Liver Disease Flashcards
What separates the 2 main lobes of the liver
The falciform ligament
How many segments is the liver split into
8
What supplies blood to the liver
Hepatic artery (oxygenated blood) Hepatic portal vein (nutrients)
What connects the gall bladder to the common hepatic duct
cystic duct
What cells make up the liver and how are they arranged
Hepatocytes
Sheets of hepatocytes are separated by sinusoids
Hepatic tissue can be arranged into lobules - hexagons
What is found in the centre and corners of each lobule
Central vein located at the centre
Portal tract at the corner of each lobule
What is the portal tract made up of
Hepatic artery
Portal vein
Bile duct
What functional units are found in hepatic tissue and where are they found
Acini are functional units of hepatic tissue found between 2 central veins
Where are the 3 zones of acini found in hepatic tissue
Zone 1 = closest to portal tract
Zone 3 = closest to central vein
Zone 2 = found between the 2 other zones
What is the metabolic function of the liver
Detoxification and breakdown of toxins, hormones and drugs
What are the synthetic functions of the liver
- Bile (emulsification of fat)
- Protein (production and activation)
- Carbohydrate (gluconeogenesis)
- Lipid (cholesterol, triglycerides)
- Red blood cells (in foetal liver)
- Clotting factors
What responses does the liver have to injury
- Hepatocyte degeneration and intracellular accumulation
- Hepatocyte necrosis and apoptosis
- Inflammation
- Regeneration
- Fibrosis
What symptoms are associated with liver injury
- Jaundice
- Oedema
- Ascites
- Cerebral dysfunction
What is jaundice cause by and what does it look like
Increased serum bilirubin and bilirubin deposition in tissues and causes discolouration of skin and sclera
What is ascites
Accumulation of fluid in the abdominal cavity
Describe how bilirubin is formed
- Hb in RBCs is released
- Heme from Hb is oxygenised by Heme Oxygenase
- This forms Biliverdin
- Biliverdin is reduced to unconjugated bilirubin by biliverdin reductase
- Unconjugated bilirubin gains a glucuronate to form conjugated bilirubin
What are the 3 site classifications of jaundice and what does each mean
Prehepatic - takes place before the bilirubin reach the liver
Intrahepatic - Takes place within the liver
Post-hepatic - takes place after the bilirubin leaves the liver
What are the prehepatic causes of jaundice
Excess bilirubin production:
- haemolytic anaemia
- Internal bleeding
- Ineffective erythropoiesis
What are the intrahepatic causes of jaundice
Impaired conjugation
Impaired excretion
Reduced Uptake
What can cause impaired conjugation in intrahepatic jaundice
- Physiological jaundice in newborns/ can occur in breast feeding
- Diffuse hepatocellular disease
What can cause impaired excretion in intrahepatic jaundice
- Intrahepatic bile duct disease
- Drugs
What can cause reduced uptakes in intrahepatic jaundice
drugs
What is the mechanism of postheaptic of jaundice
Extrahepatic biliary obstruction
What can cause extra hepatic biliary obstruction and cause post hepatic jaundice
Gallstones
Pancreatic cancer
Extrahapetic biliary atresia
Biliary strictures
What can cause hepatic oedema/ascites
Portal hypertension - high blood pressure in the portal venous system
Hypoalbuminaemia - low level of albumin in the circulation
How can cerebral dysfunction occur with liver injury and what symptoms are associated with it
- Increased production of ammonia in liver injury
- Ammonia disrupts neurotransmission
- Symptoms include disturbance in consciousness, rigidity, hyper-reflexia, asterixis
What is hepatitis
Inflammation of the liver following injury, can be acute or chronic
Name some causes of hepatitis
Viral
Alcohol
Drugs/toxins
Autoimmune
How is Hepatitis A spread and is it chronic or acute
Faecal-oral spread
not chronic
How is Hepatitis B spread and is it chronic or acute and how can it progress
Parenteral spread
Chronic in 5-10%
Can progress to chronic hepatitis and hepatocellular carcinoma
How is Hepatitis C spread and is it chronic or acute and how can it progress
Parenteral spread
Chronic in 5-10%
Can progress to chronic hepatitis and hepatocellular carcinoma
When does hepatitis D tend to occur
Tends to occur as a co infection with hepatitis B = fulminant disease
What can super infection of hepatitis D cause
Chronic progressive hepatitis
How is hepatitis E spread and is it chronic
Spread via water droplets and not chronic
What are the symptoms of acute hepatitis
- Mostly non-specific symptoms initially, like nausea, vomiting and pain
- Specific symptoms = profound loss of appetite, dark urine and jaundice
- Some progress to acute liver failure
Describe the macroscopy of acute hepatitis
Mild hepatomegaly
Congestion
Describe the microscopy of acute hepatitis
- Scattered foci of lobular necrosis and inflammation
- Apoptotic bodies (councilman bodies)
- Hepatocyte ballooning and necrosis
- Disruption of architecture (lobular disarray)
- Inflammation of portal tracts
How long do symptoms have to show for before you can diagnose chronic hepatitis
> 6 months
What are the causes of chronic hepatitis
- Hepatitis B or B + D
- Hepatitis C
- Autoimmune Hepatitis
- Drug-induced hepatitis
What 3 histological features of chronic hepatitis can be seen
Inflammation (predominantly lymphocytic)
Hepatocyte necrosis
Fibrosis
Where can you see inflammation histologically in chronic hepatitis
Portal tracts
Periportal interface hepatitis (piecemeal necrosis)
Lobular
What is periportal interface hepatitis
Inflammation within the lobular boundaries
What types of necrosis can you see histologically in chronic hepatitis and describe them
- Bridging necrosis - portal tract to central vein or portal tract to portal tract
- Confluent necrosis - larger area necrosis
What is fibrosis and what can it result in
This is the replacing of the liver tissue for scar tissue and can eventually cause cirrhosis
What is cirrhosis
Cirrhosis is irreversible end stag liver disease that disrupts the vascular architecture and blood flow of the liver
Name some of the causes of cirrhosis
- Alcohol
- Viral hepatitis (B,C and D)
- Autoimmune hepatitis
- Primary and secondary biliary cirrhosis
- Metabolic causes e.g. haemochromatosis, Wilson’s disease, Alpha-1-antitrypsin deficiency
- Drugs
- Idiopathic
- Venous outflow obstruction
What complications can cirrhosis cause
Hepatic failure
Portal hypertension
Hepatic encephalopathy
Oesophageal varices - obstructed portal veins
Describe the mechanism of how cirrhosis causes hepatic encephalopathy
- Portal blood bypasses liver
- Toxic or metabolic effect on the brain
Describe the mechanisms by which portal hypertension can cause ascites
High intrasinusoidal pressure Leakage from hepatic lymphatics Hypoalbuminaemia Na+ Water Retention
What are ascites
Build up of fluid in the abdomen
Portal hypertension results in what
Ascites
Portal systemic venous shunts
Splenomegaly (congestive)
Describe the effects of portal systemic venous shunts
- Oesophagus: varices
- Rectum: haemorrhoids
- Falciform ligament
- Anterior abdominal wall
What problems come about as a result of hepatic failure
- Jaundice
- Hypoalbuminaemia
- Coagulopathy
- DIC - disseminated intravascular coagulation
- Raised serum area
- Hepatorenal syndrome
- Gynaecomastia, spider nave
- Encephalopathy
What are the 3 stages of Alcoholic liver disease
- Alcoholic Steatosis
- Alcoholic Hepatitis
- Alcoholic Cirrhosis
What happens in alcoholic steatosis
- Fatty change in the liver = soft yellow liver
- Fibrosis
What happens alcoholic hepatitis
- Fatty cahnge
- Fibrosis
- Hepatocyte necrosis
- Inflammation
- Iron deposition
- Mallory’s hyaline (protein) deposition
What are benign primary liver tumours called
Liver cell adenoma
What kinds of malignant primary liver tumour can you get
- Hepatocellular carcinoma
- Cholangiocarcinoma
- Angiosarcoma
- Hepatoblastoma (mainly children)
Describe the morphology of secondary liver tumours
- Hepatomegaly
- Typically multiple nodules; rarely a solitary nodule
When do hepatocellular carcinomas often develop
In a cirrhotic liver
List the aetiologies (factors) of hepatocellular carcinomas
- Hep B virus
- Hep C virus
- Haemochromatosis
- Aflatoxin
- Alcohol, age, gender
Describe the clinical features of hepatocellular carcinomas
- Abdominal pain
- Weight loss
- Hepatomegaly
- Raised serum alpha-feto protein (also seen in cirrhosis, yolk sac tumours)
- Metastases occur later: lungs
- Survival <6 months usually
- Death due to cachexia, varices, encephalopathy
Describe the macroscopy of hepatocellular carcinoma
Hepatomegaly -
- univocal mass: yellow/white, soft, haemorrhage, necrotic
- Multifocal
- Diffusely infiltrative
Describe the microscopy of hepatocellular carcinoma
- Well differentiated tumours resemble normal liver trabeculae
- Poorly differentiated tumours may mimic metastases
