GI Topic 1 - Bile, Gallbladder Flashcards
What happens to the haem groups released from the breakdown of haemoglobin?
- Converted to biliverdin by haem oxygenase
- Biliverdin converted to unconjugated bilirubin by biliverdin reductase
What happens to ferrous iron released in the breakdown of haemoglobin?
Recycled
Describe the functional differences between bile salts and bile acids
Bile salts are more amphipathic - have hydrophilic and lipophilic parts - so are good emulsifiers
What is the treatment for haemolytic jaundic in newborns?
High dose phototherapy and blood transfusion
List the symptoms of biliary colic
- Epigastric/R hypochondrium/back pain
- Vomiting
- Worsened by eating (gallbladder contraction)
- No jaundice/fever, LFTs normal
Where is the reticuloendothelial system found?
Spleen, bone marrow, liver
How is choledocholithiasis treated?
- Can use ERCP to attempt stone removal - incision at sphincter of Oddi to increase the duct diameter, extract stones with balloon/basket
- Cholecystectomy prevents recurrance
Where does haemoglobin breakdown occur?
In the macrophages of the reticuloendothelial system - spleen, bone marrow, liver
What is the function of bile?
- Promotes intestinal absorption of fats by emulsification and formation of micelles
- Eliminates and excretes cholesterol
- Exerts a hormone-like effect on intestinal metabolic pathways
Describe the formation of primary bile acids
- In hepatocytes in the liver
- From cholesterol
- Main primary acids - cholic acid and chenodeoxycholic acid
What causes acute cholecystitis?
Impacted gallstone in gallbladder - wall oedema/inflammation and development of bacterial infection in the wall
Describe the bilirubin levels in post-hepatic jaundice
- Normal plasma unconjugated bilirubin
- Very high plasma conjugated bilirubin
- High urine conjugated bilirubin
- No urobilin in urine
- No stercobilin in faeces
List the steps involved in the synthesis of bile
- Formation of primary bile acids
- Conjugation of bile acids to bile salts
- Formation of secondary bile salts
How is physiological jaundice in newborns treated?
Treat with phototherapy - converts unconjugated bilirubin to water-soluble substances to be excreted
After digestion, what ends the secretion of bile?
Sympathetic nervous action, vasoactive intestinal polypeptide (VIP) and somatostatin stimulate gallbladder relaxation and closure of the sphincter of Oddi
What kind of epithelium lines the gallbladder?
Columnar epithelial lining - reabsorbs water and electrolytes from bile
Where do gallstones commonly impact in the biliary ducts?
Just above the ampulla of Vater - where duct narrows
Describe the features of conjugated bilirubin
- Hydrophilic/water soluble
- Transported into bile canaliculi for accummulation in bile
How can bilirubin be measured?
- Serum
- Urine - as bilirubin or urobilin
- Faeces
- Blood gas analysis
- Transcutaenous
Describe the typical presentation of choledocholithiasis
- Obstructive jaundice (pain)
- Cholangitis
- Acute pancreatitis
When does biliary stasis occur, leading to gallstone formation?
During fasting/starvation e.g. total parenteral nutrition
List the components of bile
- Bile acids (salts when conjugated)
- Water
- Electrolytes
- Cholesterol
- Phospholipids
- Bile pigments - bilirubin
- Bicarbonate
Describe the formation of secondary bile salts
Formed by intestinal bacteria by dehydroxylation
Describe the blood supply of the gallbladder
- Cystic artery from right hepatic artery from common hepatic artery (from coeliac trunk of aorta)
- Cystic veins drain to the hepatic portal vein
What is an empyema?
Abcess in the gallbladder
How does the structure of bile salts aid emulsification?
Amphipathic - hydrophilic and lipophilic
Hydrophilic part prevents droplets reforming
Lipophilic part binds to and disperses large triglyceride lipid droplets
What happens to globin monomers produced in the breakdown of haemoglobin?
Converted to amino acids then recycled
What volume of bile is stored in the gallbladder?
30-50ml
Describe LFTs in obstructive jaundice
- High ALP, associated rise in GGT
- Steadily increasing bilirubin - level indicates duration of obstruction
- Raised AST/ALT - less prominent, more transient
List the risk factors for gallstones
- Female
- Risk increases with age
- Caucasian > non-caucasian
- Obesity
- Low fibre diet
- Family history
- Inflammatory bowel disease
Define cholangitis
Infection of the bile duct
What is a potential complication of haemolytic jaundic in neonates?
Kernicterus - bilirubin accummulates in basal ganglia and brainstem nuclei, causing brain damage
Describe the signs/symptoms of post-hepatic (obstructive) jaundice
- Pale stool/dark urine
- Yellow sclerae
- Abdominal tenderness
- Palpable gallbladder?
- Pruritis (scratch marks)
- Features of chronic liver disease
- Hepatomegaly
Describe the biliary apparatus in the interdigestive period
- Bile stored in the gallbladder
- Gallbladder relaxed
- Sphincter of oddi contracted
What stimulates bile secretion?
- Fatty acids and amino acids (mostly fat) entering the duodenum stimulates enteroendocrine cells to release cholecystokinin (CCK) in the duodenum
- CCK and vagal stimulation results in gallbladder smooth muscle contraction and sphincter of Oddi relaxation, leading to release of bile
What causes obstructive jaundice?
- Obstruction of hepatic, cystic or common bile duct (prevents bile release into small intestines)
- E.g. gallstones, pancreatitis, pancreatic tumours
Describe the enteric bilirubin metabolism
- Conjugated bilirubin converted by beta-glucuronidase to U-bilirubin
- U-bilirubin converted to mesobilinogen, stercobilinogen and urobilinogen
- Mesobilinogen is converted to mesobilin by intestinal microflora and excreted in urine
- Stercobilinogen is converted to stercobilin by intestinal microflora and excreted in faeces
- Urobilinogen is converted to urobilin by intestinal microflora and excreted in urine
What proportion of bile acids are recirculated?
95% of bile acids recirculated, 6-8x per day
Define cholecystitis
Inflammation of the gallbladder
How are bile acids conjugated to form bile salts?
Conjugated by adding an amino acid (taurine or glycine)
Describe the structure of the biliary tree
- Biliary canaliculi
- Interlobular bile ducts
- Septal bile ducts
- Intrahepatic ducts
- Right and left hepatic ducts
- Common hepatic duct (+ cystic duct)
- Common bile duct
What is the sphincter of Oddi?
Muscular valve, controls flow of bile and pancreatic fluid into the duodenum
Describe the features of mixed gallstones
Most common, cholesterol and bile pigments
What is the treatment for acute cholecystitis?
Antibiotics, analgesia, elective cholecystectomy when symptoms settle
What happens to the porphyrin ring produced in the breakdown of haemoglobin?
Converted to bilirubin then transported to the liver for modification and excretion
Describe haemoglobin turnover in the body
6g per day
How is serum bilirubin measured?
- Conjugated - diazo reagent
- Total - diazo reagent and caffiene to displace albumin from unconjugated bilirubin
How often are red blood cells replaced?
Every 120 days
Where is bile produced and stored?
Synthesised in the liver, stored in the gallbladder
Describe the anatomical location of the gallbladder
- Behind the duodenum, through the head of the pancreas
- In the gallbladder fossa on the inferior surface of the right lobe of the liver
How is urine bilirubin measured?
- Clinistix colour change - measures conjugated only as unconjugated is not water soluble
- Urobilin - clinisitx, raised indicates pre-hepatic or hepatic jaundice, absence indicates post-hepatic jaundice
How is bilirubin measured in faeces?
Visual inspection - pale, grey, loose = post-hepatic jaundice
Describe the transport of unconjugated bilirubin
- Hydrophobic - water insoluble
- Bound to albumin in blood
What is a mucocoele?
Distended gallbladder filled with clear uninfected fluid
What causes biliary colic?
Occurs when gallstone becomes impacted - usually in the neck of the gallbladder or Hartman’s pouch
List the causes of hepatic jaundice
- Impaired uptake of unconjugated bilirubin by liver
- Impaired conjugation of bilirubin e.g. Gilbert’s syndrome (reduced glucuronyl transferase activity)
- Impaired transport of conjugated bilirubin into bile canaliculi
Describe the enterohepatic circulation
- Recirculation of bile acids
- Mainly reabsorbed in the terminal ileum by active transport into the portal circulation
- Small amount of faecal loss - liver compensates by making more
- Hydrophilic bile acids bound to albumin in blood to facilitate transport back to the liver
- Venous blood from the ileum feeds into the hepatic portal vein, which drains to the liver sinusoids
Give examples of causes of pre-hepatic jaundice
Malaria, yellow fever, quinine-based anti-malaria drugs, genetic disorders e.g. sickle cell anaemia
What process produces bile pigments?
Break down of haem groups from haemoglobin in macrophages of the reticuloendothelial system
What causes impaired transport of bilirubin into bile canaliculi?
Conditions that cause liver damage causing cholestasis due to swelling and oedema resulting from inflammation
E.g. primary biliary cholangitis (autoimmune destruction of bile ducts), cirrhosis, hepatotoxic drugs e.g. paracetamol, viral hepatitis
Describe the conjugation of bilirubin
- Unconjugated bilirubin bound to albumin in blood transported by sinusoidal bilirubin transported into hepatocytes
- Conjugated by UDP-glucuronyl transferase (from UDP-glucaronic acid)
Describe the flow of bile from the gallbladder
- Cystic duct from the gallbladder joins with the common hepatic duct to form the common bile duct
- Common bile duct and main pancreatic duct join to form the hepatopancreatic ampull (of Vater)
- Ampulla opens into the 2nd part of the duodenum through the greater duodenal papilla
- The flow of bile and pancreatic fluid is mediated by the sphincter of Oddi
Describe normal bilirubin levels compared with bilirubin levels in jaundice
- Normal total bilirubin (adult) <21 ummol/L
- Normal conjugated bilirubin (adult) <7
- Total >30 - jaundice visible in sclera
- Total >100 - jaundice visible in skin
Describe the gross structure of the gallbladder
Fundus inferiorly, body and neck superiorly, narrows into cystic duct
List the potential complications of gallstones
- Gallbladder - biliary colic, acute cholecystitis, empyema, mucocoele, cancer
- Common bile duct - obstructive jaundice, cholangitis, pancreatitis
- Small intestine - gallstone ileus
What causes bile pigment gallstones?
Increased haem
What process occurs while bile is stored in the gallbladder?
Bile is concentrated - epithelial cells reabsorb water and electrolytes
How does transcutaneous measurement of bilirubin work?
Measures yellowness of skin on forehead/sternum
Uses bilirubinometer
How is choledocholithiasis diagnosed?
Ultrasound +/- ERCP/MRCP
List the symptoms of acute cholecystitis
Pain, nausea, vomiting, fever, abdominal tenderness
Raised inflammatory markers, can have abnormal LFTs/jaundice
List the possible pathogeneses of gallstones
- Cholesterol supersaturation
- Biliary stasis
- Increased bilirubin production
List the types of gallstones
- Cholesterol only
- Mixed
- Bile pigment
What are the implications for surgery in patients with post-hepatic jaundice?
- Need bile salts to absorb fat soluble vitamins - A, D, E, K
- Need vitamin K to synthesise coagulation factors (needed for gamma glutamyl carboxylase)
- Give vitamin K pre-surgery to post-hepatic patients
Define cholelithiasis
Gallstones within the gallbladder
List the types of neonatal jaundice
- Physiological
- Haemolytic
Where is the gallbladder palpated?
- Fundus may be palpated at linea semilunaris
- Linea semilunaris - where the lateral border of the rectus abdominus muscle meets the margin of the 9th costal cartilage
Define choledocholithiasis
Gallstones in bile ducts
What causes cholesterol supersaturation leading to gallstone formation?
- Cholesterol is solubilised by bile, increased cholesterol causes supersaturation
- Especially occurs in increased oestrogen (pregnancy, obesity, oral contraceptive pill, liver disease)
- Or in reduced bile acid - small bowel resection, Crohn’s disease - when enterohepatic circulation is ineffective
What is the effect of gallstones in:
- Cystic duct
- Common bile duct
- Duodenal papillae
- Painful contractions
- No bile in gut, steatorrhoea, post-hepatic jaundice
- Post-hepatic jaundice, no bile or pancreatic secretion into gut, malnutrition, acute pancreatitis
Define emulsification
The breakdown of large lipid droplets into small, uniformly distributed lipid droplets
What causes haemolytic jaundice in newborns?
- Rhesus incompatibility - mother sensitised by previous rhesus positive foetus or rhesus positive blood transfusion
- Causes foetal haemolysis - raised unconjugated bilirubin
How does increased bilirubin secretion occur? How does it lead to formation of gallstones?
- Bilirubin is soluble in bile following conjugation with glucuronide
- Pigmented stones develop when
- There is increased red blood cell breakdown - haematological conditions e.g. sickle cell anaemia, malaria, valvular heart disease, post-chemotherapy
- Failure of hepatic conjugation
What is Murphy’s sign?
- Murphy’s sign = tenderness over gallbladder fundus (palpate upwards towards costal margin during deep inhalation) - gallbladder tenderness
Describe the bilirubin levels in pre-hepatic jaundice
- Very high plasma unconjugated bilirubin
- Normal/slightly raised plasma conjugated bilirubin
- No conjugated bilirubin in urine
- Slightly raised urobilin in urine
- Slightly raised stercobilin in faeces
How does emulsification aid digestion of lipids?
Increases the surface area on which lipase enzymes can act
Describe the structure of haemaglobin
- 4 globin monomers
- 4 haem groups
- Ferrous iron
- Porphyric ring
What causes physiological jaundice in newborns?
- Need to destroy foetal haemoglobin and replace with adult haemoglobin
- Underdeveloped liver (no glucuronyltransferase) can’t cope with the haemoglobin breakdown
- Bilirubin peaks at 3-5 days, lasts <14 days
List the techniques used to image the gallbladder
- MRCP - magnetic resonance cholangiopancreatography
- ERCP - endoscopic retrograde cholangiopancreatography
- PTC - percutaneous transhepatic cholangiography
What is the function of the gallbladder?
Stores and concentrates bile
Describe typical features of cholesterol-only gallstones
- Solitary, large, oval stones
- Soft clay-like
- Stay in gallbladder
How is jaundice defined?
Raised bilirubin levels - hyperbilirubinaemia
Define cholecystectomy
Removal of gallbladder
Describe the bilirubin levels in hepatic jaundice
- Slightly raised plasma unconjugated bilirubin
- High plasma conjugated bilirubin
- Slightly raised urine conjugated bilirubin
- Slightly raised urobilin in urine
- Slightly raised stercobilin in faeces
Describe the contents of lipid micelles
- Micelle = very small lipid aggregates with hydrophilic (polar) head groups on outside and hydophobic (non-polar) tails pointing in
- Made of bile salts, fatty acids, monoglycerides, phospholipids, cholesterol and fat soluble vitamins (A, D, E, K)
Describe the process of fat absorption
- Bile salts emulsify fat globules in intestines - allows digestion by lipases
- Bile salts form micelles with free fatty acids produced from lipase digestion (micelles = bile salts and triglycerides)
- Micelles continuously breakdown and reform - contents released, some able to diffuse across intestinal lining (as monoglycerides and free fatty acids)
- Triglycerides reform in epithelial cells, packaged into chylomicrons, enter blood via lymph
What is the treatment for biliary colic?
- Resolves spontaneously if stone goes back into the body/fundus of the gallbladder
- If recurrent cholecystectomy
List the types of jaundice and their causes
- Pre-hepatic - increased haemolysis
- Hepatic - liver damage
- Post-hepatic - blockage of bile ducts
What is the result of acidic chyme entering the duodenum?
- Stimulates endocrine cells (S cells) to release secretin
- Secretin stimulates duct cells in the liver to release more bicarbonate into bile to neutralise the chyme
