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76 Mesenteric physiology
pathologic conditions including cirrhosis, ovarian bromas
(Meigs’ syndrome), bowel cancer, peritoneal carcinomato-
sis, visceral inammation, ovarian torsion, and peduncu-
lated uterine leiomyomata (due to mechanical impairment
of venous outow) [137–139].
Peritoneal uid secretion increases dramatically during
postsurgical repair or inammation [127]. Just as secre-
tion increases, so too does absorption and uid volumes
(reected in abdominal drain outputs) then decrease. ese
reect changes in mesothelial functionality as the latter
must rst proliferate and reperitonealize to cover surfaces
not ordinarily exposed (i.e., mesentery, fascia, abdominal
wall, retroperitoneum).
Numerous cell types occur in peritoneal uid.
Macrophages and mesothelial cells account for 36% of the
cellular population, while lymphocytes and polymorpho-
nuclear cells make up 18% and 7%, respectively. Peritoneal
dialysis exploits the absorptive capacity of mesenteric meso-
thelia. is capacity is considerable given the volume pro-
duced daily [127].
MESOTHELIAL LYMPHATICS
As previously mentioned (see Chapter 4), a connective tissue
continuity occurs between the intestine and the connec-
tive tissue lattice within the mesentery [9,10]. A lymphatic
network is housed within this lattice (Figures 6.6 and 6.7).
In addition, a lymphatic continuity occurs between intes-
tine and adjacent mesentery [140].
Although the concept of continuity may be taken for
granted, it is extremely important in the context of the
distribution of cellular or molecular entities. Mesenteric
lymphatic spread from the colon was elegantly demon-
strated by Boni etal. ey separately injected a colon cancer
cell line into the antimesenteric border and mesenteric bor-
der of a rat colon [141]. ey then investigated the pattern of
lymphatic spread. In rats injected into the anti-mesenteric
border, mesenteric nodal spread was limited to a minority
of animals, while carcinomatosis occurred in the major-
ity. Carcinomatosis is characterized by a diuse peritoneal
studding with individual tumor deposits. In advanced carci-
nomatosis, the deposits coalesce and become matted. In rats
injected into the mesenteric margin, nodal spread occurred
in the majority of animals and carcinomatosis was infre-
quent. eir observations can be explained by the lymphatic
contiguity between the mesocolon and the intestine.
e observations of Boni et al., taken in conjunction
with clinical observations in gastric and ovarian cancer,
may have additional implications. In gastric, ovarian, and
sometimes appendiceal cancer, the pattern of spread may
be peritoneal (leading to carcinomatosis) rather than nodal.
Although carcinomatosis is generally attributed to disper-
sion in peritoneal uid, it could also be explained by spread
through lymphatic channels in submesothelial connective
tissue. e development of nodal spread, and the relative
lack of overlap between carcinomatosis and nodal patterns
of lymphatic spread, may be explained by alterative lym-
phatic systems within the mesentery.
GREATER OMENTUM
According to current embryologic theories, the greater
omentum is related to the mesentery in so far as both derive
from the same developmental forerunner. Based on this,
Myofibroblast with cytokeratin remnants,
red=alpha smooth muscle actin, blue=Hoechst,
green=cytokeratin
Transfected fibroblast with SV40 T-antigen,
red=TRITC phalloidin that stains actin in any cell,
green=antibody to SV40 T-antigen, nuclear stain
(e) (f )
Figure 6.5 (Continued) Panel demonstrating different mesenchymal cell types generated following the exvivo culture of
mesenteric mesothelium. (e) and (f) Myobroblasts with intracytoplasmic cytokeratin.
Greater omentum 77
Right
mesocolon
Small bowel
mesentery
Mesenteric organ
(a)
Surface
mesothelium
Submesothelium
connective tissue
Connective
tissue
lattice
Connective
tissue of
mesentery
(b)
Lymphatic network
within the
connective tissue
(c)
Figure 6.6 2.5D snapshots of 3D digital sculptures. (a) The ileocecal junction where the small intestinal mesentery
continues as the right mesocolon. (b) The connective tissue lattice and surface mesothelium contained in the mesentery.
Adipocytes have been conceptually removed to illustrate the nature of the lattice. Ordinarily the compartments generated
in the lattice are packed with adipocytes. (c) Mesenteric lymphatics with connective tissue removed.
78 Mesenteric physiology
it is not unreasonable to suggest that cellular and molecu-
lar activities associated with the greater omentum should
be included in any discussion on mesenteric functionality.
Atthe least, this could provide important clues of function
and avenues for future research.
e omentum has appropriately been termed the “abdom-
inal policeman,” as it adheres to areas of inammation and
prevents the diusion of pathologic processes throughout
the peritoneal cavity. In this manner, it can mechanically
seal perforations, localize inammation, limit the spread of
infection, and simultaneously prompt local revasculariza-
tion and tissue regeneration [142–144].
e greater omentum contains adipocy tes, macrophages,
B cells, T cells, mast cells, and dendritic cells [145]. Lynch
etal. noted that while iNKT and CD1d
+
cells amass in the
greater omentum, this phenomenon is reduced in obesity
and in patients with colorectal cancer [144]. us, it would
appear that the policeman activity of the greater omentum
extends beyond the simple mechanical and may also include
immune protection against the development of malignancy
[146]. Lysaght et al. aimed to characterize T lymphocytes
in visceral adiposity (using omentum) and peripheral blood
from 35 patients with esophageal adenocarcinoma. T cell
activation markers CD69 and CD107a were increased in
Mesenteric lymphatics
100 µm
25 µm
Lymphatic
vessels in
connective
tissue
Connective
tissue
septation
25 µm
100 µm
Surface
mesothelium
Submesothelia
l
connective
tissue
(a) (b)
(c) (d)
Figure 6.7 Photomicrographs based on serial sections of mesentery. (a) Section stained with podoplanin (a lymphatic
and mesothelial surface marker) demonstrating lymphatic channels beneath the surface mesothelium of the mesen-
tery. (b)Corresponding serial section stained with Masson’s trichrome highlight connective tissue. Correlating A and B,
the lymphatic channels identied occurred within the submesothelial connective tissue. (c) Podoplanin positive vessels
(i.e., lymphatics) within the connective tissue septations that spanned the mesentery and together generated the connective
tissue lattice. (d) Corresponding serial section stained with Masson’s trichrome to highlight connective tissue septations.
References 79
expression in omental CD4
+
and CD8
+
T cells, compared
with corresponding levels in peripheral blood. CD45RO
+
T cells were more prevalent in omentum compared with
peripheral venous blood. While the relevance of these nd-
ings is under investigation, they indicate that the greater
omentum, like the mesentery, is likely to be far more active
than previously appreciated [146]. ese observations have
yet to be investigated in the context of the mesenteric com-
ponent of visceral adiposity.
FUTURE STUDIES
From the earlier discussion, it can be seen that the mesen-
tery does not act simply in a bystander manner providing
a scaff ld for the passage of blood vessels to and from the
intestine. It occupies a unique anatomic position between
the intestine and the body proper. e histologic, connec-
tive tissue, lymphatic, and immunologic continuity between
all three mean it is optimally placed to exert a key inu-
ence over local and systemic homeostatic processes. It is
ideally placed to sample microbial environmental cues and
orchestrate appropriate systemic as well as local mucosal
responses. It is important to further investigate this regula-
tory hub, or signal box, and to characterize its role in nor-
mality and disease.
e mesentery is a highly active immunological, endo-
crine, and metabolic organ. Mesenteric mesothelium has
regenerative and pluripotential properties that are impor-
tant in response to injury within the abdomen, but that may
be deranged in hernia or adhesion development. Future
studies should aim to investigate the regenerative capacity
of mesenteric mesothelium and the role that this may have
in abdominal pathology.
SUMMARY
Mesenteric physiology is an emerging fi ld. e recent
clarication of mesenteric anatomy from duodenojejunal
exure to mesorectal level provides an ideal platform to
better characterize the physiologic relevance of this organ
in general. Scientic and clinical communities are now
provided with exciting opportunities that will enhance our
understanding of its function in normality and hence its
role in disease processes.
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7
Pathology of the mesentery
J. CALVIN COFFEY, JONATHON RODDY, MIRANDA KIERNAN, AND SHAHEEL M. SAHEBALLY
The problem, when solved, will be simple.
On wall of General Motors
Research Laboratory
AIM
e rst aim is to dene the concept of a mesenteropathy
and describe a classication system for these. A second aim
is to describe the mesenteric and peritoneal manifestations
of mesenteropathy subtypes.
INTRODUCTION
e functional and anatomical distinctiveness of the mes-
entery has generated increasing interest in mesenteric
diseases. In keeping with this, a range of pathologies can
be identifi d that are readily and directly associated with
the mesentery. Several more are increasingly associated
through recent experimental ndings. As with diseases of
other organs, the mesentery appears to be vulnerable to a
range of pathologies including inammatory, vascular, con-
nective tissue, and neoplastic.
Aim 85
Introduction 85
Primary mesenteropathies 86
Crohn’s disease (primary mesenteropathy) 86
Mesenteric manifestations in Crohn’sdisease 86
Mesenteric manifestations correlate with local and
systemic disease manifestations inCrohn’s disease 87
Mesenteric and mucosal abnormalities directly
correlate in Crohn’s disease 87
Mesenteric and intestinal mesenchymal abnormalities
overlap 87
Mesenteric and mucosal transcriptional proles 87
Fibrocytes are a biomarker in Crohn’s disease 87
Circulating brocytes and disease activity in Crohn’s
disease 90
Circulating brocyte levels change following intestinal
resection in Crohn’sdisease 90
Miscellaneous support for mesenteric involvement 90
Appendicitis and Crohn’s disease 90
CRP production in Crohn’s disease 90
Mesenteric production of substance P inCrohn’s
disease 90
Summary 90
Non- (i.e., mal) rotation 92
Anatomy 92
Clinical implications of non (i.e., mal) rotation 93
Molecular basis of non (i.e., mal) rotation 93
Volvulus 93
Epiploic appendagitis 95
Mesenteric ischemia 95
Internal herniation 95
Desmoid tumor 95
Mesenteric cysts 97
Sclerosing mesenteritis 97
IgG4-related sclerosing mesenteritis 97
Mesenteric neurologic pathology 97
Secondary mesenteropathies 97
Appendicitis 98
Phlegmon 98
Mesenteric adenitis 98
Lymphoma 99
Peritoneal carcinomatosis 99
Neuroendocrine tumors 100
Castleman’s disease 101
Mesenteric lymph node cavitation syndrome 101
Indeterminate mesenteropathies 101
Adhesion formation 101
Congenital adhesion formation 101
Diabetes and metabolic syndrome 103
Irritable bowel syndrome 103
Future directions 103
Summary 104
References 104