Liver disease Flashcards
What is the function of the liver?
- Intermediate metabolism
- Storage
- Protein synthesis
- Production of bile
- Detoxification
What are the consequences of hepatic dysfunction?
Consequences on…
* Bile production
* Metabolic
* Circulation
* Detoxification
* Coagulation
What can cause jaundice (icterus)?
Pre-hepatic
* Haemolysis - yellow/white MM
Hepatic
* Hepatocyte dysfunction
* Intrahepatic cholestasis
Post-hepatic
* Extra-hepatic cholestasis
What is seen with metabolic dysfunction?
- Non-specific signs
- Loss of condition
- Weight loss
- Hypoglycaemia
- Hypoalbuminaemia
- Only in chronic disease
- Can contribute to ascites
What is seen with circulatory disturbances?
- Ascites
- Hypoalbuminaemia
- Portal hypertension
- Sodium and water retention
- Polyuria / polydipsia - cannot concentrate urine (reversible)
- Portosystemic shunts
- cirrhosis
-portal hypertension
What problems with detoxification occur with liver damage?
- Hepatic encephalopathy
- defective urea formation from ammonia
- increase blood NH3 leads to CNS signs
What are signs of hepatic encephalopathy?
What can worsen hepatic encephalopathy?
- Anorexia, V & D, PU/PD
- Dullness, aggression, staggering,
blindness, head-pressing, seizures - Worse if…
-High protein meal
-Gastrointestinal bleed
-Dehydration, acid-base imbalance - Increased sensitivity to anaesthetics
What is the consequence of lack of coagulation?
- Defective production and storage of clotting factors
- Vitamin K malabsorption
- Portal hypertension = GI bleeding
What are signs of liver dysfunction in dogs?
- Icterus
- Faecal changes
-Grey (acholic)
-Melaena - Hepatic encephalopathy
- Drug intolerance
- Ascites
- Stunted growth (if young)
- Vomiting and diarrhoea
- Polyuria & polydipsia
- Non-specific signs
-Anorexia
-Weight loss
-Weakness
-Poor coat and skin condition
Where is jaundice most evident?
- Sclera - white part of the eye
How would you classify different hepatopathies?
Primary =
*Inflammatory disease (infectious/ non-infectious)
* Non-inflammatory disease (non-infectious)
Secondary =
* Non-specific + reversible changes
- Anorexia
- Toxaemia
- Nutritional imbalance
- Metabolic changes
- Infection
What is reactive hepatopathies?
- Most common liver abnormality
- Little loss of hepatic function
- Reversible
- Treat by correcting underlying disease
What are different results of liver biopsies in order of how common they are?
- Reactive
- Chronic hepatitis
- Neoplasia
- Toxic
- Steroid
- Nodular hyperplasia
- Cholangitis
- PSS
- Copper
What can cause reactive hepatopathy?
- IBD
- Bacterial infections
- Periodontal disease
- Rickettsial infections
- Acute pancreatitis
- Diabetes mellitus
- Hyperadrenocorticism
- Hypoadrenocorticism
- Hyperthyroidism
- Haemolytic anaemia
- Septicaemia
- Shock
- Right heart failure
- PLE
- Severe protein restriction & starvation
What are infectious inflammatory causes of liver disease?
(bacterial/viral/protozoal)
Bacterial
* Leptospirosis
* Bacterial cholangiohepatitis
Viral
* Infectious canine hepatitis
* Canine Herpes virus
* FIP
Protozoal
* Toxoplasma
What are non-infectious inflammatory causes of liver disease?
- Toxic hepatic disease
- Drug-induced hepatic disease
- All forms of chronic hepatitis
- Canine chronic hepatitis
- Feline lymphocytic cholangitis
What are non-inflammatory causes of liver disease?
- Congenital portosystemic shunt
- Juvenile hepatic fibrosis
- Feline hepatic lipidosis
- Neoplasia
- Telangiectasis and Peliosis
- Surgical
- Trauma
- Liver lobe torsion - Entrapment
What is feline hepatic idiosyncrasies? What can cause it?
- Relative deficiency of glucuronyl transferase
Causes =
* Aspirin
* Paracetamol
* Phenols, pine tars, morphine, benzenes, alcohols, barbiturates
What does paracetamol toxicity cause in cats?
- Relative deficiency of glucuronidation + glutathione conjugation
- Methaemoglobinaemia
- Haemolytic anaemia - depression + dyspnoea
- Facial oedema
- Hepatocellular damage - liver failure + icterus
How do you treat paracetamol toxicity?
- N-acetylcycsteine
- Vitamin C
- Supportive Tx - IV fluids, antibiotics, activated charcoal
What are clinical signs of liver failure in cats? (compared to dogs)
- Anorexia and weight loss most common
- Icterus relatively common
- Polyuria / polydipsia - less severe
- Hepatoencephalopathy, increased hypersalivation
- Microhepatica & cirrhosis rarely seen
- Pyrexia common in suppurative cholangitis
- Chorioretinitis or uveitis (FIP, toxoplasmosis)
What are differential diagnoses for jaundice in cats?
- Cholangitis complex
- FIP (dry-form)
- Lymphoma
- (Cirrhosis)
- Neoplasia
- Lipidosis
- Toxoplasmosis
- Haemolytic anaemia
- Toxic hepatopathy
- Pancreatitis
- Panleucopenia
- Biliary obstruction / bile duct rupture
What are the steps to diagnosing liver disease?
- History & clinical signs
- Physical examination
- Laboratory evaluation
- Diagnostic imaging
- Liver biopsy
What would you look for on physical exam of liver disease?
- Icterus - present in serum before eye (can have severe disease without icterus)
- Ascites
- Hepatomegaly / microhepatica
- Pain - abdominal
What lab tests would you do for live rdisease?
- Haematology
- Serum biochemistry
- Urinalysis
- Coagulation (before liver biopsy)
- Liver function tests
- Peritoneal fluid cytology (ascites)
Regarding liver enzymes what are the hepatocellular + cholestatic markers?
- Hepatocellular markers = ALT + AST
- Cholestatic markers = ALP + GGT
With serum biochemistry what will tell you about the liver function?
- Serum proteins (especially albumin)
- Glucose, urea, cholesterol
- Bilirubin
- (Ammonia)
- Bile acids
- Not liver enzymes - only tell damage (leakage enzymes)
What would happen to biochemistry results as liver failure progresses?
- Acute hepatitis = raised ALT + ALP
- Chronic hepatitis = raised bile acids
- Cirrhosis = raised bilirubin + decreased albumin
- End stage liver failure = increased clotting + decreased glucose
What is the difference between chronic hepatitis + cirrhosis?
- No clinical signs with chronic hepatitis
What different diagnostic imaging can be done for liver disease?
- Survey radiographs
- Contrast radiographs - portovenography
- Ultrasonography
- Scintigraphy
What can ultrasonography tell you with liver damage?
- Liver size
- Heterogenous parenchyma disease
- Biliary obstruction
- Biliary calculi
- Masses
- Vasculature
- portosystemic shunts
- arteriovenous fistulas
What are indications to do a liver biopsy?
- Persistent increases in liver enzymes
- Altered liver size
- Monitoring progressive liver disease
- To evaluate response to treatment
What needs to be done before taking a liver biopsy?
- Check clotting profile first
What are contraindications for percutaneous biopsy?
- Lack of operator experience
- Small liver, unless ultrasound available
- Focal disease
- Extrahepatic cholestasis
- Bleeding disorder
- Severe anaemia
What are different techniques for liver biopsy?
- Percutaneous
- blind
- ultrasound guided ‘tru-cut’ technique
- Laparoscopy
- Coeliotomy
What dogs are predisposed to juvenile hepatic fibrosis?
What is the pathology of juvenile hepatic fibrosis?
- GSD
- Rottweiler
- Progressive fibrosis
- Minimal inflammatory reaction
- Central vein fibrosis + occlusion most common
What can be secondary to juvenile fibrosis / cirrhosis?
How do they develop?
- Acquired shunts
- develop from redundant vessels - between portal vein + CVC, portal hypertension often leads to ascites
What are different types of canine chronic hepatitis?
- Idiopathic chronic hepatitis
- Lobular dissecting hepatitis
- Drug-induced chronic hepatitis
- Copper-associated hepatitis
- all lead to cirrhosis
When would survival be shorter with chronic hepatitis?
If -
- hypoalbuminaemia
- severity of necrosis and fibrosis in the biopsy
- Bridging fibrosis
What breeds are predisposed to hepatic portal hypoplasia?
- Small terrier breeds
- often have no clinical signs or portosystemic shunts
+ increased bile acids
What are the different feline cholangitis complex + what are the difference?
- Suppurative cholangitis - neutrophils
- Lymphocytic cholangitis - lymphocytes + plasma cells
What is idiopathic hepatic lipidosis? What does it lead to?
- Massive hepatic fat accumulation
*leads to
- biliary stasis
- liver failure
- anorexia
- death
What are clinical signs of hepatic neoplasia + what are the different types?
- Similar to inflammatory liver disease
- Hepatomegaly - can be irregular shape
- Primary tumours
- Infiltrative
- Metastatic
What are different primary neoplasias?
- Hepatocytes
-Hepatocellular carcinoma
-hepatoma - Biliary - cholangiocarcinoma
- Connective tissue
-fibroma / sarcoma
-haemangioma / haemangiosarcoma
What are the principles of treating liver disease?
- Eliminate causative agent
- Suppress ongoing disease
- Optimise regenerative capacity
- Control complications
What does therapy tailored to the clinical picture consist of?
- Dietary modification
- Ursodeoxycholic acid (UDCA)
- Anti-oxidant drugs & glutathione donors
- Treatment of complications
What does therapy tailored to biopsy results consist of?
- Inflammatory cells (Neutrophils/Lymphocytes) = antibiotics / immunosuppressives
- Fibrosis = anti-fibrotic drugs
- Copper accumulation = decoppering drugs
- Positive bacterial culture = appropriate antibiotic
What dietary management would be needed for hepatic encephalopathy?
- minimise ammonia production =
-protein restriction + modification - high biological value = dairy + vegetable
What dietary management would be needed for chronic active inflammation?
- Reduce inflammation
- Prevent copper accumulation=
- low copper + high zinc
- fat soluble vitamins = A, D, E, K,
- Taurine + L-carnitine for cats
- Add cottage cheese to a standard hepatic diet - high in protein
What antibacterial therapy would be needed for hepatic encephalopathy?
- Use based on clinical picture
- Ampicillin
- Metronidazole
What antibacterial therapy would be needed for bacterial cholangiohepatitis?
- Need culture + sensitivity (bile + tissue)
What are advantages of glucocorticoids?
- Improved well-being
- Appetite stimulation
- Anti-inflammatory
- Immunosuppression
- Anti-fibrotic
What are disadvantages of glucocorticoids?
- Steroid hepatopathy
- Predispose to infection
- Fluid retention
- Catabolic
What are breeds affected by copper associated hepatopathies?
- Bedlington terriers
- WHWT
- Skye terrier
- Dalmatian
- Labrador
- Doberman
What are different decoppering agents?
- Copper chelators
-d-penicillamine
-2,2,2-tetramine (trientine) - Copper absorption blocker
-oral zinc (give 1hr before feeding)
What are the advantages / disadvantages of using adjunctive therapy?
Advantages
* Do not need biopsy results
* Broad spectrum of activity
* Wide safety margin
* Combination therapy used
Disadvantages
* Cost
* Worse compliance if given many drugs
What are different examples of adjunctive therapy?
- Ursodeoxycholic acid (UDCA)
- S-Adenosyl methionine (SAMe)
- Milk thistle
- Vitamin E
What is ursodeoxycholic acid?
- Hydrophilic ‘beneficial’ bile salt
- alters bile composition
- stimulates bile flow - contraindicated if complete biliary obstruction
- modulates inflammatory/immune response
What is S-adenosyl methionine?
- ‘Glutathione (GSH) donor’
= endogenous molecule central to = - hepatic metabolism
- detoxification
What benefit does Silybum mariarnum have? (milk thistle)
- Free-radical scavenger
- Inhibits inflammation
- Inhibit lipid peroxidase
- Inhibit collagen deposition
- Increase glutathionine
What are the advantages / disadvantages milk thistle?
Advantages
* Wide safety margin
* No absolute contraindications
* Broad spectrum of activity
Disadvantages
* Cost
* Evidence for efficacy
What are complications of liver disease?
- Hepatic encephalopathy + coma
- Ascites + oedema
- Haemorrhage + anaemia
With hepatic encephalopathy, what should be done?
- Identify + treat precipitating cause
-Dehydration
-Diuretics
-Alkalosis
-Hypokalaemia
-Gastrointestinal bleeding - Reduce ammonia concentrations
-low protein diet
-Lactulose
-Antibiotics (ampicillin / metronidazole) - Lactulose retention enema if coma
What can be done to treat ascites + oedema?
- Low sodium diet
- Diuretics
- spironlactone
- occasionally add in furosemide
- Paracentesis
- drain a minimal volume for patients comfort
- Could worsen bodywide protein status
What can be done to treat hemorrhage and anaemia?
- Vitamin K injections
- Fresh blood transfusions
- B vitamin injections
- H2 blockers if GI haemorrhage
What is high cobalamin associated with in cats?
- Hepatic + neoplastic disease
