1. We have investigated fluid movements between superficial ascending vasa recta (AVR) and the interstitium of exposed papillae of the renal medullae in 15-day-old Sprague-Dawley rats anaesthetized with Hypnorm and Hypnovel. 2. Using a development of the red cell micro-occlusion technique, fluid filtration and reabsorption rates per unit area of vessel wall (Jv/A) were determined in 54 single perfused AVR at known microvascular pressures (P,,). The relation between Jv/A and P, was nonlinear suggesting hydraulic permeabilities (Lp) of 50-100 x 10-7 cm s-1 cmH2T-when P, was between 0-10 cmH2O and 150-200 x 10-7 cm s' cmH20-when P, was 10-15 cmH2O.3. Rates of fluid reabsorption into the AVR estimated by a densitometric technique in a further fourteen vessels were consistent with Lp values of 50-100 x 10-7 cm s-1 cmH2O-when P, was-2 to 0 cmH2O. 4. The effective oncotic pressures of perfusates containing bovine serum albumin (BSA) were consistent with minimum values for the reflection coefficients of the walls of the AVR to BSA of between 0 59 and 0-72. 5. The concentration of native serum albumin in the papillary interstitial fluid was 9-1 + 0-6 mg ml-1 (mean + S.E.M., n = 16, from 9 rats), which is approximately 25% of the plasma level. 6. After their microinjection into the medullary interstitium, Patent Blue V and Evans Blue-albumin cleared within 1 min. There was no evidence of preferential movement of either dye towards the base of the exposed renal medulla.7. Because Lp of the AVR is high, mean pressures of only -3 cmH2O are necessary to account for the total clearance of fluid from the medullary interstitium into the AVR. From published data and from our own observations, it appears that differences in hydrostatic and oncotic pressure across the walls of the AVR are more than sufficient to provide this driving force. The possibility of the clearance of protein from the interstitium into the AVR is discussed.The reabsorption of fluid from the renal interstitium into the ascending vasa recta (AVR) is the final stage in the conservation of water by the formation of a concentrated urine. The details of this process are unclear. In most microvascular beds, net fluid uptake from tissues to blood occurs when the oncotic pressure of the plasma exceeds the sum of the oncotic pressure of the pericapillary fluid and the hydrostatic pressure difference across the microvascular walls (Starling, 1896). In these tissues there are lymphatics, which act both as an overflow and as a route for clearing plasma protein from the interstitial fluid. It has been argued that in tissues, such as the intestinal mucosae and the renal cortex, the steady uptake of fluid into the blood depends on a parallel but much smaller flow of lymph which, by clearing interstitial proteins, maintains the oncotic pressure differences across the capillary walls (Michel, 1984;Levick, 1991). In the inner zone of the renal medulla, however, lymphatics are difficult to demonstrate and it is concluded that they are either sparse (Cuttino, Jennette, Clark &...

Kupffer cell migration and leukocyte-vessel wall interactions cause temporary slowing and/or stoppage of blood flow through individual liver sinusoids. Such temporal heterogeneity of flow was quantified in anesthetized mice and rats. Video recordings of red blood cell flow in 44 networks containing 8-16 sinusoids each were analyzed for 5- to 10-min periods. Flow was graded "fast," "slow," "stopped," or "reversed" based on red blood cell velocity. The mean numbers of flow changes (between grades) per minute in zone 1 vs. zone 3 were 1.39 vs. 0.78 (mouse) and 1.25 vs. 0.09 (rat). The mean percentage of time for each flow grade differed significantly between zones 1 and 3 and between species. For example, fast flow was present in zone 1 sinusoids for 51% of the time in mice and for 74% in rats; in zone 3 the corresponding numbers were 76 and 95%. Flow stasis was present in zone 1 sinusoids for 19% of the time in mice and for 7% in rats; in zone 3 the corresponding numbers were 2 and 0%. Thus considerable intermittence of perfusion exists, and the flow conditions create very different microenvironments for hepatocytes in zone 1 vs. zone 3.

The acute and chronic effects of mouse hepatitis virus type 3 on the microcirculation of the liver in both semisusceptible C3HeB/FeJ and fully resistant A/J mice were studied. In the C3HeB/FeJ mice, abnormalities of microcirculatory flow were noted as early as 12 hr after infection and by 24 hr, localized avascular foci appeared. Disturbances were characterized by granular blood flow, sinusoidal microthrombi, distortion of sinusoids by edematous hepatocytes and necrotic lesions. Following the acute infection, Day 10, two patterns of chronic disease were observed. Eighty percent of the mice developed chronic granulomatous hepatitis whereas in the remaining 20% a more severe chronic aggressive hepatitis was observed which was characterized by ongoing hepatocellular necrosis and a marked mononuclear cell infiltrate. In both cases, in vivo microcirculatory abnormalities were found predominantly around visible lesions. Onset of the microcirculatory abnormalities was found to be concomitant with a rise in monocyte related procoagulant activity. Procoagulant activity rose acutely and remained elevated throughout the chronic phase but was higher in animals with severe disease. In contrast to the above, normal blood flow and histology were seen in the resistant A/J mice at all times following infection, and procoagulant activity remained at basal levels despite active viral replication as demonstrated by immunofluorescence studies and recovery of infectious virus. These observations suggest a role for monocyte procoagulant activity in the development of microcirculatory abnormalities following mouse hepatitis virus type 3 infection which may be important in the pathogenesis of the disease.

Kupffer cells are generally considered fixed tissue macrophages of the liver. However, we have evidence that this opinion is incorrect. High-resolution in vivo video microscopy shows that Kupffer cells have the ability to migrate along sinusoidal walls. Images recorded from anesthetized mice show active locomotion of cells with or against the direction of blood flow or in the absence of flow. The size, changing morphology, and uptake of carbon or microspheres strongly suggest that these are Kupffer cells. Quantitative measurements were made on 29 migrating Kupffer cells. The mean speed of migration was 4.6 +/- 2.6 (SD) microns/min and was not significantly different whether migration occurred with or against the flow. When fluorescent microspheres were given in vivo as a phagocytic challenge, Kupffer cells containing few microspheres migrated more slowly (0.9 +/- 0.9 microns/min, n = 10), whereas those containing many microspheres were never seen to migrate. Individual Kupffer cells were able to move independently, i.e., in directions different from those of neighboring Kupffer cells. These findings may have major implications for the role of Kupffer cells in scavenging foreign particles and as antigen-presenting cells.

1. We have investigated the hypothesis that ascending vasa recta (AVR) in the rat renal medulla are able to remain open when the external pressure is greater than the internal. 2. Individual vasa recta were cannulated in anaesthetized rats with Evans Blue albumin solution and then occluded downstream prior to the first branchpoint. When the intraluminal pressure was lowered, the lumina collapsed at a mean pressure of approximately -4 0 cmH2O for both AVR and descending vasa recta. 3. The studies were extended to include microvessels from rat spinotrapezius muscle and mesentery and frog mesentery; mean closing pressures were -32, -4-2 and -5-3 cmH2O, respectively.

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Cirrhosis is defined as the scarring of the liver acini in zone 3, zone 1 or in both; the resulting nodules are scarred and modified remnants of acini of various orders. The division of the nodules into "micronodules" and "macronodules" is difficult to justify as their two dimensional appearance changes at different planes of section. Early scar formation precedes changes in the microcirculatory dynamics. Sprouting of vascular branches, especially of arterioles, takes the leading role in the development of mature scars, i.e. of fibro-vascular membranes. The fibrous repair is at the same time the road builder for collateral flow. The pathophysiology of the collateral circulation is the basic determinant in the formation of the cirrhotic patterns. The three microcirculatory phases in the cirrhotic process are due to a changeover of the intrahepatic circulatory path from the normal trichotomy of the preterminal vascular branches to convoluted collateral channels. The three phases of the cirrhotic process are: The Triadal Nodule. It receives blood from the TPV and THA and from the perinodular plexus. The nodular parenchyma may already be segregated from the ThV, a situation that leads to portal hypertension. The Para-triadal Nodule. It is a conglomerate of nodules that often are not completely separated from each other; they are derived from neighbouring acini of various orders which receive blood from large triads contained in the perinodular scar. The blood arrives into the sinusoids primarily via the perinodular plexus. Some sinusoids may receive additional blood through sclerosing remnants of terminal afferent branches and through irregular vascular twigs which, along with septa, enter the nodules at various sites. The A-triadal Nodule. It is completely separated from neighbouring nodules by thick scars, its parenchyma totally segregated from afferent and efferent vascular branches. The nodules receive blood only from a dense perinodular plexus of wide capillaries.

Mouse hepatitis virus type 3 infection results in strain-dependent liver disease. The effects of mouse hepatitis virus type 3 on the microcirculation of the liver in both fully susceptible (Balb/cJ) and fully resistant (A/& mice were studied. In Balb/cJ mice, 6 to 12 h r following infection, abnormalities in liver blood flow were observed which consisted of granular blood flow in both terminal hepatic and terminal portal venules. In addition, sinusoidal microthrombi were present predominantly in periportal areas. By 24 to 48 hr, liver cell edema and small focal lesions were prominent. At 48 hr, thrombi and hepatocellular necrosis were widespread, and blood was shunted from damaged areas into patent sinusoids. In sharp contrast to these abnormal findings, normal streamlined blood flow was present in the resistant A/J animals at all time points following infection. Since large amounts of virus were demonstrated by immunofluorescene in and by recovery and growth from livers of both resistant and susceptible strains, the presence of the virus per se cannot explain the abnormalities observed.