Liver Flashcards
Liver function
Carbohydrate metabolism - glycogen and gluconeogensis
Fat metabolisms - FA, cholesterol, lipoprotein and bile acid synthesis + ketogenesis
Protein metabolism - Synthesis of plasma proteins, deamination and transamination of amino acids, urea synthesis and nitrogen removal
Hormone metabolism - activation of vitamin D aka 25 OH D, metabolise polypeptide and steroid hormones
Toxin and drug excretion
What types of assessment of liver function are available?
Clinical assessment
Imaging
Biopsy
Biochemical tests using blood and urine
Limitations to types of liver function assessment?
Imaging - expensive and does not reveal anything about the functions but rather structure
biopsy - takes a long time with a vary invasive procedure. Further analysis and interpretation is needed by specialist
Biochemical tests - may lack in accuracy causing more FP tests
Clinical assessment/symptoms of liver disease
Dupuytren contracture, palmer erthyema, spinder naevi, male gynaecomastia, ascites, jaundice
Pale stool or dark urine
Hepatic encephalopathy - affects brain function
What biochemical tests are available in primary care? How are they beneficial? and what are some limitations?
LFTs are great screening tools to assess the presence of disease, prognostic. Uses patterns in the results to produce a differential diagnosis; cholestatic or hepatic
They are cheap, easy to use, quick to produce results and non-invasive.
Can be used to measure efficacy of treatment for liver disease and assess severity of cirrhosis
LFT can be abnormal due to heart failure, sepsis, infection/inflammation
What does the LFT measure?
Serum bilirubin AST or ALT ALP Serum albumin May also include PT or INR to determine synthetic function and severity of disease.
What parts of the LFT will be abnormal in hepatocellular injury?
AST or ALT
Serum bilirubin and albumin
- albumin and bilirubin is the cheapest method but least sensitive
- e.g. raised ALT and AST indicate liver cells dying in hepatitis C
What parts of the LFT will be abnormal in cholestasis?
Cholestatic enzymes; ALP, gamma-glutamyltransferase (GGT)
Urinalysis of liver function?
Can be measured using urobilinogen.
Bilirubin reaches gut and is converted to urobilinogen by gut bacteria to be ecreted in the urine
Urobilinogen in the urine indicates the bilirubin is reaching the gut, whilst high plasma bilirubin and no urobilinogen in the urine means bilirubin is not reaching the gut due to cholestasis
What does the ALP indicate in LFTs?
ALP secreted by cells lining biliary tract and is an inducible enzyme
It is raised in bone disease
How are the transaminases used in indicating heptocellular damage?
ALT more specific to liver
High AST can also be seen in MI, muscle injury and CCF
Thus, ALT:ASt ratio is used
What is GGT and how can it be used to determine cholestasis?
Catalyses transfer of gamma glutamyl groups from peptides to appropriate acceptors
Useful in conjunction with ALP to clearly indicate cholestasis or rule it out.
- increase in ALP & normal GGT indicates liver bone or other
- If both increase then suggest hepatic cause
- Only GGT is due to alcohol intake
Hepatocellular pattern
Disproportionate elevation in serum ALT & AST compared to ALP
Elevated serum bilirubin
Cholestatic pattern
Disproportionate elevation in ALP compared to ALT & AST
Serum bilirubin elevated
What does jaundice indicate?
Hyperbilirubinemia due to hepatocellular (toxin or infections) damage or cholestasis (cirrhosis, tumour or gallstones).
What is cholestasis and what may cause it?
Obstruction of bile flow
- pregnancy, gallstones, pancreatic carcinoma
Non-obstructive causes
- drug induced
- inherited
- primary biliary cirrhosis, primary sclerosing cholangitis - inflammatory conditions
- total parenteral nutrition
Describe acute hepatitis
Damage to hepatocyte characterised by short term increase in transaminases and rising bilirubin
Caused by viral infection, such as hepatitis, EBV, CMV or toxins
Describe chronic hepatitis
Autoimmune, Hep B and C or alcohol
Usually antinuclear and anti-smooth muscle antibodies often very high with a raised IgG
What is serum albumin a test for?
Crude indicator for synthetic capacity of the liver
Also decreased in acute phase response
Function of bilirubin as a test?
Only conjugated bilirubin is filtered in the kidney because it is water-soluble
- Differentiate between intra-heptic and extra obstruction
What secretes ALP?
Cells lining biliary tract
What are some patterns of isolated hyperbilirubinemia?
Elevated bilirubin, but normal ALT, AST and ALPs
Describe what jaundice indicate?
Elevated bilirubin either due to hepatocellular damage, by toxins or infections, or cholestasis by gallstones, tumour or cirrhosis
What is acute hepatitis?
Damage to hepatocytes - associated with short term increase in transaminase and rise in bilirubin
Caused by viral infection
What is chronic hepatitis?
Persistent for more than 6 months
- Autoimmune, hep B or C
- Autoimmune hep affects older women and is associated with an increase in anti-nuclear and anti-smooth muscle antibodies as well as IgG
What is cholangitis?
Inflammation of bile duct - strongly associated with IBD
PSC- primary sclerosing cholangitis
- 60+% of cases are pANCA Ab positive
Biliary obstruction, complete or intermittent
What is steatosis?
Fate of alcoholism and some metabolic conditions - inflammatory response
- collagen deposition
- Can lead to cirrhosis
How common is cirrhosis in patients with steatosis?
10-30% of patients develop cirrhosis within 10 years
Describe fibrosis
The continual inflammation can lead to fibrosis - altered ECM remodeling
- results in pro-fibrogenesis environment