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240 Cards in this Set
- Front
- Back
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what are the components of the respiratory system?
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lungs and airways
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what are the functions in respiration?
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breathing/ventilation, external respiration, transport of gases, internal respiration
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what is breathing?
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movement of air in and out of the lungs
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what is external respiration?
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exchange of O2 in the inspired air for carbon dioxide in the blood
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what is transport of gases?
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conveyance of O2 and CO2 to and from the cells
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what is internal respiration?
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exchange of CO2 for O2 in the vicinity of the cells
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what are the 2 major portions of the respiratory system?
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conducting and respiratory
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what is considered the vestibule of the nasal cavity?
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nostril - air intake
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what are the 2 segments of the nasal cavity?
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respiratory segment and the olfactory segment
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what kind of epithelium composes the nasal cavity?
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ciliated, pseudostratified columnar epithelium
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what makes up the nasal cavity?
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nasal septum, conchae = turbinates, and ciliatedpseudostratified columnar epithelium
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how do the conchae function?
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they are inner folds which mix air by turbination - moisten
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what does the olfactory region of the nasal cavity comprise?
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comprises the olfactory epithelium and the underlying lamina propria that houses Bowman's glands and a rich vascular plexus
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the nasopharynx is subdivided into what 3 regions?
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the superiuor nasopharynx, the middle oral pharynx, and the inferior laryngeal pharynx
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what kind of epithelium lines the nasopharynx?
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respiratory epithelium
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what kind of epithelium lines the oral and laryngeal regions?
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stratified squamous epithelium
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what kind of tissue is the lamina popria comprised of?
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composed of loose to dense, irregular type of vascularized ct
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what does the lamina propria house?
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seromucous glands and lymphoid elements
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what is the nasopharynx fused with?
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the epimysium of the skeletal muscle components of the pharynx
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which aspect of the nasopharynx houses the pharyngeal tonsil?
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the lamina propria of the posterior aspect of the nasopharynx
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the phayrngeal tonsil is…
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an uncapsulated collection of lymphoid tissue
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where is the larynx located?
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situated between the pharynx and trachea
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what is the function of the larynx?
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responsible for phonation and prevents the entry of solids or liquids into the respiratory system during swallowing
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what reinforces the wall of the larynx?
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several hyaline cartilages and elastic cartilages
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specifically, the hyaline cartilages are the…
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unpaired thyroid and cricoid cartilges and the inferior aspect of the paired arytenoids
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specifically, the elastic cartilages are the…
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unpaired epiglottis, the paired corniculate and cuneiform caritlages, and the superior aspect of the arytenoids
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what forms the cylindrical support for the larynx?
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thyroid and cricoid cartilages
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what provides a cover over the laryngeal aditus?
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epiglottis
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during respiration, the epigottis is in which position?
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vertical position - permitting the flow of air
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during swallowing, the epiglottis is in which position?
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horizontal position - closing the laryngeal aditus
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the lumen of the larynx is characterized by which 2 pairs of shelf-like folds?
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the superiorly positioned vestibular folds and the inferiorly placed vocal folds
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which one of the folds are immovable?
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the vestibular folds
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the lamina propria of the vestibular folds is composed of…
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loose ct, houses seromucous glands, adipose cells, and lymphoid elements
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the free edge of each vocal fold is reinforced by…
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dense, regular elastic ct - the vocal ligament
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the vocalis muscle which is attached to the vocal ligament…
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assists the other intrinsic muscles of the larynx in altering the tension on the vocal folds
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which muscle regulates the width of the space between the vocal folds (rima glottidis)?
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the vocalis muscle
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during silent respiration…
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the vocal folds are partially abducted (pulled apart)
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during forced inspiration…
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the vocal folds are fully abducted
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during phonation…
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the vocal folds are strongly adducted forming a narrow interval between them
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what kind of cells line the larynx?
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pseudostratified ciliated columnar epithelium
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what kind of cells line the superior surfaces of the epiglottis and vocal folds?
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stratified squamous nonkeratinized epithelium
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the cilia of the larynx beat in which direction?
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towards the pharynx transporting mucus and trapped particulate matter towards the mouth to be expectorated or swallowed
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where is the trachea located?
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a tube that begins at the cricoid cartilage of the larynx and ends when it bifurcates to form the primary bronchi
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what reinforces the wall of the trachea?
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10-12 horseshoe-shaped hyaline cartilage rings (C-rings)
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what connects the hyaline cartilage rings?
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trachealis muscle (smooth muscle); open ends of these rings face posteriorly; trachea also is rounded anteriorly but flattened posteriorly
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the perichondrium of each C-ring is connected to the perichondria lying directly above and below it by….
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fibroelastic ct
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the fibroelastic ct of the trachea provides…
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flexibility to the trachea and permits elongation during inspiration
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contraction of the trachealis muscle…
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decreases the diameter of the tracheal lumen resulting in faster airflow which assists in dislodging of foreign material
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what are the 3 layers of the trachea?
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mucosa, submucosa, and adventitia
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the mucosal lining of the trachea is composed of…
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pseudostratified ciliated columnar (respiratory) epithelium, the subepithelial ct (lamina propria), and a thick bundle of elastic fibers separating the mucosa from the submucosa
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what are the 6 cell types that compose the respiratory epithelium?
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goblet cells, ciliated columnar cells, basal cells, brush cells, serous cells, and cells of the diffuse neuroendocrine system (DNES); all of these cells come into contact with the basement membrane, but do not reach the lumen
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in respiratory epithelium, what constitutes approx. 30% of the total cell population?
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ciliated columnar cells
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in respiratory epithelium, what constitutes another approx. 30% of the total cell population?
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basal cells
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where are basal cells located?
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on the basement membrane, but their apical surfaces do not reach the lumen
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basal cells…
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are undiff., considered to be stem cells that proliferate to replace defunct goblet, ciliated; columnar, and brush cells?
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in respiratory epithelium, what consitutes approx. 3% of the total cell population?
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brush cells (small-granule mucous cells)
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brush cells…
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are narrow, columnar cells, with tall microvilli?
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brush cells function is unknown but they are associatd with…
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nerve endings
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in respiratory epithelium, what constitutes another 3% of the total cell population?
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serous cells
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serous cells are…
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columnar cells
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what cells have apical microvilli and apical granules containing an electron-dense secretory product?
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serous cells
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in respiratory epithelium, what consitutes approx. another 3-4% of the total cell population?
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DNES cells (cells of the diffuse neuroendocrine system) aka small-granule cells
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DNES cells…
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contain numerous granules in their basal cytoplasm
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where are the contents of the granules in DNES cells released into?
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the ct spaces of the lamina propria
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which cells are thought to release pharmacological agents thought to control func. of other cells?
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DNES cells
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which part of the trachea contains loose, fibroelastic ct?
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lamina propria
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which part of the trachea contains lymphoid elements and mucous/seromucous glands?
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lamina propria
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what separates the lamina propria from the underlying submucosa?
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a dense layer of elastic fibers - the elastic lamina
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which part of the trachea is composed of dense, irregular fibroelastic ct?
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submucosa
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which part of the trachea is composed of a fibroelastic ct?
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adventitia
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which part of the trachea houses C-rings of hyaline cartilage?
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adventitia
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which part of the trachea is associated with the trachealis muscle?
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adventitia
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the epithelial lining of bronchioles ranges from…
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ciliated simple columnar with occasional goblet cells in larger bronchioles to simple cuboidal with occasional clara cells and no goblet cells in smaller bronchioles
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which cells are columnar with dome-shaped apices that have short, blunt microvilli?
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clara cells
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which cells are believed to protect the bronchiolar epitheliumby lining it with their secretory product?
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clara cells
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clara cells degrade toxins in the inhaled air via…
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cytochrome P-450 enzymes in their smooth endoplasmic reticulum
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which cells divide to to regenerate the bronchiolar epithelium?
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clara cells
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the lamina propria of what has no glands, but is surrounded by a loose meshwork of helically
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lamina propria of bronchioles
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oriented smooth muscle layers?
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do the walls of bronchioles and their branches have cartilage?
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NO
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elastic fibers in the bronchial tree…
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radiate from the fibroelastic ct that surrounds the the smooth muscle coats and connect to elastic fibers ramifying from other branches of the bronchial tree
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terminal bronchioles…
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form the smallest and most distal region of the conducting portion of the respiratory system
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what is the epthelium of terminal branches composed of?
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clara cells and cuboidal cells, some with cilia
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the narrow lamina propria of terminal branches consists of…
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fibroelastic ct and is surrounded by one or two layers of smooth muscle cells
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terminal bronchioles branch…
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to give rise to respiratory bronchioles
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in bronchiolar epithelia, what prevents cells from sticking to one another?
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lipoprotein
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the respiratory portion of the respiratory system is composed of…
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respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli
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what is the first region of the respiratory system where exchange of gases can occur?
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respiratory bronchioles
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respiratory bronchioles are similar in structure to terminal bronchioles, BUT…
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their wall is interrupted by the presence of thin-walled, pouch-like structures known as alveoli where gaseous exchange occur
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what supplies the alveolar duct, atrium, and alveolar sac?
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rich capillary network
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what are linear arrangements of alveoli without walls of their own?
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alveolar ducts; An alveolar duct that arises from a respiratory bronchiole branches, and each of the resultant alveolar ducts usually ends as a blind outpouching composed of two or more small clusters of alveoli, in which each cluster is known as an alveolar sac. These alveolar sacs thus open into a common space, the atrium.
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alveoli are small air sacs composed of…
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highly attenuated type I pneumocytes and larger type II pneumocytes
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what forms the primary structural and functional unit of the respiratory system?
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alveolus
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what is the function of alveoli?
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their walls permit the exchange of CO2 and O2 between the air in their lumina and blood in adjacent capillaries
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size and number of alveoli?
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0.002 mm3 and approx. 300 million
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what is the function of type I pneumocytes?
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gas transfer and they comprise 95% of the alveolar surface
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type I pneumocytes are…
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simple squamous epithleium
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what is the function of type II pneumocytes?
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seccrete surfactant which is released from the trans-Golgi network into secretory vesicles - composite bodies - which are the immediate precursors of lamellar bodies although type II are more numerous than type I, they occupy only about 5% of the alveolar surface
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brush cells…
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are air quality meters and are rare
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what is the function of alveolar macrophages (dust cells)?
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phagocytose particulate matter in the lumen of the alveolus as well as in the interalveolar spaces
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these cells maintain a sterile environment within the lungs by phagocytosing particulate matter such as dust and bacteria; also assist type II pneumocytes in the uptake of surfactant
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alveolar macrophages (dust cells)
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interalveolar septum…
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is the region between 2 adjacent alveoli which is lined on both sides by alveolar epithelium may be very narrow housing only a continuous capillary and its basal lamina or it may be wider including ct elements such as type III collagen and elastic fibers, macrophages, fibroblasts, mast cells, and lymphoid elements
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the thin portion of the alveolar septum…
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is for the diffusion of gas; lined on both sides by alveolar epithelium, has capillary epithelium, and basal lamina
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the thick portion of the alveolar septum…
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is for the diffusion of fluid; lined on both sides by alveolar epithelium, has capillary epithelium, and basal lamina with trapped cells and fibers
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what is the region of the interalveolar septum that is traversed by O2 and CO2 as these gases go from the blood to the lumen of the alveolus, and vice versa
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blood-gas barrier
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the blood-gas barrier…
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is the thinnest region of the interalveolar septum where gases can be exchanged
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the blood-gas barrier is composed of what 3 structures…
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surfactant and type I pneumocytes; fused basal laminae of type I pneumocytes and endothelial cells of the capillary; and
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endothelial cells of the continuous capillary
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for ventilation, where does the airway lie?
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the visceral pleura
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the bronchioles branch into…
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terminal bronchioles, respiratory bronchioles, and finally alveoli
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where does respiratory gas exchange occur?
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respiratory bronchioles and alveoli
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what is essential for gas exchange?
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a thin fluid layer in the alveoli and respiratory bronchioles
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where does the fluid come from?
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the fluid is the result of ion secretion from interstitial fluid formed by ultrafiltration across capillaries
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what can increase the diffusion distance for oxygen absorption?
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pulmonary edema
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what do the bands of smooth muscle surrounding the airway do?
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they constrict air flow to the alveoli
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how many alveoli provide how much gas exchange?
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300 million alveoli provide about 140 M2 of gas exchange for both lungs
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ventilation exchanges air to maintain…
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partial pressure gradients for O2 delivery and CO2 removal from the blood
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what is the traditional way of measuring lung volumes?
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simple water seal spirometer and lung volumes are recorded as an ink trace on a rotating drum
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under resting conditions, the lung are about half filled to…
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the functional residual capacity
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during periods of tidal or quiet breathing…
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about 500 ml of air is exchanged per breath above the FRC - tidal volume
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volume refers to…
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air movements due to a specific change in ventilation
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capacity refers to…
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the sum of two or more volumes
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FRC is about…
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2.4L
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what is anatomical dead space?
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of the 500 ml per breath of tidal volume (Vt), it is the 150 ml of air which is not taken into the alveoli
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the remainder of the volume (350ml)…
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expands the alveoli and exchanges with alveolar air
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when inspiring air above the FRC…
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expiration is passive due to elastic recoil of the chest wall and alveoli
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expiration that utilizes the ERV…
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requires active contraction of the expiratory muscles
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what are the most important muscles involved in raising the rib cage?
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external intercostals
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other muscles that help in raising the rib cage are…
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the sternocleidomastoid - lift upward on the sternum; anterior serrati - which lift many of the ribs; scaleni - which lift the first two ribs
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which muscles pull the rib cage downward during expiration?
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abdominal recti - pull downward on the lower ribs at the same time that they and other abdominal muscles also compress the abdominal contents upward against the diaphragm; internal intercostals
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after expiration of a tidal breath…
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the pressure in the alveoli is equal to the ambient atmospheric pressure
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what happens when air is drawn into the airway when the thoracic cavity expands?
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a negative pressure in the alveoli is created
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what is the outer membrane of the lung, basically the inner lining of the thoracic cavity?
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parietal pleura
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where does lymphatic fluid fill?
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the very thin space between the parietal and visceral pleura
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visceral pleura has elastic elements that collapse the lung and exert an inward force that must be overcome by…
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the inspiratory muscles to prevent collapse
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inspiratory muscles to prevent collapse…
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exert an outward force called pleural pressure
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at the FRC, the pleural pressure is opposed by the relaxed thoracic muscles so…
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there is no difference between alveolar air pressure and external atmospheric pressure
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what is the recoil pressure that tends to collapse the lung?
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the transpulmonary pressure
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a tidal inspiration generates an additional…
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neg. 2.5 cm H2O pressure as inspiratory muscles contract; this generates neg. 7.5cm H2O pleural pressure and neg. 2.5cm H2O negative alveolar pressure
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when inspiratory muscles relax…
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recoil of elastic elements generates positive pressure to expire alveolar air to FRC; transpulmonary pressure can be seen as postive pressure
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summary of inspiration:
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1. lungs tend to collapse, +5 cm H20 2. chest wall exerts pressure to prevent collapse, -5 cm H2O at FRC 3. expansion of chest wall pulls against the recoil pressure of the lungs at pleural an additional -2.5 cm H2O will fill the lungs with a tidal volumepressures more negative than than -5 cm H2O
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what is the mediastinum?
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the compartment between the lungs
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collapsed lung:
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1. lungs tend to collapse, +5 cm H20 2. chest wall exerts pressure to prevent collapse, -5 cm H2O at FRC 3. open chest wounds or surgical procedures produce pneumothorax (air in the chest) that can lead to collapse of one or both lungs
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what is lung compliance?
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the amount of filling per unit of pressure gradient
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what 4 common diseases affect Va and affect ventilation?
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1. asthma: airway smooth muscle constricts, increases airway resistance and thus Va 2. pulmonary fibrosis: loss of elastic elements of alveoli 3. emphysema: fusion of alveoli due to smoking or other irritation 4. respiratory distress syndrome: present in premature infants; lack of surfactin reduces alveolar compliance
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Even with large pressure, very little inspiration occurs because…
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the biggest factor in compliance (2/3) is the surface tension of the thin layer of fluid lining the alveoli
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the surface tension is overcome by…
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surfactant which lowers the surface tension of this fluid layer and greatly increases compliance
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surfactant is made by…
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type II alveolar cells in late gestation so premature infants may be lacking it and experience respiratory distress syndrome
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what does surfactin do?
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it’s a mixture of compounds that reduce the surface tension of the fluid layer lining the alveolar air space
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without surfactin…
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compliance is greatly reduced and ventilation is very difficult; especially for newborns with weak inspiratory muscles
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in emphysema…
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the alveolar divisions are lost and the airspace is expanded; the elasticity of the alveolar wall is lost
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in emphysema…
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lungs are more compliant but gas exchange is greatly reduced and expiration is difficult
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asthma results from…
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airway constriction and lung compliance is near normal
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in asthma…
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airway smooth muscle is constricted by parasympathetic stimulation or by various allergens/toxins
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what relaxes airway smooth muscle constriction in asthma?
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relaxed by sympathetic neurotransmitters binding to Beta2 receptors
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how can obstructive pulmonary disease be evaluated?
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by measuring the percentage of a forced vital capacity expired in one second
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gas exchange BIG picture:
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oxygen is loaded and CO2 is unloaded at the respiratory surface; oxygen is delivered and CO2 is removed; the immediate function of the systemic circulation is respiratory gas exchange with the tissues
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alveolar ventilation mixes…
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fresh air with residual air
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oxygen in alveolar air must….
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become dissolved in the fluid layer and diffuse into blood as a solute
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CO2 must also…
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diffuse from the bloos to the alveolar air and be expired
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the gas phase is exchanged by…
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alveolar ventilation
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gases are dissolved in blood according to…
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partial pressure gradient and solubility
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alveolar ventilation is regulated…
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to maintain a relatively constant partial pressure for O2 and CO2
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as air enters the airway, it becomes humidified…
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which decreases the PO2
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in the alveoli, O2 delivery to the blood and CO2 delivered by the blood…
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lower PO2 and increase PCO2
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increased Va will cause
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a reduction of blood PCO2 - hypocapnia
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decreased Va will cause
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a reduction in PO2 - hypoxia and an increase in PCO2 - hypercapnia
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functional residual capacity is…
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2300-2400 ml
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each tidal breath will exchange…
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350 ml of fresh air
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the composition of the alveolar air remains relativley constant as long as…
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Va matches the requirement of the body for oxygen delivery and CO2 removal
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to regulate alveolar gas composition during exercise…
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Va will increase as vital capacity becomes utilized
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when tidal breath is expired…
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the first volume is dead space; then mixed alveolar and dead space, and the last half of the tidal volume is the alveolar air
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Fick's law:
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flux (ml/min) = -D x A x dc/dx
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D…
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diffusion coefficient: more soluble solutes and gases diffuse more rapidly
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A…
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area: local factors increase capillary perfusion with increased activity
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dc/dx…
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slope = dc/dx; the steeper the slope, the greater the rate of diffusion
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CO2 is about 20 times more soluble than O2…
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thus it has a much greater diffusion coefficient so therefore a much smaller partial pressure gradient can result in a net flux equivalent to that of O2
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systemic arterial PO2 is…
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lower than alveolar PO2 even though alveolar capillary blood equlibrates with alveolar air
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what is an anatomical shunt?
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venous blood with a reduced PO2 mixes with pulmonary blood from the alveoli; lung tissue consumes oxygen as well and has its won arterial branch from the aorta
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mixing of oxygen depleted blood with oxygen rich blood…
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lowers systemic arterial PO2 below that of alveolar PO2
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physiological shunts include…
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patent ductus arteriosus and cardiac septal defect
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the amount of air exchanged in the alveoli is termed…
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alveolar ventilation (Va) and is calculated as ventilation rate x alveolar volume
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the rate of pulmonary blood flow is…
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5000 ml/min - systemic blood flow
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at any given time there is…
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500 ml of blood in the lungs (10% of total)
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under resting conditions…
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there is about 70 ml of blood in the alveolar capillaries
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the stroke volume at rest is about…
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70 ml/beat; thus the alveolar capillary blood is replaced about once per second
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what ratio is important for maintaining the alveolar (and arterial gas) composition constant?
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Va/q
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pulmonary embolism…
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can reduce blood flow to the lungs
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as the body's oxygen demand changes, what is adjusted to maintain constant PO2 and PCO2 in the alveoli?
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alveolar ventilation
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dorsal respiratory group (inspiration)…
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is responsible for tidal "quiet" breathing; passive expiration
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the vagus and glossopharyngeal nerves…
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stretch receptors (Hering-Breuer reflex) and chemoreceptors (brain; carotid and aorta)
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pneumotaxic center…
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regulates depth of inspiration; high output increases frequency
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ventral respiratory group (expiration and inspiration)…
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increased Va with exercise
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the respiratory center in the medulla has…
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spontaneously active "pattern generator" nerves that give rise to the intrinsic breathing rhythm of the respiratory muscles
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what in the brain, aorta, and carotid arteries detect changes in blood composition and stimulate or inhibit the intrinsic pattern?
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sensory neurons
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pattern generator neurons in the respiratory center generate…
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a "ramp" signal from inspiratory neurons
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if all inputs to the respiratory center are cut off…
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the pattern of breathing follows the intinsic ramp signal from the inspiratory neurons
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during normal breathing the intrinsic ramp signal is modified by…
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inputs from the lungs, higher brain centers, and chemoreceptors
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intrinsic breathing rhythm is controlled by…
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stretch receptors in the lungs (Hering Breuer reflex)
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cutting inputs from these receptors will produce…
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deeper levels of inspiration
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ventilation is also controlled by blood gas composition…
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pH snesitive neurons are located in the medulla; the most sensitive chemosensory neurons detect a lowering of pH due to an increase in PCO2
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what detects elevated PCO2 and lowered pH?
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chemosensitive neurons in the medulla
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the CSF is less well buffered so…
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a change in PCO2 will produce a greater reduction in pH
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what is cheyne-stokes breathing?
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occurs in patients with reduced blood flow that can lead to a delayed transport of blood from the lungs to the brain; this allows brain PCO2 to rise and cause a burst of ventilation that breathing is episodic with periods of apnealowers PCO2 and ventilation
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a small increase in arterial PCO2…
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will lower the pH of the CSF bathing chemosensitive cells of the medulla and stimulate Va
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a small increase in arterial PCO2…
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will also cause a large increase in ventilation and thus lower sensitivity during sleep which can cause sleep apnea
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hyperventilation…
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lowers alveolar and thus arterial PCO2
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during hyperventilation…
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suppression of the "inspiratory drive" via the pH-sensitive neurons occurs
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a given degree of reduction of PO2 below 40 mm Hg results in…
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a greater amount of O2 unloading to support increased metabolic activity
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the hemoglobin molecule…
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is a tetramer of 2 alpha-beta dimers
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what results in progressively greater O2 affinity to hemoglobin?
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subunit interaction between the alpha-beta dimers plus rotation of the two alpha-beta dimers; O2 is loaded until near saturation where affinity is reduced
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the affinity of the hemoglobin for O2 is measured…
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as the partial pressure at which the hemoglobin is half saturated = P50
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lower the P50…
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the greater the affinity
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hemoglobin (Hb)…
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is located in rbcs and is able to bind 1.34 ml O2/gram
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what is the normal Hb level in the blood?
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15 g/100 ml which gives an O2 binding capacity of 20 ml O2/100 ml of blood
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hemoglobin is almost completely saturated at…
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alveolar PO2
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CO2 produced by the tissues produces H+ which causes…
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decreased affinity to increase O2 unloading
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lowering the pH from 7.4 to 7.2 results in…
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the release of O2 from oxyhemoglobin
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what other 2 factors favor unloading?
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increasing temperature and the presence of 2,3 bisphosphoglycerate (BPG)
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what is the regulation of oxygen binding by hydrogen ions called?
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Bohr effect
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funcitonally, the Bohr effect facilitates…
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O2 loading at the lungs and unloading at the tissues
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H+ arising from dissociation of H2CO3…
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binds to Hb to decrease O2 affinity and facilitate O2 unloading and delivery to the tissues
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what is the chloride shift?
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HCO3- leaves the rbc in exchange for Cl- entry
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low PCO2 in alveolar air shifts equilibrium which associates H+ and HCO3- which…
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then raises pH and increases O2 affinity to facilitate O2 loading by Hb
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fetal hemoglobin has a steeper slope indicating…
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a greater affinity so the fetus can load oxygen from the maternal circulation
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fetal rbcs have a higher oxygen affinity than maternal rbcs because…
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fetal hemoglobin does not bind 2,3-BPG as well as maternal hemoglobin does
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myoglobin…
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is found in red (skeletal) muscle and permits O2 storage; a monomer which has a high O2 affinity which allows oxygen transfer to tissues
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what else has high affinity to hemoglobin with often lethal results?
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carbon monoxide, CO, with hemoglobin
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what 3 forms is CO2 carried by the blood?
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dissolved, carbamino CO2, and as bicarbonate
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in which form is CO2 most carried in?
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bicarbonate
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what is the Haldane effect?
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the unloading of O2 at the tissues which facilitates the formation of carboxy hemoglobin (HBCO2)
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hyperventilation…
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lowers alveolar PCO2 and thus the PCO2 returning to the heart and systemic circulation = hypocapnia
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as with O2 loading, CO2 is…
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unloaded at the alveoli and comes to equilibrium with the alveolar PCO2
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the [H+] in the cytosol is how many times greater than that of the plasma and ECF?
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2.5x
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what does an increase in PCO2 result in?
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carbonic acid formation and acidosis
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the concentration of H2CO3 is a direct function of…
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PCO2
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PCO2 and thus the carbonic acid concentration is regulated by…
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alveolar ventilation
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increased Va will…
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decrease ECF PCO2 and reduce the concentration of carbonic acid in the plasma
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at high altitude…
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the ambient PO2 declines so that alveolar PO2 is depressed and respiration becomes driven by O2 demand
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at high altitude, hyperventilation to get sufficient O2…
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reduces PCO2 so PO2 is the primary factor that stimulates Va
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