Investigations of Liver & Pancreatic Disease Flashcards
Liver function for carbohydrates?
- Glycogen storage & synthesis
- Glycolysis & gluconeogenesis
Liver function regarding proteins?
- Synthesis & catabolism
- Clotting factors, amino acid metabolism & urea synthesis
2 major components of the liver?
- Hepatocellular component
- Biliary tract
Liver function regarding lipids?
- Lipoprotein & cholesterol synthesis
- Fatty acid metabolism
- Bile acid synthesis
Liver function regarding bile acid and bilirubin?
Bile acid & bilirubin excretion (via conjugation)
Liver function regarding drugs?
Drug detoxification & excretion
Liver function regarding steroid hormones?
Steroid hormone inactivation & excretion
Liver function regarding iron?
Iron storage
Liver function regarding vitamins?
Vitamin A, D, E & B12 storage & metabolism
Causes of liver disease;
- Poisoning
- Drugs
- Infection (viral & non-viral)
- Alcohol
- Inadequate perfusion (e.g. CHF, hypovolaemia, sepsis)
- Fatty liver
- Autoimmune
- Metabolic
- Tumours & metastases
How are oestrogen levels affected in liver disease?
Oestrogen levels are increased
How can increased oestrogen in liver disease present?
- gynaecomastia (decrease in testosterone and increase in oestrogen)
- spider naevi
- liver palms
- testicular atrophy
Systemic symptoms of liver disease?
- jaundice
- oestrogen excess symptoms
- bruising (clotting factors)
- pigmentation
- clubbing
- dependent oedema
- ascites (portal vein hypertension, low albumin etc)
- encephalopathy (build up of toxins)
- osteomalacia / osteoporosis (impaired vit D activation)
Why can liver disease lead to osteomalacia/osteoporosis?
Liver required for activation of vitamin D which is required for absorption of calcium.
Spider naevi cause?
Can be from excess oestrogen seen in liver disease
What are the routine LFTs?
- Alkaline phosphatase (ALP)
- ALT (alanine aminotransferase)
- Bilirubin
- Albumin
- Total protein
- GGT (g glutamyl transferase)
Specific test for viral hepatitis?
What is the main test of the synthetic capacity of the liver?
Albumin
What is the main test of the exretory capacity of the liver?
bilirubin
Specific test for viral hepatitis?
Serology:
Hep A, B, C, D & EB, CMV, HIV
Specific tests for chronic active / autoimmune hepatitis?
- Anti smooth muscle
- anti liver/kidney
- anti microsomal and anti nuclear antibodies
Specific liver test for primary biliary cirrhosis?
Anti mitochondrial antibodies
Specific liver test for hereditary haemochromatosis?
Ferritin, transferrin saturation, liver biopsy, genetic testing
Specific liver test for Wilson’s disease?
Caeruloplasmin, urine copper, plasma copper, liver biopsy
Specific liver test for A1AT deficiency?
α1-antitrypsin, genetic testing
Specific liver test for hepatocellular cancer?
AFP
What are the 2 main liver enzymes tested?
- ALT (alanine)
- AST (aspartate)
ALT is more specific for liver than AST (as AST also released from red cells)
Acute vs chronic hepatitis;
What are the 3 stages of alcoholic liver disease relating to the patterns of histological changes?
- Fatty liver (steatosis)
- Alcoholic hepatitis
- Cirrhosis
How do levels of bilirubin change with biliary tract damage?
Impaired excretory function –> increased conjugated bilirubin
Which enzyme indicates biliary tract damage?
Alkaline phosphatase (ALP) –> elevated due to increased production by cells lining the bile canaliculi and overflow into blood
What are the other sources of ALP?
Liver, Bone, Intestine, Placenta
What is used to separate liver and bone ALP isoenzymes?
Electrophoresis
Which other enzyme can be used to support the liver as the source of raised ALP?
Gamma glutamyltransferase (γGT) - this is elevated due to structural damage
What can raised γGT be due to?
- 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)
Primary Biliary Cirrhosis vs Primary Sclerosing Cholangitis;
Primary Biliary Cirrhosis:
- Chronic cholestatic condition with destruction of bile ducts
- Strong female predilection
- Pruritus, jaundice, non-specific tiredness
- Often incidental finding with an isolated raised ALP
- ↑IgM and specifically raised anti-mitochondrial antibodies (AMA)
Primary Sclerosing Cholangitis:
- Progressive disease characterised by diffuse inflammation and fibrosis of the biliary system.
- Men affected more than women
- Autoimmune and often related to IBD
- Progression over years from minor elevations of ALP to a very severe cholestatic condition with deep jaundice.
What are the novel biochemical markers of liver fibrosis?
–ELF score
»PIIINP
»TIMP-1
»Hyaluronic acid
What do bilirubin levels give you an insight into?
Excretory capacity of the liver and free flow of bile
3 ways in which bilirubin is measured?
- Total
- Unconjugated –> Pre-hepatic & Hepatic
- Conjugated –> Post-hepatic (Obstructive) & Hepatic
What serum bilirubin level induce jaundice?
> 40-50 μmol/L
Where is bilirubin derived from?
Haem
Describe the life cycle of bilirubin
- Derived from haem
- Transported in plasma bound to albumin to the liver
- Conjugated in the liver to form soluble form
- Conjugated bilirubin excreted in bile
- In colon, bilirubin acted on by bacteria and then excreted in faeces (give its dark brown colour)
Pre-hepatic aetiology of hyperbilirubinaemia (jaundice)?
–Haemolysis e.g. Rhesus incompatibility
–Ineffective erythropoiesis e.g. spherocytosis
Post-hepatic aetiology of hyperbilirubinaemia (jaundice)?
–Gallstones
–Biliary Stricture
–Cancer i.e. cholangiocarcinoma, head of pancreas
–Cholangitis
What is Criger-Najjar syndrome?
- A rare inherited disorder affecting the metabolism of bilirubin resulting in non-haemolytic jaundice.
- Decreased activity of UDP glucuronyl transferase
- High levels of unconjugated bilirubin can lead to brain damage in infants
2 main methods 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)
When trying to interpret a raised bilirubin;
- What does elevated AST/ALT levels and a normal ALP indicate?
- What does a normal AST/ALT and elevated ALP indicate?
a) approx 90% have hepatitis
b) approx 90% have obstructive jaundice
Is urinary bilirubin present in prehepatic jaundice?
No - bilirubin is unconjugated
Is bilirubin present in post-hepatic jaundice? Is it present in stools?
Yes - dark urine
No - pale stools
Liver disease overview
Of those with liver disease, what % of patients have abnormal LFTs?
Only 3-4%
What lifestyle factors should make you consider measuring LFTs?
Alcohol, obesity, diabetes, recent travel, drug use
Where does the common bile duct enter into the duodenum?
Via the sphincter of Oddi
Endocrine function of the pancreas?
Islets of Langerhans;
- Insulin, Glucagon
- Pancreatic polypeptide
What cells of the pancreas are responsible for its endocrine function?
Islets of Langerhans
What cells of the pancreas are responsible for its exocrine function?
Ductal and acinar
Exocrine secretions of the pancreas?
- Bicarbonate
- Digestive enzymes
- Trypsin, Chymotrypsin & Elastase
- Carboxypeptidases
- Amylase
- Lipase
Examples of disorders of the pancreas;
- Acute Pancreatitis
- Chronic Pancreatitis
- Pancreatic Insufficiency
- Cystic Fibrosis
- Carcinoma of the Pancreas
Causes of pancreatitis;
Symptoms of acute pancreatitis?
Severe epigastic pain, sudden onset, radiating to the back
How can acute pancreatitis affect;
a) urea?
b) albumin
c) calcium
d) glucose
e) pH
f) LFTs
a) uraemia
b) hypoalbuminaemia (as albumin is a negative acute phase protein)
c) hypocalcaemia (binding of Ca2+ to fatty acids released through damage to pancreas)
d) hyperglycaemia
e) metabolic acidosis
f) abnormal LFTs
Diagnosis of acute pancreatitis?
–Amylase or Lipase
–Imaging
–Clinical History
What is a negative acute phase protein?
Negative acute phase proteins decrease in plasma concentration by greater than 25% in response to inflammation. The two main negative acute phase proteins are albumin and transferrin.
Aside from pancreatitis, what else can midly raised amylase be seen in?
- Drugs (thiazides, furosemide, glucocorticoids, azathioprine)
- Non-pancreatic abdominal disease
- Renal disease (due to reduced excretion of amylase by kidneys)
- Inflammation of the salivary glands (e.g. mumps)
- Artefactually due to assay interferences
- Macroamylasaemia
What cells does chronic pancreatitis involve the progressive loss of?
Progressive loss of both islet cells and acinar tissue
What is macroamylasaemia?
Macroamylasemia is a condition characterised by a serum amylase activity increase due to complex macromolecules whose large size prevents its urinary excretion.
Presentation of chronic pancreatitis?
»Abdominal pain
»Malabsorption (often presenting feature)
»Impaired glucose tolerance
»Alcohol often an important factor
Are tests of exocrine function (amylase/lipase) useful in diagnosis of chronic pancreatitis?
No - except during acute exacerbations
Diagnosis of chronic pancreatitis?
- Imaging
- Pancreatic Function test for investigating insufficiency
- »Direct
- »Indirect
- Miscellaneous: Vitamin D, calcium, FBC, LFTs, glucose, lipids
What does a ‘direct’ pancreatic function test involve?
Invasive;
- Intubation to collect aspirates in the duodenum
- Secretin, CCK, Lundh Tests
What does an ‘indirect’ pancreatic function test involve?
Non-invasive;
- Pancreatic enzyme analysis in stools (Elastase)
- Trypsinogen (IRT) measured in blood in CF screening
- Pancreolauryl & NBT-PABA tests
What tends to be the presenting feature of chronic pancreatitis?
Malabsorption
