Flashcards in Gastrointestinal III Deck (47)
1. The main cause is haemolysis:
a. Hereditary spherocytosis (congenital acholuric jaundice)
b. Autoimmune red cell destruction
2. Excessive production of bilirubin occurs as a result of break- down of red cells.
3. The bilirubin is unconjugated and, therefore, is not excreted in the urine (hence ‘acholu- ric’ jaundice).
4. The bile may contain so much bilirubin that pure pigment stones are formed.
5. Mismatched transfusions causing extensive haemolysis will result in acholuric jaundice, as will the absorption of large haematomas.
1. Acute viral hepatitis
2. Alcohol-induced hepatic damage
3. Drug- induced liver injury
4. Decompensated cirrhosis
Post hepatic jaundice
Obstruction of the extrahepatic bile ducts is an important cause of jaundice surgically. Important causes include:
1. Congenital biliary atresia
2. Gall stone impaction in the common bile duct
3. Strictures of the bile duct (e.g. following cholecystectomy)
4. Sclerosing cholangitis
5. Carcinoma of the bile duct
6. Extrinsic compression, e.g. carcinoma of the head of the pancreas
7. Malignant nodes in the porta hepatis
8. Damage to the bile duct at surgery.
In this type of jaundice the bilirubin is conjugated and the urine is dark. As bile cannot get into the intestine due to obstruction, the stools are pale.
1. In acute liver injury, transaminases (AST and ALT) are elevated, as is the bilirubin.
2. Liver damage results in impairment of bilirubin conjugation and also failure to excrete conjugated bilirubin and also any stercobilinogen absorbed from the gut.
3. The urine is darkened by the presence of excessive bilirubin and urobilin that cannot be excreted by the liver.
4. As liver damage progresses, urobilinogen disappears from the urine because little or no bilirubin is being excreted by the liver.
Aetiological factors include:
1. Cirrhosis – over 70% of hepatocellular carcinomas in the UK arise in cirrhotic livers
2. Geographical – common in Africa and the Far East
3. Hepatitis B
4. Aflatoxins – these are mycotoxins produced by Aspergillus flavus. The fungus contaminates food stored in hot, humid conditions and may be responsible for the geographical distribution
5. Anabolic steroids, androgenic steroids, and oral contraceptive agents have been implicated.
Hepatocellular carcinoma spread
1. Spread of the tumour is by intrahepatic veins.
2. Lymphatic spread occurs to lymph nodes at the porta hepatis, but distant metastases are uncommon.
3. Hepatocellular carcinoma produces alpha-fetoprotein which is secreted into the blood stream, where it forms a useful diagnostic marker.
4. The prognosis is poor, most patients being dead within six months of diagnosis.
Adenocarcinoma of bile duct epithelium.
Aetiological factors include the
1. Liver fluke
2. Clonorchis sinensis
3. Primary sclerosing cholangitis (often in association with ulcerative colitis).
4. Distinction of the tumour from metastatic adenocarcinoma can be difficult.
5. The prognosis is poor, most patients being dead within a few months of presentation.
These include simple cysts, hydatid cysts and choledochal cysts
Simple liver cysts
These are usually small and multiple. They may be associated with:
1. Congenital polycystic disease of the kidney
2. Von Hippel Lindau disease
3. Simple cysts of the liver have little clinical significance.
1. These are due to the parasite Echinococcus granulosus.
2. They may reach over 20cm in diameter.
3. They have an outer fibrous, laminated capsule and contain numerous ‘daughter’ cysts.
4. Cyst fluid is highly allergenic, and spillage at surgery may precipitate a Type I anaphylactic hypersensitivity reaction.
These are rare congenital cysts of the bile duct which may be intra- or extrahepatic. They may present with jaundice or cholangitis.
1) Portal venous pressure is normally in the range 7–10mmHg.
2) In portal hypertension, portal pressure exceeds 10mmHg averaging around 20–25mmHg, and may rise as high as 50–60mmHg.
3) Portal hypertension leads to opening up of sites of portosystemic anastomosis.
Portal Hypertension causes: Prehepatic
Pre-hepatic (obstruction of the portalvein)
1) Congenital atresia or stenosis
2) Portal vein thrombosis
3) Extrinsic compression, e.g. tumour
Portal Hypertension causes: Hepatic
Hepatic (obstruction to portal flow within the liver)
2) Hepatoportal sclerosis
Portal Hypertension causes: Post-hepatic
1) Budd–Chiari syndrome: idiopathic hepatic venous thrombosis
b. Contraceptive pill,
c. Congenital obliteration
d. Tumour invasion of hepatic veins
e. Constrictive pericarditis
Portal venous system anatomy (see diagram) Formation of the portal vein
A portal vessel is one that has capillaries at each end
1) The portal venous system drains blood to the liver from the abdominal part of the alimentary canal (excluding the lower part of the anus)
a. the spleen
b. the pancreas
c. the gall bladder
2) The portal vein is formed by the junction of the splenic vein and superior mesenteric vein behind the neck of the pancreas
3) The inferior mesenteric vein ascends above the point of origin of its artery to enter the splenic vein behind the body of the pancreas.
Portal vein system anatomy: passage of the portal vein
1) The portal vein ascends behind the first part of the duodenum entering the free edge of the lesser omentum in the anterior wall of the foramen of Winslow.
2) At this point the portal vein is immediately posterior to the bile duct and the hepatic artery.
3) The portal vein then ascends to the porta hepatis, where it divides into the right and left branches and breaks up into the capillaries running between the lobules of the liver.
4) These capillaries drain into radicles of the hepatic vein, eventually emptying into the IVC.
5) There are no valves in the portal system, so that obstruction, e.g. due to cirrhosis of the liver, causes a rise in pressure throughout the system.
6) In order for the blood to escape, the blood passes through any anastomosis between the portal and systemic system, and the anastomotic veins become dilated and may bleed.
Portal vein system: Collateral system
The site of collateral pathways between portal and systemic venous systems are as follows:
1) Between the oesophageal branch of the left gastric vein and the oesophageal tributaries of the azygos system
a. In portal hypertension; oesophageal varices will develop that may be the source of severe haematemesis
2) Also forms between superior rectal branch of the inferior mesenteric vein and the inferior rectal veins draining into the systemic system
a. Dilated veins in the anal canal form which can bleed
3) Between the portal tributaries in the mesentery and retroperitoneal veins, resulting in retroperitoneal varices
4) Between the portal veins in the liver, the veins of the abdominal wall via veins accompanying the ligamentum teres in the falciform ligament; this may result in the formation of a group of dilated veins radiating out from the umbilicus, known as a caput Medusae
5) Between portal branches in the liver and the veins of the diaphragm in relation to the bare area of the liver.
Gall stones (cholelithiasis): cholesterol stones
1) Pure cholesterol stones form less than 10% of stones.
a. They are usually solitary (the cholesterol ‘solitaire’), up to 5 cm in diameter, and have a characteristic radial arrangement of crystals on cross- section.
b. Cholesterol stones usually form in bile which is supersaturated with cholesterol.
c. Lecithin is important because lecithin-cholesterol mixed micelles can solubilise more cholesterol than can micelles of bile acids alone.
d. Following Crohn’s disease of the terminal ileum or ileal resection the bile salt pool is reduced because of lack of absorption of bile salts, and the liver can not make good the losses.
e. Such patients are prone to cholesterol stones.
Gall stones (cholelithiasis): Mixed stones
1) In 80% of patients gallstones are composed predominantly of cholesterol with smaller amounts of calcium salts and bile pigments.
a. They are referred to as mixed stones, are usually multiple with a faceted surface, and have a characteristic laminated surface on cross-section.
b. Only about 10% of them contain sufficient calcium to be visible on a plain x-ray.
Females and cholesterol stones
1) Oestrogen increases the hepatic synthesis of cholesterol, and this may explain why females of child- bearing age have a higher incidence of cholesterol stones.
2) Stasis occurs during pregnancy due to the smooth- muscle-relaxing effect of progesterone.
Gallbladder motility and gallstones
Motility of the gall bladder is also decreased during starvation and total parenteral nutrition, due to decreased stimula- tion of the gall bladder by CCK. Stones may also form after vagotomy, because of lack of vagal potentiation of CCK.
Gall stones (cholelithiasis): Pigment stones
1) The major constituent is the calcium salt of unconjugated bilirubin.
2) They are associated with chronic haemolytic disease where there is breakdown of red cells with release of excessive bilirubin.
3) Pure pigment stones occur in sickle cell disease, thalas- saemia and hereditary spherocytosis.
4) Pigment stones are found in the Far East, where they are associated with biliary tract infections with E. coli and Bacteroides fragilis.
5) These organisms produce beta-glucuronidase which splits bilirubin diglucuronide and releases free bilirubin. The latter combines with calcium to form the relatively insoluble calcium bilirubinate.
Consequences of gallstones
1) Inflammation of the gall bladder
a. Acute cholecystitis
b. Chronic cholecystitis
c. Acute-on- chronic cholecystitis
2) Obstructive jaundice due to impaction of a stone at the lower end of the common bile duct
3) Secondary biliary cirrhosis may result
4) Ascending cholangitis
5) Empyema of the gall bladder
7) Gall stone ileus – a fistula occurs between the gallbladder and duodenum, and a large stone enters the small bowel, causing obstruction, usually at the terminal ileum
6) Pancreatitis, usually associated with multiple small
7) Carcinoma of the gall bladder
8) Perforation of the gall bladder
1) Cholecystitis is inflammation of the gall bladder and is usually associated with stones.
2) Occasionally it occurs without stones, i.e. acalculous cholecystitis due to infection with E. coli, Clostridia, or rarely Salmonella typhi.
3) Acalculous cholecystitis may also occur after prolonged starvation or total parenteral nutrition possibly due to stasis.
1) Invariably due to gallstones
2) The gall bladder wall becomes thickened by fibrosis and relatively indistensible.
3) The gall bladder wall is infiltrated with chronic inflammatory cells – lymphocytes, plasma cells and macrophages.
4) Glandular outpouchings are formed by the lining of the mucosa and are known as Aschoff-Rokitansky sinuses.
5) If obstructive jaundice occurs, it is due to a stone impacted in the common bile duct.
6) The gall bladder does not usually distend, as the wall is relatively rigid due to fibrosis consequent on the associated chronic cholecystitis.
1) This occurs when a stone impacts in the neck of the gall bladder in the absence of infection in the bile.
2) The bile is absorbed from the gall bladder, and mucus is secreted into it from the mucus-secreting cells of the epithelium.
3) The lack of inflammation in the wall allows the gall bladder to distend to several times its normal size and usually palpable below the costal margin.
4) The wall of a mucocele is usually very thin and is easily ruptured at surgery.
1) This occurs when a stone impacts in the neck of the gall bladder in the presence of infection in the bile.
2) Suppuration takes places within the gall bladder and the gall bladder distends with pus.
3) A tender gall bladder may be palpable below the costal margin.
Cholesterolosis (Strawberry gallbladder)
1) This is a condition where lipid-laden macrophages accumulate in the gall bladder mucosa to produce yellowish flecks in a reddish mucosa, appearing like the surface of a strawberry – hence the alternative name ‘strawberry gall bladder’.
2) This is often a symptomless condition but may accompany or predispose to cholesterol stones.
Gallbladder tumour: Benign
An ‘adenomyoma’ is usually a fundal nodule composed of glandular structures mixed with hyperplastic smooth muscle fibres. It may be a hyperplastic condition rather than a true neoplasm. Adenomas of the gall bladder are rare and usually present as pedunculated polyps. Both are usually clinically silent but may show up on an ultrasound scan of the gall bladder and raise suspicion of a more sinister lesion.
Gallbladder tumour: Malignant
1) 0.5% of people with longstanding gall stones develop carcinoma of the gall bladder.
2) The tumour is most often an adenocarcinoma, although in 10% of cases squamous cell carcinomas may occur.
3) The tumour is usually advanced at presentation, having invaded directly into the liver or adjacent organs.
4) Infiltration into the bile duct or metastases to the nodes of the porta hepatis will cause obstructive jaundice.
5) Tumours are rarely resectable at presenta- tion, and five-year survival rates are less than 1%.
Congenital bile duct disease
1) Extrahepatic biliary atresia and choledochal cysts.
2) Biliary atresia presents as obstructive jaundice in the neonatal period.
3) A choledochal cyst is a cystic dilatation of the common bile duct, the cyst reaching up to 5cm in diameter.
4) Complications include
a. Obstructive jaundice
b. Cholangitis and stone formation.
c. Malignant transformation may occur.
1) This is a rare condition of unknown aetiology, characterised by non-bacterial inflammatory narrowing of the bile ducts.
2) There is a known association with chronic inflammatory bowel disease, particularly ulcerative colitis.
3) Complications include:
a. chronic biliary obstruction with secondary biliary cirrhosis
b. Episodes of ascending cholangitis
c. Malignant transformation to cholangiocarcinoma
Bile duct cancer
1) 90% are adenocarcinomas.
2) Ulcerative colitis is a common, associated condition.
3) Chronic parasitic infection of the bile ducts is an aetiological factor in the Far East.
4) Malignant transformation of choledochal cysts is also an aetiological factor.
5) Most cases present with obstructive jaundice or ascending cholangitis if infection supervenes.
6) Prognosis is poor, many patients surviving less than a year. The overall five-year survival rate is less than 15%.
1) Gall stone disease
b. Coxsackie virus
4) Hypercalcaemia e.g.hyperparathyroidism
6) Post operative,e.g.after upper GI operations where
pancreas is handled
8) Drugs: corticosteroids, oestrogen-containing
contraceptives, azathioprine, thiazide diuretics
10) Vascular insufficiency e.g.shock, polyarteritis nodosa
11) Scorpion bites
1) The appearances of the pancreas in acute pancreatitis may be explained by release of pancreatic enzymes.
2) Protease release causes widespread destruction of the pancreas and increases further enzyme release, with consequent further damage.
3) Release of lipase causes fat necrosis resulting in characteristic yellowish-white flecks on the pancreas, mesentery and omentum, often with calcium deposition.
4) Other enzymes, e.g. elastase, destroy blood vessels, leading to haemorrhage within the pancreas and a haemorrhagic exudate into the peritoneum.
5) Haemorrhage may be extensive, leading to acute haemorrhagic pancreatitis.
Pancreatitis: Biochemical changes
1) Increased serum amylase. Amylase is released
from the damaged acini and enters the blood stream. The serum amylase is released in the
acute phase (24–48 h) but later falls to normal. Occasionally with acute haemorrhagic pancreatitis the destruction of pancreatic acini is so swift and complete that the serum amylase may not be raised by the time the patient reaches hospital.
2) Hypocalcaemia. This arises because of deposition of calcium in areas of fat necrosis.
3) Hyperglycaemia. This occurs because of associated damage to the pancreatic islets.
4) Abnormal liver function tests may occur, especially raised bilirubin and alkaline phosphatase due to mild obstruction of the bile ducts by oedema.
1) Pancreatic pseudocyst; this is a localised collection of fluid in the lesser sac of peritoneum\pancreatic abscess;
2) Pancreatic necrosis
3) Stress-induced gastric erosions resulting in
haematemesis or melaena
4) Acute renal failure
5) Toxic psychosis
6) Multiple organ failure
7) Chronic pancreatitis.
1) The commonest cause is chronic alcohol consumption.
2) Other causes include
a. Cystic fibrosis
d. Rare familial pancreatitis.
3) Pathological changes include:
a. Parenchymal destruction
c. Loss of acini
e. Duct stenosis with dilatation behind the stenosis.
4) At operation the gland feels hard and irregular and may be mistaken for carcinoma. Calcification is often seen on plain abdominal x-ray. This is thought to be due to calcification of protein precipitates in the ducts.
Pancreatitic Cancer: Causes
1) Cigarette smoking
2) High fat diet
3) Diabetes mellitus
4) Familial pancreatitis
In two-thirds of cases the tumour is in the head of the pancreas. Most pancreatic cancers are adenocarcinomas
Pancreatitic Cancer: presentation
1) Presentation is usually with obstructive jaundice due to compression of the common bile duct.
2) Cancers elsewhere in the pancreas tend to remain silent until they are advanced, when the patient presents with dull back pain, nausea, weight loss and cachexia.
3) Extensive tumours infiltrating the gland may present with diabetes mellitus.
4) Some cases develop flitting venous thromboses (thrombophlebitis migrans). This is known as Trousseau’s sign.
Pancreatic cancer: Metastasis
1) Pancreatic carcinoma is characterised by early local spread to adjacent structures, lymph nodes and liver.
2) Pulmonary and peritoneal metastases may occur later.
3) The prognosis is poor because metastases or inoperable local extension are present at the time of diagnosis.
4) For carcinoma of the head of the pancreas, the five-year survival is <10%. The overall survival rate for tumours of the body and tail of the pancreas is even less.
Insulinomas constitute 75% of endocrine tumours of the pancreas, and are most commonly found in the body and tail. They are derived from beta cells.
The classic diagnostic criteria (Whipple’s triad) are:
(i) hypoglycaemic symptoms caused by fasting
(ii) (ii) a reduced blood glucose during symptomatic episodes
(iii) (iii) relief of symptoms by intravenous glucose.
The majority are solitary non-metastasising lesions. 10% are malignant.
Although gastrin is usually produced by gastric antral G cells, tumours of the G cells, i.e. gastrinomas, most commonly originate in the pancreas. They are multiple in 50% of cases and malignant in 60%. Ten percent occur in extrapancreatic sites, e.g. duodenum. Excess gastrin production results in the Zollinger–Ellison syndrome, i.e. gastric hypersecretion, widespread pep- tic ulceration, and diarrhoea. Gastrinomas may occur as one of the MEN syndromes.
Vipomas are associated with the production of VIP and result in a syndrome of watery diarrhoea, hypoka- laemia and achlorhydria.
This is much less common than insulinoma. It results in hypersecretion of glucagon, producing secondary diabetes. Other features include anaemia, weight loss, and characteristic rash known as a necrolytic migra- tory erythema. The tumour arises from the alpha cells of the pancreas. Twenty-five percent are benign and confined to the pancreas.