Liver and Biliary System 2 Flashcards
What type of necrosis is most common in the liver?
Coagulative
How does coagulative necrosis appear histologically?
- Intact but dead hepatocytes
- Shrunken cells / intensely eosinophilic / altered nuclei
How is necrosis classified in the liver?
According to location e.g. focal, zonal or diffuse
Describe focal necrosis in the liver
- Aggregates of necrotic hepatocytes; random
- With disseminated infections > haematogenous / septicaemia
Describe zonal necrosis of the liver
- In particular part of lobule / acinus, but: in whole liver
- Centrolobular / periacinar necrosis
- Mid-zonal necrosis
- Periportal necrosis
How would disseminated multifocal necrosis appear grossly?
- White spots = necrosis
- Red rings = blood / haemorrhage
- EITHER disseminated or random or zonal (centrolobular is most common)
Describe the 3 zones in the liver
- Periportal = zone 1, Surrounding triads
- Mid-zonal = zone 2
- Centrolobular = zone 3
Which zone of necrosis is the most common and why?
Centrobular / periacinar necrosis (zone 3)
- Hepatocytes most at risk of hypoxia
- Metabolically active (cytochrome P450)
Describe massive (diffuse) necrosis
- Necrosis of entire lobe(s)
- With extensive zonal necrosis or circulatory disorder (infarction)
Describe the cause of massive (diffuse) necrosis in pigs and the associated diseases
- Vitamin E / selenium deficiency = Hepatosis dietetica
- Associated with oedema of gall bladder wall and “Mulberry heart disease” (multifocal myocardial haemorrhage and myofibre degeneration)
- Necrosis of whole acini > no surviving parenchyma > can’t regenerate
What are the different outcomes of hepatic necrosis?
• Removal of dead hepatocytes
• Resolution by either:
- regeneration of hepatocytes
- or: replacement of parenchyma by fibrous scar tissue (due to destruction of reticular framework)
Describe the reticulin framework and explain how it effects the outcome of necrosis
- Fibres that support cords of hepatic sinusoids
- If this is retained then the liver has a huge capacity to regenerate and it will reform lobules
- If this is lost the liver has to repair in other ways which can lead to chronic liver disease due to the laying down of fibrosis
What is the influencing factor on where fibrosis occurs at the site of necrosis?
Depends on the distribution of injury
What are the 4 different types of fibrosis?
- Periportal/biliary fibrosis
- Centrolobular/periacinar fibrosis
- Diffuse/bridging fibrosis
- Post-necrotic scarring (after massive necrosis)
Describe the 3 types of bridging fibrosis
Central-central: connects central veins (with chronic congestion)
Porto-portal: follows portal inflammation which extends to portal venules
Porto-central: after centrolobular necrosis
What is the outcome of bridging fibrosis?
Extensive fibrosis between hepatic cords
- Blue represents collagen – this prevents the exchange of oxygen and nutrients between the blood and hepatocytes which is impairing liver function
Describe hepatic cirrhosis and how it occurs
= end stage liver disease due to several causes
• Liver tries to repair itself but cant due to the ongoing fibrosis and degeneration -> hypoxia
What are the 3 characteristic features of hepatic cirrhosis?
DEGENERATION disruption of entire liver architecture
REGENERATION regenerative nodules of hepatocytes
REPAIR bridging fibrosis [central pathogenic process]
What are the two possible progressions of fibrosis in the liver?
- Worsen to cirrhosis
- Be reversible
Describe the features of regenerative nodules that occur in cirrhosis
- Composed of hepatocytes that look normal
- Lack of lobular organisation [no cords, no central vein, no portal triad]
- Often hydropic degeneration of hepatocytes
- Surrounded by fibrous connective tissue
What process acts as a further attempt of regeneration in liver
Bile duct proliferation
Describe the further characteristics of cirrhosis as it progresses?
- Parenchymal injury and fibrosis are diffuse throughout the whole organ
- Balance between regeneration and constrictive scarring -> nodularity
- Reorganisation of vascular structure [anastomoses] -> acquired extra-hepatic shunts
Describe the gross appearance of hepatic cirrhosis
Lots of nodular fibrosis, the liver between the nodules is paler and contracted due to fibrosis and scarring
Cut surface: pale areas of fibrosis with some prexisting tissue and new nodules
Describe the histological appearance of hepatic cirrhosis
Regenerative nodules with surrounding fibrosis. In-between there are the remains of the pre-existing hepatic parenchyma – shrunken and irregular
What are the causes of hepatic cirrhosis?
- Majority of veterinary cases: idiopathic
- Dogs: persistent CAV-1 or leptospira infection?
- Parasitic cirrhosis
- Post-necrotic
- Cardiac
- Pigments
- Biliary
- Toxins
Which 3 conditions occur in sequelae to hepatic cirrhosis?
- Jaundice
- Ascites
- Hepatoencephalic syndrome
Describe jaundice and its causes
- Due to high bilirubin levels in blood
- Yellow tinge of all tissues [sclera, omentum, mesentery, fat, aorta…]
- Seen only grossly [bilirubin is in solution] – not histo
- Always diffuse!
Describe the 3 types of jaundice
Pre-hepatic = excessive haemolysis Hepatic = severe hepatic injury Post-hepatic = obstructed bile flow (cholestasis)
Why does ascites occur in sequalae to hepatic cirrhosis?
Due to portal hypertension
What is Hepatoencephalic syndrome?
Failure of liver to remove ammonia from the blood
What are the products of the degradation of haemoglobin?
- Haem
- Biliverdin
- Bilirubin
What are the components of bile?
- water
- cholesterol
- bile salts: Na and K salts of bile acids
- bile pigments (bilirubin) from Hb molecule
Describe pre-hepatic jaundice
Due to excessive haemolysis of erythrocytes in peripheral blood -> unconjugated bilirubin in blood
What are the causes of pre-hepatic jaundice?
- Infections: Leptospirosis, Equine infectious anaemia, Anthrax, etc
- Massive internal haemorrhage [bilirubin from disintegrating erythrocytes]
- Icterus neonatorum [bilirubin glucoronyl transferase still insufficient]
Describe the causes of hepatic jaundice
Due to severe hepatic injury by:
a) toxic substances
b) infectious agents [e.g. leptospirosis]
Describe the pathophysiology of hepatic jaundice
- Either: damaged hepatocytes do not uptake bilirubin or perform conjugation -> unconjugated bilirubin in blood
- or: severe hepatocyte swelling blocks outflow of bile from canaliculi -> conjugated bilirubin accumulates in liver and is reabsorbed into the blood
Describe the pathophysiology of post-hepatic jaundice
Due to obstruction of normal bile flow -> conjugated bilirubin accumulates in the liver and is reabsorbed into the blood
What are the causes of post-hepatic jaundice?
- Obstruction of ducts [e.g. liver fluke…]
- Fibrous tissue in cirrhosis
- Cholangitis
- Gall stones
- Pressure on ducts [abscesses, granulomas, neoplasms]
- Closure of excretory duct [duodenal papilla]
The liver is responsible for the synthesis of which substances?
- Glucose
- Low density lipoproteins
- Urea
- Soluble plasma proteins
Which 2 molecules are catabolised in the liver?
- Lipids
- Ketone bodies
Which substances is secreted/excreted by the liver?
Bile
What are the other functions of the liver?
- Detoxification
- Carbohydrate, lipid and protein metabolism
Which conditions are associated with disturbances of liver functions?
- Jaundice
- Hypoalbuminemia: reduced synthesis and secretion of albumin -> ascites
- Coagulopathy
- Hyperammonaemia
- Portal hypertension
Why do coagulopathies occur when there are disturbances with liver function?
Reduced synthesis and secretion of clotting factors
Describe the lesions seen with hepatic encephalopathy
- Cerebral oedema (Status spongiosus)
- Neuronal necrosis and swelling
- Degeneration of astrocytes [Alzheimer type II cells]
Which 2 conditions can be mistaken for neoplasia in the liver?
Nodular hyperplasia
Regenerative nodules
Describe nodular hyperplasia
- Not a neoplasm
- Common in old dogs
- Usually multiple, expanding, compressing adjacent tissue
- Contain portal areas
Describe regenerative nodules
- Not a neoplasm
- Common in old dogs
- Multiple or numerous
- Adjacent tissue usually fibrotic
- Loss of lobular architecture
Name the 5 hepatic primary neoplasms
- Hepatocellular adenoma
- Hepatocellular carcinoma
- Bile duct adenoma
- Bile duct carcinoma
- Haemangiosarcoma
Where do primary hepatic neoplasms arise from?
Hepatocytes and biliary epithelium
Describe the features of a hepatocellular adenoma and its gross appearance
- Usually single tan coloured, surrounding tissue looks normal
- Sharply delineated
- No portal areas / lobular structure
- Compression of adjacent tissue without invasion
- May become quite large
- No metastasis
How does a hepatocellular adenoma look histologically?
Hepatocytes with no lobular architecture, lack sinusoids, some areas of blood in between
Describe the features of a hepatocellular carcinoma, including its 3 growth patterns
- Compression and invasion of adjacent tissue
- Metastasis [invasion of portal vessels]
- Growth pattern:
• Trabecular
• Acinar
• Solid
Describe the gross appearance of a hepatocellular carcinoma
Less of a boundary between normal and abnormal, also multifocal lesions where it has spread within the organ (intra-organ metastasis).
Describe the histological appearance of a hepatocellular carcinoma
Neoplastic cells (vary in size, large nuclei), also some non-neoplastic (smaller)
Describe the features and gross appearance of a bile duct adenoma
- Often cystic [cystadenoma]
- Usually single
- Sharply delineated
- Compression of adjacent tissue
- May become quite large
Describe the features and gross appearance of a bile duct carcinoma
- Commonly spreads along biliary tract
- Metastasis [spread to hepatic serosa, via lymph nodes to lungs]
- Often inducing desmoplasia
- Neoplastic tissue and fibrous tissue – feel very firm
- Sunken centre in the middle of the nodules
Describe how the liver can act as different sites for a haemangiosarcoma
Liver as primary site
or: as site of metastases
or: as one of several sites with multicentric development
Describe the 3 routes of metastasis to the liver
a) portal vein [from pancreas and intestine]
b) veins / arteries at sites of entry [any other neoplasms]
c) contact metastases [serosa; from malignant tumours in abdominal cavity]
Which tumour type most commonly metastasises to the liver?
Lymphoma
Describe the characteristic appearance of carcinomas in the liver
Carcinomas have a characteristic sunken centre in the middle of nodules due to necrosis
