Lectures Flashcards
Name the ducts present in order from the porta hepatitis in liver to gallbladder and duodenum
Right and left hepatic ducts coming from porta hepatitis, common hepatic duct branching into cystic duct which connects to liver and the bile duct connecting to duodenum.
Describe features of the galldbladder
Composed of a fundus, body and neck
Serves as a reservoir for bile
Lies against inferior surface of right lobe of liver
Composed of columnar epithelium
Discuss function of bile salts
Bile saltsact as emulsifiers to allow lipids to be absorbed into the bloodstream
Bile salts can be synthesised from cholesterol
Hydrophobic portion binds to and dispenses large triglyceride lipid droplets, and prevents large droplets from reforming.
Increases surface area on which triglyceride lipase can act.
Discuss regulation of bile secretion
Between meals (interdigestive period), the sphincter of Oddi is contracted therefore bile cannot enter the dudodenum. Pressure increases in the common bile duct and bile flows into the gallbladder.
Epithelial cells reabsorb water and electrolytes, thus concentrating the bile.
Once fatty acids and amino acids enter the duodenum, cholecystokinin (CCK) is released by endocrine cells.
This stimulates contraction of the gallbladder smooth muscle via the vagus nerve, also relaxes sphincter of Oddi, thus resulting in bile release.
Chyme in duodeunum stimulates other endocrine cells to release secretin which stimulates liver duct cells to release bicarbonate into bile and stimulate bile production.
Describe recycling of bile via enterohepatic circulation
Bile salts need to be recycled as they are not enough to fully process fats in a meal.
Transporters move bile salts from the digestive tract to the intestinal capillaries at the terminal ileum, they are transported from the intestinal capillaries to the liver via the hepatic portal vein.
Hepatocytes take up bile salts from the blood and increase bile salt secretion into the bile canaliculi
Discuss bile pigments
Bile pigments are generated from the breakdown of the haem group of haemoglobin in macrophages, via the reticuloendothelial system in the spleen/bone marrow/liver.
The porphyrin ring from the haem group is converted to bilirubin for transport to the liver for modification and excretion.
Bilirubin metabolism
Once haem is broken down to bilirubin it is bound to albumin in order to be transported around the blood due to its normal hydrophobic nature.
Unconjugated bilirubin is transported to the liver and undergoes phase II conjugation (glucuronidation) to become conjugated.
This form of bilirubin is hydrophilic, is transported out of hepatocytes and into bile canaliculi for accumulation in bile in gallbladder.
Metabolism after gallbladder
Once bile is released into the small intestine, the conjugated bilirubin is converted to urobilinogen by intestinal bacteria.
80% of this is converted to stercobilin which gives faeces it brown colour
20% is reabsorbed and recirculated to the liver, it then travels to the kidneys where it is converted to urobilin which gives urine its yellow colour.
Gallstone definitions
Cholelithiasis - formation of gallstones in the gallbladder
Cholecystitis - Inflammation of gallbladder
Choledocholthiasis = Gallstones in ducts
Risk factors for gallstone
5 Fs - Female, fair, fertile, forty, fat
Also, family history, caucasian, low fibre diet, inflammatory bowel disease.
Approx 80% asymptomatic
Types of gallstones
Cholesterol stones
Bile pigment stones
Mixed stones
Discuss cholesterol stones
Cholesterol stones are the most common, they are usually solitary, oval and large
These form when bile becomes supersaturated with cholesterol. Cholesterol is usually soluble in bile, however insufficient bile salts lead to precipitation of cholesterol and a failure to keep it in solution.
These can typically occur when oestrogen levels are high e.g. obesity and pregnancy, this increase leads to a decrease in bile acids in bile.
Low bile acid can also occur from bile loss from gut such as in malabsorption in Crohns which leads to decreased enterohepatic recirculation
Alsom increased cholesterol present in bile from obesity
Bile pigment stones
Multiple, hard, irregular, associated with chronic haemolysis (e.g. Sickle cell)
Pigment stones are formed due to increased hepatic secretion of conjugated bilirubin
Pigment stones can occur when there is increased red blood cell breakdown especially in haematological situations such as sickle cell or malria
Pigment stones are largely composed of calcium nilirubinate
Mixed Stones
Mixed stones can be composed of cholesterol, bile pigments and calcium salts
Multiple, multi-faceted, layers of cholesterol
Complications of gallstones
Biliary colic
Acute cholecystitis
Obstructive jaundice
Micelles
Micelles are small lipid aggregates which the bile salts help to form, they have hydrophilic head groups and hydrophobic tails. They are made from bile salts, fatty acids, monoglycerides, phospholipids, cholesterol and fat-soluble vitamins
Continuously breakdown and reform, each time the contents are released some is able to diffuse across the intestinal lining
TAGs reform in epithelial cells and are packaged into chylomicrons which enter the blood via lymph
Biliary colic
Pain related to the gallbladder that occurs when a gallstone transiently obstructs the cystic duct and the gallbladder contracts
Usually provoked by eating, especially when the gallbladder is stimulated to contract. Often settles if the stone moves back into the body/fundus of the gallbladder. Surgery (cholecystectomy) often indicated if problem is recurrent
Pain is often in the epigastrium or RUQ and radiates to back.
Doesn’t cause jaundice or fever and LFTs are commonly normal.
Acute cholecystitis
Inflammation of the gallbladder wall due to the impacted stone blocking flow of bile in biliary tree. Gallbladder is initially sterile but often becomes secondarily infected by bacteria within the gallbladder wall.
Clinical features include; pain, fever and abdominal tenderness
Often raised inflammatory markers seen, sometimes abnormal LFTs seen, potentially jaundice
Treatment uually involves antibiotics and possible surgery - cholecystectomy
Obstructive jaundice
Obstruction of hepatic, cystic or common bile duct, preventing bile from being released into the small intestine (cholestasis)
Can be caused by; chledocholithiasis = gallstones obstructing cystic duct
pancreatic cancer = tumour growth in head of pancreas can block bile flow to duodenum
pancreatitis = inflammation and swelling of head of pancreas can block bile flow
Clinical obs;
increase in conjugated bilirubin as it is not being excreted in the bile, therefore it spills into the blood. Thus, decreased urobilinogen in urine from lack of conjugated bilirubin in GI tract, also decrease in stercobilinogen, therefore pale stool seen.
Also, due to increased conjugated bilirubin in blood, the kidneys filter this leading to an increase in its concentration in urine
LFTs; Alkaline phosphate increased early, sometimes an increase in GGT, bilirubin increases steadily, therefore good indicator of duration of obstructive process
AST’ALT increase is less prominent, often transient
Pre-hepatic jaundice
Result of elevated haemolysis by reticuloendothelial system, resulting in liver being overloaded by unconjugated bilirubin and an inability to cope with it.
Could be the result of tropical diseases such as malaria, yellow fever or sickle cell anaemia
Clinical obs;
Large increase in UCB due to increased haemolysis.
Small inrease in CB due to metabolism, if more of this is in urine then more urobilinogen will be present in the urine
bilirubin will not be seen in urine as it is mainly unconjugated and therefore bound to albumin this is what causes the symptoms of jaundice
Hepatic jaundice
Caused by conditions resulting in liver damage, cholestasis due to swelling and oedema, resulting from inflammation
This could affect bilirubin metabolism in numerous ways;
impaired uptake of UCB, impaired bilirubin conjugation e.g. Gilbert’s syndrome, impaired transport of CB into bile canaliculi e.g. primary biliary cholangitis
Liver damage can be caused by;
cirrhosis (e.g. alcohol induced), hepatotoxic drugs (e.g. paracetemol overdose), viral hepatitis
Clinical obs;
General increase in both UCB & CB, typically more CB than UCB as bile exrection is a rate limiting step. LEvels of UCB an CB depend on which liver funciton is impaired.
Increased UCB if conjugation is impaired, increased CB if CB is not being excreted efficiently
CB can be detected in urine if CB plasma levels increase due to kidney filtering of CB
Increase in urobilinogen if more CB is excreted into bile
Discuss blood supply to the ovary
Via ovarian artery, this arises from the aorta at the level of the renal artery
Discuss venous drainage to the ovary
Via the ovarian vein, this drains to the inferior vena cava on the right and to the left renal vein on the left
Lymphatics of ovaries
Drain to aortic nodes at level of renal vessels
