The Lungs: Detailed Overview

1. Overview and Essential Functions

1. Gas exchange (ventilation-perfusion matching) - delivering O2 to the body and removing CO2 produced by cellular metabolism.
2. Host defense - protecting against airborne pathogens, chemicals, and particulates.

• Murray & Nadel's Textbook of Respiratory Medicine, pp. 32-33

2. Gross Anatomy

Size and Weight

• In life, each human lung weighs approximately 450-500 g (total ~900-1000 g), of which nearly 40-50% is blood.
• At end-expiration (FRC), gas volume is about 2.5 L; at maximal inspiration (TLC), it may reach 6 L.
• Lung density varies from 0.30 g/mL at FRC to 0.14 g/mL at TLC - not uniform; ~1 g/mL near the hilum, ~0.1 g/mL peripherally.
• The height of the lungs at FRC is approximately 24 cm.

Shape and Position

• Pyramid-shaped, paired organs located in the thoracic cavity on either side of the mediastinum.
• Connected to the trachea by the right and left main bronchi.
• Inferiorly bordered by the diaphragm; enclosed by the pleurae which attach to the mediastinum.
• Suspended from the mediastinum by the lung root (a collection of structures entering and leaving each lung: main bronchus, pulmonary artery, two pulmonary veins, bronchial vessels, lymphatics, and nerves).

Lobes and Fissures

Surfaces and Borders

• Costal surface - convex, faces the ribs
• Mediastinal surface - concave medially, contains the hilum
• Diaphragmatic surface (base) - concave, rests on the diaphragm
• Apex - projects 2-3 cm above the clavicle into the neck

Bronchopulmonary Segments

• Right lung: 10 segments
• Left lung: 8-10 segments (some fused)

3. The Airway Tree

Trachea

• Cartilaginous and fibromuscular tube extending from the cricoid cartilage (~C6/C7) to the carina (~T4/T5).
• Bifurcates into right and left main bronchi at the carina.
• Right main bronchus: wider, shorter, more vertical (explains why foreign bodies and aspiration commonly go right).

Bronchi

• Mucosa (pseudostratified columnar ciliated epithelium)
• Lamina propria (with lymphoid tissue)
• Smooth muscle (spiral bands)
• Submucosa (seromucous glands between cartilaginous plates)
• Cartilaginous plates (provide structural rigidity)

Bronchioles

• No cartilage; wall maintained by smooth muscle.
• Terminal bronchioles: the last purely conducting airways; lined by ciliated pseudostratified to simple columnar epithelium, with club cells (formerly Clara cells) that produce a surface-active agent aiding lung expansion.
• Respiratory bronchioles: transitional airways where gas exchange begins; wall alternates between thick regions (club cell epithelium + smooth muscle) and thin alveolar regions.

Alveolar Ducts and Sacs

• Alveolar ducts: passages lined entirely by rows of alveoli; rings of smooth muscle in interalveolar septa.
• Alveolar sacs: terminal enlarged spaces surrounded by clusters of alveoli.

4. The Terminal Respiratory Unit (TRU) / Acinus

• Each TRU contains approximately 100 alveolar ducts and 2000 alveoli
• At FRC, each TRU is ~5 mm diameter with a volume of ~0.02 mL
• There are approximately 150,000 TRUs in adult human lungs
• Gas-phase diffusion is so rapid within a TRU that O2 and CO2 partial pressures are essentially uniform throughout the unit
• Most disorders of oxygenation arise from ventilation-perfusion inequalities, not diffusion failure
• Murray & Nadel's, p. 40

5. Alveoli: The Gas-Exchange Units

Alveolar Lining Cells

The Air-Blood Barrier

1. Alveolar epithelium (Type I cell)
2. Fused basal laminae of epithelium and endothelium (thin side ~0.2-0.4 µm)
3. Capillary endothelium
4. Plasma
5. Red blood cell membrane + intracellular cytoplasm

Pulmonary Surfactant

• Produced by AT2 cells; composed mainly of dipalmitoylphosphatidylcholine (DPPC) and surfactant proteins (SP-A, SP-B, SP-C, SP-D).
• Reduces surface tension at the air-liquid interface, preventing alveolar collapse during expiration.
• Deficiency causes Respiratory Distress Syndrome (RDS) in premature infants.

Interalveolar Septum

• Alveolar epithelial cells + basal lamina
• Capillary endothelial cells + basal lamina
• Connective tissue elements (collagen, elastin, fibroblasts, macrophages, mast cells) between the two basal laminae
• This is the site of the air-blood barrier

6. Connective Tissue Framework

• Collagen: provides tensile strength; prevents overdistension.
• Elastin: provides elastic recoil; enables the lung to spring back after expansion.
• Glycosaminoglycans and proteoglycans: fill the interstitial matrix with a gel-like structure; regulate epithelial cell phenotype and cytokine signaling.

• Axial (peribronchovascular) connective tissue: surrounds airways and pulmonary vessels; expands with interstitial edema first.
• Peripheral (subpleural) connective tissue: forms interlobular septa and visceral pleura.
• Parenchymal interstitium: alveolar walls.

7. Circulation: Dual Blood Supply

Pulmonary Circulation (functional)

• Pulmonary arteries: carry deoxygenated blood from the right ventricle at low pressure (~25/10 mmHg) to pulmonary capillaries around alveoli.
• Pulmonary capillaries (~8-10 µm diameter) form a dense network around alveoli for gas exchange.
• Pulmonary veins (4 total, 2 from each lung): carry oxygenated blood back to the left atrium.
• Blood pressure in pulmonary vessels increases at the rate of 1 cm H2O per cm height going down the lung, so vessels at the base are more distended than at the apex.

Bronchial Circulation (nutritive)

• Bronchial arteries (typically 2 left, 1 right) arise from the thoracic aorta.
• Supply the conducting airways (trachea to terminal bronchioles), visceral pleura, lymph nodes, and pulmonary nerves.
• Bronchial veins drain into the azygos/hemiazygos system.

8. Lymphatic Drainage

• Superficial (subpleural) plexus: drains toward the hilum via interlobular septa.
• Deep (peribronchovascular) plexus: runs alongside bronchi and pulmonary arteries.

9. Innervation

• C-fibers (J-receptors): near alveolar capillaries; respond to congestion, chemical irritants, causing rapid shallow breathing.
• Stretch receptors (Hering-Breuer reflex): in airway smooth muscle; inhibit inspiration when lungs are over-inflated.
• Irritant receptors: in airway epithelium; trigger cough and bronchoconstriction.

10. Pleura

• Costodiaphragmatic recess: most clinically important; site of pleural effusion accumulation; used for thoracentesis.
• Costomediastinal recess: between the costal and mediastinal parietal pleura.

11. Cellular Anatomy: Key Cell Types

Airway Lining Cells

Mesenchymal Cells

• Fibroblasts: produce extracellular matrix (collagen, elastin, glycosaminoglycans); highly heterogeneous - airway fibroblasts (collagen-rich) differ from alveolar fibroblasts (cytoskeletal-oriented).
• Myofibroblasts: key in secondary septum formation during alveologenesis; deposit elastin at septal tips; become fibrotic foci in IPF (idiopathic pulmonary fibrosis).
• Smooth muscle cells: two subtypes differing in origin and function; provide tone in airways (bronchoconstriction) and vessels.
• Pericytes: surround pulmonary capillaries.

Immune/Inflammatory Cells

• Alveolar macrophages (dust cells): primary phagocytes of the alveolar space; remove inhaled particles, bacteria, dead cells; first line of innate defense.
• Dendritic cells: antigen-presenting cells in airway epithelium and alveoli; bridge innate and adaptive immunity.
• Mast cells: in airway connective tissue; release histamine and leukotrienes in allergic/asthmatic responses.
• Lymphocytes: in bronchial-associated lymphoid tissue (BALT).

12. Molecular Anatomy: Key Molecules

• Surfactant proteins:
  • SP-A, SP-D: hydrophilic; innate immune defense (opsonization of pathogens)
  • SP-B, SP-C: hydrophobic; critical for surfactant film formation and function
• Extracellular matrix: collagen types I, III, IV; elastin; fibronectin; laminin; proteoglycans (heparan sulfate, versican, decorin)
• Tight junction proteins (claudins, occludins): maintain epithelial barrier integrity
• Aquaporins (especially AQP5 in AT1 cells): water transport across alveolar walls
• Ion channels (ENaC, CFTR): regulate fluid clearance from alveolar surface; CFTR mutations cause cystic fibrosis

13. Lung Volumes and Capacities (Reference Values)

14. Clinical Correlations

Summary