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B. Glomerular Diseases

Autoantibodies e.g.

Renal vein thrombosis, venous congestion

Hydrostatic pressure f

B. Glomerular Diseases

Autoantibodies e.g.

Renal vein thrombosis, venous congestion

Hydrostatic pressure f

Photos from: Doerr,W. ed. Organpathologie. Stuttgart: Thieme; 1974

Disorders of Glomerular Permselectivity, Nephrotic Syndrome

The glomerular filter (fenestrated endothelium, basement membrane, slit membrane between podocytes) is not equally permeable for all blood constituents (selective permeability or permselectivity). Molecules larger in diameter than the pores do not pass the filter at all. Molecules of clearly smaller diameter will e in practice pass through, as will water, i.e., c their concentration in the filtrate is approxi--■5 mately the same as that in plasma water. If B these substances are not reabsorbed or secret-£ ed in the kidney, their clearance (C) is identical g to the GFR, and the fractional excretion (C/ -q GFR) is 1.0. If molecules are only slightly smalls ler in diameter than the diameter of the pores, only some of them can follow water through 10 the pores, so that their concentration in the filtrate is lower than in plasma (^ A1). .g However, permeability is determined not

¡5 only by the size, but also by the charge of the m molecule. Normally, negatively-charged molecules can pass through much less easily than neutral or positively-charged molecules (^A1). This is due to negative fixed charges that make the passage of negatively-charged particles difficult.

In glomerulonephritis (^ p. 102) the integrity of the glomerular filter may be impaired, and plasma proteins and even erythrocytes can gain access to the capsular space (^A2). This results in proteinuria and hematuria. Close observation of proteinuria indicates that it is especially the permeability for negatively-charged proteins that is increased. This behavior can be demonstrated most impressively by infusing differently charged polysaccha-rides, because polysaccharides—in contrast to proteins—are hardly reabsorbed by the tubules. Negatively-charged (-) dextrans are normally less well filtered than neutral (n) or cationic (+) dextrans. This selectivity is lost in glomerulonephritis and filtration of negatively-charged dextrans is massively increased (^ A2). One of the causes of this is a breakdown of negatively-charged proteoglycans, for example, by lysosomal enzymes from inflammatory cells that split glycosaminoglycan. As has been shown by electrophoresis, it is espe-104 cially the relatively small, markedly negatively-charged albumins that pass across the membrane (^ A3). Even an intact glomerulus is permeable to a number of proteins that are then reabsorbed in the proximal tubules. The transport capacity is limited, though, and cannot cope with the excessive load of filtered protein at a defective glomerular filter. If tubular protein reabsorption is defective especially small proteins appear in the final urine (tubular proteinuria).

Renal loss of proteins leads to hypopro-teinemia. Serum electrophoresis demonstrates that it is largely due to a loss of albumin (^ A4), while the concentration of larger proteins actually tends to increase. This is because the reduced oncotic pressure in the vascular system leads to increased filtration of plasma water in the periphery and thus to a concentration of the other blood constituents. Filtration in the peripheral capillaries is facilitated not only by the reduced oncotic pressure, but also by damage to the capillary wall that may also be subject to inflammatory changes. As a result of protein filtration in the periphery, protein concentration and oncotic pressure rise in the interstitial spaces, so that the filtration balance shifts in favor of the interstitial space (^ A5). If the removal of proteins via the lymphatics is inadequate, edemas form (^ A7).

If proteinuria, hypoproteinemia, and peripheral edema occur together, this is termed nephrotic syndrome. As the lipoproteins are not filtered even if the filter is damaged, but hypoproteinemia stimulates the formation of lipoproteins in the liver, hyperlipidemia results and thus also hypercholesterolemia (^ A6). It remains debatable whether a loss of glomerular lipoprotein lipase contributes to the effect.

Hypoproteinemia favours peripheral filtration, the loss of plasma water into the interstitial space leads to hypovolemia which triggers thirst, release of ADH and, via renin and angiotensin, of aldosterone (^ p. 122). Increased water intake and increased reabsorption of sodium chloride and water provide what is needed to maintain the edemas. As aldosterone promotes renal excretion of K+ and H+ (^ p. 98), hypokalemia and alkalosis develop.

A. Abnormalities of Glomerular Permselectivity and Nephrotic Syndrome

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