Hepatobiliary Function Flashcards
What does the liver do? (4 things)
functions to produce bile + secretion,
metabolism of carbs, protein, lipids
bilirubin production and excretion
detoxify
What does the hepatic portal system connect?
connects 2 beds.. 1) that of the abdominal + pelvic parts part of the abdominal part of the esopaghus to the lower anal canal, together with the pancreas, gallbladder, and spleen
2) hepatic sinusoidal “capillary bed”
What does the liver do regarding carbohydrate metabolism?
gluconeogenesis
storage of glucose as glycogen
release of glucose
what does the liver do for protein metabolism?
what are two plasma proteins that are key to the liver?
synthesis of NONESSENTIAL amino acids
modification of amino acids for use in pathways for carbohydrates
synthesis of almost all plasma protein (albumin and clotting factors!!
conversion of Ammonia (created by protein) to urea
what does liver failure result in?
hypoalbuminea, which may lead to edema
What does the liver do for lipid metabolism?
fatty acid oxidation
synthesis of lipoproteins, cholesterol, phospholipids
how does hepatic encephalopathy affect liver function?
Ascites (distended abdomen)?
what about Caput Medusae?
Esophageal Varices?
Bruising
metabolism of ammonia is impaired (urease).. so the ammonia will accumulate and penetrate the blood brain barrier. VERY BAD
Lack of albumin! we’re losing a lot of protein within the circulation and that decreases oncotic pressure and lead to edema + ascites.
caput medusae + esophageal varices = portal hypertension. this pressure is finding other ways to relieve the pressure in the liver!
lack of coagulation factor, so prone to more bruising.
What is cirrhosis?
what causes cirrhosis?
chronic liver disease in which normal liver cells are damaged and replaced by scar tissue
excessive alcohol intake –> this can lead to accumulation of fat within hepatocytes (which is called steatohepatitis (fatty liver accompanied by inflammation) –> leads to scarring of liver and cirrhosis
What is portal hypertension caused by?
what does it lead to?
what’s the normal sinusoidal pressure of the liver and what’s the affected liver pressure?
cirrhosis can cause portal hypertension
develops when there is resistance to portal blood flow, which most often occurs in the liver!
usually sinusoidal pressure is 3-5, but greater than 5 happens with cirrhosis.. it damages the hepatic sinusoidal pressure and so blood goes elsewhere to try and release the portal hypertension.
it goes through porto-systemic collaterals to try and relieve the pressure
What can portal hypertension cause (2 big ones?)
esophageal varices (between systemic + portal system at the inferior end of esophagus)
Caput Madusae (connect systemic + portal system around umbilicus
What creates the ammonia in our body?
what would happen with cirrhosis and the ammonia?
breakdown of our protein.
in the liver it goes through the urea cycle to create urea.. with cirrhosis we have a problem with this cycle which leaves ammonia to go to the brain and damage the brain.
What is the composition of bile?
Bile salts (50%) Bile pigments (2% e.g. bilirubin) Cholesterol Phospholipids Ions H2O
What is the function of bile?
where is it going to be used?
emulsifying fat, helping eliminating that fat!.. usually fat isn’t soluble so that’s why we have bile.
small intestine, in the duodenum
Primary bile acids? where are these synthesized?
secondary bile acids? where are these synthesized?
colic acid
chenodeoxycholic acid
liver
deoxycholic acid
lithocholic acid
lumen of small intestine
where does conjugation happen? what’s happening?
what’s the pKa going to do? what does this mean?
in the liver
we’re adding either glycine or taurine
decreases! makes it more water soluble and acidic!
what are the actual bile molecules?
what do bile salts do?
they are amphipathic
form micelles with the products of lipid digestion.
What does bile secretion result in?
know what is the stimulus for bile to be secreted
know the pathway of bile
know which part bile is reabsorbed and by what form of transport?
in the liver, bile is formed and secreted within canaliculi.. the bile is going to be modified with electrolytes and go down to the gallbladder which is storage site and concentrated (losing electrolytes)
they’re going to leave upon a stimulus of high fats, i.e. CCK!
the bile will go to the duodenum, it’ll travel to jejunum and micelle formation is happening, and in the ileum there is active absorption of bile acids! ACTIVE TRANSPORT
called the enterohepatic circulation of bile.
mechanism of bile secretion and absorption?
what does secretin do in this pathway?
- bile creation
- storage in gallbladder
- CCK stimulates the gallbladder to contract and eject bile and the sphincter of oddi to relax.
- reabsorbs in the ileum and goes through portal circulation back to the liver!
secretin adds more ions and H2O into the bile duct to be stored in the bile! (adding more volume to the bile)
how is canalicular bile secreted?
by ductal cells in response to osmotic effects of anion transport
we know that bile is recirculated to the liver at the ileum, but some gets out before the ileum… why?
how does this get across the membrane?
unconjugated bile.. anything that is more hydrophobic will not want to stay there longer.
PASSIVE TRANSPORT
!What takes bile from the portal system (blood) across the basolateral membrane of the hepatocytes?
which one doesn’t require Na? which does?
Na dependent transport protein –> NTCP,
Na independent transport protein –> OATP
OATP!
What happens at the level of the Hepatocyte/bile canaliculi?
we have 2 more transport systems that take bile acid once they’ve gotten into the hepatocyte and bring it in.
BSEP (bile salt excretory pump)
MRP2
what happens once the bile acids have been exerted to the small intestine? like what’s going to happen to get the bile acids back to the liver?
anything to note of either transporter?
It is taken up by the enterocyte by ASBT (apical sodium dependent bile acid transporter) –> NEEDS SODIUM
and then from the enterocyte to the portal system it needs OSTa-OSTb (organic solute transporter alpha-beta).
How much bile returns to the liver?
how much do we synthesize?
90-95%.
So we just constantly have to synthesize 5-10%, or what’s lost through feces
If we have a resection of the ileum, how is this going to affect our bile?
what’s going to happen to our bile synthesis?
we will not be able to absorb as much bile,
so more of it will need to be synthesized more by the liver.. go up!
Bile acids are created in the liver.. what ion comes with it?
what brings more stuff into the bile duct? why is this important?
conjugated biles tend to be negative, so they attract + charged cations.. creating a gradient for water to follow and other stuff to come in.
with the addition of secretin, this will bring in more HCO3, Na, and H2O.. the HCO3 Brought in helps neutralize the acid that goes into the duodenum.
What happens during concentration in the gallbladder?
what happens when there’s a stimulus?
electrolytes are lost
Na, Cl, HCO3, H2O too.
CCK contracts the gallbladder and relaxes the bile sphincter of oddi.
What happens during periods of inter digestion (no meal in the system) for the sphincter and gallbladder?
gallbladder is relaxed, sphincter of oddi is closed..
What is Bilirubin?
where does it come from?
what happens after bilirubin is formed?
where does it go once it’s made into what it is?
bile pigment.
hemolysis of red blood cells.. so breakdown of RBC leads to hemoglobin –> produces biliverdin –> Bilirubin
bilirubin is not water soluble which is why it can’t penetrate the blood brain barrier. so it’s transported with albumin and taken by the liver.
we need to make sure the bilirubin is not secreted so we conjugate (with glucoronic acid) it in the liver with UDP glucoronyl transferase!
this conjugated bilirubin goes to the small intestine and the intestine deconjugates it to urobilinogin and that can leave back to the liver (through the portal system) or keep going and processed to urobilin/stercobilin.
if the urobilinogen is taken to the kidney (via the portal system) it is oxidized to urobilin giving urine it’s yellow color
What gives the stool a darker color?
Urobilin + Stercobilin
what would happen if we blocked UDP glucoronyl transferase?
we would have a ton of bilirubin, and not any conjugated bilirubin.
abundance of unconjugated!
this leads to jaundice.
What is Jaundice?
symptoms?
how are you tested for this?
Hyperbilirubinemia
yellow discoloration of the sclera, skin, mucous membranes
you measure total serum bilirubin
bilirubin test results are expressed as DIRECT (conjugated), INDIRECT (unconjugated), or total bilirubin.
hemolytic anemia and jaundice?
what’s built up?
a lot of breakdown of red blood cells and so a lot of bilirubin.. but the UDP enzyme can’t work faster so you have a buildup of jaundice
so the liver might be overwhelmed!
buildup of unconjugated
heart failure and jaundice?
what’s built up?
heart failure means less transport of blood to the liver which means a buildup of unconjugated because it can’t go anywhere
Gilbert’s syndrome?
what’s built up?
what’s good to know about this one vs Crigler-Najjar?
prevention of conjugating bilirubin because of a mutation in the gene for UDP gluconyltransferase! (turns to uridine diphosphate gluconosyltransferae!)
it doesn’t wipe it out completely, it just changes the activity level to about 30% of normal function (CN has 20% or none at all)
so you have higher levels of unconjugated!
Crigler-Najjar Syndrome
types?
treatment (5)
** what treatment is only for type 2, and wouldn’t work for type 1?**
higher levels of unconjugated bilirubin.
Mutations for UDP glucoronyltransferase!
Type 1 - super severe (completely inactivates this)
type 2 - less severe (20% of activity left.
1) phototherapy to solubilize bilirubin.
2) blood transfusion to clear up the bilirubin in the blood.
3) calcium phosphate + carbonate to chelate the bilirubin
4) liver transplant
5) Phenobarbitol (treats type 2 to aid in conjugation) –> doesn’t help with type 1
Dubin-Johnson?
what is affected?
what is at high levels?
what is usually the only symptom?
what does the liver look like?
high levels of CONJUGATED bilirubin
mutations in the multi drug resistance protein 2 (MRP2)! this one was located on the bile canaliculi.
so blockage of transport further down. because it usually transports bilirubin out of liver cells and into the bile.
mild jaundice throughout life
black pigmentation of the liver from metabolites.
what happens during physiological neonatal jaundice?
what’s breaking down?
what’s up with the enzyme
what’s built up?
bilirubin production is elevated because there’s a ton of fetal erythrocytes that are breaking down!
UDP glucoronyl transferase starts being formed at birth so your baby won’t be able to conjugate bilirubin so you have jaundice for a bit.
you end up having a large amount of unconjugated bilirubin during 1st week of postnatal.
they speed up the process through a UV light
What can individuals with type 1 crigler-najjar eventually get?
what are the major clinical features?
what’s the immediate treatment?
Kernicterus = brain damage caused by accumulation of unconjugated bilirubin in brain and nerve tissue.
(bilirubin induced neurologic dysfunction)
cerebral palsy, sensoryneural hearing loss, gaze abnormalities
phototherapy!
Rotor syndrome?
what is built up?
what is affected?
is there pigmentation of the liver?
build up of both unconjugated and conjugated but mostly conjugated!
mutations in OATP1B1 and OATP1B3 –> which is found in your hepatocytes that transport bilirubin from the blood into the liver so that they can be cleared from the body.
no pigmentation of liver cells
what’s the primary treatment in neonates for unconjugated hyperbilirubinemia?
how does it work?
phototherapy! –> blue light, wave length at 459nm
works by isomerization that changes transbilirubin into water-soluble cis-bilirubin isomer. that way it can be excreted!
Cholethiasis?
what types?
How can you get gallstones from water or bile acids?
gallstones.
formed from excess cholesterol or from pigment of bilirubin (from bile)
too much absorption of each from the bile would leave gallstones too.
where are the different locations that gallstones can be found?
(going from most common to least common)
also what are their pathologies
large gallstones staying in the gallbladder. asymptomatic for the most part
small stones kind of blocking the cystic duct –> causes biliary pain.
small stones occluding the cystic duct entirely –> acute cholecystitis (inflammation of gallbladder)
small stones blocking the distal bile duct –> causes jaundice, biliary pain, risk of cholangitis and pancreatitis
What are Liver Function Tests? (LFTs)
What are the 3 enzymes we use?
What do elevated levels of each tell you?
they’re pretty imprecise.
you do biochemical and functional tests:
ALT + AST
(alanine aminotransferase and aspartate aminotransferase)
alkaline phosphatase
**elevated ALT/AST: primarily result of hepatocyte injury
**elevated alkaline phosphatase -> primarily result of bile duct injury; e.g. chosestasis
Why do we look at Albumin for liver function?
impairment to hepatocyte or liver, we’re going to see albumin decreased because it’s exclusively synthesized in the liver!
What is a PT (prothrombin time)?
what should we see with people with bad livers?
reflects the degree of hepatic synthetic function.
increases as the ability of a cirrhotic liver to synthesize clotting factors diminishes.
worsening coagulopathy correlates with the severity of hepatic dysfunction.
What are the relative amounts of the 4 bile acids?
Cholic acid > chemodeoxycholic acid > deoxycholic acid > Lithocholic acid
(so more primary than secondary)
Gallstones result in what kind of bilirubin?
high levels of conjugated!
