SA Liver Flashcards
When may ammonia be raised?
Liver failure
Congenital and acquired portosystemic shunts
How may urine be affected by liver disease?
Isosthenuria or inappropriately low USG
Bilirubinuria
Ammonium biurate crystals or uroliths
When investigating liver function, what can we test?
Hepatocellular injury
Cholestasis
Hepatocellular function
Hepatic portal circulation
Where are enzymes mostly found?
Inside cells (no function in blood)
How are proteases stored?
As inactive zymogens
Give 5 changes that indicate reduced hepatocellular function
Decreased uptake and excretion of bilirubin and bile acids
Decreased conversion of ammonia to urea
Decreased synthesis of metabolites
Decreased synthesis of coagulation proteins
Decreased immunologic function
Which enzymes are produced by pancreatic acinar cells?
What else do they produce?
Proteases (trypsin, chymotrypsin, elastase)
Lipases
Amylase
Also bicarbonate
Give some other functions of pancreatic enzymes
Proteases aid B12 absorption
Aid zinc absorption
Antibacterial activity
Intestinal mucosal modulation
What tests can we carry out to test exocrine pancreatic function?
Enzyme assays for amylase and lipase (poor specificity) DGGR lipase (more specific) 'Specific' canine pancreatic lipase (cPL) (more specific and sensitive than lipase and amylase) (Test available at external labs or in-house SNAP tests) TLI (trypsin-like immunoreactivity) (not as sensitive as cPL)
What is the function of amylase?
Why may it be increased?
Catalyses hydrolysis of complex starches
Can increase due to decreased GFR
What is the function of lipase?
Why may it be increased?
Catalyses hydrolysis of triglycerides Can increase (mildly) due to decreased GFR
When testing DGGR lipase, what are the cut-off values for diagnosis of pancreatitis?
> 34 U/L in cats
>216 U/L in dogs
After finding an elevation in lipase, what tests would you carry out to confirm a diagnosis of pancreatitis?
PLI (specific pancreatic lipase)
Imaging (ultrasound)
Biopsy
Fluid analysis
When would you test for TLI (trypsin-like immunoreactivity)?
In animals with clinical signs of maldigestion/malabsorption
High sensitivity/specificity for exocrine pancreatic insufficiency
Less useful for pancreatitis
What does a TLI test detect?
Trypsin, trypsinogen, and trypsin bound to protease inhibitors (most TLI in blood is trypsinogen, do not want free trypsin in the blood)
What value of cPL (specific canine pancreatic lipase) indicates pancreatitis?
> 400ug/L
Which cells are present in the pancreas?
PP cells (produce pancreatic polypeptides) B cells (produce insulin) Delta cells (produce somatostatin) Alpha cells (produce glucagon) Acinar cells (produce digestive enzymes)
What can we test to investigate liver function?
Hepatocellular injury (damage to hepatocytes -> leakage of enzymes)
Cholestasis (reduced/blocked bile excretion -> release of enzymes induced by retained bile)
Hepatocellular function (decreased production/catabolism of substances)
Hepatic portal circulation (decreased extraction of substances absorbed from the GI)
In which case may increased AST be artefactual?
Leakage from RBCs
Which are the liver ‘leakage’ enzymes?
ALT (largely liver-specific but also muscle. SA)
AST and LDH (both liver and muscle)
SDH and GLDH (liver specific in all species. Used in LA)
ALP and GGT are indicative of liver damage in horses and ruminants
What is cholestasis?
Decreased bile flow and excretion
What are the 3 kinds of cholestasis?
Intrahepatic (due to hepatocellular swelling)
Extrahepatic (due to bile duct obstruction)
Functional (nothing mechanically abnormal)
What can you use as markers for cholestasis?
Bilirubin
Bile acids (more sensitive)
Cholesterol
ALP and GGT (cholestatic enzymes; GGT is more specific)
What are the 2 major isoforms of ALP?
Liver-ALP (L-ALP)
Bone-ALP (B-ALP)
C-ALP is induced by what?
In which species?
Corticosteroids
Dogs
Where is haem broken down to bilirubin?
Macrophages
What is bilirubin conjugated with in the liver?
Glucoronic acid
What are the 3 types of hyperbilirubinaemia?
Pre-hepatic: secondary to haemolysis of RBCs
Hepatic: due to decreased bilirubin uptake, conjugation, and excretion. Often due to concurrent hepatocyte dysfunction and intra-hepatic cholestasis
Post-hepatic: Secondary to obstruction of extra-hepatic bile duct
Does conjugated or unconjugated bilirubin predominate with pre-hepatic bilirubinaemia?
Unconjugated at first, then an increasing proprotion of conjugated as time passes
Also, some degree of cholestasis
Does conjugated or unconjugated bilirubin predominate with post-hepatic bilirubinaemia?
Conjugated
Why may jaundice persist long after liver function has returned to normal?
Due to delta-bilirubin, bound to albumin
Will be no bilirubinuria
Give some functions of the liver
Removal of bacteria
Produces clotting factors
Storage of glycogen, iron, copper and vitamins
Detoxification of body wastes, drugs, and xenobiotics
Synthesis of cholesterol and bile acids
Synthesis of plasma proteins
Breakdown of RBCs
Carbohydrate, lipid and amino acid metabolism
What produces bile acids?
Hepatocytes
Describe the route of bile acids
Produced by hepatocytes
Released into biliary system then intestine
Over 90% are reabsorbed from the ileum, enter portal vein, return to liver, recirculated
Small amount lost in faeces; replaced by liver
Why may bile acids be increased?
Reduced uptake/excretion by hepatocytes (reduced hepatocyte mass/function)
Disruption of enterohepatic circulation (portosystemic shunts, cholestasis)
Which value for bile acid concentration indicates increased production and hepatobiliary pathology?
Values >25-30 mmol/L
How can you test for post-prandial SBA?
(Post-prandial serum bile acids) Take resting sample Fatty meal Post-prandial sample 2 hours after feeding If >25-30 mmol/L -> abnormal
What is meant by a ‘reactive hepatopathy’?
Many extrahepatic diseases cause elevation in liver enzymes
eg hypoxia, GI and pancreatic disease, sepsis
What haematology may we see in liver disease?
Often unremarkable but we may see:
Acanthocytes
Microcytosis
Ovalocytes (cats with hepatic lipidosis)
What are the 3 cholestatic markers?
Bilirubin, GGT, ALP
What must you always do before taking a liver biopsy?
Check clotting profile
Liver makes clotting factors-impaired liver function may result in reduced clotting factors
Where does the liver get its blood supply?
Hepatic portal vein (70-80%) Hepatic artery (20-30%)
What are the 3 major types of icterus
Pre-hepatic (haemolysis)
Hepatic (hepatocyte dysfunction, intrahepatic cholestasis)
Post-hepatic (extra-hepatic cholestasis)
Give some clinical signs of metabolic dysfunction
Non-specific signs (loss of condition, weight loss)
Hypoglycaemia (can cause seizures/collapse)
Hypoalbuminaemia (only in chronic disease; can contribute to ascites)
What do copper-coloured irises indicate in cats?
Portosystemic shunt
Give some circulatory disturbances caused by liver disease
Ascites
PUPD
Portosystemic shunts
How do hepatic encephalopathies occur?
Liver is unable to turn NH3 into urea (decreased functional liver mass and/or portosystemic shunt)
Increased blood NH3 (plus other toxins)
Leads to altered CNS function
Give some CNS signs seen with hepatic encephalopathies
Anorexia, vomiting and diarrhoea, PUPD
Dullness, aggression, staggering, blindness, head-pressing, seizures
When are hepatic encephalopathies worse?
After a high protein meal
GI bleed
Dehydration, acid-base imbalance
Why is bleeding seen with liver disease?
Defective production and storage of clotting factors
Vitamin K malabsorption
Portal hypertension -> GI bleeding
Give some clinical signs of a portosystemic shunt
Ascites Stunted growth (if young) Vomiting and diarrhoea PUPD Non-specific signs (anorexia, weight loss, weakness, poor coat and skin condition)
How can we classify hepatopathies?
Primary (inflammatory or non-inflammatory)
Secondary
Give some causes of reactive hepatopathies
IBD Bacterial infections Periodontal disease (can cause bacteraemia) Riskettsial infections Acute pancreatitis Diabetes mellitus Hyper/hypoadrenocorticism R-HF Hyperthyroidism Septicaemia
Give some bacterial causes of an inflammatory, infectious hepatopathy
Leptospirois Bacterial cholangiohepatitis (ascending infection from intestines)
Give some viral causes of an inflammatory, infectious hepatopathy
Infectious canine hepatitis
Canine herpes virus
FIP
Give a protozoal cause of an inflammatory, infectious hepatopathy
Toxoplasma
Give some causes of an inflammatory, non-infectious hepatopathy
Toxic hepatic disease
Drug-induced hepatic disease
All forms of chronic hepatitis (canine chronic hepatitis, feline lymphocytic cholangitis)
Give some causes of a non-inflammatory hepatopathy
Congenital portosystemic shunt Juvenile hepatic fibrosis Feline hepatic lipidosis (rare) Neoplasia Telangiectasia (permanent dilation of blood vessels) and peliosis (blood-filled cavities throughout liver) -> fragile liver Surgical: trauma, liver lobe torsion Amyloidosis
Which enzyme are cats deficient in which makes them more sensitive to certain toxins/drugs?
Glucuronyl transferase (results in difficulty conjugating toxins)
How does paracetamol toxicity occur in cats?
Deficient in glucuronyl transferase therefore deficiency of glucuronidation
Results in methaemoglobinaemia -> haemolytic anaemia, facial oedema, hepatocellular damage (liver failure and icterus)
What is the treatment for paracetamol poisoning in cats?
N-acetlycysteine
S-adenosyl methionine
Vitamin C
Supportive care: ABs, IV fluids, activated charcoal if recent ingestion
Give some differentials for icterus in cats, starting with the most common (*)
*Cholangitis complex
*FIP (dry form)
*Lymphoma
*Lipidosis
*Pancreatitis
Cirrhosis
Neoplasia
Toxoplasmosis
Haemolytic anaemia
Toxic hepatopathy
Panleucopenia
Biliary obstruction/ bile duct rupture
What will you see first- an increase in serum bilirubin or visible icterus?
Increase in serum bilirubin
What is microhepatica a sign of?
Portosystemic shunt
What should you always do before taking a liver biopsy?
Coagulation tests/check clotting profile
What do liver enzyme tests tell you?
If liver is affected by something, NOT if its function is impaired
Which liver enzymes can you test?
Hepatocellular markers: ALT, AST
Cholestatic markers: ALP, GGT
Which liver function tests can you do?
Bile acids (most sensitive) Serum proteins (esp. albumin) Glucose, urea, cholesterol (produced in liver) Bilirubin Ammonia
What do you see first with chronic hepatitis: altered lab results or clinical signs?
Altered lab results
When might you typically do a portovenogram?
Looking for a portosystemic shunt
What can you look at on a radiograph to give you an idea of liver size?
Position of gastric axis
What is the best way to diagnose most liver conditions?
Liver biopsy
Give some indications for a liver biopsy
Persistent increase in liver enzymes
Altered liver size
Monitoring progressive liver disease
To evaluate response to treatment
How can you perform a liver biopsy?
Percutaneous (blind; US-guided with ‘Tru-cut’)
Laparoscopy
Coeliotomy
Give some contraindications for doing a percutaneous liver biopsy
Lack of operator experience Small liver (unless US-guided) Focal disease (easy to miss) Extrahepatic cholestasis Bleeding disorder Severe anaemia
Which dog breeds are more prone to juvenile hepatic fibrosis?
GSD, Rottweiler
Describe the pathology of juvenile hepatic fibrosis
- Progressive fibrosis
- Minimal inflammatory reaction
- Central vein fibrosis and occlusion most common
How do acquired shunts occur?
Secondary to liver disease (juvenile hepatic fibrosis, cirrhosis)
Where do acquired shunts develop?
From redundant vessels (between portal vein and caudal vena cava)
Which clinical sign is often seen with acquired portosystemic shunts but rarely congenital?
Ascites
What is the most common canine chronic liver disease?
Canine chronic hepatitis
Give some types of canine chronic hepatitis
What may they all lead to?
-Idiopathic chronic hepatitis
-Lobular dissecting hepatitis
-Drug-induced chronic hepatitis
-Copper-associated hepatitis
May all lead to cirrhosis
Which 3 factors may lead to a shorter survival time for canine chronic hepatitis?
Hypoalbuminaemia
Severe necrosis and fibrosis in biopsy
Bridging fibrosis
What is cirrhosis?
Shrunken liver from fibrosis (micro/macro-nodular regeneration)
End-stage of many diseases
Which breeds are more affected by hepatic portal hypoplasia?
Small terrier breeds
What makes up feline cholangitis complex?
- Suppurative cholangitis (neutrophils)
- Lymphocytic cholangitis (lymphyocytes and plasma cells; indicates immune-mediated)
- (Sclerosing cholangitis- end stage of others)
- Can get both in combination with IBD and pancreatitis
What does idiopathic hepatic lipidosis lead to?
Biliary stasis
Liver failure
Anorexia
Death
Give some examples of primary liver tumours
Hepatocellular carcinoma Hepatoma Cholangiocarcinoma Fibroma/sarcoma Haemangioma/haemangiosaecoma
How do you treat hepatic encephalopathy?
Low protein diet
Lactulose
ABs (ampicillin or metronidazole)
How do you treat chronic active inflammation of the liver?
Glucocorticoids
Diet: low copper, high zinc, high protein quality, anti-oxidants. Taurine and L-carnitine for cats
Which liver conditions can you treat with glucocorticoids?
Chronic active inflammation
Hepatic fibrosis
Which dog breeds are affected by copper-associated hepatopathies?
WHWT Skye and Bedlington terrier Labrador Dalmation Doberman
Which agents are ‘de-coppering agents’?
Copper chelators: D-penicillamine, Trientine (222-tetramine)
Copper absorption blocker: oral zinc
What is UDCA?
Ursodeoxycholic acid
Alters bile composition and stimulates bile flow (CI if complete biliary obstruction)
What is SAMe?
S-Adenosyl methionine
Precursor for GSH production (molecule central to hepatic metabolism and detoxification)
How do you treat bacterial cholangiohepatitis?
Do culture and sensitivity and give appropriate ABs
How do you treat an immune-mediated process in the liver?
Prednisolone +/- azathioprine
How do you treat liver fibrosis?
Prednisolone +/- alter the diet/ give UDCA (modulates immune response)
How do you treat copper accumulation?
Penicillamine, trientine, zinc
Give some complications of liver disease
Hepatic encephalopathy and coma
Ascites and oedema
Haemorrhage and anaemia
How can we treat ascites and oedema caused by liver disease?
Low sodium diet
Diuretics (spironolactone)
Paracentesis (only drain a minimal volume, as can worsen bodywide protein status)
Which two liver leakage enzymes indicate hepatocellular damage?
ALT (largely liver-specific)
AST (not liver-specific; also to muscle)
How would you identify cholestasis on cytology?
Presence of dark green-black granular pigment between hepatocytes
What in unconjugated bilirubin bound to in the blood?
Albumin
Which haematology changes might you see with liver disease?
Microcytosis (PPS or severe liver insufficiency, likely due to altered iron transport/metabolism)
Ovalocytes/elliptocytes (cats with hepatic lipidosis)
Acanthocytes (spiked cell membrane; lipid disorders, disruption of normal vasculature)
What may you see on a urinalysis of a pet with liver disease?
Isosthenuria or low SG
Bilirubinuria (>2 in dogs, any in cats)
Ammonium biurate crystals or uroliths (40-70% of patients with PSS)
