(61) Diseases of the Liver and Pancreas Flashcards
Describe the basic structure of the liver
- hepatocytes constitute 60% of liver mass
- each hepatocyte is in contact with sinusoid, bile canaliculus and neighbouring hepatocyte
Describe the hepatocyte organelles
- nucleus
- mitochondria (oxidative phosphorylation, TCA cycle, fatty acid oxidation)
- RER (protein, lipid, enzyme synthesis)
- SER (bilirubin conjugation, drug detoxification)
- lysosomes (intracellular scavengers - copper, ferritin)
Where in the hepatocyte does bilirubin conjugation and drug detoxification occur?
SER
What are the functions of the liver in terms of carbohydrates?
- glycogen storage and synthesis
- glycolysis and gluconeogenesis
What are the functions of the liver in terms of proteins?
- synthesis and catabolism
- clotting factors, amino acid metabolism, urea synthesis
What are the functions of the liver in terms of lipids?
- lipoprotein and cholesterol synthesis
- fatty acid metabolism
- bile acid synthesis
What are the functions of the liver in terms of excretion and detoxification?
- bile acid and bilirubin excretion
- drug detoxification and excretion
- steroid hormone inactivation and excretion
What are the miscellaneous functions of the liver?
- iron storage
- vitamin A, D, E and B12 storage and metabolism
Describe the functional capacity of the liver
- excess of hepatic capacity for normal anabolic and catabolic processes
- hepatic repair and regeneration following damage is a dynamic process
What is measured in LFTs?
- alkaline phosphate
- ALT (alanine aminotransferase)
- bilirubin
- albumin
- total protein
- GGT (y glutamyl transferase)
Name 4 general types of liver function tests
- production of metabolites
- clearance of endogenous substances
- clearance of exogenous substances
- imaging, biopsy
What are 3 general tests for liver damage?
- hepatocellular damage
- biliary tract damage
- imaging, biopsy
What sorts of things can cause liver disease?
- poisoning
- drugs
- infection
- alcohol
- fatty liver
- autoimmune
- metabolic
- tumours and metastases
What are markers of hepatocyte damage?
Aminotransferases (ALT and AST) - found in the cell and only released by cellular damage
- tumour markers = a-fetoprotein (primary HCC)
Which 2 types of aminotransferases are measured for hepatocyte damage?
- alanine transaminase = ALT
- aspartate transaminase = AST
Out of ALT and AST, which is more specific for liver damage?
ALT
AST is also found in muscle and red blood cells
What is a tumour marker for primary hepatocellular carcinoma?
a-fetoprotien
What is there increased levels of in biliary tract damage?
- increased conjugated bilirubin (due to impaired excretory function)
- increased synthesis of enzymes by cells lining bile canaliculi (ALP, yGT)
- alkaline phosphatase (ALP)
Why is alkaline phosphatase (ALP) elevated in biliary tract damage?
Due to increased production by cells lining bile canaliculi and overflow into blood, due to:
- cholestasis (intra- or extra-hepatic)
- infiltrative disease
- space-occupying lesions (tumours)
- cirrhosis
Alkaline phosphatase (ALP) has multiple sites of production including…
- liver
- bone
- intestine
- placenta
Liver and bone ALP isoenzymes can be separated by what?
Electrophoresis
Why is gamma glutamyltransferase (yGT) measured as part of LFTs?
Elevated due to structural damage (biliary tract damage) - can support a liver source of raised ALP
Elevated gamma glutamyltransferase can be induced by…
- alcohol
- enzyme inducing agents eg. anti-epileptics
- fatty liver eg. due to alcohol, diabetes or obesity
- heart failure
- prostatic disease
- pancreatic disease (acute and chronic pancreatitis, cancer)
- kidney damage (ARF, nephrotic syndrome, rejection)
Describe the biochemical markers of fibrosis
Historically only imaging, biopsy and predictive score, but now novel biochemical markers: ELF score - PIIINP - TIMP-1 - hyaluronic acid
Bilirubin is measured as…
- total
- unconjugated (pre-hepatic and hepatic)
- conjugated (hepatic and post-hepatic = obstructive)
What do bilirubin levels indicate?
Excretory capacity of the liver and free flow of bile
Jaundice occurs at serum bilirubin levels of what?
More than 40-50umol/L
Describe the pre-hepatic aetiology of hyperbilirubinaemia/jaundice
- haemolysis eg. rhesus incompatibility
- ineffective erythropoieis eg. spherocytosis
Describe the post-hepatic (obstructive) causes of hyperbilirubinaemia/jaundice
- gallstones
- biliary stricture
- cancer ie. cholangiocarcinoma, head of pancreas
- cholangitis
Describe the hepatic causes of hyperbilirubinaemia - unconjugated
- pre-microsomal
- microsomal
- inherited disorders of conjugation eg. Gilbert’s syndrome, Crigler-Najjar syndrome
Describe the hepatic causes of hyperbilirubinaemia - conjugated
- post-microsomal/impaired excretion
- intrahepatic obstruction
- inherited disorders of excretion eg. Dubin-Johnson syndrome, Rotor sydrome
Haemoglobin break down produced bilirubin which becomes bound to albumin, what happens next?
Bilirubin is converted to bilirubin glucuronide by the enzyme UDP glucuronyl transferase
Gilbert’s and Crigler-Najjar are syndromes of what?
Decreased activity of UDP glucuronyl transferase (disorders of conjugation)
Dubin-Johnson and Rotor are syndromes of what?
Reduced ability to excrete bilirubin glucuronide (conjugated bilirubin)
Blood test - What is the diagnosis if AST/ALT are elevated and ALP is normal? (in the case of jaundice)
Approx 90% will have hepatitis
Blood tests - What is the diagnosis is AST/ALT are normal but ALP is elevated? (in the case of jaundice)
Approx 90% will have obstructive jaundice
What would a urine test show in prehaptic causes of jaundice?
No urinary bilirubin
What would a urine test show in hepatic causes of jaundice?
Variable depending on degree of obstruction due to either disease or inflammatory oedema
What would a urine test show in post-hepatic causes of jaundice?
Dark urine (and pale stools)
What are the specific tests for viral hepatitis?
Serology (Hep, A, B, C, D and EB, CMV, HIV)
What are the specific tests for chronic active and autoimmune hepatitis?
- anti-smooth muscle antibodies
- anti-liver/kidney antibodies
- anti-microsomal antibodies
- anti-nuclear antibodies
What are the specific tests for primary biliary cirrhosis?
Anti-mitochondrial antibodies
What are the specific tests for hereditary haemachromatosis?
Ferritin, transferrin saturation, liver biopsy, genetic testing
What are the specific tests for Wilson’s disease?
- caeruloplasmin
- urine copper
- plasma copper
- liver biopsy
What are the specific tests for a1-antitrypsin deficiency?
- a1-antitrypsin
- genetic testing
What are the specific tests for hepatocellular carcinoma?
AFP (alpha feto-protein)
List the systemic effects of liver disease
- jaundice
- oestrogen symptoms
- bruising
- pigmentation
- clubbing
- dependent oedema
- ascites
- encephalopathy
- osteomalacia/osteoporosis
What are the oestrogen symptoms due to liver disease?
- gynaecomastia
- spider nevi
- liver palms (palmar erythema)
- testicular atrophy
How useful are routine LFTs?
1% of subjects with abnormal LFTs have liver disease (alcohol-related, Gilbert’s syndrome, obesity, diabetes, side effects of medication)
Which signs and symptoms would encourage measurement of LFTs?
- pain
- itchy
- jaundice
- TATT
- bruising
Which lifestyle factors would encourage measurement of LFTs?
- alcohol
- obesity
- diabetes
- recent travel
- drug use
LFTs would be measured in the case of which diseases?
- hepatits
- haemochromatosis
- liver cancer
- drugs
Describe the pancreas
Elongated, flatted gland lying on posterior abdominal wall
- head lies within duodenal loop
- drains via main pancreatic duct joined to common bile duct
- opens into duodenum via sphincter of Oddi
- essential endocrine and exocrine function
Where do pancreatic endocrine secretions come from?
Islets of Langerhans
Where do pancreatic exocrine secretions come from?
Ductal and acinar cells
What are the endocrine secretions of the pancreas?
- insulin, glucagon
- pancreatic polypeptide
What are the exocrine secretions of the pancreas?
- bicarbonate
- digestive enzymes (trypsin, chymotrypsin, elastase, carboxypeptidases, amylase, lipase)
What is pancreatic polypeptide?
PP, a 36 amino acid peptide produced and secreted by PP cells (originally termed F cells) of the pancreas which are primarily located in the Islets of Langerhans. It is part of a family of peptides that also includes Peptide YY (PYY) and Neuropeptide Y (NPY)
Name 5 disorders of the pancreas
- acute pancreatitis
- chronic pancreatitis
- pancreatic insufficiency
- cystic fibrosis
- carcinoma of the pancreas
What are the features of acute pancreatitis?
- acute necrotising liquefaction
- inflammatory
What is the aetiology of acute pancreatitis
- gallstones
- alcohol
- drugs
- hypertriglycerideaemia
- trauma
- infectious
- rare tumours
- autoimmune
- scorpion toxins
What are the symptoms of acute pancreatitis?
- severe epigastric pain
- sudden onset
- radiating to back
What are the potential biochemical features of acute pancreatitis?
- uraemia
- hypoalbuminaemia
- hypocalcaemia
- hyperglycaemia
- metabolic acidosis
- abnormal LFTs
How is acute pancreatitis diagnosed?
- amylase or lipase
- imaging
- clinical history
How does chronic pancreatitis present?
Progressive loss of both islet cells and acinar tissue
- abdominal pain
- malabsorption
- impaired glucose tolerance
- alcohol often an important factor
What is often the presenting feature of chronic pancreatitis?
Malabsorption
Are tests of exocrine function eg. amylase/lipase of value in chronic pancreatitis?
NO, of no value except for during acute exacerbations
How is chronic pancreatitis diagnosed?
- imaging
- pancreatic function test for investigating insufficiency (direct and indirect)
- miscellaneous: vitamin D, calcium, LFTs, glucose, lipids, FBC
What do direct (invasive) pancreatic function tests involve?
Intubation to collect aspirated in the duodenum
- secretin, CCK, Lundh tests
What is the Lundh test?
Direct test of pancreatic function in which duodenal contents are collected for two hours following a meal containing carbohydrate, protein and fat.
Low enzymic activity - amylase, trypsin or lipase - indicates pancreatic insufficiency
It is less informative than the secretin / CCK-PZ test
What do indirect (non-invasive) pancreatic function tests involve?
- pancreatic enzyme analysis in stools (elastase)
- trypsinogen (IRT) measured in blood in CF screening
- pancreolauryl and NBT-PABA tests
