Case Scenario

A 26 year old lady with 22 weeks of pregnancy attends the 1st 1ntenatal booking visit. On enquiry she has had 3 normal full term deliveries and one caesarean section for a twin pregnancy at 38 weeks of pregnancy and one abortion at 19 weeks. She feels easily tired too and sleepy She is really tiring to look after the children nowadays this is also during the last week. On Examination She is anaemic. She is otherwise fit and well. Hb level 10.5 gm/dl Microcytic hypochromic (MCV <80 fL) Macrocytic (MCV >100 fL) Treatment- Haematinics
fL = femto-litre = 1015 L = 1 m3

Normal blood film

Severe iron deficiency anaemia

TY CSU IMU

Red cells Macrocytosis

White cells - Hypersegmented neutrophils

TY CSU IMU

Haemoglobin level: The cut-off point for the women by WHO 12 g/dl. Men 13 g/dl Anaemia is a reduction in the number of RBCs or the Haemoglobin content of blood below normal for age and sex of the individual Acute/ Chronic

What is anaemia?

ALL ANAEMIA CASES

34.3
NUTRITION

32.1
DISEASE RELATED

33.6
UNEXPLAINED

ANAEMIA WITH NUTRI. DEFICIENCY

48.3
IRON

18.8
FOLIC ACID

17.2
B12 9.9
IRON FA & B12

5.8
FA & B12

Normocytic (MCV 80-100 fL) Microcytic hypochromic / normochromic (MCV <80 fL) Macrocytic (MCV >100 fL)

fL = femto-litre = 1015 L = 1 m3
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Diagnosis

Peripheral blood film Flow cytometry automatic counters

fL = femto-litre = 1015 L = 1 m3
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Iron Vitamin B12 Folic acid It is regulated by erythropoietin - secreted by kidneys - stimulates the bone marrow

12

Daily Requirement :Adult male Adult Female Infants Children Pregnancy 0.5 1 mg 1 2 mg 60 g / kg 25 g / kg 3 5 mg

Dietary Sources Diet contains 10 to 15 mg iron/day

Rich Liver, Egg yolk, Oyster, Dry fruits, Wheat germs, yeast

Medium Meat, Chicken, Fish, Spinach, Banana, Apple Poor Milk and its products, Root vagetables

IRON ABSORPTION
The average daily diet contain 10-15 mg of iron. 5% to 10% absorbs dietary iron = 0.5 to 1 mg/day Adequate for male and postmenopausal

Menstruating/pregnant woman require 1 to 3 mg/day Menstrual loss is 30 mg/period. Absorption occurs all over the intestine, but
magnify in the upper part.

To absorb- iron Ferric to ferrous by acid reducing agent. From gut to Intestinal mucosal cells by 1. Divalent metal transporter. From mucosa to plasma by 2. Ferroportin transporter Absorbed ferrous to plasma by F transporter or oxidised to ferric form and ferric form +apoferritin= ferritin is stored in the mucosal cells.

GUT

MUCOSAL CELLS

PLASMA Ferrous Ferroportin Ferric + Transferrin

Ferric
Ferrous

Ferrous

Divalent metal transporter 1

Ferrous Ferric + Apoferritin Ferritin

Circulate in the plasma

Plasma

Cells
Membrane + Transferrin Receptors Endocytosis

Ferric + Transferrin

Released iron

STORAGE

RE cells Liver, Spleen, Bone-marrow, hepatocytes, myocytes as ferritin and haemosiderin

Plasma Iron

from Old RBC 120 days Iron Store Intestinal absorption

An Iron common pool

Erythrpoiesis, Other cells, Restorage

Bleeding heavy menstruation gastric (PU, cancer occult bleeding) or piles hookworm infestation use of NSAIDs for pain / inflammation

23

Increased Physiological Demand for Iron Pregnancy and Lactation Infancy, children and adolescents (rapid growth)

24

Inadequate Absorption post-gastrectomy generalized malabsorption (severe small bowel disease, Crohns disease / celiac disease)
Inadequate Intake -- Rare for adult, but extreme poverty

25

Normal blood film

Severe iron deficiency anaemia

TY CSU IMU

Hb is low MCV is low ( <80fL) microcytes MCHC is low hypochromic Ferritin is low Total iron binding capacity (TIBC) is increased Serum iron is low Transferrin saturation is < 19%

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Excess Iron Required 1. In pregnancy Expansion of RBC mass Foetus Loss during delivery 2. Lactating mother

2. Liquid formulation stain teeth. Less satisfactory.

200 mg elemental iron daily in 3 divided doses gives maximum haemopoietic response. Infant and children 3 to 5 mg/kg

30 mg/day is for prophylaxsis Absorption is better taken in empty stomach. May have side-effects more.

Parental Iron Therapy

Indications Not tolerated. Failure to absorb. No- compliance In presence of severe deficiency Along with erythropoietin

Total Iron requirement = 4.4 x body wt kg x Hb deficit g/dl

Parental Iron Therapy

1. Iron dextran injection : Dose 1 ml 2. Iron sorbitol injection : 50 mg of iron/ml Dose 1.5 mg of iron / kg

D. Deferrioxamine 5-10 mg in 100 ml saline may be left in the stomach after lavage to prevent further iron absorption.

E. IV infusion desferrioxamine 80 mg/kg/24h or IM 2 g in sterile water every 12 hourly.

Vitamin B12(Cyanocobalamine)

TY CSU IMU

Vitamin B12(Cyanocobalamine) Cobalamins - Active cellular co enzyme. Necessary for DNA synthesis. Formed from Cyanocobalamin and hydroxocobalamin.

Vitamin B12(Cyanocobalamine) is Extrinsic factor in the food. Principal sources - Meat (particularly liver), eggs and dairy products.

Absorption Vitamin B12 absorption needs Intrinsic factor, glycoprotein secreted by parietal cells in the stomach, binds to vitamin B12 in the duodenum. This vitamin B12intrinsic factor complex subsequently aids in the absorption of vitamin B12 in the terminal ileum. Then transported bound to plasma glycoprotein - transcobalamin II. Excess B12 is stored in the liver (80%) and the rest in the kidney, adrenal, pancreas and other organs.

Vit B12 and folic acid are essential vitamins for normal DNA synthesis Deficiency leads to impaired DNA synthesis; reduced cell division, but RNA and protein synthesis continue large (macrocytic) and fragile RBCs. Daily requirement- 2.4 ug. 2.6 ug for pregnant mother Average adult stores ~ 3000 - 5000g

Red cells Macrocytosis

White cells - Hypersegmented neutrophils

TY CSU IMU

Partial or total gastrectomy Diseases of distal ileum Nutritional deficiency: very rare but possible in strict vegetarians after many years without meat, egg or dairy products Fish tapeworm (sequestration of B12 by the worms) Prolonged exposure to N2O anaesthesia (N2O inactivates the vitamin)

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Therapy

Since almost all cases of B12 deficiency are due to malabsorption, parenteral treatment is needed, and for life.
Hydroxycobalamin (produces higher and more sustained blood level) or cyanocobalamin.

Vit. B12 and folic acid have no known toxic effects even in high doses which are excreted in the urine and faeces

Rare (allergic) effects: itching, fever, nausea, dizziness, anaphylaxis (especially hydroxycobalamin)

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Folic acid (Pteroyl glutamic acid)

Folic acid (Pteroyl glutamic acid)

Folates are co-factors in the synthesis of purines and pyrimidines which are essential for DNA synthesis To be effective folates must be in the tetrahydro (FH4) form. The enzyme dihydrofolate reductase reduces dietary folic acid to FH4 (tetrahydrofolate) Folates are found in the green vegetables (heat labile), liver (more heat stable), yeast, nuts, cereals, fruits

 Folic acid is readily and completely absorbed in the duodenum and proximal jejunum Is subsequently transported into the blood stream by active and passive transport. Since body stores are relatively low and daily requirement high, deficiency (and anaemia) can occur within 1-6 months Excreted in urine and stool and destroyed by catabolism

 The average daily diet contains 500 -700g of folate of which 50 - 200g is absorbed. Daily requirement 400 ug. per day Pregnancy- 600 to 800 ug. per day

Often by dietary insufficiency (poverty, elderly) For alcoholics and liver disease, poor diet and very low liver storage Pregnancy (deficiency associated with neural tube defect) Haemolytic anaemia Dialysis Patients

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Mal- absorption (e.g. coeliac disease or tropical sprue)

Drugs that interfere with folate absorption e.g. Phenytoin, Oral contraceptives and Isoniazid Methotrexate, Pyrimethamine, Trimethoprim can interfere with metabolism

55

Parenteral administration is rarely needed because folic acid is well absorbed even in mal-absorption syndromes Dont use in undiagnosed megaloblastic anaemia. 600 to 800 micrograms of folate for pregnant mothers

56

ERYTHROPOINTIN

In 1906, Paul Carnot, a professor of medicine in Paris, France, and his assistant, DeFlandres, proposed the idea that hormones regulate the production of red blood cells.

Erythropoietin is produced in the kidney and liver, and is involved in the production and differentiation of erythrocytes.

Anaemia of chronic renal failure (epoietin is given i.v., s.c., or i.p.) Anaemia in AIDS patients Cancer (chemotherapy) related anaemia Surgery and autologous blood transfusion (orthopaemic, cardiac procedures) Myelodysplasia

60

Abuse: sportsman to enhance performance

Side effects:

Flu-like symptoms, Hypertension, Encephalopathy with headache, Disorientation convulsion blood viscosity (due to RBC mass)

Colony Stimulating Factors (CSF)

Cytokinase stimulate growth, differentiation and functional activitty of colonies of myeloid cells Some have been developed for clinical use. Filgrastim Lenograstim Molgramostim

Recombinant human G-CSF Produced in E.coli

63

Clinical Uses

severe neutropenia after autologous hematopoietic stem cell transplantation and high-dose cancer chemotherapy reduces morbidity secondary to bacterial and fungal infections neutropenia of AIDS patients receiving zidovudine

64

Filgrastim is administered by subcutaneous injection or intravenous infusion over at least 30 minutes half-life of 3.5 hours

Adverse reactions mild to moderate bone pain skin reactions following subcutaneous injection rare cutaneous necrotizing vasculitis

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Contents

Treatment of Iron deficiency (oral and parental preparations of iron) Management of iron overload Treatment of B12 deficiency (oral and parental preparations of B12) Treatment of Folic acid deficiency Erythropoietin & G-CSF therapy

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