8.3: Hepatobiliary system Flashcards
What is the inflow of blood via the hepatic artery
25%
What is the inflow of blood to the liver via the portal vein
75%
What does the outflow of blood from the liver occur via
Bile
3x hepatic veins
What is the purpose of blood delivered to the liver by the portal vein
Contains all products of digestion absorbed from the GI tract
All useful and non-useful products are processed in the liver before being released back into the hepatic veins which join the IVC 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
Morphological structure of liver
Lobules
Portal triads (tracts)
3 functions of morphology of liver
Acinus
Blood flow
Vile flow
Describe the Structure of the hepatic lobule
Hexagonal structural unit of liver tissue In
Each corner consists of a portal triad - links with 3 adjacent lobules
What is the centre of a liver lobule
Central vein
Function of central vein at liver lobule centre
Collects blood from hepatic sinusoids -> hepatic veins -> systemic venous system
What can be found within a liver lobule
Rows of hepatocytes
Each has sinusoid-facing side and bile canaliculi-facing side
Portal triad
3 uses of bile
Cholesterol homeostasis
Absorption of lipids and lipid soluble vitamins
Excretion of: xenobiotics, cholesterol metabolites, adrenocortical and steroid hormones, alkaline phosphatase
Two bile pigments
Bilirubin - yellow
Biliverden - green
4 lipid soluble vitamins
A
D
E
K
How much bile is produced per day
500mls
Two cells that secrete bile
Hepatocytes - 60%
Cholangiocytes - 40%
In Primary secretion of bile
Bile secretions reflect serum concentrations
Secretion of bile salts, lipids and organic ions
In Secondary modification of bile
Alternation of pH
H2O drawn into bile via osmosis via paracellular junctions
Luminal glucose and organ is acids reabsorbed
HCO3- Cl- actively secreted into bile by CFTR
IgA exocytosed
What is Hillary excretion of bile salts and toxins performed by
Biliary transporters
2 main transporters of bile salts
Basolateral membrane (importing)
Apical surface (exporting)
Which structure is the remenant of the umbilical vein of the foetus?
Ligamentum Teres
What parts of the liver does the middle hepatic vein separate?
Anterior segment of right hepatic lobe from the medial segment of the hepatic lobe
How many hepatic segments are there?
8
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
The centre of the lobule is the central vein.
Outline its drainage
Collects blood from hepatic sinusoids -> hepatic veins -> systemic venous system
Within a lobule there are rows of hepatocytes, what does each side of the row of hepatocytes face?
Each has a sinusoid-facing side -> picks up stuff from the inflow of blood
Bile canaliculi facing side → Makes bile by taking nutrients, processing it and shifting it across to the biliary canaliculi
What does a portal triad consist of ? What is 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 and spleen. Hepatocytes process nutrients, deoxify 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 (micro-function) of the liver and what does it consist of ?
Hepatic acinus
Consist of 2 adjacent 1/6th hepatic lobules sharing 2 portal triads. They extend into hepatic lobules as far as the central vein
Do sinusoidal endothelial cells have a basement membrane?
No
Describe the structure of sinusoidal endothelial cells and how does this adapt the endothelium to its structure?
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 collecting 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
Function - phagocytosis - detoxify substances arriving in liver from portal circulation
Another name for perisinusoidal cells?
Hepatic stellate cells
3 Functions of perisinusoidal cells?
Store Vit A in liver cytosolic droplets
Activated in response to liver damage
Deposit collagen in the EMC
What does a cholangiocyte secrete into bile?
HCO3- and H2O
3 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)
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
3 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, releasing 6 ATP in the process
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
What is transamination
Keto-acids can be converted into multiple amino acids depending on the specific transaminase enzyme responsible for conversion
This will occur in the liver
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 in muscle cells and then transported to the liver where it is converted to alanine via an aminotransferase enzyme. Nitrogen is also transported to the liver in the form of glutamine made from glutamate and ammonia catalysed by glutamine synthetase.
- Alanine converted goes from pyruvate to glucose through via gluconeogenesis. Glucose returned to muscle cell for glycolysis.
- Alanine also converted to glutamate. Glutamate to urea, gets deaminated and returned to blood.
How are fatty acids from triglyceride breakdown converted into acetyl CoA?
Beta-oxidation
How can Acetyl CoA be used as an alternative tissue energy source before running it through the TCA cycle?
2 Acetyl CoA can be converted into Acetoacetyl CoA via enzyme thiolase
Add another Acetyl CoA to Acetoacetyl CoA to get HMG CoA
HMG CoA can be cleaved to form a free Acetoacetate and another Acetyl CoA
What is the main energy reserve stored in the liver and muscle?
Glycogen
What is the main functions 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 are the 2 major functions of cholesterol?
Maintaining membrane integrity
Steroidogenesis
What do hepatocytes store?
Vit. A, D, E, K, B12
Store iron as ferritin
Copper
What vitamin is responsible for blood clotting?
Vit. K
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 97% of bile made up of?
97% water
3 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
Where can you find biliary transporters?
Apical surface of hepatocytes and cholangiocytes
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 are bile acids synthesised from
Cholesterol
What 2 compounds are the Na+ and K+ salts of bile acids conjugated in the liver to ?
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 the 2 primary acids by gut bacteria?
Cholic acid → Deoxycholic acid
Chenodeoxycholic acid → Lithocolic acid
2 functions of bile salts?
Reduce surface tension of fats
Emulsify fat prior to its digestion and absorption
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?
It is closed
Bile diverted into gall bladder for storage
What happens to the Sphincter of Oddi when you eat?
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 enterohepatic circulation?
Allows for recycling of metabolised and non-metabolised compounds
What % of bile salts is reabsorbed from the terminal ileum?
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 primary bile salts are converted into secondary bile salts in the colon?
5%
All deoxycholic acid is absorbed
99% lithocolic acid is excreted in stool
What happens to bile salts absorbed from the colon?
Return back to the liver and are re-excreted in bile
2 functions of the gallbladder
Stores bile (50ml) - concentrates and acidifies it
Contraction is controlled by CCK - binds to CCKA receptors and neuronal plexus of GB wall
Is free bilirubin H2O soluble?
No, it’s insoluble
Where does majority of BR come from?
Haemoglobin (75%) - erythrocyte breakdown
Where does the rest of BR come from?
22% from catabolism of other haemoproteins
3% from ineffective Bone Marrow erythropoiesis
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
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
15% enters enterohepatic circulation
1% enters systemic circulation and excreted by kidneys
Which compound gives faeces its brown colour?
Stercobilin
If BR cannot get into the guy, what condition does it 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
