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BASIC ASPECTS OF
ANAEMIA
Prabin Shah
BScMLT,MSc(Biochemistry)
OBJECTIVES.
Definition.
Pathophysiology.
Classification.
Clinical features.
Investigation.
Definition.
Anaemia is present when the haemoglobin level
in the blood is below the lower extreme of the normal
range for the age and sex of the individual.
Classification of Anaemia.
1. Morphological
2. Etiological (causes)
Based on morphology of red cell on
stained blood films and red cell size.
1. Macrocytic
2. Microcytic
3. Normocytic
a)Macrocytic
(Megaloblastic Anaemia)
 Vit B12 deficiency
 Folic acid deficiency
 Drug induced disorder
of DNA synthesis
Microcytic  Iron deficiency anaemia
Deficiency of globin
synthesis
Normocytic Recent blood loss
Endocrine abnormality
Hemolytic disease
Renal disease
Liver disease
Based on etiological
classification.
I. Anaemia due to impaired red cell
production.
II. Based on increased destruction of RBC’s
a) Deficiency of essential
nutrients.
1) Fe
2) Vit B12
3) Folic acid
4) Vit C
I. Anaemia due to impaired red cell
production.
b) Defect in stem cell / erythroid precursor.
1) Aplastic anaemia
2) Red cell aplasia
c) Infiltration of bone marrow.
1) Leukemia
2) Multiple myeloma
3) Carcinoma
d) Endocrine abnormalities.
1) Myxedema
2) Addisons disease
3) Pituitary insufficiency
e) Chronic liver diseases.
f) Cirrhosis of liver.
II. Based on increased destruction of RBC’s.
A) Intra corpuscular disease.
B) Extra corpuscular disease.
Intra corpuscular disease
1) Hereditary.
a) Enzyme deficiency
# G6PD deficiency.
# Pyruvate kinase.
b) Membrane defect.
# Hereditary spherocytosis.
# Hereditary ovalocytosis.
c) Hb abnormalities.
# Haemoglobinopathies.
# Sickle syndrome.
# Thalassemia.
 B) Extracorpuscular disease.
1) Acquired.
# Hypersplenism.
# Fragmentation syndromes.
# Immune haemolytic anaemia.
PATHOPHYSIOLOGY.
Loss of blood.
Excessive mature red cell destruction.
Impaired red cell production.
Clinical features
Depending upon the Hb level the signs and symptoms
of anaemia is of 4 main factors;
 The speed of onset of anaemia: Rapidly progressive
anaemia causes more symptoms than anaemia of slow-
onset as there is less time for physiologic adaptation.
 The severity of anaemia: Mild anaemia produces no
symptoms or signs but a rapidly developing severe
anaemia (Hb below 6.0 g/dl ) may produce significant
clinical features.
 The age of the patient: The young patients due to
good cardiovascular compensation tolerate anaemia
quite well as compared to the elderly, due to associated
cardio vascular disease.
 The Hb dissociation : In anaemia the affinity of Hb
for O2 is depressed. As a result, oxyhaemoglobin is
dissociated more readily to release free O2 for cellular
use.
SYMPTOMS: Tiredness, easy fatigability, generalised
muscular weakness, lethargy and
headache.
In older patients: Cardiac failure, angina pectoris,
confusion and visual disturbances.
Signs
1. Pallor: Pallor is the most common and characteristic
sign which may be seen in the mucous membranes,
conjunctiva, nail & skin.
2. Cardiovascular system: A hyper dynamic
circulation may be present with tachycardia,
collapsing pulse, cardiomegaly, dyspnoea on exertion
and in the case of elderly congestive heart failure.
3. Central nervous system: The older patients may
develop symptoms referable to the CNS such as
attacks of faintness, giddiness, headache,
drowsiness, numbness and tingling sensations of the
hands and feet.
4) Ocular manifestations: Retinal haemorrhages may
occur if there is associated vascular disease or
bleeding diathesis.
5) Reproductive system: Menstrual disturbances such
as amenorrhea and menorrhagia
6) Renal system: Mild proteinuria and impaired
concentrating capacity of the kidney may occur in
severe anaemia
7) Gastrointestinal system: Anorexia, flatulence,
nausea, constipation and weight loss may occur.
Investigations
 Full medical history, signs and symptoms is examined
for evidence of anaemia.
• Colour of skin, conjunctivae, scleral and nails.
• Changes in retina.
• Atrophy of the papillae of tongue, rectal examination
for evidence of bleeding.
• Presence of hepatomegaly, splenomegaly,
lymphadenopathy and bony tenderness are looked for.
A. Hb estimation: Hb value below the lower limit of
the normal range for particular age and sex the
patient is said to be anaemic. In pregnancy, there is
haemodilution and the lower limit in normal
pregnant women is less ( 10.5 g/dl ) than in the non –
pregnant state.
B. Peripheral blood film examination:
• Romanowsky dyes.
• The blood smear is examined for
1) Variation in size (Anisocytosis )
 Normal – 6.7 – 7.7 µm ( mean value – 7.2 µm )
 Increased variation in size of red cell – anisocytosis.
 Macrocytosis – cells larger than normal.
 Microcytosis – cells smaller than normal.
 Dimorphic – both microcytosis and macrocytosis.
2. Variation in shape (Poikilocytosis)
- Increased variation in shape of the red cells.
- Abnormal shape determines the cause of anaemia.
3. Inadequate haemoglobin
formation.(Hypochromasia)
- Normally the intensity of pink staining of Hb in a
Romanowsky stained blood smear gradually decreases
from the periphery to the centre of the cell.
 Increased central pallor - Hypochromasia.
- lowered Hb content.
[ Eg: IDA, Chronic infections]
- due to thinness of red cells.
[ Eg: Thalassemia ]
• Deep pink staining of red cells due to increased
Hb concentration. - Hyperchromasia.
- Eg: Megaloblastic anaemia.
Spherocytosis.
4. Compensatory erythropoiesis : Changes are
associated with compensatory increase in
erythropoietic activity.
a) Polychromasia - Red cells having more than one
type of colour.
Polychromatic red cells are slightly larger, stained
bluish- grey.
b) Erythroblastaemia – Presence of nucleated red
cells in the peripheral blood film.
This appears in various types of severe anaemias
except in aplastic anaemia.
c) Basophilic stippling.
Is diffuse and uniform basophilic granularity
in the cells.
Classical punctate basophilia is seen in :
- Aplastic Anaemia.
- Thalassemia.
- Myelodysplasia.
- Infections & Lead poisoning.
d) Howell – Jolly bodies.
Purple nuclear remnants usually found
singly and are larger than basophilic stippling.
Eg: Megaloblastic Anaemia.
5) Miscellaneous changes.
a) Spherocytosis : Presence of spheroidal rather than biconcave
disc-shaped red cells.
Seen in - Hereditary spherocytosis.
Autoimmune Haemolytic anaemia.
ABO Haemolytic disease of newborn.
b) Schistocytosis : Fragments of erythrocytes.
Seen in - Thalassemia.
Megaloblastic anaemia.
Iron deficiency anaemia.
Haemolytic anaemia.
c) Irregularily contracted red cells.
- Found in drug and chemical induced
haemolytic anaemia.
d) Leptocytosis.
- Presence of unusually thin red cells.
Eg: Iron deficiency anaemia,Thalassemia.
Target cell : Form of leptocyte.
- There will be a central round stained
area & a peripheral rim of Hb.
Eg: Iron deficiency anaemia.
Thalassemia.
e) Sickle cells / Drepanocytes.
Sickle - shaped red cells found in sickle cell
disease.
f) Crenated red cells.
Erythrocytes which develop numerous
projections from the surface.
g) Acanthocytosis.
Presence of coarsely crenated red cells.
Eg: Splenectomised subject.
Chronic liver disease.
h) Burr cells.
Cell fragments having one/ more spines.
BURR CELLS ACANTHOCYTES
CRENATED CELLS SICKLE CELLS
i) Stomatocyctosis.
Central area having slit-like or mouth like
appearance.
- Chronic alcoholism.
- Hereditary stomatocytosis.
j) Ovalocytosis or elliptocytosis:
Oval or elliptical shape of red cells.
- Megaloblastic anaemia
- Hypochromic anaemia.
C) Red cell indices.
 Iron deficiency & Thalassemia - MCV, MCH, &
MCHC are reduced.
 In anaemia due to acute blood loss & haemolytic
anaemia - MCV, MCH & MCHC are all within normal
range.
 In megaloblastic anaemias - MCV is raised above the
normal range.
D) Leucocytes and platelet count.
This helps to distinguish pure anaemia from
pancytopenia in which red cells, granulocytes and
platelets are all reduced.
 In anaemia due to haemolysis or haemorrhage -
neutrophil , platelet counts are elevated.
 In infection and leukemias – leukocytes are high
and immature leukocytes appears in the blood.
E) Reticulocyte count.
Normal : 0.5 – 2.5 %
 It is done to assess the marrow erythropoietic
activity.
 In acute haemorrhage & haemolysis – the
reticulocyte response is indicative of impaired
marrow function.
F) Bone marrow examination.
G) Erythrocyte sedimentation rate.
 ESR is a non specific test.
 Screening test for anaemia.
 Anaemia cause rise in ESR level.

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Anaemia

  • 1. BASIC ASPECTS OF ANAEMIA Prabin Shah BScMLT,MSc(Biochemistry)
  • 3. Definition. Anaemia is present when the haemoglobin level in the blood is below the lower extreme of the normal range for the age and sex of the individual. Classification of Anaemia. 1. Morphological 2. Etiological (causes)
  • 4. Based on morphology of red cell on stained blood films and red cell size. 1. Macrocytic 2. Microcytic 3. Normocytic
  • 5. a)Macrocytic (Megaloblastic Anaemia)  Vit B12 deficiency  Folic acid deficiency  Drug induced disorder of DNA synthesis
  • 6. Microcytic  Iron deficiency anaemia Deficiency of globin synthesis
  • 7. Normocytic Recent blood loss Endocrine abnormality Hemolytic disease Renal disease Liver disease
  • 8. Based on etiological classification. I. Anaemia due to impaired red cell production. II. Based on increased destruction of RBC’s
  • 9. a) Deficiency of essential nutrients. 1) Fe 2) Vit B12 3) Folic acid 4) Vit C I. Anaemia due to impaired red cell production.
  • 10. b) Defect in stem cell / erythroid precursor. 1) Aplastic anaemia 2) Red cell aplasia c) Infiltration of bone marrow. 1) Leukemia 2) Multiple myeloma 3) Carcinoma
  • 11. d) Endocrine abnormalities. 1) Myxedema 2) Addisons disease 3) Pituitary insufficiency e) Chronic liver diseases. f) Cirrhosis of liver.
  • 12. II. Based on increased destruction of RBC’s. A) Intra corpuscular disease. B) Extra corpuscular disease. Intra corpuscular disease 1) Hereditary. a) Enzyme deficiency # G6PD deficiency. # Pyruvate kinase.
  • 13. b) Membrane defect. # Hereditary spherocytosis. # Hereditary ovalocytosis. c) Hb abnormalities. # Haemoglobinopathies. # Sickle syndrome. # Thalassemia.
  • 14.  B) Extracorpuscular disease. 1) Acquired. # Hypersplenism. # Fragmentation syndromes. # Immune haemolytic anaemia.
  • 15. PATHOPHYSIOLOGY. Loss of blood. Excessive mature red cell destruction. Impaired red cell production.
  • 16. Clinical features Depending upon the Hb level the signs and symptoms of anaemia is of 4 main factors;  The speed of onset of anaemia: Rapidly progressive anaemia causes more symptoms than anaemia of slow- onset as there is less time for physiologic adaptation.  The severity of anaemia: Mild anaemia produces no symptoms or signs but a rapidly developing severe anaemia (Hb below 6.0 g/dl ) may produce significant clinical features.  The age of the patient: The young patients due to good cardiovascular compensation tolerate anaemia quite well as compared to the elderly, due to associated cardio vascular disease.
  • 17.  The Hb dissociation : In anaemia the affinity of Hb for O2 is depressed. As a result, oxyhaemoglobin is dissociated more readily to release free O2 for cellular use. SYMPTOMS: Tiredness, easy fatigability, generalised muscular weakness, lethargy and headache. In older patients: Cardiac failure, angina pectoris, confusion and visual disturbances.
  • 18. Signs 1. Pallor: Pallor is the most common and characteristic sign which may be seen in the mucous membranes, conjunctiva, nail & skin. 2. Cardiovascular system: A hyper dynamic circulation may be present with tachycardia, collapsing pulse, cardiomegaly, dyspnoea on exertion and in the case of elderly congestive heart failure. 3. Central nervous system: The older patients may develop symptoms referable to the CNS such as attacks of faintness, giddiness, headache, drowsiness, numbness and tingling sensations of the hands and feet.
  • 19. 4) Ocular manifestations: Retinal haemorrhages may occur if there is associated vascular disease or bleeding diathesis. 5) Reproductive system: Menstrual disturbances such as amenorrhea and menorrhagia 6) Renal system: Mild proteinuria and impaired concentrating capacity of the kidney may occur in severe anaemia 7) Gastrointestinal system: Anorexia, flatulence, nausea, constipation and weight loss may occur.
  • 20. Investigations  Full medical history, signs and symptoms is examined for evidence of anaemia. • Colour of skin, conjunctivae, scleral and nails. • Changes in retina. • Atrophy of the papillae of tongue, rectal examination for evidence of bleeding. • Presence of hepatomegaly, splenomegaly, lymphadenopathy and bony tenderness are looked for.
  • 21. A. Hb estimation: Hb value below the lower limit of the normal range for particular age and sex the patient is said to be anaemic. In pregnancy, there is haemodilution and the lower limit in normal pregnant women is less ( 10.5 g/dl ) than in the non – pregnant state. B. Peripheral blood film examination: • Romanowsky dyes. • The blood smear is examined for
  • 22. 1) Variation in size (Anisocytosis )  Normal – 6.7 – 7.7 µm ( mean value – 7.2 µm )  Increased variation in size of red cell – anisocytosis.  Macrocytosis – cells larger than normal.  Microcytosis – cells smaller than normal.  Dimorphic – both microcytosis and macrocytosis.
  • 23. 2. Variation in shape (Poikilocytosis) - Increased variation in shape of the red cells. - Abnormal shape determines the cause of anaemia. 3. Inadequate haemoglobin formation.(Hypochromasia) - Normally the intensity of pink staining of Hb in a Romanowsky stained blood smear gradually decreases from the periphery to the centre of the cell.
  • 24.  Increased central pallor - Hypochromasia. - lowered Hb content. [ Eg: IDA, Chronic infections] - due to thinness of red cells. [ Eg: Thalassemia ] • Deep pink staining of red cells due to increased Hb concentration. - Hyperchromasia. - Eg: Megaloblastic anaemia. Spherocytosis.
  • 25. 4. Compensatory erythropoiesis : Changes are associated with compensatory increase in erythropoietic activity. a) Polychromasia - Red cells having more than one type of colour. Polychromatic red cells are slightly larger, stained bluish- grey. b) Erythroblastaemia – Presence of nucleated red cells in the peripheral blood film. This appears in various types of severe anaemias except in aplastic anaemia.
  • 26. c) Basophilic stippling. Is diffuse and uniform basophilic granularity in the cells. Classical punctate basophilia is seen in : - Aplastic Anaemia. - Thalassemia. - Myelodysplasia. - Infections & Lead poisoning. d) Howell – Jolly bodies. Purple nuclear remnants usually found singly and are larger than basophilic stippling. Eg: Megaloblastic Anaemia.
  • 27.
  • 28. 5) Miscellaneous changes. a) Spherocytosis : Presence of spheroidal rather than biconcave disc-shaped red cells. Seen in - Hereditary spherocytosis. Autoimmune Haemolytic anaemia. ABO Haemolytic disease of newborn. b) Schistocytosis : Fragments of erythrocytes. Seen in - Thalassemia. Megaloblastic anaemia. Iron deficiency anaemia. Haemolytic anaemia.
  • 29. c) Irregularily contracted red cells. - Found in drug and chemical induced haemolytic anaemia. d) Leptocytosis. - Presence of unusually thin red cells. Eg: Iron deficiency anaemia,Thalassemia. Target cell : Form of leptocyte. - There will be a central round stained area & a peripheral rim of Hb. Eg: Iron deficiency anaemia. Thalassemia.
  • 30.
  • 31. e) Sickle cells / Drepanocytes. Sickle - shaped red cells found in sickle cell disease. f) Crenated red cells. Erythrocytes which develop numerous projections from the surface. g) Acanthocytosis. Presence of coarsely crenated red cells. Eg: Splenectomised subject. Chronic liver disease. h) Burr cells. Cell fragments having one/ more spines.
  • 32. BURR CELLS ACANTHOCYTES CRENATED CELLS SICKLE CELLS
  • 33. i) Stomatocyctosis. Central area having slit-like or mouth like appearance. - Chronic alcoholism. - Hereditary stomatocytosis. j) Ovalocytosis or elliptocytosis: Oval or elliptical shape of red cells. - Megaloblastic anaemia - Hypochromic anaemia.
  • 34. C) Red cell indices.  Iron deficiency & Thalassemia - MCV, MCH, & MCHC are reduced.  In anaemia due to acute blood loss & haemolytic anaemia - MCV, MCH & MCHC are all within normal range.  In megaloblastic anaemias - MCV is raised above the normal range.
  • 35. D) Leucocytes and platelet count. This helps to distinguish pure anaemia from pancytopenia in which red cells, granulocytes and platelets are all reduced.  In anaemia due to haemolysis or haemorrhage - neutrophil , platelet counts are elevated.  In infection and leukemias – leukocytes are high and immature leukocytes appears in the blood.
  • 36. E) Reticulocyte count. Normal : 0.5 – 2.5 %  It is done to assess the marrow erythropoietic activity.  In acute haemorrhage & haemolysis – the reticulocyte response is indicative of impaired marrow function. F) Bone marrow examination.
  • 37.
  • 38. G) Erythrocyte sedimentation rate.  ESR is a non specific test.  Screening test for anaemia.  Anaemia cause rise in ESR level.