Blood cells & Hemopoietic System

Composition of Blood
Blood consists of:  Blood cells
– – –

Red blood cells Platelets White blood cells

Plasma

Composition of Blood
Plasma  Carries cells
– – – Transport gases Aid in body defense Prevent blood loss

Composition of Blood
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When blood is removed from circulation, it clots Clot consists of:
– Blood cells – Fibrin strands – formed from conversion of plasma protein – Fibrinogen

Serum – yellowish liquid

Composition of Blood

Blood is kept in fluid state by Anticoagulants – EDTA, Heparin, Citrate After Centrifugation separates into:
– Lower layer 42 – 47 % - Red cells – Hematocrit – Intermediate layer – 1% - Leukocytes – Buffy coat – Top layer – 55% – yellowish fluid – Plasma

Plasma Proteins
Most

abundant solutes in plasma. Major proteins are albumin, globulins and fibrinogen Albumin: The most important protin; Its functions like, 1. Maintenance of blood volume, 2. Plasma osmotic pressure 3. carrier protein. Globulin: The 2nd most important protein It comprises mainly of three types, 1. alpha globulin 2. beta globulins 3. gamma globulins Fibrinogen: It has impotent role in clotting of

Blood cells
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Erythrocytes (red blood cells) Leucocytes (white blood cells) Thrombcytes (Platelets)

Site of haemopoiesis
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first few weeks of gestation the yolk sac is the main site of haemopoiesis. Definitive haemopoiesis derives from a population of stem cells - first observed on the dorsal aorta termed the AGM (aorta-gonads-mesonephros) region. These common precursors of endothelial & haemopoietic cells (haemangioblasts) are believed to seed the liver, spleen and bone marrow

Sites of Hemopoiesis

Fetus – 0 t0 2 months – Yolk Sac 2 to 7 months – Liver, Spleen 5 to 9 months – Bone marrow Infants – Bone marrow ( All bones) Adults - Vertebrae, ribs, sternum, skull, sacrum, Pelvis, Proximal end of femur

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HEMATOPOISIS
Bone marrow consists mainly of two portions;
– Red bone marrow – Yellow bone marrow

In adults – BM is restricted to
- Pelvis - Sternum - Vertebrae

Blood cells precursors

Blood forming population of bone marrow is made up of three types of cells
– – – Self renewing stem cells Differentiated progenitor cells Functional mature blood cells

Haematopoiesis

Regulation of Hematopoisis

Blood cells are produced by the BM according to need & regulatory factors Cytokine – family of glycoproteins – stimulate
– – – Proliferation Differentiation Functional activation of various BM precursors

Regulation of Hematopoisis
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Erythropoietin (EPO) Thrombopoitin (TPO) Cytokines (CSFs)
– – – G-CSF M-CSF GM-CSF

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Androgens Growth factors Trace elements(iron,Cu) B12,Folic acid.

Regulation of Hematopoisis

Erythrocytes

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Most numerous of the formed elements Small,biconcave disk,large surface area. Contain hemoglobin Function is to transport oxygen. Total life in circulation is approximately is 120 days.

Erythrocytes

Erythrocytes

Erythrocytes

Leucocytes
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1% of total blood volume. Function in inflammatory and in immune process. They include grannulocytes,lymphocytes and monocytes.

Granulopoiesis

Grannulocytes
Phagocytic cells  They have identical grannulation,spherical in shape and have distinctive multilobar nucleus.  Mainly these are of three types.  Neutrophils  Basophils  Eosinophils

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Neutrophils 50-60% They get neutral stain with an acidic and basic dye, so they called neutrophils. Because they have multilabar neucleus (3-5),so they also called Polymorphoneuclear leucocytes. Functions in defence mechnism against microorganisms. Grannule of these cells contains certain enzymes which have important role in these defence mechanisms. Total life in circulation is only 10 hours.

 Eosinophils

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Granules stain red with acidic dye (Eosin). 1-3% of total WBCs. Main role in allergic conditions and in parasitic infections.

 Basophils

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Granules of these cells stain blue with basic dye. 0.3-0.5% of total WBCs. Granules contain
– heparin (anticoagulant) – histamine (vasodilator).

Monocytes and Macrophages
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Largest cells of the WBCs series. 3-8% of total WBCs. Total life Spain of these is 1-3 days, in tissues survive for many days. Mainly these are phagocytic cells. Many types due to their various locations - Histiocytes in tissue - Kupffer cell in liver - Microglial cells in brain

Monocytes – Larger than other peripheral blood cells – Nuecleus –Central oval or indented – Cytoplasm  Blue –abundant  Fine granules  Ground glass

Monocytes

 Lymphocytes

20-30% of total WBCs  No grannules in cytoplasms and also called agrannulocytes.  Two types

• B-cells • T-cells
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Important role in immune responses. B-cells also produce antibodies.

Lymphocytes

 Thrombocytes

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Originate from megakaryocytes. They form platelet plug to control bleeding. In their cytoplasmic granules, certain mediators have important role in hemostasis. They have no nucleus and can never replicate. Total life is 8-9 days.

All blood cell precursors are derived from primitive cells
– pluripotent stem cells. – Colony forming units (burst forming units) – Disorders of the stem cells is the aplastic anaemia & leukemia's – Potential cures of these disorders is done by successful BM transplantation

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Sources of stem cells for transplant are Bone marrow, Peripheral blood and Umbilical cord blood BM and Peripheral blood transplant may be Autologous Allogenic Umbilical cord transplants are the best option in children's, because less risk factors of Graft-verses-Host disease.

Regulation of Erythropoiesis

Normal haemoglobins in adult blood

Red cell

In order to carry haemoglobin into close contact with the tissues and for successful gaseous exchange, the red cell, 8 µm in diameter, must be able:
– to pass repeatedly through the microcirculation whose minimum diameter is 3.5 µ m, – to maintain haemoglobin in a reduced (ferrous) state and – to maintain osmotic equilibrium despite the high concentration of protein (haemoglobin) in the cell. – Its total journey throughout its 120-day lifespan has been estimated to be 480 km (300 miles).

Red cell metabolism
Embden-Meyerhof pathway

In this series of biochemical reactions, glucose that enters the red cell from plasma by facilitated transfer is metabolized to lactate This ATP provides energy for maintenance of red cell volume, shape and flexibility. The Embden-Meyerhof pathway also generates NADH - to reduce functionally dead methaemoglobin (oxidized haemoglobin) containing ferric iron to functionally active, reduced haemoglobin. The Luebering Rapoport shunt - generates 2,3DPG which forms a 1 : 1 complex with haemoglobin - is important in the regulation of

Red cell membrane

The red cell membrane comprises a lipid bilayer, integral membrane proteins and a membrne skeleton Approximately 50% of the membrane is protein, 20% phospholipids, 20% cholesterol molecules and up to 10% is carbohydrate. Carbohydrates occur only on the external surface while proteins are either peripheral or integral, penetrating the lipid bilayer. The membrane skeleton is formed by structural Horizontal Lattice proteins: maintain Biconcave shape – α and β spectrin, – ankyrin, – protein 4.1 and

The structure of the red cell membrane. Some of the penetrating & integral proteins carry carbohydrate antigens; other antigens are attached directly to the lipid layer.

Diagnostic tests

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CBC ESR

Bone marrow aspiration & Biopsy

Normal adult red cell values.

Differential Count

Differential Count

Causes of Neutrophil Leukocytosis
• Bacterial infections – Pyogenic bacterial, localized or generalised • Inflammation & tissue necrosis • Neoplasms – carcinoma or lymphoma • Acute haemorrhage • Drugs – corticsteroid therapy • hronic myeloid Leukaemia

ESR  Screening test  Anticoagulated blood aggregates & sediments to the bottom of tube  Rate of Aggregation increases in presence of fibrinogen & other proteins  It is measured as distance in mm that red cell column travels in one hour

 Bone

Marrow aspiration & Biopsy

Supplies &Equipment
Supplies & equipment Tray:
– – – Wooden Plastic Steel

Bone Aspiration Needle

Positioning the Patient
Patient is positioned – depending on the location of the procedure: – Posterior iliac crest (PIC) – patient is placed in a right or left lateral position with their knees flexed, a pillow under their head, and their eyes away – Anterior iliac crest (AIC) – patient is placed in a supine position, with their hips and knees flexed, and eyes averted away. – Sternum – Supine position, head and eyes away, light towel over face “to keep things sterile” and cover eyes.

Diagram of Posterior pelvic bone – position of Right posterior iliac crest