PATHOLOGY - Hepatobiliary Disease Flashcards
1
Q
What are the three zones of the hepatic lobules?
A
Periportal zone
Midzonal zone
Centrilobular zone
2
Q
Which zone of the hepatic lobules is most vunerable to injury?
A
Centrilobular
3
Q
What is the portal triad?
A
The portal triad consists of a branch of the hepatic artery, branch of the hepatic portal vein, lymphatic vessel and a bile ductile located at the corners of the hepatic lobules
4
Q
Describe the direction of blood flow through the hepatic lobules
A
Blood flows through the hepatic artery and hepatic portal vein through the hepatic sinusoids to the central venule within the hepatic lobules where the blood is drained
5
Q
What are the functions of the liver?
A
Bilirubin metabolism
Bile acid metabolism
Lipid metabolism
Carbohydrate metabolism
Xenobiotic metabolism
Coagulation factor production
Serum protein production
Mineral storage
Urea production
6
Q
What is the biliary system?
A
The biliary system is a branched system which transports bile from each hepatocyte into the bile ducts which come together to form the common bile duct which empties bile into the duodenum
7
Q
How does the anatomy of the biliary system differ between dogs and cats?
A
In cats, the common bile duct combines with the pancreatic duct before entering the duodenum, forming the pancreaticobiliary duct, whereas the pancreatic duct and common bile duct are seperate in dogs
8
Q
What are the functions of bile?
A
Emusifies lipids to allow for absorption of fats and fat soluble vitamins
Excretes bilirubin and excess cholesterol
Neutralises gastric acid
9
Q
What is primary hepatopathy?
A
Primary hepatopathy refers to liver disease which originates in the liver
10
Q
What is secondary hepatopathy?
A
Secondary hepatopathy refers to systemic disease which has secondary effects on the liver
11
Q
What are some of the potential causes of secondary hepatopathy?
A
Hypoxia
Hypotension
Endocrine disease
Drugs
Non-hepatic inflammatory disease
Metastatic neoplasia
Right sided congestive heart failure
Pericardial effusion
12
Q
What are the potential clinical signs of liver disease?
Remember these can be variable and non-specific to liver disease
A
Anorexia
Weight loss
Lethargy
Vomiting
Diarrhoea
Polyuria, polydipsia (PUPD)
Jaundice
Ascites
Alteration in liver size
Clinical signs of a coagulopathy
Clinical signs of hepatocutaneous syndrome
Clinical signs of hepatic encephalopathy
13
Q
What is hepatocutaneous syndrome?
Remember this is very rare
A
Hepatocutaneous syndrome is a disease characterised by degeneration of the skin cells as a consequence of nutritional imbalances resulting from metabolic abnormalities resulting from severe liver dysfunction
14
Q
What are some useful history questions to ask when investigating liver disease?
A
- Are the clinical signs acute or chronic?
- Try to determine if it is a primary or secondary hepatopathy?
- Any exposure to toxins?
- Which medications is the animal currently on?
- Vaccination status?
15
Q
What are some of the most common causes of acute liver disease?
A
Hepatotoxic drugs
Toxins
Infectious disease
Idiopathic
Metabolic disease
16
Q
List some examples of hepatotoxic drugs which can cause acute liver disease
A
NSAIDS
Paracetamol
Azathioprine
Trimethroprim-sulphonamide antibiotics
Antiepileptic drugs
Lomustine
Methimazole/carbimazole
17
Q
List some examples of toxic agents which can cause acute liver disease
A
Xylitol
Mycotoxins
Aflatoxins
Amantia mushrooms
Microcystin (found in blue green algae)
18
Q
List some infectious causes of acute liver disease
A
Leptospirosis
Canine adenovirus 1 (CAV-1)
Bacterial hepatitis
Bacterial cholangitis/cholangiohepatitis
19
Q
Give an example of a metabolic cause of acute liver disease
A
Hepatic lipidosis
20
Q
What are some of the most common causes of chronic hepatobiliary disease in dogs?
A
Chronic hepatitis
Neoplasia
Congenital portosystemic shunts
Portal vein hypoplasia
Copper-associated hepatitis
Chronic progression of acute hepatopathy
21
Q
What are some of the most common causes of chronic hepatobiliary disease in cats?
A
Chronic cholangitis (usually lymphocytic)
Infectious disease (FIP and toxoplasmosis)
Neoplasia
Congenital portosystemic shunts
Hepatic amyloidosis
22
Q
Which diagnostic tests can be done to investigate hepatobiliary disease?
A
Biochemistry
Bile acid stimulation test
Coagulation times
Haematology
Urinalysis
Diagnostic imaging
Liver biopsy/fine needle aspirate (FNA)
23
Q
Which liver enzymes are markers of hepatocellular damage?
A
Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
24
Q
Where is alanine aminotransferase (ALT) located?
A
Alanine aminotransferase (ALT) is located in the hepatic cytosol
25
Where is aspartate aminotransferase (AST) found?
Aspartate aminotransferase (AST) is found in the hepatic cytosol and mitochondria, as well as in skeletal and cardiac muscle
26
Why is AST less specific for liver damage than alanine aminotransferase ALT?
AST is more sensitive but less specific for liver damage than ALT as it is found in other tissues such as the skeletal and cardiac muscle so can increase in response to skeletal and cardiac muscle damage, not just liver damage
27
(T/F) In the presence of liver damage, AST is usually higher than ALT
FALSE. In the presence of liver damage, ALT is usually higher than AST. So, if AST is higher than ALT, this can indicate disease of the cardiac and/or skeletal muscle and warrants further investiagtion using creatine kinase (CK) and cardiac troponin levels
28
Which liver enzymes are markers of cholestasis *(abnormal bile flow)*?
Alkaline phosphatase (ALP)
Gamma glutamyl transferase (GGT)
29
Where is alkaline phosphatase (ALP) located?
Alkaline phosphatase (ALP) is membrane bound to the surface of the bile caniliculi, however, ALP does have isoforms within the bone and there is a steroid-induced ALP isoform
30
Where is gamma glutamyl transferase (GGT) located?
Gamma glutamyl transferase (GGT) is membrane bound to the surface of bile canaliculi
31
Why is ALP less specific for cholestasis than alanine aminotransferase GGT?
ALP is less specific for cholestasis than GGT as there are ALP isoforms elsewhere is the body which can be increased by other disease processes. However, it is important to not that GGT is less sensitive than ALP *(i.e. it can be at normal levels even when there is cholestasis)*
32
How can end stage liver cirrhosis affect liver enzymes?
In end stage liver cirrhosis, damage progresses and fibrotic tissue replaces the hepatocytes, causing ALT and AST levels to either decrease or remain normal even through the liver is severely damaged, as there are so few hepatocytes to release these enzymes
33
What are the main limitations of of liver enzymes for investigating hepatobiliary disease?
Liver enzymes do not assess liver function and thus they provide no information on the degree of liver dysfunction, prognosis or if there is primary or secondary hepatopathy
34
Which parameters are markers of liver function?
Bilirubin
Glucose
Urea
Albumin
Cholesterol
Bile acids
Ammonia
Coagulation factors
35
Which parameters of liver function are not in a standard biochemistry profile?
Bile acids
Ammonia
Coagulation factors
| Remember for coagulation factors you will have to do PT and aPTT
36
How is bilirubin produced and excreted?
Bilirubin is a byproduct of haem breakdown due to haemolysis. When unconjugated bilirubin is released into the bloodstream it binds to albumin which is transported to the liver where it is conjugated and excreted into the bile
37
What is jaundice?
Jaundice is the yellow staining of the tissues due to excessive bilirubin in the bloodstream
38
Where in the body can jaundice be seen?
Mucous membranes
Sclera
Skin
Gingiva
39
What are the three classifications of jaundice?
Pre-hepatic jaundice
Hepatic jaundice
Post-hepatic jaundice
40
What causes pre-hepatic jaundice?
Pre-hepatic jaundice is caused by haemolysis
41
What is a key indicator of pre-hepatic jaundice?
A decreased packed cell volume (PCV) is a key sign of pre-hepatic jaundice
42
What causes hepatic jaundice?
Hepatic jaundice is caused by abnormal uptake of bilirubin into the hepatocytes, abnormal conjugation of bilirubin, or abnormal excretion of bilirubin by the hepatocytes
43
What are key indicators of hepatic jaundice?
To determine if a patient has hepatic jaundice, you have to rule out pre- and post-hepatic jaundice and to get a definitive diagnosis a liver biopsy should be performed
44
What causes post-hepatic jaundice?
Post-hepatic jaundice is caused by impaired excretion of bilirubin in the bile
45
What are key indicators of post-hepatic jaundice?
ALP and GGT being higher than ALT and AST
Hypercholesteraemia
Biliary abnormalities on ultrasound
Increased biomarkers of pancreatitis
46
Why is hypercholesterolaemia an indicator of post-hepatic jaundice?
Cholesterol is excreted within the bile so if there is cholestasis resulting in post-hepatic jaundice, this can cause hypercholesterolaemia
47
Why are increased biomarkers of pancreatitis a potential sign of post-hepatic jaundice?
Increased biomarkers of pancreatitis is a potential sign of post-hepatic jaundice as pancreatitis is a common cause of biliary disease
48
Why are serum glucose, urea, albumin and cholesterol levels indicators of liver dysfunction?
Glucose, urea, abumin and cholesterol are all produced within the liver and thus can decrease in response to liver dysfunction
49
What is the most specific marker of liver dysfunction?
Bile acids
50
Describe normal physiological function of bile acids
Bile acids are synthesised from cholesterol in the hepatocytes and are secreted into the bile and stored in the gallbladder. In response to the ingestion of fats, cholecystokinin (CCK) triggers contraction of the gallbladder to secrete bile into the common bile duct and into the duodenum to emulsify fats for absorption. Bile acids are absorbed back into the bloodstream within the ileum and transported via the portal vein back to the hepatocytes via enterohepatic circulation
## Footnote
Bile acids increase with liver dysfunction as there is impaired reuptake of the bile acids into the hepatocytes when they return from the portal circulation to be recycled
51
What is indicated by increased serum bile acids?
Liver dysfunction
Impaired enterohepatic circulation
52
Which test should you do to assess the level of serum bile acids?
Bile acid stimulation test
53
How do you carry out a bile acid stimulation test?
Starve your patient for 12 hours and take a pre-prandial blood sample. Following this sample, feed your patient and take a post-prandial blood sample two hours after feeding
54
What is the reference range for pre-prandial serum bile acid levels?
0 - 10 μmol/L
55
What is the reference range for post-prandial serum bile acid levels?
0 - 20 μmol/L
56
What level of serum bile acids indicates hepatic dysfunction?
Serum bile acids over 40 μmol/L indicates hepatic dysfunction
57
Which dog breed has abnormally high serum bile acids even with no disease processes?
Bichon Frisé
58
Why should you not do bile acid stimulation tests in jaundiced patients?
It is pointless to do bile acid stimulation tests in jaundiced patients as serum bile acids will increase prior to the patient becoming jaundiced
59
Describe normal physiological excretion of ammonia
Ammonia (NH3) is a waste product produced by dietary protein breakdown by bacteria in the intestines. Ammonia (NH3) is transported via the hepatic portal vein to the liver where it is converted to urea via the urea cycle. The majority of urea is transported to the kidneys where it is excreted into the urine, and the rest of the urea is transported to the colon where it is converted to ammonium (NH4) which is excreted in the faeces
| Remember ammonium cannot be absorbed into the bloodstream
60
What is indicated by hyperammonaemia?
Hepatic dysfunction
Abnormal enterohepatic circulation
Abnormal urea cycle
61
Why are coagulation times indicators of liver dysfunction?
The liver produces all coagulation factors except for factor VII and von willebrands factors, and activates all vitamin K dependent coagulation factors (II, VII, IX and X) as the liver stores fat soluble vitamins *(i.e. vitamin K)*. So, if there is liver dysfunction, this can be indicated by prolonged coagulation times
62
What are potential indicators of hepatobiliary disease on haematology?
Mild anaemia
63
What are potential indicators of hepatobiliary disease on urinalysis?
Low urine specific gravity (USG) if polydipsic
Bilirubinuria
Ammonium urate crystals
64
What can radiography be used to evaluate when investigating hepatobiliary disease?
Radiography can be used to evaluate liver size, shape, position and opacity
65
What can ultrasound be used to evaluate when investigating hepatobiliary disease?
Hepatic parenchyma
Vasculature *(portal veins and hepatic veins)*
Gallbladder
Biliary ducts
Identification and sampling of nodules, masses and abdominal effusions
66
What should you always do prior to doing a liver fine needle aspirate (FNA) or biopsy?
You should always check the coagulation times prior to doing a liver fine needle aspirate (FNA) or biopsy as there is a high risk of haemorrhage. If the coagulation times are prolonged, administer plasma and vitamin K
67
What are the advantages of liver fine needle aspirate (FNA)?
Minimally invasive procedure
Little equipment required
Only requires sedation
Can take bile samples
68
What are the disadvantages of liver fine needle aspirate (FNA)?
Limited accuracy of cytology
Does not evaluate hepatic architecture
Risk of haemorrhage
Risk of gallbladder rupture with bile sampling
69
Which biopsy needle can be used for a liver biopsy?
Tru-cut needle
70
What are the advantages of a tru-cut liver biopsy?
Allows for assessment of hepatic architecture
Does not require a laparotomy
71
What are the disadvantages of a tru-cut liver biopsy?
Required general anaesthetic
Specialist equipment is required
Less accurate than surgical biopsy
Risk of haemorrhage
72
What is a surgical liver biopsy?
A surgical liver biopsy is a wedge biopsy of the liver carried out either laparoscopically or via a laparotomy
73
What are the advantages of a surgical liver biopsy?
Allows for assessment of hepatic architecture
Allows for better diagnostic samples
Allows for sampling of multiple liver lobes
Allows for bile aspirate samples
Can visualise any haemorrhage
74
What are the disadvantages of a surgical liver biopsy?
Requires general anaesthetic
More invasive procedure
Risk of haemorrhage
75
What are the two classfications of congenital portosystemic shunts?
Extrahepatic shunts
Intrahepatic shunts
76
What are the two main forms of congenital extrahepatic shunts?
Porto-caval shunt
Porto-azygos shunt
77
What is a porto-caval shunt?
A porto-caval shunt is the shunting of blood from the hepatic portal vein to the caudal vena cava
78
What is a porto-azygos shunt?
A porto-azygos shunt is the shunting of blood from the hepatic portal vein to the azygos vein
79
Which signalement is more prone to congenital extrahepatic shunts?
Small breed dogs
Cats
80
What is the most common form of a congenital intrahepatic shunt?
Patent ductus venosus
81
Which signalement is more prone to congenital intrahepatic shunts?
Large breed dogs
82
Which dog breeds can inherit congenital shunts?
Maltese
Yorkshire Terrier
Irish Wolfhound
83
What are the clinical signs of congenital shunts?
Failure to thrive
Microhepatica
Hepatic encephalopathy
Polyuria, polydipsia (PUPD)
Vomiting
Diarrhoea
Copper irises *(in cats)*
| Remember this is congenital so the animals will be young
84
Why can patients with congenital shunts present with polyuria, polydipsia (PUPD)?
Patients with congenital portosystemic shunts can present with polyuria and polydipsia (PUPD) due to the development of ammonium urate crystals
85
What is the best form of diagnostic imaging to diagnose congenital postosystemic shunts?
Ultrasound *(will require referral level experience)*
CT angiogram
86
How do you treat congenital portosystemic shunts?
Medical management of clinical signs, including hepatic encephalopathy
Referral surgery
Long term medical management if surgery not feasible
87
What is portal hypoplasia?
Portal hypoplasia is where the microscopic portal blood vessels within the liver are underdeveloped or absent
88
How do you diagnose portal hypoplasia?
Liver biopsy
89
How do you treat portal hypoplasia?
Long term medical management
90
Describe the pathogenesis of acquired portosystemic shunts
Acquired vascular shunts result from chronic liver disease which results in portal vein fibrosis and portal hypertension resulting in the development of compensatory tortuous shunting vessels
91
How do you treat acquired portosystemic shunts?
Long term medical management of clinical signs, including hepatic encephalopathy
92
Which pathogen causes canine infectious hepatitis?
Canine adenovirus 1 (CAV-1)
93
Which signalement is at increased risk of canine infectious hepatitis?
Unvaccinated patients
94
Which tissues does canine adenovirus 1 (CAV-1) have tropism for?
Endothelium
Mesothelium
Hepatocytes
95
What are the clinical signs of canine infectious hepatitis?
Pyrexia
Abdominal pain
Vomiting
Meleana
96
What are the clinical signs of peracute canine infectious hepatitis?
Sudden death with no clinical signs
| This is a rare form of canine infectious hepatitis
97
What is one of the key clinical signs of chronic canine infectious hepatitis?
Coreneal opacity ('blue eye') due to corneal oedema
98
What are the gross pathological features of canine infectious hepatitis?
Petechiation and ecchymoses of mucosal and serosal surfaces
Enlarged, friable, necrotic liver
Fibrin on the liver surface *(due to peritonitis)*
Thickening of the gallbladder
Small quantities of blood tinged ascites
99
What causes the fibrin present on the liver in canine infectious hepatitis?
Canine adenovirus 1 (CAV-1) has tissue tropism for mesothelial cells which make up the peritoneum, resulting in peritonitis and fibrin deposition
100
What is a key gross pathological feature of canine adenovirus 1 (CAV-1) infection?
Thickening of the gall bladder is a key gross pathological feature of canine adenovirus-1 (CAV-1) infection
101
What is the histological appearance of canine infectious hepatitis?
Hepatocellular necrosis
Hepatocellular and endothelial intranuclear inclusion bodies
102
How does hepatocellular necrosis appear on histology?
Eosinophilic, disorganised hepatocytes
103
Which bacteria cause leptospirosis?
Leptospira
104
Which signalement are at increased risk of leptospirosis infection?
Unvaccinated patients
Patients living in areas with a high rodent population
105
How is leptospirosis transmitted?
Leptospirosis is transmitted through contact with infected urine *(often via ingestion of stagnant water)*
106
(T/F) Leptospirosis is a zoonotic disease
TRUE.
107
Which conditons can be caused by leptospirosis?
Acute hepatopathy and/or acute renal injury
108
What are the potential biochemistry changes that can be seen on biochemistry with a leptospirosis infection?
Increased liver enzymes
Hyperbilirubinaemia
Hypoglycaemia
Hyperalbuminaemia
Azotaemia
109
How do you diagnose leptospirosis?
Take a blood sample when the patient presents and do a macroscopic agglutination test (MAT). This will take several days to give you a result so you will have to begin treatment prior to diagnosis. Repeat the test 7 to 14 days later to assess if there has been an increase in antibody levels againts leptospira to confirm your diagnosis
110
How do you treat leptospirosis?
Supportive care
Antibiotics
| Remember to barrier nurse as this is a zoonotic disease
111
Which antibiotics should you use to treat leptospirosis?
Doxycycline
112
What are the potential underlying aetiologies for chronic hepatitis?
Idiopathic *(most common)*
Infectious
Toxic
Copper-associated
113
What is the proposed cause of idiopathic chronic hepatitis?
Autoimmune disease as in chronic hepatitis, the dominating inflammatory cells are T-lymphocytes which infiltrate and cause hepatocellular necrosis and loss which overtime will cause parenchymal collapse and fibrosis
114
How can copper act as a secondary cause of chronic hepatitis?
When there is chronic hepatitis, hepatocytes can aggregate copper resulting in an abnormal accumulation of copper in the hepatocytes and seconday copper induced hepatitis
115
Which dog breeds are prone to chronic hepatitis?
English Springer Spaniels
Cocker Spaniels
Dobermans
Labradors
116
What are the clinical signs of chronic hepatitis?
The clinical signs of chronic hepatitis are very non specific such as lethargy, decreased appetite, vomiting, diarrhoea, weight loss, icterus etc
117
How do you definitively diagnose chronic hepatitis?
Liver biopsy and histopathology
118
What is the histological appearance of chronic hepatitis?
Hepatocellular necrosis in regions of inflammation
Fibrosis
Secondary copper accumulation within hepatocytes
119
How do you treat chronic hepatitis?
Immunosuppressive therapy
Symptomatic management
120
How do you monitor if there is improvement with treatment of chronic hepatitis?
Preferably repeat the liver biopsy however clients often don't opt for this so instead you can repeat haematology and biochemistry *(remember steroids will increase ALP but other liver enzymes should decrease)* and assess if clinical signs are improving
121
Which dog breeds are predisposed to copper-associated hepatopathy?
Bedlington Terrier
West Highland White Terrier
Skye Terrier
Dalmation
Labrador
Dobermann
122
Which dog breed has an autosomal recessive mutation resulting in copper-associated hepatopathy?
Bedlington Terriers have an autosomal recessive mutation of the COMMD1 gene resulting in exon two deletion. This gene has an important role in the biliary excretion of copper, with a mutation in this gene resulting in an abnormal accumulation of copper within the hepatocytes resulting in primary copper-associated hepatopathy
123
What are the clinical signs of copper-associated hepatopathy?
Lethargy
Decreased appetite
Vomiting
Diarrhoea
Weight loss
Icterus
Haemolysis *(only in Bedlington Terriers)*
124
How can you diagnose copper-associated hepatopathy?
Submit a fresh liver biopsy for copper evaluation
Histopathology to determine presence of copper in hepatocytes
125
What level of copper in a fresh liver biopsy is indicative of primary copper-associated hepatopathy?
Over 2000 μg/g
126
What level of copper in a fresh liver biopsy is indicative of secondary copper-associated hepatopathy?
Between 400 - 2000 μg/g
127
Which specific stain should be used to determine the presence of copper in hepatocytes on histology?
Rhodanine stain
128
What is the histological appearance of copper-associated hepatopathy?
Centrilobular hepatitis with macrophages with abundant intracytoplasmic copper
Hepatocellular necrosis
Fibrosis
Intrahepatic cholestasis
129
How do you treat primary copper-associated hepatopathy?
Symptomatic management
Penicillamine
Low copper diet with added zinc *(can use prescription hepatic diet)*
130
What is the mechanism of action of penicillamine when treating copper-associated hepatopathy?
Penicillamine is a chelating agent which binds to copper and transports it to the kidneys for excretion
131
Which second line drug can be used if a patient is not responsive to penicillamine?
Trientine
132
What are the benefits of dietary zinc when managing copper-associated liver disease?
Zinc helps to prevent absorption of copper by the small intestine into the bloodstream where it would usually travel to the liver
133
What are vacuolar hepatopathies?
Vacuolar hepatopathies are characterised by intraplasmocytic accumulations of glycogen and fluid within the hepatocytes resulting in hepatocellular swelling and vacuolation on histology
134
What are the possible causes of vacuolar hepatopathies?
Exogenous steroids
Endogenous steroids
Diabetes mellitus
Neoplasia
135
What are the two classifications of steroid-induced hepatopathy?
Iatrogenic steroid-induced hepatopathy
Endogenous steroid-induced hepatopathy
136
What causes iatrogenic steroid-induced hepatopathy?
Iatrogenic steroid-induced hepatopathy is caused by the sustained administration of corticosteroids
137
What causes endogenous steroid-induced hepatopathy?
Endogenous steroid-induced hepatopathy is caused by hyperadrenocorticism (cushing's disease) which increases the circulating levels of glucocorticoids
138
What changes will be seen on biochemistry for steroid-induced hepatopathy?
Increased liver enzymes however normal liver function will be maintained
139
What is the histological appearance of steroid-induced hepatopathy?
Intracytoplasmic accumulation of glycogen and fluid within the hepatocytes resulting in hepatocellular swelling and vacuolation
140
Why does steroid-induced hepatopathy cause glycogen accumulation within the hepatocytes?
Steroids induce hyperglycaemia, causing increased glycogen production and storage within the liver
141
What is hepatic lipidosis?
Hepatic lipidosis is the excessive accumulation of triglycerides (fat) within the hepatocytes
142
Describe the pathophysiology of hepatic lipidosis
Hepatic lipodosis occurs when there is an imbalance between the mobilisation of fat to the liver, usually caused by anorexia, and the liver's ability to metabolise the fat, resulting in excessive accumulation of triglycerides within the hepatocytes, which can result in intrahepatic cholestasis and hepatic dysfunction
143
Which signalement is at increased risk of hepatic lipidosis?
Middle age, overweight cats with a recent history of anorexia
144
What are some of the potential causes of hepatic lipidosis?
Pancreatitis
Cholangitis (suppurative or lymphocytic)
Inflammatory bowel disease
Neoplasia
|It is important to investigate the underlying cause
145
How do you diagnose hepatic lipidosis?
Biochemistry
Ultrasound
Fine needle aspirate (FNA)
146
What is a key sign of hepatic lipidosis on biochemistry?
Increased ALP with a normal GGT
147
How does hepatic lipidosis appear on ultrasound?
The hepatic parenchyma will appear homogenous and hyperechoic with hepatomegaly
148
How do you manage hepatic lipidosis?
Treat the underlying disease
Nutritional support *(place a tube)*
Monitor for refeeding syndrome
Symptomatic management
149
What kind of diet should you feed a patient with hepatic lipidosis?
High protein diet
150
What supportive care should you provide patients with hepatic lipidosis?
Antiemetics
Intravenous fluid therapy
Analgesia
Antioxidants
151
What is triaditis?
Triaditis is the concurrent inflammation of the biliary system, duodenum and the pancreas
152
What is the primary cause of triaditis?
The primary cause of triaditis is intestinal inflammation resulting in dysbiosis and reflux of bacteria and enteric content into the pancreaticobiliary duct
153
Which species is triaditis seen in?
Cats *(this is due to cats having a slightly different anatomy compared to dogs where dogs have a seperate pancreatic duct whereas the cats pancreatic duct combines with the common bile duct, forming the pancreaticobiliary duct)*
154
What are the clinical signs of triaditis?
Anorexia
Weight loss
Vomiting
Icterus
Hepatomegaly
Thickened intestines
Pancreatic masses
Abdominal pain
Abdominal effusion
Pyrexia
Hypothermia
Tachypnoea
Dyspnoea
Shock
155
How does triaditis appear on biochemistry?
Increased liver enzymes
Increased pancreatic specific lipase
Decreased cobalamin
Decreased folate
Hypoalbuminaemia
156
What are some of the common causes of biliary disease?
Pancreatitis
Cholecystitis
Cholelithiasis
Gallbladder mucocoeles
Neoplasia
157
What is cholecystitis?
Cholecystitis is inflammation of the gallbladder
158
What is cholelithiasis?
Cholelithiasis is a term used to describe gallstones *(when bile hardens into stone-like material)*
|Cholelithiasis is often an incidental finding with no clinical significance
159
Which species are more prone to cholelithiasis?
Dogs
160
What are some of the potential clinical signs of biliary disease?
Jaundice
Pale white faeces *(very rare)*
161
What changes can be seen on biochemistry for biliary disease?
ALP and GGT more increased than ALT and AST
Increased cholesterol
Increased bilirubin
162
What is the most useful form of diagnostic imaging for biliary disease?
Abdominal ultrasound
163
What is suppurative cholangitis/cholangiohepatitis?
Suppurative cholangitis/cholangiohepatitis is the neutrophil driven inflammation of the bile ducts, gall bladder, and surrounding liver tissue
164
Which pathogen most commonly causes suppurative cholangitis/cholangiohepatitis?
Ascending E.coli infection from the intestines into the pancreaticobiliary duct *(can cause triaditis)*
165
Which species is most commonly affected by suppurative cholangitis/cholangiohepatitis?
Cats
166
What are the clinical signs of suppurative cholangitis/cholangiohepatitis?
Pyrexia
Icterus
Lethargy
± Vomiting
|Usually presents acutely
167
How do you treat suppurative cholangitis/cholangiohepatitis?
6 to 8 weeks of antibiotics
168
What is lymphocytic cholangitis/cholangiohepatitis?
Lymphocytic cholangitis/cholangiohepatitis is the lymphocyte driven inflammation of the bile ducts, gall bladder, and surrounding liver tissue
169
What is the cause of lymphocytic cholangitis/cholangiohepatitis?
The cause of lymphocytic cholangitis/cholangiohepatitis is unknown however assumed to be autoimmune
170
Which signalement is prone to lymphocytic cholangitis/cholangiohepatitis?
Cats over 4 years old
171
What are the clinical signs of lymphocytic cholangitis/cholangiohepatitis?
Generally cats with lymphocytic cholangitis/cholangiohepatitis present with a chronic history or vague illness but will be systemically well
172
What is the histological appearance of lymphocytic cholangitis/cholangiohepatitis?
Dense aggregates of lymphocytes
Fibrosis
173
Which disease can be hard to differentiate from lymphocytic cholangitis/cholangiohepatitis?
Lymphoma
174
What can be done to differentiate between lymphocytic cholangitis/cholangiohepatitis and lymphoma?
PCR for antigen receptor rearrangements (PARR)
175
How do you treat lymphocytic cholangitis/cholangiohepatitis?
Immunosuppressive therapy
176
What is a gallbladder mucocoele?
| Only seen in dogs
A gallbladder mucocoele is a distension of the gallbladder with accumulated mucoid secretions which may progress to semi-solid materials
177
Which dog breeds are prone to gallbladder mucocoeles?
Border Terriers
Shetland Sheep Dogs
178
What are the potential consequences of a gallbladder mucocoele?
Extrahepatic biliary obstruction
Gallbladder rupture and bile peritonitis
179
How do you treat a gallbladder mucocoele?
Surgical cholecystectomy
180
(T/F) Primary hepatobiliary neoplasia is very common
FALSE. Primary hepatobiliary neoplasia is uncommon
181
List examples of primary hepatobiliary neoplasia
Hepatocellular adenoma
Hepatocellular adenocarcinoma
Hepatic lymphoma
Hepatic haemangiosarcoma (HSA)
Biliary adenoma
Biliary adenocarcinoma
182
List examples of secondary/metastatic hepatobiliary neoplasia
Lymphoma
Leukaemia
Haemangiosarcoma (HSA)
Histiocytic sarcoma
183
What is hepatobiliary nodular hyperplasia?
Hepatic nodular hyperplasia is a benign hyperplastic condition seen in older dogs
184
What changes will be seen on biochemistry for hepatobiliary nodular hyperplasia?
Increased ALP
± Increased ALT
185
How do you diagnose hepatobiliary nodular hyperplasia?
You diagnose hepatobiliary nodular hyperplasia using a liver biopsy
186
How do you treat hepatobiliary nodular hyperplasia?
No treatment is required for hepatobiliary nodular hyperplasia as it is a normal change in ageing dogs
187
What is the general approach to managing acute hepatopathies?
1. Treat the underlying cause of disease if known, however the majority of these cases are idiopathic or cannot be diagnosed
2. Supportive treatment
3. Treat any clinical consequences of hepatic disease
188
What is the general approach to managing chronic hepatopathies?
1. Treat the underlying cause of disease if known, however the majority of these cases are idiopathic or cannot be diagnosed
2. Any specific treatment should be done based on a liver biopsy results if possible
3. Supportive treatment
4. Clinical any clinical consequences of hepatic disease
189
What supportive treatment should you provide when managing hepatic disease?
Intravenous fluid therapy if clinically dehydrated
Antiemetics if indicated
Antioxidants
Nutritional support if indicated
Analgesia if indicated
Antibiotics if indicated
Vitamin K if indicated
Hepatic prescription diet if indicated
190
What are the physiological roles of antioxidants in the liver?
Within the liver, glutathione is synthesised from cysteine, glutamate and glycine. Glutathione is an antioxidant and free radical scavenger which is involved in the protective defence mechanisms of the liver as there is evidence that free radicals and oxidative stress are involved in the pathogenesis of hepatic disease
191
Which antioxidants can be used when managing hepatic disease?
S-adenosylmethionine (SAMe)
Silymarin
192
What is S-adenosylmethionine (SAMe)?
S-adenosylmethionine (SAMe) is a precursor of glutathione and thus has antioxidant effects
193
What is silymarin?
Silymarin is derived from the milk thistle plant and has antioxidant effects
194
What is N-acetylcysteine?
N-acetylcysteine is a pro drug of cysteine which helps to replenish hepatocellular cysteine and consequently glutathione concentrations
195
What is the clinical use of N-acetylcysteine?
N-acetylcysteine is used in cases of acute hepatopathies due to hepatotoxic drugs and toxins
196
(T/F) Bile acids can be hepatotoxic
TRUE. Hydrophobic bile acids can be hepatotoxic, however the reason for this is unknown
197
What is ursodeoxycholic acid (UDA)?
Ursodeoxycholic acid (UDA) is a synthetic hydrophillic bile acid which can displace hydrophobic toxic bile acid and promote bile flow
198
What are the clinical uses of ursodeoxycholic acid (UDA)?
Management of gallbladder mucocoeles
Management of acute hepatopathies with cholestasis
Management of chronic hepatopathies with cholestasis
199
When is ursodeoxycholic acid (UDA) contraindicated?
Ursodeoxycholic acid (UDA) is contraindicated in patients with biliary obstruction
200
When is vitamin K indicated in the management of hepatic disease?
Vitamin K is indicated when a patient has evidence of a coagulopathy secondary to hepatic disease
201
When would you have to administer vitamin K subcutaneously?
Vitamin K should be administered subcutaneously when a patient is anorexic or a biliary disease as fat is required to absorb vitamin K from the gastrointestinal tract
202
Why should you avoid giving vitamin K intravenously?
Intravenous administration of vitamin K can cause anaphylaxis
203
When are antibiotics indicated in the management of hepatic disease?
Primary bacterial infection
Secondary bacterial infection
Hepatic encephalopathy
204
Which antibiotics should be used in the management of hepatic disease?
Ideally, choose antibiotics based on culture and sensitivity. However, if this is not possible choose antibiotics based on the most likely bacteria to be involved which is enteric bacteria. Also be mindful of antibiotics which are metabolised by the liver and can be hepatotoxic
205
What are the features of hepatic prescription diets?
Low protein
Low copper
High in zinc
Vitamins B and E *(antioxidants)*
206
What are the indicators for prescribing hepatic diets?
Hepatic encephalopathy
Copper-associated liver disease
## Footnote
Liver diets are low in proteins and thus are contraindicated in some diseases and should not be given if you don't know the cause of liver disease
207
What is hepatic fibrosis?
Hepatic fibrosis is the excessive deposition of collagen within the liver
208
Describe the progression of hepatic fibrosis
Myofibroblasts are triggered in response to chronic inflammation resulting in excessive collagen deposition and hepatic fibrosis. As the fibrosis advances, fibrotic tracts will extend across the hepatic lobules. Eventually, the liver will become cirrhotic
209
How can hepatic fibrosis cause portal hypertension?
Hepatic fibrosis of the sinusoids will increase the resistance of portal blood flow into the liver resulting in portal hypertension due to increased hepatic resistance
210
How do you diagnose hepatic fibrosis?
Liver biopsy and histological evaluation
211
How do you stop progression of hepatic fibrosis?
Treat the underlying cause
Anti-fibrotic drugs *(however no clinical evidence that these work)*
212
Which drugs potentially have anti-fibrotic effects?
Prednisolone
Penicillamine
S-adenosylmethionine (SAMe)
213
What is hepatic cirrhosis?
Hepatic cirrhosis is a chronic, irreversible state where the normal hepatic tissue has been replaced by fibrotic tissue, resulting in end-stage liver failure
214
How does hepatic fibrosis appear on histology?
Inflammation
Progressive, bridging fibrosis
Nodular regeneration
215
What is portal hypertension?
Portal hypertension is increased blood pressure in the hepatic portal system
216
What are the potential causes of portal hypertension?
Cirrhosis
Vascular obstruction
217
What are some of the potential complications of portal hypertension?
Ascites
Acquired portosystemic shunts
Gastrointestinal ulceration
Hepatic encephalopathy
218
How do you manage ascites?
Diuretics
Abdominocentesis
219
Which diuretics can be used to manage ascites?
Spironolactone *(first line)*
Furosemide *(second line)*
220
How do you treat gastrointestinal ulceration?
Antiemetics
Gastroprotectants
Small frequent meals
Treat the underlying cause
221
Which gastroprotectants are typically used in combination for the treatment of gastrointestinal ulcers?
Omeprazole
Histamine (H2) blockers
Sucralfate
222
Which histamine (H2) blocker is contraindicated for the treatment of gastrointestinal ulcers secondary to hepatic disease?
Cimetidine
223
Why is cimetidine contraindicated in the treatment of gastrointestinal ulcers secondary to hepatic disease?
Cimetidine is contraindicated for the treatment of gastrointestinal ulcers secondary to hepatic disease as cimetidine can decrease hepatic blood flow and delay hepatic drug metabolism
224
How can gastrointestinal ulceration cause hepatic encephalopathy?
Gastrointestinal bleeding causes loss of proteins into the gastrointestinal tract. These proteins will be broken down into ammonia by intestinal bacteria. This increased protein breakdown into ammonia can overwhelm the liver’s ability to detoxify ammonia, especially in patients with pre-existing liver dysfunction, with the elevated ammonia levels in the bloodstream a key factor in the development of hepatic encephalopathy
225
What is hepatic encephalopathy?
Hepatic encephalopathy is a neurological condition resulting from liver dysfunction
226
What is one of the most common causes of hepatic encephalopathy?
Portosystemic shunts
227
Which toxin is the main cause of hepatic encephalopathy?
Ammonia
228
What are the potential clinical signs of hepatic encephalopathy?
Altered mentation
Ataxia
Head pressing
Ptyalism *(cats)*
Seizures
Blindness
| All of which will worsen after eating
229
Why do the clinical signs of hepatic encephalopathy worsen following a meal?
Eating a meal exacerbates the clinical signs of hepatic encephalopathy by providing more dietary proteins which are broken down into ammonia which builds up in the bloodstream, exacerbating hepatic encephalopathy
230
How do you manage hepatic encephalopathy?
Small, frequent, low protein meals
Antibiotics
Lactulose
Treat factors that can worsen the hepatic encephalopathy *(usually with fluid therapy)*
Treat seizures
231
Which diets can be used in the management of hepatic encephalopathy?
Hepatic prescription diets
Purina hypoallergenic food
232
What is the main risk of hepatic prescription diets in young growing animals?
Hepatic prescription diets are very low in protein which in young growing animals can cause break down endogenous proteins in order to maintain adequate growth and development
233
What can be added to hepatic prescription diets for young growing animals to slightly increase to protein content?
Cottage cheese
Tofu
234
What should never be fed to patients with hepatic encephalopathy?
Red meat as it is very high in protein
235
Why are antibiotics used in the management of hepatic encephalopathy?
Antibiotics are used to reduce the enteric bacteria which break down dietary proteins into ammonia
236
Which antibiotics can be used in the management of hepatic encephalopathy?
Ampicillin
Neomycin
Metronidazole
Amoxicillan and Clavulanic acid
237
What should you be aware of if using metronidazole to manage hepatic encephalopathy?
Metronidazole can be hepatotoxic so you should use a lower than normal dose
238
Why is lactulose used in the management of hepatic encephalopathy?
The breakdown of lactulose to lactate in the colon leads to acidification of the colon contents, which will favour the conversion of ammonia (NH3) to ammonium (NH4) which cannot be absorbed across the cell membranes into the bloodstream. Furthermore, lactulose is a laxative which will decrease the time available for ammonie (NH3) to be absorbed into the bloodstream from the gastrointestinal tract
239
What are the routes of administration for lactulose when managing hepatic encephalopathy?
Oral
Rectal enema *(if the patient is unstable)*
240
Which factors can exacerbate the clinical signs of hepatic encephalopathy?
Dehydration
Hypokalaemia
Alkalaemia
Gastrointestinal haemorrhage
241
How do you manage dehydration, hypokalaemia and alkalaemia which can worsen the clinical signs of hepatic encephalopathy?
Intravenous fluid therapy
242
Which fluids should you use when managing hepatic encephalopathy?
0.9 % NaCL fluids or Plasmolyte
243
How should you manage seizures secondary to hepatic encephalopathy?
Initially you may not know what is causing the seizures so use diazepam or midazolam for emergency treatment. Be aware that diazepam and midazolam are metabolised by the liver so if the seizures are secondary to hepatic encephalopathy this can cause the patients to become quite sedated. If you determine that hepatic encephalopathy is the cause of the seizures, use levetiracetam. Be aware patients may require propofol continuous rate infusions (CRIs)
244
What is another cause of seizures secondary to hepatopathies other than hepatic encephalopathy?
Hepatopathies can cause decreased glucose production which can result in seizures so it is important to measure glucose levels on a glucometer when a patient starts to seize as they may require dextrose infused IV fluids
245
What are the indicators for the use of steroids *(immunosuppressive therapy)* for managing hepatic disease?
Biopsy evidence of chronic inflammation *(i.e. chronic hepatitis and lymphocytic cholangitis)* with no evidence of infection, and no to mild fibrosis
246
What are the contraindications for the use of steroids *(immunosuppressive therapy)* for managing hepatic disease?
Signs of portal hypertension
Signs of gastrointestinal ulceration
Hepatic encephalopathy
Evidence of infection
Evidence of bridging fibrosis
Acute hepatopathies
247
Why are steroids contraindicated for managing hepatic disease in patients with hepatic encephalopathy?
Steroids can induce protein breakdown, increasing ammonia production which will worsen hepatic encephalopathy
248
Why are steroids contraindicated for managing hepatic disease in patients with hepatic infections?
Steroids cause immunosuppression which will worsen infections
249
Why are steroids contraindicated for managing hepatic disease in patients with bridging fibrosis?
Bridging fibrosis is a key indicator there may also be portal hypertension so it is contraindicated as portal hypertension can cause both hepatic encephalopathy and gastrointestinal ulceration
250
Why are steroids contraindicated for managing acute hepatopathies?
Steroids are contraindicated as acute hepatopathies tend to have infectious or toxic aetiologies
