Physiology and Pharmacology of the Liver Flashcards
How is carbohydrate metabolism regulated
Hormonally
Glycolysis
Breakdown of Glucose to pyruvate –> lactate (anaerobic) + acetly coA (aerobic)
Gluconeogenesis
AA –> Glucose
Glycogenesis
Store glucose as glycogen
Glycogenolysis
Releasing glucose as required
fat Metabolism of the Liver
Ketogenesis
Processing chylomicrons
Synthesis of lipoproteins and cholesterol
Horomones deactivated by liver
Insulin
Glucagon
ADH
Steroid hormones
Hormones activated by the liver
Thyroid Hormone
Vit D hormone
What does the liver store
Fat soluble vitamins - vit A (in cell), D, E, K (hepatocytes) Water solumble vitamin D Iron copper Glycogen
Detoxification
Exogenous
- ethanol and drugs
Endogenous
- bilirubin (haem breakdown)
Protection
Kuppfer Cells Immune Factors (acute phase protein)
Synthesis of proteins
Clotting factor 2, 7, 9, 10 Protein S and C Albumin Carrier proteins Apoliproteins Complement proteins
What is the role of bile
Digestion and absorption of fats
Excretion of metabolism product
What is bile produced by
Bile duct cells
Hepatocytes
Bile action between meals
Stored and concentrated in the gallbladder
Bile during a meal
Chyme in duodenum stimulates gallbladder to contract via CCK and vagal impulse
Sphincter of Oddi opens via CCK
Bile spurts into duodenum via cystic and common bile duct
How do heapatocytes secrete bile
Secrete primary juice into caniculi which drains into biliary ductules and ducts
What are secretions from hepatocytes made up of
Bilirubin Bile salts Bile Acids Lipids and phospholipids Cholesteral Na, K, Cl, HCO3, Ca IgA
Excessive cholesterol in comparison to bile may lead to
Acids + Lectin –> Microcystals –> gallstones
What is the ost common pathology of the biliary tree
Choleliathiathis
What is the gold standard treatment for symptomatic gallstones
Laparascoipc cholecystectomy
What is given to patients with unimpaired gallbladder function who have small to medium sized gallstones
Ursodeoxycholic acids
What may be given for biliary colic
Strong analgesic
- however morphine can block sphincter of Oddi
What can biliary spasm be relieved by
GTN
Atropine
Where do bile salts entering the duodenum go
Only a small amount is lost in faeces
Most reabsorbed by active transport in terminal ileum and undergoes enterohepatic recycling
A fraction of bile salts are dehydroxylated to what
Secondary bile acids then go to liver then conjugated with glycine or taurine to form bile salts
What provides the majority of cholesterol excretion
Bile salts
What is the mechanism of colveselam
Binds to bile acids preventing cholesterol from binding and causes its excretion out the body
Cholesterol must form more bile acid and will therefore not gather in plaques causes blockages
What is colveselam used for
Lipid lowering
Cholestatic jaundice
Bile acid diarrhoea
Drugs are described as xenobiotic what does this mean
Not produced normally by the body
What do drug metabolism facilitate
Converts parent drugs to more polar metabolites that are not readily excreted by the kidney and therefore allows excretion
Phase 1 involves
Oxidation
Reduction
Hydrolysis
Makes the drug more polar
CYP450
Group of haem proteins located in the endoplasmic reticulum mediating oxidation reactions
Phase 2 involves
Conjugation of a chemically reactive group resulting in inactive proteins
What is a common phase 2 reaction
Glucocordination
Hepatic Enchepalopathy caused by
Hepatic Failure prevents urea cycle converting NH3 to urea
Blood levels of NH3 increase exerting a toxic effect on the CNS
Incoordination, coma, drowsiness due to cerebral oedema
