THE ETIOLOGY AND PATHOGENESIS OF CONGENITAL
MEGACOLON'
DAVID F. AUSTIN, B.S.
ONGENITAL megacolon has at-
C tracted much interest since it was first
described by Hirschsprung in 1888 (13) .
Only in the past foul' years, however, has
the understanding of this disease come to
be based on pathologic evidence of its
etiology.
Although the literature on congenital
megacolon is extensive, until 1948 there
\\-ere reports of only 18 cases in which the
colon and rectum had been subjected to
t horough microscopic examination_
Whitehouse and Kernohan (31) collected
t hese cases and described 11 others_
Subsequently 7 cases were reported by
S\\-enson (26), 1 by Rosen (22), 4 by
Zeulzer (3 2), 4 by Lee (19, 20), 3 by
Hiatt (11 ) and 15 by Bodian (6), making
a total of 63 cases reported at the present
t ime_
ANATOMY OF THE MYENTERIC PLEXUS
The intrinsic plexus of the colon and
rectum are more complex than is com-
monly realized_ In addition to the my-
enteric (Auerbach's) and submucous
(Meissner's) plexuses, there is also a
sympathetic plexus in close association
with the myenteric plexus, as well as a
subserous plexus (fig. 1). The myenteric
plexus is composed of myelinated pre- and
post-ganglionic nerve fibers and ganglion
cells which represent the terminal synapse
of the parasympathetic innervation of
t he bO\\"eL
The normal appearance of the my-
enteric plexus in microscopic sections of
the colon and rectum has been studied
by Whitehouse and Kernohan (31), using
sections of both normal bowel and hyper-
trophic dilated bowel occurring in diseases
other than congenital megacolon _ The
findings may be summarized as follows:
',\ synopsis of a thesis s ubmitted in fulfillm ent of one of
the requirements of th e Department of P athology for
undergraduate medical students.
From the Department of Pathology. Northwes t ern U ni -
versit)- i\Iedica l School. R eceived for publication , May
14 , 1952_
235
1) ganglion cells are present in every
microscopic section of bo,,-el; 2) the de-
generative changes of the ganglion cells
described by some authors as being an
etiologic factor in megacolon are found
commonly and may be artefacts of fixa-
tion and staining ; 3) large non-myelinated
nerve t runks are uncommon in t he
region of the myenteric plexus of the
colon and rectum; 4) extreme dilatation
of the colon has little effect on the
myenteric plexus except that it increases
the distance bet\\-een ganglion cells; 5)
inflammatory changes of the colon and
rectum cause little or no change in the
myenteric plexus; 6) the rectum normally
has as many ganglion cells as other parts
of the colon _
PATHOLOGI C ANATOMY
The gross pathologic picture of mega-
colon is dominated by great dilatation of
the colon with hypert rophy of its muscu-
lature. The dilated portion narrows in t he
rectosigmoid to a diameter that is nor-
mal or slightly less than normaL This
zone of narrowing will be termed the
transitional region _ Distal to the transi-
tional region there is a segment of naITO\\-
colon and rectum, measuring 5 to 8 cm_in
length, that is visible in X-ray films taken
using a modified barium technic (25)_
The microscopic pathology has been
studied most t horoughly by Whitehouse
and Kernohan (31), and Bodian (6)
and consists primarily of one feature-
the absence of ganglion cells of the my-
enteric plexus in the nan'O\\-ed portion of
the rectum and rectosigmoid distal to
the transitional region _ The proximal
dilated portion of the colon has con-
sistently been found to have a normal
myenteric plexus_ The absence of ganglion
cells has been noted in the entire series of
63 cases, in most of which it extended to
the anal sphincter_
The transitional region has presented a
236 QUARTERLY BULLETIN, N.U.M.S.
Fig. 1. Schematic diagram of autonomic inner-
vation of the colon (redrawn from Maximow and
Bloom).
varied appearance with respect to the
level of absence of the ganglion cells. The
findings in the series of Whitehouse and
Kernohan (31) are illustrated in Figure
2 which shows the percentage of cases in
which t here was an absence of ganglion
cells at various levels. Combining this
data with that of the other reported cases
in which the t ransitional region was
studied, it is found t hat in 28 of the total
of 38 cases, t he aganglionic segment
extends from 1 to 5 cm. into the transi-
tional region at which point there is a
sudden change to t he normal number of
ganglion cells (6) (fig. 3).
. in the augmentative effects of the para-
Si,=Oid G
o
G?
Fig. 2. Diagram of rectum and sigmoid colon
showing the percentage of cases in which ganglion
cells were absent at various levels (redrawn f rom
Whitehouse and K ernohan) . . absence of ganglion cells (redrawn from Bodian).
Both Whitehouse and Kernohan (31),
and Bodian (6) noted the presence of
non-myelinated nerve trunks of various
sizes in the aganglionic myenteric plexus.
These trunks are formed of closely
packed bundles of non-myelinated fibers
which have a distinct connective tissue
sheath. As they enter the colon they oc-
cupy a position adjacent to the blood
vessels. The significance of these trunks
is unknown although Bodian postulates
that they are sympathetic in origin (6).
PATHOLOGIC PHYSIOLOGY
Most of the present evidence indicates
t hat t he myenteric plexus functions in
both the parasympathetic and the in-
trinsic control of the activity of the
colon (10). Alvarez (2) states that the
function of the myenteric plexus is to
"expedite conduction and to correlate
the activities of the muscle fibers." The
sympathetic innervation is generally con-
ceded to have an inhibitory effect on the
colon, causing retention of the fecal
contents and retardation of emptying of
the colon. The parasympathetic innerva-
tion has an augmentative effect on the
colon which accelerates emptying and
causes evacuation of the fecal contents.
It can thus be seen that a lesion affect-
ing the myenteric plexus may have a
profound effect on emptying of the bowel.
The lack of ganglion cells may result in
a relative increase in the effects of the
sympathetic system, or at least a decrease
sympathetic system, producing retention
Ganqli.on CQ.lls I No qo.nqlion. cczlLs :
+- p,"Q" cznt -~,i~( - pI"asQnt ~
1 5-20 ern. 1
_ _ _ _ _ _ _-'-.
1 1
T~",=~~ =l
Di" t o.l dilo.tad and.
hy pl2 rtrophiad
.sczC;> rrtant
t[:~ -
-
raq ion
__
D~tal na.rrow
" cz9=<>nt
_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-,-r--~~i====~=====9
I 1
1 1
I 1
I 1 1
~ 1- 5cm~-5-18ern4
Fig. 3. Diagram of rectum and sigmoid colon
showing the transition f rom the dilated to the
narrow segments in relation to the presence or
 AUSTIN-CONGENITAL MEGACOLON
of the fecal contents. In addition the
action of the rectal segment is lost, so
that there results a partial functional
obstruction of the colon such that the
fecal contents cannot be moved past this
segment. Swenson (26) and Hiatt (10)
have found that peristaltic waves in
cases of aganglionic megacolon are inter-
rupted at the level of the sigmoid colon
and are not present in the narrowed
portion of the rectum and rectosigmoid,
or, if present, are totally unrelated to
those of the rest of the colon. As a result
of the partial obstruction the bowel
contents accumulate in the colon proximal
to the pathologic segment and cause
mechanical dilatation. This dilatation is
increased by collection of gases (30).
Stasis of the bowel contents for long
periods of time accounts for the large
fecaliths encountered clinically.
Hypertrophy of the muscle layers of
the colon occurs as a consequence of the
dilatation. Starling's law concerning
smooth muscle states that a stretched
muscle will liberate more energy and
perform more work on contraction. Bay-
liss (4) and Hill (12) have shown that
release of energy is associated with
chemical changes in which large mole-
cules are split inte> a greater number of
smaller ones. This results in an increase in
the osmotic pressure of the muscle cells
and a consequent increase in size. If this
process continues over a long period of
time the mass of muscle will be increased
since the work and energy available is
proportional to the mass of the muscle
cells (28).
DISCUSSION
Experimental evidence. If the etiology
of congenital megacolon is the absence
of ganglion cells of the myenteric plexus
it should be possible to produce the
disease experimentally. Ishikawa (15),
by sectioning the pelvic nerves of 12
dogs, was able to produce constipation in
9, dilatation of the colon in 8, and hyper-
trophy of the wall of the colon in 7 cases.
Kleinschmidt (16) and Adamson (1) have
also been able to produce megacolon in
cats by sectioning the sacral nerve. Thus
it is possible to cause megacolon in
animals by removal of the parasympa-
thetic nerve supply to the colon.
237
Clinical evidence. Further evidence
supporting the belief that absence of the
ganglion cells of the myenteric plexus is
the etiologic factor in this type of mega-
colon is provided by the results of the
Swenson pull-through operation (24) and
by the results of Hiatt (11) . In these
procedures the narrowed aganglionic
segment of the colon is removed and the
portion of the colon is anastomosed to the
anal stump, after the presence of normal
ganglion cells has been demonstrated in
the dilated part. Follow-up studies on
patients upon whom this operation has
been performed indicate that the pro-
cedure gives complete relief of all symp-
toms and return of the bowel to normal
size. This is in sharp contrast to the
results with colectomy in which varying
lengths of the dilated portion of the
colon were removed (20, 24). In a high
percentage of these cases good results
were not obtained or else they were
obtained only after . a long period of
intense medical management. When col-
ostomies were performed on these patients
there was relief of the symptoms and
lessening of the hypertrophy of the colon,
but upon closure of the colostomy the
symptoms returned. Thus it can be seen
that surgical management based on the
concept that agenesis of the myenteric
plexus of the rectum and sigmoid colon is
the primary cause of congenital mega-
colon is very effective, while conversely,
treatment that disregards this concept
usually results in failure.
The effects of stimulating the auto-
nomic nervous system by drugs and the
effects of sympathectomy are confusing
and contribute little to the understanding
of the disease. Cholingeric drugs, such as
Mecholyl (5, 23), may cause evacuation
of the bowel as may sympathectomy (3,
29) or spinal anesthesia (17, 18). The
effects that are obtained by these means,
however, are of short duration.
Associated disorders. It can be postu-
lated that aganglionic megacolon may be
associated with changes in other parts of
the nervous system. It is possible that
there may be an abnormality in the
formation of the pelvic nerves, or in the
formation of the cells of the lateral
columns of the spinal cord at the sacral
238 QUARTERLY BULLETI N, N.U. M.S.
level. If such lesions do occur, one might
predict the de\'elopment of malfunction
of the urinary bladder and ureters.
S\\'enson et al. (27) have recently reported
a series of 22 cases of congenital mega-
colon on \\"hom cystometrograms were
performed . In 12 of these patients the
capacity \\"as considerably above normal,
and in 7 of the 12 cases the changes were
pronounced, showing the absence of
emptying contractions in response to
filling increments. In addition they report
3 cases of bilateral hydroureter and 1
case of unilateral hydroureter in the series
of 76 patients operated on for congenital
megacolon . It is of interest to note that
Zeulzer (32) has also described 2 cases in
which there \\"as dilatation and hyper-
trophy of the small intestine with a func-
tional obstruction in the terminal portion
of the ileum. In both cases ganglion cells
\\"ere absent from the myenteric plexus
of the entire colon. The pathologic picture
\\"as sinli~ar in every \\"ay to t hat of agang-
lionic megacolon except that the level of
absence of ganglion cells extended higher
than usual.
Fundamental etiology. All of the present
e\"idence supports the belief that absence
of the ganglion cells of the myenteric
plexus is the fundamental feature in
congenital megacolon. It seems apparent,
furthermore, that the absence of ganglion
cells is a congenital defect, that is, agen-
esis. The cause of the agenesis of the
ganglion cells may lie in an abnormality
of the organizers of the nervous system
during the development of the innerva-
tion of the 10\\'er colon. The defect proba-
bly occurs during the last stages of de-
velopment of the myenteric plexus of the
sigmoid colon and rectum. T his hy-
pothesis is consistent \\"ith the concept of
cranio-caudad direction of development.
Classification of megacolon. In the past,
congenital megacolon has been regarded
as a disease of unknown cause, char-
acterized by severe constipation wit h
bouts of obstipation, dating from early
infancy, and tending to become more
severe as the individual grows older.
Whitehouse and Kernohan (31) have
listed four criteria that are essential fo r
the diagnosis of congenital megacolon: 1)
symptoms are present from birth; 2)
marked chronic dilatation and hyper-
trophy of t he colon are present; 3) maxi-
mal involvement is present in t he sigmoid
colon ; 4) t he typical clinical picture is
present. To t his list must now be added
t he etiologic factor of the disease, namely
agenesis of the ganglion cells of the
rectum and sigmoid colon.
The absence of an observable lesion-
producing obstruction is especially im-
portant in the diagnosis of congenital
megacolon because any type of chronic
obstruction may produce the same dilata-
t ion and hypertrophy of the colon and
the same symptoms as congenital mega-
colon. This organic type of megacolon has
also been called symptomatic megacolon,
or pseudomegacolon.
As Bodian has pointed out (6), con-
genital megacolon should also be
differentiated from t hose cases of mega-
colon in which t he dilatat ion and hyper-
t rophy extend t o the anal sphincter.
Since no etiology has been discovered for
thi s type of megacolon, it has been
suggested that it be termed idiopat hic
megacolon . Agenesis of the myenteric
plexus is not a factor in this type. Bodian
(6) and Lee and Bebb (2) believe this
type to have a functional basis.
Etzel (7, 8) and Ferreira (9) have
reported many cases of megaesophagus,
50 per cent of which have been associated
wit h megacolon . These have occurred in
older individuals among the poorer
classes of people and are associated with
degenerative changes of the ganglion
cells of the myenteric plexus. A few of
these cases have also been accompanied
by megaureter. This disease, which is
believed to be due to chronic vitamin B
deficiency, should be considered a sepa-
rate entity-nut rit ional megacolon.
On this basis megacolon can be divided
into four distinct varieties, all similar in
many respects but each having a dif-
fe rent cause. The classification is a
synthesis of those proposed by Bodian
(6) and Lee and Bebb (20).
1. Aganglionic megacolon (congenital
megacolon ; Hirschsprung's disease).
Megacolon characterized by the presence
of a narrowed segment of rectum and
rectosigmoid in which the ganglion cells
of the myenteric plexus are absent .
 AUSTIN-CONGENITAL MEGACOLON
2. Organic megacolon. Megacolon
characterized by the presence of a grossly
observable lesion that causes mechanical
obstruction.
3. Nutritional megacolon. Megacolon,
often accompanied by megaesophagus
and megaureter, characterized by degen-
erative changes in the myenteric plexus,
and believed to be due to chronic vitamin
B deficiency.
4. Idiopathic megacolon (Bodian).
Megacolon characterized by dilatation of
a normally innervated colon to the anal
sphincter.
This classification should permit easy
differentiation of the different types of
megacolon and provide a sound basis for
treatment and prognosis.
SUMMARY
1. The etiology of aganglionic mega-
colon, as illustrated by the 63 cases
reported at the present time, is agenesis
of the ganglion cells of the myenteric
plexus of the rectum and rectosigmoid.
The dilated portion of the colon does not
exhibit this abnormality.
2. Dilatation and hypertrophy of the
colon is the result of chronic partial
obstruction at the level of the sigmoid
colon or the rectum caused by the dis-
ruption of the intrinsic parasympathetic
innervation of the rectum that is oc-
casioned by the lack of ganglion cells.
3. The validity of these findings is
shown by the evidence obtained in the
experimental production of megacolon
by removal of the parasympathetic
supply of the distal colon and by the
results obtained in surgical operations
directed at removal of the portion of the
bowel that lacks the normal parasympa-
thetic innervation.
4. On the basis of etiology megacolon
may be classified into four types, each
having distinctive features. Criteria are
listed for the differentiation of agangli-
onic megacolon from the other types.
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