Page 114 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Disorders of Glomerular Permselectivity, Nephrotic Syndrome
The glomerular filter (fenestrated endothe- membrane (→ A3). Even an intact glomerulus
lium, basement membrane, slit membrane be- is permeable to a number of proteins that are
tween podocytes) is not equally permeable for then reabsorbed in the proximal tubules. The
all blood constituents (selective permeability transport capacity is limited, though, and can-
or permselectivity). Molecules larger in dia- not cope with the excessive load of filtered
meter than the pores do not pass the filter at protein at a defective glomerular filter. If tubu-
all. Molecules of clearly smaller diameter will lar protein reabsorption is defective especially
in practice pass through, as will water, i.e., small proteins appear in the final urine (tubu-
Kidney, Salt and Water Balance ed in the kidney, their clearance (C) is identical that it is largely due to a loss of albumin
their concentration in the filtrate is approxi-
lar proteinuria).
mately the same as that in plasma water. If
Renal loss of proteins leads to hypopro-
teinemia. Serum electrophoresis demonstrates
these substances are not reabsorbed or secret-
(→ A4), while the concentration of larger pro-
to the GFR, and the fractional excretion (C/
GFR) is 1.0. If molecules are only slightly smal-
teins actually tends to increase. This is because
ler in diameter than the diameter of the pores,
the reduced oncotic pressure in the vascular
system leads to increased filtration of plasma
only some of them can follow water through
the pores, so that their concentration in the fil-
water in the periphery and thus to a concen-
tion in the peripheral capillaries is facilitated
However, permeability is determined not
not only by the reduced oncotic pressure, but
only by the size, but also by the charge of the
also by damage to the capillary wall that may
molecule. Normally, negatively-charged mole-
5 trate is lower than in plasma (→ A1). tration of the other blood constituents. Filtra-
cules can pass through much less easily than also be subject to inflammatory changes. As a
neutral or positively-charged molecules result of protein filtration in the periphery,
(→ A1). This is due to negative fixed charges protein concentration and oncotic pressure
that make the passage of negatively-charged rise in the interstitial spaces, so that the filtra-
particles difficult. tion balance shifts in favor of the interstitial
In glomerulonephritis (→ p.102) the integ- space (→ A5). If the removal of proteins via
rity of the glomerular filter may be impaired, the lymphatics is inadequate, edemas form
and plasma proteins and even erythrocytes (→ A7).
can gain access to the capsular space (→ A2). If proteinuria, hypoproteinemia, and pe-
This results in proteinuria and hematuria. ripheral edema occur together, this is termed
Close observation of proteinuria indicates that nephrotic syndrome. As the lipoproteins are
it is especially the permeability for negatively- not filtered even if the filter is damaged, but
charged proteins that is increased. This be- hypoproteinemia stimulates the formation of
havior can be demonstrated most impressively lipoproteins in the liver, hyperlipidemia re-
by infusing differently charged polysaccha- sults and thus also hypercholesterolemia
rides, because polysaccharides—in contrast to (→ A6). It remains debatable whether a loss of
proteins—are hardly reabsorbed by the tu- glomerular lipoprotein lipase contributes to
bules. Negatively-charged (–) dextrans are the effect.
normally less well filtered than neutral (n) or Hypoproteinemia favours peripheral filtra-
cationic (+) dextrans. This selectivity is lost in tion, the loss of plasma water into the intersti-
glomerulonephritis and filtration of negative- tial space leads to hypovolemia which triggers
ly-charged dextrans is massively increased thirst, release of ADH and, via renin and angio-
(→ A2). One of the causes of this is a break- tensin, of aldosterone (→ p.122). Increased wa-
down of negatively-charged proteoglycans, for ter intake and increased reabsorption of so-
example, by lysosomal enzymes from inflam- dium chloride and water provide what is need-
matory cells that split glycosaminoglycan. As ed to maintain the edemas. As aldosterone
has been shown by electrophoresis, it is espe- promotes renal excretion of K + and H +
104 cially the relatively small, markedly negative- (→ p. 98), hypokalemia and alkalosis develop.
ly-charged albumins that pass across the
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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