Lymphatic System and Immunity The lymphatic system contributes to homeostasis by draining interstitial fluid as well as providing the

mechanisms for defense against disease. A. Lymphatic system consists of, 1. A fluid called lymph flowing within the lymphatic vessels 2. Several structures and organs that contain Lymphatic tissue a. Specialized reticular tissue containing large numbers of Lymphocytes, and b. Red bone marrow, which is the site of lymphocyte production. B. Lymph and interstitial fluid have basically the same composition - They differ only in location - The fluid that battles the cell (= interstitial fluid) passes into the lymphatic vessels and is then called lymph C. The Lymphatic System Functions to: 1. Drain interstitial fluid lymphatic vessels drain excess interstitial fluid from tissue spaces and return it to the blood 2. Return leaked plasma proteins to the blood 3. Transports dietary lipids lymphatic vessels transport lipids and lipid-soluble vitamins (A, D, E, and k) absorbed by the gastrointestinal tract 4. roduce, maintain and transport the lymphocytes (= type of white blood cells that plays a major role in immunity 5. rotects against infection by the following mechanisms: (i) Non-specific (innate immunity) defenses: skin, antimicrobial substances, natural killer cells, phagocytes, inflammation and fever i. First line of defense is external body membranes(skin and mucosae) ii. Second line of defense is antimicrobial proteins, phagocytes, and other cells 1. Antimicrobial susttances include interferons, the complement system, ironbinding proteins and antimicrobial proteins 2. Natrual killer and phagocytes attack and kill pathogens and defective cells in the body y Inhibit spread of invaders y Inflammation is its most important mechanism. It aids disposal of microbes, toxins, or foreign material at the site of an injury and prepares the site for tissue repair

Specific (adaptive immunity) immune responses: involves lymphocytes (a type of white blood cells) called T lymphocytes (T cells) and B lymphocytes (B cells) i. Third line of defense attacks particular foreign substances y Takes longer to react than the innate system Some lymphoctyes (T cells) destroy the intruders by causing them to rupture or by releasing cytotoxic substances - Other lymphocytes (B cells) differentiate into PLASMA cells that secrete antibodies=proteins that combine with and destroy specific foreign proteins. - B cells and T cells arise from stem cells in red bone marrow - B cells mature in RBM, whereas T cells mature in Thymus gland - Before B cells leave the RBM or T cells leave the thymus, they develop immunocompetence, the ability to carry out adaptive immune responses. This process involves the insertion of antigen receptors into their plasma membranes. Antigen receptors are molecules that are capable of recognizing specific antigens. 6. Concentrate foreign substances that induce immune responses in certain organs=the lymph nodes, making it more efficient their destruction (ii) Innate (nonspecific) defense system The mechanical barriers that cover body surfaces and the cells and chemicals that act on the initial internal battlefronts are in place at birth, ready to ward off invading pathogens(harmful or diseasecausing microorganisms) and infection. It involves at least 6 different mechanisms: Physical barriers such as the skin, phagocytes such as macrophages, immunological surveillance by natural killer cells, complement, which assists antibody reactions, the inflammatory response and fever.

hagocytosis= ingestion and destruction of microbes of any foreign particulate matter by cells called phagocytes. Phagocytes participate in both nonspecific and specific defenses.

A. Phagocytes fall into two categories: a. Microphages such as neutrophils and eosinophils 1. Neutrophils the most abundant type of WBC, become phagocytic on encountering infectious material in the tissue. Phagocytize bacteria. - First cell to arrive at the scene of infection or injury.

- produce antimicrobial chemicals, called defensins that pierce the pathogen s membrane. - Neutrophils are our body s bacteria slayers, and their numbers increase explosively during acute bacterial infections such as meningitis and appendicitis. Neutrophils are chemically attracted to sites of inflammation and are active phagocytes. They are especially partial to bacteria and some fungi, and bacterial killing is promoted by a process called a respiratory burst. 2. Eosinophils granulocytes. kill parasitic worms; complex role in allergy and asthma b. Macrophages(= monocytes): fixed and wandering or free(they are mobile) 3. Monocyte an antigen presenting cell. Agranulocytes. They are the largest leukocytes. They have abundant pale-blue cytoplasm and a darkly staining purple nucleus, which is distinctivlely U or kidney shaped. When circulating monocytes leave the bloodstream and enter the tissues, they differentiate into highly mobile macrophages with prodigious appetites. Macrophages are actively phagocytic, and they are crucial in the body s denfense against viruses, certain intracellular bacterial parasites, and chronic infections such as tuberculosis. Internal Defenses: Cells and Chemical Pathogens that get through the skin and mucosae into the underlying CT are confronted by phagocytes. The chief phagocytes are macrophages ( big eaters ), which derive from WBC called monocytes that leave the bloodstream, enter the tissues, and develop into macrophages. B. Mechanism of phagocytosis and its four phases: a. Chemotaxis- the chemical attraction of phagocytes ( attract phagocytes to the site of microbe invasion) b. Adherence- attachment of the plasma membrane of phagocyte to the surface of the microorganism c. Ingestion- the membrane of the phagocyte extends projections-pseudopodia- that engulf the microorganism d. Killing- lysosomes which contain enymes that digest the proteins of the microorganisms, form phagolysosome Inflammation is a nonspecific, defensive response of the body to tissue damage. Among the conditions that may produce inflammation are pathogens, abrasions, chemical irritations, distortion or disturbances of cells, and extreme temperatures. A. Inflammation is usually characterized by four symptoms: 1.Redness 2. Pain 3. Heat 4. Swelling a. Loss of function may be a fifth symptom, depending on the site and extent of injury Inflammation can also cause the loss of function in the injured area (for example, the inability to detect sensations), depending on the site and extent of the injury. Inflammation is an attempt to dispose of

microbes, toxins, or foreign material at the site of injury, to prevent their spread to other tissues, and to prepare the site for tissue repair in an attempt to restore tissue homeostasis B. The inflammatory response serves protective and defensive roles by a. Eliminating microbes, toxins, or foreign material from the site of injury b. Preventing their spread to other organs c. Preparing the site for tissue repair d. It is an attempt to restore tissue homeostasis C. The stages of the inflammatory response are: a. Vasodilation(increase in diameter of the blood vessels), induced by chemicals released by MAST cells b. Increased permeability of the blood vessels c. hagocyte migration d. Repair Adaptive (Specific) Immunity The ability of the body to defend itself against specific invading agents such as bacteria, toxins, viruses, and foreign tissues is called adaptive (specific) immunity. Substances that are recognized as foreign and provoke immune responses are called antigens (Ags). Two properties distinguish adaptive immunity from innate immunity: (1) specificity for particular foreign molecules (antigens), which also involves distinguishing self from nonself molecules, and (2) memory for most previously encountered antigens so that a second encounter prompts an even more rapid and vigorous response. y Adaptive immunity involves lymphocytes called B cells and T cells. Both develop in primary lymphatic organs ( RBM and thymus) from pluripontent stem cells that originate in RBM. Humoral immunity also called antibody mediated immunity, is provided by antibodies present in the body s humors or fluids (blood, lymph, etc). They are produced by lymphocytes (or their offspring), antibodies circulate freely in the blood and lymph, where they bind primarily to bacteria, to bacterial toxins, and to free viruses, inactivating them temporarily and marking them for destruction by phagocytes or complement. - Refers to destruction of antigens by antibodies=immunoglobulins - It works mainly against antigens dissolved in body fluids and extracellular pathogens, primarily bacteria that multiply in body fluids but rarely enter body cells. Cellular or cell-mediated immunity when lymphocytes themselves rather than antibodies defend the body. Cellular immunity also has cellular targets-virus-infected or parasite infected tissue cells, cancer cells, and cells of foreign grafts. The lymphocytes act against such target either directly, by killing the foreign cells, or indirectly by releasing chemical mediators that enhance the inflammatory response or activate other lymphocytes or macrophages Refers to destruction of antigen-presenting cells by T cells

It is particularly effective against intracellular pathogens, such as fungi, parasites, and viral infected cells, some cancer cells; and foreign tissue transplants; thus , CMI always involves cells attacking cells

Cells of the Adaptive Immune System 4. B cells (humoral immunity)complete their development in RBM. Lymphocytes that can develop into an antibody- producing LASMA cell or a MEMORY cell. The activated B cells that do not differentiate into plasma cells remain as MEMORY B CELLS ready to respond more rapidly and forcefully should the same antigen appear at a future time. Antibodies neutralize antigens. Memory and antibody producing cells, retain memory of particular antigen. Live in lymph nodes originally in BM. 5. T cells (cellular immunity) develop from pre- T cells that migrate from RBM into the thymus, where they mature. A lymphocyte that becomes immunocompetent in the thymus and that is capable of destroying foreign cells. T cells destroy foreign cells. Cellular immunity. Cells have own defense system - Non- antibody producing lymphocytes that constitute the cell-mediated There are two major types of mature T cells that exit the thymus: helper T cells and cytotoxic T cells 6. Helper T cells also known as CD4T cells which means that, in addition to antigen receptors, their plasma membranes include a protein called CD4. Activates humoral and cellular immunities - play a central role in adaptive immunity, mobilizing both its cellular and its humoral arms. - recognize antigen fragments associated with MHC-II molecules - secrete several cytokines, most important, interleukin-2, which acts as a costimulator for other helper t cells, cytotoxic T cells, and B cells. 7.Lymphocytes Second most numerous leukocytes in the blood. Large numbers of lymphocytes exist in the body, but only a small proportion of them are found in the bloodstream. Lymphocytes are also called because most are closely associated with lymphoid tissues (lymph nodes, spleen, etc.) where they play a crucial role in immunity. T lymphocytes (T cells) function in the immune response by acting directly against virus- infected cells and tumor cells. B lymphocytes (B cells) give rise to plasma cells, which produce antibodies (immunoglobulin) that are released to the blood. Many kinds, fight off infection Originate in RBM from hematopoietic stem cells. During development, lymphocytes are Educated.

1. Immunocompetence each lymphocyte must become able (competent) to recognize its one specific antigen by binding to it. The ability is called immunocompetence 2. Self-tolerance each lymphocyte must be relatively unresponsive of self-antigens so that it does not attack the body s own cells y B and T cells are educated in different parts of the body. T cells undergo this two- to three day maturation process in the thymus. B cells become immunocompetent and self-tolerant in the bone marrow. rimary Lymphatic organs are the sites where stem cells divide and become immunocompetent, that is capable of mounting an immune response. The primary lymphatic organs are the red bone marrow (in flat bones and the epiphyses of long bones of adults) and the thymus. 8. Pluripotent bone marrow stem cells in red bone marrow give rise to mature, immunocompetent B cells and to pre-T cells. The pre-T cells in turn migrate to the thymus, where they become immunocompetent T cells. - RBMC are derived from mesenchyme and are called pluripotent stem cells or hemocytoblast. Secondary Lymphatic organs and tissues are the sites where most immune responses occur. They include lymph nodes, the spleen, and lymphatic nodules (follicles). They thymus, lymph nodes, and the spleen are considered organs because each is surrounded by a connective tissue capsule; lymphatic nodules, in contrast, are not considered organs because they lack a capsule. Lymphocyte formation: In flat bones and epiphyses of bones hemopoietic stem cells in red bone marrow give rise to NK cells, B cells and pre-T cells T cells complete their maturation and develop immunocompetence (the ability to carry out immune responses if properly stimulated) in thymus Before T cells leave the thymus or B cells leave bone marrow, they acquire several distinctive surface proteins; some function as antigens

9. Plasma cell antibody-producing machine ; produces huge numbers of antibodies (immunoglobulin) with the same antigen specificity. An effectors B cell. Lymphatic Organs and tissues Primary lymphatic organs are the sites where stem cells, divide and become imunocompetent, that is, capable of mounting an immune response. Pluriopotent stem cells in red bone marrow give rise to mature, immunocompetent B cells and to pre-T cells. The pre-T cells in turn migrate to the thymus, where they become immunocompetent T cells. Secondary Lymphatic organs and tissues are the sites where most immune responses occur. They include lymph nodes, the spleen, and lymphatic nodules (follicles). The thymus, lymph nodes, and spleen.

Thymus Is a member of both the lymphatic and endocrine systems. It houses lymphocytes and secretes hormones that regulate their later activity. It is located between the sternum and aortic arch in the superior mediastinum. The thymus is very large in the fetus and grows slightly during childhood, when it is most active. However age 14, it begins to undergo involution(shrinkage) . 10. Purpose of the Thymus Gland- to tag every cell of the body with major histocomatobility complex proteins - it is the only lymphoid organ that does not directly fight antigens. - blood-thymus barrier keeps blood borne antigens from leaking into the cortical regions to prevent premature activation of the immature lymphocytes * Major histocomatobility Complex (MHC) located in the plasma membrane of the body cells self antigens MHC molecules mark the surface of each of your body cells except RBC. MHC antigens are the reason that tissues may be rejected when they are transplanted from one person to another. Their normal function is to help T cells recognize that an antigen is foreign, not self. Important first step in any adaptive immune response. Lymph Nodes Clear tissue fluid of bacteria, viruses, fungi, or any foreign particle. Part of the Adaptive Immune system(antibodies) 11. Lymph Nodes are encapsulated (DCT) oval structures located along lymphatic vessels, and are scattered throughout the body, usually in groups. Large groups of lymph nodes are present near the mammary glands and in the axillae and groin. a. Lymph is processed enroute as it enters nodes through afferent Lymphatic vessels, is filtered to remove damaged cells and microorganisms, and exits through efferent lymphatic vessels. (i) Foreign substances filtered by the Lymph nodes are trapped by nodal reticular fibers (ii) Macrophages then destroy some foreign substances by phagocytosis and lymphocytes bring about the destruction of others by immune responses b. Lymph nodes are also the site of proliferation of B cells and T cells. - Lymph nodes function as a type of filter. As lymph enters one end of the lymph node, foreign substances are trapped by the reticular fibers within the sinuses of the lymph node. Then macrophages destroy some foreign substances by phagocytosis while lymphocytes destroy others by immune responses. The filtered lymph then leaves the other end of the lymph node.

AIDs: Acquired immunodeficiency Syndrome represents the end stage of infection by HIV. Spread from one person to another by actions or practices that involve the exchange of blood or body fluids between people. Transmitted in semen or vaginal fluid during unprotected anal, vaginal or oral sex. HIV is also transmitted by direct blood-to blood contact, such as occurs among intravenous drug users. HIV can be transmitted from an HIV- infected mother to her baby at birth or during breast-feeding. HIV consist of an inner core of ribonucleic acid (RNA) covered by a protein coat(capsid). Autoimmune disease the immune system fails to display self-tolerance and attacks the person s own tissues. Results when the body does not recognize self antigens and produces antibodies against them Blood is a connective tissue composed of a liquid extracellular matrix called blood plasma that dissolves and suspends various cells and cell fragments. Interstitial fluid is the fluid that bathes body cells and is constantly renewed by the blood. Function 1. Transportation transports oxygen from the lungs to the cells of the body and carbon dioxide from the body cells to the lungs for exhalation. It carries nutrients from the gastrointestinal tract to body cells and hormones from endocrine glands to other body cells. Transports heat and waste products to various organs for elimination from the body 2. Regulation circulating blood helps maintain homeostasis of all body fluids. Regulate pH through the use of buffers. Helps adjust body temperature through the heat absorbing and coolant properties of the water in blood plasma. 3. Protection blood can clot, which protects against its excessive loss from the cardiovascular system after an injury. WBC protect against disease by carrying on phagocytosis. Two components: blood plasma, a watery liquid of extracellular matrix that contains dissolved substances and formed elements, which are cells and cell fragments. 12. Blood plasma is about 91.5% water and 8.5 % solutes, most of which (7%) are proteins. Some of the proteins in blood plasma are also found elsewhere in the body, but those confined to blood are called plasma proteins. Among other functions, these proteins play a role in maintaining proper blood osmotic pressure, which is an important factor in the exchange of fluids across capillary walls. Blood without Red cells but with the clotting proteins - Plasma is a complex mixture of water, proteins, nutrients, electrolytes, nitrogenous wastes, hormones, and gases. Plasma proteins play a variety of roles including clotting, defense, and transport of other solutes such as iron, copper, lipids and hydroproteins: albumins, globulins, and fibrinogen 13. Red blood cells (RBCs) or erythrocytes contain the oxygen-carrying protein hemoglobin, which is a pigment the gives whole blood its red color. A healthy adult male has about 5.4 million RBC per

microliter and healthy adult female has 4.8 million. RBCs are biconcave discs. RBCs lack a nucleus and other organelles and can neither reproduce nor carry on extensive metabolic activities. The cytosol of RBCs contains hemoglobin molecules; these important molecules are synthesized before loss of the nucleus during RBC production and constitute about 33 % of the cells weight. Bag of Hemoglobin - RBCs highly specialized for their oxygen transport function. All their internal space is available for oxygen transport. - generate ATP anaerobically( w/o oxygen) do not use up any of the oxygen they transport (two alpha and two beta); a ringlike nonprotein pigment called a heme is bound to each of the four chains. At the center of each heme ring is an iron ion that can combine reversibly with one oxygen molecule, allowing each hemoglobin molecule to bind four oxygen molecules. Hemoglobin releases oxygen, which diffuses first into the interstitial fluid and then into cells. Also transports about 23 % of the total carbon dioxide, a waste product of metabolism. - key role in transporting oxygen and carbon dioxide, hemoglobin plays role in the regulation of blood flow and blood pressure - blood flowing through tissue capillaries picks up carbon dioxide, some of which combines with amino acids in the globins part of hemoglobin. As blood flows through the lungs, the carbon dioxide is released from hemoglobin and then exhaled. White blood cells or leukocytes have nuclei and do not contain hemoglobin. WBCs are classified as either granular or agranular, depending on whether they contain conspicuous chemical- filled cytoplasmic granules (vesicles) Granular y y Neutrophils phagocytosis. Destruction of bacteria with lysoyme, defensins, and strong oxidants, such as superoxide anion, hydrogen peroxide, and hypochlorite anion Eosinophils combant the effects of histamine in allergic reactions, phagocytize antigenantibody complexes, and destroy certain parasitic worms

14. Basophils liberate heparin, histamine, and serotonin in allergic reactions that intensify the overall inflammatory response. Produce histamine, the major inducer of inflammation Agranular y y y Lymphoctyes(T cells, B cells, and natural killer cells) mediate immune response, including antigen-antibody reactions. Monocytes phagocytosis(after transforming into fixed or wandering macrophages) Platelets (thromboyctes) form platelet plugs in hemostatsis; release chemicals that promote vascular spasm and blood clotting. Function of WBCs

Once pathogens enter the body, the general function of WBC is to combat them by phagocytosis or immune responses. WBCs leave the bloodstream by a process termed emigration formerly called diapedesis, in which they roll along the endothelium, stick to it, and then squeeze btwn endothelial cells. Neutrophils and macrophages are active in phagocytosis; they can ingest bacteria and dispose of dead matter. Several different chemicals released by microbes and inflamed tissues attract phagocytes, a phenomemnon called chemotaxis. The susbstacnes that provide stimuli for chemotaxis include toxins produced by microbes; kinins, which are specialized products of damaged tissues; and some of the colony-stimulating factors (CSFs). CSFs enhance the phagocytic activity of neutrophils and marcrophages.

15. Platelets break off from the megakaryocytes in red bone marrow and then enter the blood circulation. Platelets help stop blood loss from damaged blood vessels by forming a platelet plug. Their granules also contain chemicals that, once released, promote blood clotting. Aged and dead platelets are removed by fixed macrophages in the spleen and liver. The second step in blood clotting Hemostasis 16. Hemostasis is a sequence of responses that stops bleeding. Three mechansisms reduce blood loss: (1) vascular spasm, (2) platelet plug formation, and (3) blood clotting (coagulation). When successful , hemostasis prevents hemorrhage, the loss of a large amount of blood from the vessels. Hemostatic mechanisms can prevent hemorrhage from smaller blood vessels, but extensive hemorrhage from larger vessels usually requires medical intervention. 17. Vascular spasm (vasoconstriction) when arteries or arterioles are damaged, the SM in their walls contracts immediately. This reduces blood loss for several minutes to several hours. The spasm is probably caused by damaged to the SM, by substances released from activated platelets, and by reflexes initiated by pain receptors. 18. Platelet plug formation (platelet aggregation) key role in hemostasis by aggregating(sticking together), forming a plug that temporarily seals the break in the vessel wall. Help to orchestrate subsequent events that lead to blood clot formation. Platelet s don t stick together or to the S endothelial lining of BV. Intact endothelial cells release nitric oxide and prostaglandin called prostacyclin. Both chemicals prevent platelet aggregation in undamaged tissue and restrict aggregation to the site of injury. Blood Clotting 19. Serum is simply blood plasma minus the clotting proteins. When blood clots and the solids are removed, the remaining fluid is the blood serum. Serum is essentially identical to plasma except for the absence of the clotting protein fibrinogen. Blood without RC or the clotting proteins

20. Clot Blood thickens and forms a gel when taken out of the body. It consists of a network of insoluble protein fibers called fibrin in which the formed elements of blood are trapped. The process of gel formation, called clotting or coagulation, is a series of chemical reactions that culminates in formation of fibrin threads. If blood clots too easily, the result can be thrombosis- clotting in an undamaged BV. Clotting involves several substances known as clotting (coagulation) factors. 1. Two pathways, called the extrinsic pathway and intrinsic pathway, which leads to the formation of prothrombinase. 2. Prothrombinase converts prothrombin(a plasma protein formed by liver) into the enzyme thrombin 3. Thrombin converts soluble fibrinogen(another plasma protein formed by the liver) into insoluble. Fibrin forms the threads of the clot. y Normal coagulation requires vitamin K and is followed by clot retraction (tightening of the clot) and ultimately fibrinolysis (dissolution of the clot) ABO blood group is based on two glycolipid antigens called A and B. ABO and Rh blood groups are genetically determined and based on antigen-antibody responses. 21. Type A People whose RBCs display only antigen A have type A blood. Compatible A or O 22. Type- B those who only have antigen B. Compatible B or O 23. Type- AB individuals who have both A and B antigens. People with type AB do not have anti-A or anti-B antibodies in their blood plasma. They are called universal recipients because they can receive blood from donors of all four blood types. They have no antibodies to attack antigens on donated RBCs. Compatible A, B, AB or O 24. Type O those who have neither antigen A or B Called universal donors because they can donated blood . May only receive type O blood. Compatible O Blood plasma usually contains antibodies called agglutinins that react with the A or B antigens if the two are mixed. These are the anti-A antibody, which reacts with antigen A, and anti-B antibody, which reacts with antigen B. Rh blood group is named because the antigen was discovered in the blood of the Rhesus monkey. People whose RBCs have Rh antigens are designated Rh + (positive). Those who lack Rh antigens are designated Rh (negative). Normally, blood plasma does not contain anti-Rh antibodies. If an Rh- person receives an Rh + blood transfusion, the immune system starts to make anti-Rh antibodies that will remain in the blood. If a second transfusion of Rh + blood is given later, the previously formed anti-Rh antibodies will cause agglutination and hemolysis of RBCs in the donated blood, and a severe reaction may occur. 25. Rh incompatibility most common problem, hemolytic disease of the newborn (HDN) may arise during pregnancy. No direct contact occurs between maternal and fetal blood but if small amount of

Rh+ blood leaks from the fetus through the placenta into the bloodstream of an Rh- mother, the mother will start to make anti-Rh antibodies. First born usually is not affected. If mother becomes pregnant again, her anti-Rh antibodies can cross the placenta and enter the bloodstream of the fetus. If fetus is Rh-, there is no problem, because Rh- blood does not have the Rh antigens. If the fetus is Rh+ agglutination and hemolysis brought on by fetal maternal incompatibility. - injection of anti Rh antibodies called anti-Rh gama globulin can be given to prevent HDN. Anemia condition in which the oxygen-carrying capacity of blood is reduced. Characterized by reduced numbers of RBCs or a decreased amount of hemoglobin in the blood. Person feels fatigued and is intolerant of cold, both of which are related to lack of oxygen needed for ATP and heat production. Sickle-cell disease contain HB-S an abnormal kind of hemoglobin. People who have sickle cell have some degree of anemia and mild jaundice and may experience joint of bone pain, breathlessness, rapid heart rate, abdominal pain, fever, and fatigue as a result of tissue damaged. Sickle is inherited. Hemophilia inherited deficiency of clotting in which bleeding may occur spontaneously or after only minor trauma. Leukemia refers to a group of RBM cancers in which abnormal WBC multiply uncontrollably. The Heart The heart is the center of the cardiovascular system The design of the heart and the unique properties of cardiac muscle permit a lifetime of pumping with never a minute s rest. The heart pumps blood over an estimated 100,000 km (60,000 miles) of blood vessels. Overview of the Circulation 26. The circulation of blood through the body- Right atrium, right ventricle, pulmonary artery, pulmonary capaillaries, pulmonary veins, left atrium, left ventricle, aorta, arterioles, systemic capillaries, venules, veins, superior and inferior vena cavae, right atrium The heart pumps blood into two closed circuits: A. Systemic Circulation- carries oxygenated blood from the lungs to the other parts of the body. It is associated with the left side of the heart - Once blood has been oxygenated in the lungs it passes through a series of channels via the heart and body before retouring to the heart. This circuit involves passages: 1. From the left atrium and into the left ventricle of the heart, 2. To the aorta and progressively smaller arterial branches, 3. To capillaries( where exchange of O2 and CO2 with the tissues occurs), 4. To venules, 5. To progressively larger veins,

6. To vena cava, 7. Into the right atrium of the heart B. Pulmonary Circulation- carries de-oxygenated blood from the other parts of the body to the lungs to be oxygenated. It is associated with the right side of the heart - The deoxygenated blood, containing high levels of carbon dioxide from the tissues, is returned to the right side of the heart and passes through the pulmonary circulation, which includes: 1. From the right atrium and into the right ventricle of the heart, 2. To the pulmonary arteries, 3. To the arteries and capillaries of the lungs, 4. To venules 5. To progressively larger veins, 6. To pulmonary veins 7. Into left atrium of the heart. Chambers of the Heart 1. The chambers of the heart include two upper atria and two lower ventricles 2. An interatrial septum separates the atria 3. Some properties: a. The walls of the atria are thin because they only have to pump blood from the atria into the ventricles b. The right ventricle pumps blood to the lungs, therefore has less of work load than the left ventricle that pumps blood to all other parts of the body. c. Therefore the all of the left ventricle is two to four times thicker than that of the right ventricle d. Both ventricles expel the same amount of blood but with different pressures. 27. Right Ventricle Is the Volume chamber of the heart - contains ridges formed by raised bundles of cardiac muscles fibers called trabeculae carneae. - lower presure 28. Left Ventricle is the pressure chamber of the heart - It is the thickest chamber of the heart. Like the right ventricle, the left ventricle contains trabeculae carnease and has chordate tendinae that anchor the cusps of the bicuspid vale to papillary muscles

- Blood passes from the left ventricle through the aortic valve (aortic semilunar valve) into the ascending aorta. Some of the blood in the aorta flows into the coronary arteries, which branch from the ascending aorta and carry blood to the heart wall. Valves of the Heart 1. Valves, composed of dense CT covered by endothelium, prevent backflow of blood in the heart. They open and close in response to pressure changes when the heart contracts or relaxes. 29.Valves: Function of Venous valves- to keep blood flowing the wrong way a. Atrioventricular (AV) valves between the atria and their ventricles are y The tricuspid valve on the right side of the heart and three flaps=cusps y The bicuspid (mitral) valve on the left- it has only two flaps= cusps y The chordate tendineae( tendinous CT attached to the free edge of each cusp and their papillary muscles keep the flaps of the valves pointing in the direction of the blood flow and stop blood from backing into the atria o If these valves are damaged, blood may Regurgitate(flow back) into the atria when the ventricles contract o Prevent backflow into the atria when the ventricles are contracting b. Semilunar valves prevent blood from flowing back into the heart as it leaves the heart for: i. The lungs(pulmonary semilunar valve) ii. The rest of the body (aortic semilunar valve) y Prevent backflow into the ventricles when ventricles are relaxing. Cardiac muscle Tissue Cardiac muscle fibers are shorter in length and less circular in transverse section. They also exhibit branching, which gives individual cardiac muscle fibers a stair-step appearance. A typical muscle fiber usually one centrally located nucleus is present; although an occasional cell may be have two nuclei. The end of cardiac muscle fibers connect to neighboring fibers by irregular transverse thickening of the sarcolemma called intercalated disc. The wall of the heart has three layers: epicardium, myocardium, and endocardium 1. Epicardium consists of mesothelium and CT and is the same as the visceral pericardial serous membrane 2. Myocardium is composed of cardiac muscle tissue. It is responsible for its pumping action. Cardiac muscle cells are involuntary, striated and branched, and then swirl diagonally around the heart

a. They form two independent networks: one atrial and one ventricular 30. The intercalated discs (where two fibers contact each other) have two adaptations: 29. Gap junctions that allow muscle action potentials to spread from fiber to fiber. As a result the entire atrial network contracts as a whole, and so does the ventricular network Gap junctions allow the entire myocardium of the atria or the ventricles to contract as a single, coordinated unit. Cytoplasm with one cell communicates with cytoplasm in another cell a. Desmosomes they act as anchors, preventing the fiber from separating when the cardiac muscle contract vigorously. Cardiac muscle fibers are connected end to end via intercalated discs. Desmosomes in the discs provide strength, and gap junctions allow muscle action potentials to conduct from one muscle fiber to its neighbors. 31. Endocardium consists of endothelium and CT

Although heart muscle and skeletal muscle are contractile tissues, they have some fundamental differences: 1. Means of stimulation- skeletal muscle fiber stimulated to contract by a nerve ending, but cardiac muscle cells are self- excitable. a. Cardiac muscle cells have a very important property: they do not require neuronal or hormonal stimulation to contract. They contract on their own. This property is called Autorhymicity. 2. Organs versus motor unit contraction- skeletal muscle, all cells of a given motor unit are stimulated and contract at the same time. Impulses do not spread from cell to cell. a. Cardiac muscle, the heart either contracts as a unit or doesn t contract at all. This coordinated action occurs because gap junctions electrically tie all cardiac muscle cells together into a single contractile unit. 3. Length of absolute refractory period- Cardiac muscle cells, the absolute refractory period( the inexcitable period when Na+ channels are still open or inactivated) lasts approximately 250m, nearly as long as the contraction. Conducting system and pacemaker These are the cardiac muscle cells that are responsible for initiating cardiac muscle action potentials. A. Components of the Conducting System: 30. Sinoatrial (SA) node (=pacemaker) these authorhythmic muscle fibers are located in the right atrial wall just inferior to the opening of the superior vena cava a. SA node has the fastest rate of spontaneous depolarization and acts as the heart s pacemaker; it sets the sinus rhythm b. SA node will guide your heart beats if it s healthy c. The natural pacemaker of the heart d. SA node initiate action potentials 90-100 times/min faster than any other region

e. SA node sets the pace for the heart as a whole because no other region of the conducting system or the myocardium has a faster depolarization rate. 31. Atrioventricular (AV) node located near the septum between the two atria a. A delay station in the cardiac conduction system b. At the AV node, the impulse is delayed allowing the atria to respond and complete their contraction before the ventricles contract. Atrioventricular (AV) bundle (bundle of His) located in the superior portion of the invterventricular septum; it is the ONLY electrical connection between the atria and the ventricles Right & left bundle branches located in the interventricular septum they course through the interventricular septum toward the apex of the heart Conduction myofibers(Purkinje fibers) with a large diameter they conduct the action potentials to the ventricular myocardium Electrocardiogram

Electrical impulse conduction through the heart generates electrical currents that can be detected at the surface of the body. A recording of the electrical changes that accompany each cardiac cycle(heartbeat) is called an electrocardiogram(ECG or the older term, EKG) A normal ECG 32. P wave lasts about 0.08s and results from movement of the depolarization wave from the SA node through the atria. Soon after atria start to contract larger p waves= enlargement of an atrium The electrical impulses that initiate the impulse in the atria (pwave) 33. QRS complex (ventricular depolarization- spread of impulse through ventricles) ventricles start to contract. Ventricles 34. T wave (ventricular repolarization)- smaller than QRS because repolarization occurs more slowly than depolarization y T wave flatter than normal- heart muscle is receiving insufficient oxygen- coronary artery disease y Regrouping of the ventricular electronegativity P-Q interval represents the conduction time from the beginning of atrial excitation to the beginning of ventricular excitation S-T segment represents the time when ventricular contractile fibers are fully depolarized, during the plateau phase of the impulse Q-T interval beginning of ventricular depolarization to the end of ventricular repolarization Cardiac Output Since the body s need for oxygen varies with the level of activity, the heart s ability to discharge oxygencarrying blood must also be variable. 35. Cardiac Output (CO) is the amount of blood ejected by the left ventricle( or right ventricle) into the aorta (or pulmonary trunk) per minute, and it is calculated as follows:

a. CO= stroke volume X heart rate b. Both ventricles expel the same amount of blood c. The amount of blood pumped out by each ventricle in 1 minute. It is the product of heart rate (HR) and stroke volume (SV) 36. Stroke volume is defined as the volume of blood pumped out by one ventricle with each beat. a. The percent of blood ejected from the heart with every contraction b. It is around 40-55%. THE HEART never is completely empty. c. Factors that increase Stroke volume or heart rate normally increase CO. Example: stroke volume might increase to 100 ml/beat, and heart rate to 100 beats/min. Cardiac output then would be 10 L/min. During intense exercise, the heart rate may accerlerate to 150 beats/min, and stroke volume may rise to 130 ml/ beat, rsulting in a CO of 19.5 L/min. d. NORMAL CO=80 ml/beat x 75 beats/min= 6 liters/min 37. Normal blood pressure 120/80 a. Control weight, eating habits and life style. To cure blood pressure Heart Rate Several horomones and cations have major effects on the heart: 1. Hormones- epinephrine and norepinephrine from adrenal medulla- increase both heart rate and contractility a. The stimulus for release is exercise, stress and excitement b. Thyroid hormones- also enhance heart rate and contractility. One of the signs of hyperthryodisdism is tachycardia- increase heart rate at rest. 2. Cations ( Na+, K+ and Ca 2+) 3. Hormones that regulate BP are epinephrine, norepinephrine, ADH (vasopressin), angiotensin II, and ANP Other factor: a. Age- a baby has a heart rate of 120 beats/min, and then it decreases with age. Seniors may have an increased beat b. Gender- females have a higher heartbeat than males( in general) c. Physical fitness- some athletes may exhibit bradycardia, a resting heart rate of 60 beats/min due to endurance type training d. Temperature- increased body temperature as fever, increases heart rate, SA node discharges impulses faster i. During surgical repair of certain heart abnormalities, it is helpful to slow a patient s heart rate by Hypothermia. 39. Aorta is the largest artery of the body. Its four principal divisions are the ascending aorta, arch of the aorta, thoracic aorta and abdominal aorta. The portion of the aorta that emerges from the left ventricle

posterior to the pulmonary trunk is the ascending aorta. The beginning of the aorta contains the aortic valve. Ascending, transverse, thoracic, abdominal- all one blood vessel leading out of the left ventricle 1. Ascending Aorta: right and left coronary arteries- heart 2. Arch of the Aorta: brachiocephalic trunk, R common ceratoid artery- R side of head and neck, R subclavian artery- R upper limb, L common carotid artery- L side of head and neck, L subclavian artery- L upper limb. 3. Thoracic Aorta : Pericardial arteries- pericardium, Bronchial arteries- bronchi of lungs, Esophageal arteries- esophagus, Mediastinal- structures in mediastinum, Posterior intercostals- intercostals and chest muscles, subcostal arteries- same as PI, superior phrenic arteries- superior and posterior surfaces of diaphragm 4. Abdominal aorta: inferior phrenic arteries,celiac trunk Brachiocephalic Trunk 40. Internal carotid artery has no branches in the neck and supplies structures internal to the skull. The internal carotid artery supplies blood to the eyeball and other orbital structures, ear, most of the cerebrum of the brain, pituitary gland, and external nose. Brain Unpaired visceral branches 41. Celiac Trunk (artery) is the first visceral branch from the aorta inferior to the diaphragm, at about the level of the twelfth thoracic vertebra. Almost immediately the celiac trunk divides into three branches: L gastric, splenic, and common hepatic arteries Liver, stomach, spleen and diaphragm 42. Superior Mesenteric artery arises from the anterior surface of the abdominal aorta. Pertaining to the intestines Small Intestine 43. Inferior Mesenteric artery arises from the anterior aspect of the abdominal aorta at the level of the third lumbar vertebra and then passes inferiorly to the left of the aorta. Part of the small intestine and colon Paired visceral branches 44. Renal arteries usually arise from the lateral aspects of the abdominal aorta at the superior border of the second lumbar vertebra. The renal arteries carry blood to the kidneys, adrenal (suprarenal) glands, and ureters. Kidneys Common Illiac Arteries 45. Femoral artery a pulse may be felt in the femoral artery just inferior to the inguinal ligament. Is to the lower abdominal wall, groin, external genitals, and muscles of the thigh. A major branch of the femoral artery, the deep artery of the thigh (deep femoral), supplies most of the muscles of the thigh; quadriceps femoris, adductors, and hamstrings. Legs

Veins 46. Superior vena cava empties its blood into the superior part of the right atrium. It begins posterior to the right first costal cartilage by the union of the right and left brachiocephalic neck, chest and free upper limbs Return deoxygenated blood from the body 47. Inferior vena cava is the largest vein in the body. It begins anterior to the first lumbar vertebra by the union of the common iliac veins, ascends behind the peritoneum to the right of the midline, pierces the caval opening of the diaphragm at the level of the eighth thoracic vertebra, and enters the inferior part of the right atrium. The IVC drains the abdomen, pelvis, and free lower limbs. IVC is commonly compressed during the later stages of pregnancy by the enlarging uterus, producing edema of the ankles and feet and temporary varicose veins. Return deoxygenated blood from the body. Return the most

48. Pulmonary Artery- Only artery that carries poorly oxygenated blood 49. Pulmonary Vein- Only vein that carries well-oxygenated blood Respiratory system consists of the nose, pharynx (throat), larynx (voice box), trachea (windpipe), bronchi and lungs. - RS provides for gas exchange, intake of 02, and elimination of C02, whereas the cardiovascular system transports the gases in the blood between the lungs and cells and vice-versa - Provides for gas exchange- intake of O2 for delivery to body cells and elimination of CO2 produced by body cells -helps regulate blood pH - contains receptors for the sense of smell, filters inspired air, produces vocal sounds(phonation), and excretes small amounts of water and heat Divided into two: 50. Upper respiratory system nose, pharynx (throat) and associated structures. y Nasal canal, nasal pharynx, mouth, pharynx and oral pharynx. Stops at larynx

51. Lower respiratory system larynx (voice box), trachea (windpipe), bronchi and lungs y main stem bronchioles all the way down to the alveoli

Functionally, the respiratory system also consists of two parts:

52. Conducting Zone consist of series of interconnecting cavities and tubes both outside and within the lungs. These include the nose, pharynx, larynx, trachea, bronchi, bronchioles, and terminal bronchioles - Their function is to filter, warm, and moisten air and conduct it into the lungs - They don t exchange Carbon dioxide 53. Respiratory zone consists of tissues within the lungs where gas exchange occurs. These include the respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli - They are the main sites of gas exchange between air and blood - does exchange carbon dioxide and oxygen Pulmonary Ventilation Is the process by which gases are exchanged between the atmosphere and the lung alveoli (External Respiration= lungs to blood; Internal Respiration= blood to tissue) Pulmonary ventilation (breathing) consists of inspiration and expiration Three factors contribute to pulmonary ventilation: 1. changes in Gas pressure inside and outside the lungs 2. surface tension in the alveoli 3. compliance= expandability of the lungs 54. Compliance= expandability of the lung. Refers to how much effort is required to stretch the lungs and chest wall. High compliance means that the lungs and chest wall expand easily; low compliance means that they resist expansion. - it is the ease with which the lungs and thoracic wall can be expanded - higher compliance means that the lungs and thoracic cage expand easily -for example: a thin balloon is easier to inflate (higher compliance) than a thick rigid balloon - in lungs it depends on elasticity(lung CT), surface tension (surfactant), and mobility of thoracic cage Conditions that decrease compliance: a. b. c. d. Tuberculosis destroys lining tissue- produces scar Pulmonary edema causes it to become filled with fluid; RDS surfactant deficiency Paralysis impedes lung expansion or contraction

Condition that increase compliance: 55. Emphysema- the alveolar wall disintegrates, producing abnormally large air spaces. Scarring of the bronchiolar SM and mucous production, obstructing the airways. y y y y Alveoli are ruptured. You re fighting the air out. It s easier to breathe in. Lung exhibits largers but fewer alveoli Lung become less elastic and fibrotic Air becomes trapped in the lungs, and over a period of time a person becomes barrel-chested. Muscles of inhalation and exhalation Two types of Muscles are involved in establishing pressure gradients between the lungs and the atmosphere 56. Diaphragm which cause the thoracic cavity to expand in the vertical direction during inspiration - Most important breathing muscle in the body - Inspiration diaphragm descends and increases depth of thoracic cavity - Expiration diaphragm ascends and reduces depth of thoracic cavity - when diaphragm relaxes, it bulges upward again, compresses the lungs, and expels air. The diaphragm alone accounts for about two-thirds of the pulmonary airflow 57. External intercostals muscles which causes the thoracic cavity to expand in the horizontal direction during inspiration - Helps us breathe in - Inspiration EIM elevates ribs 2-12 widen thoracic cavity - between ribs and muscles. Pulls up when we breathe 58. Internal intercostals muscles depresses ribs 1-11, narrow thoracic cavity - helps us breathe out (Expiration) -angle back so that it could expel air Exchange of Oxygen and Carbon dioxide 59. How do O2 and CO2 get interchange in the lungs? Passive diffusion (higher concentration to lower concentration) The exchange of oxygen and carbon dioxide between alveolar air and pulmonary blood occurs via passive diffusion, which is governed by the behavior of gases: Dalton s law and Henry s law.

As soon as the lungs fill with air, O2 starts to diffuse from the alveoli into the blood, through the interstitial fluid, and finally into the cells CO2 diffuses in the opposite direction, from the cells, through interstitial fluid to the blood, and into the alveolar air Gas Laws: y Dalton s Law states that the total pressure of gas mixture is equal to the sum of the partial pressures of the individual gases in the gas mixture. Each gas in a mixture of gases exerts its own pressure as if all the other gases were not present o The partial pressures are important in determining the movement of O2 and CO2 between the atmosphere and the lungs, the lungs and the blood, and the blood and the body cells y Henry s Law states that the quantity of a gas that will dissolve in a liquid is proportional to the partial pressure of the gas and its solubility coefficient(its physical or chemical attraction for water) o This important in relation to NITROGEN (N2) dissolved in body fluids. o Excessive amounts of dissolved N2 may produce giddiness (euphoria) and other symptoms similar to alcohol intoxication= known as nitrogen narcosis o Example: Diver. Go to fast up to the surface results in decompression sickness. The effects result from bubbles in the nervous tissue and can be mild or severe, depending on the number of bubbles formed. Symptoms, joint pain, dizziness, shortness of breath, extreme fatigue, paralysis and unconsciousness o Hyperbaric oxygenation- technique uses pressure to cause more oxygen to dissolve in the blood and is used to treat anaerobic bacterial infections(tetanus and gangrene) External and Internal Respiration

In internal and external respiration, O2 and CO2 diffuse from areas of their higher partial pressure to areas of their lower partial pressures External respiration or pulmonary gas exchange is the diffusion of O2 from air in the alveoli of the lungs to blood in pulmonary capillaries and the diffusion of CO2 in the opposite direction. Exchange of gases between alveoli and pulmonary blood capillaries It results in the conversion of deoxygenated blood(more CO2 than O2) coming from the heart to oxygenated blood(more O2 than CO2) returning to the heart

Internal respiration is the exchange of gases between tissue blood capillaries and tissue cells.

It results in the conversion of oxygenated blood into deoxygenated blood

60. How do O2 and CO2 get interchanged at the tissue level? As pH goes down, CO2 goes up, and temperature goes up, the oxygen leaves the hemoglobin much easier. Acidity - As acidity increases (pH decreases), the affinity of hemoglobin for O2 decreases, and O2 dissociates more readily from hemoglobin. In an acid (low pH) environment, O2 dissociates more readily from hemoglobin This is referred to as the BOHR Effect The curce shifts to the right as the enivoronment becomes more acidic Higher pH (alkaline) will increase the affinity of O2 for hemoglobin Temperature Within limits as temperature increases, so does the amount of oxygen released from hemoglobin Active cells require more oxygen, and active cells(such as contracting muscle cells) liberate more acid and heat; the acid and heat, in turn, stimulate the oxyhemoglobin to release its oxygen During hypothermia(lowered body temp) cellular metabolism slows down , more O2 remains bound to the hemoglobin ( shifts curve to the left) Respiratory Center The basic rhythm of respiration set and coordinated by the inspiratory area can be modified in response to input from other brain regions, receptors in the peripheral nervous system, and other factors 61. The effect of the brain on respiration- there are several centers (nuclei) responsible for respirationthe inspiration and expiration centers, the rhythmicity center, the pneumotaxic area: all of them initiate and sustain respiration 1. Respiratory centers- located in the medulla oblongata and pons of the brain stem. Divided into three areas : Medullary rhythmicity area in the medulla oblongata, the pneumotaxic area in the pons, and the apneustic area also in the pons. A. Medullary rhythmicity basic rhythm for breathing is generated within the medulla - inspiratory area nerve impulses establish the basic rhythm of breathing. o I neurons relay their activity to send impulses to External Intercostal muscle to the phrenic motor neurons that control the contraction of the diaphragm.

- expiratory area remain inactive during quiet breathing. Latter fire immediately prior to expiration. E neurons supply activity to the expiratory muscles when expiration becomes active. B. Pneumotaxtic Area in the upper pons, which transmits inhibitory impulses to the inspiratory area. Major effect of these nerve impulses is to help turn off the inspiratory area before the lungs become too full of air. Shorten the duration of inhalation. C. Apneustic Area part of the brain stem that coordinates the transition between inhalation and exhalation. In lower pons. Area sends stimulatory impulses to the inspiratory area to activate it and prolong inhalation. Activates a prolong inspiration, inhibiting expiration. o Chronic Obstructive Pulmonary Disease Diseases is an irreversible decrease in the ability to force air out of the lungs. y Hyperventilation is an increase in the rate and depth of breathing that exceeds the body s need to remove CO2. Expel CO2 faster than it is produced, thus lowering the blood CO2 concentration and raising the blood pH. Breathing too fast. The oxygen is not getting in. Alkaline blood. Emphysema alveoli are ruptured. Your fighting the air out. It s easier to breathe in. Destruction of alveolar walls, loss of lung elasticity, air trapping 62. Asthma is characterized by episodes of coughing, dyspnea, wheezing, and chest tightnessalone or in combination. Most acute attacks are accompanied by a sense of panic. Classed as COPD but is reversible. Increase reactivity of the bronchiolar SM and mucous production, obstructing the airways.

y y