How would you explain the topography of intestinal lesions in IBD

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How would you explain the topography of
intestinal lesions in IBD ?
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(No Transcript)
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Current theory in IBD

• Inflammatory bowel disease is thought to
  result from inappropriate and ongoing activation
  of the mucosal immune system driven by the
  presence of normal luminal flora. This aberrant
  response, in geneti-cally predisposed patients,
  is most likely facilitated by defects in both the
  barrier function of the intestinal epithelium and
  the mucosal immune system .
• Podolsky, NEJM 2002

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Does that explain the topography ?
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Hypothesis bacteria, virus, worms know the
anatomy
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Ulcerative colitis surgical view
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Hypothesis specific immunological sites Peyers
patches and isolated lymphoid follicles
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Specific immunological sites

• Number, size and distribution of Peyers
  patches in the human small intestine
  Cornes, Gut 1965
• The role of Peyers patches in the age-related
  incidence of Crohns disease
• Van Kruinigen HJ,
  J.Clin.Gastroenterol 1997

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Distribution of Peyer's Patches in the Distal
Ileum
Almost without exception, the patches proximal
to the terminal 15 cm of ileum were located in
the mucosa of the antimesenteric side
Van Kruiningen HJ et al. Inflammatory Bowel
Disease, 2002
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Crohns disease surgical view
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Vascular hypothesis
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Vascular hypothesis in UC macroscopic view

• 
  Wakefield, Lancet 1995

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Vascular hypothesis in CD macroscopic view

• end arteries
• Anthony, J Clin Pathol 1997

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Vascular hypothesis animal models

• Vascular anatomy defines sites of indomethacin
  induced jejunal ulceration along the mesenteric
  margin.
  Anthony, Gut 1997
• The colonic mesenteric margin is most susceptible
  to injury in an experimental model of colonic
  ulceration. Anthony, Aliment
  Pharmacol Ther 1999

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Vascular hypothesis microscopic view

•  granulomatous vasculitis   majority of
  granulomas in CD form within walls of blood
  vessels.
  Wakefield, Gastroenterology 1991
• Early mucosal changes in Crohns disease damage
  and rupture of small capillaries before
  infiltration of LP by inflammatory cells and loss
  of overlying epithelium.
  
  
  Sankey, Gut 1993

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Alternative vascular hypothesis ?
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Alternative vascular hypothesis ?
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Alternative vascular hypothesis ?

• lacteal stained with podoplanin

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Alternative vascular hypothesis ?
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Schematic overview of the lymphoid elements of
the gut associated lymphatic system

• 
  Spahn, Gut 2004

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What the Early Pathologists Really Said

• The lymphatic channels show generalized
  dilatation and are closely packed with
  lymphocytes..
• 1939 Blackburn
• The lymphatics are obstructed by lymphocytes.
  In our series lymphatic blockade also was
  observed, but was the result of endothelial
  proliferation and desquamation.
• Warren, JAMA 1948

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What the Early Pathologists Really Said

• The lymphatics of the submucosa, in addition to
  dilatation, possessed certain noteworthy
  features. Here focal areas of endothelial
  proliferation occurred, as originally described
  by Warren. The lumina of these lymph vessels
  often contained numerous lymphocytes and a number
  of histiocytes.
  
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  Van Patter, 1952

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What the Early Pathologists Really Said

• The major findingis a pronounced edema of the
  entire bowel wall, but especially marked in the
  submucosa. with lymphangiectasis.
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  Meadows, Arch Surg 1963
• A characteristic microscopic lesion of regional
  enteritis consisting of a loose patch of
  histiocytes and often including giant histiocytes
  surrounded by small mononuclear cells,
  principally lymphocytes and plasma cells. This
  lesion is located, as commonly seen, adjacent to
  a distended lymphatic that is perivascular.
• Mottet, 1971

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Experimental model of regional enteritis
secondary to lymphatic obstruction
Day 6
Mesenteric oedema
Submucosa thickening
Granulomas
Segmental intestinal disease ulcers
(day20),aggregation of lymphocytes, fistulas.
Kalima TV et al. Scand J Gastroenterol 1976
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About dogma

• Galileo Galilei Pise 1564 Arcetri 1642