Rbc disorders 2
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Rbc disorders 2 Rbc disorders 2 Presentation Transcript

  • RBC Disorders - 2Dr.CSBR.Prasad, M.D.,
  • Iron Deficiency Anemia
  • Importance of ironIron is quantitatively the most important bioactive element in human enzymology with roles in: – Oxygen transport and storage – Oxidative metabolism – Cellular growth and proliferation
  • Haem - Proteins• Hemoglobin 70%• Myoglobin 5%• Tissue specific haem proteins – Cytochromes Eg: P450 – Oxygenases – Hydroxylases – Peroxidase – Catalase – Ribonucleotide reductase – Aconitase
  • Proteins of iron TRANSPORT & STORAGE• TRANSFERRIN: Single chain glycoprotein with two iron binding sites, responsible for iron transport in plasma and extra-cellular fluid• TRANSFERRIN RECEPTOR: Transmembrane glycoprotein with two transferrin binding sites• FERRITIN: Spherical protein of 24 subunits which binds 4500 atoms of iron• IRP: four domine cluster protein which co- ordinates translocational regualtion of iron proteins
  • Iron Distribution in Healthy Young Adults (mg)Pool Men WomenTotal 3450 2450Functional Hemoglobin 2100 1750 Myoglobin 300 250 Enzymes 50 50Storage Ferritin, hemosiderin 1000 400
  • Iron metabolism
  • Iron balanceAbsorption Excretion• 7mg/1000kcal • Exfoliated epithelial cells of• 20-30% of haem iron is the GI tract absorbed • Exfoliated cells of the skin• <5% of non haem iron is • Bile absorbed• Absorption is increased by • Urine aminoacids & ascorbic acid • Menstrual blood loss• Absorption is decreased by phytates, phosphates and NO MECHANISM tannates FOR INCREASING IRON EXCRETION
  • Free iron is highly toxicHence, storage iron is sequestered – Ferritin or – Hemosiderin
  • Ferritin & Hemosiderin• Ferritin is a ubiquitous protein-iron complex• Highest levels : – liver, spleen, bone marrow, and skeletal muscles• In the liver, most ferritin is stored within the parenchymal cells• Partially degraded protein shells of ferritin aggregate into hemosiderin granules• Since plasma ferritin is derived largely from the storage pool of body iron, its levels correlate well with body iron stores
  • Iron requirementsMEN WOMEN• Daily basal iron loss • Menstruating: 1.5mg/day <1mg/day • Pregnancy: 2mg/day or• 10mg of iron in the diet 500mg for 280days of with 10% absorption is gestation sufficient to maintain iron balance
  • Regulation of iron absorption
  • Iron absorption is regulated by HEPCIDIN• Nature: Small peptide• Source: Liver• Stimulus: Intrahepatic iron level dictates Hepcidin synthesis• Action: – Inhibits ferroportin – Hence, inhibits iron transfer from the enterocyte to plasma
  • Diseases with abnormal iron metabolism Basis: Alterations in hepcidin• Anemia of chronic disease• Mutations that disable TMPRSS6• Primary and secondary hemochromatosis – Associated with mutations in hepcidin or the genes that regulate hepcidin expression• Ineffective erythropoiesis suppresses hepatic hepcidin production, even when iron stores are high (unknown mechanim)
  • Prevalence of iron deficiency in India • Pregnant women 70-90% • Pre-school children 50%
  • Causes of iron deficiency• Nutrional – Decreased dietary intake – Increased physiological demand • Pregnancy • Lactation• Iron malabsorption Chase the• Blood loss cause
  • Causes of blood loss • Gastrointestinal • Pulmonary – Hemosiderosis • Urinary – Hematuria – Hemoglobinuria • Uterine – Menorrhagia
  • Causes of GI blood loss• Esophagus • Small intestine – web – Meckel’s divrticulum – Varices – Duodenal ulcer – Reflux – Crohn’s – Carcinoma • Large intestine• Stomach – Polyps – Ulcer – AV malformations – Carcinoma – Carcinoma – Leiomyoma – Ulcerative colitis – Gastritis – Amebiasis – Tuberculosis – Hemorrhoids
  • Iron deficiency in children• Most common between 1.5 to 4yrs• Iron deficiency in children is so important because of the possibility that there may be irreversible impairment of cognitive skills
  • Blood and BM findings in IDAPeripheral blood Bone marrow• <HGB • Erythroid hyperplasia• <MCV • Micronormoblastic• <MCH maturation• Microcytic hypochromic • Leucocytes and MKc may be• Aniospoikilocytosis normal• Pencil shaped cells• Tailed poikilocytes• There may be Thrombocytosis
  • Microcytic hypochromic anemia of iron deficiency (peripheral blood smear)
  • Why anisocytosis in iron deficiency?It’s due to differences in availability of iron in different areas of the bone marrow
  • Diagnosis of IDA
  • Laboratory evaluation of iron status • Serum iron and iron binding capacity • Serum ferritin • Bone marrow iron status (Perl’s stain) • Serum transferrin • Plasma transferrin receptor • RBC protoporphyrin
  • Serum transferrin receptor levels• Good correlation with erythron mass – Increased in hemolytic anemia• Good correlation with iron deficiency in which it’s increased• Not increased in anemia of chronic disease
  • Important points
  • Regulation of fe balance is mainly by absorption
  • Ferritn levels < 12 is indicative of fe deficiency
  • “Chase the cause in bleeding”
  • Weakness in IDA is disproportionate to HGB levels
  • Iron loss is mainly thru…..• Hair growth• Skin desquamation• Menstruation / blood loss
  • Role of acid in fe absorption
  • Common cause of anemia in children
  • How gastrectomy causes anemia?• Low or no acid secretion
  • How GJ causes anemia (IDA)
  • Causes for chronic blood loss
  • External bleeding Vs bleeding in to the tissues and Fe deficiency
  • Occult colonic carcinoma -• Ask for occult blood test on stool
  • Main causes for microcytic hypochromic anemia • Iron deficiency anemia • Thalassemia • Sideroblastic anemia • Anemia of chronic disease
  • Sequence of events in iron deficiencyAt presentation With treatment• Disappearance of iron • Disappearance of stores microcytosis• Drop in hgb • Raise in hgb• Microcytosis • Restoration of body iron pool
  • END
  • Dr.CSBR.Prasad, M.D.,Associate Professor of Pathology,Sri Devaraj Urs Medical College, Kolar-563101, Karnataka, INDIA. csbrprasad@reiffmail.com