Professional Documents
Culture Documents
HUMAN gastric juice contains water, hydro- neither precise, quantitative nor reproducible.
chloric acid, pepsin, intrinsic factor, mucus and The coefficient of variation of the concen-
electrolytes. Of these, hydrochloric acid has tration of free acid in a series of 20 consecutive
been studied most extensively by the clinical meals performed on a healthy adult ranged
investigator-partly because of the likely from 25.8 to 199.6%-quite outside acceptable
association of its erosive powers with the limits (Bell and McAdam, 1924). It is there-
development of peptic ulceration, and partly fore not surprising that Enticknap and
because of the apparent simplicity of its Merivale (1954), in an analysis of 1000 gruel
estimation. meals, concluded that they were of little diag-
nostic value. In a comparison with the
Test Meals augmented histamine test in 114 patients,
Since the end of the last century the standard Marks and Shay (1960) found that, although
method of assessing gastric acid secretion has the peak acidity in a fractional test meal was
been by the test meal, which was developed statistically related to the acid output in the
largely by von Leube (1876), Ewald and Boas augmented histamine test, the results of a test
(1885) and Rehfuss (1927). Its history and meal could not be used to predict the true
development have been reviewed by Hollander acid output in an individual patient.
and Penner (1939) and Rovelstad (1963). The As the 'test meal' was a poor stimulus of
vast amounts of data collected in these original gastric secretion, differing little from plain
studies contributed only little to our knowledge water (Bergeim, Rehfuss and Hawk, 1914), the
of the secretions of the stomach in health and incidence of achlorhydria was fairly high.
in disease. With the recent development of More potent stimuli were used-alcohol (Kast,
precise quantitative methods of assessing 1906; Ehrmann, 1912) caffeine (Katsch and
gastric function, such investigations are now Kalk, 1924) and histamine, either in single
largely of historical interest. (Bockus and Bank, 1927; Vanzant, Alvarez,
The 'fractional test meal', still performed Eustermen, Runn and Berkson, 1932), double
today, differs little from that described by (Rivers, Osterby and Vanzant, 1936), or triple
Rehfuss in 1914. Following a fast, a gastric (Hitchock, Sullivan and Wangensteen, 1955)
tube is passed and the stomach emptied. A doses. However, even with a standard dose
'test meal' of carbohydrate-bread, cereal, of histamine (usually 0.01 mg. histamine acid
gruel or biscuits, is ingested and 10 ml. of phosphate per kg. body weight) the response
had a wide variation in normal subjects and
gastric juice aspirated each 15 minutes for 2-3
hours. The acidity in each sample is estimated proved of little routine diagnostic value (Pol-
by titration with 0.1 N NaOH using two indi- land and Bloomfield, 1931; Polland, 1933).
cators - Topfer's dimethylaminoazobenzene
for 'free', and phenolphthalein for 'total' acid. Criteria of Tests of Acid Secretion
The acidity curve is drawn on a chart which Collections
shows a 'normal range' based on the curves The measurement of a secretory response
of 80 of the 100 normal students studied by requires an estimate of both the volume of
Bennett and Ryle in 1921. It is of interest that juice secreted and its acidity. Therefore, the
the other 20 students showed curves from gastric tube must be placed so that all the
extreme hypo- to hypersecretion. juice secreted is withdrawn for analysis. 'Blind'
The fractional test meal has little to com- placement of gastric tubes is unsatisfactory
mend it as a test of gastric function. It is (Callender, Retief and Witts, 1960) and radio-
July, 1965 LAWRIE and FORREST: Measurement of Gastric Acid 409
20
histamine acid phosphate histamine acid phosphate0
0.04 mg/kg. 0.04 mg/kg./hr.
1 2 3 0 1 2 3
hours hours
FIG. 1.-Augmented histamine test-acid output per
15 minutes, with an infusion test in the same
patient.
of this magnitude are prevented by the prior binations of the 15-minute collection to express
administration of an anti-histamine which is the results. These are usually quoted as the
without effect on the action of histamine on output of HC1 in mEq./hour. The average
the parietal cell (Conrad, Kowalewski and output of acid in normal subjects is 22-23
Geertruyden, 1949; Kay,of 1953). mEq./hour and that for patients with duodenal
Following intubationand 100the patient the basal ulcer 37-40 mEq./hour (Marks, 1961).
secretion is collected mg. mepyramine Histamine infusion test
maleate given intramuscularly after 30 minutes. Many of the shortcomings of the augmented
Thirty minutes later (i.e. after one hour of histamine response can be overcome if a steady
basal collection) histamine acid phosphate, state of secretory activity is induced by a
0.04 mg./kg. body weight, is injected sub- continuous infusion of histamine. In dogs, this
cutaneously and collections contained for four stimulus has been widely used to study the
15-minute periods. The volume and acidity function of gastric pouches but few reports
of each specimen is estimated and the output have been made on its use in man (Adam,
of HC1 calculated in milliequivalents. Card, Riddell, Roberts, Strong and Woolf,
As this large dose of histamine induces 1954; Hirschowitz, Londop and Wiggins, 1957).
total parietal cell activity, the response is re- By performing dose-response curves using this
lated to the parietal cell mass (Card and Marks, stimulus we have shown that a maximal plateau
1960; Marks, Komarov and Shay, 1960). It is can be obtained with a dose of histamine acid
therefore reproducible and similar figures for phosphateSmith
of 0.04 mg./kg. body weight/hour
normal individuals and patients with duodenal (Lawrie, and Forrest, 1964).
ulcer have been reported from different centres With the recent availability of pre-sterilised
(Marks, 1961). Nevertheless, it is a transient plastic equipment and slow-injection infusion
response which reaches a peak normally during pumps, a histamine infusion can now be used
the second or third 15-minute period after the for the routine assessment of the secretion of
injection of histamine and then declines to gastric acid in man. The administration of this
basal levels (Fig. 1). Thus, though the dose of relatively small dose of histamine by continuous
histamine used induces maximum secretion, intravenous infusion, though inducing maximal
this is only achieved for a limited period of response from the stomach, elicits fewer side-
time within the total response. effects than a single large dose. A small dose
Various workers have used different com- of anti-histamine (25-50 mg.) adequately miti-
July, 1965 LAWRIE and FORREST: Measurement of Gastric Acid 411
Output
HCI - OUTPUT
m.equiv 10
per 15 mins
CONC. m.equiv
HCI per litre
150
CONCENTRATION -7
Volume
I "~
pH
-p-
-6
ml per I
15 mins100-
00 5
l VOLUME
-4
3
50- 5i - _50
****'_^ -" F jJ....... .............................
0 1 2 3
RESTING BASAL HOURS
gates these side-effects. Further, the side-effects It has been shown that the test is repro-
of histamine pass off soon after the intravenous ducible (Fig. 3) and in one patient recently
infusion has been stopped. Outpatients are studied the hourly outputs of HC1 on four
little upset by the test and are able to return to separate occasions were 42.3, 41.8, 37.9 and
work immediately. 39.2 mEq. In a comparison of the response of
Nasogastric intubation of the patient is carried histamine infusions and augmented histamine
out in the normal way and continuous suction tests in 45 patients, it was also shown that the
applied with the patient flat on his left side.
A small paediatric scalp vein needle is inserted
hourly output of acid during the infusion of
histamine was significantly greater than that in
into an antecubital vein and 25 mg. of mepyra- the augmented histamine response (Fig. 4)
mine maleate injected. A solution of histamine (Lawrie and others, 1964).
acid phosphate in saline is then delivered by An incidental advantage of the histamine
slow-infusion pump to give a dose of 0.04 mg. infusion test is that errors arising from incom-
per kg. body weight per hour (Lawrie and plete aspiration of gastric contents are
others, 1964). immediately apparent. When a steady state of
The volume of gastric juice and its acidity secretion has been reached, fluctuation in the
rise during a period of about 30-45 minutes volume of the 15-minute collections indicates
following the start of the infusion. Thereafter that the tube is badly placed or blocked. As
the 15-minute aspirations maintain a fairly the test is continued until four successive 15-
constant volume and acidity and this 'plateau' minute collections are of equal value, the result
response can be maintained for many hours is not jeopardised by such adjustments.
(Fig. 2). Four successive 15-minute specimens
of similar volume and acidity constitute a one- X-ray studies following the injection of a
hour maximal output at this steady secretory radio-opaque substance have confirmed that,
with the patient on his left side, the main-
rate. tenance of a plateau indicates satisfactory tube
412 POSTGRADUATE MEDICAL JOURNAL July, 1965
6O-
r
5 5 I
OUTPUT I Normal
HCI 4r
40-
rI r
r
m. equiv
G D
I
Cf26Mean 923
hour 30- I
i
24.0 Mean 21.0
20- h a 0' r m.equiv 50- S.D. 7.9 S.D. 4.2
p our I m HCI P>0.1
10-
per hour
ABCD E F G H I J
30
30- *** *
K L M
Patients *--
*
**-
20- :::..
*-- ::-
000
FIG. 3.-Duplicate histamine infusion tests in 13 10- .
patients. (Lawrie et al., 1964). Reproduced by
permission of the Editor of The Lancet.
0
Continuous
Histamine
Infusion Augmented
0.04 mg. per Histamine Normal Duodenal Ulcer
kg. per h.
hour.
0.04 mg. per Kg. 26 107
Mean 24.0 Mean 42.3
S.D. 7.9 S.D. 13.1 P<0.001
Peakx4 Baron 70 S.E. 1.6 *S.E. 1.3
Baron Kay
Mean Card. Output HCI 60- :
m.equiv --.
Output HCI 30.1
27.6 per hour 50-
00
e0*
m.equiv. 25.8 a---*---
per hour 40 - *--1
00000
0000000
0**. *00.000000
20- ::-.
000
FIG. 4.-Comparison of mean output from 45 infusion 10-
tests with augmented histamine responses in
patients. These have been interpreted as (1) 00
Peak 15-minute x 4; (2) two highest successive
15-minute peaks (Baron, 1963b); (3) 15-45 minutes
x 2 (Kay, 1953); and (4) 0-60 minutes. (Card and
Marks, 1960)--from Lawrie, et al., 1964). Re-
produced by permission of the editor of The FIG. 6.-Results of histamine infusion test in patients
Lancet. with duodenal ulcer.
July, 1965 LAWRIE and FORREST: Measurement of Gastric Acid 413
............:
L.P.
Output HCI
10 41'9 m.equiv per hour
Before
Output HCI
m.equiv per
15 mins.
-
| Gastric
-I
5 -
5
21 I
--- 213 m.equiv per hour Freezing
I I 17 Days After
I I--I