Ganong's Review of Medical Physiology, 23rd Edition

646 SECTION VIII Renal Physiology

NORMAL GFR

The GFR in a healthy person of average size is approximately
125 mL/min. Its magnitude correlates fairly well with surface
area, but values in women are 10% lower than those in men
even after correction for surface area. A rate of 125 mL/min is
7.5 L/h, or 180 L/d, whereas the normal urine volume is about
1 L/d. Thus, 99% or more of the filtrate is normally reab-
sorbed. At the rate of 125 mL/min, in 1 day the kidneys filter
an amount of fluid equal to 4 times the total body water, 15
times the ECF volume, and 60 times the plasma volume.

CONTROL OF GFR

The factors governing filtration across the glomerular capillaries
are the same as those governing filtration across all other capillar-
ies (see Chapter 32), that is, the size of the capillary bed, the per-
meability of the capillaries, and the hydrostatic and osmotic
pressure gradients across the capillary wall. For each nephron:

GFR = Kf [(PGC – PT) – (πGC – πT)]
Kf, the glomerular ultrafiltration coefficient, is the product
of the glomerular capillary wall hydraulic conductivity (ie, its
permeability) and the effective filtration surface area. PGC is
the mean hydrostatic pressure in the glomerular capillaries,
PT the mean hydrostatic pressure in the tubule (Bowman’s
space), πGC the oncotic pressure of the plasma in the glomer-
ular capillaries, and πT the oncotic pressure of the filtrate in
the tubule (Bowman’s space).

PERMEABILITY

The permeability of the glomerular capillaries is about 50 times
that of the capillaries in skeletal muscle. Neutral substances with
effective molecular diameters of less than 4 nm are freely fil-
tered, and the filtration of neutral substances with diameters of
more than 8 nm approaches zero (Figure 38–5). Between these
values, filtration is inversely proportionate to diameter. Howev-
er, sialoproteins in the glomerular capillary wall are negatively
charged, and studies with anionically charged and cationically
charged dextrans indicate that the negative charges repel nega-
tively charged substances in blood, with the result that filtration
of anionic substances 4 nm in diameter is less than half that of
neutral substances of the same size. This probably explains why
albumin, with an effective molecular diameter of approximately
7 nm, normally has a glomerular concentration only 0.2% of its
plasma concentration rather than the higher concentration that
would be expected on the basis of diameter alone; circulating al-
bumin is negatively charged. Filtration of cationic substances is
greater than that of neutral substances.
The amount of protein in the urine is normally less than
100 mg/d, and most of this is not filtered but comes from shed
tubular cells. The presence of significant amounts of albumin
in the urine is called albuminuria. In nephritis, the negative
charges in the glomerular wall are dissipated, and albumin-

uria can occur for this reason without an increase in the size

of the “pores” in the membrane.

SIZE OF THE CAPILLARY BED

Kf can be altered by the mesangial cells, with contraction of these

cells producing a decrease in Kf that is largely due to a reduction

in the area available for filtration. Contraction of points where

the capillary loops bifurcate probably shifts flow away from

some of the loops, and elsewhere, contracted mesangial cells dis-

tort and encroach on the capillary lumen. Agents that have been

shown to affect the mesangial cells are listed in Table 38–3. An-

giotensin II is an important regulator of mesangial contraction,

and there are angiotensin II receptors in the glomeruli. In addi-

tion, some evidence suggests that mesangial cells make renin.

FIGURE 38–5 Effect of electric charge on the fractional

clearance of dextran molecules of various sizes in rats. The nega-

tive charges in the glomerular membrane retard the passage of negative-

ly charged molecules (anionic dextran) and facilitate the passage of

positively charged molecules (cationic dextran). (Reproduced with permission

from Brenner BM, Beeuwkes R: The renal circulations. Hosp Pract [July] 1978;13:35.)

TABLE 38–3 Agents causing contraction

or relaxation of mesangial cells.

Contraction Relaxation

Endothelins ANP

Angiotensin II Dopamine

Vasopressin PGE 2

Norepinephrine cAMP

Platelet-activating factor

Platelet-derived growth factor

Thromboxane A 2

PGF 2

Leukotrienes C 4 and D 4

Histamine

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0

4.0 6.0 8.0

Anionic

Neutral

Cationic

Effective molecular diameter (nm)

Fractional clearance