Filtration, passive membrane transport

When addressing excretion from the kidneys glomeruli, the principles of passive membrane diffusion are again applicable. Chemicals which are ionized (water soluble) and those that are non-ionized (lipid soluble) are reabsorbed. There are also active renal transport mechanisms, such as those in the proximal tubules for organic acids and organic bases. Toxins bound to plasma proteins, too large for renal glomerular filtration, are often excreted in bile. Active mechanisms exist to transport chemicals from plasma to liver and from liver to bile for excretion. 

Materials may be absorbed by a variety of mechanisms. Depending on the nature of the material and the site of absorption, there may be passive diffusion, filtration processes, faciHtated diffusion, active transport and the formation of microvesicles for the cell membrane (pinocytosis) (61). EoUowing absorption, materials are transported in the circulation either free or bound to constituents such as plasma proteins or blood cells. The degree of binding of the absorbed material may influence the availabiHty of the material to tissue, or limit its elimination from the body (excretion). After passing from plasma to tissues, materials may have a variety of effects and fates, including no effect on the tissue, production of injury, biochemical conversion (metaboli2ed or biotransformed), or excretion (eg, from liver and kidney). 

A membrane is defined as an intervening phase separating two phases forming an active or passive barrier to the transport of matter. Membrane processes can be operated as (1) Dead-end filtration and (2) Cross-flow filtration. Dead-end filtration refers to filtration at one end. A problem with these systems is frequent membrane clogging. Cross-flow filtration overcomes the problem of membrane clogging and is widely used in water and wastewater treatment. 

Renal handling of uric acid. Uric acid may be actively reabsorbed from the ultrafiltrate following its glomerular filtration or it may be secreted from the blood across the basolateral membrane into the proximal tubular cell. Both passive and active transport mechanisms are involved in the handling of urate. Uricosuric drugs at appropriate doses interfere with these processes. 

Figure 12.4 Mechanism of action of Na+/K+symport inhibitors (thiazides) on the distal convoluted tubule. As in the other parts of the nephron, Na+movement is powered by the energy-requiring sodium pump (P) in the basolateral membrane which exchanges intracellular Na+for K-i-in the extracellular fluid (ECF). The transport of Na-rand Cl- into the cell from the filtrate against the prevailing electrochemical gradient is facilitated by the symporter (S). The Na-Hons are then transported by the pump mechanism described above and the Cl- ions diffuse passively Into the ECF through ion channels in the basolateral membrane. Thiazide diuretics inhibit the symporter by disabling the Cl- binding site with the loss of Na-rand Cl- in the urine.

Thus, the nature of these membranes and the chemical and physical properties of the toxicant in question are important factors affecting uptake. The mechanisms by which chemical agents pass through the membranes include (1) filtration through spaces or pores in membranes (2) passive diffusion through the spaces or pores, or by dissolving in the lipid material of the membrane and (3) facilitated transport, whereby specialized transport systems carry water-soluble substances across the membrane by a lipid soluble "carrier" molecule, which complexes with the chemical. It can be seen then that, as far as the chemical properties are concerned, lipophilicity is the most important factor affecting absorption. 

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