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Flashcards in GI Exam Lecture 5 Deck (26)
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1
Q

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

A

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:

  1. Metabolism
  2. Detoxification
  3. Excretion
2
Q

________ 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 _____

A

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

3
Q

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?

A

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

4
Q

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 ______

A

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

5
Q

Show the flow of blood within the zones of hepatocyte cords

Show the flow of bile

A
6
Q

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

A

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:

  1. to the gall bladder (via cystic duct)
  2. to the intestine (via common bile duct)
7
Q

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

A

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

8
Q

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:

  1. Phase 1 reactions:
  2. Phase 2 reactions:

The products are excreted in feces (as bile) or in urine

A

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

9
Q

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?

A

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

10
Q

Bile is synthesized and secreted by hepatocytes into bile cannaliculi

Major constituents of bile ?

A

Bile is synthesized and secreted by hepatocytes into bile canaliculi:

Major constituents of bile: bile salts

11
Q

Bile Acid Synthesis:

Hepatocytes snynthesize two primary bile acids:

1.

2.

Colonic bacterial enzymes act on these to yield secondary bile acids:

A

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

12
Q

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

A

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

13
Q

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

A

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

14
Q

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

A

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

15
Q

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

A

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

16
Q

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

A

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

17
Q

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

A

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

18
Q

Gallstones are precipitated bile constituents, can accumulate in gall bladder

Gall stones are composed of ____ and _____

Prolonged storage of bile increases change of nucleation

A

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

19
Q

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

A

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

20
Q

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)

A

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

21
Q

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

A

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

22
Q

Jaundice:

yellowness

Usually accompanied by pruritis (meaning?)

Jaundice happens with hyper____

A

Jaundice:

yellowness

usually accompanied by pruritis (itching of the skin)

Jaundice becomes clinically manifest due to hyperbilirubinemia

23
Q

How does ammonia get handled by the liver?

A

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

24
Q

Hepatic Encephalopathy:

  • coma and death can result
  • Patients with ______ disease result in hepatic encephalopathy
  • development of confusion, dementia, coma if left untreated
A

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
25
Q

Liver cirrhosis:

  • An irreversible destruction of liver anatomy
  • concequence of tissue degeneration
  • clinical signs arrive from dysfunctional _____
  • portal _____ and other clinical signs are always present
  • ____, ____, ___ are major causes of cirrhosis
A

Liver cirrhosis:

  • irreversible destruction of liver anatomy
  • clinical signs arise from dysfunctional hepatocytes
  • inflammation of liver cells causes PORTAL HYPERTENSION
  • drugs, alcohol, and posions are causes of cirrhosis
26
Q

Portal hypertension:
- concenquence of cirrhosis

  • what are two common progressions of portal hypertension:
    1. (dilated abdominal veins called ______)
    2. esophageal _____
A

Portal hypertension:

common progressions:

dilated abdominal veins: caput medusae

esophageal varices