Hepatobiliary and Pancreatic Disease Flashcards
What does the liver synthesise?
albumin, clotting factors, complement, -1-antitrypsin, thrombopoietin
What is produced in the liver?
bile through conjugation of bilirubin
What does the liver break down?
drugs, insulin, ammonia
What is the action of Kupffer cells?
phagocytose old blood cells, bacteria and foreign materials from the bloodstream/gut
What is jaundice?
- Yellowing of skin and mucosal surfaces – bilirubin >40mol/L
What can jaundice cause?
itch
Unconjugated =
water-insoluble
conjugated =
water-soluble (can be excreted in urine)
What is the result of excess conjugated bilirubin?
dark urine
Describe a prehaptic cause of jaundice
haemolysis release of bilirubin from RBCs
Describe a intrahepatic cause of jaundice
liver disease; excess bilirubin in liver and bloodstream
Describe a post hepatic (obstructive) cause of jaundice
obstruction of bile outflow –> dark urine and pale stools
What are the main causes of acute liver injury?
o Viral Infections o Alcohol o Biliary obstruction (gallstones) o Adverse drug reactions
What are the main symptoms of acute liver injury?
- Jaundice, malaise
What biochemical factors are altered in acute liver injury
- Raised serum bilirubin (location determines the type of bilirubin) and transaminases
What are the main characteristics of acute liver failure?
decreased albumin, ascites, bruising, encephalopathy
What zone of liver cells are affected in acute liver injury?
Zone 3 = closest to the central vein so have the least oxygen. Less reserve for survival when infected with a toxin
What are the major characteristics of alcoholic liver injury?
Steatosis Cirrhosis Acute hepatitis with Mallory’s hyaline
What processes occur in steatosis that lead to fibrosis?
Acetaldehyde binds to hepatocytes causing damage ⇒ inflammatory reaction
Inflammation ⇒ fibrosis
What processes pccur in cirrhosis?
fibrosis (collagen) + regeneration –> Cirrhosis
Fibrosis tries to heal the area by preventing any further damage so inflammation cannot spread. As a result this area of the liver has no function and is stiffer
Causes of cirrhosis
- Alcohol
- Hep B + C
- Iron overload
- autoimmune liver disease
- gallstones
What are the main classifications of Cirrhosis?
- Morphological
- Micronodular – nodules <3mm
- Macronodular >3mm
- Mixed
- Aetiological
What are the three main complications of cirrhosis?
- liver failure
- portal hypertension
- hepatocellular carcinoma
What are the common features of liver failure?
hepatic encephalopathy (ammonia), build-up of steroid hormones ⇒ hypoestrogenism (palmar erythema and gynaecomastia), bleeding
What are the common features of portal hypertension
increased hepatic vascular resistance, AV shunting – oesophageal varices, haemorrhoids, caput medusae
Describe drug induced liver injury
- 10% of all drug reactions involve the liver
- Injury to liver cells (hepatocellular) – paracetamol overdose
- Injury to bile production/secretion cells (cholestatic) – methyl testosterone
- Always take a full drug history from a patient with deranged LFTs
What is the most common cause of acute biliary obstruction?
gallstones
What are the symptomns of acute biliary obstruction?
causes colicky pain and jaundice
What can be the main complication of acute biliary obstruction?
complicated by infection of blocked CBD - cholangitis (medical emergency)
What can chronic liver failure follow on from and what can it result in?
- A common clinical problem
- Can follow a clinical evident episode of acute liver injury
- May have insidious onset without symptoms until later stages
- Many forms culminate in cirrhosis
What is chronic hepaitis?
- inflammation of the liver lasting more than 6 months
- Sustained elevation of transaminases – require liver biopsy to classify cause
What are the main causes of chronic hepaitis?
- Viral
- Alcohol
- Drugs
- Autoimmune
What are the three main classifications of chronic hepaitis?
Type – aetiology
Grade – degree of inflammation
Stage – degree of fibrosis
What is NASH/NAFLD?
Non-alcoholic steatohepatitis/Non-alcoholic fatty liver disease
What are NASH/NAFLD associated with?
Associated with metabolic syndrome (DM II, hypertension, decreased HDL cholesterol, increased triglycerides)
What can fat deposition in hepatocytes lead to?
cirrhosis
Who is autoimmune chronic hepatitis likely to occur in?
Females > Males
Usually present in mid to late teens
Describe the main features of autoimmune chronic hepaitis
- Interface hepatitis - hepatocytes at the interface between the bloodstream and the main hepatic substance
- Plasma cells and swollen hepatocytes
- Fibrosis
- ANA, SMA, raised serum IgG and transaminases, anti-LKM (liver-kidney microsomal)
- Patients may benefit from steroids
Who is primary biliary cholangitis more common in?
Females > Males (~40-50 years old)
What are the stages of primary biliary cholangitis?
- Autoimmune destruction of bile duct epithelium – de3nse lymphocytic infiltration and granulomas
- Proliferation of small bile ducts
- Architectural disturbance – portal and bridging fibrosis
- Cirrhosis
What are the main clinical and biochemical features of primary biliary cholangitis?
Jaundice, pruritis, xanthelasmata
Raised ALP + IgM, AMA
Compare primary biliary cholangitis and primary sclerosing cholangitis:
Age/Gender
PBC = >50years, NOT children, F > M
PSC = Wide age range, M > F
Compare primary biliary cholangitis and primary sclerosing cholangitis:
Disease associations
PBC = other autoimmune diseases e.g. Sjorgens, thyroid
PSC = IBD; UC
Compare primary biliary cholangitis and primary sclerosing cholangitis:
Serum immunoglobulins
PBC = increased IgM
PSC = no signficant increase
Compare primary biliary cholangitis and primary sclerosing cholangitis:
Autoantibodies
PBC = AMA, ANA (centromeric)
PSC = non-specific, AMA rare
Compare primary biliary cholangitis and primary sclerosing cholangitis:
Colangiography
PBC = normal extrahepatic and large ducts
PSC = stricturing and beading
Compare primary biliary cholangitis and primary sclerosing cholangitis:
Bile duct injury
PBC = small ducts
PSC = large ducts
Compare primary biliary cholangitis and primary sclerosing cholangitis:
Portal inflammation
PBC = prominent
PSC = less prominent
Compare primary biliary cholangitis and primary sclerosing cholangitis:
Obliterative fibrosis of larger ducts
PBC = absent
PSC = characterisitc feature
Compare primary biliary cholangitis and primary sclerosing cholangitis:
Periportal copper
Present in PBC and PSC
What is haemochromatosis?
Iron deposition in the liver causing alteration of architecture ⇒ fibrosis ⇒ cirrhosis
AMA =
antimitochondrial antibody
ALP =
alkaline phosphatase
What are the main types of haemochromatosis?
Primary/secondary
Primary = Autosomal recessive – HFE gene
Secondary = from repeat blood transfusions
What is the treatment for haemochromatosis?
Regular venesection – test iron and ferritin
What causes alpha-1 antitrypsin deficiency?
Autosomal recessive disorder
Low levels of a-1-antitrypsin in the blood but high levels in the liver
What is the pathogenesis of a-1-antitripsin?
- Proteins build up in hepatocytes as hyaline
- Can lead to cirrhosis
- Associated with emphysema
What type of condition is wilson’s disease?
autosomal recessive
What is the pathophysiology of Wilson’s disease?
- Failure of the liver to excrete copper in bile ⇒ build-up of copper in the liver ⇒ cirrhosis
- Copper also deposits in brain tissue ⇒ neurological dysfunction
- Kayser-Fleischer rings
- Low ceruloplasmin
What are the main type of developmental/Hamartomas liver tumours?
Cysts
Haematomas
What are the main type of benign liver tumours?
Incidental finding
Adenoma, haemangioma
Liver cysts
What are the main type of maligant liver tumours?
- Metastases – common (from colon)
- Primary
- Hepatocellular carcinoma
- Cholangiocarcinoma
What are the main causes of hepatocellular carcinoma?
- Aflatoxins – fungal origin
- Hepatitis B + C viruses
- Cirrhosis (any cause)
What are the main pathologies assoicated with the biliary system?
- Congenital malformations
- Atresia
- Choledochal cysts
- Gallstones (cholelithiasis)
- Cholecystitis
- Cholangiocarcinoma
- Obstruction
Where does cholangiocarcinoma arise from anf what is it associated with?
Arises from bile duct epithelium anywhere in the biliary system (intra- and extra-hepatic)
Associated with ulcerative colitis (PSC also at risk)
What are the symptoms and clinical complications associated with cholangiocarcinoma?
- Causes obstructive jaundice, itch, weight loss and lethargy
- Can lead to rupture of common bile duct or gallbladder – prognosis poor
What are the main risk factors for gallstones?
Female, Fair, Fat, Forty, Fertile
Diabetes
What can gallstones cause?
cholecystitis, obstructive jaundice, cholangitis, pancreatitis, cholangiocarcinoma
What are the main features of acute cholescysitis?
- Usually caused by gallstones
- Initially sterile then becomes infected
- May lead to abscess/rupture
- Symptoms
- RUQ pain (biliary colic), fever, nausea/vomiting
What are the features of chronic cholecystitis?
Invariably related to gallstones
Chronic inflammation with wall thickening
What is annular pancreas?
And what can this cause?
- Embryological malformation - part of the pancreas rotates the wrong way
- 2nd part of duodenum
- Causes obstruction – polydramnios, low birth weight, poor feeding
What are the main features of acute pancreatitis?
- Causes catastrophic metabolic consequences
- High serum amylase – diagnostic
- Massive fluid losses –> SHOCK
- High mortality rates
What are the main causes of acute pancreatitis?
- mumps
- gallstones
- shock (decreased BP)
- hypothermia
- alcohol
- trauma
- scorpion sting
What are the biocehmical markers of acute pancreatitis?
decreased calcium and albumin, increased glucose
What are the main features of chronic pancreatitis?
- Multiple episodes of acute
- Causes fibrosis of pancreas – may lead to diabetes mellitus
- Reduced production of enzymes – require supplements (creon)
Describe the main features of pancreatic carcinoma
- Adenocarcinoma
- Associated with smoking and diabetes mellitus
- Presents with painless, progressive jaundice
- Weight loss
- Poor prognosis
- May be operable if small and close to ampulla
