Liver Flashcards
List 6 things which are stored in the liver
- Vitamins A, B12, D, E and K
- Iron
What are fat soluble vitamins, and list them
- Soluble in fat, stored in the body for long periods of time.
- A, D, E and K
Describe the journey of vitamin B12 in the body
- Attached to R-protein initially to protect from HCl.
- Released by pancreatic proteases.
- Binds to intrinsic factor (produced by parietal cells) for absorption.
Where does iron enter the GI system?
Duodenum
How is iron carried in the body?
By transferrin
Where is liver sent to after entering the body?
- Bone marrow
- Muscle
- Stored in liver
Describe the process of absorption of iron
- Fe3+ converted to Fe2+
- Enters intestinal epithelial cells DMT1
- Released from cell via ferroportin
Define xenobiotics
Substances absorbed across lungs/skin, ingested unintentionally as part of food/drink, or intentionally in drugs.
What are microsomal enzymes?
Found on sER of liver/kidney/lungs, catalyse majority of drug biotransformations.
List 4 types of drug biotransformations that can occur during drug metabolism
- Hydrolysis
- Oxidation
- Reduction
- Glucuronidation
Is it microsomal or non-microsomal enzymes that can be induced by drugs/diet?
Microsomal
What are non-microsomal enzymes?
Found in cytoplasm/mitochondria of hepatocytes. Catalyse non specific drug biotransformations.
Is it microsomal or non-microsomal enzymes that display polymorphism?
Non-microsomal
List 3 features of phase 1 reactions in drug metabolism
- Addition or exposure of functional groups.
- Small increase in hydrophilicity.
- Non-synthetic
List 4 features of phase 1 reactions in drug metabolism
- Conjugation reactions
- Large increase in hydrophilicty
- Are biosynthetic
- Covalent bonds form
What are Cytochrome P450s (CYPs) and what is their function?
Enzymes of the superfamily of haem-containing proteins. Primarily responsible for metabolism of drugs.
Define protein turnover
Continuous degradation and resynthesis of cellular proteins
What are the 2 types of protein degradation?
- Lysosomal and non-lysosomal
Where does lysosomal protein degradation take place?
Reticulo-endothelial system of liver
What is the input and output of nitrogen?
- Input: In the form of amino acids
- Output: NH3 usually converted to a non-toxic excretory product
What is a positive nitrogen balance and what is a common cause?
- Increased Nitrogen levels e.g. during pregnancy
What is a negative nitrogen balance and what is a common cause?
- Decreased Nitrogen levels e.g. malnutrition
What are the 2 types of malnutrition?
- Marasmus: Insufficient calorie intake
- Kwashiorkor: Insufficient protein intake (but sufficient calorie intake)
What is the role of alanine?
Principal ammonia scavenger/transporter in muscle
Describe the glucose-alanine cycle
- Glutamate in muscles picks up ammonia (from amino acids from protein stored in muscle.)
- ALT transaminates the amino group in glutamate, forming alpha-ketoglutarate.
- The amino group is added to pyruvate (formed from glycolysis) to form alanine.
- Alanine is transported to blood, then picked up by the liver. The reverse reaction occurs (alpha-ketoglutarate to glutamate.)
- The ammonia goes on to form urea via the urea cycle. The pyruvate forms glucose by gluconeogenesis and then enters the blood and is transported to muscle for the cycle to start again.
Describe the urea cycle.
- Arginine —> Ornithine (by arginase, produces urea)
- Ornithine —> Citrulline (takes in ammonia + CO2)
- Citrulline —> Arginine (takes in ammonia)
Why is there increased blood ammonia in liver disease?
Blood is not exposed enough to parenchymal liver cells due to fibrosis/cell death etc.
What is albumin? Give 2 properties.
Major protein produced by the liver.
Highly soluble, single polypeptide.
List 4 functions of albumin
1 - Binding and transport of drugs.
2 - Maintain colloid osmotic pressure.
3 - Acts as free radical scavenger.
4 - Poorly understood role as anticoagulant
Where is bile secreted from?
In liver by hepatocytes
What is the function of the gallbladder?
- Storage and concentration of bile.
What are the 2 roles of bile and why?
- Emulsifier: anionic detergent properties of bile acids.
- Excretory pathway for steroid hormones and drugs
What are the constituents of bile?
- Water
- Bile salts
- Bile acids
- Lecithin
- Cholesterol
- Bile pigment (bilirubin and biliverdin)
Where and how are bile salts manufactured?
In the liver from cholesterol. Usually conjugated to amino acids.
How are bile acids produced?
By the action of some gut bacteria
What are the small soluble units of bile called and what are they made up of?
- Mixed micelles.
- Made up of bile salts/acids, cholesterol and lecithin.
What is the path of enterohepatic circulation?
Liver –> Small intestines (duodenum, jejunum, ileum) –> Absorption into portal blood –> Back to liver
What is bilirubin?
A bile pigment that results from the breakdown of haemoglobin
Outline the breakdown of haem
Haem –> protoporphyrin –> biliverdin –> bilirubin –> bilirubin glucuronide –> urobilogen –> 80% seroglobin, 20% reabsorbed
What is bilirubin glucuronide?
Bilirubin which has been conjugated to glucuronic acid
What us stercobilin?
The brown pigment in faeces.
Where is the 20% of urobilogen reabsorbed?
Liver and kidney
What causes the gallbladder to contract, releasing bile?
Release of CCK after eating a meal
What are the 2 phases of exocrine pancreatic juice?
- Aqueous, HCO3- rich phase.
- Enzyme rich phase.
What is the purpose of the aqueous phase of pancreatic juice?
- Protect duodenal mucosa from gastric acid and buffers material entering duodenum for optimal enzyme activity.
What is the purpose of the enzyme phase of pancreatic juice?
- Digestion of food
What is the main pancreatic tissue and what other type of tissue is there?
Acinar tissue. Also has Islets of Langerhans.
What do Islets of Langerhans produce?
- Alpha cells: Glucagon
- Beta cells: Insulin
Is acinar tissue endocrine or exocrine?
Exocrine
What is the endocrine tissue of the pancreas?
Islets of Langerhans
What cells make up the pancreatic acinus?
- Duct cells
- Centroacinar cells
- Acinar cells
What is the role of the acinar cells?
Secrete enzymes for the protein phase.
What is the role of the centroacinar cells?
Secrete aqueous HCO3- for the aqueous phase
What is the role of the duct cells?
HCO3-/Cl- exchange
Outline the mechanism of HCO3-/Cl- exchange
- In resting state, CFTR chloride channels are aggregated against the luminal surface of the cell.
- Tubulovesicles - H+ pumps, scattered throughout cell.
- On stimulation, CFTR channels organise on apical membrane. Tubulovesicles organise on basolateral membrane.
- Once organised, cells can secrete HCO3-
How is HCO3- secretion stimulated?
By secretin
How is enzyme secretion stimulated?
By CCK
How are pancreatic cells inhibited?
Somatostatin
Where are lipoproteins synthesised?
In the liver
Where is cholesterol synthesised?
In the liver
What happens to cholesterol produced in the liver?
Some is mixed with lipoproteins, some is excreted via bile.
What does the beta oxidation of triglycerides produce?
Glycerol and 3 fatty acids
What enzymes are used in the beta oxidation of triglycerides?
Lipoprotein lipase and hepatic lipase
What is released when blood glucose is high? What is the liver’s response?
- Insulin.
- Inhibition of gluconeogenesis and glycogenolysis.
- Increased glucose uptake by muscle.
What is released when blood glucose is low? What is the liver’s response?
- Glucagon. Also cortisol and adrenaline.
- Increased gluconeogensis and glycogenolysis.
- Less uptake of glucose by muscle.
What is the function of lipoproteins and what are the 2 types?
- Transport fats in blood.
- HDL and LDL
- HDL protective, LDL atheroma
What is the only coagulation protein the liver doesn’t produce?
Von Willebrand factor
