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Copyright 2009, John Wiley & Sons, Inc. Chapter 23: The Respiratory System.

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1 Copyright 2009, John Wiley & Sons, Inc. Chapter 23: The Respiratory System

2 Copyright 2009, John Wiley & Sons, Inc. Respiratory System Anatomy Structurally Upper respiratory system Nose, pharynx and associated structures Lower respiratory system Larynx, trachea, bronchi and lungs Functionally Conducting zone – conducts air to lungs Nose, pharynx, larynx, trachea, bronchi, bronchioles and terminal bronchioles Respiratory zone – main site of gas exchange Respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli

3 Copyright 2009, John Wiley & Sons, Inc.

4 Nose External nose – portion visible on face Internal nose – large cavity beyond nasal vestibule Internal nares or choanae Ducts from paranasal sinuses and nasolacrimal ducts open into internal nose Nasal cavity divided by nasal septum Nasal conchae subdivide cavity into meatuses Increase surface are and prevents dehydration Olfactory receptors in olfactory epithelium

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7 Pharynx Starts at internal nares and extends to cricoid cartilage of larynx Contraction of skeletal muscles assists in deglutition Functions Passageway for air and food Resonating chamber Houses tonsils 3 anatomical regions Nasopharynx Oropharynx Laryngopharynx

8 Copyright 2009, John Wiley & Sons, Inc. Larynx Short passageway connecting laryngopharynx with trachea Composed of 9 pieces of cartilage Thyroid cartilage or Adams apple Cricoid cartilage hallmark for tracheotomy Epiglottis closes off glottis during swallowing Glottis – pair of folds of mucous membranes, vocal folds (true vocal cords and rima glottidis) Cilia in upper respiratory tract move mucous and trapped particles down toward pharynx Cilia in lower respiratory tract move them up toward pharynx

9 Copyright 2009, John Wiley & Sons, Inc. Larynx

10 Copyright 2009, John Wiley & Sons, Inc. Structures of Voice Production Mucous membrane of larynx forms Ventricular folds (false vocal cords) – superior pair Function in holding breath against pressure in thoracic cavity Vocal folds (true vocal cords) – inferior pair Muscle contraction pulls elastic ligaments which stretch vocal folds out into airway Vibrate and produce sound with air Folds can move apart or together, elongate or shorten, tighter or looser Androgens make folds thicker and longer – slower vibration and lower pitch

11 Copyright 2009, John Wiley & Sons, Inc.

12 Trachea Extends from larynx to superior border of T5 Divides into right and left primary bronchi 4 layers Mucosa Submucosa Hyaline cartilage Adventitia C-shaped rings of hyaline cartilage Open part faces esophagus

13 Copyright 2009, John Wiley & Sons, Inc. Location of Trachea

14 Copyright 2009, John Wiley & Sons, Inc. Bronchi Superior border of 5 th thoracic vertebra trachea divides into right and left primary bronchus. Right is more vertical, shorter, and wider – aspiration more likely to affect right side Carina – site where bronchi divide is an internal ridge Most sensitive area for triggering cough reflex Divide to form bronchial tree Secondary lobar bronchi (one for each lobe), tertiary (segmental) bronchi, bronchioles, terminal bronchioles

15 Copyright 2009, John Wiley & Sons, Inc. Bronchi Structural changes with branching Mucous membrane changes – ciliated simple columnar with goblet cells in larger bronchioles to ciliated simple cuboidal with no goblet cells in smaller bronchioles to mostly nonciliated simple cuboidal in terminal bronchioles (macrophages take over) Incomplete rings of cartilage become plates and then disappear in distal bronchioles As cartilage decreases, smooth muscle increases Sympathetic ANS – relaxation/ dilation Parasympathetic ANS and histamine have opposite effect – contraction/ constriction

16 Copyright 2009, John Wiley & Sons, Inc.

17 Lungs Separated from each other by the heart and other structures in the mediastinum Each lung enclosed by double-layered pleural membrane Parietal pleura – lines wall of thoracic cavity Visceral pleura – covers lungs themselves Pleural cavity is space between layers Pleural fluid reduces friction, produces surface tension (stick together) Cardiac notch – heart makes left lung 10% smaller than right

18 Copyright 2009, John Wiley & Sons, Inc. Relationship of the Pleural Membranes to Lungs

19 Copyright 2009, John Wiley & Sons, Inc. Anatomy of Lungs Lobes – each lung divides by 1 or 2 fissures Each lobe receives it own secondary (lobar) bronchus that branch into tertiary (segmental) bronchi Lobules wrapped in elastic connective tissue and contains a lymphatic vessel, arteriole, venule and branch from terminal bronchiole Terminal bronchioles branch into respiratory bronchioles which divide into alveolar ducts About 25 orders of branching

20 Copyright 2009, John Wiley & Sons, Inc.

21 Microscopic Anatomy of Lobule of Lungs

22 Copyright 2009, John Wiley & Sons, Inc. Alveoli Cup-shaped outpouching Alveolar sac – 2 or more alveoli sharing a common opening 2 types of alveolar epithelial cells Type I alveolar cells – form nearly continuous lining, more numerous than type II, main site of gas exchange Type II alveolar cells – free surfaces contain microvilli, secrete alveolar fluid (surfactant reduces tendency to collapse) Surfactant - a combination of phospholipids and lipoproteins that reduce surface tension preventing alveoli from collapsing

23 Copyright 2009, John Wiley & Sons, Inc. Alveolus Respiratory membrane Alveolar wall – type I and type II alveolar cells Epithelial basement membrane Capillary basement membrane Capillary endothelium Very thin – only 0.5 µm thick to allow rapid diffusion of gases Lungs receive blood from Pulmonary artery – deoxygenated blood Bronchial arteries – oxygenated blood to perfuse muscular walls of bronchi and bronchioles

24 Copyright 2009, John Wiley & Sons, Inc. Components of Alveolus

25 Copyright 2009, John Wiley & Sons, Inc.

26 Pulmonary ventilation Respiration (gas exchange) steps 1. Pulmonary ventilation/ breathing Inhalation and exhalation Exchange of air between atmosphere and alveoli 2. External (pulmonary) respiration Exchange of gases between alveoli and blood 3. Internal (tissue) respiration Exchange of gases between systemic capillaries and tissue cells Supplies cellular respiration (makes ATP)

27 Copyright 2009, John Wiley & Sons, Inc. Inhalation/ inspiration Pressure inside alveoli must become lower than atmospheric pressure for air to flow into lungs 760 millimeters of mercury (mmHg) or 1 atmosphere (1 atm) Achieved by increasing size of lungs Boyles Law – pressure of a gas in a closed container is inversely proportional to the volume of the container Inhalation – lungs must expand, increasing lung volume, decreasing pressure below atmospheric pressure

28 Copyright 2009, John Wiley & Sons, Inc. Boyles Law

29 Copyright 2009, John Wiley & Sons, Inc. Inhalation Inhalation is active – Contraction of Diaphragm – most important muscle of inhalation Flattens, lowering dome when contracted Responsible for 75% of air entering lungs during normal quiet breathing External intercostals Contraction elevates ribs 25% of air entering lungs during normal quiet breathing Accessory muscles for deep, forceful inhalation When thorax expands, parietal and visceral pleurae adhere tightly due to subatmospheric pressure and surface tension – pulled along with expanding thorax As lung volume increases, alveolar (intrapulmonic) pressure drops

30 Copyright 2009, John Wiley & Sons, Inc.

31 Exhalation/ expiration Pressure in lungs greater than atmospheric pressure Normally passive – muscle relax instead of contract Based on elastic recoil of chest wall and lungs from elastic fibers and surface tension of alveolar fluid Diaphragm relaxes and become dome shaped External intercostals relax and ribs drop down Exhalation only active during forceful breathing

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34 Airflow Air pressure differences drive airflow 3 other factors affect rate of airflow and ease of pulmonary ventilation Surface tension of alveolar fluid Causes alveoli to assume smallest possible diameter Accounts for 2/3 of lung elastic recoil Prevents collapse of alveoli at exhalation Lung compliance High compliance means lungs and chest wall expand easily Related to elasticity and surface tension Airway resistance Larger diameter airway has less resistance Regulated by diameter of bronchioles & smooth muscle tone

35 Copyright 2009, John Wiley & Sons, Inc. Lung volumes and capacities The minute volume of respiration is the total volume of air taken in during one minute tidal volume x 12 respirations per minute = 6000 ml/min Tidal volume is normally 500 mL Does not account for dead space

36 Copyright 2009, John Wiley & Sons, Inc. Lung Volumes Only about 70% of tidal volume reaches respiratory zone Other 30% remains in conducting zone Anatomic (respiratory) dead space – conducting airways with air that does not undergo respiratory gas exchange Alveolar ventilation rate – volume of air per minute that actually reaches respiratory zone Inspiratory reserve volume – taking a very deep breath

37 Copyright 2009, John Wiley & Sons, Inc. Spirogram of Lung Volumes and Capacities

38 Copyright 2009, John Wiley & Sons, Inc.

39 LUNG VOLUMES AND CAPACITIES Air volumes exchanged during breathing and rate of ventilation are measured with a spiromometer and the record is called a spirogram Among the pulmonary air volumes exchanged in ventilation are tidal (500 ml) inspiratory reserve (3100 ml) expiratory reserve (1200 ml) residual (1200 ml) minimal volumes. Only about 350 ml of the tidal volume actually reaches the alveoli, the other 150 ml remains in the airways as anatomic dead space Copyright 2009, John Wiley & Sons, Inc.

40 LUNG VOLUMES AND CAPACITIES Pulmonary lung capacities, the sum of two or more volumes, include inspiratory (3600 ml) functional residual (2400 ml) vital (4800 ml) total lung (6000 ml) capacities. Copyright 2009, John Wiley & Sons, Inc.

41 RESPIRATORY VOLUMES Tidal volume: During normal breathing about 500mL of air moves into and out of the lungs with each breath. The amount of air that can be inspired forcibly beyond the tidal volume is called inspiratory reserve volume (IRV). Copyright 2009, John Wiley & Sons, Inc.

42 RESPIRATORY VOLUMES Expiratory reserve volume (ERV) is the amount of air that can be evacuated from the lungs after tidal expiration. Even after the most strenuous expiration only about 1200 mL of air remains in the lungs; this is the residual volume which helps to keep the alveoli patent and prevent lung collapse. Copyright 2009, John Wiley & Sons, Inc.

43 RESPIRATORY CAPACITIES The inspiratory capacity is the total amount of air that can be inspired after a tidal expiration, so it is the sum of the TV + IRV. Functional residual capacity represents the amount of air remaining in the lungs after a tidal expiration and the combined RV + ERV. Copyright 2009, John Wiley & Sons, Inc.

44 RESPIRATORY CAPACITIES Vital capacity is the total amount of exchangeable air. It is the sum of TV + IRV + ERV. In healthy young males VC is approximately 4800 mL Total Lung Capacity is the sum of all lung volumes and is normally around 6 L. Copyright 2009, John Wiley & Sons, Inc.

45 Dead Space some of the inspired air fills the conducting passageways and never contributes to gas exchange. The volume of these conducting zones makes up the anatomic dead space. Anatomic dead space equals a mL / # of ideal body weight. This means that in an normal 500 mL TV, only 350 ml is involved in alveolar ventilation. Copyright 2009, John Wiley & Sons, Inc.

46 PULMONARY FUNCTION TESTS For evaluating losses in respiratory function and for following the course of certain respiratory diseases. It cannot provide a specific diagnosis, but it can distinguish between: obstructive pulmonary disease involving increased airway resistance such as emphysema restrictive pulmonary diseases involving a reduction in total lung capacity resulting from structural or functional changes in the lungs (TB, fibrosis due to occupational exposure). Copyright 2009, John Wiley & Sons, Inc.

47 PULMONARY FUNCTION TESTS More information can be obtained about a patients ventilation status by assessing the rate at which gas moves into and out of the lungs. the minute ventilation is the total amount of gas that flows into or out of the respiratory tract in 1 minute. During normal quiet breathing the minute ventilation in healthy people is about 6 L/min. During rigorous exercise the minute ventilation may reach 200 L/min. Copyright 2009, John Wiley & Sons, Inc.

48 PULMONARY FUNCTION TESTS Two unusual tests are FVC and FEV. FVC, forced vital capacity, measures the amount of gas expelled when a subject takes a deep breath and the forcefully exhales maximally and as rapidly as possible. FEV, forced expiratory volume, determines the amount of air expelled during specific time intervals. The volume exhaled during the first second is the FEV1. Those with healthy lungs can exhale out 80%. Those with obstructive disease exhale considerably less while those with restrictive disease exhales 80% or more even though their FVC is reduced. Copyright 2009, John Wiley & Sons, Inc.

49 PULMONARY FUNCTION TESTS Increases in TLC, FRC and RV may occur due to hyperinflation due to obstructive diseases. VC, TLC, FRC, and RV are reduced in restrictive diseases with limit lung expansion. Copyright 2009, John Wiley & Sons, Inc.

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51 Exchange of Oxygen and Carbon Dioxide Daltons Law Each gas in a mixture of gases exerts its own pressure as if no other gases were present Pressure of a specific gas is partial pressure P x Total pressure is the sum of all the partial pressures Atmospheric pressure (760 mmHg) = P N2 + P O2 + P H2O + P CO2 + P other gases Each gas diffuses across a permeable membrane from the area where its partial pressure is greater to the area where its partial pressure is less The greater the difference, the faster the rate of diffusion

52 Copyright 2009, John Wiley & Sons, Inc. Partial Pressures of Gases in Inhaled Air P N2 =0.786x 760mm Hg= mmHg P O2 =0.209x 760mm Hg= mmHg P H2O =0.004x 760mm Hg= 3.0 mmHg P CO2 =0.0004x 760mm Hg= 0.3 mmHg P other gases =0.0006x 760mm Hg= 0.5 mmHg TOTAL= mmHg

53 Copyright 2009, John Wiley & Sons, Inc. Henrys law Quantity of a gas that will dissolve in a liquid is proportional to the partial pressures of the gas and its solubility Higher partial pressure of a gas over a liquid and higher solubility, more of the gas will stay in solution Much more CO 2 is dissolved in blood than O 2 because CO 2 is 24 times more soluble Even though the air we breathe is mostly N 2, very little dissolves in blood due to low solubility Decompression sickness (bends)

54 Copyright 2009, John Wiley & Sons, Inc. External Respiration in Lungs Oxygen Oxygen diffuses from alveolar air (P O2 105 mmHg) into blood of pulmonary capillaries (P O2 40 mmHg) Diffusion continues until P O2 of pulmonary capillary blood matches P O2 of alveolar air Small amount of mixing with blood from conducting portion of respiratory system drops P O2 of blood in pulmonary veins to 100 mmHg Carbon dioxide Carbon dioxide diffuses from deoxygenated blood in pulmonary capillaries (P CO2 45 mmHg) into alveolar air (P CO2 40 mmHg) Continues until of P CO2 blood reaches 40 mmHg

55 Copyright 2009, John Wiley & Sons, Inc. Internal Respiration Internal respiration – in tissues throughout body Oxygen Oxygen diffuses from systemic capillary blood (P O2 100 mmHg) into tissue cells (P O2 40 mmHg) – cells constantly use oxygen to make ATP Blood drops to 40 mmHg by the time blood exits the systemic capillaries Carbon dioxide Carbon dioxide diffuses from tissue cells (P CO2 45 mmHg) into systemic capillaries (P CO2 40 mmHg) – cells constantly make carbon dioxide P CO2 blood reaches 45 mmHg At rest, only about 25% of the available oxygen is used Deoxygenated blood would retain 75% of its oxygen capacity

56 Copyright 2009, John Wiley & Sons, Inc.

57 Rate of Pulmonary and Systemic Gas Exchange Depends on Partial pressures of gases Alveolar P O2 must be higher than blood P O2 for diffusion to occur – problem with increasing altitude Surface area available for gas exchange Diffusion distance Molecular weight and solubility of gases O 2 has a lower molecular weight and should diffuse faster than CO 2 except for its low solubility - when diffusion is slow, hypoxia occurs before hypercapnia

58 Copyright 2009, John Wiley & Sons, Inc. Transport of Oxygen and Carbon Dioxide Oxygen transport Only about 1.5% dissolved in plasma 98.5% bound to hemoglobin in red blood cells Heme portion of hemoglobin contains 4 iron atoms – each can bind one O 2 molecule - Oxyhemoglobin Only dissolved portion can diffuse out of blood into cells Oxygen must be able to bind and dissociate from heme

59 Copyright 2009, John Wiley & Sons, Inc.

60 Relationship between Hemoglobin and Oxygen Partial Pressure Higher the P O2, More O 2 combines with Hb Fully saturated – completely converted to oxyhemoglobin Percent saturation expresses average saturation of hemoglobin with oxygen Oxygen-hemoglobin dissociation curve In pulmonary capillaries, O 2 loads onto Hb In tissues, O 2 is not held and unloaded 75% may still remain in deoxygenated blood (reserve)

61 Copyright 2009, John Wiley & Sons, Inc. Oxygen-hemoglobin Dissociation Curve

62 Copyright 2009, John Wiley & Sons, Inc. Hemoglobin and Oxygen Other factors affecting affinity of Hemoglobin for oxygen Each makes sense if you keep in mind that metabolically active tissues need O 2, and produce acids, CO 2, and heat as wastes Acidity P CO2 Temperature

63 Copyright 2009, John Wiley & Sons, Inc. Bohr Effect As acidity increases (pH decreases), affinity of Hb for O 2 decreases Increasing acidity enhances unloading Shifts curve to right P CO2 Also shifts curve to right As P CO2 rises, Hb unloads oxygen more easily Low blood pH can result from high P CO2

64 Copyright 2009, John Wiley & Sons, Inc. Temperature Changes Within limits, as temperature increases, more oxygen is released from Hb During hypothermia, more oxygen remains bound 2,3-bisphosphoglycerate BPG formed by red blood cells during glycolysis Helps unload oxygen by binding with Hb

65 Copyright 2009, John Wiley & Sons, Inc. Fetal and Maternal Hemoglobin Fetal hemoglobin has a higher affinity for oxygen than adult hemoglobin Hb-F can carry up to 30% more oxygen Maternal bloods oxygen readily transferred to fetal blood

66 Copyright 2009, John Wiley & Sons, Inc. Carbon Dioxide Transport Dissolved CO 2 Smallest amount, about 7% Carbamino compounds About 23% combines with amino acids including those in Hb Carbaminohemoglobin Bicarbonate ions 70% transported in plasma as HCO 3 - Enzyme carbonic anhydrase forms carbonic acid (H 2 CO 3 ) which dissociates into H + and HCO 3 -

67 Copyright 2009, John Wiley & Sons, Inc. Chloride shift HCO 3 - accumulates inside RBCs as they pick up carbon dioxide Some diffuses out into plasma To balance the loss of negative ions, chloride (Cl - ) moves into RBCs from plasma Reverse happens in lungs – Cl - moves out as moves back into RBCs CO 2 + H 2 O H 2 CO 3 H + + HCO 3 -

68 Copyright 2009, John Wiley & Sons, Inc.

69 CONTROL OF RESPIRATION The area of the brain from which nerve impulses are sent to respiratory muscles is located bilaterally in the reticular formation of the brain stem. This respiratory center consists of a medullary rhythmicity area (inspiratory and expiratory areas), pneumotaxic area, and apneustic area (Figure 23.24). Copyright 2009, John Wiley & Sons, Inc.

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71 Medullary Rhythmicity Area The function of the medullary rhythmicity area is to control the basic rhythm of respiration. The inspiratory area has an intrinsic excitability of autorhythmic neurons that sets the basic rhythm of respiration. The expiratory area neurons remain inactive during most quiet respiration but are probably activated during high levels of ventilation to cause contraction of muscles used in forced (labored) expiration (Figure 23.25). Copyright 2009, John Wiley & Sons, Inc.

72 Pneumotaxic Area The pneumotaxic area in the upper pons helps coordinate the transition between inspiration and expiration (Figure 23.25). The apneustic area sends impulses to the inspiratory area that activate it and prolong inspiration, inhibiting expiration. Copyright 2009, John Wiley & Sons, Inc.

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74 Regulation of the Respiratory Center Cortical influences allow conscious control of respiration that may be needed to avoid inhaling noxious gasses or water. Breath holding is limited by the overriding stimuli of increased [H + ] and [CO 2 ]. Copyright 2009, John Wiley & Sons, Inc.

75 Chemoreceptor Regulation of Respiration Central chemoreceptors (located in the medulla oblongata) and peripheral chemoreceptors (located in the walls of systemic arteries) monitor levels of CO 2 and O 2 and provide input to the respiratory center (Figure 23.26). Central chemoreceptors respond to change in H + concentration or P CO2, or both in cerebrospinal fluid. Peripheral chemoreceptors respond to changes in H +, P CO2, and P O2 in blood. A slight increase in P CO2 (and thus H + ), a condition called hypercapnia, stimulates central chemoreceptors (Figure 23.27). Copyright 2009, John Wiley & Sons, Inc.

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77 Central chemoreceptors respond to changes in H + concentration or P CO2, or both in cerebrospinal fluid. Peripheral chemoreceptors respond to changes in H +, P CO2, and P O2 in blood. A slight increase in P CO2 (and thus H + ), a condition called hypercapnia, stimulates central chemoreceptors (Figure 23.27). Copyright 2009, John Wiley & Sons, Inc.

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79 As a response to increased P CO2, increased H + and decreased P O2, the inspiratory area is activated and hyperventilation, rapid and deep breathing, occurs If arterial P CO2 is lower than 40 mm Hg, a condition called hypocapnia, the chemoreceptors are not stimulated and the inspiratory area sets its own pace until CO 2 accumulates and P CO2 rises to 40 mm Hg. Copyright 2009, John Wiley & Sons, Inc.

80 Severe deficiency of O 2 depresses activity of the central chemoreceptors and respiratory center. Hypoxia refers to oxygen deficiency at the tissue level and is classified in several ways Hypoxic hypoxia is caused by a low P O2 in arterial blood (high altitude, airway obstruction, fluid in lungs). Copyright 2009, John Wiley & Sons, Inc.

81 In anemic hypoxia, there is too little functioning hemoglobin in the blood (hemorrhage, anemia, carbon monoxide poisoning). Stagnant hypoxia results from the inability of blood to carry oxygen to tissues fast enough to sustain their needs (heart failure, circulatory shock). In histotoxic hypoxia, the blood delivers adequate oxygen to the tissues, but the tissues are unable to use it properly (cyanide poisoning). Copyright 2009, John Wiley & Sons, Inc.

82 Proprioceptors of joints and muscles activate the inspiratory center to increase ventilation prior to exercise induced oxygen need. The inflation (Hering-Breuer) reflex detects lung expansion with stretch receptors and limits it depending on ventilatory need and prevention of damage. Other influences include blood pressure, limbic system, temperature, pain, stretching the anal sphincter, and irritation to the respiratory mucosa Copyright 2009, John Wiley & Sons, Inc.

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84 DISORDERS: HOMEOSTATIC IMBALANCES Asthma is characterized by the following: spasms of smooth muscle in bronchial tubes that result in partial or complete closure of air passageways; inflammation; inflated alveoli; and excess mucus production. A common triggering factor is allergy, but other factors include emotional upset, aspirin, exercise, and breathing cold air or cigarette smoke. Chronic obstructive pulmonary disease (COPD) is a type of respiratory disorder characterized by chronic and recurrent obstruction of air flow, which increases airway resistance. The principal types of COPD are emphysema and chronic bronchitis. Copyright 2009, John Wiley & Sons, Inc.

85 DISORDERS: HOMEOSTATIC IMBALANCES Pneumonia is an acute infection of the alveoli. The most common cause in the pneumococcal bacteria but other microbes may be involved. Treatment involves antibiotics, bronchodilators, oxygen therapy, and chest physiotherapy. Tuberculosis (TB) is an inflammation of pleurae and lungs produced by the organism Mycobacterium tuberculosis. It is communicable and destroys lung tissue, leaving nonfunctional fibrous tissue behind. Copyright 2009, John Wiley & Sons, Inc.

86 DISORDERS: HOMEOSTATIC IMBALANCES Cystic fibrosis is an inherited disease of secretory epithelia that affects the respiratory passageways, pancreas, salivary glands, and sweat glands. Sudden Infant Death Syndrome is the sudden death of an apparently healthy infant, usually occurring during sleep. The cause is unknown but may be associated with hypoxia, possibly resulting from sleeping position. As such, it is recommended that infants sleep on their backs for the first six months. Copyright 2009, John Wiley & Sons, Inc.

87 End of Chapter 23 Copyright 2009 John Wiley & Sons, Inc. All rights reserved. Reproduction or translation of this work beyond that permitted in section 117 of the 1976 United States Copyright Act without express permission of the copyright owner is unlawful. Request for further information should be addressed to the Permission Department, John Wiley & Sons, Inc. The purchaser may make back-up copies for his/her own use only and not for distribution or resale. The Publishers assumes no responsibility for errors, omissions, or damages caused by the use of theses programs or from the use of the information herein.


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