Download Effects of Changes in Dietary Lipids on Intestinal Fluid

Effects of Changes in Dietary Lipids on Intestinal Fluid Loss
in the Short-Bowel Syndrome
WIESLAW BOCHENEK, M.D., JOHN B. RODGERS, JR., M.D.,
and JOHN A. BALINT, M.B., M.R.C.P., Albany, New York
Seven patients underwent massive intestinal resection.
Fecal losses of water and electrolytes were life
threatening in four patients, who required constant or
repeated intravenous replacement. All patients
received symptomatic treatment and vitamin
replacement. Lowering the amount of dietary fat, bile
salt replacement, and supplementation of diet with
micellar fat were ineffective. A regimen consisting of
50 to 7 5 % replacement of dietary long-chain fat with
medium-chain triglyceride proved beneficial, leading to
gradual decline in fecal loss of water and electrolytes
and great improvement in nutritional status. Gastric
secretory studies showed minimal increase in basal
and 12-hr overnight acid output in two patients and
no increase in maximal acid output. Pyloroplasty and
vagotomy attempted in one patient and directed toward
reduction of gastric secretion proved disastrous. Such
treatment should be reserved for patients
demonstrating massive gastric hypersecretion
unresponsive to medical management, and a
conservative program should be followed.
MASSIVE SMALL-BOWEL resection performed for inflammatory bowel disease or for other reasons can
create serious therapeutic problems. In recent years
the term "short-bowel syndrome" has been used to
describe a situation in patients who are unable to
maintain their metabolic balance because of a short
residual intestinal tract. Typically such patients
demonstrate severe diarrhea and lose excessive
amounts of water and electrolytes in their stools
to a degree that endangers life. Problems of malabsorption and related malnutrition are often of
secondary importance.
• From the Department of Medicine
Medical College, Albany, N. Y.
(Gastroenterology),
Albany
The amount of bowel removed and the site of resection determines the clinical status. Normally
most constituents in the diet are absorbed by the
proximal small bowel (1). The distal small bowel,
however, has certain important absorptive functions
such as active transport of sodium (2), absorption of
water, reabsorption of conjugated bile salts (3), and
absorption of vitamin B i 2 (4). With removal of the
proximal small intestine the ileum is often able to
compensate at least partially for the loss of jejunum
and take over the function of absorption of dietary
materials. However, with distal small-bowel resection, fluid and electrolyte losses are often great
because the jejunum has a limited capacity to absorb
these substances. The jejunum cannot actively transport conjugated bile salts, and with distal ileal resection steatorrhea develops from bile salt deficiency
(5).
Excessive loss of water and electrolytes in the
short-bowel syndrome may have another source.
Patients with massive small-bowel resection were
found by some (6) to have gastric hypersecretion.
This in itself increases the fluid volume presented
to the intestinal tract for absorption and lowers
intestinal pH, which may interfere with digestive
and absorptive processes. Malabsorption created
in this way can lead to increased fecal loss of water
and electrolytes. The studies reported here were
undertaken to determine whether changes in quantity
and mode of administration of dietary fat would
control fluid and electrolyte losses, and to determine
what role, if any, gastric hypersecretion plays in the
pathogenesis of the short-bowel syndrome.
Materials and Methods
During 1967 and 1968 four patients who had undergone extensive small bowel resection presented with
massive fecal losses of water and electrolytes. All re205
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termined using the method of Mosbach and associates
(7). Duodenal samples were collected from the same
tube through which the oil was administered.
During trials of bile salt replacement a crude bile
salt preparation was made up in skim milk to contain
1.5 g of bile salts per 100 ml (30 mM), and was given
q.Ld. with meals. During trials of micellar fat supplementation micellar fat solution was prepared in skim
milk using 30 mM bile salt, 35 mM oleic acid, and
14 mM monoolein, and was given in amounts of 100
ml q.i.d. with meals. Each dose contained 1.5 g of
bile salts, 15 g of oleic acid, and 7.5 g of monoolein.
The bile salt used was Ox Bile Extract purchased from
Nutritional Biochemicals Corp., Cleveland, Ohio. Oleic
acid (USP grade) was purchased from Fisher Chemical
Co., Springfield, N.J. It was extracted and subjected to
thin-layer and gas-liquid chromatography and found to
be 85% pure. Monoolein was purchased from Eastman
Organic Chemicals, Rochester, N.Y. More than 85%
was found in the monoglyceride spot on thin-layer
chromatography. Medium-chain triglyceride oil was
purchased from Mead Johnson Research Center, Evansville, Ind. It was prepared according to the method of
Shizas and associates (8) and used for cooking and as a
spread on toast.
quired continuous or repeated parenteral supplementation with electrolyte solutions. Data are also presented
from three other patients who also had extensive smallbowel resection. However, they did not represent a
therapeutic problem of the magnitude of the first four
patients. The seven patients were put on controlled
diets on a metabolic ward. All intake and output measurements were recorded on a 24-hr basis. Parenteral
fluids were given in amounts necessary to keep urine
output in excess of 500 ml/24 hr. Composition of the
intravenous fluid supplements was varied depending on
serum electrolyte values and consisted of sodium, potassium, chloride, calcium, and magnesium. Medications included tincture of belladonna, lomotil, deodorized tincture of opium or codeine and pancreatic
extract (cotazyme), multivitamins and folic acid given
orally, and vitamin B12 given parenterally.
Frequent determinations of blood count, serum electrolytes and other serum chemistries, and urinary and
fecal electrolytes and pH were carried out by routine
methods. Forty-eight- to 72-hr stool collections were
analyzed for fat and nitrogen content by Bio-Science
Laboratories, Van Nuys, Calif. Bile salt -concentration
in the intestinal content and in the stool after intraduodenal administration of 20 e of olive oil was deTable 1. Clinical Data
Patient
O.N.
J.A.
A.J.
F.F.
J.G.
G.K.
G.B.
Length of
Bowel
Beyond
Ligature of
Treitz
_
41 cm of
proximal
jejunum
and 15 cm
of colon
67 cm of
proximal
jejunum
and 15 cm
of colon
100 cm of
proximal
jejunum
24-hr Feces
Dietary Basal Maximal 12-hr
Serum*
Hematocrit* Weight*
Output
Output
OverFat
Fat Nitrogen
Total IProtein Albumin Adm. Dis. Adm. Dis.
per
per
night
Hour
Hour
Adm. Dis. Adm. Dis.
48
39
g
8.2
40.0
22.0
21
33
4.2
4.1
*19
35
228 15 cm
37
proximal
jejunum
98 cm of
proximal
jejunum and
25 cm
of colon
All remaining
but distal 116
cm ileum and
cecum
Transverse, 25
descending
sigmoid
colon and
_ _ _ _ _ _ •
_
*MJ7V*
- TnHiQ
'
1.3
50
6.6
5.3*
25.3
25.91
100
5.8
48
32.8
100
0.9§
2.4§
1.92
19.0
22.3
21.6§
34.5J
23.5
0.4
0.9
14.5
13.8
54.5
1.1
11.9
50
28.1
21*
No acid, No acid,
pH7.2 pH7.0
• Adm—admission; Dis—discharge.
t Patient died.
t Medium chain triglyceride on program.
9 After reanastomosis.
206
5.8*
1.8
2.3*'
22
40f
99
lb
105t
4.8
7.8
1.9
4.5
31
41
103
122
7.5
6.9
2.7
3.5
46
42
189
157
6.7
7.0
3.7
4.4
35
38
92
96
— —
50
Fmbrumry 1970 • Annals of Internal Medicine • Volume 72 • Numbmr 2
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*
4.6
^^
a/ 1()()ml -
g/
lUUFni
%
During a control period of at least 2 weeks patients
were given diets containing 50 to 100 g of fat, 100 g
of protein, and 300 g of carbohydrates. Although the
diet was kept constant, no attempt was made to monitor
strictly daily calorie intake. Daily fluid intake was
measured carefully.
Gastric analysis using the augmented histamine test
of Kay (9), oral glucose tolerance test, and X-ray
contrast studies of the entire remaining gastrointestinal
tract were obtained during this period. In Patients
A.J. and J.A. gastric analysis was repeated after intestinal reanastomosis and while on medium-chain triglyceride regimen, respectively.
Trials of experimental regimens lasted for at least
7 days unless the clinical course deteriorated, as shown
by increasing fecal volume and negative fluid balance.
In this event the patients were put back on the control
program. Therapeutic trials included decreasing total
fat intake to 25 g of long-chain triglycerides per 24
hr and trials of bile salt replacement while on the control diet, supplementing the control diet with micellar
fat, and substitution of 25 to 50 g of medium-chain
triglycerides per 24 hr for the corresponding amount
of long-chain fat.
In the presentation of the data, stool volumes are
given in absolute figures and also as a percent of oral
fluid intake in order to make the data comparable
regardless of oral intake, which varied not only from
patient to patient but also in the same patient during
different dietary regimens.
Case Histories (Table 1)
Patient O.N., a 49-year-old white woman, had suffered from Crohn's disease for 16 years. There was also
a past history of peptic ulcer disease. During the last
4 years she had been treated by successive resections
of the distal small intestine and colon and was admitted to the study 8 weeks after the fourth operation.
At that time her intestinal tract consisted of an intact
stomach, duodenum, and 41 cm of proximal jejunum
anastomosed to 15 cm of sigmoid colon with a colostomy. She presented a severe metabolic problem with
tetany from hypocalcemia and hypomagnesemia, and
gross emaciation and dehydration. Stool volumes ranged
from 3 to 11 liters per 24 hr, and she required constant
intravenous supplementation with electrolyte solutions.
Therapeutic efforts were primarily directed toward reduction of the large stool volume. During 1 year of
continuous intravenous supplementation she developed
seven episodes of gram-negative bacillus septicemia and
two fungal septicemias, which complicated the patient's
clinical course and caused her death. Initial treatment
consisted of lowering dietary fat to 50 g per 24 hr.
During this control period her enterostomy output
averaged 5,260 ml on an average oral intake of 5,330
ml/24 hr (Table 2). She was subsequently put on
micellar fat. This caused some reduction in stool output but did not permit discontinuation of intravenous
fluid therapy (Table 3). Because of the low stool pH,
which ranged from 4.5 to 5.5, and the results of gastric
analysis, which were at the upper limit of normal, it
was decided to subject the patient to vagotomy and
pyloroplasty. After the operation, enterostomy output
almost doubled, and there was no response to any of
the therapeutic regimens (Table 4). Subsequently the
patient underwent reversal of an intestinal segment to
slow down intestinal transit. This also failed to improve
her condition, and she died several weeks later.
Patient J.A., a 50-year-old white woman, had multiple small-bowel resections for Crohn's disease during a
12-year period. The last operation left the patient with
the intestinal tract consisting of stomach, duodenum,
67 cm of proximal jejunum, and 15 cm of transverse
colon with a colostomy (Table 1). Postoperative stool
volumes ranged from 3 to 5 liters daily, and she required constant intravenous fluids. The clinical course
was complicated by development of enterocutaneous
fistulae and wound abscess. On several occasions the
Table 2. Control Period
Patient
Days
Intake
(by Mouth) *
Enterostomy
Output*
«
O.N.
Before vagotomy
Net Volume
ml
•
Enterostomy
Output
% of intake
99
14
5,330
(3,600-6,900)
5,260
(3,590-6,260)
+70
O.N.
After vagotomy
6
5,620
(4,530-7,790)
9,050
(6,210-11,515)
-3,430
161
O.N.
After intestinal
reversal
9
3,360
(2,200-4,550)
3,100
(2,200-4,000)
4,770
(3,395-6,945)
5,930
(3,200-6,980)
3,510
(2,300-5,320)
4,640
(3,170-5,590)
-2,570
176
-410
113
+ 130
97
J.A.
26
A.J.
10
F.F.
First admission
17
3,900
(3,400-4,200)
2,280
(1,540-2,970)
+ 1,620
58
F.F.
7nH admission
8
4,240
(4,000-4,800)
3,390
(2,900-3,850)
+ 850
80
• Mean. Ranges are in parentheses.
Bochenek, et a/. • Dietary Lipids and Short-Bowl Syndrome
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207
Table 3. Effect of Micellar Fat
Patient
Days
Intake
(by Mouth) *
<
O.N.
Before vagotomy
Net
Volume
>
mi
4,590
(3,820-5,700)
13
Enterostomy
Output*
3,980
(2,280-5,620)
+610
Enterostomy Output
On
Micellar
Fat
During
Control
Period
% of intake
87
99
O.N.
After vagotomy
6
4,540
(4,060-5,000)
8,320
(7,400-9,180)
-3,780
183
161
AJ.
Oral
administration
7
4,770
(3,900-7,290)
6,480
(5,600-7,680)
-1,710
136
97
9
4,170
(3,400-5,010)
3,850
(3,39CM,380)
+320
92
97
+700
83
58
AJ.
Administered
via distal
enterostomy
F.F.
First admission
4,100
(4,(XXM,148)
3
3,400
(2,980-3,820)
* Mean. Ranges are in parentheses.
patient demonstrated musculai hyperexcitability and
was found to be hypocalcemic and hypomagnesemic.
Three months after the operations the fistulae and
wound healed. However, colostomy output was still
high and electrolyte solutions had to be given intravenously on a routine basis. She was admitted to the
study at this time and started on a 50 g fat diet. The
enterostomy output averaged 3,510 ml, exceeding oral
intake by 410 ml (Table 2). Substitution of 50% of
dietary fat with medium-chain triglycerides resulted in
marked decrease in stool volume, and parenteral fluids
could be discontinued (Table 5). Six months after the
operation the patient was able to take care of herself
and was discharged. Three months later she was readmitted for follow-up studies (Table 5). By that time
she looked and felt much better and had gained 20
lb. The patient has now been followed for a full year.
She is leading an active life and doing her own housework.
Patient A.J., a 53-year-old white, obese, diabetic man
with polycythemia vera, was admitted because of diffuse
abdominal pain. On the day after admission an exploratory laparotomy was performed, and a diagnosis
of venous mesenteric thrombosis was made. Approximately 130 cm of jejunum were resected. Two days
later the patient again developed abdominal symptoms
and was found to have a new area of jejunal infarction. Further resection of the small intestine was performed. It was judged unwise at that time to do an
end-to-end anastomosis. The distal end of the remaining jejunum and the proximal end of the ileum were
brought out on the anterior abdominal wall, creating
proximal and distal enterostomies. The total amount
of resected intestine was 227 cm, and the length of
the jejunum between the ligament of Treitz and proximal enterostomy was estimated surgically and radiologically to be 100 cm (Table 1). This operation gave
a rare opportunity to study a patient having a short
proximal small intestine with high enterostomy output,
in whom supplementation of nutrients, water, and elec-
Table 4. Effect of Bile Salts
Patient
Days
Intake
(by Mouth)*
«
O.N.
After vagotomy
AJ.
Administered
via distal
enterostomy
F.F.
First admission
Enterostomy
Output*
ml
•
5
4,550
(4,000-5,700)
8,240
(6,320-9,615)
-3,870
6
4,110
(3,590-5,390)
3,560
(2,890-4,140)
9
4,000
(3,900-4,050)
2,200
(1,720-2,820)
* Mean. Ranges are in parentheses.
208
Net
Volume
February 1970 • Annals of Internal Medicine • Volume 72 • Number 2
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Enterostomy Output
On Bile
Salts
During
Control
Period
% of intake
185
161
+ 550
87
97
+ 1,800
55
58
Table 5. Effect of Medium-Chain Triglycerides
Patient
Days
Daily Fat Intake
Enterostomy
Output*
Intake
(by Mouth)*
— ml
4
J.A.
8
Long-chain triglycerides
25
Medium-chain triglycerides
25
Beginning of program
18
14
F.F.
Second admission
7
8
2 months later
Long-chain triglycerides
50
Medium-chain triglycerides
50
Long-chain triglycerides
25
Medium-chain triglycerides
50
Net
Volume
•
-10
Enterostomy Output
On MediumChain
Triglycerides
During
Control
Period
% of intake
100
113
2,450
2,400
(1,650-2,060)
(2,100-10,190)
2,970
(2,010-3,160)
2,5001
2,040
(1,160-2,900)
1,180
(840-1,300)
4,000
3,030
(3,950-4,020)
+930
69
113
+1,320
47
113
+970
76
80
+ 1,660
58
80
(2,570-3,370)
3,970
2,310
(3,740-4,010)
(1,000-2,800)
* Average ranges are in parentheses.
t Patient at home; precise volume of oral intake unknown.
trolytes could be easily managed via the distal enterostomy. The postoperative course was complicated by
gangrene of the gall bladder, which required drainage.
Three and one half months after the first operation the
patient demonstrated no further complications, and the
small bowel was reanastomosed. The patient has now
been followed for 24 months. He feels well, and there
are no symptoms of malabsorption. While in the hospital he lost 70 lb, but he is now back to his previous
weight of 220 pounds.
Patient F.F., a 50-year-old man had multiple intestinal resections during a 20-year period for Crohn's
disease of the colon and terminal ileum. When admitted
to the study the estimated length of his small intestine
was 228 cm beyond the ligament of Treitz and ended
in an ileostomy (Table 1). Although he could take
care of himself and was employable after the last
resection, he was in borderline fluid and electrolyte
balance and would become dehydrated due to minor
increases in ileostomy output or prolonged sun exposure during summer months. He was found to respond to 50% substitution of dietary fat with mediumchain triglycerides and continues to take this diet at
home (Table 5). Since the commencement of this regimen the patient appears to be in good metabolic balance
and so far has not been readmitted to the hospital.
Patients G.K., J.B., and G.B. had varying lengths of
intestinal tract remaining (Table 1). Their ability to
maintain metabolic balance was not impaired to the
extent presented by the former patients, and they only
occasionally required intravenous supplementation.
Results
Table 1 gives the data on the basic disease process, length of the remaining bowel, the values of
24-hr fecal fat and nitrogen and the results of gastric
analysis, hematocrit, serum protein, and the patients' weight. All the patients had distal bowel
resection, and the results of the 24-hr fecal fat
determinations in five patients show a marked degree
of steatorrhea.
Gastric analysis showed slight elevation of basal
values in Patients J.A. and A.J. In addition, 12-hr
overnight collections in Patient A.J. gave results
above normal on two occasions. The same patient
had two more studies after restoration of the continuity of his gastrointestinal tract, which showed
normal results for basal secretion. In Patient J.G.,
although there was no basal hypersecretion, 12-hr
overnight collection gave a result above normal.
Patient G.B. did not produce acid during the basal
hour or after administration of histamine. Secretory
studies on Patients O.N., F.F., and G.K. yielded
normal results. There was no elevation of maximal
acid output in any of the patients.
CONTROL PERIOD
During the control period (Table 2) Patients O.N.
and J.A. were put on a diet containing 50 g of fat,
and Patients A.J. and F.F. received 100 g of fat/24
hr. Patients O.N. and J.A. had markedly negative
intestinal water balance. Patient A.J. was in marginal positive balance, whereas Patient F.F. was in
adequate positive balance.
EFFECT OF MICELLAR FAT
When micellar fat was used orally it caused a
Bochenek, et a/. • Dietary Lipids and Short-Bowl Syndrome
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209
decrease in enterostomy output in Patient O.N. of
12%, and increase in enterostomy output in Patients F.F. and A.J. (Table 3). On administration
via the distal enterostomy in Patient A.J. it produced
a minimal improvement in fluid balance (jejunostomy output fell from 97 to 92% of oral intake).
SUPPLEMENTATION WITH BILE SALTS
Daily doses of 6 g of bile salts were given orally
to Patients O.N. and F.F. and via distal enterostomy
with supplementary fluids to Patient A.J. (3 g of
Ox Bile Extract/100 ml of saline). This program
produced only minimal decrease in enterostomy
output in two patients and an increase in one (Table
4).
SUBSTITUTION
OF
LONG-CHAIN
TRIGLYCERIDES
WITH MEDIUM-CHAIN TRIGLYCERIDES
Fluid balance became positive with no need for
further intravenous therapy in the three patients
in whom 50% or more of dietary long-chain triglycerides were replaced by medium-chain triglycerides (Table 5). On 50 g of long-chain triglycerides and 50 g of medium-chain triglycerides
Patient F.F. showed only minimal improvement.
Further decrease in long-chain triglycerides to 25
g/24 hr resulted in 22% decrease in enterostomy
output. In Patient J.A. a diet containing 25 g medium-chain triglycerides with 25 g long-chain triglycerides resulted in a 13% decrease in enterostomy output during the first 8 days. During the
following month there was further decrease in
enterostomy output, resulting in an overall reduction
of 44% as compared with the control period. On
follow-up studies 2 months later, her enterostomy
output measured over 14 days averaged 1,180 ml/
24 hr on an oral fluid intake of 2,500 ml. At that
time discontinuation of medium-chain triglycerides
for 6 days, with long-chain triglycerides remaining
at 25 g/24 hr and without additional caloric supplements resulted in steady increase in enterostomy
output to 2,200 ml/24 hr, which continued for 3
days after reinstitution of the previous mediumchain triglyceride program (Figure 1). Subsequent
stool volume declined gradually and attained a
steady level after approximately 3 weeks, averaging
1,200 ml/24 hr. Similar effects were observed in
Patient J.G. Over a period of 6 weeks after the
program was started he gained more than 10 pounds,
and his urine output increased more than twofold.
Most of this time the patient was at home and at
work, and no exact data on oral fluid intake and
enterostomy output are available. The increase in
urine output was gradual and reached a steady
level after 4 weeks of treatment.
REFEEDING
In Patient A.J., who had both a proximal and a
distal enterostomy (Table 1, see Case Histories), the
effect of transfer of the proximal enterostomy output
into the distal enterostomy was observed. Average
oral intake during 5 days was 2,560 ml and proximal enterostomy output, 1,170 ml/24 hr. The net
volume gain averaged 1,390 ml/24 hr, and the
proximal enterostomy output expressed as percent
of oral intake decreased to 46% compared to the
control value of 97%.
FECAL LOSS OF ELECTROLYTES
Fecal losses of sodium, potassium, and chloride
were examined in Patients A.J. and J.A. Concentrations of the electrolytes in feces remained
fairly constant during the various treatment periods
so that electrolyte losses were proportional to stool
volumes (Table 6).
BILE SALT CONCENTRATIONS IN INTESTINAL CONTENT AND STOOLS
Figure 1. Effect on fecal volume of stopping and restarting
medium-chain triglyceride in Patient J.A. Oral intake was kept
constant at 2,500 m l / 2 4 hr. Bars represent average 24-hr
stool volumes during 3-day periods.
210
After intraduodenal administration of 20 g of
olive oil to Patient J.A. the highest concentrations
of bile salts in the intestinal contents were 0.5 //.mole
of dihydroxy, and 0.9 /xmole of trihydroxy bile salts
per ml. The values for stools during the same
experiment were 0.3 /xmole/ml and 0.6 /Amole/ml,
respectively, indicating severe bile salt depletion
and malabsorption.
February 1970 • Annals of Internal Medicine • Volume 72 • Number 2
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Table 6. Fecal Electrolytes
Patient
J.A.
A.J.
Regimen
Control period
On medium-chain
triglyceride
program*
Control period
Bile salts via distal
enterostomy
Micellar fat orally
Micellar fat via distal
enterostomy
Enterostomy
Output
Concentration
Sodium
ml
3,500
62
2,040
4,640
61
79
3,560
6,480
3,850
Potassium
— Cy, /
TMLq/
14
Daily Output
Chloride
Sodium
lllBr
Potassium
Chloride
J7
fittrr
64
217
22
16
87
78
82
79
15
16
86
16
TtiJu*q ~—~
49
224
124
367
45
74
117
362
94
86
292
512
53
104
335
557
82
331
62
316
• Patient obtained oral supplementation of potassium.
Discussion
This study was undertaken to determine whether
dietary manipulations would diminish water and
electrolyte loss in patients with a short small intestine and to evaluate the importance of gastric
hypersecretion in the pathogenesis of the shortbowel syndrome. All patients studied had massive
intestinal resection. Large stool volumes were due
primarily to loss of the distal small intestine and
colon, which are important in water and electrolyte
absorption. Excessive diarrhea is a common feature
after intestinal resection or bypass. However, after
an initial period of approximately 2 to 4 months,
adaptation often occurs (10-12), and marked improvement may be observed even in patients who
had massive intestinal resection. Dowling (13),
using perfusion techniques, found statistically significant increases in absorption of glucose per unit
length of intestine in patients with small-bowel resection, as compared with control subjects. This
can perhaps be explained by the findings of Poms
(14), which showed that after intestinal resection in humans, the number of epithelial cells
per unit length of intestinal villi is increased. Studies
performed on rats with resection of the jejunum
showed hypertrophy of the intestinal mucosa of the
remaining ileum and also demonstrated increases in
the activity of two microsomal enzymes, fatty acid:
coenzyme A ligase and acyl-coenzyme A:monoglyceride acyltransferase, which are involved in
reesterification of absorbed fatty acids and monoglycerides present in dietary lipids (15). If the bowel
remaining after resection is basically healthy, it
is reasonable to expect it to adapt at least to some
extent, provided good metabolic balance is maintained.
In an attempt to reduce water and electrolyte
loss diet was manipulated in order to decrease
steatorrhea without decreasing caloric intake. A
simple reduction in the amount of steatorrhea can
readily be achieved by decreasing the amount of
fat in the diet This in itself may have a beneficial
effect on fecal fluid loss. However, decrease in
dietary long-chain triglycerides to SO g/24 hr did
not benefit Patients O.N. and J.A.. In Patient J.A.
a further reduction of long-chain triglycerides to
25 g was attempted without success. It is now well
established that ileal resection or ileal disease interrupts the enterohepatic circulation of bile salts, and,
consequently, concentrations of conjugated bile salts
in the intestine may fall below the critical micellar
concentration (16, 17). Under these conditions
malabsorption of fat is observed. Oral administration of bile salts in such patients may result in
increased concentration of micellar lipids in the
small bowel and decreased fecal loss of fat (18,
19). Since all the patients in this study had distal
small bowel resection and colectomy, it was expected that some improvement could be achieved
by oral supplementation of bile salts. Malabsorption
of bile salts with resultant depletion of the bile salt
pool was demonstrated in Patient J.A. Oral administration of crude Ox Bile Extract in two patients
produced a slight decrease in enterostomy output
in one and an increase in another. Direct ileal
administration of bile salts in the third patient, A.J.,
resulted in some improvement
Oral use of micellar fat in Patients A.J. and F.F.
was associated with increase in stool volume and
in Patient O.N. with decrease. Direct ileal administration in Patient A.J. resulted in only slight reduction in jejunostomy output. It is of interest that
in this patient a significant reduction in proximal
enterostomy drainage resulted when the proximal
enterostomy drainage was instilled into the distal
enterostomy. This was probably related to efficient
reabsorption of endogenous bile salts and absorption
of electrolytes, water, and predigested fat by the
distal bowel. By contrast, in only one of three
Boehenek, et •/. • Dietary Lipids and Short-Bowl Syndrome
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211
patients did the oral administration of micellar fat
produce any benefit. It is possible that the additional
fat represented by the micellar solution proved
excessive in these patients.
Medium-chain triglycerides have been reported
to be useful in many forms of malabsorption (20,
21) and have also been used successfully in patients
with a short bowel (6, 22, 23). French (24) reported reduction of stool weight in a patient after
massive small-bowel resection while on mediumchain triglyceride supplementation; however, the
effects of medium-chain triglycerides on fecal fluid
loss have not been well studied. It was decided to
substitute part of the dietary fat with medium-chain
triglyceride to improve nutrition and to decrease
fecal loss in three patients. Considerable benefit was
observed in all three. Substitution with mediumchain triglycerides did not result in immediate
improvement in any of the three patients, but
approximately 7 days on therapy were needed before significant reduction in fecal volume was
produced. This may account for the lack of effect
in the first period of medium-chain triglyceride
therapy in Patient F.F. Similarly, discontinuation of
medium-chain triglycerides resulted in only gradual
increase in stool volume. Thus, withdrawing medium-chain triglycerides in Patient J.A., while the
rest of the diet was kept constant, caused a twofold
increase in stool volume over a 5-day period. Reinstitution of medium-chain triglycerides in the program resulted in a decrease of stool volume to the
previous level in 20 days. Long-term follow-up
of treatment with medium-chain triglycerides led
to remarkable improvement in nutritional status.
Patient J.A. reached her normal weight, and anemia
and hypoalbuminemia present after the last resection were corrected. The mechanism by which
medium-chain triglycerides cause a decrease in fecal
fluid and electrolyte loss is unknown. Because these
effects are not observed for at least several days
after initiation of medium-chain triglyceride therapy and persist for several days after its discontinuation it seems unlikely that its only action
is secondary to decrease in the degree of steatorrhea.
Similarly, inhibition of gastric secretion or improvement in water transport in the jejunum would be
expected to result in immediate changes. It is possible that medium-chain triglycerides act indirectly
by improvement in the patient's nutritional status
and bowel function. They may do this by providing
readily available calories in a form that does not
exert a strong osmotic effect in the bowel lumen.
Measurements of fecal sodium, potassium, and
chloride indicate that the amount of electrolyte loss
212
is directly related to stool volume. This finding is
understandable in view of the fact that in these
patients the remaining bowel was jejunum, where
electrolytes are absorbed in essentially isotonic
solution. Because of steatorrhea, hypocalcemia and
hypomagnesemia were common complications.
Typical neuromuscular hyperexcitability was observed in two patients and responded only to combined administration of calcium and magnesium
(25, 26). In Patient J.A. calcium and magnesium
supplementation by the oral route has been steadily
reduced with her improvement. Presumably, losses
of these cations decreased with the decrease in stool
volumes.
It has been suggested that patients with massive
intestinal resection may have increased gastric
secretion (6). This might contribute to fecal fluid
loss by presenting more endogenous fluid to the
intestine for absorption or because the low pH
might interfere with digestion and absorption. No
increase in maximal acid output was found in this
series of seven patients, but basal acid output was
slightly increased in two of them, and 12-hr overnight secretion was somewhat higher in one of
these and in one other patient. It is of interest that
in Patient A.J., who demonstrated basal hypersecretion initially, gastric analysis performed twice
after reanastomosis of his intestinal tract gave
normal values.
During intestinal digestion and absorption of fat,
inhibition of gastric secretion occurs. This has been
well documented in studies on animals (27, 28), as
well as on humans in this laboratory (29). Experimental studies on dogs suggest that massive intestinal
resections can cause gastric hypersecretion (30, 31).
However, Salmon and Wright (32), who performed
gastric analysis in nine patients before and after
small-bowel bypass, did not observe increases in
gastric secretion after the operation. Similar results
were reported by Shibata and associates (12) on
three patients after jejunocolic bypass. Our studies
indicate that if intestinal resection does affect gastric
secretion, the resulting increase, if any, is in basal
secretion and is generally not of great significance.
It may be due to loss of a normal inhibitor of
basal gastric acid secretion. Patients with massive
small-bowel resection have been reported to respond
favorably to pyloroplasty and vagotomy (6, 10).
This operation actually dramatically worsened the
condition of Patient O.N. Subsequently, the patient
underwent reversal of an intestinal segment. Followup was too short to draw any definite conclusions,
but the procedure did not appear to have been
effective. Most of the patients in whom this pro-
February 1970 • Annals of Internal Medicine • Volume 72 • Number 2
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cedure has been attempted by others (33, 34) had
longer lengths of small bowel remaining.
Treatment of patients with short-bowel syndrome
should be conservative. Therapy should consist of
appropriate fluid, electrolyte, and vitamin replacement, with the usual symptomatic measures. In
particular, a prolonged trial of substitution of medium-chain triglyceride for long-chain dietary fat is
indicated. Surgical therapy directed toward reduction
of gastric acid secretion should be reserved for
patients demonstrating massive gastric hypersecretion unresponsive to medical management.
ACKNOWLEDGMENTS: The authors thank Dr. James F. Long
for helpful advice throughout this study and Miss M. Rogers
for help with the special diets.
This work was carried out in the Clinical Research Unit of
Albany Medical College and supported by Public Health Service
Research Center grant 5 M01 FR00094 CLR from the Division
of Research Facilities and Resources; and supported in part by
Training Grant TO-1 AM05597, the National Institutes of Health,
Bethesda, Md.
Appeared in part in Clinical Research 16:528, 1968.
Received July 24, 1969; revision accepted October 14, 1969.
• Requests for reprints should be addressed to John A. Balint,
M.D., Department of Medicine, Albany Medical College, Albany,
N.Y. 12208
12. SHIBATA HR, MACKENZIE JR, LONG RC: Metabolic effects
of controlled jejunocolic bypass. Arch Surg (Chicago) 95:
413-428, 1967
13. DOWLING RH, BOOTH CC: Functional compensation after
small bowel resection in man. Lancet 2:146-147, 1966
14. PORUS RL: Epithelial hyperplasia following massive small
bowel resection in man. Gastroenterology 48:753-757, 1965
15. RODGERS JB, JR: Location of lipid reesterifying enzymes in
the small intestine and effects of jejunectomy on ileal enzyme
levels (abstract). Clin Res 17:309, 1969
16. AUSTAD WI, LACK L, TYOR MP: Importance of bile acids
and of an intact distal small intestine for fat absorption.
Gastroenterology 52:638-646, 1967
17. VAN DEEST BW, FORDTRAN JS, MORAWSKI SG, et al: Bile salt
and micellar fat concentration in proximal small bowel content of ileectomy patients. / Clin Invest 47:1314-1324, 1968
18. HOFMANN AF, GRUNDY SM: Abnormal bile salt metabolism
in a patient with extensive lower intestinal resection (abstract). Clin Res 13:254, 1965
19. HARDISON WGM, ROSENBERG IH: Bile-salt deficiency in the
steatorrhea following resection of the ileum and proximal
colon. New Eng J Med 277:337-342, 1967
20. HOLT PR, HASHIM SA, VAN ITALLIE TB: Treatment of mal-
absorption syndromes and exudative enteropathy with synthetic medium chain triglycerides. Amer J Gastroent 43:549559, 1965
21. GREENBERGER NJ, RUPPERT RD, TZAGOURNIS MT: Use of
medium chain triglycerides in malabsorption. Ann Intern
Med 66:727-734, 1967
22. ZURIER
23. PINTER
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SENIOR, Philadelphia, University of Pennsylvania Press, 1968,
p. 109-119
3. BOROSTROM B, LUNDH G, HOFMANN A: The site of absorp-
25. FLETCHER RF, HENLY AA, SAMMONS HG, et al: A case of
tion of conjugated bile salts in man. Gastroenterology 45:
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4. BOOTH CC, MOLLIN DL: The site of absorption of vitamin
B 12 in man. Lancet 1:18-21, 1959
magnesium deficiency following massive intestinal resection.
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BALINT JA, HIRSCHOWITZ BI: Hypomagnesemia with tetany
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MENGUY R: Studies on the role of pancreatic and biliary
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6. OSBORNE MP, SIZER J, FREDERICK PL, et al: Massive bowel
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8. SHIZAS AA, CREMIN JA, LARSON E, et al: Medium chain
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9. KAY A: Effect of large doses of histamine on gastric secretion
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10. LEONARD AS, LEVINE AS, WITTNER R, et al: Massive small
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30. FREDERICK PL, SIZER JS, OSBORNE MP: Relation of massive
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31. GRUNDBERG AB, LOPEZ AS, DRAGSTEDT LR: Effect of in-
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32. SALMON PA, WRIGHT WJ: Effect of small-bowel bypass on
gastric secretion in obese patients. Canad J Surg 11:365-368,
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33. THOMAS J, JORDAN GL JR: Massive resection of small bowel
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Bochenek, et a/. • Dietary Lipids and Short-Bowl S y n d r o m *
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213
Question of the Month:
Rheumatology
Question 98
The patient whose roentgenograms are shown below most likely
has which of the following:
(A)
(B)
(C)
(D)
(E)
Scleroderma
Hyperparathyroidism
Rheumatoid arthritis
Psoriatic arthritis
Chondrocalcinosis
[This Question of the Month- is from the Medical Knowledge SelfAssessment Program of the AC P. The answer and a reference are given
on p. 270 of this issue—Ed J
214
February
1970
• Annals of Internal Medicine • Volume 72 • Number
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2