Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 40

Acidification of the Urine & Bicarbonate Excretion 681

The principal reaction producing NH

4

• in cells is conver-
  sion of glutamine to glutamate. This reaction is catalyzed by
  the enzyme
  glutaminase,
  which is abundant in renal tubular
  cells (Figure 40–3).
  Glutamic dehydrogenase
  catalyzes the
  conversion of glutamate to
  α
  -ketoglutarate, with the produc-
  tion of more NH
  4

+

. Subsequent metabolism of
α
-ketoglut-
arate utilizes 2H

• , freeing 2HCO
  3

• .
  In chronic acidosis, the amount of NH
  4

• excreted at any
  given urine pH also increases, because more NH
  3
  enters the
  tubular urine. The effect of this
  adaptation
  of NH
  3
  secretion,
  the cause of which is unsettled, is a further removal of H


• 
  

from the tubular fluid and consequently a further enhance-
ment of H

• 
  

  secretion.
  The process by which NH
  3
  is secreted into the urine and
  then changed to NH
  4

  
  


• 
  

  , maintaining the concentration gradi-
  ent for diffusion of NH
  3
  , is called
  nonionic diffusion
  (see
  Chapter 2). Salicylates and a number of other drugs that are
  weak bases or weak acids are also secreted by nonionic diffu-
  sion. They diffuse into the tubular fluid at a rate that depends
  on the pH of the urine, so the amount of each drug excreted
  varies with the pH of the urine.

  
  

pH CHANGES ALONG THE NEPHRONS

A moderate drop in pH occurs in the proximal tubular fluid,
but, as noted above, most of the secreted H

• has little effect on
  luminal pH because of the formation of CO
  2
  and H
  2
  O from
  H
  2
  CO
  3

. In contrast, the distal tubule has less capacity to se-
crete H

• , but secretion in this segment has a greater effect on
  urinary pH.

FACTORS AFFECTING ACID SECRETION

Renal acid secretion is altered by changes in the intracellular
P
CO 2
, K

• concentration, carbonic anhydrase level, and adreno-
  cortical hormone concentration. When the P
  CO 2
  is high
  (res-
  piratory acidosis),
  more intracellular H
  2
  CO
  3
  is available to
  buffer the hydroxyl ions and acid secretion is enhanced, where-
  as the reverse is true when the P
  CO 2
  falls. K


• 
  

  depletion enhanc-
  es acid secretion, apparently because the loss of K

  
  


• 
  

  causes
  intracellular acidosis even though the plasma pH may be ele-

  
  

vated. Conversely, K

+

excess in the cells inhibits acid secretion.

When carbonic anhydrase is inhibited, acid secretion is inhib-

ited because the formation of H

2

CO

3

is decreased. Aldosterone

and the other adrenocortical steroids that enhance tubular re-

absorption of Na

+

also increase the secretion of H

+

and K

+

.

BICARBONATE EXCRETION

Although the process of HCO

3

• reabsorption does not actual-
  ly involve transport of this ion into the tubular cells, HCO
  3


• 
  

  reabsorption is proportional to the amount filtered over a rel-
  atively wide range. There is no demonstrable Tm, but HCO
  3

  
  


• 
  

  reabsorption is decreased by an unknown mechanism when
  the extracellular fluid (ECF) volume is expanded (Figure
  40–4). When the plasma HCO
  3

  
  


• 
  

  concentration is low, all the
  filtered HCO
  3

  
  


• 
  

  is reabsorbed; but when the plasma HCO
  3

  
  


• 
  

  concentration is high; that is, above 26 to 28 mEq/L (the renal
  threshold for HCO
  3

  
  


• 
  

  ), HCO 3 – appears in the urine and the
  urine becomes alkaline. Conversely, when the plasma HCO 3 –
  falls below about 26 mEq/L, the value at which all the secreted H+
  is being used to reabsorb HCO 3 – , more H+ becomes available to
  combine with other buffer anions. Therefore, the lower the plas-
  ma HCO 3 – concentration drops, the more acidic the urine be-
  comes and the greater its NH 4 + content (see Clinical Box 40–1).

  
  

DEFENSE OF H

+

CONCENTRATION

The mystique that envelopes the subject of acid–base balance

makes it necessary to point out that the core of the problem is

not “buffer base” or “fixed cation” or the like, but simply the

FIGURE 40–3 Major reactions involved in ammonia
production in the kidneys.

NH 4 +

[NH 3 ]

[NH 4 +]

NH 3 + H+

pH= pK'+ log

Glutamine Glutamate+ NH 4 +

Glutaminase

Glutamate α−Ketoglutarate+ NH 4 +

Glutamic

dehydrogenase

FIGURE 40–4 Effect of ECF volume on HCO 3 – filtration,

reabsorption, and excretion in rats. The pattern of HCO 3 – excretion

is similar in humans. The plasma HCO 3 – concentration is normally

about 24 mEq/L. (Reproduced with permission from Valtin H: Renal Function, 2nd

ed. Little, Brown, 1983.)

Bicarbonate filtered, excreted,

or reabsorbed (

μeq/min)

0 605040302010

0

50

100

150

Filtered (during both minimal

And exaggerated expansion)

Reabsorbed

Excreted

Minimal

expansion

Minimal

expansion

Exaggerated

expansion

Exaggerated

expansion

Plasma HCO 3 − concentration (meq/L)