Pulmonary Pathophysiology

Reduction of Pulmonary Function

1. Inadequate blood flow to the lungs hypoperfusion 2. Inadequate air flow to the alveoli hypoventilation

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.

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

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

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

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 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.
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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 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.
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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 cant 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 1antitrypsin 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. 63