Lung histology

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Lung Histology

The lung is divided into two functional components: the conducting airways (tracheobronchial tree) and the respiratory portion (gas exchange). Each has distinct histological features.

1. Overview: Conducting vs. Respiratory Portions

Component	Conducting Portion	Respiratory Portion
Structures	Trachea, bronchi, bronchioles, terminal bronchioles	Respiratory bronchioles, alveolar ducts, alveolar sacs, alveoli
Function	Air conduction & filtration	Gas exchange
Epithelium	Pseudostratified ciliated columnar (PCCE)	Squamous (Type I pneumocytes)

2. Tracheobronchial Tree

Trachea and Bronchi

The trachea and bronchi are lined by pseudostratified ciliated columnar epithelium (PCCE) - also called "respiratory epithelium." It contains five cell types:

Ciliated columnar cells - predominant; beat to move mucus toward the pharynx ("mucociliary escalator")
Goblet cells - secrete mucus; increase dramatically after cigarette smoke exposure or acute bronchial injury
Brush cells - sensory innervation
Small granule (Kulchitsky) cells - neuroendocrine cells; secrete hormones and cytokines; can give rise to small cell carcinoma
Basal cells - stem cells that give rise to ciliated cells and goblet cells

The bronchial wall also contains:

Submucosal glands - mixed salivary-type glands (mucous + serous cells + neuroendocrine cells); can give rise to mucoepidermoid carcinomas and adenoid cystic carcinomas
Cartilaginous plates - in bronchi (complete rings in trachea; partial plates in bronchi)
Smooth muscle - present throughout

Fig. 19-10 - Normal Bronchial Epithelium (H&E)

Normal lung histology - pseudostratified ciliated columnar epithelium (A) with a Kulchitsky cell marked by arrow (B)

(A) Pseudostratified ciliated columnar cells and mucous cells lining the tracheobronchial tree. (B) A Kulchitsky (neuroendocrine) cell (arrow).

3. Bronchioles

As airways get smaller, they lose cartilage and submucosal glands. Histological features transition:

Larger bronchioles: Still PCCE with cilia; smooth muscle bundles in wall
Terminal bronchioles: The smallest airways without alveoli. Epithelium transitions from ciliated PCCE to ciliated simple columnar, and finally to club cells (formerly Clara cells) - non-ciliated cuboidal/low columnar cells that:
- Produce a surfactant-like surface-active agent
- Serve as progenitor stem cells for the bronchiolar epithelium
- Are involved in xenobiotic metabolism (cytochrome P450)

Histology of Terminal Bronchiole, Respiratory Bronchiole, and Alveoli

H&E micrographs: bronchus (B) with smooth muscle (SM), alveolar ducts (AD), alveolar sacs (AS), serosa (S), respiratory bronchioles (RB), cartilage (C), blood vessels (BV)

Key labels: B = bronchus, SM = smooth muscle, BV = blood vessel, AD = alveolar duct, AS = alveolar sac, S = serosa, RB = respiratory bronchiole, C = cartilage, L = lymphoid nodule.

4. Respiratory Portion

Respiratory Bronchioles

Transitional structure: wall is partly ciliated epithelium, partly open alveoli budding off the wall
Alveoli appear directly on the bronchiolar wall - this is the defining feature distinguishing respiratory from terminal bronchioles

Alveolar Ducts

Passages lined solely by rows of alveoli opening into the lumen
Have rings of smooth muscle in knob-like interalveolar septa

Alveolar Sacs

Enlarged spaces surrounded by clusters of alveoli

Alveoli

Lined by two cell types:

Feature	Type I Pneumocyte	Type II Pneumocyte
Shape	Extremely thin, flat (squamous)	Rounded/cuboidal
% of alveolar cells	~40%	~60%
% of surface area covered	~95%	~3-5%
Function	Gas exchange	Surfactant production
Mitotic potential	None (cannot regenerate)	Yes - progenitor for Type I
Histology	Attenuated nucleus; barely visible in H&E	Prominent rounded nucleus, pale cytoplasm; "septal cell"
Lamellar bodies	Absent	Present (store surfactant)

Surfactant is a phospholipid-protein complex (primarily dipalmitoylphosphatidylcholine) that reduces alveolar surface tension, preventing collapse at end-expiration. Its deficiency in premature infants causes Respiratory Distress Syndrome (RDS/hyaline membrane disease).

The Air-Blood Barrier (Alveolar-Capillary Membrane)

The interalveolar septum (between adjacent alveoli) constitutes the air-blood barrier:

Type I pneumocyte cytoplasm
Fused basal laminae of pneumocyte + capillary endothelium (thin portion ~0.15-0.30 μm)
Capillary endothelial cell

Gas exchange occurs through the thin portion where the two basal laminae are fused. In the thick portion, connective tissue (collagen, elastin, fibroblasts) lies between the two basal laminae.

High-Magnification Alveolar Histology

High magnification H&E: terminal bronchiole showing PsEp (pseudostratified epithelium), SM (smooth muscle), CC (club cells); respiratory bronchiole with alveoli (A), SM, CC; alveolar duct with alveoli (A) and SM knobs; alveolus with capillary (C), septal cell (SC, type II pneumocyte), and thin portions of alveolar-capillary complex (arrows)

Key labels: PsEp = pseudostratified epithelium, CC = club cells, SM = smooth muscle, A = alveolus, C = capillary, SC = septal cell (Type II pneumocyte), arrows = thin portions of alveolar-capillary membrane where gas exchange occurs.

5. Other Cells in the Alveolar Space

Alveolar macrophages ("dust cells") - resident macrophages derived from monocytes; patrol the alveolar surface phagocytosing debris, pathogens, and inhaled particles. Appear as large cells with granular cytoplasm floating free in alveoli.
Clusters of neuroendocrine cells - found in alveolar spaces
Mast cells, lymphocytes, plasma cells - sparse, in interstitium

6. Summary: Key Histological Markers by Structure

Structure	Epithelium	Cartilage	Glands	Smooth Muscle
Trachea	PCCE	Complete rings (C-shaped)	Present	Yes (posterior)
Main/lobar bronchi	PCCE	Irregular plates	Present	Yes
Segmental bronchi	PCCE	Smaller plates	Present	Yes
Bronchioles	Simple ciliated columnar	Absent	Absent	Yes
Terminal bronchioles	Club cells (+ some ciliated)	Absent	Absent	Yes
Respiratory bronchioles	Cuboidal/club cells + alveoli	Absent	Absent	Yes (knobs)
Alveoli	Type I + II pneumocytes	Absent	Absent	Absent

Sources: Histology: A Text and Atlas with Correlated Cell and Molecular Biology; Schwartz's Principles of Surgery, 11th ed.

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