Liver functions Flashcards
What does the liver synthesise?
-Plasma proteins albumin (important for osmotic pressure, building and transport of large hydrophobic compounds, antioxidant, anticoagulant and antrithombic effects) globulin fibrinogen -Clotting factors -Complement factors
How can liver failure lead to odema?
- The liver produces albumin
- Liver failure dysfunction in albumin production
Decreased production less albumin in blood (hypoalbuminaemia)
3.Albumin contributes to capillary oncotic pressure…
Hypoalbuminaemia dec. capillary oncotic pressure
less of a difference in water conc. between plasma and interstitial fluid - accumulation of water in interstitial fluid (oedema)
What is the function of globulins?
- The majority of antibodies are gamma-globulins (not made by the liver), but some are alpha/beta globulins (made by the liver)
Blood transport of: - Lipids (by lipoproteins)
Iron (by transferrin)
Copper (by caeruloplasmin)
Why can liver failure lead to a comprimised immune system?
some antibodies are made in the liver - alpha/beta globulins (made by the liver)
Which clotting factors are made by the liver?
- Production of clotting factors
All, except:
Calcium (IV)
von Willebrand factor (VIII) - Production of bile salts
Necessary for intestinal absorption of vitamin K
Vitamin K is required to produce numerous clotting factors
What do complement factors (produced by liver) do?
Important part of the immune response to pathogens
What is protein metabolism?
Continuous degradation and re-synthesis of all cellular proteins
70-80% of liberated amino acids are re-utilised into proteins
Variable rate – reflecting usage and demand
Increase seen in:
Damaged tissue due to trauma
Skeletal tissue during starvation – gluconeogenesis
2 primary methods:
Lysosomal pathway
Ubiquitin-proteosome pathway
What does the liver store?
Iron
Fat soluble vitamins
Glycogen
Minerals
What minerals does the liver store?
Iron
Stored as ferritin
Copper
What are xenobiotics
Foreign chemical substance
Can be absorbed across lungs, skin or ingested
Drugs are considered xenobiotics
Excreted in bile, urine, sweat, breath
What are phase I reactions?
-Oxidation Hydroxylation (add –OH) Dealkylation (remove –CH side chains) Deamination (remove –NH) Hydrogen removal
-Reduction Add hydrogen (saturate unsaturated bonds)
-Hydrolysis
Split amide and ester bonds
Phase I reactions can:
Inactivate drug
Further activate drug
Activate drug from pro-drug (inactive form)
Make a drug into a reactive intermediate (could be carcinogenic or toxic)
What are phase II reactions?
Synthetic anabolic reactions
Glucuronidation, sulfation, Glutathione conjugation, amino acid conjugation, acetylation, methylation, water conjugation
Known as ‘conjugation’ reactions
Attachment of substituent groups (endogenous molecules)
Usually inactivate products
Catalysed by transferases
Significantly increase hydrophilicity for renal excretion
Also mainly in the liver
3 pathways for drug elimination
- Elimination (usually polar drug, excreted, unchanged)
- Phase II - then elimination
- Phase I - then Phase II - then elimination
Microsomal enzymes
Microsomal enzymes
Location - smooth endoplasmic reticulum
Sites - liver then kidney, lungs, intestinal mucosa.
Enzymes – mono-oxygenases, (CYPs,FMOs); UGTs
Reactions - majority of drug biotransformation reaction ;
oxidative, reductive & hydrolytic and glucuronidation
Note - they are inducible by drugs, diet etc…
Non microsomal enzymes
Non microsomal enzymes
Location - cytoplasm and mitochondria of hepatocytes, other tissues
Enzymes - protein oxidases, esterases, amidases, conjugases
Reactions - non specific enzymes that catalyze few oxidative,
a no. of reductive & hydrolytic reactions and also conjugation reaction
other than glucuronidation.
Note - Not inducible but having polymorphism
(pseudocholinesterase – failure to metabolise choline adequately)
