Any fool can know. The point is to understand !

-- Albert Einstein

Without Pathology, Medicine is quackery…!

Pathology ofRBC disorders (anemia)

Dr. Shashidhar Venkatesh MurthyA/Prof. & Head of Pathology

DS3102: Clinical Haematology

Less More

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Anemia Introduction:

“Anemia is, decreased red cell mass affecting tissue oxygenation” Low Hb* or Low HCT *

Types:• Failure of production – Deficiency anemia (iron)• Excess destruction – Hemolytic anemia. (immune)

What is ‘polycythemia’ ? ( RBC)

What is spurious / false anemia? ( Plasma)

O2 in - CO2 out

RBCHb + Enz

Membrane

Normal Blood Film:

Hb + Enz + Membrane

RBC

WBC

WBC

RBC

WBC

RBC

Anemia diagnosis:

Haemoglobin – 150 - 140 ±25 g gm/L

PCV/HCT - 0.47 ±0.07, 0.42 ±0.05 % lit/lit (%)

RBC count - 5.5 ±1, 4.8 ± 1 x1012/L

MCH - Hb/RBC - 30 ± 3 pg/RBC pg picogram (wt)

• Average Hb in RBC

MCV - PCV/RBC 90 ±10 – fl fl femto litres (vol)

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Mean Cell Hb 30

Mean Cell Vol 90

120

Packed Cell Volume 45

Plasma

WBC & PLT

PCV / HCT

When your thinking is brilliant, you will be

brilliant, but if your thinking is not brilliant

you will not be brilliant, no matter how

brilliant you may think you are….! -- Christian D. Larson

Fake it until you make it…! -- Mohd. Ali. Boxer.

Clinical Features of Anemia & their Pathogenesis.

Anemia: Clinical Presentation

Extreme fatigue (tiredness)

Chest pain (only in severe anemia)

Decreased oxygen supply to tissues.

Myocardial ischemia.

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Pale skin

Dizziness or lightheadedness

Anemia: Clinical Presentation

Less Hb / RBC

Decreased oxygen supply to Brain.

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RBC: Bring in O2, Take out CO2

Shortness of breath, light headedness.

Fast heart rate (tachycardia)

Anemia Clinical Presentation:

Decreased O2, Increased Co2.

Tissue hypoxia – Hypothalamus –sympathetic stimulation.

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Epithelial damage: Brittle nails

Stomatitis, Glossitis, Esophagitis.

Fast dividing cells (epith) also need iron / nutrition Cytochrome enzymes

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The mind uncontrolled and unguided will drag us down; and the mind controlled and guided will save us, free us.

 -- Swami Vivekananda

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Classification of Anemia: Pathogenesis

Decreased Production:• Nutrient Deficiency.

• Iron def., Megaloblastic (B12/Folate)

• Stem cell Deficiency :• Anemia of chronic disorders (ACD).• Aplastic anemia – bone marrow defect.

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

• Acquired – Immune Haemolytic anemia (AIHA)• Congenital – Sickle, thalassemia etc.

Top 5 Anemias1. Iron Deficiency.2. Megaloblastic.3. An. of Chronic Dis.4. Aplastic.5. Haemolytic - AIHA

Proerythroblast(Pronormoblast)

BasophilicNormoblast

PolychromatophilicNormoblast

OrthochromatophilicNormoblast

Reticulocyte

Erythrocyte

BLAST Early Intermediate Late Retic. RBC

Anemia Pathogenesis:

DNA: Megaloblastic Anemia

Hb: Iron

B12, Folate

Iron Deficiency anemia

Hemolytic anemiaImmune

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Aplastic anemia

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Laboratory Diagnosis: Normal

RBC Histogram

WBC Scattergram

Neutrophil

RBC

Lymphocyte

Neutrophil

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Classification of Anemia:

Decreased Production:• Nutrient Deficiency.

• Iron def., Megaloblastic (B12/Folate)

• Stem cell Deficiency :• Anemia of chronic disorders (ACD) – Iron transfer defect.• Aplastic anemia – bone marrow defect.

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

• Acquired / External RBC defect– Immune AIHA (Warm/Cold), Mechanical, Drugs & Parasites

• Congenital / Internal RBC defect– E.g. Sickle cell anemia, Thalassemia.

Top 5 Anemias1. Iron Deficiency.2. Megaloblastic.

Most common anemias

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Haemopoiesis in deficiency anemias

Macrocytic, pancytopeniaMicrocytic hypochromic

Iron Deficiency Normal Megaloblastic

Iron Deficiency - Megaloblastic Causes:

• Bleeding, Nutrition, Increased needs.

Pathogenesis:• Iron - Hb - MCV

Morphology:• Microcytic,

Hypochromic • Pencil cells.

Clinical Features:• koilonychia, glossitis,

stomatitis.

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Causes:• Nutrition, gastritis,

intestinal disorders, Cancer therapy.

Pathogenesis:• Abn. DNA* all cells.

Morphology:• Macrocytic,

Normochromic• Pancytopenia*

Clinical Features:• Jaundice mild, glossitis,

chelitis, stomatitis.

Whatever you think, that you will be. If you think yourselves weak,

weak you will be. If you think yourselves strong,

strong you will be!

-- Swami Vivekananda

Microcytic Anemia (IDA)

Normal

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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

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Macrocytic Anemia (Meg.):

NormalHN

Megaloblastic Anemia:

1. Oval Macrocytes, Pancytopenia – Less cell division.

2. Anisopoikilocytosis – Ineffective hempoiesis, Hemolysis.

3. Hypersegmented neutrophils. - Megaloblasts (in marrow).

Megaloblastic Bone Marrow Normal

Hypersegmented Neutrophils

Macrocyte

Megaloblast

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Anemia of Chronic Disease: Causes:

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

Pathogenesis:• Inflammatory mediators (IFN,

TNF) block iron transfer from store to RBC

• Also decrease erythropoietin prod.

Morphology:• Mild Microcytic, Hypochromic.

Clinical Features:• Mild anemia, resistant to iron…

24IDA ? IDA / ACD ACD

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

Knowledge without character is dangerous!

Aplastic A: BM Failure: immune, drugs, cancer..

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Dysplasia Normal BM Aplasia

Clinical Features:Anemia, Infections & Bleeding.1. RBC - Anemia,2. WBC - Leukopenia3. PLT - Thrombocytopenia

Stem cell damage• Drugs, Immune• Viral Infections.

Leukemia

Normocytic Pancytopenia

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

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Mechanism & Types of Anemia : Decreased Production:

• Nutrient Deficiency. • Iron, B12 / Folate

• Hemopoietic cell defect:• Anemia of chronic disorders (ACD) – low erythropoietin.• Aplastic, Hypoplastic – Drugs, Disease, Destruction.• Dysplastic & Neoplastic proliferative anemias.

Increased loss / destruction:• Blood loss anemia – bleeding, parasites, • Hemolytic anemia – Congenital / Acquired.

• Acquired / External RBC defect– Immune (Warm/Cold), Mechanical, Drugs & Parasites

• Congenital / Internal RBC defect– Defective Membrane (HS), Hb (Sickle, Thal) or Enzyme (G6PD)

Hemolytic anemia (acquired): Causes:

• Antibody to RBC – commonest (cold / warm)• Idiopathic, Drugs, infections, malaria, trauma.

Pathogenesis: • Damage Hemolysis Jaundice.

Morphology:• Spherocytes (warm) / RBC clumps (cold).

Clinical Features:• anemia, Jaundice. Splenomegaly in chronic.• Diagnosis: Coomb’s test (detects Ab on RBC)

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IgG

WARM

IgM

COLD

WARM

COLD

Congenital Hemolytic An.:

1. Membrane Disorders• Hereditary Spherocytosis (HS)

2. Enzyme Deficiencies.• G6PD Def.

3. Hemoglobin Disorders• Globin deficiency: Thalassemia• Globin abnormal: Sickle cell an.

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RBC• Cell Mem.• Enzymes• Hemoglobin

HemolysisJaundice

Clinical Features

Thalassemia

Reticulocyte: Immature RBC

Reticulocyte

RBC

Reticulocytes (Immature RBC) Increased RBC productionReticulocytosis Hemolytic anemia/bleeding 5-7 days

(Bluish, Large, high MCV)

RNA network within RBC – stained by methylene blue.

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Polychromatophil

Spherocyte

Nucleated RBC

Never say No, never say, ‘I cannot’, for you are infinite. Even time and space are as nothing compared with your

nature. You can do anything and everything.

-- Swami Vivekananda

Anemia

Diagnosis:

MCV

Microcytic Normocytic Macrocytic

Measure Ferritin

Low Normal/high

Iron def Anemia

Anemia ofchronic disease/

Congenital Hb dis.

Reticulocyte count

high low Anemia of chronic diseaseRenal failure

Marrow failure

Hemolytic anemia or blood loss

Measure B12 + folate

Megaloblasticanemia

Normal Low

Anemia Clinical Diagnosis

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If you need help, contact me…

1. Office location – MS 39-136 (Townsville)2. Office Tel: 4781 45663. Email: venkatesh.shashidhar@jcu.edu.au

Need personal guidance?Email me for an appointment.

The power of thought is not a compelling force. It is a building force, and it is only when used in

the latter sense that desirable results can be produced. 

-- Christian D. Larson

The pessimist waits for better times, and expects to keep on waiting; the optimist goes to work with the best

that is at hand now, and proceeds to create better times. 

-- Christian D. Larson