54-55 Liver Flashcards

1
Q

The majority of the liver’s blood supply comes from the _____________, and the rest comes from the _____________ (a branch of the _____________).

A
  • Portal v.

- Hepatic a. (branch of the celiac a.)

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2
Q

What are the 3 major, general functions of the liver?

A
  1. Metabolism
  2. Detoxification
  3. Excretion
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3
Q

What is the major cell type of the liver?

A

Hepatocytes

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4
Q

Generally, how are hepatocytes arranged amongst themselves?

A

They are arranged in anastomosing cords that form plates.

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5
Q

By what small vessel do plates of hepatocytes receive blood?

Is this low or high resistance?

A

Sinusoids (smaller branches of portal v. and hepatic a.)

- Low resistance

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6
Q

What vessel drains blood out of the liver?

A

Central v. (of hepatic v.)

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7
Q

What 3 vessels are part of the hepatic triad?

A
  • Hepatic a.
  • Portal v.
  • Bile duct
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8
Q

*Explain where the cells of the 3 functional “zones” of a liver lobule are.

A
  • Zone 1: hepatocytes closest to triad (therefore have largest supply of nutrients and O2)
  • Zone 2 - intermediate between zones 1 and 3.
  • Zone 3: closest to the hepatic/central vein
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9
Q
  • What’s another name for zone 1 cells?

- What’s another name for zone 3 cells?

A
  • Periportal cells (near the portal v.)

- Pericentral cells (near the central v.)

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10
Q
  • Which of the 3 zone’s cells are most susceptible to oxidative injury?
  • Which are most active in detox?
  • Which are most active in bile synthesis?
  • Which are most sensitive to ischemia?
A
  • Zone 1 cells
  • Zone 1 cells
  • Zone 3 cells
  • Zone 3 cells
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11
Q

What can happen to the 3 hepatic cell zones during liver dz?

A

Cells in zones 2 and 3 can function as zone 1 cells (blood backed up, spills out?)

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12
Q

Which hepatic cell type is the origination point of the biliary system?

A

Hepatocytes

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13
Q

Where are bile canaliculi formed w/r/t hepatocytes?

What larger vessel does the formed bile drain into?

A

B/w the hepatocytes

- Bile goes from canaliculi to biliary ductules

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14
Q
What's the name of the cells that line the biliary ductules?
*What class of epithelial cells are they?
A

Cholangiocytes

- Simple columnar epithelial cells

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15
Q

In a liver lobule, hepatocytes closest to the bile duct are farthest from the _______________.

A

Central v.

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16
Q

In what duct can bile flow bidirectionally?

What is the name of the bile duct coming from the liver before and after this duct branches off of it?

A

Cystic duct (to GB)

  • Before: common hepatic duct
  • After: CBD
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17
Q

Name all of the ducts that bile flows from, starting at the hepatocyte.

A
  1. Bile canaliculi (b/w cells)
  2. Biliary ductules
  3. Bile ducts
  4. R + L hepatic ducts
  5. Common hepatic duct
    (5. 5- Cystic duct)
  6. CBD
    (6. 5 Common pancreatic duct comes in before Sphincter of Oddi)
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18
Q

Which of the following do hepatocytes participate in the metabolism of?
Carbs, ptns, lipids

A

All 3

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19
Q

*What 2 major processes does the liver play a part in w/r/t carbohydrate homeostasis?

A
  1. GNG (conversion of other sugars to glc)

2. Glucose buffer fcn (stores glycogen)

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20
Q

How would blood sugar levels before and after meals be altered w/impaired liver function?

A

Hyperglycemia during/after meals and hypoglycemia between meals.

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21
Q

*What 3 major processes does the liver play a part in w/r/t lipid homeostasis?

A
  1. Hepatocytes are a rich store of enzymes for FA oxidation (contributes to energy generation)
  2. Convert products of carb metabolism into lipids: synthesis of lipoproteins, cholesterol and phospholipids.
  3. Convert cholesterol to bile acids.
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22
Q

*What 3 major processes does the liver play a part in w/r/t protein homeostasis?

A
  1. Synthesizes all of the non-essential AAs; also modifies AAs so they can enter pws for carb synthesis.
  2. Synthesizes almost all plasma ptns, including albumin (determines plasma oncotic pressure) and the clotting factors.
  3. Converts ammonia to urea (excreted in urine)
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23
Q

How could liver failure lead to problems w/blood oncotic pressure?
Major symptom?

A
  • Hypoalbuminemia (can’t make enough)

- Sx: Peripheral edema due to low plasma oncotic P (lack of clotting factors as well)

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24
Q

What general types of materials does the liver detox?

How many times do they pass thru the blood before being detoxed?

A
  • Endogenous or exogenous toxic molecules (including pharmaceutical drugs); bacterial toxins
  • Modifies them in “first pass metabolism” so little/none can enter systemic circulation
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25
Q

Describe the phases of “first-pass metabolism” during detoxification.
(what types of enzymes catalyze phase I rxns?)

A

1) Phase I reactions – oxidation, hydroxylation etc. – catalyzed by cytochrome P-450 enzymes.
2) Phase II reactions – conjugate the substances with glucuronide, sulfate, amino acids or glutathione.

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26
Q

What happens to the products of “first pass metabolism” after they’re processed (for detox)?

A

The products are excreted in feces (via bile) or in urine (via kidney).

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27
Q

*Are water-soluble catabolites excreted in the feces or the urine? What is the exception?

A

Urine, unless they are large, in which case they are excreted in the feces via bile.

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28
Q

Describe the overall chemical makeup of bile.

A

1) Bile acids - 65%
2) Phospholipids (mainly lecithins - phosphatidylcholine) - 20%
3) Electrolytes (similar and isotonic to plasma) 5-6%
4) Proteins - 5%
5) Cholesterol - 4%
6) Bile pigments (bilirubin for example) - 0.3%

29
Q

What are the 2 primary bile acids first synthesized in hepatocytes?

A
  • Cholic acid
  • Chenodeoxycholic acid
    (“C” are primary, non-C are not)
30
Q

How are secondary bile acids created?
Where?
Name the 3.

A

Bacterial enzymes act on primary bile acids in the colon to yield secondary bile acids

  • Ursodeoxycholic acid
  • Deoxycholic acid
  • Lithocholic acid
31
Q

*How, specifically, are primary/secondary bile acids altered to become more water soluble?
Where?
What are the bile acids then called?

A

Conjugated with glycine or taurine to produce conjugated bile acids

  • Liver
  • AKA bile salts
32
Q

Recall: where are conjugated bile acids recycled/reabsorbed in the GI tract (via enterohepatic circulation)?
What protein allows for this?

A
  • Terminal ileum

- Apical Na+ -dependent bile salt transporter (asbt)

33
Q

*What happens to the bile salts that escape the asbt’s of the terminal ileum?

A

Most are deconjugated by bacterial enzymes and passively reabsorbed in the colon.

34
Q

What cells modify the bile?

A

Cholangiocytes

35
Q

How do cholangiocytes modify the acidity or basicity of the bile? (name the xporter also)

A

Make it more basic via (Cl-/HCO3- antiporter)

36
Q

What substances are reclaimed by cholangiocytes when they act on the bile?

A

AAs, glucose, glutathione (broken down first)

37
Q

*What major hormone is stimulating cholangiocyte action/bile production, and what is the result of this stimulation?

A
  • Secretin: stimulate aquaporin channel formation, thus diluting the bile
    (In response to H+ in duodenum)
38
Q

B/w meals, constriction of what sphincter blocks outflow of bile?

A

Sphincter of Oddi

39
Q

Choliangiocytes of the liver dilute the bile. Is bile concentration changed during its storage in the GB?

A

Yes- concentrated

40
Q

Although the mech is unclear, explain how bile is concentrated in the GB.

A

There is Na+/H- exchanger which plays some role.

- Sodium is absorbed (out), water follows, which can concentrate the bile salt

41
Q

Ejection of bile from gall bladder begins within ______ minutes of meal ingestion.

A

30

42
Q

*The major stimulus for bile secretion is __________.

What is stimulated/relaxed for bile to be secreted?

A
  • CCK (but other neural pw’s also involved)

- Causes contraction of GB, relaxation of sphincter of Oddi

43
Q

Where can gallstones be found?
Why are they bad?
Major sx?

A
  • GB or anywhere in biliary tree )=
  • They obstruct biliary flow, can lead to biliary injury
  • Sx: pain, poor tolerance of fatty food
44
Q

What are gallstones composed of, predominantly? (2 types of stones)

A
  1. Cholesterol

2. Ca2+ bilirubinate (pigment)

45
Q

Why could fasting possibly lead to stone formation?

A

Prolonged storage of bile increases the chance of nucleation

46
Q

What are some major causes of cholesterol/mixed stones?

What are some major causes of pigment stones?

A
  • Dietary cholesterol, obesity, oral contraceptives, DM

- Hemolytic anemias, parasitic infections

47
Q

If a gallstone was lodged deeper in the CBD, what other organ could be affected?

A
  • Pancreas (pancreatitis)
48
Q

If there was a rupture of the GB or part of the biliary tree due to cholelithiasis, what condition of the abdominal cavity could this precipitate?

A

Peritonitits

49
Q

*Heme (RBC) degradation, which occurs in the reticuloendothelial system (RES), first forming is a pigment called ____________ (what color?).
This is then converted to _____________ (what color?).

A
  • Biliverdin (green)

- Bilirubin (yellow)

50
Q

*Bilirubin (yellow) is insoluble in aqueous solution at neutral pH, but it needs to enter the blood. To enter the blood, bilirubin leaves the RES and binds to ______________ in the blood (increases solubility in aqueous solution).
Where is this complex then transported to? (think)

A

Albumin

- Liver

51
Q

*When the bilirubin-albumin complex reaches the liver, what protein helps the liver take it up, and to what cells of the liver?

A

The albumin-bilirubin is taken up by hepatocytes via an an organic anion-transporting polypeptide (OATP) transporter.

52
Q

*Once in hepatocytes (hepatic microsomes), what happens to the bilirubin?
What enzyme + substrates are involved?

A

It is conjugated with glucoronic acid by enzyme UDP glucuronyl transferase.

53
Q

*After UDP glucuronyl transferase conjugates the bilirubin, what are its 2 fates?

A
  1. Can be exreted in urine (it’s water soluble)

2. The remaining is secreted in bile – travels to small intestine.

54
Q

*What happens to the conjugated bilirubin that was not excreted in the urine and traveled w/bile to the small intestine? (where?)
(if it does not enter enterohepatic circulation)

A

In terminal ileum and colon, it is deconjugated by bacterial enzymes – metabolized to urobilinogen.

55
Q

*What 2 fates happens to the urobilinogen at the terminal ileum/colon?

A
  1. A portion of urobilinogen is absorbed via enterohepatic circulation (to liver).
  2. The remainder is converted to urobilin and stercobilin –excreted in feces.
56
Q

Can bilirubin cross the BBB?

A

Yes- can be fatal

57
Q

*Increase of unconjugated bilirubin in plasma reflects:

A
  • Loss or absence of UGT

- Sudden oversupply of heme (e.g. in transfusion reactions)

58
Q

*In conjugated bilirubinemia there is high bilirubin in urine (dark color) due to:

A
  • Defect in the transporter that secretes conjugated bilirubin in bile
  • Blockage of bile flow – gallstone.
59
Q

What are the signs/sx of jaundice?

A

Yellowness of skin, scleras and mucous membranes

- Usually accompanied by pruritus

60
Q

What are the causes of jaundice?

A
  • Accumulation of free and conjugated bilirubin in the blood.
  • Pruritis caused by increased levels of bile acids in serum leading to skin deposits
61
Q

What levels of total plasma bilirubin must be exceeded for jaundice to occur?
What is the specific name of this condition?

A

Total plasma bilirubin is >2 mg/dl (> 34 µM) = hyperbilirubinemia.

62
Q

Discuss (up to 7) causes of hyperbilirubinemia. (*good for test)

A
  1. Excess production of bilirubin (e.g. hemolytic anemia)
  2. Decreased uptake of bilirubin into hepatic cells (e.g. OATP problem)
  3. Disturbed intracellular protein binding and conjugation
  4. Disturbed secretion of conjugated bilirubin into bile canaliculi
  5. Intrahepatic and extrahepatic bile duct obstruction
  6. Pre-surgery use of potent antibiotics (lack of bacteria to deconjugate)
  7. Newborns (lack of UDP glucuronyl transferase).
63
Q

Discuss hepatic encephalopathy.
General definition?
What types of issues/sx result?

A

General definition: the loss of brain function when a damaged liver doesn’t remove toxins from the blood.

  • Coma and death can result - if metabolic activity of liver is compromised acutely.
  • Patients with chronic liver dz may have a gradual decline of mental function because ammonia and other toxins not cleared by liver
  • SX: confusion, dementia and coma – indicates significant disease progression – can be fatal if left untreated.
64
Q
Discuss liver cirrhosis.
General definition?
What's it a consequence of?
What's a major clinical sign?
What are the major causes?
A

General definition: An irreversible destruction of the functional anatomy of the liver

  • It is a consequence of hepatic injury, fibrosis and tissue degeneration.
  • The clinical signs derive from dysfunctional hepatocytes. Portal hypertension and other clinical signs are always present.
  • Drugs (alcohol), poisons, and hepatitis are the major causes
65
Q

Discuss portal HTN.
What causes it?
What vessels are involved?
*What does it result in? (signs)

A
  • Caused by increased vascular resistance in the liver. Increased BP in the sinusoids reflects back to the portal v. (portal v. does not have valves) and other vascular beds.
  • *Results in enlargement of the spleen (splenomegaly), ascites, esophageal varices, dilated abd vv. (caput medusae), spider nevi, hemorrhoids, and other complications.
66
Q

Define esophageal varices.

What are they a consequence of?

A

Extremely dilated sub-mucosal veins in the esophagus.
- They are most often a consequence of portal HTN, commonly due to cirrhosis; patients with esophageal varices have a strong tendency to develop bleeding.

67
Q

What’s spider naevus?

A

A condition in which minor thin walled blood vessels are visible under the skin. (also consequence of portal HTN)

68
Q

What are the 2 general ways by which NH3 is produced in the GI system?

A
  1. Protein catabolism

2. Colonic bacteria

69
Q

When NH3 is made (via ptn catabolism or bacteria) in the GI system, what are the 2 routes the ammonia can take?

A
  1. Can enter the urea cycle and be excreted in the urine

2. Becomes NH4+ in acidic lumen and excreted in stool