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.