TIBC indicates low transferrin saturation - Reticulocyte Hb concentration (infant red cells) - Bone marrow iron (only in complex cases)   \     **Differential Diagnosis of microcytic/hypochromic anaemia:** - Thalassaemia (genetic mutations affecting haemoglobin production - alpha or beta chains are not produced properly) - Anaemia of chronic disease - Sideroblastic anaemia (Deficiency of Aminolevulinic Acid (ALA) enzyme which is used in haeme production. Causes iron to accumulate in mitochondria, leading to ringed sideroblasts - immature RBCs with iron deposits circling the nucleus):