hepatobiliary 1 Flashcards
Markers of Liver Disease: Hepatocellular injury
- Alanine transferase (ALT)
- Aspartate aminotransferase (AST)
Markers of Liver Disease: Induced / Cholestasis
A- lkaline phosphatase (ALP)
- Gamma-glutamyl transferase (GGT)
- Bilirubin (stasis - not induced)
Markers of Liver Disease: function
- Synthetic biochemical products
- Bile acids
- Coagulation factors
What are ALT and AST markers for? which is more liver specific? cats vs dogs hald life?
- Markers of hepatocellular injury
- ALT is the most liver specific enzyme
> Muscle and liver enzymes clinically significant in dogs and cats - Half-life shorter in cats vs dogs
is AST always included on liver profiles? why, what can affect it?
- AST another hepatocellular injury marker included on some profiles
- Muscle isoenzyme can affect AST more than ALT
ALP & GGT: where do they come from, mostly? what is one of the strongest stimuli?
- Synthesis & release from biliary tract
> Cholestasis (bile retention) is one of the strongest stimuli
Other sources of ALP, non-liver
- Corticosteroid- and other drug (e.g., antiepileptics) induced (dogs only)
- Bone
- (Renal, GI isoenzymes less clinically relevant in serum)
Elevated bilirubin usually due to:
increased production or decreased excretion of bile pigment
what does bilirubin point to for the liver?
evere liver dysfunction
* Mononuclear phagocytic system cannot process bilirubin
* Increased due to lack of function
is bilirubin elevated due to pre-hepatic, hepatic, or post-hepatic causes?
all
- * Bilirubin can be elevated from pre-hepatic, hepatic, and post-hepatic (i.e., biliary) causes
- Markers of decreased synthetic function:
what are they, when do they become abnormal?
- Decreased albumin
- Decreased cholesterol
- Decreased urea
- Decreased glucose
- These values become abnormal (>55% hepatic mass) in course of liver disease (are not sensitive or specific)
liver markers we can look at
- ALP & GGT
- Bilirubin
- Liver Synthetic Products
> Decreased albumin
> Decreased cholesterol
> Decreased urea
> Decreased glucose - Coagulation profile (PT, PTT)
- Bile acids (pre and post-prandial)
range of slinical signs that can be due to the following liver issues:
Hepatocellular damage ….
Architecture change…
Intrahepatic biliary stasis …
loss of hepatocytes, fibrosis (cirrhosis)
- None
()
Non-specific signs: - Decreased appetite;
- Lethargy;
- Weight loss;
- Vomiting, diarrhea
()
More specific signs: - Icterus (if cholestasis)
Also: - Abdominal pain
- PU/PD
()
Portal hypertension: - Ascites
Failure: - Hepatic
encephalopathy - Coagulopathy
more specific signs of liver damage
- Icterus (if cholestasis)
Also: - Abdominal pain
- PU/PD
Portal hypertension sign
Ascites
liver failure signs
- Hepatic encephalopathy
- Coagulopathy
Gastrointestinal signs can be related to liver problems in these ways
- Vomiting secondary to local inflammation, portal hypertension, encephalopathy
- Liver disease can predispose to GI ulceration (hematemesis, melena)
abdominal pain can be realted to liver problems in these ways
- Liver capsule, biliary epithelium well innervated
- Hepatomegaly (acute liver disease), biliary tract disease can cause pain
Polyuria/polydipsia can be realted to liver problems in these ways:
- Loss of renal medullary concentration gradient if low urea
- Change in osmoreceptors in the liver
- Manifestation of encephalopathy
jaundice point to pre-hepatic, hepatic, or post-hepatic issue?
can by any
pre-hepatic, hepatic, and post hepatic mechisms - which may be present in liver disease? how can we distinguish?
- Hepatic and post-hepatic mechanisms may be present in liver disease
- Ultrasound helpful in distinguishing
ascites realted to liver disease:
more common in dogs or cats? what is it? mechansim?
- Dogs > cats
- Transudate to modified transudate
- Mechanisms:
- Portal hypertension
- Low albumin, decreased oncotic pressure
- Activation of renin angiotensin aldosterone systemàsalt and water accumulation
Physical Exam Findings that we may see in liver disease?
- Jaundice
- Hepatomegaly
- Ascites
> Palpable fluid wave
> Ultrasound (point-of-care AFAST) - PE can be normal*
possible reasons for acute elevation ALT:
- Toxin, drugs
- Infection (leptospirosis, other bacteria or viral)
- Trauma
- Hypoxia
- Secondary to pancreatitis or enteritis
possible reasons for Chronic elevation ALT:
- Ongoing toxin, drugs
- Chronic infection
- Chronic inflammatory disorder
- Secondary to pancreatitis or enteritis
Assessing Liver Enzyme Elevations
* When are these values concerning:
- Any elevation in a cat (short half-lives
of enzymes) - Both ALT and ALP elevation
- > 2x upper limit in a dog
- Persistence
Primary Hepatobiliary Disorders can be put into what 3 main categories
- hepatocellular
- biliary tract
- vascular
hepatocellular types of primary hepatobiliary disorders: (7) which is more common in dog vs cat?
Hepatocellular
* Nodular hyperplasia (aging)
* Chronic hepatitis (dog»_space; cat)
* Toxicity
* Neoplasia
> Hepatoma
> Hepatocellular carcinoma
* Vacuolar hepatopathy
* Infectious
* Cirrhosis (end-stage change)
toxicities that can cause hepatocellular related primary hepatobiliary disorders:
- Mycotoxins (mushrooms, food aflatoxins)
- Xylitol sweetened foods
- Drugs
- Unidentified
infectious causes of hepatocellular related primary hepatobiliary disorders:
- Viral: infectious canine hepatitis
- Bacterial: leptospirosis
- Fungal
- Echinococcus multilocularis
- Parasitic – cuterebra
types of bililary tract primary hepatobiliary disorders (4)? which are more common in dog vs cat?
- Gall bladder mucocele (dog»_space; cat)
- Cholangitis/cholangiohepatitits (cat»_space; dog)
- Neoplasia: bile duct carcinoma
- Extrahepatic bile duct
compression/obstruction
> Pancreatitis
> Neoplasia
> Cholelithiasis
vascular-related primary hepatobiliary disorders? which is more common in dog vs cat?
- Portosystemic shunt (dog > > cat)
- Portal vein hypoplasia without portal
- hypertension (Microvascular dysplasia)
- Neoplasia
- Arteriovenous fistula
Secondary hepatobiliary disorders
- Pancreatitis
- Endocrine
> Diabetes mellitus
> Hyperadrenocorticism: steroid hepatopathy - Hypoxemia
- Trauma
- Systemic infections
- DIC
- Neoplasia
> Lymphoma
> Metastatic neoplasia
> Carcinoid: neuroendocrine tumour - Amyloidosis (Shar-Pei)
possible reasons for Acute elevation ALT:
- Toxin, drugs
- Infection (leptospirosis, other bacteria or viral)
- Trauma
- Hypoxia
- Secondary hepatobiliary disorder
possible reasons for chronic elevation of ALT?
- Ongoing toxin, drugs
- Chronic liver infection
- Chronic liver inflammatory disorder
- Secondary hepatobiliary disorder
- Neoplasia
Chronic Hepatitis - what is it? potential causes?
- Progressive inflammation of the liver
- Potential causes:
> Genetic predisposition
> Previous or unrecognized infection
> Previous toxin exposure
> Immune mediated
Copper Associated Chronic Hepatitis (CuCH) - is it primary or secondary? what can cause it?
Copper accumulation in the liver can be primary or secondary
- Genetic predisposition causes copper deposition, leading to hepatitis
> “Copper storage disease” of “Copper associated chronic hepatitis” (CuCH) - Hepatitis impairs copper excretion, leading to accumulation and further hepatitis
- Normal dogs ingesting massive quantity of copper can have acute hepatitis
Copper Storage Hepatopathy - types, what lesions are associated, and what copper levels?
- Primary Copper Hepatopathy
> Tends to be centrilobular
> Copper quantification levels typically >1000ug/g - Secondary to cholestasis:
> Often located in periportal zone (zone 1)
> Associated with lower copper concentrations (typically <750ug/g)
> Does not typically require chelation
does copper storage hepatopathy secondary to cholestasis typically require chelation?
no
copper storage hepatopathy accounts for what proportion of dogs with primary hepatopathy?
Accounted for 1/3 of all dogs with primary hepatitis in one study
Chronic Hepatitis: Genetic Predispositions, what breeds
- Varies geographically
- North American predispositions:
- Bedlington Terrier
- Doberman (many have CuCH)
- Labrador Retriever (many have CuCH)
- Dalmatian (some have CuCH)
- American & English Cocker Spaniels
- West Highland White Terrier (possible CuCH)
Chronic Hepatitis: Presentation - signalment, duration of disease prior to presentation?
- Mean age 7 years
- Dalmatians, Dobermans, Springers present younger & have female predisposition
- Duration of disease prior to presentation unknown
Chronic Hepatitis: Presentation - clinical signs? subclinical stage? enzymes? signs at presentation depend on what?
- Clinical signs can be absent or non-specific
> Decreased appetite, lethargy most common
> More specific liver signs of icterus, ascites in ~1/3 of patients
> Later stages can have signs of GI ulceration - Long subclinical stage
> ~20% have increased enzymes noted without clinical signs - Variable signs at presentation, related to stage of disease
Chronic Hepatitis: Diagnosis - what is earliest indicator?
- Elevated ALT is earliest indicator
Chronic Hepatitis: Diagnosis - enzyme tests and what they tell us
- Elevated ALT is earliest indicator
- Elevated ALP in later stages
> Typically magnitude of ALT > ALP
> End stage disease with lack of hepatocellular tissue could result in lower ALT - AST & GGT tend to mirror ALT & ALP, respectively
> Less specific
Chronic Hepatitis: Diagnosis - liver function test results and what they tell us
Liver function tests
* Elevated bilirubin in ~50%
* Decreased urea, cholesterol in 40%
* Hypoalbuminemia a late marker of synthetic failure
* Hypoglycemia rare (more common in acute liver failure)
Chronic Hepatitis: Diagnosis - serum bile acids results and when useful
Serum bile acids
* Can be elevated in later stages (not sensitive for early disease)
* Not helpful if bilirubin elevated
Chronic Hepatitis: Diagnosis - SOMETIMES HELPFUL CBC, URINALYSIS, AND PT/PTT RESULTS
Other clinicopathological abnormalities:
* CBCcanshowmildanemia
* Urinalysis can show isosthenuria if PU/PD
* PT/PTT can be prolonged in more advanced stages
Chronic Hepatitis: Diagnosis - RADIOGRAPHS what we may see, and how useful
Abdominal radiographs can show microhepatica, ascites
* Not sensitive
Chronic Hepatitis: Diagnosis - what might we see on ultrasound?
Abdominal ultrasound
* Hyperechoic liver parenchyma, or nodular changes later stages
* Liver often small in more advanced disease
* Allows investigation of alternative diagnoses and complications
> Ascites, thrombosis, portal hypertension, acquired portosystemic shunts
Chronic Hepatitis: Diagnosis - what does true diagnosis require? how to interpret?
- Diagnosis requires biopsy
> Ultrasound guided or surgical - Biopsy interpretation:
> Evaluate for extent & type of inflammation, presence of fibrosis
> Copper quantification
Chronic Hepatitis: Treatment - therapeutic targets and additional treatment targets
Therapeutic targets in CH (liver):
* Inflammation / immune mediated disease
* Fibrosis
* Oxidative injury
* Cholestasis
* Copper accumulation
Additional treatment targets:
* GI ulceration, ascites, coagulopathy
* Hepatic encephalopathy
Anti-inflammatory/immunosuppressive drugs that can be helpful for chronic hepatitis? pros and cons? what are these reserved for?
Prednisone
* Beneficial in some case series
> Quantity of life
> Quality of life
* Potential side effects
* Steroid hepatopathy development (increased ALP)
- Generally reserved for biopsy evidence of inflammation / immune mediated hepatitis
- Can consider alternative immunosuppressives (e.g., cyclosporine)
why is oxidative damage a particular concern for the liver? when might it occur?
Free radicals are normal by-product of aerobic metabolism of liver
* Increased in inflammation and toxicosis
* Hepatic antioxidant systems overwhelmed
liver Oxidative injury - what can we give to help prevent?
- S-adenosylmethionine (SAMe)
> Improves liver glutathione (GSH) levels
> Anti-inflammatory - Silymarin
> Milk thistle extract
> Silybin is major active constituent
> Protective in experimental mushroom poisoning - Vitamin E
- N-Acetylcysteine (IV)
how can cholestasis be damaging to the liver?
Cholestasis: accumulation of bile acids > hydrophobic bile acids are toxic to hepatocytes
Ursodiol - what is its use? how does it work and when should it be avoided?
Used to help in cases of cholestasis
- Synthetic non-toxic hydrophilic bile acid
- Enhances bile flow
- Stimulates excretion of inflammatory produces (copper, leukotrienes, bilirubin)
- Decreases by dilution concentrations of endogenous more toxic bile acids
- Contraindicated in post-hepatic bile duct obstruction
Copper Accumulation in CuCH - dietary reccomendations?
- Lifelong dietary copper restriction
> Diet: Hill’s l/d, Royal Canin Hepatic, homemade.diet
> Protein level of these diets is relatively low and supplementing protein warranted if not encephalopathic
Copper Accumulation in CuCH - if biopsy confirms high copper level, what is reccomended?
Copper chelation when biopsy confirmation that Cu level is high
treatment for biopsy confirmed cases of chronic hepatitis? also with high copper?
- If lymphocytic inflammatory infiltrate
> Prednisone 1-2 mg/kg/day (max at 40 mg), slowly taper once disease status improves - If confirmed high copper levels
> Dietary copper restriction
> D-penicillamine for several months until ALT normalizes (or stabilizes) - Consider serology for leptospirosis
> Or empirical treatment doxycycline for 2 weeks - Antioxidants (often SAMe & milk thistle; Vitamin E is less costly)
- Ursodiol if evidence of cholestasis on biopsy and/or biochemical profile
- Diet (if not CuCH):
> Good quality maintenance diet
> No protein restriction unless encephalopathic
how do we treat a presumptive diagnosis of chronic hepatitis?
- Initial treatment with antioxidants, +/- ursodiol (if cholestasis)
- Consider immunosuppressive trial
> Balanced with risk of complications - Consider serology for leptospirosis
> Or empirical treatment doxycycline for
2 weeks - Copper restricted diet if breed predisposed to CuCH
> Generally not using D-penicillamine without confirmed quantification due to high side effect potential
in a case of chronic hepatits where we see ascites - what should we condier for supportive care?
- We see ascites because RAAS is upregulated
- Consider spironolactone, mild sodium restriction
- Occasional abdominocentesis (to relieve tension, maintain comfort)
in a case of chronic hepatits where we see coagulopathy - what should we consider for supportive care? what kind of coagulopathy will we usually see?
- Typically a “balanced coagulopathy” – spontaneous bleeding uncommon
- Prior to biopsy, vitamin K +/- plasma
in chronic hepatitis, why might we be at an increased risk of GI ulceration? what can GI bleeding exacerbate in this case?
- Portal hypertension, other aspects of liver disease increase risk of ulceration
- GI bleeding exacerbates hepatic encephalopathy
in a case of chronic hepatitis with GI ulceration, what additional supportive care should we consider?
- Weak evidence supportive prophylactic use of gastroprotectants
- Consider sucralfate, omeprazole
in a case of chronic hepatits with a bacterial infection, what type of infection do we expect and what is rarer?
Bacterial infection of parenchyma, primary bacterial cholangiohepatitis rare with CH
supportive care for a case of chronic hepatitis with bacterial infection
- Doxycycline if leptospirosis not ruled out
- Consider antibiotics based on biopsy/ bile culture when available
Chronic Hepatitis: Prognosis
- Progressive disease, hepatic parenchyma lost over time
- Cirrhosis (diffuse fibrosis of liver) at end stage
- Median survival times 561 +/- 268 days in some studies
> Ascites, presence of cirrhosis shorter survival (MST 21 days in some studies)
