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2010-2011 Overview Fluid of life—why? Blood vessels form from mesoderm Blood produced 2 wks after vessels are formed, during the 5th week of life What is blood? Connective tissue Different from others Matrix not a solid or semi- solid material Matrix of blood is plasma ○ watery substance ○ Yellowish ○ 90% Water ○ 7% protein ○ 1% minerals ○ 2% other materials incl. atmospheric gases, chem signals, and nutrients More on plasma Atmospheric gases incl. oxygen, carbon dioxide, and nitrogen Comprises 55% of blood volume Formed elements Remaining 45% of blood volume: Erythrocytes (RBCs) White blood cells (WBCs) Thrombocytes (platelets) Hematocrit Calculates the volume of red blood cells making up the blood Can you answer these questions? What is the blood composed of? Why is the blood unlike any other connective tissue? What does a hematocrit tell you? Tests that monitor health of RBCs CBC: full blood count or hemogram Determines the amount of cytoplasm in the RBCs, the mass of Hemoglobin molecules, and the concentration of Hemoglobin. Helps to diagnose certain RBC disorders Red Blood Cells No mature nucleus No DNA soooo…. ○ Use enzymes to carry out their tasks = reticulocytes ○ Live max 120 days ○ No way to repair & replace damaged cellular components ○ Appear red b/c of hemoglobin Contains ironfacilitates the transport of O2 and CO2 4.8 million RBC / mm3 in women 5.4 million RBC/mm3 in men Blood Type Genetic Determined by the proteins on the surface of the RBC membrane ABO blood group system AB universal acceptor O universal donor-has no proteins on the membrane Blood will attack non-self so it’s important to match blood types for transfusions Rh Factor The D protein Most are positive If a woman is negative and conceives with a positive man, problems can arise—erythroblastosis fetalis This can lead to anemia, a condition marked by weakness and fatigue. Severe anemia can lead to heart failure and death. The breakdown of RBC leads to the buildup of bilirubin which can lead to jaundice and brain damage. Prevention of erythroblastosis fetalis Give Rh immune globulin to rid mother of fetal blood cells before she becomes sensitized Given whenever there is a possibility of fetal blood mixing with maternal blood following childbirth, abortion, miscarriage, prenatal testing. Once sensitized the woman will always react against Rh+ cells Can you answer these questions? 1. 2. 3. 4. 5. 6. How are RBCs different from most other cells? How does the lack of a nucleus affect RBCs lifespan? What is hemoglobin and what does it do? Why are RBCs red? What is blood type? What do the different blood types mean? Why is it dangerous for an Rh- woman to have an Rh+ baby? White Blood Cells WBC : RBC = 1 : 500 or 1000 Use blood to move from bone marrow to the tissues 5 types (differential WBC count measures them) Neutrophils (Most abundant) Lymphocytes Eosinophils Monocytes Basophils (Least abundant) WBC’s Agranulocytes AKA : Mononuclear Lack visible granules in cytoplasm Granulocytes Noticeable granules that produce specialized secretions for fighting infection Nucleus is polymorphic, lobed, unusually shaped Monocytes Lymphocytes T & B cells Eosinophils, basophils, neutrophils Neutrophils Granulocyte Most common WBC Nucleus = 2-5 lobes Found in the blood First responders in the inflammation response due to environmental exposure, some cancers, bacterial infection Predominant cell in pus Eosinophils Granulocyte 5% of WBCs Bi-lobed nucleus Combats parasitic infections (protista, worms) Secretions produced related to allergies Normally in thymus GI, ovaries, testes, spleen, uterus, lymph nodes NOT in lungs, esophagus or skin disease Basophils Granulocyte (least common) Susceptible to basic dyes Large, bi-lobed nucleus (similar to mast cells) Granules obscure the nucleus “Bas-ically all granules” Involved in allergies. Stores, secrete histamine & heparin (anticoagulant) Found where allergic reactions are taking place Agranulocytes Lymphocytes Immune cells NK cells (no prior activation needed) T lymphocytes (mature in thymus) ○ Helper: direct immune response ○ Cytotoxic: release cytotoxin to kill pathogen infected cells B lymphocytes (mature in bone marrow): Use antibodies to neutralize pathogens Monocytes Agranulocyte Largest of WBCs - shaped nucleus Mono = kissing = Love = heart Many vesicles in cytoplasm for processing pathogens Perform phagocytosis - uptake & digestion of pathogens Fragments signal T-lymphocytes to the area Platelets Cell fragments derived from larger cells called megakaryocytes. Have sticky proteins Reduce blood flow to an affected area. Reduce blood loss Sensitive to many types of hazardous chemicals and pollutants Can you answer these questions? Describe the characteristics & functions of all granulocytes, agranulocytes, and platelets. Compare and contrast the structure & function of RBCs and WBCs Why are Platelets called the “Band-Aids” of the blood? Red Blood Cell Function Carry oxygen from the lungs to the body Carry carbon dioxide from the body to the lungs Alveoli-where gas exchange happens in the lungs RBC in the capillaries that surround the alveoli oxygen enters Only if the partial pressure of oxygen outside is higher than inside In cytoplasm of RBC oxygen binds to Hemoglobin Hemoglobin Four oxygen molecules bind to hemoglobin (w/ the iron) Carries CO2 also; binds to a different area of the molecule than O2 Percent saturation: the amount of oxygen that is dissolved in a solution of hemoglobin molecules O2 sats = 98% or above Difference with myoglobin in muscle Fills w/ oxygen faster Hemoglobin collects oxygen a low partial pressures In the tissues the oxygen is released and carbon dioxide enters the RBC, binds to Hemoglobin. Partial pressures of the gases must appropriate Some cellular wastes stimulate the release of the oxygen from the hemoglobin ○ Allows RBC to give more O2 to tissues w/ high metabolic needs Carbon Dioxide Carried 3 ways in the blood 1. Carried in the blood as a gas (10%) 2. 22% is in the plasma, binds to empty hemoglobin in tissues away from alveoli & never enters a RBC 3. As a bicarbonate ion ○ Carbon dioxide is dissolved in water forming bicarbonate ion ○ Dissolves in the blood plasma and cytoplasm of RBCs Carbonic anhydrase: enzyme in RBC that stim’s the formation of bicarbonate ions Movement of gases High concentration low concentration For Oxygen: Partial pressure is higher in blood than in tissues For Carbon Dioxide: Partial pressure is higher in tissues than in blood Carbon dioxide intoxication Occurs when the CO2 is extremely high in the environment or the blood Acute: high levels in the air Subacute: toxicity caused by the body’s failure to eliminate carbon dioxide Decreases blood’s pH (what kind of acid does CO2 form when it dissolves in water?) ○ Carbonic acid! Can you answer these questions? What is the purpose of RBCs? Where does oxygen bind to the Hb molecule? Where does Hb collect oxygen? Then what happens? Describe the partial pressures that must be present for oxygen to diffuse from RBC to tissues and for carbon dioxide to move to the cells? White Blood Cell Function In general: Fight infections & disease Granulocytes: granules of toxic chemicals that kill microorganisms & regulate reactions to foreign materials in the body Neutrophil function Pass through capillaries to tissues to with infections. Attracted to affected areas by factors secreted by damaged cells/tissues Stick to injured tissues, use phagocytosis to engulf remains of bacteria and damaged cells Secretes antibiotics-harms/kills bacteria Secretes other chemicals that stim. Inflammation ↑ blood flow to the area & ↑ WBC concentration Eosinophil function Secretions defend against parasitic infections esp. protists & worms ↑ in eosinophils = parasitic infection Granules contain major basic protein to kill the parasites Secrete chemicals associated w/ allergies Basophil function Secrete histaminestim the immune response Overproduction of histamine runny nose, sneezing, watery eyes Mast cells-special kind of basophil Inflammation of tissues Secrete chemical that attract neutrophils Found in walls of small bl. vessels Monocyte function Clear granules give cytoplasm a grey appearance When they leave the bone marrow they become either: Circulating monocytes ○ Detect infections in blood ○ Bone growth & maintenance Tissue monocytes (macrophages) ○ Remove dead cells ○ Attack microorganisms that are difficult to kill (fungi) Lymphocyte function Stay tuned! We’ll talk about it later….for now, they carry out most of the duties of the immune system Can you answer these questions? Which WBC is in charge of engulfing bacteria? Which WBC is in charge of protecting us from parasites? Which WBC differentiates into cells that assist in bone growth and maintenance or are macrophages that protect against fungal infections? Which WBC secretes major basic protein? Platelets’ function Blood clotting Platelets adhere to injured area Activation of blood clot formation Important that clot forms by injury only Intact cells secrete prostacyclinprevents platelet activation Clotting Cascade 1.) BV damaged, releases “distress chemicals” 2.) Clotting factors stim. other factors that communicates presence of damaged tissues a.) platelets stick to damaged tissues & each other b.) Platelets secrete prothrombin activator & Ca2+ - Catalyze conversion of prothrombin to thrombin c.) Thrombin causes fibrinogen fibrin d.) Fibrin forms a sticky mesh that adheres to thrombocytes and other blood components (clot) - Clot forms a barrier that prevents blood loss & impedes the passage of microorganisms into tissues - Calcium ions = catalyze PT to T - Vitamin K = synthesis of clotting factors Clotting Cascade again! START: Damage to tissue Platelets adhere to exposed collagen END: Fibrin forms clot, traps more platelets Platelets adhere to damaged tissue & each other Ca2+ Thrombin converts fibrinogen to fibrin Platelets & damaged tissue secrete prothrombin activator Prothrombin thrombin Why is the cascade so complicated? So the blood doesn’t clot unintentionally! They aren’t permanent Plasminogenplasmin (digests fibrin and dissolves a clot) Healthy cells near the clot secrete TPA (tissue plasminogen activator)dissolves fibrin as well. Can you answer these questions? 1.) What is the purpose of prostacyclin? 2.) What is the purpose of a clot? 3.) What are the steps of the clotting cascade? 4.) What is the role of calcium and vitamin K in clot formation? 5.) Why is the clot cascade so complex? 6.) What do plasmin and tissue plasminogen have in common? What’s the difference? In General… Adults: bone marrow Embryo: Liver Different forms of Hb throughout development allow fetus to adapt to varying metabolic needs for oxygen 11 million/sec in an adult 1 WBC produced for every 700 RBCs In General… Adults: bone marrow Embryo: Liver 11 million/sec in an adult 1 WBC produced for every 700 RBCs GF Myeloid stem cell (progenitor) Hematopoietic stem cell Or Multipotent stem cell Or Pluripotent stem cell GF Lymphoid stem cell (progenitor) The life history of erythrocytes (RBCs) Blood oxygen decreases Stimulates erythropoietin production from kidneys and liver ErythropoietinErythropoiesis in red bone marrow (where is this found?) Immature erythrocytes have a large nucleus Hb production begins in basophilic erythroblasts Reticulocytes: lose nucleus, after 1-2 days in circulation lose organelles If the need for oxygen is great, erythropoiesis will occur at an increased rate. This means an increased amount of polychromatic erythroblasts will enter the blood stream Erythropoiesis of a single erythrocyte takes approximately 4 days Normal bone marrow has an abundance of newly formed RBCs and megakaryocytes (which produce platelets) Old erythrocytes get gobbled up! Removed by macrophages Globin (protein) is broken into individual amino acids & recycled Iron is recycled Parts of the molecule are converted to bilirubin Processed in liver, secreted in bile in small intestine ○ Bacteria convert into pigments feces color ○ Some excreted in urine yellow color A bit about WBCs: Lifetime = 13-20 days Then destroyed in lymphatic system When released from bone marrow called stabs or bands Esp. neutrophils b/c their nuclei aren’t lobed, yet, and look like a rod (stab = German for rod) or bands Functions of Lymphatic System 1.) Maintain fluid balance in the tissues ○ 30L fluid from capillaries to interstitial and only 27L pass from interstitial back into capillaries qd (every day) ○ If fluid left in the body tissue damage ○ 3L fluid enter lymph capillaries, called lymph Then to lymph vessels & return to blood 2.) Absorb fats & other substances from digestive tract (chyle) 3.) Defense ○ Nodes filter lymph & spleen filters blood of microorganisms & foreign substances Lymphatic System Structures Lymph Like plasma: ions, nutrients, wastes from interstitial spaces Hormones, enzymes from cells in tissues Lymphocytes Lymph vessels ○ Flow of lymph produced by gravity or skeletal muscle, passively drains to lower body from upper ○ Valves-no backflow ○ Lymphatic trunks drain lymph from larger areas of body Clusters of lymphatic tissue Lymphatic System Structures Lymph nodes Collections of lymphatic tissue covered by connective-tissue capsules Eliminate antigens from lymph as lymph flows thru the node. In groups along the larger lymphatic vessels Lymph node structure 2 divisions: Cortex (outer) & Medulla (inner) Cortex ○ Has “compartments” called lymphatic nodules ○ 2 layers: inner layer called germinal center where Blymphocytes are found. In the “wall” surrounding the germinal center is where T-lymphocytes are found. ○ Nodules are sep’d by trabeculae—extensions of the capsule—fibrous covering of the node ○ Cortical sinus: spaces where lymph flows through Medulla ○ Medullary sinus = space where lymph flows throught he center of the node, contains macrophages ○ Medullary cord = contains lymphocytes Lymphatic System Structures Tonsils Swollen cluster of lymphatic tissue in throat Form protective ring of lymphatic tissue around the openings between the nasal and oral cavities & pharynx Provide protection against bac and other harmful material Eventually disappear in adults Spleen Detects and responds to foreign substances in the blood Destroys worn out red blood cells Acts as a blood reservoir Structure ○ Left side of the extreme superior, posterior corner of ab cavity ○ White pulp: Contains T & B lymphocytes Assist body with infections that require a large immune response ○ Red pulp: removes old/damaged RBCs Lymphatic System Structure Thymus Deep to manubrium In newborn, extends length of thorax & grows until puberty, then decreases in size Function ○ Produce lymphocytes that move to other lymph tissues, but most degenerate before moving on ○ Produces secretions that mature T-lymphocytes Can’t destroy normal body cells (Self-tolerance) Immunity words to know: Antigen: a substance that can induce an immune response. Hapten: A molecule that can cause an immune response when attached to blood proteins. Two ways the immune system can respond to disease: Innate immunity Acquired immunity Lines of defense 1st line: Non-specific barriers broad, external defense ○ “walls & moats” skin & mucous membranes 2nd line: Non-specific patrols broad, internal defense ○ “patrolling soldiers” leukocytes = phagocytic WBC 3rd line: True immune system specific, acquired immunity ○ “elite trained units” lymphocytes & antibodies ○ B cells & T cells Bacteria & insects inherit resistance. Vertebrates acquire immunity. 1st line: Non-specific External defense Barrier ○ skin Lining of trachea: ciliated cells & mucus secreting cells Traps ○ mucous membranes, cilia, hair, earwax Elimination ○ coughing, sneezing, urination, diarrhea Unfavorable pH ○ stomach acid, sweat, saliva, urine Lysozyme enzyme ○ digests bacterial cell walls ○ tears, sweat 2nd line: Non-specific patrolling cells Patrolling cells & proteins bacteria attack pathogens, but don’t “remember” for next time ○ leukocytes phagocytic white blood cells macrophages, neutrophils, natural killer cells macrophage ○ complement system proteins that destroy cells ○ inflammatory response increase in body temp. increase capillary permeability attract macrophages yeast Leukocytes: Phagocytic WBCs Attracted by chemical signals released by damaged cells ingest pathogens digest in lysosomes Neutrophils most abundant WBC (~70%) ~ 3 day lifespan Macrophages “big eater”, long-lived Natural Killer Cells destroy virus-infected cells & cancer cells Destroying cells gone bad! Natural Killer Cells perforate cells release perforin protein insert into membrane of target cell forms pore allowing fluid to flow in & out of cell cell ruptures (lysis) natural killer cell vesicle ○ apoptosis perforin cell membrane cell membrane perforin punctures cell membrane virus-infected cell 3rd line of defense: Acquired Immunity Body adapts to specific infections Body learns the nature of the enemy (invading microorganisms) Can launch a specific attack against the enemy More successful than innate Able to prevent future infections from the same microorganism Two divisions: Primary Response and Secondary Response How are invaders recognized: antigens Antigens proteins that serve as cellular name tags ○ foreign antigens cause response from WBCs viruses, bacteria, protozoa, parasitic worms, fungi, toxins non-pathogens: pollen & transplanted tissue B cells & T cells respond to different antigens B cells recognize intact antigens ○ pathogens in blood & lymph T cells recognize antigen fragments ○ pathogens which have already infected cells “self” “foreign” B cells Humoral response = “in fluid” defense against attackers circulating freely in blood & lymph Specific response produce specific antibodies against specific antigen Types of B cells ○ plasma cells immediate production of antibodies rapid response, short term release ○ memory cells long term immunity T cells Cell-mediated response immune response to infected cells ○ viruses, bacteria & parasites (pathogens) within cells defense against “non-self” cells ○ cancer & transplant cells Types of T cells helper T cells ○ alerts immune system killer (cytotoxic) T cells ○ attack infected body cells Immunoglobins IgG: most common, fight general infections, pass from mom to child in pregnancy IgA: in mucous membranes aof the digestive system, milk, tears, saliva IgM: natural defenses against general bacterial infections IgE: stim basophils and mast cells to defend against parasites fungi and worms IgD: on membranes of B-lymphocytes., maturation of B-lymphocytes into plasma and memory cells Secondary Immune Response Body responds more quickly Memory cells “remember” past encounters with antigens and immediately px antibodies Eliminates macrophage activity Memory cells don’t last forever—they die and take their memory with them After 5 yrs of not being exposed to a particular antigen, the body loses much of the secondary immune response Inflammation Outcome of acquired immune response Increases bl circulation to affected area Bv’s dialate to increase blood flow Immune cells go to injured area Immune resp. takes place at the site it’s needed Tissues = red and warm b/c of the blood that enters the area, ↑ in temp anti-microbial Pain from pressure of swollen tissues on nerve endings Normal functions return when the tissue is fully recovered Immunization Medical strategy for building up the body’s acquired immune response Natural: exposed to foreign antigens as a part of everyday life. Artificial: therapeutic exposure to antigens Active: stimulates the primary response by introducing foreign antigens into the body: Vaccines. Passive: occurs naturally during embryological development when antibodies from the mother’s blood stream are passed to the fetus ○ Contain certain antigens from the microorganism (parts of the microorganism) Breast feeding Inject large amts of general antibodies to fight disease - Globulin injections remove certain microorganisms from the body.