hepatobilliary system Flashcards
- Which structure is the remenant of the umbilical vein of the foetus?
- Briefly outline the outflow and inflow of the liver
Ligamentum Teres
Inflow- Hepatic artery (25%), Portal vein (75%)
Outflow- Bile and 3x hepatic veins
- What is the purpose of blood delivered to the liver by the Portal Vein?
Contains all of the products of digestion absorbed from the GI tract
So all useful and non-useful products are processed in the liver before being released back into the hepatic veins which join the Inferior Vena Cava or stored in the liver for later use
- What is the purpose of blood delivered to the liver by the Hepatic Artery?
Delivers oxygenated blood from the general circulation
- What parts of the liver does the middle hepatic vein separate?
- How many hepatic segments are there?
Anterior segment of right hepatic lobe from the medial segment of the left hepatic lobe.
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- List the micro-morphological and functional components of the liver.
Morphological - Lobules + Portal triads
Functional - Acinus, blood and bile flow
- What shape is a hepatic lobule and describe the structure of 1 hepatic lobule?
Hexagon - Each corner consists of a portal triad which links with 3 adjacent lobules.
- What does a portal triad consist of? What is the function of each constituent?
Branch of hepatic artery - Brings O2-rich blood into liver to support hepatocytes increased energy demands.
Branch of portal vein - Mixed venous blood from GIT (nutrients, bacteria and toxins) and spleen (waste products). Hepatocytes process nutrients, detoxify blood and excrete waste. Bile Duct - Bile drains into bile canaliculi and then coalesce with cholangiocyte-lined bile-ducts around lobule perimeter.
- What type of cell are bile-ducts lined by and what is the function of this cell type?
Cholangiocyte
Modification of hepatic canalicular bile as it is transported along the biliary tree
- Through what vessels does blood flow through to get from the central vein to the right, left or middle hepatic veins?
Central → Intralobular → Interlobular → Right, Middle or Left Hepatic Veins
- What is the functional unit of the liver (in terms of micro-function) and what does it consist of?
Hepatic acinus
Consists of 2 adjacent 1/6th hepatic lobules sharing 2 portal triads. They extend into hepatic lobules as far as the central vein.
- At what point does blood drain out of the hepatic acinus?
- Which zones in the model below receives the most oxygen?
- Which zone has the lowest toxin risk?
central vein
Zone 1 (in the centre on the edges of the lobule) : Highest oxygen concentration (also highest toxin risk) Zone 3 (on the outskirts in centre of the lobule) : Lowest toxin risk (also lowest oxygen concentration)
- Do sinusoidal endothelial cells have a basement membrane?
- Describe the structure of their endothelium and how does this adapt the endothelium to its structure
No
Discontinuous, fenestrated endothelium
Allows lipids and large molecule movement to and from hepatocytes
- What is the difference between a bile canaliculus and a bile duct?
Bile canaliculi are thin tubes that collect bile secreted by hepatocytes and they empty into a series of progressively larger bile ductules and ducts that eventually become the common hepatic duct
- What are Kuppfer cells and what are their functions?
Sinusoidal macrophage cells attached to endothelial cells
Phagocytosis; they eliminate and detoxify substances arriving in liver from portal circulation
- What is another name for ito or perisinusoidal cells? List all the functions of these cells
Hepatic stellate cells
Store vitamin A in liver cytosolic droplets
Activated in response to liver damage Deposit collagen in the ECM
- What does a cholangiocyte secrete into bile?
HCO3- and H20
- Summarise the main hepatocyte functions
Metabolic and catabolic functions - make + use carbohydrates, lipids and proteins
Secretory and excretory functions - Synthesis and secretion of proteins, bile and waste products Detoxification and immunological functions - breakdown of ingested pathogens and processing of drugs
- List 3 non-sugar molecules that can be used to produce glucose via gluconeogenesis
Amino acids (from liver and renal cortex)
Lactate (from anaerobic glycolysis in RBCs and muscles) Glycerol (lipolysis)
- Outline the reactions of the Cori Cycle
Lactate produced via anaerobic glycolysis in a muscle cell (myocyte) is transported to the liver and is converted to pyruvate via lactate dehydrogenase
Pyruvate then converted to glucose via gluconeogenesis, using 6 ATP in the process. Glucose is transported to muscle cell Glucose via glycolysis to pyruvate → lactate in muscle cells and the cycle starts over again
- Where do amino acids undergo protein synthesis and what are some examples of the proteins that are produced?
Liver
Plasma proteins, Clotting factors and Lipoproteins
- Briefly explain what transamination is using alanine and alpha-keto glutarate as an example
Keto-acids can be converted into multiple amino acids depending on the specific transaminase enzyme responsible for conversion
This will occur in the liver Alanine + alpha-keto glutarate → Glutamate + Pyruvate
- How are fatty acids from triglyceride breakdown converted into acetyl CoA?
Beta-oxidation
- What is the main function of LDLs, VLDLs and HDLs?
LDLs - Transport cholesterol to tissues
VLDLs - Transport fatty acids to tissues. HDLs - Transport endogenous cholesterol from tissues to liver.
- What do hepatocytes store?
Vitamin A, D, E, K and B12.
Store iron as ferritin (available for erythropoiesis) Copper
- Outline how hepatocytes carry out detoxification
Phase 1 (modification) - P450 enzymes used. Reactions classified into oxidation, reduction and hydrolysis. More hydrophilic phase.
Phase 2 (conjugation) - Attach water soluble side chain to make less reactive.
- What is the majority of bile made of?
- What are the bile pigments?
97% Water
Bilirubin and biliverdin
- List the uses of bile
Cholesterol homeostasis
Absorption of lipids and lipid-soluble vitamins (ADEK)
Excretion of
- Xenobiotics/drugs - chemical substance that is foreign to animal life
- Cholesterol metabolites
- Adrenocortical and other steroid hormones
- Alkaline phosphatase
- How much bile is produced daily? What percentage do hepatocytes and and cholangiocytes secrete?
500 ml
Hepatocytes - 60% Cholangiocytes - 40%
- What colour is biliverdin?
Green
- Outline the secondary modification of bile after primary secretion by hepatocytes
Done by cholangiocytes
Alteration of pH H20 drawn into bile via osmosis Luminal glucose and organic acids reabsorbed HCO3- and Cl- actively secreted into bile by CFTR IgA is exocytosed
- What are bile acids synthesised from?
- What 2 compounds are the Na+ and K+ salts of bile acids conjugated in the liver to?
Cholesterol
Glycine and Taurine
- What are the 2 primary bile acids synthesised in the liver?
Cholic acid
Chenodeoxycholic acid
- What are the 2 secondary bile acids produced from these 2 primary acids by gut bacteria?
Cholic acid → Deoxycholic acid
Chenodeoxycholic acid → Lithocolic acid
- What are the 2 functions of bile salts?
Reduce surface tension of fats
Emulsify fat prior to its digestion and absorption
- What are the main non-essential amino acids that are formed from the deamination of alpha-ketoglutarate, pyruvate and oxaloacetate?
Alpha-keto gluatarate - glutamate and proline (also arginine)
Pyruvate - alanine (also valine and leucine) Oxaloacetate - aspartate (methionine and lysine)
- Outline the glucose-alanine cycle
Pyruvate is produced from anaerobic glycolysis and glutamate from amino acid breakdown in muscle cells
using an amino transferase, they react together and alanine is formed
alanine is taken to liver and reacted with alpha keto-glutarate to re form glutamate and pyruvate
in the liver, pyruvate uses 6ATP to be converted to glucose which is taken back to muscle cell to be used as energy
glutamate uses 4 ATP to be mad into urea and excreted out of cell.
- What are the major functions of cholesterol?
Maintaining membrane integrity.
Steroidogenesis
outline the primary secretion of bile from hepatocytes
bile secretions reflect serum concentrations
secretion of bile salts, lipids and organic ions
- Where can you find biliary transporters?
- What are biliary transporters?
Apical surface and basolateral membranes of hepatocytes and cholangiocytes
perform biliary excretion of bile salts and toxins
- List the main biliary transporters and briefly their function
Bile Salt Excretory Pump (BSEP) - active transport of BAs into bile
MDR related proteins Products of familial intrahepatic cholestasis gene (FIC1) Products of multidrug resistance genes - MDR1 → excretion of xenobiotics and cytotoxins - MDR3 → phosphatidylcholine
- What compound does a bile salt form and describe briefly the structure of this compound?
Micelles - Steroid nucleus planar with 2 faces (Amphipathic)
1st surface is hydrophilic due to hydroxyl and carboxyl groups - faces out → dissolves in water 2nd surface is hydrophobic due to nucleus and methyl - faces in → dissolves in fat Composed of FFAs and cholesterol
- What happens to the Sphincter of Oddi and therefore bile, between meals?
- What happens to the Sphincter of Oddi when you eat?
It is closed → bile diverted into gall bladder for storage
It relaxes, to release pancreatic juice and bile
- 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 is the function of the enterohepatic circulation?
- What percentage of bile salts is reabsorbed from the terminal ileum?
Allows for recycling of metabolised and non-metabolised compounds
95%
- What is the name of the system used to reabsorb bile in the terminal ileum?
Na+/Bile salt co-transport Na+-K+ ATPase system
- How much of the primary bile salts are converted into secondary bile salts in the colon?
- What happens to these absorbed bile salts?
5% are converted to secondary bile salts
All deoxycholic acid is absorbed
99% lithocolic acid is excreted in stool
They go back to the liver and are re-excreted in bile
- What are the 2 functions of the gallbladder?
Stores bile (50ml)
- Concentrates and acidifies bile
Gallbladder contraction
- controlled by CCK - CCK binds to CCKA receptors and neuronal plexus of GB wall (innervated by preganglionic parasympathetic fibres of vagus nerve)
- Is free bilirubin H20 soluble, and what colour is it?
No, H20-Insoluble
Yellow pigment
- Where does the majority of BR come from?
Haemoglobin (75%) - erythrocyte breakdown
- Where does the rest of the BR come from?
22% from catabolism of other haemoproteins
3% from ineffective Bone Marrow erythropoiesis
- What is free bilirubin bound to in the blood?
- What should the concentration results of Bilirubin and Albumin of a sample from a patient with a functioning liver be?
Albumin
Low Bilirubin - would be good as it removes bile High 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 blood and enters the hepatocytes
BR is conjugated with 2 molecules of UDP-glucuronate → bilirubin diglucuronide (direct bilirubin) Secreted across concentration gradient into biliary canaliculi → GIT
- What happens to BR once it enters the large intestine?
85% secreted in faeces
- BR → Urobilinogen → stercobilinogen → stercobilin
15% enters enterohepatic circulation
- BR → deconjugated → lipophilic form
- Urobilinogen
- Stercobilinogen
1% enters systemic circulation and excreted by kidneys
- 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 anaesthetic, 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
