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Iron in the body is used primarily for the synthesis of Hemoglobin and normal erythropoiesis requires 20-25 mg of iron per day.


Hemoglobin (2g / 67%). Ferritin or hemosiderin (1g / 27%) Myoglobin (0.2g / 3.5%) Labile pool is transported and bound to transferrin (0.94g / 3%).

All iron required for red cell production is acquired through the recycling of iron extracts from the senescent red cells. Only 5% of the iron needed for erythropoiesis, or 1 mg /d, is absorbed from GIT to balance losses in the urine, stool, sweat , and de-sequamated skin

Two different configurations : Ferritin : water soluble, hydroxyl iron, & protein (Apoprotein). Hemosiderin : insoluble Aggregate of ferritin molecules that have been stripped of apoprotein.

Metabolic pathway of IRON

Phagocytic macrophages in the liver, spleen, BM take RBC that have complete their 120-day life span. Hemoglobin is broken down into its constituents and iron is stored as ferritin or hemosiderin. Erythroid precursors in the marrow develop around the macrophages and take up the ferritin. Macrophages in the marrow and spleen remove excess ferritin and hemosiderin. Transferrin mediate iron transport from macrophages and gastro-intestinal mucosa to the immature RBC and for storage in the liver.

Iron transport

Transferrin is the principle means for moving iron and is a transport protein with two iron binding site. transferrin picks up iron from the mucosal cells of the intestine then deliver iron to receptors on surface of nucleated RBCs and reticulocytes .the macrophages then transport the iron-free transferrin back to the place . The amount of transferrin in the serum is measured directly as the total iron binding capacity(TIBC).

1. Absorption sites : maximal absorption occur in the duodenum and upper jejunum. The acidic gastric juice reduces insoluble ferric iron to its soluble ferrous state.

Factors influence iron absorption

Increase Fe absorption Decrease Fe absorption - Acids : HCl ,vit.C -Alkalis, antacids - ferrous iron (Fe+2) pancreatic secretion - Agents that solubilize iron organic iron, Ferric iron as(sugars, amino acids) Agents precipitate Iron as - Iron deficiency (Phytate in the tea and - Increased demand as in phosphate) pregnancy, infancy , excess iron adolescence,Hemolysis or bleeding decrease utilization(infection & -primary hemochromatosis inflammation)


a. Depletion of tissue iron. in negative iron balance, and to preserve the level of iron in the serum and RBC results in Depleting the tissue iron stores and this results in:
Stages of iron deficiency

Reduced levels of Ferritin and hemosiderin
Reduced levels of serum ferritin
In tissue macrophage


b. Changes in serum iron are indicative of depletion of the iron stores : Serum iron are usually low. TIBC increase. c. Progressive anaemia : initially normochronic, normocytic eventually hypochromic, microcytic tissue changes occur.

CAUSES OF IRON DEFICIENCY

Chronic blood loss: uterine blood loss. GIT blood loss. * Benign conditions: peptic ulcer. esophageal varicies. hiatus hernia. colonic diverticula or polyp. hemorrhoids. chronic aspirin use. Parasites (hook worm). *Malignancy: colonic ;colorectal Ca. Gastric Ca. Esophageal Ca. small intestinal Ca

pulmonary accumulation lead to hemosiderosis. Hypernephroma. urinary tract Bladder Ca. paroxysmal nocturnal hemoglobinuria (PNH). Increase iron requirement Iron malabsorption Poor diet

SYMPTOMS OF IRON DEFICIENCY

symptoms and signs pertaining to anaemia : 1. Non-specific symptoms :fatigue, weakness , dyspnoea, symptoms of CHF 2. Signs : Pallor, tachycardia, splenomegaly (minority of cases) b. Symptoms and signs specific to iron deficiency : 1. atrophic changes in the epithelium results from levels of heme-containing enzymes (cytochrome, succinate dehydrogenase, catalase, peroxidase, xanthine oxidase) : a. oral lesions : angular cheilosis Atrophy of the tongue papilla with intermittent glossitis, and stomatitis. Dysphagia : post-cricoid esophageal webbing (Plummer Vinson syndrome). Nail lesions : (Koilonychias) Flattening , thinning lead to brittle, spoon- shaped nail. 2. Pica : Compulsive ingestion of non nutritive substances. Children : craving for & ingestion of clay, dirt, paint Adult : to eat ice (pagophagia) clay.

Nutritional deficiency anaemiaclinical application

Angular Cheilosis
Koilonychia
Glossitis
Marrow iron stores
Plummer-Vinson syndrome

DIAGNOSIS:

Laboratory studies :CBC 1. RBC indices : MCV (55-74 fl) MCH (25-30 g/dL) RDW > 16 2. Peripheral blood smears : microcytic hypochromic poikilocyte = abnormally shaped RBCs. Anisocyte = vary in size of RBCs. 3. Blood count : normal or low reticulocytes occasionally high platelet count.

Sideroblastic anaemia

Thalassaemia trait
Anaemia of chronic disorderes
IRON deficiency
Transport iron
N or high N or high
N N
Low NR or low
Low low
*plasma iron *saturation of TIBC
Storage iron
N or high
N
N or high
low
Plasma ferritin
N or low
N
N or low
high
Plasma TIBC
N or high
N
N or high
low
Marrow iron
Differntial diagnosis of microcytic anaemia


Diagnosis cont.

MCV, Retics, Blood film Ferritin

Ferritin < 15
Ferritin ≥ 120 TIBC
trial of Fe Rx
anemia corrected
anemia not corrected
examine marrow Fe stores
Fe deficiency excluded
Fe deficiency anemia
Anemia
Ferritin 15-120
High
Normal or low
Fe absent
Fe present

TREATMENT

Determine the cause of iron deficiency. stool for occult blood loss from GIT bleeding. radiological analysis of upper & lower GIT for occult malignancy. urine analysis for hematuria. CXR for pulmonary Hemosiderosis. Pelvic exam. In woman . Treat the underlying cause.


Oral iron preperation
Initiate iron replacement therapy : oral iron therapy : Ferrous sulfate. Ferrous fumarate and gluconate. Dosage : The adult dose of ferrous sulfate is 300 mg/day gradually increased to 900 mg /day if tolerated. Adverse effect : GIT irritation : nausea, cramping, diarrhea.

Parentral iron therapy

Indications: can not tolerate the side effect of oral iron. Suffers from inflammatory bowel disease and peptic ulcers. Does not comply with prescribed dosage. Iron malabsoption. Suffers from condition such as hereditary hemorrhagic telengectasis (HHT) in which the rapid loss from continuous bleeding can not be compensated by oral iron. . Transfusion of whole blood or packed red cells is generally not indicated unless a rapid increase in haematocit is critical to the patient.

PREPARATIONS

1- Iron dextran (imferon) Intramuscular injection. it may lead to hypersensitivity reaction and anaphylaxis to the dextran and permanent stain with discoloration at the injection site. The later can be avoided by using the Z technique of IM injection. 2- Iron sorbitol (Jectofer) IV .A small test dose 0.25 ml of the drug should be administered before IM or IV to determine hypersensitivity to the agent Dose in ml = 0.0476 x weight (kg) x (Hb. deficit) + 1 ml/5kg to a maximum of 14 ml to replete iron stores. The total dose can be diluted in normal saline at 1:20 dilution and infused slowly over several hours 3- Iron sucrose IV in patient who are allergic to dextran. .

Maintain iron replacement therapy : the treatment should be extended to beyond the point where the anaemia is corrected for a pertiod of usually 6 months in order to replenish depleted iron stores. - A failure to respond to iron therapy should suggest the following : incorrect diagnosis continued loss of iron. Presence of chronic infection or inflammation will suppress BM activity . Lack of pt. Compliance. Inffective release of iron. Malabsorption of iron.

IDA CRITERIA LOW HB LOW HCT LOW MCV LOW MCH MCHC LOW / N LOW FERRITIN LOW FE HIGH TIBC HIGH RDW