Perfusion-limited transport

Figure 10.8 Perfusion-limited transport across the capillary wall allows the venous drug concentration Cy) to reach equilibrium with the tissue drug concentration (Cr)-...

When written in this form, Tt is positive for net transport into the tissue (e.g., distribution to tissue), or negative for net transport out of the tissue (e.g., absorption from site of administration). This equation for perfusion-limited transport clearly shows that for this limiting case, transport between the blood and tissue is dependent solely on the rate of blood perfusion (Q) and not on the permeability (P) or surface area for transport S) between the capillary lumen and tissue. 

While human mammary tissue apparently has limited ability to transport pyridoxal phosphate, about 23% of the label appearing in the fetal compartment was in the form of pyridoxal phosphate when human placenta was perfused with labeled pyridoxal (Sdienker et aL, 1992). Perfusion with pyridoxal phosphate resulted in limited transport unless the perfusate was recirculated, thus allowing hydrolysis to pyridoxal. The appearance of pyridoxal phosphate on the fetal side during perfusion with pyridoxal suggests that the pyridoxal was phosphorylated and secreted into the fetal circulation presumably bound to protein. 

In addition to factors Influencing luminal uptake of zinc, transfer across the basolateral membrane has been shown to be dependent on the concentration of albumin in the portal circulation (33). These investigations suggest that metabolic factors which affect the albumin concentration in the plasma may also affect the rate of portal zinc transfer. It should be noted that EDTA did not enhance zinc accumulation within the mucosal cells yet it Increased transfer to the vascular perfusate. These results suggest that basolateral membrane transport of zinc is enhanced by EDTA. We have proposed (35), as has Davies (38), that basolateral transport to the circulation is the rate limiting phase of zinc absorption. Since EDTA and zinc might be transported as a complex (42), the latter may transverse this barrier more easily and thus Increase zinc absorption. 

Indocyanine green was introduced by J. Caesar et al. in 1961 as a liver function test. Anionic tricarbocyanine dye is referred to as an ideal test substance (1.) it is tolerated very well there have been no reports of any incidents so far, and even paravenous injection is tolerated (2.) it is excreted unchanged by hepatocytes in the bile as there is no bio transformation - this is why ICG clearance is valid as a measure of hepatocellular uptake and transport processes (3.) there is no interference with drugs (except rifamycin), haemolysis, bilirubin (up to approx. 4 mg/dl) or hyperlipidaemia (4.) the substance is not subject to the enterohepatic circulation (J.) the rapid elimination, which depends on hepatic perfusion ( flow-limited ), allows the calculation of the hepatic flow volume as a whole based on ICG clearance (6.) the method is simple to perform. 

Limitations of the in vitro perfused juxtamedullary nephron preparation include 1) the availability of only a select population of juxtamedullary glomeruli near the inner surface of the kidney 2) underestimation of the contribution of flow in large vessels to preglomeru-lar resistance and 3) lack of characterization of tubular transport. 

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