Epidemiology of Bowel Diseases

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Epidemiology of Bowel Diseases

• Melanie Shale
• Physiology

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Aim of the session

• Understand the epidemiology, aetiology and
  pathophysiology of benign and malignant bowel
  disease
• Constipation
• Haemorrhoids
• Diverticular disease
• Ulcerative colitis
• Polyps
• Bowel cancer

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What is epidemiology?

• A study of the distribution and determinants of
  health related states and events in populations
  and the control of health problems the study of
  epidemic disease

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What is Aetiology?

• A branch of knowledge concerned with causes and
  origins of disease factors of causation or
  those associated with the causation of disease or
  abnormal body states

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Constipation

• What are the causes of constipation?

• Not enough fibre in the diet.
• Not enough liquids.
• Lack of exercise.
• Medications.
• Irritable bowel syndrome.
• Changes in life or routine such as pregnancy,
  older age,
• and travel.
• Abuse of laxatives.
• Ignoring the urge to have a bowel movement.
• Specific diseases such as multiple sclerosis and
  lupus.
• Poor motility of the colon and rectum.
• Muscle weakness or pain

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To understand the physiology associated with
constipation and its consequences, we must review
the defaecation reflex

• See slides 7 8

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Haemorrhoids

• A consequence of chronic constipation
• Rather than the theory that piles were a form of
  varicose vein, a sliding theory has evolved.
• The anal canal contains 3 fibro vascular
  cushions that appear in the right anterior,
  right posterior and left lateral positions.
• They are suspended by a connective tissue
  framework derived from the internal anal
  sphincter and longitudinal muscle. Within each
  cushion is a venous plexus that allow for
  enlargement of the cushion.

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Pathophysiology of haemorrhoids

• Age and passing of hard stools (which produces a
  shear stress) results in fragmentation of anal
  tissue.
• Fragmentation of the connective tissue supporting
  the cushions leads to their descent.
• Straining increases the venous pressure and
  causes the veins to become engorged.
• The prolapsed cushion has impaired venous return,
  which results in dilation of the plexus and
  venous stasis.
• Inflammation occurs with erosion of the cushions
  epithelium, resulting in bleeding.

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Laxatives?
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An abdominal massage machine??
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Treatment for constipation

• BULK PRODUCERS (Fybogel, methylcellulose)
• Hydroscopic and absorptive properties produce
  larger, softer stools often easier to pass.
• OSMOTIC AGENTS (Lactulose)
• Retain fluid in the bowel by creating osmotic
  gradients because they are poorly absorbed.
• CHEMICAL STIMULANTS (Senna, picolax).
• Mild gut stimulation / irritation increases
  motility.

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Colorectal Cancer

• A malignant neoplasm arising from the mucosa of
  the large intestine.
• Colorectal cancer is the third most common
  malignancy in the developed world accounting
  for 20,000 deaths in the UK each year.
• Colon cancer affects almost equal proportions of
  men and women, most commonly between the ages
  60-80.
• Rectal cancer is more common in men?
• The pathogenesis of colorectal cancer involves
  genetic and environmental factors, the most
  important being diet.

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Causative factors

• Genetic and environmental factors seem to promote
  mutations that most frequently cause the
  formation of adenomatous polyps.
• Polyps commonly occur in the rectum and sigmoid,
  decreasing in frequency towards the caecum.
• About 25 of patients with cancer of the large
  bowel have satellite adenomatous polyps.
• Risk of malignancy seems to be related to size,
  becoming more invasive.
• Inflammatory polyps occur in chronic ulcerative
  colitis and crohns disease of the colon.

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Colonic polyp (sessile).
Histology demonstrated benign tubular adenoma.
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Colonic polyp (pedunculated).
Histology demonstrated benign tubular adenoma.
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How cancer develops

• Believed to be as follows
• 1) Exposure to the carcinogen
• 2) Entry of the carcinogen into a cell
• 3) Initiation
• The carcinogen alters the cells genetic material
• 4) Promotion.
• Acceleration by other carcinogens (promoters)
• The cell begins to multiply out of control
• Disrupts normal body functions
• 5)Progression metastasis / migration

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Cancer and diet

• Links have been established between colorectal
  cancer and..
• Low fibre intake
• High red and processed meat consumption
• Charred / BBQ foods
• High Iron intake (necessary for bacterial growth)
• Low Ca intake (bind with bile acids could be
  mutogenic by inhibiting detoxification enzymes
  and increasing colon cell proliferation)
• Low essential fatty acid intake anticancer
  properties
• Low fruit and veg. intake antioxidant
  properties

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Diverticular disease

• Millions of people are estimated to have
  diverticular disease.
• Symptoms of diverticulitis develop in only 1 in
  5people.
• It is thought that lifestyle and dietary changes
  in the 20th century have contributed to its rise
  specifically fast paced living with convenience
  foods.
• The disease is more common among lower income
  groups and may reflect awareness (lack of) of
  fibre.
• Women have now overtaken men regarding incidence
  -dieting?
• In countries where the diet is high in fibre and
  low in refined carbohydrates, diverticular
  disease is unknown.

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Aetiology and geographical distribution

• In high fibres diets, softer stools and greater
  gut motility mean the stool is evacuated more
  frequently.
• Many researchers believe that a high intake of
  fibre is also the primary reason for low rates of
  colorectal cancer.
• In the northern European continents, 30 of
  people aged 60 and over have diverticular
  disease.
• With individuals living longer, diverticular
  disease is increasing, possibly due to age
  associated colonic weakening.
• Nearly 2/3 of people will have diverticular
  disease by 80yrs of age.

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Physiology of Diverticular Disease

• The development of diverticular is not fully
  understood but it believed to be related to
  segmental spasm of the bowel muscle.
• The resulting increase in pressure causes mucosal
  extrusion at the weakest points in the colon wall
  next to the intramural blood vessels that
  extend into the submucosa.
• Muscular hypertrophy is also a common finding in
  the sigmoid, probably to compensate for these
  pressure increases.

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Openings in the mucosa(green arrows) are the
mouths of diverticuli A smooth elevated
polypoid projection(black triangles) represents
an adenomatous polyp Presence or absence of
malignancy can not be established based on the
gross appearance of this lesion although its
modest size favours a benign lesion
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Diverticular theories

• Colonic diverticular occur more frequently in
  Western countries and therefore are caused by the
  highly western refined diet that is deficient in
  dietary fibre.
• This results in decreased faecal bulk, narrowing
  of the colon and increased intraluminal pressure
  for moving smaller faecal mass.
• Faecal impaction occurs in the sacs resulting in
  secondary erosion and inflammation and
  diverticulitis can follow.

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Diverticulitis

• The cause the inflammation in and around a
  diverticulum is probably mechanical.
• The stagnation of non-sterile faecal material may
  compromise the blood supply to the thin-walled
  sac and render it susceptible to invasion by
  colonic bacteria, causing inflammatory erosion of
  the mucosal lining.
• This sequence of events can result in perforation
  into the colonic wall, forming an intramural
  abscess.
• This increases the likelihood of bowel
  obstruction and peritonitis.

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Ulcerative Colitis

• Evidence suggests a genetic predisposition leads
  to an unregulated intestinal immune response to
  environmental, dietary or infectious agent.
• However, no inciting antigen has been identified.
• Unlike Crohns disease, current cigarette smoking
  appears to decrease the risk? mechanism not
  known
• Like Crohns, UC may affect people at any age,
  but the age-onset curve peaks at ages 15-30 and
  50-70yrs.
• Men and women are equally affected.

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Pathophysiology of U.C.

• Changes begin with degeneration of reticulin
  fibres beneath the mucosal epithelium, occlusion
  of subepithelial capillaries and progressive
  infiltration of the lamina propria with plasma
  cells, eosinophils, lymphocvytes, mast cells and
  PMNs.
• Disease usually begins in the rectosigmoid and
  may extend along the entire colon.

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Immunological aspects

• Current interests lie on defects in the mucosal
  gel barrier.
• The existence of true autoimmunity is uncertain
  and the evidence is conflicting.
• However, there is perhaps an imbalance between T
  lymphocyte subsets that are responsible for
  secreting pro-inflammatory chemical mediators.

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Inflammation

• T cell lymphocytes are normally activated in
  response to an antigen and are normally found in
  the gut wall.
• In inflammatory bowel disease, the normal
  regulation of their activity is disturbed.
• Activation of mucosal inflammatory cells also
  leads to the production of inflammatory
  mediators.
• Prostaglandins, leukotrienes, interferons and
  cytokines are partly responsible for the tissue
  damage observed.
• For some of these mediators, suppression leads to
  activation of alternative pathways, which allow
  inflammation to continue.

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U.C. quiescent stage. The quiescent stage shows
evidence of previous damage with short deformed
crypts, loss of crypts but no evidence of an
active inflammatory process. The markedly thick
muscularis mucosa (arrow) is often seen in U.C.
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Crohns Disease

• Chronic inflammation of the ileum, ileo-caecal
  region or colon that can spread through the bowel
  wall to neighbouring structures.
• Tending to affect young people between ages 20
  and 40yrs, it is most common in North America and
  Northern Europe (40 per 100,000 population)
• Studies have shown that 12-18 of patients with
  Crohns disease have at least one family member
  affected.

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Causes of Crohns disease

• The mode of inheritance is complex but it is
  likely that several genes are involved.
• Susceptibility loci for the disease have been
  reported recently on chromosomes 16, 3, 7 and 12,
  the latter three being shared with ulcerative
  colitis.
• Several environmental factors have also been
  implicated in addition to claims for initiating
  roles for gut flora, food constituents or
  specific infections (TB).

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Environmental factors

• Diet
• The possible role of diet has been examined with
  particular interest in milk, fibre and sugar.
• Anecdotally, it has been suggested that some
  patients symptoms improve when avoiding dairy
  products.
• Infective agents
• There could be an infective cause for Crohns
  Mycobacterium paratuberculosis and the measles
  virus have aroused considerable interest but no
  definitive relationships have been established
  yet.

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More environmental factors

• Smoking
• Crohns is 2-4 times more common in smokers, this
  being a significant factor in the aetiology of
  the disease.
• The mechanism however is not known.
• Stress
• The effect of stress in causing relapses in IBD
  is controversial but some studies have
  demonstrated an increased risk of symptom
  exacerbation following stressful events (divorce,
  death)

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Pathophysiology

• Whatever the initiating factors in Crohns
  disease, there is excessive activation of mucosal
  T cells, leading to trans mural inflammation.
• This again, is amplified and perpetuated by the
  release of pro-inflammatory soluble mediators
  (see next slide).
• The knowledge of this inflammatory response
  however, has improved our understanding of the
  possible modes of action of conventional
  treatments and has led to the development of new
  anti-inflammatory agents aimed at specific
  pathophysiological targets.

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Crohns Linear Longitudinal ulcers(black arrows)
Areas of normal mucosa are seen(green arrow)
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Crohn's ileitis.
Cobblestone appearance caused by inflammation
deep into bowel wall with muscosal oedema.
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DIFFERENTIATING BETWEENCROHN'S DISEASE AND
ULCERATIVE COLITIS