LIVER Flashcards

1
Q

Describe the dual blood supply of the liver

A

Portal vein: 75% of blood, but oxygen-poor

Hepatic artery: 25% of blood, but oxygenated

Both drain into hepatic sinusoids

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2
Q

Peribiliary plexus

Where? Fxn?

A

Between the bile and blood within the portal tract

Provides the means for modifying biliary secretions through the bidirectional exchange of compounds (proteins, inorganic ions, bile acids)

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3
Q

The hepatocyte is a one-cell-thick epithelium lining the vascular sinusoids fed by the portal vein & hepatic artery

What feature of the hepatocytes allows it to alter composition of blood and bile?

A

Fenestrations permit passage of big molecules like albumin –> transport electrolytes across membranes to alter blood & bile

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4
Q

Kupffer cells

A

Phagocytes associated with the endothelium of sinusoids.

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5
Q

space of Disse

Where is it?

Fxn?

A

Between the hepatic cells and endothelium

  • Allows movement of molecules
  • Contains stellate cells:
    • Storage site for retinoids
    • Source of growth factors for hepatocytes
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6
Q

During abnormal conditions, ___ will produce excessive collagen –> liver dysfunction

A

Stellate/Ito cells: storage site for retinoids & source of growth factors for hepatocytes

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7
Q

The apical surface of the hepatocyte occupies a ___ fraction of the cell membrane.

The apical surfaces of adjacent cells oppose each other to form ___.

A

Apical membrane sof adjacent cells oppose each other to form a small fraction of the cell membrane.

Apical membranes of adjacent cells oppose each other to form a channel between cells called canaliculus, which drain bile into biliary ducts

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8
Q

Pathway of bile

A
  1. Hepatocyte
  2. Canaliculi
  3. Biliary ducts
  4. Bile ducts
  5. R & L hepatic ducts leave the liver
  6. Common hepatic duct
    1. Cystic duct -> gallbladder or
    2. Common bile duct & pancreatic duct-> duodenum
      1. Between meals, sphincter of Oddi can constrict to redirect bile to gallbladder.
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9
Q

Cholangiocytes

A

classical columnar cells that line biliary ducts and modify the composition of bile:

  • Take in glucose & aa
  • Cl-/HCO3- exchanger makes the bile alkaline
  • y-glutamyl transpeptidase (GGT) on its surface breaks glutathione into amino acids
  • Dilutes bile with apical membrane aquaporins
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10
Q

Bile composition

A

10 : 3 : 1

Bile acids : phosphatidyl choline: cholesterol

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11
Q

Canalicular bile

Hepatic bile

Gallbladder bile

Bile in the intestine

A
  • Canalicular bile: bile acids, phosphatidyl choline, and cholesterol secretion from hepatocytes drives water & electrolytes across the tight junctions
  • Hepatic bile includes modifications made as it flows through the biliary ductules
  • Gallbladder bile includes more modifications that occur in gallbladder
  • in the intestine, bile is a concentrated solu
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12
Q

Cholangiocytes

A

Columnar cells lining biliary ducts that modify bile:

  • Takes in glucose & aminoacids
  • HCO3-/Cl- exchanger sends out HCO3- into bile and takes in Cl-
  • y-glutamyl transpeptidase (GGT) breaks down glutathione on the surface into aa
  • Aquaporins dilute the bile
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13
Q

What impact does eating a meal have on cholangiocytes?

A

Secretin

  • > insert aquaporins on apical membrane, thus increasing flow
  • >increase HCO3- secretion, thus increasing bile alkalinity
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14
Q

Function of gallbladder

A

storage and concentration of bile

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15
Q

How does the gallbladder concentrate bile?

A

Isotonic reabsorption of NaCl** and Na_HCO3-_ b**y the leaky gallbladder epithelium leaves bile & bile components behind

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16
Q

Bile acid monomers that become avialable as a reuslt of concentration in the gallbaldder are immediately..

A

incorporated into micelles to prevent cholesterol precipitation

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17
Q

Describe the transporters involved in gallbladder concentration of bile

A
  • Tight junctions prevent bile acid anions from entering
  • Apical & basolateral aquaporins reabsorbs a lot of water
  • Na/H and HCO3-/Cl- exchangers reabsorb NaCl, so water follows
    • Driven by Na,K-ATPase
  • Na/H exchanger is faster, so there’s net secretion of H+ into the lumen –> acidic bile is more soluble
    • ​H+ in the bile then react with HCO3- –> CO2 and water –> CO2 diffuses out of the lumen and HCO3
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18
Q

How does the pH of bile change after gallbladder modifies it?

Why is this important?

A

Goes from slightly alkaline to slightly acidic

More soluble–> reduces risk of calcium precipitation or gallbladder stones

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19
Q

Name the changes in bile composition during gallbladder storage

A
  • Water removed
  • [HCO3-] & [Cl-] fall
  • [Na+] & [H+] increases
  • [Bile acid anions] increases
20
Q

Major functions of bile

A
  • Lipid digestion & absorption
    • Emulsifies dietary fat into droplets, thus increasing its surface area for lipases to breakdown.
    • Solubilizes lipids into micelles - aggregates of fatty acids, cholesterol, and monoglycerides
    • Transport & absorption of fat-soluble vitamins
  • Waste (e.g. bilirubin & excess cholesterol) elimination from blood
  • Inhibits of bacterial growth in small intestine
  • Neuralizes of gastric acid in small intestine
21
Q

Bile acid synthesis

A

Cholesterol metabolism forms bile acids.

First & rate-limiting step: 7a-hydroxylase

22
Q

What enzyme catalyzes the rate-limiting step of bile acid synthesis?

A

the first one: 7a-hydroxylase

23
Q

What results if, after cholesterol metabolism, th ebile acid is further hydroxylated?

A

Cholic acid

24
Q

How is bile acid synthesis regulated?

A

If bile acid levels are high in the blood flowing to the liver –> suppress hepatocytes’ bile acid synthesis

25
Q

Intracellular synthesis of cholesterol by ____ adds to the pool of free cholesterol in the cell that can then be stored as an ester; hydrolyzed to form bile acids; or exported as lipoproteins

A

HMG-CoA reductase

26
Q

Statins

A

Reduce cholesterol by inhibiting HMG-CoA reductase

27
Q

What property of bile acids allow them to act as detergents for lipid emulsification & digestion?

A

Amphipathic

Forms micelles that solubilize and transport fat-soluble substances; reduces surface tension & stabilizes emulsions

28
Q

Chenodeoxycholic & cholic acids are ___ bile acids because they are produced ____

A

Primary bile acids

Synthesized by the hepatocytes from cholesterol metabolism

29
Q

LIthocholic, deoxycholic, and ursodeoxycholic acids are ____ bile acids because they are produced ____

A

Secondary bile acids

Produced in the small intestine

30
Q

Secondary bile acids are conjugated with ___. Why?

A

Gly or Taurine

Depresses their pKa so they can be ionized in the small intestine

–> can’t traverse the cell membrane, so they’re reabsorbed by the intestine epithelial cells via the apical sodium-dependent bile transport

31
Q

Describe the two forms cholesterol can be excreted as

A

Native form (2/3 of excreted cholesterol)

Bile acids (1/3)

32
Q

If you interrupt eneterohepatic circulation of bile acids, what happens to your cholesterol?

A

Cholesterol falls because more cholesterol stays as bile acids –> bile acids are pooped out

(possible tx for hypercholesterol)

33
Q

__% of bile acids are synthesized by the SER of hepatocytes

___% of bile acids are recirculated by reabsorption from the intestinal epithelium and transported by the hepatocyte from the blood to bile canaliculi via enterohepatic circulation

A

10% of bile acids newly synthesized

90% recycled from intestinal epithelium

34
Q

What happens when bile salts are no longer needed (e.g. long after a meal)?

A

Bile salts reenter enterohepatic circulation

Other components of bile are largely lost in stool

35
Q

Neuro-humoral mechanism for regulating bile excretion from the gallbladder

A

Cholecystokinin

  • Contracts the smooth muscles of gallbladder & relaxes the sphincter of Oddi
  • Binds vagal afferents to stimulate intrinsic neural reflexes & vagal pathways that contract the gallbladder
36
Q

Mechanism of bilirubin formation

A
  1. Phagocytic cells of reticuloendothelial system (e.g. Kupffer cells & spleen cells) have heme oxygenase that frees iron from heme and produces biliverdin (green pigment)
  2. Biliverdin turned into yellow bilirubin
    1. Insoluble at neutral pH
  3. Yellow bilirubin goes through blood on albumin to liver’s space of Disse to be taken into the hepatocytes via basolateral OATP transport
  4. UDP glucuronyl transferase conjugates bilirubin with glucuronic to increase its solubility
37
Q

Why do newborns often have mild jaundice?

A

Haven’t synthesized enough UDP glucuronyltransferase (UGT) to increase bilirubin solubility

38
Q

What ensures that conjugated bilirubing gets excreted?

A

Conjugated bilirubin

  • can’t be reabsorbed from the intestine
  • doesn’t bind to albumin as strongly, so it also enters urine
39
Q

Where are bilirubin conjugates deconjugated?

What results?

A

Bacterial enzymes in colon deconjugate bilirubin

  • -> Urobilinogen, which is reabsorbed
    • -> May get taken up by hepatocytes and reconjugated to give it anotehr chance for excretion
  • -> Urobilins & stercobilins are excreted
40
Q

Two types of gallstones and factors that can cause it

A
  • Cholesterol gallstone disease
    • Old age, contraceptives, estrogen, sudden weight loss, genetic factors -> cholesterol hypersecretion
    • Interruption of enterohepatic circulation -> bile acid hyposecretion
  • Bilirubin gallstones
41
Q

Signs of progression in gallstone disease

A
  1. Biliary colic: Pain caused from spasm due to transient obstruction of the cystic duct by a gallstone; usually goes away after a few hrs
  2. Acute cholecystitis: obstruction of cystic duct inflames gallbladder
  3. Chronic cholecystitis: thickened/fibrotic gallbladder
  4. Stones or sludge obstruct other parts of the biliary tree (e.g. common bile duct) –> obstructive jaundice
42
Q

Cholecystitis vs Cholestasis

A

Cholecystitis: stone in cystic duct inflames the gallbladder

Cholestasis: more serious; stone in the common bile duct blocks bile flow from liver into the duodenum

43
Q

Jaundice

Symptom & cause

A

Yellow coloration of skin & eyes, dark urine

LIver continues producing bile even though bile flow is blocked –> dead blood cells or bilirubin backs up into the bloodstream

44
Q

Cholangitis

A

Inflammation of bile ducts outside the liver due to bacterial infection of stagnant bile.

Inflammation can spread to liver

45
Q

Biliary cirrhosis

A

Inflammation and obstruction of the bile ducts inside the liver. As the inflammation spreads to the rest of the liver, normal liver cells die and are replaced by fibrous scar tissue

46
Q

Pancreatitis

A

Inflammation of the pancreas when a stone blocks the pancreatic duct or the sphincter of Oddi. Not only is the flow of bile obstructed, pancreatic secretions into the duodenum containing digestive enzymes are also blocked.

–> autodigestion

Marker: high pancreatic lipase & amylase in plasma

47
Q

Tx of gallstone disease

A

Cholecystectomy