liver physiology Flashcards
how are vessels organised in the liver
in a hexagonal portal
functions of the liver
detoxification, energy storage, immune functions , synthesis of clotting
what are lipids
Esters of fatty acids and glycerol
Large and diverse naturally occurring organic compounds that are insoluble in water
Variety of structure and functions
how are lipids stored
adipocytes, hepatocytes,
lipid functions
energy reserve, hormone metabolism
Structural part of cell membrane
lipid transport?
Lipids are often transported as TGs or FAs bound to Albumin or within lipoproteins
TGs cannot diffuse through cell membrane
FA are released through lipases to facilitate transport into the cells
In the cell FA are re-esterified to TG
fatty acid uptake and regulation
Diffusion through the lipid bilayer of the cell membrane
Facilitated transport
Increases if increased substrate (↑supply) or increase in receptor molecules (↑ demand)
transporter systems of fatty acids
induction to increased expression may result in increased uptake of FA in the hepatocytes)
FAT - fatty acid translocase
FATP - FA transport polypeptide
what do lipoproteins consists of?
core of tg’s and cholestrol esters and a surface monolayer of phospholipids
where is iron absorbed and stored
duodenum made
Stored in liver
what transports iron around the body
transferrin
ferritin?
A blood protein that contains iron
Large spherical protein
where is ferritin found
Ferritin found in the cytoplasm of cells but can also be found in the serum.
xenobiotics
foreign substances with no nutritional value
how can xenobiotics damage cells
dna damage, react with o2 to make free radicals
function of phase1 biotransformation of xenophobes
to add or expose functional groups- OH, COOH, NH2 and SH to make the xenophobe more hydrophilic to be excreted from kidneys
where are cytochrome p450 found
present in smooth er
Function of cytochrome p450 in phase 1 reactions
Uses cytochrome p450 reductive to transfer electrons to nadph
outline phase 1 reactions
oxidation, hydrolysis and reduction
addition of an oh group to make it more polar
with cytochrome p450
POSITIVE NITROGEN BALANCE
). If the intake of nitrogen is greater than the excretion
NEGATIVE nitrogen BALANCE
, if excretion greater than intake
gain or lose proteins in positive N balance
gaining protein
gain or loose protein in negative N balance
lose
kwashiorkor
protein malutrition
amino acid absorption
The first stage is via a cell surface channel where it is co transported with a sodium ion. Then via the basal membrane is is actively transported into the portal veinous circulation by an ATP consuming process. From there it travels into the liver.
difference between essential and non essential amino acids
essential- amino acid that cant be synthesized by the body and must come from diet
non - essential- can be synthesised by the body
most important hepatic protiein
albumin
alpha ketoacid?
removal of amine group from amino acid left with carbon backbone
transamination
a chemical reaction that transfers an amino group to a ketoacid to form new amino acids
enzyme- aminotransferase
what happens to amino acids in the fasting state
stored in muscle as protein, broken down into monomer form of amino acid , to make atp
gluconeogenesis
glucose alanine cycle
Excess alanine transferred to the liver and converted to pyruvate
Pyruvate can be used to produce glucose in gluconeogenesis
Glucose enters blood used by muscles
Glutamate to ammonium by oxidative deamination dissociates to ammonia , converted to urea
why is albumin important
Binding and transport
- Maintenance of colloid oncotic
pressure - Free Radicals
- Anticoagulant effects
What causes Albumin to decrease
Decreased synthesis
- Increased catabolism
- Increased loss
Consequences of decreased Albumin
Decreased colloid oncotic pressure
- Decreased ligand binding
Disease processes associated with
low Albumin
Malnutrition Liver disease Renal disease Burns / trauma Sepsis
why is bile important
Lipid digestion and absorption
Cholesterol homeostasis
Excretion of lipid soluble xenobiotics / drug metabolites / heavy metals
What is bile?
digestive fluid produced by the liver and stored in the gall bladder
what does bile formation depend on?
Formation depends on the hepatic SYNTHESIS and cannalicular SECRETION of bile acids (=major organic anion in bile)
breakdown product of red blood cells
bilirubin
where are bile acids synthesised ?
Synthesised from cholesterol in hepatocytes of the acini
what does amphipathic mean
hydrophillic and hydrophobic parts
Fat soluble vitamins
A d e k
Function of copper and storage
Helps to form rbc
Transported in plasma bound to ceruloplasmin
Three types of plasma protein
Albumin
Fibrinogen and globulin
Most common plasma protein and function
Albumin
Maintains oncotic pressure
Binds and transports large hydrophobic molecules
Which clotting factors does the liver produce
All but 8
Where is iron stored
In the liver as ferritin in kuppfer cells
What are microsomes
Fragments with endoplasmic reticulum and ribosomes
Define lipophilic
Able to pass through plasma membranes
Phase 2 reaction outline
Adding a glucaronic acid group
Increase hydrophilicity
Done by glucuronosyltransferase
What reactions are non microsomal enzymes involved in
All conjugation reactions except glucoronidation
What is the role of fad
Accept electrons from nadph
Function of complement proteins
Aid in immune response
Role of urea cycle
Series of enzymatic reactions
Convert ammonia into urea
Where does urea cycle happen
Mitochondria of hepatocytes
How does ammonia get into liver mitochondria
Glutamine synthesise
Adds ammonia to the amino acid glutamate forming glutamine
Once in the liver glutamine hydrolyses the products back into their original form
Urea cycle steps
Ammonium and co2 combine to make carbomoyl phosphate
This allows ornithine to be converted to citruiline
citruiline to arginine
Arginine is cleaved by arginase into urea and ornithine and the cycle repeats
In what three forms is energy stored in the body
Triglycerides 78%
Protein 21%
Carbohydrate 1%
Where is most body fat stored
Adipocytes
Three types of lipoprotein and where they’re formed and function
Hdl liver good cholesterol , removes excess via excretion in bile
LDL plasma delivers cholesterol to cells
Vldl synthesised in hepatocytes triglyceride delivery from liver to adipocytes
Function of lipoprotein
Transport cholesterol through the blood
Function of lipoprotein lipase
Hydrolyses triglycerides into 2 fatty acids and one monoglyceride molecule
Function of hepatic lipase
Found in liver and adrenal cells Converts IDL ( intermediate density lipoprotein ) into LDL thereby packaging it with more triglycerides to be released into the body .
describe the steps in beta oxidation of fatty acids
- CoA binds to the end of a fatty acid chain: fatty acyl CoA.
- ATP -> AMP + 2Pi.
- Fatty acyl CoA is a substrate for beta-oxidation.
- Acetyl CoA is split off from FA and 2H+ are transferred to coenzymes.
- H+ enter OP and another CoA attaches to repeat the cycl
Difference between white and brown fats
White few mitochondria , little endoplasmic reticulum , stores energy
Brown fat lots of mitochondria , expending energy and heat production
Constituents of bile
Bile salts Lecithin Hco3- Cholesterol Bile pigments
How is bile secreted
Secreted under the action of cholecystokinin
CCK released in response to increased fatty acid conc in duodenum
Gall bladder contracts
Bile released into duodenum via sphincter of oddi
Where are bile salts reabsorbed and how
In the terminal ileum via portal vein 95%
What is bilirubin
Pigment that gives bile it’s yellow colour
By products of haem metabolism
Bilirubin metabolism
Hb-> haem and glob in with macrophage
Haem —> biliverdin with haem oxidase
Biliverdin to bilirubin via biliverdin reductase
Unconjugated bilirubin transported to the liver via albumin carrier
Glucoronic acid conjugates it via glucoronyl transferase
Released in bile via duodenum
What is enterohepatic circulation
Movement of bile acid molecules from the liver to the small intestine and back to the liver
How is urobilinigen made
Intestinal bacteria in the terminal ileum reduce the cb into urobilinigen
Three types of jaundice
Pre hepatic
Hepatic
Post hepatic