Hepatobiliary Flashcards
What is the only plasma protein that is not formed by the liver?
gamma globulin
How is heme coverted into bilirubin?
Heme → biliverdin (in the mononuclear cells by heme oxygenase) → unconjugated bilirubin (lipophilic; by biliverdin reductase) → conjugated bilirubin (water soluble; via glucuronidation)
Iron metabolism in liver
Absorbed in GI –> ferroportin (regulated by hepcidin) –> transferrin –> hepatocite with apoferritin and hemosiderin
What are the two hormones that can activate phosphorylase and facilitate glycogenolysis?
Epinephrine
Glucagon
How many ATPs are produced during glycolysis, Krebs cycle and oxidative phosphorylation?
Glycolysis: 2
Krebs cycle: 2
Oxidative phosphorylation: 34
True or False: ATP provides negative feedback to inhibit the glycolysis.
True
ATP inhibit phosphofructokinase, which is the rate limiting enzyme
It covert
What does phosphofructokinase do?
It converts fructose-6-phosphate to fructose-1,6-bisphosphate.
True or False: Citrate ions from citric acid cycle provides negative feedback to inhibit the glycolysis.
True
Inhibit phosphofructokinase
Besides glycolysis, what is the pathway that is responsible for up to 30% of glucose breakdown in the liver and adipose tissue?
Pentose phosphate pathway
What are the three main types of lipids in the body?
Triglyceride (contains fatty acid)
Phospholipids (contains fatty acid)
Cholesterol (do not contain fatty acid)
How does body utilize fatty acid as source of energy?
fatty acids are converted to acetyl-CoA via 𝜷-oxidation → acetyl-CoA enters Krebs cycle → 22 ATP
List 3 hormones that facilitate lipolysis.
Thyroid hormone
Epinephrine
Cortisol
What is the normal ratio of body tissue protein and plasma protein?
33:1
For the liver bloody & oxygen supply, how many percentage are from the portal vein and how many percentage are from the hepatic artery?
Blood: 80% from portal vein, 20% from hepatic artery
Oxygen: 50% from portal vein, 50% from hepatic artery
What are the amino acid participating in the urea cycle?
Aspartate
Ornithine
Arginine
* Citrulline
What are the two hormones that facilitate protein synthesis? Which hormone facilitates protein breakdown?
Protein synthesis: insulin, growth hormone
Protein breakdown: glucocorticoid
What is the function of space of Disse?
allow excessive fluid from the liver sinusoid enter and drained from the lymphatic system
How many liver lobes are in dogs?
Four lobes with four sublobes and 2 processes
Right lateral, Right medial, Left lateral, Left medial, caudate, quadrate
What is the main difference in the bile duct anatomy in dogs and cats?
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
List 5 substances that is in the bile.
1) Bile acid
2) Cholesterol
3) Bilirubin
4) Phospholipids
5) Water
6) Bicarbonate
How many percentage of the liver removal can dogs tolerate?
70%
* The main issue is the liver being unable to accommodate the portal vein blood flow and develop portal hypertension
How soon does liver regeneration start and when is the peak?
starts within hours
Peak at 3 days
Which liver lobe is most likely to develop liver lobe torsion?
Left lateral
What are the two common concurrent endocrine disease with gallbladder mucocele?
Hyperadrenocorticism
Hypothyroidism
Explain the enterohepatic circulation of bile acid.
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% modified by bacteria (secondary bile acids) 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.
What is the reason of doing pre- and post-prandial bile acid test?
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.
How do you interpret the bile acid test.
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
What are the three differential for abnormally high bile acid test?
Hepatic dysfunction
Hepatic vascular anomaly
Bile duct obstruction
What are the surgical options for PSS?
- Suture ligation
- Gradual attenuation with ameroid constrictors
- Gradual attenuation with cellophan bands
What is normal portal vein pressure?
6-10 mmHg
What are the clinical signs to observe after PSS surgery for portal hypertension?
Seizure
Pain
Intra-abdominal hypertension
Hypovolemic shock
Vomiting, diarrhea
Distended abdomen with effusion
What are the two common causes for hepatic encephalopathy in dogs and cats, respectively?
Dog: CPSS, formation of acquired portosystemic collateral vessels (APSC) due to portal hypertension
Cat: CPSS, arginine deficiency due to hepatic lipidosis
What is the classification of HE?
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
What is the important enzyme to covert glutamine to ammonia and glutamate?
glutaminase (high level in enterocytes)
What are the two metabolic pathways for ammonia in the liver? what cells are responsible for that? what are their affinity and capacity?
1) Urea cycle, periportal hepatocytes, low affinity but high capacity
2) Glutamine synthesis, perivenous hepatocytes, high affinity but low capacity
What composes the portal triad?
Portal vein
Hepatic artery
Bile duct
which hepatic zone does acetaminophen most likely to cause injury?
zone 3
Which hepatic zone does gluconeogenesis happen? What about glycolysis?
Gluconeogenesis: zone 1
Glycolysis: zone 3 (anaerobic metabolism)
In a patient with liver disease, does the skeletal muscle help decrease ammonia level or elevate ammonia level?
Help to decrease ammonia level (contains glutamine synthase)
In the cerebrum, what is the interaction between astrocytes and ammonia?
Astrocytes have high level of glutamine synthase → metabolize ammonia → astrocyte swelling (?)
What are the 6 proposed pathogenesis of hepatic encephalopathy?
1) Astrocyte swelling (ammonia, cytotoxic and vasogenic edema)
2) Immuno-compromise and neuroinflammation
3) Oxydative stress
4) Manganese
5) Neurosteroid synthesis
6) Amino acid imbalance
True or False: Stimulation of peripheral type of benzodiazepine receptors (PTBR) by NH4 and manganese enhances synthesis of NS
True
List 4 rationales of using lactulose in treating hepatic encephalopathy.
1) Decrease colonic pH → trapping ammonium ions in the colon → decrease intestinal absorption (more NH4 form which is hydrophylic)
2) probiotic by inhibit ammonia producing bacteria
3) Reduce **intestinal transit time **→ decreased bacterial ammonia release/absorbtion and increase fecal excretion of nitrogen compounds
4) Stimulate the incorporation of ammonia with bacterial proteins
True or False: In the pathogenesis of hepatic encephalopathy, deranged GABAnergic neurotransmission plays a role.
True
What kind of amino acid imbalance is found to be associated with HE?
Increased aromatic amino acids and decreased branched-chain amino acids
List 10 possible precipitating factors for HE in dogs and cats?
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
How does hypokalemia worsen hepatic encephalopathy
-
Increased Ammonia Production
Hypokalemia induces intracellular acidosis. To compensate for low potassium levels, the body shifts hydrogen ions (H⁺) into cells in exchange for potassium. This cellular acidosis leads to increased renal production of ammonia.
Additionally, intracellular acidosis in the kidney’s tubular cells promotes ammoniagenesis, leading to elevated blood ammonia levels. -
Increased Alkalosis (Metabolic)
Hypokalemia often accompanies metabolic alkalosis, which decreases blood hydrogen ion concentration. This alkalotic state shifts more ammonia (NH₃) into its diffusible, toxic form. In an alkalotic environment, ammonia is more likely to cross the blood-brain barrier and cause neurological disturbances, worsening hepatic encephalopathy. -
Impaired Hepatic Detoxification
Hypokalemia may impair hepatic function, particularly the liver’s ability to detoxify ammonia. The liver’s urea cycle, responsible for converting ammonia into urea for excretion, can become less efficient under hypokalemic conditions, leading to further increases in circulating ammonia levels. -
Worsened Neuromuscular and Neurological Symptoms
Hypokalemia can exacerbate muscle weakness and neurological disturbances (e.g., confusion, lethargy), both of which are already present in hepatic encephalopathy. This can compound the cognitive and neuromuscular dysfunction seen in HE.
True or False: In HE patients, strict protein-restricted diet is recommended.
False
What is the neomycin dose for HE?
20 mg/kg PO q8h
In dogs and cats, what are the two main types of cholecystitis?
Neutrophilic cholecystitis
Lymphoplasmacytic follicular cholecystitis
What are the three types of necrotizing cholecystitis?
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
How do you diagnosed bile peritonitis?
effusion bilirubin concentration > 2x serum bilirubin
what are the dogs and cats choleliths mainly composed of?
Calcium carbonate
Bilirubin pigments (bilirubin or calcium bilirubinate)
What is the function of SAMe?
It is a glutathione precursor and antioxidant
Why is gall bladder mucocele a surgical disease.
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.
True or False: TNF-𝜶 stimulates hepatocyte apoptosis through the Fas-Fas ligand pathway.
True
List 10 hepatotoxin.
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
What the treatment difference in feline neutrophilic cholecystitis and lymphoplasmacytic cholecystitis?
Neutrophilic cholecystitis: broad-spectrum antibiotic while pending culture
Lymphoplasmacytic cholecystitis: immunosuppressive glucocorticoid therapy
What is the main way for the body to maintain copper homeostasis?
Biliary excretion (→ any cause of cholestasis would be expected to increase hepatic copper level)
Describe the pathophysiology of hepatorenal syndrome.
Hepatorenal syndrome is a condition in which there is progressive kidney failure that occurs in a person with cirrhosis of the liver.
How much of the liver function loss can cause HE?
> 70%
What is the proposed pathophysiology of HE related seizure and coma/CNS depression?
Seizure: Excessive glutamate activates NMDA receptors
Coma/CNS depression: Activations of GABA receptors and increased endogenous BZDs
List 10 toxin implicated in hepatic encephalopathy.
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
What are the two proposed mechanism of PU/PD in acute liver injury/failure?
1) Decrease urea production → unable to establish the concentration gradient in renal medulla
2) Decrease responsiveness to ADH
What is the half life of albumin in dogs and cats?
8 days
What is half-life of ALT in dogs and cats?
Dogs: ~60 hours
Cats: < 24 hours
True or False: Dog can synthesize conjugated bilirubin in their renal tubule.
True
What is the protein restriction for dogs and cats with liver failure?
Dog: 18-22%
Cat: 30-35%
What is the MOA of ursodial
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
What are the 4 most common PSS post-OP complications?
Hemorrhage
Hypoglycemia
Seizure
Portal hypertension
What change of the portal pressure is considered safe during PSS attenuation ?
< no greater than 10 cm of H2O
True or False: Carprofen induced liver toxicity is dose-dependent.
False
It’s idiosyncratic
What is the characteristic of hepatic lipidosis?
- Accumulation of triglycerides in more than 80% of the hepatocytes
- Intrahepatic cholestasis
- Secondary impairment of hepatic functions
IM text book said > 50%
Describe the proposed pathophysiology of hepatic lipidosis in cats.
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)
True or False: Insulin resistance is the major inciting factors for the development of feline hepatic lipidosis.
False
What are the three common electrolytes imbalances that are commonly seen in feline hepatic lipidosis?
Hypokalemia (poor prognostic indicator)
Hypomagenesemia
Hypophosphatemia
What is the recommended diet management for feline hepatic lipidosis?
High protein, low carb diet
Protein (30-40% of the metabolized energy)
Fat (50% of the metabolized energy)
Carbohydrate (20% of the metabolized energy)
What is kernicterus?
Bilirubin encephalopathy (bilirubin > 20 mg/dL; mainly unconjugated)
What are the primary functions in hepatic zone 1 and hepatic zone 3, respectively?
Zone 1: glucuronidation, 𝜷- hydroxylation, urea synthesis
Zone 3: lypolysis, glycolysis, gluconeogenesis, xenobiotic metabolism
Which hepatic zone has highest concentration of cytochrome p450?
Zone 3
which metabolizes xenobiotic chemicals and performs functions such as lipogenesis, glycolysis, bile acid synthesis and glutamine synthesis
Which hepatic zone has most hepatic progenitor cells and damage to this zone can affect liver’s regeneration?
Zone 1
True or False: Acute liver injury cause hypophosphatemia.
True
What is hepatic metabolism phase1 and phase2?
Phase 1: cytochrome P450
- Oxidation, hydrolysis, reduction, dehalogenation
Phase 2: conjugation pathway
- Glucoronidation, sulfation, glutathine conjugation, acetylation, amino acid conjugation, methylation
Definition of acute liver failure vs acute liver injury
ALF = hepatocellular damage causeing acute compromise in synthetic, excretory and regulatory function of the liver
ALI = acute hepatocellular damage with retained hepatic function
Mechanism of toxicity for:
1. Blue green algae
2. Amanita
3. Xylitol
- disruption hepatocyte cytoskeleton
- necrosis (can give penicillin to reduce protein binding)
- depletion of ATP and production of ROS
TEG findings in ALF
50% hypocoagulable
10% hypercoagulable
40% no changes
mainly increased LY and decreased MA
Best antibiotic for PSS
Rifaximin
Portal vein pressure
PVP = PBF x IHVR
PBF = portal blood flow
IHVR = intrahepatic venous resistance
Classification of portal hypertension
- Hepatic
- pre-hepatic
- post-hepatic (Budd-Chiari syndrome)
Measurement of PVP
- Direct catheterization
- Indirect catheterization of CVC and hepatic vein: wedge pressure (= sinusoid pressure) vs free pressure (CVC) –> hepatic pressure gradient = wedge - free pressure –> if >10mmHg abnormal
Consequences of portal hypertension
- spontaneous bacterial peritonitis
- hepato-renal syndrome
- hypersplenism
- portal hypertensive gastropathy
neurological complication after PSS surgery are more common in cats than in dogs
True: 20% vs 37%
Prognosis is better for intra-hepatic vs extra-hepatic shunts
False: 2.5-7% mortality in extra-hepatic vs 12.5% mortality in intra-hepatic
Treatment for copper hepatopathy
- Zinc (competitive transport in hepatocyte)
- Trientine (chelates circulating copper)
- D-penicillamine (chelates circulating and tissue copper but GI side effects and hemolytic anemia possible)
Lesion affecting the right hepatic lobe are easier to resolve by lobectomy than left sided ones
False: right lobes are more difficult to remove due to challenging access to lobar vasculature. Usually only partial lobectomy possible
