Patterns of Disease in the Liver
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What is the main type of cell found in the liver?
What makes up a portal triad?
- Hepatic artery
- Portal vein
- Bile duct
What are the spaces in between hepatocytes where blood flows through called?
What direction does blood flow in a hepatic lobule?
Blood flows from the portal triad to the central vein
What direction does bile flow in a hepatic lobule?
Bile flows from the central vein to the bile ducts in the portal triads
What are the different zones in the liver? Which is most/least oxygenated?
- Zones 1,2 and 3.
- Zone 1 is closest to the afferent blood supply and so is the most oxygenated. Zone 3 is closest to the terminal hepatic vein and is the zone with the least oxygenated blood. It is prone to hypoxic damage.
What are some of the liver defences?
What are the portals of entry to the liver?
- Direct extension - penetrating trauma (either external or in the GI tract)
- Haematogenous - sinusoid localisation (portal vein, hepatic artery or umbilical vein), kupffer cell localisation
- Retrograde biliary transport - ascending parasitic or bacterial infections gain access
What is a common liver disease caused by internal trauma in cattle?
Hardware disease (bovine traumatic reticuloperitonitis)
What poisonous plant commonly causes liver disease in many species?
How does Ragwort cause liver disease?
The toxin has anti-mitotic effects; it prevents cell division of hepatocytes but not DNA synthesis. The remaining hepatocytes are attempting to replace those lost by necrosis so you get megalocytosis (big hepatocytes), fibrosis and biliary hyperplasia.
What are some of the mechanisms of liver injury?
- Metabolic bioactivation of chemicals
- Stimulation of autoimmunity
- Stimulation of apoptosis
- Disruption of Ca2+ homeostasis
- Canalicular injury
- Mitochondrial injury
What are the main targets of liver injury?
Epithelial cells i.e. hepatocytes and biliary epithelium
What are the three patterns of hepatocellular degeneration and necrosis?
- Random - multifocal necrosis. It can be a single cell/small numbers of affected cells. Caused by viruses, bacteria and protozoa.
- Zonal - produces an enlarged, rounded liver. Specific zones degenerated. Normally centrilobular (zone 3)
- Massive - entire lobule or continuous lobules affected
Give an example of a pathogen that causes random hepatocellular necrosis
- Herpesvirus infections
- Canine infectious hepatitis
Why are herpesviruses more common in neonates/foetuses?
As herpesviruses do not like cold conditions so once an animal is able to thermoregulate they are less susceptible.
How is herpesvirus transmitted to foetuses and neonates? What is its pathogenesis?
- Infection can be transplacental, via the birth canal, infected litter mates or the dam
- Initially the viruses undergoes oronasal multiplication. It then enters the bloodstream via infected mononuclear phagocytes and causes multifocal necrosis in liver, kidneys, lung and spleen.
What can be seen on gross inspection with a liver infected with canine infectious hepatitis?
- Liver enlarged and friable. Will often see fibrin on capsular surface.
- There is a granular appearance to the serosae.
- Characteristic of CAV1 is a thickened gall bladder.
What is the pathogenesis of infectious canine hepatitis?
- Oral / urine infection
- Viral multiplication in tonsils
- Moves to local lymph nodes then to the systemic circulation (via the thoracic duct)
- Infects Kupffer cells / hepatocytes / endothelial cells / mesothelial cells
Which zone of the liver is most prone to necrosis? Why?
- Zone 3
- As this area receives the least oxygenated blood so is susceptible to hypoxia and has the greatest enzymatic activity to activate compounds to toxic forms
What are some of the possible causes of zonal necrosis?
- Severe anaemia - zone 3 is already prone to hypoxia so a further decrease in O2 supply will cause further damage
- Right sided heart failure - this will mean that deoxygenated blood is flowing through the body and zone 3 of the liver will struggle with the decreased O2 availability
- Passive congestion of the liver - hypoxia due to blood stasis and atrophy of centrilobular hepatocytes (blood builds up in the liver and as the sinusoids are full of blood they cause pressure atrophy of hepatocytes)
What is an example of a pathogen that causes massive necrosis?
What is jaundice / icterus?
When there is accumulation of bilirubin in the liver and tissues
What causes jaundice/icterus?
- Excessive bilirubin production
- Failure to remove bilirubin eg damaged hepatocytes
Describe the enteropathic circulation of bilirubin
- 1. Breakdown of old RBCs
- 2. Extrahepatic bilirubin bound to serum and delivered to the liver
- 3. Hepatocellular uptake
- 4. Glucornidation in the ER - products are water soluble and readily excreted in bile
- 5. Gut bacteria deconjugate bilirubin and degrade to colourless urobilinogens which are excreted in faeces or some are reabsorbed and excreted into urine
What are the portals of entry to the biliary system?
- Direct extension - external or internal (GI tract)
- Haematogenous - localisation within capillary beds of wall of gall bladder or small arterioles of biliary tree
- Retrograde biliary transport - ascending bacterial or parasitic infections gain access
Describe the pathogenesis of liver fluke
- Metacercaria penetrate intestinal wall
- Migrate across the peritoneum
- Pierce the liver capsule
- Create tracts of necrotic liver parenchyma
- Tracts heal by necrosis
- Flukes enter bile ducts
- Chronic cholangitis, ectasis, stenosis
What are the different responses to liver damage?
- Regeneration - replication of hepatocytes, biliary epithelium, endothelium and sinusoidal lining cells
- Fibrosis - scarring
- Biliary hyperplasia - proliferation of bile ducts
What is cirrhosis (end stage liver)?
Diffuse fibrosis with hyper plastic nodule formation (there is total absence of any normal lobular architecture)
What is a common clinical sign of cirrhosis?
Odema (caused by decreased albumin production, hypoproteinaemia and decreased oncotic pressure)
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