hepatobiliary 1 Flashcards
(68 cards)
1
Q
Markers of Liver Disease: Hepatocellular injury
A
- Alanine transferase (ALT)
- Aspartate aminotransferase (AST)
2
Q
Markers of Liver Disease: Induced / Cholestasis
A
A- lkaline phosphatase (ALP)
- Gamma-glutamyl transferase (GGT)
- Bilirubin (stasis - not induced)
3
Q
Markers of Liver Disease: function
A
- Synthetic biochemical products
- Bile acids
- Coagulation factors
4
Q
What are ALT and AST markers for? which is more liver specific? cats vs dogs hald life?
A
- 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
5
Q
is AST always included on liver profiles? why, what can affect it?
A
- AST another hepatocellular injury marker included on some profiles
- Muscle isoenzyme can affect AST more than ALT
6
Q
ALP & GGT: where do they come from, mostly? what is one of the strongest stimuli?
A
- Synthesis & release from biliary tract
> Cholestasis (bile retention) is one of the strongest stimuli
7
Q
Other sources of ALP, non-liver
A
- Corticosteroid- and other drug (e.g., antiepileptics) induced (dogs only)
- Bone
- (Renal, GI isoenzymes less clinically relevant in serum)
8
Q
Elevated bilirubin usually due to:
A
increased production or decreased excretion of bile pigment
9
Q
what does bilirubin point to for the liver?
A
evere liver dysfunction
* Mononuclear phagocytic system cannot process bilirubin
* Increased due to lack of function
10
Q
is bilirubin elevated due to pre-hepatic, hepatic, or post-hepatic causes?
A
all
- * Bilirubin can be elevated from pre-hepatic, hepatic, and post-hepatic (i.e., biliary) causes
11
Q
- Markers of decreased synthetic function:
what are they, when do they become abnormal?
A
- 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)
12
Q
liver markers we can look at
A
- ALP & GGT
- Bilirubin
- Liver Synthetic Products
> Decreased albumin
> Decreased cholesterol
> Decreased urea
> Decreased glucose - Coagulation profile (PT, PTT)
- Bile acids (pre and post-prandial)
13
Q
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)
A
- 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
14
Q
more specific signs of liver damage
A
- Icterus (if cholestasis)
Also: - Abdominal pain
- PU/PD
15
Q
Portal hypertension sign
A
Ascites
16
Q
liver failure signs
A
- Hepatic encephalopathy
- Coagulopathy
17
Q
Gastrointestinal signs can be related to liver problems in these ways
A
- Vomiting secondary to local inflammation, portal hypertension, encephalopathy
- Liver disease can predispose to GI ulceration (hematemesis, melena)
18
Q
abdominal pain can be realted to liver problems in these ways
A
- Liver capsule, biliary epithelium well innervated
- Hepatomegaly (acute liver disease), biliary tract disease can cause pain
19
Q
Polyuria/polydipsia can be realted to liver problems in these ways:
A
- Loss of renal medullary concentration gradient if low urea
- Change in osmoreceptors in the liver
- Manifestation of encephalopathy
20
Q
jaundice point to pre-hepatic, hepatic, or post-hepatic issue?
A
can by any
21
Q
pre-hepatic, hepatic, and post hepatic mechisms - which may be present in liver disease? how can we distinguish?
A
- Hepatic and post-hepatic mechanisms may be present in liver disease
- Ultrasound helpful in distinguishing
22
Q
ascites realted to liver disease:
more common in dogs or cats? what is it? mechansim?
A
- Dogs > cats
- Transudate to modified transudate
- Mechanisms:
- Portal hypertension
- Low albumin, decreased oncotic pressure
- Activation of renin angiotensin aldosterone systemàsalt and water accumulation
23
Q
Physical Exam Findings that we may see in liver disease?
A
- Jaundice
- Hepatomegaly
- Ascites
> Palpable fluid wave
> Ultrasound (point-of-care AFAST) - PE can be normal*
24
Q
possible reasons for acute elevation ALT:
A
- Toxin, drugs
- Infection (leptospirosis, other bacteria or viral)
- Trauma
- Hypoxia
- Secondary to pancreatitis or enteritis
25
possible reasons for Chronic elevation ALT:
* Ongoing toxin, drugs
* Chronic infection
* Chronic inflammatory disorder
* Secondary to pancreatitis or enteritis
26
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
27
Primary Hepatobiliary Disorders can be put into what 3 main categories
- hepatocellular
- biliary tract
- vascular
28
hepatocellular types of primary hepatobiliary disorders: (7) which is more common in dog vs cat?
Hepatocellular
* Nodular hyperplasia (aging)
* **Chronic hepatitis (dog >> cat)**
* Toxicity
* Neoplasia
> Hepatoma
> Hepatocellular carcinoma
* Vacuolar hepatopathy
* Infectious
* Cirrhosis (end-stage change)
29
toxicities that can cause hepatocellular related primary hepatobiliary disorders:
- Mycotoxins (mushrooms, food aflatoxins)
- Xylitol sweetened foods
- Drugs
- Unidentified
30
infectious causes of hepatocellular related primary hepatobiliary disorders:
- Viral: infectious canine hepatitis
- Bacterial: leptospirosis
- Fungal
- Echinococcus multilocularis
- Parasitic – cuterebra
31
types of bililary tract primary hepatobiliary disorders (4)? which are more common in dog vs cat?
* **Gall bladder mucocele (dog >> cat)**
* **Cholangitis/cholangiohepatitits (cat >> dog)**
* Neoplasia: bile duct carcinoma
* Extrahepatic bile duct
compression/obstruction
> Pancreatitis
> Neoplasia
> Cholelithiasis
32
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
33
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)
34
possible reasons for Acute elevation ALT:
* Toxin, drugs
* Infection (leptospirosis, other bacteria or viral)
* Trauma
* Hypoxia
* Secondary hepatobiliary disorder
35
possible reasons for chronic elevation of ALT?
* Ongoing toxin, drugs
* Chronic liver infection
* Chronic liver inflammatory disorder
* Secondary hepatobiliary disorder
* Neoplasia
36
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
37
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
38
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
39
does copper storage hepatopathy secondary to cholestasis typically require chelation?
no
40
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
41
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)
42
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
43
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
44
Chronic Hepatitis: Diagnosis - what is earliest indicator?
* Elevated ALT is earliest indicator
45
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
46
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)
47
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
48
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
49
Chronic Hepatitis: Diagnosis - RADIOGRAPHS what we may see, and how useful
Abdominal radiographs can show microhepatica, ascites
* Not sensitive
50
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
51
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
52
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
53
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)
54
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
55
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)
56
how can cholestasis be damaging to the liver?
Cholestasis: accumulation of bile acids > hydrophobic bile acids are toxic to hepatocytes
57
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
58
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
59
Copper Accumulation in CuCH - if biopsy confirms high copper level, what is reccomended?
Copper chelation when biopsy confirmation that Cu level is high
60
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
61
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
62
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)
63
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
64
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
65
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
66
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
67
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
68
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)
