GA

Respiratory System Flashcards

Morphogenesis

  • Begins at 4 weeks gestation.

  • Respiratory diverticulum (lung bud) develops from the foregut.

  • Development induced by retinoid acid (RA), which upregulates TBX4.

  • Originates from the endoderm germ layer, forming the epithelial lining.

  • Splanchnic mesoderm contributes cartilage, muscle, and connective tissues.

Separation from Foregut

  • Tracheoesophageal ridges form and fuse into the tracheoesophageal septum.

  • Divides the foregut into:

    • Dorsal esophagus.

    • Ventral trachea.

  • Maintains connection via the laryngeal orifice.

Clinical Correlation: Tracheoesophageal Fistula (TEF) and Esophageal Atresia (EA)

  • Associated with VACTERL anomalies.

  • Symptoms:

    • Polyhydramnios.

    • Excessive oral fluids at birth.

Development of the Larynx

  • Lined by endoderm, but muscles and cartilage originate from the 4th and 6th pharyngeal arches.

  • Changes from slit to T-shaped orifice.

  • Forms thyroid, cricoid, and arytenoid cartilages.

  • Innervated by branches of the vagus nerve (X).

  • Lung bud differentiates into the trachea and primary bronchial buds.

Week 5 Development

  • Buds become primary bronchi.

  • Right primary bronchus → 3 secondary bronchi (3 lobes).

  • Left primary bronchus → 2 secondary bronchi (2 lobes).

Lung Expansion and Pleura Formation

  • Lungs grow into pericardioperitoneal canals.

  • Pleuropericardial folds form and separate body cavities.

  • Mesoderm forms:

    • Visceral pleura.

    • Parietal pleura.

Bronchial Branching and Positioning

  • Up to 17 divisions by week 24.

  • Final shape continues after birth.

  • Right lung → 10 segments, left lung → 8 segments.

  • Regulated by FGF signaling.

Maturation of the Lungs

  • Pseudoglandular phase (5-16 weeks): Terminal bronchioles only.

  • Canalicular phase (16-26 weeks).

  • Terminal sac phase (26 weeks - birth): Primitive alveoli form.

  • Alveolar phase (36 weeks - childhood): Mature alveoli develop.

Role of Surfactant

  • Produced by type II alveolar cells from 24 weeks.

  • Reduces surface tension.

  • Essential for lung inflation after birth.

  • Surfactant increases sharply after week 34.

Initiation of Labor – Fetal Signals

  • Surfactant in amniotic fluid activates macrophages.

  • Release of IL-1β triggers prostaglandin production → uterine contractions.

First Breath and Postnatal Growth

  • Lung fluid resorbed during delivery.

  • Surfactant remains on alveoli.

  • Air replaces fluid, forming the blood-air barrier.

  • Approximately 1/6 of alveoli are present at birth; new alveoli form until about 10 years old.

Clinical Correlation: Respiratory Distress Syndrome (RDS)

  • Caused by surfactant deficiency, leading to alveolar collapse (atelectasis).

  • Common in preterm infants.

  • Treatment:

    • Artificial surfactant.

    • Maternal corticosteroids (pre-delivery) to mature alveoli.

Histology of the Respiratory Tract

Embryological Origins

  • Development from the laryngotracheal diverticulum.

  • Endodermal epithelium, mesenchymal support structures.

  • Branching morphogenesis: lung bud → bronchial tree.

Conducting Portion

  • Structures: Nasal cavity to terminal bronchioles.

  • Functions: Air conditioning (warming, moistening, filtering).

Nasal Cavity Regions

  • Vestibule (skin + vibrissae).

  • Respiratory region (respiratory epithelium).

  • Olfactory region (specialized sensory epithelium).

Respiratory Epithelium Cell Types

  • Ciliated columnar cells (mucus transport).

  • Goblet cells (mucus production).

  • Brush cells (sensory chemoreceptors).

  • Small granule (Kulchitsky) cells – DNES.

  • Basal cells (stem cells).

Lamina Propria Functions

  • Vascular loops for heat exchange.

  • Seromucous glands for moisture and trapping particles.

  • Immune cells: γδ T cells, macrophages, mast cells.

Olfactory Region: Structure and Function

  • Olfactory receptor neurons (CN I).

  • Supporting (sustentacular) cells.

  • Bowman’s glands: Serous secretions.

  • Basal cells: Regeneration.

COVID-19 and Anosmia

  • Affects supporting cells via ACE2/TMPRSS2, causing reversible damage.

Paranasal Sinuses

  • Air-filled spaces with respiratory epithelium.

  • Function: Voice resonance, mucus drainage, lightens head.

Pharynx Histology

  • Nasopharynx and oropharynx: Stratified squamous or ciliated epithelium.

  • Lymphoid tissue: Pharyngeal tonsil, immune defense.

Transition to Respiratory Epithelium

  • Terminal bronchioles → respiratory bronchioles.

  • Alveolar ducts, sacs, and alveoli.

  • Site of gas exchange.

Histology of Respiratory System

  • Three main functions: Air conduction, air filtration, gas exchange.

Air Passage of the Respiratory System

  • Nasal cavities: Two large air-filled spaces in the uppermost part of the respiratory system.

  • Nasopharynx: Lies behind the nasal cavities and above the soft palate, communicates inferiorly with the oropharynx.

  • Larynx: Hollow tubular organ containing the cartilaginous framework responsible for producing sounds.

  • Trachea: Flexible air tube extending from the larynx to the thorax, serves as a conductor of air. In the mediastinum, it bifurcates into paired main bronchi.

  • Paired main (primary) bronchi: Enter the root of the right and left lung.

Respiratory Portion: Where Gas Exchange Occurs

  • Respiratory bronchiole: Involved in both air conduction and gas exchange.

  • Alveolar ducts: Elongated airways that connect the respiratory bronchioles to the alveolar sacs.

  • Alveolar sacs: Spaces surrounded by clusters of alveoli.

  • Alveoli: Terminal respiratory unit where gas exchange primarily occurs.

  • Nasal cavities: Paired chambers separated by a bony and cartilaginous nasal septum.

  • Elongated spaces with a wide base (arid and soft palate) and a narrow apex (toward the anterior cranial fossa).

  • Skeletal framework: Bones and cartilages.

Chambers Divided into Three Regions

  • Nasal vestibule: Dilated space of the nasal cavity just inside the nostrils, lined by skin.

  • Respiratory region: The largest part (inferior two-thirds) of the nasal cavities, lined by respiratory mucosa.

  • Olfactory region: Located at the apex (upper one-third) of each nasal cavity, lined by specialized olfactory mucosa.

Bronchi Anatomy and Division

  • Tracheal bifurcation into right and left bronchi.

  • Differences between right (wider, shorter) and left bronchi.

  • Lobar divisions:

    • Right: 3 lobes, 10 segments.

    • Left: 2 lobes, 8 segments.

  • Bronchopulmonary segments:

    • Significance in surgical resection.

    • Independent blood supply and connective tissue septa.

Histological Structure of Bronchi

  • Cartilage rings replaced by irregular cartilage plates.

Layers of Bronchial Wall

  • Mucosa (pseudostratified epithelium).

  • Muscularis (smooth muscle).

  • Submucosa (connective tissue, glands).

  • Cartilage layer (decreasing cartilage plates).

  • Adventitia (connective tissue continuity).

Bronchioles

  • Subdivision into pulmonary lobules and acini.

Histology of Bronchioles

  • No cartilage or glands.

  • Epithelial changes: Pseudostratified to cuboidal.

  • Presence and role of club cells.

Club Cells

  • Structure and secretory functions.

  • Clinical relevance (COPD, asthma biomarkers).

Respiratory Bronchioles

  • Transition zone for air conduction and gas exchange.

  • Presence of alveolar outpocketings.

Alveoli Function

  • Main site of gas exchange.

  • Large surface area ( \approx 75m^2) for efficient gas exchange.

Histology of Alveoli

  • Structure of alveolar ducts and alveolar sacs.

  • Composition and role of the interalveolar septum.

Type I Alveolar Cells

  • Thin squamous cells.

  • Major role in forming the air-blood barrier.

Type II Alveolar Cells

  • Cuboidal secretory cells.

  • Secretion of surfactant, progenitor cells for type I cells.

Alveolar Surfactant

  • Composition and synthesis: DPPC.

  • Prevents alveolar collapse.

  • Clinical implications (Respiratory Distress Syndrome).

Surfactant Proteins

  • SP-A: Surfactant regulation and immunity.

  • SP-B and SP-C: Formation of surfactant film.

  • SP-D: Immune defense.

Alveolar Macrophages

  • Removal of particulate matter and pathogens.

  • Role in diseases.

Collateral Air Circulation

  • Significance of alveolar pores (Kohn’s pores).

  • Clinical importance in obstructive lung disease.

Pulmonary and Bronchial Circulations

  • Gas exchange vs. nutritional supply.

  • Circulation pathways and anastomosis.

Lymphatic Drainage of the Lungs

  • Dual lymphatic pathways.

  • Important lymph node groups (bronchopulmonary, tracheobronchial).

Nervous Supply of the Respiratory System

  • Autonomic nervous system effects.

  • Control of airway diameter and glandular secretions.

Clinical Correlation: Cystic Fibrosis

  • Chronic obstructive pulmonary disease of children and young adults.

  • Autosomal recessive disorder with a mutation in the CFTR gene (Cystic Fibrosis Transmembrane Conductance Regulator) on chromosome 7.

  • Abnormal epithelial transport of Cl- affects the viscosity of secretions.

Clinical Correlation: COPD

  • Pathophysiology and genetic factors (alpha 1-antitrypsin deficiency).

Clinical Correlation

  • Inflammation causes and stages → red hepatization, gray hepatization.

COVID-19 Respiratory Effects

  • SARS-CoV-2 mechanisms (ACE2 receptors).

  • Pathology (diffuse alveolar damage, vascular complications).

Anatomy of Pleura and Mediastinum

Pleura

  • Serous membrane covering lungs and thoracic cavity.

    • Visceral pleura: Covers lung surface.

    • Parietal pleura: Lines thoracic cavity walls.

  • Continuous at the lung hilum.

Parietal Pleura Subdivisions

  • Costal pleura: Inner ribs and intercostal spaces.

  • Diaphragmatic pleura: Covers the diaphragm.

  • Mediastinal pleura: Lateral mediastinum.

  • Cervical pleura: Dome over lung apex (cupula).

Innervation and Pain Perception

  • Parietal:

    • Somatic innervation (intercostal and phrenic nerves).

    • Sensitive to pain, pressure, and temperature.

  • Visceral:

    • Autonomic innervation (pulmonary plexus).

    • Insensitive to pain.

Pleural Capacity and Recess

  • Space between pleural layers with lubricating fluid.

  • Costodiaphragmatic recess: Common fluid collection site.

  • Costomediastinal recess: Near the anterior mediastinum.

Clinical Case: Pneumothorax

  • Definition: Air in the pleural cavity → lung collapse.

  • Types: Spontaneous, traumatic, tension.

  • Signs/symptoms: Sudden chest pain, dyspnea, absent breath sounds.

Clinical Case: Pleural Effusion

  • Definition: Fluid in the pleural space.

  • Types: Transudate (CHF), exudate (infection, malignancy).

  • Diagnosis: Dullness to percussion, meniscus sign on CXR.

Mediastinum

  • Central thoracic compartment between pleural sacs.

  • Extends from the thoracic inlet to the diaphragm.

  • Divided by the sternal angle (T4-T5) into superior and inferior (anterior, middle, posterior) regions.

Superior Mediastinum

  • Borders: Thoracic inlet to the sternal angle.

  • Contents: Thymus, aortic arch, brachiocephalic veins, trachea, esophagus, vagus and phrenic nerves, thoracic duct.

Anterior Mediastinum

  • Location: Between the sternum and pericardium.

  • Contents: Thymic remnants, fat, lymph nodes, small vessels (internal thoracic branches).

Middle Mediastinum

  • Location: Central compartment.

  • Contents: Heart, pericardium, ascending aorta, pulmonary trunk, SVC, pulmonary veins, tracheal bifurcation, main bronchi, phrenic nerves.

Posterior Mediastinum

  • Location: Behind the pericardium and heart.

  • Contents: Esophagus, descending thoracic aorta, thoracic duct, azygos and hemiazygos veins, vagus nerves, sympathetic chains.

Clinical: Mediastinal Masses

  • Anterior: Thymoma, thyroid mass, teratoma, lymphoma.

  • Middle: Lymphadenopathy, bronchogenic cysts.

  • Posterior: Neurogenic tumors (Schwannoma, neuroblastoma).

Clinical: Mediastinitis

  • Inflammation of the mediastinum.

  • Causes:

    • Acute: Post-surgical, esophageal perforation.

    • Chronic: TB, histoplasmosis.

  • Symptoms: Chest pain, fever, widened mediastinum on imaging.

Histology of Upper Airway: Larynx and Trachea

Larynx

  • Connects oropharynx to the trachea.

  • Functions: Airway passage and phonation.

  • Composed of hyaline and elastic cartilage.

Laryngeal Anatomy

  • Epiglottis, arytenoid cartilages.

  • Joints, ligaments, and intrinsic muscles.

Laryngeal Folds

  • Ventricular folds (false vocal cords): Upper, immobile.

  • Vocal folds (true vocal cords): Lower, mobile.

  • Ventricle between them.

Vocal Folds and Sound

  • Contain vocalis muscle and ligament.

  • Vibrate to produce sound.

  • Controlled by intrinsic/extrinsic muscles.

Phonation Mechanics

  • Air passes through rima glottidis, causing vibration.

  • Tension increases pitch.

  • Modified by oral and nasal structures.

Ventricular Folds

  • Above ventricle.

  • Contribute to resonance, not phonation.

  • No muscle.

Clinical Correlation: Laryngitis

  • Acute: Viral infection.

  • Chronic: Smoking, pollutants.

  • Symptoms: Hoarseness, loss of voice.

Laryngeal Epithelium

  • Vocal cords and epiglottis: Stratified squamous.

  • Rest of larynx: Ciliated pseudostratified columnar.

Trachea

  • 2.5 cm wide, 10-12 cm long.

  • Extends from the larynx to the thorax.

  • Divides into main bronchi.

Tracheal Wall Layers

  • Mucosa.

  • Submucosa.

  • Cartilaginous layer.

  • Adventitia.

Cartilage Support

  • C-shaped hyaline cartilages.

  • Prevent collapse during expiration.

  • Trachealis muscle bridged open end.

Tracheal Epithelium

  • Ciliated pseudostratified columnar.

  • Cells: Ciliated, goblet, brush, basal, small granule.

Ciliated and Goblet Cells

  • Ciliated: 250 cilia per cell, mucociliary escalator.

  • Goblet: Mucinogen, increases in irritation.

Brush and Small Granule Cells

  • Brush: Chemosensory.

  • Small Granule: Endocrine function.

Basal Cells

  • Stem cell population.

  • Near basal lamina.

  • Replace other cell types.

Basement Membrane

  • Thick reticular lamina.

  • Thicker in smokers, asthmatics.

  • Below epithelium.

Lamina Propria and Submucosa

  • Loose connective tissue.

  • Contains BALT, immune cells.

  • Submucosal glands → glycoproteins.

Cartilage and Adventitia

  • 16 to 20 C-shaped rings.

  • May ossify with age.

Adventitia

  • Vessels and nerves.