936
chapter
39 Water, Electrolytes, and Acid-Base Balance
Tubular lum en
- H
Na1
N H Î
C f
2
I
Tubular cell
G lutam ine
-NH-
G lutam lnase
--------
G lutam ic acid
G lutam ate
d eh y d ro g en ase
a-K eto g lu tarate
C 0
2
+ H p or glucose
-------------- H+- -------------
-------------- Na+--------------
Lum en capillary
I
t - *1
2 ~ M a +
FIGURE 39-8
Formation of ammonia in the renal tubule cells from glutamine and
secretion of ammonium ion in the urine.
compensatory changes in an attempt to restore homeosta-
sis (Table 39-1). Acidosis due to respiratory failure leads
to compensatory renal changes, which lead to increased
reclamation of HC03 .
In assessment of acid-base disorders, commonly mea-
sured electrolytes are serum Na+, K+, H+ (as pH),
Cl- , and HCO^. Other anions (e.g., sulfates, phosphates,
proteins) and cations (e.g., calcium, magnesium, proteins)
are not measured routinely but can be estimated indirectly,
since (to maintain electrical neutrality) the sum of the
cations must equal that of the anions. Serum Na+ and K+
content accounts for 95% of cations, and Cl- and HCO
3
for about 85% of anions. The concentration of phosphate,
sulfate, and proteins can be calculated from the formula:
Unmeasured anions = [Na+] + [K+] —
[Cl- ] —
[HCOj"]
The unmeasured anion is commonly known as the
an-
ion gap,
which is normally 12 ± 4 mEq/L. This value is
useful in assessing the acid-base status of a patient and
in diagnosing metabolic acidosis. Disorders that cause a
high anion gap are metabolic acidosis, dehydration, ther-
apy with sodium salts of strong acids, therapy with certain
antibiotics (e.g., carbenicillin), and alkalosis. A decrease
in the normal anion gap occurs in various plasma dilution
states, hypercalcemia, hypermagnesemia, hypernatremia,
hypoalbuminemia, disorders associated with hyperviscos-
ity, some paraproteinemias, and bromide toxicity.
Respiratory acidosis
is characterized by accumula-
tion of CO2, rise in PCO2 (hypercapnia or hypercarbia),
decrease in [HCOj~]/[PcoJ, and decrease in pH (see
Henderson-Hasselbalch equation, Chapter 1 ). It may result
from central depression of respiration (e.g., narcotic or
barbiturate overdose, trauma, infection, cerebrovascular
accident) or from pulmonary disease (e.g., asthma, ob-
structive lung disease, infection). Increased [H+] is in
part buffered by cellular uptake of H+ with corresponding
loss of intracellular K+. In acute hypercapnia, the primary
compensatory mechanism is tissue buffering. In chronic
hypercapnia, the kidneys respond to elevated plasma Pco
2
increasing the amount of HCO^ formed by carbonic an-
hydrase in the tubules and by excreting more H+.
The primary goal of treatment is to remove the
cause of the disturbed ventilation. Immediate intubation
and assisted ventilation also aid in improving the gas
exchange.
Metabolic acidosis
with increased anion gap occurs in
diabetic or alcoholic ketoacidosis; lactic acidosis from hy-
poxia, shock, severe anemia, alcoholism, cancer; toxic-
ity from ingestion of salicylates, methanol, paraldehhyde,
and ethylene glycol; and renal failure. Lactic acid aci-
dosis caused by deprivation of tissue oxygenation, inhi-
bition of gluconeogensis, and some drugs and toxins is
due to accumulation of L-lactate, which is the end prod-
uct of glycolysis (Chapter 13). Frequently, L-lactate (sim-
ply referred to as lactate), is the metabolite measured
in assessing metabolic acidosis. However, D-lactate may
be produced under certain clinical conditions, such as
diminished colonic motility, short bowel syndrome, je-
junoileal bypass, due to overgrowth of D-lactate produc-
ing gram-positive organisms (e.g.,
Lactobacillus
species,
Streptococcus bovis).
Carbohydrate malabsorption and in-
gestion of large amounts of carbohydrate may also ex-
asperate the development of D-lactate acidosis. In addi-
tion, an impairment of D-lactate metabolism may also
contribute to D-lactic acidosis. D-Lactate is converted to
pyruvate by D-2-hydroxy acid dehydrogenese, a mitochon-
drial enzyme present in liver, kidney, and other tissues.
The clinical manifestations of D-lactic acidosis include
episodes of encephalopathy and metabolic acidosis. Since
serum D-lactate is not a normally measured clinical param-
eter, the critical indices of suspicion of D-lactic acidosis in
the clinical conditions mentioned above include increased
anion gap metabolic acidosis with negative tests for
L-lactate and ketoacidosis. Metabolic acidosis with normal
anion gap occurs in renal tubular acidosis, carbonic anhy-
drase inhibition, diarrhea, ammonium chloride adminis-
tration, chronic pyelonephritis, and obstructive uropathy.
In both groups, plasma HCOj" levels decrease and tissue
buffering occurs by exchange of extracellular H+ for in-
tracellular K+. Thus, plasma K+ levels may increase.
Metabolic acidosis produces prompt stimulation of res-
piratory rate and decrease in PCO
2
. This effect cannot be
sustained, however, because of tiring of respiratory
