Chapter -5
RESPIRATORY SYSTEM
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Introduction to Respiratory System
The cells of the human body require a constant stream of oxygen to stay alive. The respiratory system provides oxygen to the body’s cells while removing carbon dioxide, a waste product that can be lethal if allowed to accumulate. There are 3 major parts of the respiratory system: the airway, the lungs, and the muscles of respiration. The airway, which includes the nose, mouth, pharynx, larynx, trachea, bronchi, and bronchioles, carries air between the lungs and the body’s exterior. The lungs act as the functional units of the respiratory system by passing oxygen into the body and carbon dioxide out of the body. Finally, the muscles of respiration, including the diaphragm and intercostal muscles, work together to act as a pump, pushing air into and out of the lungs during breathing.
Nose and Nasal Cavity:
The nose and nasal cavity form the main external opening for the respiratory system and are the first section of the body’s airway, the respiratory tract through which air moves. The nose is a structure of the face, made of cartilage, bone, muscle and skin that supports and protects the anterior portion of the nasal cavity. The nasal cavity is a hollow space within the nose and skull that is lined with hairs and mucus membrane. The function of the nasal cavity is to warm, moisturize, and filter air entering the body before it reaches the lungs. Hairs and mucus lining the nasal cavity help to trap dust, mold, pollen and other environmental contaminants before they can reach the inner portions of the body.
Mouth: The mouth is the secondary external opening for the respiratory tract. Mostly, normal breathing takes place through the nasal cavity, but the oral cavity can be used as supplement or replace the nasal cavity’s functions when needed. Because the pathway of air entering the body from the mouth is shorter than the pathway for air entering from the nose, the mouth does not warm and moisturize the air entering the lungs.
Pharynx: The pharynx, also known as the throat, is a muscular funnel that extends from the posterior end of the nasal cavity to the superior end of the esophagus and larynx. The pharynx is divided into 3 regions: the nasopharynx, oropharynx, and laryngopharynx. The nasopharynx is the superior region of the pharynx found in the posterior of the nasal cavity. Inhaled air from the nasal cavity passes into the nasopharynx and descends through the oropharynx, located in the posterior of the oral cavity. Air inhaled through the oral cavity enters the pharynx at the oropharynx. The inhaled air then descends into the laryngopharynx, where it is diverted into the opening of the larynx by the epiglottis.
Larynx: The larynx, also known as the voice box, is a short section of the airway that connects the laryngopharynx and the trachea. The larynx is located in the anterior portion of the neck, just inferior to the hyoid bone and superior to the trachea. Several cartilage structures make up the larynx and give it its structure. The epiglottis is one of the cartilage pieces of the larynx and serves as the cover of the larynx during swallowing. Inferior to the epiglottis is the thyroid cartilage, which is often referred to as the Adam’s apple as it is most commonly enlarged and visible in adult males. The thyroid holds open the anterior end of the larynx and protects the vocal folds. Inferior to the thyroid cartilage is the ring shaped cricoid cartilage which holds the larynx open and supports its posterior end.
Trachea: The trachea connects the larynx to the bronchi and allows air to pass through the neck and into the thorax. The rings of cartilage making up the trachea allow it to remain open to air at all times. The open end of the cartilage rings faces posteriorly toward the esophagus, allowing the esophagus to expand into the space occupied by the trachea to accommodate masses of food moving through the esophagus.
Bronchi and Bronchioles: At the inferior end of the trachea, the airway splits into left and right branches known as the primary bronchi. The left and right bronchi run into each lung before branching off into smaller secondary bronchi. The secondary bronchi carry air into the lobes of the lungs two in the left lung and three in the right lung. The secondary bronchi in turn split into many smaller tertiary bronchi within each lobe. The tertiary bronchi split into many smaller bronchioles that spread throughout the lungs. Each bronchiole further splits into many smaller branches less than a millimeter in diameter called terminal bronchioles. Finally, the millions of tiny terminal bronchioles conduct air to the alveoli of the lungs.
Lungs: The lungs are a pair of large, spongy organs found in the thorax, lateral to the heart and superior to the diaphragm. Each lung is surrounded by a pleural membrane that provides the lung with space to expand as well as a negative pressure space relative to the body’s exterior. The negative pressure allows the lungs to passively fill with air as they relax. The left and right lungs are slightly different in size and shape due to the heart pointing to the left side of the body. The left lung is therefore slightly smaller than the right lung.
Muscles of Respiration
Surrounding the lungs are sets of muscles that are able to cause air to be inhaled or exhaled from the lungs. The principal muscle of respiration in the human body is the diaphragm, a thin sheet of skeletal muscle that forms the floor of the thorax. When the diaphragm contracts, it moves inferiorly a few inches into the abdominal cavity, expanding the space within the thoracic cavity and pulling air into the lungs. Relaxation of the diaphragm allows air to flow back out the lungs during exhalation.
Physiology of the Respiratory System
Pulmonary Ventilation: Pulmonary ventilation is the process of moving air into and out of the lungs to facilitate gas exchange. The respiratory system uses both a negative pressure system and the contraction of muscles to achieve pulmonary ventilation. The negative pressure system of the respiratory system involves the establishment of a negative pressure gradient between the alveoli and the external atmosphere. The pleural membrane seals the lungs and maintains the lungs at a pressure slightly below that of the atmosphere when the lungs are at rest. This results in air following the pressure gradient and passively filling the lungs at rest. As the lungs fill with air, the pressure within the lungs rises until it matches the atmospheric pressure. At this point, more air can be inhaled by the contraction of the diaphragm and the external intercostal muscles, increasing the volume of the thorax and reducing the pressure of the lungs below that of the atmosphere again.
External Respiration: External respiration is the exchange of gases between the air filling the alveoli and the blood in the capillaries surrounding the walls of the alveoli. Air entering the lungs from the atmosphere has a higher partial pressure of oxygen and a lower partial pressure of carbon dioxide than does the blood in the capillaries. The difference in partial pressures causes the gases to diffuse passively along their pressure gradients from high to low pressure through the simple squamous epithelium lining of the alveoli. The net result of external respiration is the movement of oxygen from the air into the blood and the movement of carbon dioxide from the blood into the air. The oxygen can then be transported to the body’s tissues while carbon dioxide is released into the atmosphere during exhalation.
Internal Respiration: Internal respiration is the exchange of gases between the blood in capillaries and the tissues of the body. Capillary blood has a higher partial pressure of oxygen and a lower partial pressure of carbon dioxide than the tissues through which it passes. The difference in partial pressures leads to the diffusion of gases along their pressure gradients from high to low pressure through the endothelium lining of the capillaries. The net result of internal respiration is the diffusion of oxygen into the tissues and the diffusion of carbon dioxide into the blood.
Asthma
Asthma is a chronic inflammatory disorder of the airways associated with variable (usually reversible) airflow obstruction and enhanced bronchial hyper responsiveness to a variety of stimuli.
Causes
Asthma is characterized by excessive sensitivity of the lungs to various stimuli. There is increasing evidence to suggest genetics play an important role in the etiology of the disease.
Apparently, environmental factors interact with inherited factors to increase the risk of asthma. Environmental triggers range from viral infections and allergies, to irritating gases and particles in the air. Each person reacts differently to the factors that may trigger asthma.
Physiological factors that may trigger or increase asthma symptoms include:
Viral upper respiratory infections.
- Heavy exercise.
- Untreated conditions such as rhinitis, sinusitis, and gastroesophageal reflux (GERD).
- Drugs: NSAIDS such as aspirin. ibuprofen, acetaminophen, naproxen sodium and Kyotorphin; statin drugs (cholesterol reducing medications) and other anti-inflammatory drugs.
- Stress and strong emotions.
- Menstrual cycle/hormone changes.
- Pet fur or feathers, pet urine, saliva and dander.
- House-dust mites.
- Cockroach waste and decomposed body of dead animals.
- Mold and mildew spores. (Leaking plumbing, leaking roof etc.)
- Tobacco smoke and wood smoke.
- Perfumes, hairsprays, scented lotions, and cologne.
- Air fresheners, incense sticks and scented candles.
- Cleaning solutions, pesticides and paint fumes.
- Pollen from trees, grasses and weeds.
- Mold and mildew spores. (wet rotting leaves on the ground)
- Changes in humidity (high humidity).
- Exposure to cold air or hot humid air.
- Industrial emissions, vehicle or truck exhaust, and other air pollutants such as coal dust.
- Ozone: [O3] is a highly reactive form of oxygen that results from sunlight mixing with hydrocarbons (also called volatile organic compounds) and nitrogen oxides released in fuel combustion)
Food Allergy: Food allergies involve the body’s immune system reacting to proteins found in food. The body treats these proteins the same way as it would be a disease. Different people react to different types of food although some types have a greater chance of becoming a trigger. Between 2% to 10% of people are affected by food allergies, with a greater percentage occurring in children. Reactions can occur within a few minutes or over a period of several hours. Undiagnosed and untreated, severe attacks can be fatal.
Based upon causes, the asthma is divided into two types:
a. Intrinsic asthma: Usually develop beyond age 40 and have many causes other than exposure to allergens.
b. Extrinsic asthma: Most commonly develop in childhood and caused by exposure to definite allergens.
Classification of Asthma
1. Mild Intermittent Asthma:
It occurs in people with daytime symptoms that occur no more frequently than twice a week and night-time symptoms that occur no more than twice a month. These people are usually asymptomatic with normal Peak Expiratory Flow Rate between exacerbations. Exacerbations vary in intensity but are usually brief, lasting only hours to days. They do not take daily medications for long term control, only short for quick relief.
2. Mild Persistent Asthma:
It is characterized by daytime symptoms that occur more than twice a week but less than once a day with night-time symptoms more frequent than twice a month. These people are asymptomatic but have abnormal pulmonary function tests. Exacerbations begin to limit their activity. They usually take one medication on a daily basis for long term control. Using medications for quick relief on a daily basis indicates a need for additional long-term therapy.
3. Moderate Persistent Asthma:
It occurs in people who have daytime symptoms every day and night-time symptoms more than once a week. Exacerbations limit their activity and occur at least twice a week and may last for several days. These individuals take one or two long term control medications. Also using medications for quick relief on a daily basis indicates a need for additional long-term therapy.
4. Severe Persistent Asthma:
It is characterized by continual daytime symptoms and frequent night-time symptoms. They experience limited physical activity and exacerbations are frequent. These people often take two medications daily for long term control. Also using medications for quick relief on a daily basis indicates a need for additional long-term therapy.
Pathophysiology
The various common allergens are pollens, dust, mites, some food material and certain drugs which precipitate the asthmatic attack. The allergens upon exposure stimulate production of IgE which further bind to mast cells. Upon re-exposure to same allergen, the said allergens readily bind to IgE and result in degranulation of mast cell to release certain inflammatory mediators such as histamine, leukotrienes, prostaglandins etc.
In a response to above changes, WBCs migrate into the area to engulf the allergens. The phagocytic reaction causes release of basic proteins which are lytic agents for tissue and further promote inflammation.
With exposure to a trigger, a cascade of cellular responses cause:
- Increased production of thick tenacious mucus with impaired muscularly function.
- Mucosal swelling due to increased vascular permeability and vascular congestion.
- Bronchial smooth muscle contraction
- These changes cause bronchial hyper responsiveness and obstruction. Airway obstruction increases resistance to air flow and decreases flow rates, including expiratory flow. Impaired expiration causes hyperinflation distal to the obstruction and increases the work of breathing. These changes are not uniform throughout the lungs but regional. Continued air trapping causes increased intrapleural and alveolar gas pressures resulting in decreased perfusion of the alveoli, the result is hypoxia.
- Late Asthma Response occurs in cases of significant allergen exposure. The symptoms can recur 4 to 12 hours after the initial attack due to persistent cellular activation. It can be more severe than the initial attack.
- Untreated inflammation can cause long term airway damage that is irreversible (airway remodeling).
Symptoms
- Coughing, especially at night, during exercise or when laughing.
- Shortness of breath.
- Chest tightness.
- Wheezing (a whistling or squeaky sound in chest when breathe, especially while exhaling).
- Any asthma symptom is serious and can become deadly if left untreated.
- Symptoms may be triggered by exposure to an allergen (such as ragweed, pollen and pet hair or dust mites), irritants in the air (such as smoke, chemical fumes or strong odours) or extreme weather conditions.
Diagnosis
Exacerbations of asthma symptoms equates to an individual’s control of their asthma. To prevent long term complications of airway remodeling, early detection with an accurate diagnosis is needed to exclude other diseases and causes for difficulty breathing. For example, Chronic obstructive pulmonary disease, Congestive heart failure, Pulmonary embolisms or mechanical obstruction (from tumors).
Medical History and Physical Examination:
The first step in diagnosing asthma is to look for signs of asthma or allergies. These signs include wheezing (high pitched whistling sounds when breathe out) and a runny nose or swollen nasal passages, and allergic skin conditions (such as eczema).
Lung Function Tests:
Lung function tests are asthma tests that assess lung function. The two most common lung function tests used to diagnose asthma are spirometry and methacholine challenge tests.
Asthma and COPD (Chronic Obstructive Pulmonary Disease) cause problems by narrowing the bronchial tubes (or airways),
resulting in shortness of breath. Narrowed airways are difficult to breathe through. The greater the narrowing, the more difficult breathing becomes.
Spirometry:
It is a simple breathing test which is of great value for measuring exactly how much bronchial tubes have narrowed. Spirometer measures the amount (volume) and speed (flow) of air that can be inhaled and exhaled, giving an indication of how well lungs are performing. It is often used to determine the amount of airway obstruction. This enables to make decisions about lung condition and to plan the best treatment for asthma.
Methacholine Challenge Test:
This lung function test for asthma is more commonly used in adults than in children. It might be performed if symptoms and screening spirometry do not clearly or convincingly establish a diagnosis of asthma. Methacholine is an agent that, when inhaled, causes the airways to spasm (contract involuntarily) and narrow if asthma is present. A methacholine challenge test is a type of bronchoprovocation test, which measures lung function after exposure to factors that commonly trigger wheezing and other asthma symptoms.
Purpose of the Methacholine Challenge Test is:
- To identify bronchial hyper responsiveness in people who have normal results on standard pulmonary function tests.
- To diagnose mild asthma in some atypical cases, such as persistent cough
- To diagnose occupational (workplace) asthma caused by certain dusts or chemicals.
- To help determine the risk of developing asthma, evaluate asthma severity and assess response to asthma treatment.
- To evaluate the effectiveness of asthma medications and determine the risk for developing asthma in the future.
Exhaled Nitric Oxide Test:
It is a quick and easy way to measure inflammation (swelling) in the bronchial tubes of the lungs. During inflammation, higher than normal levels of nitric oxide (NO) are released from epithelial cells of the bronchial wall. The concentration of NO in exhaled breath, or fractional exhaled nitric oxide (FeNO), can help to identify airway inflammation, and thereby support a diagnosis of asthma when other objective evidence is lacking.
Allergy Tests:
Allergy skin tests are vital in finding out whether asthma is due to inhalant allergens. Drops of a number of allergen extracts are placed on the skin (usually the forearm) and the skin is pricked lightly through the drops. A positive reaction will cause some itching and a bump at the site within 10 minutes.
Prevention and Treatment
- Identify and avoid asthma triggers.
- Identify and treat attacks early and monitor breathing.
- Other measures include dust free house.
- Intake of selective type of food.
- Avoid exposure to extreme cold condition.
- Get vaccinated for influenza and pneumonia
Pharmacological Treatment:
Drug therapy depends on frequency and severity of attacks. The bronchodilators are often considered rescue inhalers, while the other medications are considered more prophylactic or therapeutic medications
1. Bronchodilators (Sympathomimetics): The mechanism of action for sympathomimetic bronchodilators is to bind the receptors in airway smooth muscle thus causing bronchodilation and increased ciliary beat frequency. e.g. Albuterol, Salbutamol and Terbutaline.
2. Anticholinergic agents: The effect of anticholinergic bronchodilators are bronchodilation through inhibition of bronchoconstriction secondary to blockade of the effects of acetylcholine. The mechanism of action for anticholinergic bronchodilators is non-selective antagonism of muscarinic receptors leads to down regulation of cGMP which results in bronchodilation. Additional acetylcholine is released in response, thus overcoming the effect in smooth muscle. e.g. Ipratropium, Aclidinium.
3. Corticosteroids: The effect of inhaled corticosteroids is reduced airway inflammation. Overall airway bronchial hyper-responsiveness decreases. Improved asthma control and increased sensitivity of β-receptors in smooth muscle. The mechanism of action for inhaled corticosteroids is to suppress granuloma formation, reduce arachidonic acid metabolism, up-regulate β-adrenergic receptors on leukocytes, and decrease synthesis of prostaglandins and leukotrienes.
4. Biologic Response Modifiers (Monoclonal Antibodies): The effect of Biologic Response Modifiers is decreased frequency of allergen induced asthma exacerbations. The mechanism of action for Biologic Response Modifiers is, when the monoclonal antibody binds to Ige, interferes with mast cell binding. This prevents mast cell degranulation and release of inflammatory mediators. Cytokine release seen in the late phase of an allergic reaction is also prevented through blocking the receptors on dendritic cells, epithelial cells, eosinophils, monocytes and platelets. E.g. Omalizumab.
5. Leukotriene Receptor Antagonists: The effect of leukotriene receptor antagonists is prevention of allergen induced bronchoconstriction. The mechanism of action for leukotriene receptor antagonists is antagonism of cysteinyl-leukotriene receptors, thus preventing histamine release. e.g. Montelukast and Zafirlukast
6. Mast Cell Stabilizers: The effect of mast cell stabilizers is prevention of bronchocon-striction and inflammation. The mechanism of action of mast cell stabilizers is to antagonize mast cell degranulation to prevent the release of histamine and other mediators of allergic reaction. Agents do not interfere with Ige. The anti-inflammatory mechanism is unknown. e.g. Cromolyn and Nedocromil
7. Methylxanthine Derivatives: The mechanism of action for methylxanthine derivatives is bronchodilation. The mechanisms of action include prostaglandin antagonism, stimulation of endogenous catecholamines, inhibition of calcium influx into smooth muscle (preventing muscle contraction), antagonism of adenosine receptors, and inhibition of release of mediators from leukocytes and mast cells. E.g., Theophylline.
Chronic Obstructive Airways Diseases
- Respiratory failure
- Bronchitis
- Emphysema
Respiratory failure is inadequate gas exchange by the respiratory system, with the result that levels of arterial oxygen, carbon dioxide or both cannot be maintained within their normal ranges. A drop in blood oxygenation is known as hypoxemia; a rise in arterial carbon dioxide levels is called hypercapnia. The normal reference values are: oxygen PaO2 more than 80 mmHg (11 kPa), and carbon dioxide PaCO2 lesser than 45 mmHg (6.0 kPa). It is classified into type I or type II which relates to the absence or presence of hypercapnia respectively.
2. Bronchitis
Bronchitis is an inflammation of the lining of the bronchial tubes, the airways that connect the trachea (windpipe) to the lungs. Bronchitis is more specifically when the lining of the bronchial tubes becomes inflamed or infected. People with bronchitis breathe less air and oxygen into their lungs; they also have heavy mucus or phlegm forming in their airways.
Bronchitis can be acute or chronic. An acute medical condition occurs quickly and can cause severe symptoms, but it lasts only a short time (no longer than a few weeks). Acute bronchitis is most often caused by viruses that can infect the respiratory tract and attack the bronchial tubes. Infection by certain bacteria can also cause acute bronchitis. Most people have acute bronchitis at some point in their lives.
Chronic bronchitis can be mild to severe and is longer lasting from several months to years. With chronic bronchitis, the bronchial tubes continue to be inflamed (red and swollen), irritated, and produce excessive mucus over time. The most common cause of chronic bronchitis is smoking.
Acute Bronchitis
Acute bronchitis is swelling and inflammation of the main air passages to the lungs. This swelling narrows the airways, making it harder to breath and causing other symptoms, such as a cough.
Prevention
The majority of instances of chronic bronchitis can be prevented by quit smoking and avoiding second-hand smoke.
Flu and pneumococcal vaccines can help to prevent repeated infections that may lead to the disease.
Certain industries (for example, chemical, textile, thermal etc.) and farm workers are often associated with air-borne chemicals and dust; avoiding air-borne chemicals and dust with appropriate masks may prevent or reduce the individual's chance of developing chronic bronchitis.
Good control of asthma may prevent chronic bronchitis from developing. The genetic predisposition to chronic bronchitis is not currently preventable.
Emphysema
Emphysema is a long-term, progressive disease of the lungs that primarily causes shortness of breath due to over-inflation of the alveoli (air sacs in the lung). In people with emphysema the lung tissues involved in exchange of gases (oxygen and carbon dioxide) is impaired or destroyed. It is included in a group of diseases called chronic obstructive pulmonary disease or COPD. Emphysema is called an obstructive lung disease because the destruction of lung tissue around smaller airways (bronchioles), makes these airways unable to hold their shape properly when exhale. This makes them inefficient at transferring oxygen into the blood, and in taking carbon dioxide out of the blood.
Surgery:
People with severe emphysema sometimes undergo surgery to reduce lung volume or carry out lung transplantation. Lung volume reduction surgery removes small wedges of the damaged, emphysematous, lung tissue. This is thought to enhance lung recoil and to improve the function of the diaphragm. In severe cases, this can improve lung function, exercise tolerance and quality of life
Lung transplantation improves quality of life, but not life-expectancy, for people with severe emphysema. Lifelong drug therapy is necessary to prevent the immune system from rejecting the new tissue. One or both lungs may be transplanted.
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