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 These are substances required for formation of blood and
treatment of anemias.
 Anemia could occur due to
blood loss(acute, chronic)
decreased RBC synthesis either
1- due to defficiency of essential factors, i.e IRON,
2- or Bone marrow depression , erythropoietin
Increased destruction of RBC (hemolytic anemia).

 Iron is an essential body constituent.
 Total body iron in an adult=2.5-5.0 g(average 3.5g)
 More in men=50mg/kg than female =38mg/kg
 Distributed into
 Hb=66% (contain 4Fe containing heme residue), To raise 1 gm/dl
of Hb 200 mg of Fe is needed.
 Iron stores as ferritin and hemosiderin=25% Fe³ is stored as
ferritin with a large protein apoferritin.
 Myoglobin=3%
 Parenchymal iron=6% parenchymal Fe occur as a prosthetic gp in
many cellular enzymes cytochrome, peroxidases, catalases,
xnthine oxidases and some mitochondrial enzymes.

Daily requirement of IRON
 Adult male=0.5-1mg(13 µg/kg)
 Adult female=1-2mg(21 µg/kg)
 Infants =25 µg/kg
 Pregnency=3-5 mg(80 µg/kg)
 Rich : liver, egg yolk, oyster, dry eans, wheat germ, yeast.
 Medium: meat, chicken, fish, spinach, banana, apple.
 Poor: milk and its product, roots vegetables
 Average daily diet contain 10-20 mg of iron

IRON absorption
 Dietry Iron is present:
 as heme iron (absorption is better as compared to inorganic iron)
 as inorganic iron, major part is this one and in ferric form
 Neded to be reduced to ferrous form before absorption.
 Two separate transporter in intestinal mucosa exist
 DMT1( DIVALENT METAL TRANSPORTER): carries ferrous to
mucosal cells.
 This ferrous along with iron released from heme is transported
across basolateral membrane by another transporter called

Factors affecting iron absorption
 Acid: by favoring dissolution and reduction of ferric iron
 Reducing substance: vit C, amino acid containing SH
These reduces ferric ironand form absorbable complexes.
Meat: by increasing Hcl secretion and providing heme iron.


Alkalies (antacid) renders iron insoluble, opposes its
PO4, Tetracycline, presence of other foods in stomach.(all
form complexes)
Mucosal block
 The gut has the mechanism of preventing entry of excess of
Iron in the body.
 Iron reaching inside the mucosal cell is either transported to
plasma or oxidized to ferric form and complexed with
apoferritin to form ferritin which remained stored in the
mucosal cells and is lost when they are shed(life span=2-4
days ) this is called “ferritin curtain”.

Iron Transportation
 Free iron iron is highly toxic.
 On entering in plasma it rapidly converted to ferric form and
complexed with a glycoprotein transferrin (2 ferric residues
 Iron is transported into erythropoitic and other cells thru
attachment of transferrin(Tf) to transferrin receptors(TfR)
that are membrane bound.
 The complex is engulfed by endocytosis, iron dissociates
from complex at acidic pH of intracellular vesicles;
 The released iron is utilized for Hb synthesis or other
purposes, while Tf and TfR returned back to cell surface.

Iron storage ,utilization and excretion
 Iron is stored in reticuloendothelial cells in liver, spleen, bone
marrow, hepatocytes, myocytes as ferritin and hemosiderin after
entering these cells thru TfR
 Apoferritin synthesis is regulated by iron status of the body.
 Iron is conserved by the body, Daily excretion in adult male is 0.5-
1 mg, mainly as exfoliated GI mucosal cells, some RBCs & in bile
all lost in faeces.
 In mensturating women, monthly menstural loss may be averaged
to 0.5-1 mg/day.
 Excess iron is required during pregnency for expansion of RBC
mass, transfer to fetus, and loss during delivery, totalling to about
700 mg.

Indications for iron
 In treatment /prevention of iron deficiency anemia,
 In children with rapid growth periods,
 Pregnant and, lactating women,

Iron preparation
 Iron defeciency anemia can be treated by
 Oral iron
 Or Parenteral iron
Oral iron absorbs more rapidly as parenterals if iron absorption
is normal in GIT.
 VARIOUS iron preparations provide different amount of
elemental iron,

Preparation potency Elemental iron Usual adult
/tab dose(tab/day)

Ferrous 325 mg 65 mg 3-4

Ferrous 200 mg 65 mg 3-4
Ferrous 325 36 3-4
Ferrous 200 66 3-4
12 fumarate(No
Adverse effects after oral intake of iron
 Nausea, vomiting, epigastric discomfort, abdominal cramps,
constipation and diarrhea----dose related effects.
 Metallic taste, teeth staining, heart burn, colic, constipation.
These can be reduced if taken with meals or after meals.
Large amount of oral iron cause gasteroenteritis,bloody
diarrhea followed by shock, lethargy and dyspnea.
Chronic iron toxicity can lead to hemochromatosis i.e.
deposition of iron in heart, liver, pancrease and other organs
that can lead to organ failure and death. This can be treated
by phlebotomy i.e. one unit of blood is can be removed every

 In case of overdosage urgent treatments are needed and for
that whole bowel irrigation is done to flush out unabsorbed
 Egg yolk and millk is given to complex iron.
 Desferroxamine (0.5-1g rptd 4 -12 hrly as reqd), a potent
iron chelator , given systemically(IM) to bind iron that has
already been absorbed and to promote the excretion in urine
and feces.
 In case of chronic iron toxicity desferroxamine treatment is
in effective and only phlebotomy is useful.

Parenteral preparations of iron
 Reserved for patients who are un tolerable to the
effects of oral iron and pt with chronic blood loss who
can’t be maintained with oral iron alone.
 Pt with IBD involving proximal small intestine,
patients with various post gastrectomy conditions.
 Total iron requirement must be calculated for
parenteral iron therapy=4.4 x body wt x Hb
The rate of responsiveness of parenteral iron is not
>than optimal doses of oral iron preparation.

 The ionized salts of iron used orally can’t be injected b/c of protein
precipitating action. Two origionally complexed preparation are
 Iron dextran (imferone): as a colloidal solution containing 50 mg of
elemental iron g/ml
 Iron sorbitol-citric acid complex(jectofer): 50mg iron/ml
 Iron sodium gluconate complex: a newer product
 All IM doses are 30%higher than IV doses
 A test dose (few drops) can be injected first to screen sensitive patient.
 IM inj is given at gluteal region using Z track technique(to avoid staining
of tissues) Iron dextran is given 2 ml daily or on alternate day
 while More Than 1.5-2 ml of iron- sorbitol should not be injected at one

Adverse effect of parenteral iron
 Local pain and tissue staining(dark brown color of tissues at
the injected site)
 Headache, light headedness, fever, arthralgia, nausea,
vomiting, back pain, flushing, urticaria, bronchospasm, rarely
anaphylaxis and death.

Maturation factors

Vitamin B 12
 Vitamin B12 has the largest and most complex chemical structure
of all the vitamins. It is unique among vitamins in that it contains a
metal ion cobalt. For this reason cobalamin is the term used to
refer to compounds having vitamin B12 activity.

 Methylcobalamin and 5-deoxyadenosyl cobalamin are the forms of

vitamin B12 used in the human body . The form of cobalamin used
in most supplements, cyanocobalamin, is readily converted to 5-
deoxyadenosyl and methylcobalamin in the body.

 In mammals, cobalamin is a cofactor for only two enzymes,

methionine synthase and L-methylmalonyl-CoA mutase

Vitamin B12
 Vitamin B12 and folic acid belongs to B vitamin group.
 Their deficiency can lead to megaloblastic anemia,
characterized by the presence of large RBC in the peripheral
 It is water soluble in nature and synthesized only by
microorganism, plants and animals acquire from them.
 Dietary source: Liver, kidney, sea fish, egg yolk, meat cheese,
 Daily requirement: 1-3µg, pregnency and lactation3-5µg

Metabolic function of vitamin B 12

21 folic acid
 Two essential enzymatic reaction in humans require vitamin B 12 .
 1-Vitamin B 12 as methyl cbl is involved in transformation of HCYS to
methionine. Methylcobalamin is required for the function of the ,
methionine synthase. This enzyme is required for the synthesis of the
amino acid methionine from homocystein. methionine in turn is
required for the synthesis of S-adenosylmethionine, a methyl group
donor used in many biological methylation reactions, including the
methylation of a number of sites within DNA and RNA. Methylation of
DNA may be important in cancer prevention. Inadequate function of
methionine synthase can lead to an accumulation of homocysteine, which
has been associated with increased risk of cardiovascular diseases.
 In the absence of vitB12 methyl THF can’t be converted to THF which is
the precurser of thymidylate and purines reqd for the snthesis of DNA in
rapidly dividing cells

 The other enzymatic reaction that reqr vit B 12 as a cofactor is
isomerization of methyl melonyl co A to succinyl coA.
methylmelonyl coA (methyl melonyl coA mutase) Succinyl coA
and deoxyadenosyl cbl)
deoxy adenosyl cbl is a coenzyme of the transformation of
methylmelonyl coA to succinyl coA (which then enters the kreb
cycle) by means of methyl melonyl coA mutase enzyme.
 This biochemical reaction plays an important role in the
production of energy from fats and proteins.

 Vitamin B12 is absorbed from only when it form complexes
with Intrinsic factor , a glycoprotein that is released from
gastric mucosal cells, this complex is then absorbed in distal
ileum by a highly specific transport system.
 Deficiency of vit B 12 occur due to malabsorption of vit
either due to lack of intrinsic factor or due to malfunctioning
of transport mechanism.

 Treating vit B 12 deficiency
 As a general tonic to allay fatigue
 Mega doses can used in neuropathies and psychiatric
 Allergic reaction

vitB 12 is available as parenteral preparation as cyanocobalamin
or hydroxy cobalamin
 Hydroxy cobalamin is prefered b/c it is highly protein bound
so stay more in circulation
 Initially 100-1000µg im daily orevery other day for1-2 wks
to replnish body store maintennance therapy=100-1000µg
once a month for life.