Chapter 23 The Respiratory System Structurally, the respiratory system is divided into upper and lower divisions or tracts. The upper respiratory tract consists of the nose, pharynx and associated structures. The lower respiratory tract consists of the larynx, trachea, bronchi and lungs. Upper respiratory tract Lower respiratory tract Functionally, the respiratory system is divided into the conducting zone and the respiratory zone. The conducting zone is involved with bringing air to the site of external respiration and consists of the nose, pharynx, larynx, trachea, bronchi, bronchioles and terminal bronchioles. The respiratory zone is the main site of gas exchange and consists of the respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli. Air passing through the respiratory tract traverses the: Nasal cavity Pharynx Larynx Trachea Primary (1 o ) bronchi Secondary (2 o ) bronchi Tertiary (3 o ) bronchi Bronchioles Alveoli (150 million/lung) The external nose is visible on the face. The internal nose is a large cavity beyond the nasal vestibule. The internal nasal cavity is divided by a nasal septum into right and left nares. Three nasal conchae (or turbinates) protrude from each lateral wall into the breathing passages. Tucked under each nasal concha is an opening, or meatus, for a duct that drains secretions of the sinuses and tears into the nose. Receptors in the olfactory epithelium pierce the bone of the cribriform plate. 1
The pharynx is a hollow tube that starts posterior to the internal nares and descends to the opening of the larynx in the neck. It is formed by a complex arrangement of skeletal muscles that assist in deglutition. It functions as: a passageway for air and food a resonating chamber a housing for the tonsils The pharynx has 3 anatomical regions: The nasopharynx; oropharynx; and laryngopharynx In this graphic, slitting the muscles of the posterior pharynx shows the back of the tongue in the laryngopharynx. The nasopharynx is separated from the oropharynx by the hard and soft palate. The nasopharynx lies behind the internal nares. It contains the pharyngeal tonsils (adenoids) and the openings of the Eustachian tubes (auditory tubes) which come off of it and travels to the middle ear cavity. The oropharynx lies behind the mouth and participates in both respiratory and digestive functions. The main palatine tonsils (those usually taken in a tonsillectomy) and small lingual tonsil are housed here. The laryngopharynx lies inferiorly and opens into the larynx (voice box) and the esophagus. It participates in both respiratory and digestive functions. The larynx, composed of 9 pieces of cartilage, forms a short passageway connecting the laryngopharynx with the trachea (the windpipe ). The thyroid cartilage (the large Adam s apple ) and the one below it (the cricoid cartilage) are landmarks for making an emergency airway (called a cricothyrotomy). Anterior view of the larynx 2
The epiglottis is a flap of elastic cartilage covered with a mucus membrane, attached to the root of the tongue. The epiglottis guards the entrance of the glottis, the opening between the vocal folds. For breathing, it is held anteriorly, then pulled backward to close off the glottic opening during swallowing. The rima glottidis (glottic opening) is formed by a pair of mucous membrane vocal folds (the true vocal cords). The vocal folds are situated high in the larynx just below where the larynx and the esophagus split off from the pharynx. Cilia in the upper respiratory tract move mucous and trapped particles down toward the pharynx. Cilia in the lower respiratory tract move them up toward the larynx. As air passes from the laryngopharynx into the larynx, it leaves the upper respiratory tract and enters the lower respiratory tract. Air passing through the respiratory tract Nasal cavity Pharynx Larynx Trachea Primary bronchi Secondary bronchi Tertiary bronchi Bronchioles Alveoli (150 million/lung) Upper respiratory tract Lower respiratory tract The trachea is a semi-rigid pipe made of semicircular cartilaginous rings, and located anterior to the esophagus. It is about 12 cm long and extends from the inferior portion of the larynx into the mediastinum where it divides into right and left primary (1 o, mainstem ) bronchi. It is composed of 4 layers: a mucous secreting epithelium called the mucosa, and three layers of CT (submucosa, hyaline cartilage, and adventitia). The tracheal cartilage rings are incomplete posteriorly, facing the esophagus. Esophageal masses can press into this soft part of the trachea and make it difficult to breath, or even totally obstruct the airway. 3
The right and left primary (1 o or mainstem ) bronchi emerge from the inferior trachea to go to the lungs, situated in the right and left pleural cavities. The carina is an internal ridge located at the junction of the two main stem bronchi a very sensitive area for triggering the cough reflex. The 1 o bronchi divide to form 2 o and 3 o bronchi which respectively supply the lobes and segments of each lung. 3 o bronchi divide into bronchioles which in turn branch through about 22 more divisions (generations). The smallest are the terminal bronchioles. The bronchi and bronchioles go through structural changes as they branch and become smaller. The mucous membrane changes and then disappears. The cartilaginous rings become more sparse, and eventually disappear altogether. As cartilage decreases, smooth muscle (under the control of the Autonomic Nervous System) increases. Sympathetic stimulation causes airway dilation, while parasympathetic stimulation causes airway constriction. All the branches from the trachea to the terminal bronchioles are conducting airways they do not participate in gas exchange. The cup-shaped outpouchings which participate in gas exchange are called alveoli. The first alveoli don t appear until the respiratory Respiratory bronchioles give way to alveolar ducts, and the epithelium (simple cuboidal) changes to simple squamous, which comprises the alveolar ducts, alveolar sacs, and alveoli. bronchioles where they are rudimentary and mostly nonfunctioning. 4
Taken together, these structures form the functional unit of the lung, which is the pulmonary lobule. Wrapped in elastic C.T., each pulmonary lobule contains a lymphatic vessel, an arteriole, a venule and a terminal bronchiole. The pulmonary lobule As part of the pulmonary lobule, alveoli are delicate structures composed chiefly of type I alveolar cells, which allow for exchange of gases with the pulmonary capillaries. Alveoli make up a large surface area (750 ft 2 ). Type II cells secrete a substance called surfactant that prevents collapse of the alveoli during exhalation. Alveoli macrophages (also called dust cells ) scavenge the alveolar surface to engulf and remove microscopic debris that has made it past the mucociliary blanket that traps most foreign particles higher in the respiratory tract. The alveoli (in close proximity to the capillaries) form the alveolar-capillary membrane ( AC membrane ). Blood Supply to the Lungs The lungs receive blood via two sets of arteries Pulmonary arteries carry deoxygenated blood from the right heart to the lungs for oxygenation Bronchial arteries branch from the aorta and deliver oxygenated blood to the lungs primarily perfusing the muscular walls of the bronchi and bronchioles Ventilation-Perfusion Coupling Ventilation-perfusion coupling is the coupling of perfusion (blood flow) to each area of he lungs to match the extent of ventilation (airflow) to alveoli in that area In the lungs, vasoconstriction in response to hypoxia diverts pulmonary blood from poorly ventilated areas of the lungs to well-ventilated regions In all other body tissues, hypoxia causes dilation of blood vessels to increase blood flow As organs, the lungs are divided into lobes by fissures. The right lung is divided by the oblique fissure and the horizontal fissure into 3 lobes. The left lung is divided into 2 lobes by the oblique fissure. Each lobe receives it own 2 o bronchus that branches into 3 o segmental bronchi (which continue to further divide). 5
The apex of the lung is superior, and extends slightly above the clavicles. The base of the lungs rests on the diaphragm. The cardiac notch in the left lung (the indentation for the heart) makes the left lung 10 % smaller than the right lung. The lungs are separated from each other by the heart and other structures in the mediastinum. Each lung is enclosed by a double-layered pleural membrane. The parietal pleura line the walls of the thoracic cavity. The visceral pleura adhere tightly to the surface of the lungs themselves. On each side of the thorax, a pleural cavity is formed. The integrity of this space (really potential space) between the parietal and visceral pleural layers is crucial to the mechanism of breathing. Pleural fluid reduces friction and produces a surface tension so the layers can slide across one another. To understand how this mechanical coupling between the lungs, the pleural cavities and the chest wall results in breathing, we first need to discuss some physics of gases called the gas laws. The pleura, adherent to the chest wall and to the lung, produces a mechanical coupling for the two layers to move together. The respiratory system depends on the medium of the earth s atmosphere to extract the oxygen necessary for life. The atmosphere is composed of these gases: Nitrogen (N 2 ) 78% Oxygen (O 2 ) 21% Carbon Dioxide (CO 2 ) 0.04% Water Vapor variable, but on average around 1% The gases of the atmosphere have a mass and a weight (5 x 10 18 kg, most within 11 km of the surface). Consequently, the atmosphere exerts a significant force on every object on the planet (recall that pressure is measured as force applied per unit area, P = F/A.) We are accustomed to the tremendous force pressing down on every square inch of our body. 6
A barometer is an instrument that measures atmospheric pressure. Baro = pressure or weight Meter = measure Air pressure varies greatly depending on the altitude and the temperature. There are many different units used to measure atmospheric pressure. At sea level, the air pressure is: 14.7 lb/in2 = 1 atmosphere 760 mmhg = 1 atmosphere 76 cmhg = 1 atmosphere 29.9 inhg = 1 atmosphere At high altitudes, the atmospheric pressure is less; descending to sea level, atmospheric pressure is greater. Gases obey laws of physics called the gas laws. These laws apply equally to the gases of the atmosphere, the gases in our lungs, the gases dissolved in the blood, and the gases diffusing into and out of the cells of our body. To understand the mechanics of ventilation and respiration, we need to have a basic understanding of 3 of the 5 common gas laws. Boyle s law applies to containers with flexible walls like our thoracic cage. It says that volume and pressure are inversely related. If there is a decrease in volume there will be an increase in pressure: V 1/P Dalton s law applies to a mixture of gases. It says that the pressure of each gas is directly proportional to the percentage of that gas in the total mixture: P Total = P 1 + P 2 + P 3 Since O 2 = 21% of atmosphere, the partial pressure exerted by the contribution of just O 2 (written po 2 or P A O 2 ) = 0.21 x 760 mmhg = 159.6 mmhg at sea level. Henry s law deals with gases and solutions. It says that increasing the partial pressure of a gas over (in contact with) a solution will result in more of the gas dissolving into the solution. The patient in this picture is getting more O 2 in contact with his blood - consequently, more oxygen goes into his blood. Medicimage/Phototake 7
Gas will always move from a region of high pressure to a region of low pressure. Applying Boyle's law: If the volume inside the thoracic cavity, the pressure. Ventilation and Respiration Pulmonary ventilation is the movement of air between the atmosphere and the alveoli, and consists of inhalation and exhalation. Ventilation, or breathing, is made possible by changes in the intrathoracic volume. Ventilation and Respiration In contrast to ventilation, respiration is the exchange of gases. External respiration (pulmonary) is gas exchange between the alveoli and the blood. Internal respiration (tissue) is gas exchange between the systemic capillaries and the tissues of the body. Ventilation and Respiration External respiration in the lungs is possible because of the implications of Boyle s law: The volume of the thoracic cavity can be increased or decreased by the action of the diaphragm, and other muscles of the chest wall. By changing the volume of the thoracic cavity (and the lungs remember the mechanical coupling of the chest wall, pleura, and lungs), the pressure in the lungs will also change. Ventilation and Respiration Changes in air pressure result in movement of the air. Contraction of the diaphragm and external intercostal (rib) muscles increases the size of the thorax. This decreases the intrapleural pressure so air can flow in from the atmosphere (inspiration). Relaxation of the diaphragm, with/without contraction of the internal intercostals, decreases the size of the thorax, increases the air pressure, and results in exhalation. Ventilation and Respiration Certain thoracic muscles participate in inhalation; others aid exhalation. The diaphragm is the primary muscle of respiration all the others are accessory. 8
Ventilation and Respiration The recruitment of accessory muscles greatly depends on whether the respiratory movements are quiet (normal), or forced (labored). Airflow and Work of Breathing Differences in air pressure drive airflow, but 3 other factors also affect the ease with which we ventilate: 1. The surface tension of alveolar fluid causes the alveoli to assume the smallest possible diameter and accounts for 2/3 of lung elastic recoil. Normally the alveoli would close with each expiration and make our Work of Breathing insupportable. Surfactant prevents the complete collapse of alveoli at exhalation, facilitating reasonable levels of work. Airflow and Work of Breathing 2. High lung compliance means the lungs and chest wall expand easily. Compliance is decreased by a broken rib, or by diseases such as pneumonia or emphysema. Airflow and Work of Breathing Measuring Ventilation Ventilation can be measured using spirometry. Tidal Volume (V T ) is the volume of air inspired (or expired) during normal quiet breathing (500 ml). Inspiratory Reserve Volume (IRV) is the volume inspired during a very deep inhalation (3100 ml height and gender dependent). Expiratory Reserve Volume (ERV) is the volume expired during a forced exhalation (1200 ml). Measuring Ventilation Spirometry continued Vital Capacity (VC) is all the air that can be exhaled after maximum inspiration. It is the sum of the inspiratory reserve + tidal volume + expiratory reserve (4800 ml). Residual Volume (RV) is the air still present in the lungs after a force exhalation (1200 ml). The RV is a reserve for mixing of gases but is not available to move in or out of the lungs. 9
Measuring Ventilation Measuring Ventilation Old and new spirometers used to measure ventilation. A graph of spirometer volumes and capacities Measuring Ventilation Only about 70% of the tidal volume reaches the respiratory zone the other 30% remains in the conducting zone (called the anatomic dead space). If a single V T breath = 500 ml, only 350 ml will exchange gases at the alveoli. In this example, with a respiratory rate of 12, the minute ventilation = 12 x 500 = 6000 ml. The alveolar ventilation (volume of air/min that actually reaches the alveoli) = 12 x 350 = 4200ml. Exchange of O 2 and CO 2 Using the gas laws and understanding the principals of ventilation and respiration, we can calculate the amount of oxygen and carbon dioxide exchanged between the lungs and the blood. Exchange of O 2 and CO 2 Dalton s Law states that each gas in a mixture of gases exerts its own pressure as if no other gases were present. The pressure of a specific gas is the partial pressure P p. Total pressure is the sum of all the partial pressures. Atmospheric pressure (760 mmhg) = P N2 + P O2 + P H2O + P CO2 + P other gases Since O 2 is 21% of the atmosphere, the P O2 is 760 x 0.21 = 159.6 mmhg. Exchange of O 2 and CO 2 Each gas diffuses across a permeable membrane (like the AC membrane) from the side where its partial pressure is greater to the side where its partial pressure is less. The greater the difference, the faster the rate of diffusion. Since there is a higher P O2 on the lung side of the AC membrane, O 2 moves from the alveoli into the blood. Since there is a higher P CO2 on the blood side of the AC membrane, CO 2 moves into the lungs. 10
Exchange of O 2 and CO 2 P N 2 = 0.786 x 760 mmhg = 597.4 mmhg P O 2 = 0.209 x 760 mmhg = 158.8 mmhg P H 2O = 0.004 x 760 mmhg = 3.0 mmhg P CO 2 = 0.0004 x 760 mmhg = 0.3 mmhg P other gases = 0.0006 x 760 mmhg = 0.5 mmhg Total = 760.0 mmhg Partial pressures of gases in inhaled air for sea level Exchange of O 2 and CO 2 Henry s law states that the quantity of a gas that will dissolve in a liquid is proportional to the partial pressures of the gas and its solubility. A higher partial pressure of a gas (like O 2 ) over a liquid (like blood) means more of the gas will stay in solution. Because CO 2 is 24 times more soluble in blood (and soda pop!) than in O 2, it more readily dissolves. Exchange of O 2 and CO 2 Even though the air we breathe is mostly N 2, very little dissolves in blood due to its low solubility. Decompression sickness ( the bends ) is a result of the comparatively insoluble N 2 being forced to dissolve into the blood and tissues because of the very high pressures associated with diving. By ascending too rapidly, the N 2 rushes out of the tissues and the blood so forcefully as to cause vessels to pop and cells to die. In the blood, some O 2 is dissolved in the plasma as a gas (about 1.5%, not enough to stay alive not by a long shot!). Most O 2 (about 98.5%) is carried attached to Hb. Oxygenated Hb is called oxyhemoglobin. CO 2 is transported in the blood in three different forms: 1. 7% is dissolved in the plasma, as a gas. 2. 70% is converted into carbonic acid through the action of an enzyme called carbonic anhydrase. CO 2 + H 2 O H 2 CO 3 H + - + HCO 3 3. 23% is attached to Hb (but not at the same binding sites as oxygen). The O 2 transported in the blood (P O2 = 100 mmhg) is needed in the tissues to continually make ATP (P O2 = 40 mmhg at the capillaries). CO 2 constantly diffuses from the tissues (P CO2 = 45 mmhg) to be transported in the blood (P CO2 = 40 mmhg) Internal Respiration occurs at systemic capillaries 11
The amount of Hb saturated with O 2 is called the SaO 2. Each Hb molecule can carry 1, 2, 3, or 4 molecules of O 2. Blood leaving the lungs has Hb that is fully saturated (carrying 4 molecules of O 2 oxyhemoglobin). The SaO 2 is close to 95-98%. When it returns, it still has 3 of the 4 O 2 binding sites occupied. SaO 2 = 75% Transport of O2 and CO2 The relationship between the amount of O 2 dissolved in the plasma and the saturation of Hb is called the oxygen-hemoglobin saturation curve. The higher the P O 2 dissolved in the plasma, the higher the SaO 2. Measuring SaO 2 has become as commonplace in clinical practice as taking a blood pressure. Pulse oximeters which used to cost $5,000 can now be purchased at your local pharmacy. Although P O 2 is the most important determinant of SaO 2, several other factors influence the affinity with which Hb binds O 2 Acidity (ph), P CO 2 and blood temperature shift the entire O 2 Hb saturation curve either to the left (higher affinity for O 2 ), or to the right (lower affinity for O 2 ). 3660 Group, Inc/NewsCom As blood flows from the lungs toward the tissues, the increasing acidity (ph decreases) shifts the O 2 Hb saturation curve to the right, enhancing unloading of O 2 (which is just what we want to happen). This is called the Bohr effect. At the lungs, oxygenated blood has a reduced capacity to carry CO 2,and it is unloaded as we exhale (also just what we want to happen). This is called the Haldane effect. 12
Fetal and Maternal Hemoglobin Fetal hemoglobin (Hb-F) has a higher affinity for oxygen (it is shifted to the left) than adult hemoglobin A, so it binds O 2 more strongly. The fetus is thus able to attract oxygen across the placenta and support life, without lungs. Control of Respiration The medulla rhythmicity area, located in the brainstem, has centers that control basic respiratory patterns for both inspiration and expiration. The inspiratory center stimulates the diaphragm via the phrenic nerve, and the external intercostal muscle via intercostal nerves. Inspiration normally lasts about 2 sec. Control of Respiration Exhalation is mostly a passive process, caused by the elastic recoil of the lungs. Usually, the expiratory center is inactive during quiet breathing (nerve impulses cease for about 3 sec). During forced exhalation, however, impulses from this center stimulate the internal intercostal and abdominal muscles to contract. Control of Respiration Other sites in the pons help the medullary centers manage the transition between inhalation and exhalation. The pneumotaxic center limits inspiration to prevent hyperexpansion. The apneustic center coordinates the transition between inhalation and exhalation. Control of Respiration Other brain areas also play a role in respiration: Our cortex has voluntary control of breathing. Stretch receptors sensing over-inflation arrests breathing temporarily (Herring Breuer reflex). Emotions (limbic system) affect respiration. The hypothalamus, sensing a fever, increases breathing, as does moderate pain (severe pain causes apnea.) Response to Pollutants Initial Response Mucous layer thickens. Goblet cells over-secrete mucous. Basal cells proliferate. Advanced Response to Irritation Mucous layer and goblet cells disappear. Normal columnar epithelium in the respiratory tract Basal cells become malignant & invade deeper tissue. 13
Diseases and Disorders Asthma is a disease of hyper-reactive airways (the major abnormality is constriction of smooth muscle in the bronchioles, and inflammation.) It presents as attacks of wheezing, coughing, and excess mucus production. It typically occurs in response to allergens; less often to emotion. Bronchodilators and antiinflammatory corticosteroids are mainstays of treatment. Diseases and Disorders Chronic bronchitis and emphysema are caused by chronic irritation and inflammation leading to lung destruction. Patients may cough up green-yellow sputum due to infection and increased mucous secretion (productive cough). They are almost exclusively diseases of cigarette smoking. Pulse Picture Library/CMP mages /Phototake Diseases and Disorders Pneumonia is an acute infection of the lowest parts of the respiratory tract. The small bronchioles and alveoli become filled with an inflammatory fluid exudate. It is typically caused by infectious agents such as bacteria, viruses, or fungi. Diseases and Disorders Normal Lungs Pneumonia Patient Du Cane Medical Imaging, Ltd./Photo Researchers, Inc 14