Lung
General
Histology
Author: Hirotsugu Hashimoto, M.D., Ph.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Last author update: 16 September 2021
Last staff update: 22 June 2023
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PubMed search: Pulmonary histology[TIAB]
Table of Contents
Definition / general | Essential features | Physiology | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Electron microscopy description | Electron microscopy images | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Hashimoto H. Histology. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lungnontumorhistology.html. Accessed March 30th, 2025.
Definition / general
- Lung: organ participating in and in charge of respiration, namely, gas exchange
- Lung histology: basic microscopic structures of the unaffected lung (i.e. nonneoplastic, noninflammatory and nondegenerated lung tissue)
Essential features
- Bronchus has cartilage and bronchial glands, while bronchiole lacks them (Mills: Histology for Pathologists, 5th Edition, 2019)
- Bronchi and bronchioles up to terminal bronchioles are pure conducting airways, while respiratory bronchioles and alveoli play a role in gas exchange
- There are 2 different definitions of a lobule (secondary lobule), namely, Miller's definition and Reid's definition (Radiology 2006;239:322)
- Miller: small lung units separated by interlobular septa and pulmonary veins, according to lung anatomy (Radiology 2006;239:322)
- Reid: an approximately equal sized unit (about 10 mm in diameter) of areas containing 3 to 5 acini, regardless of the interlobular septum, on the basis of bronchography (Radiology 2006;239:322)
- The term "primary pulmonary lobule," which indicates alveolar structures distal to respiratory bronchioles, is not commonly used; therefore, a lobule usually means a secondary lobule (Radiology 2006;239:322)
- Pulmonary acinus is defined as the largest unit participating in gas exchange, although there are different definitions of acinus (Radiology 2006;239:322)
- One definition of the acinus is a lung unit supplied by a single terminal bronchiole; the other is a lung unit supplied by a respiratory bronchiole
Physiology
- Ciliated cell: transports foreign bodies and mucous stream from the bronchus or bronchiole toward the proximal airway (Mills: Histology for Pathologists, 5th Edition, 2019)
- Mucous cell (goblet cell): secretes sulfomucin
- Basal cell: acts as a stem cell differentiating into other cells
- Neuroendocrine cell (Kulchitsky cell): secretes hormones (e.g. catecholamine, serotonin and gastrin releasing peptide) (Lowe: Stevens & Lowe's Human Histology, 4th Edition, 2014)
- Club cell (formerly Clara cell): plays a key role in lung remodeling, secretes surfactant and repairs airway epithelium
- Type I alveolar epithelium: responsible for respiration; namely, taking oxygen from the outside into the body and transporting carbon dioxide in the opposite direction
- Type II alveolar epithelium: secretes surfactant and plays a role as a precursor cell of type I alveolar epithelium (Lung Cancer 1994;10:S53)
- Pulmonary artery: supplies hypooxgenic blood into the lung in order to exchange the gas between airway and blood
- Bronchial artery: feeds bronchial wall, bronchiole wall and other connective tissue except alveolar septum with oxygen rich blood (Pawlina: Histology - A Text and Atlas, 8th Edition, 2018)
- Pulmonary vein: transports oxygen rich blood from the lungs to the left atrium
- Lymphatics: dual system, namely, flow along bronchovascular bundle from hilum and flow along interlobular septum from visceral pleura
Gross description
- Location: periphery of the pulmonary hilum
- Lungs consist of the branched bronchus (airways) and vasculatures
- Broncho (bronchiolo) vascular bundle: includes bronchus (bronchiole) and pulmonary artery (peripheral branch) located in the center of pulmonary lobe (or lobule)
- Pulmonary vein: located in the interlobular septum (Katzenstein: Diagnostic Atlas of Non-Neoplastic Lung Disease, 1st Edition, 2016)
- Peripheral lung: shows sponge-like appearance with fine wall reflecting the microscopic appearance of alveoli
Gross images
Contributed by Hirotsugu Hashimoto, M.D., Ph.D.
Cut surface of the lung
Microscopic (histologic) description
- Bronchus:
- Airway lined by pseudostratified ciliated epithelium
- Mucosal and submucosal layer are separated by elastic membrane confirmed by elastic staining (e.g. elastica Masson staining and elastica van Gieson staining), although it is not clearly observed by H&E staining alone
- Bronchial glands exist in the submucosa; cartilage and annular muscular layer exist in the wall between submucosa and adventitia
- References: Pawlina: Histology - A Text and Atlas, 8th Edition, 2018, Lowe: Stevens & Lowe's Human Histology, 4th Edition, 2014
- Bronchiole:
- Small airway, usually 1 mm in diameter or less, lined by single layer of ciliated epithelium
- Lacks bronchial glands and cartilage
- Ciliated cell:
- Tall columnar epithelium, with cilia on the edge of airway side
- Height becomes shorter as bronchiole heads toward periphery
- Reference: Mills: Histology for Pathologists, 5th Edition, 2019
- Mucous cell (goblet cell):
- Tall columnar epithelium with clear cytoplasm containing mucin, lacking cilia
- Basal cell:
- Laying on the basal membrane of bronchus or bronchiole with high nucleocytoplasmic ratio (Lung Cancer 1994;10:S53)
- Neuroendocrine cell (Kulchitsky cell):
- Laying scattered on the basal membrane with granular scant cytoplasm and relatively high nucleocytoplasmic ratio
- Usually difficult to distinguish from basal cell only by H&E staining
- Club cell (formerly Clara cell):
- Toll epithelial cell, no cytoplasmic mucin, no cilia
- Number of club cells increase as bronchiole heads toward periphery
- Bronchial gland:
- Mixed gland composed of both serous and mucinous epithelium
- Its duct opens to bronchial lumen
- Interlobular septum:
- Fibrous tissue separating Miller's secondary lung lobule, which contains pulmonary vein and lymphatic vessel
- Note that not every secondary lobule is separated by this septum
- Bronchovascular bundle:
- Fibrous tissue connecting from pulmonary hilum, which contains bronchus, pulmonary artery, bronchial artery and lymphatic vessel
- Alveolar duct:
- Terminal airway opening to alveolus, of which alveolar entrance rings constitute the walls
- Alveolar entrance rings contain elastic fibers and smooth muscles
- Alveolus:
- Sac-like structure lined by alveolar epithelium
- Alveolar septum contains pulmonary capillaries
- Strictly speaking, alveolar structure is not sac shaped but is a polyhedral architecture
- Type I alveolar epithelium (pneumocyte):
- Thin flat epithelium covering about 90 - 95% of alveolar lumen in area, about 40% of all alveolar epithelia in number
- Type II alveolar epithelium (pneumocyte):
- Cuboid epithelium covering 5 - 10% of the alveolar lumen in area, about 60% of all alveolar epithelia in number
- Pulmonary artery:
- Elastic artery in the central (hilar) side and muscular artery in the peripheral (alveolar) side
- Runs in the bronchovascular bundle along bronchus
- Lumen size is almost similar to bronchus beside it
- This muscular artery often contains abundant elastic fiber in the tunica media
- Reference: Katzenstein: Diagnostic Atlas of Non-Neoplastic Lung Disease, 1st Edition, 2016
- Pulmonary vein:
- Vein composed of collagenous fiber, smooth muscle and elastic fiber in various rates
- The central part contains a lot of elastic fiber but there is less in the periphery
- Runs in the interlobular septum or periphery of Miller's secondary lung lobule
- Bronchial artery:
- Muscular artery supplied by thoracic aorta or costal artery
- Size is far smaller than bronchus beside it
- Lymphatic vessel:
- Thin vasculature lined by endothelia
- Runs with bronchovascular bundle or interlobular septum
- Anthracotic pigment:
- Black pigment, which usually is deposited in the bronchovascular (or bronchiolovascular) bundle and pleura
Microscopic (histologic) images
Contributed by Hirotsugu Hashimoto, M.D., Ph.D.
Bronchovascular bundle
Bronchial wall
Miller's secondary lung lobule
Miller's secondary lung lobule (elastica Masson)
Peripheral airway (bronchiole to alveoli)
Alveoli
Positive stains
- Mucous cell (goblet cell): MUC2 and MUC5AC
- Basal cell: cytokeratin 5/6, cytokeratin 34 beta E12, p63 and p40
- Neuroendocrine cell (Kulchitsky cell): CD56, synaptophysin and chromogranin A (Mills: Histology for Pathologists, 5th Edition, 2019)
- Alveolar epithelium: cytokeratin 7
- Type II alveolar epithelium: TTF1, surfactant apoprotein A (SP-A) and napsin A
Negative stains
- Mucous cell (goblet cell): MUC6
- Basal cell: TTF1
- Alveolar epithelium: cytokeratin 20, cytokeratin 5/6, cytokeratin 34 beta E12 and p40
Electron microscopy description
- Club cell (formerly Clara cell): elevated higher than ciliated cells nearby (Lowe: Stevens & Lowe's Human Histology, 4th Edition, 2014)
- Type I alveolar epithelium: fewer organelles
- Type II alveolar epithelium: lamellar body and electron dense vesicles in the cytoplasm; microvilli on the alveolar surface
Electron microscopy images
Images hosted on other servers:
Type II alveolar epithelium (pneumocyte)
Additional references
Board review style question #1
Which of the following is expressed in the alveolar epithelium?
- Cytokeratin 5/6
- Cytokeratin 7
- Cytokeratin 20
- p40
Board review style answer #1
B. Alveolar epithelium expresses cytokeratin 7 but does not express cytokeratin 20, high molecular weight cytokeratins (e.g. cytokeratin 5/6 and 34 beta E12) or p40.
Comment Here
Reference: Lung nontumor - Normal histology
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Reference: Lung nontumor - Normal histology
Board review style question #2
Which of the following is located in the center of Miller's secondary lung lobule shown here in the H&E and elastic stain?
- Alveolar septum
- Alveoli
- Bronchiole
- Bronchus
Board review style answer #2
C. Bronchiole. A bronchiolovascular bundle, including terminal bronchiole, is located in the center of Miller's secondary lung lobule. A bronchiole lacks bronchial glands and cartilage.
Comment Here
Reference: Lung nontumor - Normal histology
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Reference: Lung nontumor - Normal histology
