A simplified two-pore filtration model explains the effects of hypoproteinemia on lung and soft tissue lymph flux in awake sheep.

We used a simplified two-pore filtration model to examine the effects of hypoproteinemia on lung and soft tissue lymph flux in awake sheep (n = 7). To induce hypoproteinemia, we subjected each animal to 3 days of batch plasmapheresis (6 units per day). Data were collected in near steady-state conditions, 15-18 hr following completion of the last plasmapheresis episode. At this time, plasma protein concentration had fallen by 34%, while lung and soft tissue lymph protein concentrations had fallen by 55 and 62%, respectively. Lung and soft tissue lymph flows increased 52 and 87%, respectively. The plasma-to-lymph osmotic pressure gradients for lung and soft tissue lymph were unchanged by protein depletion (soft tissue, 7.7 mm Hg; lung, 4.8 mm Hg). We applied these results to a heteropore model of the microvascular barrier that consisted of two types of pores: those which plasma proteins could not cross (sigma = 1) and those which proteins could cross without restriction (sigma = 0). We varied the proportion of small pores to large pores until the measured data fit a model in which the calculated microvascular hydrostatic pressures in normal and hypoproteinemic conditions were equal. This was based on the assumption that microvascular hydrostatic pressure did not change with plasma protein depletion. These conditions could be satisfied when the small pores accounted for 90% of total barrier porosity. According to the model, lymph flow increased in hypoproteinemia because of an increase in protein-free liquid flux through the large percentage of small pores; protein flux through the small percentage of large pores remained unchanged. The net result was an increase in lymph flow and a decrease in the lymph protein concentration. The model reproduced these changes even though the plasma-to-lymph osmotic pressure gradients were unchanged. We conclude that a simplified heteropore model can explain the effects of hypoproteinemia on lung and soft tissue lymph flux.