Page 171 - Color_Atlas_of_Physiology_5th_Ed._-_A._Despopoulos_2003

Reabsorption of Organic Substances Increased urinary excretion of amino acids (hyper-
aminoaciduria) can occur. Prerenal hyperaminoacid-
The filtered load of a substance is the product uria occurs when plasma amino acid concentrations
of its plasma concentration and GFR. Since the are elevated (and reabsorption becomes saturated,
GFR is high (ca. 180 L/day), enormous quanti- as in A), whereas renal hyperaminoaciduria occurs
due to deficient transport. Such a dysfunction may
ties of substances enter the primary urine each be specific (e.g., in cystinuria, where only L-cystine, L-
day (e.g., 160 g/day of D-glucose). arginine and L-lysine are hyperexcreted) or unspecific
Fractional excretion (FE, ! p. 154) of D-glu- (e.g., in Fanconi’s syndrome, where not only amino
cose is very low (FE ! 0.4%). This virtually acids but also glucose, phosphate, bicarbonate etc.
Kidneys, Salt, and Water Balance mal tubule. If the plasma glucose conc. exceeds mal tubule by way of Na symport, whereas urea is
are hyperexcreted).
complete reabsorption is achieved by second-
Certain substances (lactate, sulfate, phosphate,
ary active transport (Na -glucose symport) at
+
dicarboxylates, etc.) are also reabsorbed at the proxi-
the luminal cell membrane (! B and p. 29 B1).
+
About 95% of this activity occurs in the proxi-
subject to passive back diffusion (! p. 166). Urate
and oxalate are both reabsorbed and secreted
10–15 mmol/L, as in diabetes mellitus (nor-
(! p. 160), with the predominant process being re-
mally 5 mmol/L), glucosuria develops, and uri-
absorption for urate (FE ! 0.1) and secretion for oxa-
late (FE ! 1). If the urinary conc. of these poorly
nary glucose conc. rises (! A). Glucose reab-
soluble substances rises above normal, they will start
sorption therefore exhibits saturation kinetics
to precipitate (increasing the risk of urinary calculus
(Michaelis-Menten kinetics; ! p. 28). The
of cystine can lead to cystine calculi.
Renal glucosuria can also occur when one of
Oligopeptides such as glutathione and angio-
the tubular glucose carriers is defective.
tensin II are broken down so quickly by luminal
7 above example illustrates prerenal glucosuria. formation). Likewise, the excessive urinary excretion
Low-affinity carriers in the luminal cell membrane of peptidases in the brush border that they can be
the pars convoluta (sodium-glucose transporter type
2 = SGLT2) and high-affinity carriers (SGLT1) in the reabsorbed as free amino acids (! C1). Dipep-
pars recta are responsible for D-glucose reabsorp- tides resistant to luminal hydrolysis (e.g., car-
tion. The co-transport of D-glucose and Na occurs in nosine) must be reabsorbed as intact mole-
+
each case, namely at a ratio of 1 : 1 with SGLT2 and cules. A symport carrier (PepT2) driven by the
1 : 2 with SGLT1. The energy required for this form of inwardly directed H gradient (! p. 174) trans-
+
secondary active glucose transport is supplied by the ports the molecules into the cells tertiary ac-
+
electrochemical Na gradient directed towards the tive H symport; ! p. 26, 29 B4). The dipep-
+
cell interior. Because of the co-transport of two Na + tides are then hydrolyzed within the cell
ions, the gradient for SGLT1 is twice as large as that
for SGLT2. A uniporter (GLUT2 = glucose transporter (! C2). The PepT2 carrier is also used by cer-
type 2) on the blood side facilitates the passive trans- tain drugs and toxins.
port of accumulated intracellular glucose out of the Proteins. Although albumin has a low siev-
cell (facilitated diffusion, ! p. 22). D-galactose also ing coefficient of 0.0003 (! p. 154, 2400 mg/
makes use of the SGLT1 carrier, while D-fructose is day are filtered at a plasma conc. of 45 g/L
passively absorbed by tubule cells (GLUT5). (180 L/day · 45 g/L · 0.0003 = 2400 mg/day).
The plasma contains over 25 amino acids, and Only 2 to 35 mg of albumin are excreted each
about 70 g of amino acids are filtered each day. day (FE ! 1%). In the proximal tubule, albumin,
Like D-glucose, most L-amino acids are reab- lysozyme, α 1-microglobulin, " 2-microglobulin
+
sorbed at proximal tubule cells by Na -coupled and other proteins are reabsorbed by receptor-
secondary active transport (! B and p. 29 B3). mediated endocytosis (! p. 28) and are
At least 7 different amino acid transporters are “digested” by lysosomes (! D). Since this type
in the proximal tubule, and the specificities of of reabsorption is nearly saturated at normal
some overlap. J max and K M (! p. 28) and, there- filtered loads of proteins, an elevated plasma
fore, saturability and reabsorption capacities protein conc. or increased protein sieving
vary according to the type of amino acid and coefficient will lead to proteinuria.
carrier involved. Fractional excretion of most 25-OH-cholecalciferol, which is bound to DBP (vi-
amino acids ! to 1% (ranging from 0.1% for L- tamin D-binding protein) in plasma and glomerular
158 valine to 6% for L-histidine). filtrate, is reabsorbed in combination with DBP by re-
ceptor-mediated endocytosis (! p. 292).
Despopoulos, Color Atlas of Physiology © 2003 Thieme
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