Alveolar membrane

Ethylene is slightly more potent as an anesthetic than nitrous oxide, and the smell of ethylene causes choking. Diffusion through the alveolar membrane is sufficiendy rapid for equilibrium to be estabUshed between the alveolar and the pulmonary capillary blood with a single exposure. Ethylene is held both ia cells and ia plasma ia simple physical solution. The Hpoid stroma of the red blood cells absorb ethylene, but it does not combine with hemoglobin. The concentration ia the blood is 1.4 mg/mL when ethylene is used by itself for anesthesia. However, ia the 1990s it is not used as an anesthetic agent. 

Taylor AE, KA Gaar Jr. (1970). Estimation of equivalent pore radii of pulmonary capillary and alveolar membranes. Am J Physiol 218 1133-1140. 

For an efficient pulmonary absorption process, the alveolar membrane seems to be an optimal absorption site for a number of reasons. 

The alveolar membrane forms the largest surface area in the lung. 

An alternative method which could be used to establish the fraction of protein that actually reaches the alveoli is the so-called co-aerosohzation. If a protein is aerosolized from a solution that also contains another low molecular weight substance (deposition marker), it can be assumed that the fractions of protein and deposition marker reaching the alveoli will be the same. The deposition marker should be a substance with a known alveolar epithelial membrane passage (e.g. tobramycin or a decapeptide) which does not undergo absorption after oral administration. The fraction of the deposition marker that is deposited in the alveoli can be established from plasma (and urine) measurements of the deposition marker. The maximum fraction of protein that can pass the alveolar membrane whl then be known. The ratio between the deposited fraction and the fraction that has been absorbed into the systemic circulation (as can be estabhshed form plasma or urine analysis) will provide an estimation of the protein passage across the alveolar membrane. 

Too often results are compromised by a poor experimental set-up of the studies and nontransparent data. Even essential information such as the relevant physicochemical characteristics of the drug in relation to the chosen aerosol system or the fraction that is deposited in the alveoli is often not provided. This makes it impossible to evaluate the impact of such studies. As a result, it is unclear until now to what extent and at what rate macromolecular drugs (> 20 kDa) can be absorbed by the lung. Moreover, the routes by which macromolecules pass through the different pulmonary membranes, especially the alveolar membrane, are unknown. Appropriate experiments and models that provide adequate answers to these questions are required in the coming years. 

Inhalation in the form of an aerosol (p. 12), a gas, or a mist permits drugs to be applied to the bronchial mucosa and, to a lesser extent, to the alveolar membranes. This route is chosen for drugs intended to affect bronchial smooth muscle or the consistency of bronchial mucus. Furthermore, gaseous or volatile agents can be administered by inhalation with the goal of alveolar absorption and systemic effects (e.g inhalational anesthetics, p. 218). Aerosols are formed when a drug solution or micron-ized powder is converted into a mist or dust, respectively. 

Practically speaking, this concept explains the basis for the establishment of partial pressure equilibrium of anesthetic gas between the lung alveoli and the arterial blood. Gas molecules will move across the alveolar membrane until those in the blood, through random molecular motion, exert pressure equal to their counterparts in the lung. Similar gas tension equilibria also will be established between the blood and other tissues. For example, gas molecules in the blood will diffuse down a tension gradient into the brain until equal random molecular motion (equal pressure) occurs in both tissues. 

Liposomes were formed from 1,2-dipalmitoylphosphatidylcholine (DPPC) and cholesterol (Choi) and the effect of liposomal entrapment on pulmonary absorption of insulin was related to oligomerization of insulin (Liu et al. 1993). Instillation of both dimeric and hexameric insulin produced equivalent duration of hypoglycemic response. However, the initial response from the hexameric form was slightly slower than that from dimeric insulin, probably due to lower permeability across alveolar epithelium of the hexameric form caused by larger molecular size. The intratracheal administration of liposomal insulin enhanced pulmonary absorption and resulted in an absolute bioavailability of 30.3%. Nevertheless, a similar extent of absorption and hypoglycemic effects was obtained from a physical mixture of insulin and blank liposomes and from liposomal insulin. This suggests a specific interaction of the phospholipid with the surfactant layer or even with the alveolar membrane. 

To estimate inhalation contact exposure, some assumptions must be made which err on the side of conservatism and which should be modified as more complete data become available. It is necessary to know the droplet size spectrum of the spray because the diameter of the droplet influences its movement down the respiratory system (11). The functional unit of the lung is the alveolus, which is the terminal branch in the system. It is presumed that pesticide particles which are soluble in respiratory tract fluid and are 5p or less in diameter will reach the alveolus where they will be readily absorbed through the cells of the alveolar membrane into the pulmonary capillary beds and hence into the circulatory system. A recent review by Lippmann at al. (12) discusses in depth the deposition, retention and clearance of inhaled particles. 

An increase in permeability of the alveolar membrane is seen in a number of pulmonary disease states including adult respiratory distress syndrome and fibrosis. Conversely, asthma does not appear to alter alveolar membrane permeability. Increased permeability will be seen in association with inflammatory reactions, where there is an influx of polymorphs and other cells into the airways. Inhalation of toxicants, such as smoke and industrial dusts, is associated with increased permeability. 

Q10 The transfer of CO across the respiratory surface (TCo) can be used to estimate the efficiency of gas transfer in the lung. A small concentration of CO is added to inspired air it diffuses across the alveolar membranes into the blood. The increase in arterial blood content of CO over a short period of time is measured to estimate the rate of CO transfer. A small concentration of CO must be used as this gas combines strongly with haemoglobin at the same position as oxygen to produce carboxyhaemoglobin. 

TCo decreases when alveolar membranes are thickened or fibrosed, when fluid accumulates in the alveoli and when ventilation is uneven or mismatched with perfusion. 

Benzene is lipid soluble and highly volatile at room temperature. As such, benzene readily crosses the alveolar membranes and is taken up by circulating blood in pulmonary vessels. The lung also serves as an excretion pathway for unmetabolized benzene, particularly following acute exposures. Benzene can also be readily absorbed from the gastrointestinal tract and from intact skin. Circulating benzene is preferentially taken up by lipid-rich tissues such as adipose and nervous tissue. Benzene has also been detected in the bone marrow, liver, kidneys, lungs, and spleen. 

Regan S, Turgeon C. 1986. Lack of antiglomerular basement membrane antibody binding to alveolar membranes after hydrocarbon exposure in rats. J Clin Lab Immunol 20 147-149. 

Perhaps the greatest source of danger in industrial and research laboratories lies in the inhalation of Hg vapor. Mercury vapor can diffuse through alveolar membrane and reach the brain whereby the vapor may interfere with coordination. The relative toxicity of various compounds toward tissue depends on their relative ease of formation of the Hg2+ ion. 

The mechanism of absorption for metallic mercury vapors is rapid diffusion across alveolar membranes (Berlin et al. 1969 Clarkson 1989). Mercury distribution in the brains of mercury-sensitive SJL/N mice exposed for 10 weeks (5 days per week) to relatively high concentrations (0.5-1.0 mg/m3) of mercury vapor was found to be affected by the magnitude of exposure (Warfvinge 1995). In animals exposed to 0.5 mg/m3 for 19 hours a day or 1 mg/m3 for 3 hours a day, mercury was found in almost the entire brain, whereas in those exposed to 0.3 mg/m3 for 6 hours a day, mercury was primarily found in the neocortical layer V, the white matter, the thalamus, and the brain stem. In mice exposed to 1 mg/m3 for just... 

Uptake of O2 by the blood in the lungs is governed primarily by the PO2 of alveolar air and by the ability of O2 to diffuse freely across the alveolar membrane into the blood. At the PO2 normally present in alveolar air 102mmHg) and with a normal membrane and normal hemoglobin A, more than 95% of hemoglobin will bind O2. At a PO2 >110 mm Hg, more than 98% of normal hemoglobin A binds O2. When all hemoglobin is saturated with O2, further increase in the PO2 of alveolar air simply increases the concentration of d02 in the arterial blood. 

Taylor, A.E. and Gaar, K.A. (1970) Estimation of pore radii of pulmonary and alveolar membranes. The American Journal of Physiology, 218, 1133-1140. 

Route of exposure. For example, HCN is readily absorbed across the pulmonary alveolar membrane, but skin presents a greater barrier to absorption. However, the integrity of the absorbing surface can also be a factor thus cyanides are more readily absorbed through recently abraded skin than intact skin (BaUantyne, 1994a). 

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