GUT the liver Flashcards
What are the cells of the liver and what is there composition?
-Hepatocytes(60%)
-Kupffer cells(30% of NPC)
-Liver sinusoidal endothelial cells(LSEC)(remaining 10%)
-Stellate cells(remaining 10%)
What is the heptic lobule?
-Functional unit
-Hexagonal plates of hepatocytes around central hepatic vein
What is at the each of the 6 corners of the hepatic lobe?
at each of 6 corners is triad of branches of portal vein, hepatic artery and bile duct
How does the liver’s microstructure support its roles?
-Massive surface area for exchange of molecules
-Liver has dual blood supply:
-Sophisticated separation of blood from bile.
What is the composition of blood supply in the liver for the dual blood supply?
75% from portal vein
25% from hepatic artery
Where are kupffer cells found?
found in sinusoids
What do kuppfer cells represent?
Represent approx 80% of all fixed tissue macrophages
What do kupffer cells function as?
and function as mononuclear phagocyte system (MPS)
Where are kupffer cells exposed to blood from and what does it contain?
exposed to blood from gut that contain pathogenic substances.
What do kupffer cells clear?
clear gut-derived endotoxin from portal blood
What are the steps in carbohydrate metabolism ini fed state?
- Glucose is absorbed from small intestine and isolated into hepatocytes via GLUT2.
- 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.
What happens in carbohydrate metabolism in fasting state?
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
What are the 4 things that happen in the liver for fat metabolism?
- Triglycerides oxidized in
hepatocytes to produce
energy - Lipoproteins synthesised in
liver - Excess carbohydrates &
proteins converted into FA
& TGs – stored in adipose - Synthesis of large
quantities of cholesterol &
phospholipids – some
packaged as lipoproteins
How are amino acids metabolised in liver?
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.
What is Hepatic encephalopathy?
↓Cerebral blood flow & O2 consumption due to liver disease
What is Bile?
Complex fluid = water, electrolytes + mix of organic molecules
Organic molecules = bile acids, cholesterol, bilirubin and phospholipids
Where is bile secreted from?
- By hepatocytes
- By epithelial cells lining bile ducts
What is secretion of bile stimulated by in epithelial cells lining bile ducts?
this is stimulated by hormone Secretin in response to acid in duodenum.
What are the steps involved in the synthesis of bile?
- Cholesterol is converted into primary bile acids in the presence of 7alpha-hydrolase, O2, NADH, CytP450
- The primary bile acids are converted into bile salts by conjugating with glycine and taurine.
- Bile salts will go into the small intestine where it becomes primary bile acids, or with intestinal bacteria, secondary bile acids
What is bile essential for and via what?
Essential for fat digestion & absorption via emulsification
What does bile and pancreatic juice do?
Bile + pancreatic juice neutralises gastric juice as it enters the small intestine aids
digestive enzymes
What waste products in the blood does bile eliminate?
Eliminates waste products from blood in particular bilirubin & cholesterol
What pigments are responsible for the golden yellow colour of bile?
Bilirubin and biliverdin, are bile pigments
responsible for the golden yellow colour of bile.
What do bile salts reduce and responsible for?
they reduce surface tension and, responsible for the
emulsification of fat preparatory to its digestion and
absorption.
What are gallstones and what is it caused by?
Abnormal conditions caused by an imbalance in
the chemical make-up of bile inside the
gallbladder leading to gallstones
What are the 2 types of gallstones?
-Cholesterol
-Pigment
What are the risk factors that cause cholseterol stones?
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
Why are gallstones more common in women than men?
risk factors = obesity, excess oestrogen (e.g. during
pregnancy), HRT
What do plasma proteins transport?
Plasma proteins transport nutrients like glucose, amino acids, lipids, and vitamins
absorbed from the digestive tract to different parts of the body.
What is vitamin k essential for in the coagulation factor synthesis?
Vitamin K is essential for formation of pro-thrombin
and factors VII, IX & X
What can severe liver disease result in and due to what?
Severe liver disease, excessive bleeding may result
due to lack of these factors.
What does warfarin work against and what does it do?
Warfarin works against vitamin K, making your blood
clot more slowly
What is bilirubin?
Yellow pigment formed from
breakdown of haemoglobin
What is the function of bilirubin and how much is made in a day?
useless & toxic but made in large
quantities (~6g/day) must be
eliminated
What is jaundice?
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.
What may discoloration be accompanied by in jaundice?
Discoloration may be accompanied by pale faeces, and dark urine (conjugated
bilirubinaemia).
What is Pre-hepatic(haemolytic) jaundice?
*Excessive breakdown RBC e.g. neonatal jaundice
*Excess unconjugated bilirubin
What is hepatic jaundice?
*Hepatocyte damage (>80%)
e.g. cirrhosis; drugs; hepatitis A,B,C,E;
*Excess conjugated &/or unconjugated bilirubin
What is post-hepatic(obstructive)?
*Excess conjugated bilirubin
*Obstruction to passage into duodenum
*Enters circulation & into urine (very dark)
e.g. gallstones, carcinoma of pancreas/bile ducts
What does liver detoxify?
The liver detoxifies the blood of substances originating from the gut or other
parts of the body.
What are the phases involved in biotransformation/detoxification?
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
What does narrow therapeutic index mean?
Accidental/deliberate overdose common
What is alcohol broken down into and by what?
-Ethanol is converted into acetaldehyde which is then broken down into acetate by the ALDH2 enzyme
What deficiency do asian males have and what can this cause?
50% of Asians have a deficiency in ALDH2
due to mutation of 1 copy of gene
-Accumulation of acetaldehdye resulting in
Alcohol Flush Reaction
What are the different stages of liver due to alcohol consumption?
1.Normal liver
2.Steatosis
3.Steatohepatitis
4.Fibrosis
5.Cirrhosis
6.Hepatocellular carcinoma
What are the impacts of ethanol metabolism on other metabolic processes in the liver?
- The NADH + H+ can impact
