Abstract:During pregnancy, oxygen diffuses from maternal to fetal blood through villous trees in the placenta. In this paper, we simulate blood flow and oxygen transfer in feto-placental capillaries by converting three-dimensional representations of villous and capillary surfaces, reconstructed from confocal laser scanning microscopy, to finite-element meshes, and calculating values of vascular flow resistance and total oxygen transfer. The relationship between the total oxygen transfer rate and the pressure drop throu… Show more
“…The model also assumes negligible interstitial flow in the villous tissue and does not account for transport of certain solutes via paracellular channels or energy-dependent membrane transporters [3,23]. Finally, our model does not explicitly account for nonlinear oxygen-haemoglobin binding kinetics (the effects of which are evaluated in [26]) and the particulate nature of capillary blood flow that could result in subtle spatial oxygen gradients (e.g. see [34] for an extensive overview).…”
Section: Discussionmentioning
confidence: 99%
“…Extending a regression formula proposed previously [3,26], we approximate the relationship between N and Da −1 (S.I., Sec. 3) using…”
Section: Theory Of Solute Transport In Feto-placental Networkmentioning
confidence: 99%
“…2B). Here the parameter Da F = µ 2 Da/α 3 c , where α c ≈ 5.5, accounts for transport across concentration boundary-layers within capillaries [26]. Setting this term to one side for a moment, the remaining terms provide a smooth transition between flowlimited transport (N ≈ N max /Da when Da −1 1) and diffusion-limited transport (N ≈ N max when Da −1 1, Fig.…”
Section: Theory Of Solute Transport In Feto-placental Networkmentioning
confidence: 99%
“…where D p is the solute diffusion coefficient in plasma. The parameter B = 1 for most solutes, but for species that bind to hemoglobin B quantifies the facilitated transport by red blood cells [21,26]. For example, for oxygen [21,26]…”
Across mammalian species, solute exchange takes place in complex microvascular networks. In the human placenta, the primary exchange units are terminal villi that contain disordered networks of fetal capillaries and are surrounded externally by maternal blood. We show how the irregular internal structure of a terminal villus determines its exchange capacity for diverse solutes. Distilling geometric features into three parameters, obtained from image analysis and computational fluid dynamics, we capture archetypal features of the structure-function relationship of terminal villi using a simple algebraic approximation, revealing transitions between flow- and diffusion-limited transport at vessel and network levels. Our theory accommodates countercurrent effects, incorporates nonlinear blood rheology, and offers an efficient method for testing network robustness. Our results show how physical estimates of solute transport, based on carefully defined geometrical statistics, provide a viable method for linking placental structure and function and offer a framework for assessing transport in other microvascular systems.
“…The model also assumes negligible interstitial flow in the villous tissue and does not account for transport of certain solutes via paracellular channels or energy-dependent membrane transporters [3,23]. Finally, our model does not explicitly account for nonlinear oxygen-haemoglobin binding kinetics (the effects of which are evaluated in [26]) and the particulate nature of capillary blood flow that could result in subtle spatial oxygen gradients (e.g. see [34] for an extensive overview).…”
Section: Discussionmentioning
confidence: 99%
“…Extending a regression formula proposed previously [3,26], we approximate the relationship between N and Da −1 (S.I., Sec. 3) using…”
Section: Theory Of Solute Transport In Feto-placental Networkmentioning
confidence: 99%
“…2B). Here the parameter Da F = µ 2 Da/α 3 c , where α c ≈ 5.5, accounts for transport across concentration boundary-layers within capillaries [26]. Setting this term to one side for a moment, the remaining terms provide a smooth transition between flowlimited transport (N ≈ N max /Da when Da −1 1) and diffusion-limited transport (N ≈ N max when Da −1 1, Fig.…”
Section: Theory Of Solute Transport In Feto-placental Networkmentioning
confidence: 99%
“…where D p is the solute diffusion coefficient in plasma. The parameter B = 1 for most solutes, but for species that bind to hemoglobin B quantifies the facilitated transport by red blood cells [21,26]. For example, for oxygen [21,26]…”
Across mammalian species, solute exchange takes place in complex microvascular networks. In the human placenta, the primary exchange units are terminal villi that contain disordered networks of fetal capillaries and are surrounded externally by maternal blood. We show how the irregular internal structure of a terminal villus determines its exchange capacity for diverse solutes. Distilling geometric features into three parameters, obtained from image analysis and computational fluid dynamics, we capture archetypal features of the structure-function relationship of terminal villi using a simple algebraic approximation, revealing transitions between flow- and diffusion-limited transport at vessel and network levels. Our theory accommodates countercurrent effects, incorporates nonlinear blood rheology, and offers an efficient method for testing network robustness. Our results show how physical estimates of solute transport, based on carefully defined geometrical statistics, provide a viable method for linking placental structure and function and offer a framework for assessing transport in other microvascular systems.
“…Similar models were proposed by Pearce etal. [60] (see Fig. 4c), who quantified the sensitivity of these simulations to uncertainties in the geometry and parameters.Fig.4Models of transport in the human placenta.…”
Pregnancy complications are a major clinical concern due to the related maternal and fetal morbidity. Many are caused through defective placentation, but research into placental function is difficult, principally because of the ethical limitations associated with the in-vivo organ and the difficulty of extrapolating animal models. Perfused by two separate circulations, the maternal and fetal bloodstreams, the placenta has a unique structure and performs multiple complex functions. Three-dimensional imaging and computational modelling are becoming popular tools to investigate the morphology and physiology of this organ. These techniques bear the potential for better understanding the aetiology and development of placental pathologies, however, their full potential is yet to be exploited. This review aims to summarize the recent insights into placental structure and function by employing these novel techniques.
In pregnancy, fetal growth is supported by its placenta. In turn, the placenta is nourished by maternal blood, delivered from the uterus, in which the vasculature is dramatically transformed to deliver this blood an ever increasing volume throughout gestation. A healthy pregnancy is thus dependent on the development of both the placental and maternal circulations, but also the interface where these physically separate circulations come in close proximity to exchange gases and nutrients between mum and baby. As the system continually evolves during pregnancy, our understanding of normal vascular anatomy, and how this impacts placental exchange function is limited. Understanding this is key to improve our ability to understand, predict, and detect pregnancy pathologies, but presents a number of challenges, due to the inaccessibility of the pregnant uterus to invasive measurements, and limitations in the resolution of imaging modalities safe for use in pregnancy. Computational approaches provide an opportunity to gain new insights into normal and abnormal pregnancy, by connecting observed anatomical changes from high-resolution imaging to function, and providing metrics that can be observed by routine clinical ultrasound. Such advanced modeling brings with it challenges to scale detailed anatomical models to reflect organ level function. This suggests pathways for future research to provide models that provide both physiological insights into pregnancy health, but also are simple enough to guide clinical focus. We the review evolution of computational approaches to understanding the physiology and pathophysiology of pregnancy in the uterus, placenta, and beyond focusing on both opportunities and challenges.
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