Blood(The Applied Physiology) for Nurses.pptx

Blood(The Applied Physiology) for Nurses.pptx

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  THE BLOOD (APPLIED PHYSIOLOGY) Prof.Nagamani.T
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  CONTENTS (4 HRS) Blood–Functions, Physical characteristics  Formation of blood cells  Erythropoiesis– Functions of RBC, RBC life cycle  WBC– types, functions  Platelets– Function and production of platelets  Clotting mechanism of blood, clotting time,bleeding time, PTT  Hemostasis– role of vasoconstriction ,platelet plug formation in hemostasis, coagulation factors, intrinsic and extrinsic pathways of coagulation  Blood groups and types  Functions of reticuloendothelial system, immunity  Application in nursing
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  INTRODUCTION  Blood isone of the most important components of life. Almost any animal that possesses a circulatory system has blood.  Our body consists of 4-6 litres of blood with an average pH of 7.35 to 7.45  Every tissue in the body requires an adequate supply of oxygen, nutrients and hormones.  The waste products should be removed from the tissues from time to time.  These functions are carried out by the blood  The heart and blood vessels are the mechanism by which a constant circulation is maintained through out the body.
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  WHAT IS BLOOD Blood is a fluid connective tissue that consists of plasma, blood cells and platelets. It circulates throughout our body delivering oxygen and nutrients to various cells and tissues. It makes up 8% of our body weight. An average adult possesses around 5-6 litres of blood.
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  COMPOSITION OF BLOOD Composition of Blood: Plasma, RBCs, WBCs and platelets
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  COMPONENTS OF BLOOD There are many cellular structures in the composition of blood. When a sample of blood is spun in a centrifuge machine, they separate into the following constituents:  Plasma, buffy coat and erythrocytes. Thus blood contains RBC, WBC, platelets and plasma.
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  PLASMA  The liquidstate of blood can be contributed to plasma as it makes up ~55% of blood.  It is pale yellow in colour and when separated.  Blood plasma consists of salts, nutrients, water and enzymes.  Blood plasma also contains important proteins and other components necessary for overall health.  Hence, blood plasma transfusions are given to patients with liver failure and life-threatening injuries.
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  Components of BloodPlasma  Blood plasma has several protein components. Proteins in blood plasma are:  Serum globulin  Serum albumin  Fibrinogen  The serum contains only globulin and albumin. Fibrinogen is absent in serum because it is converted into fibrin during blood clotting.
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  TYPES OF BLOODCELLS  Blood consist of cells known as formed elements of blood. These cells have their own functions and roles to play in the body. The blood cells which circulate all  Red blood cells (Erythrocytes)  White blood cells (Leucocytes)  Thrombocytes ( Platelets)
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  RED BLOOD CELLS(ERYTHROCYTES)  Red blood cells consist of Haemoglobin, a protein. They are produced by the bone marrow to primarily carry oxygen to the body and carbon dioxide away from it.  RBCs are biconcave cells without nucleus in humans; also known as erythrocytes. RBCs contain the iron-rich protein called haemoglobin; give blood its red colour.  RBCs are the most copious blood cells produced in bone marrows. Their main function is to transport oxygen from and to various tissues and organs.
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  WHITE BLOOD CELLS(LEUCOCYTES)  White blood cells are responsible for fighting foreign pathogens (such as bacteria, viruses, and fungi) that enter our body. They circulate throughout our body and originate from the bone marrow.  Leucocytes are colourless blood cells. They are colourless because it is devoid of haemoglobin.  They are further classified as granulocytes and agranulocytes. WBCs mainly contribute to immunity and defence mechanism. Types of White Blood Cells  There are five different types of White blood cells and are classified mainly based on the presence and absence of granules.  Granulocytes  Agranulocytes
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  TYPES OF WHITEBLOOD CELLS
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  GRANULOCYTES  They areleukocytes, with the presence of granules in their cytoplasm. The granulated cells include- eosinophil, basophil, and neutrophil. Eosinophils  They are the cells of leukocytes, which are present in the immune system.  These cells are responsible for combating infections in parasites of vertebrates and for controlling mechanisms associated with allergy and asthma.  Eosinophil cells are small granulocyte, which are produced in the bone marrow and makes 2 to 3 per cent of whole WBCs. These cells are present in high concentrations in the digestive tract.
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  Basophils  They arethe least common of the granulocytes, ranging from 0.5 to 1 per cent of WBCs.  They contain large cytoplasmic granules, which play a vital role in mounting a non-specific immune response to pathogens, and allergic reactions by releasing histamine and dilating the blood vessels.  These white blood cells have the ability to be stained when exposed to basic dyes, hence referred to as basophil.  These cells are best known for their role in asthma and their result in inflammation and bronchoconstriction in the airways.  They secrete serotonin, histamine and heparin.
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  Neutrophils  They arenormally found in the bloodstream.  They are predominant cells, which are present in pus.  Around 60 to 65 per cent of WBCs are neutrophils with a diameter of 10 to 12 micrometres.  The nucleus is 2 to 5 lobed and the cytoplasm has very fine granules.  Neutrophil helps in the destruction of bacteria with lysosomes, and it acts as a strong oxidant.  Neutrophils are stained only using neutral dyes. Hence, they are called so.  Neutrophils are also the first cells of the immune system to respond to an invader such as a bacteria or a virus.  The lifespan of these WBCs extends for up to eight hours and is produced every day in the bone marrow.
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  AGRANULOCYTES  They areleukocytes, with the absence of granules in their cytoplasm. Agranulocytes are further classified into monocytes and lymphocytes. Monocytes  These cells usually have a large bilobed nucleus, with a diameter of 12 to 20 micrometres.  The nucleus is generally half-moon shaped or kidney- shaped and it occupies 6 to 8 per cent of WBCs.  They are the garbage trucks of the immune system.  The most important functions of monocytes are to migrate into tissues and clean up dead cells, protect against bloodborne pathogens and move very quickly to the sites of infections in the tissues.  These white blood cells have a single bean-shaped nucleus, hence referred to as Monocytes.
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  Lymphocytes  They playa vital role in producing antibodies.  Their size ranges from 8 to 10 micrometres.  They are commonly known as natural killer cells.  They play an important role in body defence.  These white blood cells are colourless cells formed in lymphoid tissue, hence referred to as lymphocytes.  There are two main types of lymphocytes – B lymphocytes and T lymphocytes.  These cells are very important in the immune systems and are responsible for humoral and cell- mediated immunity.
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  PLATELETS (THROMBOCYTES)  Tinydisc-shaped cells that help regulate blood flow when any part of the body is damaged, thereby aiding in fast recovery through clotting of blood.  Thrombocytes are specialized blood cells produced from bone marrow.  Platelets come into play when there is bleeding or haemorrhage.  They help in clotting and coagulation of blood. Platelets help in coagulation during a cut or wound.
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  FUNCTIONS OF BLOOD Blood is a fluid connective tissue connecting blood cells, plasma and platelets.  It circulates all through the circulatory system of humans, delivering nutrients and oxygen to different cells and tissues.  It also passes metabolic waste products away from the very same cells.  On an average, blood constitutes about 8% of the mass of the body, and an adult’s body has around 5-6 litres of blood.
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   Blood comprisesblood cells suspended in the blood plasma.  Plasma accounts for 55% of the volume of the blood, it mainly comprises glucose, proteins, hormones, mineral ions, carbon dioxide and even the blood cells.  In plasma, albumin is the chief protein, and it operates to control the colloidal osmotic pressure of blood.  Mainly, blood cells are RBCs (red blood cells), WBCs (white blood cells) and platelets.
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   In thevertebrate blood, the most abundantly found blood cell is red blood cells.  It contains an iron-containing protein – haemoglobin, promoting oxygen transport by associating reversibly to this respiratory gas, and highly increasing their blood solubility.  On the contrary, carbon dioxide is usually transported extracellularly as bicarbonate ions are transported in the plasma.
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  IMPORTANT FUNCTIONS OFBLOOD Defense – Role of Blood in Defense  There are different forms of WBCs protecting from exterior threats such as the pathogenic bacteria which enter the bloodstream in a wound. Various other WBCs find and destroy the internal threats like the cells having mutated DNA, which can grow and multiply to become carcinogenic, or even the body cells infected with the viruses.  Blood platelets and some of the proteins that are dissolved in plasma interact to produce clots blocking the ruptured sites of blood vessels when the vessels get damaged, leading to bleeding. Hence, the body is prevented from any further loss of blood.
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  Transportation – Roleof Blood in Transportation  The food we consume has nutrients that are absorbed in the digestive tract. Most of the nutrients directly pass from the bloodstream to the liver, which is processed and released into the bloodstream to deliver to the cells of the body.  Oxygen diffuses into the blood that moves from the lungs to the heart, which then is pumped to the entire body. Additionally, the blood picks the by-products and cellular wastes too, and passes them to different structures to be eliminated.
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  Homeostasis – Roleof Blood in Maintaining Homeostasis  The body temperature is regulated through the negative-feedback loop. When blood passes through the vessels of the skin, heat can be dissipated to the environment and the blood getting back to the body can be cooler. On the contrary, on a colder day, blood gets diverted from the skin to preserve a warmer tone. If conditions are extreme, it can lead to frostbite.  Also, blood aids in maintaining the balance of chemicals in the body. The pH of tissues is regulated by the buffers found in the blood, such as proteins and associated compounds. Further, blood also aids in regulating the water content of the cells.
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   Blood aidsin eliminating urea, lactic acid and carbon dioxide  Involved in immunological functions, such as circulation of the white blood cells, identifying foreign particles by the antibodies  It responds to broken blood vessels, coagulation, converting blood from liquid to a semisolid gel that stops bleeding  Involved in hydraulic functions  Performs messenger functions, even that of transporting hormones and signalling tissue damage
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  FUNCTIONS OF WBC There are five types of white blood cells:  Neutrophils: Help protect your body from infections by killing bacteria, fungi and foreign debris.  Lymphocytes: Consist of T cells, natural killer cells and B cells to protect against viral infections and produce proteins to help you fight infection (antibodies).  Eosinophils: Identify and destroy parasites, cancer cells and assists basophils with your allergic response.  Basophils: Produce an allergic response like coughing, sneezing or a runny nose.  Monocytes: Defend against infection by cleaning up damaged cells.
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  FUNCTIONS OF PLATELETS
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  FORMATION OF BLOODCELLS (HEMATOPOIESIS)  Hematopoiesis/ hemopoiesis is the production, Development and the maturation of Blood cells.  Blood cells formation, or hematopoiesis, occurs in red bone marrow, or myeloid tissue.  The cellular components of blood are developed from the Hematopoietic stem cells also known as Pluripotent Stem cells or totipotent stem cells which further differentiate and mature into typical blood cells.  The Pluripotent stem cells give rise to two types of Stem cells or lineages – * Myeloid stem cells/Lineage – Differentiate in the Redbone marrow and form Erythrocytes, Granulocytes (Neutrophils, Eosinophils, and Basophils), Monocytes and Thrombocytes * Lymphoid stem cells/Lineage – differentiates in the Redbone marrow and then migrates to the lymphoid tissue. They form T- and B- Lymphocytes.
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   The immaturecell divides, matures and eventually becomes a mature RBC, WBC or Platelet. It includes;  The production of erythrocytes is called as Erythropoiesis; the leukocytes are called as Leucopoiesis and that of platelets is Thrombopoiesis.  Leucopoiesis is further subdivided into – * Granulopoiesis – formation of granulocytes * Monopoiesis – formation of monocytes * Lymphopoiesis – formation of lymphocytes
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  ERYTHROPOISES (FORMATION OF REDBLOOD CELLS  It is the process of formation, development, and maturation of red blood cells.  Life span. 100 to 120 days.  Lost RBCs. Lost cells are replaced more or less continuously by the division of hemocytoblasts in the red bone marrow.  Immature RBCs. Developing RBCs divide many times and then begin synthesizing huge amounts of hemoglobin.  Reticulocyte. Suddenly, when enough hemoglobin has been accumulated, the nucleus and most organelles are ejected and the cell collapses inward;  Mature erythrocytes. Within 2 days of release, they have rejected the remaining ER and have become fully functioning erythrocytes; the entire developmental process from hemocytoblast to mature RBC takes 3 to 5 days.  Erythropoietin. The rate of erythrocyte production is controlled by a hormone called erythropoietin; normally a small amount of erythropoietin circulates in the blood at all times, and red blood cells are formed at a fairly constant rate.  Control of RBC production. An important point to remember is that it is not the relative number of RBCS in the blood that controls RBC production; control is based on their ability to transport enough oxygen to meet the body’s demands.
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  SITE OF HEMATOPOIESIS The site of Hematopoiesis depends on the age of the person as follows –  In human embryo – Yolk sac is the main site of Hematopoiesis  By the 3rd to 7th month of Intra-uterine life – Hematopoiesis occurs in liver and spleen.  By the 7th month till birth – it starts in the bone marrow.  From birth till maturity – occurs in bone marrow, spleen, and liver.  In adults – Hematopoiesis occurs in the Central skeleton (Vertebrae, Sternum, Ribs, Skull, Sacrum, and pelvis), proximal ends of the long bones like Femur, Tibia, and Humerus.
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   Regulation ofErythropoiesis – Erythropoietin is the hormone produced mainly by the kidneys, helps to regulate the process of Erythropoiesis so that the number of RBCs is sufficient to sustain adequate tissue oxygen levels.
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   Reticulocytes arecalled as the juvenile RBCs or Immature RBCs.  Reticulocytes spend 1-2 days in the marrow then 1- 2 days in circulation where it gets mature into Erythrocytes and attains biconcave shape.  Normal range of Reticulocytes –  Adults – 0.5 – 2.5%  Infants – 2 – 6%
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  STRUCTURE OF ERYTHROCYTES Erythrocytes, also referred to as Red Blood Cells (RBCs) is a significant cellular component of blood. These cells circulate in the blood carrying oxygen from the lungs to all the tissues of the body. It is responsible for imparting blood with its characteristic colour.  Mature erythrocytes in humans are rounded, small and biconcave, as though dumbbell-shaped. As the cell is flexible, it can reform to take up a bell shape when it passes through the super tiny blood vessels.
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   RBCs orerythrocytes exhibit a diameter of 7-8 µm possessing an atypical structure in comparison to most other body cells of humans. The RBC structure resembles a donut, they are biconcave wherein their periphery is thicker than their central portion. Courtesy to this feature, the total surface of the cell membrane is maximized enabling exchange of gases and their transport.  These cells are anuclear and do not have any other intracellular organelles as they are lost in erythropoiesis. There are two main structures – cytoplasm engirdled by a cell membrane.
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   Cytoplasm –It is filled with haemoglobin which in turn contains acidophilia causing erythrocytes to stain intense red with eosin on the samples of tissues stained with hematoxylin and eosin.  Cell membrane – This membrane is a lipid layer containing two types of membrane proteins – peripheral and integral.  The RBC membrane is a two-dimensional structure comprising a cytoskeleton and a lipid bilayer bound together. The lipid bilayer has different types of cholesterol, phospholipids, sphingolipids, and integral membrane proteins like the glycophorin.
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   The peripheralmembrane proteins extend into the cytoplasm only, as they are found on the inner surface of the plasma membrane. The proteins are interconnected by several intracellular filaments which form a complex mesh-like cytoskeletal network through the inner cell membrane. This network is responsible for imparting strength and elasticity to RBCs enabling its even passage into the thinnest and smallest capillaries without any breakage/leakage.  Integral membrane proteins are innumerable, stretching throughout the thickness of the cell membrane. It binds haemoglobin serving as anchor points for the cytoskeletal network of RBCs. Additionally, they express antigens of ABO blood groups. Erythrocyte surface antigens are necessary for blood transfusions.
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  RED BLOOD CELLS– FUNCTION Basic and important functions of RBCs:  Delivers oxygen from the lungs to the tissues all through the body ( exchange of gases)  Facilitates carbon dioxide transport  Acts as a buffer and regulates hydrogen ion concentration  Contributes to blood viscosity  Carries blood group antigens and Rh factor
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  LEUKOPOIESIS  It isthe process of formation or production of leucocytes which normally occurs in the blood-forming tissue of the bone marrow. There are 3 independent series, which leads to the formation of 3 different types of white cells –  Granulocytes – Granulopoiesis  Lymphocytes – Lymphopoiesis  Monocytes – Monopoiesis/ Monocytopoiesis  The formation of White Blood cells is regulated by –  Stimulation by cytokines and Colony stimulating factor.  Produced by Macrophages & T – lymphocytes.  Activated by coming in contact with foreign organisms.
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  GRANULOPOIESIS  Granulopoiesis isthe process of formation or production of Granulocytes that are the type of White blood cells that contains the granules in their cytoplasm, which begins at the Myeloblast and passes through the stages of a Promyelocyte, Myelocyte, Metamyelocyte and Band cells and ultimately results in the formation of 3 types of Granulocytes – Neutrophils, Eosinophils & the Basophils.
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  LYMPHOPOIESIS  Lymphopoiesis isthe process of formation or production of Lymphocytes, a type of white blood cells that lack the granules in their cytoplasm, which begins at the Lymphoblast and passes through the stage of Prolymphocyte and ultimately results in the formation of mature Lymphocytes.
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  MONOPOIESIS/ MONOCYTOPOIESIS  Monopoiesisor Monocytopoiesis is the process of formation of production of Monocytes, a type of White blood cells that lack the granules in their cytoplasm, which begins at the Monoblast, passes through the stage of Promonocyte and ultimately results in the formation of mature Monocytes.
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  THROMBOPOIESIS  Thrombopoiesis isthe formation or production of Thrombocytes or Platelets in the bone marrow which is formed by fragmentation of mature Megakaryocyte membrane projections, begins at Megakaryoblast and passes through the stages of Promegakaryocyte and then the Megakaryocytes ultimately results in the formation of mature Thrombocytes or Platelets.
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  HAEMOGLOBIN  Haemoglobin (Hb)is a type of globular protein present in red blood cells (RBCs), which transports oxygen in our body through blood.  The standard abbreviation for Haemoglobin is “Hb”  The haemoglobin level is measured in g/dL of the blood.  In a healthy individual, the level ranges from 12 to 20 g/dL. Generally Hb level in males is greater compared to females. The normal level in males is 13.5 to 17.5 g/dL and in females, it is 12 to 15.5 g/dL.
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   Haemoglobin developin the cells of the bone marrow. Eventually, they turn into red blood cells.  Hence, Haemoglobin is a hemeprotein found in only in red blood cells (RBC) or the erythrocytes of blood. They are said to occupy 1/3rd of the volume of RBCs. 90- 95% of the dry weight of red blood cells is by haemoglobin. Functions:  Transport of oxygen: Every 100 ml of oxygenated blood carries 5 ml of O2 to the tissues.  Transport of Carbon dioxide: Every 100 ml of deoxygenated blood carries 4 ml of CO2 to the alveoli.
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  Types of Haemoglobin The main types of Haemoglobin are –  Haemoglobin A: Most common form of Haemoglobin found in the adult human being. It is a combination of two alpha and two beta chains.  Haemoglobin A2: It is indicative of 2-3% of Haemoglobin found in the adult human being and is a combination of two alpha and two delta chains.  Haemoglobin F: It is seen in newborns blood (1% in its Haemoglobin) and is the combination of two alpha and two gamma chains.
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  Diseases related toHaemoglobin  Haemoglobin deficiency leads to the lower oxygen-carrying capacity of the blood. It can be due to nutritional deficiency, cancer, kidney failure or any genetic defects.  Higher than normal haemoglobin level is associated with various heart and pulmonary diseases.  Sickle cell anaemia – It is due to a defect in the haemoglobin gene.  Thalassemia – It is caused due to less production of haemoglobin. There are two types of thalassemia, 𝜶- thalassemia and 𝞫-thalassemia. It is also caused due to defective genes and severity depends on how many genes are missing or defective.  Haemoglobin level is commonly used as a diagnostic tool. The HbA1c level, i.e. glycosylated Hb or Hb linked with sugar is a marker for average glucose level in the blood of a diabetic patient.
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  CLOTTING MECHANISM OFBLOOD Blood Coagulation  It is defined as the process by which a blood clot forms and potentially leads to hemostasis, the cessation of blood loss from a damaged vessel, followed by repair.  Blood coagulation or clotting is an important phenomenon to prevent excess loss of blood in case of injury or trauma.  The blood clot or ‘coagulum’ is formed by a network of fibrin threads. In this network, deformed and dead formed elements (erythrocytes, leukocytes and platelets) get trapped.
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   Prothrombin isthe inactive form of thrombin that is present in the plasma. Thrombokinase converts prothrombin to active thrombin which in turn activates fibrinogen to fibrin. All these clotting factors help in blood coagulation.  An injury stimulates platelets or thrombocytes to release various factors that initiate the blood clotting cascade. Calcium ions play an important role in blood coagulation.
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  FACTORS INVOLVED INBLOOD COAGULATION  Coagulation of blood occurs through a series of reactions due to the activation of a group of substances called clotting factors.  There are 13 clotting factors identified and named after the scientists who discovered them or as per the activity.  Only factor IX or Christmas factor is named after the patient in whom it was discovered.
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  BLOOD COAGULATION PATHWAY The process of blood coagulation leads to haemostasis, i.e. prevention of bleeding or haemorrhage.  Blood clotting involves activation and aggregation of platelets at the exposed endothelial cells, followed by deposition and stabilisation of cross-linked fibrin mesh.  Primary haemostasis involves platelet aggregation and formation of a plug at the site of injury, and secondary haemostasis involves strengthening and stabilisation of platelet plug by the formation of a network of fibrin threads.  The secondary haemostasis involves two coagulation pathways, the intrinsic pathway and the extrinsic pathway. Both pathways merge at a point and lead to the activation of fibrin, and the formation of the fibrin network.
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  PLATELET ACTIVATION  Theblood circulating in the blood vessel does not clot under normal circumstances. The blood coagulation process is stimulated when there is any damage to the endothelium of blood vessels.  It leads to platelet activation and aggregation.  When collagen is exposed to the platelets due to injury, the platelets bind to collagen by surface receptors.  This adhesion is stimulated by the von Willebrand factor released from endothelial cells and platelets.  This forms additional cross-linking and activation of platelet integrins, which facilitate tight binding and aggregation of platelets at the site of injury. This leads to primary haemostasis.
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  BLOOD COAGULATION CASCADE/PROCESS  The process of coagulation is a cascade of enzyme catalysed reactions wherein the activation of one factor leads to the activation of another factor and so on. The three main steps of the blood coagulation cascade are as follows:  Formation of prothrombin activator  Conversion of prothrombin to thrombin  Conversion of fibrinogen into fibrin
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  1. Formation ofprothrombin activator  The formation of a prothrombin activator is the first step in the blood coagulation cascade of secondary haemostasis. It is done by two pathways, viz. extrinsic pathway and intrinsic pathway. Extrinsic Coagulation Pathway  It is also known as the tissue factor pathway. It is a shorter pathway. The tissue factors or tissue thromboplastins are released from the damaged vascular wall. The tissue factor activates the factor VII to VIIa. Then the factor VIIa activates the factor X to Xa in the presence of Ca2+. Intrinsic Coagulation Pathway  It is the longer pathway of secondary haemostasis. The intrinsic pathway begins with the exposure of blood to the collagen from the underlying damaged endothelium. This activates the plasma factor XII to XIIa.  XIIa is a serine protease, it activates the factor XI to XIa. The XIa then activates the factor IX to IXa in the presence of Ca2+ ions.  The factor IXa in the presence of factor VIIIa, Ca2+ and phospholipids activate the factor X to Xa.
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  2. Conversion ofprothrombin to thrombin  Prothrombin or factor II is a plasma protein and is the inactive form of the enzyme thrombin. Vitamin K is required for the synthesis of prothrombin in the liver.  The prothrombin activator formed above converts prothrombin to thrombin.  Thrombin is a proteolytic enzyme. It also stimulates its own formation, i.e. the conversion of prothrombin to thrombin.  It promotes the formation of a prothrombin activator by activating factors VIII, V and XIII.
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  3. Conversion offibrinogen into fibrin  Fibrinogen or factor I is converted to fibrin by thrombin.  Thrombin forms fibrin monomers that polymerise to form long fibrin threads.  These are stabilised by the factor XIII or fibrin stabilising factor.  The fibrin stabilising factor is activated by thrombin to form factor XIIIa.  The activated fibrin stabilising factor (XIIIa) forms cross- linking between fibrin threads in the presence of Ca2+ and stabilises the fibrin meshwork.  The fibrin mesh traps the formed elements to form a solid mass called a clot.
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  CLOTTING TIME  Clottingtime is a general term for the time required for a sample of blood to form a clot, or, in medical terms, coagulate.  The Clotting Time Blood Test helps determine the time it takes for a sample of blood to form a blood clot while in a glass test tube of standard size. It was once regularly used to diagnose clotting disorders Normal clotting time (CT)  The expected range is 3 to 8 minutes.  The glass tube method clotting time is 5 to 15 minutes.  The siliconized tube’s clotting time is 19 to 60 minutes (reference: Interpretation of diagnostic test by Jacques Wallach M.D.)
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  BLEEDING TIME (BT) Bleeding time is the functional test of primary hemostasis that checks how quickly the blood clots stop the bleeding.  This test diagnoses bleeding problems related to the abnormalities of:  Platelets functions. Platelets response to vascular injury.  Vascular response to injury.  Blood vessel elasticity also influences the bleeding time.  The ability of the blood vessels to constrict.  Bleeding times is the best single screening test for acquired causes like uremia or congenital functional or structural disorder of platelets. NORMAL Values Of Bleeding G Time (BT)  Bleeding time normal: 3 to 6 minutes  Borderline: 7 to 11 minutes.  Abnormal value: 10 to 15 minutes
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  PROTHROMBIN TIME (PT) The prothrombin time (PT) test measures how long it takes for a blood clot to form based on a protein produced by the liver called prothrombin.  With the PT test, the reference range is between 10 to 12 seconds
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  PARTIAL THROMBOPLASTIN TIME(PTT)  The partial thromboplastin time (PTT) test also measures the speed of clotting but differs from the PT test in that it aims to establish how blood clots within a blood vessel (intrinsic pathway).  PTT test, the reference range is between 25 and 33 seconds.
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  HEMOSTASIS  Platelets arekey players in hemostasis, the process by which the body seals a ruptured blood vessel and prevents further loss of blood. Although rupture of larger vessels usually requires medical intervention, hemostasis is quite effective in dealing with small, simple wounds.  There are three steps to the process: vascular spasm, the formation of a platelet plug, and coagulation (blood clotting). Failure of any of these steps will result in hemorrhage—excessive bleeding.
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  STAGES OF HEMOSTASIS When a blood vessel is injured, a series of reactions initiate, resulting in hemostasis, which occurs in three stages; • Vasoconstiction • Platelet plug formation • Coagulation of blood ( Blood Clotting)
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  VASOCONSTRICTION  When avessel is severed or punctured, or when the wall of a vessel is damaged, vascular spasm occurs.  This vascular spasm occurs to reduce pressure to the damaged area of the vessel, and minimize blood loss.  This phenomenon typically lasts for up to 30 minutes, although it can last for several hours.
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  FORMATION OF THEPLATELET PLUG  In the second step, platelets, which normally float free in the plasma, encounter exposed connective tissue found inside the damaged vessel.  This causes platelets to clump together, become sticky, and bind to the exposed collagen and endothelial lining.  This process is assisted by a glycoprotein in the blood plasma called von Willebrand factor, which helps stabilize the growing platelet plug.  As platelets collect, they simultaneously release chemicals from their granules into the plasma that further contribute to hemostasis. Among the substances released by the platelets are:  Adenosine diphosphate (ADP) – helps additional platelets to adhere to the injury site, reinforcing and expanding the platelet plug  Serotonin – maintains vasoconstriction  Prostaglandins and phospholipids – maintain vasoconstriction and help to activate further clotting chemicals  A platelet plug temporarily seals a small opening in a blood vessel, which allows the body time to make more sophisticated and durable repairs.
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  COAGULATION  These sophisticatedand durable repairs made beyond the plug formation are collectively called coagulation, the formation of a blood clot.  The process is sometimes characterized as a cascade, because one event prompts the next as in a multi-level waterfall.  The result is the production of a gelatinous but robust clot made up of a mesh of an insoluble protein called fibrin, which is derived from a plasma protein called fibrinogen.  This mesh traps platelets and blood cells
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  BLOOD GROUPS ANDTYPES
• 83.
   Karl Landsteiner,an Austrian scientist discovered the ABO blood group system in the year 1900.  In his experiments, he mixed different blood types and noted that the plasma from certain blood type produced agglutinates or formed clusters which were caused by the absence of molecules on red blood cells and resulting in antibodies to defeat that molecule.  He then made a note of the agglutination and divided the blood types into 4 different groups.  For the discovery of ABO blood group, he was awarded the Nobel Prize.  The blood grouping system is pivotal in blood transfusion.  Our immune system recognizes another blood type as foreign and attacks it if introduced in the body causing a transfusion reaction.
• 84.
  ABO AND RHBLOOD GROUPS  During the blood transfusion, the two most important group systems examined are the ABO-system and the Rhesus system.  The ABO blood group system consists of 4 types of blood group – A, B, AB, and O and is mainly based on the antigens and antibodies on red blood cells and in the plasma. Both antigens and antibodies are protein molecules in which antigens are present on the surface of Red Blood Cells and antibodies are present in the plasma which is involved in defending mechanisms.  On the other hand, the Rh blood group system consists of 50 defined blood group antigens. In the Rh system, the most important antigens are D, C, c, E, and e.
• 85.
  1. ABO BLOODGROUP SYSTEM  The basis of ABO grouping is of two antigens- Antigen A and Antigen B. The ABO grouping system is classified into four types based on the presence or absence of antigens on the red blood cells surface and plasma antibodies.  Group A – contains antigen A and antibody B.  Group B –contains antigen B and antibody A.  Group AB –contains both A and B antigen and no antibodies (neither A nor B).  Group O – contains neither A nor B antigen and both antibodies A and B.
• 86.
   The ABOgroup system is important during blood donation or blood transfusion as mismatching of blood group can lead to clumping of red blood cells with various disorders.  It is important for the blood cells to match while transfusing i.e. donor-recipient compatibility is necessary.  For example, a person of blood group A can receive blood either from group A or O as there are no antibodies for A and O in blood group A.  Individuals of blood group O are called as universal donors, whereas individuals of blood group AB are universal recipients.
• 88.
  2. RH BLOODGROUP SYSTEM  In addition to the ABO blood grouping system, the other prominent one is the Rh blood group system.  About two-thirds of the population contains the third antigen on the surface of their red blood cells known as Rh factor or Rh antigen; this decides whether the blood group is positive or negative.  If the Rh factor is present, an individual is rhesus positive (Rh+ve); if an Rh factor is absent individual is rhesus negative (Rh-ve) as they produce Rh antibodies.  Therefore, compatibility between donor and individual is crucial in this case as well.
• 89.
  THE RETICULOENDOTHELIAL SYSTEM(RES)  The RES is also known as the mononuclear phagocyte system. This system consists of cellular and noncellular components.  The reticuloendothelial system (RES) is a heterogeneous population of phagocytic cells in systemically fixed tissues that play an important role in the clearance of particles and soluble substances in the circulation and tissues, and forms part of the immune system.  Substances that are cleared include immune complexes, bacteria, toxins, and exogenous antigens
• 90.
   The RES:Consists of the phagocytic cells located in reticular connective tissue, primarily monocytes and macrophages. Since phagocytosis is their primary role, mononuclear phagocytic system has been suggested as an alternative name. The composition of the reticuloendothelial system includes  Kupffer cells of the liver  Microglia of the brain  Alveolar macrophages  Bone marrow  Lymph nodes  Macrophages in the intestine and other tissues.
• 91.
  REGULATION OF THERES The reticuloendothelial system is also under the leading role of the nervous system and is regulated by chemicals in the body fluids. The state of the cerebral cortex has a great influence on the activity of macrophages in the reticular endothelium.  The more the cortex is excited, the more activity in the reticuloendothelial system is inhibited. eg when a person's painful cerebral cortex is in an excited state, the function of the reticuloendothelial system is inhibited.  If the cerebral cortex is in a state of inhibition, such as during sleep or anesthesia, activity on phagocytic cells is enhanced.  The chemical regulation of endocrine and vitamins also has a certain effect on the function of the reticuloendothelial system. eg. Experiments have shown that in the absence of vitamin C or injection of adrenaline, the phagocytic activity of the reticuloendothelial system becomes sluggish, the phagocytic capacity is also weakened, and the production of collagen fibers is also poor
• 92.
  FUNCTIONS OF THERETICULO-ENDOTHELIAL SYSTEM:
• 93.
   i. Phagocytosis:They engulf foreign particles, bacteria and parasites and in this way, act as a great defensive mechanism.  ii. Formation of Antibodies: The antitoxic and antibacterial bodies are manufactured by this system. This is also a great protective mechanism.  iii. Formation of R.B.C: Red blood cells develop from the R.E. cells. Turnbull holds that they develop from the extravascular R.E. cells (haemocytoblasts).  iv. Formation of Leucocytes: The granulocytes, lymphocytes and monocytes—are all derived from the R.E. system.  v. Destruction of Red Cells and White Cells: The senile red cells and white cells are engulfed and destroyed by the R.E. cells. In adult life, it takes place chiefly in the spleen and liver.
• 94.
   vi. Scavengersof Tissue Debris and Bacteria in Infections Processes: The R.E. cells help in the scavenging process.  vii. Formation of Bile Pigments: The R.E. cells manufacture bilirubin from haemoglobin.  viii. Storage Function: A large amount of lipids, cholesterol and iron are stored in the R.E. cells.  ix. Manufacture of Plasma Proteins: Serum globulin and certain other plasma proteins are manufactured, to some extent, by the R.E. cells.  x. Formation of Tissue Cells: Since the cells of this system are undifferentiated, they can be converted into ordinary connective tissue cells, such as fibroblasts, under suitable stimulus. This is seen during repair stage of inflammatory process.
• 95.
  IMMUNITY  Immunity isthe ability of the body to defend itself against disease-causing organisms.  Everyday our body comes in contact with several pathogens, but only a few results into diseases.  The reason is, our body has the ability to release antibodies against these pathogens and protects the body against diseases. This defence mechanism is called immunity.
• 97.
  TYPES OF IMMUNITY Thereare two major types of immunity:  Innate Immunity or Natural or Non-specific Immunity.  Acquired Immunity or Adaptive Immunity. Innate Immunity  This type of immunity is present in an organism by birth.  This is activated immediately when the pathogen attacks. Innate immunity includes certain barriers and defence mechanisms that keep foreign particles out of the body.  This immunity helps us by providing the natural resistance components including salivary enzymes, natural killer cells, intact skin and neutrophils, etc. which produce an initial response against the infections at birth prior to exposure to a pathogen or antigens.  It is a long-term immunity in which our body produces the antibodies on its own. Our body has few natural barriers to prevent the entry of pathogens.
• 98.
  Barriers in InnateImmunity:  Physical Barriers: These include the skin, body hair, cilia, eyelashes, respiratory tract, and gastrointestinal tract. The skin acts as a physical barrier, preventing pathogen entry. Mucus in the nose and ears also traps pathogens.  Physiological Barriers: Stomach acid breaks down food molecules, killing many germs. Saliva and tears have antibiotic properties.  Cellular Barriers: Leukocytes (white blood cells), neutrophils, lymphocytes, basophils, eosinophils, and monocytes play a role. They are present in blood and tissues.  Cytokine Barriers: Cells secrete interferons when invaded by viruses. Interferons coat infected cells, preventing nearby cells from getting infected.
• 99.
  Cells Involved InInnate Immunity  Phagocytes: These circulate through the body and look for any foreign substance. They engulf and destroy it defending the body against that pathogen.  Macrophages: These have the ability to move across the walls of the circulatory system. They release certain signals as cytokines to recruit other cells at the site of infections.  Mast Cells: These are important for healing wounds and defence against infections.  Neutrophils: These contain granules that are toxic in nature and kill any pathogen that comes in contact.  Eosinophils: These contain highly toxic proteins that kill any bacteria or parasite in contact.  Basophils: These attack multicellular parasites. Like the mast cells, these release histamine.  Natural Killer Cells: These stop the spread of infections by destroying the infected host cells.  Dendritic Cells: These are located in the tissues that are the points for initial infections. These cells sense the infection and send the message to the rest of the immune system by antigen presentation.
• 100.
  Acquired Immunity  Acquiredimmunity or adaptive immunity is the immunity that our body acquires or gains over time. Unlike the innate immunity, this is not present by birth.  The ability of the immune system to adapt itself to disease and to generate pathogen-specific immunity is termed as acquired immunity. It is also known as adaptive immunity.  An individual acquires the immunity after the birth, hence is called as the acquired immunity.  It is specific and mediated by antibodies or lymphocytes which make the antigen harmless.  The main function of acquired immunity is to relieve the victim of the infectious disease and also prevent its attack in future.