Liver Function Tests and Cases Flashcards
What vessel drains blood from the liver
Hepatic vein
What vessels supply blood to the liver (2)
Hepatic artery
Portal artery
What are the basic functions of the liver (6)
Intermediary metabolism Protein synthesis Xenobiotic metabolism Hormone metabolism Bile synthesis Reticul-endothelial function
What is involved in the intermediary metabolism (6)
Glycolysis Glycogen storage Glucose synthesis Amino-acid synthesis Fatty acid synthesis Lipoprotein metabolism
What is intermediary metabolism
Enzyme-catalysed processes within cells that extract energy from nutrient molecules and use that energy to construct cellular components
Approximately how many proteins does the liver produce
Approximately 1200 plasma proteins - including clotting factors and albumin
What are three key steps of metabolism carried out in the liver
Chemical modification
Conjugation
Excretion
What chemical modifications take place in the liver (3)
P450 enzyme system
Acetylation/de-acetylation
Oxidation/reduction
What are some key conjugations that occur in the liver (2)
Glucuronate
Sulphate
What three classes of hormones does the liver synthesis (3)
Vitamin D (hydroxylation) Steroid hormone (conjugation, excretion) Peptide hormone (catabolism)
What is the parent hormone from which all steroids are derived
Cholesterol
What are the functions of bile (3)
Excretion
Micelle formation
Digestion
What are the constituents of bile (7)
Water Bile salts/acids Bilirubin Phospholipids Cholesterol Proteins Drugs and Metabolites
What protein transports bilirubin from phagocytes to hepatocytes
Albumin
What do hepatocytes do to bile
Convert it from free bilirubin to cnojugated bilirubin
What do the Kupffer cells of the liver do (3)
Clearance of infection and LPS
Antigen presentation
Immune modulation (cytokines, etc…)
What are the retoculoendothelial functions of the liver (2)
Kupffer cell function
Erythropoesis
What is included in LFTs (8)
Alanine transaminase ALT Aspartate transaminase AST Alkaline phosphate ALP Albumin Bilirubin Gamma glutamyl transferase GGT Clotting factors PT Alpha feteproteins AFT
What are serum markers of liver cell damage (4)
ALT
AST
ALP
GGT
What is a live tumour marker
AFP
What are serum markers of liver function (3)
Albumin
Pro-thrombin time PT
Bilirubin
What measures the synthetic function of the liver (2)
Albumin
PT
What constitutes the portal triad
Bile duct
Portal arteriole
Portal venule
What cells are present in the sinusoids
Kupffer cells
Where are ALT and AST present
Within cytoplasm of hepatocytes
What causes a raised ALT and AST
Hepatocyte death
What other organs are ALT and AST present in, in lower amounts (4)
Muscle
Kidney
Brain
Pancreas
What LFT rises more in alcohol related damage
AST
What is raised in cirrhosis
AST/ALT ratio
Where is GGT found (7)
Liver Kidney Pancreas Spleen Heart Brain Seminal vesicles
Where in the liver is GGT found (2)
Hepatocytes
Epithelium of small bile ducts
What causes an elevated GGT (3)
Chronic alcohol use
Bile duct disease
hepatic metastasis
Where is ALP found (2)
Liver isoenzyme found in sinusoidal and canalicular membranes
What causes a marked rise in ALP (2)
Obstructive jaundice
Bile duct damage
What causes a moderate rise in ALP (2)
Viral hepatitis
Alcoholic liver disease (i.e. hepatocyte damage)
What are some other sources of ALP (5)
Bone Small intestine Kidney WBCs Placenta
What non-liver causes can cause a rise in ALP
Bone disease (especially metastatic and pregnancy)
What is albumin
The major protein synthesised by the liver (8-14g/day)
What is the molecular mass of albumin
65,000
What is the half life of albumin
20 days
What is the role of albumin (2)
Contributes to oncotic pressure
Binds steroids/drugs/bilirubin/calcium
What causes low albumin levels (3)
Low production (chronic liver disease, malnutrition)
Loss (e.g. gut, kidney)
Sepsis (3rd spacing)
What is PT a good measure of liver function
Half life of hours
Acute marker of liver function/damage
What is AFP
Alpha-feto protein
Glycoprotein with a molecular weight of 69,000/albumin superfamily
What are the normal levels of AFP in adulthood
Low concentrations/no known function
What is AFP used for (5)
Used in diagnosis of hepatocellular carcinoma (but may rise too late, or not at all)
Also raised in hepatic damage/regeneration
Raised in pregnancy
Raised in testicular cancer
What does raised bilirumin cause
Jaundice
What bilirubin is raised with pre-hepatic haemolysis
Unconjugated bilirubin
What bilirubin is raised in hepatic disorders
Both unconjugated and conjugated
What bilirubin is raised in post-hepatic disorders
Conjugated bilirubin
Where does conjugated bilirubin appear
Urine
Jaundice
Raised bilirubin
Normal enzymes (2)
Haemolysis
Gilbert’s disease
Jaundice
Raised ALP
Dilated bile ducts
Obstruction (gallstones, cancer)
Jaundice
Raised ALP
Undilated bile ducts (3)
Drugs
Primary biliary cirrhosis/primary sclerosing cholangitis
Pergnancy
Jaundice
Raised ALT/AST
Acute or chronic hepatocellular damage
Should bilirubin be detected in the urine
No! Large amounts can be detected with the naked eye though (dark urine)
Is urobilinogen detected in urine
Normally detected in small amounts in the urine
What causes an increase in urine urobilinogen (3)
Haemolysis
Hepatitis
Sepsis
What causes absence of urobilinogen
Obstructive jaundice
What clinical syndrome is associated with pale stools and dark urine
Obstructive jaundice
Beyond LFTs, what other blood tests can be used to determine the cause of liver pathology (10)
Viral serology Auto-antibodies Iron studies Copper studies Detailed drug history Radiological imaging - US and CT Fibroscan Histopathology ERCP
What other tests can be used to determine liver function (3)
Dye tests - indocyanine green/bromsulphalein (measure excretory capacity of liver, measure hepatic blood flow)
Breath tests - aminopyrien/galactose (carbon 14) - measure residual functioning liver cell mass.
Serum bile acids - elevated, especially in cholestasis (10-100s in cholestasis of pregnancy, 25x in PBC/PSC)
24 year old male medical student
noticed that his sclera went yellow after an end of term party, has noticed this a few times
fit, no PMH
SH single binge drinker, denies other drugs
not on any medication
no abnormalities on examination
no bilirubinuria on dipstick testing
bil 36 umol/L (<17) alb 40 g/L (35-51) ALT 35 IU/L (<40) AST 36 U/L (<40) alk phos 86 U/L (30-130) GGT 35 U/L (11-42)
Elevated conjugated bilirubin in fasting bilirubin test.
Gilberts.
38 year old female secretary presented with itch and jaundice, dark urine
PMH removal of a benign breast lump
UTI 5/7 earlier treated by GP
SH single, 21 units of alcohol/week, smokes 15/day
O/E no signs of chronic liver disease
bilirubinuria seen on dipstick of urine
bil 236 umol/L (<17) alb 38 g/L (35-51) ALT 65 IU/L (<40) AST 55 U/L (<40) alk phos 1024 U/L (35-51) GGT 59 U/L (11-42)
US - no bile duct obstruction
Drug induced cholestasis (intrahepatic, secondary to augmentin)
The jaundice should resolve over the next 3 weeks.
74 year old retired publican
3 week history of itch, pale stools, dark urine, yellow sclera
2 month history of weight loss-12 kg’s
PMH cardiomyopathy, peripheral neuropathy,
O/E jaundiced, no signs of chronic liver disease but epigastric fullness noted
bilirubinuria noted on urine dipstick
O/E: Courvoisier’s sign (in the presence of a painless palpable gallbladder, jaundice is unlikely to be caused by gallstones)
bil 120 umol/L (<17) alb 29 g/L (35-51) ALT 36 IU/L (<40) AST 45 U/L (<40) alk phos 450 U/L (35-51) GGT 98 U/L (11-42)
US - dilated common bile duct and possible pancreatic mass.
Pancreatic adenocarcinoma
CT scan and biopsy confirmed this plus local spread.
Liver looked cirrhotic.
A palliative stent was placed in the CBD
Jaundice and itch resolves, but he passed away 3 months later
18 year old female jaundiced art student
returned from trip to Goa 1 week previously
felt terrible for the last 10 days, fevers, diarrhoea, joint pain, last 2 days had turned yellow
admitted to taking “some tablets” in a nightclub + had small tattoo done
no PMH, anti-malarial tablets only
O/E jaundiced, no signs of chronic liver disease or IVDU
bil 168 umol/L (<17) alb 38g/L (35-51) ALT 2500 IU/L (<40) AST 2380 U/L (<40) alk phos 190 U/L (35-51) GGT 39 U/L (11-42)
US - no bile duct dilation, but swollen liver
Acute hepatitis A
Jaundice resolves and made a full recovery
a 54 year old lawyer noted by GP to have abnormal liver function tests PMH hernia repair meds nil alcohol 2 units/ day denied ever taking any drugs O/E palmar erythema and 5 spider naevei
bil 29 umol/L (<17) alb 27 g/L (35-51) ALT 49 IU/L (<40) AST 46 U/L (<40) alk phos 55 U/L (35-51) GGT 62 U/L (11-42) INR 1.3
US - coarse liver texture and large spleen
HepC serology confirmed
Admitted to using heroin once in the 70s.
Liver biopsy confirmed cirrhosis.
Chronic Hepatitis C infection
19 year old student split up with boyfriend / exams taken 32 g paracetomol / Alcohol++ PMH nil / no previous psychiatric Hx meds nil denied ever taking any drugs O/E alert / vomiting / resps. 28
bil 25 umol/L (<17) alb 40 g/L (35-51) ALT 550 IU/L (<40) AST 3400 U/L (<40) alk phos 200 U/L (35-51) GGT 450 U/L (11-42) INR 2.8 ABG Ph 7.2 BE -13
Paracetamol overdose.
Treated with n-actyl cysteine
Transfered to transplant centre, received a transplant 3 days later - survived