Week 13 Flashcards
Describe acute hepatitis, including causes and clinical and histological features:
Inflammatory disease with less marked bile stasis
Diffuse hepatocyte injury seen as swelling, with inflammatory cell infiltrate in all areas: especially in portal tracts and interface but also in parenchyma
Acute
HBV may look like acute hepatitis plus fibrosis (specific feature is ground glass cytoplasm in hepatocytes=accumulation of surface antigen)
Describe acute cholestasis/cholestatic hepatitis, including causes and clinical and histological features:
Inflammation with more marked acute bile stasis
Caused by extra hepatic biliary obstruction or drug injury (eg antibiotics)
Histology: brown bile (bilirubin) pigments +/- acute hepatitis
Describe fatty liver disease, including causes and clinical and histological features:
Potentially chronic and may develop fibrosis and progress to cirrhosis
Give examples of drug-induced liver disease:
Drugs can cause almost any pattern of liver disease
Most drug hepatotoxicity idiosyncratic (rare but usually single clinical pattern) thus difficult to investigate e.g. Augmentin (co-amoxiclav: may cause acute cholestatic hepatitis)
Occasional predictable liver damage e.g. paracetamol, methotrexate
Don’t forget non-prescribed drugs e.g. over internet or herbal
Describe the diagnostic path of space-occupying liver masses:
Focal liver lesions = space occupying lesions (SOLs)
Non-neoplastic are either developmental/degenerative (eg cysts) or inflammatory (eg abscess)
Neoplastic can be benign or malignant
List commonly encountered hepatic neoplasms including primary liver tumours
and metastases:
Benign: hepatocellular adenoma, bile duct adenoma, haemangioma
Malignant: hepatocellular carcinoma, cholangio-carcinoma, angiosarcoma and liver mets
Describe the common clinical manifestation of liver disease and explain the mechanisms by which liver disease leads to these:
Portal hypertension: cirrhosis increases resistance to blood flow through the liver, thus increasing pressure in the portal circulation
This causes; portal-systemic shunts and varices, ascites, and splenomegaly (hypersplenism)
Reduced effective circulatory volume (due to splanchnic vasodilation from porto-systemic shunting) causes compensatory vasopressors, leading to sodium retention causing ascites and renal vasoconstriction causing hepato-renal syndrome
Other complications include liver failure, hepatocellular carcinoma
Hepatic encephalopathy has precipitating factors leading to reduction of hepatic or cerebral function, stimulation of an inflammatory response and increasing ammonia levels
Common precipitating factors of hepatic encephalopathy:
- GI bleeding
- Infections
- Electrolyte imbalance
- Constipation
- Excess dietary (esp animal) protein
Discuss how to investigate a patient with liver disease:
Chronic liver disease:
- US
- FBC, liver screen, PCR for viral hepatitis
- Autoimmune liver disease: ANA/SMA/LKM; AMA (in PBC), immunoglobulins
- ferritin (haemochromatosis), caeruoplasmin (wilson’s), alpha1 anti-trypsin deficiency
Acute liver injury:
- US
- HAV, HBV, HEV, CMV antigens (PCR)
- ANA, SMA, LMK (AIH) and immunoglobulins
- paracetamol levels
AST/ALT ratio lower in NAFLD and higher in ALD
Describe the common management strategies for patients with liver disease:
Patients with NAFLD can see remission of condition with loss of 10% of their BMI
Describe basic gross and microscopic structure and anatomical relationships between the extrahepatic bile ducts, gallbladder and pancreas:
Right and left hepatic duct join to form the common hepatic duct
The cystic duct flows from the gallbladder joining the common hepatic duct to form the common bile duct
The pancreatic duct joins the common bile duct at the ampulla of vater which flows into the duodenum through the major duodenal papilla
List the different kinds of gallstones, their chief constituents, and risk factors or conditions
predisposing to their formation:
Bile becomes lithogenic if there is excessive secretion of cholesterol or decreased secretion of bile salts
Excessive secretion of bilirubin (eg haemolytic anaemia) can cause its precipitation in concentrated bile in the gallbladder
Discuss the contribution of gallstones to acute and chronic cholecystitis, obstructive jaundice,
acute pancreatitis and ascending cholangitis; and outline the main features and consequences
of these conditions:
Acute cholecystitis is initiated by stone obstruction of cystic duct causing supersaturation of bile and chemical irritation
Chronic cholecystitis may be a sequel to repeated attacks of acute cholecystitis
Inflammation is secondary to chemical damage from supersaturated bile rather than bacterial infection
Mucocoele of gallbladder can form around gallstones caused by inappropriate secretion of mucus and decreased gallbladder motility
Describe pancreatic carcinoma:
66% in head of pancreas, ductal adenocarcinoma is most common subtype
Perineural invasion
Pre-malignant pancreatic intraepithelial neoplasia is asymptomatic
There is no standard effective therapy
RFs: smoking and germ-line mutations (BRCA)
Signs and symptoms: painless obstructive jaundice, new onset diabetes, abdo pain due to pancreatic insufficiency or nerve invasion
Double duct sign on radiology may indicate tumour in head of pancreas obstructing pancreatic duct and CBD
Describe common presentations of pancreatico-biliary disease:
Acute pancreatitis
2 of 3:
- pain in keeping with pancreatitis (severe pain in the centre of the abdomen, radiating to the back)
- amylase 3 times upper limit of normal
- characteristic CT appearance
Discuss how to assess and investigate the patients with pancreatico-biliary disease:
US to assess for gallstones
MRCP to assess for CBD stones
CT if diagnostic doubt or concern about complications
How are pancreatic-biliary disorders are managed and treated?
Initial:
ABCs, fluids, oxygen, organ support, (abx)
Further:
Treat cause
ERCP, lap cholecystectomy, alcohol addictions advice, stop medication (DMARDs)
Describe cirrhosis:
Definition is three-fold: diffuse process with fibrosis and nodule formation
End-stage liver disease, result of chronic inflammation over many years
- persistence of injury causing agent
- (fibrous) scarring and hepatocyte regeneration (leads to nodules)
- eventually irreversible and cirrhosis develops
Describe haemangioma:
Benign blood vessel tumour
Biopsy avoided because of risk of bleeding
Describe hepatic adenoma:
Rare
Mainly in young women, often associated with hormonal therapy
Risk of bleeding and rupture so excision if large
Describe hepatocellular carcinoma:
Most common primary liver tumour
Usually arises in cirrhosis and associated with elevated serum AFP (alpha feto-protein)
Screening available
What is the pathogenesis of cirrhosis?
Hepatocyte injury leads to progressive liver cell loss, which causes chronic inflammation, and hepatocyte regeneration
Chronic inflammation causes fibrosis, and hepatocyte regeneration causes hyperplastic nodules
Both of these cause architectural abnormality in the liver, leading to ischaemia which causes further liver cell loss.
What secretory protein production is impaired in liver failure?
Albumin, transport proteins, coagulation and fibrinolysis (e.g. factors II, V, VII-XIII), complement and protease inhibitors
How are hepatitis A and E transmitted?
Faeco-oral, contaminated food and water, person-person
What is the main determinant of severity of hepatitis A infection?
Age, mostly asymptomatic in children under 5 years old
Subsequently develop life-long immunity
