Pulmonary Pathophysiology 1 Reduction of Pulmonary Function 1

Pulmonary Pathophysiology 1

Reduction of Pulmonary Function 1. Inadequate blood flow to the lungs – hypoperfusion 2. Inadequate air flow to the alveoli hypoventilation 2

Nosocomial infections • Factors that reduce airflow also compromise particle clearance and predispose to infection. • Restricted lung movement and ventilation may arise due to: – Positioning – Constricting bandages – Central nervous system depression – Coma • High rate of pneumonia in hospital patients due in large part to impaired ventilation and clearance. 3

Signs and Symptoms of Pulmonary Disease • Dyspnea – subjective sensation of uncomfortable breathing, feeling “short of breath” • Ranges from mild discomfort after exertion to extreme difficulty breathing at rest. • Usually caused by diffuse and extensive rather than focal pulmonary disease. 4

Dyspnea cont. • Due to: – Airway obstruction • Greater force needed to provide adequate ventilation • Wheezing sound due to air being forced through airways narrowed due to constriction or fluid accumulation – Decreased compliance of lung tissue 5

Signs of dyspnea: • Flaring nostrils • Use of accessory muscles in breathing • Retraction (pulling back) of intercostal spaces 6

Cough • Attempt to clear the lower respiratory passages by abrupt and forceful expulsion of air • Most common when fluid accumulates in lower airways 7

Cough may result from: • Inflammation of lung tissue • Increased secretion in response to mucosal irritation – Inhalation of irritants – Intrinsic source of mucosal disruption – such as tumor invasion of bronchial wall • Excessive blood hydrostatic pressure in pulmonary capillaries – Pulmonary edema – excess fluid passes into airways 8

• When cough can raise fluid into pharynx, the cough is described as a productive cough, and the fluid is sputum. – Production of bloody sputum is called hemoptysis • Usually involves only a small amount of blood loss • Not threatening, but can indicate a serious pulmonary disease – Tuberculosis, lung abscess, cancer, pulmonary infarction. 9

• If sputum is purulent, and infection of lung or airway is indicated. • Cough that does not produce sputum is called a dry, nonproductive or hacking cough. • Acute cough is one that resolves in 2 -3 weeks from onset of illness or treatment of underlying condition. – Us. caused by URT infections, allergic rhinitis, acute bronchitis, pneumonia, congestive heart failure, pulmonary embolus, or aspiration. 10

• A chronic cough is one that persists for more than 3 weeks. • In nonsmokers, almost always due to postnasal drainage syndrome, asthma, or gastroesophageal reflux disease • In smokers, chronic bronchitis is the most common cause, although lung cancer should be considered. 11

Cyanosis • When blood contains a large amount of unoxygenated hemoglobin, it has a dark redblue color which gives skin a characteristic bluish appearance. • Most cases arise as a result of peripheral vasoconstriction – result is reduced blood flow, which allows hemoglobin to give up more of its oxygen to tissues- peripheral cyanosis. • Best seen in nail beds • Due to cold environment, anxiety, etc. 12

• Central cyanosis can be due to : – Abnormalities of the respiratory membrane – Mismatch between air flow and blood flow – Expressed as a ratio of change in ventilation (V) to perfusion (Q) : V/Q ratio • Pulmonary thromboembolus - reduced blood flow • Airway obstruction – reduced ventilation • In persons with dark skin can be seen in the whites of the eyes and mucous membranes. 13

• Lack of cyanosis does not mean oxygenation is normal!! – In adults not evident until severe hypoxemia is present – Clinically observable when reduced hemoglobin levels reach 5 g/ dl. – Severe anemia and carbon monoxide poisoning give inadequate oxygenation of tissues without cyanosis – Individuals with polycythemia may have cyanosis when oxygenation is adequate. 14

Pain • Originates in pleurae, airways or chest wall • Inflammation of the parietal pleura causes sharp or stabbing pain when pleura stretches during inspiration – Usually localized to an area of the chest wall, where a pleural friction rub can be heard – Laughing or coughing makes pain worse – Common with pulmonary infarction due to embolism 15

• Inflammation of trachea or bronchi produce a central chest pain that is pronounced after coughing – Must be differentiated from cardiac pain • High blood pressure in the pulmonary circulation cause pain during exercise that often mistaken for cardiac pain (angina pectoris) 16

Clubbing • The selective bulbous enlargement of the end of a digit (finger or toe). • Usually painless • Commonly associated with diseases that cause decreased oxygenation – Lung cancer – Cystic fibrosis – Lung abscess – Congenital heart disease 17

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Respiratory Failure • The inability of the lungs to adequately oxygenate the blood and to clear it of carbon dioxide. • Can be acute: – ARDS or pulmonary embolism – Direct injury to the lungs, airways or chest wall – Indirect due to injury of another body system, such as the brain or spinal cord. 19

• Chronic respiratory failure – Due to progressive hypoventilation from airway obstruction or restrictive disease • Respiratory failure always presents a serious threat – Dysnpea always present, but may be difficult to detect a change in a chronic patient – Since nervous tissue it highly oxygen-dependent, see CNS signs and symptoms – Memory loss, visual impairment, drowsiness – Headache due to increased intracranial pressure due to cerebral vasodilation 20

Two principal patterns: 1. Hypoxic Respiratory Failure: Seen when p. O 2 falls to or below 60 mm Hg Typically seen in chronic bronchititis and emphysema, in lung consolidation due to bacterial infection, or in lung collapse, pulmonary hypertension, pulmonary embolism and ARDS. Initially, produces headache and nervous agitation, soon followed by a decline in mental activity, and confusion. 21

• With a progressive lowering of p. O 2, more widespread tissue damage and loss of consciousness can be expected. • In the event of brain stem hypoxia, CNS output to the heart and systemic arterioles can produce circulatory shock • Renal hypoxia can cause loss of homeostatic balance and accumulation of wastes to complicate the problem 22

Hypoxic-Hypercapnic Respiratory Failure • When arterial p. CO 2 (normally 40 mm Hg) exceeds 45 mm HG, condition is called hypercapnia • Most often, obstructive conditions produce this form of respiratory failure, as can hypoventilation from CNS problem, thoracic cage or neuromuscular abnormalities 23

• Attempts to compensate include increased heart rate and vasodilation, which produces warm, moist skin. • CNS effects produce muscular tremors, drowsiness and coma. • Hypercapnia also produces acidosis. 24

Pulmonary Disorders • Acute Respiratory Failure: – Acute Respiratory Distress Syndrome (or Adult Respiratory Distress Syndrome) • Rapid and severe onset of respiratory failure characterized by acute lung inflammation and diffuse injury to the respiratory membrane with noncardiogenic edema. 25

ARDS • Identified in last 25 years • Affects 200 -250 thousand people each year in U. S. • Mortality in persons < 60 is 40% (↓ 67%) • Those over 65 and immunocompromised still have mortality over 60 % • Most survivors have almost normal lung function 1 year after acute illness. 26

Pathophysiology of ARDS • All disorders causing ARDS acutely injure the respiratory membrane and produce severe pulmonary edema, shunting, and hypoxemia. – Shunting: blow flow is normal, but gas exchanged is decreased. V/Q ratio changes: the same effect as if blood were shunting or bypassing the lungs. 27

• Damage can occur directly: – Aspiration of acidic gastric contents – Inhalation of toxic gases • Or indirectly: – Chemical mediators from systemic disorders 28

Result is massive inflammatory response by lungs • Initial injury damages the pulmonary capillary epithelium, causing platelet aggregation and intravascular thrombus formation. • Platelets release substances that attract and activate neutrophils. • Damage also activates the complement cascade which also activates neutrophils and the inflammatory response. 29

• Role of neutrophils is central to the development of ARDS. • Neutrophils release inflammatory mediators: – Proteolytic enzymes – Toxic oxygen products – Prostaglandins and leukotrienes – Platelet activating factors • These damage the respiratory membrane and increase capillary permeability, allowing fluids, proteins, and blood cells to leak into alveoli → pulmonary edema and hemorrhage 30

• Reduces pulmonary ventilation and compliance • Neutrophils and macrophages release mediators that cause pulmonary vasoconstriction → pulmonary hypertension • Type II alveolar cells also damaged, see decreased surfactant production • Alveoli fill with fluid or collapse. • Lungs become less compliant, and ventilation decreases. 31

• After 24 – 48 hours hyaline membranes form • After about 7 days, fibrosis progressively obliterates the alveoli, respiratory bronchioles and interstitium • Result is acute respiratory failure 32

• In addition, chemical mediators often cause widespread inflammation, endothelial damage and increased capillary permeability throughout the body • This leads to systemic inflammatory response syndrome, which leads to multiple organ dysfunction syndrome (MODS) • Death may not be caused by ARDS alone, but by MODS 33

Clinical manifestations: • Symptoms develop progressively: – Hyperventilation→ repiratory alkalosis→ dyspnea and hypoxemia→ metabolic acidosis→ respiratory acidosis → further hypoxemia → hypotension, decreased cardiac output, death 34

Evaluation and Treatment • Diagnosis based on physical examination, blood gases and imaging • Treatment is based on early detection, supportive therapy and prevention of complications, esp. infection • Often requires mechanical ventilation 35

• Many studies underway for treatment: – Prophylactic immunotherapy – Antibodies against endotoxins – Inhibition of inflammatory mediators – Inhalation of nitric oxide to reduce pulmonary hypertension – Surfactant replacement 36

Postoperative Respiratory Failure • Same pathophysiology as ARDS, but usually not as severe. • Smokers are at risk, esp. if have pre-existing lung disease. • Also individuals with chronic renal failure, chronic hepatic disease, or infection • Thoracic and abdominal surgeries carry greatest risk • Individuals usually have a period of hypotension during surgery, and many have 37 sepsis.

Prevention includes: • Frequent turning • Deep breathing (spirometry) • Early ambulation to prevent atelectasis and accumulation of secretions • Humidification of air to loosen secretions • Supplemental oxygen and antibiotics as appropriate • Respiratory failure may require mechanical ventilation for a time. 38

Obstructive Pulmonary Disease • Characterized by airway obstruction that is worse with expiration. More force is required to expire a given volume of air, or emptying of lungs is slowed, or both. • The most common obstructive diseases are asthma, chronic bronchitis, and emphysema. • Many people have both chronic bronchitis and emphysema, and together these are often called chronic obstructive pulmonary disease - COPD 39

• Major symptom of obstructive pulmonary disease is dyspnea, and the unifying sign is wheezing. • Individuals have increased work of breathing, V/Q mismatching, and a decreased forced expiratory volume. 40

Asthma • More intermittent and acute than COPD, even though it can be chronic • Factor that sets it apart from COPD is its reversibility • Occurs at all ages, approx. half of all cases develop during childhood, and another 1/3 develop before age 40 • 5 % of Adults and 7 -10 % of children in U. S. have asthma 41

• Morbidity and mortality have risen in past 20 years in spite of increased numbers and availability of antiasthma medications. • Runs in families, so evidence genetics plays a role. • Environmental factors interact with inherited factors to increase the risk of asthma and attacks of bronchospasm • Childhood exposure to high levels of allergens, cigarette smoke and/or respiratory viruses increases chances of developing asthma. 42

• The major pathological feature of asthma is inflammation resulting in hyperresponsiveness of the airways. • Major events in an acute asthma attack are bronchiolar constriction, mucus hypersecretion, and inflammatory swelling. 43

• Exposure to allergens or irritants causes mast cells to release granules and trigger the release of many inflammatory mediators such as histamine, interleukins, immunoglobulins, prostaglandins, leukotrines and nitric oxide. • See vasodilation and increased capillary permeability • Chemotactic factors attract neutrophils, eosinophils and lymphocytes to the area – bronchial infiltration 44

• Smooth muscle spasm in bronchioles due to Ig. E effect on autonomic neurons - ACh • Vascular congestion • Edema formation • Production of thick, tenacious mucus • Impaired mucociliary function • Thickening of airway walls • Increased bronchial responsiveness • Untreated, this can lead to airway damage that is irrevesible. 45

• Obstruction increases resistance to air flow and decreases flow rates • Impaired expiration causes hyperinflation of alveoli distal to obstruction, and increases the work of breathing 46

Clinical manifestions • During remission individual is asymptomatic and pulmonary function tests are normal • Dyspnea • Often severe cough • Wheezing exhalation • Attacks usually of one to two hours duration, but may be severe and continue for days or even weeks. 47

• If bronchospam is not reversed by usual measures, the individual is considered to have severe bronchospasm or status asthmaticus • If continues can be life threatening. 48

Management • Avoid triggers (allergens and irritants) • Patient education • Acute attacks treated with corticosteroids and inhaled beta-agonists • Chronic management based on severity of asthma and includes regular use of inhaled antiinflammatory medications – corticosteroids, chromolyn sodium or leukotriene inhibitors. • Inhaled bronchodilators *** • Immunotherapy – allergy shots, etc. 49

• Bronchoconstriction may be a normal means of restricting airflow and intake of irritants and allergens. Their long term use may actually increase exposure to these factors and cause more pronounced and chronic symptoms. • Antiinflammatory agents have better long term effects. 50

COPD • Pathological changes that cause reduced expiratory air flow • Does not change markedly over time • Does not show major reversibility in response to pharmacological agents • Progressive • Associated with abnormal inflammatory response of the lungs to noxious particles or gases. 51

• Fourth leading cause of death in U. S. • Increasing in incidence over the past 30 years • Primary cause is cigarette smoking • Both active and passive smoking have been implicated • Other risks are occupational exposures and air pollution • Genetic susceptibilities identified 52

Chronic Bronchitis • Hypersecretion of mucus and chronic productive cough for at least 3 months (usually winter) of the year for at least two consecutive years. • Incidence may be increased up to 20 times in persons who smoke and more in persons exposed to air pollution. 53

Pathophysiology • Inspired irritants result in inflammation of the airways with infiltration of neutrophils, macrophages, and lymphocytes into the bronchial wall. • Causes bronchial edema and increases size and number of mucus glands and goblet cells. • Mucus is thick and tenacious, and can’t be cleared because of impaired ciliary function. • Increases susceptibility to infection and injury 54

• Initially affects only larger bronchi, but eventually all airways involved. • Airways collapse in early expiration, blocked by mucus, and air is trapped in distal portion of the tract. • Leads to ventilation/perfusion mismatch • Hypoxemia occurs • Air trapping prevents respiratory muscles from functioning efficiently (barrel chest), and get hypoventilation and hypercapnia. 55

Treatment • Best treatment is PREVENTION because changes are not reversible. • Cessation of smoking halts progression of the disease • Bronchodilators, expectorants, and chest physical therapy are used as needed. • Acute attacks may require antibiotics, steroids and possibly mechanical ventilation. • Chronic oral steroids as a last resort. • Home oxygen therapy 56

Emphysema • Abnormal, permanent enlargement of the gas-exchange airways and destruction of the alveolar walls. • Obstruction results from changes in lung tissue rather than mucus production and inflammation. • Major mechanism is loss of elastic recoil 57

• Major cause is cigarette smoking • Other causes are air pollution and childhood respiratory infections • Primary emphysema linked to an inherited deficiency of the enzyme alpha 1 antitrypsin which inhibits action of many proteolytic enzymes which can affect lung tissue. • With this deficiency, smokers are even more susceptible. 58

Pathophysiology • Begins with the destruction of the alveolar septa, which eliminates portions of the capillary bed, and increases the volume of air in the alveolus. • Inhaled oxidants inhibit the activity of endogenous antiproteases, and stimulate inflammation with increased activity of proteases. 59

• See continued alveolar loss and loss of elastic recoil • Expiration becomes difficult • Hyperinflation of alveoli produce large air spaces (bullae) and air spaces adjacent to the pleura (Blebs) • These are not effective in gas exchange and result in hypoxemia • Air trapping causes hyperexpansion of the chest, which puts respiratory muscles at a mechanical disadvantage. 60

• This makes breathing so difficult that late in the disease individuals develop hypoventilation and hypercapnia. 61

Clinical manifestations • • • Dyspnea Barrel chest Minimal wheezing Prolonged expiration Hypoventilation and polycythemia late in the progression of the disease 62

Treatment • • Similar to chronic bronchitis Stop smoking Bronchodilating drugs Breathing retraining Relaxation exercises Antibiotics for acute infections Severe COPD may require inhaled or oral steroids, and home oxygen • Some can benefit from lung reduction surgery or lung transplant. 63