SP4: Liver Diseases Flashcards
Describe the anatomy of the liver
- 2 main lobes
- separated by flaciform ligament
- 8 segments based on branches of blood supply
- hepatic artery = oxygenated blood
- hepatic portal vein = nutrients from small colon
- gallbladder connects to common hepatic duct via cystic duct
What caries bile from the liver to duodenum
It is produced in the gallbladder, carried in the cystic duct to the common hepatic duct which carries the bile to the duodenum
Describe liver histology
- tissue is made of hepatocytes
- sheets of hepatocytes are separated by sinusoids (where the blood vessels will travel through)
- hepatic tissue is arranged into lobules = functional units
- central vein is located at the centre of each lobule
- portal tract is present at each corner of a lobule (contains hepatic artery, portal vein and bile duct)
What are acini
They are located between two central veins (centre of one lobule to another) - this is divided into 3 zones
Zone 1 = Closest to portal tract
Zone 3 =Closest to central vein
What are the functions of the liver
Detoxification and breakdown of toxins, hormones and drugs
Synthesis of : bile, protein, gluconeogenesis, cholesterol, triglycerides, RBCs in foetal liver, clotting factors
Storage of glucose (as glycogen), vitamins and minerals
What happens in response to liver damage
- Hepatocyte degeneration - so intracellular accumulation
- Hepatocyte necrosis and apoptosis
- Inflammation
- Regeneration
- Fibrosis and formation of scar tissue
What are the symptoms of liver damage
- Jaundince (due to increased bilirubin giving yellowing)
- Oedema (fluid retention in tissues)
- Ascites (distension of abdomen)
- Cerebral dysfunction (drowsiness and confusion)
Outline the process of bilirubin metabolism
- Hb released from RBCs
- Heme oxygenase converts heme to biliverdin
- Biliverdin reductase reduces this to unconjugated bilirubin
- This is converted to conjugated bilirubin
What is jaundice
Raised serum bilirubin with bilirubin deposition in tissues
This can be classified by site or type
What are the pre-hepatic causes of jaundice
This is jaundice before bilirubin reaches the liver and is caused by
- Haemolytic anaemia : RBCs in circulation breakdown releasing haemoglobin and so bilirubin
- Internal bleeding : blood escaped from blood vessels is broken down
- Ineffective erythropoiesis
What are the intra-hepatic causes of jaundice
This is jaundice when the bilirubin has reached the liver and is caused by
- Impaired conjugation of bilirubin and diffuse hepatocellular disease
- Impaired excretion: intrahepatic bile duct disease
- Reduced uptake
What are the post-hepatic causes of jaundice
This is jaundice after bilirubin has left the liver and is caused by
- Extrahepatic biliary obstruction
- gallstones produced in gallbladder
- pancreatic cancer that compresses biliary tree
- extrahepatic biliary atresia : no lumen in biliary tree so bile cannot flow
- biliary strictures : narrowing causing bilirubin to accumulate
What are the hepatic causes of oedema and ascites
- Portal hypertension : high blood pressure in portal venous system
- Hypoalbuminaemia : low level of albumin in circulation which would normally help retain fluid in circulation due to osmolality
Outline the mechanism of oedema and ascites
- high intrasinusodial pressure
- leakage from hepatic lymphatics
- Na + and water retention
What are the effects of portal hypertension
Portal systemic venous shunts
- oesophagus = varices
- rectum = haemorrhoids
- ant. abdominal wall (caput medusae)
Splenomegaly (congestive) = enlarged spleen
How is cerebral dysfunction caused
Increased ammonia production in liver injury disrupts the urea cycle and this affects neurotransmission in the brain and CNS causing the following symptoms
- decreased consciousness
- rigidity
- hyper-reflexia
- asterixis (resting hand tremour)
What is hepatitis
Inflammation of the liver following injury - can be acute/chronic
What are the causes of hepatitis
- Viral
- Alcohol
- Drugs/toxins
- Autoimmune
What is hepatitis A
liver infection caused by faecal-oral spread; not chronic
What is hepatitis B
liver infection caused by parenteral spread (IV, sex)
this is chronic in 5-10% and so can progress to chronic hepatitis an hepatocellular carcinoma
What is hepatitis C
liver infection caused by parenteral spread which is chronic in >50% and can progress to chronic hepaptitis and hepatocellular carcinoma
What is delta hepatitis viris/ Hepatitis D
It is a defective RN virus which is infective if encapsulated by HBV
- it results from co infection with hep B and results in fluminant disease (rapidly escalating)
- it is a chronic progressive disease
What is hepatitis E
Water bourne and non chronic
What are the symptoms of acute hepatitis
- mostly non-specific; nausea, voomiting, abdo pain
- specifics; loss of apetite, dark urine, jaundice
- small portion can progress to acute liver failure
Describe the pathological features of acute hepatitis
Macro = mild hepatomegaly (enlargement) and congestion
Micro;
- scattered foci of lobular necrosis and inflammation
- apoptotic bodies (of hepatocytes) = Councilman body
- hepatocyte ballooning an necrosis
- disruption of architecture causing lobular structure
- inflammation of portal tracts thus many inflammatory cells
What is a councilman body
Present in acute hepatitis where there are hepatocytes undergoing apoptosis and these are eosinophilic with irregular nuclei
What is chronic hepatitis
Necroinflammatory disease in which hepatocytes are the target of attack caused by
- Hep B / B + D
- Hep C
- Autoimmune hepatitis
- Drug-induced hepatits
What three histological changes occur in chronic hepatitis
- Inflammation (predominantly lymphocytic)
- portal tracts
- periportal interface hepatitis (piecemeal necrosis within lobular boundaries)
- lobular - Hepatocyte necrosis
- bridging necrosis = portal to central/ portal to portal
- confluent necrosis = larger area - Fibrosis
- portal/ periportal/ bridging and eventually cirrhosis
What is cirrhosis and what histological changes can be seen
Irreversible and end stage liver disease
- diffuse process
- fibrous nodules (regenerative hepatocytes surrounded by fibrosis)
- disruption of vascular architecture and blood flow
What complications can arise with cirrhosis
- Portal hypertension
2. Hepatic failure
What are the causes of cirrhosis
- alcohol
- viral hepatitis (B,C,D)
- autoimmune hepatitis
- primary and secondary biliary cirrhosis (damaged biliary tree)
- metabolic causes
- drugs
- ideopathic thus not causal
- venous outflow obstruction
What are the metabolic causes of cirrhosis
- Haemochromatosis = impaired iron metabolism so there is iron acculimation within the tissue
- Wilson’s disease = defective copper metabolism so there is copper accumilation
- Alpha-1-antitrypsin deficiency = these proteins would normally protect the liver and lung from injury but they are insufficient
What are the complications of cirrhosis
- hepatic failure
- hepatic encephalopathy = cerebral dysfunction due to ammonia
- oesophageal varicies
What is hepatic encephalopathy
This is where cerebral dysfunction arises due to ammonia because the portal blood bypasses liver which can have toxic or metabolic effects on the brain meaning there is a decreased consciousness which can potentially lead to coma
What are oesophageal varices
These are massive haemorrhages due to portal dynamic shunts - the abnormal vessel dilation increases the risk of bleeding and this manifests as haemorrhoids in the rectum
Describe the cell pathology of cirrhosis
- cannot make out hexagonal lobules
- there are large spaces between sheets of hepatocytes
What are the 8 features of hepatic failure
- Jaundice (increased bilirubin as hepatocyte dysfunction)
- Hypoalbuminaemia (decreased synthesis of albumin)
- Coagulopathy (decreased clotting factor synthesis)
- Disseminated intravascular coagulation (muli clots form)
- Raised serum urea (as urea cycle disturbance)
- Hepatorenal syndrome (reduced renal blood flow)
- Gynaecomastia (liver cant break down oestrogen)
- Encephalopathy
What happens in alcoholic steatosis
- fatty change; red liver tissue becomes soft and yellow
- fibrosis
- if alcohol consumption isnt reduced it can cause alcoholic hepatitis
What happens in alcoholic hepatitis
- fatty change
- fibrosis
- hepatocyte necrosis
- inflammation : inflammatory cells seen in biopsy
- Mallory’s hyaline (protein deposition); iron deposition
What is alcoholic cirrhosis
Irreversible tissue breakdown due to alcohol
What are the four malignant primary liver tumours
- Hepatocellular carcinoma (most common)
- Cholangiocarcinoma (developed from biliary tree)
- Angiosarcoma (originates from blood vessels in liver tissue)
- Hepatoblastoma (mainly in children)
What are the sources of secondary metastatic tumours in the liver and what is the morphology
- Carcinoma (GIT and breast)
- Melanoma (skin)
Causes hepatomegaly and multiple nodule formation
Describe the aetiology of hepatocellular carcinoma
- majority develop in a cirrhotic liver
- hep B, C
- haemochromatosis
- aflatoxin from fungi
- alcohol, age, gender
What are the clinical features of hepatocellular carcinoma
- abdo pain, weight loss, hepatomegaly
- raised serum alpha-feto protein
- metastasis occur late stage in the lungs
- survival <6 months (poor prognosis)
- death is due to cachexia (XS weightloss and muscle wasting), varices (rupture of portal shunts), encephalopathy
Describe the pathology of hepatocellular carcinoma
Macroscopy
- Unifocal mass = yellow/white, soft, haemorrhage, necrotic
- Multifocal
- Diffusely infiltrative
Microscopy
- well differentiated tumours resembling normal liver trabeculae (rows)
- poorly differentiated tumours mimic metastases
