its from basic to understand properly

1. CARDIOVASCULAR SYSTEM OF BLOOD
HAEMETINICS
SUBIKSHA.M
1ST YEAR MPHARM
DEPT.OF PHARMACOLOGY
PSG COLLEGE OF PHARMACY,
COIMBATORE.
1

2. CONTENT
 INTRODUCTION OF BLOOD
 ANAEMIA & ITS TYPES
 DEFINTION OF HAEMETINIC
 IRON
 ABSORPTION, TRANSPORT, UTILIZATION, STORAGE & EXCREATION
 PREPRATIONS OF IRON
ORAL IRON & PARENTERAL IRON
 ACUTE IRON POSINING & ITS TREATMENT
 VITAMIN B12
 FOLIC ACID
 ERTHYROPOIETIN
 REFERENCE.
2

3. BLOOD
 Blood is a liquid connective tissue that consists of blood plasma (liquid extracellular
matrix) plus formed elements (red blood cells, white blood cells, and platelets).
BLOOD FUNCTION:
 Transports oxygen, carbon dioxide, nutrients, hormones, heat, and wastes.
 Regulates pH, body temperature, and water content of cells.
 Protects against blood loss through clotting, and against disease through phagocytic
white blood cells and proteins such as antibodies, interferons, and complement.
3

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4

5. BASIC TERMS
PLURIPOTENT STEM CELL: Cell that have the capacity to self renew by dividing and
to develop into the three primary germ cell layers of the early embryo.
MYELOID STEM CELL: Derived from hematopoietic stem cells & undergoes
differentiation to produce precursors of erythrocytes, platelets, dendritic cell, mast
cells, monocytes & granulocytes.
LYMPYLOID STEM CELL: Mature, infection-fighting cells that develop from
lymphoblasts & major part of the immune system.
MARCOPHAGE: Specialized cells involved in the detection, phagocytosis and
destruction of bacteria and other harmful organisms.
PLASMA CELL: A type of immune cell that makes large amounts of a specific
antibody.
5

6. FORMATION OF BLOOD
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7. RBC PRODUCTION 7

8. DESTRUCTION OF RBC’S 8

9. ANAEMIA
Anaemia is defined as reduced haemoglobin concentration in blood below the lower limit
of the normal range for the age and sex of the individual.
9

10. NORMAL RANGE
RBC count: Normal range of RBC count in health men- 5.5 ± 1.0×1012/l & women-4.8
±1.0×1012/l
PCV: The packed cell volume (PCV) or haematocrit is the volume of erythrocytes per
litre of whole blood indicating the proportion of plasma and red cells & range of
normal PCV in health men-0.47 ± 0.07L/L (40-54%) & women-0.42 ± 0.05L/L (37-
47%).
Haemaglobin count: Normal range of HB count in health men 15.5 ± 2.5 g/dl (13-18
g/dl) and women 14.0 ± 2.5 g/dl (11.5-16.5 g/dl).
Mean corpuscular volume (MCV): It is the measure of average size or volume of
RBC in blood. The normal value is 85 ± 8 fl (77-93 fl)*.
PCV in L/L
RBC count/L
10

11. Mean corpuscular haemoglobin (MCH): The average quantity of haemoglobin
present in single of red blood cell. The normal range is 29.5 ± 2.5 pg (27-32 pg)*.
Hb/L
RBC count/L
Mean corpuscular haemoglobin concentration (MCHC): The average concentration
of haemoglobin in red blood cell. The normal value is 32.5 ± 2.5 g/dl (30-35 g/dl).
Hb/dl
PCV in L/L
Red cell distribution width (RDW): RDW is an assessment of varying volume of red
cells based on size of red cells. For example, fragmented red cells have a tiny size
while the macrocytes and reticulocytes have large size.
CONT… 11

12. PATHOPHYSIOLOGIC CLASSIFICATION
Depending upon the pathophysiologic mechanism, anaemias are classified into 3
groups:
 Anaemia due to blood loss: This is further of 2 types:
 Acute post-haemorrhagic anaemia
 Anaemia of chronic blood loss
 Anaemia due to impaired red cell formation: A disturbance due to impaired red
cell production from various causes may produce anaemia.
 Cytoplasmic maturation defects:
Deficient haem synthesis: iron deficiency anaemia
Deficient globin synthesis: thalassaemic syndromes
12

13. CONT…
 Nuclear maturation defects:
Vitamin B12 and/or folic acid deficiency: megaloblastic anaemia
 Haematopoietic stem cell proliferation and differentiation abnormality: e.g.
Aplastic anaemia
Pure red cell aplasia
 Bone marrow failure due to systemic diseases: (anaemia of chronic disorders)
 Anaemia of inflammation/infections, disseminated malignancy.
 Anaemia in renal disease.
 Anaemia due to endocrine and nutritional deficiencies.
 Anaemia in liver disease.
13

14. CONT…
 Bone marrow infiltration: e.g.
 Leukaemia’s
 Lymphomas
 Myelosclerosis
 Multiple myeloma
 Congenital anaemia: e.g.
 Sideroblastic anaemia
 Congenital dyserythropoietic anaemia
 Anaemia due to increased red cell destruction (haemolytic anaemias): This is
further divided into 2 groups:
 Intra corpuscular defect (hereditary and acquired).
 Extra corpuscular defect (acquired haemolytic anaemias).
14

15. 15
MORPHOLOGIC CLASSIFICATION
Based on the red cell size, haemoglobin content and red cell indices, anaemias are classified
into 3 types:
 Microcytic, hypochromic: MCV, MCH, MCHC are all reduced.
e.g. in iron deficiency anaemia and in certain noniron deficient anaemias
(sideroblastic anaemia, thalassaemia, anaemia of chronic disorders).
 Normocytic, normochromic: MCV, MCH, MCHC are all normal.
e.g. after acute blood loss, haemolytic anaemias, bone marrow failure,
anaemia of chronic disorders.
 Macrocytic: MCV is raised.
e.g. in megaloblastic anaemia due to deficiency of vitamin B12 or folic acid.

16. CONDITION
Acute post-haemorrhagic anaemia: A condition that
develops when you lose a large amount of blood
quickly.
Thalassaemic syndrome: It is an inherited blood
disorder that causes your body to have less
hemoglobin than normal. Hemoglobin enables red
blood cells to carry oxygen. It can cause anemia
16
https://medlineplus.gov/images/PX0000N0_PRESENTATION.jpeg
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17. CONT…
Megaloblastic anaemia: It is a form of anemia characterized
by very large red blood cells and a decrease in the number of
those cells.
Aplastic anaemia: It is a condition that occurs when your
body stops producing enough new blood cells. The condition
leaves you fatigued and more prone to infections and
uncontrolled bleeding. A rare and serious condition, aplastic
anemia can develop at any age.
https://cfch.com.sg/wp-content/uploads/2020/06/Aplastic-Anaemia.png
https://www.spectrumhealthlakeland.org/health-wellness/health-library/GetImage/440326
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18. CONT…
Pure red cell aplasia: A type of aplastic anemia
affecting the precursors to red blood cells but usually
not to white blood cells. In PRCA, the bone marrow
ceases to produce red blood cells.
Sideroblastic anaemia: In this condition, the iron inside
red blood cells is inadequately used to make
hemoglobin, despite normal amounts of iron.
https://imagebank.hematology.org/getimagebyid/1550?size=3
Image source from harsh mohan page no:277
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19. CONT…
Haemolytic anaemias: It is a disorder in which red blood
cells are destroyed faster than they can be made. The
destruction of red blood cells is called hemolysis.
Congenital dyserythropoietic anaemia: It is a rare
blood disorder, similar to the thalassemia's. CDA is one of
many types of anemia, characterized by ineffective
erythropoiesis, and resulting from a decrease in the
number of red blood cells (RBCs) in the body and a less
than normal quantity of hemoglobin in the blood.
https://rarediseases.info.nih.gov/files/glossary/english/HemolyticAnemia-346367561-540px.png
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20. CONT…
Intra corpuscular defect: It is disorders, the patient's red blood cells (RBCs) have an
abnormally short life span because of an intrinsic RBC factor.
Extra corpuscular defect: It is disorders, the RBC has a short life span because of a
non-intrinsic RBC factor.
PERNICIOUS ANAEMIA
It deficiency in the production of red blood cells through a lack of vitamin B 12. Common
causes include a weakened stomach lining or an auto-immune condition. Symptoms
include fatigue and weakness.
20

21. CONT…
Sickle cell anaemia: An inherited disease in which the red blood cells have an
abnormal crescent shape, block small blood vessels
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22. SYMPTOMS
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23. HAEMETINIC
Haematinic’s are substances that are essential to the proper formation of the
components of blood & used to treat anaemia.
Anaemia occurs when the balance between production and destruction of RBCs is
disturbed by:
 Blood loss (acute or chronic)
 Impaired red cell formation due to:
 Deficiency of essential factors, i.e. iron, vitamin B12, folic acid.
 Bone marrow depression (hypoplastic anaemia), erythropoietin deficiency.
 Increased destruction of RBCs (haemolytic anaemia)
23

24. IRON
Iron is important for the body. Lauha bhasma (calcined iron) has been used in ancient
Indian medicine.
In the early 19th century Blaud developed his famous ‘Blaud's pill’ consisting of
ferrous sulfate and potassium carbonate for anaemia.
Distribution of iron in body: Total body iron in an adult is 2.5–5 g (average
3.5 g). It is more in men (50 mg/kg) than in women (38 mg/kg).
Distributed into:
Haemoglobin (Hb) : 66%
Iron stores as ferritin and haemosiderin : 25%
Myoglobin (in muscles) : 3%
Parenchymal iron (in enzymes, etc.) : 6%
24

25. CONT…
Haemoglobin is a protoporphyrin; each molecule having 4 iron containing haeme
residues. It has 0.33% iron.
Iron is stored only in ferric form, in combination with a
large protein apoferritin.
aggregates
Apoferritin + Fe3+ Ferritin Haemosiderin
(not reutilized)
The most important storage sites are reticulo
endothelial (RE) cells. Parenchymal iron occurs as
prosthetic group in many cellular enzymes
cytochromes, peroxidases, catalases, xanthine oxidase
and some mitochondrial enzymes.
25

26. DIETARY SOURCE OF IRON
Daily requirement:
 Adult male: 0.5–1 mg (13μg/kg)
 Adult female: 1–2 mg (21 μg/kg)
(menstruating)
 Infants : 60 μg/kg
 Children : 25 μg/kg
 Pregnancy : 3–5 mg (80 μg/kg)
(last 2 trimesters)
26

27. ABSORPTION,TRANSPORT,UTILIZATION & STORAGE
Image source: K.D. TRIPATHI page no: 646
27

28. IRON ABSORPTION
Iron is absorbed via two mechanism:
Active transport of ferrous iron &
Absorption of iron with complexed haeme.
 It absorption occurs all over the intestine, but majority in the upper part of intestine.
 Dietary iron is present either as haeme (absorbs upto 35%) or as inorganic iron (or)
non-haeme iron (absorbs upto 5%).
 Major part of dietary iron is inorganic and in the ferric form & needs to be reduced to
the ferrous form before absorption.
 At the luminal membrane the divalent metal transporter 1 (DMT1) carry's ferrous iron
into the mucosal cell. This along with the iron released from haeme is transported
across basolateral membrane by another iron transporter ferroprotin (FP).
28

29. Factors facilitating iron absorption
 Acid: By favouring dissolution and reduction of ferric iron.
 Reducing substances: Ascorbic acid, amino acids containing SH radical. These
agents reduce ferric iron and form absorbable complexes.
 Meat: By increasing HCl secretion and providing haeme iron.
Factors impeding iron absorption
 Alkalies (antacids) render iron insoluble, oppose its reduction.
 Phosphates (rich in egg yolk)
 Phytates (in maize, wheat) By complexing iron
 Tetracyclines
 Presence of other foods in the stomach.
29

30. Mucosal block
The gut has a mechanism to prevent entry of excess iron in the body.
Iron reaching inside mucosal cell is either transported to plasma or oxidized to ferric
form and complexed with apoferritin to form ferritin.
This ferritin generally remains stored in the mucosal cells and is lost when they are
shed (lifespan 2–4 days). This is called the ‘Ferritin curtain’.
30

31. TRANSPORT & UTILIZATION
 Free iron is highly toxic.
 Ferrous form of iron is entering plasma it immediately converted into ferric form &
complexed with glycoprotein transferrin (Tf).
 Iron circulate into plasma two ferric iron bound to transferrin (Tf).
 Iron is transported inside erythropoietic & other cells through attachment of
transferrin that bound to transferrin receptor (TfR).
 Complex is engulfed by receptor mediated endocytosis.
 Iron dissociated from complex at acidic pH of intracellular vesicles & relased iron is
utilized for haemoglobin synthesis.
31

32. STORAGE
 Stored in RE cells of liver, spleen, bone marrow, hepatocytes & myocytes.
 Apoferritin synthesis is regulated by iron status of body.
 Low-less apoferritin & more transferrin is produced.
 High-more apoferritin synthesized to trap iron.
EXCRETION
 Highly conserved(one way substance)
 Exfoliated G.I mucosal cells, some RBCs and in bile & other routes are desquamated
skin, very little in urine and sweat.
 In menstruating women loss may be 0.5–1 mg/day.
32

33. Preparations and dose
 Oral iron
 Preferred route
 Ferrous salts preferred-cheap, high iron content, better absorption.
 Gastric irritation & constipation depends on quantity of iron
 Elemental iron.
Drugs used in oral are:
 Ferrous sulfate: (hydrated salt 20% iron, dried salt 32% iron) .
 Ferrous gluconate (12% iron).
 Ferrous fumarate (33% iron)
 Colloidal ferric hydroxide (50% iron).
 Carbonyl iron: It is high purity metallic iron in very fine powder form (particle
size<5M), prepared by decomposition of iron pentacarbonyl, a highly toxic
compound.
33

34. Other forms of iron present in oral formulations
 Ferrous succinate (35% iron)
 Iron choline citrate
 Iron calcium complex (5% iron)
 Ferric ammonium citrate (20% iron)
 Ferrous aminoate (10% iron)
Better absorbed and/or produce less bowel upset due to lower iron content.
More expensive.
 Combination of oral iron:
 CONVIRON Cap: Fe.sulfate (dried) 60 mg B12 15 μg, folic acid 1.5 mg, B6 1.5 mg,
vit. C 75 mg
 FESOVIT-SPANSULE Cap: Fe.sulfate (dried) 150 mg B12 15 μg, folic acid 1 mg,
nicotinamide 50 mg, B6 2 mg
34

35. ORAL IRON
 Sustained release is costly & irrational.
 Liquid formulation stain the teeth.
 200mg elemental iron divided into: 3 doses
 Better absorption on empty stomach – irritate GI mucosa.
 Larger dose after meal / smaller dose in between meals.
ADVERSE EFFECTS
 Epigastric pain, heartburn, nausea, vomiting.
 Bloating, staining teeth, metallic taste.
 Constipation is common than diarrhea.
NOTE: Combination of iron with strychnine, arsenic and yohimbine and all fixed dose combination of haemoglobin in
any form are banned in India. A Technical Advisory Board (India) has recommended that B complex vitamins and zinc
should not be included in iron and folic acid containing haematinic preparations.
35

36. PARENTERAL IRON
 Oral iron is not tolerated: bowel upset is too much.
 Failure to absorb oral iron: malabsorption; inflammatory bowel disease. Chronic
inflammation (rheumatoid arthritis) decreases iron absorption.
 Non-compliance to oral iron.
 In presence of severe deficiency with chronic bleeding.
 Along with erythropoietin: oral ion may not be absorbed at sufficient rate to meet
the demands of induced rapid erythropoiesis.
36

37. CONT…
CACULATIONS:
Iron requirement (mg) = 4.4 × body weight (kg) × Hb deficit (g/dl)
DRUGS USED IN PARENTERAL IRON
 Iron-dextran:
 High molecular weight colloidal solution=50 mg elemental iron
 Only preparations by i.m. & i.v.
 Dextran is antigenic - anaphylactic reactions
 Small test dose for sensitivity testing.
 By im, circulates through lymphatic without transferrin.
 Dose needs to be adjusted due to local binding.
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TJz-V7Ta3SIpvGyjT9uAUqYJHxWbW2I9FIA5XTe6PYv8FAvUBGVmykU-
hqtyA6hftIWcxsE8ivi8kGPA2HjOLZcu2cQxffd9kg
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38. CONT…
IM
 2ml daily/ alternate days/ 5ml on each side.
 Given in gluteal region using Z track technique.
IV
 IV bolus given daily slowly over 5–10 min.
 Diluted in 500 ml of glucose/saline solution over 6–8 hours.
 Injection should be terminated if the patient complains of giddiness, paresthesia's or
tightness in the chest.
ADVERSE EFFECT
 Local: Pain at site of injection, pigmentation of skin, sterile abscess.
 Systemic: Fever, headache, joint pains, flushing, palpitation, chest pain, dyspnoea,
lymph node enlargement & an anaphylactoid reaction
https://pbs.twimg.com/media/DB6K0qXWsAIq4pw.jpg
38

39. CONT…
Ferrous-sucrose
 Iron hydroxide with sucrose
 Highly alkaline, so given only by IV only 5 mins daily
 Total dose can’t be given by infusion.
 Safer than older preparation’s, less antigenic.
https://mimsshst.blob.core.windows.net/drug-resources/PH/packshot/Biorose6001PPS0.JPG
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40. CONT…
Ferric carboxymaltose
 Rapidly taken up by RE cell, liver and spleen on IV.
 100mg daily/1000mg in 100ml saline slowly IV
 Rapid increase in Hb & stores.
 Less antigenic
 Not recommended <14 years.
ADR: Pain at injection, rashes, headache, nausea, hypotension.
https://indmed.in/wp-content/uploads/2018/07/400636.jpg
40

41. THERAPEUTIC USES
 Iron deficiency anaemia: A condition in which
blood lacks adequate healthy red blood cells. It
is due to insufficient iron.
 Hb level by 0.5–1 g/dl increase.
 Continued till normal level 2–3 months or more
thereafter to replenish the stores.
1. PROPHYLAXIS: Pregnancy, infancy, chronic
illness, menorrhagia, acute blood loss.
2. MEGALOBLASTIC ANAEMIA: Along with
vit.B12 & folic acid depending upon iron status.
https://www.healthunbox.com/wp-content/uploads/2019/12/compressed-wguu.jpg
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42. ACUTE IRON POISONING
It occurs mostly in infants and children
Manifestations are vomiting, abdominal pain, haematemesis, diarrhoea, lethargy,
cyanosis, dehydration, acidosis, convulsions; finally shock, cardiovascular collapse
and death (in few cases death occurs early within 6 hours).
The pathological lesion is haemorrhage and inflammation in the gut, hepatic necrosis
and brain damage
42

43. IRON POISONING-TREATMENT
 To prevent further absorption of iron from gut
 Induce vomiting or perform gastric lavage with sodium bicarbonate.
 Give egg yolk and milk orally: to complex iron. Activated charcoal does not
adsorb iron.
 To bind and remove iron already absorbed
 Desferrioxamine
 DTPA or calcium edetate.
 Supportive measures
 Fluid and electrolyte balance should be maintained and acidosis
43

44. MATURATION FACTORS
Deficiency of vit B12 and folic acid, which are B group vitamins, results in megaloblastic
anaemia characterized by the presence of large red cell precursors in bone marrow and
their large and short-lived progeny in peripheral blood. Vit B12 and folic acid are
therefore called maturation factors.
1) VITAMIN - B12
2) FOLIC ACID
44

45. VITAMIN-B12:
 Cyanocobalamin and hydroxocobalamin are complex cobalt containing compounds
present in the diet and referred to as vit B12.
 Vit B12 occurs as water soluble, thermostable red crystals.
 It is synthesized in nature only by microorganisms; plants and animals acquire it
from them.
Daily requirement: 1–3 μg, pregnancy and lactation 3–5 μg.
45

46. DIETARY SOURCE
 The only vegetable source is legumes (pulses)
which get it from microorganisms harboured in their
root nodules.
 Vit B12 is synthesized by the colonic microflora, but
this is not available for absorption in man.
 The commercial source is Streptomyces griseus; as
a by-product of streptomycin industry
46

47. Utilization of vit B12
 Vit B12 is present in food as protein conjugates and is released by cooking or by
proteolysis in stomach facilitated by gastric acid.
 Intrinsic factor (a glycoprotein) secreted by stomach forms a complex with B12.
 Attach to specific receptors present on intestinal mucosal cells at the ileum.
 Absorbed by active carrier mediated transport.
 Transported in blood in combination with a β globulin, transcobalamin || (TC||).
 Excess vit B12 is stored in liver cells as 5’-deoxyadenosylcobalamin.
 Not degraded in the body
 It is secreted in bile(normally) or excreted in urine by glomerular filtration
(therapeutic doses).
47

48. METABOLIC FUNCTION
Homocysteine to methionine:
Methionine synthase is a vitamin B12-
dependent enzyme that catalyzes the
formation of methionine from homocysteine
using 5-methyltetrahydrofolatr(5-
methylTH4), a folate derivative, as a
methyl donor.
Another pathway catalyzed by betaine
homocysteine methyl transferase also
remethylates homocysteine to methionine
using betaine as a methyl donor.
https://image.slidesharecdn.com/hematinics-180729002345/95/hematinics-15-638.jpg?cb=1532824017
48

49. CONT…
 One carbon transfer: It mediated by the folate cofactor is a group of biochemical
reaction with set of enzymes & coenzymes. In B12 deficiency THFA gets trapped in
the methyl form and a number of one carbon transfer reactions suffer. Purine and
pyrimidine synthesis is affected because of ‘folate trap’. It inavailability of
thymidylate for DNA production.
49

50. CONT…
 Malonic acid to Succinic acid:
Malonic acid Succinic acid
It is an important step in propionic acid metabolism It links the carbohydrate and lipid
metabolisms. This reaction does not require folate and has been considered to be
responsible for demyelination seen in B12 deficiency, but not in pure folate deficiency.
 Methionine to S-adenosyl methionine:
Methionine S-adenosyl methionine:
It may be more important in the neurological damage of B12 deficiency, because it is
needed in the synthesis of phospholipids and myelin.
 Vit B12 is essential for cell growth and multiplication.
DAB12
DAB12
50

51. PREPARTION
 Cyanocobalamin: 35 μg/5 ml liq.
 Hydroxocobalamin: 500 μg, 1000 μg inj.
 Hydroxocobalamin preferred over cyanocobalamin
 Higher protein binding, better retention in blood
 Prophylactic – 3-10μg/day orally
 Therapeutic dose – hydroxocobalamin 1mg IM/Sc daily for 2 weeks
 Cyanocobalamin – 100μg IM/SC daily for 1 weeks.
 Methylcobalamin:
 The active coenzyme form of vit B12 for synthesis of methionine and S-adenosyl
methionine that is needed for integrity of myelin.
 Neurological defects in diabetic alcoholic and peripheral neuropathy.
https://canada.teligent.com/wp-content/assets/Screen-Shot-2018-07-22-
at-12.35.18.png
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52. https://5.imimg.com/data5/VR/PM/MY-25963348/methylcobalamin-injection-500x500.jpg
https://5.imimg.com/data5/LB/KO/MY-68942766/hydroxocobalamin-injection-500x500.jpg
52

53. THERAPEUTIC USES
 Prophylaxis
 Tobacco amblyopia
 Neuropathies, psychiatric disorder, cutaneous
sarcoid.
 Vitamin B12 deficiency: It is condition lead to
a reduction in healthy red blood cells. The
nervous system may also be affected.
 Megaloblastic anaemia
 Addisonian pernicious anaemia
 Nutritional deficiency
 Increased demand: pregnancy, infancy
https://c8.alamy.com/comp/TCNEM9/vitamin-b12-deficiency-infographic-3d-medical-vector-illustration-on-
white-background-TCNEM9.jpg
53

54. FOLIC ACID
 It occurs as yellow crystals which are
insoluble in water, but its sodium salt is freely
water soluble.
 It contains 2 to 8 molecules of glutamic acid.
 DAILY REQUIRMENTS:
 An adult 0.2 mg/day.
 During pregnancy, lactation 0.8 mg/day.
 Total body folate in the adult is ~ 10mg.
 Stores are sufficient for only 3-4 months.
https://i.pinimg.com/564x/b5/e7/98/b5e798b090121a23f729b9268294ca8e.jpg
54

55. UTILIZATION
 Folic acid is present in food as polyglutamates; glutamate residues are split off the
upper intestine before being absorbed.
 Transported in blood mostly as methyl-THFA which is party bound to plasma proteins.
 Folic acid is rapidly extracted by tissues and stored in cells as polyglutamates.
 Liver takes up a large part and secretes methyl-THFA in bile which is mostly
reabsorbed from intestine: enterohepatic circulation occurs.
 Alcohol interferes with release of methyl-THFA from hepatocytes.
 When pharmacological doses are given, 50–90% of the absorbed dose may be
excreted in urine.
55

56. METABOLIC FUNCTION
 Conversion of homocysteine to
methionine: Vit B12 acts as an
intermediary carrier of methyl group .
This is the most important reaction
which releases THFA from the
methylated form.
 Generation of thymidylate: Essential
constituent of DNA:
 Conversion of serine to glycine:
Needs THFA and results in the
formation of methylene-THFA which is
utilized in thymidylate synthesis.
https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcQcsPLE8QKQ4DgqLYKugKeE-
PcTFWR5FI6zDRv5LPgwXDKXV_E7yNxblspYWq8Cy2NZMeU&usqp=CAU
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57. Purine synthesis:
 de novo building of purine ring requires formyl-THFA and methenyl-THFA (generated
from methylene-THFA) to introduce carbon atoms at position 2 and 8.
https://www.easybiologyclass.com/wp-content/uploads/2015/06/Nucleotide-biosynthesis-purine-pyrimidine-biosynthesis-de-novo-
salvate-easybiologyclass.jpg
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58. FOLIC ACID DEFICIENCY
 Folate deficiency occurs due to:
 Inadequate dietary intake
 Malabsorption.
 Drug induced: prolonged therapy with
anticonvulsants (phenytoin, phenobarbitone,
primidone) and oral contraceptives—interfere with
absorption and storage of folate
 Megaloblastic anaemia.
 Epithelial damage: glossitis, enteritis, diarrhoea,
steatorrhoea.
 Neural tube defects, including spina bifida in the
offspring, due to maternal folate deficiency.
 General debility, weight loss, sterility.
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59. Preparations and dose
 Liquid oral preparations and injectables are available only in combination formulation.
 Oral therapy is adequate except when malabsorption is present or in severely ill
patient-given i.m.
 Dose: therapeutic 2 to 5 mg/day, prophylactic 0.5 mg/day.
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60. THERAPEUTIC USES
 Megaloblastic anaemias:
 Nutritional folate deficiency: injection of folicacid 5 mg/day & oral of folic acid 2-
5mg/day
 Increased demand: Pregnancy, lactation, infancy, during treatment of severe iron
deficiency anaemia, haemolytic anaemias
 Pernicious anaemia: folate stores may be low and deficiency may be unmasked
when vit B12 induces brisk haemopoiesis.
 Malabsorption syndromes: Tropical sprue, coeliac disease, idiopathic steatorrhoea.
 Antiepileptic therapy: Megaloblastic anaemia can occur due to prolonged
phenytoin/phenobarbitone therapy.
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61. CONT…
 Prophylaxis: Routine folate supplementation (1 mg/day) is recommended during
pregnancy to reduce the risk of neural tube defects in the newborn.
 Methotrexate toxicity: Folinic acid is an active coenzyme form which does not need
to be reduced by DHFRase before it can act. Methotrexate is a DHFRase inhibitor;
its toxicity is not counteracted by folic acid, but antagonized by folinic acid
 To enhance anticancer efficacy of 5-fluorouracil (5-FU): Folinic acid is now routinely
infused i.v. along with 5-FU (see p. 864), because THFA is required for inhibition of
thymidylate synthase by 5-FU.
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62. ERYTHROPOIETIN
 Erythropoietin (EPO) is a sialoglycoprotein hormone (MW 34000) produced by
peritubular cells of the kidney that is essential for normal erythropoiesis.
 Anaemia and hypoxia are sense by kidney cells and induce rapid secretion of EPO
→ acts on erythroid marrow
 Stimulates proliferation of colony forming cells of the erythroid series.
 Induces haemoglobin formation and erythroblast maturation.
 Releases reticulocytes in the circulation.
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63. THERAPEUTIC USES
 Anaemia of chronic renal failure
 Hb< 8mg/dl
 Epoetin25-100U/kg SC or IV 3 times a week.
 Anaemia in AIDS patients treated with zidovudine.
 Cancer chemotherapy induced anaemia.
 Preoperative increased blood production for autologous transfusion during surgery.
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64. ADVERSE EFFECTS
 Increased clot formation in the A-V shunts
 Hypertensive episodes
 Serious thromboembolic events
 Seizures
 Flu like symptoms
64

65. SUMMARY 65

66. DISCUSSION:
Low ferritin levels are known for being the reason for iron deficiency anemia
If high ferritin levels is temporary presence of Covid-19 can be detected by measuring the
ferritin levels. It has been seen in research that high ferritin levels indicate the severity of
Covid-19 as in fifty percent of cases, covid patients with extremely high ferritin levels have
died.
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