Liver

Question 1

Which quadrant is the liver found?

Answer 1

Upper right

Question 2

How many main lobes are there?

Answer 2

2 - right and left

Question 3

What are the names of the other two lobes?

Answer 3

caudate and quadrate

Question 4

Name some ligaments in the liver

Answer 4

• coronary ligament
• ligamentum teres
• left triangular ligament
• falciform ligament (seperates left and right lobe)

Question 5

Name veins and arteries of the liver

Answer 5

left hepatic vein
hepatic portal vein
hepatic artery proper

Question 6

Where is the gallbladder found?

Answer 6

junction of segment 4 and 5

near the quadrate lobe

Question 7

The Couinaud Classification

Answer 7

• Features the liver as 8 functionally independent segments
  Each segment has an:
• Artery (centrally)
• Hepatic vein (peripherally)
• Bile duct (centrally)
  e.g. caudate lobe
• Each segment can therefore be cut out without damaging those remaining
• The sections are labelled clockwise (from the centre)

Right = 1,2,3,4. Left = 5,6,7,8

Question 8

Blood supply to the liver

Answer 8

• The liver takes 25% of the resting cardiac output.

It has a dual blood supply:
 - 20% arterial blood from 
 hepatic artery for 
 oxygenation
 - 80% venous blood which 
 drains from gut through the 
 hepatic portal vein (nutrient 
 filled blood from gut)

• All blood from the liver the drains into the inferior vena cava via the hepatic vein

Question 9

What are the two main categories the micronanatomy structures can be divided into?

Answer 9

Morphological units – lobules and portal tracts/triads

Functional units – acinis, blood flow and bile flow

Question 10

Lobules

Answer 10

• Hexagonal
• Divided into three parts (concentric centrilobular, midzonal and periportal)
• Have portal triads (hepatic portal vein, hepatic artery, bile duct)
• Blood flows towards the central canal (and bile the opposite way)
• Periportal hepatocytes are near the portal triad
• Periportal hepatocytes are predisposed to viral hepatitis
• Centrilobular hepatocytes are near the central canal (blood out of liver)
• Centrilobular hepatocytes are predisposed to ischaemia

Question 11

Portal tracts/triad

Answer 11

• Around the edges of adjoining lobules are the portal tracts
• made of arteriole, branch of portal vein and a bile duct

Question 12

How does blood flow through the lobule?

Answer 12

• De-oxygenated, nutrient rich blood from the portal vein
• Oxygenated blood from the hepatic artery
• Flow towards central vein

Question 13

Acinis

Answer 13

• Defined as a unit of hepatocytes divided into zones dependant on proximity to arterial blood supply
• elliptic or diamond shaped

Zone 1, periportal - close to portal triad (predisposed to viral hepatitis, nearest to the entering vascular supply and receives the most oxygenated blood making it least susceptible to ischaemic injury, involved in gluconeogenesis, oxidation of fatty acides and cholesterol synthesis)

Zone 2, transition zone – close to central canal (medium risk of ischaemia/toxins)

Zone 3, Pericentral - most susceptible to ischaemic injury, low toxin risk and is involved in glycolysis, lipogenesis and P450 based drug detoxification

Question 14

Flow of bile

Answer 14

Bile is produced by hepatocytes and flows along canaliculus to the bile duct.

Question 15

What is the role of the liver?

Answer 15

Functions to metabolise proteins, carbohydrates, lipids and also detoxifies the blood

• Protein synthesis and metabolism (transamination)
• Carbohydrate metabolism
• Glycolysis
• Glycogenesis
• Glycogenolysis
• Gluconeogenesis
• Lipid metabolism
• Bile acid (+ sodium) production.
• Detoxification – at the SER and using lysosomes.
• Metabolise, modify/detoxify exogenous compounds.

Question 16

What are the cell types in the liver?

Answer 16

• Hepatocytes
• Endothelial cells
  (lining blood vessels and sinusoidal vessels which are fenestrated and allow large molecules to move to and from hepatocytes)
• Cholangiocytes (bile duct epithelial cells, lining biliary structures)
• Kupffer cells
  (liver macrophages, break down RBCs, secrete cytokines to activate HSC, poliferation, contraction and fribrogenesis)
• Hepatic stellate cells
  (Vitamin A storage cells, may be activated to a fibrogenic myofibroblastic phenotype)

Question 17

Hepatocytes

Answer 17

Are large cells with pale and rounded nuclei

Abundant

Question 18

Kupffer and stellate cells

Answer 18

Flattened, dense cell nuclei that appear to be in the sinusoids are Kupffer cells (macrophages) or hepatic stellate cells (in space between endothelial cells and hepatocytes, can be activated when needed)

Question 19

Histology of hepatocytes

Answer 19

Histologically, hepatocytes feature in cords or
sheets that radiate from a central vein (which they
drain into).

Question 20

What do the nuclei look like for stained endothelial cells, kupffer cells and hepatocytes?

Answer 20

Endothelial cells – nuclei red and flat

Kupffer cells – blue cytoplasm, red nuclei

Hepatocytes – nuclei red and round

Question 21

What can alpha keto glutarate, pyruvate and oxoloacetate be made into (amino acids)?

Answer 21

a keto glutarate - glutamate, proline, arginine

oxoloacetate - aspartate, methionine, lysine

pyruvate - alanine, valine, leucine

Question 22

What is the function of bile?

Answer 22

• Emulsification and absorption of fat: to increase surface area for lipase activity
• Cholesterol homeostasis: excreting excess as needed
• Toxin excretion: endogenous (e.g. bilirubin) and exogenous (e.g. drugs)

Question 23

Synthesis of fatty acids

Answer 23

Liver can convert amino acids and glucose into fate for storage

1. The first step in formation of acetoacetate in the liver is the enzymatic condensation of two molecules of acetyl-CoA, catalyzed by thiolase
2. Acetoacetyl-CoA then condenses with acetyl-CoA to form HMG-CoA which is cleaved to free acetoacetate and acetyl-CoA.

Question 24

Utilisation of glucose

Answer 24

Glucose can be directly converted to glycerol or via the TCA cycle and be converted to acetyl CoA via pyruvate
Acetyl CoA can be converted to cholesterol (via HMG CoA reductase) or can also be converted to fatty acids (via the intermediate malonyl CoA).

Question 25

What is a lipoprotein?

Answer 25

Triacyl glycerols, apoproteins, phospholipids and cholesterol

Question 26

Utilisation of amino acids

Answer 26

- Glutamate, aspartate, alanine and glutamine are present in cells at much higher concentrations than the other 16. - All four have major metabolic functions in addition to their roles in proteins - Glutamate is special because it is chemically related to alpha keto glutatarate - Glutamate can be reversibly converted into oxoglutarate by transaminases or by glutamate dehydrogenase - In addition, glutamate can be reversibly converted into glutamine, an important nitrogen carrier, and the most common free amino acid in human blood plasma - Alanine is the principal amino acid released from muscle tissue during starvation - It is an important substrate for hepatic gluconeogenesis, and alanine transamination is required for the proper maintenance of fasting blood glucose concentrations

Question 27

Alanine transamination with alpha ketrohlutarate

Answer 27

alanine+alpha ketogultarate = pyruvate + glutamate

Question 28

What does glutamate metabolism produce?

Answer 28

NH3 - toxic so liver converts it to water soluble urea

Question 29

Liporoteins, their roles and bile

Answer 29

- The liver produces two lipoproteins: VLDL and HDL. - VLDL has a high triacylglycerol component and it’s major role is to deliver fatty acids to body tissues (lipoprotein lipase cleaves the fatty acids from triglycerides) - HDL are often referred to have high protein content but low fat content. Their role is to mop up excess cholesterol in the circulation and return to the liver - Once VLDL have delivered fatty acids to tissues, they are converted to LDL which are very high in cholesterol. - The LDL deliver cholesterol to tissues which then use the cholesterol to make hormones and to maintain cell membrane integrity - Any excess cholesterol is returned to the liver and excreted in bile.

Question 30

Liver storage

Answer 30

- Storage of fat soluble vitamins (A,D,E,K) - Stores sufficient for 6-12 months - Stored Vit B12 - Stored copper - Vit K store is small: Vit K is essential in blood clotting - Storage of iron as ferritin: available for erythropoeisis

Question 31

Liver - detoxification

Answer 31

P450 enzymes Phase 1 - more hyrdrophilic Phase 2 - attach water soluble side chain to make less reactive

Question 32

What is a hepatic lobule?

Answer 32

A structural unit of the liver with rows of hepatocytes with a sinusoid facing side and a bile caniculi facing side.

Question 33

Biliary tree

Answer 33

- The biliary tree describes the anatomical structures responsible for the transit and storage of bile - Starts in millions of bile canaliculi adjacent to the hepatocytes (bile producing cells) Canaliculi -> small ductules -> small bile ducts -> larger bile ducts for each liver segment -> right and left hepatic ducts -> common hepatic duct - Connected to this duct is the cystic duct, which connects the gall bladder to the biliary tree Common hepatic duct and the cystic duct -> common bile duct, which extends towards the duodenum At its distal end the pancreatic duct joins and the vessel is then called the ampulla of Vater, which opens up into the medial wall of the duodenum at the duodenal papilla

Question 34

What is a hepatic acinus?

Answer 34

A functional unit of the liver with two adjacent areas one sixth of lobules that share two portal triads and extend to the central vein.

Question 35

What do hepatocytes contain (organelles)?

Answer 35

- nucleus - lysozymes - glyocogen - peroxisomes (detoxification, waste management and cholesterol/bile synthesis) - cytoplasmic enzymes - smooth ER - mitochondria (lots) - rough ER - Golgi

Question 36

What does bile contain?

Answer 36

- cholesterol (in high/low amounts) for homeostasis of cholesterol - bile salts to solubilise fatss - bilirubin and drug metabolites (for excretion in faeces of both endogenous and exogenous) lots of water

Question 37

Which cells secrete and modify bile?

Answer 37

hepatocytes (primary secretion) cholagniocytes (epithelial cells of bile duct) - secondary modification, alter pH, water movement, reabsorption of sugars and acids, secretion of HC03- and Cl-

Question 38

Primary bile acids and secondary bile acids

Answer 38

Two primary bile acids are made in the liver - cholic acid and chenodeoxycholic acid Two secondary bile acids are made from primary ones by gut bacteria - deoxycholic (from cholic acid) acid and lithocholic acid

Question 39

What does the gallbladder do?

Answer 39

- stores bile (50ml) - acidifies bile by absorbing bicarbonate - concentrates bile by reabsorbing ions and creating an osmotic gradient

Question 40

When is bile released?

Answer 40

constantly synthesised and stored in gallbladder | CCK stimulates gallbladder contraction for a large amount

Question 41

Why is bile yellow/green?

Answer 41

contains bilirubin and biliverdin

Question 42

How much bile is made daily?

Answer 42

500ml

Question 43

What is enterohepatic circulation?

Answer 43

- Means that substances can cycle between the gut and liver by continuous reabsorption in the gut, carriage in portal blood to liver, and hepatocyte secretion into bile canaliculi, to be secreted (in bile) via the common bile duct - Bile can be recycled so useful - Liver processes some drugs by excreting them via bile and eventually the faeces. But they may get reabsorbed in the small intestine and re-enter the portal circulation cyclically

Question 44

What are sinuosoids?

Answer 44

Where blood flows from one side of lobule to the other