Week 9- Hepatobiliary System Flashcards
Where is the liver situated?
Underneath the right pec
What is found right on top of the liver?
The diaphragm
What is the name of the ligament that divides the left lobe of the liver from the right? Where is it found
Falciform ligament. It is found going from the left side of inferior vena cava to the gallbladder fossa
What does the inflow of blood supply of the liver consist of?
Hepatic artery (25%) Portal vein (75%)
What does the outflow of blood supply of the liver consist of?
Bile
3 hepatic veins
What 2 ducts join to form the bile duct?
Common left and common right hepatic duct
What is the point of the common right and left hepatic ducts joining called?
Hyloconfluence/hylum
What is the duct where the gall bladder comes off the liver called?
Cystic duct
What is the section of the bile duct between the hyloconfluence and cystic duct called?
Common hepatic duct
What is the section of the bile duct after the cystic duct called?
Common bile duct
What are the 3 hepatic veins called?
Right, middle and left hepatic veins
What does the right hepatic vein split the right side of the liver into?
Anterior (right medial) and posterior (right lateral)
How many segments does the liver have?
8
What is segment 1 of the liver sandwiched between?
Inferior vena cava and portal vein
What does the left hepatic vein split the left side of the liver into?
Left medial and left lateral
What goes in and out of each liver segment?
Portal vein and hepatic artery going in
Bile duct coming out
What does a hepatic lobule look like?
Hexagonal structure, each corner has a portal triad and centre has a central vein
What do portal triads of hepatic lobules link with?
3 adjacent lobules
What is the role of a central vein in a hepatic lobule?
To collect blood from hepatic sinusoids to deliver it to hepatic veins and into the systemic venous system
What 2 sides do hepatocytes contain?
Sinusoid facing side
Bile canaliculi facing side
Where are hepatocytes in hepatic lobules found?
In the lobules
What is the role of the hepatic artery?
Brings oxygen rich blood into the liver to support hepatocytes high energy demands
What is the role of the portal vein?
Hepatocytes process nutrients, detoxify blood and excrete waste, takes away mixed venous blood from GI tract and spleen
Where does bile produced by hepatocytes drain to?
Bile canaliculi
Describe a hepatic acinus
It is a functional unit consisting of 2 adjacent 1/6 hepatic lobules (looks like a diamond shape) that share 2 portal triads and extend into hepatic lobules as far as the central vein
How many zones is the hepatic acinus split into?
3
Describe the 3 zones of the hepatic acinus
Zone 1- Receives blood most so highest 02 and toxin risk
Zone 2- Less blood, lower o2 and toxin risk
Zone 3- Least blood, lowest o2 and toxin risk- where central vein is
If a person was in a car accident and bleeding out, which zone of the hepatic acinus would suffer most first and why?
Zone 3 as it has the lowest blood supply and oxygen
Describe sinusoidal endothelial cells
No basement membrane
Fenestrated (discontinuous epithelium)
Allow lipids and large molecules to move to and from the hepatocyte
Describe Kuppfer cells
Sinusoidal macrophage cells
Attached to endothelial cells
Carry out phagocytosis (detoxification)
Describe hepatic stellate cells
Exist in dormant state
Store vit A in liver cytosolic droplets
When activated act as fibroblasts and cause scarring (cirrhosis)
Proliferate, chemotatic and deposit ECM
Describe hepatocytes
80% of liver mass
Main working cell
Synthesise albumin, clotting factors and bile salts
Metabolise drugs
What do hepatocytes receive nutrients from?
Sinusoids
What are the 3 main categories of functions of the liver?
Metabolic and catabolic
Secretory and excretory
Detoxification and immunological
Describe the Cori cycle
When glucose runs out lactate is produced, this is carried to the liver which converts it back into pyruvate and carries out gluconeogenesis so the muscle can be provided with more sugar
What is the name of the cycle that the liver is involved with to do with carbohydrate metabolism?
Cori cycle
Describe how the liver is involved with protein synthesis and state the main proteins it synthesises
Amino acids come from the diet (fed state) or the muscle (fasted state) and are joined up to make proteins in the liver, mainly plasma proteins (albumin), clotting factors and lipoproteins
What special amino acids does the liver produce?
Non essential amino acids (via transamination)
What can you look at via blood tests to get an indication of how their liver is doing?
Albumin levels
ALT/AST (transaminases that help produce non essential amino acids)
Why is it difficult for the muscle to utilise amino acids to produce glucose for energy? How does it get over this problem?
Conversion of amino acids to pyruvate requires lots of energy
Removal of nitrogen as urea requires lots of energy
Transfers the problem to the liver as the glucose alanine cycle
Describe the glucose alanine cycle
In the muscle cells alanine is formed from glutamate and pyruvate via alanine transaminase
Alanine shuttles along alpha ketoglutarate to liver
Alanine is converted back to pyruvate and glutamate producing energy
In liver glutamate is converted to urea which goes to blood
and pyruvate is converted to glucose which goes to the muscle for glycolysis
When is fat synthesised in the liver?
When glycogen stores are full
Describe how the liver metabolises triglycerides
In adipose tissue they are converted to fatty acids and carried to the liver where they are converted to acetyl coA via beta oxidation. This can then enter the TCA cycle and produce energy
How does the liver metabolise triglycerides if you want to outsource the energy source?
Fatty acids are converted to 2 acetyl coA via beta oxidation in the liver, these combine with one more acetyl coA and form acetoacetate which can be transported to other tissues
Describe how lipoproteins are synthesised in the liver
Glucose in the liver is converted either directly to glycerol or via pyruvate into acetyl coA which can then be made into fatty acids or cholestrol.
Glycerol and 2 fatty acids combine to form triacylglycerol these together with apoproteins, phospholipids and cholesterol combine to form lipoproteins
What is components in the liver are required to produce lipoproteins?
Triacylglycerol (from glycerol and fatty acids)
Apoproteins
Phospholipids
Cholesterol
Which lipoproteins does the liver produce
HDL
VLDL
What does the liver store? State what the most important thing it stores is
Fat soluble vitamins (A,D,E,K, K is most important as stores are small whereas others last 6-12 months)
Iron (stored as ferritin)
Copper
How does the liver carry out detoxification?
Uses P450 enzymes Phase 1 (modification)- makes it more hydrophilic Phase 2 (conjugation)- attaches a water soluble side chain to make it less reactive
What is the name of the muscle where the common bile duct and pancreatic ducts join?
Sphincter of oddi
Where does the common bile duct come out into the duodenum?
At the ampulla
What is the other name for bile salts?
Bile acid
What colour is bile?
Different colours depending on whats in it usually yellow or green
What are uses of bile?
Helps w cholesterol homeostasis
Absorption of lipids and lipid soluble vitamins
Excretion of xenobiotics/drugs, cholesterol metabolites, adrenocortical/steroid hormones and alkaline phosphotase
How much bile is produced daily?
500ml
What pigments are present in bile and what colours do they make bile?
Bilirubin- yellow
Biliverdin- green
What 2 cell types secrete bile and what % of total bile do they secrete?
Hepatocytes (60%)
Cholangiocytes (40%)
In bile production what is the main function of hepatocytes?
Primary secretion of bile (which reflects serum concentrations)
In bile production what is the main function of cholangiocytes?
Secondary modification ie alteration of pH, luminal glucose and organic acids absorbed, HCO3- and Cl- secreted into bile via CFTR, IgA exocytosed
What performs the excretion of bile salts and toxins?
Biliary transporters
What are some of the main biliary transporters?
Bile sale excretory pump (BSEP)
MDR related proteins
Products of multidrug resistant genes
What is bile synthesised from?
Cholesterol
What are sodium and potassium salts of bile acids conjugated 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 primary acids by gut bacteria?
Deoxcycholic acid
Lithocolic acid
How do bile salts work?
Reduce the surface tension of fats
Emulsify fat prior to its digestion and absorption
Describe a bile salt micelle
Hydrophilic exterior to dissolve in water
Hydrophobic interior dissolves in fat
In a bile salt micelle where are FFAs and cholesterol found?
Inside
What makes up a triglyceride?
Monoglyceride
2 fatty acids
What coenzyme does lipase need to digest triglycerides?
Colipase
What muscle plays a main role in regulating secretion vs storage of bile and how?
The sphincter of Oddi
Between meals it is closed and bile is diverted into the gall bladder for storage
When eating it relaxes
What chemical causes the gallbladder to contract?
Cholecystikinin (CCK)
What causes the release of CCK?
Gastric contents entering the duodenum
Where are bile salts reabsorbed and how much?
95% in the terminal ileum
What cotransporter is involved with reabsorbtion of bile salts?
Na+/bile co transporter
What happens to the 5% of bile salts that arent reabsorbed?
They are converted to secondary bile acids in the colon- deoxycholic acid is reabsorbed and 99% os lithocolic acid is secreted in the stool
Where do reabsorbed bile salts go?
To the liver where they can be re excreted
What is the function of the gallbladder?
Stores bile (50ml)- concentrates and acidifies it
What does CCK bind to on the gallbladder?
CCKa receptors
What nerve fibres innervate the gallbladder?
Preganglionic parasympathetic fibres of the vagus nerve
How essential is the gallbladder?
Not at all, you can easily live without it
What is free bilirubin?
Indirect/unconjugated, water insoluble
What is the main source of bilirubin?
75% from erythrocyte breakdown
How does bilirubin circulate before it gets to the liver?
Bound to albumin
How is bilirubin conjugated?
Via 2 molecules of UDP glucuronate to form bilirubin diglucuronide
Via what transporter is bilirubin diglucuronide secreted into the biliary canaliculi?
cMOAT
How much BR is secreted into bile daily?
200-250 mg
What happens to BR?
85% excreted in faeces
15% enters enterohepatic circulation
What compound makes poo brown?
Stercobilin
What happens in obstructive jaundice and what is a visible sign of it?
No bile is secreted into the large intestine so no stercobilin is produced and poo is white
What are causes of jaundice?
Pre hepatic- producing a lot more bilirubin eg sickle cell patients break down RBCs a lot more Intrahepatic- liver isnt working properly, either not taking up much bilirubin, decreased conjugation or secretion or flow obstruction in the billary trees Post hepatic (obstructive)- mechanical blockage
What is biliary colic?
Stones in gallbladder try to get out but they cant
What is cholecystitis?
When stones in the gallbladder get stuck in the cystic duct and cause infection
What is cholangitis?
When the stone gets out of the gallbladder and gets stuck in the bile duct causing the bile to become infected
What is ERCP?
A process by which gallstones are removed if they’re near the end of the biliary system by going in through the stomach and ampulla and up the bile duct
What is PTC?
A process by which gallstones are removed if they’re near the top of the biliary system by going in through the abdomen and finding a hepatic duct
