Gastrointestinal II

Question 1

Liver functions

Answer 1

1) Production of bile
2) Storage, e.g. glycogen, vitamins A, D, E and K and B12
3) Metabolism of proteins, fat and carbohydrate
4) Detoxification and inactivation of hormones, drugs and toxin
5) Reticulo-endothelial function via Kupffer cells
6) Haemopoieses (fetus)

Question 2

Bile production

Answer 2

1) Bile is produced continuously at the rate of 500–1500mL/day by hepatocyte secretion and the addition of secretions from the ducts.
2) Bile contains bile salts and HCO3 which aid digestion. Bile acts as an excretory route for bile pigments, cholesterol, steroids and a number of drugs. Bile salts are essential for lipid digestion.
3) HCO3 assists in neutralising gastric acid entering into the duodenum.

Question 3

Bile flow

Answer 3

Three factors regulate bile flow: hepatic secretion, gall bladder contraction, and choledochal sphincter resistance.

1) In the fasting state, pressure in the bile duct is 5–10 cm of water, and bile produced by the liver is diverted into the gall bladder.
2) After a meal the gall bladder contracts, the choledochal sphincter (sphincter of Oddi) relaxes, and bile enters the duodenum in squirts as ductal pressure intermittently exceeds sphincteric pressure.
3) During contraction, pressure in the gall bladder reaches 25cm of water and that in the bile duct 15–20cm of water. More than 90% of the bile salts secreted into the small intestine are reabsorbed, largely in the terminal ileum, and return to the liver in the portal circulation.
4) The total pool of bile salts is recycled as many as 6–8 times per day.
5) Secretin increases in the production of HCO3 rich secretion from the duct epithelium. Also under the effect of secretin, the volume flow of bile increases, but the content of bile acids does not increase.

Question 4

Bile function

Answer 4

1) Bile salts are steroid molecules formed from cholesterol by hepatocytes.
2) The primary bile salts synthesized in the liver are cholate and chenodeoxycholate.
3) Intestinal bacteria alter these primary bile salts to produce secondary bile salts by a process of dehydroxylation.
4) Secondary bile salts are deoxycholate and lithocholate. Deoxycholate is reabsorbed and enters bile while lithocholate is insoluble and is excreted in faeces.
5) Bile salts are detergents creating micelles. Lecithin and cholesterol, other constituents of bile, are transported in bile within micelles-aggregates the fat soluble material within aqueous solution.
6) Lecithin increases the amount of cholesterol that can be solubilised in the micelles. If more cholesterol is present in the bile than can be solubilised in micelles, crystals of cholesterol may form which is a nidus for development of cholesterol gallstones.

Question 5

Enterohepatic circulation

Answer 5

1) Bile salts remain in the intestinal lumen throughout the jejunum, where they are responsible for fat absorption.
2) More than 80% of bile salts are actively absorbed in the distal ileum and pass back in the portal blood to the liver, where they are resecreted.
3) The bile salts that are not absorbed enter the colon, where they are converted to secondary bile salts, some of which are reabsorbed in the colon, the remainder being lost in the faeces.
4) The entire bile salt pool circulates twice through the enterohepatic circulation during each meal, recycling occur- ring 6–8 times per day. About 10–20% of the total bile salt pool is lost in the stool daily, the amount being restored by hepatic synthesis.

Question 6

Bile breakdown

Answer 6

1) The breakdown of red cells by the reticulo-endothelial system results in the degradation of the haem groups of haemoglobin, with the formation of biliverdin.
2) Biliverdin is reduced to bilirubin which enters the blood stream, attaches to albumin, and is carried to the liver. This is unconjugated bilirubin.
3) In the liver it is conjugated with glucuronic acid, making it into the water soluble bilirubin diglucuronide (conjugated bilirubin).
4) This is excreted in the bile and enters the intestine, where it is reduced by intestinal bacteria, resulting in urobilinogen and stercobilinogen.
5) Urobilinogen is readily absorbed from the gut and passes back to the liver, where it is taken up and released back into the bile. A small amount of absorbed urobilinogen enters the systemic circulation and is excreted in the bile as urobilin. Stercobilinogen is excreted in the faeces as stercobilin.

Question 7

Liver storage function

Answer 7

The liver stores glycogen, vitamins A, D, E and K and vitamin B12, iron and copper. The liver contains a large store of vitamin B12. Even if absorption totally ceases, the store will last for 3–6 years.

Question 8

Liver and protein

Answer 8

Protein catabolism results in the deamination of amino acids, with the formation of ammonia. Ammonia is dissipated by conversion to urea in the liver. The liver synthesises all non-essential amino acids and all the plasma proteins with the exception of the gammaglobulins, which are produced by plasma cells.

Question 9

Liver and Carbs

Answer 9

1) Liver and skeletal muscle are the two major sites of glycogen storage.
2) When blood glucose levels are high, glycogen is deposited in the liver (glycogenesis).
3) When blood glucose is low, liver glycogen is broken down to glucose (glycogenolysis), the glucose being released into the blood.
4) The liver is also a major site of gluconeogenesis, i.e. the conversion of amino acids, lipids, or simple carbohydrates sub-stances, e.g. lactate, into glucose. The liver can thus perform glycogenesis, glycogenolysis, or gluconeogenesis, depending upon the hormonal stimulus to the hepatocytes.

Question 10

Liver and lipids

Answer 10

1) Hepatocytes synthesise and secrete very low density lipoproteins and other lipoproteins which are a major source of cholesterol and triglycerides for most tissues in the body.
2) Hepatocytes are the principal source of cholesterol in the body and are the major site of excretion of cholesterol. In certain physiological (starvation) and pathological (diabetic ketoacidosis) states, ß-oxidation of fatty acids provides a major source of energy for the body e.g. ketones.

Question 11

Liver in DKA

Answer 11

1) Diabetic ketoacidosis is the result of severe insulin deficiency combined with excessive glucagon production. The altered hormonal state promotes lipolysis, gluconeogenesis and glycogenolysis while inhibiting glycolysis.
2) This results in over- production of glucose by the liver. Peripheral tissues cease to utilise glucose because of low insulin levels and become dependent on fatty acids and ketone bodies. In diabetic ketoacidosis the production of ketone bodies continues unchecked.
3) This does not occur in starvation, as the level of ketone bodies is controlled by insulin levels which, although low, are sufficient to inhibit further lipolysis.

Question 12

Liver and reticuloendothelial function

Answer 12

1) The reticulo-endothelial function of the liver is carried out by the Kupffer cells which line the hepatic sinusoids.
2) They remove bacteria and toxins absorbed from the colon and which arrive in the liver via the portal circulation. They also remove effete and abnormal erythrocytes from the blood.
3) In the embryo, haemopoiesis occurs in the liver, the bone marrow gradually taking over after the twentieth week of gestation. In a number of diseases, e.g. chronic haemolytic anaemia or megaloblastic anaemia, foci of haemopoiesis may appear in the liver (extramedullary haemopoiesis).

Question 13

Hiatus hernia: types

Answer 13

Commonest mechanical disorder of the oesophagus. It implies that part of the stomach is above the oesophageal opening in the diaphragm. There are two types: sliding and rolling.

Question 14

Hiatus hernia: sliding

Answer 14

Sliding This is the most common type. Obesity and raised intra-abdominal pressure are contributory factors, but loss of diaphragmatic muscular tone may also occur. Pregnancy is also a contributing factor. Occasionally, sliding hiatus hernia may occur in apparently normal people. The stomach ‘slides’ through the oesophageal opening in the diaphragm. Reflux occurs with consequent chronic oesophagitis.

Question 15

Hiatus hernia: Rolling

Answer 15

Rolling The fundus of the stomach passes along- side the oesophagus into the chest. The cardio- oesophageal junction remains intra-abdominal, and reflux does not occur. The presence of the fundus of the stomach alongside the lower oesophagus may lead to dysphagia. The fundus may become incarcerated, and strangulation with perforation may occur.

Question 16

Achalasia

Answer 16

1) This occurs most frequently in the fourth decade of life.
2) There is an incomplete relaxation of the lower oesophagus, with increased resting pressure in the lower oesophageal sphincter.
3) Peristalsis is absent over the affected segment. The cause of the condition is unknown, but there is reduction or absence of ganglion cells in the myenteric plexus.
4) Above the involved area, the oesophagus dilates and food collects in the dilated oesophagus. Dysphagia occurs and is worse for liquids than solids.
5) Overspill from the dilated oesophagus into the bronchial tree may result in pneumonitis and lung abscess.
6) Carcinoma complicates achalasia in 3% of cases. It is usually of the squamous cell variety.

Question 17

Oesophageal cancer

Answer 17

1) Most carcinomas of the oesophagus squamous
2) In the lower third, adenocarcinomas are the predominant type.
3) Squamous cell carcinoma usually commences as an ulcer, spreading to become annular and constricting, causing dysphagia. Dysplasia usually precedes malignant change.
4) Lymphatic spread within the submucosa occurs beyond the recognisable margins of the tumour viewed endoscopically. Lymphatic metastases occur early. Local extension within the mediastinum occurs and may result in tracheo-oesophageal fistulae.
5) Invasion into the aorta may occur, with fatal haemorrhage. Most patients die of local spread and bronchopneumonia.
6) Haematogenous spread to the liver and lungs may occur. By the time of presentation the tumour has often spread to adjacent organs, and surgical resection is only possible in 30–40%. The remainder require palliation.
7) Prognosis is extremely poor, most patients surviving less than six months. The five-year survival rate is only 5%.
Other malignant tumours of the oesophagus are rare. Malignant melanomas, small cell anaplastic carcinomas, and sarcomas may occur.

Question 18

Peptic ulcers: location

Answer 18

1) Stomach
2) Duodenum
3) Lower oesophagus
Gastrojejunal anastomosis (gastric drainage procedure)
4) Meckel’s diverticulum which contains gastric mucosa.

Question 19

Acute peptic ulceration

Answer 19

Can be part of an acute gastritis secondary to severe stress or severe hyperacidity.

1) Steroids
2) NSAIDs
3) Aspirin
4) Excessive alcohol
5) Acute pancreatitis
6) Major trauma/head injury (Cushing’s ulcer)
7) Burns (Curling’s ulcer)
8) Zollinger–Ellison syndrome may lead to multiple acute ulcers in the stomach, duodenum and occasionally the proximal jejunum.

Question 20

Chronic peptic ulceration

Answer 20

1) Acid hypersecretion

2) helicobacter-associated gastroduodenitis
3) Non-steroidal anti-inflammatory drugs
4) Steroids
5) Smoking
6) Alcohol
7) Diet
8) Stress
Other associations:
1) Uraemia
2) Hyperparathyroidism
3) Hypercalcaemia
4) Chronic obstructive airways disease
5) Alcoholic cirrhosis

Question 21

Complications

Answer 21

1) Perforation resulting in peritonitis
2) Bleeding due to an erosion of a vessel in the base of the ulcer
3) Penetration into underlying structures e.g. pancreas or liver
4) Scarring – this may result in pyloric stenosis
5) Malignant change – this may occur rarely in gastric
ulcers but never in duodenal ulcers

Question 22

Gastric cancer

Answer 22

High in incidence in Japan and China where the intake of dietary nitrate is high.
Eating smoked fish and highly spiced foods have been implicated.
There has been a marked increase in the incidence of adenocarcinoma of the proximal stomach, especially around the cardia, with a corresponding decrease in incidence of distal gastric cancer.

Question 23

Gastric cancer risk factors

Answer 23

1) Increasing age
2) 90% of gastric cancers occur in those aged over 55 years
3) More common in men than women
4) Helicobacter pylori; there is a 2.5-fold increased risk of gastric cancer in infected individuals.
5) Diets with low levels of fresh fruit and 
vegetables increase the risk of gastric cancer.
6) Smoking;
7) Blood group A
8) Pernicious anaemia;
9) Atrophic gastritis;
10) Menetrier’s disease
11) Previous gastric surgery; following partial 
gastrectomy the risk is increased 3–6 fold with a 
peak 20–30 years after surgery
12) Benign gastric ulcer;
13) Loss of expression of cell adhesion modules including E-chadherin and β-catenin, mutations and deletions of tumour suppressor genes, notably p53, K-ras and the APC gene, and over-expression of oncogenes, e.g. c-myc and erbB-2 have been demonstrated

Question 24

IBD: Crohns

Answer 24

1) Chronic inflammatory disorder of unknown aetiology.
2) It affects the small bowel most commonly, but any part of the gastrointestinal tract from the mouth to the anus may be affected.
3) Characterised by a transmural inflammation with non- caseating granulomas. Thickened and fissured bowel leads to intestinal obstruction and fistula formation.

Question 25

IBD: Crohns: Morphology

Answer 25

1) GHLA-DR1, HLA-DQw5, are more frequent in patients with Crohn’s disease than normal controls.
2) Crohn’s disease is classically segmental, with areas of involved bowel separated by normal bowel known as ‘skip’ lesions.
3) Small discrete ulcers similar to aphthous ulcers of the mouth, hence often described as aphthoid, develop on the mucosa.
4) Later, more characteristic longitudinal ulcers develop, progressing into deep fissures.
5) Fibrosis later occurs leading to narrowing of the bowel lumen. This narrowing can be seen on a barium enema where only a narrow column of barium passes through the affected area, giving rise to Cantor’s ‘string’ sign.
6) Where longitudinal fissures cross oedematous transverse folds of mucosa, a cobblestone appearance results.
7) The regional lymph nodes show reactive hyperplasia and occasionally granulomas.
8) Microscopy shows a transmural inflammation, demonstrating collections of lymphocytes, plasma cells and non-caseating granulomas.

Question 26

IBD: Crohns: Complications

SOFT DMC

Answer 26

1) Widespread involvement of the small intestine may lead to malabsorption syndromes, and extensive surgery may lead to ‘short bowel’ syndrome
2) Fistula formation is common and may lead to enterocutaneous fistulae after surgery.
3) >50% patients have anal lesions: either skin tags, fissures, or fistulae.
4) Acute complications include intestinal obstruction, perfo- ration, haemorrhage, and toxic dilatation (rare in UC)
5) There is also an increased risk of carcinoma in both large and small bowel.
6) Gallstones and renal calculi may occur as a result of malabsorption syndromes.

Question 27

IBD: Crohns: Extra-GI signs

U CAPE

Answer 27

1) Finger clubbing
2) Erythema nodosum
3) Pyoderma gangrenosum
4) Uveitis
5) Rarely systemic amyloidosis may occur

Question 28

IBD: UC

Answer 28

Ulcerative colitis is a chronic inflammatory disease which involves the whole or part of the colon. The inflammation is initially confined to the mucosa and nearly always involves the rectum, extending to involve the distal or whole colon. In severe cases the inflammation may extend into the muscle coats.

Question 29

IBD: UC: RF

Answer 29

1) There is an association with HLA-DR2.
2) Association with diseases that are known to have a genetic predisposition, e.g. ankylosing spondylitis and sclerosing cholangitis.
3) Ulcerative colitis is a diffuse inflammatory disease confined initially to the mucosa.
4) Unlike Crohn’s disease it is confined to the large intestine and is continuous in its distribution.
5) In some cases it is confined to the rectum (proctitis), or to the rectosigmoid (distal proctitis).
6) Abscesses form in the crypts of Lieberkuhn, penetrate the superficial mucosa, spread horizontally and cause the overyling mucosa to slough.
7) The margins of the ulcers are raised as mucosal tags that project into the lumen (inflammatory pseudopolyps). Except in the most severe forms the muscle layers are spared. Occasionally the last few centimetres of the terminal ileum is ulcerated, i.e. the so-called condition of ‘backwash’ ileitis.

Question 30

IBD: UC: Complications

PURE SPICE

Answer 30

1) Toxic dilatation
2) Haemorrhage
3) Stricture and perforation
4) Carcinomas may occur, the overall incidence being around 2%.

Question 31

IBD: UC: Extra-GI

Answer 31

1) Extracolonic complications include seronegative arthritis (sacroilitis, ankylosing spondylitis)
2) Sclerosing cholangitis
3) Cirrhosis
4) Pericholangitis
5) Iritis
6) Uveitis
7) Episcleritis
8) Erythema nodsum
9) Pyoderma gangrenosum
10) Apthous stomatitis
11) Rarely systemic amyloidosis may occur.

Question 32

Diverticular disease

Answer 32

1) Diverticulae are herniations of mucosa through the colonic wall.
2) They occur at weak points where blood vessels pierce the bowel wall.
3) They consist of mucosa and submucosa that have pierced the muscular coats. They are pulsion diverticula, being pushed out by increased intraluminal pressure.
4) Although they may involve the whole of the colon, they are most common in the sigmoid colon.
5) Patients with diverticular disease have shortened, thickened colonic muscle which reflects work hypertrophy from years of a low fibre diet and consequent small hard stools.
6) High intraluminal pressures occur, pushing the diverticulae out through the wall.

Question 33

Diverticular disease complications

Answer 33

1) Diverticulitis
2) Perforation:
a. (i) into the local tissues, where it becomes walled off and leads to a paracolic abscess
b. (ii) into the general peritoneal cavity, giving rise to faecal peritonitis
c. (iii) into an adjacent viscus:
i. colovesical fistula (bladder)
ii. vaginocolic fistula (vagina)
iii. ileocolic fistula (ileum)
3) Bleeding, which can be profuse, may occur from erosion into an adjacent vessel.
4) Repeated attacks of diverticulitis may result in fibrosis and narrowing of the bowel, leading to intestinal obstruction.

Question 34

Volvulus

Answer 34

1) Volvulus is rotation of a segment of the intestine on an axis formed by its mesentery.
2) It may cause partial or complete obstruction of the intestine and may result in strangulation of the bowel.
3) Volvulus may occur around a fixed point: e.g. on the apex of a loop of bowel, e.g. fixation of the bowel to the back of the umbilicus via a Meckel’s diverticulum or an adhesive band.
4) A long sigmoid colon is a predisposing factor in sigmoid volvulus. Caecal volvulus may occur if the caecum is hypermobile owing to incomplete embryological fixation of the ascending colon.
5) As the bowel twists on its mesentery, closed loop obstruction occurs when the rotation has reached 180 degress. At 360 degrees, strangulation occurs which leads to gangrene and perforation.

Question 35

Intussusception

Answer 35

1) Invagination of one segment of bowel into another in a ‘telescoping’ fashion.
2) The segment of bowel invaginating is the intussusceptum, the adjacent or receiving segment is the intussuscipiens.
3) The commonest form occurs when the terminal ileum is telescoped into the right side of the colon – an ileocolic intussusception.
4) The apex of the intussusception may be a
a. Polyp
b. Meckel’s diverticulum
c. Intra- mural haematoma
d. Hypertrophied Peyer’s patch.
e. The process of intussusception may result in gangrene of the intussusceptum.

Question 36

Intestinal ischaemia

Answer 36

1) This may be due to occlusive or non-occlusive ischaemia.
2) Occlusive ischaemia occurs as a result of thrombosis or embolism reducing flow or completely occluding a vessel.
3) Non-occlusive ischaemia results from reduced flow in the vessel, with failure to sustain adequate flow to sustain mucosal integrity, e.g. hypotension, vasoconstriction, or abnormal blood viscosity.
4) Total vascular occlusion results in intestinal infarction, the extent depending on the degree of collateral supply: e.g. with superior mesenteric artery occlusion, approximately 25 cm of jejunum will survive via flow from the coeliac axis via anastomosis between the superior and inferior pancreatico-duodenal arteries.

Question 37

Acute ischaemia of colon

Answer 37

This may result in:

1) Mucosal infarction
2) Mural infarction (not involving the muscularis propia)
3) Transmural infarction
4) Mucosal infarction often results from systemic hypotension and may be followed by complete regeneration.
5) Mural infarction is followed by fibrous stricture formation.
6) Transmural infarction results in gangrene of the involved area, with subsequent perforation. Surgical treatment is required in the latter case.

Question 38

Chronic ischaemia of colon

Answer 38

Chronic mesenteric ischaemia describes a condition where there is inadequate blood flow to the small intestine because of partial occlusion of the superior mesenteric artery.

1) The condition is sometimes described as mesenteric claudication or mesenteric angina.
2) It occurs after a meal when the blood flow is inadequate to cope with the increased motility, secretion and absorption required.
3) Cramping upper, or central abdominal pain occurs about 20min after food. Patients become afraid to eat because of the pain, and lose weight.
4) In the large bowel, chronic ischaemia may lead to ischaemic colitis.
5) This is usually a mural infarction and results in dark red bleeding initially from ulcerated ischaemic mucosa.
6) It results usually at the ‘watershed’ area around the splenic flexure of the colon.
7) The colon loses its normal outline and appears as a ‘drain pipe’ on barium enema. Strictures may occur.

Question 39

Haemorrhoids

Answer 39

Haemorrhoids are vascular cushions occurring in the submucosa of the lower rectum and anal canal. There is an internal component covered by mucosa and an external component covered by skin.

Question 40

Internal haemorrhoids

Answer 40

1) Internal haemorrhoids are a plexus of superior haemorrhoidal veins above the mucocutaneous junction.
2) They occur in three primary positions when the anal canal is viewed with the patient in the lithotomy position.
a. 3 o’clock
b. 7 o’clock
c. 11 o’clock

Question 41

External haemorrhoids

Answer 41

External haemorrhoids occur below the mucocutaneous junction in the tissue beneath the epithelium of the anal canal and the skin of the perianal region. The two plexuses of internal and external haemorrhoids anastomose freely. The internal haem- orrhoids drain via the superior haemorrhoidal veins and the portal vein, while the external haemorrhoids drain into the systemic circulation. Hence they are a site of portosystemic anatomosis.

Question 42

Haemorrhoids: Clinical

Answer 42

Haemorrhoids may become symptomatic due to straining with chronic constipation, pregnancy, obesity, low fibre diet, or portal hypertension.
Haemorrhoids are classified into three categories:
(i) First degree, which manifest only by bleeding
(ii) Second degree, which manifest by prolapsing on defaecation but return spontaneously
(iii) Third degree, which prolapse and require manual reduction. Occasionally, haemorrhoids prolapse and become congested and oedematous and will not reduce.
The venous return is obstructed by pressure from the anal sphincter, and thrombosis occurs. Infarction of the overlying skin and muscle may occur if surgical relief is not carried out. Rarely, septic emboli may occur from thrombosed piles and result in liver abscesses.

Question 43

Anorectal abscess

Answer 43

Infection occurs in an anal crypt and extends into one of the pararectal spaces causing abscess formation.
Infecting organisms include:
(i) E. coli
(ii) Proteus vulgaris
(iii) Faecal streptococci
(iv) Bacteroides
(v) Staph. Aureus
The infection is usually with mixed organisms.
Abscesses may also result from:
(i) infection of hair follicles, sweat glands and sebaceous glands
(ii) Following excoriation from scratching in pruritus ani; infection of a fissure- in-ano
(iii) Infection of a perianal haematoma
(iv) Infection of a thrombosed haemorrhoid
(v) Following injection of haemorrhoids
(vi) Crohn’s disease
See anorectal abscess diagram

Question 44

Fissure in ano

Answer 44

A fissure represents a breach in the anal epithelium overlying the internal anal sphincter commencing just below the dentate line.

1. They are painful because they occur in the area of somatic sensation below the dentate line.
2. They are most common in the midline posteriorly because the anal mucosa is least well supported there, being in the ‘V’ shape where the two levator ani muscles join posteriorly, at the point of acute angulation between anal canal and rectum.
3. A small number occur in the midline anteriorly.
4. Chronic inflammation occurs in the fissure. Above the fissure there is usually a hypertrophied papilla adjacent to the anal crypt.
5. Below the fissure there is usually a tag of oedematous fibrotic skin called a sentinel pile because it stands as a sentinel just below the fissure.
6. Fissures often occur as a result of chronic constipation, passage of a hard stool tearing the anal mucosa.
7. Other causes include Crohn’s disease, tuberculosis, and carcinoma of the anal canal, which must be carefully distinguished from a benign simple fissure-in-ano.

Question 45

Fistula in ano

Answer 45

A fistula is an abnormal connection between two epithelial surfaces.

1. By definition it must have at least two openings, as opposed to a sinus which is a blind-ended track with only one opening onto an epithelial surface.
2. Most fistulae-in-ano originate in the anal crypts. An abscess is formed and, when it ruptures, a fistula occurs.
3. Perianal abscesses should be incised and drained promptly, but even then a fistula may result.
4. Fistulae may result from perianal Crohn’s disease, tuberculosis, or neoplasm.

Question 46

Perianal haemoatoma/Thrombosed pile

Answer 46

This is sometimes called a thrombosed external pile.

1. It is characterised by a tense, painful, bluish rounded elevation beneath the skin at the anal verge.
2. It may occur following a sudden increase in venous pressure, e.g. heavy lifting, straining, or paturition.
3. There is usually no previous history of, or association with, internal haemorrhoids.
4. Spontaneous resolution occurs, but evacuation of the thrombus is usually undertaken.
5. Differentiation from a prolapsed internal haemorrhoid is important, as treatment is different.

Question 47

Polyps see diagram

Answer 47

Polyps see diagram

Question 48

Polyps: adenomas

Answer 48

1. Most adenomas are tubular, tubulovillous, or villous. Adenomas may give rise to adenocarcinoma. The malignant potential of an adenoma depends on size, growth pattern, and degree of epithelial dysplasia.
2. Malignant change is found in
   a. 1% of adenomas under 1cm in diameter
   b. 10% of adenomas 1–2cm in diameter
   c. 40% larger than 2 cm.
3. Malignant potential depends upon the type of adenomas: about 5% of tubuloadenomas, 20% of tubulovillous adenomas and 40% of villous adenomas become malignant.
4. Sessile lesions are more likely to become malignant than pedunculated ones.
5. Villous adenomas are usually sessile and may grow to a very large size. They may secrete copious amounts of potassium rich mucus, resulting in hypokalaemia.

Question 49

Inflammatory polyps

Answer 49

Inflammatory polyps (pseudopolyps) 
These are associated with ulcerative colitis and result from mucosal ulceration.

Question 50

Hamartomas

Answer 50

1. These are rare.
2. They may be solitary, e.g. juvenile polyps
3. May be present throughout the gastrointestinal tract as in Peutz–Jegher’s syndrome.

Question 51

Malignant epithelial polyps

Answer 51

1. The vast majority of adenocarcinomas arise within pre-existing adenomas.
2. A very small number of polyps are carcinoid tumours with a low malignant potential.
3. Complete local excision is usually curative.

Question 52

Familial polyposis coli (familial adenomatous poly- posis – FAP)

Answer 52

1. This is a rare condition inherited as an autosomal dominant, with equal sex incidence.
2. Hundreds of polyps of various sizes carpet the colon and rectum.
3. Cancer develops before the age of 40 in almost all untreated patients.
4. The gene responsible for FAP is on the long arm of chromosome 5.
   FAP results from point mutations in a tumour suppressor gene, APC, localised on chromosome 5q and subsequent deletion of the accompanying normal allele results in loss of tumour suppressor function that leads to colorectal cancer.

Question 53

Gardner’s syndrome

Answer 53

This is FAP-associated with desmoid tumours, osteomas of the mandible or skull, and sebaceous cysts.
Desmoid tumours
Osteomas
Multiple polys
Epidermoid cysts
Sebacious cysts

Question 54

Colorectal cancer aetiology: Syndromes

Answer 54

(1) FAP
(2) Autosomal dominant hereditary non-polyposis colorectal cancer (HNPCC). There are 
two types:
1. Cancer family syndrome (CFS: Lynch syndrome 2 with early onset – age 20–30 years) and associated with other adenocarcinomas, especially endometrial carcinoma
2. Hereditary site-specific colon cancer (HSSCC: Lynch syndrome 1) which shows the same characteristics except for extracolonic carcinomas.

Question 55

Colorectal cancer aetiology: Risk factors

Answer 55

1) First degree relatives of patients with colorectal cancer have a 2–3 fold increased risk of the disease
2) Dietary factors may be important, i.e. low fibre, high fat diets. High fat leads to an increase in bile acid production, and bile acids are promoters of carcinogenesis. Dietary fibre contains plant lignans which are converted to human lignans by bacterial action in the colon. Lignans may protect against cancer. Low fibre diets also prolong intestinal transit time and, therefore, allow for a prolonged contact between any carcinogens and the bowel mucosa;
3) Inflammatory bowel disease – carcinoma may develop. There is a greater risk in ulcerative colitis than Crohn’s disease
4) Schistosomal colitis
5) Exposure to irradiation
6) Ureterocolostomy – this 
operation is rarely performed nowadays.

Question 56

Colorectal cancer: Molecular genetics

Answer 56

1) The oncogenes most frequently altered in colorectal cancer are c-Ki-ras and c-myc.
2) Loss or mutations of tumour suppressor genes may also occur.
3) Mutations and deletions of the APC gene have also been identified in sporadic (non-hereditary) colorectal cancer.
4) Other genes implicated are MCC, DCC, BCL-2 and p53 genes.
5) BCL-2 is a key inhibitor of apoptosis; over-expression renders the cell more resistant to degrees of damage which would normally result in apoptosis and elimination of the cell.
6) The p53 gene is also implicated in colorectal cancer. The p53 gene checks the integrity of the genome prior to mitosis. The p53 gene product effects the G1 phase of the cell cycle, allowing time for successful DNA repair or diverting cells towards apoptosis.

Question 57

Colorectal cancer: Blood borne metastasis

Answer 57

The liver and lungs are most common

Question 58

Lymph node metastasis

Answer 58

1) Regional lymph nodes along the vessels are involved but not necessarily in a progressive and orderly fashion.
2) Positive nodes may be found at some distance from the primary, intervening nodes being unaffected.
3) Retrograde spread along lymphatics may occur, with metastases in the lymph nodes at the porta hepatis resulting in obstructive jaundice.

Question 59

Transcoelomic spread

Answer 59

This may occur, producing seedings on serosal surfaces, with resulting ascites.
Rarely seedings on the ovaries may occur with development of Krukenberg-type tumours, but this is more common with carcinoma of the stomach.

Question 60

Colorectal cancer: Complications

Answer 60

1. Obstruction
2. Perforation
   a. Direct perforation of the tumour
   b. Perforation of the caecum in closed loop obstruction with a competent ileocecal valve
   c. Perforation into an adjacent organ with development of a fistula, e.g. colovesical, and symptoms relating to direct extension

Question 61

Prognosis: Dukes classification

Answer 61

Dukes A:
Confined to the bowel wall (90% survival 5yrs)

Dukes B:
Spread through bowel wall (70% survival)

Dukes C:
Spread to lymph nodes (30% survival)

Dukes D:
Distand metastasis

Question 62

Carcinoid tumours

Answer 62

1. These are apudomas that arise from the enterochromaffin cells throughout the gut.
2. They may be associated with multiple endocrine neoplasia (MEN Type I and Type II).
3. They are commonest in the midgut, the appendix being the most common site and the small intestine the second most common location.
4. A small number occur in the large bowel. Mostly they are firm, yellowish, submucosal nodules. Those in the appendix are often an incidental finding at appendicectomy.
   Small tumours are usually asymptomatic. Approximately 30% of small bowel carcinoids cause symptoms such as obstruction, pain or bleeding or the carcinoid syndrome.

Question 63

Carcinoid syndrome

Answer 63

1. Extensive metastases from carcinoid, particularly to the liver, result in a clinical syndrome, i.e. carcinoid syndrome, which consists of :
   a. Cutaneous flushing
   b. Diarrhoea
   c. Bronchoconstriction with wheezing
   d. Right-sided cardiac valvular disease (usually pulmonary stenosis) due to collagen deposition.
2. Biologically active substances secreted by carcinoids are usually inactivated in the liver, but when hepatic metastases occur, these substances are released directly into the systemic circulation, where they produce the symptoms of carcinoid.
3. The principal cause of the symptoms and signs of carcinoid syndrome is 5-hydroxytryptamine (5-HT). The 5-HT in the circulation is degraded to 5-hydroxy- indole-acetic acid (5-HIAA), which can be measured in the urine as a diagnostic marker of the disease.

Question 64

Appendicitis: risk factors

Answer 64

1) Faecolith (hard pellets of faeces which reside in the appendiceal lumen)
2) Food residues
3) Lymphoid hyperplasia (in childhood and with some 
viral infections)
4) Occasionally associated with carcinoid tumour
5) Specific inflammations including:
a. Yersinia pseudotuberculosis
b. Typhoid
c. Tuberculosis
d. Actinomycosis
e. Crohn’s disease

Question 65

Appendicitis: pathology

Answer 65

1) Acute inflammation results from a breach in the epithelium which permits infection in the wall by bowel flora.
2) Ulceration occurs and a polymorph response with exudation of cells and fibrin into the lumen.
3) Eventually all layers of the appendiceal wall are involved, with inflammation of the serosal surface.
4) Fluid exudate increases within the wall and increases tissue pressure and this compresses the veins until such time as venous pressure equates to arterial pressure and ischaemia occurs.
5) Gangrene and perforation ensue. 

6) Appendicitis is uncommon at the extremes of life, the lumen of the appendix being relatively large in infancy and the diet soft, while in old age the appendix tends to atrophy and the lumen becomes obliterated.

Question 66

Appendicitis: Complications

Answer 66

1) Resolution
2) Perforation with generalised peritonitis
3) Perforation within local adhesions, resulting in an appendix mass which may subsequently suppurate and form an appendix abscess

Question 67

Anus: Warts (condyloma acuminata)

Answer 67

1. Warts are the commonest benign tumour of the anal canal.
2. Usually associated with HPV infection and usually sexually transmitted.
3. There is an increased risk of anal carcinoma.

Question 68

Anus: Warts (condyloma acuminata) and AIN

Answer 68

1. Intraepithelial neo- plasia (AIN) is associated with condylomas and HIV positivity.
2. There is an increased incidence in homosexual males.
3. Dysplastic changes or carcinoma in situ may be seen in the squamous epithelium and is graded AINI to AINIII.
4. These changes are similar to cervical intraepithelial neoplasia (CIN) in females, which may coexist.
5. AINIII may progress to invasive squamous cell carcinoma and is associated with HPV16.
6. AIN may occur in the absence of pre-existing condylomata and HIV positivity.

Question 69

Anal cancer: @ the anal margin

Answer 69

1. Bowen’s disease (intraepithelial squamous cell carcinoma) and squamous cell carcinoma may occur at the anal margin, the latter being the most common.
2. It is distinguished from carcinoma of the anal canal.
3. It is more common in elderly men and is usually a well-differentiated keratinising carcinoma.
4. Squamous cell carcinomas appear as ulcerated lesions with rolled margins and cause pain or bleeding.
5. Lymphatic spread is to the inguinal nodes.
6. The five- year survival rate is 80% with appropriate treatment.

Question 70

Anal cancer: @ the anal canal

Answer 70

1. Anal canal tumours are usually poorly differentiated.
2. They are more common in women and have a worse prognosis than those of the anal margin tumours.
3. There are three types of tumour relating to the different types of epithelium in the anal canal, namely:
   a. squamous cell carcinoma (arising below the dentate line)
   b. adenocarcinoma (arising above the dentate line)
   c. ‘basaloid’ carcinoma arising from the transitional zone

Question 71

Spread of anal canal cancer

Answer 71

1. Squamous cell carcinomas grow upwards into the lower rectum and outwards to the sphincters.
2. They spread to the inguinal nodes initially but after invading across the dentate line they may spread to the pelvic nodes.
3. Adenocarcinomas spread to the pelvic nodes initially but may spread to the inguinal nodes if the tumour invades downwards beyond the dentate line.
   Squamous cell carcinomas and ‘basaloid’ carcinomas are radiosensitive.