LFTs 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
- List some metabolic consequences of liver failure.
Reduction in blood sugar due to a lack of glycogen 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?
Chemical modification (e.g. redox, acetylation by CYP450 enzymes)
Conjugation (glucuronidation or sulphation)
Excretion
- Outline the roles of the liver regarding hormone metabolism.
Vitamin D 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 bilirubin
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 roles of Kupffer cells?
Clearance of infection and lipopolysaccharide (LPS) Antigen presentation Immune modulation (e.g. cytokine production)
- What are the main markers of liver synthetic function?
Albumin
Prothrombin time
- Where is ALT and AST found?
Within the cytoplasm of hepatocytes
- What is the function of ALT and AST?
Catalyse the transfer of alanine and aspartate to the alpha-keto group of alpha-ketoglutarate, thereby producing pyruvate and oxaloacetate
- Other than the liver, where else is ALT and AST found?
Muscle, kidney, bone, pancreas
- Describe the rise in ALT and AST seen in alcoholic liver disease.
AST: ALT > 2:1 in alcoholic 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.
Alcohol abuse
Bile duct disease (e.g. gallstones)
Hepatic metastases
- What is the likely function of ALP?
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) Pregnancy
- 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 (e.g. chronic liver disease, malnutrition) Increased loss (e.g. gut, kidney) Sepsis (3rd 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
- Which tissues produce alpha-fetoprotein in the foetus?
Yolk sac
GI epithelium
Liver
- What causes a high alpha-fetoprotein?
Hepatocellular carcinoma
Pregnancy
Testicular cancer
- Which investigation is crucial for differentiating between causes of jaundice?
Biliary ultrasound scan
- Under what circumstance 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
Sepsis
- List some other investigations that may be used as part of a liver panel.
Coeliac serology Hepatitis serology Alpha-1 antitrypsin Caeruloplasmin Immunoglobulins Ferritin
- Name a dye test used to assess liver function.
Indocyanine green/bromsulphalein – measures excretory capacity of the liver and hepatic blood flow
- Name a breath test used to assess liver function.
Aminopyrine/galactose (carbon 14) – measures residual functioning of liver cell mass
- List some causes of elevated serum bile acids.
Obstetric cholestasis
PBC/PSC
- What is an important cause of jaundice with LFT changes consistent with biliary obstruction?
Drug-induced cholestasis
- What is the most common cause of drug-induced cholestasis?
Co-amoxiclav
- State 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 pancreatic cancer)
- State three causes of ALT > 1000.
Toxins (paracetamol)
Viruses
Ischaemia (e.g. post-resuscitation)
- How often should patients with cirrhosis be followed up to check for hepatocellular carcinoma?
Every 6 months
- How is paracetamol overdose treated?
N-acetyl cysteine
Liver transplant
