P a g e 52 A & P II SWARTZ NOTES Page 52

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1 P a g e 52 A & P II SWARTZ NOTES Page 52 THE LYMPHATIC SYSTEM AND IMMUNITY The lymphatic system consists of a fluid called lymph, vessels that convey lymph called lymphatics, and a number of structures and organs, all of which contain lymphatic (lymphoid) tissue. Essentially, lymphatic tissue is a specialized form of reticular connective tissue that contains large numbers of lymphocytes. The stroma (framework) of lymphatic tissue is a meshwork of reticular fibers and reticular cells (fibroblasts and fixed macrophages). One exception to this is the thymus gland, which has a stroma of epithelioreticular tissue. Lymphatic tissue is organized in various ways. Accumulations of lymphatic tissue not enclosed by a capsule are referred to as diffuse lymphatic tissue. This is the simplest form of lymphatic tissue and is found in the lamina propria (connective tissue) of mucous membranes of the gastrointestinal (GI) tract, respiratory passageways, urinary tract, and reproductive tract. It is also normally found in small amounts in the stroma of almost every organ of the body. Lymphatic nodules are unencapsulated oval-shaped concentrations of lymphatic tissue that usually consist of a central, lighter-staining region consisting of large lymphocytes (germinal center) and a peripheral, darker-staining region of small lymphocytes (cortex). Most lymphatic nodules are solitary, small, and discrete. Some lymphatic nodules occur in multiple, large aggregations in specific parts of the body. Among these are the tonsils in the pharyngeal region and aggregated lymphatic follicles (Peyer's patches) in the ileum of the small intestine. Aggregations of lymphatic nodules also occur in the appendix. The lymphatic organs of the body--the lymph nodes, spleen, and thymus gland--all contain lymphatic tissue enclosed by a connective tissue capsule. Since bone marrow produces lymphocytes, it is also a component of the lymphatic system.

2 P a g e 53 The lymphatic system has several functions. 1. Lymphatics drain protein-containing fluid from tissue spaces that escape from blood capillaries. The proteins, which cannot be directly reabsorbed by blood vessels, are returned to the cardiovascular system by lymphatics. 2. Lymphatics also transport fats from the gastrointestinal (GI) tract to the blood. 3. Lymphatic tissue also functions in surveillance and defense, that is, lymphocytes, with the aid of macrophages, protect the body from foreign cells, microbes, and cancer cells. 4. Lymphocytes recognize foreign cells and substances, microbes, and cancer cells, and respond to them in two general ways. Some lymphocytes (T cells) destroy them directly or indirectly by releasing various substances. Other lymphocytes (B cells) differentiate into plasma cells that secrete antibodies against foreign substances to help eliminate them. Overall, the lymphatic system concentrates foreign substances in certain lymphatic organs, circulates lymphocytes through the organs to make contact with the foreign substances, and destroys the foreign substances and eliminates them from the body. LYMPHATIC VESSELS Lymphatic vessels originate as microscopic vessels in spaces between cells called lymph capillaries. Lymph capillaries may occur singly or in extensive plexuses. They originate throughout the body, but not in avascular tissue, the central nervous system, splenic pulp, nor bone marrow. They are slightly larger and more permeable than blood capillaries. Lymph capillaries also differ from blood capillaries in that they end blindly. Blood capillaries have an arterial and a venous end. In addition, lymph capillaries are structurally adapted to ensure the return of proteins to the circulation when they leak out of blood capillaries. The endothelial cells lining lymph capillaries overlap one another forming pores which permits fluid to flow easily into the capillary but prevents the flow of fluid out of the capillary, much like a one-way valve would operate. During edema, there is an excessive accumulation of fluid in the tissue, causing tissue swelling.

3 P a g e 54 Just as blood capillaries converge to form venules and veins, lymph capillaries unite to form larger and larger lymph vessels called lymphatics. Lymphatics resemble veins in structure, but have thinner walls and more valves, and contain lymph nodes at various intervals. Lymphatics of the skin travel in loose subcutaneous tissue and generally follow veins. Lymphatics of the viscera generally follow arteries, forming plexuses around them. Ultimately, lymphatics converge into two mid channels--the thoracic duct and the right lymphatic duct. LYMPHATIC TISSUE (1) Lymph Nodes: The oval or bean-shaped structures located along the length of lymphatics are called lymph nodes. They are scattered throughout the body, usually in groups, and range from 1 to 25 mm (0.04 to 1 inch) in length. A lymph node contains a slight depression on one side called a hilus = hilum, where blood vessels and efferent lymphatic vessels leave the node. Each node is covered by a capsule of dense connective tissue that extends into the node. The capsular extensions are called trabeculae,. Internal to the capsule is a supporting network of reticular fibers and reticular cells (fibroblasts and macrophages). The capsule, trabeculae, and reticular fibers and cells constitute the stroma (framework) of a lymph node. The parenchyma of a lymph node is specialized into two regions: cortex and medulla. The parenchyma is the functional aspect of the lymph node. The outer cortex contains densely packed lymphocytes arranged in masses called lymphatic nodules. The nodules often contain lighter-staining central areas, the germinal centers, where lymphocytes are produced. The inner region of a lymph node is called the medulla. In the medulla, the lymphocytes are arranged in strands called medullary cords. The circulation of lymph through a node involves afferent (to convey toward a center) lymphatic vessels, sinuses in the node, and efferent (to convey away from a center) lymphatic vessels. Afferent lymphatic vessels enter the convex surface of the node at several points. They contain valves that open toward the node so that the lymph is directed inward. Once inside the node,

4 P a g e 55 the lymph enters the sinuses, which are a series of irregular channels. Lymph from the afferent lymphatic vessels enters the cortical sinuses just inside the capsule. From here it circulates to the medullary sinuses between the medullary cords. From these sinuses the lymph usually circulates into one of two efferent lymphatic vessels. The efferent vessel is located at the hilus of the lymph node. It is wider than the afferent vessels and contains valves that open away from the node to convey the lymph out of the node. Lymph nodes are scattered through the the body, usually in groups. Typically, these groups are arranged in two sets: superficial and deep. Lymph passing from tissue spaces through lymphatics on its way back to the cardiovascular system is filtered through the lymph nodes. As lymph passes through the nodes, it is filtered of foreign substances. These substances are trapped by the reticular fibers within the node. Then, macrophages destroy the foreign substances by phagocytosis, T cells may destroy them by releasing various products, and/or B cells may produce antibodies that destroy them. Lymph nodes also produce lymphocytes, some of which can circulate to other parts of the body Clinical Application Knowledge of the location of lymph nodes and the direction of lymph flow is important in the diagnosis and prognosis of the spread of cancer by metastasis. Cancer cells usually spread by way of the lymphatic system and produce aggregates of tumor cells where they lodge. Such secondary tumor sites are predictable by the direction of lymph flow from the organ primarily involved (2) Tonsils: Tonsils are multiple aggregations of large lymphatic nodules embedded in a mucous membrane. The tonsils are arranged in a ring at the junction of the oral cavity and pharynx. The single pharyngeal tonsil or

5 P a g e 56 adenoid is embedded in the posterior wall of the nasopharynx. The paired palatine tonsils are situated in the tonsillar fossae between the pharyngopalatine and glossopalatine arches. These are the ones commonly removed by a tonsilectomy. The paired lingual tonsils are located at the base of the tongue and may also have to be removed by a tonsillectomy. The tonsils are situated strategically to protect against invasion of foreign substances. Functionally, the tonsils produce lymphocytes and antibodies. (3)Spleen: The oval spleen is the largest mass of lymphatic tissue in the body, measuring about 12 cm (5 inches) in length. It is situated in the left hypochondriac region between the fundus of the stomach and diaphragm. Its visceral surface contains the contours of the organs adjacent to it, namely the gastric impression (stomach), renal impression (left kidney), and colic impression (left flexure of colon). The diaphragmatic surface of the spleen is smooth and convex and conforms to the concave surface of the diaphragm to which it is adjacent. The spleen is surrounded by a capsule of dense connective tissue and scattered smooth muscle fibers. The capsule, in turn, is covered by a serous membrane, the peritoneum. Like lymph nodes, the spleen contains a hilus, trabeculae, and reticular fibers and cells. The capsule, trabeculae, and reticular fibers and cells constitute the stroma of the spleen. The parenchyma of the spleen consists of two different kinds of tissue called white pulp and red pulp. White pulp is essentially lymphatic tissue, mostly lymphocytes, arranged around arteries called central arteries. In various areas, the lymphocytes are thickened into lymphatic nodules referred to as splenic nodules (Malpighian corpuscles). The red pulp consists of venous sinuses filled with blood and cords of splenic tissue called splenic cords, or cords of Billroth's. Veins are closely associated with the red pulp. Splenic cords consist of erythrocytes, macrophages, lymphocytes, plasma cells, and granulocytes.

6 P a g e 57 The splenic artery and vein and the efferent lymphatics pass through the hilus. Since the spleen has no afferent lymphatic vessels or lymph sinuses, it does not filter lymph. One key splenic function related to immunity is the production of B lymphocytes, which develop into antibody-producing plasma cells. The spleen also phagocytizes bacteria and worn-out and damaged red blood cells and platelets. In addition, the spleen stores and releases blood in case of demand, such as during hemorrhage. In this regard, the spleen is considered to be a blood reservoir. (4) Thymus Gland: Usually a bilobed lymphatic organ, the thymus eland is located in the superior mediastinum, posterior to the sternum and between the lungs. The two thymic lobes are held in close proximity by an enveloping layer of connective tissue. Each lobe is enclosed by a connective tissue capsule. The capsule gives off extensions into the lobes called trabeculae, which divide the lobes into lobules. Each lobule consists of a deeply staining peripheral cortex and a lighter-staining central medulla. The medulla contains characteristic thymic corpuscles known as Hassall's corpuscles. Hassall's corpuscles are concentric layers of epithelial cells. Their significance is not known. The thymus gland is conspicuous in the infant, and it reaches its maximum size of about 40 grams during puberty. After puberty, most of the thymic tissue is replaced by fat and connective tissue. By the time the person reaches maturity, the gland has atrophied substantially. The role of the thymus in immunity is to help produce T cells that destroy invading microbes directly or indirectly by producing various substances. LYMPH CIRCULATION When plasma is filtered by blood capillaries, it passes into interstitial spaces. At this point it is known as interstitial fluid. When this fluid passes from interstitial spaces into lymph capillaries, it is called lymph. Lymph from lymph capillaries is then passed to lymphatics that run toward lymph nodes. At the nodes, afferent vessels penetrate the capsules at numerous points, and the

7 P a g e 58 lymph passes through the sinuses of the nodes. Efferent vessels from the nodes either run with afferent vessels into another node of the same group or pass on to another group of nodes. From the most proximal group of each chain of nodes, the efferent vessels unite to form lymph trunks. The principal trunks are the lumbar, intestinal, bronchomediastinal, subclavian, and juglar trunks. The principal trunks pass their lymph into two main channels, the thoracic duct and the right lymphatic duct. The thoracic duct also known as the left lymphatic duct is about 38 to 45 cm (15 to 18 inches) in length and begins as a dilation in front of the second lumbar vetebra called the cisterna chyli. The thoracic duct is the main collecting duct of the lymphatic system and receives lymph from the left side of the head, neck, and chest, the left upper extremity, and the entire body below the ribs. The cisterna chyli receives lymph from the right and left lumbar trunks and from the intestinal trunk. The lumbar trunks drain lymph from the lower extremities, wall and viscera of the pelvis, kidneys, suprarenals, and the deep lymphatics from most of the abdominal wall. The intestinal trunk drains lymph from the stomach, intestines, pancreas, spleen, and visceral surface of the liver. In the neck, the thoracic duct also receives lymph from the left jugular, left subclavian, and left bronchomediastinal trunks. The left jugular trunk drains lymph from the left side of the head and neck; the left subclavian trunk drains lymph from the upper left extremity; and the left bronchomediastinal trunk drains lymph from the left side of the head and neck; the left subclavian trunk drains lymph from the upper left extremity; and the left bronchomediastinal trunk drains lymph from the left side of the deeper parts of the anterior thoracic wall, upper part of the anterior abdominal wall, anterior part of the diaphragm, left lung, and left side of the heart. The right lymphatic duct is about 1.25 cm (0.5 inch) 1onz and drains lymph from the upper right side of the body. The right lymphatic duct collects lymph from its trunks as follows.

8 P a g e It receives lymph from the right jugular trunk, which drains the right side of the head and neck 2. From the right subclavian trunk, which drains the right upper extremity 3. And from the right bronchomediastinal trunk, which drains the right side of the thorax, right lung, right side of the heart, and part of the convex surface of the liver Ultimately, the thoracic duct empties all of its lymph into the junction of the left internal jugular vein and left subclavian vein, and the right lymphatic duct empties all of its lymph into the junction of the right internal jugular vein and right subclavian vein. Thus, lymph is drained back into the blood and the cycle repeats itself continuously. The flow of lymph from tissue spaces to the large lymphatic ducts to the subclavian veins is maintained primarily by the milking action of muscle tissue. Skeletal muscle contractions compress lymph vessels and force lymph toward the subclavian veins. Lymph vessels, like veins, contain valves, and the valves ensure the movement of lymph toward the subclavian veins. Another factor that maintains lymph flow is respiratory movements. These movements create a pressure gradient between the two ends of the lymphatic system. Lymph flows from the abdominal region, where the pressure is higher, toward the thoracic region, where it is lower. Edema: An excessive accumulation of interstitial fluid in tissue spaces may be caused by an obstruction such as an infected node or a blockage of vessels in the pathway between the lymphatic capillaries and the subclavian veins. Another cause of edema is excessive lymph formation and increased permeability of blood capillary walls. A rise in capillary blood pressure in which interstitial fluid is formed faster than it is passed into lymphatics may also result in edema.

9 P a g e 60 NONSPECIFIC RESISTANCE TO DISEASE The human body continually attempts to maintain homeostasis by counteracting harmful stimuli in the environment. Frequently, these stimuli are diseaseproducing organisms, called pathogens. or their toxins. The ability to ward off disease is called resistance. Lack of resistance is called susceptibility. Defenses against disease may be grouped into two broad areas: Nonspecific resistance and specific resistance. Nonspecific resistance is inherited and represents a wide variety of body reactions against a wide range of pathogens. Specific resistance or immunity involves the production of a specific antibody against a specific pathogen or its toxin. Immunity is developed during a person's life; it is not inherited. The skin and mucous membranes of the body are commonly regarded as the first line of defense against disease-causing microorganism. They possess certain mechanical and chemical factors that are involved in combating the initial attempt of a microbe to cause disease. Mechanical Factors: The intact skin consists of two distinct portions known as the dermis and epidermis. Mucous membranes, like the skin, also consist of an epithelial layer and an underlying connective tissue layer. But unlike the skin, a mucous membrane lines a body cavity that opens to the exterior. The epithelial layer of a mucous membrane secretes a fluid called mucus, which prevents the cavities from drying out. Since mucus is slightly viscous, it traps many microbes that enter the respiratory and digestive tracts. The mucous membrane of the nose has mucus-coated hairs that trap and filter air containing microbes, dust, and pollutants. The mucous membrane of the upper respiratory tract contains cilia, microscopic hairlike projections of the epithelial cells. These cilia move in such a manner that they pass inhaled dust and microbes that have become trapped in mucus toward the throat. This so-called "ciliary escalator" keeps the "mucus blanket" moving toward the throat. Coughing and sneezing speed up the 'escalator."

10 P a g e 61 Since some pathogens can thrive on the moist secretions of a mucous membrane, they are able to penetrate the membrane if present in sufficient numbers. This penetration may be related to toxic products produced by the microbes, prior injury by viral infections, or mucosal irritations. Although mucous membranes do inhibit the entrance of many microbes, they are less effective than the skin. There are several other mechanical factors that help to protect epithelial surfaces of the skin and mucous membranes. One such mechanism that protects the eyes is the lacrimal apparatus. It consists of a group of structures that manufactures and drains away tears, which are spread over the surface of the eyeball by blinking. The continual washing action of tears helps to keep microbes from settling on the surface of the eye. Saliva produced by the salivary glands, washes microbes from the surfaces of the teeth and the mucous membrane of the mouth, much as tears wash the eyes. Microbes are additionally prevented from entering the lower respiratory tract by a small lid of cartilage called the epiglottis that covers the voice box during swallowing. The cleansing of the urethra by the flow of urine represents another mechanical factor that prevents microbial colonization in the urinary system. Chemical Factors: Mechanical factors alone do not account for the high degree of resistance of skin and mucous membranes to microbial invasion. Certain chemical factors play an important role. Sebum, produced by the sebaceous (oil) glands of the skin, forms a protective film over the surface of the skin and inhibits the growth of certain bacteria. Perspiration flushes some microbes from the skin. Gastric juice is a collection of hydrochloric acid, enzymes, and mucus produced by the glands of the stomach. The very high acidity of gastric juice (ph ) is sufficient to preserve the usual sterility of the stomach. The acidity of gastric juice destroys bacteria and almost all important bacterial toxins.

11 P a g e 62 The acidic ph of the skin, between 3.0 and 5.0, is due in part to the acid products of bacterial metabolism. This acidity probably discou rages the growth of many microbes that contact the skin. One of the components of sebum is unsaturated fatty acids. These fatty acids kill certain pathogenic bacteria. Lysozyme is an enzyme capable of breaking down cell walls of various bacteria under certain conditions. Lysozyme is normally found in perspiration, tears, saliva, nasal secretions, and tissue fluids. Antimicrobial Substances: In addition to the mechanical and chemical barriers of the skin and mucous membranes, the body also produces certain antimicrobial substances. Among these are interferon, complement, and properdin. Interferon: Host cells infected with viruses produce a protein called interferon. There are three principal types of interferon called alpha, beta, and gamma. In humans, interferon has been shown to be produced by lymphocytes and other leucocytes and fibroblasts. Once released from virus-infected cells, interferon diffuses to uninfected neighboring cells and binds to "surface receptors. This induces uninfected cells to synthesize another antiviral protein that i n h i b i t s intracellular viral replication. Interferon appears to be the body's first line of defense against infection by many different viruses. It appears to decrease the virulence (disease-producing power) of viruses associated with chicken-pox, genital herpes, rabies, rubella, chronic hepatitis, shingles, eye infections, encephalitis, and types of the common cold. Complement: Another antimicrobial substance that is very important to nonspecific resistance (and immunity) is complement. Complement is actually a group of eleven proteins found in normal blood serum. The system is called complement because it

12 P a g e 63 "complements" certain immune and allergic reactions involving antibodies. The function of antibody is to recognize the microbe as a foreign organism, form an antigen-antibody complex, and activate complement for attack. The antigen - antibody complex also fixes (attaches) the complement to the surface of the invading microbe. Once complement is activated, it destroys microbes as follows: 1. Some complement proteins initiate a series of reactions leading to cell lysis caused by holes in the plasma membrane of the microbe. 2. Some complement proteins interact with receptors on phagocytes, promoting phagocytosis. This is called opsonization or immune adherence. 3. Some complement proteins contribute to the development of inflammation by causing the release of histamine from mast cells, leucocytes, and platelets. Histamine increases the permeability of blood capillaries, a process that enables leucocytes to penetrate tissues in order to combat infection or allergy. 4. Some complement proteins serve as chemotactic agents, attracting large numbers of leucocytes to the area. Properdin: Properdin, like complement, is also a protein found in serum. It is a complex consisting of three proteins. Properdin, acting together with complement, leads to the destruction of s e v e r a l types of b a c t e r i a, the e n h a n c e m e n t of phagocytosis, and triggering of inflammatory responses. PHAGOCYTOSIS When microbes penetrate the skin and mucous m e m b r a n e s, or bypass the antimicrobial substances in blood, there is another nonspecific resistance of the body called phagocytosis. Very simply, phagocytosis means the ingestion and destruction of microbes or any foreign particulate matter by certain cells called phagocytes.

13 P a g e 64 Kinds of Phagocytes: The kinds of phagocytes that participate in the process fall into two broad categories: microphages and macrophages. The granulocytes of blood are called microphages. However, not all granulocytes exhibit the same phagocytic capabilities. Neutrophils have the most prominent phagocytic a c t i v i t y. Eosinophils are believed to have some phagocytic capability, and the role of basophils in phagocytosis is debatable. When an infection occurs, both microphages ( e s p e c i a l l y n e u t r o p h i l s ) and monocytes migrate to the infected area. During this migration, the monocytes enlarge and develop into actively phagocytic cells called macrophages. Since these cells leave the blood and migrate to infected areas, they are called wandering macrophages. Some of the macrophages, called fixed macrophages or histiocytes enter certain tissues and organs of the body and remain there. Fixed macrophages are found in the liver (stellate reticuloendothelial cells), lungs (alveolar macrophages), brain (microglia), spleen, lymph nodes, and bone marrow. Mechanism: Phagocytosis will be divided into two phases: adherence and ingestion. adherence (attachment) is the formation of firm contact between the plasma membrane of t he phagocyte and the microbe (or foreign material). In some instances, adherence occurs easily, and the microbe is readily phagocytized. In other cases, adherence is more difficult, but the particle can be phagocytized if the phagocyte traps the particle to be ingested against a rough surface, like a blood vessel, blood clot, or connective tissue fibers, where it cannot slide away. This is sometimes called nonimmune (surface) phagocytosis. Bacteria can also be phagocytized if they are first coated with comp lement or antibody to promote the attachment of the microbe to the phagocyte. This is opsonization (immune adherence). A final factor that helps adherence is chemotaxis, the attraction of phagocytes to microbes by certain chemicals, such as microbial products, components of white blood cells and tissue cells, and chemicals derived from complement. Following adherence, ingestion occurs. In the process of ingestion, projections of the cell membrane of the phagocyte, called pseudopodia, engulf the microbe. Once the microbe is surrounded, the membrane folds inward, forming a sac around

14 P a g e 65 the microbe called a phagocytic vesicle. The vesicle pinches off from the membrane and enters the cytoplasm. Within the cytoplasm, the vesicle collides with lysosomes that contain digestive enzymes and bactericidal substances. Upon contact, the vesicular and lysosomal membranes fuse together to form a single, larger structure called a phagolysosome (digestive vesicle). Within the phagolysosome, most bacteria are usually killed within 30 minutes. It is assumed that destruction occurs as a result of the contents of the lysosomes, namely lactic acid which lowers the ph in the phagolysosome, the production of hydrogen peroxide, lysozyme, and the destructive capabilities of enzymes that degrade carbohydrates, proteins, lipids, and nucleic acids. Any indigestible materials that cannot be degraded further are found in structures called residual bodies. The cell disposes of materials in residual bodies by exocytosis, in which the residual body migrates to the plasma membrane, fuses to it, ruptures, and releases its contents. Inflammation: When cells are damaged by microbes, physical agents, or chemical agents, the injury sets of an inflammation (inflammatory response). The injury can be viewed as a form of stress. They symptoms of inflammation are: redness, pain, heat, and swelling. A fifth symptom can be the loss of function of the injured area. The inflammatory response serves a protective and defensive role. It is an attempt to neutralize and destroy toxic agents at the site of injury and to prevent their spread to other organs. Thus the inflammatory response is an attempt to restore tissue homeostasis. The inflammatory response is one of the body's internal systems of defense. The response of a tissue to a rusty nail wound is similar to other inflammatory responses, such as the sore throat that results from bacterial or viral invasion. The basic stages of the inflammatory response are:

15 P a g e Vasodilation and increased permeability of blood vessels. Vasodilation is an increase in diameter in the blood vessels. Increased permeability means that substances normally retained in blood are permitted to pass from blood vessels. Vasodilation allows more blood to go to the damaged area and increased permeability permits defensive substances in the blood to enter the injured area. The increased blood supply removes toxic products and dead cells, preventing them from complicating the injury. Vasodilation and increased permeability are caused by the release of certain chemicals by damaged cells in response to injury. One such substance is histamine It is present in many tissues of the body, especially in mast cells in connective tissue, circulating basophils and blood platelets. Histamine is released in direct response to any injured cells containing it. Neutrophils, another type of white blood cell attracted to the site of injury, can also produce chemicals that cause the release of histamine. Other substances that play a role in vasodilation and increased permeability of blood vessels are kinins. These chemicals also attract neutrophils to the injured area. Inflammation also results in an increased synthesis of Prostaglandins (PG). Prostaglandins are strong vasodilators and they intensify the effect of histamine and kinins. Prostaglandins also bring about increased permeability of blood vessels. In addition to the responses in the area of injury, the body may also respond by increasing the metabolic rate and quickening the heartbeat so that more blood circulates to the injured area per minute. Within minutes after the injury, the quickened metabolism and circulation, and especially, the dilation and increased permeability of capillaries produce heat, redness, and swelling. Pain, whether immediate or delayed, is a cardinal symptom of inflammation. 2. Phagocyte migration: Generally, within an hour after the inflammatory process is initiated, phagocytes (microphages and macrophages) appear on

16 P a g e 67 the scene. As the flow of blood decreases, microphages (neutrophils) begin to stick to the inner surface of the endothelial lining of blood vessels. This is called margination. Then, the neutrophils begin to squeeze through the wall of the blood vessel to reach the damaged area. This migration, which resembles amoeboid movement, is called diapedesis. The movement of neutrophils depends on chemotaxis which is the attraction of neutrophils by certain chemicals. Neutrophils are attracted by microbes, kinins, and other neutrophils. A steady stream of neutrophils is ensured by the production and release of additional cells from bone marrow. This is brought about by a substance called leucocytosis-promoting factor, which is released from inflammed tissues. Neutrophils attempt to destroy the invading microbes by phagocytosis. Neutrophils also contain chemicals with antibiotic activity called defensins, so named because of their apparent role in preventing and overcoming infections. Defensins are active against bacteria, fungi, and viruses, unlike other antibiotics that are directed against specific microbes. As the inflammatory response continues, monocytes follow the neutrophils into the infected area. These monocytes then become transformed into wandering macrophages that enhance the phagocytic activity of fixed macrophages. Fixed macrophages mobilize under the stimulus of inflammation and also migrate to the infected area. The macrophages enter the picture during a later stage of the infection. They are several t i m e s more phagocytic than neutrophils and large enough to engulf tissue that has been destroyed, neutrophils that have been destroyed and invading microbes. 3. Release of nutrients: Nutrients stored in the body are used to support the defensive cells. They are also used in the increased metabolic reactions of the cells under attack. 4. Fibrin formation: The blood contains a soluble protein called fibrinogen. Fibrinogen is then converted to an insoluble, thick network called fibrin, which localizes and traps the invading organisms, preventing their spread. This network eventually forms a fibrin clot that prevents hemorrhage and isolates the infected area.

17 P a g e Pus formation: In all but very mild inflammations, pyogenesis occurs. Pus is a thick fluid that contains living, as well as nonliving, white blood cells and debris from other dead tissue. If pus cannot drain out of the body, an abcess develops. An abscess is an excess of accumulation of pus in a confined space. Common examples are pimples and boils. When inflamed tissue is shed, many times it produces an open sore called an ulcer on the surface of an organ or tissue. Ulcers may result from prolonged inflammatory response to a continuously injured tissue. FEVER: The most frequent cause of fever, an abnormally high body temperature, is infection from bacteria and their toxins and viruses. The high body temperature inhibits some

18 P a g e 69 SUMMARY OF NONSPECIFIC RESISTANCE Component Functions Component Functions Skin and mucous membranes Acid ph of skin Discourages growth of microbes Mechanical factors Intact Skin Forms a physical barrier to the entrance of microbes Unsaturated fatty acids Antibacterial substance in sebum Mucous membranes Inhibit the entrance of many microbes, but not as effective as intact skin Lysozyme Antimicrobial substance in perspiration, tears, saliva, nasal secretions, and tissue fluids Mucus Traps microbes in respiratory and digestive tracts Antimicrobial substances Hairs Filter microbes and dust in nose Interferon (IFN) Protects uninfected host cells from viral infection Cilia Together with mucus, trap and remove microbes and dust from upper respiratory tract Complement Causes lysis of microbes, promotes phagocytosis, contributes to inflammation, serves as chemotactic agent Lacrimal apparatus Tears dilute and wash away irritating substances and microbes Properdin Works with complement to bring about same responses as complement Saliva Washes microbes from surfaces of teeth and mucous membranes of mouth Phagocytosis Ingestion and destruction of foreign particulate matter by microphages and macrophages Epiglottis Prevents microbes from surfaces of teeth and mucous membranes of mouth Inflammation Confines and destroys microbes and repairs tissues Urine Washes microbes from urethra Fever Inhibits microbial growth and speeds us body reactions that aid repair Chemical Factors Gastric Juice Destroys bacteria and most toxins in stomach

19 P a g e 70 IMMUNITY (SPECIFIC RESISTANCE TO DISEASE) Despite the variety of mechanisms of nonspecific resistance, they all have one thing in common. They are designed to protect the body from any kind of pathogen. They are not specifically directed against a particular microbe. Specific resistance to disease, called immunity, involves the production of a specific type of cell or specific molecule k n o w n as an antibody to destroy a particular antigen. If antigen 1 invades the body, antibody 1 is produced against it. If antigen 2 invades the body, antibody 2 is produced against it, and so on. The branch of science dealing with the responses of the body when challenged by antigens is known as immunology. Antigens: An antigen or immunogen is any chemical substance that, when introduced into the body, causes the body to produce specific antibodies, which can react with the antigen. Antigens have two important characteristics. The first is immunogenicity which is the ability to stimulate the formation of specific antibodies. The second is reactivity, the ability of the antigen to react specifically with the produced antibodies. An antigen with both of these characteristics is called a complete antigen. Concerning the characteristics of antigens, chemically, the vast majority of a n t i g e n s are proteins, nucleoproteins (nucleic acid + protein), lipoproteins (lipid + protein), glycoproteins (carbohydrate + protein), and certain large polysaccharides. In general, they have molecular weights of 10,000 or more. The entire microbe, such as a bacterium or virus, or components of microbes may act as an antigen. Egg white is a nonmicrobial example of an antigen. Antibodies do not form against the antigen. At specific regions on the surface of the antigen called antigenic determinant sites, specific

20 P a g e 71 chemical groups of the antigen combine with the antibody. This combination depends upon the size and shape of the determinant site and the manner in which it corresponds to the chemical structure of the antibody. The combination is very much like a lick and key. The number of antigenic determinant sites on the surface of an antigen is called valence. Most antigens are multivalent, that is, they have several antigenic determinant sites. A determinant site that has reactivity but not immunogenicity is called a partial antigen or hapten. A hapten can stimulate an immune response if it is attached to a larger carrier molecule so that the combined molecule has two determinant sites. As a rule, antigens are foreign substances. They are not usually part of the chemistry of the body. The body's own substances, recognized as "self," do not act as antigens; substances identified as "nonself," however, stimulate antibody production. However, there are certain conditions in which the distinction between self and nonself breaks down, and antibodies that attach the body are produced. These conditions result in what are called autoimmune disease. Antibodies: An antibody is a protein produced by the body in response to the presence of an antigen and is capable of combining specifically with the antigen. This is essentially the complementary definition of an antigen. The specific fit of the antibody with antigen depends not only on the size and shape of the antigenic determinant site but also on the corresponding antibody site, much again like a lock and key. An antibody, like an antigen, also has a valence. Most antigens are multivalent, most antibodies are bivalent or multivalent, and the majority of human antibodies are bivalent.

21 P a g e 72 Antibodies belong to a group of proteins called globulins, and for this reason they are known as immunoglobulins or lg. Five different classes of immunoglobulins are known to exist in humans. These are designated as IgG, IgA, IgM, IgD, and IgE. Each has a distinct chemical structure and a specific biological role. IgG antibodies enhance phagocytosis, neutralize toxins, and protect the fetus and newborn. IgA antibodies provide localized projection on mucosal surfaces; IgM antibodies are especially effective against microbes by causing agglutination and lysis. IgD antibodies may be involved in stimulating antibody-producing cells to manufacture antibodies. IgE antibodies are involved in allergic reactions. During stress IgA levels decrease. This decrease can lower resistance to infection. Structure: Since antibodies are proteins, they consist of polypeptide chains. Most antibodies contain two pairs of polypeptide chains. Overall the antibody molecule sometimes assumes the shape of the letter Y. At other times, it resembles the letter T. In performing its role in immunity, the antibody is believed to behave as a switch. Cellular and Humoral Immunity: The ability of the body to defend itself against invading agents such as bacteria, toxins, viruses, and foreign tissues consists of two closely allied components. One component consists of the formation of specially sensitized lymphocytes that have the capacity to attach to the foreign agent and destroy it. This is called cellular or cellmediated immunity and is particularly effective against fungi, parasites, intracellular viral infections, cancer cells, and foreign tissue transplants. In the other component, the body produces circulating antibo dies that are capable of attacking an invading agent. This is called humoral or antibody-mediated immunity and is particularly effective against bacterial and v i r a l infections.

22 P a g e 73 Cellular immunity and humoral immunity are the product of the body's lymphoid tissue. The bulk of lymphoid tissue is located in the lymph nodes, but is also found in the spleen and gastrointestinal tract, and to a lesser extent, in bone marrow. The placement of lymphoid tissue is strategically designed to intercept an invading agent before it can spread too extensively into the general circulation. Formation of T Cells and B Cells: Lymphoid tissue consists primarily of lymphocytes that may be distinguished into two kinds. T cells are responsible for cellular immunity. B cells develop into specialized cells (plasma cells) that produce antibodies and provide humoral immunity. Both types of lymphocytes are derived originally in the embryo from lymphocytic stem cells in bone marrow. Before migrating to their positions in lymphoid tissues, the descendants of the stem cells follow two distinct pathways. About half of them first migrate to the thymus gland, where they are processed to become T cells. The name T cell is derived from the processing that occurs in the thymus gland. The thymus gland in some way confers what is called immunologic competence on the T cells. This means that they develop the ability to differentiate into cells that perform specific immune reactions. They then leave the thymus gland and become embedded in lymphoid tissue. Immunologic competence is conferred by the Thymus gland shortly before birth and for a few months after birth. The remaining stem cells become B lymphocytes. They are given this name because in birds they are processed in the Bursa of Fabricius, a small pouch of lymphoid tissue attached to the intestines. Once processed, B cells migrate to lymphoid tissue and take up their positions there. Unlike the various nonspecific resistance factors previously discussed, the responses of T cells and B cells very much depend on the ability of the cells to recognize specific antigens. Macrophages process and present antigens to T cells and B cells.

23 P a g e 74 There are literally thousands of different T lymphocytes and each type is capable of responding to a specific antigen or set of antigens. This forms the basis for cellular immunity. At any given time, most T cells are inactive. When an antigen enters the body, only the particular T cell specifically programmed to react with the antigen becomes activated. Such an activated T cell is said to be sensitized. Activation occurs when macrophages phagocytize the antigen and present it to the T cell. Sensitized T cells increase in size, differentiate, and divide, each differentiated cell giving rise to a clone, or population of cells identical to itself. Several subpopulations of cells within the clone can be recognized: killer T cells, helper T cells, suppressor T cells, delayed hypersensitivity T cells, amplifier T cells, and memory T cells. Killer T Cells also known as Cytotoxic T cells are especially effective against slowly developing bacterial diseases such as tuberculosis and brucellosis, some viruses, fungi, transplanted cells, and cancer cells. Most of the protection provided by T cells is the result of secretion of very powerful proteins called lymphokines. Helper T cells which cooperate with B cells to help amplify antibody production also secrete proteins that amplify the inflammatory response in killing by macrophages. Suppressor T cells which dampen parts of the immune response inhibit production of antibodies by plasma cells. Delayed hypersensitivity T cells are the source of several lymphokines that are key factors in the hypersensitivity or allergy response. Amplifier T cells stimulate helper T cells, suppressor T cells, and B cells to exaggerated levels of activity. Memory T cells are programmed to recognize the original invading antigen.

24 P a g e 75 Natural K i l l e r cells which are similar to T cells have the ability to kill certain cells spontaneously without interacting with lymphocytes or antigens. Whereas Killer T cells leave their reservoirs of lymphoid tissue to meet a foreign antigen, B cells respond differently. They differentiate in the cells that produce specific antibodies that can circulate in the lymph and blood to reach the site of invasion. When a foreign antigen has been prepared and presented by macrophages to B cells and lymph nodes, the spleen or lymphoid tissue in the gastrointestinal tract B cells specific for the a n t i g e n are activated. Some of them enlarge and divide and differentiate into a clone of plasma cells under the influence of thymic hormones. Plasma cells secrete the antibody. B cells proliferation and differentiation into plasma cells is also influenced by a substance as interleukin 1, secreted by macrophages. 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. Different antigens stimulate different B cells to develop into plasma cells and their accompanying memory B cells because the B cells of a particular clone are capable of secreting only one kind of antibody. In most cases only the interaction of macrophage and B cell is required for the sequence of responses that results in antibody secretion. However, in some cases, interaction of B cells with helper T cells and suppressor T cells is involved. Primary and anamnestic responses occur during microbial infection. When you recover from an infection without taking antibiotics, it is usually because of the primary response. If at a later time you contact the same microbe, the anamnestic response could be so swift that the microbes are quickly destroyed and you do not exhibit any signs or symptoms.

25 P a g e 76 The immune response of the body whether cellular or humoral is much more intense after a second or subsequent exposure to an antigen than after the initial exposure. This can be demonstrated by measuring the amount of antibody in serum called the antibody titer. After an initial contact with an antigen, there is a period of several days during which no antibody is present. Then there is a slow rise in the antibody titer followed by a gradual decline. Such a response of the body to the first contact is the primary response. During the primary response in which the body is said to be primed or sensitized, there is proliferation of i m m u n o c o m p e t e n t lymphocytes. When the antigen is contacted again, whether for the second t i m e, or for a time after the second time, there is an i m m e d i a t e proliferation of immunocompetent lymphocytes, and the antibody titer is far greater than that for the primary response. This accelerated, more intense response is called the anamnestic or secondary response. The reason for the anamnestic response is that some of the immunocompetent lymphocytes formed during the primary response remain as memory cells. These memory cells not only add to the pool of cells that can respond to the antigen -- their response is more intense as well. The Skin and Immunity The skin not only provides nonspecific resistance to disease because of its mechanical and chemical factors, but it is also an active component of the immune system. The epidermis of the skin contains four principal kinds of cells: melanocytes, keratin ocytes, Langerhans cells, and Granstein cells. The last three types of cells assume a role in immunity. When a normal cell becomes transformed into a cancer cell, the tumor cell assumes cell surface components called tumor-specific antigens. It is believed that the immune system usually recognizes tumor-specific antigens as "nonself" and destroys the cancer cells carrying them. Such an immune response is called immunologic surveillance. Cellular immunity is p r o b a b l y the basic mechanism involved in tumor destruction.

26 P a g e 77 Despite the mechanism of immunologic surveillance, some cancer cells escape destruction, a phenomenon called immunologic escape. DEVELOPMENTAL ANATOMY OF THE LYMPHATIC SYSTEM The lymphatic system begins its development by the end of the fifth week. Lymphatic vessels develop from lymph sacs that arise from developing veins. Thus, the lymphatic system is also derived from mesoderm. DISORDERS AND HOMEOSTATIC IMBALANCES Hypersensitivity (Allergy): A person who is overly reactive to an antigen is said to be hypersensitive or allergic. Whenever an allergic reaction occurs there is tissue injury. The antigens that induce an allergic reaction are called allergens. Almost any substance can be an allergen for some individuals. Common allergens include certain foods such as milk or eggs, antibiotics such as penicillin, cosmetics, chemicals in plants such as poison ivy, pollens, dust, molds, and even microbes. There are four basis types of hypersensitivity reactions: Type I (anaphylaxis), Type II (cytotoxic), Type III (immune complex), and Type IV (cell-mediated). The first three involve antibodies, and the last example involves T cells. Type I (anaphylaxis) Reactions: Occur within a few minutes after a person sensitized to an allergen is reexposed to it. Anaphylaxis which means "against protection" results from the interaction of humoral antibodies IgE with mast cells and basophils. In response to certain allergens, some people produce IgE antibodies which bind to the surfaces of mast cells and basophils. This binding is what causes a person to be allergic to the allergens. In response to the attachment of IgE antibodies to basophils and mast cells, the cells release chemicals called mediators of anaphylaxis, among which are histamine and prostaglandins. Collectively, the mediators increase blood capillary

27 P a g e 78 permeability, increase smooth muscle contraction, and increase mucus secretion. As a result, a person may experience edema and redness, along with other inflammatory responses; difficulty in breathing from constricted bronchial tubes; and a "runny" nose from excess mucus secretion. Some anaphylactic reactions, such as hay fever, bronchial asthma, hives, and eczema, are referred to as localized. Other anaphylactic reactions are considered systemic. An example is acute anaphylaxis (anaphylactic shock), which can produce life-threatening system effects such as circulatory shock and asphyxia and can be fatal within a few minutes. Transplantation Transplantation involves the replacement of an injured or diseased tissue or organ. Usually the body recognizes the proteins in the transplanted tissue or organ as foreign and produces antibodies against them. This phenomenon is known as tissue resection. Rejection can be somewhat reduced by matching donor and recipient HLA antigens by administering drugs that inhibit the body's ability to form antibodies. White blood cells and other nucleated cells have surface antigens called HLA antigens. These are unique for each person, except for identical twins. The more closely matched the HLA antigens between donor and recipient, the less the likelihood of tissue rejection. Immunosuppressive Therapv Until recently, immunosuppressive drugs suppressed not only the recipient's immune rejection of the donor organ, but also the immune response to all antigens as well. This causes patients to become very susceptible to infectious diseases. A drug called cyclosporine derived from a fungus, fungi imperfecti, has largely overcome this problem with regard to kidney, heart, and liver transplants.

28 P a g e 79 Autoimmune Disease At times immunologic tolerance breaks down and the body has difficulty in discriminating between its own antigens and foreign antigens. This loss of immunologic tolerance leads to an autoimmune disease (autoimmunity). Such diseases are immunologic responses mediated by antibodies against a person's own tissue antigens. Hodgkin's Disease Hodgkin's disease is a malignant disorder, usually arising in lymph nodes, the cause of which is unknown. The disease is initially characterized by a painless, nontender lymph node most commonly in the neck but occasionally in the axilla, inguinal, or femoral region. About one-quarter to one-third of patients also have an unexplained and persistent fever and/or night sweats. Fatigue and weight loss are also associated complaints, as is pruritus. Treatment consists of radiation therapy, chemotherapy, and combinations of the two. Hodgkin's disease is curable. AIDS (Acquired Immune Deficiency Syndrome) This is a disease which threatens to run to epidemic proportions in the United States and worldwide unless a cure is found for it. The cause of AIDS is a virus called human T- lymphotropic virus, type III (HTLV-III). A variant of this virus known as HTLV-I causes a rare type of leukemia in humans and attacks and transforms T cells. The reason the AIDS virus lowers the body's immune system is that the virus primarily attacks helper T cells. As a consequence, several key roles of helper T cells in the immune response are inhibited. Symptoms of AIDS may develop for months or years and include malaise; a low-grade fever or night sweats; coughing; shortness of breath; sore throat; extreme fatigue; muscle aches; unexplained weight loss; enlarged lymph nodes in the neck, axilla, and groin; and blueviolet or brownish spots on the skin known as Kaposi's sarcoma. These spots are usually found on the legs, the lower extremities.

29 P a g e 80 The deterioration of host defenses allows for the development of cancer and opportunistic infections of various kinds. The two diseases that most often kill AIDS victims are Kaposi's sarcoma and Pneumocystis carinii pneumonia. Kaposi's sarcoma is a deadly form of skin cancer prevalent in equatorial Africa but previously almost unknown in the United States. Pneumocystis carinii pneumonia is a rare form of pneumonia caused by the protozoan Pneumocystis carinii. It results in shortness of breath, persistent dry cough, sharp chest pains, and difficulty in breathing. AIDS victims are also subject to a form of herpes that attacks the central nervous system and a bacterial infection that usually causes tuberculosis in chickens and pigs. Among the high-risk groups who are susceptible to AIDS are homosexual and bisexual males, intravenous drug abusers, sexual partners of individuals in AIDS risk groups, and infants born to mothers at risk. Other risk groups include hemophiliacs under treatment with blood plasma products, and Haitian immigrants. It is also found among infants in other patients who have received blood transfusions. Current testing of blood has virtually eliminated future contamination by blood transfusion or therapy. The pattern of AIDS transmission closely resembles the occurrence of hepatitis B (serum hepatitis), a liver disease that commonly strikes homosexual drug addicts using contaminated needles and sometimes patients getting blood transfusions. Like hepatitis B, AIDS appears to be transmitted by intimate direct contact involving muscosal surfaces or by parenteral routes, which means by injection. Two fluids considered most highly contagious are semen and blood. Airborne transmission and spread via food, water, insects, and casual contact seem unlikely. Treatment of AIDS is currently by means of various drugs such as AZT. Some people who carry the AIDS virus will develop the AIDS-related complex (ARC). This condition may include fever, diarrhea, malaise, and a generalized swelling of lymph nodes. ARC may follow several courses. It may resolve, persist for a long period, or progress to full-blown AIDS.

30 P a g e TERMS RELATED TO LYMPHATIC SYSTEM AND IMMUNITY Adenitis E n l a r g e d, t e n d e r, and inflamed l y m p h n o d e s resulting from an infection. 2. Elephantiasis Great enlargement of a limb ( e s p e c i a l l y limbs) lower and scrotum resulting from obstruction lymph glands of or vessels by a parasitic worm. 3. Lymphadnectomy Removal of a lymph node. 4. Lymphadenopathy Enlarged, sometimes tender lymph glands. 5. Lymphangioma Benign tumor of the lymph vessels. 6. Lymphangitis Inflammation of the lymphatic vessels. 7. Lymphedema Accumulation of lymph fluid producing subcutaneous tissue swelling. 8. Lymphoma Any tumor composed of lymph tissue. 9. Lymphostasis A lymph flow stoppage. 10. Splenomegaly Enlarged spleen.

31 P a g e 82 Swartz NHCC THE RESPIRATORY SYSTEM CHAP. 16 Page 82 THESE NOTES ARE ONLY AN OUTLINE OF THE MATERIAL PRESENTED IN CHAP. 16, HUMAN ANATOMY AND PHYSIOLOGY, HOLE, 4TH ED., PP YOUR LECTURE EXAM. # 3 ILL COVER ALL OF THE MATERIAL IN YOUR TEXTBOOK ON THE ABOVE-MENTIONED PAGES, BUT NO OTHER MATERIAL. BE SURE TO READ ALL OF IT. The Respiratory System: primary functions- obtaining 0 & removing CO2. R e s p. o r g a n s filter particles from incoming air, help to control the temp. & water content of the air, aid in producing sounds used in speech, & func. in the sensation of smell & the regulation of ph. Respiration = exchanging gases between the atmosphere & the body cells Parts of respiration: (1) breathing or pulmonary ventilation = movement of air in & out of the lungs. (2) exchange of gases between the air in the lungs & the blood. (3) transport of gases by the blood between the lungs & the body cells. (4) exchange of gases between the blood & the body cells. Cellular resp. = utilization of 0 2 & the production of CO 2. Organs of resp. system: nose, nasal cavity, sinuses, pharynx, larynx, trachea, bronchial tree, & lungs. Upper resp. tract = resp. organs outside the thorax. Lower resp. tract = resp. organs inside the thorax. Nosenostrils let air in. Hairs help prevent entrance of coarse particles in air. Nasal cavity- nasal septum divides this cavity into left & rt. portions. Nasal cavity is separated from the cranial cavity by the cribriform plate of the ethmoid bone & from the mouth by the hard palate. Nasal conchae = turbinate bones- divide nasal cavity into superior, middle, & inferior meatuses. Conchae also support the mucous membrane lining nasal cavity & increase its surface area, Upper portion of nasal cavity contains olfactory receptors (func. in smell). Nest of cavity conducts air to & from nasopharynx. Mucous membrane lining nasal cavity has pseudostratified ciliated columnar epithelium with many mucus-secreting goblet cells. Also, this membrane is highly vascular. Air passes over the membrane, heat radiates from the blood & warms the air, thus, temp. of incoming air adjusts to body temp. Incoming air also moistened by mucous membrane. Sticky mucus traps dust & other entering particles. Paranasal sinuses are air-filled spaces in the maxillary, frontal, ethmoid, & sphenoid bones of the s k u l l. These spaces open into the nasal cavity & are lined with mucous membranes. Mucus drains from these sinuses into the nasal c a v i t y. Sinuses reduce weight of the skull & are resonant chambers that affect the quality of the voice. The pharynx = throat- located behind the mouth cavity & between the nasal cavity & the larynx. Func.- passageway for food & air & aids in c r e a t i n g sounds. The larynx = an enlargement in the airway at the top of the trachea & below the pharynx. Func. - passageway for air & prevents foreign objects from entering the trachea. It also houses the vocal cords & is called the voice box. Larynx is composed of muscles & cartilages bound together by elastic tissues. The thyroid cartilage = Adam ' s apple is more prominent in males because of effect of male sex hormones on development of the larynx. The cricoid cartilage- below the thyroid cartilage & is the lowest portion of the larynx. The epiglottic cartilage is attach-

32 P a g e 83 ed to the upper border of the thyroid cartilage & supports a flaplike structure called the epiglottis. The epiglottis usually stands upright & allows air to enter the larynx. During swallowing, however, the larynx is raised by muscular contractions, & the epiglottis is pressed downward by the base of the tongue. This allows the epiglottis to partially cover the opening into the larynx, thereby helping to prevent foods & liquids from entering the air passages. The arytenoid cartilages are located above & on either side of the cricoid cartilage. The corniculate cartilages are attached to the tips of the aryytenoid cartilages. The corniculate cartilages serve as attachments for muscles that help to regulate tension on the vocal cords during speech & aid in closing the larynx during swallowing. The cuneiform cartilages, found in the mucous membrane between the epiglottic & the arytenoid cartilages, stiffen soft tissues in this region. Inside the larynx there are 2 pairs of horizontal folds: the upper ones are the vestibular folds & are known as the false vocal cords- they do not function in the production of sounds. Muscle fibers within these folds help to close the larynx during swallowing. The lower folds are the true vocal cords. They contain elastic fibers & they are responsible for vocal sounds, which are created by forcing air between the vocal cords, causing them to vibrate from side to side. This action generates sound waves that can be formed into words by changing the shapes of the pharynx & oral cavity & by using the tongue & lips. The pitch of the vocal sound is controlled by changing the tension on the cords. Increasing the tension produces higher pitched sounds & decreasing the tension creates a lower pitch. The intensity or loudness of a vocal sound is related to the force of the air passing over the vocal cords. During normal breathing, the vocal cords remain relaxed, & the opening between the vocal cords are called the glottis, appears as a triangular slit. When food or liquid is swallowed, muscles within the larynx close the glottis, & this prevents foreign substances from entering the trachea. The trachea is a flexible cylindrical tube about 2.5 cm. in diameter & 12.5 cm. long. It extends downward in front of the esophagus & into the thoracic cavity, where it splits into the right & left primary bronchi. The inner wall of the trachea is lined with ciliated pseudostratified columnar eipthelium containing numerous goblet cells. This membrane, like the one lining the larynx, continues to filter incoming air, thereby moving entrapped particles upward to the pharynx. Within the tracheal wall there are about 20 C-shaped pieces of hyaline cartilage arranged one above the other. Smooth muscle & conn. tissue fill the posterior aspect of these cartilagenous rings, which prevent the trachea from collapsing & blocking the airway. The smooth muscle & c.t. allow the esophagus to expand as it carries food to the stomach. The bronchial tree consists of the branched airways leading from the trachea to the microscopic alveolar air sacs. It begins with the right & Left primary bronchi arising from the trachea at the level of T-5 (vertebra). The openings of these tubes are separated by a ridge of cartilage_ called the carina. Each bronchus, accompanied by large blood vessels, enters its respective lung. A short distance from its

33 P a g e 84 origin, each primary bronchus divides into secondary or lobar bronchi-2 on the left & 3 on the right, which in turn branch into finer & finer tubes. The branching is as follows (largest to smallest). Tertiary or segmental bronchi-supply a portion of the lung called a bronchopulmonary segment. There are 10 of these segments in the right lung & 8 in the left lung. Bronchioles are small branches of segmental bronchi. They enter the lobules, which are the basic units of the lung. Terminal bronchioles branch from a bronchiole. There are 50 to 80 terminal bronchioles within a lung lobule. Two or more respiratory bronchioles branch from each terminal bronchiole. They are relatively short & they have a few air sacs branching from their sides & they can therefore en-gage in gas exchange, being the first structures in the resp. system that can do so. Alveolar ducts branch & extens from each respiratory bronchiole. They are from 2 to 10 long. Alveolar sacs are thinwalled closely packed outpouchings of the alveolar ducts. Alveoli are thinwalled microscopic air sacs opening only on the side communicating with the alveolar sac. Air can therefore diffuse freely into the alveoli. The structure of the bronchus, a respiratory tube, is similar to that of the trachea. The cartilagenous rings are replaced with cartilagenous plates, however, & they completely surround the tube giving it a cylindrical form. The percentage of cartilage gradually decreases as finer branch tubes appear, & the cartilage completely disappears at the level of the bronchioles. Smooth muscle becomes more prominent as the cartilage decreases. The amount of muscle is limited in the alveolar ducts, however. Elastic fibers are abundant in the conn. tissue surrounding the resp. tubes. These fibers play an important role in the breathing mechanism. The lining of the larger tubes consists of a layer of ciliated pseudostratified columnar cells, while a single layer of simple squamous cells lines the alveoli. Concerning the functions of the respiratory tubes, the branches of the bronchial tree serve as air passages that continue filtering incominc_ air & distribute it to alveoli in all parts of the lungs. The alveoli provide a large surface area of thin epithelial cells through which gas exchange occurs. During these exchanges, 0 diffuses through the alveolar walls & enters the blood in nearby capillaries, while CO 2 diffuses through these walls from the blood & enters the alveoli. There are about 300 million alveoli in a normal adult lung & these spaces have a total surface area of 70 to 80 square meters! The lungs are soft spongy cone-shaped organs located in the thoracic cavity. The right & Left lungs are separated medially by the heart & the mediastinum, & the lungs are enclosed by the diaphragm & the thoracic cage. Each lung occupies most of the thoracic space on its side, & is suspended in the cavity by its attachments, including a bronchus & some large blood vessels. These tubes enter the lung on its medial surface through a region called the hilus. A layer of serous membrane, the visceral pleura, is firmly attached to the surface of each lung, & this membrane folds back at the hilus to become the parietal pleura. The parietal pleura forms part of the mediastinum & lines the inner wall of the thoracic cavity. The potential space between the visceral & parietal pleura is called the pleural cavity, & it contains a thin film of serous fluid. This fluid lubricates the adjacent pleural surfaces, thereby reducing friction as they move against one another during breathing. The fluid also helps to hold the pleural membranes together.

34 P a g e 85 The right lung is larger than the left one. The right lung is divided into 3 lobes: a superior, middle, & inferior lobe. The left lung is divided into 2 lobes: a superior lobe & an inferior lobe. (obvious test questions!) Each lobe is supplied by a lobar bronchus. Lobes are subdivided by conn. tissue into lobules, each lobule containing terminal bronchioles, alveolar ducts, alveolar sacs, alveoli, nerves, blood vessels & Lymphatic vessels. PLEASE TAKE TIME TO STUDY THE CHART IN THE BLUE BOX (CHART PARTS OF THE RESPIRATORY SYSTEM) AT THE TOP OF PAGE 585 IN YOUR TEXTBOOK. THERE WILL BE A FEW TEST QUESTIONS FROM THIS CHART. Breathing, or pulmonary ventilation, is the movement of air from outside the body into the bronchial tree & alveoli followed by a reversal of the air movement. These actions are termed inspiration or inhalation & expiration or exhalation. Concerning inspiration, atmospheric pressure is the force that causes air to move into the lungs. Atmospheric pressure is due to the weight of the air. Normal air pressure at sea level = 760 mm Hg. (millimeters of mercury). The air pressure on the inside of the lungs, the alveoli, & on the outside of the thoracic wall is about the same. If the pressure on the inside of the lungs & alveoli (intra-alveolar pressure) decreases, air from the outside will be pushed into the airways by atmospheric pressure. This happens during normal inspiration. Muscle fibers in the dome-shaped diaphragm below the lungs are stimulated to contract by impulses from the phrenic nerves. The diaphragm moves downward, the size of the thoracic cavity increases, & the intra-alveolar pressure decreases slightly below that of normal atmospheric pressure. Air is forced into the airways by atmospheric pressure & the lungs expand. The external intercostal muscles may be stimulated to contract while the diaphragm is contracting & moving downward. This raises the ribs & elevates the sternum, increasing the size of the thoracic cavity still further. Air pressure inside is thus further reduced & more air is forced into the airways. The expansion of the lungs is aided by the fact that the parietal & visceral pleura are separated by only a thin film of serous fluid. The water molecules in this fluid have a great attraction for one another, & the resulting surface tension holds the 1.1oist surfaces of the pleural membranes tightly together. PLEASE STUDY THE BRIEF CHART (CHART MAJOR EVENTS IN INSPIRATION) IN THE BLUE BOX AT THE TOP OF PAGE 587 IN YOUR TEXTBOOK. THERE WILL BE A FEW TEST QUESTIONS FROM IT. The alveolar cells secrete a substance called surfactant that reduces surface tension & decreases the tendency of the alveoli to collapse. The ease with which the lungs can be expanded as a result of pressure changes occurring during breathing is called compliance or distensibility. In a normal lung, compliance decreases as the lung volume increases. (I love these types of relationships & they lend them-selves beautifully to test questions!) The reason for this inverse relationship is because an inflated lung is more difficult to expand than a deflated one. Conditions that obstruct air passages, destroy lung tissue or impede lung expansion will decrease compliance. The forces responsible for normal expiration come from elastic recoil of tissues & surface tension. The lungs contain a lot of elastic tissue & as they expand during inspiration, the elastic tissue is stretched. The diaphragm lowers compressing the abdominal organs beneath it. As the

35 P a g e 86 diaphragm & the external intercostal muscles relax following inspiration,' the elastic tissues cause the lungs & the thoracic cage to recoil, & they return to their original positions. Elastic tissues within abdominal organs cause them to spring back into their original locations, there-by pushing the diaphragm upward. At the same time, surface tension that develops between the moist surfaces of the alveolar linings tends to cause the alveoli to decrease in diameter. Each of these factors tends to increase the intraalveolar pressure slightly above atmospheric pressure, thereby forcing the air inside the lungs out through the respiratory passageways. Normal expiration is, therefore, a passive process. The recoil of elastic fibers within the lung tissues tends to reduce the pressure in the pleural cavity. The pressure between the pleural membranes (intrapleural pressure) is usually slightly less than atmospheric pressure. If a person needs to exhale more air than normal, the posterior internal intercostal muscles can be contracted. These muscles pull the ribs &, the sternum down & inward increasing the pressure in the lungs. The abdominal wall muscles squeeze (if you can think of a better scrabble word than squeeze, you ' re a better man than I am- equinox is a few less points than squeeze because " q " & " z" are 10 point letters & " x" is only an 8 point letter) the abdominal organs inward, causing the pressure in the abdominal cavity to increase thereby forcing the diaphragm still higher against the lungs. These actions squeeze abdominal air out of the lungs. PLEASE STUDY CHART MAJOR EVENTS IN EXPIRATION ON PAGE 588 IN YOUR TEXTBOOK.- A FEW MORE TEST QUESTIONS! I AM GOING TO ASK A NUMBER OF TEST QUESTIONS ON THE VARIOUS RESPIRATORY AIR VOLUMES. _ I SUGGEST YOU STUDY THEM CAREFULLY IN YOUR BOOK ON PAGE 5 8 9, INCLUDING THE MATERIAL IN THE TEXT AS WELL AS THE MATERAL IN THE BLUE BOX- CHART RESPIRATORY AIR VOLUMES. _ IN OTHER WORDS, BE THOROUGHLY FAMILIAR WITH THE TERMS TIDAL VOLUME, INSPIRATORY RESERVE VOLUME, EXPIRATORY RESERVE VOLUME, VITAL CAPACITY, RESIDUAL VOLUME, & TOTAL LUNG CAPACITY. _ KNOW WHAT LUNG VOLUMES MAKE UP THE VITAL CAPACITY & WHAT LUNG VOLUMES MAKE UP THE TOTAL LUNG CAPACITY. _ KNOW ALL THE LUNG VOLUMES IN CC (CUBIC CENTIMETERS) OR LITERS. BE THOROUGHLY FAMILIAR WITH THE TERMS ANATOMIC DEAD SPACE & PHYSIOLOGIC DEAD SPACE & WHAT THESE TWO VOLUMES EQUAL IN CC. BE FAMILIAR WITH THE GRAPH FROM THE SPIROMETER IN THE GREEN BOX AT THE TOP OF PAGE IN YOUR TEXTBOOK. IF YOU DON ' T KNOW HOW TO READ THE GRAPH VALUES, PLEASE COME & SEE ME BEFORE THE EXAM! The white line on the graph is formed by a stylus with ink as you breathe. READ THE MATERIAL CAREFULLY ON PAGES & IN YOUR TEXTBOOK CONCERNING RESPIRATORY DISORDERS (PARALYSIS OF BREATHING MUSCLES, BRONCHIAL ASTHMA, EMPHYSEMA, LUNG CANCER, & PRIMARY PULMONARY CANCER). THERE WILL BE SOME QUESTIONS ON THIS MATERIAL IN THE TEST! Concerning alveolar ventilation, the amount of new atmospheric air that is moved into the respiratory passages each minute is called the minute respiratory volume. This vol. can be calculated by multiplying the tidal volume by the breathing rate. e.g., if the tidal vol. is 500 cc & the breathing rate is 12 breaths/min., then the minute resp. vol. = c c X 12 = 6,000 cc per minute. Not all of this new air reaches the alveoli. Must of it remain in the air passages in the physiologic dead

36 P a g e 87 space. The amount of new air that does reach the alveoli & is available for gas exchange is calculated by subtracting the physiologic dead space (150 cc) from the tidal volume (500 cc). If the resulting volume (350 cc) is multiplied by the breathing rate (12 breaths per minute in an average normal healthy adult), the alveolar ventilation rate (4,200 cc/min.) is obtained. This ventilation rate is a major factor affecting the concentration of 0 2 & CO in the alveoli. It affects the exchange of gases between the alveoli & the blood. (Do you get the feeling that I ' m going to do something with these numbers & computations? You ' re right!) PLEASE STUDY THE NONRESPIRATORY AIR MOVEMENTS (COUGHING, SNEEZING, LAUGHING, CRYING, HICCUPING, YAWNING, & SPEECH) IN YOUR TEXTBOOK ON PAGES 590 & 591. BE SURE TO READ THE MATERIAL ON THESE 2 PAGES IN YOUR TEXTBOOK AS WELL AS STUDY THE CHART- CHART NONRESPIRATORY AIR MOVEMENTS, ON PAGE 591 (BLUE BOX AT TOP OF PAGE). THERE WILL BE SOME TEST QUESTIONS FROM THIS MATERIAL! Control of Breathing: Respiratory muscles can be controlled voluntarily. Normal breathing, however, is a rhythmic involuntary act that continues even when a person is unconscious. The Respiratory Center: Breathing is controlled by a poorly defined collection of neurons in the brain stem called the respiratory center. Cranial & Spinal nerves transmit impulses from this center periodically to various breathing muscles causing inspiration & expiration. The center can also adjust the rate & depth of breathing. Therefore cellular 0 2 needs & the removal of CO 2 are met even in strenuous exercise. Components of the resp. center are widely scattered throughout the pons & Medulla oblongata. The medullary rhythmicity area (obviously in the medulla oblongata) includes 2 groups of neurons extending throughout the entire length of the medulla oblongata. They are termed the dorsal respiratory group & the ventral respiratory group. The dorsal resp. group is responsible for the basic rhythm of breathing (good test question). Neurons of this group send impulses to the diaphragm & other resp. muscles to contract. The vol. of air entering the lungs increases. The ventral respiratory group is quiet during normal breathing. When there is a need for more forceful breathing, neurons in this group send impulses that increase resp. movement. Other neurons in this group send impulses which activate muscles associated with forceful expiration. Neurons in the pneumotaxic area transmit impulses to the dorsal resp. group continuously & regulate the duration of inspiratory bursts originating from the dorsal group. In this way the pneumotaxic neurons control the rate of breathing. When pneumotaxic signals are strong, the inspiratory bursts are of short duration, & the rate of breathing is increased. Conversely, when the pneumotaxic signals are weak, the inspiratory bursts are of longer duration, & the rate of breathing is decreased. Factors Affecting Breathing: Breathing rate & depth are influenced by respiratory center controls & several other factors. These other factors include the presence of certain chemicals in body fluids, the degree to which the lung tissues are stretched, & the person ' s emotional state.

37 P a g e 88 There are chemosensitive areas within the resp. center. These areas are located within the ventral portion of the medulla oblongata near the origins of the vagus nerves (tenth cranial nerves), & they are very sensitive to changes in the blood concentrations of CO 2 & H ions. If the conc. of CO, or H ions rises, the chemosensitive areas signal the resp. center, & te rate of breathing is increased. CO 2 combines with water in the blood or CSF (cerebrospinal fluid) to form carbonic acid (H 2 CO 3 ). This carbonic acid becomes ionized releasing H ions & HCO 3 ions (bicarbonate ions). The hydrogen ions influence the chemosensitive areas, not the presence of carbon dioxide molecules. A person's breathing rate increases when air rich in CO is inhaled. As a result of increased breathing rate, more CO 2 is lost in exhaled air, & the blood conc. of CO 2 & H ions are reduced. Low blood 0 2 conc. has little effect on the chemosensitive areas in the resp. center. Changes in blood 0 2 conc. are sensed by chemoreceptors within carotid & aortic bodies. These are located within the walls of large arteries (carotid arteries & aorta) in the neck & thorax. When these receptors are stimulated by low 0 2 conc., impulses are transmitted to the resp. center & the breathing rate is increased. The blood 0 2 conc. must reach a very low level to trigger this mechanism. 0 2 plays only a minor role in the control of normal resp. Although the chemoreceptors of the carotid & aortic bodies are stimulated by changes in the blood conc. of CO 2 7 H + ions, these substances have a much more powerful effect when they act on the chemosensitive areas of the resp. center. The effects of CO 2 & H + ions on the carotid & aortic bodies are, therefore, relatively unimportant. An exception to the normal pattern of chemical control may occur in patients suffering from COPD (chronic obstructive pulmonary diseases), such as asthma & bronchitis. Over a period of time, these pts. seem to adapt to the presence of high levels of CO 2, & in these pts. (patients) low 0 2 levels may serve as effective respiratory stimuli. An inflation reflex, the Hering-Breuer reflex, helps to regulate the depth of breathing. This reflex occurs when stretch receptors in the visceral pleura, bronchioles, & alveoli are stimulated as a result of lung tissues being overstretched. The vagus nerves (10th cranial nerves are involved) send sensory impulses to the pneumotaxic area, & the duration of inspiratory movements is reduced. This action prevents overinflation of the lungs during forceful breathing. An emotional upset can also alter the normal breathing pattern. Fear increases the breathing rate. Pain also increases breathing rate. Thus, a person may gasp due to a sudden fright or initially in a cold shower. The resp. muscles are voluntary & the breathing pattern can there-fore be altered consciously. Breathing can be stopped altogether for a time. If a person decides to stop breathing, the blood conc. of CO 2 & H + ions rise, & the conc. of 0 2 falls. These changes stimulate the resp. center & soon the need to inhale overpowers the desire to hold the breath. On the other hand, a person can hold his breath for a longer period of time by hyperventilating = breathing rapidly & deeply in advance. This action lowers blood CO 2 conc.

38 P a g e 89 STUDY CHART FACTORS AFFECTING BREATHING- ON PAGE 596 IN YOUR TEXTBOOK (BLUE BOX MIDDLE OF THE PAGE). ALSO READ EXERCISE & BREATHING- A PRACTICAL APPLICATION IN THE BROWN BOX AT THE TOP OF PAGE 596. A FEW TEST QUESTIONS WILL COME FROM THIS MATERIAL! ALSO READ THE MATERIAL ON HYPERVENTILATION IN BROWN TYPE AT THE BOTTOM RIGHT HAND COLUMN OF PAGE 596. Alveolar Gas Exchange: The alveoli exchange gases between the air & the blood. Other parts of the resp. system merely move air in & out of the air passages. The alveoli are microscopic air sacs clustered at the distal ends of the finest resp. tubes- the alveolar ducts, like a sprig of grapes. Each alveolus consists of a tiny space surrounded by a thin wall separating it from adjacent alveoli. There are minute openings called alveolar pores in the walls of some alveoli. The Respiratory Membrane: The alveloar wall is lined by a single layer of simple squamous cells. (Squamous is another great scrabble word even though it has 8 letters. You can run it from a preexisting word on the board with your 7 letters & you also have the advantage that a nonscientific person might challenge you & lose his turn). There are also a dense network of capillaries (also lined with a single layer of simple squamous cells termed an endothelium rather than an epithelium) surrounding the alveoli. There are at least 2 thicknesses of epithelial cells & basement membranes between the air in an alveolus & the blood in a capillary. These layers make up the respiratory membrane, through which gas exchange occurs between alveolar air & blood. Diffusion through the Respiratory Membrane: Gas molecules diffuse from areas of high conc. to areas of lower conc. of the gas. Gas molecules also move from areas of high pressure to areas of lower pressure. The pressure of a gas determines its rate of diffusion. Ordinary air is approximately 78% nitrogen, 21% oxygen, & 0.04% CO 2 by volume. In a mixture of gases like air, each gas is responsible for a portion of the total weight or pressure produced by the mixture. The amount of pressure that each gas creates is called the partial pressure of that gas, & this pressure is directly related to the conc. of the gas in the mixture. The partial pressure of oxygen (PO 2 ) = 160 mm Hg. (21% of 760 mm Hg. or.21 X 760 mm Hg). Similarly, the 2 PCO 2 = 0.3 mm Hg. (.0004 X 760 mm Hg.) & the PN 2 = approx. 593 mm Hg. (.78 X 760 mm Hg). When a mixture of gases dissolves in blood, each gas exerts its own partial pressure in proportion to its own conc. Each gas will diffuse between the liquid & its surroundings, & this movement will tend to equalize its partial pressure in the 2 regions. For example, the P0 2 of capillary blood is less than the PO of alveolar air. The 0 2, therefore, diffuses from the alveolar air into the blood. Transport of Gases: The transport of 0 & CO 2 between the lungs & the body cells is a function of the blood. As these gases enter the blood, they dissolve in the plasma (liquid portion) & they combine chemically with other substances & are carried in that form. READ SOME DISORDERS INVOLVING GAS EXCHANGE- A CLINICAL APPLICATION IN THE BROWN BOX AT THE TOP OF PAGE 598 IN YOUR TEXTBOOK. ALSO READ THE SECTION IN BROWN TYPE AT THE BOTTOM OF THE LEFT HAND COLUMN ON PAGE

39 P a g e CONCERNING HYPOXIA. PAY PARTICULAR ATTENTION TO THE SX (SYMPTOMS)! Oxygen Transport: Almost all of the oxygen carried in the blood is combined with hemoglobin that occurs in the r.b.c. ' s. The Hgb is responsible for the color of these cells. Hgb (hemoglobin) has a complex structure consisting of 2 subunits called heme & globin. Globin is a protein consisting of 574 amino acids arranged in 4 polypeptide chains. Each chain is associated with a heme group, & Each heme group contains an iron atom. Each iron atom can combine loosely with an oxygen atom. As 0 2 dissolves in the blood, it combines radidly with Hgb, thereby forming oxyhemoglobin. The amount of 0 2 that combines with Hgb is determined by the P0 2. The greaer the P0, the more O 2 that will combine with Hgb, until the Hgb molecules are saturated with 0 2. The chemical bonds that form between 0 2 & Hgb are relatively unstable, & as the P0 2 decreases, 0 2 is released from oxyhemoglobin molecules. This happens in tissues where cells have used 0 2 in their respiratory processes & the free 0 2 diffuses from the blood into nearby cells. As the conc. of CO 2 increases, oxyhemoglobin tends to release more 0 2. As the blood becomes more acidic or as the temp. increases, more 0 2 is released. The amount of 0 2 released from oxyhemoglobin increases as the PCO 2 increases. The amount of 0 2 released from oxyhemoglobin increases as the ph decreases. The amount of oxygen released from oxyhemoglobin increases as the temp. increases. (These relationships make for good test questions!) Because of the above mentioned factors, more 0 2 is released to skeletal muscles from the blood during periods of exercise, since the increased muscular activity causes an increase in the PCO 2, a decrease in the ph value, & a rise in the local temp. Similarly, less active cells receive smaller amounts of 0 2. Carbon Monoxide: CO is a gasproduced in gasoline engines because of incomplete combustion of fuel. It has a toxic effect because it combines with Hgb more effectively than 0 2. CO does not dissolve readily from Hgb. When a person breathes CO, increasing quantities of Hgb become unavailable for 0 2 transport, & the body cells suffer. Read the tx (treatment ) of CO poisoning in brown type on page 600. Note particularly that both 0 2 & CO 2 are administered to the victim & why! Carbon Dioxide Transport: READ THIS SECTION IN YOUR TEXTBOOK ON PAGES 602 & 603, PAYING PARTICULAR ATTENTION TO THE TERMS CARBAMINOHEMOGLOBIN, THE ROLE OF BICARBONATE IONS (HCO minus) IN CARBON DIOXIDE TRANSPORT, THE TERM CARBONIC ANHYDRASE, THE CONCEPT OF THE CHLORIDE SHIFT. THESE CONCEPTS ARE ESPECIALLY IMPORTANT AND WE WILL DISCUSS THEM IN LECTURE THOROUGHLY. THEY WILL DEFINITELY COME UP ON THE EXAM! READ CHART GASES TRANSPORTED IN THE BLOOD (BLUE BOX, TOP OF PAGE 604). STUDY THE MATERIAL ON PAGES 604 & 605 VERY CAREFULLY (UTILIZATION OF OXYGEN- (1) CELLULAR RESPIRATION & (2) CITRIC ACID CYCLE. MEMORIZE THE COMPONENTS OF THE ANAEROBIC & AEROBIC PHASES OF CELLULAR RESPIRATION ON PAGE 605. PAY PARTICULAR ATTENTION TO THE CITRIC ACID CYCLE ON PAGE 605, LEARNING THE NAMES OF THE VARIOUS COMPONENTS OF THE CYLCE & PAYING ATTENTION TO THE NUMBER OF CARBON ATOMS IN EACH COMPONENT. THROUGHOUT THE COURSE, I HAVE EMPHASIZED SOME OF THE TERMS AT THE END

40 Page 91 P a g e 91 OF EACH CHAPTER IN YOUR TEXTBOOK IN THE SECTION ENTITLED " CLINICAL TERMS RELATED TO THE SYSTEM UNDER DISCUSSION. " IN MANY INSTANCES, ONLY SOME OF THE TERMS ARE IMPORTANT & OTHERS ARE RELATIVELY UNIMPORTANT. IT IS MY SINCERE BELIEF, BASED ON MY CLINICAL EXPERIENCE & EDUCATIONAL BACKGROUND, THAT ALL OF THE TERMS IN THE " CLINICAL TERMS RELATED TO THE RESPIRATORY SYSTEM, " ON PAGE 606 OF YOUR TEXTBOOK ARE IMPORTANT. I WILL INCLUDE MANY OF THEM ON YOUR EXAMINATION. THE TERMS YOU SHOULD KNOW INCLUDE ANOXIA, APNEA, ASPHYXIA, ATELECTASIS, BRADYPNEA, BRONCHIOLECTASIS, BRONCHITIS, CHEYNE- STOKES RESPIRATION (PAY PARTICULAR ATTENTION TO THIS TERM), DYSPNEA, EUPNEA, HEMOTHORAX, HYPERCAPNIA, HYPERPNEA, HYPERVENTILATION, HYPDXEMIA, HYPDXIA, LOBAR PNEUMONIA, PLEURISY, PNEUMOCONIOSIS, PNEUMOTHORAX, RHINITIS, SINUSITIS, TACHYPNEA, & TRACHEOTOMY. Good luck on the exam. The following is a copy of the aerobic & the anaerobic phases of cellular respiration taken from your textbook (page 605). Energy Glucose (6 Carbon Atoms) Pyruvic Acid (3 Carbon atoms) 2 molecules ATP Of ATP Acetyl Coenzyme A (2 Carbon atoms) Oxaloacetic acid (4 Carbon Atoms) Citric Acid Cycle Citric Acid CO 2 2H+ O 2 Ketoglutaric acid (5 Carbon atoms) H 2 O CO 2 + H Energy 36 ATP molecules Heat

41 P a g e 92 Page 91B The following are important air volumes and lung capacities that one can measure: (1) Tidal Volume :"'V)-- Formal breathing, that is, the volume of air inhaled and exhaled in a normal respiratory cycle (approximately 500 ml. in both males and females). (2) Inspiratory Reserve Volume (IPV)-- The maximum volume of air that one can inhale at the end of the inspiratory position (approximately 3,300 ml. in the male & 1,900 ml. in the female). (3) Expiratory Reserve Volume (ERV)-- The maximum volume of air that one can exhale at the end of the expiratory _ p osition (a p proximately 1,000 ml. in males & 700 ml. in females). (4) Residual Volume (RV)-- The volume of air remaining in the lungs that can never be expired even with the maximum effort (approximately 1,200 ml. in the male & 1,100 ml. in the female). (5) Vital Ca p acity (VC)-- The maximum volume of air that one can ex p ire immediately following a maximum inspiratory effort (approximately 4,900 mi. in the male & 3,100 ml. in the female). (6) Inspiratory Ca p acity (IC)-- The maximum volume of air that can be ins p ired from the resting respiratory level (approximately 3,800 ml. in the male & 2,400 ml. in the female). (7) Functional Residual Capacity (FRC)-- The volume of air remaining in the lungs at the resting expiratory level (approximately 2,200 ml. in the male & 1,800 ml. in the female). (8) Total Lung Capacity (TLC)-- The amount of air contained in the lungs at the end of maximum inspiration (approximately 6,000 ml. in the male & 4,200 ml. in the female). Any increase in the partial pressure of CO in the arterial blood is called hypercapnia. This stimulates the chemosensitive area in the medulla & chemoreceptors in the carotid & aortic bodies. This causes the inspiratory area to become active, & the rate & depth of respiration increases. If arterial blood PCO 2 is less than 40 mm Hg., the condition is called hypocapnia. Cheyne-Stokes respiration is a repeated cycle of irregular breathing beginning with shallow breaths that increase in depth & rapidity, then decrease & cease altogether for 15 to 20 seconds. Cheyne-Stokes is normal in infants. It is also often seen just before death from pulmonary, cerebral, cardiac, & kidney disease. Oxygen is carried in the blood in the form of oxyhemoglobin. Carbon dioxide is carried in the deoxygenated blood in several forms. The smallest percentage, 7%, is dissolved in plasma. 23% of the carbon dioxide combines with the globin portion of hemoglobin to form carbaminohemoglobin. 70% of the CO 2 is transported in the plasma in the form of bicarbonate ions. The reaction is: carbonic anhydrase CO 2 + H 2 O H 2 C0 3 H + + HCO - carbon water carbonic hydrogen bicarbonate dioxide acid ions ions

42 P a g e 93 Page 91C As CO 2 diffuses into tissue capillaries & enters rbc's, it reacts with water in the presence of carbonic anhydrase, to form carbonic acid. The carbonic acid dissociates into hydrogen ions & bicarbonate ions. The hydrogen ions combine mainly with Hgb (hemoglobin). The bicarbonate ions leave the rbc's & enter the plasma. In exchange chloride ions (Cl - ) diffuse from plasma into the rbc's. This exchange of negative ions maintains the ionic balance between p lasma & rbc ' s & is known as the chloride shift. Just as an increase in CO 2 in the blood causes oxygen to split from Hgb, the binding of 0 2 to Hgb causes the release of CO 2 from blood. In the presence of 0 2, less CO i binds in the blood. This reaction, called the Haldane effect, occurs because when 0 2 combines with Hgb, the Hgb becomes a stronger acid. In this state, Hgb combines with less CO,. Also, the more acidic Hgb releases more hydrogen ions that bind to bicarbonate ions to orm carbonic acid. The carbonic acid breaks down into water & carbon dioxide. The CO 2 is released from the blood into the alveoli. In tissue capillaries, blood p icks up more CO 2 as 0 2 is removed from Hgb. In pulmonary capillaries, blood releases more CO 2 as 0 2 is picked up by Hgb. The apneustic center in the lower pons coordinates the transition between inspiration & expiration. Boyle's Law states that the pressure of a gas in a closed container is inversely proportional to the volume of the container. Eupnea = normal quiet breathing. Shallow chest breathing = costal breathing. Deep abdominal breathing = diaphragmatic breathing. Charles' Law states that the volume of a gas is directly proportional to its absolute temperature, assuming that the pressure remains constant. Dalton's Law states that each gas in a mixture of gases exerts its own pressure as if all the other gases were not present. 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 & its solubility coefficient, when the temperature remains constant. The amount of oxygen released from Hgb is determined by several factors in addition to the P0 2. For example, in an acid environment, oxygen splits more readily from Hgb. This is referred to as the Bohr effect, & is based on the belief that when hydrogen ions bind to the Hgb, they alter the structure of Hgb & thereby decrease its oxygen-carrying capacity. Hypoxia refers to a general low level of oxygen availability.

43 P a g e 94