Investigating Canine & Feline Liver Disease Flashcards
how many lobes does the liver have
six lobes
what is the blood supply to the liver
dual blood supply
25% hepatic artery
75% portal vein (carries blood from GIT, GB, pancreas & spleen to the liver)
what are the functions of hepatocytes
metabolic and detoxifying functions
what are the functions of the liver (9)
- metabolism carbohydrates (glycogenesis, glycogenolysis, gluconeogenesis)
- bile acid synthesis and secretion
- storage of minerals (Fe, Cu) and vitamins
- metabolism lipids
- immune functions
- makes albumin
- production of coagulation factors
- drug metabolism and excretion
- production of urea from ammonia
when does liver failure occur
until >70% functional capacity is lost
hepatic injury must be considerable
chronic and recurrent
what is the biliary system
branched structure that transports bile from each individual hepatocytes
where does the biliary system connect to
duodenum by common bile duct
what is the anatomic difference in pancreatic duct in cats vs dogs
dogs have a separate duct where cats have pancreatic duct that joins with common bile duct
what are the functions of the bile
emulsifies fat
neutralizes acid
what is a secondary (or ‘reactive’) hepatopathy
non specific reaction by hepatocytes to disorders other than primary hepatobiliary diseases
more common than primary
what are the signs of a secondary hepatopathy
increased liver enzymes
+/- ultrasound changes
+/- histopathology changes
what are the categories of secondary hepatopathies (7)
- hypoxia/hypotension
- non hepatic inflammatory diseases
- drugs (dogs)
- endocrinopathies
- metastatic neoplasia
- right sided CHF
- pericardial effusion
what are hypoxic/hypotension changes that can cause secondary hepatopathies (4)
- shock
- surgery
- seizures
- anemia
what are non hepatic inflammatory diseases changes that can cause secondary hepatopathies (4)
- GI disease
- pancreatitis
- sepsis
- toxemia
what drugs can cause secondary hepatopathies (2)
- glucocorticoids
- phenobarbital
what endocrinopathies can cause secondary hepatopathies (6)
- cushings
- addisons
- diabetes mellitus
- hyperthyroidism (cats)
- hypothyroidism (dogs)
- hyperlipidemia (min schnauzers)
what are the clinical signs of secondary hepatopathies
extermely variable
none are pathognomonic for liver disease
anorexia, depression/lethargy, polyuria/polydipsia, vomiting/diarrhea, weight loss
jaundice, ascites, alerations in liver size, coagulopathies, hepatocutaneous syndromes (dogs),
hepatic encephalopathy, altered mentation, circling, headpressing, pytalasim (cats), coma (rare)
what are breeds associated with chronic hepatitis (4)
- springer spaniels
- dobermanns
- cocker spaniels
- labradors
what breeds are associated with copper storage disease (2)
- bedlington terriers
- labs (USA)
what breeds are associated with gall bladder mucoceles (2)
- shetland sheepdogs
- border terriers
what is the signalment for feline hepatic lipidosis
middle aged overweight cats with recent history of anorexia
what abnormalities are common in young ages (2)
- portosystemic shunts
- portal vein hypoplasia
what are history questions to ask (4)
- acute or chronic problem
- try to differentiate between primary or secondary problem
- toxin exposure/current meds?
- vaccination status (Leptospirosis, CAV-1)
what history questions would differentiate between a chronic and acute liver disease (6)
- healthy until recently? acute
- recent toxin exposure? acute
- drug administration? acute
- often weeks/months of non-specific signs - chronic
- often no clinical signs - chronic
- possible weight loss - chronic
what would be seen on a clinical exam with acute liver disease (3)
- fever
- dehydration
- cranial abdominal pain
what would be seen with clinical pathology with acute liver disease
marked increase in ALT and AST
what could be seen on clinical exam with chronic liver disease
poor body condition
what clinical pathology changes can be seen in chronic liver disease (2)
- persistent increase in liver enzymes
- +/- hypoalbuminemia
what are chronic liver diseases in dogs
what are chronic liver diseases in cats
what are hepatotoxic drugs (7)
- NSAIDs
- paracetamol (cats)
- azathioprine
- TMPS antibiotics (dogs)
- diazepam (cats)
- lomustine
- carbimazole/methimazole
what are infectious causes of acute hepatic disease (4)
- leptospirosis
- CAV-1
- clostridium spp
- acute neutrophilic cholangitis (cats)
what are metabolic causes of acute hepatic disease
- hepatic lipidosis (cats)
what are toxins that can cause acute hepatic disease (4)
- xylitol (chewing gum)
- mycotoxins, alfatoxicosis
- amanita mushrooms
- cyanobacteria – microcystin toxicosis (blue green algae)
what are neoplasia’s that can cause acute hepatic disease
- diffuse infiltration (lymphoma)
what are biochem indicators of liver damage (2)
1. ALT: alanine aminotransferase
2. AST: aspartate transaminase
what are biochem indicators of cholestasis (3)
1. ALP: alkaline phosphatase
2. GGT: Gamma-glutamyl transferase
3. bilirubin
what is cholestasis
the flow of bile from your liver is reduced or blocked
what are biochem indicators of liver function (7)
- bile acids
- ammonia
- bilirubin
- glucose
- urea
- albumin
- cholesterol
what do hepatocellular leakage enzymes tell you
indicate hepatocellular membrane damage
what are hepatocellular leakage enzymes
1. ALT: alanine aminotransferase
2. AST: aspartate aminotransferase
where is ALT found in the hepatocyte
in the cytosol
where is AST found in the hepatocyte
mitochondria and the cytosol
why is AST less specific than ALT to hepatocellular damage
because AST is also found in skeletal muscle, cardiac myocytes and kidneys
what occurs if AST > ALT
check CK and troponins
need further investigations
what is the half life of ALT in dogs
60 hours
what is the half life of ALT in cats
3-4 hours
what is the half life of AST in dogs
22 hours
what is the half life of AST in cats
77 minutes
following an injury which enzmye ALT or AST is likely to increase first
ALT increases in the first 12 hours and peaks 1-2 days and takes about 2-3 weeks to return to reference intervals
AST release is later at about 24 hours and the magnitude is usually less and it returns to reference intervals around 48 hours
what are membrane bound markers
ALP
GGT
where are membrane bound markers found
membrane bound location at bile canalicular surface
what does an increase in membrane bound markers indicate
increased enzyme production stimulated by impaired bile flow (“cholestasis”)
what is the half life of ALP in dogs
77 hours
what is the half life of ALP in cats
6 hours
at what time following an injury do ALP and GGT increase
ALP increases at around 4.5 days
GGT increases at around 7 days
why is ALP the least specific marker
because there are other isoforms of it
where are ALP isoforms found (2)
- bone: osteoblasts, young growing animals, bone neoplasia
- steroid induced (dogs): exogenous (topical or systemic corticosteroid meds), endogenous (cushings disease)
which is the more specific membrane bound marker ALP or GGT
GGT
what is the problem with GGT as a membrane bound marker
it is more specific than ALP but it is less sensitive
it is not always increased
if you have a patient with no clinical signs but there is an elevation in liver enzymes what should you do
progressive monitoring important as function may not be abnormal until advanced disease
monitor every 2-4 weeks following an acute insult
may take months for a full recovery
be aware of high risks groups (dobermann, springer spaniels)
can the severity of increase in liver enzymes give you an indication of prognosis
no they cannot
does liver damage equal liver dysfunction
no
what is the primary source of bilirubin
RBCs
how is bilirubin metabolized
transported to the liver and conjugated, secreted into bile and then stored in the gall bladder and excreted via the bile ducts
what are the categories of jaundice
- pre hepatic
- hepatic
- post hepatic
what are causes of pre hepatic jaundice
hemolysis of red blood cells ex. hemolytic anemia
increased production exceeds capacity of hepatic excretion
what are causes of hepatic jaundice (3)
- abnormal uptake
- defective conjugation
- abnomral excretion of bilirubin by hepatocytes
what are causes of post hepatic jaundice (3)
- impaired excretion of bilirubin
- obstruction of common bile duct or gall bladder (ex. pancreatitis, neoplasia, choleliths, cholecystitis)
- bile duct rupture
how would you determine if the cause of jaundice is pre hepatic
look at PCV
how would you determine if the cause of jaundice is post hepatic (4)
- ALP, GGT > ALT, AST
- hypercholesterolemia?
- ultrasound biliary system assess for obstruction of bile duct, GB rupture
- pancreatic assessment (cPLI)
how do you determine if the cause of jaundice is hepatic
rule out pre and post hepatic etiology
consider biopsy
where is albumin synthesized
liver
what is the half life of albumin
1-3 weeks
how long does it take for significant decreases of albumin to occur
this develops very slowly
at what % of liver function can hypoalbuminemia occur
30% liver function
at what point would ascites occur
with significant hypoalbuminemia <15 g/l
why does ascites occur with hypoalbuminemia
albumin is a major source of plasma colloid osmotic pressure
what are other causes of hypoalbuminemia besides decreased liver production (2)
- gastrointestinal: protein losing enteropathy
- renal loss: protein losing nephropathy
what are the sources of cholesterol
in the diet and made in the liver
what is the major excretory pathway of cholesterol
bile
what does hypocholestermia indicate
liver failure
what does hypercholestermia indicate
- extrahepatic bile duct obstruction
- intrahepatic cholestatic disease
- marked hepatic regeneration
where is urea produced
synthesized by hepatocytes from ammonia generated by catabolism of amino acids
how is urea excreted
kidneys
why does urea decrease with severe liver dysfunction
due to failure to convert ammonia to urea
what other reasons beside failure to convert ammonia to urea can urea be decreased (3)
- decreased protein intake
- protein anabolism
- PUPD
where is blood glucose derived from (2)
- glycogenolysis: breakdown of glycogen in the liver
- gluconeogenesis: production of glucose from amino acid precursors in the liver
what other causes are there for hypoglycemia (6)
- hypoadrenocortism (addison’s)
- sepsis
- paraneoplastic
- insulinoma
- young/small toy breeds
- xylitol toxicity
what % of hepatic function would hypoglycemia be seen
severe hepatic compromise
<30% function
not common
what are the most specific test of liver dysfunction
bile acids
describe how bile acids are synthesized (6)
- synthesized from cholesterol and stored in the liver
- ingestion of food stimulates a gall bladder contraction to help absorb fats
- secreted into the duodenum
- 95% reabsorbed by the ileum
- enter the portal circulation
- enter the liver
what are 3 reasons why bile acids may be abnormally high
- reduction in hepatocellular mass
- impaired hepatocyte function
- distubred enterohepatic circulation (portal blood flow to liver or obstruction of biliary flow from liver)
what are ddx of high bile acids (3)
- portosystemic shunt
- diffuse hepatic disease
- biliary stasis
what is normal bile acid level pre prandial
0-10 umol/l
what is normal bile acid level 2 hours post prandial
0-20 umol/l
how is the bile acid stimulation test work
sensitivity improves measuring a pre prandial sample (starve patient 12 hours before measuring)
feeding causes gall bladder to contract and releases bile acids
what do bile acids not tell you (4)
- no information about reversibility of conditions
- doesn’t determine specific etiology
- not helpful in differentiating a hepatic from a post hepatic jaundice
why do bile acids not differentiate between a hepatic or post hepatic jaundice
bile acid increase occurs prior to jaundice in hepatobillary disease
don’t run if jaundice
what occurs if bile acids are higher in the pre sample vs the post sample (3)
- gall bladder contracted just prior to the pre sample
- delayed gastric emptying
- lab error
interpret the higher of the two results
what breed can have high bile acids
maltese
but also a breed that can get portosystemic shunts
describe the ammonia cycle (3)
- endogenous NH3 enters the liver and enters the urea cycle
- converted to urea by liver
- excreted by the kidneys or enters the colon where it is converted to NH4+
what are the causes of hyperammonia (3)
- abrnomal portal blood flow
- hepatic dysfunction
- urea cycle abnormality
what coagulation factors does the liver produce
all of them except for VIII and vWF
what % of coagulation factor depletion is needed for prolonged clotting times
>%70
what can radiography evaluate
- liver shape and size
- choleliths
unhelpful with ascites
what is ultrasound useful for (3)
- assessment of hepatic parenchyma, portal vein branches
- assessment of biliary tract – investigations post hepatic jaundice
- identify and sample nodules, massess, abdominal effusions
what does ascites cause (4)
- imbalance in starlings laws (decreased oncotic pressure –> hypoalbuminemia, increased hydrostatic pressure –> portal hypertension)
- leakage from organs (bile)
- inflammation (peritonitis)
- leakage from vessels (blood)
what is portal hypertension
high blood pressure in the hepatic portal system
what are the consequences of portal hypertension (4)
- ascites
- hepatic encephalopathy
- multiple acquired shunting
- gastrointestinal ulceration
what os post hepatic portal hypertension
the caudal vena cava
what are the types of hepatic portal hypertension
- post sinusoidal: central vein
- sinusoidal: sinusoid
- pre sinusoid: portal vein
what is pre hepatic portal hypertension
portal vein
if the ascitic fluid is low protein transudate what could the site of origin of portal hypertension be (3)
- pre hepatic
- intra hepatic
- pre sinusoidal
what are common causes of a low protein transudate (3)
- ligation of portosystemic shunts
- portal vein thrombosis
- portal vein hypoplasia
if the ascitic fluid is high protein transudate what could the site of origin of portal hypertension be (4)
- post hepatic
- intra hepatic
- post sinusoidal
- sinusoidal intrahepatic
what are causes of high protein transudates (2)
- chronic hepatitis
- right sided failure
dif you have a low protein transudate what should you check
check serum albumin –> if that is low you need to rule out GI (PLE) or a kidney loss (PLN)
if it is normal –> then it is due to portal hypertension
if the transudate is high in protein what type of portal hypertension is this and why
its post sinusoidal
somewhere between the hepatic sinusoids and the heart –> the fluid is higher in protein because the sinusoids in the liver are lined with fenestrated endothelial and are permeable to albumin
what should you do before you decide to do a liver biopsy
check coagulation times and platelet numbers
if they are prolonged give plasma or vitamin K
monitor for signs of hemorrhage (RR, HR, mucus membranes)
what are the pros of a FNA biopsy (5)
- minimally invasive
- little equipment
- sedation
- useful for lymphoma, mast cell tumours, and hepatic lipidosis
- bile samples
what are the cons of a FNA biopsy (4)
- accuracy of cytology limited (30-50% agreement with histology)
- doesn’t evaluate hepatic architechture
- only cells that exfoilate
- iatrogenic damage gall bladder
what size of needle is used for a FNA biopsy
23g
what are the pros of using a cutting needle biopsy (3)
- larger sample size allows exam of hepatic architecture
- avoids laparotomy
- sample focal disease
what are the cons of using a cutting needle biopsy (5)
- general anesthesia
- specialist equipment
- less accurate than surgical biopsies
- difficult with small livers or ascites
- hemorrhage
what are the pros of a surgical biopsy (3)
- better diagnostic samples: larger sample allows better exam of hepatic architecture
- can get samples from multiple liver lobes and bile aspirate
- can visualize hemorrhage
what are the cons of surgical biopsy (3)
- general anesthesia
- more invasive procedure
- risk of hemorrhage
what are the clinical signs of biliary disease
non specific
+/- jaundice
+/- pale white feces
what biochem changes can be seen with biliary disease (3)
- increase cholestatic liver enzymes: ALP, GGT > ALT, AST
- increase in cholesterol
- increase in bilirubin
what are examples of biliary disease (5)
- pancreatitis obstructing common bile duct
- cholecystitis
- gall bladder mucocele (dogs)
- neoplasia: biliary carcinoma/adenoma (cats)
- cholelithiasis (dogs > cats)
what is gall bladder mucocele
distention of gallbladder by an innappropriate accumulation of mucus
thick gelatinuous bile within gall bladder
what will the gall bladder look like on US with gall bladder mucocele
kiwi appearance
what secondary diseases should you check for if you suspect gall bladder mucocele
hypothyroidism
cushings
what breed is gall bladder mucocele
shetland sheep dog (sheltie)
how is gall bladder mucocele treated
surgical cholecystectomy required
what is bile peritonitis
inflammatory response of the lining of the abdominal cavity to the presence of free bile
what are the causes of bile peritonitis (5)
- trauma
- chronic inflammation
- obstructive lesions (cholelithiasis)
- neoplasia
- ruptured mucocele
how would bile peritonitis present
- emergency
- signs of sepsis
- abdominal pain
- ascites
what would the fluid look like in bile peritonitis
yellow/brown
measure bilirubin (>2x serum)
how would you treat bile peritonitis
ex lap
consider referral
what is chronic hepatitis
inflammation of hepatic parenchyma
what are the breed related forms of chronic hepatitis
- lab
- english springer spaniel
- cocker spaniels
- dobermans
what are indicators of poor prognosis with chronic hepatitis (3)
- ascites
- jaundice
- hepatic encephalopathy
how is chronic hepatitis treated
immunosuppressives
what is cholangitis
inflammation of the biliary duct
what is commonly seen with cholangitis in cats
triaditis
duodenitis, pancreatitis, cholangitis
what are the histological classifcations of cholangitis (4)
- neutrophilic cholangitis
- lymphocytic cholangitis
- chronic cholangitis due to liver fluke (tropical, subtropical climates)
- destructive cholangitis (uncommon, dogs)
how is cholangitis diagnosed
biopsy
what is neutrophilic cholangitis
suppurative inflammation on histology
what is the signalment of neutrophilic cholangitis
tend to be younger cats
what are the clinical signs of neutrophilic cholangitis
typically systemically unwell
pyrexia
lethargy
jaundice
what is the etiology of neutrophilic cholangitis
ascending infection from intestines –> anatomical problem in cats
E. coli most common
how is neutrophilic cholangitis treated
6-8 weeks of antibiotics
what is lymphocytic cholangitis
suspected immune mediated disease
what is the signalment of lymphocytic cholangitis
most cats are middle aged or older
what are the clinical signs of lymphocytic cholangitis
long course (several weeks to months) of vague illness
systemically well – normothermic
increase in GGT
how do you treat lymphocytic cholangitis
immunosuppressive (steroids)
what is vacuolar hepatopathies
hepatocytes become markedly distended with cystolic glycogen
what is vacuolar hepatopathies associated with (3)
- glucocorticoid administration
- hyperadrenocorticism (cushing’s disease)
- endogenous release of corticosteroids in response to chronic stress, illness, inflammation or neoplasia
what biomarker is often elevated in vacuolar hepatopathies
ALP
what are primary hepatobiliary neoplasias (3)
- biliary adenomas/carcinomas (cats), hepatocellular adenomas/carcinomas (dogs)
- hepatic lymphoma
- hepatic hemangiosarcoma
what are secondary/metastatic hepatobiliary neoplasias (5)
- lymphoma
- leukemia
- mast cell tumour
- histiocytic
- HSA
what is nodular hyperplasia
benign hyperplastic in older dogs
what is increased in nodular hyperplasia
increase in ALP (+/- increase in ALT), diagnosed on biopsy
