Anatomy of the Lung

Overview

• Base — rests on the diaphragm
• Apex — projects above rib I into the root of the neck
• Two surfaces — costal (adjacent to ribs/intercostal spaces) and mediastinal (against the mediastinum and vertebral column)
• Three borders — inferior (sharp, separates base from costal surface), anterior (sharp), and posterior (smooth and rounded)

Lobes and Fissures

Right Lung — 3 lobes, 2 fissures

• Superior (upper) lobe — anterolateral thoracic wall, apex into neck
• Middle lobe — anteroinferior (unique to right lung)
• Inferior (lower) lobe — posterior and inferior thoracic wall

Left Lung — 2 lobes, 1 fissure

• Superior lobe — anterolateral wall, with the lingula projecting as a tongue-like extension over the cardiac notch
• Inferior lobe — posterior and inferior wall
• Cardiac notch — concavity on medial surface due to heart projection into left pleural cavity

Hilum and Root

• 1 pulmonary artery (superior at hilum)
• 2 pulmonary veins (inferior at hilum)
• Main bronchus (somewhat posterior)
• Bronchial vessels, nerves, lymphatics

On the right, the lobar bronchus to the superior lobe branches from the main bronchus within the root and lies superior to the pulmonary artery. On the left, it branches within the lung.

Bronchial Tree

1. Main (primary) bronchi → enter hilum
2. Lobar (secondary) bronchi → one per lobe
3. Segmental (tertiary) bronchi → each supplies a bronchopulmonary segment

Bronchopulmonary Segments

Blood Supply

Pulmonary (Functional) Circulation

• Pulmonary arteries — carry deoxygenated blood from the right ventricle to the lungs for gas exchange
• Pulmonary veins (2 per side) — return oxygenated blood to the left atrium

Bronchial (Nutritive) Circulation

• Right bronchial artery — usually from the 3rd posterior intercostal artery
• Left bronchial arteries (×2) — arise directly from the thoracic aorta at T5 level and below the left bronchus
• Bronchial arteries run on posterior surfaces of bronchi supplying pulmonary tissue

• Partly into pulmonary veins / left atrium
• Right side → azygos vein; Left side → superior intercostal vein or hemiazygos vein

Innervation

Lymphatic Drainage

1. Superficial (subpleural) plexus → around the margins of the lung → bronchopulmonary nodes at the hilum
2. Deep (peribronchial) plexus → along the bronchi → pulmonary nodes within the lung → bronchopulmonary (hilar) nodes → tracheobronchial nodes → right and left bronchomediastinal trunks

Cellular Architecture of the Airway (Microscopic)

Clinical Correlates

• Foreign body aspiration → tends to lodge in the right lower lobe (wider, more vertical right main bronchus)
• Cardiac notch on left lung → used in pericardiocentesis approach
• Lingula of left lung → left-sided equivalent of right middle lobe; commonly affected in aspiration
• Bronchopulmonary segments → basis for surgical segmentectomy and bronchoscopic localization of lesions
• Phrenic nerve (anterior to root) vs vagus nerve (posterior to root) — important in thoracic surgery

Embryology of the Lung

Origin

Initial Specification (~Week 4)

• At ~week 4 (Carnegie Stage 10), a cluster of Nkx2-1 (TTF-1 / thyroid transcription factor-1)-expressing cells in the ventral foregut endoderm become specified as respiratory progenitors — the earliest known marker of the respiratory lineage
• WNT signaling (WNT2 and WNT2B from foregut mesoderm; β-catenin in endoderm) is critical for specification — loss of canonical WNT signaling prevents Nkx2-1 expression and lung formation
• The respiratory diverticulum appears as a ventral outpouching of the foregut
• The tracheoesophageal septum forms, dividing the trachea (ventral) from the esophagus (dorsal)
  • Failure → tracheoesophageal fistula (TEF) ± esophageal atresia (~1 in 3,500 live births)

Five Stages of Lung Development

Stage 1 — Embryonic (Weeks 4–7)

• Left and right lung buds bud from the posterior respiratory primordium into the surrounding mesenchyme
• Left-right asymmetry is already specified at this stage (as part of visceral situs determination)
• Pleural cavities begin separating from pericardial and peritoneal spaces by week 3
• All lung lobes become enclosed in pleura (mesothelium — a thin squamous epithelial layer)
• Lung buds rapidly elongate and initiate branching as they transition to the next stage

Stage 2 — Pseudoglandular (Weeks 5–17)

• Named for the gland-like histologic appearance: epithelial tubules separated by thick mesenchyme
• The lung bud undergoes branching morphogenesis → main bronchi → lobar bronchi → segmental bronchi → terminal bronchioles (all 23 generations of conducting airways established by week 16)
• Key molecular drivers of branching:
  • FGF10 (fibroblast growth factor 10) from mesenchyme → signals through FGFR2b on epithelium → stimulates bud outgrowth
  • Sprouty genes (Spry1, Spry2) act as negative feedback inhibitors of FGF signaling to shape branching pattern
  • BMP4 at bud tips restricts branching
  • Wnt7b in epithelium → maintains airway smooth muscle differentiation
• Proximal epithelial cells are tall columnar; distal cells are cuboidal
• Vasculature branches in parallel with the epithelium; smooth muscle cells surround developing airways and vessels
• No gas exchange possible at this stage — acini not yet formed
• Clinical note: Arrest here → congenital pulmonary airway malformation (CPAM), bronchogenic cysts, pulmonary sequestration

Stage 3 — Canalicular (Weeks 16–28)

• Airway branching is nearly complete
• Epithelial acini appear at the distal ends of terminal bronchioles
• Terminal bronchioles divide into respiratory bronchioles → alveolar ducts
• Vasculature becomes abundant and closely apposed to the epithelium (primitive air-blood barrier begins to form)
• Mesenchyme becomes progressively thinner between epithelial tubules
• Type I (AT1) and Type II (AT2) alveolar epithelial cells begin to differentiate:
  • AT1 cells: flat, squamous; cover ~95% of alveolar surface; responsible for gas exchange
  • AT2 cells: cuboidal; produce surfactant (begin appearing in late canalicular stage)
• Gas exchange becomes theoretically possible from the late canalicular phase (~24–26 weeks)
• Viability threshold: Premature infants ≥22–25 weeks may be viable; AAP defines lower limit at 22 weeks

Stage 4 — Saccular (Weeks 26–36 / Terminal Sac Phase)

• Primitive saccules develop at the distal ends of the bronchial tree — wide-lumen, thin-walled structures lined by AT1 and AT2 cells
• AT1 cell differentiation increases air space size; fusion of epithelial and endothelial basal laminae brings AT1 cells and capillaries into close contact → primitive alveolo-capillary barrier
• AT2 cells (Type II pneumocytes) produce and secrete surfactant — a lipoprotein complex that lowers alveolar surface tension and prevents collapse during expiration
  • Surfactant = phospholipids (predominantly DPPC) + surfactant proteins (SP-A, B, C, D)
  • SP-B and SP-C are critical for surface tension reduction
• Vasculature has fully invested the lung parenchyma
• Gas exchange sufficient for immediate postnatal survival is now possible

Respiratory Distress Syndrome (RDS): Premature birth before adequate surfactant production causes alveolar collapse, hypoxia, and respiratory failure. Management: antenatal betamethasone (<34 weeks) to accelerate surfactant production; postnatal exogenous surfactant replacement; CPAP/ventilatory support.

Stage 5 — Alveolar (Week 36 → Early Childhood, ~8 years)

• Secondary septation: primitive saccule walls develop secondary septa (crests) that subdivide them into true alveoli, dramatically increasing gas-exchange surface area
  • At birth: ~50 million alveoli
  • Adult: ~300–500 million alveoli
  • Total surface area at maturity: ~70 m²
• Septa form, lengthen, and thin as the interstitial fibroblasts lay down elastin and collagen scaffolding
• The alveolar surface area continues to grow postnatally through multiplication of alveoli (predominantly 0–2 years) and then through alveolar enlargement with lung volume growth

Alveolar Structure at Maturity

Key Molecular Signals Summary

Congenital Abnormalities by Stage

Embryology of the Lung

Origin

• Endoderm → respiratory epithelium
• Mesoderm → smooth muscle, vessels, cartilage, pleura
• Ectoderm → innervation

Five Developmental Stages

Alveolar Cell Types (at maturity)

Key Molecular Drivers

Surfactant & RDS

• Surfactant = phospholipids (mainly DPPC) + proteins SP-A, SP-B, SP-C, SP-D
• Produced by AT2 cells starting in the saccular phase
• SP-B and SP-C are essential for surface tension reduction
• Deficiency in premature neonates → Respiratory Distress Syndrome (RDS)
• Prevention: antenatal betamethasone (<34 weeks gestation)
• Treatment: postnatal exogenous surfactant + CPAP/ventilation