ANAEMIA - RUDRA MISTRY
ANAEMIA
ANAEMIA—GENERAL CONSIDERATIONS
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.
In Adults, The Lower Extreme Of The Normal Haemoglobin Is Taken As 13.0 G/Dl For Males
And 11.5 G/Dl For Females.
PATHOPHYSIOLOGY
Subnormal Level Of Haemoglobin Causes Lowered Oxygen- Carrying Capacity Of The Blood.
This, In Turn, Initiates Compensatory Physiologic Adaptations Such As Follows:
-> Increased Release Of Oxygen From Haemoglobin
-> Increased Blood Flow To The Tissues
-> Maintenance Of The Blood Volume
-> Redistribution Of Blood Flow To Maintain The Cerebral Blood Supply.
GENERAL CLINICAL FEATURES
The Haemoglobin Level At Which Symptoms And Signs Of Anaemia Develop Depends Upon 4
Main Factors:
1. 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.
2. The Severity Of Anaemia
Mild Anaemia Produces No Symptoms Or Signs But A Rapidly Developing Severe Anaemia
(Haemoglobin Below 6.0 G/Dl) May Produce Significant Clinical Features.
3. The Age Of The Patient
The Young Patients Due To Good Cardiovascular Compensation Tolerate Anaemia Quite Well As
Compared To The Elderly.
The Elderly Patients Develop Cardiac And Cerebral Symptoms More Prominently Due To
Associated Cardiovascular Disease.
4. The Haemoglobin Dissociation Curve
In Anaemia, The Affinity Of Haemoglobin For Oxygen Is Depressed As 2,3-BPG In The Red
Cells Increases.
As A Result, Oxyhaemoglobin Is Dissociated More Readily To Release Free Oxygen For Cellular
Use, Causing A Shift Of The Oxyhaemoglobin Dissociation Curve To The Right.
IRON DEFICIENCY ANAEMIA
The Commonest Nutritional Deficiency Disorder Present Throughout The World Is Iron
Deficiency But Its Prevalence Is Higher In The Developing Countries.
The Factors Responsible For Iron Deficiency In Different Populations Are Variable And Are
Best Understood In The Context Of Normal Iron Metabolism.
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ANAEMIA - RUDRA MISTRY
PATHOGENESIS
Iron Deficiency Anaemia Develops When The Supply Of Iron Is Inadequate For The
Requirement Of Haemoglobin Synthesis.
Initially, Negative Iron Balance Is Covered By Mobilisation From The Tissue Stores So As To
Maintain Haemoglobin Synthesis.
It Is Only After The Tissue Stores Of Iron Are Exhausted That The Supply Of Iron To The
Marrow Becomes Insufficient For Haemoglobin Formation And Thus A State Of Iron
Deficiency Anaemia Develops.
The Development Of Iron Deficiency Depends Upon One Or More Of The Following Factors:
1. Increased Blood Loss
2. Increased Requirements
3. Inadequate Dietary Intake
4. Decreased Intestinal Absorption.
CLASSIFICATION OF ANAEMIAS
PATHOPHYSIOLOGIC
1. Anaemia Due To Increased Blood Loss
Acute Post-Haemorrhagic Anaemia
Chronic Blood Loss
2. Anaemias Due To Impaired Red Cell Production
Cytoplasmic Maturation Defects
-> Iron Deficiency Anaemia
-> Thalassaemic Syndromes
Nuclear Maturation Defects
-> Vitamin B12 And/Or Folic Acid Deficiency: Megaloblastic Anaemia
Defect In Stem Cell Proliferation And Differentiation
-> Aplastic Anaemia
-> Pure Red Cell Aplasia
Anaemia Of Chronic Disorders
Bone Marrow Infiltration
Congenital Anaemia
3. Anaemias Due To Increased Red Cell Destruction (Haemolytic Anaemias)
Extrinsic (Extracorpuscular) Red Cell Abnormalities
Intrinsic (Intracorpuscular) Red Cell Abnormalities
MORPHOLOGIC
Microcytic, Hypochromic
Normocytic, Normochromic
Macrocytic, Normochromic
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ETIOLOGY OF IRON DEFICIENCY ANAEMIA.
1. Increased Blood Loss
Uterine E.G. Excessive Menstruation In Reproductive Years, Repeated
Miscarriages, At Onset Of Menarche, Post-Meno- Pausal Uterine Bleeding
Gastrointestinal E.G. Peptic Ulcer, Haemorrhoids Hookworm Infestation,
Cancer Of Stomach And Large Bowel, Oesophageal Varices, Hiatus Hernia,
Chronic Aspirin Ingestion, Ulcerative Colitis, Diverticulosis
Renal Tract E.G. Haematuria, Haemoglobinuria
Nose E.G. Repeated Epistaxis
Lungs E.G. Haemoptysis
2. Increased Requirements
Spurts Of Growth In Infancy, Childhood And Adolescence
Prematurity
Pregnancy And Lactation
3. Inadequate Dietary Intake
Poor Economic Status
Anorexia E.G. In Pregnancy
Elderly Individuals Due To Poor Dentition, Apathy And Financial Constraints
4. Decreased Absorption
Partial Or Total Gastrectomy
Achlorhydria
Intestinal Malabsorption Such As In Coeliac Disease
CLINICAL FEATURES
Iron Deficiency Anaemia Is Much More Common In Women Between The Age Of 20 And 45
Years Than In Men; At Periods Of Active Growth In Infancy, Childhood And Adolescence;
And Is Also More Frequent In Premature Infants.
Initially, There Are Usually No Clinical Abnormalities.
But Subsequently, In Addition To Features Of The Underlying Disorder Causing The Anaemia,
The Clinical Consequences Of Iron Deficiency Manifest In 2 Ways—Anaemia Itself And
Epithelial Tissue Changes.
1. Anaemia
The Onset Of Iron Deficiency Anaemia Is Generally Slow.
The Usual Symptoms Are Weakness, Fatigue, Dyspnoea On Exertion, Palpitations And Pallor
Of The Skin, Mucous Membranes And Sclerae.
Older Patients May Develop Angina And Congestive Cardiac Failure. Patients May Have Unusual
Dietary Cravings Such As Pica.
Menorrhagia Is A Common Symptom In Iron Deficient Women.
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ANAEMIA - RUDRA MISTRY
2. Epithelial Tissue Changes
Long-Standing Chronic Iron Deficiency Anaemia Causes Epithelial Tissue Changes In Some
Patients.
The Changes Occur In The Nails , Tongue, Mouth, And Oesophagus Causing Dysphagia From
Development Of Thin, Membranous Webs At The Postcricoid Area.
LABORATORY FINDINGS
The Following Laboratory Tests Can Be Used To Assess The Varying Degree Of Iron
Deficiency
BLOOD PICTURE AND RED CELL INDICES
The Degree Of Anaemia Varies.
It Is Usually Mild To Moderate But Occasionally It May Be Marked (Haemoglobin Less Than 6
G/Dl) Due To Persistent And Severe Blood Loss.
The Salient Haematological Findings In These Cases Are As Under.
1. Haemoglobin
The Essential Feature Is A Fall In Haemoglobin Concentration Up To A Variable Degree.
2. Red Cells
The Red Cells In The Blood Film Are Hypochromic And Microcytic, And There Is Anisocytosis
And Poikilocytosis
Hypochromia Generally Precedes Microcytosis.
Hypochromia Is Due To Poor Filling Of The Red Cells With Haemoglobin So That There Is
Increased Central Pallor
RBC Count Is Below Normal But Is Generally Not Proportionate To The Fall In Haemoglobin
Value.
3. Reticulocyte Count
The Reticulocyte Count Is Normal Or Reduced But May Be Slightly Raised (2-5%) In Cases
After Haemorrhage.
4. Absolute Values
The Red Cell Indices Reveal A Diminished MCV (Below 50 Dl), Diminished MCH (Below 15 Pg),
And Diminished MCHC (Below 20 G/Dl).
5. Leucocytes
The Total And Differential White Cell Counts Are Usually Normal.
BONE MARROW FINDINGS
Bone Marrow Examination Is Not Essential In Such Cases Routinely But Is Done In
Complicated Cases So As To Distinguish From Other Hypochromic Anaemias.
The Usual Findings Are As Follows
1. Marrow Cellularity
The Marrow Cellularity Is Increased Due To Erythroid Hyperplasia (Myeloid-Erythroid Ratio
Decreased).
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ANAEMIA - RUDRA MISTRY
2. Erythropoiesis
There Is Normoblastic Erythropoiesis With Predominance Of Small Polychromatic Normoblasts
(Micronormoblasts)
3. Other Cells
Myeloid, Lymphoid And Megakaryocytic Cells Are Normal In Number And Morphology.
4. Marrow Iron
Iron Staining On Bone Marrow Aspirate Smear Shows Deficient Reticuloendothelial Iron Stores
And Absence Of Siderotic Iron Granules From Developing Normoblasts.
BIOCHEMICAL FINDINGS
The Serum Iron Level Is Low (Normal 40-140 µg/Dl); It Is Often Under 50 µg/Dl.
When Serum Iron Falls Below 15 µg/Dl, Marrow Iron Stores Are Absent.
Total Iron Binding Capacity (TIBC) Is High (Normal 250- 450 µg/Dl) And Rises To Give Less
Than 10% Saturation (Normal 33%).
In Anaemia Of Chronic Disorders, However, Serum Iron As Well As TIBC Are Reduced.
Serum Ferritin Is Very Low (Normal 30-250 Ng/Ml) Indicating Poor Tissue Iron Stores.
The Serum Ferritin Is Raised In Iron Overload And Is Normal In Anaemia Of Chronic
Disorders.
Red Cell Protoporphyrin Is Very Low (Normal 20-40 µg/Dl) As A Result Of Insufficient Iron
Supply To Form Haem.
Serum Transferrin Receptor Protein Which Is Normally Present On Developing Erythroid Cells
And Reflects Total Red Cell Mass, Is Raised In Iron Deficiency Due To Its Release In
Circulation
MEGAOBLASTIC ANEAMIA
Megaloblastic Anaemias Are Associated With Macrocytic Blood Picture And Megaloblastic
Marrow Erythropoiesis.
The Megaloblastic Anaemias Are Disorders Caused By Impaired DNA Synthesis And Are
Characterised By A Distinctive Abnormality In The Haematopoietic Precursors In The Bone
Marrow In Which The Maturation Of The Nucleus Is Delayed Relative To That Of The
Cytoplasm.
The Underlying Defect For The Asynchronous Maturation Of The Nucleus Is Defective DNA
Synthesis Due To Deficiency Of Vitamin B12 (Cobalamin) And/or Folic Acid (Folate)
LABORATORY FINDINGS
The Investigations Of A Suspected Case Of Megaloblastic Anaemia Are Aimed At 2 Aspects:
-> General Laboratory Investigations Of Anaemia
-> Special Tests To Establish The Cause Of Megaloblastic Anaemia
GENERAL LABORATORY FINDINGS
BLOOD PICTURE AND RED CELL INDICES
1. Haemoglobin
Haemoglobin Estimation Reveals Values Below The Normal Range.
The Fall In Haemoglobin Concentration May Be Of A Variable Degree.
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ANAEMIA - RUDRA MISTRY
2. Red Cells
Red Blood Cell Morphology In A Blood Film Shows The Characteristic Macrocytosis.
However, Macrocytosis Can Also Be Seen In Several Other Disorders Such As:
-> Haemolysis
-> Liver Disease,
-> Chronic Alcoholism,
-> Hypothyroidism,
In Addition, The Blood Smear Demonstrates Marked Anisocytosis, Poikilocytosis And Presence
Of Macro-Ovalocytes.
3. Reticulocyte Count
The Reticulocyte Count Is Generally Low To Normal In Untreated Cases.
4. Absolute Values
The Red Cell Indices Reveal An Elevated MCV (Above 120 Dl) Proportionate To The Severity
Of Macrocytosis, Elevated MCH (Above 50 Pg) And Normal Or Reduced MCHC.
5. Leucocytes
The Total White Blood Cell Count May Be Reduced.
Presence Of Characteristic Hypersegmented Neutrophils (Having More Than 5 Nuclear Lobes)
In The Blood Film Should Raise The Suspicion Of Megaloblastic Anaemia.
6. Platelets
Platelet Count May Be Moderately Reduced In Severely Anaemic Patients.
Bizarre Forms Of Platelets May Be Seen.
BONE MARROW FINDINGS
The Bone Marrow Examination Is Very Helpful In The Diagnosis Of Megaloblastic Anaemia.
Significant Findings Of Marrow Examination Are As Under
1. Marrow Cellularity
The Marrow Is Hypercellular With A Decreased Myeloid-Erythroid Ratio.
2. Erythropoiesis
There Is Erythroid Hyperplasia Due To Characteristic Megaloblastic Erythropoiesis.
Megaloblasts Are Abnormal, Large, Nucleated Erythroid Precursors, Having Nuclear-
Cytoplasmic Asynchrony I.E. The Nuclei Are Less Mature Than The Development Of
Cytoplasm
Megaloblasts With Abnormal Mitoses May Be Seen.
3. Other Cells
Granulocyte Precursors Are Also Affected To Some Extent.
4. Marrow Iron
Prussian Blue Staining For Iron In The Marrow Shows An Increase In The Number And Size
Of Iron Granules In The Erythroid Precursors.
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ANAEMIA - RUDRA MISTRY
Ring Sideroblasts Are, However, Rare.
Iron In The Reticulum Cells Is Increased.
5. Chromosomes
Marrow Cells May Show Variety Of Random Chromosomal Abnormalities Such As Chromosome
Breaks, Centromere Spreading Etc.
BIOCHEMICAL FINDINGS
There Is Rise In Serum Unconjugated Bilirubin And LDH As A Result Of Ineffective
Erythropoiesis Causing Marrow Cell Breakdown.
The Serum Iron And Ferritin May Be Normal Or Elevated.
SPECIAL TESTS FOR CAUSE OF SPECIFIC DEFICIENCY
In Evaluating A Patient Of Megaloblastic Anaemia, It Is Important To Determine The Specific
Vitamin Deficiency By Assay Of Vitamin B12 And Folate.
In Sophisticated Clinical Laboratories, Currently Automated Multiparametric, Random Access
Analyzers Are Employed Based On Separation Techniques By Chemiluminescence And Enzyme-
Linked Fluorescence Detection Systems Which Have Largely Replaced The Traditional
Microbiologic Assays For Vitamin B12 And Folate
PYQs
7 MARKS
1. Discuss Laboratory Investigations In Iron Deficiency Anaemia. [2022-W]
2. Define And Classify Anaemia. Describe Laboratory Investigations Of
Megaloblastic Anaemia [2016-W]
15 MARKS
1. Define Anaemia. Write Etiology, Clinical Features And Laboratory Diagnosis Of
Iron Deficiency Anaemia. [2023-W]
2. Define And Classify Anemia, Discuss Lab Diagnosis Of Iron Deficit Anemia
[2023-S].
3. Define Anemia. Classify Anemia. Enlist The Laboratory Investigate For
Diagnosis And Classification Of Anemia. [2019-S]
