AI generated questions -Hepatic encephalopathy

Question 1

2 main ways ammonia is generated in the GI

Answer 1

1. enterocyte glutamine metabolism. 2. microbiome (urease producing bacteria -cleavage urea to ammonia)

Question 2

Kidney, why they produce ammonia?

Answer 2

in order to make bicarbonate- glutamine in metabolized in the kidneys (to NH4+ and bicarbonate)

Question 3

which cells are the common ones in the CNS?

Answer 3

The astrocytes. They contribute up to 50% of brain volume. contain glutamate synthetase and mitigate increasing ammonia by converting glutamate to glutamine and consuming 1 ammonia molecule

Question 4

: What is the role of ammonia in the pathogenesis of hepatic
encephalopathy (HE)?

Answer 4

Central role in HE pathogenesis
○ Generated in GI tract through enterocyte metabolism and intestinal
microbiome activity
○ Complex interplay with triggers allows HE to occur even with modest or
normal ammonia levels

Question 5

How is ammonia generated and removed in the body relating to HE?

Answer 5

Generated in the GI tract by enterocytes by metabolism of glutamine
and by urease producing bacteria and by kidney metabolism of
glutamine (in the kidneys to produce bicarbonate)
○ Removed by kidneys through urea excretion and by muscle and CNS
activity (astrocytes, both by synthesize glutamine)

Question 6

: What role do skeletal muscles play in ammonia metabolism in HE?

Answer 6

Produce glutamine that consume ammonia, later upon catabolism of
glutamine– ammonia will be generated
○ Acts as an ammonia buffer when systemic concentrations rise

Question 7

How does the CNS contribute to managing increased ammonia levels in
HE?

Answer 7

Astrocytes convert glutamate to glutamine, consuming ammonia
○ Key in mitigating increasing ammonia concentrations

Question 8

How is inflammation related to HE in dogs with cPSS?

Answer 8

○ Dogs with cPSS and HE have higher CRP levels than dogs without HE
○ Both ammonia and systemic inflammation predictive of HE
○ pro inflammatory cytokines alter the cerebral endothelial permeability to
neurotoxins and potentiate ammonia toxicity. cytokines cross the BBB,
and activate microglia that produce local cytokines, causing cerebral
vasodilatation and hyperemia due to loss of cerebral autoregulation.
○ hepatic necrosis releases pro inflammatory cytokines. the cytokines alter the
permeability of the cerebral endothel- increase permeability of neurotoxins
and potentiate ammonia toxicity. cytokines cross the BBB, activating
microglia- that release local cytokines. all this causes cerebral vasodilatation
and htperemia- secondary to loss of cerebral autoregulation.

Question 9

What is the significance of manganese (Mn) in HE?

Answer 9

Essential trace element but can be neurotoxic
○ can be Extremely increased concentrations in blood of dogs and cats
with PSS

Question 10

How do non-absorbable disaccharides manage HE?

Answer 10

Metabolized by colonic bacteria into SCFAs, decreasing systemic
ammonia
○ Acidify colonic content to trap ammonia
○ Act as osmotic laxatives for ammonia removal

Question 11

What dietary management is proposed for high-grade HE?

Answer 11

○ Initial Short-Term protein restriction necessary
○ Increase protein intake gradually once stabilized, considering life-stage
requirements

Question 12

: What is the starting dose protocol for lactulose in HE management?

Answer 12

0.5 mL/kg orally, every 8-12 hours, titrated for 2-3 soft stools per day

Question 13

How is a lactulose enema administered for HE?

Answer 13

○ 1 part lactulose to 3 parts warm water, 10 mL/kg via Foley catheter,
retain 30-60 mins, repeat as required

Question 14

: What is the protocol for using lactose in managing HE?

Answer 14

Empirical dosing to effect 2-3 soft stools per day
○ Consider protein content; suggested in cats

Question 15

: What is the dosing protocol for neomycin in HE, and what are its risks?

Answer 15

○ 20 mg/kg orally every 12h
○ Risk of oto- and nephrotoxicosis if absorbed systemically

Question 16

What is rifaximin’s role in HE treatment, and what limits its use?

Answer 16

Dosed at 5 mg/kg orally every 12-24 hours
○ Nonabsorbable antibiotic; expense and limited anecdotal use restrict its
application in dogs

Question 17

What dietary consideration is given to pets with cPSS in HE management?

Answer 17

○ Prefer high-quality standard life-stage diets over expensive,
protein-restricted “hepatic diets”

Question 18

What is hepatic encephalopathy (HE)?

Answer 18

● Neuropsychiatric syndrome involving neurologic abnormalities.
● Occurs with >70% loss of liver function or portal blood bypassing the liver

Question 19

What role does ammonia play in the pathogenesis of hepatic encephalopathy?

Answer 19

Ammonia has a central role.
● Generated in the GI tract via enterocyte glutamine metabolism and intestinal
microbiome.
● Kidneys excrete urea, contributing to acid/base balance.
● Skeletal muscles release glutamine, potentially contributing to ammonia
levels.

Question 20

· what role play the astrocytes in hepatic encephalopathy?

Answer 20

● Contain glutamine synthetase, converting glutamate to glutamine.
● Mitigates increasing ammonia concentrations.
● Consumes ammonia in the process.

Question 21

What role does inflammation play in hepatic encephalopathy?

Answer 21

Pro-inflammatory cytokines released following hepatic necrosis.
● Alter cerebral endothelial permeability to neurotoxinsPotentiate ammonia toxicity.

Question 22

What is the management approach for hepatic encephalopathy?

Answer 22

● Non-absorbable disaccharides (lactulose, lactitol).
● short term Protein restriction in high-grade HE.
● Antibiotics to reduce bacterial numbers in the intestinal microbiota.

Question 23

· What is portal hypertension?

Answer 23

● ↑ Portal pressure due to altered hepatic resistance and capacitance.
● Can be pre-hepatic, hepatic (pre-sinuoidal, sinusoidal, post-sinuoidal), or
post-hepatic.

Question 24

How does hepatic sinusoidal portal hypertension develop?

Answer 24

Inflammatory/fibrotic hepatopathies lead to endothelial changes secondary to
oxidation, inflammatory mediators and physical changes to sinusoidal
endothelium.
● SECs become less able to compensate for ↑ in portal blood flow. producing
less vasodilators and more vascoconstrictirs (endothilin 1 , Ag II)
● local Vasodilators release causes splanchnic arteries to dilate, exacerbating
hypertension.

Question 25

What causes ascites in portal hypertension?

Answer 25

↑ Hydrostatic pressure from PH.
● Expansion of systemic blood volume secondary to RAAS activation and ADH
● ↓ Oncotic pressure due to hypoalbuminemia.

Question 26

What is the role of RAAS activation in ascites formation?

Answer 26

Contributes to intrahepatic PH.
● ↑ Renin and aldosterone.
● Spironolactone may be effective for ascites and suppression of intrahepatic PH
(might worth giving before ascites development)

Question 27

· How is portal hypertension and ascites managed?

Answer 27

● Diuretics like spironolactone and furosemide.
● Therapeutic drainage with diuretic use for refractory ascites

Question 28

What are the risks associated with coagulopathy in liver disease?

Answer 28

● Higher risk of thrombosis.
● Splanchnic and PV thrombosis in advanced liver disease

Question 29

· How do hepatocytes contribute to coagulation?

Answer 29

Synthesize pro- and anticoagulants and pro- and anti fibrinolytics
● Responsible for vitamin K-dependent activation

Question 30

· What did a retrospective study find about PCV changes in dogs with hepatic disease
going into elective intervention?

Answer 30

42% had a ΔPCV ≥6%. only 2 needed intervention.
● Splanchnic thrombosis increasingly recognized.
● 42% of dogs with PV thrombosis, had hepatopathy

Question 31

How is protein restriction utilized in the management of hepatic encephalopathy?

Answer 31

Necessary in high-grade HE.
● Protein intake titrated towards life-stage requirements.

Question 32

· What are the effects of spironolactone in managing portal hypertension?

Answer 32

Counteracts RAAS activation.
● May mitigate hepatic fibrosis and sinusoidal capillarization

Question 33

How does lactulose contribute to the management of hepatic encephalopathy?

Answer 33

Metabolized into short-chain fatty acids.
● Shifts microbiome to ↓urease-producing bacteria.
● Acidifies colonic content, trapping ammonia.
● Acts as an osmotic laxative.

Question 34

· What are the key features of hepatic encephalopathy pathophysiology?

Answer 34

● Ammonia plays a central role.
● enterocytes metabolize glutamine and produce ammonia, urease producing
bacteria metabolized urea to ammonia
● Astrocytes mitigate via glutamine synthetase, consuming ammonia is the
process of synthesizing glutamine
● Inflammation alters cerebral endothelial permeability.
● Manganese may have neurotoxic effects.

Question 35

How does portal hypertension contribute to the development of ascites?

Answer 35

● Increased hydrostatic pressure from portal hypertension.
● Expansion of systemic blood volume.
● Decreased oncotic pressure due to hypoalbuminemia.

Question 36

What are the goals of managing portal hypertension and ascites?

Answer 36

● Reduce portal pressure.
● Alleviate ascites.
● Suppress intrahepatic portal hypertension.
● Prevent worsening of the disease process.

Question 37

What are the potential consequences of portal hypertension on the
circulatory system?

Answer 37

● Splanchnic arteries dilate due to local release of vasodilators.
● Increased splanchnic and portal flow exacerbate hypertension.
● Release of angiogenic mediators may lead to the development
of portosystemic shunts.

Question 38

How does the kidney contribute to the management of ammonia in the
body?

Answer 38

● Excretion of hepatocyte-derived urea.
● Generation of ammonia from glutamine metabolism.
● Contributes to acid/base balance.

Question 39

What role does inflammation play in the pathophysiology of hepatic
encephalopathy?

Answer 39

● Pro-inflammatory cytokines alter cerebral endothelial
permeability.
● Potentiate ammonia toxicity.
● Activate microglia and induce local cytokine release.

Question 40

What are the potential therapeutic approaches for refractory ascites in
portal hypertension management?

Answer 40

● Therapeutic drainage in conjunction with diuretic use if
refractory or not effective fast enough..
● Spironolactone first and furosemide if not effective enough
● aiming for Reduction of body weight by 0.5-1.5% per day.

Question 41

How do non-absorbable disaccharides contribute to reducing
systemic ammonia concentrations in hepatic encephalopathy?

Answer 41

● Metabolized by colonic bacteria into short-chain fatty acids.
● Shift microbiome composition to favor bacteria that utilize
ammonia.
● Acidify colonic content, trapping ammonia as non-absorbable
NH4+.
● Act as osmotic laxatives, speeding removal of trapped
ammonia and urease-producing bacteria

Question 42

What is the rationale for using antibiotics in the management of
hepatic encephalopathy, and what are the preferred types of
antibiotics for this purpose?

Answer 42

● Reduce bacterial numbers in the intestinal microbiota and
microbial ammoniagenesis.
● Non-absorbable antibiotics are preferred if purely targeting
intraluminal bacteria.
● Some responses may be due to resolving occult infections.

Question 43

What are the key factors contributing to the development of ascites in
liver disease?

Answer 43

● Increased hydrostatic pressure from portal hypertension.
● Expansion of systemic blood volume.
● Decreased oncotic pressure due to hypoalbuminemia.