The Liver and Biliary System Flashcards
What structure separates the right and left liver lobes?
Falciform ligament
Where does blood supply to the liver come from and in which percentage?
Hepatic portal vein carries nutrient rich blood from the GI system via umbilical, superior mesenteric and inferior mesenteric veins - 60-70%
Hepatic artery come off coeliac trunk of abdominal aorta, carrying oxygen-rich blood to the liver - 30-40%
What structures make up the porta hepatis?
Hepatic artery
Portal vein
Bile duct
What makes up the hepatic parenchyma?
connective tissue and hepatic parenchymal cells
Explain fluid exchange within the liver
Fenestrated connecting sinusoids of hepatic artery and portal vein allow for oxygen rich and nutrient rish clood to flow into space of disse
What cell make up the parenchymal cells of the liver and describe their location?
Hepatocytes - lie in plates and cords Endothelial cells Kuppfer cells - in sinusoid Peri-sinusoidal (fat storing) cells - in space of disse Liver associated lymphocytes
What is the function of hepatocytes?
Receive nutrients and toxins from portal vein through exchange with blood at sinusoidal surface
What three surface exist around a hepatocyte?
- Sinusoidal - exports proteins (albumin and prothrombin) in hepatic vein along wih amino acids, glucose, lipids and urea
- Intercellular
- Canalicular - transports bilirubin, bile salts and gluconarides into bile ducts
What is the name of the strong connective tissue which encapsulates the liver?
Glissons Capsule
What is Cirrhosis?
Nodules and fibrosis which happen profusely hroughou the liver. It is end-stage liver failure, a result of chronic inflammaion over many years
How does cirrhosis develop?
Begins as persistent injury to hepatocytes, causing progressive liver cell loss. This leads to chronic inflammation (fibrosis) or hepatocyte regeneration and hyperplasia (nodules)
List the causes of cirrhosis
- Alcohol or Alcohol-like fatty liver disease
- Hepatitis
- Biliary disease
- Unknown (e.g. auto-immune)
- Haemachromatosis - excess iron causes damage and functional impairment of liver
Identify the complications of cirrhosis
Portal hypertension - increased resistance to blood flow through liver increases pressure in portal circulartion. This can back into spleen, pancreas, etc and can cause ascites, splenomegaly, and portal shunts and varices
Liver failure - results in lack of liver function and associated problems with this
List the functions of the liver
- Amino acid, carbohydrate and lipid metabolism
- plasma protein and enzyme synthesis
- Production of bile
- Detoxification
- Storage of proteins, glycogen, vitamins and minerals
- Immune functions
What functions are carried out in zone 1 of acinus?
- glycogen synthesis
- respiratory chain
- TCA cycle
- Fatty acid oxidation
- gluconeogenesis
- bile excretion and production
- Synthesis of urea and cholesterol
What functions are carried out in zone 3 of acinus?
- glucolysis
- lipogensis
- ketogenesis
- glutamine synthesis (ammonia detoxification)
- xenobiotic metabolism
What is the livers involvement in carbohydrate metabolism?
Glycogenesis to store glycogen in order to stabilise glucose levels
Neoglucogenesis
From what can glucose be made in neoglucogenesis?
- Amino acids
- lactate
- glycerol
- fatty acids
What is the livers role in lipid metabolism?
- Cholesterol synthesis
- lipogenesis
- synthesis of TAGs and lipoproteins
What circulating proteins are synthesised in the liver
- Albumin
- glycoproteins
- clotting factors
- prohormones
- apoproteins
What vitamins and minerals can the liver store?
Lipid soluble vitamins - A, D, E and K, and enough vitamin B12 to last 2-3 years
Minerlas include iron, copper and folate
How do disorders of the lievr arise?
- enzyme deficiency
- trauma
- hypoxia
- nutritional deficiency
- toxic/chemical damage
- substrate excess
What is Reyes Syndrome?
rare disorder in children characterised by encephalitis with liver failure.
How is Reyes Syndrome caused?
Excess aspiring consumption which children cant metabolise as well - causes mitochondrial dysfunction and micro-vesicular steatosis
How is Reyes Syndrome treated?
support for liver failure
Attend to symptoms - e.g. hypoglycaemia, bleeding tendency, acidosis, hyperammonaemia etc.
Where is bile produced and stored?
Produced in the liver
Stored in the gallbladder
What makes up bile?
- bicarbonate
- cholesterol
- bile pigments
- bile salts
How is Unconjugated Bilirubin produced?
Haem is broken down by haem oxygenase to Fe2+ and Biliverdin
Biliverdin is ring structure and broken down by biliverdin reductase to give UCB
What does UCB bind to to get to liver?
Serum Albumin
How is conjugated bilirubin produced?
UCB binds with UDP-Glucuronic acid under UDP gluconyrl transferase to produce CB and UDP
What happens to Conjugated bilirubin after it is produced in the liver?
It is hydrophilic so is transported into bile canaliculi for transportation. If sphincter of oddi is closed, stored in gallbladder until released into GI tract and acted upon by bacteria
Describe the process of enteric bilirubin metabolism
- In SI, CB to unconjugated by beta-glucoronidase to produce urobilinogen.
- 90% of this is converted by intestinal microflora into stercobilin and excreted in faeces
- Some excreted in urine as mesobilin
- Remainder transported back to liver where half renters biliary system, and half trasnported to kidney where it is converted to urobilin and excreted in urine
How are bile salts/acids formed?
Breakdown of cholesterol
What are the functions of bile salts?
- Emulsification for lipid digestion
- Micelle formation for lipid transport
What is hyperbilirubinaemia more commonly known as?
Jaundice
Describe how the 3 different types of jaundice are caused
- Pre-hepatic jaundice is where there is excess bilirubin due to problems before the liver, due to increased haemolysis from yellow fever, anti-malarials or sickle-cell anaemia.
- Hepatic Jaundice is where there is a problem with any part of hepatic involvement due to cirrhosis, hepatitis or hepatotoxic drugs (e.g. paracetemol overdose)
- Post-hepatic jaundice is due to obstruction of the bile ducts, preventing biliurbin getting to SI for unconjugation and excretion. Can be due to gallstones, pancreatitis or pancreatic tumour.
Why is neonatal jaundice common?
Newborns have immature livers, with deficient glucoronyl transferase. They therefore cant cope with amount of new RBCs and level of haemolysis.
What is the danger of neonatal jaundice?
If bilirubin crosses immature BBB, can be deposited in basal ganglia and cause Kernicterus- brain damage
How is Bile Secretion regulated?
Presence of fatty acids and amino acids in the duodenum causes Cholecystokinin to be released from I cells. This causes gallbladder contraction and sphincter of Oddi relaxation
What is the effect of acidic chyme in the duodenum?
Causes S cells to release Secretin - causes secretion of bicarbonate for neutralisation and therefore stimulates bile production.
Where are bile salts reabsorbed?
Distal ileum into enterohepatic circulation
How can bilirubin be used as a liver function test?
Direct biliurbin measured by adding diazo reagent to convert to azobilirubin (ble/purple) and absorbance measured
Total bilirubin can be measured by adding diazo reagent with caffeine to displace UCB from albumin
What does AST>ALP show?
Hepatocellular disease
What does ALP > AST show?
Cholestasis disease
What does a rasied ALP with no increase GGT show?
Possible bone disease
What does a raised ALP with increased GGT show?
Likely cholestatsis disease, but confirm with ultrasound
What is cholecystitis?
Inflammation of gallbladder
What is cholelithiasis?
Gallstoen within gallbladder
What is cholecystectomy?
Gallbladder removal
What is choledocholithias?
Gallstone within bile duct
What is cholangitis?
Inflammation of bile duct
Describe the process of bile transfer through the liver and associated ducts
Biliary canaliculi - Interlobular bile ducts - Septal bile ducts - Intrahepatic bile ducts - R/L hepatic ducts - Common hepatic ducts - Common Bile duct - Main pancreatic duct - enter ant hepatopancreatic ampulla of vater
List the three anatomical regions of the gallbladder
Fundus
Body
Neck
Tenderness under the liver due to cholecystitis is known as what?
Murphys sign
What is the function of the gallbladder?
Stores and concentrates bile - water and salt absorption
What epithelium does the gallbladder have?
Columnar epithelium - for absorption
What causes gall bladder contraction? (and sphincter of oddi relaxation)
- Vagal stimulation upon stomach expansion
- CCK action due to fat in duodenum
What causes gallbladder relaxation? (and sphincter of Oddi contraction)
- Sympathetic nerves
- Vasoactive Intestinal Peptide
- Somatostatin
How does Crohn’s Disease cause gallstones?
Inflammation of the ileum means no bile reabsorption so therefore gall stones can develop
What 6 Fs are risk factors for Gallstones?
Female Fair (caucasian) Fertile Forty Fat (and low fibre diet) Family history
What are the 3 main types of gallstone?
- Cholesterol stone
- Bile pigment stone
- Mixed stones - most common with layers of bile, cholesterol and calcium
what 3 stages are involved int he formation of gallstones?
- Cholesterol Supersaturation - cholesterol build up leads to super saturation in gallbladder due to water reabsorption here. Occurs at high levels of oestrogen and low levels of bile acids
- Biliary stasis - durign periods of fasting or starvation (e.g. cancer treatment)
- Increased secretion of bilirubin due to conjugation failure or increased haemolysis
What are the complications of gallstones within the gallbladder?
Biliary Colic - pain as stone lodged in neck
Acute cholecystitis - inflammation due to not functioning properly
Empyema - completely filled with pus
Mucocele or cancer
What are the complications if gallstones are within common bile duct?
Obstructive jaundice
Cholangitis
Pancreatitis
What are the complications if gallstones are within small intestine?
Gallstone ileus
What is Acute hepatitis?
Inflammation of the liver, presenting with raised ALT and AST, jaundice and clotting derangements
List common causes of acute hepatitis
- Hep A, B, C, D and E
- Epstein-barr virus
- cytomegalovirus
- leptospirosis (bacteria)
- fever
- syphillis
- malaria
- alcohol, toxins or drugs
- autoimmune
- Wilsons
- Haemachromatosis
What does the presence of Surface Antigen (sAg) show?
Marker of infection
What does the presence of Surface Antibody (sAb) show?
Marker of immunity
What does the presence of Core Antibody (cAb) show?
Patient has had infection previously
What does the presence of E Antigen (eAg) show?
High Infectivity
What does the presence of E Antibody (eAb) show?
Low infectivity
What are the RNA hepatitis viruses?
A, E, D and C
What are the DNA hepatitis viruses?
Hep B
What are the non blood-bourne and blood-bourne versions of hepatitis?
Non-blood bourne: A and E
Blood-bourne: C, D and E
How can Hep A be transmitted?
Faeco-oral trasmission from person to person (human only reservoir)
How is Hepatitis A shed out of the body?
Out of biliary tree eventually leaving in faeces - incubation of roughly 30 days
What forms of hepatitis can be vaccinated against?
A: good immunity so easily vaccinated against
B: Can be vaccinated against
How do you treat Hepatitis A?
No exact treatment but maintain hydration and avoid alcohol
How is Hepatitis E transmitted?
Faecal contamination of water supply or infected meat
How is Hepatitis B transmitted?
Transfusion, Body fluid contamination, mother to baby, contaminated needles and syringes, infection into open cuts and sores
How is acute Hepatitis B treated?
There is no treatment but a mature immune system usually clears the infection
How can Chronic Hepatitis B be treated?
- Pegylated Interferon alpha
- Antivirals such as tenofavir and entecavir
What does Hepatitis D require to survive?
Hepatitis B - helps this to replicate
How is Hepatitis C transmitted?
Injections and transplants
How is Hepatitis C treated?
Direct Acting Antivirals - Telepravir
