PL1025 19/10/22 Blood Physiology Total Body Water: - - Approx 60% of body weight0 ▪ E.g. 70kg male has 40-45L of water Divided between Extracellular Fluid (ECF) and Intracellular Fluid (ICF) ECF = Interstitial Fluid (ISF) and Plasma Composition of Blood: - Plasma = 55% of blood Formed elements = 45% of blood PLASMA: Components of plasma: Plasma proteins – 7% Other solutes – 1% Water – 92% Transports organic and inorganic molecules, formed elements, and heat Plasma is a component of the ECF compartment o o o - - 1. Plasma Proteins: - Albumins (60%) - major contributors to osmotic pressure of plasma; transports lipids and steroid hormones - Globulins (35%) – transports ions, hormones, and lipids; immune function - Fibrinogen (4%) – essential component of clotting system; can be converted to insoluble fibrin - Regulatory proteins (<1%) – enzymes, proenzymes, hormones 2. Other Solutes: - Electrolytes – normal extracellular fluid ion composition essential for vital cellular activities (e.g. Sodium, potassium, calcium, chlorine, bicarbonate - Organic nutrients – used for ATP production, growth, and maintenance of cells - Organic wastes – carried to sites of breakdown or excretion (e.g. urea, bilirubin) FORMED ELEMENTS OF BLOOD: - Platelets -0.1% White Blood Cells - ^^ - Red Blood Cells - 99.9% White Blood Cells: - Neutrophils – 50-70% Eosinophils – 2-4% Basophils - <1% Lymphocytes – 20-30% Monocytes – 2-8% Red Blood Cells: - Mature cells are non-nucleated Size and unusual shape – biconcave RED BLOOD CELLS: Erythrocyte Production: - - Begins in utero 6-7 months the bone marrow takes over Children – all bone marrow involved Later life – only sternum, vertebrae, ribs and pelvis Requirements: - Adequate nutrition Protein Vitamins (e.g. B12 Folic Acid) Hormone – Erythropoietin released by the kidney Lack of RBC and/or Hb -anaemia (reduced oxygen carrying capacity of the blood) Sequence of Events in Red Blood Cell Production: Erythropoiesis: - 2.5 million RBCs are produced per second Lifespan of 120 days Old RBCs are removed from blood by phagocytic cells in the liver, spleen and bone marrow ▪ Iron recycled back into haemoglobin production Role of Erythropoietin in Production of Erythrocytes: - In absence of any disease, access to high altitude will initiate a psychological increase in RBC production to combat the lack of oxygen in the air Synthetic EPO available (e.g., patients with chronic renal failure) - Use of EPO for blood doping in sport – potentially very dangerous increased viscosity leading to heart failure and/or stroke polycythaemia Functions of Red Blood Cells: - - Contain haemoglobin (Hb) Oxygen transport Carbon dioxide transport Blood buffer – to maintain normal blood pH of 7.4 Structure of Haemoglobin: - - 4 polypeptide chains In foetus HbF Foetal Hb binds to oxygen much more easily than Hb A – very useful in utero Changes to HbA around 6 months Each linked to one haemoglobin molecule Each haemoglobin molecule contains one iron atom to which Oxygen associates Haemoglobinopathies – Abnormal Hb e.g. HbS Sickle cell disease, thalassaemia, anaemia, can vary from mild to severe Anaemia - Many Causes: Sickle Cell disease genetic disorder Sickle Cell haemolytic anaemia sickled cells are fragile – need for blood transfusions – cells become trapped in microcirculation obstruct blood flow cause ischaemia and pain which can be severe, also stroke, jaundice, respiratory symptoms Red Blood Cell Breakdown: - Lifespan of around 120 days – cells become very fragile Trapped in spleen (RBC ‘graveyard’) Heme separated from globin globin recycled as amino acids Heme breakdown yields iron recycled Other heme breakdown products yield biliverdin bilirubin Bilirubin – yellow pigment which is taken to the liver and secreted in bile Jaundice – results from high levels of bilirubin in blood – can also occur in liver disease where the diseased liver is unable to handle even the normal levels of bilirubin Blood Groups: - Determined by the antigen present on the red cell membrane - Blood group O Rh negative = ‘Universal donor’ – no antigens to react with patient’s plasma Each blood group is either Rhesus + or Rhesus – Blood Transfusion: - - Patients blood is typed and then crossmatch is performed between donor cells and patient’s serum If antigen on donor’s cell encounters corresponding antibody E.g. Patient blood group ‘B’ receives a transfusion of group ‘A’ blood Result: ‘A’ antigens on donors red cells contact ‘A’ antibodies in patients blood causing Antigen-Antibody reaction Agglutination of patient’s RBC with haemolysis and release of Hb and K+ into circulation Kidney damage and liver damage Role of Platelets: - Damage to endothelium allows platelets to bind to exposed collagen o Von Willebrand factor increases bond by binding to both collagen and platelets o Platelets stick to collagen and release ADP, serotonin and thromboxane A2 o = platelet release reaction Blood Clotting: - - - Two distinct pathways activated in a cascade fashion using a variety of chemicals – clotting factors (produced in liver) Vitamin K and Ca++ : essential for normal clotting Both pathways can be assessed in cases of bleeding disorders Both pathways converge at prothrombinase to become the common pathway Ultimately, Fibrinogen converted to Fibrin Clot retraction/dissolution also important – fibrinolysis – with conversion of inactive plasminogen to the active form plasmin – breakdown the clot Synthetic clot busters available Factor VIII and IX are examples of clotting factors lack of them leads to Haemophilia A and B (respectively) WHITE BLOOD CELLS: - Divided into granulocytes and agranulocytes Granulocytes: o Neutrophil o Eosinophil o Basophil Agranulocytes: o Monocyte o Lymphocyte Agranulocytes: - Lymphocytes o Specific/adaptive immune response Monocytes: o Become fixed tissue macrophages o Take up residents in different organs – first line of defence o Phagocytic and secretory functions o Secretions include: ▪ Interleukins ▪ TNFa ▪ Prostaglandins ▪ Bradykinin Lymphocytes: B Cells: - - Provide humoral immunity Produce antibodies (plasma cells) which binds to antigen – makes antigens recognisable to immune system so they can be destroyed - Opsonisation NK (Natural Killer) cells: separate population of lymphocytes o Immunological surveillance, cytotoxic cells Memory cells T Lymphocytes: - Originate from stem cell in bone marrow Cell-mediated immunity Helper T cells facilitate immune response – directly stimulate B cell function Release lymphokines Immune System: - Immunity: a state of resistance against infection from a particular pathogen Antigen: immune system normally rexognises ‘foreign’ (non-self) from ‘self’ antigens Immune system detects presence of antigens and initiates a complex series of steps designed to neutralise them 2 basic types of immunity: o Non-specific (Innate) – born with o Specific (Adaptive) Components of Non-specific/Innate Immunity: Physical Barriers: - Prevent approach of/ deny access to pathogens Phagocytes: - Remove debris and pathogens Immunological surveillance: - Destroys abnormal cells Lysed abnormal cell – ruptured abnormal cell Interferons (Interleukins): - Immune system mediators Help destroy pathogenic organisms Complement System: (GOOD) - Collection of proteins that are activated in a cascade fashion Inflammatory response: - Blood flow increased Phagocytes increased Capillary permeability increased (easier for things to get out) Compliment activated Clotting reaction walls off region (localise inflammatory response to avoid spreading) Regional temperature increased Specific defences activated Fever: - Mobilises defences Accelerates repairs Inhibits pathogens Respiratory Tract: - Cilia trapping particles GI Tract: - Lined with IgA antibodies in saliva and all along tract; Acidic pH of stomach will destroy many pathogens The Inflammatory Response: - A component of innate/ non-specific immunity - - Chemotaxis: a process where white blood cells are attracted to a site of infection Vasodilation: allows more blood to pour into area C reactive protein (CRP) increases as part of the Inflammatory Response useful diagnostic marker for infection IL-1 and IL-6 from macrophages target the: o Hypothalamus: the body’s thermostat fever Specific Immunity: - Responds to threats on an individualised basis o Innate Immunity: ▪ - Genetically determined: no prior exposure of antibody production involved o Acquired Immunity: Produced by prior exposure/antibody production ▪ Passive Immunity: Produced by transfer of antibodies from another person • 1. Natural Passive Immunity: Conferred by transfer of maternal antibodies across placenta/in breast milk • 2. Induced Passive Immunity: Conferred by administration of antibodies to combat infection OR: ▪ Active Immunity: Produced by antibodies that develop in response to antigens • 1. Naturally Acquired Active Immunity: Develops after exposure to antigens in environment • 2.Induced Active Immunity: Develops after administration of antigen to prevent disease
