Physical Characteristics of Blood • Thicker (more viscous) than water and flows more slowly than water • Temperature of 100. 4 degrees F • p. H 7. 4 (7. 35 -7. 45) • 8 % of total body weight • Blood volume – 5 to 6 liters in average male – 4 to 5 liters in average female – hormonal negative feedback systems maintain constant blood volume and osmotic pressure
Blood components • 55% = plasma: mainly water – 7 to 8% dissolved substances (sugars, amino acids, lipids & vitamins), ions, dissolved gases, hormones – most of the proteins are plasma proteins: provide a role in balancing osmotic pressure and water flow between the blood and extracellular fluid/tissues – loss of plasma proteins from blood – decreases osmotic pressure in blood and results in water flow out of blood into tissues swelling – most common plasma proteins: albumin, globulins, clotting proteins (fibrin)
Blood: Cellular elements • 45% of blood is the cellular elements or formed elements • 99% of this (44. 55% of total blood) is erythrocytes or RBCs – formed by differentiation of hematopoietic stem cells (HSCs) in the red bone marrow of long bones and pelvis – makes about 2 million per second! – made from an immature cell = reticulocyte – as they mature in the marrow they lose most organelles and its nucleus – lives only about 120 days – destroyed by the liver and spleen – liver degrades the hemoglobin to its globin component and the heme is degraded to a pigment called bilirubin - bile – Iron(Fe+3) • • transported in blood attached to transferrin protein stored in liver, muscle or spleen attached to ferritin or hemosiderin protein in bone marrow being used for hemoglobin synthesis
-1% found in the Buffy coat : -leukocytes (WBCs) and platelets (thromobocytes) -neutrophils: phagocytic properties -release agents which destroy/digest bacteria -eosinophils: parasitic defense cells -also involved in the allergic response -release histaminase to slows down inflammation caused by basophils -basophils: release heparin, histamine & serotonin -heighten the inflammatory response and account for hypersensitivity (allergic) reaction -monocytes: enter various tissues and differentiate into phagocytic macrophages -lymphocytes: T and B cells
Hematopoiesis HSC
Hematocrit • Percentage of blood occupied by cells – female normal range • 38 - 46% (average of 42%) – male normal range • 40 - 54% (average of 46%) • testosterone • Anemia – not enough RBCs or not enough hemoglobin • Polycythemia – too many RBCs (over 65%) – dehydration, tissue hypoxia, blood doping in athletes
Blood Groups and Blood Types • RBC surfaces are marked by genetically determined glycoproteins & glycolipids – agglutinogens or isoantigens – distinguishes at least 24 different blood groups • ABO, Rh, Lewis, Kell, Kidd and Duffy systems
RH blood groups • Antigen was discovered in blood of Rhesus monkey • People with Rh agglutinogens on RBC surface are Rh+. Normal plasma contains no anti-Rh antibodies • Antibodies develop only in Rh- blood type & only with exposure to the antigen – transfusion of positive blood – during a pregnancy with a positive blood type fetus • Transfusion reaction upon 2 nd exposure to the antigen results in hemolysis of the RBCs in the donated blood
Hemolytic Disease of Newborn • Rh negative mom and Rh+ fetus will have mixing of blood at birth • Mom's body creates Rh antibodies unless she receives a Rho. Gam shot soon after first delivery – can lead to miscarriage or spontaneous abortion of future Rh+ children – Rho. Gam binds to loose fetal blood and removes it from body before she reacts • In 2 nd child, hemolytic disease of the newborn may develop causing hemolysis of the fetal RBCs
• Symptoms – oxygen-carrying capacity of blood is reduced – fatigue, cold intolerance & paleness Anemia • lack of O 2 for ATP & heat production • Types of anemia – iron-deficiency = lack of absorption or loss of iron • type of nutritional anemia • failure to take in essential raw ingredients not made by the body – pernicious = lack of intrinsic factor for vitamin B 12 absorption from the digestive tract • B 12 is essential for normal RBC formation and maturation • binding of B 12 to intrinsic factor allows its absorption • intrinsic factor – synthesized by the small intestine – hemorrhagic = loss of RBCs due to bleeding (ulcer) – hemolytic = defects in cell membranes cause rupture • rupture of too many RBCs by external factors such as malaria (normal RBCs) or genetic disorders like sickle cell anemia (defective RBCs) – thalassemia = hereditary deficiency of hemoglobin – aplastic = destruction of bone marrow (radiation/toxins) • failure of the bone marrow to produce enough RBCs • may selectively destroy the ability to produce RBCs only • but may also destroy the myeloid stem cells – affect WBCs and platelets
Sickle-cell Anemia (SCA) • Genetic defect in hemoglobin molecule (Hb -S) that changes 2 amino acids in the globin protein – at low very O 2 levels, RBC becomes deformed by changes in hemoglobin molecule within the RBC • sickle-shaped cells do not pass through capillaries well and get stuck = causing occlusions and decreased blood flow to organs • also rupture easily = causing anemia & clots • Found among populations in malaria belt – Mediterranean Europe, sub-Saharan Africa & Asia • Person with only one sickle cell gene – increased resistance to malaria because RBC
Blood Clotting – in a test tube blood separates into liquid (serum) and a clot of insoluble fibers (fibrin) in which the cells are trapped – in the body the clot “plugs” damaged blood vessels and initiates healing – ultimate step is conversion of fibrinogen (soluble plasma protein) into insoluble fibrin • Substances required for clotting are Ca+2, enzymes synthesized by liver cells (clotting factors and plasma proteins) and substances released by platelets or damaged tissues – thrombin – released by damaged cells, catalyzes the conversion of fibrinogen to fibrin – 12 clotting factors involved • Clotting is a cascade of reactions in which each clotting factor activates the next in a fixed sequence resulting in the formation of fibrin threads – prothrombinase & Ca+2 convert prothrombin into thrombin – thrombin converts fibrinogen into fibrin threads
Overview of the Clotting Cascade -may be triggered through two possible paths 1. extrinsic pathway 2. intrinsic pathway -both pathways result in the release and activation of specific clotting factors -either path leads to activation of the common pathway -common pathway results in the formation of prothrombinase (clotting factors X and V) -prothrombinase activates thrombin -thrombin cleaves fibrinogen to form fibrin
The Body’s Response to Infection: The Immune System • Three lines of defense
The Body’s Response to Infection: First Line of Defense • 1. Skin – Sheds, takes pathogens with it – Has low p. H, repels microorganisms – Glands in skin secrete chemicals to slow bacterial growth • 2. Mucous membranes – Mucous traps pathogens – Can be sneezed, coughed away
The Body’s Response to Infection: Second Line of Defense • 1. White blood cells production • A. : macrophages and other phagocytes – Engulf and digest invasive organisms – Also digest old red blood cells and cellular debris – Can release chemicals to stimulate production of more white blood cells – like T and B cells • B. White blood cells: natural killer cells – Attack tumor cells and virus-infected cells – Release chemicals that break apart the cell membranes of infected cells or tumor cells
The Body’s Response to Infection: Second Line of Defense – Inflammation • 2. Inflammation: response which produces redness, warmth, swelling, and pain – After tissue injury, damaged cells release histamine – Histamine causes vasodilation which increases blood flow • this will increase more WBCs into the infected area • brings more O 2 and nutrients – BUT also brings in more fluid – some fluid gets pushed out into the surrounding tissues = Swelling
The Body’s Response to Infection: Second Line of Defense – Defensive Proteins • 3. Interferons are produced by infected cells – bind to healthy cells – stimulate production of anti-viral chemicals • 4. Complement proteins are made in response to inflammation and infection – are a class of about 20 different proteins – can coat surface of bacteria to facilitate phagocytosis – can make holes in bacterial membrane BOOM!
The Body’s Response to Infection: Second Line of Defense – Fever • 5. Fever – temperature above range of 97 -99º F – macrophages can release pyrogens • which causes temperature of tissue to increase – increased temperature inhibits bacterial growth – increases metabolism of healthy cells – promotes mitosis and tissue repair – large-scale production of pyrogens can increase overall body temperature = Fever – also increases the efficiency of immune cells
The immune system § Cells of the immune cells (macrophages, T cells, B cells) are found in specific locations called lymphatic tissues
The Body’s Response to Infection: Third Line of Defense – Lymphocytes • Lymphocytes are a specific defense because they recognize specific antigens – antigen = cell-surface protein that identifies the type of cell bearing it • also distinguishes it from antigens in another organism • when your immune system is developing – your lymphocytes learns what antigens belong to you and what don’t – develop self-tolerance • examples of non self-tolerant, foreign antigens = proteins found on or in viruses, bacteria, fungi, protozoans and worms. • Lymphocytes travel throughout the body in spaces between the cells and are carried in the blood and lymphatic system.
The Lymphatic System • Lymphocytes travel throughout the body in spaces between the cells and are carried in the blood and lymphatic system. • the lymphatic system = system of lymphatic vessels + lymph nodes + lymphatic tissues (spleen, thymus, tonsils) that filter lymph and circulate WBCs • lymph = yellow-colored fluid that is produced from your blood plasma – produced when plasma filters out of your blood and into your tissues – some of that filtrate becomes lymph
The Lymphatic System • Lymph comes from your blood plasma but is returned to you blood stream • along the way it flows through lymph nodes which house lymphocytes and macrophages • these immune cells clean the lymph of bacteria • so what gets returned to your blood is cleaned • lymph is the way we “launder” our blood http: //www. niaid. nih. gov/topics/immune. System/Pages/structure. Images. aspx
The Body’s Response to Infection: Third Line of Defense – Lymphocytes • Two types of Lymphocytes – A. T cells – B. B cells
Lymphocytes • Lymphocytes are produced from stem cells in the red bone marrow. • they are named by the location where they were first identified • B cells develop in the bone marrow • T cells develop in the thymus – thymus disappears over time
T and B Lymphocytes • B cells – Recognize small organisms such as bacteria by producing antibodies – antibodies = small proteins that bind foreign antigens and target the foreign cell for destruction by the host’s immune system – can respond to viruses if “helped” by T cells § Antibody: § abbreviated as Ig § made up of four protein chains § two light chains § two heavy chains – determine the type of antibody § “ends” of the antibody are specific for the foreign antigen = “Antigen-binding Site”
T and B Lymphocytes • T cells – Respond to larger organisms (e. g. fungus), viruses, and body cells that have gone awry (e. g. tumor cells) • also attack transplanted tissues! • if they attack normal cells = Auto-immune disease – Attack the antigen-bearing cell directly by secreting chemicals that kill it – help B cells and “teach” them what antibodies to make • can bind a foreign protein and then interact with a B cell • B cell then makes antibodies to that foreign protein
T and B Lymphocytes • B and T cells display cell-surface proteins that bind to foreign antigens – called antigen receptors – once they bind the T and B cells are called “activated” – activated T cells “help” B cells by physically binding them – the B cell then begins to make antibodies § B and T cells have a Memory § once the infection is cleared, there a small number of T and B cells that “remember” the infection § will become activated if the foreign antigen re-appears § faster activation than the 1 st time
Types of Immunity: Antibody and Cell. Mediated Immunity • B cell mediated immunity is called Antibody mediated immunity • B cells exposed to foreign antigens rapidly divide = clonal expansion • most B cells develop into plasma cells that make the antibodies • Rest of B cells become memory cells to provide long term immunity
Antibody and Cell-Mediated Immunity • T cell mediated immunity is called Cell-mediated immunity • T cells divide exposed to foreign antigens divide and develop into different types of cells – depends on the foreign antigen – if it’s a bacterial antigen helper T cells • help B cells make antibodies – if it’s a viral or tumor antigen cytotoxic T cells • secrete chemical to directly kill the pathogen • e. g. interferons • some stay as memory T cells
Cell-Mediated Immunity § T cells need “help” learning what a foreign antigen is § the are “presented” the foreign antigen by another cell = Antigen-Presenting cell § the APC internalizes the foreign invader and “displays” foreign antigens on its surface § the T cell binds the APC and “learns” what the foreign antigen looks like § the T cell is now activated and can develop either into helper or cytotoxic T cells foreign cell foreign antigen secrete chemicals called interleukins that enhance B cell and T cell activity also help B cells to make antibodies
Types of Immunity • immunity can also be classified into: • Passive Immunity – short-term immunity, lasts as long as the antibodies are in bloodstream. – can be passed on via fluids – e. g. antibodies found in breast milk • Active Immunity – long-term, caused by exposure to antigen and production of B and T cells. – basis for immunity from vaccinations
Vaccinations • Vaccinations attempt to take advantage of longterm immunity through exposure to parts of antigens. – Produces population of memory cells – Some antigens, such as flu, mutate quickly and require frequent vaccinations – Some antigens are difficult to make vaccines for
The Body’s Response to Infection: The Immune System – Allergy • Allergy – immune response that occurs even though no pathogen is present – Body reacts to a non-harmful substance as if it were pathogenic • called an allergen – immune cells called mast cells produce large amounts of histamine and leukotrienes inflammation – Common allergies include ragweed pollen and peanuts – Asthma might be caused by allergy
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