GUT the liver

Question 1

What are the cells of the liver and what is there composition?

Answer 1

-Hepatocytes(60%)
-Kupffer cells(30% of NPC)
-Liver sinusoidal endothelial cells(LSEC)(remaining 10%)
-Stellate cells(remaining 10%)

Question 2

What is the heptic lobule?

Answer 2

-Functional unit
-Hexagonal plates of hepatocytes around central hepatic vein

Question 3

What is at the each of the 6 corners of the hepatic lobe?

Answer 3

at each of 6 corners is triad of branches of portal vein, hepatic artery and bile duct

Question 4

How does the liver’s microstructure support its roles?

Answer 4

-Massive surface area for exchange of molecules
-Liver has dual blood supply:
-Sophisticated separation of blood from bile.

Question 5

What is the composition of blood supply in the liver for the dual blood supply?

Answer 5

 75% from portal vein
 25% from hepatic artery

Question 6

Where are kupffer cells found?

Answer 6

found in sinusoids

Question 7

What do kuppfer cells represent?

Answer 7

Represent approx 80% of all fixed tissue macrophages

Question 8

What do kupffer cells function as?

Answer 8

and function as mononuclear phagocyte system (MPS)

Question 9

Where are kupffer cells exposed to blood from and what does it contain?

Answer 9

exposed to blood from gut that contain pathogenic substances.

Question 10

What do kupffer cells clear?

Answer 10

clear gut-derived endotoxin from portal blood

Question 11

What are the steps in carbohydrate metabolism ini fed state?

Answer 11

1. Glucose is absorbed from small intestine and isolated into hepatocytes via GLUT2.
2. Glucokinase catalyses the conversion of glucose to Glucose-6-phosphate. This will cause:
   a)Glycogenesis. This is where Glucose-6-phosphate, in the presence of insulin is converted into Glucose-1-phosphate and then glycogen synthase catalyses the conversion of Glucose-6-phosphate to glycogen.
   b)Glycolysis. Glucose-6-phosphate is converted into pyruvate which is then converted into acetyl CoA.

Question 12

What happens in carbohydrate metabolism in fasting state?

Answer 12

a)Glycogenolysis. Glycogen is converted into Glucose-1-phosphate by glycogen phosphorylase. It is then converted into Glucose-6-phosphate, which is then converted into glucose by G-6-phosphatase.
b)Glucosis. Acetyl CoA is converted into pyruvate which is then converted into Glucose-6-phosphate. This is then converted into glucose by G-6-phosphatase.
-The glucose from both processes are released into the blood and then tissue

Question 13

What are the 4 things that happen in the liver for fat metabolism?

Answer 13

1. Triglycerides oxidized in
   hepatocytes to produce
   energy
2. Lipoproteins synthesised in
   liver
3. Excess carbohydrates &
   proteins converted into FA
   & TGs – stored in adipose
4. Synthesis of large
   quantities of cholesterol &
   phospholipids – some
   packaged as lipoproteins

Question 14

How are amino acids metabolised in liver?

Answer 14

1) Transamination occurs of amino acid and keto acid to give an alpha amino acid and keto acid.
2. The alpha amino acid becomes alpha keto acid and NH3 by oxidative deamination.
3. The alpha keto acid is metabolised to give products like pyruvate, Acetyl CoA which are involved in glucose and lipids.
3. NH3 will combine with CO2 and become a part of the urea cycle.
4. NHS can also go to the brain and reduce cerebral blood flow and O2 consumption.

Question 15

What is Hepatic encephalopathy?

Answer 15

↓Cerebral blood flow & O2 consumption due to liver disease

Question 16

What is Bile?

Answer 16

 Complex fluid = water, electrolytes + mix of organic molecules
 Organic molecules = bile acids, cholesterol, bilirubin and phospholipids

Question 17

Where is bile secreted from?

Answer 17

1. By hepatocytes
2. By epithelial cells lining bile ducts

Question 18

What is secretion of bile stimulated by in epithelial cells lining bile ducts?

Answer 18

this is stimulated by hormone Secretin in response to acid in duodenum.

Question 19

What are the steps involved in the synthesis of bile?

Answer 19

1. Cholesterol is converted into primary bile acids in the presence of 7alpha-hydrolase, O2, NADH, CytP450
2. The primary bile acids are converted into bile salts by conjugating with glycine and taurine.
3. Bile salts will go into the small intestine where it becomes primary bile acids, or with intestinal bacteria, secondary bile acids

Question 20

What is bile essential for and via what?

Answer 20

Essential for fat digestion & absorption via emulsification

Question 21

What does bile and pancreatic juice do?

Answer 21

Bile + pancreatic juice neutralises gastric juice as it enters the small intestine  aids
digestive enzymes

Question 22

What waste products in the blood does bile eliminate?

Answer 22

Eliminates waste products from blood in particular bilirubin & cholesterol

Question 23

What pigments are responsible for the golden yellow colour of bile?

Answer 23

Bilirubin and biliverdin, are bile pigments
responsible for the golden yellow colour of bile.

Question 24

What do bile salts reduce and responsible for?

Answer 24

they reduce surface tension and, responsible for the
emulsification of fat preparatory to its digestion and
absorption.

Question 25

What are gallstones and what is it caused by?

Answer 25

Abnormal conditions caused by an imbalance in
the chemical make-up of bile inside the
gallbladder leading to gallstones

Question 26

What are the 2 types of gallstones?

Answer 26

-Cholesterol
-Pigment

Question 27

What are the risk factors that cause cholseterol stones?

Answer 27

High fat diet
o increased synthesis of cholesterol
Inflammation of GB epithelium changes
absorptive characteristic of mucosa
o excessive absorption of H2O & bile salts 
cholesterol concentrates

Question 28

Why are gallstones more common in women than men?

Answer 28

risk factors = obesity, excess oestrogen (e.g. during
pregnancy), HRT

Question 29

What do plasma proteins transport?

Answer 29

Plasma proteins transport nutrients like glucose, amino acids, lipids, and vitamins
absorbed from the digestive tract to different parts of the body.

Question 30

What is vitamin k essential for in the coagulation factor synthesis?

Answer 30

Vitamin K is essential for formation of pro-thrombin
and factors VII, IX & X

Question 31

What can severe liver disease result in and due to what?

Answer 31

Severe liver disease, excessive bleeding may result
due to lack of these factors.

Question 32

What does warfarin work against and what does it do?

Answer 32

Warfarin works against vitamin K, making your blood
clot more slowly

Question 33

What is bilirubin?

Answer 33

Yellow pigment formed from
breakdown of haemoglobin

Question 34

What is the function of bilirubin and how much is made in a day?

Answer 34

useless & toxic but made in large
quantities (~6g/day)  must be
eliminated

Question 35

What is jaundice?

Answer 35

Is a manifestation of yellow discoloration of the skin and sclera of the eye, due to
accumulation of excess free (unconjugated) or conjugated bilirubin’ in ECF.

Question 36

What may discoloration be accompanied by in jaundice?

Answer 36

Discoloration may be accompanied by pale faeces, and dark urine (conjugated
bilirubinaemia).

Question 37

What is Pre-hepatic(haemolytic) jaundice?

Answer 37

*Excessive breakdown RBC e.g. neonatal jaundice
*Excess unconjugated bilirubin

Question 38

What is hepatic jaundice?

Answer 38

*Hepatocyte damage (>80%)
e.g. cirrhosis; drugs; hepatitis A,B,C,E;
*Excess conjugated &/or unconjugated bilirubin

Question 39

What is post-hepatic(obstructive)?

Answer 39

*Excess conjugated bilirubin
*Obstruction to passage into duodenum
*Enters circulation & into urine (very dark)
e.g. gallstones, carcinoma of pancreas/bile ducts

Question 40

What does liver detoxify?

Answer 40

The liver detoxifies the blood of substances originating from the gut or other
parts of the body.

Question 41

What are the phases involved in biotransformation/detoxification?

Answer 41

Phase 1:
-Primarily oxidation/reduction
-Occurs in smooth ER
-Catalysed primarily by family of cytochrome p450 enzyme enzymes leading to mainly to make substrate into polar compound
Phase 2:
-Conjugation
-To make it more water soluble

Question 42

What does narrow therapeutic index mean?

Answer 42

Accidental/deliberate overdose common

Question 43

What is alcohol broken down into and by what?

Answer 43

-Ethanol is converted into acetaldehyde which is then broken down into acetate by the ALDH2 enzyme

Question 44

What deficiency do asian males have and what can this cause?

Answer 44

50% of Asians have a deficiency in ALDH2
due to mutation of 1 copy of gene
-Accumulation of acetaldehdye resulting in
Alcohol Flush Reaction

Question 45

What are the different stages of liver due to alcohol consumption?

Answer 45

1.Normal liver
2.Steatosis
3.Steatohepatitis
4.Fibrosis
5.Cirrhosis
6.Hepatocellular carcinoma

Question 46

What are the impacts of ethanol metabolism on other metabolic processes in the liver?

Answer 46

1. The NADH + H+ can impact