case 5- secretion and excretion in the liver Flashcards
what are particulates phagocytosed by
Kupffer cells
what is the blood supply to the liver
75% from portal vein
Rich in absorbed nutrients
Recycled bile acids/salts
25% from hepatic artery
Regular systemic arterial blood
where do both of these feed into
both feed into hepatic sinusoids
Single venous drainage pathway - central vein with feeds into hepatic vein and back to heart via the vena cava
what is zone one of the liver
Zone 1:
periportal
Amino acid catabolism
Glycogenesis
Cholesterol synthesis
what is zone three of the liver
Zone 3:
Pericentral
Lipid synthesis
Ketogenesis
Glutamine synthesis
Drug metabolism
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what is zone three
a mixture of both
where do you first see fibrosis occur
around the central veins
what are hepatocytes
polarised epithelial cells
what does fenestrated mean
Fenestrated means there are holes in the cells and these around found in the sinusoid (blood)
what does the bile canaliculi have
mitochondrion
Bile canaliculus
Junctional complex
what are the functions of bile
secretion of bile acids or salts to aid intestinal lipid digestion and absorption
Secretion of water and electrolytes
Excretion of waste products (those that are not easily excreted by the kidney)
Excretion of hormones
Excretion of drugs and other xenobiotics
what is the composition of bile
around 1000ml per day to the -1 secreted by the liver
Around 500ml per day to the -1 reaches the duodenum
bile salts/acids and phospholipids and cholesterol
Bilirubin (conjugated)
Metabolites of hormones and drugs
Heavy metal ions
Electrolytes (HC03- neutralise acid) and water (as a vehicle)
what are some features of primary bile acids
primary bile acids (synthesised in the liver) are weakly ionised, hence ‘bile acids’. (Bile acid plus hydrogen=undissociated)
what are bile acids produced from
cholesterol
what are bile acids conjugated with
Conjugation with taurine, glycine, sulphate, glucuronate, makes them more water soluble and charged, hence ‘bile salts’ (BA-X-)
what is secondary
Secondary = bacterial modification in terminal ileum and colon
what are unconjugated and conjugated bile salts secreted via
un-conjugated (BA-) and conjugated bile salts (BA-Z and BA-Y) secreted via:
Bile salt export pump (BSEP)
Multidrug resistance - associated protein 2 (MRP2)
Z = taurine and glycine
Y = sulphate and glucuronate
what are both of these
both are ABC transporters with wide substrate speceificities
what is the cholesterol transporter
ABCA1
what is MDR1
p-glycoprotein
what is the bile salt export pump
BSEP
what is ABCG2
sulphated steroids
what is ABCG5/8
cholesterol
where is active uptake of conjugated bile salts
Active uptake of conjugated bile salts in terminal ileum via Na+ bile salt co transporter (ASBT) and organic solute transporter (OST)
what is the co transport mechanism of bile salts in the liver
Co transport with Na+ via Na+-taurocholate co transporting peptide (NTCP)
how are organic anions secreted
basolateral uptake by exchange with Cl- via OATP (large family)
Conjugation with glucuronate or sulphate (Y)
Apical secretion via MRP2
Sulphated sex steroids (St-Y) via another ABC transporter ABCG2
NB transporter diversity - also seen in kidney and BBB
how are organic cations and lipids excreted
cytotoxic drugs, local anaesthesia and antibiotics
Small cations = facilitated diffusion via organic cation transporters (OCT1/3) ad then by exchange with H+ (MATE1)
Bulky molecules via OATP and the multi drug resistance transporter 1 (MDR1)
cholesterol via ABCG5/8
Phospholipids via a flippase (MDR3)
describe the excretion of bilirubin
breakdown of haem to bilirubin following phagocytosis
The intermediate step is biliverdin
Carried by albumin to liver and taken up via OATP and ??
Conjugation with glucuronate (Y) in ER and secretion via MRP2
conjugated and actively secreted by the liver
Eventually move to the small intestine towards the ileum
The bacteria deconjugate some of the bilirubin and convert it to urobilinogen (colourless)
Most then converted to stercobilin (Brown) in colon
Some urobilinogen is reabsorbed and excreted as urobilin (yellow) via the kidney
describe jaundice
unconjugated = haemolysis or failure of liver too conjugate. Normal urine and neurotoxicity (kernicterus)
Conjugated = chloleostasis (blockage in biliary system). Dark urine
Mixture = acute liver disease e.g hepatitis
what happens if NH3 crosses the BBB
neurotoxicity
confusion-cognition changes-coma
what is the biliary system
ductal secretion
what is the fluid secretion carried out by
Fluid secretion by cholangiocytes
what is 30-50% of hepatic bile secreted by
30-50% of hepatic bile is secreted by epithelial cells (cholangiocytes) lining the bile ducts
what is the mechanism for HCO3- rich isotonic fluid
HCO3- rich, isotonic fluid, mechanism similar to pancreatic duct:
Secondary active transport of Cl- and HCO3-
Paracellular Na+ transport with isosmotic water flow
what is it stimulated by
stimulated by secretin, VIP, glucagon
Na+ is reabsorbed via what
Na+ reabsorbed via apical NHE and basolateral Na+,K+ -ATPase
chloride is reabsorbed in exchange for what
Some Cl- reabsorbed in exchange for HCO3- but net H+ secretion
