Respiratory System and Anemia

Structure of the Respiratory System

There are three steps in this process: (1) ventilation, the movement of air into and out of the lungs; (2) diffusion, the movement of gases between air spaces in the lungs and the bloodstream;(3) perfusion, the movement of blood into and out of the capillary beds of the lungs to body organs and tissues

Nasal passages, sinuses and nasopharynx.LarynxLungs

Respiratory System

Sources: Porths PathophysiologyPathophysiology, The Biologic Basis for Disease for Adult and ChildrenHandbook of PathophysiologyFundamentals of Nursing

Conducting AirwaysThe conducting airways consist of the nasal passages, mouth and pharynx, larynx, trachea, bronchi, and bronchioles.

Functions of the Respiratory SystemThe primary function of the respiratory system, which consists of the airways and lungs, is gas exchange.In addition to gas exchange, the lungs serve as a host defense by providing a barrier between the external environment and the inside of the body.Finally, the lung is also a metabolic organ that synthesizes and metabolizes different compounds.Nasopharyngeal AirwaysThe nose is the preferred route for the entrance of air into the respiratory tract during normal breathingThe oropharynx extends posteriorly from the soft palate to the epiglottis. The oropharynx is the only opening between the nose, mouth, and lungs. Both swallowed food on its way to the esophagus and air on its way to the larynx pass through it. Obstruction of the oropharynx leads to immediate cessation of ventilation. The oropharynx is the only opening betweenthe nose, mouth, and lungs.

LarynxThe larynx connects the oropharynx with the trachea. divided into two categories: those associated with speech and 2.those associated with protecting the lungs fromsubstances other than air.cavity of the larynx is divided into two pairs:vestibular folds protective functionvocal folds vibrations-glottis, the vocal fold elongation, a complex set of muscles responsible for opening and closing.-epiglottis, located above the larynxDuring swallowing, the larynx is pulled superiorly and the free edges of the epiglottis move downward to cover the larynx, thus routing liquids and foods into the esophagus.

cough reflexWhen confronted with substancesother than air, the laryngeal muscles contract and close offthe airway. At the same time, the cough reflex is initiated as a means of removing a foreign substance from the airwayTracheobronchial Tree The tracheobronchial tree, which consists of the trachea, bronchi, and bronchioles, can be viewed as a system of branching tubes flowing through the lobes of the lungs. There are approximately 23 levels of branching, beginning with the conducting airways and ending with the respiratory airways, where gas exchange takes place.The trachea, or windpipe, is a continuous tube that connects the larynx and the major bronchi of the lungsexpand anteriorly as swallowed food passes through it. The trachea extends to the superior border of the fifth thoracic vertebra, where it divides to form the right and left main or primary bronchi. Between the main bronchi is a keellike ridge, called the carina.

(A) Anterior view of respiratory structures, ncluding the lobes of the lung, the larynx, trachea, and the main bronchi on the left and the main pulmonary artery and vein on the right. (B) The carina is located at the bifurcation of the right and left mainstem bronchi.

Porths Pathophysiology

Lungs and the Respiratory AirwaysThe bronchioles terminate in gas-exchange airways, where oxygen (O2) enters the blood and carbon dioxide (CO2) is removed from it. The gas-exchange airways consist of respiratory bronchioles, alveolar ducts, and alveoliThe lungs are the functional structures of the respiratory system. In addition to their gas exchange function, they inactivate vasoactive substances such as bradykinin, they convert angiotensin I to angiotensin II, and they serve as a reservoir for blood storage.LobulesLobulesThe gas exchange function of the lung takes place in the lobules of the lungs, which are the smallest functional units of the lungs. A branch of a terminal bronchiole, an arteriole, the pulmonary capillaries, and a venule supply each lobuleIt is here where gas exchange takes place and enters in the bronchioles the alveolar ducts and sacs.AlveoliThe alveoli are the terminal air spaces of the respiratory tract and the actual sites of gas exchange between the air and the blood.Each alveolus is a small outpouching of respiratory bronchioles, alveolar ducts, and alveolar sacs.Alveoli has pores of Kohn which are small holes in the alveolar walls allowing the mixing of air.Alveoli are interconnectiong spaces that has no separate walls as compared to the bronchioles. Bronchioles doesnt mixed air.The alveolar epithelium is composed of two types of cells: type I and type II alveolar cells.The alveoli also contain brush cells and macrophages.

Type I and II alveolar cellsType IThe type I alveolar cells, also known as type I pneumocytes, are extremely thin squamous cells with a thin cytoplasm and flattened nucleus that occupy about 95% of the surface area of the alveoli. They are joined to one another and to other cells by occluding junctions. These junctions form an effective barrier between the air and the componentsof the alveolar wall. Type I alveolar cells are not capable of cell division.Type IIThe type II cells synthesize pulmonary surfactant, a substance that decreases the surface tension in the alveoli and allows for greater ease of lung inflation. They are also the progenitor cells for type I cells. After lung injury, they proliferate and restore both type I and type II alveolar cells. retain airway patency despite large changes in volume.

Surfactant is a complex material produced by type II alveolar cells and composed of multiple phospholipids and specifi c associated proteins. Th e physiologic function of surfactant is to enhance the anatomic stability of the lungs. Th e presence of surfactant covering the alveolar epithelial surface reduces surface tension, allowing expansion of alveoli with a transpulmonary distending pressure of less than 5 cm H 2 O.

Alveolar Macrophages The macrophages are present in both the connective tissue of the septum and in the air spaces of the alveolus. They are responsible for the removal of offending substances from the alveoli. In the air spaces, they scavenge the surface to remove inhaled particulate matter, such as dust and pollen

Schematic illustration of type I and type II alveolar cells and their relationship to the alveoli and pulmonary capillaries. Type I alveolar cells constitute most of the alveolar surface. Type II alveolar cells, which produce surfactant, are located at the corners between adjacent alveoli. Also shown are the endothelial cells, which line the pulmonary capillaries, and an alveolar macrophage.The Pulmonary Circulation. The right and left pulmonary veins and arteries and the branching capillariesare illustrated. Note the pulmonary artery carries venous blood, and the pulmonary vein carries arterial blood.

Pulmonary Vasculature and Lymphatic SupplyPulmonary and Bronchial Circulations, distributes blood to the conducting airways and the supporting structures of the lung

Lymphatic Circulation, Both of these systems have numerous interconnections, and both form networks that drain into the hilar lymph nodes at the base of each lung.

Innervationparasympathetic stimulation, through the vagus nerve, that is responsible for the slightly constricted smooth muscle tone in the normal resting lung.Stimulation of the parasympathetic nervous system leads to airway constriction and increased glandular secretionpreganglionic and postganglionic fibers contain excitatory (cholinergic) motor neurons that respond to acetylcholine.Stimulation of the sympathetic nervous system causes airway relaxation, blood vessel constriction, and inhibition of glandular secretionNeurotransmitters of the sympathetic nervous system include the catecholamines norepinephrine and epinephrine.The lungs are encased in a thin, transparent, double layered serous membrane called the pleura. A thin film of serous fluid separates the outer parietal and inner visceral pleural layers, allowing the two layers to glide over each other and yet hold together, allowing no separation between the lungs and the chest wallVentilationVentilationVentilation is the mechanical movement of gas or air into and out of the lungs. Ventilation often is misnamed respiration, which is actually the exchange of O2 and CO2 during cellular metabolism. Respiratory rate is actually the ventilatory rate, or the number of times gas is inspired and expired per minute.CO2, the gaseous form of carbonic acid (H2CO3), is a product of cellular metabolism. The lung eliminates about 10,000 milliequivalents (mEq) of carbonic acid per day in the form of CO2, which is produced at the rate of approximately 200 ml/ minute.Functional Components of the Respiratory System

Neurochemical Control of Ventilation

The respiratory center in the brainstem controls respiration by transmitting impulses to the respiratory muscles, causing them to contract and relax.The respiratory center is composed of several groups of neurons located in the brainstem: the dorsal respiratory group (DRG), the ventral respiratory group (VRG), the pneumotaxic centerapneustic center. Lung Receptors send impulses from the lungs to the dorsal respiratory group:Irritant ReceptorsStretch ReceptorsJ-receptorsChemoreceptorsChemoreceptors monitor pH, Paco2, and Pao2. Central chemoreceptors monitor arterial blood indirectly by sensing changes in the pH of cerebrospinal fluid (CSF).Mechanics of BreathingThe mechanical aspects of inspiration and expiration are known collectively as the mechanics of breathing and involve:(1) major and accessory muscles of inspiration and expiration.(2) elastic properties of the lungs and chest wall, (3) Resistance to airflow through the conducting airways

Elastic Properties of the Lung and Chest Wall

Elastic recoil is the tendency of the lungs to return to the resting state after inspiration. Normal elastic recoil permits passive expiration, eliminating the need for major muscles of expiration.Compliance is the measure of lung and chest wall distensibility. It represents the relative ease with which these structures can be stretched.Airway Resistance.-Bronchoconstriction-BronchodilationWork of Breathing, The work of breathing is determined by the muscular effort (and therefore oxygen and energy) required for ventilation.Measurement of Gas Pressure

Measurement of Gas PressureBarometric pressure (PB) (atmospheric pressure) is the pressure exerted by gas molecules in air at specific altitudes. At sea level, barometric pressure is 760 of mercury (mm Hg, or torr) or 14.7 pounds per square inch(PSI).A respiratory pressure of +15 mm Hg means that the pressure is 15 mm Hg above atmospheric pressure, and a respiratory pressure of 15 mm Hg is 15 mm Hg less than atmospheric pressure.

Gas TransportGas transport, the delivery of oxygen to the cells of the body and the removal of CO2, has four steps:1. Ventilation of the lungs2. Diffusion of oxygen from the alveoli into the capillary blood3. Perfusion of systemic capillaries with oxygenated blood4. Diffusion of oxygen from systemic capillaries into the cellsSteps in the transport of CO2 occur in reverse order:1. Diffusion of CO2 from the cells into the systemic capillaries2. Perfusion of the pulmonary capillary bed by venous blood3. Diffusion of CO2 into the alveoli4. Removal of CO2 from the lung by ventilation If any step in gas transport is impaired by a respiratory or cardiovascular disorder, gas exchange at the cellular level is compromised.Distribution of Ventilation and PerfusionEffective gas exchange depends on an approximately even distribution of gas (ventilation) and blood (perfusion) in all portions of the lungs.The heart pumps against gravity to perfuse the pulmonary circulation. As blood is pumped into the lung apexes of a sitting or standing individual, some blood pressure is dissipated in overcoming gravityGravity and the Alveolar Pressure

Partial Pressure of Respiratory Gases in Normal Respiration

The values of Po2, Pco2, and Pn2 fluctuate from breath to breath. -CO2, Carbon dioxide-O2, oxygen-Pco2-partial pressure of carbon dioxide-Ph2o, partial pressure of water; -Pn2, partial pressure of nitrogen-Po2, partial pressure of oxygen.Dead air space

Dead space refers to the air that must be moved with each breath but does not participate in gas exchange. The movement of air through dead space contributes to the work of breathing but not to gas exchange. There are two types of dead space:Anatomic dead space: that contained in the conducting airways. Alveolar dead space: that contained in the respiratory portion of the lungUnderstanding Oxygen and transportOxygen TransportOxygen is carried on 2 forms:1.Dissolved 2.Bound to hemoglobinDissolved Oxygen is the only form of that diffuses across cell members and and produces partial pressure (PO2) which in turn drives diffusion.The transport of O2 involvestransfer from the alveoli to the pulmonary capillaries in the lung.(2) hemoglobin binding and transport.(3) the dissociation from hemoglobin in the tissue capillaries.

Alveolar Capillary transfer

In the lung, O2 moves from the alveoli to the pulmonary capillaries as a dissolved gas. Its movement occurs along a concentration gradient. It moves from the alveoli, where the partial pressure of PO2 is about 100 mm Hg, to the venous end of the pulmonary capillaries with their lesser O2 concentration and lower PO2. The dissolved O2 moves rapidly between the alveoli and the pulmonary capillaries, such that the PO2 at the arterial end of the capillary is almost, if not exactly, the same as that in the alveoli.Hemoglobin Binding and TransportOxygen, which is relatively insoluble in plasma, relies on hemoglobin for transport in the blood. Once oxygen has diffused into the pulmonary capillary, it moves rapidly into the red blood cells and reversibly binds to hemoglobin to form HbO2. The hemoglobin molecule contains four heme units, each capable of attaching an oxygen molecule. Hemoglobin is 100% saturated when all four units are occupied and is usually about 97% saturated in the systemic arterial blood. The capacity of the blood to carry O2 is dependent both on hemoglobin levels and the ability of the lungs to oxygenate the hemoglobin.

Oxygen Dissociation in the Tissues

The dissociation or release of O2 from hemoglobin occurs in the tissue capillaries where the PO2 is less than that of the arterial blood. As oxygen dissociates from hemoglobin, it dissolves in the plasma and then moves into the tissues where the PO2 is less than that in the capillaries. The affinity of hemoglobin for O2 is influenced by the carbon dioxide (PCO2) content of the blood and its pH temperature and 2,3-diphosphoglycerate (2,3-DPG), a by-product of glycolysis in red blood cells. Under conditions of high metabolic demand, in which the PCO2 is increased and the pH is decreased, the binding affinity of hemoglobin is decreased. During decreased metabolic demand, when the PCO2 is decreased and the pH is increased, the affinity is increased.Oxygen and Carbon DioxideTransportArterial Blood Gas RangesParameterRange1. pH = acid or base7.357.452. PCO2 = partial pressure of carbon dioxide3545 mm Hg3. HCO3 = bicarbonate2226 mEq/L4. PO2 = partial pressure of oxygen80100 mm Hg34Oxygen transportSteep O2 released to HgbPlateau O2 loaded Hgb

OxyHemoglobin Dissociation Curve

Oxygen Transport / Pulmonary VentilationEffect of Anemia

SpirogramLung Capacities

AGING AND THE PULMONARY SYSTEMNormal alterations include: (1) loss of elastic recoil, (2)stiffening of the chest wall, (3) changes in gas exchange, and (4)increases in flow resistance

Alterations of Pulmonary FunctionSigns and Symptoms of Pulmonary DiseaseDyspnea is a subjective experience of breathing discomfort that is comprised of qualitatively distinct sensations that vary in intensity.Cough is a protective reflex that helps clear the airways by an explosive expiration. Inhaled particles, accumulated mucus, inflammation, or the presence of a foreign body initiates the cough reflex by stimulating irritant receptors in the airway.Abnormal Breathing Patterns-Kussmaul respirations are characterized by a slightly increased ventilatory rate, very large tidal volume, and no expiratory pause.-

Labored breathing occurs whenever there is an increased work of breathing, especially if the airways are obstructed, as in chronic obstructive pulmonary disease (COPD).Cheyne-Stokes respirations are characterized by alternating periods of deep and shallow breathing. Apnea lasting 15 to 60 seconds is followed by ventilations that increase in volume until a peak is reached, after which ventilation (tidal volume) decreases again to apnea.Hypoventilation is inadequate alveolar ventilation in relation to metabolic demandsHyperventilation is alveolar ventilation that exceeds metabolic demandsClubbingClubbing is the selective bulbous enlargement of the end (distal segment) of a digit (finger or toe) (Figure 35-1) whose severity can be graded from 1 to 5 based on the extent of nail bed hypertrophy and the amount of changes in the nails themselves. It is usually painless. Clubbing is commonly associated with diseases that interfere with oxygenation, such as bronchiectasis, cystic fibrosis, pulmonary fibrosis, lung abscess, and congenital heart disease.

Pain caused by pulmonary disorders originates in the pleurae airways, or chest wall.i.e., Infection and infllammation of the parietal pleura (Pleuritiis or pleurisy) Pericardial friction rub- Costochondritis - Caused by pressing on the sternum or ribs.Conditions Caused by Pulmonary Disease or InjuryHypercapnia, or increased CO2 concentration in the arterial blood (increased Paco2), is caused by hypoventilation of the alveoli.Causes:-depression of the respiratory center by drugsdiseases of the medulla, including infections of the central nervous system or traumaabnormalities of the spinal conducting pathways, as in spinal cord disruption or poliomyelitis;diseases of the neuromuscular junction or of the respiratory muscles themselves, as in myasthenia gravis or muscular dystrophy;thoracic cage abnormalities, as in chest injury or congenital deformity; large airway obstruction, as in tumors or sleep apnea increased work of breathing or physiologic dead space, as in emphysemaHypoxemia, or reduced oxygenation of arterial blood (reduced Pao2), is caused by respiratory alterations, whereas hypoxia, or reduced oxygenation of cells in tissues, may be caused by alterations of other systems as well.

Hypoxemia results from problems with one or more of themajor mechanisms of oxygenation:1. Oxygen delivery to the alveoli a. Oxygen content of the inspired air (Fio2)2. Ventilation of the alveoli3. Diffusion of oxygen from the alveoli into the blooda. Balance between alveolar ventilation and perfusion ( V/Q mismatch)b. Diffusion of oxygen across the alveolocapillary membrane4. Perfusion of pulmonary capillariesCAUSES OF HYPOXEMIAMECHANISMCOMMON CLINICAL CAUSESDecrease in inspiredoxygen (decreased Fio2)High altitudeLow oxygen content of gas mixtureEnclosed breathing spaces (suffocation)Hypoventilation of thealveoliLack of neurologic stimulation of the respiratorycenter (oversedation, drug overdose,neurologic damage)Defects in chest wall mechanics (neuromusculardisease, trauma, chest deformity, air trapping)Large airway obstruction (laryngospasm, foreignbody aspiration, neoplasm)Increased work of breathing (emphysema, severeasthma)Ventilation-perfusionmismatchAsthma, Chronic bronchitis ,PneumoniaAcute respiratory distress syndromeAtelectasisPulmonary embolismAlveolocapillarydiffusion abnormalityEdemaFibrosisEmphysemaDecreased pulmonarycapillary perfusionIntracardiac defectsIntrapulmonary arteriovenous malformationsO2 is dependent into two factorsThe amount of oxygen, measured by the fraction of air that is composed of O2, called FiO2.-Alveolar minute minute ventilation (tidal volume respiratory rate)

Diffusion of oxygen from the alveoli:-Balance between the air perfusing into the alveoli (V)-Amount of blood perfusing around the capillaries of the alveoli (Q)

alveolocapillary barrier inadequacy, if this is thickened that happens in edema(Tissue swelling) and fibrosis (formation of fibrous lesions).These factors could result in compensatory hyperventilation and resulting respiratory alkalosis(dec. PaO2 Inc. pH)

Ventilation-Perfusion Abnormalities. (Data from Glenny RW:Adv Physiol Educ 32[3]:192195, 2008.)

Acute Respiratory FailureRespiratory (lung) failure is defined as inadequate gas exchange, that is, hypoxemia, in which Pao2 is 50 mmHg, or hypercapnia, in which Paco2 is 50 mmHg with a pH of 7.25.If in hypercapneic the condition is usually of inadequate alveolar ventilation. And ventilatory support must be given: i.e., bag valve mask, intubation etc.Respiratory failure is a potential complication of major surgical procedures that involves the CNS, Thorax and upper abdomen.Common complications: atelectasis, pneumonia, pulmonary edema, and pulmonary emboli.Prevention includes frequent turning and position changes, deep breathing exercise, early ambulation these prevents atelectasis and accumulation of secretions, humudification.

Disorders of the Chest WallChest wall restriction-Obesity and kyphoscoliosis(lateral bending and rotation ofthe spinal column with distortion of the thoracic cage) are risk factors.Diagnosis of chestrestriction is made by pulmonary function testing (reduction in forced vital capacity [FVC]), arterial blood gas measurement (hypercapnia), and radiographs-Flail chest results from the fracture of several consecutive ribs in more than one place, or the fracture of the sternum and several consecutive ribs. These multiple fractures result in instability of a portion of the chest wall, causing paradoxical movement of the chest with breathing.Treatment is internal fixation by controlled mechanical ventilation until the chest wall has stabilized.FLAIL Chest

Flail chest. Normal respiration: A, inspiration; B, expiration. Paradoxical motion: C, inspiration, area of lung underlying unstable chest wall sucks in on inspiration; D, expiration, unstable area balloons out. Note movement of ediastinum toward opposite lung during inspiration.Pleural AbnormalitiesPneumothorax is the presence of air or gas in the pleural space caused by a rupture in the visceral pleura (which surrounds the lungs) or the parietal pleura and chest wall.As air separates the visceral and parietal pleurae, it destroys the negative pressure of the pleural space. This disrupts the state of equilibrium that normally exists between elastic recoil forces of the lung and chest wall.Primary (spontaneous) pneumothorax, which occurs unexpectedly in healthy individuals (usually men) between ages 20 and 40 years, is most often caused by the spontaneous rupture of blebs (blister-like formations) on the visceral pleura, although there may be underlying pleural disease with emphysema-like changes.Secondary (traumatic) pneumothorax can be caused by chest trauma, such as a rib fracture, stab or bullet wounds, or a surgical procedure that tears the pleuraIatrogenic pneumothorax is most commonly caused by transthoracic needle aspirationtension pneumothorax, Tension Pneumothorax. Air in the pleural space causes the lung to collapse around the hilus and may shift trachea and mediastinal contents (heart and great vessels) toward the other lung.

Pleural effusion is the presence of fluid in the pleural space. The source of the fluid is usually blood vessels or lymphatic vessels lying beneath either pleura, but occasionally an abscess or other lesion may drain into the pleural space.Empyema Empyema (infected pleural effusion) is the presence of pus in the pleural space. It is thought to develop when the pulmonary lymphatics become blocked, leading to an outpouring of contaminated lymphatic fluid into the pleural space.Commonly documented infectious microorganisms include Staphylococcus aureusEscherichia colianaerobic bacteriaKlebsiella pneumoniae.PULMONARY DISORDERSRestrictive Lung DisordersAspirationAspiration is the passage of fluid and solid particles into the lung. It tends to occur in individuals whose normal swallowing mechanism and cough reflex are impaired by a decreased level of consciousness or central nervous system abnormalities.

Predisposing Factors-altered level of consciousness caused by substance abuse, sedation, or anesthesia.-seizure disorders-cerebrovascular accident-neuromuscular disorders that cause dysphagia

Clinical manifestations of aspiration include:sudden onset of choking and intractable cough with or without vomitingFeverDyspnea WheezingAspiration of oral or pharyngeal secretions can lead to aspiration pneumonia, especially if the oral cavity is colonized with bacteria.Treatment of aspiration, pneumonia, or pneumonitis, Include:-supplemental oxygen and may require mechanical ventilation with positive end-expiratory pressure (PEEP).-Fluids are restricted to decrease blood volume and minimize pulmonary edema.-Corticosteroids may be administered during the first 72 hours after aspiration.-AntibioticsAtelectasisAtelectasis is the collapse of lung tissue. There are three types of atelectasis: compression, absorption, and surfactant impairment:1. Compression atelectasis is caused by the external pressure exerted on lung tissue, such as occurs with tumors, or by fluid or air in the pleural space.2. Absorption atelectasis results from gradual absorption of air from obstructed or hypoventilated alveoli or from inhalation of concentrated oxygen or anesthetic agents. 3. Surfactant impairment results from decreased production or inactivation of surfactant, which is necessary to reduce surface tension in the alveoli and thus prevent lung collapse during expiration.Clinical manifestations of atelectasis are similar to those of pulmonary infection: dyspnea, cough, fever, and leukocytosis.Prevention and treatment of postoperative atelectasis usually include deep breathing exercisesBronchiectasisBronchiectasis is persistent abnormal dilation of the bronchi. Itusually occurs in conjunction with other respiratory conditionsthat are associated with chronic bronchial inflammation, suchas obstruction of an airway with mucous plugs, atelectasis, aspirationof a foreign body, infection, cystic fibrosis, tuberculosis,congenital weakness of the bronchial wall, or impaired defensemechanisms.Pores of Kohn. A, Absorption atelectasis caused by lack of collateral ventilation through pores of Kohn. B, Restoration of collateral ventilation during deep breathing.

a. Types of bronchiectasis.B, Left posterior oblique projection of a left bronchogram showing cylindrical bronchiectasis affecting the entire lower lobe except for the superior segment. Few side branches fill. The basal airways are crowded together, indicating volume loss of the ower lobe, a common feature in bronchiectasis

TreatmentBronchiectasis is treated with sputum culture antibiotics, bronchodilators, anti-inflammatory drugs, chest physiotherapy, and supplemental oxygen. In selected individuals with localized areas of involvement, surgery may be indicated to remove the affected portion of the lung BronchiolitisBronchiolitis is diffuse inflammation of the small airways or bronchioles. It is most common in childrenbut can occur in otherwise healthy individuals in association with an upper or lower airway viral infection (e.g., respiratory syncytial virus [RSV]).Clinical manifestations include:rapid ventilatory ratemarked use of accessory muscleslow-grade fever;4. dry, nonproductiveCoughhyperinflated chest

Diagnosis is made by spirometry and bronchoscopy with biopsy

Bronchiolitis is treated with appropriate antibiotics, steroids, and chest physical therapy (humidified air, coughing and deep breathing, postural drainage).

Bronchiolitis obliteransBronchiolitis obliterans is a late-stage fibrotic process that occludes the airways and causes permanent scarring of the lungs. This process can occur in all causes of bronchiolitis Bronchiolitis obliterans can be further complicated by the development of pneumonia (calledbronchiolitis obliterans organizing pneumonia [BOOP]) in which the alveoli and bronchioles become filled with plugs of connective tissue.Pulmonary FibrosisPulmonary fibrosis is an excessive amount of fibrous or connective tissue in the lung. When no specific cause for the development of fibrosis is known, it is called idiopathic pulmonary fibrosis. The fibrotic process results from chronic inflammation, alveolar epithelialization, and myofibroblast proliferation. Fibrosis causes a marked loss of lung compliance. The lung becomes stiff and difficult to ventilate, and the diffusing capacity of the alveolocapillary membrane may decrease, causing hypoxemia.Diffuse pulmonary fibrosis has a poor prognosis. Specific Causes:include inhalation of harmful substancesinorganic dustsorganic dustsunderlyingautoimmune systemic disorders,

Idiopathic Pulmonary fibrosis. Idiopathic pulmonary fibrosis (IPF)The median survival is only 2 to 4 years after diagnosisChronic inflammation and fibroproliferation of the interstitial lung tissue occur around the alveoli with disruption of the alveolocapillary basement membrane.This causes decreased oxygen diffusion across the alveolocapillary membrane and hypoxemia. As the disease progresses decreased lung compliance leads to increased work of breathing, decreased tidal volume, and resultant hypoventilation with hypercapnia.

The primary symptom of IPF is: -increasing dyspnea on exertiondiagnosis is confirmed by pulmonary function testing (decreased FVC), high-resolution CT, and lung biopsy.Treatment with corticosteroids alone causes remission in approximately 50% of individualExposure to Toxic Gases. Inhalation of gaseous irritants can cause significant respiratory dysfunction. Commonly encountered toxic gases include ammonia, hydrogen chloride, sulfur dioxide, chlorine, phosgene, and nitrogen dioxide.Prolonged exposure to high concentrations of supplemental oxygen can result in a relatively rare iatrogenic condition known as oxygen toxicity. The basic underlying mechanism of injury is a severe inflammatory response mediated primarily by oxygen free radicals.PneumoconiosisPneumoconiosis represents any change in the lung caused by inhalation of inorganic dust particles, which usually occurs in the workplace. As in all cases of environmentally acquired lung disease, the individuals history of exposure is important in determining the diagnosisThe dusts of silica, asbestos, and coal are the most common causes of pneumoconiosisClinical manifestations with advancement of disease may include cough, sputum production, dyspnea, decreased lung volumes, and hypoxemia. In most cases, diagnosis is made by performing chest x-ray or CT and by obtaining careful occupational historyTreatment is usually palliative and focuses on preventing further exposure and improving working conditions.

Silicosisis a type of pneumoconiosis resulting from the inhalation of free silica (silicon dioxide) and silica-containing compounds as occurs in mining and industries involved with the extraction and processing of ores; preparation and use of sand; and manufacture of pipe, building, and roofing materials.clinical manifestations do appear, they include cough and dyspnea. although corticosteroids may produce some improvement in the early, more acute stages. Coal worker pneumoconiosis (coal miner lung, black lung) is caused by coal dust deposits in the lung. Although coal dust itself is relatively well tolerated by the lung, it is frequently inhaled as a mixture of coal, silica, and quartz, which is strongly inflammatory.Individuals usually are seen with a productive cough and wheezing

asbestosisAsbestos exposure affects not only factory workers but also individuals who live in areas of asbestos emission. Asbestos exposure can result in a type of pulmonary fibrosis called asbestosis, but can also cause lung cancer, mesothelioma (cancer of the pleura), or pleural plaques, especially in those also exposed to cigarette smokeHypersensitivity Pneumonitis.is an allergic, inflammatory disease of the lungs caused by inhalation of organic particles or fumes.Many allergens (antigens) can cause this disorder, including grains, silage, bird droppings or feathers, wood dust (particularly redwood and maple), cork dust, animal pelts, coffee beans, fish meal, mushroom compost, grain molds, mists from standing water, and fumes from paints and resins.initiated by alveolar macrophages and results in immunoglobulin G (IgG) antibody productionAllergic alveolitis can be acute, subacute, or chronic. Theacute form causes a fever, cough, dyspnea, and chills a few hoursafter exposure that resolve without treatment in 1 to 3 days.Chronic allergic alveolitis causes weight loss, fever, fatigue, and gradually progressive respiratory failure.Treatment consists of avoidance of the offending agent and corticosteroid administration.

Systemic Disorders and the LungsPulmonary EdemaPulmonary edema is excess water in the lung. The normal lung contains very little fluid. It is kept dry by lymphatic drainage and a balance among capillary hydrostatic pressure, capillary oncotic pressure, and capillary permeability.The most common cause of pulmonary edema is left-sided heart disease. filling pressures on the left side of the heart increase and cause a concomitant increase in pulmonary capillary hydrostatic pressure. When the hydrostatic pressure exceeds oncotic pressure, fluid moves into the interstitium, or interstitial space (the space within the alveolar septum between alveolus and capillary)

Another cause of pulmonary edema is capillary injury that increases capillary permeability.Pulmonary edema also can result from obstruction of thelymphatic system.Postobstructive pulmonary edema (POPE, or negative pressure pulmonary edema)

Acute Lung Injury/Acute Respiratory Distress SyndromeAcute lung injury (ALI)/acute respiratory distress syndrome (ARDS) represents a spectrum of acute lung inflammation and diffuse alveolocapillary injury.Common predisposing factors :genetic factorsSepsismultiple trauma PneumoniaBurnsAspirationcardiopulmonary bypass surgeryPancreatitisdrug overdoseSmoke or noxious gas inhalation11. Oxygentoxicity12. radiation therapy and DIC

PathophysiologyAll disorders that result in ARDS cause acute injury to the alveolocapillary membrane producing massive pulmonary inflammation, increased capillary permeability, severe pulmonary edema, shunting, V/Q mismatch, and hypoxemia. The alveolocapillary injury can occur directly, aspiration of highly acidic gastric contents or the inhalation of toxic gases; or indirectly, as from circulating inflammatory mediators released in response systemic disorders, such as sepsis and trauma Lung inflammation and injury damages the alveolar epithelium and the vascular endothelium. Because the pulmonary edema is not secondary to heart failure, ARDS is often referred to as noncardiogenic pulmonary edema. ARDS progresses through three overlapping phases characterized by histologic changes in the lung: exudative (inflammatory), proliferative, and fibrotic

Exudative (Inflammatory) Phase (Within 72 Hours)The initial lung injury damages the alveolocapillary membrane. Lung injury activates neutrophils, platelets, macrophages, lung epithelial and endothelial cells, and uncontrolled inflammation. The role of neutrophils is central to the development and progression of ARDS. Activated neutrophils release a battery of harmful inflammatory mediators, among them proteolytic enzymes, oxygen free radicals (superoxide radicals, hydrogen peroxide, hydroxyl radicals), arachidonic acid metabolites

Acute Respiratory Distress Syndrome (ARDS). Cross-sectionalview of alveoli in ARDS. (Modified from Des Jardins T, Burton GG: Clinicalmanifestations and assessment of respiratory disease, ed 3, St Louis, 1995, Mosby.

Fibrotic Phase (14 to 21 Days).

About 2 to 3 weeks after the initial injury, remodeling and fibrosis occur. The fibrosis progressively obliterates the alveoli, respiratory bronchioles, and interstitium, leading to a decrease in functional residual capacity (FRC) and continuing V/Q mismatch with severe right-to-left shunt. The result of this overwhelming inflammatory response by the lungs is acute respiratory failure.

CLINICAL MANIFESTATIONS. The clinical manifestations of ARDSare progressive as follows:Dyspnea and hypoxemia with poor response to oxygensupplementationHyperventilation and respiratory alkalosisDecreased tissue perfusion, metabolic acidosis, and organdysfunctionIncreased work of breathing, decreased tidal volume, andhypoventilationHypercapnia, respiratory acidosis, and worsening hypoxemiaDecreased cardiac output, hypotension, and deathEVALUATION AND TREATMENT:-early detection and management of contributing etiologies-supportive therapy to prevent progression of lung injury, and prevention of complications suchas pneumonia and stress ulcer. Traditional therapy includes:-mechanical ventilation with PEEP and high oxygen concentrations.-Alternative modalities of ventilation are being evaluated, including low-volume ventilation, noninvasive positive-pressure-ventilation- permissive hypercapnia-prone positioning-extracorporeal gas exchange- partial liquid ventilation

Obstructive Pulmonary DiseaseAsthma,chronic bronchitis, and emphysema.AsthmaAsthma is a chronic inflammatory disorder of the bronchial mucosa that causes bronchial hyperresponsiveness, constriction of the airways, and variable airflow obstruction that is reversible.59 Asthma occurs at all ages, with approximately half of all cases developing during childhood.Asthma is most commonly a familial disorder and more than 100 genes have been identified that may play a role in the susceptibility and pathogenesis of asthma, including those that influence the production of IL-4, IL-5, and IL-13; IgE; eosinophils; mast cells; adrenergic receptors; leukotrienes; nitric oxide; and transmembrane proteins in the endoplasmic reticulum.PathohysiologyMany cells and cellular elements contribute to the persistent inflammation of the bronchial mucosa and hyperresponsiveness of the airways, including macrophages (dendritic cells), T helper 2 (Th2) lymphocytes, B lymphocytes, mast cells, neutrophils, eosinophils, and basophils. There is both an immediate (early asthmatic response) and a late (delayed) response.

Early asthmatic responseCD4+ T cells Differentiation - IL-4, IL-5, IL-8, IL-13, IL-17, andIL-22. IL-4 stimulates B-cell activation This produces IgE.. IL-5 stimulates the activation, migration, and proliferation of eosinophils, which cause direct tissue injury and release of toxic neuropeptides that contribute to increased bronchial hyperresponsiveness fibroblast proliferation epithelial injury, and airway scarringIL-8 activates neutrophils that contribute to a more exaggerated inflammatory responseIL-13 impairs mucociliary clearance, enhances fibroblast secretion, and contributes to bronchoconstriction and airway remodelingIL-17 increases neutrophilic inflammationIL-22 stimulates airway epithelial cells, which playan important role in stimulating further innate and adaptiveimmune responses.IgE binds to receptors on the surface of mast cells. Once bound to antigen, the IgE causes the mast cells to degranulate, releasing a large number of inflammatory mediatorsTogether these mediators cause vasodilation, increased capillary permeability, mucosal edema, bronchial smooth muscle contraction (bronchospasm), and tenacious mucus secretion from mucosal goblet cells with narrowing of the airways and o bstruction to airflowThe late asthmatic response begins 4 to 8 hours after the early responseChemotactic recruitment of lymphocytes, eosinophils, and neutrophils during the acute response causes a latent release of inflammatory mediatorsEosinophil mediators cause direct tissue injury with fibroblast proliferation and airway scarring.toxic neuropeptides contribute to increased bronchial hyperresponsiveness.A decrease in the number or function of T regulatory (Treg) cells are associated with asthma. Untreated inflammation can lead to long-term airway damage that is irreversible, known as airway remodeling (subepithelial fibrosis, smooth muscle and mucous gland hypertrophy).Airway obstruction increases resistance to airflow and decreases flow rates, especially expiratory flow. Impaired expiration causes air trapping, hyperinflation distal to obstructions and increased work of breathing.Hyperventilation is triggered by lung receptors responding to increased lung volume and obstruction. The result is early hypoxemia without CO2 retention.Hypoxemia further increases hyperventilation through stimulation of the respiratory center, causing Paco2 to decrease and pH to increase (respiratory alkalosis)With progressive obstruction of expiratory airflow, air trapping becomes more severe and the lungs and thorax become hyperexpandedThis leads to a fall in tidal volume with increasing CO2 retention and respiratory acidosis. Respiratory acidosis signals respiratory failur

Pathophysiology of Asthma. Allergen or irritant exposure results in a cascade of inflammatory events leading to acute and chronic airway dysfunction. IgE, Immunoglobulin E; IL, Interleukin.

CLINICAL MANIFESTATIONS-experiences chest constriction-expiratory wheezing-dyspnea-nonproductive coughing, prolonged expiration-tachycardia-tachypnea-pulsus paradoxus -status asthmaticusEvaluation and Treatmentimmediate administration of oxygen and inhaled beta-agonist bronchodilatorsleukotriene antagonists can be considered. In more severe asthma, long-acting beta agonists can be used to control persistent bronchospasmlong-acting beta agonists (LABAs) (salmeterol and formoterol) are recommended to be used in onjunction with inhaled corticosteroids as step 3 therapy for persistent asthmaImmunotherapy has been shown to be an important tool in reducing asthma exacerbations and can now be given sublingually. Monoclonal antibodies to IgE (omalizumab) have been found to be helpful in selected individuals.

Chronic Obstructive Pulmonary DiseaseChronic obstructive pulmonary disease (COPD) is defined as a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients. Its pulmonary component is characterized by airflow limitation that is not fully reversible Its pulmonary component is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases.The clinical phenotypes of COPD are chronic bronchitis and emphysema An inherited mutation in the 1-antitrypsin gene results in the development of COPD (emphysema) at an early age, even in nonsmokers The pathologic changes of COPD occur in large central airways, small peripheral airways, and the lung parenchyma, the dominant features of chronic bronchitis and emphysema.

Risk factors for COPD include:tobacco smoke (cigarette, pipe, cigar, and environmental tobacco smoke)occupational dusts and chemicals (vapors, irritants, and fumes)indoor air pollution from biomass fuel used for cooking and heating (in poorly vented dwellings), outdoor air pollutionany factor that affects lung growth during gestation and childhood (low birth weight, respiratory tract infections).

Genetic susceptibilities have been identified, including polymorphisms of genes that code for tumor necrosis factor, surfactant, proteases, antiproteases, and risks for lung cancer.

Chronic BronchitisChronic bronchitis is defined as hypersecretion of mucus and chronic productive cough that continues for at least 3 months of the year (usually the winter months) for at least 2 consecutive years.PATHOPHYSIOLOGY.Inspired irritants result in airway inflammation with infiltration of neutrophils, macrophages, and lymphocytes into the bronchial wall. Tobacco smoke directly injures airway epithelial cells. Continual bronchial inflammation causes bronchial edema and increases the size and number of mucous glands and goblet cells in the airway epithelium. Thick, tenacious mucus is produced and cannot be cleared because of impaired ciliary function The lungs defense mechanisms are, therefore, compromised, increasing susceptibility to pulmonary infection, which contributes to airway injury Frequent infectious exacerbations are complicated by bronchospasm with dyspnea and productive cough.Initially chronic bronchitis affects only the larger bronchi, but eventually all airways are involved. The thick mucus and hypertrophied bronchial smooth muscle narrow the airways and lead to obstruction, particularly during expiration when the airways are constricted. Obstruction eventually leads to ventilation- perfusion mismatch with hypoxemia. The airways collapse early in expiration, trapping gas in the distal portions of the lung. Air trapping expands the thorax, putting the respiratory muscles at a mechanical disadvantage. This leads to decreased tidal volume, hypoventilation, and hypercapnia

Chronic Bronchitis. Inflammation and thickening of mucousmembrane with accumulation of mucus and pus leading to obstruction characterized by productive cough. (Modified from Des Jardins T, Burton GG: Clinical manifestations and assessment of respiratory disease, ed 3, St Louis, 1995, Mosby.)

Pathogenesis of Chronic Bronchitis and Emphysema (Chronic Obstructive Pulmonary Disease [COPD])CLINICAL MANIFESTATIONS:-decreased exercise tolerance-wheezing, and shortness of breath-Individuals usually have a productive cough (smokers cough)-of airway obstruction (decreased FEV1) is shown by spirometry-Marked hypoxemia leads to polycythemia (overproduction of erythrocytes) and cyanosis-If not reversed, hypoxemia leads to pulmonary hypertension and eventually results in cor pulmonale and can lead to severe disability or death.EVALUATION AND TREATMENT. Diagnosis is based on history of symptoms, physical examination, chest radiograph, pulmonary function tests, and blood gas analyses; these tests reflect the progressive nature of the disease. Prevention of chronic bronchitis is the best treatment because pathologic changes are not reversible. By the time an individual seeks medical care for symptoms, considerable airway damage is present. If the individual stops smoking, disease progression can be halted. Bronchodilators (long-acting inhaled anticholinergics or long-acting inhaled beta agonists for symptomatic persons with COPD and FEV1