Hepatobiliary System Flashcards
What is meant by the term ‘hepatobiliary’ system?
Hepato = liver
Biliary = bile ducts
Where does the liver lie anatomically?
Sits right up in the chest, pushes up against the diaphragm
If you can feel the liver (or the gallbladder) from pressing down on the abdomen, it is too big / abonormal as they lie inside the chest
What is the morphological anatomy of the liver? Fill in the labels on the diagram:
What is the lingamentum teres?
reminence of the umbilical vein of the fetus
Where is the left of the liver found?
Draw a line on the diagram below:
The liver is divide in half by the middle hepatic vein, which travels from the left side of the inferior vena cava where it crosses the liver to the gallbladder
So part of the right lobe also forms the left side
What vessels / ducts go into and out of the liver (inflow and outflow)?
Inflow = hepatic artery
Portal vein (75%)
Outflow = Bile duct split into 2 main ducts: the left and right hepatic ducts, which join to form the common hepatic duct (off which the gallbladder comes away from
then the common bile duct; 3x hepatic veins (left, right and middle)
What percentage of blood flow do the hepatic artery and portal vein deliver?
Hepatic artery- 25%
Portal veind- 75%
Why does the liver have 2 different blood supplies?
The liver receives a blood supply from two sources. The first is the hepatic artery which delivers oxygenated blood from the general circulation. The second is the hepatic portal vein delivering deoxygenated blood from the small intestine containing nutrients.
What are the different sectors the hepatic veins divide it into?
Middle hepatic vein divides the liver into the right and left side
Right hepatic vein divides the right side into the anterior and posterior sectors
Left hepatic vein divides the liver into the lateral and medial
How many functioning segments are in the liver?
Where are the different segments found?
8
Segment 1 - sandwiched between the IVC at the back and portal vein at the front
Left hepatic vein divides the liver into the lateral and medial, and right hepatic vein divides the liver into anterior and posterior
The segments travel clockwise on the right side - 5, 6, 7, 8
Which branches of the in/outflows travel to which segments?
Why is it important to know which vessels travel to which segments?
Right anterior branch of the portal vein corresponds to the anterior segments 5 and 8
Clinically e.g. taking out a part of the liver during surgery, tie off the blood supply to that segment
What are the 2 micro-morphological parts of the liver?
What is found in each of these structures? Label them on the diagram below:
- Hepatic lobules; 2. Portal triads
The central vein joins to the interlobular vein, joining to form the hepatic veins, which eventually return to the IVC
What is a hepatic lobule?
Hepatic lobule - hexagonal structural unit of the liver
with a portal triad on each corner
collects blood from hepatic sinusoids, a central vein in the centre,
within each lobule rows of hepatocytes separating the sinusoids and the bile canaliculi (bile capillary ducts)
What is the portal triad composed of?
Composed of the hepatic artery, portal vein and bile capillary duct
What is a portal triad?
found on the corner of each hepatic lobule, composed of the hepatic artery, portal vein and bile capillary duct
What is the function of the portal vein?
Portal vein - brings mixed venous blood from the GI tract (anything absorbed e.g. nutrients, bacteria, toxins, all processed in the liver first) and spleen (waste products e.g. bilirubin)
What is the function of the hepatic artery?
Hepatic artery - brings O2 rich blood supply to the hepatocytes
What are the functions of the hepatocytes?
process nutrients, detoxify blood, and excrete waste
What is the function of the bile duct?
Bile duct - bile produced by hepatocytes drains into the bile canaliculi
Coalesce with cholangiocyte-lined bile ducts around lobule perimeter
How is bile produced by the hepatocytes?
Sinusoids contain the nutrients brought in by the portal vein from the GI tract
Nutrients cross the hepatocytes - the hepatoytes process the nutrients to produce bile
Bile is secreted into the bile duct
What is the hepatic acinus?
What is the structure of the hepatic acinus? Label on the diagram below:
Hepatic acinus - a functional unit of the liver, consists of 1/6th each of 2 hepatic lobules
(diamond shaped)
Forms a diamond shape, with a central vein on each of the 2 opposite corners of the diamond, and a portal triad on each of the other 2 opposite corned of the diamond
How many zones is the acinus split into?
3
What is the three zone model of the acinus? Use the diagram below to explain it, how does the blood flow?
Points A are the portal triads, where the blood enters the hepatic acinus, and Points B are where the blood drains out of the hepatic acinus via the central vein
Zone 1 - closest to the portal triad and so highly oxygenated blood, but at high risk to toxins. This is because the hepatocytes in zone 1 receive early exposure to whatever is in the blood, good (O2) or bad (toxins) contents
Zone 2 - inbetween zones 1 and 3
Zone 3 - closest to the central vein and so less oxygenated blood, but lower risk to toxins
What are the 5 different liver cell types, where are they found and what is their function?
Sinusiodal cells
Kuppfer cells
Hepatic Stellate cells
Hepatocytes
Cholangiocytes
What are the main features of sinusiodal endothelial cells?
found in the sinusoids forming the walls, no basement membrane, leaky / fenestrated to allow lipids and large moleules to move in and out of the hepatocytes
What are the main features of Kuppfer cells?
sinusoidal macrophages attached to the endothelial cells, carry out phagocytosis to eliminate and detoxify substances arriving in the liver from portal circulation
What are the main features of hepatic stellate cells?
lie dormant usually,
store vitamin A in liver cytosolic droplets
when ativated act as fibroblasts,
when the liver is damaged lay down scar tissue (decreasing function of the liver)
Proliferate, chemotactic and deposit collage in ECM
What are the main features of the hepatocytes?
work forces of the liver forming 80% of the liver mass
Cubical
synthesise many substances e.g. albumin, clotting factors, bile salts, etc.
involved in drug metabolism
receive nutrients, and build the sinusoids (forming the sinusoid walls)
What are the main features of cholangiocytes?
- found at the ends of the bile ducts, secrete HCO3- and H2O into the bile
What are the 3 main functions of hepatocytes?
- Metabolic and catabolic = synthesis and ultilsation of carbohydrates, lipids and proteins
- Secretory and excretory = synthesis and secretion of proteins, bile, and waste products
- Detoxification and immunological = breakdown of ingested pathogens and processing of drugs
What is meant by these terms for cabohydrate metabolism?
Glycolysis - ?
Glycogenesis - ?
Glycogenolysis - ?
Gluconeogenesis - ?
Lipolysis - ?
Lipogenesis - ?
Glycolysis - refers to either the anaerobic conversion of glucose to lactate in RBCs, renal medulla, and skeletal muscle. Or refers to aerobic oxidation of glucose in the CNS, heart, skeletal muscle, and most organs
Glycogenesis - synthesis of glycogen from glucose in the liver and muscle
Glycogenolysis - breakdown of glycogen to glucose in the liver and muscle
Gluconeogenesis - production of glucose from non-carbohydrate molecules e.g. amino acids, lactate, glycerol
Lipolysis - breakdown of triglycerides / triacylglycerols into fatty acids and glycerol
Lipogenesis - synthesis of triglycerides / triacylglycerols for storage
How is carbohydrate metabolism monitored by the liver to modify hepatocyte function?
e.g. if the muscles are working hard:
When there is insufficient oxygen in the muscle cells for aerobic respiration, anaerobic respiration produces pyruvic acid, which is converted to lactate
Lactate travels to the liver, where it undergoes gluconeogenesis to form glucose once again so it can be used by the muscle cells
This is known as the Cori cycle
How does protein synthesis take place in the liver?
Amino acids come from the fed state (ingested food) or fasted state (breakdown of muscle) and are transported into the liver
They are used as building blocks to produce proteins e.g. albumin, clotting factors and lipoproteins
What is the difference between essential and non-essential amino acids?
How does the liver synthesise non-essential amino acids? What is looked for in blood tests to see if this liver function is working?
Essential = cannot be synthesised by the liver, non-essential = can be synthesised by the liver using other molecules (11 out of 20 amino acids are non-essential)
Transamination using transaminases, different transaminases can produce different amino acids e.g. alanine transaminase (ALT) and aspartate transaminase (AST) are looked for in blood tests
What are the non-essential amino acids?
Glutamate and proline (can be synthesised from alpha-keto glutarate)
Alanine (can be synthesised from pyruvate)
Aspartate (can be synthesised from oxaloacetate)
What is the glucose-alanine cycle?
Deamination
What are the 4 amino acids in highest concentration in the blood?
How does protein metabolism take place in the hepatocytes?
4 amino acids have the highest concentration in the blood - alanine, aspartate, glutamine, glutamate
Glutamate from amino acid breakdown and the pyruvate from glycolysis form alanine and alpha-keto glutarate
These are both transported into the liver via the blood, where they are once again converted back to glutamate and pyruvate.
The liver converts the pyruvate to glucose, and the glutamate to urea.
Why is the glucose-alanine cycle used?
Muscle can potentailly utilise amino acids to produce glucose for energy
BUT
Converting pyruvateto glucose
+ removing nitrogen as urea
Requires ENERGY
Solution: transfer problem to liver
How is fat used as an energy source? Where and how is it stored?
Fat is the main energy source, used 100x more than glycogen - stored in adipose tissue, glucose and amino acids converted to fat when glycogen stores are full
How does triglyceride metabolism take place in hepatocytes?
Fat in the adipose tissues are broken down to fatty aids, which are transported to the liver and oxidised to acetyl-CoA and enter the TCA cycle
How are fatty acids exported from the liver as an energy source?
Fatty acids are oxidised using Beta-oxidation to form 2x acetyl-CoAs, which combine to form acetoacetate. Acetoacetate is transported out as an energy sourc
How does lipoprotein synthesis take place in the liver?
Lipoproteins are synthesised from glucose - glucose can be converted directly to glycerol or via pyruvate to acetyl CoA. Acetyle CoA can then be converted to fatty acids or cholestrol
A glycerol, 2 fatty acids, apoproteins, and phospholipids (within which there is cholestrol) that combine to form lipoproteins
What are the 2 types of lipoproteins?
- VLDL (very low density lipoproteins) - transport fatty acids to adipose tissues to be stored as triglycerides. One that is done, it is now LDL and it transports cholestrol to other tissues; 2. HDL (high density lipoproteins) - high protein content and they travel to pick up excess cholestrol around the body
What are 2 major roles of cholestrol?
Cholestrol - keeps the integrity of membranes, building block for production of hormones (i.e. steroid hormones)
What are the storage functions of hepatocytes?
Stores fat soluble vitamins - A, D, E and K; K especially important as K stores are much smaller and K is important for clotting factors
Also stores iron, copper etc.
What is the detoxification function of hepatocytes?
Detoxifies substances in 2 steps:
- Phase 1 - P450 enzymes make substance more hydrophillic (modification)
- Phase 2 - attach water soluble side chain to make them less reactive (conjugation)
What is the purpose of the biliary system?
Produces bile
What is the biliary system composed of? Fill in the diagram below:
The joining of the hepatic and pancreatic ducts is via a structure called the sphincter of oddi - the ducts exit out into the duodenum
What is the composition of bile?
What is the colour of bile and what causes the colour changes?
It is mostly composed of water, the terms bile salts and bile acids are interchangeable
Bilirubin (yellow) and bilivirden (green) are the bile pigments - different compositions of these pigments mean bile colour can range from yellow to green
What are the 3 main uses of bile?
- Cholesterol homeostasis
- Absorption of lipids and lipid soluble vitamins (A,D,E,K)
- Excretion of xenobiotics (anything foreign to the body), cholesterol metabolites, steroid hormones and alkaline phosphatase
What are the 2 main cells responsible for bile production? What part of the process of bile production are each of these 2 types cells responsible for?
- Hepatocytes - secrete 60% of bile = primary secretion of bile salts, lipids and organic ions
- Cholangiocytes - secrete 40% of bile = secondary modification, adding water, bicarbonates and chloride leading to the alteration of the pH
What is excreted in the bile depends on what is found in the plasma
What are biliary transporters and what is their function in the biliary system?
The diagram shows a biliary canaliculi - two hepatocytes surrounding the bile
Biliary transporters are found on the surfaces of hepatocytes and cholangiocytes to bring in substances such as bile salts, drug metabolites, etc.
How are bile salts made?
What are the 2 primary bile salts made in the liver?
What are these 2 bile salts converted to once they enter the bowel via the biliary tube?
Bile salts synthesised from cholesterol, the Na+ and K+ components of the bile salts are conjugated in liver to glycine and taurine
Cholic acid and Chenodeoxycholic acid
The gut bacteria convert these to secondary bile salts - deoxycholic acid and lithocholic acid respectively
What is the function of bile salts? How do they achieve this function?
Reduce surface tension of fats - essentially emulsify fat prior to digestion
Bile salts have a hydrophilic (outside - hydroxyl and carboxyl groups) and hydrophobic face (inside - nucleus and methyl group)
Bile salts coat the fat globules forming emulsification droplets
Lipase and co-lipase act on these to break them down to miscelles (holding units of digested fats)
What does amphipathic mean?
Has hydrophobic and hydrophillic phases
Bile salts form micelles
Hydrophillic face, faces outwards so they can dissolve in water
Hydrophobic face, faces inwards so it can dissolve in fat
Bile acids are able to coat a fat globule
How is the secretion of bile and bile flow (via the transporters) regulated?
Using the Sphincter of Oddi - connects the hepatic and pancreatic ducts
Between meals, the Sphincter of Oddi remains closed so the bile produced is stored in the gallbladder
During meals, the Sphincter of Oddi opens so bile can enter the duodenum, gastric contents also include cholecystokinin (CCK)
Causes the gallbladder to contract (releasing more bile)
What is the enterohepatic circulation?
What is its function and what is it composed of?
95% of bile salts are reabsorbed back into the portal venous system
Hepatocytes in the liver produce bile salts, bile salts are released into the bowel during meal times. As the bile salts approach the terminal ileum, after having carried out its functions on lipids, they are reabsorbed by enterocytes
They travel back via the portal venous system to the liver to be reused
Where is the gallbladder found?
What are the 2 functions of the gallbladder and is it necessary for survival?
Found under the liver, on the right
- Stores bile
- During a meal, cholecystokinin (CCK) binds to CCK receptors, which triggers the contraction of the gallbladder so bile is released into the duodenum - innervated by the parasympathetic branch of the vagus nerve
Not necessary for survival
What is bilirubin?
Toxic - must be processed properly, a H2O-insoluble, yellow pigment
What is free bilirubin often referred to?
Indirect / unconjugated bilirubin = free bilirubin
What happens to bilirubin once it has been made?
Binds to albumin as it is insoluble
When it gets to the liver, it is released
Bilirubin inside the liver is then conjugated with 2 molecules of UDP-glucuronic acid so it can dissolve into the bile fluid
It travels down the concentration gradient through a transporter into the bile canaliculi
Where is bilirubin made / sourced?
Sourced from - 75% from erythrocyte / Hb breakdown, 22% from catabolism of other hemoproteins, 3% from ineffective
Which common disease does bilirubin link to?
bone marrow erythropoeisis
jaundice
How does bilirubin function?
Free BR bound to albumin in blood
Most disociats in liver and enters hepatocytes
BR conjugated with 2x molecules of UDP-glucuronate–> bilirubin diglucuronide
Secreted across conc gradient into biliary canaliculi –> GIT
Where and how is bilirubin excreted?
85% excreted in the faeces - bilirubin is converted to urobilinogen and stercobilinogen (both which are colourless and odourless), and then finally converted to stercobilin (brown)
14% enters the enterohepatic circulation
1% enters the systemic circulation and is excreted by the kidneys
What is jaundice?
Characteristed by yellow pigment of the skin and eyes due to high bilirubin levels
- Pre-hepatic jaundice
- Intrahepatic jaundice
- Post-hepatic jaundice
What is pre-hepatic jaundice?
too high bilirubin production e.g. with SCA RBCs constantly broken down forming bilirubin
What is intrahepatic jaundice?
liver failure / liver is not working properly, so not enough bilirubin is being taken up so more is in systemic circulation, decreased conjugation of bilirubin (not processed properly), decreased secretion so it cannot get rid of bilirubin, or outflow obstruction
What is post-hepatic jaundice?
= anything outside of the liver, due to obstruction e.g. gallstones meaning bile cannot come out etc.
What is:
choleliathesis?
cholecystisis?
cholangitis?
pancreatitis?
Choleliathesis - gallstones (v. painful as they try to get out but cannot)
Cholecystisis - gallstones in the gallbladder get stuck in the cystic duct causing back up of bile and infection of the gallbladder
Cholangitis - gallstone stuck in the common bile duct, bile gets infected
Pancreatitis - gallstone stuck in the main pancreatic duct so pancreatic juice cannot be released into the bowels
What is an ERCP? Why is it used?
Endoscopic retrograde cholangiopancreatography
A procedure that allows for the examination of the pancreatic and bile ducts - balloons can be inflated to get rid of gallstones from the biliary tree (generally from the lower half of the biliary tree)
What is a PTC? Why is it used?
Percutaneous Transhepatic Cholangiography
Used when the gallstone is further up the biliary tree, closer to the liver
Place wire through the abdomen up the liver, and keep pushing through the blockage until it has cleared
Define Cirrhosis
- Whole liver involved
- Fibrosis
- Nodules of regenerating hepatocytes
- Distortion of liver vascular architecture; intra- and extra- hepatic shunting of blood
How do you classify cirrhosis?
By nodule size:
Micronodular
Macronodular
OR by aetiology:
Alcohol/insulin resistance
Viral hepatitts
What are the complications of cirrhosis?
Portal HTN
Hepatic encephalopathy
Liver cell cancer
Can you reverse cirrhosis?
Yes
What are the two main causes of acute hepatitis?
Viruses
Drugs
What is the histology buzz word for acute hepatitis?
Spotty necrosis
What are the three main causes of chronic hepatitis?
Viral hepatitis (B, C, D)
Drugs
Auto Immune
