L10 & L11: Functions of the Liver Flashcards
Major blood supply to liver
Portal venous blood (70-80%)
Macrophages in liver
Kupfer cells
Hepatic stellate cell, when activated over a long period time….
…makes collagen deposition contributing to fibrosis.
Which is NOT in the portal triad? A. Hepatic artery B. Hepatic vein C. Portal vein D. Bile duct
B. Hepatic vein
Which zone contains cells closest to the portal triad?
Zone 1 - Periportal cells; see pathogens first, most active in detoxification
Which zone contains cells furthest from portal triad?
Zone 3 - Pericentral cells; die first in ischemia, most active in bile synthesis
Where are non-essential aa’s synthesized?
liver
What protein maintains plasma oncotic pressure?
albumin from liver
Liver converts ammonia to
Urea.
Note: too much NH3+ can cross BBB and cause mental injury
Drug design should take into account
First pass metabolism
1st pass metabolism consists of what phases?
Phase I: oxidation/hydroxylation of substances via p450
Phase II: solubilize substances via conjugation
What happens to large water-soluble catabolites and molecules bound to plasma proteins, steroid hormones, etc. that can’t be excreted via kidney?
Liver excretes these products in bile, so it can be defecated
Bilirubin is a byproduct of
heme metabolism
Calcified bilirubin produces
gall bladder stones
Composes 65% of bile
bile acids
Bile acids are derived from
cholesterol in hepatocytes
Rate limiting enzyme for bile acid synthesis
7-alpha hydroxylase
under negative feedback of bile acids (the more we recycle back, the more we suppress the synthesis of bile acids. You lose bile acids and thus the feedback regulation when you resect the ileum though.
95% of bile acids recycled back to liver via
ASBT
Is 7-alpha hydroxylase more active when ASBT is lost (eg. during ileal resection), or present (healthy ileum)?
ASBT recycles bile acids. Bile acids negatively regulate 7-alpha hydroxylase. Thus, when ASBT is gone, can’t recycle the bile acids, so 7-alpha hydroxylase needs to make more bile acids
Why does ileal resection promote steatorrhea?
Ileal resection –> no recycled bile –> bile synthesis de novo –> doesn’t ever really catch up –> less bile –> fatty stool
What happens when some of the bile acids enter the colon?
Colonic bacteria can work on them and make 2ndary bile acids. 3 types. Both primary and secondary are conjugated bile acids. These conjugated bile acids are called bile salts (more water soluble) and these are not capable of crossing intestinal membrane. the only way they can come back is through ASBT
Can conjugated bile acids, or unconjugated bile acids, be reabsorbed by intestine?
Unconjugated. If conjugated, need ASBT active transport.
Lithocholic acid is sulfated so…
not transported by ASBT so lost in stool. Method for getting rid of toxic versions of 2ndary bile acid.
Who has the highest bile acid synthesis rate?
Ileum resected people (almost 10x as much)
If you feed bile acid orally to ileum resection patients…
…it restores proper negative feedback to 7-alpha hydroxylase…so BRINGS DOWN the synthesis rate of bile acids.
Storing bile too long…or prolonged intervals between meals…
…promotes precipitation of gallstones
1st step of cholesterol crystals
nucleation (inhibited by “anti-nucleating” proteins, which suppress gallstone precipitation)
What relaxes sphincter of Oddi and contraction of gallbladder?
CCK release from duodenal I-cells (remember CCK-RP and monitor peptide story)
CCK contracts gallbladder via
A. Endocrine
B. Paracrine
C. Both
C. Both
Endocrine - CCK acts directly on gallbladder
Paracrine - CCK activates CNX-afferents, causing efferent ACh release on gallbladder
Cholelithiasis
gallstones INSIDE gallbladder
Cholangitis
infection of cholangiocytes leading to infection of liver (bacterial infection)
What color is biliverdin?
yellow
What color is bilirubin?
Green
What does conjugation do, to a substance?
It makes it soluble
UDP glucuronyl transferase (UGT)
Conjugates bilirubin in liver
Jaundice in newborn
Increased unconjugated (thus insoluble) bilirubin remains in skin. Caused by slow synthesis of UGT.
Why is pee yellow?
Conjugated bilirubin is soluble
Why are feces yellow?
Urobilin and Stercobilin
Increased UNCONJUGATED bilirubin (makes JAUNDICE) is explained by
Less UGT
Too much heme degradation
Dark urine (high bilirubin) but no jaundice, is likely explained by
Gallstone blockage of bile flow
Defect in transporter that secretes conj. bilirubin in bile
UGT is intact since no jaundice. Problem is downstream to UGT.
Is pruritus (itchy skin) due to increased bile acids, or increased bilirubin?
Bile acids. Whereas build up of bilirubin promotes jaundice.
Major source of ammonia in body
colonic bacteria make 50% of ammonia because they have urease enzyme. Kidney can also make ammonia. Liver can also contribute, but minor.
Liver has a high “reserve function” for
urea cycle (last to be damaged)
Urea cycle damage promotes
hepatic encephalophathy
Liver cirrhosis pathogenesis…
injury liver, promotes over activation of hepatic stellate, makes a lot of collagen, promotes collagen deposition, eventually decreases elasticity of vascular bed, and pressure increases causing backup of blood into portal veins…portal hypertension…
Might need to do portal-caval shunt
Portal hypertension patients may exhibit what signs
Spider nevi
Ascites
Esophageal varices
Caput medusae in abdomen
Portal-caval shunt
Connect portal vein to systemic circulation….but now you have hepatic encephalopathy because blood is not treated with urea cycle…basically screwed
