Hepatobiliary Flashcards

1
Q

What is the only plasma protein that is not formed by the liver?

A

gamma globulin

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2
Q

How is heme coverted into bilirubin?

A

Heme → biliverdin (in the mononuclear cells by heme oxygenase) → unconjugated bilirubin (lipophilic; by biliverdin reductase) → conjugated bilirubin (water soluble; via glucuronidation)

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3
Q

What are the two hormones that can activate phosphorylase and facilitate glycogenolysis?

A

Epinephrine
Glucagon

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4
Q

How many ATPs are produced during glycolysis, Krebs cycle and oxidative phosphorylation?

A

Glycolysis: 2
Krebs cycle: 2
Oxidative phosphorylation: 34

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5
Q

True or False: ATP provides negative feedback to inhibit the glycolysis.

A

True

ATP inhibit phosphofructokinase, which is the rate limiting enzyme

It covert

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6
Q

What does phosphofructokinase do?

A

It converts fructose-6-phosphate to fructose-1,6-bisphosphate.

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7
Q

True or False: Citrate ions from citric acid cycle provides negative feedback to inhibit the glycolysis.

A

True

Inhibit phosphofructokinase

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8
Q

Besides glycolysis, what is the pathway that is responsible for up to 30% of glucose breakdown in the liver and adipose tissue?

A

Pentose phosphate pathway

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9
Q

What are the three main types of lipids in the body?

A

Triglyceride (contains fatty acid)
Phospholipids (contains fatty acid)
Cholesterol (do not contain fatty acid)

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10
Q

How does body utilize fatty acid as source of energy?

A

fatty acids are converted to acetyl-CoA via 𝜷-oxidation → acetyl-CoA enters Krebs cycle → 22 ATP

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11
Q

List 3 hormones that facilitate lipolysis.

A

Thyroid hormone
Epinephrine
Cortisol

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12
Q

What is the normal ratio of body tissue protein and plasma protein?

A

33:1

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13
Q

For the liver bloody & oxygen supply, how many percentage are from the portal vein and how many percentage are from the hepatic artery?

A

Blood: 80% from portal vein, 20% from hepatic artery
Oxygen: 50% from portal vein, 50% from hepatic artery

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14
Q

What are the amino acid participating in the urea cycle?

A

Aspartate
Ornithine
Arginine
* Citrulline

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15
Q

What are the two hormones that facilitate protein synthesis? Which hormone facilitates protein breakdown?

A

Protein synthesis: insulin, growth hormone
Protein breakdown: glucocorticoid

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16
Q

What is the function of space of Disse?

A

allow excessive fluid from the liver sinusoid enter and drained from the lymphatic system

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17
Q

How many liver lobes are in dogs?

A

Four lobes with four sublobes and 2 processes

Right lateral, Right medial, Left lateral, Left medial, caudate, quadrate

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18
Q

What is the main difference in the bile duct anatomy in dogs and cats?

A

Dogs:
- Common bile duct enters the duodenum at the major duodenal papilla adjacent to the pancreatic duct (not conjoined)
- The accessory pancreatic duct (which is the main pancreatic enzymes secretion site) enters the duodenum a the minor duodenal papilla

Cats:
- The common bile duct and the pancreatic duct conjoin before enter the duodenum at the major duodenal papilla
- Only approximately 20% of cats have a smaller, accessory pancreatic duct that exits at a minor duodenal papilla

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19
Q

List 5 substances that is in the bile.

A

1) Bile acid
2) Cholesterol
3) Bilirubin
4) Phospholipids
5) Water
6) Bicarbonate

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20
Q

How many percentage of the liver removal can dogs tolerate?

A

70%
* The main issue is the liver being unable to accommodate the portal vein blood flow and develop portal hypertension

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21
Q

How soon does liver regeneration start and when is the peak?

A

starts within hours
Peak at 3 days

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22
Q

Which liver lobe is most likely to develop liver lobe torsion?

A

Left lateral

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23
Q

What are the two common concurrent endocrine disease with gallbladder mucocele?

A

Hyperadrenocorticism
Hypothyroidism

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24
Q

Explain the enterohepatic circulation of bile acid.

A

Cholesterol enters the liver → breaks down to unconjugated primary bile acid → conjugates with glycine, taurine → conjugated bile acid and enters the gall bladder → enters the intestines at the level of duodenum → being actively absorbed at ileum (90%) / the rest 10% becomes unconjugated by bac and enters the colon → the reabsorbed (95%) conjugated and unconjugated bile acids are efficiently extracted by hepatocyte transporters → only 5% remains in the systemic circulation for us to measure.

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25
Q

What is the reason of doing pre- and post-prandial bile acid test?

A

Providing food is a challenge to see if the liver can handle extra bile acid after the bile acid is secreted into the GI tract.

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26
Q

How do you interpret the bile acid test.

A

Bile acid concentrations >25-30 μmol/L in dogs and > 25 μmol/L in cats are suggestive of hepatobiliary disease.

  • whether pre- or post- is higher doesn’t really matter

Eclinpath

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27
Q

What are the three differential for abnormally high bile acid test?

A

Hepatic dysfunction
Hepatic vascular anomaly
Bile duct obstruction

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28
Q

What are the surgical options for PSS?

A
  • Suture ligation
  • Gradual attenuation with ameroid constrictors
  • Gradual attenuation with cellophan bands
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29
Q

What is normal portal vein pressure?

A

6-10 mmHg

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30
Q

What are the clinical signs to observe after PSS surgery for portal hypertension?

A

Hypovolemic shock
Vomiting, diarrhea
Abdominal pain
Distended abdomen with effusion

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31
Q

What are the two common causes for hepatic encephalopathy in dogs and cats, respectively?

A

Dog: CPSS, formation of acquired portosystemic collateral vessels (APSC) due to portal hypertension

Cat: CPSS, arginine deficiency due to hepatic lipidosis

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32
Q

What is the classification of HE?

A

Type A: due to acute hepatic failure
Type B: due to portal systemic bypass (e.g. CPSS) with normal hepatic function
Type C: due to cirrhosis, PH or acquired portal systemic shunting
- Episodic, persistent, minimal

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33
Q

What is the important enzyme to covert glutamine to ammonia and glutamate?

A

glutaminase (high level in enterocytes)

34
Q

What are the two metabolic pathways for ammonia in the liver? what cells are responsible for that? what are their affinity and capacity?

A

1) Urea cycle, periportal hepatocytes, low affinity but high capacity
2) Glutamine synthesis, perivenous hepatocytes, high affinity but low capacity

35
Q

What composes the portal triad?

A

Portal vein
Hepatic artery
Bile duct

36
Q

which hepatic zone does acetaminophen most likely to cause injury?

A

zone 3

37
Q

Which hepatic zone does gluconeogenesis happen? What about glycolysis?

A

Gluconeogenesis: zone 1
Glycolysis: zone 3

38
Q

In a patient with liver disease, does the skeletal muscle help decrease ammonia level or elevate ammonia level?

A

Help to decrease ammonia level (contains glutamine synthase)

39
Q

In the cerebrum, what is the interaction between astrocytes and ammonia?

A

Astrocytes have high level of glutamine synthase → metabolize ammonia → astrocyte swelling (?)

40
Q

What are the 6 proposed pathogenesis of hepatic encephalopathy?

A

1) Ammonia
2) Inflammation or infection
3) Oxidative stress
4) Amino acid imbalance
5) Neurosteroids
6) Maganese

41
Q

True or False: Synthesis of NS is regulated by the peripheral type benzodiazepine receptor (PTBR).

???

A

True

42
Q

List 5 rationales of using lactulose in treating hepatic encephalopathy.

A

1) Decrease colonic pH → trapping ammonium ions in the colon → decrease intestinal absorption
2) inhibit ammonia production by the colonic bacteria
3) Reduce intestinal transit time → decreased bacterial ammonia release
4) Stimulate the incorporation of ammonia with bacterial proteins
5) Increase fecal excretion of nitrogen compounds

43
Q

True or False: In the pathogenesis of hepatic encephalopathy, deranged GABAnergic neurotransmission plays a role.

A

True

44
Q

What kind of amino acid imbalance is found to be associated with HE?

A

Increased aromatic amino acids and decreased branched-chain amino acids

45
Q

List 10 possible precipitating factors for HE in dogs and cats?

A

1) High protein meal
2) GI bleeding
3) Arginine deficiency in cats
4) Hypokalemia
5) Alkalosis
6) Azotemia
7) Sedation uses
8) Blood transfusion
9) SIRS
10) diuretic administration

46
Q

True or False: In HE patients, strict protein-restricted diet is recommended.

A

False

47
Q

What is the neomycin dose for HE?

A

20 mg/kg PO q8h

48
Q

In dogs and cats, what are the two main types of cholecystitis?

A

Neutrophilic cholecystitis
Lymphoplasmacytic follicular cholecystitis

49
Q

What are the three types of necrotizing cholecystitis?

A

Type I: areas of necrosis without gallbladder rupture
Type II: acute inflammation with rupture
Type III: chronic inflammation with adhesions and/or fistulae to adjacent organs

50
Q

How do you diagnosed bile peritonitis?

A

effusion bilirubin concentration > 2x serum bilirubin

51
Q

what are the dogs and cats choleliths mainly composed of?

A

Calcium carbonate
Bilirubin pigments (bilirubin or calcium bilirubinate)

52
Q

What is the function of SAMe?

A

It is a glutathione precursor and antioxidant

53
Q

Why is gall bladder mucocele a surgical disease.

A

The cause of gallbladder mucocele is thought to be a combination of increased mucin production & decrease GB motility. On histopathology exam, cystic mucinous hyperplasia is often found. If we just treat medically, mucocele can recur.

54
Q

True or False: TNF-𝜶 stimulates hepatocyte apoptosis through the Fas-Fas ligand pathway.

A

True

55
Q

List 10 hepatotoxin.

A

1) Carprofen
2) Acetaminophen
3) Xylitol
4) Alfatoxin
5) Sago palm
6) Phenobarbital
7) Aspirin
8) Amiodarone
9) Azole antifungals
10) Diazepam (oral)
11) Methimazole
12) Tetracycline
13) Blue-green algae

56
Q

What the treatment difference in feline neutrophilic cholecystitis and lymphoplasmacytic cholecystitis?

A

Neutrophilic cholecystitis: broad-spectrum antibiotic while pending culture
Lymphoplasmacytic cholecystitis: immunosuppressive glucocorticoid therapy

57
Q

What is the main way for the body to maintain copper homeostasis?

A

Biliary excretion (→ any cause of cholestasis would be expected to increase hepatic copper level)

58
Q

Describe the pathophysiology of hepatorenal syndrome.

A

Hepatorenal syndrome is a condition in which there is progressive kidney failure that occurs in a person with cirrhosis of the liver.

59
Q

How much of the liver function loss can cause HE?

A

> 70%

60
Q

What is the proposed pathophysiology of HE related seizure and coma/CNS depression?

A

Seizure: Excessive glutamate activates NMDA receptors

Coma/CNS depression: Activations of GABA receptors and increased endogenous BZDs

61
Q

List 10 toxin implicated in hepatic encephalopathy.

A

1) Ammonia - Increased brain tryptophan and glutamine
2) Endogenous benzodiazepam
3) Aromatic fatty acid - Decreased DOPA neurotransmitter synthesis
4) Maganeses
5) Tryptophan - direct neurotoxicity
6) Glutamine - Alters BBB amino acid transport
7) Bile acids
8) GABA
9) Short chain fatty acids (SCFA)
10) Decreased alpha-ketoglutaramate

62
Q

What are the two proposed mechanism of PU/PD in acute liver injury/failure?

A

1) Decrease urea production → unable to establish the concentration gradient in renal medulla
2) Decrease responsiveness to ADH

63
Q

What is the half life of albumin in dogs and cats?

A

8 days

64
Q

What is half-life of ALT in dogs and cats?

A

Dogs: ~60 hours
Cats: < 24 hours

65
Q

True or False: Dog can synthesize conjugated bilirubin in their renal tubule.

A

True

66
Q

What is the protein restriction for dogs and cats with liver failure?

A

Dog: 18-22%
Cat: 30-35%

67
Q

What is the MOA of ursodial

A

1) Cytoprotective effect: protect hepatocytes and cholangiocytes from bile acid-induced damage
2) Shift the concentration of bile acids from hydrophobicity to hydrophilicity (less toxic)
3) Induce the secretion of bile acids
4) Immunomodulating effect on hepatocytes

68
Q

What are the 4 most common PSS post-OP complications?

A

Hemorrhage
Hypoglycemia
Seizure
Portal hypertension

69
Q

What change of the portal pressure is considered safe during PSS attenuation ?

A

< no greater than 10 cm of H2O

70
Q

True or False: Carprofen induced liver toxicity is dose-dependent.

A

False

It’s idiosyncratic

71
Q

What is the characteristic of hepatic lipidosis?

A
  • Accumulation of triglycerides in more than 80% of the hepatocytes**
  • Intrahepatic cholestasis
  • Secondary impairment of hepatic functions

** IM text book said > 50%

72
Q

Describe the proposed pathophysiology of hepatic lipidosis in cats.

A

Anorexia/Fasting & Stress → Negative energy balance → lipolysis → overwhelmed fatty acid oxidation → excessive fatty acids cumulate in the hepatocytes in the form of triglycerides (by esterification)

73
Q

True or False: Insulin resistance is the major inciting factors for the development of feline hepatic lipidosis.

A

False

74
Q

What are the three common electrolytes imbalances that are commonly seen in feline hepatic lipidosis?

A

Hypokalemia (poor prognostic indicator)
Hypomagenesemia
Hypophosphatemia

75
Q

What is the recommended diet management for feline hepatic lipidosis?

A

High protein, low carb diet

Protein (30-40% of the metabolized energy)
Fat (50% of the metabolized energy)
Carbohydrate (20% of the metabolized energy)

76
Q

What is kernicterus?

A

Bilirubin encephalopathy (bilirubin > 20 mg/dL; mainly unconjugated)

77
Q

What are the areas of the brain that is affected in kernicterus?

A

Caudate nucleus
Globus pallidus
Thalamus
Deep cerebellar nuclei
Cortical gray matter

78
Q

What are the primary functions in hepatic zone 1 and hepatic zone 3, respectively?

A

Zone 1: glucuronidation, 𝜷- hydroxylation, urea synthesis

Zone 3: lypolysis, glycolysis, gluconeogenesis, xenobiotic metabolism

79
Q

Which hepatic zone has highest concentration of cytochrome p450?

A

Zone 3

which metabolizes xenobiotic chemicals and performs functions such as lipogenesis, glycolysis, bile acid synthesis and glutamine synthesis

80
Q

Which hepatic zone has most hepatic progenitor cells and damage to this zone can affect liver’s regeneration?

A

Zone 1

81
Q

True or False: Acute liver injury cause hypophosphatemia.

A

True

82
Q

What is hepatic metabolism phase1 and phase2?

A

Phase 1: cytochrome P450
- Oxidation, hydrolysis, reduction, dehalogenation
Phase 2: conjugation pathway
- Glucoronidation, sulfation, glutathine conjugation, acetylation, amino acid conjugation, methylation