GI Exam Lecture 5 Flashcards
The liver receives portal blood from ____
The majority of the liver’s blood supply is _____ from the GI tract via the _____
Major functions of the liver are:
1.
2.
3
The liver receives portal blood from all the GI organs
The majority of the liver’s blood supply is venous blood from the GI tract via the portal vein
Major functions of the liver are:
- Metabolism
- Detoxification
- Excretion
________ are the major cell types in the liver
They are arranged in cords called ____
Liver receives high blood flow - ensures that cells receive high quantities of O2 and nutrients
Explain what sinusoids are and what supplies them
Blood drains from the liver to the central branches of the _____
Hepatocytes are major cell types in the liver
They are arranged in cords that form plates
Liver receives high blood flow to ensure that hepatocytes receive high quantities of both O2 and nutrients
The plates of hepatocytes are supplied by sinusoids, which are low resistance cavities supplied by branches of portal vein and hepatic artery
Blood drains from liver into central branches of the hepatic vein
Explain what the hepatic triad is
Then explain the following within the liver:
Zone 1
Zone 2
Zone 3
Which one is most effected by viruses? Which zone is most affected by ischemia?
Which cells are most active in bile synthesis?
Hepatic Triad: consists of branches of the hepatic artery, portal vein, and bile duct
Zone 1 or periportal cells: hepatocytes closest to triad - most sensitive to oxidative injury - have largest supply of nutrients and O2, most active in deoxification
Zone 2: between zones 1 and 3
Zone 3 or pericentral cells: closes to central branch of hepatic vein, most sensitive to ischemia - most active in bile synthesis
What is the origination point of the biliary formation?
Apical membranes of adjacent hepatocytes form a channel called a _____
These ____ drain bile from the liver and transport to the biliary ductules, these ductules are lined by columnar epithelial cells - the ______
Hepatocytes are the origination point of the biliary system
Apical membranes of adjacent hepatocytes forms a channel called a caniculus
These caniculi drain bile from liver and transport to the biliary ductules - these ductules are lined by columnar epithelial cells - the cholangiocytes
Show the flow of blood within the zones of hepatocyte cords
Show the flow of bile
Biliary ductals drain into large bile ducts - coalesce into right and left hepatic ducts
These then form the common hepatic duct
From the common hepatic duct bile can then flow either into:
1.
2
Biliary ductals drain into large bile ducts - coalesce into right and left hepatic ducts
These then form the common hepatic duct
From the common hepatic duct, bile can then flow either:
- to the gall bladder (via cystic duct)
- to the intestine (via common bile duct)
Metabolic Functions of the Liver:
Hepatocytes participate in major metabolism of which nutrient?
How does the liver create bile acids (from what molecule)?
Impaired liver function can cause _____ during meals and ______ in between meals
Metabolic Functions of the liver:
Hepatocytes participate in metabolism of major nutrients: carbs, lipids, and proteins
Carbs: liver plays a role in gluconeogenesis, also impaired liver function results in hyperglycemia during meals and hypoglycemia between meals
Lipids: liver enzymes participate in fatty acid oxidation
Liver converts significant portion of cholesterol into bile acids
Protein: liver makes all non-essential AA’s, also converts ammonia from proteins into urea
Detoxification Function of Liver:
Liver protects the body from toxic substances (endogenous or exogenous toxic molecules like drugs and bacterial toxins)
-The liver modifies these toxins via a “________ metabolism” so that little or none can enter circulation
This is achieved in two phases:
- Phase 1 reactions:
- Phase 2 reactions:
The products are excreted in feces (as bile) or in urine
Detoxification Function of Liver:
Liver protects the body from toxic substances
Liver modifiess them in “first pass metabolism” so little or none can enter systemic circulation
This is achieved in two phases:
- Phase 1: catalyzed by cytochrome P-450 enzymes, toxins are modified (oxidized, hydroxylation)
- Phase 2: conjugate these substances with extra things to make them water soluble
Products are excreted in feces (via bile) or in urine
Kidneys play important role in excretion of small water soluble catabolites
Large water soluble catabolites and molecules bound to plasma proteins cannot be excreted through kidney
So what does the liver do?
Kidneys play an important role in excretion of small water-soluble catabolites
Large water soluble catabolites and molecules bound to plasma proteins cannot be excreted through the kidney
Liver helps by excreting these in bile - ultimately excreted in feces
Bile is synthesized and secreted by hepatocytes into bile cannaliculi
Major constituents of bile ?
Bile is synthesized and secreted by hepatocytes into bile canaliculi:
Major constituents of bile: bile salts
Bile Acid Synthesis:
Hepatocytes snynthesize two primary bile acids:
1.
2.
Colonic bacterial enzymes act on these to yield secondary bile acids:
Hepatocytes synthesize two primary bile acids: cholic acid, and chenodeoxycholic acid
Colonic bacterial enzymes act on these to yield secondary bile acids: Urosodeoxy, Deoxycholic, lithocholic acid
In hepatocytes, both primary and secondary bile acids are conjugated with ____ or ____ - produces conjugated bile acids or bile salts which are more water soluble
The only exception to this rule is ______, which is preferentially sulfated in the hepatocyte rather than being conjugated
In hepatocytes, both primary and secondary bile acids are conjugated with glycine or taurine - produces conjugated bile salts or bile acids (more water soluble)
Only exception to this rule is lithocholic acid - which is preferentially sulfated in hepatocyte rather than being conjugated with glycine or taurine and excreted
Conjugated bile acids are fully ionized in intestinal lumen - _______ absorbed into the terminal ileum via ______ transporter
Some (that escape) are deconjugated by _______ - unconjugated forms are reabosorbed passively in colonic epithelium
Conjugated bile acids are fully ionized in intenstinal lumen - actively absorbed in terminal ileum via apical Na dependent bile salt transporter (asbt)
Some (that escape) are deconjugated by colonic bacterial enzymes - unconjugated forms are reabsorbed passively in colonic epithelium
Majority of bile acid pool is recycled from the intestine back into the liver - via __________
Conjugated bile acids are unable to passively cross the intestinal epithelial lining
When chyme reaches the _______ and lipid absorption is completed, conjugated bile acids are reabsorbed by a symptorter known as ______
A minor fraction of bile acids
Majority of bile acid pool is recycled from the intestine back into the liver via enterohepatic circulation
Conjugated bile acids are unable to passively cross the intestinal epithelial linings
When chyme reaches the terminal ileum, and lipid absorption is completed, conjugated bile acids are reabsorbed by a symporter known as apical Na dependent bile acid transporter
A minor fraction of bile acids enters the colon - become decongugated and is reabsorbed passively
Role of the Gallbladder:
Bile is stored in the _____
In between meals, outflow of bile is blocked by the sphincter of ____
In the gall bladder, bile becomes more concentrated
Mechanisms not clear but there is a ____ exchanger and it plays some role
____ is absorbed which also brings water which can result in concentrated bile salt
Bile is stored in the gallbladder
In between meals, outflow of bile is blocked by the sphincter of Oddi
In the gall bladder, bile becomes more concentrated
Mechanism is not known, but there is a Na-H exchanger which plays some role
Sodium is absorped which also brings water which can result in concentrated bile salt
Normally, conjugated bile acids are reabsorbed in the _____
When there is a _____ resection, you get bile salt diarrhea
Bile acids pass into colon, irritating colon and net water secretion by colon
Normally, conjugated bile acids are reabsorbed in the ileum (due to symporter apical Na dependent bile acid transporter)
Where there is a ileal resection, you get bile salt diarrhea
Ejection of bile from gall bladder begins within 30 minutes of meal ingestion
Major stimulus for bile secretion is ____
causes contraction of gallbladder and relaxation of sphincter of Oddi
Other internal neural reflexes and vagal pathways are also involved
Ejection of bile from gall bladder begins within 30 minutes of meal ingestion
Major stimulus for bile secretion is CCK
causes contraction of gallbladder and relaxation of spchinter of Oddi
Gallstones are precipitated bile constituents, can accumulate in gall bladder
Gall stones are composed of ____ and _____
Prolonged storage of bile increases change of nucleation
Gallstones are precipitated bile contituents, accumulate in gall bladder or elsewhere in bile tree
Gall stones are composed of cholesteroal of Ca2+ bilirubinate
Prolonged storage of bile increases change of nucleation
Formation of Bilirubin:
Heme degradation in the RES - first forms pigment biliverdin (green) - this is then converted into ____ (yellow) which is insoluble in aquoeous soliution at neutral pH
It then binds to ______ (increases solubility) transported via bloodstream to liver, then taken up by hepatocytes via ________
In hepatic microsomes, bilirubin is gonjugated with _____ acid by the enzyme _____
Some newborns develop jaundice because the enzyme is synthesized slowly after birth
Heme degradation in the RES - first forms green pigment biliverdin - this is then converted to bilirubin (yellow) which is insoluble
Bilirubin then binds to albumin (increases its solubility) transported in blood stream to liver - taken up into hepatocytes by OATP transporter
In hepatic microsomes, bilirubin is conjugated with glucoronic acid by UGT enzyme
some newborns develop jaundice because UGT is synthesized slowly after birth
Conjugated bilirubin is water soluble - portion of it is excreted in urine. The remaining is secreted in ___
In the terminal ileum and colon, it is deconjugated by bacterial enzymes and metabolized to ___
A portion of it is absorbed back to liver via enterohepatic circulation
Remainder is converted to _____ and ____ (brown pigment) and excreted in feces
Bilirubin can cross BBB (fatal if not excreted)
Conjugated bilirubin is water soluble - portion of it is excreted in urine. Remainder of it is secreted in bile and travels to the small intestine.
In terminal ileum and colon, it is deconjugated by bacterial enzymes and metabolized to urobilinogen
A portion of that is absorbed via enterohepatic circulation
The remainder is converted to urobilin and stercobilin (brown pigment) excreted in feces
Bilirubin can cross BBB
Increase of conjugated bilirubin in plasma suggests:
- loss or absence of ____
- sudden oversupply of ____ (blood transfusion)
- liver failure
In high conjugated biliruben, there is high biliruben in urine (dark color) due to defect in transporter or blockage of bile flow
Increase of conjugated bilirubin in plasma reflects:
- loss or absence of UGT
- sudden oversupply of heme
- liver failure
Conjugated bilirubenemia: high bilirubin in urine (dark color) due to defect in transported that secretes conjugated bilirubin into bile, or blockage of bile flow
Jaundice:
yellowness
Usually accompanied by pruritis (meaning?)
Jaundice happens with hyper____
Jaundice:
yellowness
usually accompanied by pruritis (itching of the skin)
Jaundice becomes clinically manifest due to hyperbilirubinemia
How does ammonia get handled by the liver?
Ammonia (NH3) is very toxic
can cross BBB
Nh3 is product of protein breakdown
liver handles it in urea cycle, becomes NH4+ and gets excreted in stool
Hepatic Encephalopathy:
- coma and death can result
- Patients with ______ disease result in hepatic encephalopathy
- development of confusion, dementia, coma if left untreated
Hepatic Encephalopathy:
- coma and death can result
- patients with chronic liver disease may have gradual decline of mental function (NH3 and bilirubin cross BBB cause issues) resulting in hepatic encephalopathy
- development of confusion, dementia, and coma indicates significant disease progression
