GI 10 and 11: Liver and bile Flashcards
Wht are the 3 main functions of the liver
metabolism, detoxification, excretion
What is the portal circulation?
Blood from GI organs goes to portal vein instead of straight to vena cava –> allows liver to have a first “look over” of blood from GI tract (detox!!)
Hepatocyte
liver cell
Organizing structure hepatocytes are in
plates
what kinds of vessels supply hepatocytes
sinusoids (low resistance cavities that are supplied by portal vein and hepatic artery)
Hepatic triad
Branches of hepatic artery, portal vein and bile duct
Zone 1
Periportal cells - cells closest to triad, very sensitive to oxidative injury and hve largest O2 and nutrient supply. These are most active in detoxiication
Zone 2
intermediate zone between zones 1 and 3
Zone 3
Pericentral cells - closest to hepatic vein, mmost sensitive to ischemia and very active in bile synthesis
where does biliary system start?
Hepatocytes
Canaliculi in liver connect what?
apical membranes of adjacent hepatocytes
Cholangiocytes
Canaliculi drain bile from liver and transport to biliary ductules - these ductules are lined by cholangiocytes which are a kind of columnar epithelial cell
Zones 1-3 in level of oxygenation
Zone 1 > zone 2 > zone 3
Biliary ductules drain into what
bile ducts - which coalesse into right and left hepatic ducts, and then into hepatic duct and go to either gall bladder (via cystic duct) or small intestine via common bile duct
What metabolism do hepatocytes play a role in
carbohydrates
lipids
proteins
what do heptocytes do for carb metabolism
gluconeogenesis
glycogenolysis
Impaired liver fxn results in hyperglycemia during and after meals, and hypoglycemia between meals
Hepatocyte fxn in lipid metabolism
Rich store of enzymes for FA oxidation - contributes to generating energy
convert carbs to lipids - synthesis of lipoproteins, cholesterol, phospholipids (metabolism classes will cover this gain)
Convert cholesterol to bile acids
Role ofl liver in protein metabolism
synthesize non-essential AA’s nd modifies these so they can go into biosynthetic pathways for carb synthesis
synthesizes plasma proteins (including albumin)
converts ammonia to urea
How does liver protect body from toxins
Senses endogenous or exogenous toxic molecules (so anything cells produce and are in blood, but also any drugs or bacterial toxins), done in 2 phases
phase 1 of liver detoxification
oxidation, hydroxylation - catalyzed by cytochrome p450 enzymes
phase 2 of liver detoxification
cnjugate substances with glucuronide sulfate, AA’s, or GSH to make the m water soluble, then excrete products in feces via bile or in urine via kidney
Wht role does liver play in excretion?
Large water soluble catabolites and molecules can be excreted via bile –> go to feces
Constituents of bile
bile salts phospholipids proteins cholesterol bile pigments (bilirubin) electrolytes (isotonic to plasma)
2 primary bile acids synthesized by hepatocytes
cholic acid and chenodeoxycholic acid
Secondary bile acids and how are they synthesized
Colonic bacterial enzymes act on primary bile acids to form secondray ones, whch are ursodeoxycholic acid, deoxycholic acid, and lithocholic acid)
how are bile salts made / how are bile acids made more soluble
in hepatocytes, primary and secondary bile cids are conugated with glycine nd taurine with exception of lithocholic cid which is sulfated instead
Conjugated bile acids are absorbed __ by ____
Deconjugated bile acids are absorbed ___ by ____
in ileum by ASBT
In colon by passive diffusion
How are bile acids brought back to liver
entoerhepatic circulation
If you have an ileal resection what happens to bile circulation
you lose a shit ton of bile recycling
What can cholangiocytes do to bile
modify it - Glucose, AAs are reclaimed by transporters, and chloride is exchanged for HCO3- so bile is slightly alkaline
where is bile stored
gallbladder
in between meals, outflow of bile is blocked by what
constriction of sphincter of oddi
How does bile concentrate
unknown mechanism but Na/H exchanger plays a role, sodium is absorbed which will bring water with
What hormone is the main player in getting bile to be secreted from GB into duodenum
CCK
Ach can also be dumped on GB to get it to squeeze from neural reflexes
What are gallstones
precipitated bile constituents
What comprises gallstones
cholesterol or calciu-biliruinate pigment stores
What usually prohibits gallstone generating
anti nucleating proteins
If you skip breakfast what might happen
gallstones
What is bilirubin a consequence of
heme degeneration
What does bilirubin bind to in blood
albumin
what takes bilirubin into hepatocytes
organic anion transporting polypeptide transporter (OATP)
in microsomes of hepatocytes, bilirubin is conjugated to what via what enzyme
Glucoronic acid by UDP glucuronyl transferase
Why do some newborns develop jaundice
UDP glucunoryl transferase is not synthesized quickly after birth
Conjugated bilirubin is water soluble or insoluble
soluble and part of it is xcreted in urine (remainder is secreted in bile nd travels to small intestine to do so)
In terminal ileum, what happens to biliruben
deconjugated by bacterial enzymes and metabolized to urobilinogen
Can bilirubin cross BBB?
yes and it can cause neurological damage and be fatal if it isn’t yeeted
Increase in unconjugated bilirubin would be a reflection of what
loss/absence of UGT
sudden oversupply of heme
liver failure
High conjugated bilirubinemia would be do to
defect in OATP , blockage of bile flow
Jaundice
yellow color of skin and conjunctiva due to accumulation of bilirubin due to hemolysis, hepatic dysfunction, or gallbladder duct issues
What is a product of protein catabolism the liver must deal with to safely excrete
ammonia - turns to urea via urea cycle
What are the 2 main generators of ammonia for us
protein catabolism and colonic bacteria
Is urea ammonia membrane permeable
yes
What happens to ammonium and urea
excreted in stool and urine
Hepatic encephalopathy
Chronic liver disease –> declining mental fxn, caused by detox function being fucked –> this is fatal
Liver cirrhosis
irreversible scarration and destrution of liver, caused by injury, fibrosis, and tissue degeneration from dugs, poisons, and hepatitis
Portal hypertension
Increased BP in sinusoids reflects to portal vein –> results in splenomegaly , ascites, and other complications
caused by increased vscular resistance in lier
