469CHAPTER 41 Structure and Development of the Lower Respiratory System from the right tracheobronchial nodes drains into the right bron chomediastinal trunk, whereas the left tracheobronchial nodes d[.]
CHAPTER 41 Structure and Development of the Lower Respiratory System from the right tracheobronchial nodes drains into the right bronchomediastinal trunk, whereas the left tracheobronchial nodes drain into the thoracic duct Understanding the lymphatic drainage of the pleura is of clinical value All lymph from the visceral pleura eventually reaches parabronchial and hilar lymph nodes by flowing on the surface or in lymphatic trunks that course through the lung Lymphatic vessels in the parietal pleura are in communication with the pleural space via 2- to 6-mm stomas found on the mediastinal pleura or the intercostal surfaces of the lower thorax.28 The parasternal nodes in the second and third interspaces receive lymph from a significant portion of the parietal pleura; thus, biopsy of these nodes may reveal an etiology of the pleural effusion The portion of lymph that drains caudally from the lower parietal pleural region into retroperitoneal nodes can explain metastases of a tumor to adrenals and kidneys Bronchus-associated lymphoid tissue (BALT) appears as isolated nodules in the connective tissue of the lamina propria of the bronchial tree and produces primarily immunoglobulin G and secretory IgA.29 Collections of BALT cells tend to occur at airway bifurcations and are covered by a special epithelium that can pinocytose and transport solutes and particulate antigens BALT is sparse at birth but starts accumulating thereafter It is prominent in the lungs of children and in diseased lungs of patients with bronchiectasis Although more than 50% of the cells are B lymphocytes, T lymphocytes are also found (18%), along with follicular dendritic cells Sometimes these nodules bulge into the bronchial lumen.29 Additional lymphoid tissue in the lung is a rich supply of lymph nodes within the lung, at the carina, and along the trachea Diaphragm Although the diaphragm is the principal muscle of respiration, it is not essential for breathing in the awake state It becomes essential during deep anesthesia because other muscles of respiration become inactive The diaphragm is a musculotendinous sheet that is the main source of inspiratory muscle force.24,28 Anatomically, it separates the thoracic from the abdominal cavity It has two distinct muscular components: the sternocostal portion and the crural These two portions have distinct embryologic origins and have separate segmental innervations and varying muscle fiber composition There are changes in fiber composition following birth The muscle fibers vary morphologically, physiologically, and cytochemically The diaphragm has three openings near its central portion for the aorta, inferior vena cava, and esophagus The vagus nerve passes through the esophageal hiatus, whereas the azygos vein and thoracic duct pass through the aortic hiatus 469 There are small paravertebral perforations for splanchnic nerves Because of the way that the fibers originate from the bones and traverse to the central tendon, triangular areas may result in spaces or clefts in the diaphragm Anteriorly, these are called Morgagni foramina; posteriorly, they are known as the foramina of Bochdalek Both are potential sites for hernias The phrenic nerve innervates the diaphragm During contraction in adults, the dome of the diaphragm descends and the lower ribs elevate In infants, because of their compliant rib cage, descent opposes elevation of the lower ribs and results in the subcostal retractions.28 Other muscles of respiration include the intercostals, the majority of which are arranged to enhance inspiration by elevating the lower ribs, and the abdominal muscles, which are powerful muscles of expiration but not participate in expiration during quiet breathing Scalenes act to elevate the first two ribs and are active even during quiet breathing Although the sternocleidomastoid muscles usually are not active in quiet breathing, when inspiratory efforts are marked, they become the most important accessory muscles of inspiration This is well seen in infants with respiratory distress who elevate the upper portion of their sterna Summary The respiratory portion of the lung is a complex organ with more than 40 cell types It undergoes remodeling over the first few years of life Altered structure, whether due to congenital abnormalities or injury and repair, is a critical determinant of survival and quality of life Understanding the structure of the lung is critical to the management and treatment of lung disease in critically ill children Key References Hislop AA Fetal and postnatal anatomical lung development In: Greenough A, Milner AD, eds Neonatal Respiratory Disorders 2nd ed Oxford, UK: Oxford University Press; 2003 Maeda Y, Dave V, Whitsett JA Transcriptional control of lung morphogenesis Physiol Rev 2007;87:219-244 Langston CK, Reed M Human lung growth in late gestation and the neonate Am Rev Respir Dis 1984;129:607 Wiebe BM, Laursen H Human lung volume, alveolar surface area, and capillary length Microsc Res Tech 1995;32:255-262 Leak LV, Ferrans VJ Lymphatics and lymphoid tissue In: Crystal RG, West JB, eds The Lung: Scientific Foundations Vol New York: Raven Press; 1994:779-786 The full reference list for this chapter is available at ExpertConsult.com e1 References Moore KL, Dalley AF Clinically Oriented Anatomy (Thorax Chapter) 5th ed Philadelphia: Lippincott, Williams & Wilkins; 2006 Hislop AA Fetal and postnatal anatomical lung development In: Greenough A, Milner AD, eds Neonatal Respiratory Disorders 2nd ed Oxford, UK: Oxford University Press; 2003 Smith LJ, McKay KO, van Asperen PP, et al Normal development of the lung and premature birth Paediatr Respir Rev 2010;11:135-142 Maeda Y, Dave V, Whitsett JA Transcriptional control of lung morphogenesis Physiol Rev 2007;87:219-244 Beers MF, Shuman H, Liley HG, et al Surfactant protein B in human fetal lung: developmental and glucocorticoid regulation Pediatr Res 1995;38:668-675 Forget BG Progress in understanding the hemoglobin switch N Engl J Med 2011;365:852-854 Newton DA, Romano C, Gattoni-Celli S Semiallogeneic cell hybrids as therapeutic vaccines for cancer J Immunother 2000;23:246-254 Saphir O Autopsy Diagnosis and Technique 3rd ed New York: Paul B Hoeber; 1951 Copland I, Post M Lung development and fetal lung growth Paediatr Respir Rev 2004;5(suppl A):S259-S264 10 Horsfield K, Cumming G The morphology of the bronchial tree in man J Appl Physiol 1968;24:373-383 11 Rehan V, Torday J Vitamin D and lung development in early life In: Litonjua AA, ed Vitamin D and the Lung Louisville, KY: Humana Press; 2012:41-57 12 Weibel E Morphometry of the Human Lung New York: Academic Press; 1963 13 Munkholm M, Mortensen J Mucociliary clearance: pathophysiological aspects Clin Physiol Funct Imaging 2014;34:171-177 14 Chilvers MA, O’Callaghan C Local mucociliary defence mechanisms Paediatr Respir Rev 2000;1:27-34 15 DiAugustine RP, Sonstegard KS Neuroendocrinelike (small granule) epithelial cells of the lung Environ Health Perspect 1984;55:271-295 16 Watson TM, Reynolds SD, Mango GW, et al Altered lung gene expression in CCSP-null mice suggests immunoregulatory roles for Clara cells Am J Physiol Lung Cell Mol Physiol 2001;281:L1523-L1530 17 Stripp BR, Reynolds SD Maintenance and repair of the bronchiolar epithelium Proc Am Thorac Soc 2008;5:328-333 18 Loosli CG, Potter EL Pre- and postnatal development of the respiratory portion of the human lung with special reference to the elastic fibers Am Rev Respir Dis 1959;80:5-23 19 Langston CKK, Reed M Human lung growth in late gestation and the neonate Am Rev Respir Dis 1984;129:607 20 Dunnell MS Postnatal growth of the lung Thorax 1962;17:329 21 Thurlbeck WM Postnatal human lung growth Thorax 1982;37:564 22 Wiebe BM, Laursen H Human lung volume, alveolar surface area, and capillary length Microsc Res Tech 1995;32:255-262 23 Fehrenbach H Alveolar epithelial type II cell: defender of the alveolus revisited Respir Res 2001;2:33-46 24 Murray JF The Normal Lung 2nd ed Philadelphia: WB Saunders; 1986 25 Leak LV, Ferrans VJ Lymphatics and lymphoid tissue In: Crystal RG, West JB, eds The Lung: Scientific Foundations Vol New York: Raven Press; 1994:779-786 26 Hislop A, Reid L Intra-pulmonary arterial development during fetal life-branching pattern and structure J Anat 1972;113:35-48 27 Brenner O Pathology of the vessels of the pulmonary circulation Arch Intern Med 1935;56:211 28 Hinshaw HC, Murray JF Diseases of the Chest 4th ed Philadelphia: WB Saunders; 1977 29 Randall TD Bronchus-associated lymphoid tissue (BALT) structure and function Adv Immunol 2010;107:187-241 e2 Abstract: Lungs increase in volume from about 250 mL at birth to 6000 mL in the adult Each lung lobe is subdivided into 19 bronchopulmonary segments, which receive a primary segmental bronchus and a tertiary pulmonary artery branch and are drained by pulmonary veins The airway branching pattern in the lung undergoes multiple generations, yielding a total of 27 or 28 divisions when counting begins from the primary bronchus The aggregate length of the airways in the adult lung spans approximately 1500 miles (2400 km) The bronchial mucosa contains several epithelial cell types, with the ciliated cell comprising more than 90% of the epithelial cell population in the conducting airways, but the proportion and number of cilia per cell decrease from the proximal to distal airways The acinus, which is approximately spherical in shape and has a diameter of about mm and a length of 0.5 to cm, is the gas exchange portion of the lung At the alveolar level, many changes occur in the postnatal period Although there is disparity concerning the time in which alveolarization is completed, alveoli in a normal adult number from 300 to 500 million and have a diameter of 150 to 200 mm The two epithelial cells of the alveolus are the gas-exchanging type I cell and type II cell, which are responsible for the production of pulmonary surfactant and have a central role in repair The alveolar-capillary unit is composed of three major constituents: the epithelial lining of the alveolus, capillary endothelial cells, and a mixture of cellular and extracellular interstitial components Following birth, the pulmonary vasculature undergoes extensive remodeling When fully matured, the thickness of the pulmonary artery is only about 60% that of the aorta The large pulmonary arteries traverse the lung with the cartilaginous airways and extend from the hilum nearly halfway down the bronchial tree Smaller pulmonary arteries measure between 100 and 1000 mm in diameter, branch with the bronchial tree, and lie close to bronchi and bronchioles Pulmonary veins not course with the bronchial tree; instead, they are seen within the interlobular septae Key words: Lower respiratory system, development, pulmonary artery, lungs 42 Physiology of the Respiratory System ROBINDER G KHEMANI AND JUSTIN C HOTZ • Children younger than years have nearly equal peripheral and central airway resistance This makes them more susceptible to developing respiratory failure with illnesses that affect the lower airway (such as bronchiolitis) In healthy adults, the critical closing capacity for most alveoli is much lower than functional residual capacity (FRC); thus, small losses in alveolar volume not result in alveolar collapse During infancy, the critical closing capacity for many alveoli lie above FRC, making infants prone to developing atelectasis and respiratory failure Spontaneously breathing infants attempt to counteract this by stopping exhalation before reaching airway • • PEARLS closure through laryngeal-breaking (sometimes termed autoPEEP [positive end-expiratory pressure]), as an attempt to maintain a higher FRC During airway obstruction, it is more efficient to breathe less often but with a higher tidal volume, as the resistance to airflow in the intrathoracic airways reduces with increasing volume In contrast, when elastic work predominates (i.e., parenchymal lung disease), it is more efficient to breathe more often with lower tidal volume, as elastic work increases further as volume increases Physiology of the Respiratory System Boyle’s Law The respiratory system’s vital function is to enable gas exchange The components responsible for effective gas exchange are complex and multifactorial They comprise central nervous system control of respiratory drive and airway tone, the resistive properties of the upper and lower airways, elastic properties of the lung and chest wall, diffusion across the alveolarcapillary membrane, transport of gases in the blood, diffusion of gases into the cells of the body, and the use of oxygen and production of carbon dioxide (CO2) within cells as a byproduct of metabolism This chapter introduces key concepts to better understand how they become deranged during critical illness and are modified by therapies applied in intensive care To facilitate understanding of these concepts, a compartment-based model of the respiratory system is presented This framework is used to highlight pieces of respiratory physiology most relevant for pediatric intensive care practitioners.1 There are four main respiratory compartments: (1) central nervous system control; (2) extrathoracic upper airways; (3) the intrathoracic compartment, which includes the lower airways and pulmonary parenchyma; and (4) the extrathoracic space, including the chest wall and abdomen Important principles of gas exchange are also covered in this chapter Some concepts are relevant to multiple topics covered in this text; we hope that this framework facilitates linking physiologic concepts with clinical care An introduction to a few important principles is therefore presented first The first step of gas exchange is alveolar ventilation, which requires movement of air in and out of the lungs This movement is driven by Boyle’s law, which states that within a structure, there is an inverse relationship between pressure and volume such that a rise in volume results in a fall in pressure or vice versa During normal breathing, the diaphragm contracts and is displaced downward This expands the thoracic cavity and generates negative pleural and airway pressure Because the airway pressure is negative relative to the atmosphere, the pressure gradient causes air to flow from the atmosphere into the lungs During exhalation, elastin fibers in the alveoli recoil and the respiratory muscles relax, causing the volume of the thoracic cavity to decrease This makes the pressure inside the airways more positive relative to the atmosphere, causing air to flow from the airways back out into the atmosphere 470 Equation of Motion of the Respiratory System Motion of gas within the respiratory system requires force to overcome the flow-resistive, inertial, and elastic properties of the airways, lung parenchyma, and chest wall Under normal circumstances, this force is generated by the respiratory muscles At each instant, the applied pressure in the respiratory system (PRS) must equal the sum of the pressure required to overcome elastic recoil (PER) and the pressure lost to viscous (resistive) forces (PR) PRS PER PR CHAPTER 42 Physiology of the Respiratory System PER is a function of the elastance of the respiratory system (1/compliance) and the change in lung volume during a respiratory cycle (i.e., tidal volume [V]) PR is a function of the resistance in the airways and the flow (Q) This is typically expressed as the equation of motion of the respiratory system: PRS (V/C) RQ Under circumstances of unassisted breathing, PRS is generated entirely by the respiratory muscles and is referred to as PMUS However, if the patient is receiving positive pressure ventilation, some or all of this pressure is shared between the patient and the ventilator Decreases in respiratory system compliance (or increases in respiratory system elastance, such as from alveolar edema or consolidation) or increases in airway resistance (i.e., from bronchoconstriction or upper airway obstruction) will result in an increase in PRS During unassisted breathing, this manifests as larger patient effort needed to generate this pressure; during controlled mechanical ventilation, it results in higher delta pressure (peak inspiratory pressure [PIP] – positive end expiratory pressure [PEEP]) on the ventilator Transmural Pressures While the equation of motion of the respiratory system relates to the net pressure gradient for gas to flow into the lungs, there are individual pressure gradients across the various components of the respiratory system that drive either the rate of gas flow or the expansion of volume of the tissue (Fig 42.1) The first is the airway pressure gradient, which drives airflow from the atmosphere into the alveoli and is defined as: Pbs PALV where Pbs is the pressure at the body surface (or mouth), which is normally atmospheric, and PALV is the alveolar pressure Larger reductions in alveolar pressure during inspiration result in more airflow The remaining pressures are typically measured during static conditions (no airflow), as they provide information about elastic recoil properties of the lung, chest wall, and the entire respiratory Pbs Pbs Pbs PpI PpI PALV PpI Pbs 471 system At the alveolar level, the important pressure gradient is expressed as the transpulmonary pressure (PTP), defined as PTP PALV Ppl where PALV is the alveolar pressure and Ppl is the pleural pressure PTP is equal to elastic recoil of the lungs when there is no airflow During healthy conditions, PTP is typically slightly positive (to keep alveoli expanded) at end exhalation and becomes more positive with increasing lung volume (such as during tidal ventilation) Transchest wall pressure (PTC) is defined as PTC Ppl Pbs where Ppl is the pleural pressure and Pbs is the pressure at the body surface that is usually atmospheric (i.e., 0) PTC and Ppl represent the elastic recoil of the chest when there is no airflow and, like PTP , they increase and decrease with lung volume Finally, the transmural pressure across the respiratory system (PRS; lung and chest wall) is defined as PRS PALV Pbs where PALV is the alveolar pressure and Pbs is the pressure at the body surface PRS is equal to the net passive elastic recoil pressure of the whole respiratory system when airflow is zero Central Nervous System Control Respiratory centers in the brainstem set the rhythm for normal breathing, transmitted through efferent nerve pathways that terminate at the respiratory muscles Afferent nerve pathways send information back to the respiratory centers in the brainstem on the adequacy of gas exchange (chemoreceptors), the state of lung inflation (mechanoreceptors), and pathologic disturbances (nociceptors) Based on this feedback, respiratory centers alter the amplitude and rate of efferent nerve impulses being sent to the respiratory muscles By using this feedback loop, a stable amount of oxygen and carbon dioxide can be maintained at the cellular level.2 Respiratory Centers and Efferent Nerve Transmission to the Respiratory Muscles The respiratory centers are housed within the medulla and pons, in the ventral respiratory group of the ventrolateral brainstem The ventral respiratory group is a collection of three nuclear groups (the pre-Botzinger complex, nucleus ambiguous, and the nucleus retroambigualis) These neurons are considered upper motor neurons of the respiratory system They innervate motor neurons in the anterior horns of the spinal cord and cause contraction in muscles contained in the upper airway, the diaphragm, and the intercostals Derangement in these respiratory control centers from congenital lesions (e.g., central hypoventilation syndrome), acquired conditions (e.g., acute or chronic forms of encephalopathy), or therapies (e.g., sedation and anesthesia) are common in critical care and may contribute to respiratory failure in children Receptors and Feedback to the Respiratory Centers PpI Pbs • Fig 42.1 Pressure involved in respiration Gradients must occur to allow for gas to flow into the lungs Pbs, Pressure at body surface; Ppl, pleural pressure Chemoreceptors sense the concentration of oxygen, CO2, and hydrogen (H1) ions at various locations within the central and peripheral nervous systems The central chemoreceptors are located near the ventral-lateral surface of the medulla, in contact with the cerebrospinal fluid (CSF) As arterial CO2 content increases, more CO2 diffuses into the CSF and binds with water to ... Important principles of gas exchange are also covered in this chapter Some concepts are relevant to multiple topics covered in this text; we hope that this framework facilitates linking physiologic concepts... obstruction) will result in an increase in PRS During unassisted breathing, this manifests as larger patient effort needed to generate this pressure; during controlled mechanical ventilation, it results... infants prone to developing atelectasis and respiratory failure Spontaneously breathing infants attempt to counteract this by stopping exhalation before reaching airway • • PEARLS closure through