Hepatobiliary System

Question 1

What is meant by the term ‘hepatobiliary’ system?

Answer 1

Hepato = liver

Biliary = bile ducts

Question 2

Where does the liver lie anatomically?

Answer 2

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

Question 3

What is the morphological anatomy of the liver? Fill in the labels on the diagram:

Answer 3

Ligamentum teres = reminence of the umbilical vein of the fetus

Question 4

Where is the left of the liver found?

Draw a line on the diagram below:

Answer 4

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

Question 5

What vessels / ducts go into and out of the liver (inflow and outflow)?

Answer 5

Inflow = hepatic artery (25%); 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 called the common bile duct; 3x hepatic veins (left, right and middle)

Question 6

Why does the liver have 2 different blood supplies?

Answer 6

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.

Question 7

Looking at the diagram below, what are the different sectors the hepatic veins divide it into?

Answer 7

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

Question 8

How many functioning segments are in the liver?

Where are the different segments found?

Answer 8

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

Question 9

Which branches of the in/outflows travel to which segments?

Why is it important to know which vessels travel to which segments?

Answer 9

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

Question 10

What are the 2 micro-morphological parts of the liver?

What is found in each of these structures? Label them on the diagram below:

Answer 10

1. Hepatic lobules; 2. Portal triads

Hepatic lobule - hexagonal structural unit of the liver, with a portal triad on each corner, hepatic sinusoids, a central vein in the centre, rows of hepatocytes separating the sinusoids and the bile canaliculi (bile capillary ducts)

Portal triad - found on the corner of each hepatic lobule, composed of the hepatic artery, portal vein and bile capillary duct

The central vein joins to the interlobular vein, joining to form the hepatic veins, which eventually return to the IVC

Question 11

What is the portal triad composed of?

What is the function of the hepatic artery?

What is the function of the portal vein?

What are the functions of the hepatocytes?

What is the function of the bile duct?

Answer 11

Composed of the hepatic artery, portal vein and bile capillary duct

Hepatic artery - brings O₂ rich blood supply to the hepatocytes

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)

Hepatocytes - process nutrients, detoxify blood, and excrete waste

Bile duct - bile produced by hepatocytes drains into the bile canaliculi

Question 12

How is bile produced by the hepatocytes?

Answer 12

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

Question 13

What is the hepatic acinus?

What is the structure of the hepatic acinus? Label on the diagram below:

Answer 13

Hepatic acinus - a functional unit of the liver, consists of 1/6^th each of 2 hepatic lobules

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

Question 14

How many zones is the acinus split into?

What is the three zone model of the acinus? Use the diagram below to explain it, how does the blood flow?

Refer to oxygenated blood and toxin risk, and why:

Answer 14

3

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

Question 15

What are the 5 different liver cell types, where are they found and what is their function?

Answer 15

Sinusoidal 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

Kuppfer cells - sinusoidal macrophages attached to the endothelial cells, carry out phagocytosis to eliminate and detoxify substances arriving in the liver from portal circulation

Hepatic Stellate cells - lie dormant usually, store vitamin A, when ativated act as fibroblasts, when the liver is damaged lay down scar tissue (decreasing function of the liver)

Hepatocytes - work forces of the liver forming 80% of the liver mass, 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)

Cholangiocytes - found at the ends of the bile ducts, secrete HCO₃^- and H₂O into the bile

Question 16

What are the 3 main functions of hepatocytes?

Answer 16

1. Metabolic and catabolic = synthesis and ultilsation of carbohydrates, lipids and proteins
2. Secretory and excretory = synthesis and secretion of proteins, bile, and waste products
3. Detoxification and immunological = breakdown of ingested pathogens and processing of drugs

Question 17

What is meant by these terms for cabohydrate metabolism?

Glycolysis - ?

Glycogenesis - ?

Glycogenolysis - ?

Gluconeogenesis - ?

Lipolysis - ?

Lipogenesis - ?

Answer 17

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

Question 18

How is carbohydrate metabolism monitored by the liver to modify hepatocyte function?

e.g. if the muscles are working hard:

Answer 18

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

Question 19

How does protein synthesis take place in the liver?

Answer 19

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

Question 20

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?

Answer 20

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

Question 21

What are the non-essential amino acids?

Answer 21

Glutamate and proline (can be synthesised from alpha-keto glutarate)

Alanine (can be synthesised from pyruvate)

Aspartate (can be synthesised from oxaloacetate)

Question 22

What are the 4 amino acids in highest concentration in the blood?

How does protein metabolism take place in the hepatocytes?

Answer 22

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.

Question 23

How is fat used as an energy source? Where and how is it stored?

How does triglyceride metabolism take place in hepatocytes?

How are fatty acids exported from the liver as an energy source?

Answer 23

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

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

Fatty acids are oxidised using Beta-oxidation to form 2x acetyl-CoAs, which combine to form acetoacetate. Acetoacetate is transported out as an energy source

Question 24

How does lipoprotein synthesis take place in the liver?

What are the 2 types of lipoproteins?

What are 2 major roles of cholestrol?

Answer 24

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

1. 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

Cholestrol - keeps the integrity of membranes, building block for production of hormones (i.e. steroid hormones)

Question 25

What are the storage functions of hepatocytes?

Answer 25

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, opper etc.

Question 26

What is the detoxification function of hepatocytes?

Answer 26

Detoxifies substances in 2 steps:

1. Phase 1 - P450 enzymes make substance more hydrophillic (modification)
2. Phase 2 - attach water soluble side chain to make them less reactive (conjugation)

Question 27

What is the purpose of the biliary system?

Answer 27

Produces bile

Question 28

What is the biliary system composed of? Fill in the diagram below:

Answer 28

The joining of the hepatic and pancreatic ducts is via a structure called the sphincter of oddi - the ducts exit out of the duodenum

Question 29

What is the composition of bile?

What is the colour of bile and what causes the colour changes?

Answer 29

It is mostly composed of water, the terms bile salts and bile acids are interchangeable (they refer to the same thing)

Bilirubin (yellow) and bilivirden (green) are the bile pigments - different compositions of these pigments mean bile colour can range from yellow to green

Question 30

What are the 3 main uses of bile?

Answer 30

1. Cholesterol homeostasis
2. Absorption of lipids and lipid soluble vitamins
3. Excretion of xenobiotics (anything foreign to the body), cholesterol metabolites, steroid hormones and alkaline phosphatase

Question 31

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?

Answer 31

1. Hepatocytes - secrete 60% of bile = primary secretion of bile salts, lipids and organic ions
2. 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

Question 32

What are biliary transporters and what is their function in the biliary system?

Answer 32

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.

Question 33

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?

Answer 33

Bile salts synthesised from cholesterol, the Na⁺ and K⁺ components of the bile salts are combined with glycine and taurine

Cholic acid and Chenodeoxycholic acid

The gut bacteria convert these to secondary bile salts - deoxycholic acid and lithocholic acid respectively

Question 34

What is the function of bile salts? How do they achieve this function?

Answer 34

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)

Question 35

How is the secretion of bile and bile flow (via the transporters) regulated?

Answer 35

Using the Sphincter of Oddi - connects the hepatic and pancreati 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), which causes the gallbladder to contract (releasing more bile)

Question 36

What is the enterohepatic circulation?

What is its function and what is it composed of?

Answer 36

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 bak via the portal venous system to the liver to be reused

Question 37

Where is the gallbladder found?

What are the 2 functions of the gallbladder and is it necessary for survival?

Answer 37

Found under the liver, on the right

1. Stores bile; 2. 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 (kinda like the appendix)

Question 38

What is bilirubin?

What is free bilirubin often referred to?

Where is bilirubin made / sourced?

Which common disease does bilirubin link to?

Answer 38

Toxic - must be processed properly, a H₂O-insoluble, yellow pigment

Indirect / unconjugated bilirubin = free bilirubin

Sourced from - 75% from erythrocyte / Hb breakdown, 22% from catabolism of other hemoproteins, 3% from ineffective bone marrow erythropoeisis

Question 39

What happens to bilirubin once it has been made?

Answer 39

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

Question 40

Where and how is bilirubin excreted?

Answer 40

85% excreted in the faeces - bilirubin is converted to urobilinogen and stercobilinogen (both which are colourless and odourless), and tehn finally converted to stercobilin (brown)

14% enters the enterohepatic circulation

1% enters the systemic circulation and is excreted by the kidneys

Question 41

What is jaundice?

What are the 3 different causes of jaundice?

Answer 41

Characteristed by yellow pigment of the skin and eyes due to high bilirubin levels

1. Pre-hepatic jaundice = too high bilirubin production e.g. with SCA RBCs constantly broken down forming bilirubin
2. 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
3. Post-hepatic jaundice = anything outside of the liver, due to obstruction e.g. gallstones meaning bile cannot come out etc.

Question 42

What is:

choleliathesis?

cholecystisis?

cholangitis?

pancreatitis?

Answer 42

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

Question 43

What is an ERCP? Why is it used?

Answer 43

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)

Question 44

What is a PTC? Why is it used?

Answer 44

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