Chemistry: GBM formed by collagen, laminin, other extracellular matrix proteins such as negatively charged heparan sulfate proteoglycans. GBM provides support and has a sieving function.
Determinants of rate: GFR= Kf (ultrafiltration coefficient) x Pu (net ultrafiltration pressure).
Pu is 10 mm Hg at afferent arteriole end and 2-0 mmHg at efferent arteriole end of glomerular capillaries (gc). Pu= P(hydrostatic)gc- P(osmotic)gc P(hydrostatic)bs. When Pu = 0 by the time the capillary blood reaches the efferent arteriole, there is filtration equilibrium and GFR becomes proportional to RPF (constant filtration fraction).
P(hydrostatic)gc = 45-60 mm Hg all along the capillary (higher than in other capillaries in the body), is under both autoregulation (intrinsic) and extrinsic control, decreases with increasing afferent arteriole resistance (induced by AVP or AII, opposed by PG or ANP) and increases with efferent arteriole resistance (AII).
P(osmotic)gc = 20 at start and increases to 30 mm Hg at end of gc as filtration occurs and plasma proteins become concentrated. It opposes filtration , increases in dehydration, and decreases with plasma protein concentration in starvation, liver and kidney diseases.
Kf is 50x greater than in other capillaries. Kf depends on surface area for filtration (SA) and on Lp, the fluid conductivity per unit area (how easily the fluid goes through). Contraction of mesangial cells (AVP, AII) reduce SA; prostaglandins relax mesangial cells and increase SA. Excess mesangial cell proliferation (induced by PDGF and EGF) after inflammation and excess matrix production (induced by TGF) during scarring reduce SA
Lp has not been measured. It is though not to be limiting for filtration.
Principle: If a solute is freely filtered (same concentration in glomerular filtrate as in plasma), is neither reabsorbed nor secreted and is not metabolized by the kidneys, then, in the steady state, the amount filtered equals the amount excreted, VU= GFRxP, so VU/P = C = GFR. Inulin, DPTA, EGTA, and iothalamate all have these properties and have been used to measure GFR, but these must be injected as they do not occur naturally in the body.
Creatinine (Cr) is produced in the body from muscle phosphocreatine and its properties approach those of inulin. However, at normal GFR, 10% of excreted creatinine is secreted. Because of measurement limitations, measured Pcr is 10% higher than true Pcr, so these two errors cancel each other and Ccr = Cinulin in normal subjects. In theory, if GFR decreases Pcr must increase so GFRx Pcr (and VUcr) remain constant when a steady state is achieved. But when GFR is reduced to 1/20, Pcr does not increase 20 times but only 10 times because of Cr secretion. So changes in Pcr are an index but not an exact measure of GFR and of its changes.
BUN also varies inversely with GFR (uremia, azotemia). However BUN can also increase due to increased urea reabsorption (as in dehydration and volume depletion resulting in a high BUN/Pcr, typical of prerenal azotemia) or because of excess protein in the diet. In patients starved or with liver disease BUN may remain low or normal in spite of reduced GFR.
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