Diseases of the Liver Flashcards
Where does the majority of the liver’s blood supply come from?
80% of it’s blood comes from the portal vein and 20% comes from the hepatic artery.
What are our indicators of liver damage?
Enzymes and bilirubin
What are our indicators of liver function?
Bile acids, ammonia, urea (BUN), glucose, albumin, coagulation factors
How do we classify acute liver injury based on ALT?
1-3 x reference= mild
3-5 x reference= moderate
5 + x reference= severe
Where does ALT live within a hepatocyte?
cytosol
Where does AST live within a hepatocyte?
mitochondria and cytosol
If we saw 3-5 x increase in both ALT and AST on blood work, what should we be thinking?
severe liver injury, probably due to necrosis
If we saw a 5 x increase in AST and only a 2 x increase in ALT on blood work, what should we be thinking?
muscle injury due to the fact AST comes mostly from muscle
What is the half life of ALT?
56 hours
What is the half life of AST?
12 hours
Increases in ALKP and GGT indicate what?
Cholestasis
What is the half life of ALKP?
77 hrs in the dog, 6 hrs in the cat (ALKP is highly specific for liver disease in the cat for this reason)
What is the half life of GGT?
80 hrs in the dog
What else can cause increases in ALKP?
Intestines, kidneys, placenta, bones (increases seen in young growing dogs, but neoplasia can cause this too), drugs (corticosteroids, phenobarbitol), endocrinopathies (Cushing’s, Diabetes, Hypothyroidism, etc)
Where does bilirubin come from?
Liberated from RBCs and transported to the liver. Stored in the gallbladder. Conjugated and excreted via the bile ducts.
Bilirubin is broken down to what in the intestines?
Urobilinogen
If an animal is jaundiced, what can you safely assume?
Confirms liver disease, you do not have to run a bile acids test.
What are the 3 types of jaundice?
- Pre-hepatic (hemolysis like from IMHA)
- Hepatic (liver disorder resulting in intrahepatic bile duct occlusion)
- Post-hepatic (obstruction of common bile duct and gallbladder, ex: pancreatitis and EHBO [extra hepatic biliary obstruction])
How could you rule in whether the jaundice is pre-hepatic?
Decreased PCV or RBCs
How could you rule in whether the jaundice was post-hepatic?
Ultrasound to look for an obstruction
Pancreatic assessment ( snap cPL)
Increased cholesterol
Potential surgical emergency
How could you rule in whether the jaundice was hepatic?
You’d need to rule out pre and post hepatic and consider a liver biopsy. Look at your indicators of liver function: is there hypoalbuminemia?, hypoglycemia?, prolonged PT/PTT?, low BUN? If so we can suspect liver failure.
What is the Bile Acid Stimulation Test good for?
Most specific marker of liver function.
What is the bile acid stim test not good for?
Hepatic and Post-hepatic jaundice
How would you perform a bile acid stimulation test?
- Pull a pre-prandial sample
- Feed a high fat meal like Hill’s A/D
- Pull a post-prandial sample 2 hours later
What are the normal results for a bile acid stimulation test?
Normal Pre <10 umol/L
Normal Post <20 umol/L
When would you see a severe increase in the post-prandial sample?
Acquired or congenital PSS (shunts) (>100 umol/L) 97% sensitive, diffuse parenchymal hepatic disease (failure or cirrhosis) 76% sensitive, biliary stasis, (*MILD increases seen with Cushing’s, Diabetes, and other diseases).
What is a resting ammonia level good to check for?
Hepatic encephalopathy, very sensitive for hepatic parenchymal diseases, can detect chronic hepatitis with more confidence.
Where is ammonia generated?
GI tract
If you have excess ammonia in your blood what could it mean?
Failure of the liver to detoxify into urea or you could have a PSS.
You can get hypoalbuminemia with
33
In dogs, why can you get hypoglycemia related to liver issues?
- PSS
- Fulminant failure
- Young/Toy breeds
What types of crystals would you see in urine with a PSS?
Urate crystals
If you had prolonged clotting times in a patient you knew had liver disease, what could you do for the animal?
Plasma or Vitamin K
~Even if clotting times normal, some people still give Vitamin K (Can give it the day before a liver biopsy)
How would you FNA the liver?
23g 1 inch needle using US guidance with light sedation.
When an animal has ascites it is important that you qualify what that means. What are the 4 different major types of fluid?
- Transudate
~Protein <2.5 g/dL, Cell count <1000 cells/mL
~May see mesothelial cells
~Causes: Hypoalbuminemia PLN, PLE, Liver failure/portal hypertension - Modified transudate
~Protein 2.5-7.5 g/dL, Cell Count 1K-5K cells/mL
~Causes: Right sided congestive heart failure, neoplasia, liver disease - Non-septic exudate
~Protein >3 g/dL, Cell count >5000 cells/mL
~neutrophils with no bacteria
~FIP - Septic exudate
~Protein >3 g/dL, Cell count >5000 cells/mL
~Neutrophils with intracellular bacteria
~GI perforation
What is the time duration of acute liver disease?
<2 weeks
What are the 3 subdivisions of acute liver disease?
- Single cell necrosis
- Acute hepatic failure
- Fulminant hepatic failure
What is single cell necrosis?
Isolate cells are damaged, usually subclinically or clinically silent, enzyme increases present on routine analysis.
What is acute hepatic failure?
Widespread necrosis, could be subclinical.
What are the clinical signs of acute hepatic failure?
Mental dullness, vomiting, PU/PD (this can be from decreased BUN in the interstitial space, Central Diabetes Insipidus, Psychogenic polydipsia), possible icterus, anorexia.
What will our lab work look like with acute hepatic failure?
Increases in ALT, ALP and bilirubin might be increased, liver function might be maintained (ie: bile acids, ammonia may be normal, etc)
What is fulminant hepatic failure?
Massive necrosis, animal will be clinical.
What are the clinical signs of fulminant hepatic failure?
Anorexia, vomiting, diarrhea, mental dullness, hepatic encephalopathy, seizures, bleeding disorders, icterus, hepatomegaly (on x-rays or US).
What will our lab work look like with fulminant hepatic failure?
ALT markedly increased, ALP increase follows, Bilirubin increased, liver function tests fail
If you measured an ammonia level and it showed ammonia levels of 50 mmol/L you have a diagnosis of hepatic encephalopathy. What would you use to treat?
Lactulose up the rear end.
Should also give patients FFP (fresh frozen plasma) because they likely will have a coagulopathy as well.
What would a liver look like on US with diffuse disease?
Diffuse hypoechogenecity and hepatomegaly
What is our standard treatment for acute liver disease?
- Treat/remove underlying cause (decontamination) if there is one.
- Fluid therapy (try to avoid any alkalinizing fluids like Ringer’s Lactate or LRS as they may make the situation worse.)
- Glucose (Dextrose) and K+ CRI if needed
- FFP/Blood
- Vitamin K1
- Antiemetics (If using Cerenia/Maropitant, 1/2 the dose due to the fact it is metabolized by the liver.)
- N-acetyl cysteine (used specifically for Tylenol toxicity, an antioxidant)
- sAME (Denamarin)–an antioxidant
- Phosphatidylcholine–for liver repair
- Silymarin (comes from milk thistle)–an antioxidant
What kind of diet would you feed to an animal with acute liver disease?
Liver diet but not always necessary. (Copper deficient, Na+ deficient, more plant based proteins.) Food and proteins are needed for liver regeneration. With hepatic lipidosis, protein nutrition is the most important.
What are some different etiologies of acute liver disease?
- Toxins (Acetominophen, Carprofen, Diazepam, Aflatoxin [a type of mycotoxin produced by Aspergillus, highly toxic and carcinogenic], Sago palm, Amanita mushroom, Blue-Green Algae, Xylitol)
- Metabolic (Lipidosis)
- Infectious (Infectious canine hepatitis, Ehrilichia, Toxoplasmosis, Babesiosis)
- Hypoxia (Vascular injury)
What species, dogs or cats suffers from acute hepatic failure from Tylenol toxicity?
Dogs (because dogs have glutathione, they will survive the initial damage from methemoglobin, and then a few days later will see increases in liver enzymes.)
What are the signs of Tylenol toxicity in a cat?
Facial edema, brown-bloody mucous membranes, methemoglobinemia, Heinz Bodies, Hemolytic anemia
What can you do if an animal ingested Tylenol <6 hrs ago?
Induce emesis
How can you treat Tylenol toxicity?
- N-acetyl cysteine (140 mg/kg q 6 hrs diluted in 5% Dextrose given over 5 minutes and the dose is halved each time.)
- sAME (Denamarin)
- Ascorbic acid (Vitamin C)
- Cimetidine (microsomal p450 inhibitor and prokinetic)
In what breed of dogs would you see a non-dose dependent liver failure that develops with Carprofen?
Labs
How soon would you see a idiosyncratic drug reaction with Carprofen?
14-30 days
How soon would you want to check liver enzymes before going on Carprofen?
2-4 weeks prior
What species is Diazepam toxicity seen in?
Cats usually within 7 days of oral dosing (idiosyncratic reaction)
With Diazepam toxicity you get necrosis of what part of the liver?
Centrilobular necrosis and then progresses to panlobular necrosis. Also effects the muscles and you can get necrosis and death.
What other signs will you get with Diazepam toxicity?
Hypoglycemia, coagulopathy, icterus and ARF (acute renal failure). Death.
How would you treat Diazepam toxicity?
Supportive care, Vitamin K, blood, N-acetyl cysteine
Where do dogs normally get aflatoxin toxicity from?
Contaminated/spoiled dog food or improperly stored food.
What will we see on clin path for dogs with aflatoxicosis?
Liver enzymes often normal, but we will see hypoalbuminemia, bleeding (prolonged PT/PTT), and abdominal effusion.
What is the specific treatment for aflatoxicosis?
Plasma and Vitamin K
With xylitol ingestion what will we see?
Xylitol stimulates the release of insulin and causes profound hypoglycemia within 1 hr. There are markedly elevated liver enzymes within 9-72 hours. (Panlobular necrosis which can progress to fulminant liver failure, which can be fatal). We may also see icterus and bleeding.
What is the #1 plant we worry about animals ingesting in the cycad family?
Sago palm
There is typically a delay in clinical signs after ingestion of sago palm of how long?
24-48 hours
Chinaberry effects what types of animals?
Monogastrics
What is the most important liver disease of cats?
Hepatic lipidosis (there is an imbalance in lipid metabolism, lipid accumulates in hepatocytes, and a subsequent loss in hepatic function.) Hepatocytes swell in centrilobular area, bile ducts swell, intrahepatic cholestasis insues (jaundiced), fat soluble vitamin deficiency develops (Vitamin K included), they become hypokalemic, hypoglycemic.
What is the proposed mechanism by means of which cats develop hepatic lipidosis?
Increased triglyceride deposition associated with starvation due to mobilization of fatty acids from lipid stores.
All cats that get diagnosed with hepatic lipidosis, what else should you be looking for?
An underlying cause (pancreatitis, IBD, kidney disease, hypertyroidism or cancer like lymphoma are all causes.) As soon as you have an endocrinopathy or inflammatory process you have activation and a massive amount of fatty acids delivered to the liver.
What is the typical history on a cat with hepatic lipidosis?
Obese cat with a history of anorexia or partial anorexia. The cat may now be vomiting, have diarrhea or be bleeding. Icterus is often seen.
What types of changes do we expect on blood work with a cat with hepatic lipidosis?
ALP increased with normal or mildly increased ALT and GGT.
What is the treatment for a cat with hepatic lipidosis?
- FEED!!!!! (tube feeding-nasogastric or esophagostomy or parenteral feeding)
- Fluids
- Plasma
- Anti-emetics
- Vitamins K, B complex, E
- L- carnitine [helps burn fat and shuffle it to the mitochondria], Taurine [important for conjugating bile acids], Arginine (essential amino acid) [used for part of the urea cycle pathway].
- SAMe
What types of dogs acquire infectious canine hepatitis?
Young (although can happen at any age), unvaccinated dogs, often seen in more rural areas with poor herd immunity
What are the signs of infectious canine hepatitis?
Vomiting, diarrhea, GI bleeding, cornea edema “blue eye”, uveitis, liver enzymes up (treat symptomatically) .
What is a problematic bacteria that can cause infection in the liver and also other organs like the kidney, lung and eyes.
Leptospirosis (Causes liver abscesses, bacteremia, acute renal failure and lung hemorrhage).
What are the signs of hepatic encephalopathy?
Severe mental dullness, stupor/coma, head pressing, circling, ataxia, disorientation, seizures, in cats (they may just sit there salivating, do not confuse with nausea.)
Hepatic encephalopathy can progress to what?
Cerebral edema and death.
How would you treat hepatic encephalopathy?
Prevent formation of toxic substances from the GIT. (Can sterilize the gut using an antibiotic like Metronidazole at a 1/2 dose or trap ammonia in the intestines by using lactulose as an enema repeated 3x daily.) Give supportive care (fluids, FFP, SAMe, Ursodiol, provide K+ and glucose), treat primary cause if possible. Dietary protein restriction (Hill’s L/D or K/D or a home made diet consisting of vegetables and dairy protein only like cottage cheese.) Start feeding asap frequent small meals.
Chronic hepatitis is not a diagnosis it’s a _______.
Syndrome
Canine chronic liver disease is defined as:
- No improvement 6 months or longer
- Inflammation
- Progresses to fibrosis and cirrhosis
- Causes: viral, bacterial, drugs (Phenobarbital), toxicities, auto immune disease, copper accumulation, idiopathic (cause not found).
- Increased ALT is your clue
Copper associated chronic liver disease is seen most commonly in what dog breeds?
Bedlington Terrier, WHWT, Spaniels, Standard Poodles, Dalmations, Dobermans
What is the normal copper concentration in a dog liver and what is it in a dog with copper associated chronic liver disease?
Normally 400 ppm but can get up to around >1200 ppm in a dog with copper storage diseases. These dogs have problems converting copper into the soluble form into the blood. Copper accumulates in zone 3/centrilobular.
What dogs do we typically see idiopathic hepatic fibrosis in?
Young dogs, especially German Shepherds. They get hepatic fibrosis without inflammation. There is profound lymphoplasmocytic infiltration which can cause a lobular dissecting hepatitis.
What is chronic cholangiohepatitis?
Chronic biliary tree infection.
How would you diagnose a chronic biliary tree infection?
Bile culture, may consider a cholecystecomy in the future. Will have a dyslipidemia (Hypothyroidism or Cushing’s as an underlying cause).
What are some causes of chronic liver disease?
- Vacuolar hepatopathies
- Hepatic fibrosis and cirrhosis 2ndary to inflammation [Ito cells produce collagen into the space of Disse, ECM produced that affects hepatocyte function and sinusoidal blood flow. Can get portal hypertension as a result.]
What are vacuolar hepatopathies?
There is nothing wrong with the liver, other than it’s accumulated vacuoles. Can be due to things like Diabetes, Cushing’s or storage diseases. You’d want to treat the underlying condition.
What is the pathogenesis of chronic liver disesae?
The initial injury is around the portal triads/Zone 1.
To diagnose hepatic fibrosis and cirrhosis how would you?
Need biopsy and special staining to see fibrosis.
What is the clinical picture for a dog with chronic hepatitis?
Middle aged dog with a slight increase in ALT, dog may or may not be in failure so function tests may be normal (ie: albumin, BUN, etc.) Check clotting factors and do a function test (Ammonia tolerance test is the test of choice, but do NOT do this test if pet already has hepatic encephalopathy!!!!) Pet will have microhepatica on x-rays or US, perform a biopsy (tru cut core needle biopsy) to confirm results.
How would you treat chronic hepatitis?
- Treat the underlying cause although it is rarely found. (withdraw drugs, treat infections with antibiotics, copper storage diseases can use chelators like Penicillamine or Zn-gluconate.)
- Protein restricted diet ONLY if the pet is showing signs of hepatic encephalopathy
- With inflammation may treat with Prednisolone or Azathioprine (Imuran–immunosuppressive.)
- If there is fibrosis may treat with Prednisolone or Colchicine (You can aggravate condition esp if root cause is viral.)
- Replace fat and water soluble vitamins
- Antioxidants (Vitamin E, SAMe)
- Ursodiol/Ursotan: changes bile from hydrophobic to hydrophilic. Promotes bile flow, cytoprotective, immunomodulating, antifibrotic.
- Vitmain K, FFP
- For 2ndary ulcers: Proton pump inhibitors, sucralfate, H2 blockers
- For 2ndary infections: Metronidazole at 1/2 dose 7.5 mg/kg BID
- For animals with ascites most likely from portal hypertension (b/c of low oncotic pressures and hypoalbuminemia), abdominocentesis may KILL THEM, only draw off a small amount of fluid if they are tachypneic, otherwise don’t. You can give Spirinolactone 2 mg/kg/day and titrate every 14 days then add Furosemide 1-2 mg/kg/day. Monitor the patient by measuring around it’s girth at around L2 vertebra.
- Once stable consider a low Na+ diet.
What is feline inflammatory liver disease (ILD)?
There are 3 types
- ) Suppurative cholangitis
- ) Lymphocytic cholangitis
- ) Lymphocytic portal hepatitis (flukes)
In cats it is common for them to get hepatitis as a triad, what are the other 2 disease processes that they get?
Pancreatitis and inflammatory bowel disease (IBD)
If you wanted to diagnose a suppurative cholangitis in cats, what would you do?
Culture cat livers and bile
With cholangitis in a cat, what would the CBD (common bile duct) look like?
Anechoic and tortuous, 2-4 mm in diameter with echogenic walls.
What types of cats are affected by suppurative cholangitis or cholangiohepatitis?
Middle aged to older cats. These cats are severely ill with abdominal pain, fever and jaundiced and may appear like they have hepatic lipidosis.
On cytology of a cat with suppurative cholangitis/cholangiohepatitis what would you see?
Neutrophilic infiltrate into the periportal area that leads to hepatic necrosis.
On clin path what can you appreciate with cats that have suppurative cholangitis/cholangiohepatitis?
Bilirubin, ALT, ALP and GGT increased.
Neutrophilic left shift
How would you treat a cat with suppurative cholangitis/cholangiohepatitis?
- Antibiotics (4 quadrant coverage typically)
~some sort of Penicillin (Amoxicillin Clavulanic Acid) or Cephalosporin or Fluroquinolone (Pradofloxacin, not Enrofloxacin!) for gram negatives in combo WITH Metronidazole for anaerobes. - Supportive care- IV fluids
- Vitamin K, SAMe (Denamarin), UDCA (Ursodiol)
What might you see on an US of a cat with suppurative cholangitis/cholangiohepatitis?
Hyperechoic liver, biliary stasis, gallbladder thickening, inspissation and choleliths.
What kinds of cats will we typically see lymphocytic cholangitis in?
Geriatric Persians in North America
What are the clinical signs of lymphocytic cholangitis?
Jaundice, and ascites
May still be eating
Hepatomegaly and lymphadomegaly
What can you appreciate on clin path with cats that have lymphocytic cholangitis?
ALT, ALP, GGT increased
Hyperglobulinemia
Lymphopenia (Stress leukogram)
How would you diagnose lymphocytic cholangitis?
Histopathology
How would you treat lymphocytic cholangitis?
- Prednisolone/vs Chlorambucil (spares them from developing Diabetes)/vs Methotrexate
- Antibiotics?
- UCDA (Ursodiol)
- SAMe (Denamarin)
- Colchicine?
- Diuretics?
What will you see clinically with hepatocutaneous syndrome?
Ulcerations, erosions, alopecia of the face, ears, mucocutaneous junctions, feet, ventrum.
What would you see on an abdominal ultrasound with hepatocutaneous syndrome?
Swiss cheese liver–hyperechoic network surrounding hypoechoic areas.
How would you treat hepatocutaneous syndrome?
IV amino acids + electrolytes (Aminosyn), egg yolk, Vitamin E, zinc, omega 3 fatty acids
POOR PROGNOSIS
What would you see on clin path with hepatocutaneous syndrome?
Hypoalbuminemia, hypoaminoacidemia
What is the function of bile?
- Digestion and absorption of fat
2. Excretion of cholesterol and bilirubin
How are soluble bile salts formed?
Cholesterol is turned into cholic acid and chenodeoxycholic acid. Each of those via taurine and glycine are turned into glycol and tauro- conjugated bile acids (soluble). If there is any change in the ability of hepatocytes to conjugate bile salts they become insoluble (hydrophobic) so we start developing issues with cholestatic disease. As soon as they become hydrophobic we see increases in ALP, GGT.
What is the most important neuroendocrine hormone that is released by the duodenum as well as the antral pylorus that moves through the portal vasculature and drained by the liver that tells the gallbladder to contract.
CCK (Cholecystokinin)
What is EHBO (Extrahepatic biliary obstruction)?
The obstruction of the flow of bile from the gallbladder into the duodenum. Hallmark clinical sign is icterus.
What are some causes for EHBO?
- Stricture (has to do with the duct itself)
- Intraluminal obstruction (stone “cholelithiasis” or sludge from mucocele that slipped through)
- Extrinsic compression (pancreatitis, neoplasia, trauma, peritonitis, bile duct inflammation)
What is the most common cause of EHBO in a dog?
Pancreatitis (edema, inflammation and fibrosis)
What is the most common cause of EHBO in cats?
Tumors and inflammatory disease (FIP) of biliary tract, pancreas or both.
What are the clinical signs of EHBO?
Icterus, vomiting, anorexia, mental dullness, acholic feces (clay colored feces, lack of bile salts that give stools their brown pigment), fever, abdominal pain, dehydration, hepatomegaly.
What might you appreciate on clin path in animal with EHBO?
Increased bilirubin, ALP/GGT (1000-3000), and cholesterol. Neutrophilia.
What might you appreciate on imaging in a patient with EHBO?
Radiographs my reveal choleliths.
US may show distended gall bladder and dilated tortuous bile duct, gall bladder wall thickening. Retrograde dilation of the common bile duct and gall bladder and a tortuous common bile duct. Appears as if there are too many tubes due to dilation of the hepatic ducts. “Octopus liver”
How would you treat EHBO?
- Supportive care- fluid therapy, electrolytes with Vitamin K
- Surgery if there is obstruction or rupture of GB.
- +/- antibiotics
What is cholecystitis?
Inflammation of gall bladder which could become necrotic.
What are the 3 classes of necrotizing cholecystitis?
Class 1: No rupture
Class 2: Bile peritonitis
Class 3: Omental adhesions
Bacterial infections may progress to cholecystitis due to what type of bacteria?
E. coli and possibly Clostridium
