Respiratory system Brno, September 2019 Lecture 12 • Functions • Epithelial lining • Nasal cavity • Larynx • Pharynx • Trachea • Lungs + Bronchial tree • Blood-air barrier • Development of the respiratory system • Lung regeneration Non-respiratory functions: • synthesis, activation and inactivation of vasoactive substances, hormones, neuropeptides, eicosanoids, lipoprotein complexes. • hemostatic functions (thromboplastin, heparin) • lung defense: complement activation, leucocyte recruitment, cytokines and growth factors • speech, vomiting, defecation, childbirth Respiratory system – Functions Respiratory function supply of O2 + elimination of CO2 Respiration = overall exchange of gasses between atmosphere and cells Involves: • pulmonary ventilation • gas exchange: External + Internal respiration • gas transport Respiratory system – Overall composition Upper respiratory tract • nasal cavity • paransal sinuses • nasopharynx • oropharynx Anatomic Functional Lower respiratory tract • larynx • trachea • bronchi (extra- + intrapulmonary) • bronchioles (up to terminal) • respiratory bronchioles • alveolar ducts • alveolar sacs • alveoles Conducting portion Respiratory portion Conducting portion – General features Function • Transport • Moistening • Filtering • Warming Composition Bone and/or cartilage (mechanical support) Mucosal lining • Epithelium • Lamina propria Conducting portion – Nasal cavity + Paranasal sinuses Left + Right nasal cavity (separated by osseous/cartilagineous nasal septum) Nostril Superior concha Sphenoid sinus Internal naris Nasopharynx External naris Frontal sinus Middle nasal concha Inferior nasal concha Lining of the nasal cavity Roof + Superior concha Nostrils + Vestibule Remaing surfaces Olfactory epithelium Dermis • keratinizing squamous ep. • hairs • sweat + sebaceous glands • in vestibule transits to airway ep. Airway mucosa „respiratory“ Conducting portion – Nasal cavity + Paranasal sinuses Support: bone and/or cartilage No submucosa and/or hypodermis Olfactory region Respiratory region Nasal cavity - Airway musosa = respiratory mucosa – lines most of the conducting portion of the respiratory system Respiratory region Ciliated pseudotratified collumnar epithelium (min. 5 types of cells) Lamina propria mucosae • loose connective tissue • arterial and venous plexuses • many seromucinous glands • abundant lympoid elements (nodules, mast cells, plasma cells) Mucous layer Basal cells (stem cells) Ciliated cells (most abundant) Goblet cells (mucin) Brush cells (chemosensory) (similar to cells of taste buds) Small granule cells (Kulchitsky) DNES – diffuse neuroendocrine system Airway mucosa Vein Gland Pseudostartified epithelium Airway mucosa – Nasal concha (Concha nasi) Kisselbach plexus (nose bleeding) Airway mucosa - Epithelium Exposure to toxic compounds Squamous metaplasia • pseudostratified cilliated collumnar ep. changes to squamous stratified ep. • may develop into cell dysplasia (precancerous) Airway mucosa - Epithelium Ciliated cells Goblet cell Airway mucosa - Mucus Goblet cell Mucus • mainly glycoproteins in water • ensures moisturing od mucosa and air • contains IgA immunoglobulins (mucosal immunity) • traps airborne particles (dust etc) • helps selfcleaning of the airways - more watery - thicker, lubricating Airway mucosa - Mucus Airway mucosa - Mucus Cilia movement drives mucus towards pharynx. Speed of mucocilliary transport - 5 mm / minute. Airway mucosa - Mucus Macrophages in the mucus layer Nasal cavity – Vestibule (Vestibulum nasi) Location: 5 – 6 mm wide zone at the edge of nostrils Lining: transition of dermis to respiratory mucosa – hairs with sebaceous glands Nasal cavity – Olfactory epithelium Olfactory region Location: • rooof of the nasal cavity • superior aspect of nasal septum • superior concha Colour: yellow Size: approx. 7-10 cm2 Nasal cavity – Olfactory epithelium Pseudotratified collumnar epithelium • 70 – 100 mm thick • 3 types of cells Lamina propria mucosae • loose connective tissue • arterial and venous plexuses • axons of sensory cells • Bowman´s glands (tubular, branched, serous) Nasal cavity – Olfactory epithelium Olfactory cell Supporting cell (sustentacular) Basal cell • short basophilic • stem cells to supporting and olfactory cells (regeneration of neurons !!!) Basal cell Olfactory cell • bipolar neuron apical aspect – dendrite olfactory vesicle • 10-20 nonmotile cilia emerge from one vesicle • modified cilia contain the odorant receptors • basal aspect - axon Supporting cell (sustentacular) • striated border - microvilli • secretory granules • provide physical support + nourishement Nasal cavity – Olfactory epithelium Nasal cavity – Olfactory epithelium Bone underlying the olfactory region Unmyelinated nerve Large vein Bowman’s glands Nasal cavity – Olfactory epithelium Flipped upside down compared to all previous pictures !!! Axons of olfactory cells (Fila olfactoria) Passage through the cribriform plate Synapse with secondary neurons in the olfactory bulb (N. olfactorius) Nasal cavity – Paranasal sinuses (Sinus paranasales) • sinus maxillaris (15-25 cm3) • sinus ethmoidalis • sinus frontalis • sinus sphenoidalis Mucous lining • similar to airway mucosa • thinner • less glands • no sumbmucosa Nasopharynx (Pars nasalis pharyngis) + Oropharynx (Pars oralis pharyngis) Nasopharynx • pseudostratified cilliated columnar epithelium • tonsila pharyngea – infiltration of lamina propria by lymphocytes • entry of Eustachian tube Oropharynx • stratified squamous epithelium Junction of respiratory and digestive tracts Larynx Voicebox - responsible for phonation Larynx – Overall anatomy Shape of sand-glass Vestibule Ventricular folds (immovable) Vocal folds (movable) Intraglottic cavity Laryngeal ventricleConstriction = paired folds Frontal section Epiglottis Approx. 4 cm Larynx – Reinforecemnt Cartilages joint by ligaments and operated by muscles • Hyaline • Elastic Vocal folds Ventricular folds Inferior aspect Superior aspect Larynx Ventricular fold Vocal fold Laryngeal ventricle cartilage cartilage Epiglottis Larynx – Histology Ventricular fold (Plica ventricularis) Vocal fold (Plica vocalis) Vocal ligament (elastic) Vocal muscle (striated) No glands !!! Glands (seromucous) Stratified squamous ep. Pseudostratified ciliated collumnar ep. Larynx – Mucosal lining Ventricular fold Vocal fold Reinke´s oedema exudate in Reinke´s space = hoarse voice Larynx Transition of epithelia on inferior aspect of vocal fold Lamina propria mucosae M. vocalis Stratified squamous ep. Pseudostratified ciliated collumnar ep. Larynx - Epiglottis Lingual surfaceLaryngeal surface Stratified squamous ep. Pseudostratified ciliated collumnar ep. Trachea Conducting portion Extrapulmonary position Length approx.: 12 cm Diameter approx.: 2 cm • hyaline • 10 to 12 rings • C-shaped Tracheal cartilage Trachea - Crossection Annular ligaments Trachealis muscle Tracheal cartilage Airway epithelium Fibro-musculo-cartilaginous layer Trachea - Wall Esophagus Pseudostratified ciliated collumnar ep. Tracheal muscle Trachea Cartilage Cartilage Trachea - Wall Pseudostratified ciliated collumnar ep. Perichondrium Cartilage Lamina propria mucosae • fibroelastic connective tissue + lymphoid cells Submucosa • thick, dense fibroelastic connective tissue • numerous seromucous glands – Tracheal glands • rich blood and lymph supply Adventitia • fibroelastic connective tissue Esophagus Trachea Bronchial tree Primary bronchi – Extrapulmonary • the same structure as trachea • smaller diameter then trachea • accompanied by the pulmonary arteries, veins, and lymphatics Begins at bifurcation of trachea Bronchial tree 18 to 25 dichotomic divisions in total Right lungLeft lung 2 secondary bronchi – 2 lung lobes (Lobar bronchi) 3 secondary bronchi – 3 lung lobes (Lobar bronchi) Tertiary bronchi (Segmental bronchi) • total number of 10 • diameter about 8 mm • further ramification 8x - 10x Bronchopulmonary segment • about 10 % of lung • own vasculature • enclosed in fibrous capsula • used in surgery Medium + Small bronchi • diameter down to 1 mm • cartilage in their wall Primary bronchioles • diameter about 1 mm • no cartilage • one PB serve one pulmonary lobule Terminal bronchioles • 5 – 7 TB branched from one PB • diameter about 0,5 mm Pulmonary lobule • pyramidal shape • surrounded by very thin fibrous capsule • volume 1 – 2 cm3 DO NOT MIX !!! Bronchi macroscopic picture Bronchial tree – Bronchi (Lobar to Small) Diametr of bronchi • elastic fibres • smooth muscle • cartilage • glands • goblet cells • height of epithelium Mucosa • typical airway epithelium (or bilayered collumnar) • elastic fibers in lamina propria • bronchial glands in LP • BALT in LP (bronchi-associated lymphoid tissue) Submucosa • contains fewer glands • discontinuous layer of smooth muscle separates from lamina propria mucosae • muscle becomes more prominen in smaller size bronchi Fibrocartilaginous layer • cartilaginous plates Bronchus – Cartilaginous plates Trachea Bronchus Bronchus - Intrapulmonary CP CP CP CP Bronchus - Intrapulmonary Bronchus - Intrapulmonary Bronchioles - Primary + Terminal – General features Wall • mucosa + muscle layer (bundles) + elastic and colagen fibers • NO cartilage • NO glands Epithelial lining • simple collumnar to simple cuboidal ep. • many epithelial cells have cilia • NO Goblet cells • Club cells (formerly Clara cells) Club cells • dome-shaped • apex with microvili • secretions (antimicrobials, surfactant-like material) • P450 enzyme (detoxification) • stem cells to the area Bronchiole Alveole Alveole Alveole Alveole Bronchiole Alveoli Alveoli Bronchiole Blood vessel Epithelium Collagen fibers Muscle bundles Respiratory portion Respiratoryportion REMINDER Pulmonary lobule • defined by ONE primary bronchiole • Include 5 to 7 Terminal bronchioles • pyramidal shape • surrounded by very thin fibrous capsule • volume 1 – 2 cm3 Terminal bronchiole NO alveoli Respiratory bronchiole Outpocketing alveoli Respiratory portion Alveolar duct - wall made by: • groups of cuboidal cells • individual alveoli • elastic fibers • smooth muscle cells surrounding alveolar entries Atrium entry into alveolar sac Alveolar sac group of alveoles opened into common atrium Respiratory portion Respiratory portion Respiratory portion NO alveoli Some alveoli Terminal bronchiolus – NO connection into alveoli Terminal bronchiolus Alveolus Alveolus Alveolus Alveolus Alveolus Respiratory bronchiolus – openings into alveoli Respiratory bronchiolus AD - Alveolar duct AS – Alveolar sac A - Alveolus V – Vein PA – Perialveolar artery Alveoli Features • diameter approx. 200 mm • total number approx. 300 millions • total surface about 100 – 140 m2 • interalveolar septa (elastin + type III collagen) • alveolar pores (Kohn´s; 8 – 60 mm diameter) Continuous capillaries Place of gas exchange Alveoli Elastic fibers Capillary Alveolar macrophage – „dust cell“ • migratory • some migrate up to pharynx and get swallowed/expectorated • some migrate via lymph vessels • some become resident in lungs Type I Pneumocyte (membranous) • very flat – about 80 nm thickness • occluding junctions • about 95% of alveolar surface Type II Pneumocyte (granular) • cuboidal (10 mm) • more numerous than type I pneumocytes • lamellar bodies – surfactants SP-A, -B, -C, -D • stem cells to alveolar lining (type I and II pneu.) RDS (Respiratory Distress Syndrome of neonates) lack of surfactants in premature born - collapse of alveoli Alveoli - Surfactant Cytoplasm of type I pneumocyte Lumen of alveolus Alveoli - Surfactant Surfactant Alveoli – Macrophages Macrophages Alveoli – Interalvealar septum Alveoli – Blood-Air barrier Thickness: 0,1 – 1,5 μm Exchange of gasses: passively by diffusion based on gradient Nucleus of endothelial cell Surfactant layer Type I pneumocyte Fused basal laminae Endothelium Alveoli – Blood-Air barrier I - Type I pneumocyte II - Type II pneumocyte Alv - Alveolus Cap - Capillary Mac - Macrophage ac ac ac ap ap ap lv lv lv lv Alveoli – Blood-Air barrier Capilaries Type II pneumocyte Alveoli – Blood-Air barrier Erythrocyte Pleura Sheet that lines pleural cavities (left and right) Visceral pleura – covers the lungs Parietal pleura – lines cavity wall Visceral pleura Parietalal pleura Pleura Mesothelium (simple squamous ep.) Connective tissue (about 1 mm) Blood supply Pulmonary circulation „functional“ Bronchial circulation „nutritive“ Pulmonary artery Bronchial artery Bronchial capilaries Pulmonary vein Tertiary bronchus Bronchopulmonary segment Lung development Endoderm • epithelium • glands Mesenchyme • connective tissue • cartilage • muscles Early week 4: Respiratory (laryngotracheal) diverticulum of the foregut (ventral aspect) Lung development Late week 4 Early week 4 Early week 5 Intricate interactions with the surrounding mesoderm Insternal aspect of the ventral wall of the pharynx Lung development • Lumen first obliterate and then recanalize • Pharyngeal ventricle + Ventricular and Vocal plicas develop • Pharyngeal cartilages + Ligaments + Muscles develop (from 4. and 5. pharyngeal arch) Inside aspect of the ventral wall of the pharynx week 12week 6 Lung development – Further branching of bronchi Late week 6 Late week 5 Late week 8 Before birth - 18 x Total number of branchings After birth - 7x until 8 years of age Lung development – Development of pleuro-pericardial folds • by subsequent growth in caudal and lateral directions, the bronchial buds penetrate into primitive pleural cavities • the splanchnic mesoderm, which covers the outside of the lung, is transformed into the visceral pleura • the somatic mesoderm, covering the body wall from the inside, becomes the parietal pleura • the space between the parietal and visceral pleura is the pleural cavity Lung development – Lung histogenesis (maturation) Pseudoglandular period (week 5 to 17) • terminal bronchioles are formed • blindly ended terminal bronchioles - resemble gland • cuboidal epithelial lining (endodermal) • NO respiratory bronchioles and/or alveoli Canalicular period (week 13 to 25) • development of respiratory bronchioles, sacs, and vascularisation • respiration and survival is possible but only with intensive • still severe non-maturity Terminal sac period (week 24 to birth) • considerable increase of terminal sacs and alveoli with well differentiated pneumocytes • sufficiently formed blood-air barrier • since week 26 - survival without intervention is possible (fetal weight about 1000 g) Alveolar period (week 32 – 8 years) • longest period • development of lungs becomes finalized Thank you for your attention ! ahampl@med.muni.cz Building A1 – 1st floor