L25. Histology of the Liver and Pancreas

Question 1

Describe the liver

Answer 1

A large gland (solid organ) that is located in the right upper quadrant under the diaphragm.

Question 2

What does the liver consist of?

Answer 2

Hepatocytes make up the large proportion of the liver (75% of the weight)

Question 3

What are the functions of the liver?

Answer 3

1. Storage of glycogen
2. Gluconeogenesis: break down of lactic acid, amino acid and glycerol into glucose
3. Synthesis of cholesterol
4. Lipoprotein production
5. Production of ketone (for energy)
6. Plasma protein production: colloid osmotic pressure of blood
7. Production of non-essential amino acids
8. Detoxification of metabolic wast (ammonia cycle)
9. Storage of iron for Hb production
10. Destruction of hormones
11. Destruction of toxins: alcohol and drugs
12. Makes bile

Question 4

Describe the hepatocytes

Answer 4

Polyhedral (6 surfaces) cells that are about 25um across.
They have 1-2 nuclei
Are tetraploid or polyploid (have multiple copies of DNA)
HIGHLY SYNTHETIC CELLS:
Prominent rough ER (Golgi) - protein synthesis
Prominent smooth ER - fat metabolism
Many mitochondria -energy consuming

Question 5

What is the turnover of hepatocytes?

Answer 5

Hepatocytes are of epithelial origin

They have a life span of 150 days

Question 6

How to hepatocytes regenerate?

Answer 6

By cell division (not by stem cells)
MATURE hepatocytes divide in a tightly regulated manner
This means that liver has the capability to regenerate tissue (important in the transplant setting)
- limited regeneration as can’t repair after severe hepatocyte damage (Hep B or C)

Question 7

Describe the blood supply to the liver

Answer 7

TWO blood supplies
Systemic blood supply through the hepatic arteries
Venous blood supply from the portal vein system (from the gut)

Question 8

Describe the oxygenation of the liver in terms of the blood supply

Answer 8

The liver receives a mix of oxygenated and deoxygenated blood (about 20% of oxygenated and 80% deoxygenated)

Question 9

What is the significance of having a portal blood supply to liver?

Answer 9

The portal system arises from blood draining from the gut and into the liver. This is important as the liver acts as a screening process for what the blood has received from the gut. This includes all metabolites (digestive products), nutrients and toxins.

Question 10

Describe the connective tissue of the liver

Answer 10

The liver has a very thin capsule called the GLISSON’S CAPSULE that surrounds the blood vessels and the ducts as well.

This is a relatively little amount of protective connective tissue

Question 11

How are the hepatocytes supported by CT?

Answer 11

Made up of reticular fibres (collagen type III)

They act only as shape forming support - a scaffold rather than protective

Question 12

What are the liver lobules? Describe their shape

Answer 12

Lobules are the building blocks of the lobes. They are polygonal in shape from 0.7-2mm.
They are made up of STACKS of hepatocytes in plates which are then stacked on top of each other to form the lobule.
Each plate has thousands off hepatocytes within it.

Question 13

How are the lobules arranged within a lobe?

Answer 13

They are arranged edge to edge with one another with a very narrow space between them. There are open spaces surrounding some of the corner edges of each lobule and this is the site for the portal triads.

Question 14

Describe the blood vessels associated with a single liver lobule.

Answer 14

The CENTRAL VEIN is located in the centre of the lobule running the length of it.
At some of the corners there is a portal triad (roughly 3-4 triads per lobule). Within this triad is the portal vein and the branches of the hepatic arteries and a bile duct.

Question 15

Describe the blood flow through the lobules

Answer 15

Blood is always flowing from the outside in: from the portal vein and the hepatic arteries in the triads leading INTO the central vein which anastomose together eventually forming the hepatic veins which drain into the IVC

Question 16

What are the liver sinusoids?

Answer 16

Both the veins and the arteries in the portal triads give rise to a network of sinusoids
They are branching vessels of the veins and arteries to provide efficient supply of the hepatocytes (each hepatocytes is in direct contact with at least 2 sinusoids).

These sinusoids are the first site of the mixing of the deoxygenated blood from the portal system and the oxygenated blood from the systemic system.

Question 17

What is the space of Disse?

Answer 17

The sinuoids and the hepatocytes have a special relationship that enables a very efficient exchange and sensing of the hepatocytes to the contents of the blood.

Sinusoids have a FENESTRATED wall, the gaps large enough for plasma to diffuse out and bathe the hepatocytes directly (not large enough for RBCs) hence the extracellular space of the hepatocytes is made up of plasma from the sinusoids.

Question 18

Describe the surface of the hepatocytes that is related to the sinusoidal surfaces.

Answer 18

The hepatocytes have microvilli to increase the surface area for exchange.

Question 19

What is the difference between a classic lobule and a hepatic lobule?

Answer 19

A classic lobule has a central vein at the centre and it supplies the lobule

The hepatic lobule (hepatic acinus) is a METABOLIC UNIT that puts the portal triad at the centre to emphasise that one portal triad supplies MULTIPLE LOBULES a metabolic organisation

(Different ways of looking at it)

Question 20

Describe the concept of zonation in the lobules from the portal triads to the central vein. Relate this to the pathological problems that can happen in lobules

Answer 20

As the blood from the portal triads run from the outside in there is a zone formation of different contents of the blood as it passes through.

Zone 1 is closest to the portal triad and hence receives the most oxygenated blood (protected from infarction) but also receives the most toxins. Thus pathology involving toxins to the liver affect this zone.

Zone 2 is in the middle

Zone 3 is the closest to the central vein and hence receives the least toxins (protected from toxic damage) but also the least oxygenation and pathology involving ischaemia and infarction occurs here first.

Question 21

Describe bile production and the function of bile

Answer 21

Bile is synthesised by hepatocytes from cholesterol and bile salts act as surfactants to emulsify the fat in the gut to allow for lipid digestion. Bile is reabsorbed in the ileum and recycled.

Question 22

Describe bile pigments

Answer 22

Bile is a dark green colour due to the bile pigments. These pigments are a breakdown product of haemoglobin called BILIRUBIN.

Old RBCs are destroyed in the spleen and liver

Question 23

How is bile transported from the hepatocytes?

Answer 23

Bile is produced in the liver and drain into very small spaces in between the hepatocytes. These small spaces form a reticular system of drainage that form CANNALICULI channels carrying blood from the INSIDE TO THE OUTSIDE forming the bile duct in the portal triad.
The bile ducts join to make the common bile duct

Question 24

What is the gall bladder?

Answer 24

A muscular sac that is attached to the liver and the duodenum.
Bile from the common bile duct heads to the SPHINCTER OF ODDI at the major duodenal papilla but as the sphincter is normally closed, bile backs up into the cystic duct and into the gall bladder.

Question 25

Describe the epithelium of the gall bladder and the function of it

Answer 25

It is an active organ made up of simple columnar eptihelium.
It has an absorptive function to pull water out: concentrates the bile

it also has smooth muscle strands in the walls and so acts as a contractile organ to squeeze bile out on demand

Question 26

What are gall stones?

Answer 26

Spontaneous precipitates of cholesterol and bile salts that can lodge in the gall bladder or in ducts

Question 27

Describe the hormonal signalling in the gall bladder

Answer 27

Fat in the duodenum stimulates specialised cells to release CCK into the blood. It circulates and acts in the gall bladder to contract and the spincter of oddi to relax so bile squirts into the duodenum.

Question 28

Describe the pancreas

Answer 28

A large gland (epithelial origin) nestled in the loops of the small intestine

Question 29

Describe the ducts of the pancreas and where they lead

Answer 29

Ducts drain the pancreas called the pancreatic duct along the body of the pancreas and it eventually joins the common bile duct draining to the spinchter of oddi.
Another secondary pancreatic duct from the uncinate ligament drains into the minor duodenal papilla

Question 30

What does the pancreas release?

Answer 30

Pancreatic juice containing proteases, lipases, amylases, nucleases and bicarbonate ions

Question 31

Describe the pancreatic acini

Answer 31

Pancreatic glands are formed from acini: football shaped organisation of cells with a duct in the middle of them.

The cells are granular in the centre (lighter staining with zygmogens) and darker staining on the outisde (nuclei and other machinery)

Question 32

What is meant by the dual function of the pancreas

Answer 32

Endocrine: insulin production and secretion in Islets of Langerhans

Exocrine: production of digestive enzymes

Question 33

Describe Zymogen activation and need for them

Answer 33

The pancreatic enzymes are released in active form to prevent any autodigestion of the pancreatic tissue. These inactive forms are called Zymogens.
They are activated by other enzymes present only in the duodenum and also activated by bile.

Question 34

What is the risk in bile activated pancreatic enzymes?

Answer 34

The common pathway where bile meets pancreatic juices just before the Sphincter of Oddi. This is usually not too problematic when the flow is one way but in the case of gall stones blocking the duct, flow backs up leading to active enzymes into the pancreas
= very dangerous and lethal auto-digestion that can spread to the blood vessels and aorta.