1. بسم الله الرحمن الرحيم

2. IRON METABOLISM

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

4. Iron compartment in the body :
Hemoglobin (2g / 67%).
Ferritin or hemosiderin (1g / 27%)
Myoglobin (0.2g / 3.5%)
Labile pool is transported and bound to transferrin (0.94g / 3%).

5. Requirements for exogenous iron
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

6. IRON Storage

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

8. 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.

9. 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).

10. Iron Absorption
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.

11. 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)

12. IRON DEFICINECY ANEMIA

13. Stages of iron deficiency
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:
Reduced levels of
Ferritin and
hemosiderin
Reduced levels
of serum ferritin
In tissue macrophage

14. 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.

15. 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

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

17. 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.

18. Nutritional deficiency anaemia clinical application
Angular
Cheilosis
Glossitis
Koilonychia
Marrow iron stores
Plummer-Vinson
syndrome

20. 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.

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

23. Diagnosis cont. b. serum iron studies :
the level of serum iron is low or normal depending on what patient eat before the measurement.
TIBC > 400 µg/dL
Transferrin saturation <15 %
Serum Ferritin < 15 ng/ml.
Soluble transferrin receptor ; increased
C. Bone marrow studies :
Absence of iron in macrophage when the sample is subjected to Perl's stain (Prussian blue stain)

24. Fe deficiency excluded
Anemia
MCV, Retics, Blood film
Ferritin
Ferritin ≥ 120
Ferritin < 15
Ferritin
TIBC
High
Normal or low
trial of Fe Rx
anemia
corrected
anemia
not corrected
examine
marrow Fe stores
Fe absent
Fe present
Fe deficiency anemia
Fe deficiency excluded

25. 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.

26. 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.

27. 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.

28. 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 = 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. .

29. - A failure to respond to iron therapy should suggest the following :
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.

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