A three-dimensional model of the human pulmonary acinus.

A three-dimensional (3-D) model of the human pulmonary acinus, a gas exchange unit, is constructed with a labyrinthine algorithm generating branching ducts that fill a given space completely. Branching down to the third respiratory bronchioles is generated with the proposed algorithm. A subacinus, a region supplied by the last respiratory bronchiole, is approximated to be a set of cubic cells with a side dimension of 0.5 mm. The labyrinthine algorithm is used to determine a pathway through all cells only once, except at branching points with the smallest path lengths. In choosing each step of a pathway, random variables are used. Resulting labyrinths have equal mean path lengths and equal surface areas of inner walls. An alveolus can be generated by attaching alveolar septa, 0.25 mm long and 0.1 mm wide, to the inner walls. Total alveolar surface area and numbers of alveolar ducts, alveolar sacs, and alveoli in our 3-D acinar model are in good accordance with those reported in the literature.     

Morphometric changes in the human pulmonary acinus during inflation

Despite decades of research into the mechanisms of lung inflation and deflation, there is little consensus about whether lung inflation occurs due to the recruitment of new alveoli or by changes in the size and/or shape of alveoli and alveolar ducts. In this study we use in vivo (3)He lung morphometry via MRI to measure the average alveolar depth and alveolar duct radius at three levels of inspiration in five healthy human subjects and calculate the average alveolar volume, surface area, and the total number of alveoli at each level of inflation. Our results indicate that during a 143 ± 18% increase in lung gas volume, the average alveolar depth decreases 21 ±5%, the average alveolar duct radius increases 7 ± 3%, and the total number of alveoli increases by 96 ± 9% (results are means ± SD between subjects; P < 0.001, P < 0.01, and P < 0.00001, respectively, via paired t-tests). Thus our results indicate that in healthy human subjects the lung inflates primarily by alveolar recruitment and, to a lesser extent, by anisotropic expansion of alveolar ducts.     

Perfusion heterogeneity in the pulmonary acinus

There is little information on the distribution of acinarperfusion because it is difficult to resolve blood flow within such small regions. We hypothesized that the known heterogeneity of arteriolar blood flow and capillary blood flow would result in heterogeneous acinar perfusion. To test this hypothesis, the passage offluorescent dye boluses through the subpleural microcirculation ofisolated dog lobes was videotaped by using fluorescence microscopy. Asthe videotapes were replayed, dye-dilution curves were recorded fromeach of the tributary branches of Y-shaped venules that drained anacinus. From the dye curves, we calculated the mean appearance time ofeach curve. The difference in mean appearance times between venulartributary branches was small in most cases. In 43% of the observedvenular branch pairs, the dye curves were essentially superimposable(the mean appearance-time difference was <5%); and in another 42%,the mean appearance-time difference between curves was 5-10%.From these results, we conclude that acinar perfusion is unexpectedlyhomogeneous.

     

Evidence for minimal oxygen heterogeneity in the healthy human pulmonary acinus

It has been suggested that the human pulmonary acinus operates at submaximal efficiency at rest due to substantial spatial heterogeneity in the oxygen partial pressure (Po(2)) in alveolar air within the acinus. Indirect measurements of alveolar air Po(2) could theoretically mask significant heterogeneity if intra-acinar perfusion is well matched to Po(2). To investigate the extent of intra-acinar heterogeneity, we developed a computational model with anatomically based structure and biophysically based equations for gas exchange. This model yields a quantitative prediction of the intra-acinar O(2) distribution that cannot be measured directly. Temporal and spatial variations in Po(2) in the intra-acinar air and blood are predicted with the model. The model, representative of a single average acinus, has an asymmetric multibranching respiratory airways geometry coupled to a symmetric branching conducting airways geometry. Advective and diffusive O(2) transport through the airways and gas exchange into the capillary blood are incorporated. The gas exchange component of the model includes diffusion across the alveolar air-blood membrane and O(2)-hemoglobin binding. Contrary to previous modeling studies, simulations show that the acinus functions extremely effectively at rest, with only a small degree of intra-acinar Po(2) heterogeneity. All regions of the model acinus, including the peripheral generations, maintain a Po(2) >100 mmHg. Heterogeneity increases slightly when the acinus is stressed by exercise. However, even during exercise the acinus retains a reasonably homogeneous gas phase.     

Distribution of alcohol dehydrogenase isoenzymes in the human liver acinus

 By the use of a newly developed technique of ultrathin-layer electrophoresis, class I and class II alcohol dehydrogenase activity could be demonstrated in microdissected samples of the periportal, intermediate, and perivenous zones of the liver acinus in men and women. It could be demonstrated that both classes exhibit low activity in the periportal zone. From there, a rising gradient in the direction of the perivenous end was apparent. This increase, however, was found to be significant only in women. The analysis of class I alcohol dehydrogenase isoenzymes showed that the expression of α-, β-, and γ-containing isoforms did not differ in relation to the intraacinar position. The constant proportions of the isoenzymes to the maxima and minima of the total alcohol dehydrogenase activity support the view that the adult liver-specific isoenzyme pattern is determined during postnatal development. Accepted: 1 February 1999     

Streamline crossing: An essential mechanism for aerosol dispersion in the pulmonary acinus

The dispersion of inhaled microparticles in the pulmonary acinus of the lungs is often attributed to the complex interplay between convective mixing, due to irreversible flows, and intrinsic particle motion (i.e. gravity and diffusion). However, the role of each mechanism, the exact nature of such interplay between them and their relative importance still remain unclear. To gain insight into these dispersive mechanisms, we track liquid-suspended microparticles and extract their effective diffusivities inside an anatomically-inspired microfluidic acinar model. Such results are then compared to experiments and numerical simulations in a straight channel. While alveoli of the proximal acinar generations exhibit convective mixing characteristics that lead to irreversible particle trajectories, this local effect is overshadowed by a more dominant dispersion mechanism across the ductal branching network that arises from small but significant streamline crossing due to intrinsic diffusional motion in the presence of high velocity gradients. We anticipate that for true airborne particles, which exhibit much higher intrinsic motion, streamline crossing would be even more significant.     

Three-dimensional convective alveolar flow induced by rhythmic breathing motion of the pulmonary acinus

Low Reynolds number flows (Re<1) in the human pulmonary acinus are often difficult to assess due to the submillimeter dimensions and accessibility of the region. In the present computational study, we simulated three-dimensional alveolar flows in an alveolated duct at each generation of the pulmonary acinar tree using recent morphometric data. Rhythmic lung expansion and contraction motion was modeled using moving wall boundary conditions to simulate realistic sedentary tidal breathing. The resulting alveolar flow patterns are largely time independent and governed by the ratio of the alveolar to ductal flow rates, Qa/Qd. This ratio depends uniquely on geometrical configuration such that alveolar flow patterns may be entirely determined by the location of the alveoli along the acinar tree. Although flows within alveoli travel very slowly relative to those in acinar ducts, 0.021%相似文献   

Convective gas transport in the pulmonary acinus: Comparing roles of convective and diffusive lengths

To investigate the relative importance of convection and diffusion in the transport of oxygen in the pulmonary acinus, it is often useful to locate the transition from convection-dominated to diffusion-dominated transport. Traditionally, this is done by estimating the values of a Peclet number. This dimensionless number compares the bulk ductal flow velocity at an acinar generation with a diffusion velocity over a characteristic length scale. Here, we revisit the convection–diffusion transition by comparing the relative importance of convective and diffusive lengths. We introduce the ratio of such lengths (L_conv/L_diff) to quantify the extent of convective transport in the acinus over an inhalation phase. We distinguish between convection along the acinar airways and within alveoli, respectively. Results for L_conv/L_diff suggest that convection in acinar ducts may play a potential role in more peripheral airways compared with values obtained for a Peclet number. Within alveoli, however, independent of acinar depth, oxygen transport is governed by diffusion as soon as molecules enter within alveolar cavities.     

Finite element 3D reconstruction of the pulmonary acinus imaged by synchrotron X-ray tomography

The alveolated structure of the pulmonary acinus plays a vital role in gas exchange function. Three-dimensional (3D) analysis of the parenchymal region is fundamental to understanding this structure-function relationship, but only a limited number of attempts have been conducted in the past because of technical limitations. In this study, we developed a new image processing methodology based on finite element (FE) analysis for accurate 3D structural reconstruction of the gas exchange regions of the lung. Stereologically well characterized rat lung samples (Pediatr Res 53: 72-80, 2003) were imaged using high-resolution synchrotron radiation-based X-ray tomographic microscopy. A stack of 1,024 images (each slice: 1024 x 1024 pixels) with resolution of 1.4 mum(3) per voxel were generated. For the development of FE algorithm, regions of interest (ROI), containing approximately 7.5 million voxels, were further extracted as a working subunit. 3D FEs were created overlaying the voxel map using a grid-based hexahedral algorithm. A proper threshold value for appropriate segmentation was iteratively determined to match the calculated volume density of tissue to the stereologically determined value (Pediatr Res 53: 72-80, 2003). The resulting 3D FEs are ready to be used for 3D structural analysis as well as for subsequent FE computational analyses like fluid dynamics and skeletonization.     

高原鼢鼠和高原鼠兔肺细叶的结构特征

高原鼢鼠和高原鼠兔是青藏高原土著动物,对低氧具有很好的适应性.为了探讨在低氧环境中两者肺细叶结构的适应特征,应用体视学方法测量了肺细叶相关指标.结果发现 :高原鼢鼠和高原鼠兔肺单位面积肺泡数显著高于SD大鼠,单个肺泡面积和弹性纤维/肺实质比显著低于SD大鼠;高原鼢鼠肺泡隔厚度最厚,高原鼠兔最薄,且三种动物具显著差异; 高原鼢鼠和高原鼠兔气-血屏障的算术平均厚度(Ta)和调和平均厚度(Th) 均显著低于SD 大鼠;在三个级别的微血管中,高原鼠兔中膜肌层厚度显著低于高原鼢鼠,两种高原动物均显著低于SD大鼠;高原鼢鼠和高原鼠兔的微血管密度(MVD)显著高于SD大鼠.以上结果表明,高原鼢鼠和高原鼠兔肺细叶结构特征表现出一定趋同,这些特征有利于在低氧条件下提高肺气体扩散容量;但是,肺泡隔厚度和微血管中膜肌层厚度/血管外径比又表现出明显的差异,可能是不同生境造成的[动物学报 54(3):531-539,2008].     

Numerical simulation of airflow and microparticle deposition in a synchrotron micro-CT-based pulmonary acinus model

The acinus consists of complex, branched alveolar ducts and numerous surrounding alveoli, and so in this study, we hypothesized that the particle deposition can be much influenced by the complex acinar geometry, and simulated the airflow and particle deposition (density = 1.0 g/cm³, diameter = 1 and 3 μm) numerically in a pulmonary acinar model based on synchrotron micro-CT of the mammalian lung. We assumed that the fluid–structure interaction was neglected and that alveolar flow was induced by the expansion and contraction of the acinar model with the volume changing sinusoidally with time as the moving boundary conditions. The alveolar flow was dominated by radial flows, and a weak recirculating flow was observed at the proximal side of alveoli during the entire respiratory cycle, despite the maximum Reynolds number at the inlet being 0.029. Under zero gravity, the particle deposition rate after single breathing was less than 0.01, although the particles were transported deeply into the acinus after inspiration. Under a gravitational field, the deposition rate and map were influenced strongly by gravity orientation. In the case of a particle diameter of 1 μm, the rate increased dramatically and mostly non-deposited particles remained in the model, indicating that the rate would increase further after repeated breathing. At a particle diameter of 3 μm, the rate was 1.0 and all particles were deposited during single breathing. Our results show that the particle deposition rate in realistic pulmonary acinar model is higher than in an idealized model.     

Diffusional water permeability of human erythrocytes and their ghosts

The diffusional water permeability of human red cells and ghosts was determined by measuring the rate of tracer efflux by means of an improved version of the continuous flow tube method, having a time resolution of 2-3 ms. At 25 degrees C, the permeability was 2.4 x 10(3) and 2.9 x 10(3) cm s-1 for red cells and ghosts, respectively. Permeability was affected by neither a change in pH from 5.5 to 9.5, nor by osmolality up to 3.3 osmol. Manganous ions at an extracellular concentration of 19 mM did not change diffusional water permeability, as recently suggested by NMR measurements. A "ground" permeability of 1 x 10(3) cm s-1 was obtained by inhibition with 1 mM of either p- chloromercuribenzoate (PCMB) or p-chloromercuribenzene sulfonate (PCMBS). Inhibition increased temperature dependence of water permeability for red cells and ghosts from 21 to 30 kJ mol-1 to 60 kJ mol-1. Although diffusional water permeability is about one order of magnitude lower than osmotic permeability, inhibition with PCMB and PCMBS, temperature dependence both before and after inhibition, and independence of osmolality showed that diffusional water permeability has qualitative features similar to those reported for osmotic permeability, which indicates that the same properties of the membrane determine both types of transport. It is suggested that the PCMB(S)- sensitive permeability above the ground permeability takes place through the intermediate phase between integral membrane proteins and their surrounding lipids.     

Diffusional boundary spreading in the ultracentrifuge

A common approximation for deriving solutions to the Lamm equation is to neglect diffusion. This paper presents a singular perturbation technique that allows one to estimate the band spreading due to nonzero diffusion coefficient. We illustrate the general mathematical technique by its application to sedimentation when pressure effects are important. Comparison of the approximate solution with accurate numerical solutions shows that the relative errors are of the order of 1% both for concentration and concentration gradient for parameters of chemical interest.