“No doubt knowledge is valuable,but above it is Character”

Knowledge without character is dangerous!

….. foundation of clinical medicine

Shashidhar Venkatesh MurthyA/Prof & Head of PathologyCollege of Medicine & Dentistry

Clinical Pathology: RBC Disorders: Deficiency Anemia

Pathogenetic Classification of Anemia: Decreased Production: Nutrient Deficiency.

Iron def (IDA) / Megaloblastic (MBA) Hemopoietic cell defect:

Anemia of chronic disorders (ACD) Aplastic anemia (AA). Dysplastic anemia. Myelodysplastic Syndromes

Increased loss / destruction: Blood loss anemia – Acute / Chronic - bleeding. Hemolytic anemia – Congenital / Acquired.

Acquired / External injury. Immune AIHA (Warm/Cold) Mechanical, Drugs & Parasites

Congenital / Internal RBC defect Defective Membrane (Spherocytic an) Defective Hemoglobin (Sickle cell an.) Deficient Enzyme (G6PD)

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Top 6 Anemias:1. Iron Def. A2. Megaloblastic3. Anem. Of Chronic Dis.4. Aplastic An.5. Immune Hemolytic – Warm6. Immune Hemolytic - Cold2

Proerythroblast(Pronormoblast)

BasophilicNormoblast

PolychromatophilicNormoblast

OrthochromatophilicNormoblast

Reticulocyte

Erythrocyte

BLAST Early Intermediate Late Retic. RBC

Anemia Pathogenesis:

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DNA: B12, Folate

B12/Folate Metabolism:R Binders, Stomach, IF, Colon, Methionine, Homocysteine – DNA synthesis – cell division.

Megaloblastic anemia

Hb: Iron Iron Metabolism: “limited”,10%, Recycle, Ferritin, Transferrin, Hepcidin, forms Hb in cytoplasm.

Iron Deficiency anemia

Hemolytic anemiaImmuneMech.Infection

Aplastic anemia Dysplastic anemia

Our destiny is in our hands, What we think and do in the present

determines what shall happen to us in the future. 

-- Christian D. Larson

Iron Deficiency - Megaloblastic

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Causes: Bleeding, Nutrition,

Increased needs. Pathogenesis:

Iron - Hb - MCV Morphology:

Microcytic, Hypochromic Pencil cells.

Clinical Features: glossitis, chelitis, stomatitis. koilonychia, dysphagia

Causes:• Nutrition, gastritis, intestinal

disorders, Cancer therapy. Pathogenesis:

• DNA Cells - all cells. Morphology:

• Macrocytic, Normochromic• Pancytopenia*

Clinical Features:• glossitis, chelitis, stomatitis.• Mild Jaundice & Bruising

Microcytic Anemia (IDA)

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Normal

Iron Deficiency Anemia:

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1.Microcytic, Hypochromic – excess cell division, low Hb.2.Anisopoikilocytosis. – varying supply, abnormal hemopoiesis.3.Pencil forms. - ? cause

L

Macrocytic Anemia (Meg.):

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NormalHN

Megaloblastic Anemia:

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1. Oval Macrocytes, Pancytopenia: cell division.

2. Anisopoikilocytosis: Hemolysis.

3. Hypersegmented neutrophils: Large cells / Megaloblasts (in bone marrow).

Megaloblastic Bone Marrow Normal

Hypersegmented Neutrophils

MacrocyteMegaloblast

Pernicious Anemia: Vit B12

Autoimmune atrophic gastritis in aged. IF & Parietal cell antibody (Type I,II,III)

Reduced Tetra-hydrofolate (FH4) Decreased DNA synthesis.

Other causes of Vit B12 def. (not pernicious) Gastrectomy Achlorhydria Chronic Pancreatitis Ileal resection Mal absorption syndromes. Tapeworm infestation Malignancy, pregnancy, hyperthyroidism etc.

Clinical: MBA+ neurological deficits (spinal dorsal tract)

Loss of proprioception.

B12 Animal/bacteriaFolate Green Veg

Nothing can stop the man with the right mental attitude from achieving his goal;

nothing on earth can help the man with the wrong mental attitude!

-- Thomas Jefferson

Haemopoiesis in deficiency anemias

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Macrocytic, pancytopeniaMicrocytic hypochromic

Iron Deficiency Normal Megaloblastic

Anemia of Chronic Disease: Etiology:

Chronic Infections, inflammations, malignancy & anemia of renal disease*.

Pathogenesis: IFN, TNF, IL block iron

transfer from macrophage store to RBC.

Erythropoietin*. Morphology:

Mild Microcytic, Hypochromic.

Clinical Features: Mild anemia, resistant to

iron therapy.

Aplastic Anemia: BM Failure

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Dysplasia Normal BM Aplasia

Clinical Features:1. RBC - Anemia,2. WBC - Infections3. PLT - Bleeding

Stem cell damage• Drugs, Immune• Viral Infections.

Stem Cell Cancer:Myelodysplastic Sy.Leukemia

Normocytic Pancytopenia

Learning Objectives: Diseases of RBC Anaemia: Overview, Classification, pathogenesis,

diagnosis, clinical features & complications. - common

Study TOP 10 ANEMIAMajor (detailed)

1. Iron Deficiency anemia.2. Megaloblastic anemia.3. Imm. Hemolytic (Warm/Cold)4. Anemia of Chronic Disease.5. Aplastic Anemia

Minor (brief note)6. Myelodysplastic Syndrome7. Sickle Cell Anemia8. Thalassemia syndromes.9. G6PD deficiency anemia.10. Hereditary Spherocytosis.