Physiology and Pharmacology of the Liver Flashcards
Functions of Liver?
- Carb metabolism
- Fat metabolism
- Protein metabolism
- Degradation fro insulin, steroid, glucagon & ADH
- Activation of Vit D to hydroxyvitamin D2
- Storage Vit A, B12, E, D + K, copper, iron, glycogen
- Coagulation
- Synthesis of plasma proteins
- Protective
- Detoxification
Examples of carb etabolism?
Gluconeogenesis
Glycogenolysis
Glycogenesis
Glycolysis
What is gluconeogenesis?
Producing glucose form amino acids
What is glycogenolysis?
Release glucose as required
Glycogenesis?
To store polymerised glucose as glycogen
Glycolysis?
Form pyruvate, thence lactat or acetyl Co-A
What is involved in fat metabolism?
- Processing of chlyomicron remenants
- Synthesis of lipoproteins & cholesterol
- Ketogenesis (starvation)
What is involved in protein metabolism?
- Trans and de-amination of amino acids
- Convert ammonia to urea
- Synthesis of plasma proteins
When is bile secreted?
Between meals
Where is bile stored?
Stored and concentrated in gall-bladder
What happens in regards to bile during a meal?
Chyme in duodenum stimulates the GB smooth muscle to contract via CCK
- Sphincter of Oddi opens
- Bile spurts into duodenum via cystic and common bile ducts
What does bile consist of?
Cholic and chenodeoxycholic acids
What is cholelthiasis?
Concentration of bile in gall bladder caused by resorption of water- producing a supersaturated solution that is unstable
Cholesterol may crystallise and over time produce gall stones
What is the best treatment for symptomatic gall stones?
Laparoscopic cholecystectomy
What is given to patients with impaired GB function with small-medium sized radiolucent stones? And the drugs adverse affect?
Ursodeoxycholic acid
Diarrhoea
What does atropine or GTN relieve?
Biliary spasm
Bile acid sequesterants?
Colesevalam
Colestipol
Colestyramine
What do bile acid sequesterants do?
Bind to bile acids preventing reabsorption
Lower plasma cholesterol indirectly
What are bile acid sequesterants used for? And what are their adverse affects/limitations?
Used in hyperlipidaemia, cholestatic jaundice and bile acid diarrhoea
-Unpalatable, Causes diarrhoea, reduced absorption of fat soluble vitamins
Where does Phase 1 of drug metabolism occur?
Right Liver
3 processes in phase 1 of drug metabolism?
Oxidation
Reduction
Hydrolysis
What is the effect of drug metabolism phase 1?
Makes drug more polar
Adds chemically reactive group permitting conjugation
Where does phase 2 of drug metabolism occur?
Left liver
What happens in phase 2 of drug metabolism?
Conjugation An endogenous compound is added increasing polarity Then excreted (some drugs excreted unchanged and don't go through the phases)
What does drug metabolism do?
Acts to convert patent drugs to more polar metabolites that are not readily reabsorbed by kidney facilitating excretion
What is CYP450? What does it stand for? What does it do?
Cytochrome P450
Metabolizing enzyme in liver
Paracetamol and other drugs mess this up so liver can’t metabolise (do it’s job)
What does not occur in severe hepatic failure?
What condition is this known as?
Detoxification of NH3 to urea
Hepatic encephalopathy
What effect does a lack of detoxification of NH3 to urea have?
Blood NH3 levels rise
Resulting in coma
What do you use in hepatic encephalopathy?
Lactulose
Converts ammonia to ammonium which is not absorbed/digested in SI
Examples of plasma protein secretions?
Albumin
Alpha globulins
Beta globulins
What do alpha globulins do?
Transport lipoproteins, lipids, hormones and bilirubin
What do beta globulins do?
Transferrin (transports Fe3+, store bound to ferritin)
Fibrinogen (inactive from of fibrin, clotting blood)
What is albumin?
Most abundant plasma protein
Small, negatively charged, water soluble, liver synthesizes about 14g/day
What do lipoproteins do?
Transport dietary fats + synthesized fats. Only liver can metabolise and excrete cholesterol
What vitamins does the liver store and for how long?
Vitamin A- 10 months
Vitamin D- 3 weeks
Vit B12- Few years
What does cholesterol synthesis require?
C atoms-Acetyl Co-A
Reducing power-NADPH
Energy- ATP
What is the role of HMG-CoA reductase?
Catalyiss irreversible form of mevalonic acid
Rate limiting enzyme
Statins target this to lower cholesterol
Products form cholesterol?
Vitamin D- Regulates calcium + phosphorous metabolism
Steroid hormones- Corticosteroids, androgens, estrogens
Bile salts-Main metabolic product of cholesterol
