ChemPath: LFTs and cases Flashcards
List some functions of the liver.
- Intermediary metabolism
- Protein synthesis
- Xenobiotic metabolism
- Hormone metabolism
- Bile synthesis
- Reticulo-endothelial system
Define intermediary metabolism.
Enzyme-catalysed processes within cells that extract energy from nutrient molecules and use that energy to construct cellular components.
List some examples of processes that count as intermediary metabolism.
- Glycolysis
- Glycogen storage
- Gluconeogenesis
- Amino acid synthesis
- Fatty acid synthesis
- Lipoprotein metabolism
List some metabolic consequences of liver failure.
- Reduction in blood sugar due to a lack of glycogen / metabolism
- Lactic acidosis (reduced ability to metabolise lactic acid)
- Increased ammonia (no longer able to process amino acids)
What are the main stages of xenobiotic metabolism in the liver?
Glucuronidation increases the solubility of
Outlie the roles of the liver regarding hormone metabolism.
- Vitamin D (25-hydroxylation)
- Steroid hormones (conjugation and excretion)
- Peptide hormones (catabolism)
What are the constituents of bile?
- Water
- Bile acids/salts
- Bilirubin
- Phospholipids
- Cholesterol
- Proteins
- Drugs and metabolites
What are the functions of bile?
- Excretion
- Micelle formation
- Digestion
Describe the metabolism and excretion of bilirubin.
- Red cells are broken down to produce haem, iron and globin
- Heme breaks down to form unconjugated bilirubin
- Unconjugated bilirubin is bound to albumin in plasma
- This unconjugated bilirubin travels to the liver where it becomes glucuronidated
- The conjugated bilirubin is released into the bile
What are the main cells of the reticuloendothelial system found in the liver?
Kupffer cells
What are the roles of Kupffer cells?
- Clearance of infection and lipopolysaccharides (LPS)
- Antigen presentation
- Immune modulation (e.g. cytokine production)
What is another key reticuloendothethial function of the liver besides the role of Kuppfer cells?
Erythropoesis
What are the main serum markers of liver cell damage?
- ALT
- AST
- ALP
- GGT
What are the main markers of liver synthetic function?
- Albumin
- Pro-thrombin time/INR (important in acute setting)
- Bilirubin
What is the tumour marker of primary liver malignancy?
AFP
What cells are ALT and AST found in?
Within the cytoplasm of hepatocytes
What is the function of ALT and AST?
ALT - catalyzes the transfer of an amino group from L-alanine to α-ketoglutarate to form pyruvate and L-glutamate
AST - catalyzes the interconversion of aspartate and α-ketoglutarate to oxaloacetate and glutamate.
Both these reactions catalysed are reversible
Other than the liver, where else is ALT and AST found?
Muscle, kidney, bone, pancreas
eg. can be released in rhabdomyolysis
Describe the rise in ALT and AST seen in alcoholic liver disease.
AST: ALT > 2:1 in alcoholic liver disease
In the absence of alchol AST:ALT ratio >1 indicated advanced fibrosis or cirrhosis
Describe typical ALT and AST levels in cirrhosis.
- May be raised
- May be normal in long-standing chronic liver disease
What is the role of gamma-glutamyl transferase?
Catalyses the transfer of gamma-glutamyl groups between peptides
Where is GGT found?
Hepatocytes and epithelium of small bile ducts
NOTE: also found in kidney, pancreas, spleen, heart, brain and seminal vesicles
List some causes of raised GGT.
- Chronic alcohol abuse
- Bile duct disease (e.g. gallstones)
- Hepatic metastases
What is the likely function of ALP?
Precise function unknown
Catalyse the hydrolysis of a large number of organic phosphate esters at an alkaline pH.
Where is ALP found?
Liver isoenzyme is found in the sinusoidal and canalicular membranes (bile ducts)
Other sources: bone, small intestine, kidneys, placenta, white blood cells
List some hepatobiliary causes of raised ALP.
- Obstructive jaundice
- Bile duct damage (e.g. PSC, PBC)
Elevated to a lesser degree in viral and alcoholic hepatitis
List some non-hepatobiliary causes of raised ALP.
- Bone disease (e.g. Paget’s, bone tumours)
- Pregnancy
How much albumin is produced by the liver per day?
What is the half-life of albumin?
- 8-14 g/day produced by liver
- Half-life of 20 days
What are the main roles of albumin?
- Major contributor to plasma oncotic pressure
- Binds to steroids, drugs, bilirubin, calcium
List some causes of low albumin.
- Low production - chronic liver disease, malnutrition
- Increased loss - gut, kidney (nephrotic syndrome)
- Sepsis - third spacing (endothelium becomes leaky and albumin leaks into the tissues)
Why is PT a better acute marker of liver function than albumin?
Most clotting factors have half-lives that are a matter of hours as opposed to 20 days with albumin
What are the main roles of alpha-fetoprotein?
- In the foetus, it plays a role in foetal transport and immune regulation
- No known function in adults
Which tissues produce alpha-fetoprotein in the foetus?
- Yolk sac
- GI epithelium
- Liver
What causes a high alpha-fetoprotein?
- Hepatocellular carcinoma
- Pregnancy
- Testicular cancer
List how the cause of jaundice may be classified and give examples?
How might the cause of jaundice be identified?
Which investigation is crucial for differentiating between causes of jaundice with raised ALP?
Biliary ultrasound scan
- Dilated ducts - obstruction (gallstones, cancer)
- Non-dilated ducts - drugs, PSC/PBC, pregnancy
Under what circumstances may bilirubin be detected in the urine?
- There should be NO bilirubin in the urine.
- Only conjugated bilirubin can be seen in the urine as it is soluble.
- This would only occur when the bile duct is blocked leading to backflow of conjugated bilirubin into the circulation.
How is urobilinogen produced?
It is a breakdown product of bilirubin in the intestines by bacteria
What is the significance of absent urobilinogen in the urine?
- Suggests obstructive jaundice
- Urobilinogen is soluble so some of it should enter the enterohepatic circulation and be excreted in the urine
- Its absence in the urine suggests that bilirubin is not entering the intestines
List some causes of increased urobilinogen in the urine.
- Haemolysis
- Hepatitis (due to reduced intrahepatic urobilinogen cycling)
List some other investigations that may be used as part of a liver panel.
- Fasting lipids (for fatty liver)
- Fasting glucose
- Coeliac serology
- Hepatitis serology (HBV surface antigen, HCV antibody)
- Alpha-1 antitrypsin
- Caeruloplasmin (Wilsons = low)
- Immunoglobulins (anti-LKM, anti-SM, AMA)
- Ferritin
- ANCA screen (PSC)
List some more specialised investigatons for the liver
Name a dye test used to assess liver function.
Indocyanine green/bromsulphalein
- Measures excretory function of the liver
- Measures hepatic blood flow
Name a breath test used to assess liver function.
Aminopyrine - measures residual functioning of liver cell mass
- Can be used to predict survival in alcoholic hepatitis
- Can be used to distinguish cirrhosis without biopsy (70-80% sensitivity)
List some causes of elevated serum bile acids.
- Obstetrics cholestasis (10-100x)
- PBC/PSC (25x)
What is the gold-standard investigation for liver pathology?
Liver biopsy
What are non-invasive alternatives to liver biopsy?
- Fibroscan - measures liver elasticity as a marker of fibrosis
- Serum markers of fibrosis
What is an additional cause of jaundice with LFT changes consistent with biliary obstruction?
Drug-induced cholestasis
NOTE: biliary USS will be normal (i.e. undilated ducts whereas dilated suggests an obstruction). It usually resolves over 3 weeks.
What are common causes of drug-induced cholestasis?
- Penicillin antibiotics
- Anabolic steroids
What is Courvoisier’s law.
Painless jaundice in the presence of a palpable non-tender gallbladder is unlikely to be caused by gallstones (i.e. it is more likely to be cancer)
State three causes of ALT >1000.
- Toxins (paracetamol)
- Viruses
- Ischaemia
How often should patients with cirrhosis be followed up to check for hepatocellular carcinoma?
Every 6 months with liver ultrasound
How is paracetamol overdose treated?
- N-acetylcysteine (within 24 hours, ideally within 8 hours)
- Liver transplant - if in acute liver failure
Label this diagram.
