How much surface area is in the lungs

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Impact of this question views around the world. You can reuse this answer Creative Commons License. In regions with less pronounced absorption like the colon, variations in the fluid content between the studies were much smaller 22—30 ml Wang and Urban, Gastrointestinal fluid consists of secretions from the large gastrointestinal glands pancreas, liver , submucosal glands Brunner's glands and intraepithelial mucus-producing cells.

There are changes in pH and ion concentrations along the gastrointestinal tract, but the average total protein content in the fasted state was relatively constant at 1. Gastric juice contains mainly pepsin 0. Determination of the lining fluid in the lung LLF , also called epithelial lining fluid ELF or airway surface liquid ASL , is more complicated than for the gastrointestinal fluids because lung volumes are much smaller.

The total volume of LLF can be estimated based on bronchoalveolar lavage BAL or by extrapolation of the thicknesses of the fluid layer covering the respiratory epithelia. BAL is a diagnostic technique that uses instillation of sterile saline 0. The procedure has been refined over time; older protocols used the instillation of 3—7 l of fluid with ml aliquots while current protocols recommend — ml Klech and Pohl, This adaptation was needed because concentrations of protein and drug levels are based on the concentration of urea.

Urea as non-polar small molecular weight molecule crosses the alveolar epithelium and is expected to be present in the same concentration in the blood and in the lung fluid. However, urea also leaks into the airspace and in this way may reach higher levels than in the blood with the consequence of overestimation of the LLF volume Baldwin et al. Determinations of the LLF volume based on the thickness of the fluid layer on top of the epithelia require a technique that does not alter the native structure of the LLF.

Traditionally, transmission electron microscopy has been used using fixation with glutaraldehyde and staining with OsO 4 in perfluorocarbon to preserve the mucus layer. To avoid tissue shrinkage by the fixation, cryofixation instead of chemical fixation has been developed Kesimer et al. Furthermore, cryofixation allowed the visualization of the substructure of this layer, while the fixation with glutaraldehyde and staining with ruthenium red could not Kesimer et al.

Most published data were obtained with conventional fixation technique. The indication of an average thickness for bronchi does not reflect the physiological condition of a highly variable and partly discontinuous mucus layer. Focal increases of the layer of 20 times can occur and some small bronchi may completely lack a mucus layer Hiemstra, and could cause heterogenous absorption of the drugs.

There is currently no optimal method to determine the volume of the LLF. Calculation by the urea method poses the problem of overestimation due to leakage of urea. Estimations based on the thickness of the lining fluids needs to avoid fixation artifacts and are complicated by the variable indications of the entire lung surface area.

Most existing data were obtained with the measurement of urea in BAL. In the literature different volumes of 12 ml Schlesinger, , 20—40 ml Lenfant, , 25 ml Walters, , 10—30 ml Olsson et al. Greater variations of 15—70 ml were given by Bohr et al. Bohr et al. Based on the body weight-dependent data obtained in sheep 0.

This study used the instillation of the impermeant tracer I-albumin in perfused postnatal sheep lungs and changes in the tracer concentration were measured. Using low temperature scanning electron microscopy Fronius et al.

Animal experiments may offer a platform to establish new techniques for determination of these data. LLF has a heterogeneous composition that varies from the larger to the smaller airways. The periciliary layer consists mainly of water with antibacterial factors, ions and contains tethered mucins MUC1 and MUC4 and heparin sulfate Rubin and Henke, The ion content of the layer is regulated by sodium uptake via the sodium channel and chloride export transporters calcium-activated chloride channel and cystic fibrosis transmembrane ion conductance regulator.

The network is formed by entanglement and non-covalent calcium-dependent crosslinking of adjacent polymers. The LLF of the alveolar region is composed of a watery layer hypophase and surfactant Fehrenbach, The hypophase contains surfactant proteins, complement proteins and antioxidants Kobzik, and provides the milieu for alveolar macrophages that migrate on top of the alveolar epithelial cells Fehrenbach, The correct position of the macrophages inside the hypophase was only realized when perfusion fixation instead of immersion fixation of the lung samples was used Filippenko, and demonstrates that improved analytic methods may help to obtain more relevant physiological data.

Due to the variations in the employed BAL protocols total protein levels were given as 5. Older protocols using larger BAL volumes measured 1.

The protein content of the LLF in the alveoli 5. According to the hypothesis by Baldwin et al. Other studies report albumin levels in ELF of 3. These values indicate a low drug binding of ELF. Composition of the lung lining fluid of large airways bronchi, A and alveolus B.

The blue arrow indicates exchange between alveolus and blood vessel BV. Alveolar type I cells AT1 represent the predominating cell type of the epithelial lining of the alveolus.

Surfactant production small arrows occurs in endoplasmic reticulum and Golgi apparatus of the alveolar type II cells AT2 and the surfactant layer self assembles upon secretion from the cells. Several parameters affect the modeling of lung deposition, including the selected lung morphology, the respiratory parameters, determining air flow pattern through the lung and the clearance velocity, particle properties such as size and shape of particles and the deposition mechanisms.

Mathematical calculations for deposition commonly refer to spherical particles and selected morphometric lung models for healthy, adult subjects. The major limitation for the application of deposition models is the intersubject variability of morphological and physiological parameters, which affects the validation of models with experimental data Rosati et al. Moreover, linking the simulation data deposition and pharmacokinetics to the used lung surface area and lining fluid is problematic.

In the MPPD software calculations are based on Differences in lung deposition are, however, not only influenced by lung surface area and airflow but also by fluid dynamics of the inhaled air. Comparing different simulation programs Majid et al. In addition to that, the dose at the alveolar epithelium is not only determined by deposition but also by clearance. Hofmann and Asgharian used an asymmetric, multipath model for computational assessment of mucociliary clearance velocities in bronchial airways of the human and rat lung Hofmann and Asgharian, The experimental slow bronchial clearance values of particles smaller than 6.

For acinar deposition deposition in airways that are partly or fully alveolated , computational predictions were lower than the experimental values. This might be caused by translocation of particles initially deposited in the bronchioles to the acinar region because of the slow bronchial clearance in bronchioles Hofmann and Sturm, The interstitial-sequestration model has been developed as improvement of the ICRP model for insoluble materials Gregoratto et al.

Differences in surface area of the human lung have practical consequences on the doses that are applied to animals in order to create realistic exposure scenarios. For calculation of the NF various combinations of human and rat surface areas have been used in the literature, e.

Due to the fact that lung area can be more accurately determined in rats than in humans the values used in the studies varied by a factor of 1. The dose adaptation factor, however, also contains other parameters and the effect of different lung areas used for the normalization factor might be compensated or amplified by changes in the ratios of minute ventilation and deposition fraction.

The U. Environmental Protection Agency summarized studies on minute ventilation in rats; data obtained by plethysmography in studies between and varied between 0. Minute ventilation in humans ranged between 6. Less pronounced inter-study differences 0.

Minute ventilation is usually calculated based on body weight using recommended allometric equations. Minute ventilation normalized to body weight varied relatively little between different studies, 0. The ratio of the deposition fraction is influenced in a complex manner as described above. The link between lung lining fluid and results in pharmacokinetic studies is complicated by the fact that usually plasma levels are predicted.

Lung tissue levels are not easy to obtain in humans; the disadvantages of BAL measurements have already been mentioned, lung biopsies are not representative for the entire lung and represent only one time point and lung microdialysis is a highly invasive technique Feuerstein and Zeitlinger, Lung microdialysis would be the ideal technique because continuous measurements of lung concentrations are possible. Since the probe for microdialysis sampling of the interstitial fluid has to be inserted under visual control during thoracotomy, only very few data have been generated and drug levels are usually measured in blood samples.

Blood levels are usually very low, caused by multiphasic absorption and downstream of the lung. Inhaled drugs are absorbed by branches of the pulmonary artery, which runs in parallel to the bronchial tree, and then follow the blood stream through the left atrium of the heart, the left ventricle, the aorta, and the arteries and capillaries of the upper extremity to reach the cubital vein, where blood samples are collected.

A variety of parameters determine drug plasma levels and the influence of specific parameters to the results of the prediction is difficult to discern. However, when looking only on absorption a potential link might be apparent. The study by Gaohura et al. In their study the authors predicted these ratios for tuberculostatic drugs based on 25 ml lining fluid and m 2 lung surface area.

Results were in reasonable agreement within 2. When comparing simulated LLF and peak plasma concentrations of rifampicin in vivo plasma levels were at the maximum 2-fold higher and LLF concentrations almost 8-times higher. Lowering the pH of the lining fluid and inclusion of transporter activity in the model reduced the degree of underestimation of the LLF:plasma ratio but the trend remained and it might also be suggested that the great surface area that was used in the predictions played a role.

Under the assumption that a greater lung surface enables better uptake of the compounds and result in higher plasma levels the LLF:plasma ratio would decrease. Another reason could be that the volume of LLF in the model was too low and, as a consequence, the drug concentration to high. Variable data for lung surface and LLF in the literature illustrate the problems in choosing the right preset values for simulation of lung absorption.

Reported variations in the LLF result in differences of 7 times in the potential dissolution volume of the drug. For the absorption area differences are in the same order of magnitude 7. Improved and new techniques helped in a better determination of physiological data and new technologies may prove that the current textbook data are not correct.

Data derived from animals, where more invasive methods can be applied, may be helpful to better include the dynamic changes of lung parameters during oral inhalation of drugs. Several factors influence deposition of particles and absorption of drugs and it is, therefore, difficult to link the effect of individual parameters to the result of the simulation.

The primary function of the lung is gas exchange. The alveoli allow this gas exchange to occur. Each alveoli has a network of capillaries that carry oxygen-poor red blood cells. The capillaries bring the red blood cells very close to the air space in the alveoli. When you inhale, your lungs expand to hold the incoming air. How much air they hold is called lung capacity and varies with a person's size, age, gender and respiratory health.

The maximum amount of air an average adult male's lungs can hold is about six liters that's the same as about three large soda bottles. There's some math involved to get to that number, but basically, it's adding up air from a normal breath, extra air you can force in, additional air you can force out after regular exhaling and the air that's left in the lungs after all that.

Every day, you breathe in just over 2, gallons of air—enough to almost fill up a normal-sized swimming pool. That's a lot of air. It's the amount needed to oxygenate approximately 2, gallons of blood pumped through your heart daily. Because lungs are constantly exposed to the external environment, they need some protection from dust, germs and other unwanted matter.

That's where mucus comes in. Your bronchial tubes are lined with cilia they're like thin little hairs that carry mucus up into your throat to trap those yucky intruders until you cough, sneeze , clear your throat or swallow to get rid of them. The diaphragm is the chief muscle of breathing. This dome-shaped wall of muscle does the most of the breathing work by expanding and contracting the chest to draw air in and out of your lungs.