Page 189 - Color_Atlas_of_Physiology_5th_Ed._-_A._Despopoulos_2003

!
+
+
+
2 –
H ions are buffered by filtered HPO 4 . Non- rier (! p. 162) reabsorbs NH 4 (instead of K )
reabsorbed phosphate (5–20% of the filtered so that it remains in the renal medulla. Recircu-
+
quantity, ! p. 178) is therefore loaded with H + lation of NH 4 through the loop of Henle yields
+
ions, about half of it in the proximal tubule (pH a very high conc. of NH 4 + NH 3 + H towards
+
7.4 ! ca. 6.6), and the rest in the collecting the papilla (! D3). While the H ions are then
duct (pH 6.6 ! 4.5) (! C1). When acidosis oc- actively pumped into the lumen of the collect-
curs, increased quantities of phosphate are ing duct (! A2, D4), the NH 3 molecules arrive
mobilized from the bone and excreted. The re- there by non-ionic diffusion (! D4). The NH 3
+
sulting increase in H excretion precedes the gradient required to drive this diffusion can
Kidneys, Salt, and Water Balance + H ), about 25–50 mmol/day on average diet, + stitium where the pH is about two pH units
develop because the especially low luminal pH
production associated with
+
increased NH 4
acidosis (see below).
value (about 4.5) leads to a much smaller NH 3
+
conc. in the lumen than in the medullary inter-
NH 3
Excretion of ammonium ions (NH 4
+
+
higher and the NH 3 conc. is consequently
is equivalent to H disposal and is therefore an
about 100-times higher than in the lumen.
indirect form of H excretion (! D). NH 4 is not
+
+
2 –
+ H
a titratable form of acidity. Unlike HPO 4
Disturbances of acid–base metabolism (see also
+
–
+
H 2PO 4 , the reaction NH 3 + H
NH 4 does
p. 142ff.). When chronic non-respiratory acidosis
not function in the body as a buffer because of
+
of non-renal origin occurs, NH 4 excretion rises to
its high pK a value of ca. 9.2. Nevertheless, for
about 3 times the normal level within 1 to 2 days due
+
tion (at the expense of urea formation) and renal glu-
is spared by the liver. This is equivalent to one
taminase activity. Non-respiratory alkalosis only
H disposed since the spared HCO 3 ion can
+
–
+
+
decreases the renal NH 4 production and H secre-
7 every NH 4 excreted by the kidney, one HCO 3 - to a parallel increase in hepatic glutamine produc-
buffer a H ion. With an average dietary intake
+
of protein, the amino acid metabolism pro- tion. This occurs in conjunction with an increase in fil-
–
– tered HCO 3 (increased plasma concentration,
–
duces roughly equimolar amounts of HCO 3 ! p. 144), resulting in a sharp rise in HCO 3 excretion
+
and NH 4 (ca. 700–1000 mmol/day). The liver and, consequently, in osmotic diuresis (! p. 172).
utilizes about 95% of these two products to To compensate for respiratory disturbances
produce urea (! D1): (! p. 144), it is important that increased (or
– + H 2N-C-NH 2 + CO 2 + 3 H 2O decreased) plasma P CO 2 levels result in increased (or
2 HCO 3 + 2 NH 4
+
! decreased) H secretion and, thus, in increased (or
O [7.13] decreased) HCO 3 resorption.
–
Thus, one HCO 3 less is consumed for each The kidney can also be the primary site of an acid–
–
+
NH 4 that passes from the liver to the kidney base disturbance (renal acidosis), with the defect
and is eliminated in the urine. Before ex- being either generalized or isolated. In a generalized
porting NH 4 to the kidney, the liver incor- defect, as observed in renal failure, acidosis occurs
+
because of reduced H excretion. In an isolated de-
+
porates it into glutamate yielding glutamine; fect with disturbance of proximal H secretion, large
+
only a small portion reaches the kidney as free portions of filtered HCO 3 are not reabsorbed, lead-
–
+ +
NH 4 . High levels of NH 4 NH 3 are toxic. ing to proximal renal tubular acidosis. When impaired
+
In the kidney, glutamine enters proximal renal H secretion occurs in the collecting duct, the
tubule cells by Na symport and is cleaved by urine can no longer be acidified (pH ! 6 despite aci-
+
+
mitochondrial glutaminase, yielding NH 4 and dosis) and the excretion of titratable acids and NH 4 +
–
–
glutamate (Glu ). Glu is further metabolized is consequently impaired (distal renal tubular acido-
–
sis).
by glutamate dehydrogenase to yield α-ke-
2 –
toglutarate , producing a second NH 4 ion
+
+
(! D2). The NH 4 can reach the tubule lumen
on two ways: (1) it dissociates within the cell
+
to yield NH 3 and H , allowing NH 3 to diffuse
(non-ionically, ! p. 22) into the lumen, where
+
it re-joins the separately secreted H ions; (2)
the NHE3 carrier secretes NH 4 (instead of H ).
+
+
+
176 Once NH 4 has arrived at the thick ascending
limb of the loop of Henle (! D4), the BSC car-
Despopoulos, Color Atlas of Physiology © 2003 Thieme
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