Liver Disease Flashcards
1
Q
what are 3 broad causal mechanisms that you should consider in cases of jaundice?
A
- Inc # RBC broken down
- Generalised liver Dx affecting functional parenchyma
- Cholestasis
2
Q
Which domestic animal species develop hepatogenous photosensitisation?
A
Herbivores that eat green stuff –> chlorophyll!
3
Q
How does grass become a photodynamic agent that contributes to hepatogenous photosensitisation??
A
Chlorophyll in plants made into phylloerythrin by gut flora (natural photodynamic agent) –> usually made soluble in liver and secreted
4
Q
Which liver disease contributes to hepatogenous photosentitisation?
A
Cholestasis (days) –> phylloerythrin back spills out of erythrocytes into sinusoids –> circulation –> sunlight activates –> free radicals generated –> tissue ulceration
5
Q
What are symptoms of hepatic encephalopathy?
A
head pressing
ataxia
ptyalism
generalised behavioural changes
6
Q
What functional changes in the liver contribute to hepatic encephalopathy?
A
Reduced liver functional mass (E.g. by repeat toxicity)
PSS
7
Q
Which compound in the blood primarily causes hepatic encephalopathy?
A
Ammonia
8
Q
In which types of liver disease can hypoalbuminaemia develop and why?
A
Liver produces albumin. Dramatically reduced parenchyma (e.g. cirrhosis/ liver failure)
9
Q
Why is hypoalbuminaemia usually chronic?
A
T1/2 albumin very long
10
Q
Describe the symptoms of hypoalbuminaemia
A
Decreased oncotic pressure in blood stream Transudate oedema (ascites)
11
Q
What are various hepatic causes of ascites?
A
Hypoalbuminaemia
Chronic liver fluke
Portal vein hypertension
Inc hepatic lymph formation due to inc pressure in hepatic sinusoids (Right heart failure, scarring, tumor, amyloid in perisinusoidal spaces)
12
Q
What are various causes of portal vein hypertension?
A
Compression of portal vein
Enlarged GIT
13
Q
Define polyuria
A
Inc urination
14
Q
Define polydipsia
A
Inc drinking
15
Q
Define acholic
A
White fresh faeces!
16
Q
In what circumstances might an animal have acholic faeces
A
Loss of conjugated bilirubin into bile due to major extra-hepatic bile duct obstruction
17
Q
Why does hepatic Dx potentially predispose haemorrhage?
A
clotting factors are produced in the liver?
18
Q
Describe portosystemic shunting PSSSSSSSSS
A
Diversion of blood from portal vein (bypassing liver) to tributaries of portal vein (e.g caudal vena cava/ splenic vein etc)
19
Q
What happens to liver subsequent of PSS?
A
Microhepatica due to hypoplasia
20
Q
Why does liver become hypoplastic subsequent of PSS?
A
Deprivation of trophic factors
21
Q
What could cause liver rupture?
A
severe congestions, hepatic lipidosis etc. anything causing extreme tension on hepatic capsule
22
Q
What is a common cause of cranial liver displacement?
A
Diaphragmatic hernias
23
Q
What is a common cause of caudal displacement of the liver?
A
Hepatomegaly, space-occupying masses in the thorax
24
Q
Which clinical signs in a dog might make you suspect liver disfunction?
A
Ascites Neurologic signs Jaundice PU & PD Stool changes
25
which conditions predispose livers to diffuse hepatic atrophy?
1. Nutritional (catabolism)
2. PSS
3. Impaired mitotic division (low trophic factors)
26
Which conditions cause local hepatic atrophy?
Local compression
| Local obstruction of bile drainage
27
Why can sublethal injury to hepatocytes lead to hydropic degeneration?
Loss of control of fluid and ionic movements across membranes --> influx Na+ & water
28
Define steroid hepatopathy
glycogen accumulation
29
Which conditions stimulate steroid hepatopathy?
Hyperadrenocorticism
e. g. from pituitary tumour in adrenal cortex
e. g. iatrogenic --> excessive admin corticosteroids
30
Define hepatic lipidosis
Excessive accumulation of triglycerides in hepatocyte cytoplasm
31
What is a cause of hepatic lipidosis?
Any process that overloads or impairs lipid metabolism of hepatocytes
e.g. diabetes/ high energy diet/ starvation/ sublethal injury to hepatocytes/ preg tox/ ketosis/ endocrine disorders/ equine hyperlipaemia
32
What gross anatomical changes of the liver are seen in early hepatic lipidosis?
Zonal pattern in early stages (Zone 3 rappoport's acinus)
33
What gross anatomical changes of the liver are seen in moderate/severe hepatic lipidosis?
Megahepatica, rounded borders, diffuse cream yellow colour, soft, friable, greasy cut surface
34
What is amyloid?
An extracellular glycoprotein --> amorphous/ pink/ homogenous
35
In what circumstances does hepatic amyloidosis develop in domestic animals?
Active inflammation or tissue damage in the body, meaning that there is inc hepatic synthesis and release of SAA
36
Which pigment might result in a yellow or green liver?
Bilirubin accumulation (jaundice/ cholestasis)
37
Which pigment might result in a spotted black liver?
melanin
38
Which pigment might result in a diffusely black liver?
"lipofuscin like pigment" from ingestion of random plants, or black pigment from fasciola hepatica waste
39
What are some causes of multifocal hepatic necrosis?
viral/ bacterial/ protozoal infections --> multifocal pattern due to haematogenous origin
40
Define embolic
Originating from blood
41
What contributes to zonal necrosis of the liver?
Necrosis of acinar areas of hepatocytes
| Due to toxins or hypoxia (mainly) :)
42
Define telangiectasis
Dilation of local areas of capillaries leading to gross appearance as red/ purple bumps on skin
43
Define massive necrosis
Necrosis of an entire acini, not necessarily the whole liver
44
What insults result in massive necrosis?
Very severe toxic or hypoxic insult
45
In what circumstances do hepatic fibrosis develop?
Scarring following liver surviving episode of hepatocellular necrosis
46
Which cells in the liver can proliferate and grow up to become hepatocytes?
hepatocytes, oval cells, ductal cells
47
Which cells produce collagen in the liver?
stellate cells
48
Define cirrhosis
End stage liver marked by degeneration of hepatocytes, inflammation and fibrous thickening of tissue.
49
How can liver cirrhosis affect circulation?
Can lead to portal hypertension due to increased resistance into the sinusoids
50
What gross features are indicative of cirrhosis
involvement of the entire liver, diffuse fibrosis, regenerative hyper plastic parenchymal nodules, permanent distortion of liver architecture, development of new vascular anastomoses
51
What 3 general disorders can result from portal hypertension?
1. Congestion of viscera normally drained by portal vein
2. Ascites
3. Acquired portosystemic shunting
52
What causes acquired portosystemic shunting?
Anything reducing portal venous inflow and diversion of portal venous blood away from liver. Usually multiple vessels
53
How can congenital and portosystemic shunting be distinguished?
```
Congenital= one anamolous vessel & due to DEC portal venous inflow/ INC arterial inflow
Acquired= Generally multi anomalous vessels & due to portal hypertension
```
54
Describe the differences in the location of portosystemic shunts in small and large breed dogs
Small --> outside liver but inside abdomen
| Large --> inside liver (usually remnant of foetal vessel)
55
Which disorders are likely to contribute to focal hepatitis?
Hardware dx --> pyogenic abscess
Ruminal acidosis --> infection of ulcers that enter blood and travel to liver
Bacteria crawling up bile duct to liver!
56
A drop in circulating blood glucose elicits what response?
gluconeogenesis
57
Which stain is used to assess hepatocellular glycogen storage disease histologically?
PAS (Acid schiff)
58
Oriental breed cats have an inherited form of which systemic liver disfunction?
Amyloidosis
| Progressive accumulation of Amyloid A which leads to hepatomegaly
59
Blood in liver sinusoids would suggest which disfunction? (at whole body level)
Right-sided congestive heart failure
60
Why do atrophic/ cirrhotic/ PSS livers demonstrate increased bile acids??
Their reduced functional mass means that they don't have enough efficient live hepatocytes to reabsorb the high percentage of bile acids
61
What are causes of hydronic degeneration of hepatocytes?
Sublethal injury that damages cell membranes causing uncontrolled movement of fluid & ions across cell membranes.
e.g. sublethal hypoxia, sublethal toxaemia, prolonged cholestasis
62
Define steroid hepatopathy
Glycogen accumulation in hepatocytes
63
Define bridging fibrosis
Fibrotic pattern joining one structure to another e.g. portal area to central vein
64
Why is portal hypertension a consequence of cirrhosis?
Increase pressure in the portal vein is due to increased resistance to portal venous blood flow into sinusoids
65
What are 3 consequences of portal hypertension?
1. Congestion of viscera normally drained by portal vein
2. Ascites
3. Acquired portosystemic shunting
66
Define "hepatitis"
inflammation of the hepatic parenchyma
67
What pattern of hepatitis is most likely to progress to cirrhosis?
Severe DIFFUSE hepatitis
68
Which conditions commonly lead to hepatic abscess formation in cattle?
1. direct foreign body implantation e.g. hardware disease
2. direct extension from adjacent suppurative lesions e.g. hardware
3. Ascending infx up bile duct
4. Haematogenous infx
69
What are potential consequences of hepatic abscessation?
1. Production --> weight loss/ decreased milk production/ liver condemnation
2. Health --> Perforated liver (+/- peritonitis), Eroded hepatic veins (thrombus + inflammation), systemic spread (death from toxaemia)
70
Describe the aetiopathogenesis of Black's disease
Liver damage due to low O2 conc --> Clostridial spores germinate --> proliferation + toxin release --> necrosis --> toxins become systemic --> widespread vascular injury --> death + rapid carcass putrefaction
71
What is the causative agent of Black's disease?
Clostridium novyi Type B
72
What is bacillary haemoglobinuria?
Similar pathogenesis to Black's disease but gross lesions are usually a single large focal necrotic centre. Clinical signs include jaundice/ anaemia due to exotoxins causing hepatic necrosis & intravascular haemolysis
73
The gross appearance of multifocal hepatitis suggests which agents of disease? (bing bing bing bing bing)
Multifocal hepatic necrosis due to
1. Bacteraemia
2. Systemic protozoal infection
3. Some viraemias
4. Systemic fungal infection
5. Migrating parasites
74
What is a useful microscopic tool suggesting multifocal hepatitis is due to parasite migration?
Linear/ squiggly tunnels containing haemorrhage/ necrotic debris/ fibrin wherever liver capsule is breached
75
Name a few parasites that commonly migrate through the liver?
```
Liver fluke (cattles/sheeps)
Round worm (piggies)
Tapeworm (sheep)
```
76
What is a viral cause of zonal hepatitis (Note, don't think this is the same as zonal necrosis?! [Which is from toxaemia/ hypoxia])
Canine adenovirus-1
77
What are 3 characteristic features of chronic hepatitis in doggies?
1. Deposition collagen in perisinusoidal space
2. Periportal hepatitis
3. Frequent progression to cirrhosis
78
Which dog breed are predisposed to a form of chronic hepatitis?
Doberman's --> immune-mediated pathogenesis
79
What are two mechanisms by which certain dog breeds can develop copper storage disorders?
1. Primary copper storage disease --> usually breed related
| 2. Secondary --> copper accumulation due to cholestasis
80
Why exactly does copper storage in the liver cause pathogenesis?
Copper has a 2+ valency, causes free radical generation & the per oxidation of cell membranes, fuck!
81
Define cholangitis
inflammation of bile ducts
82
Define cholecystitis
Inflammation of gall bladder
83
Define Cholangiohepatitis
Inflammation on bile ducts in portal areas (usually spreads to involve whole liver parenchyma)
84
Which liver lobe is more susceptible to parasitic insults?
Left --> closer route for entry!
85
How do the gross lesions of chronic fascioliasis present in cattle?
Bile duct fibrosis, severe duct mucosal erosion & ulceration
86
How do the gross lesions of chronic fascioliasis present in sheep?
Dilation of thin walled vessels & catarrhal inflammation
87
How do bacteria reach the biliary tree?
Migrate from duodenum up bile duct
88
Outline the aetiology of facial eczema in ruminants?
Sporadesmin fungal mycotoxin origin
89
Outline the pathogenesis and typical lesions of facial eczema in ruminants
Sporadesmin ingested --> carried from GIT to liver via portal vein --> liver can't modify so tries to excrete through biliary system --> concentrates in bile and becomes increasingly toxic --> burns biliary epithelium --> obstructive jaundice & photosensitisation
90
How will acute and chronic lesions in the liver differ in an animal presenting with hepatogenous photosensitisation from sporadesmin poisoning?
```
Acute= swollen & jaundiced liver
Chronic= Fibrotic, atrophic left lobe, fibrous thickening of bile duct walls
```
91
How common are gall stones in domestic animals?
Uncommon- don't have diet high in cholesterol!
92
Are gall stones in domestic animals usually of clinical concern?
Rarely- usually soft
93
Why is the liver most affected by toxins?!
1. First pass metabolism, receives most afferent blood from portal vein
2. May naturally concentrate toxins e.g. Cu/ Sporadesmin
3. Hepatic biotransformation (metabolises stuff)
94
What is the major purpose of hepatic biotransformation in the liver?
Make incoming fat soluble molecules into water soluble so can be excreted from hepatocytes & eliminated in poo/ urine
95
What happens during phase 1 hepatic biotransformation?
Oxidation in SER
96
What can be two adverse consequences of phase 1 hepatic oxidative biotransformation?
Generation of toxic metabolites or free radicals
97
What happens during phase 2 hepatic biotransformation?
Conjugation, usually with reduced glutathione to increase water solubility
98
What role does glutathione play in liver metabolism?
Anti-oxidant activity to mop up free radicals!
99
What is the difference between primary and secondary poisoning?
```
Primary= animal ate poison
Secondary= animal eats other animal who had previously ingested toxin
```
100
What is a predictable hepatotoxin?
A toxin that in a sufficient dose, will cause predictably cause hepatic injury in virtually all susceptible animals
101
What is an example of a predictable hepatotoxin?
Paracetamol in catties
102
What is an idiosyncratic hepatotoxin?
toxin that causes hepatic injury in a minority of exposed animals
103
What factors influence the response of an individual animal to exposure of a hepatotoxin?
age/ gender/ diet/ nutritional status/ endocrine function/ genetics/ previous drug exposure
104
In what circumstances are large domestic animals likely to consume fatal doses of hepatotoxins?
E.g. Ruminants with limited food supply
Naive eating habits
high stocking density --> starvation
105
what clinical signs might you expect in an animal with acute hepatotoxitiy?
few... it'll be dead asap
106
What is the most common lesion seen in animals that have died from an acute hapatotoxic insult?
Zone 3 zonal hepatitis or massive necrosis
107
Why are periacinar hepatocytes so vulnerable to toxic injury?
Highest activity of Mixed function oxidase (MFO) enzymes
| Damaged by the products of biotransformation
108
What are the main gross anatomical changes you might find in a liver that has been exposed to long term hepatotoxins?
Cirrhosis (hyperplastic nodules & fibrosis)
109
What are some common toxins that cause chronic hepatotoxicity in domestic animals
Aflatoxins
| Pyrrolizidine alkaloids
110
What are some common toxins that cause acute hepatotoxicity?
Amatoxins
| Blue green algae
111
Why are kitties particularly prone to paracetamol poisoning?
They are less effective at conjugating metabolites (phase 2) therefore generate more toxic intermediates. What is metabolised via Phase 1 produces toxic metabolites. Glutathionine levels in catties are insufficient to mop up free radicals
112
What are some common species of plants that contain pyrrolizidine alkaloids?
Paterson's curse
113
Why is acute pyrrolizidine poisoning far less common than chronic poisoning?
For acute onset of signs, requires large volume of toxic plant species (e.g. paterson's curse) to be ingested
114
What clinical signs might you observe in an animal with chronic pyrrolizidine poisoning?
Variable - depend on individual animal. Jaundice, photosensitisation, hepatic encephalopathy
115
What is the most diagnostically useful microscopic lesion that can be used to diagnose chronic pyrrolizidine alkaloid poisoning?
Hepatic megalocytes and karymegaly
116
What are Alfatoxins?
Toxins produced by fungi
117
How do aflatoxin cause injury to the liver?
Toxins are biotransformed by MFO enzymes into toxic metabolites --> can bind to DNA/RNA and inhibit mitosis and protein synthesis
118
Which animals are most susceptible to aflatoxins?
Birds > pigs > calves > horses > dogs
119
Which domestic animals is most often affected by ACUTE aflatoxicosis?
Garbage eating dogs!!
120
How does lantana cause jaundice?
Gall bladder paralysis
| Canaliculi disruption
121
Outline the aetiopathogenesis of chronic copper poisoning in sheep
Dietary copper intake --> Cu usually excreted in bile --> cholestasis = Cu accumulation in hepatocytes --> Cu valency (++) forms reactive oxygen species --> peroxidation of lipid membranes
122
How do sheep die of copper poisoning?
Cooper concentrates in hepatocytes --> apoptosis --> Cu accumulation in adjacent cells --> increase plasma conc --> acute intravascular haemolysis --> hypoxic damage --> further copper release --> death
123
Which tumours are more common in the liver, metastatic tumours or primary hepatobiliary tumours?
Metastatic tumours --> due to liver's central location in body, huge afferent blood flow from GIT, storage function etc.
124
Which tumours commonly metastasise to the liver?
Carcinomas
Sarcomas
Haemangiosarcomas
Malignant haematopoietic cells
125
What are the most common primary tumours of the liver?
```
Hepatocullular adenoma (benign tumour of hepatocytes)
Hepatocellular carcinoma (malignant tumour of hepatocytes)
```
126
What is the difference between primary and secondary photosensitisation?
```
Primary= Direct deposits e.g. from ingested substance
Secondary= photodynamic compounds deposited due to liver DAMAGE
```
127
Why do cats die of paracetamol poisoning?
RBC are exposed to the free radicals (oxidising agents) from toxin metabolites --> Heinz inclusion bodies on RBC --> cells lyse --> PCR drops
