Respiratory System Patho Notes PDF
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Dallas Baptist University
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These notes provide an overview of the respiratory system, covering its anatomy, functional components, and various diseases, including acute and chronic conditions. They discuss the neurochemical control of ventilation, mechanics of breathing, and gas transport, emphasizing the importance of understanding the respiratory system in relation to other body systems.
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1 Respiratory System I Damjanov—Chapter 8 Stevens/Lowe—Ch 11 Robbins—Ch 13 I. Introduction / Basics Anatomy—you need to review normal—a few facts to recall o Respiratory system is divi...
1 Respiratory System I Damjanov—Chapter 8 Stevens/Lowe—Ch 11 Robbins—Ch 13 I. Introduction / Basics Anatomy—you need to review normal—a few facts to recall o Respiratory system is divided into… ▪ Upper tract – nose/pharynx, larynx ▪ Middle tract –some books divide the respiratory tract into three divisions with the middle representing the trachea; many only use upper and lower divisions ▪ Lower tract – trachea, bronchi, lungs o Airways are divided into ▪ Conducting airways… Serve only as a tube through which air is conducted Naso-, oropharynx, larynx, trachea, segmental bronchi, and non-respiratory subsegmental bronchioles ▪ Respiratory airways… Serve as location for gas exchange Respiratory bronchioles, alveolar ducts and alveoli (alveolar units) o The alveolus and capillary walls compose the alveolarcapillary membrane (or alveolocapillary) where pulmonary gas exchange takes place Functional components of the respiratory system include… o Neurochemical Control of Ventilation ▪ Respiratory center, central and peripheral chemoreceptors ▪ Central nervous system responds to neurochemical stimulation of ventilation and sends signals to chest wall muscles o Mechanics of Breathing ▪ Major & accessory muscles of respiration, lung elasticity, airway resistance, alveolar surface tension, work of breathing ▪ Respiratory system responds to impulses, effecting respiratory mechanics and therefore, affects adequacy of ventilation o Gas Transport ▪ Distribution of ventilation and perfusion, oxygen transport, carbon dioxide transport ▪ Depends on variety of chemical and physical activities 2 o Control of Pulmonary Circulation ▪ Distribution of pulmonary blood flow ▪ Plays a role in the appropriate distribution of blood flow to alveolar units In general, diseases of the nose and throat are studied along with those of the ear -- ENT Most frequent diseases of the airways and lungs are infectious or inflammatory in nature Other diseases include o Those caused by exposure to environmental agents AND o Cancers II. Overview of Major Diseases of the Respiratory System A. Categories of Pathology Acute Respiratory Conditions Infectious Diseases Obstructive Airway Diseases Restrictive Airway Diseases Immune / Allergic Diseases Granulomatous Diseases Neoplastic Diseases Diseases of the Pleura Pediatric Respiratory Diseases B. Basics of Respiratory Pathology 1. The respiratory tract is an open system, maintaining continuous contact + with the external environment This is the major reason that infectious diseases are the most common pathology in the respiratory tract 2. Another frequent source of pathology is exposure to environmental air- + borne allergens Allergic rhinitis and asthma are extremely common and increasing in frequency and severity 3 3. Environmental pollutants, gases, and particulate matter may cause + pulmonary disease or exacerbate existing disease EX: second-hand smoke causes bronchitis, asthma, and carcinoma in individuals who DO NOT smoke, but who are exposed to cigarette smoke There are new questions about the role of second-hand smoke in coronary artery disease among a traditionally low-risk population 4. Environmental air-borne pollutants may also function as carcinogens + Certain cancers are more common in areas where air is heavily polluted with known carcinogens EX: near coal producing or coal burning areas Near oil refineries EPA standards and work has reduced much of this risk 5. Since the heart and lungs function as a unit, diseases of one system will + adversely affect the other system III. Acute Respiratory Conditions A. Respiratory failure is defined by the presence of a low oxygen level in the blood, while ventilatory failure implies elevated blood CO2 + Normal respiratory function controls blood gas levels within physiologic limits o Normal PaO2 = 80-100 mmHg o Normal PaCO2 = 35-45 mmHg Ventilation, Respiration, and Perfusion o Effective gas exchange depends on an approximately even distribution of gas (ventilation) and blood flow (perfusion) in the lungs o Ventilation technically refers to the mechanical movement of gases into and out of the lungs, specifically, the alveoli o Respiration technically refers to exchange of oxygen and carbon dioxide at the cellular level during cellular metabolism o Pulmonary perfusion is the amount of blood flow in the pulmonary capillary bed relative to its capacity o Clinically, in general… + ▪ Ventilation refers to the CO2 component of gas exchange Ventilatory failure, therefore, implies failure of CO2 elimination and rise of blood CO2—i.e., hypercarbia or hypercapnia 4 ▪ Respiration refers to the O2 component of gas exchange + Respiratory failure, therefore, implies failure of O2 intake and the lowering of blood O2—i.e., hypoxia or hypoxemia Respiratory failure—i.e., hypoxemia, then, is a PaO2 below 60 mmHg o Central cyanosis (i.e., lips, tongue) occurs when PaO2 is below 50 mmHg o Loss of consciousness occurs when PaO2 is below 30 mmHg Two types of respiratory failure (hypoxemia) occur: + o Type I ▪ PaO2 is low, but PaCO2 is normal ▪ PaCO2 is normal, because CO2 is 20 times more soluble in blood than O2 and more diffusible than O2 ▪ Diffusion of CO2 in the lung is so efficient that diffusion defects that cause hypoxemia, do not always cause hypercarbia o Type II ▪ PaO2 is low, but PaCO2 is elevated above 50 mmHg ▪ i.e., the diffusion defect is so large as to overcome the extra diffusibility of CO2 and cause a rise in PaCO2 Ventilation / Perfusion Mismatch + o Low V / Q --This is a mismatch of inadequate ventilation of well- perfused areas of the lung ▪ Inadequate ventilation can be due to… Obstruction of the airway leading to the alveoli OR Alveoli are collapsed or filled with fluid ▪ EX: asthmatic bronchoconstriction reduces ventilation pulmonary edema, pneumonia both fill alveoli ▪ When blood passes through portions of pulmonary capillary bed that receive no ventilation, right-to-left shunting of blood occurs… Leading to hypoxemia o High V / Q – This is a mismatch of well-ventilated , but poorly perfused areas of the lung ▪ Inadequate perfusion causes wasted ventilation ▪ EX: pulmonary embolus impairs blood flow to a segment of lung, but ventilation continues 5 B. Chronic respiratory failure has accompanying major effects on the cardiovascular system Pulmonary Hypertension + Vasoconstriction in the pulmonary bed occurs in response to hypoxemia If this occur chronically, the pulmonary arteries develop intimal proliferation and the lumina are occluded This increases the pulmonary artery pressure and creates back pressure on the right heart causing RVH failure and hypertrophy ➔ cor pulmonale Polycythemia + Hypoxemia stimulates the release of erythropoietin from the kidneys Erythropoietin then stimulates the production of RBC, increasing the hematocrit as a compensatory mechanism in hopes of carrying more oxygen This increased blood viscosity may predispose to thrombosis C. Clinical Picture of ventilatory / respiratory disturbances Normal ventilation and respiration are due to… o Activation of muscles of respiration o Expandability of the thorax and ability to retract o Surface tension of the alveoli maintaining partial expansion Dyspnea is… + o Difficult or labored breathing o This may be perceived by the patient as “shortness of breath” (SOB), tightness in the chest, air hunger Causes of Dyspnea Airway obstruction o Suffocation ▪ Obstruction by foreign bodies Such as due to food bolus lodging in pharynx or larynx Or inedible material, small objects in children ▪ Intentional, i.e., homicide o Drowning ▪ Wet drowning – water is aspirated, fills lungs Fresh water – lakes, pools Sea water – more severe pulmonary edema due to hypertonic saline 6 ▪ Dry drowning – laryngospasm prevents water from entering, but also completely occludes airway, so no air can enter either Alveolar – septal lesions o Emphysema or fibrosis impair breathing and cause dyspnea o Atelectasis – we will discuss further Central nervous system dysfunction o Imbalances of the neurochemical receptors that regulate breathing o Due to CNS pathology in the control centers (brainstem, pressure) Retraction means… + o A “drawing back” o Related to breathing, this means a drawing back or pulling in-between the ribs, suprasternal or substernal areas due to excessive use of the accessory muscles o These exaggerated breathing motions indicate difficulty with breathing Tachypnea is… + o Rapid breathing, while Bradypnea is … + o Slow breathing D. Collapse of the lung is called ‘atelectasis’ Incomplete expansion or actual collapse of the alveolar units is called atelectasis Two forms occur o Macroatelectasis or Focal ▪ A segment of lung is collapsed ▪ EX: mucus plug causes distal airway collapse o Microatelectasis ▪ Diffuse distribution of collapsed alveoli due to hypoventilation ▪ EX: drowsiness following sedation or anesthesia CNS injury with depression / lethargy Several conditions lead to atelectasis Obstruction of an airway leads to resorption of air distal to the obstruction Compression of the lung due to accumulation of air or fluid in the pleural space Scarring and contraction of lung tissue can cause collapse 7 Loss of normal surfactant from terminal air spaces leads to generalized failure of lung expansion o Developmental surfactant deficit o Acquired surfactant deficit---we will discuss later IV. Infectious Diseases of the Respiratory System A. Introduction Infections of the upper respiratory tract are frequent, but most are minor and self-limited o URI’s cause 75% of all diagnosed human infections o URI’s comprise 95% of all respiratory tract infections Lower tract infections are less common, but more significant o LRI’s are only 5% of all respiratory infections o Most common in immune suppressed populations ▪ Elderly, pediatric patients, chronic illnesses, immunosuppressed patients (meds or AIDS) B. Upper respiratory infections Etiology & Pathogenesis + o Most caused by viral agents ▪ Rhinovirus, respiratory syncytial virus, parainfluenza, influenza, adenovirus, ▪ Bacterial Strep Diphtheria o Seasonality ▪ Influenza – winter ▪ Rhinovirus – spring & fall o Since they are short-lived, few agents developed to treat these + infections o Focal changes in the respiratory mucosa may predispose it to secondary infection with a bacteria ▪ Otitis media ▪ Sinusitis o Infection is by air-borne transmission—droplets + 8 Pathology + o Non-specific signs of inflammation in the mucosa ▪ Edema, inflammatory cells, capillary congestion o Ulceration of the mucosa may occur o White exudates that on the mucosa usually indicate a bacterial infection ▪ Exudates usually form due to presence of PMN’s ▪ EX: strep pharyngitis OR diptheria Clinical Picture + o Features well known to all o Nasal congestion with watery discharge o Sneezing o Dry, irritated throat o Elevated temperature o Malaise o Ear, nose, or throat pain o Headache, stuffy feeling NOW LET’S LOOK AT INFECTIONS IN THE LOWER RESPIRATORY TRACT (LRI’s) B. Infection of bronchi and bronchioles is most commonly due to viruses Again, mostly viral, mostly self-limited However, even self-limited can be significant o EX: influenza causes a tracheobronchitis ▪ Causes necrosis of epithelial lining o Respiratory syncytial virus ▪ Causes bronchiolitis in young children o Scarring of airways can result Severe inflammation of the bronchioles may be seen with adenoviral and measles infections o Heals by fibrosis, obliterates bronchioles 9 C. Infective inflammation and consolidation of the lung is called + ‘pneumonia’ 5th leading cause of death in the US Two major presentations: o 1) Alveolar pneumonia ▪ Focal = limited to alveoli Typically occurs as secondary problem when fluid (pulmonary edema) is already present in alveoli This is called hypostatic pneumonia Can involve alveoli and adjacent bronchi Most commonly due to bacterial agents i.e., elderly with borderline heart function, post shock o 2) Interstitial pneumonia ▪ Involves mostly the alveolar septa ▪ Diffuse process, often bilateral ▪ Most commonly due to viral agents D. Bronchopneumonia occurs when organisms colonize bronchi and extend into alveoli Etiology & Pathogenesis o May be due to bacteria, viruses, fungi ▪ Bacteria Normal upper respiratory flora may cause disease if aspirated into lower respiratory tract GI flora may infect lungs If bacteria become blood-borne If stomach acid lowered, enteric bacteria can ascend colonize and be aspirated into trachea Air-borne transmission from infected individuals ▪ Viruses Primary infection – communicable disease Reactivation of latent virus in immunosupppressed patients o Primary infection centers in bronchi, then spreads to adjacent alveoli o Alveoli then fill with inflammatory exudates and areas consolidate ▪ Inititally involves lobules, then whole lobes 10 o Most common in infancy and old age ▪ Predisposed by debility and immobility o Being immobile causes retention of secretions ▪ These gravitate to dependent lung areas ▪ Become infected ▪ :-, most common site for bronchopneumonia is lower lobes o Two groups ▪ Primary or community-acquired Usually due to gram-positive bacteria Strep, Hemophilus influenza, staph Remember, H. influenza is a bacteria, not the same pathogen as influenza virus ▪ Secondary or hospital acquired (nosocomial) Occurs after two days of hospitalization These are usually due to gram-negative bacteria Klebsiella, E. coli, Pseudomonas Pathology o Acute inflammation of bronchi and alveoli with presence of pus o Pleura may be involved, causing pleuritis & pleurisy (inflammation & pain of pleura) o Following treatment… ▪ Recovery usually involves focal organization of exudates and subsequent fibrosis Clinical Picture ICB o Constitutional signs + ▪ High fever, sometimes abrupt ▪ Chills ▪ Severe weakness o Focal signs + ▪ Focal chest pain ▪ Productive cough o Airway obstruction due to inflammatory exudates and airway + edema ▪ Dyspnea ▪ Tachypnea o Inflammatory changes ▪ Tissue sloughing, bleeding results in… ▪ Mucopurulent, blood-tinged sputum or hemoptysis 11 o Physical Exam + ▪ Air hungry, distressed ▪ Frequent cough Early it is dry, as pneumonia progresses cough becomes productive ▪ Rales, rhonchi o Confirmatory studies + ▪ Chest x-ray Localizes infection Method to follow progress / regress ▪ Sputum culture Sometimes helpful—difficult to assess infectious agent from upper respiratory flora ▪ Blood studies Blood count – leukocytosis (high white blood cell count) Blood culture – if bacteremia occurs, may culture bacteria from blood Blood gas – ABG assesses pulmonary function and signifies if impaired oxygen uptake (hypoxemia) or blocked CO2 elimination (hypercarbia) is present Treatment + o Treatment of viral bronchopneumonias is symptomatic and supportive ▪ May require observation, IV fluids, oxygen o Treatment of bacterial bronchopneumonias also involves antibiotic therapy o If severe and the patient is debilitated (elderly) or immune incompetent (children), mechanical ventilation may be required Complications + o Rapid progression may occur in patients with… ▪ Virulent pathogen ▪ Debilitation OR ▪ Delay in treatment (antibiotics) o Pleuritis ▪ Pus accumulates in the pleural space ▪ May encapsulate forming empyemas or be evenly distributed as pyothorax ▪ Fibrosis may obliterate the pleural cavity, resulting in restriction of lung expansion 12 o Abscess ▪ Focal changes cause destruction of bronchial walls ▪ This can lead to… Dilatation of the bronchi (bronchiectasis) Bronchiectasis may also be due to thick mucus (cystic fibrosis), mass (foreign body or tumor), or idiopathic Poor clearing of pus/fluid from bronchiectatic areas, no matter the etiology of the bronchiectasis, may cause chronic infection which causes ongoing tissue destruction ▪ Destruction of bronchial walls may also create abscesses, ICB which may be… Single, focal OR Military – more than one location Abscess is a collection of pus bordered by an inflammatory wall—a pocket of pus ▪ Sometimes an enlarging abscess erode through a bronchus and create a fistulous connection to airway Spills pus into bronchus Can be copious (voluminous) amount o Chronic lung disease ▪ Necrosis of lung tissue (necrotizing pneumonia) may cause diffuse fibrosis – i.e., honeycomb lung o Septicemia ▪ Bacteremia (usually in more significant numbers than transient bacteremia) plus the toxins produced by bacteria induce clinical illness called sepsis or septicemia— ▪ Recall our discussion of mechanisms of septic shock E. Lobar pneumonia occurs when organisms widely colonize alveolar spaces in a focal area of lung Pattern of disease seen in adults o Usually those who are elderly, poor (homeless), alcoholics and those with poor social and medical care o Often caused by Pneumococcus & Klebsiella ▪ Strep pneumoniae causes 50% of all bacterial pneumonias Organisms gain entrance to distal alveoli, rather than colonizing bronchi o Rapid spread through alveoli and bronchioles 13 o Acute inflammatory exudates in alveoli o Whole lobe consolidates Clinical Picture o Usually severely ill o Associated bacteremia o Prompt treatment.. ▪ Recovery via resolution—normal structure and function o If advanced when presents or delay in appropriate treatment… ▪ Exudates organizes, leading to scarring and permanent lung damage with functional abnormalities Complications as we noted earlier for pneumonias in general F. Atypical pneumonia is characterized by inflammation in alveolar septa Etiology & Pathogenesis + o Unlike the airspace inflammation of lobar and bronchopneumonias, inflammation in atypical pneumonias is in alveolar septa o Organisms include… ▪ Viruses Most cases self-limited, but may cause severe or fatal pneumonia as well Always more severe or significant in immunocompromised patients May follow anti-rejection therapy for transplant patients Organisms Influenza Measles Varicella (chicken pox) Cytomegalovirus (CMV) ▪ Fungal infections Fungal infections generally seen in immunosuppressed patients OR in those exposed to particular agents seen in a specific geographic region Pneumocystis carinii Especially AIDS patients Candida Sometimes occurs when a patient has been treated for long periods with antibiotics 14 Seen in neonates, especially premies, as evidence of systemic candadiasis ▪ Chalmydia Seen more commonly in neonates ▪ Mycoplasma pneumoniae Also called “walking pneumonia” because patients can usually remain active, working, etc, but just feel poorly, run-down o These organisms cause diffuse lung involvement ▪ X-ray pattern is “reticular” in appearance due to the septal, not alveolar involvement Clinical Picture + o Low-grade fever o Slower onset o Dry cough often paroxysmal (sudden, episodic fits of coughing) o Dyspnea o Malaise o Unless neonate, no signs of septicemia o Normal or mild increase in WBC, usually lymphocyte predominance on differential count o Protracted course 4-8 weeks, if not treated o Sometimes accompanied by wheezing, especially Mycoplasma Unless specific organism indicates the contrary, treatment is with + erythromycin family of meds—more effective against Mycoplasma & Chlamydia P/Review V. Obstructive Airway Disease A. Introduction / Basics Terms o Chronic obstructive pulmonary disease (COPD) o Chronic limitation of air flow Airflow may be reduced due to… o 1) Increase in airway resistance ▪ Airways are narrowed by some process 15 ▪ Main diseases in this category are… Asthma Bronchitis (chronic) o 2) Outflow pressure is reduced ▪ I.e., elastic recoil of lungs is diminished ▪ Main disease in this category is… Emphysema ▪ Often, individual patients will have a mixture of disease processes, but usually one predominates clinically B. Asthma is due to the episodic narrowing of small airways—i.e., + reversible, reactive airway disease Asthma is single most common cause of dyspnea, cough, and wheezing Etiology & Pathogenesis o Affects 10% of children and 5% of adults o Obstruction of small airways by… ▪ Excess, thick mucus (mucus plugging) ▪ Bronchospasm o These elements fluctuate with time and are reversible, at least in part o Bronchospasm is related to low-grade chronic inflammation of the airways, triggers initiate acute exacerbation Triggers of bronchospasm o Allergens – dust, pollen o Infections, especially viral o Occupational/environmental exposure to allergens or particulate irritants, gases (ozone in smog, sulphur, etc) o Drug induced – aspirin o Exercise induced o Cold air induced Clinical Picture + o Most people have mild disease o Severe asthma ▪ May over time result in cor pulmonale ▪ Severe, acute bronchospasm which is poorly responsive to drug therapy, is called status asthmaticus o May lead to need for mechanical ventilation or even death 16 o Wheezing, dyspnea o +/- cyanosis o Anxious if PaO2 is low C. Chronic bronchitis causes increased airway resistance in larger airways + Definition o Functional pulmonary disorder in which a “cough productive of sputum on most days for 3 months of the year for at least two years” Etiology & Pathogenesis + o Smoking causes 90% of chronic bronchitis o Other causes include ▪ Environmental pollution ▪ Injury from prior infection of the lungs ▪ Cystic fibrosis o Airway changes demonstrate ▪ Thickening of bronchial and bronchiolar walls ▪ Cells of chronic inflammation (macrophages, lymphocytes) ▪ Squamous epithelial metaplasia into columnar ▪ Mucous gland hyperplasia D. Generalized emphysema has two main forms—pink puffers and blue bloaters Definition + o Emphysema is a permanent dilatation of any part of the respiratory portion of the airways – i.e., respiratory bronchiole, alveolar duct, alveolus; e.g. air spaces distal to terminal bronchiole o Tissue is destroyed, but without scarring o Practically, this means loss of Etiology + o Practically, this means ▪ Loss of elastic recoil in lungs as respiratory tissue is destroyed ▪ Diminished surface area available for gas exchange o Most common cause is smoking ▪ Acquired a1-antitrypsin o Is also seen in hereditary a1-antitrypsin deficiency 17 Pathogenesis o Parenchymal (tissue) destruction by secreted extracellular proteases because the normal defensive protease inhibitors are inactivated or absent o In cigarette induced emphysema, a series of changes occur in response to irritant o 1) Irritants cause accumulation of inflammatory cells in alveoli o 2) Proteolytic enzymes are released from inflammatory cells ▪ Alveolar walls destroyed o 3) Cigarette smoke also induces free radical formation, ▪ Further damaging alveolar walls ▪ Inactivates tissue anti-proteolytic enzymes, i.e., a1-antitrypsin, :- allows leukocyte proteolytic enzymes to proceed unopposed a1-antitrypsin naturally protects tissue from leukocyte related proteolytic enzyme destruction o 4) Leukocyte enzyme, elastase, destroys elastic tissue This mechanism is validated by the clinical and histological changes seen in hereditary a1-antitrypsin deficiency o i.e., a1-antitrypsin deficiency patients develop emphysema without cigarette smoking o This gives us insight into the mechanism of acquired emphysematous changes seen in smokers Pathology o Changes of emphysema can produce one of two patterns o Centrilobular ▪ Widened airspaces in center of lobule, mostly affects respiratory bronchiole o Panacinar (total, respiratory unit=resp. bronchiole, a. duct, alveolus) ▪ All airways distal to terminal bronchiole are affected Clinical Picture ICB o Two groups o “Pink puffers” – emphysema + ▪ Reduced oxygen uptake, but increase blood oxygen by rapid respiratory rate – compensatory tachypnea Type I respiratory failure ▪ Minimal sputum production ▪ Breathless on exertion ➔ become hypoxic ▪ Barrel-chested, hyperinflated chest x-ray 18 ▪ Air hungry, lean forward to facilitate / diminish work of breathing ▪ Cachectic (wasted) o “Blue bloaters” – chronic bronchitis + ▪ Peribronchial fibrosis causes adjacent vascular changes Pulmonary hypertension develops Right heart strain ➔ cor pulmonale Peripheral edema, large abdomen (bloated) All of these worsen hypoxia ▪ Pronounced hypoxia, worsened by coughing or exertion Clinically cyanotic ▪ Marked sputum production, dyspnea ▪ Chest x-ray -- cardiomegaly and reticular pattern P/Review ll Fine’