Physiology and pharmacology of the Liver Flashcards
what is the metabolic hub of the body
The liver
the liver is the largest organ in the body true/false
true
what are the main regulatory functions of the liver
regulation of carbohydrate, lipid and amino acid metabolism
What is carbohydrate metabolism comprised of
GLUCONEOGENESIS - glucose produced from amino acids
GLYCOLYSIS - to form pyruvate thence lactate (anaerobic) , to acetyl co-A (aerobic)
GLYCOGENESIS- to store polymerised glucose as glycogen
GLYCOGENOLYSIS - to release glucose from glycogen as required
What is fat metabolism comprised of
processing of chylomicron remnants
synthesise of lipoproteins (eg. LDLs, HDLs, for export) and cholesterol (for steroid hormone and bile acid synthesis)
ketogenesis (in starvation)- important for neuronal function
What is protein metabolism comprised of
Synthesis of plasma proteins
Transamination and deamination of amino acids
Conversion of ammonia to urea via urea cycle
What hormones are deactivated in the liver
Insulin
Glucagon
Anti-diuretic hormone
Steroid hormones
What hormones are activated in the liver
Conversion of thyroid hormone to the more active triiodothyronine
Conversion of vitamin D to 25-hyfroxyvitamin D2 which is further converted in the kidney
What are the major functions of the liver
Storage of
- Fat soluble vitamins A (Ito cells) DEK (in hepatocytes)
- Water soluble vitamin B12 - long term storage of 3-5 years
- Iron, copper
- glycogen
Synthesis of proteins
Protection
What proteins are synthesised by the liver
-for metabolic processes of the organ
-for export
coagulation factors II, VII, IX, and X
Proteins C and S (involved in coagulation)
Albumin
Complement proteins
Apolipoprotiens
Carrier proteins eg. molecules which bind to hormones to keep them in solution
What are the protective functions of the liver
Kupffer cells (liver phagocytes) - digest/destroy particulate matter (bacteria) and senescent (old) erythrocytes
MORE- GET FROM SLIDES
What is the purpose of bile
participates in the digestion and absorption of fats and the excretion of products of metabolism
Incorporates otherwise insoluble fats into stabilised lipid droplets
Where is bile made/secreted from
Produced and secreted by hepatocytes and bile duct cells
Where is bile stored/concentrated
In the gall bladder
Removes water
Can cause solids to precipitate out (cholesterol) causing gall stones
What stops bile flowing from common bile duct to duodenum between meals
The closure of the sphincter of Oddi
What is bile released in response to
Enter of chyme into the duodenum -stimulates gall bladder smooth muscle to contract - VAGUS nerve also plays a role
What is the pH of bile
Slightly Alkaline
Neutralises acidic chyme to create optimum pH for enzymes
What does bile contain
Primary bile acids Secondary bile acids Water and electrolytes Lipids and phospholipids Cholesterol IgA Bilirubin
What are the primary bile acids
Cholic, and chenodeoxycholic acids
Converted by bacteria into secondary bile acids
What are the secondary bile acids
Deoxycholic and lithocholic
Reabsorbed via portal system back to liver and resecreted back into bile
How does the liver adapt when low in salts
Uses cholesterol to make more bile acids
What is the most common pathology of the biliary tract
Cholelithiasis
What is a gallstone
Crystalised cholesterol that over time grows into a gallstone
What is the best treatment for symptomatic gallstones
Laproscopic cholecystectomy
What happens to the majority of bile
Most is reabsorbed by active transport in the terminal ileum and undergoes enterohepatic recycling
What are bile acid sequestrants
Promote the secretion of bile acids
Colveselam, Colestipol, colestyramine
Neither digested nor-absorbed by gut
Act by binding to bile acids, preventing their reabsorption
Bile acid sequestrants increase the circulating fat levels true/false
FALSE
reduce circulating fat levels by lowering plasma LDL cholesterol
What can bile acid sequesterants be used to treat
Hyperlipiddaemia (limited effect)
Cholestatic jaundice (itch)
Bile acid diarrhoea
What enzyme mediate phase 1 of drug metabolism in the liver
Cytochrome P450s
What does phase 1 of drug metabolism in the liver involve
Makes drugs more polar by
Oxidation
Reduction
Hydrolysis
Why can’t lipophilic drugs be excreted, how do you make them more easily excreted
End up getting reabsorbed by kidney
Adding a polar aged to the lipohylic substance allows it to be excreted and not reabsorbed by the kidney
What does phase 2 of drug metabolism in the liver involve
Conjugation
Adds an endogenous group on increasing polarity
Example of a drug which is activated in the liver
Codeine which is activated to morphine in the liver
Which phase of liver metabolism is anabolic
Phase 2
Which phase of liver metabolism is catabolic
Phase 1
What happens in hepatic failure (liver failure)
Detoxification of ammonia via urea cycle to urea (excreted by kidneys) fails
Blood ammonia levels rise (hyper ammonia) excreting toxic effect on CNS causing incoordination, drowsiness, coma and ultimately death
How can you treat hepatic failure
Administer Lactuolose
Antibiotics - suppress colonic flora and this inhibit
