Clinical Science (1970)39,305-318.
S U G A R ABSORPTION A N D INTESTINAL MOTILITY
I N CHILDREN WHEN MALNOURISHED
A N D AFTER T R E A T M E N T
W. P. T. J A M E S
Medical Research Council, Tropical Metabolism Research Unit,
University of the West Indies, Mona, Kingston, Jamaica
(Received 28 November 1969)
SUMMARY
1. The ability of malnourished children to absorb lactose, sucrose and glucose was
tested by perfusing the jejunum. Intestinal motility was measured simultaneously in a
perfused segment by a dye dilution technique. These tests were repeated on the same
children after 6-16 weeks of treatment.
2. There was a significant correlation between the rate of hydrolysis of disaccharide
perfusing the jejunum and the level of disaccharidase activity within the jejunal
mucosa.
3. All ten malnourished children had diminished glucose absorption, eight had reduced lactose and six had impaired sucrose hydrolysis and absorption. Children with
the most severe mucosal damage had the lowest rate of sugar absorption. The malabsorption of disaccharide was related to the impairment of hydrolysis and not to the
malabsorption of the monosaccharide products.
4. Primary hypermotility of the intestine was not a feature of the malnourished
group.
5. Water absorption from all infusions occurred only in the treated group. Water
entry into the intestinal lumen in the malnourished group was greatest with the
most poorly absorbed sugars.
6. The mean transit time of fluid passing down the intestine was inversely correlated
with the sugar remaining unabsorbed within the lumen.
7. Treating the malnourished child in hospital produced an increase in glucose,
lactose and sucrose absorption. The generalized nature of the malabsorption and the
reversibility of the defects suggests that lactose intolerance in these children is related
to the nutritional state and not to a genetic predisposition to lactase deficiency.
INTRODUCTION
The cause of diarrhoea, a characteristic of the syndrome of protein-calorie malnutrition is
Correspondence:Dr W.P. T. James, GastroenterologyDepartment,Central Middlesex Hospital, Park Royal,
London, N.W.lO.
L
305
306
W. P. T. James
still not determined. Clinical observations suggest that lactose in the diet is an important
aggravating factor (Dean, 1952), and balance studies have indicated that lactose intolerance
plays a role in about two thirds of the cases of diarrhoea among malnourished African children
(Bowie, Brinkman & Hansen, 1965). Jejunal biopsy studies and lactose tolerance tests in children
who have previously had malnutrition suggest that lactase deficiency persists after treatment
(Cook & Lee, 1966; Bowie, Barbezat & Hansen, 1967). Evidence has been found for a genetic
predisposition to lactase deficiency among some African tribes (Cook & Kajubi, 1966),
and Cook has suggested that the deficiency predisposes to the development of malnutrition
(Cook, unpublished observations).
The present investigation was undertaken to test directly malnourished children’s ability
to absorb lactose, sucrose and glucose, and to identify some of the factors responsible for the
diarrhoea. Further studies were made on the same children after treatment in hospital to assess
the children’s capacity to recover from any defects in intestinal function. A preliminary communication incorporating part of this work has been published (James, 1968a).
METHODS
Ten children, aged 8-12 months, were investigated when first admitted to hospital with proteincalorie malnutrition, and they were retested after a period in hospital which varied from 6-16
weeks. Data from four other children, who were tested only after hospital treatment, are
included. Some of the clinical details are given in Table 1. The child’s whole body potassium
content was obtained by counting him on admission in a 471 liquid scintillation whole body
TABLE
1. Some of the clinical and biochemical features of the fourteen childrenstudied by jejunal perfusionwhen
malnourished (M) and/or after treatment (T)
Child
J.D.
G.M.
C.P.
K.R.
M.G.
D.B.
R.G.
L.W.
M.S.
D.A.
J.H.
J.B.
C.C.
I.D.
Age
(months)
10
11
21
11
8
10
16
15
10
8
13
11
7
12
Whole
Oedema Palpable Admission
Hb
body
(@I+)
liver
weight
(g/100 ml) potassium
(cm)
(kg)
(mEq/kg)
0
0
0
+++
+
0
+++
++++
0
++++
+
0
0
0
0
2
0
2
3
0
3
0
2
0
2
0
0
2
~~
5.0
4.8
5.2
5.7
11.7
10.9
12.0
10.0
5.7
11.0
3.0
4.7
5.3
5.6
5.0
6.5
5.3
3.5
5.5
8.6
5.0*
8.8
101
8.3
-
41 .O
39.2
449
27.7
28.1
55.1
345
33.4
39.5
29.7
-
-
-
-
-
EWHt
(%)
M
T
62
74
61
74
84
57
66
64
63
91
74
62
53
82
100
110
90
100
100
94
96
96
89
107
94
86
94
94
Day from
admission
to infusion
M
T
3
1
2
1
1
5
22
2
2
2
-
79
43
95
98
69
6 4
115
88
54
45
135
103
93
79
~
* Transfused before investigation and given folic acid and antibiotics.
t EWH = Expected weight for height: the child’s weight was expressed as a percentage of the 50th percentile
weight of a normal North American child of the same height (Nelson, 1959).
307
Sugar absorption in malnutrition
counter (Packard Instrument Co.) as described by Garrow (1965). The potassium content of
the body reflected not only the presence of acute potassium depletion e.g. from diarrhoea,
but also the reduction in the body's total potassium capacity due to a fall in lean body mass.
(Alleyne, Millward & Scullard, unpublished observations).
All the children had a history of diarrhoea, but no child had more than mild diarrhoea at
the time of investigation. Antibiotics were not given routinely, although R.G., with severe
pneumonia and diarrhoea, received antibiotics as well as blood transfusion and folic acid
before his jejunal perfusion was performed. When first admitted children were given 4.3%
glucose in 0.18% sodium chloride solution orally every 2 h and no child was studied until well
enough for the investigation, for which parental consent was given. The children tolerated the
jejunal perfusions without incident, and were able to feed normally by the next day. Jejunal
biopsies were obtained on a separate occasion. These were performed with a paediatric Watson
capsule using a modsed technique to speed the passage of the capsule (James, 1968b). Biopsies
were taken from just beyond the ligament of Treitz, and the position of the capsule was confirmed by X-ray fluoroscopy. Part of the biopsy specimen weighing 4-10 mg was quickly
rinsed in ice-cold saline, blotted with filter paper and weighed on an electromagnetic balance.
The disaccharidase activity of the biopsy was estimated within 24 h and the biopsy was stored
until assay in a small sealed container at -20".
Jejunal perfusions were performed by means of a tube incorporating five parts (Fig. 1).
25 crn
15cm
-A
1
-------aMercury
c -------
E
-32 filled
balloon
FIG.1. Diagram of the series of tubes used for the constant perfusion of an 'open' segment of
jejunum.
Tube diameters were as follows:
Diameter (mm)
Tube Outer Inner
Tube Outer Inner
A
B
C
1.0
1.0
08
08
3-0
25
D
E
1.0
1.5
0.8
1.2
Tubes A, E and C corresponded with the usual triple lumen perfusion system and tubes B and
D were additions to allow dye dilution measurements to be made. The child was sedated with
chloral hydrate or paraldehyde and the tube was then passed into the stomach. The tube was
slowly advanced until the proximal opening, A, was located 2-3 cm beyond the ligament of
Treitz. The position of the tube was confirmed by X-ray screening. In all, five solutions were
infused each for 2 h in a random order. The rate of infusion was controlled at 1.5 ml/min by a
Watson-Marlow peristaltic flow pump (type MHRE). Preliminary tests had shown that with
the tube in the upper jejunum, malnourished children were often unable to tolerate infusion
rates above 1.5 ml/min; after treatment children absorbed all the infused solutions-if isotonic
-at this infusion rate. The osmolarity of the infusion solution was therefore increased by
adding sodium chloride. With this addition both malnourished and recovered children
308
W. P. T. James
tolerated the infusion rate of 1-5 ml/min and in both groups sufficient fluid passed down the
distal segment for adequate collections to be made.
All infused solutions contained 155 mEq/l sodium chloride, 0-5 g/100 ml polyethylene glycol
(PEG) as a nonabsorbable marker, and one of five concentrations of sugar; 2.5,5.0 and 10.0 g
glucose/100 ml, 5 g lactose/100 ml, or 5.0 g sucrose/100 ml. The children were lightly sedated
throughout the study, and were given an intravenous infusion of Hartman's solution to ensure
adequate hydration.
The sugar solution was infused through tube A. After an hour for equilibration of the whole
40 cm segment, 1 ml of 5 g/100 ml bromosulphthalein (BSP) was given with a constant
delivery syringe over 30 s through tube B, opening 15 cm distal to tube A. This syringe was
found to deliver 1 .0 0 ~ 0 .0 1ml. From the time of the midpoint of the BSP injection, collections
of intestinal fluid were made every 2 min from tube C. Air passed down tube D into the distal
end of tube C and was gently aspirated up tube C carrying any fluid with it. Aspiration was
performed with a Roberts pump modified to permit the collection of the samples in a test tube
surrounded by melting ice. This system of tubes, originally described by Dillard, Eastman &
Fordtran (1965), allowed the rapid collection of fluid from the end of tube C. It had been found
in experiments conducted with the tubes in water to which dye was added, that 15 s elapsed
between the entry of dye-stained fluid into tube C and its appearance in the collecting test tube.
Under these simulated conditions no turbulence of dye, which would have indicated direct
suction of water into tube C, was noticed.
During the periods of collection from the intestine as each 2 rnin sample was obtained after
the BSP injection a 50 pl aliquot was transferred to tubes with 0-1 N sodium hydroxide for the
estimation of the dye concentration. The intestinal fluid samples collected over 20 rnin periods
after the BSP injection were then pooled and stored at -20". In all three 20 rnin collections
were made for each sugar solution infused.
Immediately before the BSP injection a 1.5 ml sample of intestinal fluid was removed from
Tube E and the same amount was again gently aspirated 30 and 50 rnin after the BSP injection.
When one test solution had been infused for 2 h the whole procedure was repeated with a new
solution and an hour for equilibration of the segment was allowed before the BSP injection.
In two malnourished children all five solutions were not infused because they developed
profuse diarrhoea during the tests and these were therefore stopped.
Chemical estimations
Jejunal biopsies were assayed for disaccharidase activities by Dahlqvist's method (1964) as
modified by Burgess, Levin, Majalonabis & Tonge (1964). This method has been shown to
allow linear hydrolysis of disaccharide for the 15 rnin of incubation (McMichael, Webb &
Dawson, 1966). The results were expressed in pmol disaccharide hydrolysed at 37" h-' g wet
weight of mucosa-l.
The concentration of PEG was measured turbidimetrically (Hyden, 1955) and the individual
sugars were estimated in the same solutions after protein precipitation. Glucose was estimated
with glucose oxidase Type 11 (Sigma Chemical Company) (Huggett & Nixon, 1957); sucrose
by estimating the glucose produced after incubation with invertase Grade VI (Sigma Chemical
Company) (Gray & Ingelfinger, 1966); and total carbohydrate by the anthrone method
(Scott & Melvin, 1953)with separate standards for each sugar present in the samples. Galactose
oxidase (Worthington Biochemical Corporation assay kit) was used to measure the galactose
Sugar absorption in malnutrition
309
concentration. This enzyme preparation was found to have a small but variable amount of
P-galactosidase activity, so a series of lactose and galactose standards were used. The combined
results of the anthrone test and galactose assay in conjunction with the values for the standards,
permitted the calculation of lactose and galactose concentration by use of a simultaneous
equation. This method with a series of standard mixtures gave values within 5% of the known
galactose and lactose concentrations. The concentration of fructose present in the intestinal
samples from the sucrose infusions was calculated from the results of the anthrone assay
since the concentrations of glucose and sucrose were known.
The amount of disaccharide hydrolysed ( H ) was calculated in terms of its monosaccharide
products (Gray & Ingelfinger, 1966):
where D, and Ds are the infused and collected millimolar concentrations of disaccharide,
V is the infusion rate in ml/h and PEG, and PEG, are the infusion and collected sample concentrations of PEG.
The rate of product absorption was found by subtracting the amount of unabsorbed monosaccharides passing the end of the segment from the rate of hydrolysis:
A
=
PEG,
H-(M,+Mz)Vx- PEG,
where MI and M2 are the millimolar concentrations of monosaccharide components of lactose
or sucrose. These calculations were used for determining the amount of disaccharide hydrolysed and absorbed in the first 15 cm. The amount of sugar in the samples from tube E, taken
in order to estimate the rates of sugar absorption in the upper and lower segments,was found
to represent less than 2% of the sugar passing down the intestine at this point. No correction
for this small amount was made in calculating the absorption from the distal 25 cm segment.
Total absorption in the 40 cm of jejunum was therefore calculated from the above formulae
and the absorption in the distal 25 cm was found by difference.
The rate of water absorption A,,, in ml/h from the 25 cm distal test segment was calculated
from the formula
where PEG, and PEG, and PEG, are the concentrations of PEG in the infused solution, the
solution aspirated from tube E and that from tube C respectively; V, is the volume removed
from tube E in ml/h.
RESULTS
Table 2 shows the mean rates of sugar absorption of the two segments of jejunum in the
children on admission and after treatment.
In the treated children the absorption from both segments was greater than on admission.
The greater absorption from the first segment in the treated group tended to reduce the amount
available for further absorption in the second segment so that the difference between the two
nutritional groups was best shown when the whole 40 cm segment was considered. Each
3 10
W. P. T. James
child’s absorption rate from this length of jejunum is shown in Table 3. The average rate of
absorption from the lowest concentration of glucose solution infused (2.5 g/lOO ml) was not
significantly different in the malnourished and treated groups. As the glucose concentration
was increased the differences were more marked. At the highest concentration of glucose
infused (10 g/100 ml) the children when malnourished absorbed only 32% of the infused
glucose compared with 67% after treatment, and three of the eight malnourished children
TABLE
2. The absorption rates of each infused sugar (mmol monosaccharide/h) from the first (15 cm)
and second (25 cm) segments in children when malnourished (M) and after treatment (T)
Sugar
1st 15 crn
Infusion
Concentration
rate
(silo0 ml)
(mmolih)
Glucose
Glucose
Glucose
Lactose
Sucrose
25
5.0
100
5.0
5.0
M
12.5
25.0
50.0
25.0
26.3
2nd 25 cm
T
3.5+1.1*
4.2k1.0
6.4+ 1.2
3.0k1.0
3.4k1.7
P
M
5.2k0.5
NS
9.5kI.O < so01
14.2k 1.6 < .0025
NS
5.4? 1.1
9.2k1.2 < ,005
P
T
3.8k0.8 4 4 t 0 . 5
NS
6.8k0.9 9.9k0.8
NS
9.6k2.5 19.5k2.8
NS
4 4 + 1.3 1O.Ok1.0 < .0025
NS
8.3k2.0 9 . 0 + 0 6
* Mean k SEM
NS = P > 0 0 5
TABLE
3. The rate of sugar absorption (mmol monosaccharide/h) from a 40 cm segment of jejunum in
malnourished (M) and treated (T) children when perfused with five different sugar solutions
Infusion rate (mmol/h)
Concentration (g/100 ml)
Child
J.D.
G.M.
C.P.
K.R.
M.G.
D.B.
R.G.
L.W.
M.S.
D.A.
J.H.
J.B.
C.C.
I.D.
Glucose
125
2.5
Glucose
25.0
5.0
Glucose
500
10.0
Lactose
25.0
5.0
Sucrose
26.3
M
T
M
T
M
T
M
T
M
7.9
1.6
11.6
1.5
12.5
5.6
9.6
8.3
6.2
7.8
12.9
11.6
2.8
11.1
13.7
15.0
14.9
13.6
20.4
14.9
19.5
16.2
20.3
21.3
24.6
16.1
23.2
13.2
21.8
21.4
23.9
14.8
-
40.1
25.1
38.6
27.0
42.4
36.4
49.5
24.3
32.1
27.3
29.0
47.9
36.5
15.5
5.6
2.6
13.6
19.6
109
19.9
14.3
149
21.0
20.5
18.3
11.2 21.5
- 144
17.0 2 4 4
1.4 11.8
0
19.8
7.9 21.7
12.5 24.8
12.0 16.2
21.1
21.5
20.2
23.5
10.6
1.8
11.9
13.7
12.2
-
22.4
-
10.1
209
16.3
147
14.3
_
_
7.7
9.9
12.5
6.2
-
_
_
7.1
8.9
12.5
5.3
12.0
10.8
11.9
10.4
Mean
7.4
9.6
k SEM
+ I 3 k0.7
P between adjacent columns >0.05
-
11.0 19.4
+1.3 t 1 . 0
< 0.005
9.9
25.3
4.9
0.4
25.7
26.0
14.6
20.8
-
-
16.0 33.7
k3.7 k2.6
< 0.005
0
02
7.9
7.7
3.2
-
-
7.3 15.4
k2.1 k1.6
< 0.0025
5.0
T
11.6 18-2
+ 2 6 51.3
>0.05
311
Sugar absorption in malnutrition
were unable to absorb as much glucose as when they were infused with the 5 g/100 ml glucose
solution. After treatment all the children progressively increased their absorption of glucose
as the infused concentration was increased.
When lactose was infused only one malnourished child, M.S., was able to absorb well;
eight of the ten malnourished children absorbed less than 50% of the infused lactose and all of
them except D.A. showed a substantial increase in lactose absorption after treatment. Similar
increases were seen when sucrose was infused, but in both groups more was absorbed than with
lactose.
Fig. 2 shows that there was a significant correlation between the rate of hydrolysis of lactose
and sucrose passing down the lumen of the intestine and the lactase and sucrase activities of
25
-
.
/
a
9
0
0
A
I
‘ A
A
I A
A
I
I
II
2
II
3
I
4
Disaccharide hydrolysed (pmol h-l g wet wt-l)
FIG.2. The relationship between the results obtained by two techniques for assessing lactose and
sucrose hydrolysis. The hydrolysis rate of infused disaccharide passing down the jejunum is
plotted against the activity of lactase and sucrase in jejunal biopsy tissue. The regression line for all
points below 4 units disaccharidase activity is shown. Malnourished: A = sucrose, A = lactose.
Recovered: o = sucrose, 0 = lactose.
y = 594xt-4.47 r = 0.6719 P< 0001.
the jejunal mucosa. This relationship was seen in those children who had disaccharidase levels
below 4 units; above this level the infusion of disaccharide was insufficient to show the capacity
of the jejunum for hydrolysis.
Table 4 shows the net movement of water across the second 25 cm segment in the two groups
of children perfused with each solution. Malnourished children on average had no net
absorption of water except with the lowest concentration of glucose infused and with the
sucrose infusion. After treatment the children had a net absorption of water from all five
solutions.
Table 5 shows the mean transit times and flow rates of fluid passing down the distal segment
in the two groups of children during each infusion. In malnourished children the mean transit
time fell with each increase in glucose concentration, but after recovery the mean transit times
were longer. During the lactose perfusion the mean transit time was almost twice as long in the
W. P. T. James
312
children when recovered as on admission (P<0.005);with sucrose the difference was not
significant. In the malnourished group the flow rate reached a maximum during the infusion
with 5 g/100 ml glucose; on recovery there was an increase in flow rate with each rise in the
infused concentration of glucose, but despite the greater flow rate during the infusion with the
TABLE
4. Water absorption (ml/h) from the second 25 crn segment
of jejunum during perfusion of the segment with five consecutive
sugar solutions
Sugar
Concentration
(g/100 ml)
Glucose
Glucose
Glucose
Lactose
Sucrose
2.5
5.0
100
5.0
5.0
Malnourished
-4.8k 8.8*
+41.4+24.6
+ 67.8 k 14.7
+ 16.2+ 18.4
-3.4k13.8
Treated
-21.6f 16.9
- 4 4 4 k 7.7
- 2.6 f 17.8
- 1.Of 12.0
-8.4k11.2
* Mean k SEM : Water absorption is indicated by a minus sign
and water entry by a plus sign.
TABLE
5. The mean transit time (MTT) and flow rate (F) of fluid perfusing a 25 cm
segment in children when malnourished and after treatment
Malnourished
Sugar
Glucose
Glucose
Glucose
Lactose
Sucrose
Concentration
(g/100 ml)
2.5
5.0
10.0
5.0
5.0
MTT
(min)
(6)
(8)
(7)
(8)
(6)
19.6+2.3*
13.8k1.6
12.6f2.1
143k1.9
24.754.7
Treated
F
(ml/min)
2.7f0.3
3.1 f 0 . 4
3.1f0.5
2.5f0.3
1.9f0.4
(8)
(10)
(11)
(12)
(10)
MTT
(min)
F
(ml/min)
24.1f2.9
24.7f3.6
18.2k2.2
27.3k3.2
19.2k1.5
1.9k0.4
2.1k0.4
3.5k0.5
2.0k0.4
2.6k0.4
Numbers in brackets indicate the number of children injected with BSP with each
solution infused.
* Mean k SEM.
highest glucose concentration, the mean transit time in the recovered children was longer.
This implies an increased volume of the intestinal segment of the children after treatment.
Fig. 3 shows the relationship between the reciprocal of the mean transit time (MTT) and the
flow rate ( F ) during all the infusions. These two parameters are related by the formula
1 - -*F
1
MTT V
--
where V is the volume of the segment. From this graph it can be calculated that at the flow rate
of 1 ml/min the mean segment volume in the malnourished children was 17-5 ml compared with
Sugar absorption in malnutrition
313
23.8 ml after recovery. At higher flow rates e.g. 5 ml/min the values for V in the malnourished
and treated groups would be 51.5 ml and 80.7 ml respectively. This indicates that the malnourished child’s intestine is smaller and less distensible than after treatment (Dillard et al.,
1965).
[I
12-0
I3O
A
11.0
,
A
/
/
/
A
10.0
9.0
8.0
5 7.0
-IE
x
6.0
:::I
5.0
4.0
::f
1.0
0
1.0 2.0
,*
,
A Malnourished
I
I
-0
,
Recovered
50 6.0 7.0 0.0 9.0 10.0
Flow rate (rnl/rnin)
3.0 4.0
FIG.3. The relationship between the reciprocal of the mean transit time of fluid passing down the
second 25 cm segment of intestine and the flow rate in ml/min. The results from all the children
when malnourished and recovered are included, and the least square lines for the two nutritional
groups are shown.
Fig. 4 shows the series of dye dilution curves obtained from one child, R.G., both when he
was malnourished and after treatment. When malnourished most of the peaks of the curves
occurred sooner after the dye injection and were sharper than on recovery. With the only
solution (2.5 g glucose/100 ml) absorbed as well in the malnourished as in the recovered state
(cf. Table 3) the shape and the delay in the dye dilution curve were the same as on recovery.
This shows that when the malnourished child was able to absorb the infused sugar, the motility
of his intestine was normal.
Fig. 5 demonstrates that there is a correlation between the unabsorbed sugar in the lumen
and the mean transit time of fluid moving down the intestine. The rate of passage of unabsorbed sugar was calculated by multiplying the molar concentration of unabsorbed sugar by
the flow rate of fluid down the intestine.
314
W. P. T. James
R.G.
Malnourished
60
Sugar infusion
h.
7
50 -
A 5.0 4 % Lactose(l)
2.5 g % Glucose(2)
010.0g % Glucose(3)
A 5 0 g % Glucose(4)
rn 5.0 g x Sucrose(5)
I
c
0
W
c
20
10
30
40
5.09% Glucose(1)
Recovered
0
E 40a
5 . 0 g % Lactose(2)
5.0 g % Sucrase(3)
10.0 g % Glucose ( 4 )
2 . 5 g X Glucose(5)
A
I
0
10
20
30
40
50
60
Time (mln)
FIG.4.Dye dilution curves obtained during perfusion of a segment of jejunum in a child when
malnourished (upper) and recovered (lower series). The order in which each infusion was given is
indicated by the figures in parentheses.
The mean concentration of glucose and galactose in the lumen during lactose infusions was
48 mg/100 ml and 118 mg/100 ml in the malnourished children and 151 mg/100 ml and 115 mg/
100 ml after treatment. Glucose and fructose concentrations during sucrose infusions were
152 mg/100 ml and 322 mg/100 ml in the malnourished state, and 158 mg/100 ml and 502 mg/
100 ml after recovery. The reduction in the absorption of disaccharides in the malnourished
children was therefore related to the low rate of disaccharide hydrolysis rather than to the
concomitant fall in monosaccharide absorption.
DISCUSSION
These results show that in the malnourished child there is a marked reduction in the capacity
of the intestine to absorb not only disaccharides but glucose also. This suggests that there is a
generalized defect of intestinal function in malnutrition. Neither iron deficiency nor folic acid
deficiency, both known to produce intestinal dysfunction (Naiman, Oski, Diamond, Vauter &
Schwackman, 1964; Winawar, Sullivan, Herbert & Zamcheck, 1965), was a prominent feature
in any of these children except R.G. Iron or folic acid depletion could not therefore have been
315
Sugar absorption in malnutrition
responsible for the abnormalities found. When these studies were repeated after the children
had received an adequate calorie and protein diet in hospital, the defects found in the malnourished state had been reversed.
The low rate of lactose hydrolysis and absorption in these malnourished Jamaican children
is in keeping with the incidence of lactose intolerance in malnourished East and South African
children (Cook, 1967; Bowie et al., 1965). Since the defect is not an isolated disaccharidase
deficiency nor an irreversible phenomenon, it does not seem to be genetically determined ; nor
can lactase deficiency be considered to be the primary condition predisposing to malnutrition.
This study has emphasized that lactase deficiency with limited disaccharide hydrolysis results
from malnutrition per se.
M(.
A Malnourished
Recovered
f 30
c
e
+
c
2
A
20
10
A
A
I
I
10
\
I
20
30
Unabsorbed sugar (rnrnol/h)
I
40
I
50
FIG.5. The mean transit time of fluid passing down the second 25 cm segment of jejunum, plotted
against the amount of unabsorbed sugar passing down the segment per unit time. The regression
line for all the points is indicated.
y = - 0 2 2 9 5 ~ +43.68 ; r = 0.4243; P< 0.001.
Three of the children, K.R., M.G., and G.M., had consistently low rates of sugar absorption
when malnourished, and this suggested that their intestinal damage was most severe. This
was confirmed by finding that all three had a ‘flat’ intestinal mucosa whilst the others had varying degrees of mucosal abnormality. The increased absorption of glucose and disaccharides
after treatment was associated with improvement in the appearances of the mucosa, but the
mucosa did not revert completely to normal. The only child, D.A., with a deterioration in sugar
absorption and with lower disaccharidases after treatment, had an episode of fever and
316
W. P. T. James
diarrhoea a week before the final series of tests ; the deterioration in intestinal function may
be ascribed to this episode.
At high concentration of infused glucose absorption is predominantly by a carrier-mediated
mechanism which is not energy-dependent but is affected by the concentration gradient
across the mucosal membrane (Olsen & Ingelfinger, 1968). An increase in absorption with
higher concentrations of glucose therefore is to be expected. That this did not occur, particularly in those children (K.R. and M.G.) with the most severe mucosal damage, suggests that the
rate of flow down the intestine had increased so much that the intestine was no longer able to
maintain its rate of absorption. A fall in absorption is also apparent at high infusion concentrations of glucose in children with gastroenteritis (Torres-Pinedo, Rivera & Fernandez,
1966), and at high lactose infusion concentrations in lactase deficient adults studied by McMichael et al. (1967). Acclerated transit of fluid induced by mannitol has also been shown to
reduce fat and xylose absorption (Launiala, 1969). Sladen & Dawson (1969) studied the
effects of flow rate on the absorption of glucose in normal adults and showed that the total
glucose absorbed from an intestinal segment may be improved either by increasing the infusion
concentration or increasing the flow rate. A rise in flow rate reduced the concentration gradient
of glucose down the segment and made higher concentrations available to a greater length of
intestine. Since the intestine normally has a great capacity for glucose absorption (Borgstrom,
Dahlqvist, Lundh & Sjovall, 1957) a fall in absorption as the flow rate increases may only be
seen in a diseased intestine; increasing the flow rate no longer reduces the concentration
gradient down the intestine substantially because glucose absorption is less than normal. Any
increase in flow rate will further diminish absorption as the time available for mucosal contact
becomes a critical factor. Malabsorption of compounds with more limited rates of mucosal
uptake or absorption than glucose, e.g. lactose, xylose and fat, probably occurs more readily
when the motility increases and the transit time falls (Barreiro, McKenna & Beck, 1968;
Middleton & Thompson, 1969).
In the malnourished children the pattern of flow of fluid down the intestine may well have
changed from the normal process of slow mixing to a more rapid laminar flow with less mixing
of fluid within the lumen. There was certainly an abrupt fall in mean transit times when K.R.,
M.G. and G.M. were infused with the highest concentration of glucose; they had the lowest
observed mean transit times of 5 , 6 and 9 min. In other studies, where maximum distension of
the small intestine had already occurred at the lowest rates of infusion (Sladen & Dawson,
1969), laminar flow may already have been established. Under physiological circumstances
the conversion from slow mixing to laminar flow may be very important in determining the
amount of solute absorbed.
It is unlikely that the high osmolarity of the infused solution produced a temporary malfunction of the intestine (Kameda, Abei, Nasrallah & Iber, 1968): there was no evidence that
the children’s capacity to absorb sugars declined during a single infusion or during the day’s
perfusion studies.
If hypermotility were a primary feature of the intestinal malfunction in the malnourished
children, then the mean transit time should have remained short, irrespective of the sugar
solution infused. This was not found to be so when the lowest concentration of glucose was
infused (Table 5 and Fig. 3). A reduction in mean transit time or an increase in flow rate of
fluid down the intestine was related to the amount of sugar remaining unabsorbed within the
lumen. This unabsorbed sugar produced an increase in the net movement of water into the
Sugar absorption in malnutrition
317
lumen (Table 4) which in turn increased the flow rate. The smaller size of the malnourished
child's intestine and its reduced distensibilityaccentuated the speed of flow and reduced the mean
transit time even further. These interrelated processes are evidencefor the action of unabsorbed
osmotically-activesugars on the rapid movement of fluid down the intestine, thereby producing
diarrhoea (Fischer & Sutton, 1949). Secondary effects from bacterial fermentation of unabsorbed carbohydrate (Torres-Pinedo, Lavastida, Rivera, Rodriguez & Ortiz, 1966a) and
inhibition of colonic water absorption by bile salts swept into the colon (Hoffman, 1968)
may also contribute to the diarrhoea affecting these children when malnourished.
Clinically these studies show that it is unwise to treat the oedematous child with hypertonic
fluids by mouth for this is likely to aggravate the diarrhoea. The results support the practice
of feeding frequently with small quantities of isotonic or hypotonic fluids without lactose.
All the malnourished children responded to such a diet. Oral glucose was readily tolerated;
sucrose could be introduced soon in most cases, and even lactose was tolerated in increasing
amounts after 2-3 weeks of treatment. With continued provision of an adequate diet in hospital
the defects in intestinal function were shown to be reversible.
ACKNOWLEDGMENTS
I thank Dr R. Torres-Pinedo for his advice, Nurse S. M. Donaldson and the nursing staff for
their care of the children, Miss J. Garel and S. Miles for technical assistance and Dr E. M.
Bateson and his staff for X-ray facilities. I also thank Miss B. Robinson for help with the
manuscript.
I am indebted to Professor J. C . Waterlow for encouragement and advice throughout the
study.
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