Hepatobiliary System Flashcards
Surface anatomy of liver
Lives within chest where rib’s protect
Ligamentum teres
Remnants of the umbilical vein of foetus that would have come from umbilicus to falciform ligament (which is a fold of the peritoneum) and joined with the left portal vein
Describe the inflow (blood supply) of the liver
- Hepatic artery- 25% of blood
- Portal vein- 75% of blood
What is the purpose of blood delivered to the liver by the Portal Vein?
It supplies the liver with metabolic substrates- is the first organ to do so
Processes any ingested substances- detoxifies toxins
What is the purpose of blood delivered to the liver by the Hepatic Artery?
Supply oxygenated blood to the liver
Describe the outflow of the liver
- Bile that liver produces that comes out of common bile duct
- 3 hepatic veins take blood out to inferior vena cava which goes straight into heart
How many hepatic segments are there
8
Micro morphology of liver
Has two lobules the portal and hepatic. They are hexagonal structures and each corner has a portal triad
Portal triads co gain branch of hepatic artery and portal vein and bile duct
Hepatic lobules have central vein in the middle and portal has bile duct
Centre of the lobule is the central vein. Outline the drainage of a hepatic lobule
Hepatic lobule collects blood from the hepatic sinusoids → hepatic veins → systemic venous system
Within lobule there are rows of hepatocytes. What does each side of the row of hepatocytes face?
Within lobules there are rows of hepatocytes (yellow)- each has a sinusoid-facing side (blue) to pick up stuff from blood & bile canaliculi-facing side (green) to make bile by taking nutrients, processing it and shifting it across to the biliary canaliculi
Hepatic artery
Brings oxygen rich blood into liver support hepatocytes
Portal vein
Mixed venous blood from GIT (carrying nutrients, bacteria, toxins) and spleen (waste products) come to it
Hepatocytes process nutrients, detoxify blood and excrete waste
Bile duct
Bile produced by hepatocytes drains into bile canaliculi (green) which join with cholangiocyte-lined bile ducts around lobule perimete
What is the micro-function of the liver?
Acinus which is a functional unit of liver. Diamond shaped consisting of 1/6 of 2 adjacent lobules and is between 2 triads
Blood flow
Bile flow
Describe the 3 zone model of the acinus
- Blood comes into hepatic acinus via point A (portal triad)
- Blood drains out via point B (central vein)
- Hepatocytes in zone 1 receives early exposure to blood contents- both good like O2 and bad like toxins
- Zone 2 has intermediate O2 and intermediate toxin risk
- Zone 3 has low O2 and low toxin risk- this is where we see liver damage if liver ischaemia happens
Sinusoidal endothelial cells, describe their structure & their function
- No basement membrane
- Fenestrated (discontinuous endothelium)
- Allow lipids and large molecule movement to and from hepatocytes
Kuppfer cells, what are they and what is their function?
- They are sinusoidal macrophage cells
- Attached to endothelial cells
- They do phagocytosis to eliminate and detoxify substances arriving in liver from portal circulation
Hepatic stellate cells aka perisinusoidal cells, what are their 2 functions?
- Found in space of disse
- Exist in dormant state
- Store Vit A in liver cytosolic droplets
- Activated in response to liver damage and proliferate, chemotactic and deposit collagen in ECM, (they act like fibroblasts)
Hepatocytes, summarise the main hepatocyte functions
- 80% of liver mass and are cubical
- Metabolic and catabolic → synthesis and utilisation of carbs, lipids, proteins
- Secretory and excretory → synthesis and secretion of proteins (e.g. albumin), bile, waste
- Detoxification and immunological functions → breakdown of ingested pathogens and drug processing
Cholangiocytes, what do they secrete into bile (2)?
Secrete HCO3- and H2O into bile
Carb metabolism terms
- What is glycolysis?
- Anaerobic conversion of glucose → lactate (RBCs, renal medulla, skeletal muscle)
- Aerobic oxidation of glucose → (CNS, heart, skeletal muscle, most organs)
- Glycogenesis?Synthesis of glycogen from glucose (liver and muscle)
- Glycogenolysis?Breakdown of glycogen to glucose
- Gluconeogenesis?Production of glucose from non-sugar molecules:
- List 3 non-sugar molecules that can be used to produce glucose via gluconeogenesisAmino acids (from liver and renal cortex)Lactate (from anaerobic glycolysis in RBCs and muscles)Glycerol (lipolysis)
- What is the name of the process where lactate from muscles is transported to liver and converted to glucose to then return to muscles to be metabolised back into lactate?Cori Cycle
- Outline the reactions of the Cori CycleLactate produced via anaerobic glycolysis in a muscle cell (myocyte) is transported to the liver and is converted to pyruvate via lactate dehydrogenasePyruvate then converted to glucose via gluconeogenesis, releasing 6 ATP in the processGlucose via glycolysis to pyruvate → lactate in muscle cells and the cycle starts over again!https://s3-us-west-2.amazonaws.com/secure.notion-static.com/e43625ef-bce4-4504-a0e5-796d012b683b/Untitled.png
- What is the name of the process where lactate from muscles is transported to liver and converted to glucose to then return to muscles to be metabolised back into lactate?Cori Cycle
- List 3 non-sugar molecules that can be used to produce glucose via gluconeogenesisAmino acids (from liver and renal cortex)Lactate (from anaerobic glycolysis in RBCs and muscles)Glycerol (lipolysis)
- Lipolysis?Breakdown of triglycerides to glycerol and FFAs
- Lipogenesis?
How are non-essential amino acids made by liver?
- Through transamination- different keto acids can be converted into multiple amino acids depending on the transaminase enzyme
- alpha-keto glutarate → glutamate, proline, arginine GAP
- Pyruvate → alanine, valine, leucine LAV
- Oxaloacetate → aspartate, methionine, lysine LAM
What problem does glucose alanine cycle solve
Muscle can potentially utilise amino acids to produce glucose for energy but to convert pyruvate to glucose requires energy and to remove nitrogen as urea requires energy
This cycle transfers the problem to the liver
What 4 amino acids are in higher concs in cells than other 16?
alanine, aspartate, glutamate, glutamine
Glutamate is most important as it’s related to alpha ketoglutarate (key intermediate in Krebs)
What amino acid is principally released from muscle during starvation and how?
Alanine:
Glutamate is released from A.A. breakdown and the NH2 is transaminated onto pyruvate to form alanine
What then happens to the alanine in the glucose-alanine cycle?
Transamination with alpha-ketoglutarate becomes pyruvate and glutamate
Alanine + alpha-ketoglutarate → pyruvate + glutamate
What happens to glutamate and pyruvate?
Uses 4 ATP then converted to urea which is transported away in blood for disposal
Uses 6 ATP and pyruvate converted to glucose which goes to muscle for glycolysis
What does fat do
- Main energy store in body (100x more than glycogen)
- Stored in adipose and liver
- When glycogen stores full, liver converts excess glucose and amino acids to fat for storage
Describe triglyceride breakdown in muscle and liver cells
Triglyceride broken down into FFAs which are shuttled into liver
FFA converted to acetyl CoA which can enter TCA cycle
How can acetyl CoA be used as an alternate fuel source (ketone body)?
2 acetyl coA join to make acetoacetyl coa and is then converted into HMG-COA reductase. This is cleaved to make acetoacetate
- How can glucose entering liver be converted into components of lipoproteins?
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- Directly into glycerol
- Into pyruvate then acetyl CoA which can form cholesterol and fatty acids
- How do these products come together to form lipoproteins?Glycerol and fatty acids form triacylglycerolsApoproteins, phospholipids and cholesterol get added to make lipoproteins
What 2 lipoproteins are made by liver?
- VLDL- transport fatty acids to tissues- this forms LDL once fatty acids delivered, which are high in cholesterol to deliver to tissues for cell membrane integrity and to make hormones- excess cholesterol is returned to liver and excreted as bile
- HDL- high protein and low fat content- pick up excess cholesterol in circulation to return to liver
- What does the liver/hepatocytes of the liver store (3)?
VIC
- Fat soluble vitamins (ADEK) & vitamin B12- stores sufficient for 6-12 months except Vit K (essential for blood clotting) where store is small
- Iron as ferritin- available for erythropoeisis
- Copper
Detoxification in hepatocytes
- What enzyme performs it?P450 enzymes
- What are the 2 phases?1) Modification- making substance more hydrophilic2) Conjugation- attach water soluble side chain to make the substance less reactive
What are the uses of bile?
- Cholesterol homeostasis
- Absorption of lipids and lipid-soluble vitamins (ADEK)
-
Excretion of:
- Xenobiotics/drugs
- Cholesterol metabolites
- Adrenocortical and other steroid hormones
- Alkaline phosphatas
How much bile is made
500ml a day
Why bile yellow/green?
Due to pigments like bilirubin and biliverdin
- What colour is bilirubin?Yellow
- What colour is biliverdin?Green
How are hepatocytes involved in bile production?
- Primary secretion- secrete 60% of total bile
- Bile secretions reflect serum concs
- Secretion of bile salts (aka bile acids), lipids and organic ions
How are cholangiocytes involved in bile production?
- Secrete 40% of total bile
- Secondary modification:
- Alteration of pH (alkaline electrolyte solution) (secrete HCO3- into bile)
- H2O drawn into bile by osmosis via paracellular junctions
- Luminal glucose and organic acids reabsorbed
- HCO3- and Cl- actively secreted into bile by CFTR (Cystic Fibrosis Transmembrane Regulator)
- IgA exocytosed and got rid of
Where can you find biliary transporters?
Apical surface & basolateral membranes of hepatocytes and cholangiocytes
What are biliary transporters and what do they do?
Perform excretion of bile salts and toxins
- Bile Salt Excretory Pump (BSEP)- active transport of BAs into bile
- MDR related proteins (MRP1 & 3)
- Products of multidrug resistance genes- MDR1 (excretion of xenobiotics and cytotoxins) and MDR3 (Phosphatidylcholine)
- Products of the familial intrahepatic cholestasis gene (FIC1)
What are bile salts made from
- Synthesised from cholesterol
- Na+ & K+ salts of bile acids (e.g. cholic acid) conjugated in liver to glycine and taurine, to form glycocholate and taurocholate
What are the 2 primary bile acids synthesised in liver and what secondary acids are produced from them by gut bacteria?
- Cholic acid → deoxycholic acid
- Chenodeoxycholic acid → lithocolic acid
What is the function of bile salts and what is their molecular structure described as (one word VSAQ response)?
- Reduce surface tension of fats
-
Emulsify fat prior to its digestion and absorption
- They are amphipathic- have 2 faces- 1 hydrophilic (hydroxyl and carboxyl) which faces OUT and dissolves in water
- 1 hydrophobic (nucleus and methyl) which faces IN and dissolves in fat
How is bile flow + secretion regulated?
- Between meals the Sphincter of Oddi is closed- bile is diverted into gall bladder for storage
- When eating, Sphincter of Oddi relaxes- gastric contents with FFAs and AAs enter duodenum causing release of cholecystokinin (CCK) which causes gall bladder to contract
- What happens to bile salts once they enter the ileum?
-
- 95% of bile salts are reabsorbed from terminal ileum by Na+/bile salt co-transport ATPase system- these go back to liver and re-excreted into bile through biliary transporters (enterohepatic circulation)
- 5% is converted to secondary bile acids in colon- all deoxycholic acid is absorbed but 99% of lithocolic acid is excreted into stool
What are the functions of the gallbladder, what triggers it’s contraction?
1) Stores bile (50 ml)- concentrates and acidifies it
2) Contraction triggered by CCK which binds to $CCK_A$ receptors & neuronal plexus of GB wall innervated by preganglionic parasympathetic fibres of vagus nerve
When gastric contents (FFAs, AAs > CHOs) enter the duodenum, what chemical is released by the duodenum and what does it do?
Cholecystokinin
Causes gall bladder to contract to release bile
What are the properties of free (indirect/unconjugated) bilirubin?
- H2O insoluble
- Yellow pigment
Where does free BR come from?
- 75% from Hb (erythrocytes) breakdown
- 22% from catabolism of other haemoproteins
- 3% from ineffective bone marrow erythropoiesis
Billirubin in blood
- What is free bilirubin bound to in the blood?Albumin
- What should the concentration results of Bilirubin and Albumin of a sample from a patient with a functioning liver be?Low Bilirubin - would be good as it removes bileHigh Albumin
- Describe the conversion of indirect bilirubin into direct bilirubin and then how is this taken up into the GIT?
Most of the bilirubin dissociates with the albumin in the liver and enters the hepatocytes
BR conjugated with 2 molecules of UDP-glucuronate → bilirubin diglucuronide (direct bilirubin)
Secreted across concentration gradient into biliary canaliculi → GIT
What happens to bilirubin in gut?
- We excrete 200-250mg BR into bile a day
- 85% excreted into faeces
- BR (green square) → urobilinogen → stercobilinogen → stercobilin (brown compound)
- 15% enters enterohepatic circulation
- BR → deconjugated → lipophilic form
- Urobilinogen
- Stercobilinogen
- 1% enters systemic circulation & excreted by kidneys in urine
What is an ERCP and what is it used for?
Endoscopic Retrograde Cholangiopancreatography
If you have a distal blockage in biliary system, we can put tube with deflated baloon into duodenum through stomach to access ampulla
Usually blockage is stones, so balloon goes behind stones, blows up then pulls stones out
What is PTC and what is it used for?
Percutaneous Transhepatic Cholangiography
If we have tumour in liver that causes blockage of liver ducts, we put a needle into hepatic bile duct which we take to get to blockage to clear it
Which compound gives faeces its brown colour?
Stercobilin
If BR cannot get into the gut, what condition does this cause?
Obstructive Jaundice
BR cannot be converted into stercobilin and so the faeces becomes very pale
This causes the bile to leave via the kidneys so this causes dark urine
How would you clear a blockage that prevents blood getting out distally from the pancreatic side of the biliary system?
Endoscopic Retrograde Cholangiopancreatography (ERCP)
Put camera into duodenum and access ampulla via Sphincter of Oddi
Run deflated balloon past the stones in the bile duct and then inflate the ballloon
Then pull the stones from the bile duct
- How would you clear the blockages of ducts in the liver?
Run needle into skin with local anesthetic, into the liver and into the bile duct and to wherever the blockage might be
Then remove the blockage through the Sphincter of Oddi so they can enter the duodenum
This is called Percutaneous Transhepatic Cholangiography
Bike formation
Bile made in the liver. Hepatocytes make bile acids,cholesterol,bilirubin. This is transported into bile canaliculi to combine with bicarbonate to form bile
