Respiratory System PDF

Intro ○ The structure of the respiratory system is uniquely suited to its primary function,the transport of gasses (O2) and out (CO2) of the body ○ In addition, the respiratory system provides a large volume of tissue that is constantly exposed to the outside environment, and thus, potential infecti...

Intro ○ The structure of the respiratory system is uniquely suited to its primary function,the transport of gasses (O2) and out (CO2) of the body ○ In addition, the respiratory system provides a large volume of tissue that is constantly exposed to the outside environment, and thus, potential infection and injury ○ Finally, the pulmonary system includes a unique circulation that must handle the blood flow; the lungs are the only organ that receives the whole cardiac output in the body Anatomy of the lung Regions of the respiratory tract ○ Airflow through the respiratory system can be broken down into 3 interconnected regions: the upper airway, the conducting airway, and the alveolar airway (AKA the lung parenchyma or acinar tissue). ○ The upper airway consists of the entry systems, the nose/nasal cavity and mouth that lead into the pharynx ○ The larynx extends from the lower part of the pharynx to complete the upper airway ○ The nose is the primary point of entry for inhaled air; therefore, the mucosal epithelium lining the nasopharyngeal airways is exposed to the highest concentration of inhaled allergens, toxicants and particulate matter ○ With this in mind, it is easy to understand that in addition to olfaction, the nose and upper airway provides 2 additional crucial functions in airflow: Filtering out large particulates to prevent them from reaching the conducting and alveolar airways and Serving to warm and humidify air as it enters the body ○ Particulates larger than 20-50um tend to not be inhaled through the nose, whereas particulates on the order of 5-10um impact on the nasopharynx and do enter the conducting airway ○ Most of these latter particles settle on mucous membranes in the nose and pharynx ○ Because of their momentum, they don’t follow the airstream as it curves downwards into the lungs and they impact on or near the tonsils and adenoids, large collections of immunologically active lymphoid tissue in the back of the pharynx Cystic fibrosis ○ Among whites, cystic fibrosis is one of the most common genetic disorders; greater than 3% of the US population are carriers for this autosomal recessive disease ○ The gene that is abnormal in cystic fibrosis is located on the long arm of the chromosome 7 and encodes the cystic fibrosis transmembrane conductance regulator (CFTR), a regulated Cl- channel located on the apical membrane of various secretory and absorptive epithelia ○ The number of reported mutations in the CFTR gene that cause cystic fibrosis is large (>1000) and the mutations are now grouped into 5 classes based on their effects on cellular function: Class I mutations do not allow for synthesis of the protein Class II mutations have protein processing defects Class III mutations have a block on their channel regulation Class IV mutations display altered conductance of the ion channel Class V mutations display reduced synthesis of the protein ○ The severity of the defect varies with the class and the individual mutation ○ The most common mutation causing cystic fibrosis is loss of the phenylalanine residue at amino acid position 508 of the protein (F508), a class II mutation that limits the amount of CFR protein that gets to the plasma membrane ○ One outcome of cystic fibrosis is repeated pulmonary infections, particularly with pseudomonas aeruginosa, and progressive, eventually fatal destruction of the lungs ○ There is also suppressed chloride secretion across the wall of the airways ○ One would expect Na+ reabsorption to be depressed as well, an indeed in sweat glands it is ○ However, in the lungs, it is enhanced, so that the Na+ and water move out of the airways, leaving their other secretions inspissated and sticky ○ This results in a reduced periciliary layer that inhibits function of the mucociliary and escalator and alters the local environment to reduce the effectiveness of antimicrobial secretions Alveoli ○ The alveoli are lined by 2 types of epithelial cells ○ Type I cells are flat cells with large cytoplasmic extensions and are the primary lining cells of the alveoli, covering approximately 95% of the alveolar epithelial surface area ○ Tyep II cells (granular pneumocytes) are thicker and contain numerous lamellar inclusion bodies ○ Although these cells make up obly 5% of the surface area, they represent approximately 60% of the epithelial cells in the alveoli. ○ Type II cells are important in alveolar repair as well as other lung cellular functions ○ One prime function of the type II cell is the production of surfactant ○ Typically lamellar bodies, membrane bound organelles containing whorls of phospholipid, are formed in these cells and secreted into the alveolar lumen by exocytosis ○ Tubes of lipid called tubular myelin form from the extruded bodies and the tubular myelin in turn forms a phospholipid film ○ Following secretion, the phospholipids of surfactant line up in the alveoli with their hydrophobic fatty acid tails facing the alveolar lumen ○ This surfactant layer plays an important role in maintaining alveolar structure by reducing surface tension ○ Surface tension is inversely proportional to the surfactant concentration per unit area ○ The surfactant molecules move further apart as the alveoli enlarge during inspiration, and the surface tension increases, whereas it decreases when they move closer together during expiration ○ Some of the protein-lipid complexes in surfactant are taken up by endocytosis in type II alveolar cells and recycled ○ Complexes in surfactant are taken up by endocytosis in type II alveolar cells and recycled. ○ The alveoli are surrounded by pulmonary capillaries ○ In most areas, air and blood are separated only by the alveolar epithelium and the cxapillary epithelium, so they are about.5 um apart ○ The alveoli also contain other specialized cells, including pulmonary alveolar macrophages (PAMs and AMs), lymphocytes, plasma cells, neuroendocrine cells and mast cells ○ PAMs are an important component of the pulmonary defense system ○ Like other macrophages, these cells come originally from the bone marrow ○ PAMs are actively phagocytic and ingest small particles that evade the mucociliary escalator and reach the alveoli ○ They also help process inhaled antigens for immunologic attack, and they secrete substances that attract granulocytes to the lungs as well as substances that stimulate granulocyte and monocyte formation in the bone marrow ○ PAM function can also be detrimental– when they ingest large amounts of the substance in cigarette smoke or other irritants, they may release lysosomal products into the extracellular space to cause inflammation The diaphragm ○ The diaphragm has 3 parts: the portion, made up of muscle fibers that are attached to the ribs around the bottom of the thoracic cage; the crural portion, made up of fibers that are attached to the ligaments along the vertebrae; and the central tendon into which the costal and crural fibers insert ○ The central tendon is also the inferior part of the pericardium ○ The crural fibers pass on either side of the esophagus and can compress it when they contract ○ The costal and crucial portions are innervated by different parts of the phrenic nerve and can contract separately ○ For example, during vomiting and eructation, intra abdominal pressure is increased by contraction of the costal fibers but the crural fibers remain relaxed, allowing material to pass from stomach into the esophagus ○ The other important inspiratory muscles are the external intercostals, which run obliquely downward and forward from rib to rib ○ The ribs pivot as if hinged at the back, so that when the external intercostals contract they elevate the lower ribs ○ This pushes the sternum outwards and increases the anteroposterior diameter of the chest ○ The transverse diameter also increases but to a lesser degree ○ Either the diaphragm or the external intercostal muscles alone can maintain adequate ventilation at rest ○ Transection of the spinal cord above the 3rd cervical segment is fatal without artificial respiratory, but transection below the fifth cervical segment is not because it leaves the phrenic nerves that innervate the diaphragm intact; the phrenic nerves arise from cervical segments 3-5 ○ Conversely, in patients with bilateral phrenic nerve palsy but intact innervation of their intercostal muscles, respiration is somewhat labored but adequate to maintain life ○ The scalene and SCM muscles in the neck are accessory inspiratory muscles that help elevate the thoracic cage during deep labored respiration Lung pleura ○ The pleural cavity and its folding serve as a lubricating fluid/area that allows for lung movement within the thoracic cavity ○ There are 2 layers that contribute to the pleural cavity: the parietal pleura and the visceral pleura ○ The parietal pleura is a membrane that lines the chest cavity containing the lungs ○ The visceral pleura is a membrane that lines the lung surface ○ The pleural fluid (15-20mL) forms a thin layer between the pleural membrane and prevents friction between the surfaces during inspiration and expiration