Liver

Question 1

Describe the location of the liver?

Answer 1

Liver sits into the diaphragm.

Question 2

Describe the structure of the liver

Answer 2

The liver is a large triangular organ in the upper right quadrant of the abdomen.

4 lobes: Right lobe, left lobe, caudate lobe and quadrate lobe.
On the anterior side you can see 2 lobes, the right lobe is bigger than the left lobe.

There are a number of ligaments which join to various parts of the body e.g falciform ligament joins to the diaphragm.
Gall bladder is also attached to the liver.gallbladder in junction of segments 4 and 5

Question 3

Describe the blood supply in the liver?

Answer 3

Blood being delivered to the liver comes from arteries and veins.
Hepatic portal vein and hepatic artery.
These are very close together.

Blood leaves the liver via the hepatic vein into the inferior vena cava.

Rich blood supply - 25% of resting cardiac output.
Dual blood supply:
20% arterial blood from the hepatic artery (left and right branches)
80% venous blood draining from the gut through the hepatic portal vein (HPV)

Blood from the liver drains into the inferior vena cava via the hepatic vein

Therefore the liver is poorly oxygenated compared to the other organs in the body

Question 4

Other than hepatocytes, what other cell carries out major functions in the liver?

Answer 4

Kupffer cells - tissue macrophages

Question 5

how many segments are the liver divided into and why?

Answer 5

• 8 functionally independent segments.
• each of the segments contains its own blood supply and venous drainage.
• each of the segments contains its own

Centrally: portal vein, hepatic artery and bile duct
Peripherally: hepatic vein

Each segment can be resected without damaging those remaining

Question 6

what is the calot’s triangle bound by and what is this used for?

Answer 6

Calot’s triangle bound by the cystic duct, bile duct and cytic artery. It is this triangular space which is dissected in a cholectystcomy to identify a window to safely expose the gallbladder

Question 7

What is the purpose of blood delivered to the liver by;

1. Hepatic portal vein?
2. Hepatic artery?

Answer 7

2. Hepatic artery: liver requires oxygen, glucose etc

1. Portal vein: taking the absorbed product from the gut to the liver. The liver has a huge metabolic.

Question 8

describe the circulation from the hepatic portal vein?

Answer 8

Nothing from the gut goes to the systemic circulation until it goes through the liver and then it goes to the systemic circulation.

Question 9

describe the structure of a liver lobule and what you can on the periphery?

Answer 9

The classical lobule is hexaganol and divided in concentric centrilobular, midzonal and periportal parts.

The portal lobule centred on a portal triad

On the outside, there is a large blue hepatic portal vein and red branch of hepatic artery.
They combine to a hepatic sinusoids, that passes through the lobule into a central canal that drains into the vena cava (out of the liver)
De-oxygenated, nutrient rich blood from the portal vein
Oxygenated blood from the hepatic artery
Flow towards central vein

Bile duct flows next to them but in the opposite direction, from the central canal to the periphery of the lobule.

Find these at the corner of each hexagon.
6 triads linking to one canal

Question 10

what are portal tracts/triad composed of and what is found at the edges of them?

Answer 10

• Branch of hepatic artery
• A branch of the portal vein
• A bile duct

Around the edges of adjoining lobules are ’portal tracts’

Question 11

what are the cells found in the liver?

Answer 11

Hepatocytes
make up 80% mass of the liver. Cords (sheets) of hepatocytes. Coordinated into sheets. Radiating from a central vein

Endothelial cells
Lining blood vessels and sinusoids

Sinusoidal endothelial cells
Fenestrated – allows lipid and other large molecule movement to and from hepatocytes

Cholangiocytes (aka bile duct epithelial cells)
Lining biliary structures

Kupffer cells
Fixed phagocytes (liver macrophages)
Secretion of cytokines that promote HSC Activation - proliferation, contraction and fibrogenesis

Hepatic stellate cells
Vitamin A storage cells (Ito cells), may be activated to a fibrogenic myofibroblastic phenotype. Activation = ECM production (fibrogenesis)

Question 12

How do kupffer cell look like and hepatocytes?

Answer 12

• Flattened, dense cell nuclei that appear to be in the sinusoids are Kupffer cells or hepatic stellate cells
• Hepatocytes are large cells with pale and rounded nuclei.

Question 13

what does acinus refer to?

Answer 13

Acinus
Functional unit
Less clearly identified

Unit of hepatocytes divided into zones dependent on proximity to arterial blood supply.

Acinus refers to the cluster of cells and describes its phenoytic appearance like a “berry” it’s latin derivation. It is the elliptical shaped appearance of the histological appearance and is demarcated by zone:

1. Periportal
2. Transition zone
3. Pericentral

The terminal acinus is centred on the the portal tract and each hepatic acinusis centred on the line connecting two portal triads

Depending on how close the liver tissue is to the blood going in or out that has consequences on its function.
It is a diamond shape and split into 3 zones.
1. closest to portal triad
3. closest to a vein, further away from the portal triad.

Question 14

Hepatocytes within which zone are most susceptible to;

1. Ischaemia?
2. Viral hepatitis?

Answer 14

Periportal zone 1 is nearest to the entering vascular supply and recieves the most oxygenated blood making it least susceptible to ischaemic injuyr but making it most suscptible to viral hepatitis or hemosderin deposition in haemachromatosis. It is involved in gluconeogenesis, oxidation of fatty acides and cholesterol synthesis.

Conversely zone 3 is least susceptible to ischaemic injury and is involved in glycolysis, lipogenesis and P450 based drug detoxification.

Ischaemia- zone 3 because it is further away from the portal triad
Viral hepatitis- virus is going to enter the blood so Zone 1 because it is closest to triad

Question 15

where is bile produced?

Answer 15

Bile produced by hepatocytes.
Flows along canaliculus to bile duct.
Opposite direction to blood flow

Question 16

describe the liver function of carbohydrates?

Answer 16

Important to control blood glucose (endocrine course)
After a meal, blood glucose and is taken up by tissues
Stored as glycogen mainly in muscle and liver
Breakdown liver glycogen maintains blood glucose concentration between meals (muscle cannot release glucose back into blood)
24h fast will exhaust liver glycogen (80g) - the glycogen is lost. Then you need to generate glucose from other sources.

Question 17

What do hepatocytes do?

Answer 17

Metabolism of carbohydrate:
Liver and muscle are connected.

Glucose goes inside the muscle cell, glycolysis takes place, to produce pyruvate and then TCA which produces 1 ATP, 3 NADH and 1 FADH2.
However if there isn’t oxygen, pyruvate is fermented to lactate.

DURING anaerobic, the muscle transfers the lactate to the liver.
The liver converts it back to pyruvate using lactate dehydrogenase. Then gluconeogenesis takes place, which produces glucose. 6 ATP is required.

Question 18

How might ‘hitting the wall’ when running a marathon be

associated with liver function?

Answer 18

Hitting the wall is associated with the loss of glycogen store.
At this point you have to switch to other metabolism to produce energy. It is also a slower process.
Carbohydrate is the preferred option to produce energy

Question 19

Hepatocytes synthesis of protein

Answer 19

• From the diet (not all amino acids can come from the diet)
• muscle breakdown

Liver takes the amino acids and secretes large number of proteins e.g. plasma proteins factors lipoproteins.

Question 20

why is transamination important and give an example

Answer 20

some amino acids has to be generated by the body as it cannot be obtained from the diet .E.g.

1. Alanine from the diet enters the liver
2. takes the amino group from the alanine and transfer to a-keto glutarate
3. this produces pyruvate + glutamate
4. this is reversible.

Question 21

what is transamination

Answer 21

Different keto-acids can be converted to multiple amino acids depending on the transaminase enzyme (vital for production of non-essential amino acids.

alpha-ketoglutarate = e.g. glutamate, proline, arginine

pyruvate= e.g. alanine, valine, leucine

oxaloacetate=e.g. aspartate, methionine, lysine

Question 22

what is deamination?

Answer 22

Removal of an amino group.

Muscle cell:

• Pyruvate from glycolysis and glutamate and that can be used to produce alanine.
• alanine is transferred to liver
• deamination which produces pyruvate + glutamate
• that glutamate can be utilised to produce glucose
• removal of the amino group from the glutamate using 4 ATP
• this also produces urea which is excreted (this is how nitrogen is removed)
• the pyruvate can be generated to produce glucose which requires 6ATP
• the glucose can be used in glycolysis

Question 23

what happens when there is too much glycogen in the liver

Answer 23

Fat contains more energy than anything else in the body.
More energy stored in fat than in glycogen. 100 fold.

Stored in the adipose and liver.
When glycogen stores full, liver can convert excess glucose and amino acids to fat for storage.
1. Triglycerides from adipose tissue cell converted to fatty acids by breaking it down.
2. this is sent to liver. Beta oxidation to make acetyl coA
3.Acetyl coA then enters the TCA cycle. This generates energy

ORRRRR
generate ketones;

1. Triglycerides from adipose tissue cell converted to fatty acids by breaking it down.
2. this is sent to liver. Beta oxidation to make 2 acetyl coA
3. combine to form acetoacetate which is secreted into the blood
4. tissues can use these

Question 24

how does lipoprotein synthesis take place in the hepatocyte?

Answer 24

1. Glucose enters the liver
2. this can be converted to GLYCEROL or pyruvate
3. pyruvate to acetyl coA which can be converted back to fatty acids or cholesterol.
4. combine glycerol and fatty acids which produces triacylglycerol.
5. combine the triacylglycerol + apoproteins phospholipid + cholesterol to give lipoproteins
6. the Liver produces 2 types, VLDL ( has a very high fatty content and transports fatty acids to tissues, stored in the adipose tissue.) and
   HDL ( very little fatty acids) , circulate the blood to pick up excess cholesterol.

LDL is converted from VLDL which transports cholesterol to tissues

VLDL gets triglycerides into adipose tissue
LDL gets cholesterol
HDL mops up cholesterol

Question 25

What is one of the major

roles for cholesterol in cells?

Answer 25

-Hormones
-cell membrane integrity
-

Question 26

what are the other functions of the liver?

Answer 26

Storage of fat soluble vitamins (A,D,E,K). Stores sufficient 6-12 month except Vit K where store is small. Vit K essential blood clotting

Storage of iron as ferritin. Available for erythropoiesis

Detoxification:
important for drug metabolism.
If there is a toxic compound the liver will try and :
1. P450 enzymes
Phase 1 : make it more hydrophilic so it is easier to excrete
2. phase 2; attach water soluble side chain to make it less reactive so less likely to leave the blood, until it reaches the kidney which has mechanism to pull it out.