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Ontstaanswijze van
diverticulose en
diverticulitis
André J.P.M. Smout
Afd. MDL-ziekten
UMC Utrecht
Delft, 29 januari 2008
taenia
mesenterium
taenia
taenia
vasa recta
high
pressure
high
pressure
Laplace’s law
in diverticular disease
P = k .T / r
pressure
radius
wall tension
highest intraluminal pressure in gut segments with smallest diameter
i.e. sigmoid
Colonic manometry
Two types of colonic contractions
segmenting contractions
mass contractions
high-amplitude peristaltic contractions
do not lead to significant transit
continuously present (day-time)
lead to transit of large volumes
3-10 times per day
Two types of colonic contractions
segmenting contractions
mass contractions
high-amplitude peristaltic contractions
60 cm
50 cm
40 cm
30 cm
20 cm
10 cm
5 min.
200 mmHg
Increased colonic motility in diverticular disease
Motility
Index
1200
1000
health
800
IBS
600
asymptomatic
diverticulosis
painful
diverticular disease
400
200
0
Fasting
Postprandial
G.H. Ritsema
Thesis, Utrecht, 1989
Retrograde HAPC in diverticular disease
1 min
transverse
descending
descending
sigmoid
sigmoid
Bassotti G et al. Dis Colon Rectum 2001;44:1814-1820
Enteric nervous system
• Submucosal plexus (Meissner)
• Myenteric plexus (Auerbach)
Interstitial cells
of Cajal
Smooth muscle cells
• Circular layer
• Longitudinal layer
Altered neuronal regulation in
diverticular disease
More excitatory (cholinergic) neurons
Fewer inhibitory (nitrergic) neurons
Tomita R et al. Hepatogastroenterology 2000;47:692-696
Increased sensitivity of smooth muscle to
exogenous acetylcholine
Huizinga JD et al. Scand J Gastroenterol 1999;34:363-368
Golden M et al. Lancet 2003;361:1945-1951
Reduction of ICCs
Bassotti G et al. J Clin Pathol 2005;58:973-979
Golden M et al. Lancet 2003;361:1945-1951
Ageing
Ageing associated with deterioration of collagen in extracellular matrix,
mediated by changes in:
• matrix metalloproteinases (‘collagenases’)
• tissue inhibitors of metalloproteinases
Wess LA et al. Gut 1995;37:91-94
Mimura T et al. Dis Colon Rectum 2004;47:371-379
premature development of
diverticulosis in
connective tissue disorders:
• Marfan syndrome
• Ehlers-Danlos syndrome
• Williams syndrome
• scleroderma
Pathogenesis of colonic diverticula
connective tissue disorders
IBS
narrow lumen
ageing
abnormal colonic motility
abnormal collagen
weak spots at vasa recti
fibre deficiency
increased intraluminal pressure
weakened wall
diverticula
Pathogenesis of diverticulitis
West AB. J Clin Gastroenterol 2006;40:S126-S131
Myochosis
Thickening of circular smooth muscle layer
Myochosis
 ‘concertina-like’ appearance
Myochosis
Hypertrophy or hyperplasia of circular muscle? NEITHER !
Increased elastin content of the taeniae coli (‘elastosis’)
Whiteway J Morson BC Gut 1985;26:258-266
muscle cells
extracellular matrix
elastin fibres increased by
at least 200% compared to
healthy controls
Myochosis
Circular muscle thickened, lumen narrowed and concertina-like appearance
caused by shortening of taeniae
Myochosis
Myochosis may precede the development of diverticula
‘Prediverticular state’
Pathogenesis of colonic diverticula
taenia elastosis
myochosis
IBS
?
connective tissue disorders
narrow lumen
ageing
abnormal colonic motility
abnormal collagen
weak spots at vasa recti
fibre deficiency
increased intraluminal pressure
weakened wall
diverticula
Lancet 1975;7927;211-212
The End