GOOD MORNING

Blood AND Blood Disorders

Presented by: Sahul lerra P.G in prosthodontics B.D.C.H

contents

INTRODUCTION COMPOSITION OF BLOOD FUNCTIONS OF BLOOD PLASMA PROTEINS Functions

PHYSICAL CHARACTERISTICS OF BLOOD

Rouleaux

formation : Erythrocyte Sedementation Rate

HAEMATOPOIESIS Formed elements :

RBC

or erythrocytes Platelets or thrombocytes WBC or leucocytes

Physiological variations &Pathological variations

Poilycythhemia Oligocythemia

Bone marrow Haemoglobin Haemostasis : Blood groups

Indications for transfusion of whole blood or its derivatives

INTRODUCTION

Blood is a circulating tissue composed of fluid plasma and cells (red blood cells, white blood cells, platelets). Medical terms related to blood often begin in hemo- or hemato- (BE: haemo- and haemato-) from the Greek word "haima" for "blood". Blood is a connective tissue present in fluid form.

It is circulating in the blood vessels with a constant velocity of 0.5mts/sec. The constant motion of blood is brought about by the pumping action of heart.

Because it contains living cells,blood is alive RBC and WBC are responsible for nourishing and cleansing the body Since the cells are alive , they too need nourishment . Vitamins and minerals keep the blood healthy. The blood cells have a definite life cycle , just as all living organisms do.

Blood

Blood Volume

The average adult body contains approximately 6 quarts of blood (5 liters). This volume obviously varies with the size and health of the individual.

Composition of Blood

Blood functions
Blood performs two major functions: Transport
o o o

o
o o

oxygen and carbon dioxide food molecules (glucose, lipids, amino acids) ions (e.g., Na+, Ca2+, HCO3) wastes (e.g., urea) hormones heat

Defence of the body against infections and other foreign materials. All the WBCs participate in these defences.

Blood as a Transport Media

Vascular system provides the network for distribution Easy communication with extracellular fluid and
tissues

Aids distribution by providing transport carriers.

Contributes to maintenance of constant internal environment Homeostasis Main integrity of system Haemostasis

Blood as a Diagnostic Tool

Provides information on almost all systems of the body Lung function Liver Renal Endocrine Infection Blood disorders

Anaemia Clotting Blood groups

Blood Composition
Blood Volume 8% body volume approx 5.5L

Serum versus plasma??

Centrifuged blood plus anticoagulant (heparin, citrate, EDTA) forms two layers, 44% (PCV, haematocrit) erythrocytes, leukocytes, platelets plasma-water, electrolytes, proteins,lipids, sugars

Plasma proteins

Proteins make up 68% of the blood. separated by electrophoresis Albumins MW (4.5g%) colloid osmotic pressure Globulins (2.7g%)coagulation, immunological, transport functions Fibrinogen (0.25g%) coagulation

Electrophoresis
1. normal human serum with its diffuse band of gamma globulins;
2. serum from a patient with multiple myeloma producing an IgG myeloma protein; 3. serum from a patient with Waldenstrm's macroglobulinemia where the cancerous clone secretes an IgM antibody; Serum with an IgA myeloma protein

Plasma Proteins Functions

Osmotic Pressure ( fluid exchange) Viscosity ( peripheral resistance) Transport carriers Regulation ( hormones) Antibodies ( immunity) Coagulation ( haemostasis) Blood buffers ( acid base balance)

Functions : Different PP subserves different functions : Buffering function: PP because of presence of amino and cost carboxylic groups acts as a good buffer and are responsible for 1/8th of the total buffering power of blood. Thus they help in maintenance of pH of body fluid constant at 7.4.

By exerting colloidal osmotic pressure of 25mmHg. They help in the maintenance of blood volume and other body volumes constant. Plasma proteins are responsible for providing 50% of the viscosity of blood. Thereby helps in maintenance of blood pressure constant.

The fibrinogen and prothrombin and other coagulation factors present in plasma play an important role in coagulation of blood. Thereby defends the body against excessive loss of blood. Also these are other proteins in the plasma like plasmin (fibrinolysis) prevent thrombosis or embolism by dissolving the clot plug.

The globulins are antibodies(lg) they provide immunity against invading microorganisms.thereby prevents disease.

The albumin and globulins carry hormones, metals, nutrients drug etc., in bound form. This bound form acts as a reservoir for these materials and releases them slowly as and when they are required.

They help in maintenance of electrolyte balance They provide a nutritional source of a. a. for tissues Plasma proteins helps in the study of human genetics and in study of human races.

Rouleaux formation : When a drop of blood is kept over a glass slide and observed under microscope after placing a cover slip several RBC are found arranged like a pile of coins. Where their concave surface come closer together. This is called rouleaux formation.

Normally due to the ve charge inside the RBCs repel each other. But in the presence of protein such as fibrinogen and globulins RBCs are attracted towards each other when the blood is kept stationary. The rouleaux formation helps in increase in mass of RBC with respect to their surface area. As a result the RBC settle rapidly to the bottom of the container.

Erythrocyte Sedementation Rate : ESR ESR is defined as rate of setting down of RBC to the bottom of a tube filled with blood and mixed with anticoagulation kept in vertical position. The ESR value is expressed in mm at the end of 1 hour or mm/hr.

Method: Two methods are used to determine the ESR

Westergrens method Wintrobes method

Normal

ESR values Male =4mm/hr (3 5mm/hr) Female = 8mm/hr(7-12mm/hr)

If the value is >12mm/hr, it is abnormal).

Variations of ESR value : ESR increased in

Physiological conditions e.g., pregnancy (haemodilution), parturition and exercise, menstruation. Pathological conditions e.g., rheumatic fever, malignancy, tuberculosis, autoimmune disease, leprosy, myocardial infection, anaemia, injection of vaccines and other proteins.

ESR Decreased in This is uncommon and seen in physiological condition :- new born babies due to polyclemia Pathological condition congestive cardiac failure (CCF), polycythemia, congenital absence of fibrinogen (Afibrinogenemia), Congenital spherocytosis.

Significance of ESR : Rise in ESR value always indicates the presence of organic tissue damage. The ESR value is useful in the prognosis of disease rather than in the diagnosis of disease.

Hematopoiesis

Blood Cells and Platelets

Composition of Blood

Formed elements : There are three formed elements in blood RBC or erythrocytes WBC or leucocytes Platelets or thrombocytes.

Erythrocytes
The most numerous type in the blood. Women average about 4.8 million of these cells per cubic millimeter Men average about 5.4 x 106 per l. These values can vary over quite a range depending on such factors as health and altitude. (Peruvians living at 18,000 feet may have as many as 8.3 x 106 RBCs per l.)

Structure

Bioconcave disc (deformation, surface area Rouloux formation aids transport

Contents

No nucleus (short lifespan) Haemoglobin (haemolytic disease) Surface mucopolysaccharides (blood groups).

Average diameter 7.2 Range 6.7-7 The thickness of RBC at periphery is 2.1 and ranges from 1.72.5

The thinness at center is 1 The average surface area is 140 Volume 78-94.

Erythropoiesis

Production of red blood cells

Stem cells proerythroblasts early erythroblasts intermediate late reticulocytes

Erythropoietin: Hormone to stimulate RBC production

Sites of RBC Formation

Variations : 1. Age: New born infants 6.5 7.2 million/cu mm Old age 4-6 million/cu mm 2. Sex: Female less than that of male because of less surface area.

Physiological variations &Pathological variations

Physiological variations : Increase in RBC count is called Polycythemia while decrease in RBC count is called oligocythemia.

Poilycythhemia occurs in :
High

altitude: Where is hypoxia at high altitude stimulated from the JG cells for the secretion of erythropoietin a glycoprotein hormone which stimulates the red bone marrow for the erythropoietin and causes absolute increase in RBC count.

 Exercise:

The polycythemia is due to fluid shift from blood vessels to the ECF therefore it is relative increase in RBCs. Injection of adrenaline: Causes relative increase in RBC count due to fluid shift due to its vasodilatation effect.

After meals: Due to haemoconcentration as a result of secretion of various glands, a relative increase in RBC count. Exposure to heat, causes relative increase in RBC count due to loss of fluid in the form of sweat results in haemoconcentration

Oligocythemia : Occurs in starvation and exposure to cold. The biconcave shape and high flexibility of RBC is due to presence of a contractile protein in the inner side of the cell membrane called Spectrin. Protein in cell membrane called glocphrin contain blood group antigen which extends throughout the CM.

Pathological variations : Polycythemia : Seen in Primary polycythemia vera hypertrophy of bone marrow Secondary polycythemia occur in cases of congestive cardiac failure (CCF), congenital heart disease, bronchial asthma, emphysema in which the hypoxia stimulates the erythropoietin secretion and thus the level is increased.

Oligocythemia : is seen in Anaemias Types: All types of anaemia

Aplastic

anaemia due to bone marrow depression Haemolytic anaemia excessive breakdown of RBC From iron deficiency anaemia
Pernicious

anaemia

Vit. B12 deficiency.

Advantages of Biconcave shape and elastic nature : The biconcave shape of the RBC and highly elastic nature of its membrane helps in Increase in the surface area of the RBC to bring about rapid exchange of gases between the Hb and surrounding plasma.

Formation of thin film of Hb which facilitates quick saturation with oxygen. This facilitates rapid association and dissociation of Hb with oxygen. Squeezing of RBCs through the lumen of capillaries whose diameter is smaller than that of the RBCs themselves. This occurs without causing damage to the cell.

Diameter of RBCs can be accurately measured by using a Micrometer disc and a Micrometer slide.

Erythropoiesis or development of RBC :

Erythropoiesis in fetus : Occurs in three stages : Mesoblastic stage: Which commences at about 6th to 8th week of IUL and ends at about 3rd month of fetal life. Hepatic stage: Commences at 3rd month and ends at 5th month of IUL Myeloid stage: Commences at 5th month of IUL and continues throughout the EUL.

Bone marrow : There are two types : Red bone marrow Yellow bone marrow

The Bone Marrow

Develops in the embryo by the hollowing out of the skeletal bones forming a central cavity In this cavity develops a primitive, undifferentiated cell known as a hemocytoblast, or stem cell ALL blood formed elements ultimately develop from this undifferentiated precursor

The Bone Marrow

Blood cells develop in what is called red marrow. It comprises approximately 50% of the marrow cavity space. The remaining 50% of the space is occupied by fat and is known as yellow marrow. The ratio of red marrow to yellow marrow is an indirect representation of marrow activity, and is expressed as marrow cellularity.

The Bone Marrow

Developing cells are held within normal marrow until they have developed sufficiently to function normally. Then they are released into the circulating blood for the remainder of their life span.

The Bone Marrow

Marrow recedes during development of the individual, and in the adult occupies only the support skeleton and the proximal regions of the long bones

Functions of red marrow :

Formation

of granulocytes and to a lesser extent monocytes and lymphocytes. Formation of platelets Destruction of RBCs by red cells called littoral cells Formation of RBCs

Changes in the cell during haemopoiesis : There are some common characteristics changes that occurs during the development of blood cells such as RBCs, WBCs and platelets. Progressive decreases in the size of the cell Progressive decrease in the size of the nucleus and finally it disappear in case of RBC.

Disappearance of nucleoli from the nucleus The Chromatin in the nucleus becomes progressively coarser The amount of cytoplasm becomes more and more extensive The basophilic cytoplasm is replaced by haemoglobin to become eosinophilic in RBC

Hemoglobin

Consists of:

4 globin molecules: Transport carbon dioxide (carbonic anhydrase involved), nitric oxide 4 heme molecules: Transport oxygen

Iron is required for oxygen transport

Synthesis of Hb : Occur in free ribosomes present in the cytoplasm of intermediate normoblast. Haem is synthesized from succinyl and gucinyl Co-A. Then it conjugates with globin to form haemoglobin. The globin is made up of 4 polypeptide chains arranged in two pairs in a mirror image shape. The adult Hb designated as HbA has two and two chains.

Normal Hb concentration : Adult male : range : 14-18gm% Average: 15.5mg% Adult female: range: 12-15gm% Average: 14gm% Irrespective of sex, mean value 14.8gm% At birth; 23gm% At 3rd month 10.5mg% 1st year: 12gm%

Functioning of Hb : Hb carries O2 in the loosely bound reversibly form called oxyhaemoglobin from the lungs to the tissues. Hb carries small quantity of CO2 as carbamino. Hb from the tissues to the lungs.

Reduced Hb acts as a very good buffers and is responsible for 5/6th of total buffering power of blood (remaining 1/6th by plasma proteins) therefore it helps in the maintenance of pH of body fluid constant.

Hb Derivatives : Oxy Hb: HbO2 is formed when Hb combines with O2 Carbamino Hb HbCO2 is formed when Hb combines with CO2 Carboxy Hb (Carbomonxy Hb): HbCO is formed when Hb combine with co. Hb has more affinity of about is 200 times for CO than the affinity for O2 and HbCo is cherry red in colour.

RETICULOENDOTHELIAL CELLS (RECELLS) OR TISSUE MACROPHAGE SYSTEM : the macrophages are present in many lymphoid organs in the body, not all macrophages are RE cells. According to Samsons those cells which engulf Indian ink particles and stained by it are called RE cells. They are large cells having a diameter between 25 and 30 with a large nucleus containing 3-4 nucleoli.

They are also called as haemocytoblast. The REcells in liver Kupffers cells Bone marrow littoral cells Spleen present in pulp

Functions of RE : Formation of RBC Destruction of RBC, WBC and platelets Synthesis of bilirubin Phagocytosis of bacteria, viruses and necrotic tissue and blood cells. Synthesis and secretion of specific antibodies against specific antigen

Hemoglobin Breakdown

LEUKOCYTES (white cells)

Leukocytesor white cells, are responsible for the defense of the organism. leukocytes count is 5000-7000 /mm3. Leukocytes divide in two categories: granulocytes and lymphoid cells or agranulocytes.

The term granulocyte is due to the presence of granules in the cytoplasm of these cells. these granules have a different affinity towards neutral, acid or basic stains and give the cytoplasm different colors. So, granulocytes distinguish themselves in neutrophil, eosinophil (or acidophil) and basophil. The lymphoid cells, distinguish themselves in lymphocytes and monocytes.

Each type of leukocyte is present in the blood in different proportions: neutrophil 50 - 70 % eosinophil 2 - 4 % basophil 0,5 - 1 % lymphocyte 20 - 40 % monocyte 3 - 8 %

Neutrophil

The neutrophil are the more common leukocytes. They have a diameter of 1215 m. nucleus is divided into 2 - 5 lobes connected by a fine nuclear strand or filament . granules are small and faintly pink colored. Immature neutrophils have a band-shaped or horseshoeshaped nucleus and are known as band cells.

Neutrophils are very active in phagocyting bacteria and are present in large amount in the pus of wounds. Unfortunately, these cells are not able to renew the lysosomes used in digesting microbes and dead after having phagocyted a few of them.

Variation is neutrophil count : Neutrophilia : Polymorpho nuclear leukocytosis A condition in which neutrophil count is increased above the normal range. Occurs in all acute infections like: Tonsillitis, appendicitis, osteomellitis, furunculosis, pneumonia emphyma after hemorrhage burns myeloid leukemiai, in certain cardiac diseases.

Neutropenia : Is a condition in which neutrophil count is less than normal, it occurs in: extreme cold conditions, influenza, measles. German measles, small pox, Typhoid, Paratyphoid, chronic tuberculosis. Malaria, poisoning with Arsenic, antimony sulfonamide, Hg, pb, disease of blood and bone marrow such as a plastic anaemia, a granulocytosis. Pernicious anaemia, Hodgkins diseases.

BARR BODY : Estimated by demonstration of drum stick shaped basophilic body attached to one of the lobes of the nucleus in 1-15% of neutrophils. Helps in establishing the genetic sex of the individual as female. These bodies are called Barr bodies or sexchromatin.

Eosinophil

The eosinophils release various substances from their eosinophilic granules. These include major basic protein (MBP), plus cationic proteins, peroxidase, arylsulphatase B, phospholipase D and histaminase. The granule contents are capable of damaging the parasite membrane

. They have the same size as the neutrophils. Generally their nucleus is bi-lobed. The cytoplasm is full of granules which assume a characteristic pinkorange color As for the neutrophil, the nucleus is still easily visible.

This photo shows an eosinophil (E) and a neutrophil (N). The Eosinophil is distinguished by its red granules and bilobed nucleus.

BASOPHILS :

Size: 10-12 in diameter Nucleus: Bilobed . Cytoplasm is very rich in granules which take a dark purple color Chromatic: Coarse and ropy Cytoplasm: Coarse, few basophilic granules which contains histamine heparin.

A basophil is characterized by a lobed nucleus and it is filled by large blueblack granules that sometimes cover the nucleus. Here you can see the distinct granules against the purple nucleus.

Function : Defense: They are found near the site of chronic infections. They secrete heparin which prevents intravascular coagulation of blood.

Variations : Basophilia : In which basophil count exceeds normal limit Occurs in cases of: Chronic myeloid leukemia. Polycythemia vera. Cirrchosis of liver. Early stages of Hodgkin, disease, smallpox. Chicken pox, nasal allergy. Basophils disappear all together in. ACUTE INFECTIONS.

Monocytes are the biggest leukocytes: 16-20 m. They have a great reniform or horseshoeshaped nucleus, in some cases even bi-lobed. The cytoplasm is transparent, but with an appearance of "ground glass"

Monocytes are phagocytic and may have vacuoles in the cytoplasm. They also have a horseshoe shaped nucleus or, in immature monocytes, they may have an indented nucleus.

Lymphocyte.

Lymphocytes are quite common in the blood: 2040%, 8-10 m in diameter The cytoplasm is transparent. According to the quantity of cytoplasm, lymphocytes are divided into small, medium and large.

Lymphocytes are only slightly larger than red blood cells (small lymphocytes) they have a relatively large nucleus:cytoplasm ratio.

Lymphocyte: Lymphocytes are produced within bone marrow (a primary lymphoid organ). If they achieve immune-competence within the bone marrow, they are known as B cells, or if in the thymus (also a primary lymphoid organ), they are known as T cells. Organized lymphoid tissue elsewhere is known as secondary lymphoid tissue, and includes lymph nodes, adenoids, tonsils and mucosa associated tissue (MALT).

Inflammatory Response and Phagocytosis

Chemotaxis - Tissue macrophages attracted from injured or infected cells Diapedesis- neutrophils and monocytes stick to vascular endothelium and leave blood Phagocytosis engulfing of infectious or toxic material

Phagocytosis is the ingestion of solid particles by endocytosis.

The cytoplasmic membrane invaginates and pinches off placing the particle in a phagocytic vacuole (endosome).

The phagocytic vacuole then fuses with lysosomes and the material is degraded.

Platelets or thrombocytes : Morphology : Platelets are small irregular, non nucleated bodies containing secretory granules in their cytoplasm. They are 2-4 in diameter and have round, ovoid or rod shape nucleus. The cytoplasm apart from granules also contain microtubules, microovescicles, actomyosin like filaments, mitochondria, ER, golgibodies etc.

Life span : Platelets have a normal life span which varies from 8-12 days, half life (4 days). It can be determined by labeling the platelets with chromium 51 or phosphate 32.

Functions of platelets : Phagocytosis : The platelets engulf carbon particles, Viruses, and immune complexes by way of phagocytosis.

Hameostasis

The ability of the body to control the flow of blood following vascular injury is paramount to continued survival. The process of blood clotting and then the subsequent dissolution of the clot, following repair of the injured tissue, is termed hemostasis.

Main processes of hemostasis

1. Platelets adhesion and aggregation, formation of the platelet plug 2. Vasoconstriction 3. Blood clotting 4. Final repair by connective tissue NB! The phases are not separated but rather manyfold interconnected

Coagulation

Stages

Activation of prothrombinase Conversion of prothrombin to thrombin Conversion of fibrinogen to fibrin Extrinsic Intrinsic

Pathways

FACTORS I II III IV

NAME Fibrinogen Prothrombin Thromboplastin Calcium

V
VI VII VIII

Proaccelerin, labile factor Unknown factor

Stable factor, proconvertin Antihaemophilic factor (AHF),

IX X XI XII

Christmas factor Stuart prower factor antihaemophilic factor C Fibrin stabilizing factor

XIII Other factors HMN-K

Pre-K Ka PL

Fitz Gerald factor Pre kallikrein,

feltcher factor Kallikrein Platelet phsopholipids

Clot Formation

Adhesion of platelets, white thrombus

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Platelet Plug Formation

Platelets in normal state

http://ntri.tamuk.edu/homepage-ntri/lectures/clotting.html

The activated platelets

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Blood clots. red thrombus

http://ntri.tamuk.edu/homepage-ntri/lectures/clotting.html

Fibrinolysis

http://ntri.tamuk.edu/homepage-ntri/lectures/clotting.html

ABO Blood Groups

Agglutination Reaction

Rh Blood Group

First studied in rhesus monkeys Types

Rh positive: Have these antigens present on surface of RBCs Rh negative: Do not have these antigens present

Hemolytic disease of the newborn (HDN)

Mother produces anti-Rh antibodies that cross placenta and cause agglutination and hemolysis of fetal RBCs

Erythroblastosis Fetalis

Importance of blood grouping : For blood transfusion from one individual (donor) to another individual (recipient). In criminal practice or in forensic medicine In the study of anthrophology In the study of ethnology Predominance of certain diseases In the study of disputed paternity.

Indications for transfusion of whole blood or its derivatives WHOLE BLOOD TRANSFUSION
Is carried out when the patient has lost the whole blood due to.

Accidental injuries During and after major surgery

PACKED CELL TRANSFUSION : Is given to patients with severe anaemia in whom the Hb conc is less than 4 gms%. This causes dramatic improvement in the condition of the patient. LEUKOCYTE TRANSFUSION : In carried out in patients whose immunity is decreases (i.e., increased susceptibility for infections) or to patients suffering from agranulocytosis.

PLATELET TRANSFUSION : Is carried out in patients who is suffering from blooding disorders due to Thrombocytopenia. TRANSFUSION OF COAGULATION FACTORS : Eg: Factors VIII or AHG is given to hemophilic patient where as factors IX is given to patient suffering from Christmas disease. These factor are obtained in concentrated form from fresh plasma (human) by way of cryoprecipitation.

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