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Pulmonary Pathophysiology

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Reduction of Pulmonary Function

1. Inadequate blood flow to the lungs – hypoperfusion

2. Inadequate air flow to the alveoli - hypoventilation

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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.

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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.

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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

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Signs of dyspnea:

• Flaring nostrils• Use of accessory muscles in breathing• Retraction (pulling back) of intercostal

spaces

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Cough

• Attempt to clear the lower respiratory passages by abrupt and forceful expulsion of air

• Most common when fluid accumulates in lower airways

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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

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• 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.

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• 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.

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• 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.

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Cyanosis• When blood contains a large amount of

unoxygenated hemoglobin, it has a dark red-blue 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.

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• 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.

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• 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.

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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

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• 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 can cause pain during exercise that often mistaken for cardiac pain (angina pectoris)

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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

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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.

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• 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

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Two principal patterns:1. Hypoxic Respiratory Failure:

Seen when pO2 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.

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• With a progressive lowering of pO2, 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

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Hypoxic-Hypercapnic Respiratory Failure

• When arterial pCO2 (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

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• 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.

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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.

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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.

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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.

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• Damage can occur directly:– Aspiration of acidic gastric contents– Inhalation of toxic gases

• Or indirectly:– Chemical mediators from systemic

disorders

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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.

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• 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

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• 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.

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• 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

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• 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

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Clinical manifestations:• Symptoms develop progressively:

– Hyperventilation→ repiratory alkalosis→ dyspnea and hypoxemia→ metabolic acidosis→ respiratory acidosis → further hypoxemia → hypotension, decreased cardiac output, death

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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

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

hypertension– Surfactant replacement

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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 sepsis.

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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.

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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

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• 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.

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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

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• 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.

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• 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.

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• 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

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• Smooth muscle spasm in bronchioles due to IgE 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.

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• 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

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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.

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• 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.

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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.

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• 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.

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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.

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• 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

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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.

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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

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• 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.

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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

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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

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• 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.

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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.

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• 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.

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

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Clinical manifestations

• Dyspnea• Barrel chest • Minimal wheezing• Prolonged expiration• Hypoventilation and polycythemia late in

the progression of the disease

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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.