IRON
Iron forms the nucleus of the iron porphyrin heme ring, which together with globin chains forms
hemoglobin that reversibly binds oxygen and provides the critical mechanism for oxygen
delivery from lungs to other tissues. In the absence of adequate iron, small erythrocytes with
insufficient hemoglobin are formed resulting in microcytic hypochromic anemia.
Causes of Iron Deficiency Anemia
- Nutritional deficiency
Low intake of iron containing foods, reduced absorption as a result of mucosal damage, coadministration of drugs that chelate iron e.g. antacids and after gastrectomy iron deficiency will
take place. - Chronic blood loss
Chronic nose bleeding, Menorrhagia, Occult GI bleeding, Worm infestation and Ulers, e.g. PUD.
Pharmacokinetics of Iron
Daily requirement of Iron – Male 10mg
- Female 15 mg
Increases in growing children, pregnant and lactating women
Sources - Dietary – mostly in the organic form from meat, cereals, etc.
Body composition of Iron
Total content of Iron in the body is about 4000mg in an adult male, of which about 2/3 – 2500
mg is present in circulating red blood cells see table.
Table: Iron distribution in normal adults
Iron content (mg)
Men Women
Hemoglobin
Myoglobin
Enzymes
Transport (transferin
Storage ( ferritin and
other form)
Total
3050
430
10
8
750
4246
1700
30
8
6
300
2314
N.B. The above estimations are based on the assumptions that:
The average male adult weighs 80 kg and has a mean Hb level of 16 g/dL and the female adult
weighs 55 kg and has a mean Hb level of 14 g/dL.
Absorption
Iron is absorbed in duodenum and proximal jejunum. A normal individual with out iron deficiency
absorbs 5-10 % of daily intakes.
Absorption is increased in states with increased requirements or deficiencies (low iron stores,
pregnancy, menstruation, growing children, and blood loss) and/or dietary factors such as
heme-iron (from meat, etc), HCl and vitamin C.
Absorption is decreased from non heme iron (Fe3+), in the presence of phytates, antacids and
other chelates, and following gastric resection.
Iron crosses the stinal mucosal cell by active transport; then according to mucosal iron store, it
can either be available to transferrin to be transported to plasma or be stored in the mucosal cell
as ferritin.
Storage: Iron is stored primarily as ferritin in intestinal mucosal cells and in macrophages in the
liver, spleen and bone.
Elimination:
Very small amount are execrated in stool by exfoliation of intestinal mucosal cells and trace
amounts are execrated in bile, urine and sweat with total daily excretion not more than 1mg/day.
TREATMENT OF IRON DEFICIENCY ANEMIA
The cause should always be identified and treated whenever possible. Treatment of iron
deficiency anemia consists of administration of oral or parenteral iron preparation.
- Oral Iron Therapy:
Only ferrous salts should be used because of most efficient absorption. Ferrous sulfate, ferrous
gluconate, ferrous fumarate are the most commonly used oral iron preparations. About 25% of
oral iron given as ferrous salt can be absorbed; therefore 200-400mg elemental irons should be
given daily to correct iron deficiency most rapidly. Treatment should be continued for 3-6
months to replenish iron stores.
Side effects: Oral iron therapy can cause nausea, vomiting, epigastric discomfort, abdominal
cramps, constipation and diarrhea. - Parenteral iron therapy:
Should be reserved for patient unable to tolerate or absorb oral iron. Patients with extensive
chronic blood loss who can not be maintained with oral iron alone including patients with various
post gastrectomy conditions, previous small bowel resection, inflammatory bowel disease
involving proximal small bowel and malabsorption syndromes need parenteral iron therapy.
Drugs for parenteral administration include:
- Iron dextran
- Iron sorbitol
They may be given by deep IM or occasionally IV. Intravenous administration may result in very
severe allergic reactions and thus should be avoided if possible.
Side effect: include local pain, tissue staining, headache, light headedness, fever, arthralgia,
nausea, vomiting, urticaria, back pain, bronchospasm, and rarely anaphylaxis and death.
Acute iron Toxicity
Is exclusively seen in young children who ingest a number of iron tablets and rarely seen in
adults as a result of suicide or repeated blood transfusions.
Signs and symptoms
Necrotizing gastroenteritis with vomiting, abdominal pain and bloody diarrhea, shock, metabolic
acidosis, coma
Treatment
Whole bowel irrigation.
Deferoxamine- A potent iron chealating compound should be given systemically to bind iron and
promote excretion through urine
VITAMIN B12
Vitamin B12 is made up of a porphyrin-like ring with a central cobalt atom attached to a
nucleotide. Daily vitamin B12 requirement is 2-5 mg. It is mainly obtained from animal products
and serves as a co factor for essential biochemical reaction in humans. Ultimate source of vit
B12 is from microbial synthesis.
Pharmacokinetics
Absorbed in distal ileum after combined with intrinsic factor secreted by stomach through a
highly specific receptor mediated transport system once absorbed vit B 12 is transported to
various cells of the body bound to plasma glycoprotein, transcobalamin II. Excess vitamin B12 is
transported to the liver for storage and excreted in the urine.
Physiologic function- Acts as a coenzyme in the synthesis of DNA and is also essential for various metabolisms in
the body.
Clinical uses - Vit B12 is used to treat or prevent deficiency of vit B 12
Deficiency of Vit B 12 results in: - Megaloblastic anemia
- Neurological syndrome involving spinal cord and peripheral nerves
Causes:
The causes for Pernicious anemia are defective secretion of intrinsic factor necessary for
absorption of vitB 12, partial or total gastrectomy, diseases that affect distal ileum, malabsoption
syndrome e.g inflammatory bowel disease, small bowel resection etc.
Almost all cases of vit B12 deficiencies are caused by malabsorption
Treatment
Vit B12 therapeutic preparations are cyanocoblamin and hydroxycobalamin and For intrinsic
factor deficiency the vitamin should be given parenterally and patients with pernicious anemia
will need life-long therapy.
FOLIC ACID
Folic acids are required for essential biochemical reactions that provide precursors for the
synthesis of amino acids, purines and DNA.Daily requirement is 50 -100μg. Folic acid deficiency
is not uncommon.
Sources include yeast, liver, kidney and green vegetables.
Physiologic functions
It plays a role in the biosynthesis of purines and pyrimidines, i.e., DNA.
Folic acid Æ dehydrofolateÆ tetrahdyroflate
pyrmidens purine
Phamacokinetics
Unaltered folic acid is readily and completely absorbed in the proximal jejunum. 5 -20 mg of
folates are stored in the liver and other tissues. Body stores of folates are relatively low and
daily requirement is high and hence folic acid deficiency and magaloblasitc anemia can develop
within 1 -6 months after the in take of folic acid stops. Folates are excreted in the urine and
stool.
Deficiency:
Common among elderly patients, poor patients, pregnant ladies. It results in megaloblasiic
anemia. Congenital malformation in newborn like spina bifida are also consequences of folate
deficiency during pregnancy.
Causes
Dietary deficiency, alcoholics with liver disease, hemolytic anemia, malabsorption syndrome,
patients with cancer, leukemia, myeloprolferative disorders, chronic skin diseases, patients on
renal dialysis and patients on drugs that impair absorption or metabolism e.g. phenrytoin, oral
contraceptive, isoniazid, methotrexate etc.
Treatment
Folic acid 1mg orally per day.
N.B - Folic acid supplementation to prevent folic acid deficiency should be considered in high-risk
individuals including pregnant women, alcoholics and patients with hemolytic anemia, liver
disease, certain skin disease, and patients on renal dialysis.
DNA
101 - The administration of folic acid in the setting of vitB12 deficiency will not prevent neurological
manifestation even though it will largely correct the anemia caused by the vitamin B 12
deficiency.
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