Pathophysiology of the Respiratory System (Isra University 2022-2023) PDF

Pathophysiology Faculty of Pharmacy Isra University 2022-2023 Diseases of the Respiratory system MSc. Haneen almuhaisen PharmD, BCPS The lungs are a pair of spongy, air-filled organs located on either side of the chest (thorax). The trachea (wi...

Pathophysiology Faculty of Pharmacy Isra University 2022-2023 Diseases of the Respiratory system MSc. Haneen almuhaisen PharmD, BCPS The lungs are a pair of spongy, air-filled organs located on either side of the chest (thorax). The trachea (windpipe) conducts inhaled air into the lungs through its tubular branches, called bronchi. The bronchi then divide into smaller and smaller branches (bronchioles), finally becoming microscopic. The bronchioles eventually end in clusters of microscopic air sacs called alveoli. In the alveoli, oxygen from the air is absorbed into the blood. Carbon dioxide a waste product of metabolism travels from the blood to the alveoli where it can be exhaled. Between the alveoli is a thin layer of cells called the interstitium, which contains blood vessels and cells that The lungs are covered by a thin tissue layer called the pleura. The same kind of thin tissue lines the inside of the chest cavity -- also called pleura. A thin layer of fluid acts as a lubricant allowing the lungs to slip smoothly as they expand and contract with each breath. Pleural fluid is a serous fluid produced by the serous membrane covering normal pleurae. Most fluid is produced by the parietal circulation ( intercostal arteries) via bulk flow and reabsorbed by the lymphatic system. Thus, pleural fluid is produced and reabsorbed continuously. In a normal 70 kg human, a few milliliters of pleural fluid is always present within the intrapleural space. Larger quantities of fluid can accumulate in In humans, there is no anatomical connection between the left and right pleural cavities. Therefore, in cases the other lung will still function ,pneumothorax of or tension pneumothorax normally unless there is a simultaneous bilateral pneumothorax, which may collapse the contralateral parenchyma, blood vessels.and bronchi The visceral pleura receives its blood supply from the bronchial circulation, which also supplies the lungs. The parietal pleura receives its blood supply from the intercostal arteries, which also supply the overlying body wall. The costal and cervical portions and the periphery of the diaphragmatic portion of the parietal pleurae are innervated by the intercostal nerves. The mediastinal and central portions of the diaphragmatic pleurae are innervated by the phrenic nerves. The visceral pleurae covering the lung itself receive their innervation from the autonomic nervous system and have no sensory innervation. Only the parietal pleurae are sensitive to pain. Respiratory structures such as the airways, alveoli and pleural membranes may all be affected by various disease processes. These respiratory diseases include infections such as pneumonia and tuberculosis, as well as obstructive disorders such as asthma, bronchitis and emphysema that obstruct airflow into and out of the lungs. Other conditions such as pneumothorax, atelectasis, respiratory distress syndrome and cystic fibrosis are classified as restrictive disorders, as they limit normal expansion of the lungs. Pulmonary function may also be affected by exposure to inhaled particles or by the growth of  General Symptoms of Respiratory Disease Hypoxia — Decreased levels of oxygen in the tissues. Hypoxemia — Decreased levels of oxygen in arterial blood. Hypercapnia — Increased levels of CO2 in the blood. Hypocapnia — Decreased levels of CO2 in the blood. Dyspnea — Difficulty breathing. Tachypnea — Rapid rate of breathing. Cyanosis — Bluish discoloration of skin and mucous membranes due to poor oxygenation of the blood.  Respiratory infections Infections of the respiratory tract can occur in the upper or lower respiratory tract, or both. Organisms capable of infecting respiratory structures include bacteria, viruses and fungi.  Influenza Influenza is a viral infection that can affect the upper or lower respiratory tract. Three distinct forms of influenza virus have been identified: A, B and C. Of these three variants, type A is the most common and causes the most  Epidemiology of Influenza Infection Endemic — Outbreak of disease in a particular population that occurs in a regular, predictable manner Epidemic — Outbreak of disease affecting a large number of individuals in a population Pandemic — Outbreak of disease that is worldwide Symptoms of influenza infection: Headache Fever, chills Muscle aches Nasal discharge Unproductive cough Sore throat As a result, influenza infection may lead to co-infection of the respiratory passages with bacteria. It is also possible for the influenza virus to infect the tissues of the lung itself to cause a viral pneumonia.  Treatment of influenza: Bed rest, fluids, warmth Antiviral drugs Influenza vaccine — Provides protection against certain A and B influenza strains that are expected to be prevalent in a certain year. The vaccine must be updated and administered yearly to be effective but will not be effective against influenza strains not included in the vaccine.  Infections of the lower respiratory tract For an organism to reach the lower respiratory tract, the organism must be particularly virulent and present in very large number or the host defense barriers must be weakened. The presence of a respiratory pathogen such as the cold or influenza virus may also cause an inflammatory reaction.  Pneumonia Pneumonia is a condition that involves inflammation of lower lung structures such as the alveoli or interstitial spaces. It may be caused by bacteria, viruses or parasites such as pneumocystis carini. Pneumonia may be classified according to the pathogen that is responsible for the infection.  Classification of pneumonia: 1. Hospital acquired - Enteric Gram-negative organisms ( Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus) 2. Community acquired - Streptococcus pneumoniae, Haemophilus pneumoniae, Mycoplasma pneumoniae , Influenza A second classification scheme for pneumonia is based on the specific structures of the lung that the organisms infect and includes typical and Atypical pneumonia. Typical pneumonia Usually bacterial in origin. Organisms replicate in the spaces of the alveoli.  Manifestation s: Inflammation and fluid accumulation are seen in the alveoli. White cell infiltration and exudation that can been seen on chest radiographs. High fever, chest pain, are present. Purulent sputum is present. Some degree of hypoxemia is present. Atypical pneumonia Usually viral in origin. Organisms replicate in the spaces around the alveoli.  Manifestation s: Milder symptoms than typical pneumonia. Lack of white cell infiltration in alveoli. Lack of fluid accumulation in the alveoli. Not usually evident on radiographs. May make the patient susceptible to  Treatment of pneumonia: Antibiotics if bacterial in origin. The health-care provider should consider the possibility that antibiotic- resistant organisms are present. Oxygen therapy for hypoxemia. A vaccine for pneumococcal pneumonia is currently available and highly effective. This vaccine should be considered in high- risk individuals. Obstructive respiratory disorders Bronchial asthma Asthma is a condition characterized by reversible bronchospasm and chronic inflammation of airway passages. A key component of asthma appears to be airway ―hyperreactivity‖ in affected individuals. Exposure to certain ―triggers‖ can induce marked bronchospasm and airway inflammation in susceptible patients. The response of a patient with asthma to these  In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning.  These episodes are usually associated with widespread but variable airflow obstruction that is usually reversible either spontaneously or with treatment.   The inflammation also causes an associated increase in the existing bronchial hyperresponsiveness (BHR) to a variety of stimuli. BHR = the tendency of airways to narrow excessively in response to triggers that have little or no effect in normal individuals. Reversibility of airflow limitation may be incomplete in some patients with asthma Some Potential Asthma Triggers Allergens — Pollen, pet dander, fungi, dust mites Cold air Pollutants Cigarette smoke Strong emotions Exercise Respiratory tract Early phase of asthma: characterized by marked constriction of bronchial airways and bronchospasm that is accompanied by edema of the airways and the production of excess mucus. The bronchospasm that occurs may be the result of the increased release of certain inflammatory mediators such as histamine, prostaglandins and bradykinin.  Late phase of asthma: can occur several hours after the initial onset of symptoms and manifests mainly as an inflammatory response. The primary mediators of inflammation during the asthmatic response are the white blood cells. Eosinophils that stimulate mast cell degranulation and release substances that attract other white cells to the area.  Classifying Asthma Severity for Patients Not Currently Taking Long-Term Control Medications (≥12 years old) Persistent Intermitte Components Mild Moderate Severe nt Symptoms ≤2 >2 days/week Daily Throughout days/week but not daily the day Nighttime awakenings ≤twice/ 3-4 > Once per Often 7 month times/month week but not times/week I nightly m p SABA use for symptom ≤2 >2 days/week Daily Several ai control days/week but not > once times per r per day day m Interference with normal None Minor Some Extremely e activity limitation limitation limited nt Lung function (Normal FEV1 >80% FEV1 >80% FEV1 60-80% FEV1 59 y 75%; 60-80 y 70%) 5% Intermitten Persistent Ri t sk Exacerbations 0-2/year >2 in 1 year  Manifestations of asthma Coughing, wheezing Difficulty breathing Rapid, shallow breathing Increased respiratory rate Excess mucus production Barrel chest due to trapping of air in the lungs Significant anxiety  Complications of asthma: status asthmaticus: which is a life-threatening condition of prolonged bronchospasm that is often not responsive to drug therapy. Pneumothorax: is also a possible consequence as a result of lung pressure increases that can result from the extreme difficulty involved in expiration during a prolonged asthma attack. Marked hypoxemia and acidosis might also occur and can result in overall respiratory failure. 1 Treatment of asthma: 1. Avoidance of triggers, and allergens. Improved ventilation of the living spaces, use of air conditioning. 2- Bronchodilators (examples: albuterol, terbutaline) — Short acting β-adrenergic receptor activators. May be administered as needed in the form of a nebulizer solution using a metered dispenser or may be given subcutaneously. These drugs block 2 Treatment of cont. 3-asthma: Xanthine drugs (example: theophylline) — Cause bronchodilation but may also inhibit the late phase of asthma. These drugs are often used orally as second-line agents in combination with other asthma therapies such as steroids. Drug like theophylline can have significant central nervous system, cardiovascular and gastrointestinal side effects that limit their 3 Treatment of cont. asthma: drugs (corticosteroids) — 4- Anti-inflammatory Used orally or by inhalation to blunt the inflammatory response of asthma. The most significant unwanted effects occur with long-term oral use of corticosteroids and may include immunosuppression, increased susceptibility to infection, osteoporosis and effects on other hormones such as the glucocorticoids. 4 Treatment of cont. asthma: 5Cromolyn sodium — Anti-inflammatory agent that blocks both the early and late phase of asthma. The mechanism of action is unclear but may involve mast cell function or responsiveness to allergens. 6Leukotriene modifiers (example: Zafirlukast) — New class of agents that blocks the synthesis of the key inflammatory mediators, leukotrienes. Chronic bronchitis: is a chronic obstructive pulmonary disease that is most frequently associated with cigarette smoking (approximately 90% of cases). Chronic bronchitis may also be caused by prolonged to inhaled particulates such as coal dust or exposure other pollutants. The disease is characterized by excess mucus production in the lower respiratory tract. As a result, patients with chronic bronchitis often suffer repeated bouts of respiratory infection. Chronic bronchitis sufferers are often referred to as ―blue bloaters‖ as a result of the cyanosis and peripheral edema that is Manifestations of chronic bronchitis: Productive, chronic cough Production of purulent sputum Frequent respiratory infections Dyspnea Hypoxia, cyanosis Symptoms of cor pulmonale  Treatment of chronic bronchitis: 1.Cessation of smoking or exposure to irritants 2.Bronchodilators to open airway passages 3.Expectorants to loosen mucus 4. Anti-inflammatories to relieve airway inflammation and reduce mucus secretion 5.Prophylactic antibiotics for  Emphysema Emphysema is a respiratory disease that is characterized by destruction and permanent enlargement of terminal bronchioles and alveolar air sacs. Well over 95% of all patients with emphysema were chronic cigarette smokers. Cigarette smoke causes chronic inflammation of the alveolar airways, which results in infiltration by lymphocytes and macrophages.  Manifestations of emphysema: The major physiologic changes seen in emphysema are a loss of alveolar (lung) elasticity and a decrease in the overall surface area for gas exchange within the lungs. Comparison of Symptoms for Chronic Bronchitis and Emphysema Chronic bronchitis Emphysema Mild dyspnea Dyspnea that may be severe Productive Dry or no cough cough Cyanosis Cyanosis common rare Respiratory Infrequent infection infections common Onset usually after 50 Onset usually after 40 years of age years of age History of cigarette  Restrictive pulmonary disorders Pneumothorax Is the entry of air into the pleural cavity in which the lungs reside. In order for normal lung expansion to occur, there must be a negative pressure within the pleural cavity with respect to atmospheric pressure outside the pleural cavity. The inside of the pleural cavity is essentially a vacuum and when air enters the pleural cavity the negative pressure is lost and the lungs collapse. Because each lung sits in a separate pleural cavity, pneumothorax of Types of pneumothorax: 1. Open or communicating pneumothorax Usually involves a traumatic chest wound. Air enters the pleural cavity from the atmosphere. The lung collapses due to equilibration of pressure within the pleural cavity with atmospheric pressure. 2. Closed or spontaneous pneumothorax Occurs when air ―leaks‖ from the lungs into the pleural cavity. May be caused by lung cancer, rupture, pulmonary disease. The increased plural pressure prevents lung expansion during inspiration and the lung remains 3. Tension pneumothorax A condition in which there is a one-way movement of air into but not out of the pleural cavity. May involve a hole or wound to the pleural cavity that allows air To enter and the lung to collapse. Upon expiration, the hole or opening closes, which prevents the movement of air back out of the pleural cavity. A life-threatening condition because pressure in the pleural cavity continues to increase and may result in further lung compression or compression of large blood vessels in the thorax or the heart.  Open Pneumorthorax Expiratio Inspiration n Tension Pneumorthorax Expiratio Inspirati n on Pleural Effusion Accumulation of fluid in the pleural space Transudative vs. exudative effusion Empyema as potential sequelae to exudative effusion Manifestations of pneumothorax: Tachypnea, dyspnea Chest pain Possible compression of thoracic blood vessels and heart, especially with tension pneumothorax Treatment of pneumothorax: Removal of air from the pleural cavity with a needle or chest tube Repair of trauma and closure of opening into pleural cavity  Respiratory failure Is a condition that results when the lungs are no longer able to oxygenate the blood sufficiently or remove CO2 from it. It may occur as the end result of chronic respiratory diseases or it may be an acute event caused by factors such as pneumothorax or opioid  Causes of Respiratory Failure Acute Chronic Pneumothorax Emphysema Interstitial lung diseases Drug overdose (opioids, Cystic fibrosis sedatives) Pleural effusion — Spinal cord or brain injury Accumulation of fluids in the pleural cavity Congestive heart failure Neuromuscular disorders — Airway obstruction Muscular dystrophy, myasthenia Status asthmaticus gravis, amyotrophic lateral sclerosis Pulmonary emboli Inhalation of toxins or Diffuse noxious gases pneumonia Manifestations of respiratory failure: Hypoxemia Hypercapnia Ventilation–perfusion mismatch Cyanosis, possible but not always present Central nervous system symptoms — Slurred speech, confusion, impaired motor function Altered blood pH Initial tachycardia and increased cardiac output followed by bradycardia and decreased cardiac output Treatment of respiratory failure: Bronchodilators Correction of blood pH Oxygen therapy Mechanical ventilation