Cirrhosis and Portal Hypertension Flashcards
Chronic hepatitis refers to
Chronic viral hepatitis (B and C) and autoimmune hepatitis
not synonymous with chronic liver disease
Chronic liver disease refers to
- chronic hepatitis (B, C, AIH)
- NASH
- alcoholic liver disease (SH, pericellular fibrosis)
- metabolic diseases (Wilson’s/copper, haemachromatosis/iron)
- chronic inflammatory diseases of bile ducts
- primary sclerosing cholangitis
- primary biliary cirrhosis
- drugs
What are the common features of diseases causing chronic liver disease?
- chronic inflammation (pattern differs)
- fibrosis that can lead to cirrhosis (progression varies eg AIH 5 years un-dx)
Steatohepatitis characterizes what conditions?
- acute alcoholic hepatitis
- chronic alcoholic liver disease
- NASH
What are the elements of steatohepatitis?
- macrovesicular steatosis
- hepatocelluar ballooning
- mallory bodies
- inflammation
- varying degrees of pericellular/chicken wire fibrosis
What is the difference between acute alcoholic hepatitis and chronic alcoholic liver disease?
- in acute alcoholic hepatitis hepatocellular injury is more severe
- more Mallory bodies, more neutrophils
- pt presents with acute hepatitis
- chronic alcoholic liver disease is a more dialed down process of the disease
Presentation of acute hepatitis is not related to what condition?
NASH does not produce acute hepatitis; severe of hepatocellular injury is uncommon in NASH
presentation of acute hepatitis + steatohepatitis on biopsy = ASH
D - lobular dissaray and apoptotic bodies
significant ALT elevation, less than 6mo duration and no previous hx = acute
likely caused by hep A
(coagulative necrosis is paracetamol/toxicity and there is no biliary obstruction on ultrasound)
A - some degree of periportal fibrosis
chronic hepatitis due to HCV
C could be an additional consideration with further history investigation
What is cirrhosis?
- nodules of regenerating hepatocytes surrounded by bands of fibrous scar tissue
- diffuse disease: involves the whole liver
- irreversible; only cure is transplantation
What are the causes of cirrhosis in adults?
- alcoholic liver disease
- NASH
- chronic viral hepatitis B and C (300, 000 Australians)
- AIH
- chronic biliary disease
- metabolic diseases (wilson’s, haemochromatosis, a1-antitrypsin deficiency)
What is the pathogenesis of cirrhosis?
- stellate cells (VitA storage) in space of Disse (btw sinusoid & hepatocyte) are
- chronic/persistant apoptosis and inflammation causes release of cytokines rom Kupffer cells
- cytokines activate stellate cells; have myofibroblast phenotype - contract & produce collagen
- also get remodeling of the liver vascular supply (causes ischaemia important in progression of cirrhosis in later stages)
What complications in cirrhosis are due to parenchymal liver failure?
- hepatic encephalopathy (+circulation of GABA-like inhibitory peptides that are normally removed by the liver)
- coagulopathy - decreased clotting factors produced in liver
- hypoalbuminaemia - decreased albumin production in liver
- portal hypertension
- jaundice
What complications of cirrhosis are due to secondary endocrine disturbances?
- gynaecomastia
- spider naevi
- testicular atrophy
- feminization of hair patterns
What complications of cirrhosis are due to portal hypertension?
- 3 major clinical features:
- ascites
- splenomegaly (causing thrombocytopaenia)
- formation of varices at portosystemic anastamoses
What are the clinical signs of chronic liver disease?
- jaundice
- hepatomegaly
- splenomegaly (due to portal hypertension; causes thrombocytopaenia)
- ascites (portal hypertension and low serum albumin)
- caput medusae/abdominal wall collaterals
- skin telangiectasia (spider naevi)
- palmar erythema
- gynaecomastia
- testicular atrophy (mainly alcoholic cirrhosis and haemachromatosis)
- digital clubbing
- dupuytrens contractures
- asterixis (metabolic flap)
The greatest risk of hepatocellular carcinoma is seen in cirrhosis due to
- alcohol
- chronic viral hepatitis B and C
- haemochromatosis
How is hepatocellular carcinoma (hepatoma) related to cirrhosis?
- majority of primary liver cell carcinomas occur in cirrhosis pt
- risk related to cause of cirrhosis in addition to cirrhosis itself
- secondary metastatic carcinoma of the liver is extremely rare in cirrhosis
Multiple lesions in a cirrhotic liver is
multi-focal hepatocellular carcinoma
secondary metastases are exceptionally rare in cirrhotic livers
What defines portal hypertension?
- absolute increase in portal venous BP (>8mmHg), or
- increase in pressure gradient between the portal ven and the hepatic vein of 5mmHg or more
What are the causes of portal hypertension?
- pre-sinusoidal: portal vein thrombosis
- intra-hepatic/sinusoidal: cirrhosis
- post-sinusoidal: thrombosis or occlusion of hepatic veins (Budd-Chiari syndrome); high risk in women post-partum or taking synthetic estrogens
What are the 4 factors that contribute to portal hypertension in cirrhosis?
- increased blood flow through splanchnic vascular bed increases portal flow and stimulates contraction of vascular smooth muscle and stellate cells (even before fibrosis has advanced)
- hepatic vein is compressed by regenerating nodules, increasing resistance to flow through the liver
- small portal vein branches become trapped, distorted, and destroyed by scar tissue - obliterated small portal veins
- shunts opening up between branches of hepatic artery and portal vein (arteriovenous anastamoses) in fibrous septa
What are the main sites of porto-systemic anastomoses in cirrhosis?
- oesophagus
- rectum
- umbilicus
What is the most important site of varices in portal hypertension?
- oesophagus; extremely common (cirrhosis pt screened for them)
- treated prophylactically bc prone to cataustrophic bleeding
