The pulmonary system


Lungs exchange O2 and CO2 between the blood and air, and participate in regulation of the pH in the body.

Air comes to the lungs via trachea, which is divided into bronchi, and further into smaller bronchioles (diameter 0.5-1 mm), ending up in alveoli (diameter 0.2-0.3 mm), where the gases are exchanged. Bronchioles are supported by smooth muscle which can contract or relax as needed. Alveolus is composed of epithelial tissue, formed by type I (squamous) and type II (cuboidal or great) alveolar cells, and macrophages. Squamous cells enable the gas exchange via diffusion, and cuboidal cells secrete surfactant into the lumen to lower the surface tension of water. Alveolus contains collagen and elastic fibres, allowing alveoli to stretch and spring back during inhalation/exhalation cycle. Alveoli are surrounded by dense mesh of blood capillaries. The support for capillaries is weak, causing those to collapse if intraluminal pressure is low or alveolar pressure is increased.

Oxygen transport

At rest, lungs provide about 1 L O2 per min to the tissues via the vascular system, of which only about 1/4 is used. O2 is poorly soluble in water, and therefore about 98% of oxygen is transported as bound to haemoglobin in red blood cells.

Carbon dioxide transport

CO2 is soluble in water, and about 7% of it in the blood is directly dissolved in the water, 70% is dissolved in water as bicarbonate ion, HCO3-, and the rest is bound to haemoglobin in red blood cells.


The lungs have two circulations, pulmonary and bronchial circulation. Perfusion in the lungs can be measured using [15O]H2O PET (Mintun et al., 1986).

Pulmonary circulation

Pulmonary circulation is part of the vascular system. Pulmonary circulation receives all of the cardiac output; all venous blood is pumped from the right side of the heart via pulmonary arteries to the lungs for the gas exchange before returning via pulmonary veins into the left side of the heart.

Pulmonary capillaries have diameters between 2 and 13 µm, enabling effective exchange of molecules between blood and extravascular volume. Red blood cells are small and highly deformable and can transit rapidly, while more rigid and large white blood cells travel slowly (Doerschuk et al., 1993). Rigid particles with a diameter >10 µm may be permanently trapped in the lung capillaries.

Endothelial walls are normally tight, but inflammation leads to increased permeability.

Bronchial circulation

Bronchial circulation provides oxygenated blood to the walls of pulmonary arteries and veins, bronchi and bronchioles, nerves, lymph nodes, and visceral pleura. It is part of the systemic circulation, but can also contribute to the gas exchange when pulmonary circulation is compromised. On the other hand, pulmonary circulation participates in supplying bronchi and bronchioles with blood flow. Bronchial blood flow is low, only 1-5% of pulmonary circulation. Bronchial arteries are less than 1.5 mm in diameter.

Bronchial smooth muscle cells contain NMDA receptors (subtype of iGluRs in glutamatergic system), regulating smooth muscle contraction.

Immune cells in the lung tissue and airway mucosa mainly enter via the bronchial circulation.

Pulmonary function

Pulmonary function tests (PFTs), including spirometry, provide noninvasively information about global lung function, and can be used to assess the severity of pulmonary impairment for example in asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. Static lung imaging is already a standard clinical tool enabling the assessment of regional lung function. Improvements in spatial and temporal resolution of imaging systems will allow development of new methods for quantitation of lung physiology (Robertson & Buxton, 2012).

Ventilation imaging can be performed using SPECT or PET with 99mTc (Technegas®) or 68Ga (Galligas) labelled nanoparticles (Nozaki et al., 1995; Kotzerke et al., 2010a and 2010b; Borges et al., 2011). For pulmonary perfusion imaging, macroaggregated albumin (MAA) can be labelled with the same isotopes. Pulmonary ventilation and perfusion imaging can provide functional lung volumes that correlate well with PFT parameters (Le Roux et al., 2015 and 2017). PET-Galligas has also been used to develop and validate 4D-CT methods for assessing pulmonary ventilation (Kipritidis et al., 2014; Eslick et al., 2016).

Blood volume in lungs can be measured using [15O]CO (Sörensen et al., 2003).

Perfusion images in lung cancer can be calculated from [15O]H2O PET data (van der Veldt et al., 2010). Lung water content can be estimated from [15O]H2 PET 3.5-5.5 min p.i., when equilibrium is reached (Velasquez et al., 1991).

Several neuropeptides are implicated in the development of lung disease (Atanasova & Reznikov, 2018), and specific neuropeptide PET tracers could prove useful in the research of these disorders.

Activity of angiotensin-converting enzyme (ACE), which converts angiotensin I into angiotensin II, can be measured using 4-cis-[18F]fluorocaptopril ([18F]FCap) (Hwang et al., 1991; Markham et al., 1995; Schuster et al., 1995; Qing et al., 2000).

Input function for the lungs should be taken from the pulmonary artery or RV cavity of the heart. In FDG studies of the lungs the ROI drawn on RV cavity can be used to derive the input function (Schroeder et al., 2007). Delay correction may need to be ROI specific, and implemented as an additional parameter in the model fitting (Richard et al., 2002; Wellman et al., 2015).

See also:


Agrawal A, Rangarajan V (eds.): PET/CT in Lung Cancer. Springer, 2018. doi: 10.1007/978-3-319-72661-8.

Boutilier RG (ed.): Vertebrate Gas Exchange - From Environment to Cell. Springer, 1990. doi: 10.1007/978-3-642-75380-0.

Parthasarathi K (ed.): Molecular and Functional Insights Into the Pulmonary Vasculature. Springer, 2018. ISBN 978-3-319-68483-3.

Pedrozo Pupo JC (ed.): Learning Chest Imaging. Springer, 2013. doi: 10.1007/978-3-642-34147-2.

Pokorski M (ed.): Pulmonary Infection and Inflammation. Springer, 2016. doi: 10.1007/978-3-319-44485-7.

Robertson HT, Buxton RB. Imaging for lung physiology: What do we wish we could measure? J Appl Physiol. 2012; 113: 317-327. doi: 10.1152/japplphysiol.00146.2012.

Suresh K, Shimoda LA. Lung circulation. Compr Physiol. 2016; 6: 897-943.

Thiriet M. Anatomy and Physiology of the Circulatory and Ventilatory Systems. Springer, 2014. doi: 10.1007/978-1-4614-9469-0.

Tags: , , ,

Updated at: 2019-01-11
Created at: 2016-05-14
Written by: Vesa Oikonen