Haemopoietic System

Blood

Blood

• Specialized fluid CT, continuously flowing in closed system of blood vessels.
• It is a red, opaque, viscous (4 – 5) & slightly alkaline (pH = 7.36-7.41) fluid with specific gravity of 1.055 – 1.060.
• Volume – 7 - 8 % of human BW
• Average volume of blood:
• 5–6 L for males; 4–5 L for females (Normovolemia)
• Hypovolemia - low blood volume
• Hypervolemia - high blood volume

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Functions of Blood

• Blood performs a number of functions dealing with:
• Substance distribution
• Regulation of blood levels of particular substances
• Body protection

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Blood functions - Distribution

• Blood transports:
• Oxygen from the lungs and nutrients from the digestive tract
• Metabolic wastes from cells to the lungs and kidneys for elimination
• Hormones from endocrine glands to target organs
• Vitamins, Enzymes, Pigments, Minerals etc.

Blood functions- Regulation

• Blood maintains:
• Appropriate body temperature by absorbing and distributing heat to other parts of the body
• Acid – Base balance i.e. Normal pH in body tissues using buffer systems
• Fluid balance i.e. adequate fluid volume in the circulatory system.
• Ionic balance

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Blood functions - Protection

• Blood prevents blood loss by:
• Activating plasma proteins and platelets
• Initiating clot formation when a vessel is broken
• Blood prevents infection by:
• Synthesizing and utilizing antibodies
• Activating complement proteins
• Activating WBCs to defend the body against foreign invaders

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Composition of Blood

• 2 major components
• Liquid = plasma (55%)
• Formed elements (45%) – suspended & carried in plasma
• Erythrocytes, or red blood cells (RBCs)
• Leukocytes, or white blood cells (WBCs)
• Thrombocytes, or Platelets

Plasma

• Plasma is a straw coloured liquid consisting of:
• Water = 90-92%
• Proteins = (6-8%) Albumin, Globulins, Fibrinogen, Clotting factors
• Organic nutrients – glucose, carbohydrates, amino acids
• Electrolytes – sodium, potassium, calcium, chloride, bicarbonate
• Nonprotein nitrogenous substances – lactic acid, urea, creatinine
• Respiratory gases – oxygen and carbon dioxide

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Plasma proteins

• 3 types – Albumin, Globulins & Fibrinogen
• Albumin – most abundant (4 %) pp obtained from liver.
• Maintains plasma osmotic pressure at its normal level (25 mm Hg) – regulation of water movement between tissue & blood.
• Regulation of blood volume
• Gives viscosity to the blood

Plasma proteins

• Globulins – obtained from liver & lymphoid tissue ( 2.7%).
• 3 subtypes – Alpha, Beta & Gamma globulins
• Alpha & Beta – Transportation of some hormones & mineral salts & lipids. (TH, I2, Iron, Copper)
• Gamma – Immune response
• Fibrinogen – obtained from liver (0.25- 0.3 %)
• Helps in blood coagulation
• Gives viscosity to the blood.

Formed elements of blood

• Formed elements comprise 45% of blood
• Erythrocytes,
• Leukocytes, and
• Platelets

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Hematocrit

• Percentage of total blood volume occupied by blood cells.

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Components of Whole Blood

Withdraw blood and place in tube

1

2

Centrifuge

Plasma�(55% of whole blood)

Formed elements

Buffy coat:�leukocyctes and platelets�(<1% of whole blood)

Erythrocytes�(45% of whole blood)

• Hematocrit
• Males: 47% ± 5%
• Females: 42% ± 5%

Production of formed elements

• Hematopoiesis or hemopoiesis: Process of blood cell production
• All formed elements derived from single population – Stem cells of bone marrow i.e. Hemocytoblasts.
• Proerythroblasts: Develop into red blood cells
• Myeloblasts: Develop into basophils, neutrophils, eosinophils
• Lymphoblasts: Develop into lymphocytes
• Monoblasts: Develop into monocytes
• Megakaryoblasts: Develop into platelets

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Erythrocytes

• Red Blood Corpuscles (RBC)
• Biconcave, circular disc shaped, non-nucleated with diameter 7~8μm & thickness 1~2.5 μm.
• Shape provides increased surface area for diffusion

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RBC

Normal value of RBC

Male adult - 4.5~5.5 millions/cu.mm

Female adult - 3.8~4.6 millions/cu.mm;

Newborn- ≥ 6.0 millions/cu.mm

• Produced in red bone marrow by the process called as Erythropoiesis.
• Lack nuclei & mitochondria
• Consists of a protein molecule – Hemoglobin. Each RBC contains 280 million hemoglobins

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Characteristics of RBC

• Permeability: semi-permeable membrane, gases and urea are freely passing through.
• Hemolysis – breakdown of RBC, leading to release of Hb, in lower osmotic conditions.
• Roulex formation – RBC aggregation
• Erythrocyte Sedimentation Rate (ESR) – RBC sedimenting distance per hour. 0~15 mm/h (male), 0~20 mm/h (female).

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Functions of RBC

• Transportation of respiratory gases - Erythrocytes are dedicated to respiratory gas transport, due to presence of Hb
• Gives viscosity to the blood.
• Maintains acid-base balance.
• Production of bile pigments.

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Hemoglobin

• Coloring & respiratory pigment present in the RBC.
• Composition of hemoglobin
• A protein called globin
• made up of two alpha and two beta chains
• A heme molecule
• Each heme group bears an atom of Iron, which can bind to one oxygen molecule
• Each hemoglobin molecule thus can transport four molecules of oxygen

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Hemoglobin

• Hemoglobin reversibly binds with oxygen and most oxygen in the blood is bound to hemoglobin
• Hb + O₂ HbO₂ (oxyhemoglobin)

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Hemoglobin

• When there is a high concentration of oxygen e.g in the alveoli Hb combines with oxygen to form oxyhaemoglobin.
• When the blood reaches the tissue which have a low concentration of oxygen the Hb dissociates with the oxygen and the oxygen is released into body tissues.

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• Oxyhemoglobin – hemoglobin bound to oxygen
• Oxygen loading takes place in the lungs
• Deoxyhemoglobin – hemoglobin after oxygen diffuses into tissues (reduced Hb)
• Carbaminohemoglobin – hemoglobin bound to carbon dioxide
• Carbon dioxide loading takes place in the tissues

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Erythropoiesis

• Production of Erythrocytes
• 2.5 millions of RBC produced/sec.
• Occurs in Yolk Sac, Liver & Spleen (fetus); Red Bone Marrow of flat bones, sternum, ribs, etc.(adult)
• Haemopoietic material for erythropoiesis:

Iron (Fe++) and protein,

• Influencing factors of RBC maturity:

Vitamin B12 and folic acid

• Stimulated by Erythropoietin (EPO) from kidney cells.
• Process requires 6 -7 days.

Erythropoiesis

• A hemocytoblast is transformed into a committed cell called the proerythroblast
• Proerythroblasts develop into early erythroblasts
• The developmental pathway consists of three phases
• Phase 1 – increased ribosome synthesis in early erythroblasts
• Phase 2 – hemoglobin accumulation in late erythroblasts and normoblasts
• Phase 3 – ejection of the nucleus from normoblasts and formation of reticulocytes
• Reticulocytes then become mature erythrocytes
• Reticulocytes make up about 1 -2 % of all circulating erythrocytes

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Steps of Erythropoiesis

• 1. Increased production of Ribosomes in stem cells leading to increased mitotic cell division – production of large number of small Proerythroblasts & Erythroblasts.

This is initiated by the presence of EPO & requires the presence of folic acid & Vit B12.

• 2. Synthesis of Hb begin to take place in the presence of Iron & other proteins from diet. So that erythroblasts are converted to Pronormoblasts & Normoblasts.

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• 3. The normoblasts are converted into reticulocytes by removal of nucleus & other cell organelles. This requires the presence of folic acid & Vit B12.
• 4. The reticulocytes are released into blood circulation and gets matured as RBC in the presence of folic acid & vit B12.
• 5. Thus RBC are produced from stem cells by decreasing the size, formation of Hb & loss of nucleus & other organelles.

RBC maturation factors

• Vitamin B₁₂:
• Cobalamine, 2~5μg/d.
• Produced by gut bacteria. Good sources include meat, liver, fish, eggs and milk.
• Function: Improve utilization of FA.
• Folic acid:
• FA is essential for the synthesis of DNA.
• Synthesized by microorganisms and higher plants.
• Good sources are green leafy vegetables, yeast and organ meats.

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Regulation of Erythropoiesis

• The number of circulating erythrocytes remains constant and reflects a balance between RBC production and destruction
• Too few red blood cells leads to tissue hypoxia
• Too many red blood cells causes undesirable blood viscosity
• Erythropoiesis is hormonally controlled and depends on adequate supplies of iron, amino acids, and B vitamins

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Hormonal regulation of Erythropoiesis

• Regulated by the hormone – Erythropoietin, secreted by mainly by kidney cells.
• During hemorrhage, hemolysis or diseases, the oxygen carrying capacity of the blood decreases, such that oxygen supply to kidney cells decreases.
• This leads to increased secretion of EPO from kidney cells, which stimulates the process of erythropoiesis and hence improves oxygen carrying capacity .
• This reduced tissue hypoxia reduces further secretion of EPO.

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Erythropoietin Mechanism

Figure 17.6

Imbalance

Reduces O₂ levels in blood

Erythropoietin stimulates red bone marrow

Enhanced erythropoiesis increases RBC count

Normal blood oxygen levels

Stimulus: Hypoxia due to decreased RBC count, decreased availability of O₂ to blood, or increased tissue demands for O₂

Imbalance

Start

Kidney (and liver to a smaller extent) releases erythropoietin

Increases �O₂-carrying ability of blood

Life span & Fate of RBC

• The life span of an erythrocyte is 100–120 days
• Travels about 750 miles in that time
• Old erythrocytes become rigid and fragile, and their hemoglobin begins to degenerate
• Dying erythrocytes are engulfed by macrophages (liver, spleen and lymphatic node)
• Heme and globin are separated
• Iron is removed from the heme and salvaged for reuse
• Stored as hemosiderin or ferritin in tissues
• Transported in plasma by beta-globulins as transferrin

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• Heme is degraded to a yellow pigment called bilirubin
• Liver secretes bilirubin into the intestines as bile
• Intestines metabolize bilirubin into urobilinogen
• Urobilinogen leaves the body in feces, in a pigment called stercobilin
• Globin is metabolized into amino acids which are then released into the circulation

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Leucocytes/WBC

• Leukocytes, the only blood components that are complete cells
• Largest blood cells, with nucleus.
• But, no hemoglobin & numbers are fewer then RBC
• Normal count – 4000 to 11,000 / cu.mm
• Protects body against microbes & removes dead cells & debris.

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Physiological characteristics of WBC

• Diapedisis: Metamorphosed WBCs pass through vessel wall getting into interstitial fluid.
• Chemotaxis: It is a process that WBCs shift to some chemical material (metabolic production, antigen-antibody complex, bacteria, toxin, etc).
• Phagocytosis: It is a process that WBCs enclose and engulf exotic or extraneous material, and use intracellular enzyme digesting them.

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Types of WBC

• WBCs are classified into different types based on:
• Size
• Nuclear Shape
• Cytoplasmic Granules
• Affinity for Stain
• Two major types of leukocytes
• Granulocytes: have granules in the cytoplasm
• Ex. Neutrophils, Eosinophils, Basophils
• Agranulocytes: do not have granules in the cytoplasm.
• Ex. Monocytes, Lymphyocytes

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Granulocytes

• Granulocytes – neutrophils, eosinophils, and basophils
• Contain cytoplasmic granules that stain specifically with acidic, basic, or neutral stain
• Have lobed nuclei
• Are all phagocytic cells

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Granulocytes - Neutrophils

• Also called as Polymorphonuclear Leucocytes (PMN).
• Size = 10 – 12 μ & Nucleus is multi-lobed (2-5)
• Account for 60-75% of total WBC’s
• Neutrophils have two types of granules that:
• Take up both acidic and basic dyes
• Give the cytoplasm a light pink to purple color
• Contain peroxidases, hydrolytic enzymes, and defensins (antibiotic-like proteins)
• Function:

1. Phagocytosis: older cells, bacteria, dead tissues, and other foreign substances.

2. To execute non-specific immune activity in first front.

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Granulocytes - Eosinophils

• Eosinophils/Acidophils account for 1–4% of WBCs
• Size = 10 – 12 μ & have bilobed nucleus
• Have red to crimson granules – stained with acidic stain
• Function:
• Lead the body’s counterattack against parasitic infections (worms or helminths)
• Lessen the severity of allergies by phagocytizing immune complexes (ending allergic reactions)

Granulocytes - Basophils

• Account for 0.5-1% of all WBCs
• Size = 8 – 10 μ & have kidney shaped bilobed nucleus
• Are functionally similar to mast cells
• Have large, purplish-black (basophilic) granules that contain histamine, heparin or serotonin.
• Histamine – inflammatory chemical that acts as a vasodilator and attracts other WBCs.
• Heparin – Anti-coagulant
• Serotonin – vasoconstriction & inflammatory reaction.

Basophils

• Function:
• Secrete heparin into blood to prevent coagulation.
• Wander into tissue and become mast cell.
• Induce allergy.

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Agranulocytes - Lymphocytes

• Account for 20-25% or more of WBCs and:
• Have large, dark-purple, circular nucleus with a thin rim of blue cytoplasm
• Produced mainly by lymph nodes & spleen & are found mostly enmeshed in lymphoid tissue (some circulate in the blood)
• Most important cells of the immune system
• There are two types of lymphocytes: T cells and B cells
• T cells – matured in thymus gland & attack foreign cells directly (produces cell mediated immunity)
• B cells – matured in BM & lymphoid tissue & give rise to plasma cells, which produce antibodies (produces Humoral immunity)

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Agranulocytes - Monocytes

• Monocytes account for 2–4% of leukocytes
• They are the largest leukocytes (16- 20 μ)
• They have purple-staining, kidney bean or oval shaped nucleus
• They leave the circulation, enter tissue, and differentiate into macrophages.

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Functions of Monocytes

1. It contains many nonspecific lipase and displays the

powerful phagocytosis - Engulf and clear bacteria, vermins, older, necrotic tissues, dead neutrophils, dead cells and fragments.

2. As soon as monocytes get into tissue from blood , it becomes macrophages, activating monocyte- macrophage system to release many cytokins, such as colony stimulating factor (CSF), IL-1, IL-3, IL-6, TNFα, INF-α,β ,etc.

3. Cytokins induced by monocyte may modulate growth of granulocytes.

4. Monocyte- macrophage system plays a very important role in specific immune responsive induction and regulation by activating Lymphocytes.

5. Recognize & kill cancer cells.

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Leucopoiesis

• Production of WBC.
• Birth place: bone marrow, originating from hemopoietic stem cells, and leukopoiesis process is similar to RBC.
• Leukopoiesis is hormonally stimulated by two families of cytokines (hematopoietic factors) – interleukins and colony-stimulating factors (CSFs)
• Interleukins are numbered (e.g., IL-1, IL-2), whereas CSFs are named for the WBCs they stimulate (e.g., granulocyte-CSF stimulates granulocytes)
• Macrophages and T cells are the most important sources of cytokines

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Leucopoiesis

• All leukocytes originate from hemocytoblasts- stem cells
• Hemocytoblasts differentiate into myeloid stem cells and lymphoid stem cells
• Myeloid stem cells become myeloblasts or monoblasts
• Granulocytes form from myeloblasts
• Monoblasts enlarge and form monocytes
• Lymphoid stem cells become lymphoblasts
• Lymphoblasts develop into lymphocytes

Life span & fate of WBC

• Life span: several hours to 3 or 4 days.
• Leukocyte breakage: site are liver, spleen and lymphatic node – leading to formation of pus.

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Platelets

• Thrombocytes.
• Are smallest of formed elements, lack nucleus
• Are fragments of megakaryocytes;
• Constitute most of mass of blood clots
• Their granules contain serotonin, Ca²⁺, enzymes, ADP, and platelet-derived growth factor (PDGF)
• Normal count = 2.5 to 4.0 lakhs per cu.mm

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Platelets

• Round/oval shaped with biconvex surface.
• 2~4 μm diameter, thickness 1μm.

Platelets

• Birth place is bone marrow, originating from hemopoietic stem cells, and differentiating into burst forming unit- megakaryocyte, BFU-MK, then continuously into CFU-MK, and into megakaryocyte. one megakaryocyte can release 200~7700 platelet.
• Life-span: Averagely, 7~14 days in the blood.
• Breakage: Aged platelet can be processed by phagocytosis in liver, spleen and lymphatic node.

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Functions of Platelets

• Plays an important role in Hemostasis (stopping the bleeding when blood vessels are damaged to prevent excessive blood loss).
• Hemostasis includes:
• Vasoconstriction,
• Platelet plug formation and
• Blood coagulation (Formation of a clot)

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Role of platelets in hemostasis

• Platelets don't stick to intact endothelium because of presence of prostacyclin & NO
• When a blood vessel breaks, damaged endothelium allows platelets to bind to exposed collagen.
• Platelets are “sticky”. They stick to any rough surface and to collagen in connective tissue. They also stick to each other.
• Platelets stick to each other-🡪Plug
• Platelets then release ADP, Thromoboxane A2 & SEROTONIN.

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• Serotonin & thromboxane A₂ stimulate vasoconstriction, reducing blood flow to wound
• ADP & thromboxane A₂ cause other platelets to become sticky & attach & undergo platelet release reaction.
• This continues until a soft mass of platelet plug is formed. Thus, it blocks leakage in the blood vessels & stops further bleeding.
• Platelet plug then becomes infiltrated by meshwork of fibrin to form solid clot.

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• Platelets also enhance activation of coagulation factors to solidify platelet Plug by interlacing with fibrin (secondary hemostasis).

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Blood coagulation

• The process of conversion of blood from liquid to gel or gelatin.
• Involves series of complex reactions & requires multiple substances.
• Clotting factors – substances which are directly involved in blood coagulation.
• There are 12 factors named Roman numerals, except Ca²⁺, other factors being protein, and except FIII (TF), others are synthesized by liver with VitK .
• Blood clotting factors exists in two types: inactive and activated type [FII, FVII, FIX, FX, FXI, FXII, FXIII].

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I Fibrinogen 3000 Liver 4~5 d

II Prothrombin 100 Liver (with Vit K) 3 d

III Tissue factor - Endothelial cell -

IV Ca²⁺ 100 - -

V Proaccelerin 10 Endothelial cell, platelet 12~15 h

VII Proconvertin 0.5 Liver (with Vit K) 4~7 h

VIII Antihemophilic factor,AHF 0.1 Liver 8~10 h

IX Plasma thromboplastic 5 Liver (with Vit K) 24 h

component,PTC(Christmas factor)

X Stuart-Prower Factor 10 Liver (with Vit K) 2 d

XI Plasma thromoboplastin 5 Liver 2~3 d

antecedent,PTA

XII Contact factor or Hageman factor 40 Liver 24 h

XIII Fibrin-stabilizing factor 10 Liver, platelet 8 d

Factor Name Plasma Synthesizing Half life

Concentration site

Blood Clotting Factors

Mechanism of clotting

• It involves 3 steps namely,
• 1. Formation of Prothrombin activator
• 2. Conversion of prothrombin to thrombin
• 3. Conversion of fibrinogen to fibrin. Fibrin sticks to damaged edges, forms meshwork. Platelets, blood cells stick to meshwork, & forms solid clot.

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Pathways of blood coagulation

• The mechanism of clotting occurs by 2 pathways – Extrinsic & Intrinsic pathways, which occurs together.
• Intrinsic pathway of blood coagulation: All blood clotting factors involved in blood coagulation come from blood. Initiated by exposure of blood to negatively charged surface of glass or blood vessel collagen. This activates factor XII (a protease) which initiates a series of clotting factors. (3-6 min)
• Extrinsic pathway of blood coagulation: Damage outside blood vessels (tissue) releases tissue factor (thromboplastin) that triggers clotting. It is initiated at the site of injury in response to the release of TF. (1-2 min)
• Extrinsic pathway of blood coagulation is faster than intrinsic pathway of blood coagulation because its steps are more simple.

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Stage 1: Formation of prothrombin activator.

Stage 2: Conversion of prothrombin to thrombin.

Stage 3: conversion of fibrinogen to fibrin

clotting cascade

Fibrinolysis

• Process of liquefaction of fibrin or dissolution of solid clot.
• After the clot has formed, the process of removing it and healing the damaged blood vessel begins.
• When damage is repaired, the inactive substance called plasminogen is converted to plasmin by activators.
• Plasmin digests fibrin, dissolving clot to form soluble products that are removed by phagocytosis.
• As the clot is removed, the healing process restores the integrity of blood vessel wall.

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• Plasminogen

Plasmin

Activator

fibrin

fibrin degradation products

Regulation of coagulation

• The process of blood coagulation relies heavily on several processes that are self perpetuating i.e. once started, a positive feedback mechanism promotes their continuation.

Ex. Thrombin is a powerful stimulator of its own production.

The body therefore possess several mechanisms to control & limit the clotting reactions; otherwise, once started the clotting process would spread throughout the circulatory system.

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• The main control are-
• 1. The perfect smoothness of normal blood vessel lining; platelets do not adhere to this surface.
• 2. The binding of thrombin to a specific receptor on the cells lining the blood vessels; once bound, thrombin gets inactivated.
• 3. Presence of natural anti-coagulants (Heparin in blood), which inactivates clotting factors.

Blood groups

• History: ABO blood group system was firstly found by Karl Landsteiner in 1901.
• Blood is grouped according to types of specific antigens present on the blood cell.
• Two types – ABO system & Rh system

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• RBC membranes have glycoprotein antigens on their external surfaces
• These antigens are:
• Unique to the individual
• Recognized as foreign if transfused into another individual
• Promoters of agglutination and are referred to as agglutinogens
• Presence or absence of these antigens is used to classify blood groups

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ABO blood grouping

• This system is based on presence or absence of two types of antigens i.e. A & B on the surface of RBC.
• According to this system, there can be 4 different blood groups such as A, B, AB or O

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• According to Landstainers law, If a particular agglutinogen is present on the surface of RBC, then its corresponding agglutinin is always absent.
• People with Type A blood make antibodies to Type B RBCs, but not to Type A
• Type B blood has antibodies to Type A RBCs but not to Type B
• Type AB blood doesn’t have antibodies to A or B
• Type O has antibodies to both Type A & B
• If different blood types are mixed, antibodies will cause mixture to undergo agglutination reaction
• Agglutination: Combination of the same antigen (or named agglutinogen, glycoprotein/glycolipid on the membrane of blood cell) and antibody (or named agglutinin, in serum) results in harmful immune reactions showing hemolysis.

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Agglutination

Blood group A：A antigens on the surface of RBC, B antibodies in blood plasma.

ABO grouping

Blood group B：B antigens on the surface of RBC, A antibodies in blood plasma.

Blood group AB：both A and B antigens on the surface of RBC, no A or B antibodies at all in blood plasma.

Blood group O：neither A or B antigens on the surface of RBC, but you have both A and B antibodies in blood plasma

Inheritance of ABO blood group

Parents’ Offspring possible Offspring impossible

blood group blood group blood group

O×O O A, B, AB

A×A O, A B, AB

A×O O, A B, AB

B×B O, B A, AB

B×O O, B A, AB

B×A O, A, B, AB ____

AB×O A , B O, AB

AB×A A , B, AB O

AB×B A , B, AB O

AB×AB A , B, AB O

Genetic relationship of ABO blood group

How common is your blood type?

46.1%

38.8%

11.1%

3.9%

Blood transfusion

• A blood transfusion is a procedure in which blood is given to a patient through an intravenous (IV) line in one of the blood vessels.
• Blood transfusions are done to replace blood lost during surgery or a serious injury. A transfusion also may be done if a person’s body can't make blood properly because of an illness.
• Transfusions are preferred between people of the same blood type. (compatible)
• If blood types don't match, recipient’s antibodies agglutinate donor’s RBCs

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• Compatibility involves Matching RBCs of Donor (i.e.Antigens) & Antibodies of Recipient
• A can receive from A and O
• B can receive from B and O
• AB can receive from AB, A, B and O
• O can receive only from type O- but can donate to everyone else
• People with TYPE O blood are called Universal Donors (they can give blood to any blood type) because of absence of both A & B antigens.
• People with TYPE AB blood are called Universal Recipients (they can receive any blood type) because of absence of both A & B antibodies.

ABO Blood Groups

Table 17.4

Principles of transfusion

1. Identification of blood group must be taken before transfusion.

2. Cross-match test must be done before transfusion.

3. The same types of blood group for transfusion should be firstly considered.

4. The different types of blood group for transfusion should be very careful, small amount and slow import and if condition is better, changes in the same types of blood group for transfusion.

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Cross-match test for transfusion

RBC

RBC

Donator

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Receiver

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Main side

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Subordinate side

Serum

Serum

Main side of agglutination

Perfect match, transfusion

No match, transfusion

Transfusion under emergency

×

Subordinary side of agglutination

Decision

+: Agglutination; -: No agglutination

Transfusion reactions

• Transfusion reactions occur when mismatched (Incompatible) blood is infused
• Donor’s cells are attacked by the recipient’s plasma agglutinins causing:
• Diminished oxygen-carrying capacity
• Clumped cells that impede blood flow
• Ruptured RBCs that release free hemoglobin into the bloodstream
• Circulating hemoglobin precipitates in the kidneys and causes renal failure

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Rh blood group system

• Rh antigen (Rh factor) is about 40 kinds and Rh factors related to clinic are D, E, C, c, e and most important is D antigen.
• Membrane of RBC has D antigen meaning Rh Positive, otherwise, Rh negative.
• Most of people (99％) are Rh Positive and less than 1% persons are Rh negative.
• Anti-Rh antibodies are not normally present.
• However, if an Rh^– individual receives Rh⁺ blood, anti-Rh antibodies form & second exposure to Rh⁺ blood will result in a typical transfusion reaction.

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Rh Factors

• Scientists sometimes study Rhesus monkeys to learn more about the human anatomy because there are certain similarities between the two species. While studying Rhesus monkeys, a certain blood protein was discovered. This protein is also present in the blood of some people. Other people, however, do not have the protein.
• The presence of the protein, or lack of it, is referred to as the Rh (for Rhesus) factor.
• If your blood does contain the protein, your blood is said to be Rh positive (Rh+). If your blood does not contain the protein, your blood is said to be Rh negative (Rh-).

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A+ A-�B+ B-�AB+ AB-�O+ O-

http://www.fi.edu/biosci/blood/rh.html

Hemolytic disease of newborn (HDN)/Erythroblastosis foetalis

• Occurs when Rh- Mom Pregnant with Rh+ Fetus
• Mixing of Maternal & Fetal Blood at Birth
• Rh^– mother becomes sensitized when Rh⁺ blood causes her body to synthesis Rh⁺ antibodies. no problems with first transfusion or pregnancy
• The sensitized mother (from a previous pregnancy of an Rh⁺ baby or a Rh⁺ transfusion) with subsequent 2^nd Rh+ Fetus, Rh⁺ antibodies of a sensitized Rh^– mother cross the placenta and attack and destroy the RBCs of an Rh⁺ baby.
• The drug RhoGAM can prevent the Rh^– mother from becoming sensitized
• Treatment of hemolytic disease of the newborn involves pre-birth transfusions and exchange transfusions after birth

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Disorders of Blood

• Disorders of RBC
• Anaemia & Polycythemia
• Disorders of WBC
• Leucopenia, Leucocytosis, Leukaemia
• Disorders of Platelets
• Thrombocytopenia
• Disorders of Coagulation
• Hemophilia

Anaemia

• It is a complex symptoms/disease recognized by fall in oxygen carrying capacity of blood.
• Symptoms- Paleness, weakness, breathlessness, restlessness, loss of appetite, tachycardia, palpitations.
• It occurs due to imbalance between rate of erythropoiesis & hemolysis – such that enough Hb is not available resulting in insufficient oxygen supply to the tissues.

Types of Anaemia

• A. Due to impaired RBC production
• Iron deficiency Anaemia
• Megaloblastic Anaemia
• Hypoplastic or Aplastic Anaemia

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• B. Due to increased RBC loss
• Hemolytic Anaemia – Sickle cell A, Thalassaemia,HDN
• Normocytic or post-Hemorrhagic Anaemia

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Iron deficiency Anaemia

• Most common form – due to deficient intake of iron.
• The normal daily requirement of iron intake is 1-2 mg (M) & 3 mg (F).
• It leads to decrease in Hb concentration & insufficient supply of oxygen to cells.
• It occurs due to either intake of Iron deficient diet or Iron malabsorption due to abnormalities of stomach/intestine.

Megaloblastic Anaemia

• It is characterized by presence of abnormal RBC in the form of megaloblasts (Immature, large & fragile RBC with reduced life span).
• It occurs due to deficiency of RBC maturation factors such as Vitamin B12 or/and Folic acid. Due to which, the rate of DNA & RNA synthesis reduced, delayed cell division & hence, the cells can grow larger than normal between divisions.
• The Hb concentration is either normal or raised.
• 3 subtypes – Pernicious A, Vit B12 def. A & Folic acid def. A

• Pernicious Anaemia – is a autoimmune disorder, in which antibodies destroy the intrinsic factor or parietal cells of stomach causing less or no absorption of Vit. B12
• Vitamin B12 deficient Anaemia – is very rare, except in true vegetarians. The other causes may include Chronic gastritis, Gastrectomy, malignant diseases of GIT resulting in less absorption of Vit. B12.
• Folic acid deficient Anaemia – due to either dietary deficiency (infants, alcoholics, anorexia, pregnancy) or malabsorption from intestine.

Hypo plastic/Aplastic anaemia

• Anaemia due to reduced function of bone marrow or total absent of BM function.
• Characterized by Pancytopenia
• The condition is idiopatic, but the possible causes include-
• Cytotoxics, some anti-inflammatory, anti-convulsant, & sulphonamide drugs.
• Ionizing radiations.
• Benzene & its derivatives.
• Hepatitis, Nephritis

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Hemolytic anaemia

• Is due to excessive or abnormal destruction of RBC.
• It can be congenital or acquired.
• Congenital Hemolytic anaemia – due to genetic abnormality, there is synthesis of abnormal Hb & increased RBC membrane friability leading to reduced oxygen carrying capacity & life span of RBC.
• Most common are – Sickle cell A, Thalassemia & HDN

Sickle cell anaemia

• results from a defective gene codes for an abnormal hemoglobin called hemoglobin S (HbS)
• This defect causes RBCs to become sickle-shaped in low oxygen situations.
• Oxygen transport is impeded, capillaries may clog, spleen is enlarged & painful.
• Increased viscosity of blood leading to intravascular clotting, ischaemia etc.

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Thalassemia

• Also called as Cooley’s anaemia.
• Reduced globin synthesis or defective globin chain formation leading to reduced Hb & increased friability of RBC – early hemolysis.

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Acquired Hemolytic anaemia

• Hemolysis due to other causes –
• Ionizing radiations
• Drugs – Phenacetin, Primaquine, Sulphonamides
• Incompatible blood transfusions
• Physical damage to cells – dialysis, artificial valves

Normocytic anaemia

• In this type, cells are normal in size with normal Hb concentration but, the numbers are reduced.
• It occurs due to acute or chronic hemorrhage – loss of blood due to accidents, injuries or other diseases. (post- Hemorrhagic anaemia)

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Polycythemia

• Is a disorder of RBC characterized by excess number of RBC in the blood.
• This increases viscosity of blood, slow down the rate of flow of blood & increases the risk of intravascular clotting.
• The physiological increase occurs in high altitudes & pathological in BM Cancer (Polycythemia rubra vera)& smoking

Leucopenia

• Is characterized by decrease in WBC count (less than 4000 per cu.mm)
• Most common is Granulocytopenia (Neutropenia)
• Cause – Infections – typhoid, pneumonia
• cancer, Inflammation,
• Drugs- cytotoxics, antibiotics

Leucocytosis

• Is increased WBC count (More than 11,000 per cu.mm)
• Due to infections

Leukaemia

• Leukemia refers to cancerous conditions involving white blood cells
• Leukemias are named according to the abnormal white blood cells involved
• Myelocytic leukemia – involves myeloblasts
• Lymphocytic leukemia – involves lymphocytes
• Acute leukemia involves blast-type cells and primarily affects children
• Chronic leukemia is more prevalent in older people

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• Immature white blood cells are found in the bloodstream in all leukemias
• Bone marrow becomes totally occupied with cancerous leukocytes
• Severe anemia & thrombocytopenia occurs due to excess production of WBC’s
• The white blood cells produced, though numerous, are not functional
• Death is caused by internal hemorrhage and overwhelming infections

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• Causes – Ionizing radiations, Benzene & its derivatives, viral infections, genetic factors, cytotoxic drugs etc.

Thrombocytopenia

• Is reduced platelet count (less than 150000 per cu.mm).
• It is due to either reduced rate of platelet production (Pancytopenia due to Leukemia, cancer, IR, cytotoxics) or increased rate of destruction of platelets.
• Thrombocytopenia purpura is an autoimmune disease leading to destruction of platelets.
• Increased bleeding time & patches of hemorrhage on the skin.

Disorders of coagulation

• Hemophilia A:
• Deficiency of clotting factor VIII. The disease severity usually parallels the factor VIII levels.
• Severe (< 1% VIII): with spontaneous bleeding;
• Moderate (1-5% VIII): with occasional bleeding, usually with trauma;
• Mild (6-30% VIII): with bleeding only after surgery or trauma.
• Therapy: administration of FVIII.

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• Hemophilia B (Christmas Disease):
• Clotting factor IX deficiency.
• Decreased production of coagulation factors:
• E.g. Liver disease, vitamin K malabsorption, dietary deficiency of vitamin K.

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Questions

• Describe the various steps involved in erythropoiesis. Write the general factors influencing erythropoiesis. (10)
• Write the composition of blood (5)
• Write the normal value & life span of RBC & Platelets. (2)
• Discuss the mechanism of blood coagulation (5)
• What is ESR. Mention its significance (2)
• What is megaloblastic anemia (2)
• Write the functions of blood (5)
• Write the functions of plasma proteins (2)
• Define anemia (2)
• Write the composition & functions of blood (5)
• Enumerate the types & functions of leucocytes (5)
• Define Leukemia (2)
• Mention the normal value of Hb & RBC (2)

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• Explain ABO system of blood grouping (5)
• Functions of WBC (2)
• What is Rh factor (2)
• Describe the structure & functions of Platelets (5)
• Classify WBC. Explain the microscopic structure & functions of WBC (5)
• What is Anemia. Explain different types (5).

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