Blood flow description

Ongoing work is devoted to the accurate description of the origin and spread of excitation from the natural pacemaker to the rest of the heart. Computations of ventricular pressure development are being extended to account for blood flow dynamics in adjacent blood vessels. The thorax... 

Because PB-PK models are based on physiological and anatomical measurements and all mammals are inherently similar, they provide a rational basis for relating data obtained from animals to humans. Estimates of predicted disposition patterns for test substances in humans may be obtained by adjusting biochemical parameters in models validated for animals adjustments are based on experimental results of animal and human in vitro tests and by substituting appropriate human tissue sizes and blood flows. Development of these models requires special software capable of simultaneously solving multiple (often very complex) differential equations, some of which were mentioned in this chapter. Several detailed descriptions of data analysis have been reported. 

As with classic compartment pharmacokinetic models, PBPK models can be used to simulate drug plasma concentration versus time profiles. However, PBPK models differ from classic PK models in that they include separate compartments for tissues involved in absorption, distribution, metabolism and elimination connected by physiologically based descriptions of blood flow (Figure 10.1). 

It is possible to predict what happens to Vd when fu or fur changes as a result of physiological or disease processes in the body that change plasma and/or tissue protein concentrations. For example, Vd can increase with increased unbound toxicant in plasma or with a decrease in unbound toxicant tissue concentrations. The preceding equation explains why because of both plasma and tissue binding, some Vd values rarely correspond to a real volume such as plasma volume, extracellular space, or total body water. Finally interspecies differences in Vd values can be due to differences in body composition of body fat and protein, organ size, and blood flow as alluded to earlier in this section. The reader should also be aware that in addition to Vd, there are volumes of distribution that can be obtained from pharmacokinetic analysis of a given data set. These include the volume of distribution at steady state (Vd]SS), volume of the central compartment (Vc), and the volume of distribution that is operative over the elimination phase (Vd ea). The reader is advised to consult other relevant texts for a more detailed description of these parameters and when it is appropriate to use these parameters. 

Once the phenotype of a blood cell malignancy in a particular patient is known, the cytometrist can use the multiparameter flow description of that phenotype to define the malignant clone and to look for the absence of these cells in order to diagnose remission after... 

The portal vein lobule was first recognized in the description of the portal unit given by RP. Mall (1906). It resembles a hexagon. The periportal field constitutes the axis at the centre while the central veins form the limiting points, (s. fig. 2.13) The glandular character of the liver is the main criterion of differentiation of the portal vein lobule. Thus the direction of blood flow is from the centre towards the periphery (centrifugal) and the direction of bile flow from the periphery towards the centre (centripetal). It could also be demonstrated that the lobule periphery is enclosed by basket-like ramifications of the portal vein (= corbicula portalis). (77) This further emphasizes the significance of the hepatic lobule. 

A major objective of fundamental studies on hollow-fiber hemofliters is to correlate ultrafiltration rates and solute clearances with the operating variables of the hemofilter such as pressure, blood flow rate, and solute concentration in the blood. The mathematical model for the process should be kept relatively simple to facilitate day-to-day computations and allow conceptual insights. The model developed for Cuprophan hollow fibers in this study has two parts (1) intrinsic transport properties of the fibers and (2) a fluid dynamic and thermodynamic description of the test fluid (blood) within the fibers. 

Tamura, A., Graham, D.I., McCullogh, J., Teasdale, G.M., 1981. Focal cerebral ischaemia in rat 1. Description of techniques and early neuropathological consequences. J. Cereb. Blood Flow Metab. 1, 53-60. 

Within the vasculature of a tissue, blood flows in all directions, and the local direction of convection depends on the vascular morphology of the tissue. The situation is even more complex in tumors where the direction and magnitude of blood flow are not fixed. In tumors, blood flow is temporally and spatially inhomogeneous. Therefore, the local description of convective heat transfer term, Qb, in tissues would include a time-dependent velocity vector — a problem which is enormously complex and has thus far proven mathematically intractable. In order to circumvent a mathematical description of the details and complexities of the microcirculation in a capillary bed, primarily two approaches have been taken by investigators in this area of research (Charny, 1992). 

The arterial circulation is a multiply branched network of compliant tubes. The geometry of the network is complex, and the vessels exhibit nonlinear viscoelastic behavior. Flow is pulsatile, and the blood flowing through the network is a suspension of red blood cells and other particles in plasma which exhibits complex non-Newtonian properties. Whereas the development of an exact biomechanical description of arterial hemodynamics is a formidable task, surprisingly useful results can be obtained with greatly simplified models. 

To conclude, many important features of blood flow through arterioles and venules are qualitatively known and understood however, a rigorous theoretical description of flow as a suspension of discrete particles is not yet available. Such description is necessary for a quantitative understanding of the mechanisms of the nonuniform distribution of blood cells in microvessels. 

---