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You are watching: The lungs are made up of thick fibrous tissue

StatPearls . Endowment Island (FL): StatPearls Publishing; 2021 Jan-.



The lungs room a pair of main organs the respiration, current in the thoracic cavity alongside the mediastinum. They space covered through a slim double-layered serous membrane referred to as the pleura.

The respiratory system consists of 2 components, the conducting portion, and the respiratory tract portion. The conducting part brings the waiting from outside to the website of the respiration. The respiratory portion helps in the exchange of gases and also oxygenation of the blood.

The conducting section of the respiratory tract system includes the nose, nasopharynx, larynx, trachea, and a whole series of successive narrowing segments of bronchi and bronchioles. The conducting part end in ~ the terminal bronchiole. The respiratory portion begins indigenous the respiratory bronchiole and continues v the alveolar ducts, alveolar sacs, and also finally ends at the alveoli wherein the far-ranging exchange that gases takes place. The branching pattern of this conducting passages looks prefer the branching the a tree and also hence called the tracheobronchial tree <1>.

The right lung has actually three, and also the left lung has actually two lobes. Every is aeriated by a an additional (lobar) bronchus. The lobes room further divided into smaller sized pyramidal shaped sections referred to as the bronchopulmonary segments. There space ten bronchopulmonary segment in every lung with their apex directed in the direction of the hilum, and each is aeriated by a tertiary (segmental) bronchus <2>.

The alveoli space the structural and functional systems of the respiratory tract system. Over there are roughly 300 million alveoli in one adult person amounting to almost right 80 square meter of surface area for the gaseous exchange <3>.

The lungs are critical component of the pulmonary circulation wherein the deoxygenated blood pumped through the ideal ventricle that the heart is gushed v the pulmonary arteries to alveolar-capillary bed of the lung because that gaseous exchange. The oxygenated blood indigenous the capillaries of the lung is returned to the left atrium by the four pulmonary veins.

Issues of Concern

These space not in reality the problems of concern however some that the distinct features the the lung.

The lung alveoli start emerging in the prenatal stage and an extremely important because that a live birth with the energetic secretion the surfactant indigenous its kind II pneumocytes. Nevertheless, 95% that alveoli are created postnatally during the very first eight years of life, that as well a majority being in the first three years.


The conduction section of the lung begins at the trachea and also extends come the terminal bronchioles. Exterior the lungs, the conduction system is composed of the nasal cavities, nasopharynx, larynx, and also trachea. Within the lungs, the conducting portion spits into paired key bronchi. The bronchi begin as a branching pattern, splitting next into lobar (secondary) bronchial branches and also then again into segmental (tertiary) bronchi. The tertiary bronchi continue to division into small bronchioles where the first change in histology takes place as cartilage is no longer existing in the bronchioles. The finish of the conduction section of the lungs is in ~ the final segment referred to as the terminal bronchioles. The terminal bronchioles open right into the respiratory tract bronchioles <7>. This is the begin of the respiration section of the lung.

The conducting portion provides the pathway because that the movement and conditioning that the wait entering the lung. Specialized cells collaborate come warm, moisturize, and also remove particles that enter. This cells room the respiratory epithelium and comprise the whole respiratory tree. Most of the respiratory tract epithelium is ciliated pseudostratified columnar epithelium. The following five types of cells room in this region:

Ciliated cells
Goblet cells
Basal cells

The ciliated cells space the most abundant. They regulate the plot of the mucociliary escalator <8>, a main defense device of the lung that clears debris. When the mucus detailed by the goblet cells traps inhaled particles, the cilia win to move the product towards the pharynx come swallow or cough out.

Goblet cells, so called for their goblet-shaped appearance, space filled through mucin granules at your apical surface ar with the nucleus staying towards the basilar layer. Goblet cell decrease in number together the respiratory tract tree gets increasingly smaller and are eventually replaced by society cells (previously Clara cells) as soon as they with the respiratory tract bronchioles.

The basal cells attach to the basement membrane and provide the attachment layer that the ciliated cells and goblet cells. They might be believed of together the stem cells of the respiratory tract epithelium as they preserve the capability to potentiate ciliated cells and goblet cells <9>.

Brush cells, periodically referred come as form III pneumocyte cells are sparsely distributed in all locations of respiratory tract mucosa. Brush cells may be columnar, or flask-like and also are determined by their quick microvilli extended apical layer–resembling a push broom or appropriately, a brush. No role has been officially assigned to the brush cells though over there are plenty of proposed mechanisms. One famous proposal argues they have actually a chemoreceptor function, surveillance air quality, as result of their association v unmyelinated nerve endings. <10>

The bronchial mucosa also contains a tiny cluster the neuroendocrine cells, additionally known together Kulchitsky cells <11>. They have neurosecretory kind granules and also can secrete numerous factors. This contains catecholamine and also polypeptide hormones, such together serotonin, calcitonin, and gastrin-releasing factors (bombesin). Like brush cells, these neuroendocrine cells comprise only a small portion of mucosal epithelium, about 3%.

Within the bronchial submucosa are submucosal glands. This glands are composed the a mixture of serous and also mucinous cells, comparable to outstanding gland tissue.  The secretions room emptied into ducts and also then on the bronchial mucosa. Older people may show oncocytic metaplasia of these glands.  Smooth muscle bundles are current at all levels the the airway to enable for regulation that airflow. There are increasingly fewer smooth muscle fibers advancing from bronchi to alveoli.


Respiratory functions of lungs:

Non-respiratory functions of lungs:

Even despite the lungs are mostly for respiration, studies show that lock have plenty of non-respiratory functions. Few of the few important people are stated below.

It is also crucial site for degrading/inactivating necessary vasoactive chemical mediators choose bradykinin, serotonin, and also norepinephrine

Tissue Preparation

Proper ethical approval is obtained prior to the arsenal of the lung tissue. The lung is identified, dissected en-block, weighed, and also labeled. Later on the lung is perfused v 10% formalin v the trachea come the physiological peak incentive level. Underinflation or over inflation must be prevented. This helps in suitable assessment without any kind of artifacts and over/under the referee of the tissue structure. All the lobes the the lungs are determined searched for any lesions. The tissue is washed well, resolved in formalin for almost 24 hours. When the tissue handling is completed, that is required to the next level of organization embedding. The lung organ have to be put in the tissue cassette v the ventral side facing the organization cassette. The dorsal side of the lung will certainly be facing the open/upper side. This place guarantees the suitable tissue ar level. Article fixation organization trimming is a vital component to get the finest sections. If the determined lesions are too huge or small, they deserve to be isolated and embedded separately. The is vital to include the sections of connected lymph nodes for histological evaluation, which will assist in revolve to recognize the level of metastasis of the lung tumors <16>.

Histochemistry and Cytochemistry

Histochemistry of the Lung

Histochemical analyses that the lung deserve to be carried out utilizing lectin histochemistry (LC) or immunohistochemistry (IHC). Both methods deserve to be perform on tissue slides. The typical lung cells can be typed as kind I and type II pneumocytes based on histochemical analyses utilizing lectin keying (glycotyping) <17>. The alveolar macrophages in the common lung are optimistic for numerous N-linked saccharides, namely, N-acetylgalactosamine, N-acetylglucosamine, terminal β-D-galactose, and also sialyl groups. Some details lectins have the right to be offered as a marker because that cell types, such together Dolichos biflorus agglutinin because that bronchial epithelial cells, Triticum Vulgaris (succinylated) for kind I pneumocytes and Hippeastrum hybrid or Maclura pomifera lectins for form II pneumocytes. Alveolar macrophages room anti-CD68 positive, and alveolar lining present positivity because that cytokeratin.

Further, IHC and also LC can administer substantial insights into obstructive and also restrictive pathologies and also in lung cancer diagnosis.  Adenocarcinomas can be identified by differentiation mite that incorporate TTF-1 and also NapsinA.  Both these markers room expressed in more than 85% the the cases <18>. Metastasis have the right to be confirmed by IHC staining to recognize primary tumor organization of origin.  distinct expression that CK7 and also CK20 profiles, in enhancement to the lack of markers commonly expressed in primary lung cancer, can signify metastatic cancer. With the advent of cancer treatment with tyrosine kinase inhibitor (TKI), actionable gene mutations can be screened in lung cancer patient <19>. EGFR mutation and also ALK translocation space the most properly targeted oncogenes in non-small cell carcinomas and also are now considered standard treatment actions presently <19>.

Cytochemistry that the Lung

Cell analyses of the lung tissue have the right to be carried out making use of electron microscopy and have recently contained flow cytometric assays. Evaluate of non-specific esterases: alpha-naphthyl acetate esterase (ANAE) and also butyrate esterase (BUT), chloroacetate esterase (CHL), acid phosphatase (ACP), intracellular glycogen (PAS reaction), lipids (Sudan black color B reaction-SBB) and also iron (Perl"s reaction) deserve to be carry out by a semiquantitative cytochemical technique to identify diseases of the lung <20>.  ECM remodeling is the communication of pathologic alters in obstructive pulmonary diseases, and also collagen change provides insight into the disease. The second-harmonic generation (SHG) an approach used come quantify collagen has demonstrated effect evaluation of lung diseases, v a biochemically distinctive presentation of organization of collagen in asthma, COPD and idiopathic pulmonary fibrosis (IPF) <21>. Alveolar macrophage modulations using chloroacetate esterase (CHL) and also Perls" reaction (for estimation of intracellular iron) can confirm the visibility of non-small cell lung cancer. The typical increase in CHL and iron in alveolar macrophages shows non-small cell lung cancer <10>. Similarly, Galectin-3 (Gal-3) can be used as a biomarker in human pulmonary fibrosis together the levels are observed to be elevated in this disease <22>.

Microscopy Light

As stated before, the conducting portion is as much as the terminal bronchiole. Past that v the start of respiratory tract bronchiole is the respiratory component of the respiratory tract system. The respiratory section of the lung consists of respiratory tract bronchiole, alveolar duct, alveolar sac, and finally alveoli where actual respiration bring away place.

In the conducting zone, the air is moistened, warmed, and filtered before it will the begin of the respiratory an ar at the respiratory bronchioles. The respiratory tract zone is where gas exchange occurs, and blood is oxygenated in exchange because that carbon dioxide. Together the respiratory tree transitions from the conducting zone in ~ the terminal bronchioles, goblet cells diminish as club cell increase, and also the cartilage current in the conducting region is absent once it reaches the respiratory bronchioles.

The acinus is directly distal come the terminal bronchioles and also which signals the beginning of the respiratory part. The acinus is created of respiratory tract bronchioles, alveolar ducts, and also alveolar sacs. It is roughly spherical, resembling a bunch the grapes. Each respiratory tract bronchiole offers rise to numerous alveolar ducts and alveolar sacs, offering it the characteristics grape bunch appearance. The alveolar sacs are the end of the respiratory tree and also the site of gas exchange. 

Alveolar epithelium is written of form I pneumocytes, type II pneumocytes, and the occasional brush cells. Likewise present in the alveolar walls are the club cells and also alveolar macrophages. The alveolar wall surfaces contain the pores that Kohn <23><24>, which permit communication between surrounding alveoli. This permits air to circulation from one alveolus come another, which might be valuable if there is any blockage preventing air from entering alveoli with a direct route.

Type ns pneumocytes make up around 90% come 95% of the alveolar epithelium. They space flat, squamous epithelia the resemble plate-like structures that allow gas exchange. Their fragile membrane allows for simpler gas permeability between the alveoli and also the blood vessels. Despite being the primary structures that respiration, they cannot replicate and are an extremely susceptible to toxic injury.

Type II pneumocytes consist of much the the remaining cell form in the alveoli, audit for almost 5-10%. In spite of their short number, they are an essential as they secrete pulmonary surfactant. The surfactant is important to maintain an open up airway. That lowers the surface ar tension and prevents the alveoli from collapsing top top themselves throughout exhalation. By histology, this cells have foamy cytoplasm, which results from the surfactant the is stored together lamellar bodies. Kind II pneumocytes are additionally mitotically energetic and deserve to replace the quickly damaged kind I pneumocytes. Form II pneumocyte cells have the right to be recognized by your rounded shapes that bulge into the alveolar space.

Alveolar macrophages (or dust cells) might be complimentary within the alveolar room or sometimes linked to the alveolar wall. If particles make it under to the acinus, the macrophages space the critical defense and janitors the the respiratory tract epithelium. The black color staining seen in the lungs of smokers outcomes from macrophages cleaning and also sequestering particles the make their way inside.

The lungs are covered through the serous membrane, the pleural membrane, which has two great - the parietal and also the visceral layer. The visceral pleura of the lung is inside wall by a mesothelial layer through underlying connective tissue and elastic fibers. An elastin stain may be offered to determine the elastic layer.

Microscopy Electron

In this section, let us acquire into some an ext detailed research of a few of the crucial structures that the lung, which can be appreciated better under one electron microscope. 

Respiratory Bronchiole:

This is the an ar of change between conducting and also respiratory sections (where the exchange that gases begins). Structurally respiratory bronchiole is very similar to terminal bronchiole, except its walls space interrupted by numerous sac-like alveoli for gaseous exchange. It is inside wall by ciliated cuboidal epithelium. The cilia may be absent in more distal portions. A small number of non-ciliated Clara cells are likewise present. This Clara cells come to be dominant cells in the distal part. The epithelium is devoid of goblet cells. Basic tissue is composed of smooth muscle and elastic fibers. Distally the respiratory tract bronchioles divide, become narrower, and the number of alveoli increases.

Clara cells have actually three functions,

Alveolar ducts:

Respiratory bronchioles divide distally to form alveolar ducts. Alveolar ducts do not have actually walls of your own but are created by numerous openings of alveoli. This terminate into clusters that alveoli known as the alveolar sac, which opens into the atrium and finally right into alveoli. Alveolar ducts space surrounded by little aggregations the smooth muscle cells, collagen, and elastic fibers. Sphincter-like smooth muscle (knob) embedded in type III collagen roughly respiratory bronchioles and alveolar ducts regulate air movements within alveoli. Smooth muscle totally disappears at the distal end of alveolar ducts. Affluent matrix that elastic and also reticular fibers gives the just support because that duct and alveoli


The alveoli are the committed air-sacs (outpouching) that 200 µm diameter. These room the structural and functional unit that the respiratory system. These are the major site of exchange that oxygen and also carbon dioxide. There room 300 million alveoli in the lungs, and also these give roughly 140m surface ar area for the exchange that gases. The alveoli are responsible for the spongy nature of the lung. These alveoli are lined by flattened epithelial cells referred to as pneumocytes v a solitary opening. The alveolar wall or septum is comprised of three tissue components: surface ar epithelium, sustaining tissue, and considerable network of consistent capillaries. Centrally it has capillaries surrounding by a vivid network of elastin, reticular, and also collagen fibers through a layer of squamous epithelial of two surrounding alveoli on either side. In certain places, the basement membrane of the capillary endothelium come in direct call with the basement membrane of the surface ar epithelium the alveoli, v the lack of supporting tissue, hence reducing thickness (0.1-1.5µm) for far better exchange that gases. For this reason air in alveoli is separated indigenous the blood in the capillary by 3 components, surface lining and also cytoplasm of alveolar cells, fused basal laminae of closely apposed alveolar, and also endothelial cells and also their cytoplasm. This is called the blood-gas obstacle (air blood barrier). Capillaries are continuous with the endothelial cells, i beg your pardon are incredibly thin because of the clustering that nuclei and also other organelles, increasing the efficiency of exchange. Occasionally little openings, alveolar pores (of Kohn) (10-15µm in diameter) room seen i beg your pardon equalize air press within alveoli and enable air movement in between alveoli in instance of the bronchiole obstruction. Elastic fibers enable alveoli come expand during inspiration and also contract passively during expiration. The reticular fibers offer as supportive frameworks that avoid over-distention and also damage to breakable capillaries and also alveolar septa. Two types of epithelia type a constant lining roughly each alveolus. Lock are kind I pneumocytes (alveolar lining cells) and form II pneumocytes.

Type i Pneumocytes (Alveolar lining cells)

The form I Pneumocytes are simple squamous cells the are very attenuated v a dense, small, and also flattened nucleus. This cover most that the surface area, approximating around 95-97% of the full surface area. Golgi complex, endoplasmic reticulum, and also mitochondria are grouped about the nucleus, leaving a big area that cytoplasm cost-free of organelles, for this reason reducing it to a fragile blood-air diffusion obstacle (25nm). The slim cytoplasm shows countless pinocytotic vesicles. The surfactant currently the luminal surface. A basal lamina consists the adluminal side of this cells. The nearby cells are associated by chop (occluding) junctions, which prevent leakage of tissue liquid into the alveolar lumen. During fetal development, the surfactant appears in the last few weeks that gestation and coincides with the appearance of lamellar bodies in the type II cells.

Type II Pneumocytes (Great alveolar or septal cells)

The form II Pneumocytes are the cuboidal cell grouped in 2-3, large, a central, and also plump nucleus with dispersed chromatin and prominent nucleoli. They occupy around 3-5% the the surface area the alveoli interspersed among type I cells with which they have actually occluding and also desmosomal junctions. The apical surface ar is dome-shaped and also shows numerous little microvilli connected with surfactant secretion. These form II pneumocytes secrete Surfactant, a surface-active product that reduces surface tension, thus staying clear of alveolar collapse throughout expiration. The mitotic activity of the lining cells is 1% per day and also can distinguish to type II, as well as form I pneumocytes in response to damage to alveolar lining epithelium. The cytoplasm has actually abundant stormy endoplasmic reticulum, well emerged Golgi apparatus, free ribosomes, and also a moderate lot of elongated mitochondria. A common feature of this cells is the presence of lamellar bodies. this lamellar bodies are vesicles containing phospholipid (dipalmitoyl phosphatidylcholine) (1-2µm). These, as soon as discharged by exocytosis into alveoli, spreads on alveolar surface and also combines with various other carbohydrate and also protein-containing secretory products (some secreted through Clara cells) to kind surfactant, which is a tubular lattice the lipoprotein well-known as tubular myelin, i beg your pardon overcomes results of surface tension. The reduction of surface ar tension method a palliation of job-related of breathing. The surfactant is no static but continually gift turned over and also removed. The removal is through pinocytotic vesicles of type II pneumocytes, macrophages, and form I pneumocytes.

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Alveolar Macrophage (Dust cells):

The alveolar macrophages are derived from blood monocytes and sometimes by mitotic division of macrophages the the lung. They contain numerous secondary lysosomes and also lipid droplets. They phagocyte and remove unwanted materials such together inhaled particulate matter (carbon), dust, and also bacteria. They room present free within alveolar spaces and also some in inter-alveolar septa (spaces). One hundreds million macrophages day-to-day migrate come bronchi. The phagocytosed macrophages acquire trapped in mucus, transported through ciliary activity to the pharynx, and come out in sputum. Part alveolar macrophages likewise go via lymphatics to hilar lymph nodes. Industrial lung an illness like silicosis is because of inhalation the silica into air bag (as tiny particles) that are phagocytosed through macrophages. Silicated macrophages stay for a long time and also convert silica right into silicic acid, i beg your pardon stimulates the proliferation of fibroblasts and collagen, bring about fibrosis that lung and also node. A particular form of silica, like asbestos, once inhaled broadly stimulates lung fibrosis developing asbestosis and sometimes malignancy the pleura (mesothelioma). Periodically macrophages phagocytose extravasated RBCs in alveoli (especially in conditions like pulmonary congestion and congestive heart failure). These erythrocyte phagocytosed macrophages are called heart failure cells.