Pathophysiology of Respiratory System PDF Lecture 6, Summer 2024

Pathophysiology of Respiratory System Prepared by Lecture # 6 Prepared By Prof. Zeinab Al-Wahsh HU Summer 2024 1  Respiration may be defined as movement of O2...

Pathophysiology of Respiratory System Prepared by Lecture # 6 Prepared By Prof. Zeinab Al-Wahsh HU Summer 2024 1  Respiration may be defined as movement of O2 from the atmosphere to the cells and the return of CO2 from the cells to the environment The primary function of the pulmonary system is exchange of gases between the environment and blood Components of the Respiratory System  Ventilation  The movement of air between the atmosphere and the respiratory portion of the lungs  Perfusion  The flow of blood through the lungs “ movement of blood into and out of capillary of the lungs to the body organs”  Diffusion  The transfer of gases between the air-filled spaces in the lungs and the blood 2  Control of Ventilation  Primary control centers for breathing  Located in the medulla and pons  Chemoreceptors detect changes in carbon dioxide level, hydrogen ion, and oxygen levels in blood or cerebrospinal fluid (CSF).  Central chemoreceptors Located in the medulla  Peripheral chemoreceptors Located in the carotid bodies 3  Control of Ventilation (Cont.)  Hypercapnia  Carbon dioxide levels in the blood increase.  Carbon dioxide easily diffuses into CSF.  Lowers pH and stimulates respiratory center  Increasedrate and depth of respirations (hyperventilation)  Causes respiratory acidosis—nervous system depression  Hypoxemia  Marked decrease in oxygen  Chemoreceptors respond.  Important control mechanism in individuals with chronic lung disease—move to hypoxic drive 4  cyanosis are signs of central cyanosis are most easily observed on the face, lips, and earlobes, and under the tongue, it is an unreliable sign of respiratory insufficiency, it is generally a late sign of respiratory insufficiency and it may not be manifested in an anemic person with respiratory insufficiency. The conditions that commonly cause depression of the respiratory center are many such as barbiturate or narcotic overdose , severe hypercapnia and severe head injury 5  Structural Organization of the Respiratory System  Consists of the air passages and the lungs  Divided into two parts by function:  Conducting airways: through which air moves as it passes between the atmosphere and the lungs  Respiratory tissues of the lungs: where gas exchange takes place. Ventilation  Depends on the conducting airways:  Nasopharynx and oropharynx  Larynx  Tracheobronchial tree 6  Composition of the Alveolar Structures  Type I alveolar cells  Flat squamous epithelial cells across which gas exchange takes place  Type II alveolar cells  Produce surfactant, a lipoprotein substance that decreases the surface tension in the alveoli with small diameters and allows for greater ease of lung inflation (it is lower resistance to expansion and prevent collapse on expiration) Lung Circulation  Pulmonary circulation  Arises from the pulmonary artery  Provides for the gas exchange function of the lungs 7  The pulmonary veins carry oxygenated blood  Bronchial circulation Supplies the lungs and other lung structures with oxygen Distributesblood to the conducting airways Warms and humidifies incoming air  Thegas exchange airways are made up of the respiratory bronchioles, alveolar ducts, and terminal bronchioles. 8  Respiratory Pressures  Intrapulmonary pressure or alveolar pressure  Pressure inside the airways and alveoli of the lungs  Intrapleural pressure  Pressure in the pleural cavity  Intrathoracic pressure  Pressure in the thoracic cavity Note: the purpose of the pleural space is to prevent collapse of the lung : Airway Resistance  The volume of air that moves into and out of the air exchange portion of the lungs  Directly related to the pressure difference between the lungs and the atmosphere  Inversely related to the resistance the air encounters as it moves through the airways 9  Factors Affecting Alveolar-Capillary Gas Exchange  Surface area available for diffusion  Thickness of the alveolar-capacity membrane  Partial pressure of alveolar gases  Solubility and molecular weight of the gas Matching Ventilation and Perfusion  Required for exchange of gases between the air in the alveoli and the blood in pulmonary capillaries  Most of oxygen is transported by bounding to hemoglobin. O2 content = (1.34 mls X Hb)SaO2 10  Mechanisms of Carbon Dioxide Transport  Dissolved in carbon dioxide (10%)  Attached to hemoglobin (30%)  Bicarbonate (60%) ‘ the carbon dioxide is carried in the blood in the form of bicarbonate’  Acid-base balance is influenced by the amount of dissolved carbon dioxide and the bicarbonate level in the blood. Factors that help to maintain negative (subatmospheric) pressures within the pleural space include: elastic recoil of the lung , osmotic forces exerted across the pleural membranes , lymphatic removal of protein in the pleural space Control of Breathing  The lung is innervated by the parasympathetic nervous system via the vagus nerve. 11  Automatic regulation of ventilation  Controlled by : Chemoreceptors: monitor blood levels of oxygen, carbon dioxide and ventilation to meet the changing metabolic needs of the body. The most important stimulator of the respiratory center is the increase in partial pressure of CO2  Lung receptors: monitor breathing patterns and lung function  Voluntary regulation of ventilation  Integrates breathing with voluntary acts such as speaking, blowing, and singing 12  Common Respiratory Infections  Upper Respiratory Infection  Influenza  Pneumonia  Tuberculosis  Fungal infections of the lung  Hemoptysis may be caused by: 1. Active tuberculosis 2. Bronchogenic carcinoma 3. Pneumonia 4. Pulmonary infarction 13 Upper Respiratory Infection  Immune & Inflammatory Responses  Swelling & edema  Increase mucus production  Respiratory Defenses Against Infection  Cough reflex  Mucocilliary Blanket  Immune system  Cough Reflex  Expels foreign bodies & microorganisms  Removes accumulated mucus  Mucocilliary Blanket  Mucus producing cells 14  Cilia cells  Effects of Smoking on Respiratory Defenses  Alters effectiveness of some defense mechanisms  Stimulates mucus production  Paralyzes cilia  Thick mucus, trapped particles & microorganisms accumulate  Air movement  Risk of microbial growth 15  Factors Affecting the Signs and Symptoms of Respiratory Tract Infections  The function of the structure involved  The severity of the infectious process  The person’s age and general health status Pneumonia  Definition  Respiratory disorders involving inflammation of the lung structures (alveoli and bronchioles)  Causes  Infectious agents: such as bacteria and viruses  Noninfectious agents: such as gastric secretions aspirated into the lungs 16  Pneumonia  Damage to lung tissue  Successful colonization  Immune & inflammatory reaction  Toxins released by bacteria can directly damage cells Stages of Bacterial Pneumonia  Stage 1 (Hyperemia)  Initial inflammatory response  Mast cells release inflammatory mediators  Histamine & prostaglandins  Mast cell activates complement  Acts with histamine & prostaglandins 17   Blood flow &  capillary permeability  Swelling & edema  Fluid buildup   Rate of gas diffusion   Hemoglobin O2 saturation  Stage 2 (Red hepatization)  Alveoli fill with RBCs, exudates & fibrin  The stage of red hepatization in classical pneumococcal pneumonia is characterized by : a firm, heavy lung , engorged alveolar capillaries , and dry, granular, but rubbery cut surface  Stage 3 (Gray hepatization)  WBCs colonize infected lung  Fibrin deposits accumulate  Phagocytosis 18  Stage 4 (Resolution)  Inflammatory & immune responses  Cell debris, fibrin & bacteria digested  Macrophages dominate  Pneumonia caused by gram-negative organisms is associated with a poor prognosis even with antibiotic therapy.  viral pneumonia is usually mild and leaves no permanent lung damage  A chemical pneumonia caused by the irritation of gastric juice would probably be called Aspiration 19 pneumonia 20  Factors Facilitating Development of Pneumonia  Virulent organism  Impaired host defenses Risk factors for pneumonia include, immunosuppressed status , abdominal surgery , endotracheal intubation , and history of smoking Classifications of Pneumonias  According to source of infection  Community-acquired  Hospital-acquired  According to immune status of the host  Pneumonia in the immunocompromised person  The most common infecting agent for both community-acquired and nosocomial pneumonia is: Streptococcus pneumoniae 21  Types of Pneumothoraxes  Spontaneous pneumothorax Occurs when an air-filled blister on the lung surface ruptures  Traumatic pneumothorax Caused by penetrating or non- penetrating injuries  Tension pneumothorax Occurs when the intrapleural pressure exceeds atmospheric pressure 22  Atelectasis  Definition  The incomplete expansion of a lung or portion of a lung  Airless and collapsed alveoli  Causes  Airway obstruction  Lung compression such as occurs in pneumothorax or pleural effusion  Increased recoil of the lung due to loss of pulmonary surfactant.  Factors that interfere with the lung’s defense mechanisms against atelectasis include: excess mucus production , shallow breathing , pain on breathing , and inhalation of dry air into lungs 23  Types of Atelectasis  Primary  Present at birth  Secondary  Develops in the neonatal period or later in life  Absorptionatelectasis is most commonly caused by retained secretions or exudate 24  Chronic Obstructive Airway Disease Causes of Chronic Obstructive Airway Disease  Chronic bronchitis  Emphysema  Bronchiectasis Airway Responsiveness  Definition  The reaction of the airways to various stimuli  Increased airway responsiveness leads to narrowing of the airways  Movement of gases through the airways depends on:  The pressure moving the gases 25  The patency of the airways  Functions of Bronchial Smooth Muscle  The tone of the bronchial smooth muscles surrounding the airways determines airway radius  The presence or absence of airway secretions influence airway patency  Bronchial smooth muscle is innervated by the autonomic nervous system. Role of Inflammatory Mediators  Increase airway responsiveness by:  Producing bronchospasm  Increasing mucus secretion  Producing injury to the mucosal lining of the airways 26  Asthma Factors Involved in the Pathophysiology of Asthma  Genetic  Environmental  Viruses  Allergens  Occupational exposure Asthma produced bronchospasms are thought to be caused by imbalance of the parasympathetic and sympathetic nervous systems. It is called intrinsic asthma , it is less common and its etiology is unknown. 27 During an Asthma Episode Airways narrow, caused by:  tightening of the muscles that surround the airways  swelling of the inner lining, and/or  increase in mucus productio n 28  Factors Contributing to the Development of an Asthmatic Attack Allergens Respiratory tract infections Exercise Drugs and chemicals Hormonal changes and emotional upsets Airborne pollutants 29 30  Asthma  Progressive respiratory disease  Pathologic changes  Inflammation of respiratory tract  Spasm of bronchiolar smooth muscle  Mucosal edema  Viscous mucus production  The type of asthma is more likely to develop after the age of 40 is intrinsic asthma  Results in  Excess mucus production  Obstruction of airflow   Alveolar ventilation 31  Characteristics of Type B Chronic Bronchitis  Smoking history  Age of onset 30 – 40 years  Barrel chest may be present  Shortness of breath predominant early symptom  Sputum frequent early manifestation  Cyanosis  Hypercapnia and hypoxemia may be present  Frequent cor pulmonale and polycythemia  Thick mucus and hypertrophied smooth muscle may lead to closure of the airway particularly during expiration. 32  The interrelationships among the diseases comprising COPD is increased resistance to airflow Types of Chronic Obstructive Pulmonary Disease  Emphysema  Permanent enlargement of air spaces and destruction of lung tissue” alveolar walls” 33  Chronic obstructive bronchitis  Obstruction of small airways  Chronic bronchitis is characterized by abnormal enlargement of the alveoli and alveolar ducts  Chronic bronchitis is initially characterized by hyperplasia of goblet cells  Air pollution and cigarette smoking predispose to chronic bronchitis by slowing down ciliary phagocytic activity  Chronic Bronchitis  Inflammation of the bronchi  Edema & swelling  Ventilation, especially expiration is obstructed  Hypercapnia develops   Ventilation perfusion ratio  In the later stages of COPD a common 34 complication is Cor pulmonale  Emphysema  The pathologic changes occurring primarily in the respiratory bronchioles  Elasticity lost  Destruction of collagen fibers  Exact cause unknown  Smoke, 2nd-hand smoke  Chronic inflammation  Loss of elasticity causes  Airpassages & alveoli collapse   Ventilation  Walls between alveoli can be destroyed  Surface area of alveoli   Rate of diffusion 35 36 37  Pulmonary Embolism  Development  A blood-borne substance lodges in a branch of the pulmonary artery and obstructs the flow  Types  Thrombus: air accidentally injected during intravenous infusion  Fat: mobilized from the bone marrow after a fracture or from a traumatized fat depot  Amniotic fluid: enters the maternal circulation after rupture of the membranes at the time of delivery.  Blood  Pulmonary embolism may led to shock, pulmonary infarction, and pulmonary hypertension. 38 39  Risk factors include the following:  Prolonged bed rest or inactivity (including long trips in planes, cars, or trains),  Oral contraceptive use  Surgery (especially pelvic surgery)  Childbirth  Massive trauma  Burns  Cancer  Stroke  Heart attack  Heart surgery  Fractures of the hips or femur  Persons with certain clotting disorders may also have a higher risk. 40  Cor Pulmonale  Right heart failure resulting from primary lung disease and long-standing primary or secondary pulmonary hypertension  Involves hypertrophy and failure of the right ventricle  Pulmonary heart disease  Right ventricular dilatation.  The prerequisite condition for the development of cor pulmonale is pulmonary hypertension  A cause of cor pulmonale is COPD  Manifestations include the signs and symptoms of the primary lung disease and the signs of right-sided heart failure.  The treatment of cor pulmonale is aimed at correction of alveolar hypoxia 41 42  Acute Respiratory Syndrome (ARDS). ✓ Acute respiratory distress syndrome is a life- threatening condition. ✓ ARDS develops as inflammation and injury to the lung and causes a buildup of fluid in the air sacs. This fluid inhibits the passage of oxygen from the air into the bloodstream. While it shares some similarities with infant respiratory distress syndrome, its causes and treatments are different. ✓ The fluid buildup also makes the lungs heavy and stiff, and the lungs' ability to expand is severely decreased 43 44 45 46  Causes of ARDS Aspiration of gastric contents Majortrauma (with or without fat emboli) Sepsissecondary to pulmonary or non-pulmonary infections Hematologic disorders Reactions to drugs and toxins The common etiologic factor is deficiency of surfactant 47 48  ARDS  Resultof direct injury to capillaries of the lungs, alveoli or both. Causes include severe pulmonary infections, systemic sepsis, prolonged shock, burns, aspiration, and smoke inhalation  Extensivedestruction releases chemical mediators and enzymes when cells die 49  CapillaryDestruction Plasma & RBCs move into interstitial space Distance for O2 and CO2 to diffuse  Rate of gas exchange Fluid moves into alveoli Dilutes surfactant  Surface tension Atelectasis →  compliance →  ventilation → hypoxia 50  Respiratory Failure  Respiratory insufficiency is best defined as impaired ability to maintain normal blood gas values under conditions of increased demand such as exercise  Respiratory failure is defined as a clinical state in which Pao2 is 50 mm Hg or less with or without Paco2 of 50 mm Hg or higher under resting conditions.  The two types of respiratory failure are 1. Hypoxemia with hypercapnia and 2. Hypoxemia with normal or decreased Paco2 . Hypoxemic respiratory failure is numerically defined as Pao2 = 50 to 60 mm Hg, Paco2 = normal or below.  The following represent intrinsic lung disorders leading to respiratory failure Cystic fibrosis , COPD , Adult respiratory distress syndrome (ARDS) 51 Potential causes of Respiratory Failure 52  Causes of Respiratory Failure  Impaired ventilation  Upper airway obstruction  Weakness of paralysis of respiratory muscles (e.g.,. In myasthenia gravis and Guillain-Barré syndrome, the primary mechanism causing alveolar hypoventilation is  Chest wall injury  Chest wall deformities such as Kyphoscoliosis  Impaired matching of ventilation and perfusion  Impaired diffusion  Pulmonary edema  Respiratory distress syndrome 53  Pulmonary Edema  Pulmonary edema will occur if pulmonary hydrostatic pressure exceeds the osmotic pressure of the blood.  When serum, and later blood, from the pulmonary vessel fills the alveoli.  Pulmonary edema interferes with gas exchange because the diffusion pathway is disrupted by fluid.  The most common cause of pulmonary edema is: Left-sided heart failure 54 Pulmonary Edema (Cont.) 55 Copyright © 2019 by Elsevier Inc. All rights reserved.  Notes  The collection of serous fluid in the pleural space (cavity) is a condition known as pleural effusion  pleural effusion most typically is caused by congestive heart failure  When a pleural effusion contains pus, the condition is termed Empyema  Pneumothorax is best defined as Air in the pleural cavity A spontaneous pneumothorax may be caused by: pneumonia , neoplasms , emphysema , idiopathic factors a tension pneumothorax air collects within the pleural space because it flows in and cannot escape 56  Physiologically, a pneumothorax occurs because the normal subatmospheric pressure within the pleural cavity is disrupted Pulmonary fibrosis may be caused by: Tuberculosis , Pneumonia , Bronchiectasis , and Chronic pulmonary edema.  basic factors are related to the development of venous thrombosis and subsequent pulmonary embolism is hypercoagulability. Factors contributing to the development of venous thrombosis include: Injury to the vein wall , Prolonged bedrest , Congestive heart failure , and Hypercoagulability Factors that increase the risk of venous thrombosis include: Sickle cell anemia , Pregnancy , Long period of sitting , and Congestive heart failure. The single most important condition predisposing to venous thrombosis is congestive heart failure 57  The effect of pulmonary embolism is: to produce an area of lung that is ventilated but inadequately perfused.  All of the following represent conditions that may precipitate pulmonary embolism. Pregnancy , Varicose veins , Cancer.  Pulmonary hypertension may result from: Chronic respiratory acidosis and vasoconstriction , loss of pulmonary capillaries , Recurrent pulmonary emboli A local focus of necrosis in the lung is called Pulmonary infarction 58  When respiratory acidosis occurs, the kidneys compensate by Increasing excretion of H+ and Increasing HCO3 reabsorption the factors increase the incidence of bronchogenic carcinoma are Hazards of industrial pollutants , Air pollution , and Cigarette smoking 59