Iron and Anemia PDF

antifolate clotoxic drugs ↳ destroys folic acid C. Vitamins: All essential, especially: M robald...

antifolate clotoxic drugs ↳ destroys folic acid C. Vitamins: All essential, especially: M robald we Vitamin B12 (Cyanocobalamine, Folic Acid food from mehre immalre from s A Extrinsic Factor, Maturation Factor) source animal origin as liver, meat and - vegetables, fruits, liver and chicken meat - destroyed by cooking Functions 1. synthesis of DNA and nuclear maturation (required for thymidine = building block of DNA) 2. synthesis myelin of nerves. intake daye/ Effect of 1. Macrocytic anemia injection macrocytic anemia. Bez deficiency 2. Neurological symptoms 3 es heute L failure of absoption daily requirements of vitamin B12: 1000 lelen wlele - 5 Mg micrograms a - N.B.: vitamin is stored in liver in big amounts i.e. 5 mg - N.B.: Deficiency usually due to failure of absorption not deficiency in diet (except vegetarians) deficiency " pernicious - anemia Absorption of vitamin B12: tisease in guide your a M elderly women - parietal cells of stomach secrete intrinsic factor: unites with vitamin B12 → protect it from digestion by GIT enzymes. * protein - absorbed from terminal ileum by pinocytosis - Trypsin of pancreas is required for absorption. - passes to blood to bound with transcobalamin ll. (Excess stored in liver) A.F. 2024 11 D.Iron: Forms of iron in body: (3-5 grams): o 70% in hemoglobin. o 3% in muscle myoglobin. o 2% in enzymes o 25% Ferritin (main storage form): - Hemosiderin: ferritin molecules aggregate (50% iron). - mainly in liver, spleen, enterocytes, and bone marrow. o small part in plasma bound to transferrin o N.B.: free iron is toxic due to generation of reactive oxygen species ROS. ❖ Iron requirements: - 30 mg daily: Most from breakdown of hemoglobin in liver and spleen - normal adult male loses 0.5 – 1.0 mg of iron daily (in sloughed epithelial cells, hair, sweat, and blood loss) - (e.g. 2.0 mg/day) in adult female due to menstrual loss. ❖ Iron absorption: by enterocytes in duodenum. - Dietary iron: Zwölffingerdarm a. Heme b. Non-heme (salts and chelates) source in meat and meat in cereals, vegetables, fruits (plant products origin) amount 10% of total 90% bio- high (more absorbable) low availablity A.F. 2024 12  Mechanism: A. transport to enterocytes through apical membrane: bisheel ay mandan b 2 1) Heme by "heme carrier protein HCP1" 27 A ↳ deswegen Fe 2) "Non heme" = ferric (F3+) (Most): by "divalent metal transporter 1 = DMT1" but: 1) Gastric HCl (from parietal cells) helps dissolving iron N.B.: Patients suffering from reduced HCl (achlorhydria) → iron deficiency 2) reduced to ferrous (Fe2+): by Ascorbic acid (Vitamin c) N.B.: Iron not reduced in stomach will be reduced by a reductase enzyme associated with DMT1 N.B.: Other constituents of diet (e.g. oxalates, phosphates and phytic acid) react with iron and form insoluble non-absorbable compounds. F Partial. gestrechomy 2. Vit. (defi Oxalates ❖ Inside enterocyte, depending on body requirements : 3. 4. of droderm Disease 1. If stores of iron are full → stored as "ferritin": Ancylostonisses. 5 o and no increased rate of erythropoiesis ↳ Piles. o enterocytes lifespan is very short (3-4 days): iron is excreted in stools. 2. If increased demand for iron → transported out at baso-lateral border to blood by protein "ferroportin": o it is oxidized to Fe3+ by ferrioxidase enzyme. - Iron (Fe3+) binds to plasma protein "transferrin” (Normally 35% saturated) iminal ↓ baso-lateral ↓ ferritin A.F. 2024 13  Mechanism of iron absorption : Transport into enterocyte : · Absoption in duodemum : heme carier protein 7 1) Heme iron : - via HCP1 transported into enterocytes (intestinal cell) " home oxygenase enzyme bredit dom ferrous iron Fet 2) Nontheme iron - present in ferric Fet form a not soluble , hard to absorb · HC reduces Fest a Fet - DMTM transports Fet across Luminal border (enterocyte) Inside enterocyte : 1) Stored as feritin : - iron binds lo ferilin (protein) as temporary storage form -if body doesn't need additional iron a stays in enterocyte · eventually will be shed why ? Lifespan of enterocyte is only 3-4 days -hey mechanism for controlling / maintaining iron levels 2) Transport into blood : - if body needs in a exported out of enteroyle through basolateral border Hom 2 through protein ferropolis · a -needs to be oxidized Fe to before it enters bloodshream ferrioxidese enzyme -Febinds to transferin - protein that transports it to where it's needed Regulation of iron absorption : Hepcidin : major regulator Actions of hepcidin 1. inhibits iron absorption (DMT1) high hepcidin Levels : - binds to ferroportin · teropolin internalized- blocks iron from leaving cel - iron remains in enterocytes I will be sloughed off 2. inhibits release of iron from -excession in food > - decreases DMT t iron absorption mecrophages 3. inhibits release of iron from liver low hepridin levels : - ferroportin remains active - iron exported from enterocytes · into bloodstream , from macroplages , liver into circulation Factors affecting hepcidin secretion ↑ secretion ↓ secretion Hemosiderosis : bronze diabetes - ↑ hemosiderin (stored iron) vivon overload iron loading homeostasic Eythropoeisis higher - - > - - W 1 demand ↓ - hepcidin pigmentation of shin - inflammation - hypoxia > - more absoption 2 pancreatic damage diabetes 3 liver cirrhosis , hepatic carcinoma /liner cancer) ❖ Iron homeostasis = Regulation of iron absorption: (No mechanisms to regulate excretion): 1- Role of dietary iron = “mucosal block”: Excess iron in food decreases amount of DMT1, decreasing iron absorption. 2- Hepcidin: 25-amino acid hormone secreted by liver. o major regulator of iron absorption and release by macrophages. o Actions: degrade ferroportin: 1) Inhibition of intestinal absorption of iron. dief 2) Inhibition of release of iron from macrophages. 3) Inhibition of release of iron from liver. o Factors affecting hepcidin secretion: 1) Hypoxia and erythropoietin: ↑ iron demand by erythropoiesis → ↓ secretion 2) Iron loading: to maintain iron homeostasis → ↑ secretion 3) Inflammation: ↑ secretion (anemia occurs in inflammatory diseases). ❖ hemochromatosis: cause Treatment 1) Hereditary: Mutant gene leading to blood removal (500 ml) by increased iron absorbtion phlebotomy (venesection) 2) repeated blood transfusion iron chelating agents ❖ Hemosiderosis "bronze diabetes": ↑ hemosiderin in tissues in iron overload: 1) pigmentation of skin "slored iron 2) pancreatic damage leading to diabetes 3) liver cirrhosis and hepatic carcinoma. Blood Indices definition formula Normally Mean corpuscular amount of hemoglobin in a 25-32 Hb content hemoglobin “MCH” single RBC MCH = x 10 picograms RBC's count Mean Corpuscular volume of a single RBC Hematocrite value 80 – 95 μ3 MCV = x 10 Volume MCV RBC's count Mean Corpuscular Hb in 100 ml of packed red Hb content 32-38 MCHC = x 100 Hb Conc. (MCHC) cells Hematocrite value gm/dL MCHC: (within normal in normochromic but below normal in hypochromic) A.F. 2024 Nr. RB( anemia = > 4 , 5m 14 > 3 , 5f Hb > 13 , 5g(d/ > 11 , 5f  Polycythemia: increased number of RBC’s (6-8 millions/mm3). 2 types: from external factor result blood disorder Primary (Polycythemia Vera) Secondary cause Condition in RBCs forming Hypoxia (lung diseases organs > - in bone mar row and in high altitudes) WBCs and platelets increased normal Anaemia: ↓ in oxygen carrying capacity due to: ↓ RBCs &/or ↓ hemoglobin. N.B.: Intrinsic causes for hemolytic anaemia: 1. Hereditary spherocytosis: Membrane defect mutation spherical > - RBC's ↳ Less flexible e Cells are spherocytes and hemolyse when passing the spleen more likely to be destroyed in spleen mutations in membrane proteins maintaining membrane flexibility 2. G6PD deficiency (Favism): Enzyme deficiency X linked recessive: affects males more G6PD is Enzyme protecting cells against oxidative stress (ROS) May be asymptomatic but may present with acute hemolytic crisis precipitated by infections, some drugs and some foods as fava beans 3. Abnormal hemoglobin 1. genelic mutation ⑪ Thalassemias: hereditary with ↓ or absent alpha or beta chains of Hb. that ② Sickle cell anemia: reduces/allers theproduction of Ab chains - abnormal RBC abnormal HbS: precipitates at low O2 and cells take sickle shape ↳ destroyed in the spleen 2. mutation in Ab gene HbS & It may lead to occlusion of small vessels: severe pains, heart attack or stroke A.F. 2024 15  RBC dayel Nr. ❖ Morphological Classification and Causes of Anemia: Normocytic Normochromic Microcytic Hypochromic Macrocytic ( Megaloblastic) volume of characters normal MCV (Normocytic) RBC small RBCs (Microcytic) RBCs size is larger Hemoglobinin normal MCH (Normochromic) MCH < normal MCH is usually not increased Causes 1. Acute Blood Loss: body replacesplasma with I. (Iron Deficiency I. Vitamin B12 deficiency: rapid blood loss: traumatic or Anemia): 1) ↓ intake (very rare: vegeterians). surgical 1. Decreased iron intake 2) Failure of absorption: where,orbed it & 2. Bone Marrow Depression (= 2. Increased iron demand a) diseases of lower ileum - Aplastic Anemia) (children, pregnancy and b) Absence of intrinsic factor 3. Anaemia of chronic diseases: lactation). (pernicious anemia): chronic inflammation, chronic 3. Failure of iron absorption: - familial disease in old women kidney disease, auto immune a. Partial gastrectomy (↓HCl) - auto immune: antibodies attack diseases and cancer b. Diseases of upper small of parietal cells 4. Hemolytic Anemia (Premature intestine c) Removal of stomach destruction of RBCs ): c. Vitamin C deficiency (gastrectomy) o causes: d. Phytic acid, oxalates and 3) Defective storage: liver disease a) intrinsic: spherocytosis, G-6-PD phosphates in diet inhibit absorption > - II. Folic acid deficiency: enzyme deficiency, and abnormal 4. Chronic blood loss: a) ↓ intake in diet hemoglobin - Excessive bleeding during b) ↓ absorption due to diseases of b) Extrinsic: Incompatible blood menstruation small intestine transfusion (Ab), bacterial toxins, - Ankylstoma infestation c) Increased need (pregnancy): chemicals and drugs - Bleeding peptic ulcer and may lead to serious effects in piles. newborn (women should take II. Some hemolytic folic acid in pregnancy) anaemias as hereditary d) Treatment of cancers with spherocytosis & antifolate cytotoxic drugs. Thalassemia A.F. 2024 16