2. The Lung: An Environmentally Embattled Organ MCB 135K April 25, 2007

4. Two lungs activate gas exchange Chest wall Respiratory muscles Regulation of respiration by CNS centers & nerve tracts Activate ventilation Box 18.1 Pulmonary Respiratory System: Structure

5. Regulation of gaseous exchange Immunologic defenses of the body -by phagocytizing particles from inspired air & blood Metabolic functions -by synthesizing, storing or releasing into blood substances like surfactant and prostaglandins Endocrine functions -by transforming angiotensin I into angiotensin II (vasoconstrictor and stimulus for aldosterone secretion) Box 18.1 Pulmonary Respiratory System: Major Functions

7. Lung, “Battered” Organ Due to: Air pollution Smoking Air borne infections Oxygen toxicity (e.g. with the use of respirators there is increased free radical production; therefore, simultaneous administration of antioxidants is recommended)

8. Major Structural Changes in the Aveolar Ducts & Aveoli with Age Amount of elastic tissue Amount of fibrous tissue

9. TABLE 18-2 Changes with Aging in Respiratory Muscles Muscle strength fatigue when work of breathing (as during physical exercise) Atrophy of some respiratory muscles (primarily Type I muscle fibers of slow, red muscles as in long muscles of back, shoulders) Ratio of glycolytic (anaerobic) to oxidative (aerobic) metabolism Blood supply to muscle

10. Morphologic ChangesFunctional Consequences * * Tidal Volume: Amount of in and out air moving out of lungs with quiet inspiration/expiration

11. LUNG Table 18-3 Changes with Age in the Lung Morphological ChangesFunctional Significance ** * * Dead Space: Air in the air ways ** Vital Capacity (VC): Greatest amount of air expired after maximal inspiration ** Reserve Volume (RV)/Total Lung Capacity (TLC)

12. Table 18-1 Signs of Impaired Pulmonary Respiration with Aging Reduced maximum breathing capacity Less efficient emptying of the lungs Premature airway closure Progressive reduction in blood oxygenation and in PO 2 exchanges between blood and alveolar air Loss of elastic recoil (i.e. springing back of elastic fibers after stretching) Increased rigidity of internal lung structure Weakening of respiratory muscles Decreased elasticity of thorax cage and chest wall Earlier and easier fatigability

13. Chronic Obstructive Pulmonary Disease (COPD) Comprised of three distinct pathologies: Chronic bronchitis: inflammation of the bronchi and accompanied by hypersecretion of mucus & cough Emphysema: characterized by enlargement of air spaces, destruction of lung parenchyma, loss of lung elasticity and closure of small airways Chronic asthma: constriction of the bronchi

14. TABLE 18-4 Major Risk Factors for Chronic Obstructive Pulmonary Disease (COPD) Cigarette smoking Air pollution Genetic factors Bronchial inflammation Chronic respiratory tract infections Old age Family history of COPD Male sex

15. TABLE 18-5 Major Signs of Chronic Obstructive Pulmonary Disease (COPD) Structural Diffuse distention & over- aeration of alveoli Disruption of interalveolar septa Loss of pulmonary elasticity Restructuring of alveoli Increased lung volume Barrel-shaped chest Pathophysiologic Disturbed ventilation Altered air and blood flow Frequently partial obstruction of bronchi Wheezing & more work required for breathing Resulting hypoxia (low O 2 levels) and hypercapnia (high CO 2 levels) Chronic productive cough with mucus Minor respiratory infections

16. Table 18-6 (con’t.) Therapeutic strategies: 1. Administration of pharmacological agents (bronchodilators, mucus liquefiers, anti-inflammatory agents, protease inhibitors, antibiotics) 2. Administration of O 2 to be used cautiously to prevent acidosis 3. Optimizing function by: -physical exercise to strengthen abdominal muscles and diaphragm to aid in lung ventilation -meeting social, emotional and vocational needs. -use of respiratory aids in the form or aerosols, sprays, etc.

17. Lineages of Mature Blood Cells Derived from Bone Marrow Stem Cells White Blood Cells Granulocytes Neutrophils Eosinophils Basophils Lymphocytes B-cells T-cells Monocytes Erythrocytes (Red Blood Cells, RBCs) Platelets

18. Some unique characteristics of Red Blood Cells Red blood cells represent a cell population that: is easily accessible, is in continuing renewal, has a well-defined life span, has become a popular model for the study of cell function at all ages, including old age.

19. Major Functions of Blood Cells Efficient oxygen delivery to tissues and cells (erythrocytes, RBCs) Hemostasis: prevention of blood loss (e.g., through blood clotting, platelets) Immune response, primarily white blood cells (Chapter 14) Responsiveness to environmental stimuli (e.g., increase in cellular response to hypoxia) Specificity of responses to demands (only relevant lineage is stimulated without expansion of irrelevant ones; e.g. hypoxia selectively stimulates erythroid bone marrow and subsequent erythropoiesis)

20. Table 18-13 Hematological Profile of Some Older Individuals Hemoglobin Hematocrit RBC number Onset of erythropoiesis after severe bleeding Erythropoietic responses to erythropoietin administration Most of these changes are NOT experienced by centenarians

21. Table 18-14 Hormonal Regulators of Erythropoiesis Erythropoietin Testosterone Interleukin-3

22. Table 18-15 Factors Involved in Earlier and Faster (< 120 days) Removal of RBCs from Circulation in Old Subjects CausesMechanisms Earlier and greater fragility Greater tendency to aggregate Decreased availability of energy for metabolism Altered ionic balance, especially in aging associated diseases Alteration in membrane lipids increases cell fragility as well as decreases glucose transport and utilization Membrane alterations may promote RBC aggregation Decreased activity of NA + K + - ATPase Alteration in ionic balance