Liver Function 1

Question 1

Describe the liver

Answer 1

Largest solid organ
Protected by ribs RUQ
Diaphragm ‘roof’
2, 4 lobes, 8 segments
Hepatic artery, portal vein, hepatic veins, bile duct

Question 2

Which ligament runs between the right and left lobes of the liver?

Answer 2

Falciform ligament

Question 3

Which ligament is at the end of the falciform ligament?

Answer 3

Round ligament

Question 4

What cells make up the liver?

Answer 4

Hepatocytes (60%)
Kupffer cells (30%)
Stellate Cells
Endothelial cells
Biliary epithelium

Question 5

What is the role of hepatocytes?

Answer 5

Hepatocytes are involved in synthesizing protein, cholesterol, bile salts, fibrinogen, phospholipids and glycoproteins.
They ensure that our blood coagulates so we don’t bleed to death, that cell communication s good and that we are able to carry fats in the bloodstream.
Other functions of the hepatocytes include the transformation of carbohydrates (from alanine, glycerol and oxaloacetate), protein storage, start of the formation and secretion of bile and urea, and detoxification and excretion of substances.
Thanks to these main cells, we are able to fight off disease, produce waste, transport materials throughout the body and process everything from drugs and insecticides to steroids and pollutants.

Question 6

What is the role of liver endothelial cells?

Answer 6

Since they do not have tight membranes, these cells act as “scavengers” of nearby cells - collecting and circulating hepatocytes in the blood, for instance.
Responsible for transporting white blood cells and other material from the blood to the liver and for increasing the immune system’s tolerance of the liver.
They can absorb ligands, which serve as biological markers and binders for pharmaceutical drugs. When stimulated, endothelial cells secrete cytokines, which is a form of cellular communication signal.

Question 7

What is the role of Kupffer cells?

Answer 7

Kupffer cells are located within the sinusoidal lining of the liver and hold a quarter of the liver lysosomes.
The lysosomes digest and dispose of dying cells, unnecessary proteins, bacteria and foreign microbes. If stimulated, kupffer cells secrete mediators of the immune response system, and they can perform a complex array of functions–from disarming foreign substances to removing damaged red blood cells from circulation.
In a way, the kupffer cells are like bodyguards and assassins for the hepatocytes, protecting them from invaders and cell refuse.

Question 8

What is the role of hepatic stellate cells?

Answer 8

The livers reserve army.
Most of the time, this 5 to 8 percent of the liver’s cells just sit around in an inactive “quiescent” state, storing vitamin A and a number of important receptors.
When activated (by an event like liver injury), the cell promotes ion movement, the production of antibodies, genesis of natural killer T-cells and the proliferation of chemical responses to stress.
Researchers believe that hepatic stellate cells play a key role in releasing collagen scar tissue and encouraging liver scarring.

Question 9

What is bile?

Answer 9

Green/yellow fluid made up of water, electrolytes and organic molecules (bilirubin, bile acids, phospholipids and cholesterol)

Question 10

What do epithelial cells in the bile ducts secrete?

Answer 10

Water and bicarbonate

Question 11

How is bile secreted?

Answer 11

Bile is secreted by hepatocytes
Through canaliculi 
Small ducts
Left/right hepatic duct
Common hepatic duct
Common bile duct

Question 12

What are the functions of bile?

Answer 12

Responsible for fat digestion and absorption
Bile and pancreatic juice neutralise gastric juice
Gets rid of waste products of blood such as bilirubin and cholesterol

Question 13

What does the liver produce?

Answer 13

Proteins, lipoproteins, coagulation factors (fibrinogen, prothrombin, clotting factors. Vitamin K s essential for formation of prothrombin and factors II,VII,IX,X)
Hormones and pro-hormones
Carrier proteins (transferrin)

Question 14

What does the liver store?

Answer 14

Carbohydrates, fat, ADEK, B12, folate, ferritin, metals

Question 15

What are the roles of the liver?

Answer 15

Production, storage, metabolism, excretion

Question 16

How does the liver metabolise proteins?

Answer 16

• Transamination: one amino acid is converted to another (adding/removing elements from R group)
• Deamination: getting rid of excess amino acids by removing amino group (NH2). NH2 is converted to NH3 (ammonia) and NH3 enters the urea cycle. Urea is then excreted in urine.

Question 17

What proteins are synthesised by the liver?

Answer 17

Fibrinogen, albumin, globulin, CRP, complement proteins C1-4

Question 18

What is the role of the liver in response to high blood glucose levels?

Answer 18

Insulin released by pancreas, glucose is converted to glycogen and stored in the liver, decreased gluconeogenesis, decreases glycogenolysis

Question 19

What is the role of the liver in response to low blood glucose?

Answer 19

Glucagon released by pancreas, glycogen converged into glucose and released, increases gluconeogenesis and increases glycogenolysis

Question 20

What are lipids metabolised by the liver?

Answer 20

Triglycerides are oxidised in hepatocytes to produce energy
Excess proteins and carbohydrates are converted into fatty acids and triglycerides and stored in adipose tissue
Liver produced lipoproteins
Synthesises cholesterol and phospholipids

Question 21

What happens to cholesterol in the liver?

Answer 21

Cholesterol s excreted in bile or converted to bile acids

Question 22

How does the liver metabolise alcohol?

Answer 22

Alcohol dehydrogenase converts ethanol to acetaldehyde
Acetaldehyde dehydrogenase converts acetaldehyde to acetate
Acetate is broken down to water and carbon dioxide for easy elimination

Question 23

Which enzyme converts ethanol to acetaldehyde?

Answer 23

Alcohol dehydrogenase

Question 24

Which enzymes converts acetaldehyde to acetate?

Answer 24

Acetaldehyde dehydrogenase

Question 25

What occurs in phase 1 of drug metabolism?

Answer 25

Oxidation/reduction/hydrolysis

Oxidation is catalysed by cytochrome P450 in SER to make drug more active

Question 26

Which enzyme catalysts the oxidation of a drug in drug metabolism?

Answer 26

Cytochrome P450 in SER

Question 27

What occurs in phase 2 of drug metabolism?

Answer 27

Conjugation

Attachment of ionised group to the drug (glutathione/methyl/acetyl), to make drug water soluble to facilitate excretion

Question 28

What occurs in phase 3 of drug metabolism?

Answer 28

Drug eliminated via ATPase pumps

Question 29

What can you test to check liver function?

Answer 29

Albumin 
ALT (alanine aminotransferase)
ALP (alkaline phosphatase)
Bilirubin
GGT (gamma glutamyl transpeptidase)
AST (aspartate aminotransferase)

Question 30

What are the markers of hepatocellular damage?

Answer 30

• AST: liver, heart, skeletal muscle, kidneys, brain, RBC’s
  In liver 20% activity is cytosolic and 80% is mitochondrial
  Clearance by sinusoidal cells
  Half life: 17hrs
• ALT: specific to liver, very low concentrations in kidney and skeletal muscles
  In liver totally cytosolic
  Half life 47hrs

Question 31

What are the markers of cholestasis?

Answer 31

-ALP: liver and bone
Hepatic ALP present on surface of bile duct epithelia and accumulating bile salts increase to release from cell surface
Half life is 1 week
- ALP isoenzymes, 5-NT or gamma GT may be necessary to evaluate the origin of ALP

Question 32

What is GGT useful for?

Answer 32

• Hepatocytes and biliary epithelial cells, pancreas, renal tubes and intestine
• Very sensitive but non specific
• Cholestasis or hepatocellular
• Alcohol
• Helps to interpret ALP
• Isolated increase does not need further investigations, only if other LFT’s become abnormal then investigate

Question 33

How does GGT help to interpret ALP?

Answer 33

• ALP>GGT: bone disease, pregnancy

- GGT>ALP: alcohol, medications

Question 34

What happens when bilirubin is taken up into hepatocytes?

Answer 34

It is conjugated to glucuronic acid - bilirubin diglucuronide - bilirubin monoglucuronide - secreted into bile

Question 35

What happens to conjugated bilirubin?

Answer 35

It is water soluble and excreted in bile
It is degraded to urobilinogen
May be reabsorbed by gut and returned to liver
Converted to urobilin > reabsorbed into plasma for excretion by kidneys

Question 36

How does bilirubin cause the brown colour of faeces?

Answer 36

Bilirubin may be acted upon by bacterial enzymes within the gut to form bile pigment stercobilinogen > stercobilin > brown colour of faeces

Question 37

What causes pre hepatic jaundice?

Answer 37

Unconjugated hyper bilirubinaemia

Question 38

What causes post hepatic jaundice?

Answer 38

Unconjugated and conjugated hyper blirubinaemia

Question 39

What causes obstructive jaundice?

Answer 39

Failure of bilirubin to reach the gut (light coloured stool, dark urine)

Question 40

What are the clinical markers of obstructive jaundice?

Answer 40

Light coloured stool and dark urine

Question 41

What occurs in the reticuloendothelial system?

Answer 41

Heme from RBC converted to biliverdin by heme oxygenase, this then converted to bilirubin. Bilirubin-albumin taken up by liver (unconjugated). This converted to bilirubin glucuronide by UDP glucuronyl transferase. Secretion of bilirubin glucuronide, degraded to urobilinogen.
Urobilinogen gives brown colour to faeces and also goes into portal circulation and small amounts to urine

Question 42

What is albumin?

Answer 42

A protein made by the liver

Low albumin levels in chronic liver disease or malnutrition

Question 43

What is a sensitive indicator of liver fibrosis?

Answer 43

Thrombocytopenia