Gastrointestinal II Flashcards
Liver functions
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)
Bile production
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.
Bile flow
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.
Bile function
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.
Enterohepatic circulation
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.
Bile breakdown
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.
Liver storage function
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.
Liver and protein
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.
Liver and Carbs
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.
Liver and lipids
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.
Liver in DKA
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.
Liver and reticuloendothelial function
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).
Hiatus hernia: types
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.
Hiatus hernia: sliding
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.
Hiatus hernia: Rolling
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.
Achalasia
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.
Oesophageal cancer
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.
Peptic ulcers: location
1) Duodenum
2) Stomach (Duodenum > gastric)
3) Lower oesophagus
Gastrojejunal anastomosis (gastric drainage procedure)
4) Meckel’s diverticulum which contains gastric mucosa.
Causes of Acute peptic ulceration
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.
Causes of Chronic peptic ulceration
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
Complications of peptic ulcer
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
Gastric cancer
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.
Gastric cancer risk factors
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
IBD: Crohns
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.
IBD: Crohns: Morphology
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.
IBD: Crohns: Complications
SOFT DMC
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.
IBD: Crohns: Extra-GI signs
U CAPE
1) Finger clubbing
2) Erythema nodosum
3) Pyoderma gangrenosum
4) Uveitis
5) Rarely systemic amyloidosis may occur
IBD: UC
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.
