Module 5

ADVANCED AP Chapter 22   Lymphatic System and Immunity 

Lecture Outline 

The lymphatic system is important to the defense of the body, but it also plays a role in maintaining the fluid balance as well as in the absorption of lipids in the digestive tract. Immunity involves many structural levels of the body (organ, tissue, cell, chemical) working together to protect the body. 

Functions of the Lymphatic System 

• Fluid balance - Excess interstitial fluid enters lymphatic capillaries and becomes lymph (30L from capillaries into interstitial fluid, 27L return leaving 3L, called lymph). 

• Lipid absorption - Absorption of fat and other substances from digestive tract.

• Defense - Microorganisms and other foreign substances are filtered from lymph fluid by lymph nodes and from blood by spleen. 

Lymphatic Vessels - Carry lymph away from tissues. 

Lymphatic capillaries join to form lymphatic vessels. 

Lymphatic vessels: have valves that ensure one-way flow; structure is like that of small veins. 

Lymph Formation and Movement 

Movement of Lymph Through Lymphatic Vessels 

Mechanisms of movement: 

• Contraction of lymphatic vessels: Unidirectional valves divide the vessels into chambers that act as pumps; smooth muscle in walls of the chambers. 

• Contraction of skeletal muscles: surrounding muscle compresses lymphatic vessels, moving lymph along. 

Lymph nodes: distributed along vessels and filter lymph. 

Lymphatic vessels join to form larger vessels called lymphatic trunks that drain from specific body areas:  

Lymphatic trunks either connect to large veins in the thorax or to lymphatic ducts. 

Lymphatic ducts: move lymph into Right and Left Subclavian veins. 

• Right lymphatic duct drains only right side of head, right arm, right thorax. 

• Thoracic duct: drains entire remainder of the body. 

Lymphatic Tissue and Organs 

Lymphatic organs contain lymphatic tissue (lymphocytes, macrophages, and others). 

Primary lymphatic organs – red bone marrow and thymus. 

• Where lymphocytes become immunocompetent, capable of launching an immune response. 

• Pre-B cells become immunocompetent in red bone marrow. 

• Pre-T cells become immunocompetent in the thymus. 

       Secondary Lymphatic Tissues and Organs  

• Include lymphatic nodules, like the tonsils, and diffuse lymphatic tissue, lymph nodes, and spleen. 

• These are locations where lymphocytes interact with each other, other immune cells, microorganisms, and other foreign substances to produce an immune response. 

Lymph Nodes 

• Lymph nodes: small, round/bean-shaped structures 1 to 25 mm long; responsible for filtering lymph.  

Spleen  

• Located in left superior side of abdomen. LUQ = left upper quadrant 

• Can be ruptured in traumatic abdominal injuries resulting in bleeding, shock, death. 

• Filters old red blood cells.

• Destroys defective RBCs. 

• Detects and responds to foreign substances.  

Thymus  

• Thymus: bilobed gland in superior mediastinum immediately posterior to sternum. 

• Increases in size first year of life.

• Site of maturation of T cells; thymus secretes Thymic hormones (thymosin), important in T cell development. 

Categories of immunity. 

• Innate or nonspecific resistance. 

• Physical barriers: prevent entry or remove microbes. Skin, tears, saliva, mucous membranes, mucus. Considered the acid mantle. 

• Chemical mediators: promote phagocytosis and inflammation. 

• Cells: involved in phagocytosis and production of chemicals. 

• Adaptive or specific immunity. 

• Specificity: ability to recognize a particular substance. 

• Memory: ability to remember previous encounters with a particular substance and respond rapidly. 

Components of Immunity – Innate Immunity 

         Innate Immunity: Body defenses that are present at birth, genetically determined. 

Physical barriers prevent microbes and chemicals from entering the body. 

• Skin, mucous membranes. 

• Tears, saliva, urine. 

• Cilia in respiratory tract. 

• Coughing and sneezing. 

White Blood Cells  

White blood cells/ Leukocytes: most important cells of immune system. Must be able to move into infected tissues and destroy infection/pathogens. 

• Chemotaxis: movement toward the source of chemotactic factors (parts of microbes or chemicals act as chemical signals and attract W B Cs). 

• Phagocytosis: endocytosis and destruction by phagocytes (neutrophils and macrophages). 

Specific White Blood Cells  

Neutrophils. 

• Phagocytic and first cells to enter infected tissue; live only a few hours. 

• Release chemical signals such as cytokines that increase the inflammatory response by recruiting and activating other immune cells. 

• Also release lysosomal enzymes that kill microorganisms; may produce pus. 

Macrophages: large phagocytic cells. 

• Monocytes that leave blood, enter tissues. Longer-lived than neutrophils. 

• Found beneath free surfaces such as the skin, subcutaneous tissue, mucous membranes, and serous membranes. 

Basophils and mast cells. 

• Promote inflammation when activated by innate or adaptive system, release histamine. 

• Basophils are motile, leave blood and enter infected tissues. 

• Mast cells are non-motile; in C.T.  release histamine that directly triggers inflammation

Eosinophils: leave blood and enter tissues. 

• Secrete enzymes that kill some parasites. 

Natural killer cells: type of lymphocyte. Provides Immune Surveillance 

• Lyse tumor and virus-infected cells. 

• Recognize whole classes of cells, not specific kind of cell. 

Inflammatory Response  

• Any Tissue injury can cause inflammation. Normal response to tissue damage. 

• Response initiated by chemical mediators that produce vasodilation, chemotactic attraction, increased vascular permeability. The latter allows fibrinogen and complement to enter tissue. Fibrinogen converted to fibrin, walls off infected area. 

Local inflammation: confined to a specific area of the body. Symptoms are redness, heat, swelling, pain, loss of function. 

Systemic inflammation: occurs in many parts of the body. Same symptoms as local, but in addition:  

• Increase in neutrophil numbers released by red bone marrow. 

• Fever due to production of pyrogens by various kinds of cells. Improves performance of immune system. 

Inflammatory Response Process  

1. As a result of injury, such as a splinter piercing the skin, bacteria enter the tissue, causing additional damage.  

2. This damage stimulates the release or activation of chemical mediators, such as histamine, complement, etc. 

3. Chemical mediators cause vasodilation which increases blood flow, bringing phagocytes and other WBCs to the area, as well as increased vascular permeability (leaky capillaries) that allows fibrinogen and complement to enter the tissue from the blood. The increase in blood flow and vascular permeability result in redness and swelling, two of the cardinal signs of inflammation. 

4.        Chemical mediators, such as fibrin  increase at the injury site as well. Fibrinogen is converted to fibrin, which walls off the infected area, preventing the spread of infection.

5. The process of releasing chemical mediators and attracting phagocytes and other white blood cells continues until the bacteria are destroyed. (Positive feedback) 

6.        Phagocytes, such as neutrophils and macrophages, remove microorganisms and dead tissue (Pus), and the damaged tissues are repaired. 

Adaptive Immunity 

Involves the ability to recognize, respond to, and remember a particular substance. 

Antigens: large molecules. Foreign or Self.  Triggers the adaptive immune response

• Foreign antigens: not produced by body, introduced from outside. 

• Bacteria, viruses, other microorganisms that cause disease. 

• Pollen, animal dander, feces of mites, foods, drugs can cause overreaction of immune system called allergic reaction. 

• Self-antigens: produced by body.

• Response to self-antigens resulting in tissue destruction: auto immune diseases. 

Comparison of Innate and Adaptive Immunity 

Adaptive Immunity 

Types. 

• Antibody-mediated (aka Humoral immunity): B cells give rise to antibodies 

• Cell-mediated: T cells. 

• Cytotoxic T cells – destroy infected cells. 

• Helper T cells and regulatory T cells – promote or inhibit both antibody-mediated and cell-mediated immunity. 

Cells of Adaptive Immunity and Their Primary Functions 

Antigenic Determinants and Antigen Receptors  

• Lymphocytes must interact with and recognize an antigen for the adaptive immunity response to occur. 

• Lymphocytes interact with specific regions of an antigen called antigenic determinants or epitopes. 

• Lymphocytes of a given clone have identical antigen receptors on their surfaces that combine with a specific antigenic determinant of a given antigen. Like the lock-and-key model for enzymes. 

Major Histocompatibility Complex Molecules  

Immune cells must be able to distinguish between self-antigens and foreign antigens. They must be able to also detect if a self-cell has been compromised by infection or mutation. Most lymphocyte activation involves surface proteins called major histocompatibility complex (MHC) molecules. These are proteins so they are Genetically determined.  

Major Histocompatibility Complex Molecules (cont.) 

• Display antigens produced in or processed by the cell on the cell’s plasma membrane. 

• Antigens produced in the cell are endogenous antigens – proteins produced through genetic expression and protein synthesis. 

• Antigens processed by a cell are exogenous antigens – substances obtained from the external environment, usually by phagocytosis, then broken down in the cytoplasm. 

Two types of MHC molecules: 

• MHC class I molecules display endogenous antigens; found on all nucleated cells; function as a “red flag” to prompt immune cells to destroy the displaying cell. 

• MHC class II molecules display exogenous antigens received from antigen-presenting cells (APCs) such as B cells, macrophages, monocytes, etc. 

MHC Class I Molecule and Endogenous Antigen 

1. When a virus reproduces inside a cell, viral proteins are produced within the cell.  

2. Some of these viral proteins are broken down in the cytoplasm. 

3. The viral protein fragments/antigens enter the rough endoplasmic reticulum and combine with MHC class I molecules to form complexes. 

4. The MHC class I/antigen complex then move through the Golgi apparatus to be further transported to the plasma membrane. 

5. MHC class I/antigen complexes on the cell’s plasma membrane can bind to T-cell receptors on the surface of T cells. This combination is a signal that activates T cells. Activated T cells can destroy infected cells, which stops viral replication. 

MHC Class II Molecules and Exogenous Antigens  

1. Antigen-presenting cells/phagocytes can take in foreign antigens by phagocytosis. 

2. Once inside the cell the antigen is broken down to form processed antigens. 

3. Vesicles contain MHC class II molecules combine with the phagocytic vesicles that contain the antigens.

4. The MHC class II/antigen complexes are transported to the plasma membrane, where they are displayed to other immune cells. 

5. The displayed MHC class II/antigen complex can stimulate immune cells. 

• MHC class II/antigen complexes on a cell’s surface can bind to T-cell receptors on T cells.  

• The display does not result in destruction of the antigen-presenting cells like with MHC class I molecules. Stimulates other immune cells to respond to the antigen. 

Clonal selection is the mechanism that results in a large population of identical lymphocytes called clones. 

• Occurs when a lymphocyte proliferates (divides repeatedly) and differentiates (becomes specialized) when exposed to a specific antigen. 

• All blood cells, including lymphocytes, are derived from stem cells in the red bone marrow. 

• Some stem cells give rise to pre-T cells, that enter the blood and migrate to the thymus where they divide and processed by the action of thymosin. 

• Other stem cells give rise to pre-B cells that are processed in the red bone marrow. 

Both B cells and T cells are released into the blood and move to lymphatic tissue where they can encounter antigens. The B cells and T cells will then divide producing many cells able to recognize the specific antigen.   

Lymphocyte Proliferation 

Cells from original clones must proliferate before antigen can be attacked effectively. 

1. Proliferation of helper T cells occurs first: APCs present antigen with MHC class II; T cells with appropriate receptors respond. 

2. Helper T cells aid in proliferation and activation of B cells or cytotoxic T cells: B cell activation results in plasma cells (that make antibodies) and memory B cells. 

Proliferation of Helper T Cells 

1. An antigen-presenting cell, such as a macrophage, engulfs, processes, and displays an antigen on its plasma membrane by way of an MHC class II molecule. 

2. A helper T cell interacts with the macrophage through its T-cell receptor.  

3. Costimulation occurs by a CD4 glycoprotein of the helper T cell or by cytokines.  

4. The active helper T cell secretes cytokines.  

5. The helper T cell stimulates itself to divide and produce clones/daughter cells. 

6. The “daughter” helper T cells can be stimulated to divide again if they are exposed to the same antigen that stimulated the “parent cell. This greatly increases the number of helper T cells specific to this antigen. 

7. The increased number of helper T cells can facilitate the activation of B cells or cytotoxic T cells. 

8. Some “daughter” cells will become inactive memory helper T cells, which become active in future encounters with the same antigen. 

Antibody-Mediated Immunity 

• Involves the production of antibodies in response to extracellular antigens. Exposure to the antigens can lead to activation of B cells and then the production of antibodies that destroy the antigen. 

• Effective against extracellular antigens including bacteria, viruses, protozoans, fungi, parasites, and toxins when they are outside cells. Can also cause immediate hypersensitivity (allergic) reactions. 

Proliferation of B Cells  

1. Before a B cell can be activated by a helper T cell, the B cell must take in and process the same antigen that activated the helper T cell. The antigen binds to a B-cell receptor, and both the receptor and the antigen are taken into the cell. 

2. The B cell uses an MHC class II molecule to present the antigen to the helper T cell. 

3. Costimulation of the B cell occurs through surface molecules, such as CD4, as well as through the release of cytokines by the helper T cell. 

4. The B cell divides, and the resulting “daughter” B cells divide, and so on, eventually producing many B cells that recognize the same antigen. 

5. Many of the daughter cells differentiate to become plasma cells, which produce antibodies. Antibodies are part of the immune response that eliminates the antigen. 

6. Daughter cells that do not differentiate to become plasma cells reduce in size and become inactive memory B cells. Memory B cells may become active in future encounters with the same antigen. 

Structure of Antibodies 

Antibodies are proteins produced by B cells, specifically plasma cells, in response to an antigen. Sometimes called  immunoglobulins (Ig) 

• Classes: IgG, IgM, IgA, IgE, IgD. 

• Structure – Y-shaped consisting of four polypeptide chains. 

• Variable region: Part that combines with antigen. 

• Constant region: Responsible for activities of antibodies like activating complement or attaching to various kinds of WBCs 

Effects of Antibodies and Their Functions –

Direct Effects - The antibody can bind the antigen and interfere with the antigen’s ability to function,  This is often called neutralization.

The antibody can bind to two different antigens, rendering the antigens ineffective. 

The binding can precipitate the antigens and trap them for a phagocytic wbc to come and engulf it.

The ability of antibodies to join antigens together is the basis for many clinical tests, such as blood typing, because, when enough antigens are bound together, they become visible as a clump (Agglutination). 

Indirect Effects of Antibodies  

Antibodies (IgE) can initiate an inflammatory response. The antibodies attach to mast cells or basophils through their constant region. When antigens combine with the variable region of the antibodies, the mast cells or basophils release chemicals through exocytosis, and inflammation results. For example, people who have hay fever inhale antigens (usually, plant pollen), which are then absorbed through the respiratory mucous membrane. The combination of the antigens with antibodies stimulates mast cells to release inflammatory chemicals, such as histamine. The resulting localized inflammatory response produces swelling and increased mucus production in the respiratory tract. 

Antibody Production 

Primary response. The primary response occurs when a B cell is first activated by its specific antigen. The B cell proliferates to form plasma cells and memory cells. The plasma cells produce antibodies. Usually, IgM is the first antibody made, but later other classes are produced. The primary response normally takes 3-14 days to produce enough antibodies to be effective. Disease symptoms generally develop. 

Secondary response. The secondary response or memory response, occurs when another exposure to the same antigen causes the memory cells to rapidly form plasma cells and additional memory cells. The secondary response is faster and produces more antibodies than the primary response. Generally, the person does not get sick. Memory B cells can persist for many years, even a lifetime. 

Cell-Mediated Immunity 

Cell-mediated immunity most effective against cytoplasmic microbes through the action of cytotoxic T cells responding to endogenous antigens. 

Cytotoxic T cells function in two ways: 

1. Lyse virus-infected cells, tumor cells, and tissue transplants. Major lysin is perforin, which forms a hole in the plasma membrane of the target cell. 

2. Produce cytokines, which promote phagocytosis and inflammation. 

As in antibody mediated immunity, memory cells are produced. 

Proliferation of Cytotoxic T Cells  

1. When viruses infect cells, some viral proteins are broken down and become processed endogenous antigens that are combined with MHC class I molecules and displayed on the surface of the infected cells. T cells can distinguish between virally infected cells and noninfected cells because MHC class I/antigen complexes are on the surface of infected cells, but not on the surface of uninfected cells. 

2. Binding of the T-cell receptor to the MHC class I/antigen complex is a signal for activating Cytotoxic T cells.  

4. Helper T cells provide costimulation by releasing cytokines which can also activate cytotoxic T cells.  

5. The activated cytotoxic T cell divides, the resulting daughter cells divide, and so on, eventually producing many activated cytotoxic T cells. Active Cytotoxic T cells directly kill/lyse infected/abnormal cells. 

Stimulation and Effects of T Cells  

1. After T cells are activated by an antigen on the surface of a target cell, they undergo a series of divisions to produce cytotoxic T cells and memory T cells. 

2. Memory T cells can provide a secondary response and long-lasting immunity in the same fashion as memory B cells. 

4. An effect of cytotoxic T cells is the destruction of target cells. Cytotoxic T cells can directly contact other infected cells and cause them to lyse. Virally infected cells have viral antigens, tumor cells have tumor antigens, and tissue transplants have foreign antigens on their surfaces that can stimulate cytotoxic T-cell activity. A cytotoxic T cell binds to a target cell and releases chemicals that cause the target cell to lyse. The major method of lysis involves a protein called perforin, which is like the complement protein C9. Perforin released by cytotoxic T cells forms a channel in the plasma membrane of the target cell. Water enters the cell through the channel, causing the cell to swell and lyse. 

5. The cytotoxic T cell then moves on to destroy additional target cells. 

Ways to Acquire Adaptive Immunity: Active or Passive Immunity  

     Active – you make antibodies.  

     Passive – you receive antibodies from someone else. 

Immunization: deliberate exposure to antigen or antibody. 

Active natural immunity: natural exposure to an antigen. 

Active artificial immunity: vaccination. Deliberate exposure to an antigen (vaccine). 

Passive natural immunity: transfer of antibodies from a mother to her fetus or baby, via crossing placenta or breastmilk. 

Passive artificial immunity: transfer of antibodies (or cells) from an immune animal to a nonimmune human. Available for rabies, tetanus, snake venoms, etc. 

ADVANCED ANATOMY AND PHYSIOLOGY CHAPTER 23 

Respiratory System 

Lecture Outline 

The respiratory system operates at multiple levels. Pulmonary gas exchange occurs when our blood travels through our lungs and picks up O2 and drops off CO2. Tissue gas exchange occurs when O2 is delivered to our cells and CO2 is carried away from our cells. Finally, cellular Pulmonary gas exchange occurs when our cells use O2 to make needed energy and create CO2 as waste. All actions of the respiratory system are essential for life.  

To accomplish gas exchange, four simultaneous processes occur: 

• Pulmonary ventilation: breathing. 

• External Respiration or Pulmonary gas exchange: gas diffusion across alveoli; oxygen moves from alveolar air to blood, while carbon dioxide moves from blood to alveolar air. 

• Gas transport: gas travels in blood. 

• Internal Respiration or Tissue gas exchange: gas exchange at the tissues; O2 from blood to cells and CO2 from cells to blood. 

Functions in addition to Pulmonary gas exchange: 

• Production of chemical mediators: ACE, an enzyme involved in blood pressure regulation via renin angiotensin system. 

• Voice production: Movement of air past vocal folds makes sound and speech. 

Larynx: voice box that houses cartilages and ligaments used for speech. 

Functions of Larynx 

1. Maintain an open passageway for air movement. 

2. Epiglottis prevent swallowed material from moving into larynx. 

3. Vocal folds are primary source of sound production. 

Lower Respiratory Tract –  

Trachea/Windpipe – a tube of connective tissue and smooth muscle; supported by 15 to 20 hyaline cartilage C-shaped rings (tracheal rings) open posteriorly

Trachea Divides to form: 

• Left and right main bronchi (primary). 

Tracheobronchial tree: trachea and network of air tubes in lungs. 

Trachea to terminal bronchioles is ciliated for removal of debris. 

Cartilage: holds tube system open; smooth muscle controls tube diameter. 

As tubes become smaller, cartilage decreases, smooth muscle increases. 

Four classes of passages (largest to smallest): 

Bronchodilation: smooth muscle relaxes. 

• Decreased resistance to air flow, so airflow increases. 

Bronchoconstriction: smooth muscle contracts. 

• Increased resistance to air flow, so airflow decreases. 

• Asthma attack – inflammatory reaction causes severe bronchoconstriction. 

• Sympathetic nervous system triggers bronchodilation via beta-1 receptors.

Alveoli: sites of pulmonary gas exchange. 300 million alveoli in the two lungs 

Branching from terminal bronchioles to alveoli: 

Respiratory membrane: site of pulmonary gas exchange. O2 enters blood, CO2 exits blood 

Membrane is very thin; composed of alveolar cell layer, capillary endothelial layer, basement membranes, and interstitial space. 

Blood Supply 

Two sources of blood to lungs: 

• Pulmonary artery brings deoxygenated blood to lungs from right ventricle to be oxygenated in capillary beds that surround the alveoli. Oxygenated Blood leaves via the pulmonary veins and returns to the left atrium. 

Pleura – it is the pleura that attaches the lungs to the thoracic wall.  It acts as a suction and if it is punctured the lungs can collapse.

• Pleural cavity surrounds each lung and is formed by the visceral and parietal pleura 

• Visceral pleura: adherent to lung. Simple squamous epithelium, serous. 

• Parietal pleura: adherent to internal thoracic wall. 

Behavior of Gases – gases follow pressure gradient, move from area of high pressure to area of lower pressure 

Muscles of pulmonary ventilation change the volume of the thoracic cavity, which then changes pressure, causing air to flow into or out of the lungs. 

Muscles of Ventilation in Quiet Ventilation Compared to Labored Pulmonary Ventilation  

Quiet Inspiration – inhalation is an active process (quiet exhalation is passive) 

• Diaphragm contracts and flattens downward. 

• External intercostals contract and raise the ribs and sternum. 

Forced Inspiration 

• The pectoralis muscles contract to raise the ribs and sternum more to give a greater increase of thoracic volume. 

Quiet Expiration – passive process, no muscle contraction needed 

• Diaphragm relaxes and raises 

• External intercostals relax and ribs rebound down. 

Forced Expiration 

• Abdominal muscles contract and push the diaphragm up more. 

• Internal intercostals contract to pull the ribs inward to decrease thoracic volume more. 

Pressure Gradients and Airflow 

Air flows down its pressure gradient, from higher pressure to lower pressure. 

• During inspiration, air flows into the lungs, down its pressure gradient. 

• During expiration, air flows out of the lungs, down its pressure gradient. 

Measurement of Lung Function - Lung Volumes and Lung Capacities  

Spirometry: spirometer measure volumes of air that move in and out of respiratory system 

Pulmonary volumes: 

• Tidal volume (TV): amount of air inspired or expired with each breath. At rest: approx. 500 mL 

• Inspiratory reserve volume (IRV): amount that can be inspired forcefully after inspiration of the tidal volume (3000 mL at rest). 

• Expiratory reserve volume (ERV): amount that can be forcefully expired after expiration of the tidal volume (1100 mL at rest). 

• Residual volume (RV): volume still remaining in respiratory passages and lungs after most forceful expiration (1200 mL). 

Pulmonary capacities: sum of two or more pulmonary volumes. 

• Inspiratory capacity (IC): tidal volume plus inspiratory reserve volume. 

• Functional residual capacity (FRC): expiratory reserve volume plus residual volume. 

• Vital capacity (VC): sum of inspiratory reserve volume, tidal volume, and expiratory reserve volume. 

• Total lung capacity (TLC): sum of inspiratory and expiratory reserve volumes plus tidal volume and residual volume. 

Respiratory rate: number of breaths taken per minute. 

Minute volume: total air moved into and out of respiratory system each minute; formula for Minute volume is: Tidal volume X Respiratory rate. 

Factors Affecting Pulmonary Ventilation 

• Increased vital capacities correlate with male gender, taller height, being active, being slender, and being healthy.  Well-trained athletes can have a vital capacity 30 to 40% higher than people with a sedentary lifestyle. 

• Persons with lung disease like emphysema, have enlarged alveoli because the walls have degenerated, giving less surface area for gas exchange. 

Physiology of the Respiratory System 

Oxygen Partial Pressure Gradients 

1. The PO2 of alveolar air averages 104 mm Hg. The PO2 in the pulmonary capillaries is 40 mm Hg. Thus, because the PO2 is higher in the alveolar air, O2 diffuses into the pulmonary capillaries, down its partial pressure gradient. 

2. By the time blood reaches the venous ends of the pulmonary capillaries, an equilibrium has been achieved and the PO2 in the blood is 104 mm Hg. 

3. There is a slight decrease in the PO2 of blood in the pulmonary veins to about 95 mm Hg, due to mixing of deoxygenated blood from the bronchial veins with blood leaving the pulmonary capillaries. 

4. The PO2 of arterial blood as it arrives in the tissues is still 95 mm Hg compared to the PO2 of the interstitial fluid, which is 40 mm Hg. The PO2 in individual tissue cells is around 20 mm Hg. Thus, O2 diffuses out of the capillaries into the interstitial fluid and across the plasma membrane of individual cells. The individual cells then use the O2 to produce ATP, which releases CO2 as a by-product. 

Carbon Dioxide Partial Pressure Gradients 

• As cells produce CO2, the intracellular PCO2 increases to 46 mm Hg and the interstitial fluid PCO2 is 45 mm Hg (see step 5). The PCO2 of arterial blood as it arrives in the tissues is 40 mm Hg. Thus, CO2 diffuses out of the cells, into the interstitial fluid and into the blood, down its partial pressure gradient. By the time blood has reached the venous end of the capillary network, it has achieved an equilibrium with the interstitial fluid and has a PCO2 of 45 mm Hg.  

• The PCO2 of the blood when it returns to the arterial end of the pulmonary capillaries is still 45 mm Hg compared to a PCO2 of 40 mm Hg in the alveoli (see steps 1 and 2). Thus, at the alveoli, CO2 diffuses out of the blood down its partial pressure gradient. At the venous end of the pulmonary capillaries, PCO2 has achieved an equilibrium with the alveoli and has decreased to 40 mm Hg.  

Oxygen and Carbon Dioxide Transport in the Blood 

Hemoglobin: 

• Protein synthesized by RBCs; occupies much of red blood cell volume. 

• Adult has 4 subunits, each containing one iron-based heme group, so 1 hemoglobin can carry up to 4 O2. 

• Hemoglobin exhibits cooperativity -

Transport of Oxygen 

• About 98.5% of O2 transport is by hemoglobin. 

• About 1.5% is dissolved in plasma. 

Transport of Carbon Dioxide 

About 7% dissolves in the plasma. 

About 23% binds to the globin of hemoglobin. 

About 70% is transported as bicarbonate ion dissolved either in the cytoplasm of RBCs or in the plasma of the blood. 

Carbon Dioxide Transport  

• At tissue capillaries: as CO2 enters red blood cells, reacts with water to form bicarbonate and hydrogen ions. Chloride ions enter the RBC and bicarbonate ions leave (chloride shift) to balance charge. Hydrogen ions combine with hemoglobin. Lowering the concentration of bicarbonate and hydrogen ions inside red blood cells promotes the conversion of CO2 to bicarbonate ion. 

• At pulmonary capillaries: CO2 leaves red blood cells. The bicarbonate ions are exchanged for chloride ions, and the hydrogen ions are released from hemoglobin. 

Carbon Dioxide Transport  

• Reaction to form bicarbonate 

• The enzyme carbonic anhydrase catalyzes both steps of the reversible reaction. 

• At the tissues, where CO2 levels are higher, HCO3- is removed from the red blood cell, HCO3- diffuses out of the red blood cell while Cl- diffuses in.  

Systemic Gas Exchange 

1. In the tissues, carbon dioxide (CO2) diffuses into the plasma and into red blood cells. Some of the carbon dioxide remains in the plasma.  

2. In red blood cells, carbon dioxide reacts with water (H2O) to form carbonic acid (H2CO3) in a reaction catalyzed by the enzyme carbonic anhydrase (CA).  

3. Carbonic acid dissociates to form bicarbonate ions and hydrogen ions 

4. In the chloride shift bicarbonate to diffuses out of the red blood cells and chloride ions to diffuse into them. 

5. Oxygen (O2) is released from hemoglobin (Hb). Oxygen diffuses out of red blood cells and plasma into the tissue. 

Oxygen-hemoglobin dissociation curve describes the percent saturation of hemoglobin at different PO2 values.   You DON’T HAVE TO MEMORIZE VALUES, JUST KNOW HOW TO INTERPRET GRAPH.

• At PO2 of 104 mm Hg, hemoglobin is 98% saturated. 

• At PO2 of 60 mm Hg, hemoglobin is 90% saturated. 

• Due to affinity of hemoglobin for oxygen over wide range of values. 

• At PO2 of 40 mm Hg (such as at the tissues), PO2 is 40 mm Hg and so venous blood leaving tissues is 75% saturated. 

• Used as a reserve if blood PO2 levels decrease further, as during exercise. 

Effect of pH and PO2 on O2 Transport 

• as pH of blood declines (more acidic), oxygen bound to hemoglobin also declines. 

• So, hemoglobin releases more O2 at lower pH .  Hemoglobin has a lower affinity to oxygen.

Tissues that are producing more ATP release more CO2, which lowers the pH. In addition, the increased activity raises the temperature in the tissues. 

When tissues are more active, they use oxygen faster which lowers O2 in the tissues which causes more O2 release from hemoglobin 

Effect of Temperature on O2 Transport 

• An increase in temperature due to increased metabolism causes more oxygen to be released from hemoglobin to the tissues. 

Regulation of Pulmonary ventilation Neural Control 

Regulation of pulmonary ventilation can be under voluntary control as when eating or speaking, yet during sleep or when focused on other tasks, is regulated involuntarily. 

Respiratory Areas in the Brainstem  

Medullary respiratory center in the medulla oblongata 

• Ventral respiratory group (VRG) – produces the normal, involuntary rhythm of breathing called eupnea. 

• Has a collection of neurons active during both inspiration and expiration. 

• establishes the basic rhythm of pulmonary ventilation. 

• Dorsal respiratory group (DRG) – receives input from chemoreceptors and mechanoreceptors and other sources to modify the respiratory rhythm.  

Chemoreceptors - Chemoreceptor Reflex 

Effect of PO2 on Respiratory Rate 

• Hypoxia: decrease in oxygen levels below normal values. 

• Carotid and aortic body chemoreceptors respond to ONLY a large drop in blood Po2 by increased stimulation of respiratory center to keep it active. 

Effect of PCO2 on Respiratory Rate 

CO2 is the Major regulator of pulmonary gas exchange during rest or exercise. 

• Even a small increase in carbon dioxide in blood triggers a large increase in rate and depth of pulmonary gas exchange.  The reason CO2 is so tightly regulated is that even a little increase in CO2 can alter blood pH.

Chemosensitive area in medulla oblongata is more important for regulation of PCO2 and pH. 

Carotid bodies respond rapidly to changes in blood pH because of intense exercise. 

Regulation of Blood CO2 

(1) Blood CO2 is in its normal range.  

(2) Blood CO2 increases outside its normal range, which disturbs homeostasis.  

(3) The control centers for blood CO2, the medullary chemoreceptors, detect a decrease in blood pH (blood becomes more acidic) and respond by increasing breathing rate.  

(4) The effectors, the diaphragm and other respiratory muscles, respond by increasing their contraction rate, which increases the rate of breathing.  

(5) As a result, more CO2 is exhaled, which causes pH to rise (blood becomes less acidic). (6) Blood CO2 returns to its normal range and homeostasis is maintained.  

The opposite happens with decreased CO2. 

Effect of pH on Respiratory Rate 

Chemosensitive area of medulla oblongata and carotid and aortic bodies respond to blood pH changes. 

• Chemosensitive areas respond indirectly through changes in carbon dioxide. 

• Carotid and aortic bodies respond directly to pH changes. 

Lower pH triggers increase in rate and depth of breathing, reducing carbon dioxide and raising pH to normal.