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 β†’ biliverdin (in the mononuclear cells by heme oxygenase) β†’ unconjugated bilirubin (lipophilic; by biliverdin reductase) β†’ 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 β†’ acetyl-CoA enters Krebs cycle β†’ 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 β†’ breaks down to unconjugated primary bile acid β†’ conjugates with glycine, taurine β†’ conjugated bile acid and enters the gall bladder β†’ enters the intestines at the level of duodenum β†’ being actively absorbed at ileum (90%) / the rest 10% becomes unconjugated by bac and enters the colon β†’ the reabsorbed (95%) conjugated and unconjugated bile acids are efficiently extracted by hepatocyte transporters β†’ 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 ΞΌmol/L in dogs and > 25 ΞΌmol/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 β†’ metabolize ammonia β†’ 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 β†’ trapping ammonium ions in the colon β†’ decrease intestinal absorption
2) inhibit ammonia production by the colonic bacteria
3) Reduce intestinal transit time β†’ 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-𝜢 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 (β†’ 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 β†’ 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 β†’ Negative energy balance β†’ lipolysis β†’ overwhelmed fatty acid oxidation β†’ 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