Investigation of Liver & Pancreatic Disease Flashcards
What is involved in investigation of the liver?
- structure & function of the liver
- effects of liver disease
- tests of liver function
- tests of liver damage
- specific diagnostic tests
What is investigated when looking at the structure & function of the liver?
the hepatocellular component and the biliary tract
What is the function of the liver with regards to carbohydrates and proteins?
carbohydrates:
- glycogen storage & synthesis
- glycolysis & gluconeogenesis
proteins:
- synthesis & catabolism
- clotting factors, amino acid metabolism & urea synthesis
What are the functions of the liver with regards to lipids, excretion and miscellaneous?
lipids:
- lipoprotein & cholesterol synthesis
- fatty acid metabolism
- bile acid synthesis
excretion & detoxification:
- bile acid & bilirubin excretion
- drug detoxification & excretion
- steroid hormone inactivation & excretion
miscellaneous:
- iron storage
- vitamin A, D, E and B12 storage and metabolism
What is meant by the functional capacity of the liver?
- excess of hepatic capacity for normal anabolic & catabolic processes
- hepatic repair & regeneration following damage is a dynamic process
What are the different causes of liver disease?
- poisoning
- drugs
- infection (viral and non-viral)
- alcohol
- inadequate perfusion
- fatty liver
- autoimmune
- metabolic
- tumours & metastases
What are the systemic effects of liver disease?
- jaundice
- excess of oestrogen
- bruising
- pigmentation
- clubbing
- dependent oedema
- ascites
- encephalopathy
- osteomalacia / osteoporosis
What does excess oestrogen as a result of liver disease cause?
- gynaecomastia
- spider naevi
- liver palms
- testicular atrophy
What is meant by spider naevi?
a spider naevus is a type of telangiectasis (swollen blood vessels) found slightly beneath the skin surface
they often contain a central red spot and reddish extensions which radiate outwards like a spider’s web
What is gynaecomastia?
an enlargement of the male breast tissue due to a hormone imbalance
Do all patients have symptoms of liver disease?
NO!
sometimes there may be no physical signs of liver disease
What are LFTs?
What would you test for when looking at the carbohydrate function of the liver?
tests of liver function
you would test for glucose
What LFTs would you perform for the protein and lipid functions of the liver?
proteins:
- synthesis & catabolism - albumin
- clotting factors - prothrombin time
- amino acid metabolism & urea synthesis - urea
lipids:
- lipoprotein & cholesterol synthesis - cholesterol
- fatty acid metabolism - triglycerides
- bile acid synthesis - bile acids
What LFTs would you use when looking at the excretion and miscellaneous functions of the liver?
excretion & detoxification:
- bile acid & bilirubin excretion - bilirubin
- drug detoxification & excretion - drugs, steroid hormones
miscellaneous:
- iron storage - ferritin
- vitamin K - prothrombin time
What are the 4 categories of available liver function tests?
- production of metabolites
- clearance of endogenous substances
- clearance of exogenous substances
- imaging, biopsy
What is looked for in tests of liver damage?
- hepatocellular damage
- biliary tract damage
- using imaging / biopsy
What are the 6 routine LFTs?
- alkaline phosphatase
- alanine aminotransferase (ALT)
- bilirubin
- albumin
- total protein
- GGT (gamma-glutamyl transferase)
What is the specific test for viral hepatitis?
serology to look for:
- hepatitis A, B, C, D & EB
- HIV
- CMV
What is the specific test to look for chronic active & autoimmune hepatitis?
anti-smooth muscle, anti-liver/kidney, anti-microsomal and anti-nuclear antibodies
What is the specific test for primary biliary cirrhosis?
anti-mitochondrial antibodies
What is the specific test for hereditary haemachromatosis?
- ferritin
- transferrin saturation
- liver biopsy
- genetic testing
What is the specific test for Wilson’s disease?
- caeruloplasmin
- urine copper
- plasma copper
- liver biopsy
What is the specific test for a1-antitrypsin deficiency?
- a1 antitrypsin
- genetic testing
What is the specific test for hepatocellular cancer?
AFP
What tests are used to look for hepatocyte damage?
Are they sensitive and specific?
aminotransferases - ALT (alanine) & AST (aspartate)
ALT is more specific for the liver than AST
they are only released by cellular damage
- viral hepatitis
- toxic insults
- infiltrative
tests are sensitive but not specific
What are common causes of acute and chronic hepatitis?
acute:
- paracetamol
- viral hepatitis B & E
chronic:
- viral hepatitis B & C
- alcohol
- Wilsons disease
- alpha-1-antitrypsin deficiency
- autoimmune hepatitis
What is the difference in development of acute and chronic hepatitis?
acute:
- severe hepatic dysfunction developing within 6 months of the first onset of liver disease
- and in the absence of pre-existing liver disease
chronic:
- clinial or biochemical features of liver disease persisting for more than 6 months
- graded according to necroinflammatory activity and degree of fibrosis
What are the characteristic features of acute and chronic hepatitis?
acute:
- hepatic encephalopathy
- prolonged and persistent PT/INR
- grossly hepatic picture
- deep jaundice
- possible hypoglycaemia
chronic:
- abnormal transferases 2-10 x ULN
- AP & bilirubin usually normal unless cirrhosis has developed
- PT/INR mildly abnormal
- low albumin
What are the 3 stages associated with alcoholic liver disease?
there are 3 stages relating to the patterns of histological change in liver tissue associated with ethanol ingestion
- fatty liver (steatosis)
- alcoholic hepatitis
- cirrhosis
What is steatosis (fatty liver)?
What changes are present?
a response to excess alcohol in all individuals which is reversible with abstinence
biochemical changes:
- minimal biochemical changes
- very mild increased ALT
- occasionally cholestatic picture
- raised GGT
What is alcoholic hepatitis?
What are the biochemical changes present?
- appearances of steatosis and creeping fibrosis with potential for progression to cirrhosis
- often occurs after a heavy bout of drinking on the back of heavy chronic drinking
biochemical features:
- very wide spectrum of results
- anaemia
- raised ALT and AST
- can progress to prolonged jaundice, fever & hepatic failure
What is cirrhosis in alcoholic liver disease?
How is it diagnosed?
- final stage of alcoholic liver disease
- disturbance of normal hepatic architecture following recurrent episodes of necrosis, cell death and attempts to regenerate
- requires a histological diagnosis with a wide spectrum of results
What tests are used in biliary tract damage and why?
- impaired excretory function
- increased conjugated bilirubin
- increased synthesis of enzymes by cells lining the bile canaliculi
- ALP and GGT
Why is alkaline phosphatase (ALP) raised in biliary tract damage?
elevated due to increased production by cells lining the bile canaliculi and overflow into the blood
this is due to:
- cholestasis (intra- or extrahepatic)
- infiltrative diseases
- space-occupying lesions (tumours)
- cirrhosis
multiple sites of production - liver, bone, intestine, placenta
How can ALP isoenzymes be identified?
liver and bone ALP isoenzymes are separated by electrophoresis
Why is gamma glutamyltransferase (GGT) elevated in biliary tract damage?
- can support a liver source of raised ALP
- elevated due to structural damage
- can be induced by:
- alcohol
- enzyme inducing agents e.g. anti-epileptics
- fatty liver e.g. due to alcohol, diabetes or obesity
- heart failure
- prostatic disease
- pancreatic disease (acute & chronic pancreatitis, cancer)
- kidney damage (ARF, nephrotic syndrome, rejection)
What is primary biliary cirrhosis?
What are the symptoms?
a chronic cholestatic condition with destruction of bile ducts
it has a strong female predilection
symptoms are pruritus, jaundice and non-specific tiredness
What tests are used in primary bilary cirrhosis?
- it is often an incidental finding with an isolated raised ALP
- raised IgM and specifically raised anti-mitochondrial antibodies (AMA)
What is primary sclerosing cholangitis?
a progressive disease characterised by diffuse inflammation and fibrosis of the biliary system
men are affected more than women
it is autoimmune and often related to IBD
What are the tests for primary sclerosing cholangitis?
progression over years from minor elevations of ALP to a very severe cholestatic condition with deep jaundice
What are the biochemical markers of fibrosis?
historically only imaging, biopsy & predictive scores
novel biochemical markers:
- ELF score
- PIIINP
- TIMP-1
- hyaluronic acid
How is bilirubin measured?
What does it show?
it shows the excretory capacity of the liver and free flow of bile
it is measured as:
- total
- unconjugated - pre-hepatic & hepatic
- conjugated - post-hepatic (obstruction) & hepatic
What is serum bilirubin when there is jaundice?
jaundice at serum bilirubin > 40-50 umol/L
What are the pre-hepatic and post-hepatic (obstructive) causes of hyperbilirubinaemia producing jaundice?
pre-hepatic aetiology:
- haemolysis e.g. Rhesus incompatibility
- ineffective erythropoiesis e.g. spherocytosis
post-hepatic (obstructive) causes:
- gallstones
- biliary stricture
- cancer i.e. choloangiocarcinoma, head of pancreas
- cholangitis
What are the hepatic causes of hyperbilirubinaemia leading to jaundice?
unconjugated:
- pre-microsomal
- microsomal
- inherited disorders of conjugation e.g. Gilberts, Crigler-Najjar
conjugated:
- post-microsomal / impaired excretion
- intrahepatic obstruction
- inherited disorders of excretion e.g. Dubin-Johnson, Rotor
What are examples of inborn errors of bilirubin metabolism?
- decreased activity of UDP glucuronyl transferase
- Gilbert’s, Crigler-Najjar
- reduced ability to excrete bilirubin glucuronide
- Dubin-Johnson, ROTOR
What blood tests are performed in the presence of jaundice and what do they show?
- AST / ALT elevated and normal ALP
- approx 90% have hepatitis
- AST / ALT normal and elevated ALP
- approx 90% have obstructive jaundice
What are the results of urine tests in the presence of jaundice?
prehepatic - unconjugated bilirubin:
- no urinary bilirubin
hepatic - hepatocellular:
- variable depending on degree of obstruction due to either disease or inflammatory oedema
post-hepatic - obstruction:
- dark urine & pale stools
How useful are routine LFTs?
only 3-4% of subjects with abnormal LFTs have liver disease
- alcohol-related
- Gilbert’s syndrome
- obesity
- diabetes
- side effects of medication
When should LFTs be measured?
signs and symptoms:
- pain, itchy, jaundice, TATT, bruising
lifestyle:
- alcohol, obesity, diabetes, recent travel, drug use
is liver disease present?
- hepatitis, haemochromatosis, liver cancer, drugs
what is the severity?
- chronic hepatitis vs acute onset
What is the pancreas?
Where is the head located?
an elongated, flattened gland lying on the posterior abdominal wall
the head lies within the duodenal loop
it has an essential endocrine & exocrine function
How does the pancreas drain?
What does it open into?
the pancreas drains via main pancreatic duct joined to the common bile duct
it opens into the duodenum via the sphincter of Oddi
What are the endocrine secretions of the pancreas?
secreted from islets of Langerhans
- insulin, glucagon
- pancreatic polypeptide
What are the exocrine secretions of the pancreas?
secreted from the ductal & acinar cells
- bicarbonate
- digestive enzymes
- trypsin, chymotrypsin & elastase
- carboxypeptidases
- amylase
- lipase
What are the 5 main disorders of the pancreas?
- acute pancreatitis
- chronic pancreatitis
- pancreatic insufficiency
- cystic fibrosis
- carcinoma of the pancreas
What is the I GET SMASHED mnemonic for causes of pancreatitis?
I - idiopathic
G - gall stones
E - ethanol (alcohol)
T - trauma
S - steroids
M - mumps / malignancy
A - autoimmune
S - scorpion stings
H - hypercalcaemia / hypertriglyceridemia
E - ERCP
D - drugs
What are the symptoms of acute pancreatitis?
How is it diagnosed?
symptoms:
- severe epigastric pain
- sudden onset
- radiating to the back
diagnosis:
- amylase or lipase
- imaging
- clinical history
What are the potential biochemical features in acute pancreatitis?
- uraemia
- hypoalbuminaemia
- hypocalcaemia
- hyperglycaemia
- metabolic acidosis
- abnormal LFTs
What is chronic pancreatitis?
progressive loss of both islet cells and acinar tissue
What is the presentation of chronic pancreatitis like?
- abdominal pain
- malabsorption
- impaired glucose tolerance
- alcohol is often an important factor
malabsorption is often the presenting feature
What tests are performed for chronic pancreatitis?
What is involved in diagnosis and management?
tests of exocrine function (i.e. amylase / lipase) are of NO value except during acute exacerbations
diagnosis & management:
- imaging
- pancreatic function test for investigating insufficiency (direct or indirect)
- miscellaneous - vitamin D, calcium, FBC, LFTs, glucose, lipids
What are direct (invasive) tests of pancreatic function?
- intubation to collect aspirates in the duodenum
- secretin, CCK, Lundh tests
What are indirect (non-invasive) tests of pancreatic function?
- pancreatic enzyme analysis in stools (elastase)
- trypsinogen (IRT) measured in blood in CF screening
- pancreolauryl & NBT-PABA tests
