Bicarbonate
kidney
Pediat. Res. 8: 735-739 (1974)
renal acidosis
small intestine
The Transport of Bicarbonate by the
Small Intestine of a Patient with
Proximal Renal Tubular Acidosis
Department of Pediatrics, University o f Maryland Hospital, Baltimore, Rosewood State Hospital, Owings Mills,
Maryland, the Department o f Pediatrics, North Shore University Hospital, Manhasset, and the Department o f
Pediatrics, Cornell University Medical College, New York, New York, USA
Extract
1935, although the syndrome he described was probably
caused by vitamin D toxicity. Many hypotheses have been
Transintestinal intubation with a double lumen tubing was presented t o explain the pathogenesis of PRTA: ( 1 ) decreased
done o n an infant with primary proximal renal tubular acidosis hydrogen ion ( H + ) secretion or diffusion into the proximal
(PRTA), and in a comparative control patient with congenital renal tubule lumen; (2) defective function of cellular carbonic
hydrocephalus. The duodenum and first part of the jejunum
anhydrase; ( 3 ) reduced cellular transport of HC03- independwere perfused at a rate of 2.5 ml/min with Krebs-Henseleit
ent of carbonic anhydrase o r pCOz ; and (4) abnormal sodium
isotonic buffer containing 1 mM L-tyrosine and 20 mM
(Na+) or chloride (Cl-) reabsorption (14, 17-20), Renal
D-glucose, with or without 30 mEq/liter bicarbonate (HC03-).
HC03- threshold has been uniformly decreased (1 8).
A nonabsorbable marker, polyethylene glycol (PEG), was
The renal tubular and the small intestinal transport
added. All perfusate samples were measured for pH, partial
mechanisms are similar in man and animals (2, 6 , 7, 11). In t h e
pressure of carbon dioxide (pC02), bicarbonate (HC03-),
small intestine there is secretion and reabsorption of bicarbonosmolality, glucose, sodium ( ~ a ' ) , potassium (K+), chloride
ate across t h e intestinal mucosa with a net absorption of
(C1-), tyrosine, and PEG. In the PRTA patient, HC03HC03- (15). In t h e following report we describe the cellular
lumen-to-blood fluxes were 0.9-1.42 pEq/min/cm of intestine
transport of HC03- by t h e upper segments of the small
as compared with 1.43-1.77 yEq/min/cm in the control
intestine of one patient with PRTA and a comparative patient
patient. In contrast, the PRTA patient had a blood-to-lumen
with congenital hydrocephalus. Using methods of transintestiflux of HC03- of 0.4 yEq/min/cm compared with 0.059
nal intubation (22, 23), we have shown that the PRTA patient
pEq/min/cm in the control patient. This difference in HC03secreted large quantities of HC03- in the small intestine and
secretion occurred while the PRTA patient's serum HC03- had a defective C1- secretory mechanism. However, the H +
level was 11.8-12.5 mEq/liter and that of the control subject secretory mechanisms were not altered.
was normal. Moreover, when the blood HC03- levels of the
PRTA patient were increased t o 19-20 mEq/liter b y
intravenous administration of HC03- the intestinal secretion
MATERIALS AND METHODS
of this anion increased to 2.4 pEq/min/cm. This could account
The subjects for this study were a patient with PRTA and a
for a total HC03- loss of 5,000-10,000 pEq/min/cm intestine.
The massive secretion of HC03- in the upper segments of the patient with congenital hydrocephalus of similar age, weight,
small intestine in PRTA was associated with an adequate and height. After informed parental concent was obtained,
reduction in pCOz levels of the perfusates but with a defective these patients were given one per 05 intestinal intubation and
the intestinal transport capacity was assessed. The research
C1- secretory mechanism.
protocol was reviewed and approved b y appropriate human
experimentation committees.
Speculation
There may be a defective CI-/HC03- "pump" in PRTA
patients in the intestinal mucosa a n d renal tubule which
enables them to secrete large quantities of bicarbonate in the
upper segments of the small intestine and in the renal tubule.
This may result from an impairment in C1- secretory
mechanisms since they are able to secrete hydrogen ion ( H + )
in a normal fashion. The quantitative loss of HC03- in the
upper segments of the small intestine in PRTA patients is more
significant than that occurring through the kidneys, and it may
play a very important role in the pathogenic processes of this
entity.
-
PATIENT 1
-
Primary proximal renal tubular acidosis is an apparently
self-limited disorder of young children, which is caused by a
defect in bicarbonate (HC03-) reabsorption in the proximal
renal tubule (13). It was first described by Lightwood (8) in
KB, a Caucasian female infant, was first evaluated a t the
University of Maryland Hospital a t age 9 months for failure t o
thrive. She was born full term, birth weight 3.062 kg. She
developed and grew normally until age 5 months. Thereafter,
the rate of growth slowed. The parents, two siblings, and the
remainder of t h e family were of normal height.
At age 9 months, her weight was 6.6 kg (<3%), her height
was 68.5 cm (25%), and her head circumference was 41 cm
(3%). The remainder of the physical examination, including a
slit lamp exam, was unremarkable. Some of the pertinent
laboratory findings are described. Urinalyses were normal with
a pH range of 5.5-7.0. There was n o glycosuria, and specific
gravity ranged from 1,008-1,025. Creatinine clearance and
amino acid levels in urine were normal. The calcium excretion
was 29 mg/24 h r and phosphate excretion was 219 mg/24 hr.
' 35
1
736
SCHOENEMAN, LIFSHITZ , AND DIAZ-BENSUSSEN
IVP was normal. The serum electrolytes were normal except
for HC03- levels which were consistently between 12-16
mEq/liter. Arterial blood gasses ranged between pH 7.35 and
7.45; p 0 2 , 90-95 m m Hg; p C 0 2 , 23-35 m m Hg; oxygen
saturation, 96%; standard HC03-, 14.3-18 mEq/liter base
excess, -5 t o -8. The bone marrow was normal and there
were n o cystine deposits. An ammonium chloride load was
administered using 150 mEq11.73 m Z / 2 4 hr in three divided
doses for 5 days. As seen in Figure 1 , the patient was able t o
acidify her urine t o a low of p H 4.8 at a blood HC03- level of
7 mEq/liter. However, the urine p H did not fall until the blood
HC03- level was about 16 mEq/liter, as reported by others
(15, 16, 28). The patient was treated with NaHC03 given
orally. The dose required t o maintain a normal serum HC03concentration was 1 0 mEq/kg/24 hr. At this time the
intestinal intubation studies were performed. She was followed
as an outpatient and her weight increased 5.0 kg in 3 months.
Subsequently, the patient was lost t o follow-up for 9 months.
The mother has been hospitalized for a "nervous breakdown"
but various individuals who cared for the child continued
giving the medication.
At this time her weight was 9.75 kg, and she showed
persistent compensated metabolic acidosis after 4 days
without HC03- therapy. The venous blood gasses off therapy
were as follows: pH 7.36; p C 0 2 31 m m Hg, HC03- 17
mEq/liter, p 0 2 2 3 mm Hg, O2 saturation 39%. Serum
electrolytes were as follows: Na+ 138, C1- 108, K + 4.7 (in
milliequivalents per liter). The urine pH ranged between 6.5
and 8.5. Therapy was begun with Polycitra given orally. The
serum HC03- returned t o normal levels with a maintenance
intake of only 4 mEq/kg/24 hr. There was n o evidence of
rickets or nephrocalcinosis.
her length was 69.0 cm, and the head circumference was 48.0
cm. She had mild generalized spasticity and was apparently
blind. Her urinalysis was normal, as were serum HC03- and
arterial blood gases.
TRANSINTESTINAL INTUBATION STUDIES
The studies were performed a t 9 and 8 months of age in t h e
PRTA and control infants, respectively. The patients were
allowed only clear liquids for 1 2 hours before intestinal
intubation and were kept fasted during t h e study. Maintenance
fluids with 10% glucose were given intravenously. Oral
NaHC03 therapy was discontinued 2 4 hr before the test o n
t h e child with PRTA. Blood pH and serum HC03- and
electrolytes were measured in blood obtained by heel stick a t
baseline and hourly throughout t h e perfusion study. The
patients were sedated with 1 mg/kg of Thorazine intramuscularly every 4 hr throughout the study.
Intubation of the small bowel with a double lumen
polyethylene tube was begun the evening before t h e test.
The tube was inserted gently through the mouth into t h e
stomach and allowed t o proceed t o the small bowel by gravity
and peristalsis. The proximal tube, through which test
solutions were perfused, was 20 cm above the distal tube
through which perfusates were withdrawn. The proximal tube
was placed in t h e end of the first portion of t h e duodenum.
The position of the tube was verified by x-rays and dye
injection.
Two solutions of a modified Krebs-Henseleit buffer (for
composition, see legend t o Table 1) with and without 24.2
mEq/liter of HC03-, were perfused. Both buffers had 2 0 mM
D-glucose, 1 mM L-tyrosine, and a water-soluble marker, PEG
(29) at a concentration of 6 0 0 mg/100 ml. The buffers wer:
bubbled with O2 : C 0 2 (9515) gas and maintained at 3 7
PATIENT 2
throughout. They were perfused with a Harvard peristaltic
pump a t a rate of 2.5 ml/min. The perfusate was collected by
EB, an 8-month-old Negro female infant, was born a t the gravity drainage into a graduated cylinder under mineral oil
University of Maryland Hospital t o a 32-year-old mother, para and measured t o the nearest 0.1 ml.
0030. Delivery was frank breach and birth weight was 1,800 g,
Three 15-min fractions were collected over a 45-min period
length 4 7 cm, head circumference 30.5 cm. The infant had a
for each buffer. A 2-hr initial equilibration period was allowed
lumbar myelomeningocele and hydrocephalus with Dandyfor the first buffer. Thereafter a 30-min wash period was
Walker abnormalities. She had repair of myelomeningocele and
included for t h e second buffer and the effluent discarded
placement of venitriculoatrial shunt in infancy. However, her
before collection of t h e next three samples. The patient with
neurologic development was markedly retarded, she was blind,
PRTA was perfused twice with both buffers. Subsequently,
she had had past episodes of Escherichia coli meningitis, and
she was given NaHC03 intravenously in a dose sufficient t o
she had had multiple shunt revisions. The lastest admission, at
raise t h e blood HC03- t o 2 4 mEq/liter in 180 min. During this
8 months of age, was again for revision of the nonfunctioning period buffer solutions with and without HC03- containing
shunt. Two weeks after this successful revision, she was given
140 mEq/liter ~ a were
+ perfused as above for 90 min each.
the intestinal intubation. At this time her weight was 6.20 kg,
All perfusate samples were measured immediately o n
withdrawal for pH, p C 0 2 , total COz , HC03-, and volume. The
osmolality and the concentrations of Na', K + , C1-, glucose,
tyrosine, and PEG were also measured, and the amounts of
each transported were calculated (1). The lumen-to-blood flux
(absorption) of HC03- was calculated from the perfusion of
HC03--containing buffer solutions. The blood-to-lumen flux
(secretion) of HC03- was determined from the HC03--free
perfusion fluid. The total bidirectional flux was calculated b y
adding both of t h e above mentioned amounts of HC03transported. The rate of transport for electrolytes was
expressed as microequivalents transported per minute per
K B PRTA
Controls
centimeter of intestine; for carbohydrates as micromoles per
minute per centimeter of intestine; and for tyrosine as
millimicromoles per minute per centimeter of intestlne. The
transport of water was calculated from the volume of solutions
8
10
12
14
16
18
20
22
24
perfused and recovered in the effluent, and from the
S E R U M C02 ( m E q 1 1 )
concentration of PEG measured in each.
The pH and pCO, were measured at 37' with a Radiometer
Fig. 1. Relation of pH of urine to concentration of bicarbonate in
serum in a patient with proximal renal tubular acidosis (PRTA). pH meter and microelectrode chain (28). The C 0 2 , HC03-,
Control data is derived from the work of Rodriguez-Soriano et al. (5). and base excess were calculated from the Henderson-Hasselbach equation (21). In addition, the HC03- concentration was
Urine pH and serum CO, were simultaneous measurements.
,.-.
PROXIMAL RENAL TUBULAR ACIDOSIS
determined using an Oxford titrator (3). The osmolality was
determined cryoscopically with an osmometer (30). Na' and
K + were measured in a flame photometer (31). C1- levels were
quantified in an automatic chloridometer (32), and glucose by
glucose oxidase method (10). PEG levels were determined by
the Malawer and Powell technique (9), and the concentration
of tyrosine by spectrofluorometry (27). The data were
analyzed statistically according to the method of Natrella (14).
1.5-
-
.
I!
u
-
.5
5
ID-
W
i
RESULTS
The intestinal bidirectional flux of HC03- in the patient
with PRTA and in the control subject is shown in Figure 2. In
the control patient, with serum HC03- concentrations ranging
from 19.8 t o 23.2 mEq/liter, the HC03- lumen-to-blood flux
ranged from 1.43 t o 1.77 pEq/min/cm intestine. The
blood-to-lumen flux was minimal, never exceeding levels of
0.059 pEq/min/cm. The total bidirectional flux of HC03across the upper segments of the small intestine was 1.6
pEq/min/cm.
In the PRTA patient, with serum HC03- concentrations
between 11.8 t o 12.5 mEq/liter, the HC03- lumen-to-blood
flux ranged from 0.99 t o 1.42 pEq/min/cm intestine. The
blood-to-lumen flux was increased eightfold over the amount
secreted by the control patient. This blood-to-lumen flow
accounted for the apparent lesser absorption rates of this
anion across the intestine and, therefore, the total bidirectional flux was unaltered. At lower serum HC03- levels of 7-8
mEq/liter, the blood t o lumen flux of HC03- became minimal
with fluxes approaching those of the control patient.
The intestinal bidirectional fluxes of HC03- during intravenous NaHC03- administration in the PRTA patient are
shown in Figure 3. The secretion of HC03- in the upper
segments of the small intestine was increased markedly when
the serum HC03- was elevated. The blood-to-lumen flux of
HC03- was raised from 0.3 t o 0.8 pEq/min/cm intestine when
the serum HC03- concentrations were augmented. During the
perfusion of HC03-, there was an initial net lumen-to-blood
flux of HC03- of 1.3 pEq/min/cm. However, as intravenous
NaHC03 infusion proceeded, the intestinal absorption of this
anion was apparently decreased. When the serum HC03-
x
E.B.? 8/12 Control
K . B . ? 9/12 PRTA
total flux
m
i8
$I?*
;2
S E R U M H C 0 j (m E q / I )
X
x
Fig. 2. Intestinal bidirectional flux of HCO; in a patient with
proximal renal tubular acidosis (PRTA). The lumen-to-blood flux
(absorption) of HC0,- was calculated from the perfusion of HC03containing buffer solutions. The blood-to-lumen flux (secretion) of
HCO; was determined from the HC0,--free perfusion fluid. The total
bidirectional flux was calculated by adding both of the above
mentioned amounts of HCO; transported.
Fig. 3. Intestinal bidirectional flux of HCO; in a patient with
proximal renal tubular acidosis (PRTA) during intravenous bicarbonate
administration. The patient was given NaHCO, intravenously in a dose
sufficient to raise the blood HC03- t o 24 mEq/liter in 180 min. During
perfusion of intestine with HC0;-containing
solutions ( 0 ) the
absorption of HCO; reversed t o secretion as serum HCO; level was
raised. During perfusion of intestine with HC0;-free perfusion fluid
( X ) the intestine secretion of this ion was increased as serum HCO;
level was augmented.
concentration reached 19 to 20 mEq/liter the amount of
HC03- transported from lumen t o blood was similar to that
secreted by the intestine with an apparent absorption of only
0.2 pEq/min/cm intestine. Subsequently, when the serum
HC03- concentrations were further increased, there was a
reversal in the lumen-to-blood flux reaching a net secretion of
HC03- of 1.1 pEq/min/cm. Inasmuch as HC03- absorption in
this patient was around 1.3 pEq/min/cm, these results indicate
a total HC03- secretion of at least 2.4 pEq/min/cm intestine
when normal serum HC03- concentrations were attained.
Therefore, the blood-to-lumen flux of the PRTA patient was
100-fold increased over the levels found in the control patient
at normal serum HC03- concentrations.
The pC02 content of the perfusates increased when there
was absorption of HC03-, as reported by others (24, 25). In
the PRTA patient, the pC02 levels of the perfusates increased
from 13.2 f 4.0 mm Hg to 33.1 f 7.8 mm Hg (mean f SD)
when HC03- was absorbed from the buffer solutions. This
increase was similar t o the one found in the control patient
(10.0 mm Hg f 2.0 to 21.5 mm Hg f 10.0, P > 0.05). The
pC02 content of the perfusates decreased when there was
maximum HC03- secretion during intravenous administration
of HC03- in the PRTA patient. The p C 0 2 level went from
28.5 t o 13.0 mm Hg during the 180 min of intravenous HC03infusion.
The secretion of electrolytes by the intestine of the PRTA
patient and the comparative control are shown in Table 1.
Both patients secreted C1-, ~ a ' , and water into the intestinal
lumen at all times. The secretion of these electrolytes and
water was higher when HC03- solutions were perfused. In
addition, the secretion of C1- was higher than that of Na+
when HC03- solutions were perfused. However, the blood-tolumen flux of C1- was higher than that of Na+ when HC03solutions were perfused. However, the blood-to-lumen flux of
C1- in the control patient was about twofold that of the PRTA
738
SCHOENEMAN, LIFSHITZ, AND DIAZ-BENSUSSEN
Table 1. Electrolyte and water intestinal transport1
Patient
Bicarbonate buffer
PRTA
Control
Bicarbonate-free buffer
PRTA
Control
Bicarbonate buffer2
PRTA
Bicarbonate-free buffer2
PRTA
C1 -,pEq/min/cm
Na+
K+
Hz0 , pl/min/cm
-2.98 (1.74-4.22)
-4.92 (-4.5-5.34)
-2.29 (-0.91-3.67)
-2.95 (-2.12-3.78)
-0.13 (-0.06-0.2 )
-0.22 (-0.13-0.31)
-23.9 (-1 1.6-36.2)
-32.1 (-21.9-43.3)
-1.40 (-1.17-1.63)
-0.53 (-0.23-0.83)
-1.65 (-1.13-2.17)
-2.26 (-1.2 -3.32)
-0.06 (-0.05-0.07)
-0.10 (0.02-0.18)
-13.3 (-6.5-20.1)
-16.5 (-7.3-25.7)
-4.25 (-3.05-5.45)
-3.45 (-2.03-4.88)
+0.34 (+0.09-0.19)
-26.5 (-16.8-35.2)
-1.24 (-0.41-2.07)
-1.67 (-0.68-2.66)
C0.07 (+0.05 -0.09)
-
5.3 (0.5-10.1)
'Data are means; ranges are shown within parentheses. n = 4 determinations per mean. Negative signs (-) signify secretion. Positive signs (+)
signify absorption. The composition of the buffers was, in milliequivalents per liter: Na+ 142, K+ 5.95, Ca++ 2.55, H,PO, - 1.2, and Mg++ 1.2.
The C1- was 118 in the HCO; buffer and was 142 in the buffer without HC0,During an intravenous infusion of sodium bicarbonate.
patient. On the other hand, when HC03--free buffers were
perfused, the reverse occurred. Intravenous HC03- administration increased the secretion of C1- in the PRTA patient to
levels found in t h e control subject. There were n o differences
found in K + and H 2 0 secretion.
The intestinal transport of glucose and tyrosine by the
PRTA patient and by the control subject is shown in Table 2.
The PRTA patient transported more glucose and tyrosine than
the control subject in all instances. There was no difference in
the intestinal transport of these solutes within either buffer.
DISCUSSION
The results of this investigation show that the absorption of
HC03- across upper segments of the small intestine of the
child with PRTA is very similar to that of the comparative
control infant. However, the secretion of HC03- by the
duodenum of the PRTA patient is markedly increased and is
associated with a decreased C1- secretion by the duodenum.
Under normal circumstances, secretion of HC03- in the
human ileum is interrelated with transport of C1-, ~ a +and
,
H+. Turnberg e t al. (24, 25) showed that HC03- transport
might occur via simultaneous double exchange of Cl-/HC03and Na+/H+. This occurs actively, against steep electrochemical gradients mediated by active H + ion secretion with
inhibition by acetazoleamide (25). HC03- transport may also
occur without mediation of H + ion secretion o r reabsorption
as a primary anion transport system on a neutral or an
electrogenic secretory mechanism (16). In our experiments,
the p C 0 2 levels of the perfusates were elevated whenever
HC03- absorption occurred in both control and PRTA
patients. This data suggest that the mechanism of HC03reabsorption in the upper segments of the small intestine is
similar t o that in the kidney. Secretion of H + ion must occur
for formation of H 2 C 0 3 in the lumen and conversion of this
molecule t o water and C 0 2 . Therefore, the H + secretory
mechanisms of the small intestine in the PRTA patient were
similar t o the control subject.
These data are in agreement with those of RodriguezSoriano e t al. (19), who postulated that H + ion secretion was
not decreased in PRTA; and is consistent with the hypothesis
which postulates that increased HC03- secretion is related t o a
defective C1- transport mechanism (12, 17-20). The net
fluxes of C1- during HC03- absorption and secretion by the
upper segments of the small intestine in the PRTA patient
suggested a defective exchange mechanism for C1-/HC03-. It is
of interest that C1- secretion was similar t o Na* secretion in
the PRTA patient in all instances, whereas in the control
infant, C1- secretion was in excess of Na+ when HC03- was
absorbed and the reverse occurred when HC03- was secreted.
The data from t h e control infant are similar t o those predicted
Table 2. Intestinal absorption o f glucose and tyrosine1
Patient
PRTA2
Control
Glucose,pmol/min/cm
66.23
25.30
5
?
38.16
20.44
' Data are means + SD. n = 8-12
'P
< 0.05.
Tyrosine, mpmol/min/cm
1,653.4 5 195.0
709.7 + 456.1
determinations per mean. P < 0.05
by a normally functioning double exchange pump for HC03transport postulated by Turnberg et al. (24). It is tempting t o
speculate the presence of a defect in this "pump" in PRTA
patients which would allow a net secretion of HC03- without
concomitant secretion of Na+.
Theoretically, the ventriculoatrial shunt of the control
patient could induce C1- secretion rate in excess of Na* by the
intestine. It is known that spinal fluid has higher C1- than Na+
levels (4). However, there is n o other data available on this
question, and if this mechanism were taking place we would
expect t o see similar ratios of cl-/Na* secretion in the
intestine during perfusion of HC03--containing and HC03-free buffers. In fact, the ratios were reversed in our control
patient, in that Na+ secretion was in excess of C1- secretion b y
a factor of 4-5.
The mechanisms of HC03- transport by the upper segments
of the small intestine are shown in Figure 4. Both normal and
patients with PRTA had similar absorption rates of HC03-,
herea as there seemed t o be a much greater amount of
secretion of HC03-, and a decreased secretion of Cl- by the
PRTA patients. Although the relation between Cl-/HC03transport is still not elucidated, it seemed t o be disrupted in
the upper segments of the small intestine of the PRTA patient.
Inasmuch as other diseases involving renal transport defects
have been shown t o have similar abnormalities a t both the
level of renal tubule and gastrointestinal mucosal cell (2, 1 I ) ,
we feel that the defect in gut Cl-/HC03- in PRTA may be
similar to the one in the kidney of these patients. The
quantitative HC03- loss occurring in the small intestine
seemed t o be very significant, compared with the average
losses of HC03- in the kidney of PRTA patients. In our PRTA
patient there was a HC03- loss of approximately 2.4
pEq/min/cm of intestine, when she had a normal serum HC03concentration. In PRTA patients the total HC03- loss through
the kidneys might be as high as 200 pEq/min at normal serum
HC03- levels. Because the total small intestinal surface area is
200-500 m2 (S), the HC03- secretion through the intestine
may be as high as 4,800-10,000 pEq/min at normal serum
HC03- levels. However, exact estimates of true lumen-to-blood
or blood-to-lumen fluxes remain t o b e ascertained by more
"4
PROXIMAL RENAL TUBULAR ACIDOSIS
NORMAL
BLOOD
PRTA
A-h
5. Davenport, H. W.:
6.
t
CELL
7.
8.
ABSORPTION
6-S E C R E T I O N
Fig. 4. Mechanism of HC0,- transport in proximal renal tubular
acidosis (PRTA). Diagrammatic representation of increased HC0,- and
decreased C1- blood-to-lumen fluxes in the upper segments of the small
intestine observed in t h e PRTA patient.
a c c u r a t e i s o t o p i c t r a c e r s ; in a d d i t i o n , i n t e s t i n a l i n t u b a t i o n
studies to d e t e r m i n e ileal r e a b s o r p t i v e response r e m a i n to be
done.
The possibility o f c o n t a m i n a t i o n of the p e r f u s a t e s b y biliary
a n d p a n c r e a t i c s e c r e t i o n s into t h e i n t e s t i n e d u r i n g t h e s t u d y
should be c o n s i d e r e d . H o w e v e r , this c o u l d b e e x p e c t e d t o
a f f e c t a b s o l u t e values but not c o m p a r a t i v e a b s o r p t i v e o r
s e c r e t o r y r a t e s a s p e r f o r m e d in o u r e x p e r i m e n t s . S l a d e n a n d
D a w s o n ( 2 3 ) h a v e shown t h a t c o n t a m i n a t i o n is negligible in
the n o r m a l f a s t i n g u p p e r j e j u n u m , a n d t h a t t h e r a t e s o f w a t e r
a n d e l e c t r o l y t e a b s o r p t i o n a r e similar in d o u b l e a n d triple
lumen p e r f u s i o n t e c h n i q u e s .
The s y n d r o m e of familial chloride d i a r r h e a s e e m s to
i l l u s t r a t e a d e f e c t in C1- h a n d l i n g by t h e i n t e s t i n a l m u c o s a t h a t
is similar to a d e f e c t in the h a n d l i n g o f a d i f f e r e n t m o l e c u l e ,
H C 0 3 - , in our p a t i e n t w i t h P R T A . P a t i e n t s w i t h familial
c h l o r i d e d i a r r h e a lose C1- a t r a t e s of 5 p E q / m i n / c m in the
ileum (26), a n d h a v e c h r o n i c d i a r r h e a a n d alkalosis. T u r n b e r g
e t al. (24, 2 5 ) p o s t u l a t e d a reversal o f t h e n o r m a l C l - / H C 0 3 e x c h a n g e p u m p o f the ileum. T h e r a t e of C1- s e c r e t i o n in
patients with familial chloride diarrhea is o f the s a m e order o f
m a g n i t u d e a s the H C 0 3 - losses i n o u r p a t i e n t w i t h a d e f e c t i v e
C1- s e c r e t o r y m e c h a n i s m .
SUMMARY
Proximal r e n a l t u b u l a r acidosis ( P R T A ) h a s b e e n t h o u g h t to
be c a u s e d by a d e f e c t in H C 0 3 - r e a b s o r p t i o n by the r e n a l
t u b u l e . We h a v e u s e d t r a n s i n t e s t i n a l i n t u b a t i o n t o s t u d y
H C 0 3 - t r a n s p o r t in t h e d u o d e n u m of a n o r m a l a n d a P R T A
p a t i e n t , a n d h a v e t h e o r i z e d t h a t in t h i s disease, a s i n o t h e r s
involving t r a n s p o r t d e f e c t s , t h e i n t e s t i n a l m u c o s a l cell h a s a
similar a b n o r m a l i t y a s the r e n a l tubule cell. W e h a v e f o u n d
t h a t there is no d e f e c t i n a b s o r p t i o n o f H C 0 3 - b y t h e P R T A
duodenum, but r a t h e r a m a r k e d e x c e s s o f s e c r e t i o n of H C 0 3 - .
In a d d i t i o n , the s e c r e t i o n of H C 0 3 - b y t h e s m a l l i n t e s t i n e
i n c r e a s e d 1 0 0 - f o l d in the P R T A p a t i e n t w h e n t h e s e r u m
H C 0 3 - c o n c e n t r a t i o n s w e r e elevated t o n o r m a l levels by
intravenous infusion of N a H C 0 3 . T h e intestinal secretion of
H C 0 3 - w a s a s s o c i a t e d w i t h d e c r e a s e d s e c r e t i o n o f C1- by t h e
u p p e r s e g m e n t s o f the s m a l l i n t e s t i n e o f the P R T A p a t i e n t .
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The present address of Dr. M. Schoeneman, Resident in Pediatrics,
is: Albert Einstein College of Medicine, Department of Pediatrics,
Division of Nephrology, Bronx, New York 10461 (USA). The
present address of Dr. S. Diaz-Bensussen is: Hospital de Pediatria,
Centro Medico National, I.M.S.S., Mexico City, Mexico.
Requests for reprints should be addressed to: F. Lifshitz, M.D.,
Department of Pediatrics, North Shore University Hospital,
Manhasset, New York 11030 (USA).
Accepted for publication April 1, 1974.
31. Flame
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34.
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Copyright O 1974 International Pediatric Research Foundation, Inc.
35.
Printed in U.S.A.