day 4 - Lower gastrointestinal disease & quiz

Question 1

The lower gastrointestinal tract comprises

Answer 1

The lower gastrointestinal tract comprises the duodenum through to the rectum. It consists of small bowel (duodenum, jejunum, ileum) and colon (caecum, ascending, transverse, descending and sigmoid).
The bowel changes from the small bowel to colon at the level of the ileocaecal valve which is at the junction of the ileum and caecum. The appendix arises from the caecum.

Question 2

At a microscopic level the mucosa of the small and large bowel differ in appearance.

Answer 2

At a microscopic level the mucosa of the small and large bowel differ in appearance. The small bowel mucosa is in the form of villous (finger like) projections, which protrude from the surface of the bowel. Pathological processes, which often affect the villous architecture, result in symptoms and signs of malabsorption. In contrast the colonic mucosa comprises a flat mucosa with crypts that descend down to the muscularis mucosa.

Question 3

what is Infectious Enterocolitis

Answer 3

Enterocolitis is inflammation of the small and or large bowel. Some infections are described in more detail in the lecture on ‘Waterborne, foodborne and viral infections of the gastrointestinal tract’.

Question 4

Bacterial Enterocolitis

Bacteria can cause disease in different ways:

Answer 4

Ingestion of toxin – Staph. aureus, Clostridium perfringens
• These organisms secrete toxins, which contaminate food and ingestion of the toxin results in the enterocolitis

Enterotoxic organisms – Vibrio cholerae, E. coli, Cl. difficile
• To cause disease these organisms need to be ingested. While within the GI tract they secrete toxins, which damage the mucosa

Enteroinvasive organisms – Salmonella, Shigella and some E. coli
• The organism itself is ingested and invades the mucosa, resulting in damage

Question 5

endoscopic and macroscopic characteristics of C. Diff infection

Answer 5

Endoscopically and macroscopically it is characterised by an acute inflammatory exudate, which adheres to the surface mucosa giving the appearance of a pseudomembrane. Microscopically there is acute inflammation of the mucosa with neutrophils erupting out of crypts giving a volcano-like appearance.

Question 6

where is C. Diff normal found and when is it a problem

Answer 6

This is a normal gut commensal, which causes an antibiotic-associated colitis usually occurring in patients taking broad-spectrum antibiotics which is thought to lead to an overgrowth resulting in the Cl. difficile acting as a pathogen. Rarely it may occur in the absence of antibiotics, usually after surgery or in patients with chronic debilitating illnesses.

Question 7

causes of Parasitic and Protozoal Enterocolitis

Answer 7

Although uncommon in this country they are an important cause of enterocolitis worldwide. They can be categorised as follows:
• Round worms – Strongyloides, Ascaris, hookworms
• Flatworms – tapeworms, flukes
• Protozoa – Entamoeba histolytica, Giardia lamblia

Question 8

what is Entamoeba histolytica

Answer 8

A protozoan spread by the faecal-oral route. The amoebae burrow into the crypts of the colonic mucosa and through the muscularis mucosa. They produce acute dysentery. Macroscopically there are numerous ulcers affecting the colonic mucosa. Microscopically the parasites spread out on penetrating the muscularis mucosa resulting in a flask shaped ulcer with a narrow neck and a broad base. In ~4% of patients the parasites penetrate portal vessels and spread via the blood stream to the liver to produce solitary or less frequently multiple hepatic abscesses, some of which can reach up to 10cm in diameter. Occasionally the amoebae can spread to the lungs, heart, kidneys and even brain, forming abscesses at these sites.
The main problem with entamoeba histolytica is that the abscesses remain long after the dysentery has gone and like all abscesses can be hard to treat.

Question 9

what is Giardia lamblia

Answer 9

An intestinal parasite spread by contaminated water. The parasite attaches itself to the small intestinal mucosa, but do not appear to invade. The resulting small intestinal morphology varies from virtually normal villi to marked blunting of the villi with a mixed inflammatory infiltrate of the lamina propria. Regardless of the effects on the villi the attachment of the parasites to the villi results in malabsorptive diarrhoea.

Question 10

causes of Viral Enterocolitis

Answer 10

In young patients:
• Rotavirus In adults:
• Norwalk virus (winter vomiting virus) In immunocompromised patients:
• Cytomegalovirus
• Human Immunodeficiency Virus Infection
A diarrhoeal illness occurs in 30-60% of patients with HIV, when other pathogens have been excluded. The cause is not known but it may be due to pathogens that have not yet been identified or direct damage to the mucosa by the HIV infection itself.

Question 11

characteristics of malabsorption

Answer 11

Malabsorption is characterised by suboptimal absorption of fats, fat –soluble and other vitamins, proteins, carbohydrates, electrolytes and minerals and water.

Question 12

The clinical features of malabsorption are:

Answer 12

• Abdominal pain and bloating
• Flatus
• Diarrhoea
• Streatorrhoea
• Weight loss
• Failure to thrive
• Vitamin and metal deficiencies

Question 13

causes of malabsorption

Answer 13

It may occur as a result of one or more of the following:

1. Failure of intraluminal digestion – i.e. digestive enzymes in saliva, gastric juices, digestive
   enzymes in the small bowel or bile salts fail to digest the food into small enough elements for
   absorption
2. Failure of terminal digestion – failure of the disaccharidases and peptidases in the luminal
   brush border of the small intestinal mucosa to break down carbohydrates and peptides
3. Failure of transepithelial transport – failure of nutrients, fluid and electrolytes to cross the epithelium of the small intestine and into the vasculature

The list of causes for malabsorption is long but the more clinically relevant include:

• Coeliac disease (coeliac sprue)
• Tropical sprue
• Lactose intolerance
• Pancreatic insufficiency (e.g. cystic fibrosis or chronic pancreatitis in alcoholics)
• Whipple’s disease
• Parasitic infection (e.g. Giardia lamblia)
• Surgery (short gut syndrome, gastrectomy)
• Crohn’s disease
• Obstructive jaundice

Question 14

what happens in coeliac disease

Answer 14

This disease affects the mucosa of the small intestine resulting in impaired nutrient absorption (malabsorption), which improves on withdrawal of wheat gliadins and related grain proteins from the diet.

Largely a disease of whites (esp Irish 1:100). The genetic susceptibility is linked to the HLA DQw2 locus. It results in immune mediated intestinal injury with malabsorption. Investigation may be on serum looking for antigliadin and antiendomysial antibodies. If these are positive then a biopsy may be taken to confirm. On endoscopy (macroscopically) the mucosa may look smooth. The changes are more prominent in the proximal than the distal small intestine.

Microscopically there is flattening of the intestinal villi, with elongation of crypts resulting in a mucosa which more resembles that of large bowel. Within the epithelium there is an increase in lymphocytes (intraepithelial lymphocytosis) and studies have shown these to be predominantly cytotoxic T cells with increased numbers of T helper cell within the lamina propria.

Once a diagnosis of villous atrophy (flattening) is made on the initial biopsy a further biopsy may be taken to confirm the return of normal villous architecture on a gluten free diet. A further biopsy may be taken following a gluten challenge to confirm gluten as the etiological agent. Some centres consider a raised antibody titre and improvement of clinical symptoms on a gluten free diet as enough for a diagnosis.

Coeliac disease is also associated with an increased incidence of T cell lymphoma and less frequently other malignancies including GI tract and breast.

Question 15

what is Tropical Sprue and how do you treat it

Answer 15

Coeliac-like disease, which occurs predominantly in people living in the tropics. No specific causal agent has been identified but bacterial overgrowth have been implicated. Affects the entire small intestine and the microscopic appearances can be variable. Patients frequently have folate or B12 deficiency, which may lead to pernicious anaemia. Treatment is with broad-spectrum antibiotics and there appears to be no association with T cell lymphoma.

Question 16

what is Whipple’s Disease

Answer 16

A rare systemic disorder, usually in males (M:F 10:1) aged 30-40 years, which may affect any organ in the body but principally affects the intestine, central nervous system and joints. The casual organism is a Gram positive actinomycete called Tropheryma whippelii. The main abnormality in the intestine is seen on biopsy at a microscopic level, with the small intestinal mucosa distended by PAS positive macrophages within the lamina propria. These macrophages can be seen to contain rod shaped bacilli on electron microscopy.

Question 17

types of Small Bowel Neoplasms

Answer 17

Benign
• Lipoma, leiomyoma, adenoma

Malignant
• Carcinoid (neuroendocrine) neoplasms
• Carcinoma
• Lymphoma
• Sarcoma (gastrointestinal stromal neoplasms)

Question 18

what are Carcinoid (Neuroendocrine) Neoplasms

Answer 18

Derived from neuroendocrine cells and can secrete bioactive products such as gastrin, 5HT, somatostatin, VIP, insulin and other endocrine products. Their malignant potential depends on their site of origin: those from the appendix or rectum tend to be locally invasive and cured by resection whereas those of the small intestine, stomach and colon tend to be highly invasive and metastasise. Carcinoid neoplasms occur in sites other than the GI tract, such as lung.

Question 19

what happens in carcinoid syndrome

Answer 19

The classical carcinoid syndrome is characterised by flushing, diarrhoea, wheezing, abdominal fibrosis and cardiac valvular fibrosis, stenosis and regurgitation. Under normal circumstances isolated gastrointestinal tract carcinoid neoplasms secreting 5HT do not produce carcinoid syndrome as their endocrine products drain into the portal system and undergo first pass metabolism by the liver. Once the GI tract carcinoid neoplasm has metastasised to the liver its products are able to drain into the hepatic vein and directly into the systemic circulation producing carcinoid syndrome. Pulmonary carcinoid neoplasms drain directly into the systemic circulation and therefore do not need liver metastasis to cause carcinoid syndrome.

Question 20

what are Gastrointestinal Stromal Neoplasms (GISTs)

Answer 20

Usually occur in the stomach or small intestine and can show smooth muscle or neural differentiation. They may behave as benign or malignant neoplams. A high mitotic rate, presence of necrosis and neural differentiation are features which suggest malignancy.

Question 21

The gastrointestinal tract is the most common extranodal site for lymphomas. The most common lymphomas of the GI tract are:

Answer 21

• MALT lymphoma – a B cell neoplasm, which arises from the mucosa-associated lymphoid tissue present normally in the small intestine and colon. MALT lymphomas can also occur in the stomach in the presence of H. pylori. The stomach under normal conditions does not usually have mucosa-associated lymphoid tissue, but H. pylori induces a chronic inflammatory cell infiltrate from which the lymphoma arises. Treatment of H. pylori may eradicate the lymphoma. MALT lymphomas of the small intestine and colon are not so straightforward as they cannot be treated with antibiotics because there is no infectious agent driving the inflammatory response.
• Enteropathy associated lymphomas – such as those associated with coeliac disease. Usually T cell lymphomas.
• Other B cell lymphomas (mantle cell lymphomas and follicular lymphomas).

Question 22

what is inflammatory bowel disease?

Answer 22

This is divided into Crohn’s disease and ulcerative colitis (UC).

Question 23

what is Crohn’s disease

Answer 23

Crohn’s disease is a granulomatous disease that may affect any part of the gastrointestinal tract from oesophagus to anus but most often affects the small intestine and colon.

Question 24

what is ulcerative colitis

Answer 24

Ulcerative colitis is a nongranulomatous disease limited to the colon.

Question 25

extra intestinal inflammatory manifestations of crown’s and ulcerative colitis

Answer 25

Eyes Uveitis, episcleritis, conjunctivitis

Joints Monoarticular arthritis, ankylosing spondylitis, sacroiliitis

Skin Erythema nodosum, pyoderma gangrenosum, vasculitis

Liver Fatty change, sclerosing cholangitis, hepatitis, cirrhosis

Calculi increase incidence of calculi in both the urinary tract and gallbladder

Question 26

aetiology of IBD’s

Answer 26

There is no known aetiological agent for Crohn’s disease or UC although different mechanisms have been suggested and include: inflamm/immuno reactions

Question 27

Crohn’s Disease epidem

Answer 27

It has an increased incidence in whites compared to non whites occurring at any age with a peak incidence of 20-30 years. Smoking is considered a strong risk factor.

Question 28

clinical features of crohn’s disease

Answer 28

It usually has an insidious onset with abdominal pain, diarrhoea and weight loss, or the patient may present with features of perianal disease such as skin tags, fistulae, fissures and abscesses.

When fully developed Crohn’s disease is characterised pathologically by:

• Sharply delimited and typically transmural involvement of the bowel by an inflammatory
process with mucosa damage
• Presence of non caseating granulomas
• Fissuring with the formation of fistulas

Question 29

pathological features of crohn’s disease

Answer 29

The inflammation from Crohn’s disease affects the full thickness of the bowel wall (transmural), with deep fissuring. The islands of residual mucosa surrounded by the deep ulcers give a cobble stone appearance.
Inflammation of the serosa (the external surface of the bowel) results in the mesentery adhering and wrapping around it (fat wrapping). If the serosal surface is inflamed it may adhere onto another structure such as another bowel loop, bladder or the uterus.

If the fissuring ulcers extend, a fistula may develop between these two structures resulting in pneumaturia (air in the urine) and faeces in the urine if the fistula is between bladder and bowel or air or faeces per vaginam if the fistula is between the bowel and the uterus.
The transmural inflammation affects the muscularis propria (the main muscle coat of the bowel), resulting in neuromuscular hyperplasia and thickening of the bowel wall which may result in stricture formation necessitating surgery.

Microscopically there is full thickness ulceration with granuloma formation (although these are only present in ~50% of biopsies usually due to sampling error). There is marked inflammation of the lamina propria with neutrophils entering the epithelium lining crypts (cryptitis), and collections of neutophils destroying crypts (crypt abscesses).

There is a 5-6 fold increase of colonic carcinoma in patients with Crohn’s disease although this is not as high as in patients with UC.

Question 30

ulcerative colitis epi

Answer 30

The disease can occur at any age with a peak incidence at 20-25 years. In the USA whites are more commonly affected than blacks.

Question 31

pathology in ulcerative colitis

Answer 31

C affects the rectum and extends proximally in a retrograde fashion to involve the entire colon (pancolitis). It is a continuous disease process and skip lesions found in Crohn’s disease are not seen. In 10% of patients with severe pancolitis, the distal ileum may develop mild mucosal inflammation (backwash ileitis). The appendix may be involved in both ulcerative colitis and Crohn’s disease and may present as acute appendicitis.

Clinically patients tend to be more unwell than in patients with Crohn’s disease presenting with diarrhoea containing blood and mucus and may even present with toxic megacolon.

Toxic megacolon results from toxic damage to the muscularis propria and neural plexus leading to complete shutdown of neuromuscular function. In this situation the colon progressively distends and may become gangrenous. If not surgically resected the gangrenous tissue may perforate frequently leading to septic complications.
UC is a disease limited to the mucosa in contrast to the transmural inflammation in Crohn’s disease. As a result there is no serosal inflammation and no fat wrapping.

The diffuse ulcerative lesions present in UC are again restricted to the surface mucosa so the fissuring ulcers, fistula formation and thickening of the bowel wall that occur in Crohn’s disease do not occur in UC. Extensive superficial ulceration of the surface mucosa leaves small islands of residual mucosa that look like polyps (pseudo polyps).

At a microscopic level there is diffuse mucosal ulceration with cryptitis and crypt abscess formation as with Crohn’s disease, but it is limited to the mucosa. Granulomas are not a feature. The long standing inflammation may result in crypt distortion.

Question 32

risk of colon cancer in ulcerative colitis

Answer 32

With UC there is an increased risk of dysplasia and colonic carcinoma. The risk increases with the length of time the patient has the disease, classically 20 fold after 10 years, with an absolute risk of colorectal cancer 35 years after diagnosis of 30%. As a result screening is performed in patients with UC comprising regular colonoscopies at 10 year intervals. Screening programmes for UC now indicate that the rate of progression to dysplasia and carcinoma is in fact quite low provided that the initial biopsies were negative for dysplasia.

Question 33

Summary: Crohn’s Disease vs. Ulcerative colitis

Answer 33

CROHN’S DISEASE
Mouth to anus
Skip lesions
Thickened bowel wall Transmural inflammation Granulomas
Deep fissuring ulcers Fistula formation Cancer rare
Non surveillance

ULCERATIVE COLITIS
Colon only
Continuous lesion
Normal bowel wall thickness Mucosal inflammation
No granulomas Pseudopolyp formation
No fistula formation
Cancer common Surveillance

Question 34

what is diverticular disease

Answer 34

Diverticular disease includes both diverticulosis – outpouchings of mucosa through the bowel wall – and diverticulitis, in which the diverticula become inflamed. Solitary and multiple diverticula can occur throughout the colon and small bowel, but diverticular disease, with numerous diverticula, is commonest in the sigmoid colon.

• In about 60% of cases the sigmoid is the only site of diverticula
• Diverticular disease never occurs in the rectum
• It is a disease of the elderly in Western countries, affecting >60% of those over 80, and
is rare in Africa and Asia
• Diverticulosis of the right side of the colon appears to be a different disease, commoner in younger patients and in Orientals

Small intestinal diverticula are commonest in the duodenum and are rarely symptomatic. They are usually an incidental finding.

Question 35

pathogenesis of diverticular disease

Answer 35

Pathogenesis:
• There is an inverse relationship between fibre content of the diet and diverticular
disease. Fibre leads to a large residue in the bowel
• The muscularis propria is thickened, probably because of raised intra-luminal pressure
in the comparatively empty colon

Question 36

complications of diverticular disease

Answer 36

Complications:
• Diverticulitis, which can lead to perforation and abscess formation
• Fistulae – colovesical are the commonest but fistulae can also communicate with the
uterus, vagina, or abdominal wall
• Intestinal obstruction due to an inflammatory mass
• Haemorrhage – the majority of diverticula form at weak points where arteries pass
through the muscularis propria

Question 37

Mallory-Weiss tear

Answer 37

Mallory–Weiss syndrome or gastro-esophageal laceration syndrome refers to bleeding from tears (a Mallory-Weiss tear) in the mucosa at the junction of the stomach and esophagus, usually caused by severe alcoholism, retching, coughing, or vomiting.