Hepatobiliary System Flashcards
Which ligament separates the right and left lobe of the liver?
The falciform ligament
What structure anatomically separates the right and the left liver?
The middle hepatic vein
How any different segments does the liver have?
8
What is the purpose of the blood delivered to the liver by the hepatic portal vein?
Carries venous blood drained from the spleen, GI tract and associated organs
What is the purpose of the hepatic artery?
To carry blood from the aorta to the liver
Which two blood vessel compose of the dual blood supply of the liver?
- Hepatic artery
- Portal vein
What vessels are responsible for the outflow of the liver?
The hepatic veins and the bile ducts
How many hepatic veins are in the liver?
3 – right, middle and left hepatic veins
Which side of the liver are functional segments 1-4 found on?
The left side
Which side of the liver are functional segments 5-8 found on?
The right side
What is the teres ligament?
- Emerges from the posterior side of the liver
- Reminant of the fetal umbilical cord
What is the sinusoid?
Mixed arterial and venous blood which drain into the central veins
What are the two sides which all hepatocytes have?
They have a bile-canaliculi facing side and a sinusoid facing side
What is a hepatic lobule?
The hexagonal structual unit of liver tissue
What is found at each corner of a hepatocyte?
Portal triad
What is found at the center of each hepatic lobule?
Central vein
What is the function of the central vein in the middle of the hepatic lobules?
Collects blood from the hepatic sinusoids into the hepatic veins and into the systemic venous system
What is a portal triad?
Structure found at every corner of a hepatic lobule, consists of a hepatic artery, portal vein and a bile duct
What does the hepatic artery in the portal triad do?
Brings O2-rich blood into liver to support the high energy demands of hepatocytes
What does the portal vein in the portal trial do?
Brings mixed venous blood from GIT (nutrients, bacteria and toxins) and spleen (waste products)
What do hepatocytes do with blood from the portal veins?
Process nutrients, detoxify blood and excrete waste
What is the purpose of the bile duct in the portal triad?
Bile produced by hepatocytes drains into a bile canaliculi
What is a hepatic acinus?
- Functional unit of the liver
- Consists of two adjacent 1/6th hepatic lobules, which share two portal triads and extend into the hepatic lobules as far as the central vein
Describe the three zone model
Zone 1 - closest to the edge of the hepatic lobules and near the portal triad
Zone 2 - middle
Zone 3 - closest to the central vein
Describe the blood which is recieved in zone 1?
Zone 1 is closest to the portal triad, thus recieves the most oxygenated blood however has the highest risk of toxins
Describe the blood recieved in zone 3 of the hepatic acinus?
Zone 3 blood is low in oxygen, but the toxin risk is also lower
Which zone of the hepatic acinus is usually affected by ischaemia?
Zone 1
What type of endothelial cells are sinusoidal endothelial cells?
Fenestrated (discontinuous endothelium)
What do sinusoidal endothelial cells do?
Allow lipids and large molecule movement to and from hepatocytes
Where are Kuppfer cells found?
In the sinusoid, attached to the sinusoidal enodthelial cells
What are Kuppfer cells?
Sinusoidal macrophages
What is the purpose of the Kuppfer cell?
Eliminate and detoxify substances arriving in liver from portal circulation via phagocytosis
Where are the hepatic stellate cells found?
In the space of disse
Where is the space of disse found?
In the gap between the hepatocytes and the sinosoid
What are the three roles of the hepatic stellate cells?
- Store Vitain A in the liver in cytosolic droplets
- Become activated (fibroblasts) in response to liver damage
- Proliferate, chemotactic and deposit collagen in ECM
What hepatocytes responsible for synthesizing?
Albumin, clotting factors and bile salts
What are cholangiocytes and what are there functions?
Cells lining the bile ducts that secrete bicarbonate and water into the bile
What are the metabolic and catabolic functions of the hepatocyte?
Synthesis and utilization of carbohydrates, lipids and proteins
What are the secretory and excretory functions of the hepatocyte?
Synthesis andsecretion of proteins, bile and waste products
What are the detoxification & immunological functions of the hepatocyte?
Breakdown of ingested pathogens and processing of drugs
Describe how the liver participates in the cori cycle?
- Muscle cell takes up glucose and undergoes glycolysis
- This produces pyruvate
- One of the fates of pyruvate is lactate production
- Lactate is taken up by liver and converted into pyruvate using lactate dehydrogenase
- Gluconeogenesis occurs in the liver, producing glucose from pyruvate
How many ATP and GTP molecules does gluconeogenesis require?
4 ATP and 2 GTP
Describe the process of protein synthesis in the hepatocyte
- Amino acids are transported into the liver (from diet in fed state, or from muscle cells in fasting state)
- Amino acids are converted into secreted proteins like plasma proteins, clotting factors and lipoproteins which are then secreted out of the liver
Describe how non-essential amino acids are produced?
Through different transamination reactions which involve different transaminase enzymes
When alpha-keto glutarate undergoes transamination, which amino acids are produced?
Glutamate and proline
How is alanine (a non essential amino acid) produced?
Transamination of pyruvate
How is aspartate produced?
Transamination of oxaloacetate
Muscle can potentially utilise amino acids to produce glucose for energy; but converting pyruvate to glucose requires energy. How is this problem overcome?
By transferring the problem to the liver:
1. Pyruvate from glycolysis and glutamate from amino acid breakdown undergo deamination to produce alanine
2. Alanine is transferred to the liver where it undergoes another deamination reaction to produce glutamate and pyruvate
3. The glutamate is then converted into urea using 4 ATP and is then excreted
4. The pyruvate is the converted into glucose using 6 ATP and is then taken up by the muscle cells
What is the main energy store in the body?
Fat
Where is fat stored?
In adipose tissue and the liver
What happens to excess glucose when glycogen stores in the liver are full?
When glycogen stores are full, the liver converts excess glucose and amino acids to fat for storage
Describe what happens to fatty acids in the liver?
Fatty acids are converted into Acetyl CoA through beta oxidation which the enters into the TCA cycle
How is acetoacetate formed from 2 x Acetyl CoA?
- 2 x acetyl CoA makes acetoacetyl CoA
- Adding another CoA makes HMG CoA
- HMG CoA is then cleaved to form acetoacetate which is a ketone body and is used as a tissue energy source
Which two enzymes are involved in lipogenesis or fatty acid synthesis?
Fatty acid synthase and acetyl CoA carboxylase
How are the hepatocytes involved in lipoprotein synthesis?
- Glycerol and fatty acids combine to form tri-acyl glycerol in the liver
- These tri-acyl glycerol molecules combine with apoproteins to make lipoproteins
What is one of the major roles for cholesterol in cells?
Maintenance of cell membrane integrity
What is the purpose of LDL?
To transport cholesterol to tissues
What is the purpose of VLDL?
To transport fatty acids to tissues
What is the purpose of HDL?
They are empty and important for picking up excess cholesterol
What is the hepatocyte responsible for storing?
- Vitamin B12, A, D, E and K
- Iron
- Copper
What are the four fat soluble vitamins?
A, D, E and K
What process is vitamin K responsible for?
Blood clotting
How does the hepatocyte store iron?
As ferritin - ensures it is available for erythropoesis
Describe how the hepatocytes are involved in detoxification?
- P450 enzymes carry out detoxification in 2 stages
- Phase 1 is modification – making the substance more hydrophilic
- Phase 2 is conjugation – attaching a water soluble side chain to make the substance less reactive
What are the uses of bile?
- Cholesterol homeostasis
- Absorption of lipids & lipid soluble vitamins (A, D, E, & K)
What is bile involved in the excretion of?
- Xenobiotics/drugs
- Cholesterol metabolites
- Adrenocortical and other steroid hormones
- Alkaline phosphatase
Label this diagram of the biliary system
How much bile is produced?
500ml a day
Why bile yellow/green?
Bilirubin is yellow and biliverdin is green
How are hepatocytes involved in bile production?
- Primary secretion – they secrete 60% of total bile
- Secretion of bile salts, lipids and organic ions
How are cholangiocytes involved in bile production?
- Secrete 40% of total bile
- Involved in secondary modification
What is secondary modification by cholangiocytes?
- Altering pH by secreting bicarbonate into bile
- Drawing H2O into bile by osmosis via paracellular junctions
- Exocytosing IgA
- Reabsorbing luminal glucose and organic acids
- Secreting bicarbonate and chloride into bile by cystic fibrosis transmembrane regulator
What are biliary transporters and what do they do?
Excrete bile salts and toxins
What are the main biliary transporters?
- Organic anion transporting peptides (for bile salt uptake)
- Na+ taurocholate-cotransporting polypeptide (for bile salt uptake)
- Bile salt excretory pump (for active transport of bile salts into bile)
- MDR related proteins (for excretion of xenobiotics and cytotoxins)
- Products of familial intrahepatic cholestasis gene (FIC1)
What are bile salts (acids) made from? Give 2 examples
- Synthesised from cholesterol
- Na and K salts of bile acids (e.g. cholic acid) are conjugated in the liver to form glycine and taurine, which then form glycocholate and taurocholate
What are the 2 primary bile acids synthesised in the 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?
- Reduce surface tension of fats
- Emulsify fats before digestion and absorption
- Have an amphipathic structure
Describe the amphipathic structure of bile salts
- 1 hydrophilic face (hydroxyl and carboxyl) faces out and dissolves in water
- 1 hydrophobic face (nucleus and methyl) faces in and dissolves in fat
How is bile flow and secretion regulated?
- Between meals, the sphincter of oddi is closed and bile is diverted into the gall bladder for storage
- When eating, the sphincter of oddi relaxes, allowing free fatty acids and amino acids to enter the duodenum and stimulate CCK release, causing gall bladder contraction
What happens to bile salts once they enter the ileum?
- 95% is reabsorbed from the terminal ileum by Na/bile co-transport ATPase
- The reabsorbed bile salts go back to the liver and are re-excreted into bile via biliary transporters
- 5% is converted to secondary bile acids in the 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?
- Stores, concentrates and acidifies bile
- Contraction is triggered by CCK, which binds to CCKA receptors
- Contraction is also triggered by the neuronal plexus of the gall bladder wall
What is the neuronal plexus of the gall bladder wall innervated by?
Preganglionic parasympathetic fibres of the 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 contraction which releases bile
What are the properties of free (indirect/unconjugated) bilirubin?
H2O insoluble
Yellow pigment
Where does free BR come from?
75% from Hb breakdown
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 is normal as bile should be removed
- 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 albumin and enters the hepatocytes
- The enzyme glucuronyl transferase conjugates bilirubin with glucuronic acid to form bilirubin diglucuronide (direct bilirubin)
- Direct bilirubin is secreted into the biliary canaliculi in bile
What happens to bilirubin in gut?
- 200-250mg is excreted into bile every day
- Most bile acid is reabsorbed into the enterohepatic circulation in the terminal ileum
- But conjugated bilirubin passes into the colon instead
How is bilirubin excreted in faeces?
- Conjugated bilirubin passes into the colon
- Bacteria remove glucuronic acid from conjugated bilirubin, forming urobilinogen (colourless)
- Oxidation then forms stercobilin (brown)
What are pre-hepatic causes of jaundice?
- Problem occurs before bilirubin reaches the liver
- Results in excess unconjugated bilirubin
- Usually due to excessive haemolysis
- E.g. due to haemolytic anaemia, blood transfusions or haemolytic drugs
What are intrahepatic causes of jaundice?
- Can be due to damaged hepatocytes
- E.g. in hepatitis, cirrhosis, hepatic carcinoma
- Or due to inability conjugating or secreting bilirubin in bile
- E.g. in Gilbert’s, Crigler Najjar, Dubin Johnson syndrome
What is post-hepatic (obstructive) jaundice?
Something stopping the flow of bile from the liver into the intestines (causing cholestasis)
List extra-hepatic causes of obstructive jaundice
Calculous cholecystitis
Acalculous cholecystitis
Carcinoma of pancreas head
Oedema from pancreatitis
List intra-hepatic causes of obstructive jaundice
Swelling or fibrosis from cirrhosis
What is an ERCP and what is it used for?
- Endoscopic retrograde cholangiopancreatography
- If there is a distal blockage in the biliary system, a tube with an inflated balloon is inserted into the duodenum via the stomach to access the ampulla
- The balloon goes behind the stones, inflates and pulls the stones out
What is PTC and what is it used for?
- Percutaneous transhepatic cholangiography
- A tumour in the liver could cause blockage of liver ducts
- Hence a needle is inserted into the hepatic bile duct
If BR cannot get into the gut, what condition does this cause?
- Obstructive (post-hepatic) jaundice
- Bilirubin cannot be converted into stercobilin, thus faceces become very pale
- This causes the bile to leave via the kidneys instead, causing 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
- Insert a camera into the duodenum and access the ampulla via the sphincter of oddi
- Run the deflated balloon past the stones in the bile duct and then inflate the balloon, pulling the stones out
How would you clear the blockages of ducts in the liver?
- Percutaneous transhepatic cholangiography
- Insert needle into skin with local anaesthetic, into the liver and then into the bile duct where the blockage is
- Remove the blockage through the sphincter of oddi
