Iron Deficiency Aneamia

IDA

Commonest anaemia in india Defination--- Any anaemia which respond to adequate dose of Iron is called IDA

Causes Of Iron deficiency

Deficient diet Decreased absorption Increased requirements Pregnancy Lactation Blood loss Gastrointestinal Menstrual Blood donation Hemoglobinuria

IDA - Etiology

Blood loss
Bleeding Parasites, Gynecologic, ulcers

Increased need
Pregnancy, Lactaion,Growing children

Poor diet / poor absorption

Malnutrition , malabsorption, intestinal

surgery, gastric atrophy.

Iron metabolism

Iron is important for formation of Hb,myoglobin and other substances such as the cytochromes,cytochrome oxidase,peroxidase and catalases

Total iron-@3-4 Gm in body

Functional form 70%

Storage

form

30%
Ferritin 2/3rd Haemosiderin 1/3rd

HB= 65% Myoglobin-4% Cytocrome oxidase- 1% Transferin-0.1%

Iron stores About two-thirds of the total body iron is in the circulation as haemoglobin (2.53 g in a normal adult man). Iron is stored in reticuloendothelial cells, hepatocytes and skeletal musclecells (5001500 mg). About two-thirds of this is stored as ferritin and one-third as haemosiderin in normal individuals. Small amounts of iron are also found in plasma (about 4 mg bound to transferrin), with some in myoglobin and enzymes.

Daily Iron Loss Male: 1mg/day Females: 2mg/day

Daily Iron Requirement Male: 1mg/day Females: 2mg/day

Requirements Each day 0.51.0 mg of iron is lost in the faeces, urine and sweat. Menstruating women lose 3040 mL of blood per month, an average of about 0.50.7 mg of iron per day. Blood loss through menstruation in excess of 100 mL will usually result in iron deficiency as increased iron absorption from the gut cannot compensate for such losses of iron. The demand for iron also increases during growth (about 0.6 mg per day) and pregnancy (12 mg per day).

In the normal adult the iron content of the body remains relatively fixed

Dietary intake

The average daily diet contains 1520 mg of iron, although normally only 10% of this is absorbed. Absorption may be increased to 2030% in iron deficiency and pregnancy.

Sources of Iron

Liver,egg Leafy vegitables Whole wheat Jaggery Razma cereals

Heam iron(animal origin) Non Heam Iron

Non-haem iron is mainly derived from cereals, vegitables and grains . it forms the main part of dietary iron. Haem iron is derived from haemoglobin and myoglobin in organ meats. Haem iron is better absorbed than non-haem iron,

Absorption of Iron:
Mainly from Duodenum. Heme-Fe+2 from Meat (Myoglobin, hemoglobin) Non heme iron (Fe+3 reduced by Vit C & ferrireductase(FR) to Fe+2 for absorption)

Factors affecting Iron Absorption Haem iron is absorbed better than non-haem iron
Ferrous iron is absorbed better than ferric iron

Gastric acidity helps to keep iron in the ferrous state and soluble in the upper gut Formation of insoluble complexes with phytate or phosphate decreases iron absorption Iron absorption is increased with low iron stores and increased erythropoietic activity, e.g. bleeding, haemolysis, high altitude There is a decreased absorption in iron overload, except in hereditary haemochromatosis, where it is increased

Heam transporter

Apoferritin

Divalent metal transporter

apotransferritin

Iron Absorption
Dietary haem iron is more rapidly absorbed than nonhaem iron derived from vegetables and grain. Most haem is absorbed in the proximal intestine. The intestinal haem transporter (haem carrier protein 1) has been identified and found to be highly expressed in the duodenum. It is upregulated by hypoxia and iron deficiency.

Iron Absorption
Non-haem iron absorption occurs primarily in the duodenum. Non-haem iron is dissolved in the low pH of the stomach and reduced from the ferric to the ferrous form by a brush border ferrireductase.

Enterocytes are able to sense the bodys iron requirements

Iron Absorption
Once inside the mucosal cell, iron may be transferred across the cell to reach the plasma, or be stored as Ferritin. the bodys iron status is probably the crucial deciding factor. Iron stored as ferritin will be lost into the gut lumen when the mucosal cells are shed; this regulates iron balance

Transport in the blood The normal serum iron level is about 1332 mol/L

Iron is transported in the plasma bound to transferrin, a -globulin that is synthesized in the liver. Each transferrin molecule binds two atoms of ferric iron and is normally one-third saturated.

Mucosal block theory

Iron absorption in Iron deficiency (more TF less Ferritin is formed) Iron absorption in iron overload (More Ferritin shed with stool)

Views to explain mucosal block theory (1) saturation of apoferritin and apotransferrin (2) Rate of apotransferrin synthesis in liver ,in iron overload so less iron will be absobed Rate of apotransferrin synthesis in liver ,in iron deficiency so more iron will be absorbed (3)Receptors on brush borders of Enterocytes in ID and in iron overload

Most of the iron bound to transferrin comes from macrophages in the reticuloendothelial system and not from iron absorbed by the intestine.

Transferrin-bound iron becomes attached by specific receptors to erythroblasts and reticulocytes in the marrow and the iron is removed

In an average adult male, 20 mg of iron, chiefly obtained from red cell breakdown in the macrophages of the reticuloendothelial system, is incorporated into Hb every day.

Iron is stored in reticuloendothelial cells, hepatocytes and skeletal musclecells (5001500 mg). About two-thirds of this is stored as ferritin and one-third as haemosiderin in normal individuals.

Ferritin is a water-soluble complex of iron and protein. It is more easily mobilized than haemosiderin for Hb formation. It is present in small amounts in plasma.

Haemosiderin is an insoluble ironprotein complex found in macrophages in the bone marrow, liver and spleen. Unlike ferritin, it is visible by light microscopy in tissue sections and bone marrow films after staining by Perls reaction.

Iron metabolism

Iron = 4-5g Per person Hb 65 % of total iron Reticuloendothelial system + liver = 15-30 % Myoglobin = 4% Intracellular oxidating heme compounds = 1% Transferrin = 0.1 % Absorption of Iron:

Ferritin

Mianly from Duodenum. Heme-Fe+2 from Meat (Myoglobin, hemoglobin) Fe+2 from small intestine (Fe+3 reduced by Vit C & ferrireductase(FR) to Fe+2 for absorption) Iron + Apotransferrin [protein from liver] Transferrin (Bound) is taken up by endocytosis into erythroblasts and cells of the liver, placenta, etc. with the aid of transferrin receptors. Ferritin one of the chief forms in which iron is stored in the body, storage occurs mainly in the intestinal mucosa, liver, bone marrow, red blood cells, and plasma. (4500 Fe+3 ions i.e. 600mg as readily available store). Hemosidrin In marcophages of liver and bone marrow (250mg) slow release. 97 % recycled by phagocytes of liver, spleen and bone marrow 26

Transport of Iron:

Storage & Recycling:

IDA - Pathogenesis:
Decreased

Iron stores Decreased Hb Synthesis Delayed maturation of erythroblasts (cytoplasmic) Decreased cytoplasm, more division (microcytes) Decreased hb content (hypochromia) Iron Def.Anemia.

Microcytic Anemia (IDA)

Hypochromic Microcytic RBC

Transferrin
Transport Fully

Protein For Iron In Blood

Saturated Transferrin = TIBC

300 - 350ug/dl Fe
Normal

Transferrin - 1/3 Filled With Iron

100 - 120ug/dl Fe (Serum Iron)

Normal

IDA

Serum iron
Serum ferritin TIBC %transferrin saturation Red cell protoporphyrin microgram/dl MCV

50-150 microgram/dl
30-100 microgram/dl

Decreased <30g/dl Decreased <15

300-360 microgram/dl Increased >360 25-50% <30 microgram/dl Decreased <10% Increased >100

100 fl

Decreased <50

MCH
MCHC BM iron store PBF

32 pg
34% 2-3++ normal

Decreased <15
Decreased < 20 depleted Microcytic Hypochromic

Clinical Features:
General

features of Anemia

Pallor, Weakness, Lethargy, Breathlessness on exertion Palpitations heart failure pedal edema Special features in IDA: Angular cheilitis, atrophic glossitis, Oesophageal atrophy/web dysphagia, Koilonychia, brittle nails, gastric atrophy.

Angular cheilitis

Angular cheilitis & Glossitis

Koilonychia in Iron def.

Koilonychia in Iron def.

Low Hb=Anemia

MCV

Low microcytic Measure Ferritin Low Iron def Anemia

Normal normocytic

High macrocytic Measure B12 + folate Normal Low Megaloblastic anemia

Normal/high
Anemia of chronic disease/ Congenital Hb dis.

Reticulocyte count

Hemolytic anemia or blood loss

high

low

Anemia of chronic disease Renal failure Marrow failure

Anemia with Low MCV and Low Retics

Differential diagnosis Iron deficiency (Micro Hypo - severe) Anemia of chronic disease (mild micro/hypo) Laboratory evaluation Iron, iron-binding capacity, and ferritin Blood smear Micro/hypo, Pencil cells.

Anemia with High MCV

Differential diagnosis Megaloblastic anemia B12, Folate Nonmegaloblastic anemia No def. High retics bleeding, hemolysis * Laboratory evaluation Serum B12, RBC folate levels. Blood film macroovalocytes, pancytopenia Bone marrow dysplasia, neoplasia.

Anemia with Normal MCV

Differential diagnosis Primary bone marrow failure Aplastic anemia, drugs, chemotherapy Secondary bone marrow failure Uremia, Endocrine disorders, AIDS, Anemia of chronic disease Laboratory evaluation Blood smear & Iron, TIBC, Ferritin. Bone marrow smear and iron stores Kidney, Thyroid & liver function tests, Cortisol levels Erythropoietin level

Anemia with high Retics

Differential diagnosis: Bleeding blood loss internal/external Hemolysis immune, mechanical, toxic, inf. Laboratory evaluation Blood film, nRBC, spherocytes, Parasites, Retics. Hemolysis indirect Bilirubin, Haptoglobin, Direct and indirect Coombs test Hemoglobin electrophoresis, G6PD screen etc.

Seeing much, suffering much and studying much are the three pillars of learning.
Benjamin Disraeli