Pulmonary circulation

Fig. 3. Schematic representation showing the anatomical basis for differences in the quantitative supply of absorbed material to the Hver. By swallowing (oral route), the main fraction of the absorbed dose is transported direcdy to the Hver. FoUowing inhalation or dermal exposure, the material passes to the pulmonary circulation and thence to the systemic circulation, from which only a portion passes to the Hver. This discrepancy in the amount of absorbed material passing to the Hver may account for differences in toxicity of a material by inhalation and skin contact, compared with its toxicity by swallowing, if metaboHsm of the material in the Hver is significant in its detoxification or metaboHc activation.

Prostacyclin (epoprostanol) is one of the few drugs effective for the treatment of Primary Pulmonary Hypertension (PPH) a rare but frequently fatal illness of young adults. Increased blood pressure in the pulmonary circulation leads to right-heart failure. Continuous infusion of epoprostanol leads to a decrease in blood pressure however, it is unclear whether this is due to direct dilator activity of the IP receptor acting on smooth muscle, or a more indirect mechanism. 

Once the oxygen has diffused from the alveoli into pulmonary circulation, it must be carried, or transported, in the blood to cells and tissues that need it. Furthermore, once the carbon dioxide has diffused from the tissues into the systemic circulation, it must be transported to the lungs, where it can be eliminated. This section considers mechanisms by which these gases are transported. 

Start with the theoretical lungs shown above and remember that blood entering the systemic circulation has a component that is shunted past the pulmonary circulation (Qs) and another component that passes through it (Qt - Qs). 

Two different circulatory systems, the bronchial and the pulmonary, supply the lungs with blood [133], The bronchial circulation is a part of the systemic circulation and is under high pressure. It receives about 1% of the cardiac output and supplies the conducting airways, pulmonary blood vessels and lymph nodes [133], It is important for the distribution of systemically administered drugs to the airways and to the absorption of inhaled drugs from the airways [18]. The pulmonary circulation comprises an extensive low-pressure vascular bed, which receives the entire cardiac output. It perfuses the alveolar capillaries to secure efficient gas exchange and supplies nutrients to the alveolar walls. Anastomoses between bronchial and pulmonary arterial circulations have been found in the walls of medium-sized bronchi and bronchioles [18, 65, 67],... 

One important mechanism of serotonin elimination is the (re-) uptake, e.g. by platelets. Furthermore, serotonin is metabolized by monoaminox-idase to 5-hydroxyindoleacetaldehyde and, subsequently, by an aldehyde dehydrogenase to 5-hydroxyindolacetic acid. The vascular effects of serotonin are complex. The direct interaction with vascular smooth muscle induces a vasoconstriction, whereas the stimulation of 5-HT-receptors on the endothelium induces the release of vasorelaxant factors with a dilatation as a result. An intravenous application of serotonin increases the pressure in the pulmonary circulation. A continuous infusion results... 

Gases diffuse from areas of high partial pressure to areas of low partial pressure thus, the tension of anesthetic in the alveoli provides the driving force to establish brain tension. In fact, the tension of anesthetic in all body tissue will tend to rise toward the lung tension as equilibrium is approached. Consequently, factors that control or modify the rate of accumulation of anesthetic in the lung (e.g., rate of gas delivery, uptake of gas from the lung into the pulmonary circulation) will simultaneously influence the rate at which tension equilibria in other body compartments is established. 

The alveolar tension-time curve always declines in an exponential manner, but the position of the curve can be greatly affected by the rate of delivery of anesthetic gases and the rate of their uptake into the pulmonary circulation. For this reason, it is important to consider factors that modify or regulate delivery and uptake. 

Any decrease in cardiac output will allow the tension of the inhaled agent in the blood to increase more rapidly. This occurs because transit time through the pulmonary circulation is slowed. In this way, equilibrium between the tensions in alveoli and blood is accelerated. 

Adenosine affects vascular smooth muscle tone in the pulmonary circulation. In the feline pulmonary vascular bed, under conditions of controlled pulmonary blood flow and constant left atrial pressure, adenosine was shown to produce dose-dependent, tone-dependent responses (Neely and Matot 1996 Cheng et al. 1996). At low baseline pulmonary vascular tone adenosine induces vasoconstriction via A3AR and the release of prostanoids, whereas at elevated pulmonary vascular tone it produces vasodilatation by acting on A2AR, without nitric oxide release or the activation of guanylate cyclase or KATp channels (Neely and Matot 1996 Cheng et al. 1996). 

In human as well as in some experimental models, such as the canine (Mentzer et al. 1975) and feline (Neely et al. 1989), adenosine has been demonstrated to act as a vasodilator in the lungs during conditions of elevated tone. However, the contribution of A3AR to this effect is not clear. Earlier studies have postulated A2 receptors to mediate adenosine-induced vasodilatation (Berne 1963 Phillis et al. 1987 McCormack et al. 1989). In the pulmonary circulation of rabbits and rats, adenosine has been reported to produce vasodilation via A2aAR or A2BAR, respectively (El-Kashef et al. 1999 Haynes et al. 1995,1999). Accordingly, in an isolated blood-perfused rat lung, adenosine-induced vasodilatation was shown to be... 

McCormack DG, Clarke B, Barnes PJ (1989) Characterization of adenosine receptors in human pulmonary arteries. Am J Physiol 256(2) H41-H46 McWhinney CD, Dudley MW, Bowlin TL, Peet NP, Schook L, Bradshaw M, De M, Borcherding DR, Edwards CK 3rd (1996) Activation of adenosine A3 receptors on macrophages inhibits tumor necrosis factor-alpha. Eur J Pharmacol 310(2-3) 209-216 Mentzer RM Jr, Rubio R, Berne RM (1975) Release of adenosine by hypoxic canine lung tissue and its possible role in pulmonary circulation. Am J Physiol 229(6) 1625-1631 Meyerhof W, Mtiller-Brechlin R, Richter D (1991) Molecular cloning of a novel putative G-protein coupled receptor expressed during rat spermiogenesis. FEBS Lett 284(2) 155-160... 

The respiratory system is responsible for mediating gas exchange between the external environment and the bloodstream. The upper respiratory tract conducts air to the lower respiratory passages and ultimately to the lungs. It also humidifies and conditions inspired air and serves to protect the lungs from harmful substances. In the lungs, gas exchange takes place between the alveoli and the pulmonary circulation. 

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