Define anemia. Give the morphological and etiological classification of anemia. Write normal values of Haemoglobin 10 mark question
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Anemia — Definition, Classification & Normal Haemoglobin Values
1. DEFINITION OF ANEMIA
Anemia is a state characterized by a reduced mass of red blood cells (RBCs) and haemoglobin (Hgb) concentration in blood, resulting in reduced oxygen-carrying capacity and delivery to the body's tissues and organs.
Because direct measurement of red cell mass is cumbersome and not readily available in clinical practice, anemia is operationally defined as a reduction below the normal range for Hgb concentration and haematocrit (Hct). These values depend on gender, race, and age.
"Anemia is simply defined as blood counts below normal for a given population." — Harrison's Principles of Internal Medicine 22E
WHO Definition (Widely Adopted)
The World Health Organization (WHO) defines anemia as:
| Group | Hgb Threshold |
|---|---|
| Adult men | < 13.0 g/dL |
| Adult women | < 12.0 g/dL |
| Pregnant women | < 11.0 g/dL |
This definition has been adopted by KDIGO (Kidney Disease: Improving Global Outcomes) and major clinical practice guidelines.
— Brenner and Rector's The Kidney, 2-Volume Set
2. CLASSIFICATION OF ANEMIA
There are two major systems of classification:
A. MORPHOLOGICAL CLASSIFICATION (By Red Cell Size / MCV)
Pioneered by hematologist Max Wintrobe, this classifies anemia based on Mean Corpuscular Volume (MCV) and is the most practical approach for guiding initial diagnostic workup:
i. Microcytic Anemia (MCV < 80 fL)
Due to any process that interferes with haemoglobin production; less haemoglobin → smaller red cells.
| Cause | Mechanism |
|---|---|
| Iron deficiency anemia | Inability to synthesize heme; commonest cause |
| Thalassemia | Defects in globin protein synthesis |
| Anemia of chronic disease/inflammation | Inhibition of iron reutilization via cytokines |
| Sideroblastic anemia | Defects in heme synthesis |
| Lead poisoning | Inhibits heme synthesis enzymes |
ii. Normocytic Anemia (MCV 80–100 fL)
Includes a broad differential; this is a drawback of the morphological classification scheme.
| Cause |
|---|
| Aplastic anemia |
| Anemia of chronic disease (most cases) |
| Acute blood loss |
| Sickle cell anemia (homozygous) |
| Renal disease (↓ erythropoietin) |
| Endocrinopathies |
| Bone marrow infiltration / myeloma |
| Pure red cell aplasia |
iii. Macrocytic Anemia (MCV > 100 fL)
Further subdivided:
a) Megaloblastic (Oval macrocytes) — Defects in DNA synthesis:
- Vitamin B₁₂ deficiency
- Folate deficiency
- Medications (chemotherapy, methotrexate, some antiseizure drugs)
- Myelodysplastic syndrome (MDS)
b) Non-megaloblastic (Round macrocytes) — Membrane defects:
- Liver disease
- Alcohol use
- Hypothyroidism
- Reticulocytosis (compensatory)
- Dysproteinemia
- Hypoxia, Smoking
— Harrison's Principles of Internal Medicine 22E; Goldman-Cecil Medicine
B. ETIOLOGICAL CLASSIFICATION (By Mechanism)
This classification is based on the pathophysiological mechanism producing anemia and uses the reticulocyte count as a key guide:
- Elevated reticulocytes → increased loss or destruction of RBCs
- Low reticulocytes → underproduction
I. Blood Loss
| Type | Examples |
|---|---|
| Acute blood loss | Trauma, surgery, GI bleeding |
| Chronic blood loss | GI tract lesions (peptic ulcer, carcinoma), gynecologic disturbances (menorrhagia) |
II. Increased RBC Destruction (Hemolytic Anemias)
A. Inherited / Intracorpuscular Defects:
| Category | Specific Examples |
|---|---|
| Red cell membrane disorders | Hereditary spherocytosis, hereditary elliptocytosis |
| Enzyme deficiencies (HMS shunt) | G6PD deficiency, glutathione synthetase deficiency |
| Enzyme deficiencies (Glycolytic) | Pyruvate kinase deficiency, hexokinase deficiency |
| Haemoglobin abnormalities | Sickle cell disease, unstable haemoglobins (hemoglobinopathies) |
| Deficient globin synthesis | Thalassemia syndromes |
| Acquired genetic defect | Paroxysmal nocturnal haemoglobinuria (PNH) — deficiency of PI-linked glycoproteins |
B. Acquired / Extracorpuscular Defects:
| Category | Specific Examples |
|---|---|
| Antibody-mediated | Autoimmune hemolytic anemia, hemolytic disease of the newborn (Rh disease), transfusion reactions, drug-induced |
| Microangiopathic hemolytic anemia (MAHA) | HUS, DIC, TTP |
| Cardiac traumatic hemolysis | Defective cardiac valves |
| Infections of RBCs | Malaria, babesiosis |
| Toxic/chemical injury | Oxidant drugs, snake venom |
| Membrane lipid abnormalities | Abetalipoproteinemia, severe liver disease |
| Sequestration | Hypersplenism |
III. Decreased RBC Production (Hypoproliferative)
A. Inherited Genetic Defects:
| Defect | Example |
|---|---|
| Stem cell depletion | Fanconi anemia, telomerase defects |
| Erythroblast maturation defects | Thalassemia syndromes, Diamond-Blackfan anemia |
| Transient erythroblastopenia | Parvovirus B19 infection |
B. Nutritional Deficiencies:
| Deficiency | Effect |
|---|---|
| Iron deficiency | Impaired haemoglobin synthesis |
| Vitamin B₁₂ / Folate deficiency | Impaired DNA synthesis → megaloblastic anemia |
| Copper deficiency | Impaired erythropoiesis |
C. Erythropoietin (EPO) Deficiency:
- Chronic kidney disease — most important cause
D. Bone Marrow Failure / Infiltration:
- Aplastic anemia (immune-mediated destruction of progenitors)
- Myelophthisis — leukemia, lymphoma, metastatic carcinoma, myelofibrosis
E. Anemia of Chronic Inflammation:
- Inflammatory cytokines → ↑ hepcidin → iron sequestration → functional iron deficiency
— Robbins, Cotran & Kumar Pathologic Basis of Disease; Harrison's Principles of Internal Medicine 22E
3. NORMAL VALUES OF HAEMOGLOBIN
| Population Group | Normal Hgb (g/dL) |
|---|---|
| Adult males | 13.5 – 17.5 g/dL |
| Adult females | 12.0 – 16.0 g/dL |
| Pregnant women | 11.0 – 13.0 g/dL |
| Newborns | 14.0 – 20.0 g/dL |
| Infants (3 months) | 9.5 – 13.0 g/dL |
| Children (1–6 years) | 11.0 – 14.0 g/dL |
| Children (6–14 years) | 11.5 – 15.5 g/dL |
| Elderly | Slightly lower than adult norms |
Key clinical thresholds (WHO):
- Men: Anemia if Hgb < 13.0 g/dL
- Non-pregnant women: Anemia if Hgb < 12.0 g/dL
- Pregnant women: Anemia if Hgb < 11.0 g/dL
"The average normal haemoglobin content of blood is 16 g/dL in men and 14 g/dL in women, all of it in red cells." — Ganong's Review of Medical Physiology, 26th Edition
Summary
| Feature | Morphological Classification | Etiological Classification |
|---|---|---|
| Basis | MCV / red cell size | Mechanism / pathophysiology |
| Categories | Microcytic, Normocytic, Macrocytic | Blood loss, Hemolysis, Underproduction |
| Tool used | MCV on CBC | Reticulocyte count + peripheral smear |
| Utility | Guides initial workup | Identifies root cause |
Both classification systems are complementary and should be used together for comprehensive evaluation of anemia.
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