This PPT for all Medicos and Non medical Students for better understanding of Anemia in clinical practice

1. ANAEMIA
Pandian M
Dept. of Physiology

2. Anemia is defined as a decrease in the O2
carrying capacity of the blood either due to
1. A decrease in the total number of
erythrocytes (RBC count), each having a
normal quantity of hemoglobin or
2. A diminished concentration of hemoglobin
per erythrocyte (decrease in Hb content of
blood) or
3. A combination of both below the normality for
that particular age and sex.

3. Classification:
We classify the anemia according to aetiology
& morphology.
Aetiological (Whitby’s) classification
Morphological (Wintrobe’s) classification.

4. Aetiological classification:
I. Anaemia due to blood loss
(Haemorrhagic anaemia):
BLOOD
LOSS
ACUTE CHRONIC

5.  Acute blood loss:
 Trauma or accident.
 After rapid hemorrhage, the body replaces
the fluid portion of the plasma in 1 to 3 days,
but this leaves a low concentration of red
blood cells.
 If a second hemorrhage does not occur, the
red blood cell concentration usually returns
to normal within 3to 6 weeks.

6.  Chronic blood loss:
 Worm infestation
 Peptic ulcer
 Bleeding piles
 Menstrual disorders.
 In chronic blood loss, a person frequently
cannot absorb enough iron from the
intestines to form hemoglobin as rapidly as it
is lost. Red cells are then produced that are
much smaller than normal and have too
little hemoglobin inside them,

7. II. Anemia due to decreased R.B.C.
production
1) Deficiency Of Nutrients –
i)Deficiency of vitamins: Vit.B12 ,Folic Acid, Vit.C
help in the synthesis of nucleic acid. Vit.C
also help in absorption of iron from gut.
ii) Deficiency Of Minerals : Iron, Copper, Cobalt,
Zinc, Nickel & Manganese (help in haem
formation).
iii)Deficiency of Proteins: Help in globin
formation.

8. 2)Endocrine disorders:
Hypothyroidism, Hypopituitarism, Addison’s
disease, Hypogonadism (hormones increase
erythropoietin production).
3)Chronic Diseases: Tuberculosis, Liver
Cirrhosis,renal disorders & lung disorders
(activate tissue macrophages so RBCs are
removed from blood faster than can be formed
in bone marrow.

9. 4). Anemia due to bone marrow depression or
hypo functioning of bone marrow (aplastic anemia)
i) Idiopathic: (Spontaneous or unknown cause)
(Autoimmune)
ii) Irradiation: (excessive exposure to X rays) or
gamma ray irradiation. For instance, a person
exposed to gamma ray radiation from a nuclear
bomb blast can sustain complete destruction of
bone marrow, followed in a few weeks by lethal
anemia.

10. iii)Exposure to Chemotherapy (anti cancer
drugs), Sulphonamides, Chloramphenicol &
anti malarial drugs (produce G6PD
deficiency in normal individuals).
iv)Drug Idiosyncrasy (abnormal reaction to a
drug no relationship to dose or duration of
therapy).

11. III)Due to increased destruction of RBCs
(Haemolytic anaemia)
1)Intracorpuscular defects
2)Extracorpuscular defects

12. Intra-corpuscular Defect (Hereditary)-
i)Membrane Defect: Spherocytosis (contractile
protein – spectrin is defective due to genetic
glycolysis defect).
ii)Enzyme Defects:
G6 Phosphate Dehydrogenase deficiency.
(required for formation of NADP which maintains
glutathione in reduce state. Reduced
glutathione protects Hb & RBC membrane from
oxidative stress.

13. iii) Haemoglobinopathies:
Abnormal formation of Hb due to disorders of
globin synthesis.
Two types:
1) Formation of abnormal polypeptide
chains due to substitution of an abnormal
amino acid chain in HbA. e.g: Sickel Cell
haemoglobin (HbS) & Anaemia.

14. Substitution of Valine for glutamic acid at
position 6 in beta chain of HbA.
When HbS is reduced in low oxygen tension it
becomes insoluble & precipitates into
crystals within RBCs. Crystals elongate to
change shape of RBCs to sickle shape.
These cells are fragile so undergo
haemolysis.

15. 2) Thalassemias: Suppression in the synthesis
of polypeptide chains of HbA.
β Thalassaemia is common. Further
subdivided as
Thalassaemia 1) major & 2) minor (more
common).
In Thalessaemia minor Partial synthesis of β
chain. Survival upto adult life.
In Thalessaemia major there is complete
absence of any one chain. Short life span
dies young.

16. Extra-corpuscular Defects (Acquired)-
i)Parasitic infections like Malaria.(Plasmodium
falciparum infect & reproduce within the
RBCs. During their release into the blood
stream the RBCs cell membrane is ruptured. )
ii) Mismatched blood transfusion reactions: ABO &
Rh incompatibility.

17. iii)Exposure to chemicals like Antimalarial
Drugs (Act as oxidising agents,
reduces G6PD enzyme & enhances
damage of RBCs) & anti cancer drugs
(bone marrow depression).
iv)Exposure to biological agents like
Snake Venom (contains lecithinase
which destroys lecithin in RBC cell
membrane) & Endotoxins (direct
toxic effects).

18. v) Autoimmune hemolytic disorder
vi) Chemical injury – lead poisoning
vii)Exposure to irradiation like X rays & gamma
rays.
viii)Exposure to mechanical factors like
shaking, alternate freezing & thawing.

19. B. Morphological (Wintrobe’s) classification of
Anaemia:
Based on cell size & Haemoglobin concentration:
Blood Indices:
Significance: Give idea about morphology of RBCs
i.e size & colour of RBCs.
i)Mean Corpuscular Volume (MCV):
Average volume of the RBC.
Normal Range:78 - 94 μ3

20. ii)Mean Corpuscular Haemoglobin (MCH):
Average weight of Haemoglobin in one RBC.
Normal Range: 27 - 32 μgms
iii)Mean Corpuscular Haemoglobin
Concentration (MCHC):
Amount of Haemoglobin per 100 ml of RBCs
Normal Range: 32 - 38%

21. B. Morphological (Wintrobe’s) classification of
Anaemia:
I) Normocytic normochromic
II) Microcytic hypochromic
III) Macrocytic normochromic

23. 1.Normocytic Normochromic- e.g: Acute Blood
Loss, Haemolytic & Aplastic anaemias.
After rapid hemorrhage, the body replaces the
fluid portion of the plasma in 1 to 3 days, but
this leaves a low concentration of red blood
cells but of normal size & Hb content per cell is
also normal.
If a second hemorrhage does not occur, the red
blood cell concentration usually returns to
normal within 3to 6 weeks.

24. 2. Microcytic Hypochromic:
 eg: Iron Deficiency anaemia, Chronic blood
loss & Thalessaemia.
 In chronic blood loss, a person frequently
cannot absorb enough iron from the
intestines to form hemoglobin as rapidly as it
is lost. Red cells are then produced that are
much smaller than normal and have too little
hemoglobin inside them, giving rise to
microcytic, hypochromic anemia.

28. 3. Macrocytic Normochromic:
Megaloblastic anaemia.
eg: Vit-B12 & Folic Acid Deficiency
Cause: Defective DNA synthesis.
Failure of maturation of nucleus & cell.
Cell remains large & fragile.

32. Pathophysiology of Anaemia:
Basic pathology is tissue hypoxia.
Several cardio respiratory compensatory
responses occur.
Hypoxia → vasodilatation → increases the
venous return & cardiac output.
Decrease in RBCs → viscocity of blood (lack
of slipperiness) decreases.
Both the factors lead to hyperdynamic
circulation.

33.  Clinical features:
 Generalized muscular weakness,
 Easy fatigability,
 Loss of appetite.
 Palpitations,
 Exertional dyspnoea,

34.  Pallor,
 Platynychia, Koilonychia,
 Glossitis,
 Angular stomatitis &
 Ulcers in mouth.

35. Deficiency anaemias:
1.Iron deficiency anaemia
2.Megaloblastic anaemia :
a)Pernicious anaemia) due to deficiency of Vit
B12
b)Due to deficiency of Folic acid

37. IRON DEFICIENCY ANAEMIA
In India Iron deficiency is the commonest cause
of anaemia.
More common in
Women between age group of 20 - 45.
At periods of active growth of infancy, childhood
& adolescence.
The total body iron in a 70-kg man is about 4 - 5
gm.
This is maintained by a balance between
absorption and body losses.

38. Iron Metabolism:
Total Iron content in the body is 4 - 5 gm.
Present in following forms:
Haemoglobin contains 70% of total body
iron(2.5gm)
Storage iron is 20 - 23%.
2/3rd of iron stored as Ferritin &
1/3rd as haemosiderin.
Myoglobin present in red muscles : 5%.
Intracellular enzymes : 2 - 3 % includes
cytochrome oxidase, catalase, peroxidase.

39. Although the body absorbs only 10% of
dietary intake (1 mg of iron daily ) to maintain
equilibrium, the internal requirement for iron
is greater (20-25 mg).
An erythrocyte has a lifespan of 120 days so
that 0.8% of red blood cells are destroyed
and replaced each day .

40. A man with 5 L of blood volume has 2.5 g of iron
incorporated into the hemoglobin, with a daily
turnover of 20 mg for hemoglobin synthesis and
degradation and another 5 mg for other
requirements.
Daily Loss of Iron
A man excretes about 0.6 mg of iron each day,
mainly into the feces. Additional quantities of iron
are lost when bleeding occurs.
For a woman, additional menstrual loss of blood
brings long term iron loss to an average of about
1.3 mg/day.

41. DAILY REQUIREMENT-
10 MG IN ADULT MALES
20 MG IN FEMALES
40 MG IN PREGNANCY & LACTATION
10 % OF DIET INTAKE IS ABSORBED
DIETARY SOURCES-
MEAT EGGS & LEAFY VEGETABLES, BEET, FRUITS -
APPLE, POMOGRANATE,ANJEER ETC.
WHOLE WHEAT, JAGGERY, DATES ETC

42.  ABSORPTION OF IRON:
 Iron is absorbed from the small intestine, mainly in
doudenum & upper part of jejunum.
 Dietary iron: 2 types of iron in the diet. Haem
iron and Non-haem iron.
 Haem iron is present in Hb containing animal
food like meat, liver & spleen.
 Non-haem iron is obtained from cereals,
vegetables & beans. Milk is a poor source of iron,
hence breast-fed babies need iron supplements.

43. Absorption of Haem iron is not affected by
ingestion of other food items.
It has constant absorption rate of 20-30% which
is little affected by the iron balance of the
subject.
The haem molecule is absorbed intact
and the iron (ferrous form) is released in the
mucosal cells (enterocytes).

44. The absorption of non-haem iron varies
greatly from 2% to 100% because it is
strongly influenced by
The iron status of the body,
The solubility of iron salts,
Integrity of gut mucosa
Presence of absorption inhibitors or
facilitators.

45. Promoters of Iron Absorption:
Foods containing ascorbic acid like citrus fruits,
broccoli & other dark green vegetables. Because
ascorbic acid reduces iron from ferric to ferrous
form, which increases its absorption.
Foods containing muscle protein enhance iron
absorption due to the effect of cysteine
containing peptides released from partially
digested meat, which reduces ferric to ferrous
salts and form soluble iron complexes.

46. Gastric HCL tends to break insoluble iron
complex apart thus facilitates iron absorption.
Food fermentation aids iron absorption by
reducing the phytate content of diet.
Iron stores in the body affects iron
absorption: Decrease in iron stores (iron defi
anaemia or when erythropoisis is increased
due to hypoxia) enhances iron absorption.
Vice a Varsa.

47. Inhibitors of iron absorption:
Food with polyphenol compounds i.e
cereals like sorghum & oats.
Vegetables such as spinach and spices.
Beverages like tea, coffee, cocoa and wine.
A single cup of tea taken with meal reduces
iron absorption by up to 11%.

48. OTHER INHIBITORS: Food containing phytic acid
i.e. Bran, cereals like wheat, rice, maize &
barely.
Legumes like soya beans, black beans &
peas.
Cow’s milk due to its high calcium & casein
contents.
Some fruits inhibit the absorption of iron
although they are rich in ascorbic acid
because of their high phenol content e.g
strawberry, banana and melon.

49. INHIBITION-HOW?
The dietary phenols & phytic acids
compounds bind with iron decreasing free
iron in the gut & forming complexes that are
not absorbed.
Cereal milling to remove bran reduces its
phytic acid content by 50% .

50. Mechanism of Iron absorption:
I)Transport of iron across the brush border of
enterocyte.
II)Fate of iron in the enterocyte.
III)Transport of iron in the blood.

51. I)Absorption of haem iron:
Haem iron → In GIT acted by Proteolytic
enzymes → From lumen of GIT →Enters
the enterocyte across the brush border
by haem transport protein → Inside the
cell ferrous iron is released from the
haem by enzyme haemoxygenase.

52. II)Absorption of non - haem iron:
Present in ferric form & forms insoluble
complexes like dietary phytates, phosphates &
dietary fibers.
They are soluble at low pH.
HCL breaks these insoluble complexes &
facilitates iron absorption.
Also Vit C reduces ferric iron to ferrous iron.
Ferrous iron is transported across brush border
by iron transport protein.

53. Fate of iron in the enterocyte:
i)Depending on body’s requirement, it is actively
transported across basolateral membranes of
the enterocyte → interstitum →blood.
ii)Rest of the ferrous iron is oxidized to Ferric
form & bound to apoferritin to form ferritin
(storage form) in enterocyte.
This iron is difficult to release & it is lost when
the cell is sloughed off at the tip of villus after 2
-3 days.

55. Transport of iron in the blood:
In the blood iron binds loosely with beta
globulin Apo transferrin to form
Transferrin.
Via plasma it reaches tissue cells.
In the tissue cells the released iron
combines with apoferritin to form ferritin &
stored.
Maximum amount of iron is stored in the
hepatocytes of liver & reticuloendothelial
system (tissue macrophages lining the
hepatic & splenic sinusoids).

56. If dietary intake is more some amount of iron
is stored as compound Hemosiderin in
reticuloendothelial system as stable form
so not available for exchange.
Excess iron overload results in accumulation
of hemosiderin in tissues called as
hemosiderosis.
It damages the tissues & produces the
condition of haemochromatosis.
Damage to Pancreas →Bronze diabetes,
Liver cirrhosis, Carcinoma of liver & atrophy
of gonads.

57. Regulation of body iron (Iron balance) is
achieved by control of absorption rather than
excretion.
Iron cycle
Diet Hepatic & splenic macrophages
(2mg/day) (iron from dead RBCs (30mg/day)
↑
Plasma Transferrin → RBCs
↓ ↓
Other tissues Alveolar macrophages

58. Iron deficiency anaemia:
Causes:
1)Inadequate dietary intake of iron:
Milk fed infants,
Diet low in animal protein (pure vegetarians),
Poor economic status,
In high economic status due to junk food or
improper diet.
Anorexia in pregnancy,
Elderly individuals due to atrophy of GIT mucosa
& poor dentition.

59. 2)Impaired iron absorption
Iron chelators in diet, e.g. tannins, Histamine H2
blockers
Disrupted GI mucosa Peptic ulcer,
Loss of functional bowel- Surgical resection,
Total or partial gastrectomy.
Achlorhydria.

60. 3)Increased loss of iron:
i) GIT bleeding: In worm infestation, Peptic
ulcers, piles, ulcerative colitis.
ii)In females -Uterine bleeding :Excessive
menstruation, repeated abortions, post
menopausal bleeding.
iii) Genito Urinary tract bleeding, Stag horn
renal calculi - Hematuria,
iv)Repeated epistaxis,
v) Hemoptysis.
vi) Blood loss GI tract bleeding Aspirin
ingestion.

61. 4)Increased demand of iron:
Infancy, childhood, pregnancy & menstruation.
Clinical features –
Symptoms-
Muscle weakness, fatiguability, loss of appetite,
palpitation, exertional dyspnoea.
Signs: Pallor, platynychia, glossitis, angular
stomatitis & odema.
CVS.-increased pulse rate, bounding pulse
RS- Respiratory rate is increased.

62. Laboratory findings:
Blood picture & Red cell indices:
Haemoglobin concentration is decreased.
Severity: < 12 gm% - Mild
< 8 gm% - Moderate
< 6 gm% - severe
RBC count < 4 million/cmm of blood.
Peripheral smear: RBCs - hypochromic &
microcytic. They show anisocytosis &
poikilocytosis.

64.  Packed cell volume or Haematocrit value
(PCV) : Normal :42 -45% ↓ in iron deficiency
anaemia.
 Red cell indices: MCV,MCH & MCHC ↓.

65. Biochemical findings :
Serum iron levels: Amount of iron in blood serum
carried by a protein transferrin in plasma(normal
: 60 - 160 μg%.
Decreases < 50 μg% in Iron deficiency
anaemia
Serum bilirubin : < .4 mg%
(normal : .8 to 1 mg%

66. Total Iron Binding Capacity (TIBC):
Amount of iron that blood would carry if
transferrin levels were fully saturated.
Normal levels: 300 - 450 micrograms/dl
Increased in Iron deficiency anaemia.

67. Transferrin test: Direct measurements of
transferrin or siderophilin in blood.
Normal: 200 - 300 mg/dl
Transferrin saturation levels :Serum iron levels
TIBC
Normal levels:30 - 40%
Decreased in Iron deficiency levels < 12 %

68. Ferritin test: Measures levels of a protein
in blood that stores iron for later use by
the body
Normal :20 – 200 ng/ml.
Ferritin decreased in chronic iron
deficiency.

69. Treatment: Depending on severity & cause:
Treat the cause
Dietary advice :Rich sources of dietary iron,
Deworming, Cooking in iron pot.
Supplement therapy:
Mild to moderate :Oral supplements of ferrous
salts 150 - 180 mg daily.
Take after food but not with milk.

70. In severe iron deficiency :Blood transfusion or
PCV to prevent overload to cardio vascular
system.
Parenteral therapy: GIT Intolerance to iron or
severe anaemia in the form of Iron dextran or
Iron sucrose(risk of anaphylactic reactions).

71. Thank You

72. MEGALOBLASTIC ANEMIA
Deficiency of vitamin B12, folic acid, and intrinsic
factor from the stomach mucosa, that loss of any one
of these can lead to slow reproduction of
erythroblasts in the bone marrow.
As a result, the red cells grow too large, with odd
shapes, and are called megaloblasts. Thus, atrophy
of the stomach mucosa, as occurs in pernicious
anemia, or loss of the entire stomach after surgical
total gastrectomy can lead to megaloblastic anemia

73.  Aplastic Anemia. Bone marrow aplasia means lack of
 functioning bone marrow.
 Likewise, excessive x-ray treatment, certain industrial
 chemicals, and even drugs to which the person might
 be sensitive can cause the same effect.

74.  Also, patients who have intestinal sprue, in which
folic acid, vitamin B12, and other vitamin B
compounds are poorly absorbed, often develop
megaloblastic anemia. Because the erythroblasts
cannot proliferate rapidly enough to form normal
numbers of red blood cells, those red cells that are
formed are mostly oversized, have bizarre shapes,
and have fragile membranes.
 These cells rupture easily, leaving the person in dire
need of an adequate number of red cells.

77.  Iron is absorbed from all parts of the small intestine,
 When the quantity of iron in the plasma falls low
 , In people who do not have adequate quantities
 of transferrin in their blood, failure to transport iron to the
erythroblasts in this manner can cause severe hypochromic
anemia—that is, red cells that contain
 much less hemoglobin than normal.

78.  progressively less active, and the cells become more
 and more fragile, & wear out.
 Once the red cell membrane becomes fragile, the
 cell ruptures during passage through some tight spot
 of the circulation.
 Many of the red cells self-destruct in the spleen, where they
squeeze through the red pulp of the spleen.

79.  There, the spaces between the structural
 trabeculae of the red pulp, through which most of the cells must
pass, are only 3 micrometers wide, in comparison with the 8-
micrometer diameter of the red cell. When the spleen is
removed, the number of old abnormal red cells circulating in the
blood increases

80.  When red blood cells burst and release their hemoglobin, the
hemoglobin is phagocytized almost immediately by
macrophages in many parts of the body, but especially by the
Kupffer cells of the liver and macrophages of the spleen and
bone marrow.
 During the next few hours to days, the
 macrophages release iron from the hemoglobin and
 pass it back into the blood, to be carried by transferrin
 either to the bone marrow for the production of new red blood
cells or to the liver and other tissues for storage in the form of
ferritin.

88. REFERENCES
 Harsh Mohan Textbook of Pathology
 Rapid Review Pathology by Edward F
 Robbins and Cotran Review of Pathology by Klatt
and Kumar ·
 Robbins Basic Pathology by Kumar, Abbas &
Aster.