Liver Disease Introduction Flashcards
What does the classic liver lobule look like?
Hepatocytes are organized in radial cords forming a six-sided polyhedral prism with portal triads at each of the corners and a single central vein
What is the significance of zones 1,2 and 3 with regards to liver anatomy?
- Blood flows from portal triad to central vein (zone 1 to zone 3)
- Bile is made by zone 3 cells and flows in the opposite direction to blood
- Hypoxic damage primarily affects zone 3
- Metabolic & toxic damage primarily affects zone 1
Which zone is primarily affected by hypoxia?
Hypoxic damage primarily affects zone 3
Which zone is primarily affected by metabolic and toxic damage?
Metabolic & toxic damage primarily affects zone 1
What is the anatomy of the blood vessels around the liver?
- Abundant and double blood supply:
- Hepatic artery (~30%)
- Portal vein: (~70%)
- Portal vein can drain infectious agents and toxic substances absorbed from the gastrointestinal tract
- Liver has 2 important blood supplies – most important is hepatic portal vein, drains from gut and provides nutrients immediately to the liver
- A problem is it drains toxic agents or substances to the liver
What are the livers coping strategies in the face of disease?
- massive structural and functional reserve
- clinical signs not seen until >70% of functional liver mass lost –> liver failure
- signs seen earlier in acute disease because less time for adaptation by surviving hepatoycytes it is less able to adapt if you have a really acute process going on
- significant capacity to regenerate - liver damage from alcohol is able to reverse up to a certain point
What are some crucial roles of the liver in metabolic processes?
- Digestion/metabolism/storage of nutrients including
- fat/triglycerides
- protein
- carbohydrate/glyocgen
- cholesterol
- vitamins and minerals
- Waste management e.g. NH3, bilirubin etc.
- Immunoregulation esp Kupfer cells, IgA –
- Protein metabolism including albumin synthesis
- Production and activation of coagulation factors – think about how you can detect is liver disease is occurring? Think about 2 aspects – damage and failure of function, 2 can go on at the same time
- Drug metabolism/detoxification – giving drugs to patients with liver disease, may need to reduce dose slightly (same for kidney disease)
What is the difference between primary and secondary liver disease?
- The liver has a central role in metabolism
- This complex processing plant is inevitably affected by a variety of other diseases
- E.g. the HPV is one of the blood supplies to the liver therefore very closely linked to the intestinal tract
- 2ry liver disease >1ry liver disease in dogs – secondary hepatopathies are very common
- Can we identify an underlying cause to treat?
- If a liver disease is primary- we investigate the liver and think about specific diagnostic tests to help us assess the liver. If liver disease is 2ry we need to consider underlying causes of the 2ry hepatopathy and tackle those rather than being confused in to thinking we need to investigate the liver only.
What are some common causes of secondary hepatopathies?
- GI disease
- Pancreatitis
- Endocrine disease
- hyperadrenocorticism (very rare in cats)
- diabetes mellitus
- Hypothyroidism (dogs)/hyperthyroidism (cats)
- Right-sided congestive heart failure
- Hypoxia e.g. secondary to shock, anaemia
- Toxaemia
- Sepsis/bacteraemia
- Drug induced e.g steroids, phenobarbitone,
What are the clinical signs and history like for primary liver disease in the EARLY part of the disease?
In early disease clinical signs can be
- minimal/not evident
- subtle and non specific
- waxing and waning
- eg huge overlap with 1ry GI disease/IBD
- Signs over lap massively with other GI signs – may be subtle and non specific, think they have just eaten something that didn’t agree with it
- Don’t want to over investigate cases that have mild subtle signs, but do want to pick up on the ones that are recurring and keep coming back and not behaving as we would expect them to behave
What are some non-specific signs of liver disease?
- Depression/lethargy
- Anorexia
- Weight loss
- Vomiting/diarrhoea
- Polyuria/polydipsia
What are some signs more suggestive of liver disease?
- Jaundice
- Hepatic encephalopathy
- Ascites
- Drug intolerance
- Coagulopathy
What are some GI type clinical signs of liver disease?
- Anorexia
- Vomiting and diarrhoea
- sometimes due to portal hypertension:
- leads to vascular stasis and venous congestion à adverse effect on GI tract
- increases the risk of GI ulceration
- Weight loss
What are some potential reasons we see PUPD with liver disease?
PU/PD (various reasons suggested)
- decreased urea production –> decreased medullary solute gradient –> impaired renal concentrating mechanism –> dilute urine & compensatory PD
- Psychogenic component?
- Reduced hormone metabolism e.g. cortisol
What do some of the GI clinical signs in liver disease reflect?
When can it deteriorate rapidly?
Some of the GI signs in liver disease probably reflect metabolic derangements in the liver but once portal hypertension occurs then the situation can deteriorate rapidly especially if ascites develops. The intestinal tract doesn’t cope well with the “back pressure” of portal hypertension and ascites.
What are some mechanisms of ascites?
Mechanisms include:
- Portal hypertension (modified transudate)
- Intermdiate total cell count
- portal flow
- resistance to flow
- eg cirrhotic liver
- Hypoalbuminaemia (transudate)
- has to be significantly low eg < approx. 15g/l
- Accellular usually, but liver can usually make enough can make enough to not make a pure transudate – so usually a modified transudate – might more likely something associated with the gut to have such a big droop of albumin in the gut
- Dogs with ascites and mild hypoalbuminaemia: the low albumin alone will not be the cause of the ascites
What kind of ascites will portal hypertension cause?
Modified transudate
What kind of ascites will hypoalbuminaemia produce?
Transudate
Why is it unlikley that liver disease will produce just hypoalbuminaemia, a transudate ascites?
- Accellular usually, but liver can usually make enough can make enough to not make a pure transudate – so usually a modified transudate – might more likely something associated with the gut to have such a big droop of albumin in the gut
- Dogs with ascites and mild hypoalbuminaemia: the low albumin alone will not be the cause of the ascites
Why does liver disease produce neurological signs?
What normally happens, what happens with liver disease?
Ammonia & other encephalopathic toxins originate in the GI tract and then are not adequately processed by the liver, either because its unable to function or a PSS of some kind
- Normal situation –> detoxified in the liver
- Abnormal –> detoxification fails for several reasons:
- congenital portosystemic shunts (cPSS)
- toxins bypass the processing plant of the liver
- fulminant acute liver disease
- detoxification processes in the liver are compromised and overwhelmed
- acquired portosystemic shunts
- chronic fibrotic/cirrhotic liver disease shuts down normal HPV supply
How is ammonia usually dealt with in the liver?
What happens in term of breakdown products from urea and protein is that ammonia is produced, ammonia delivered to liver hy HPV and is dealt with adequately with the urea cycle – if this is faulty, cannot produce urea, too much ammonia in circulation
What are some neurological signs associated with liver disease?
When are they likely to be worse?
- Waxing and waning
- non-localising on neuro exam
- How is your neuro exam?
- May be associated with feeding
- Hyperactive &/or depressed/dull/clumsy
- Circling, pacing, central blindness
- Salivation, especially cats
- Seizures —> coma
- Can often miss presenting signs in puppies as they can just look like they go a bit crazy and owners don’t perceive this as a problem
- Cats can salivate profusely and can sometimes have full on seizures – can be very damaging, potential for brain damage associated with the seizure
How does the drug intolerance/metabolism alter with liver disease?
- Many drugs are metabolised in the liver:
- decreased dose &/or frequency if liver disease
- check ANY medication in a patient with liver disease
- Some drugs influence metabolism of others
- cimetidine binds cytochrome P450 –> decreased oxidative metabolism of other drugs by the liver –> increased plasma levels
- E.g. propranolol, metronidazole, phenobarbitone – might need to lower the dose of one drug because its on another drug
- phenobarbitone can enhance the metabolism of some drugs ie decreased effect
- E.g. corticosteroids, metronidazole
- Some drugs are directly hepatotoxic- not always dose dependent
- potentiated sulphonamides (not as commonly used as they ysed to be but can be hepatotoxic), azathioprine
- paracetamol, diazepam in cats
How can jaundice be pre-hepatic?
- due to haemolytic anaemia
- bilirubin production exceeds liver’s capacity to excrete it
- Associated with significant anaemia
How can jaundice be hepatic?
• decreased uptake, conjugation and excretion of bilirubin
How can jaundice be post-hepatic?
- obstruction of the biliary tree
- E.g. pancreatitis, cholelith, duodenal mass (plugs off end of bile duct)
- prevention of excretion via faeces (cannot get rid of bilirubin as we should)
What makes bilirubin water soluble?
Conjugated with glucuronic acid. Conjugation makes bilirubin water soluble
What are some cutaneous signs associated with liver disease in horses cattle and sheep?
Cutaneous signs: photosensitisation (horses, cattle, sheep)
- May be seen secondary to acute or chronic liver failure
- Compromised liver function results in phylloerythrin production (a photodynamic metabolite of chlorophyll) which enters the skin
- Phylloerythrin in the skin reacts with UV light releasing energy –> inflammation and skin damage
- Signs include pain, pruritus, dermatitis, oedema, ulceration, sloughing
- Can also see photophobia, corneal cloudiness
