HYPOCHROMIC ANEMIA & IRON METABOLISM
OBJECTIVE Iron metabolism Iron distribution & transport Dietary iron Iron absorption Iron requirements Disorders of iron metabolism Hypochromic anemia
To accept & donate electron (Fe 2+ Fe 3+ ) component of cytochromes, oxygen-binding molecules cell growth,proliferation, differentiation damage tissues H 2 O 2 OH Fe 2+ Fe 3+
Iron distribution & transport transferrin, transferrin receptor ferritin, hemosiderin (Fe 3+ ) myoglobin, iron-containing enzymes Dietary iron Iron absorption Iron requirements
Amount of iron Male Female % in average adult (g)(g) of total Hb ferritin & hemosiderin Myoglobin Heme enzyme Transferrin-bound iron The distribution of body iron
Iron distribution & transport Dietary iron ferric hydroxides ferric-protein complexs heme-protein complexes Iron absorption Iron requirements
GI Absorption of Iron
INTRACELLULAR IRON TRANSPORT
Iron distribution & transport Dietary iron Iron absorption Iron requirements
Adult men0.5-1 Postmenopausal female Menstruating female 1-2 Pregnant female1.5-3 Children1.1 Female (age 12-15) Estimated daily iron requirements, Units are mg/day
Diseases of iron deficiency 1. Iron-deficiency anemia (IDA) 2. Anemia of chronic disease (ACD) Diseases of iron overload
What is iron-deficiency anemia ? It is the lack of iron in the blood, which is necessary to make hemoglobin.
Symptoms Fatigue - Sometimes out of proportion to anemia Atrophic glossitis Pica Koilonychia (Nail spooning) Esophageal Web
Causes of Iron Deficiency Chronic blood loss Uterine GI tract Increased demands Prematurity Growth Pregnancy Malabsorption gastrectomy Poor diet
Iron Deficiency Anemia (IDA) Most common cause of anemia Microcytic hypochromic anemia MCV, MCH, MCHC are reduced blood film: small red cells (microcytic) : pale red cells (hypochromic)
Laboratory findings 1. Red cell indices & blood film 2. Bone marrow iron 3. Serum iron & iron binding capacity 4. Serum transferrin receptor (sTfR) 5. Serum ferritin 6. Zinc protoporphyrin
Nor mal Iron def. ACD Iron overload TIB C Serum iron & iron binding capacity
Chronic inflammatory diseases Infections Non-infectious Malignant diseases release of iron from macrophage to plasma red cell life span response to EPO release IL-1 & TNF
Increased iron absorption Increased iron uptake Repeated red cell transfusions
Iron-deficiency anemia (IDA) Anemia of chronic disease (ACD) Sideroblastic anemia Thalassemia Lead poisoning
IronProtoporphyrin Heme Globin + Hemoglobin Iron deficiency Chronic inflammation or malignant Thalassemia Sideroblastic anemia The Cause of Hypochromic Anemia
A defect in heme synthesis Hereditary & Acquired mitochondrial defects pyridoxal-6-phosphate mutation in the aminolevulinic acid synthase (ring sideroblasts in BM) myelodysplasia syndrome Hypochromic & microcytic red cells
Inhibits both heme & globin synthesis Interferes with the breakdown of RNA by inhibiting pyrimidine 5’nucleotidase accumulation of denatured RNA in red cells (basophilic stippling) Hypochromic anemia Ring sideroblasts (BM) Free erythrocyte protoporphyrin is raised
Differential diagnosis of hypochromic anemia IDA ACD Thalassemia Siderblastic anemia Serum iron N TIBC N N serum ferritin N/ N BM iron stores Erythroblast iron - - +ring forms Hb N N HbA 2 N electrophoresis
Hemochromatosis A genetically determined form of iron overload that results in progressive hepatic, pancreatic, cardiac, and other organ damage
Hemochromatosis It is one of the most common genetic disorders in the U.S. Present in heterozygous (one gene) form in 12% of nonblacks and 30% of blacks Present in homozygous form (2 gene) in 1 in 200 nonblacks and 1 in 100 blacks Homozygotes will die of iron overload unless they give blood frequently Homozygotes absorb three times more iron from food than other people Even heterozygotes may be at risk for iron overload, increasing risk of heart disease
Hemochromatosis: Risk Factors Higher risk in people of northern European descent Men tend to manifest symptoms earlier because they have no way to dispose of excess iron (menstruation, pregnancy, lactation) Men may develop symptoms in their 30s but may not be diagnosed until their 50s Women often develop symptoms after menopause
Hemochromatosis: Symptoms Joint pain Fatigue Lack of energy Abdominal pain Loss of sex drive Heart problems Abnormal pigmentation of the skin, making it look gray or bronze
Hemochromatosis : if untreated, may result in Arthritis Liver disease: cirrhosis, cancer, liver failure Damage to the pancreas, leading to diabetes Heart abnormalities, including arrhythmias and heart failure Impotence or early menopause Thyroid or adrenal problems
Hemochromatosis: Diagnosis and Treatment Testing: serum ferritin and transferrin saturation can reveal excess stores of iron; followed by HFE (genetic) test and possible liver biopsy Treatment: regular phlebotomy to remove excess iron Avoidance of iron supplements and sources of iron in the diet, especially heme iron Awareness of iron cooking vessels