SACCM 87: Hepatic Encephalopathy

Question 1

Describe the difference between cytotoxic and vasogenic brain edema

Answer 1

Cytotoxic - accumulation of osmotyic substances causing intracellular water accumulation and swelling
Vasogenic -inflammation causing increased vascular permeability causing extravascular fluid accumulation

Question 2

For what type of brain edema are corticosteroids considered an appropriate treatment?

Answer 2

Vasogenic edema
- as inflammation is presumably leading to an increased vascular permeability

not appropriate in cytotoxic edema - can actually worsen to intracellular fluid accumulation in these patients

Question 3

Which type of brain edema is more prominent in hepatic encephalopathy?

Answer 3

cytotoxic - brain swelling from intracellular fluid shifts

Question 4

Name one differential for nonhepatic hyperammonemia in both dogs and cats

Answer 4

Dogs: hypercobalaminemia - from intestinal malabsorption
Cats: arginine deficiency from hepatic lipidosis

Question 5

What is transamination and where does it take place?

Answer 5

Glutamine synthesis
ammonia + glutamate –> (glutamine synthetase) –> glutamine

• perivenous hepatocytes
• brain
• skeletal muscles

Question 6

Explain the pathophysiology of how ammonia causes hepatic encephalopathy

Answer 6

Ammonia readily crossses the BBB –> impairs the glutamine-glutamate recycling system

causes glutamine accumulation in the astrocytes by inhibiting release –> glutamine osmotically active –> IC swelling (i.e., cytotoxic edema)

accumulated glutamine then moves into the astrocytes’ mitochondria –> deamination –> glutamine –> ammonia and glutamate –> ammonia liberation –> NOS and ROS production

“Trojan horse” theory/hypothesis

Question 7

What coagulation factor can be used as a biomarker for hepatic function and perfusion?

Answer 7

Protein C

Question 8

What is the major inhibitory neurotransmitter of the CNS?

Answer 8

GABA

originates from intestines

Question 9

How are aromatic amino acids implicated in the development of hepatic encephalopathy?

Answer 9

AAA usually used for catecholamine neurotransmitter production (e.g., phenylalanine, tyrosine, tryptophan)

this convertion happens in the liver –> if hepatopathy present –> this convertion is overwhelmend

–> instead “false” neurotransmitters are produced (e.g., octopamine, phenylethanolamine) –> have inhibitory effect on the CNS

Question 10

What is the MOA of lactulose in hepatic encephalopathy?

Answer 10

Converts NH3+ (lipophilic and easily crosses BBB) to NH4+ –> cannot easily cross –> “trapped” in intestines

Also:
* osmotic cathartic –> decreased GI transit time
* inhibits ammonia production by bacteria
* stimulates ammonia incoorporation into bacterial proteins
* increases fecal excretion of nitric oxide compounds

Question 11

What are the dietary recommendations for patients with hepatic encephalopathy

Answer 11

• highly digestible protein (not protein restriction, i.e., moderate amounts)
• arginine supplementation (cats)
• restrict zinc
• higher ratio of branched:aromatic amino acids

Question 12

List substances that have been implicated in the development of hepatic encephalopathy

Answer 12

• ammonia
• glutamate
• GABA
• endogenous benzodiazepines
• endogenous opioids
• aromatic amino acids
• mercaptans
• manganese
• tryptophan-serotonin system alterations

Question 13

What is the proposed mechanism by which hypokalemia contributes to worsening of hepatic encephalopathy?

Answer 13

Hypokalemia promotes metabolic alkalosis –> increased NH3+ to NH4+ ratio

Hypokalemia increases renal ammonia production