Page 257 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

248 ACID-BASE DISORDERS

Tubular fluid Proximal tubule cell Interstitial fluid

Interstitial
Tubular fluid Collecting duct cell fluid

Na +
Cl – NH 4 + NH 4 + Na +
Glucose 2HCO 3 – 3HCO 3 – Regenerated NH NH NH 3
–
or HCO 3 3 3 –
+ H O ATP Cl
CO 2 2 + H + –
αKGA H HCO 3
Regenerated
Glutamate –
+ H + + H 2 CO 3 HCO 3
NH 3 dehydrogenase Cl – NH 4
Glu 3Na +
ATP CA 3Na +
NH + H + Glutaminase 2K + ATP +
3 CO + H O 2K
2 2
GluNH 2
A B
Figure 9-9 A and B, Regeneration of new HCO 3 by ammonium excretion in renal tubules. CA, Carbonic

anhydrase. (Drawing by Tim Vojt.)
chloride-responsive metabolic alkalosis (see Chapters 4 (i.e., the ratio of salt to acid is 1.0), and buffers are most
and 10). effective within 1.0 pH unit of their pK a . Phosphate is a
Hyperkalemia is associated with decreased renal very effective urinary buffer because its pK a (6.8) falls

HCO 3 reabsorption in the distal nephron, and hypoka- between the pH of distal tubular fluid (6.0) and that of

lemia is associated with increased HCO 3 reabsorption. glomerular filtrate (7.4). The amount of phosphate avail-
During hypokalemia, transcellular shifting of potassium able for buffering tubular fluid is the product of serum
ions out of renal tubular cells into ECF occurs in phosphorus concentration and the GFR (i.e., the filtered
exchange for hydrogen ions. This results in greater avail- load of phosphate). The filtered load of phosphate is
þ
ability of H for secretion by the tubular cells. When H þ relatively constant in a normal individual in phosphorus

is secreted into tubular fluid, HCO 3 is added to ECF. balance.
The opposite effect occurs with hyperkalemia, and there
are fewer hydrogen ions in tubular cells available for secre- AMMONIUM EXCRETION

tion into tubular fluid. Aldosterone increases HCO 3
reabsorption in the collecting ducts directly by Excretion of ammonium by the kidneys is essential for
stimulating the luminal H -ATPase responsible for H þ eliminating the daily fixed acid load and regenerating
þ
secretion and indirectly by increasing lumen electronega- titrated bicarbonate. Most of the ammonium to be
tivity by enhancement of sodium reabsorption. excreted is produced from glutamine in the proximal
tubule by action of the enzyme glutaminase 20,21 :
TITRATABLE ACIDITY
Titratable acidity refers to the amount of strong base glutamine ! a-ketoglutarate 2 þ 2NH þ ð1Þ
4
needed to titrate a 24-hour urine sample back to a pH a-ketoglutarate 2 þ 2H ! CO 2 þ H 2 O ðoxidationÞ
þ
of 7.40 and represents the amount of H þ excreted in
ð2Þ
the urine in combination with weak acid anions, primarily or
phosphate. When urine pH is very low (e.g., 5.0 to 5.5), 2
a-ketoglutarate þ 2H ! glucose ðgluconeogenesisÞ
þ
other weak acids such as creatinine (pK a ¼ 5.0) and urate
þ
(pK a ¼ 5.8) contribute to titratable acidity. Frequently, 2NH 4 þ þ CO 2 ! urea þ 2H ðurea cycleÞ ð3Þ
however, the term titratable acidity is considered synony-
þ
mous with urinary phosphate (pK a ¼ 6.8). Of the daily 50 It can be seen from these reactions that two H are con-
to 100 mEq of fixed or nonvolatile acid produced by met- sumed when the a-ketoglutarate produced from gluta-
abolic processes, approximately 20 to 40 mEq (40%) is mine is either oxidized or converted to glucose. This
excreted as titratable acidity. results in the simultaneous generation of two new bicar-
The pK a of a weak acid is the pH at which one half bonate ions. If the liver uses an equal number of ammo-
þ
of the buffer is in the salt and one half in the acid form nium ions for urea synthesis, two H are produced, two