week 2 Flashcards
list liver functions
amino acid, carbohydrate and lipid metabolism
storage of proteins, glycogen, vitamins and metals
plasma protein and enzyme synthesis
detoxification
production of bile
immune functions
components of portal triad
hepatic artery
portal vein
bile duct
three features of cirrhosis
diffuse process with fibrosis and nodules
components of bile
bile pigments (bilirubin - haemoglobin breakdown product) bile acids/salts - cholesterol-based mucin bicarbonate cholesterol, phospholipids
haem breakdown to bilibrubin
haem broken down to biliverdin by haem oxygenase
biliverdin converted to bilirubin by biliverdin reductase
unconjugated must be bound to albumin
conjugation of bilirubin
ligandin presents UB to glucuronic acid
occurs in liver
UB enters hepatocytes via sinusoidal bilirubin transporter
UDP glucuronyl transferase converts UB to CB
pathway of conjugated bilirubin out of body
bilirubin to urobilinogen in small intestine
some goes to large intestine and is converted to stercobilin - in faeces
some goes to liver via portal vein and is converted tp urobilin in kidney - in urine
pre-hepatic jaundice
elevated haemolysis more haemoglobin more bilirubin produced - unconjugated - hyperbilirubinarmia large increase in UB CB is normal or slight increase no bilirubin in urine increase of urobilinogen and stercobilin
hepatic jaundice
could be:
impaired uptake of CB
impaired conjugation of bilirubin
impaired transport of CB into bile canaliculi
increase in CB and UB
increase in bilirubin and urobilin in urine
stercobilin normal
post-hepatic jaundice
obstruction of hepatic, cystic or common bile duct - cholestasis gall stones pancreatitis - swelling can block pancreatic tumours UB normal large increase in CB large increase of bilrubin in blood urobilin in urine is absent stercobilin in faeces is absent
carbohydrate metabolism in the liver
storage as glycogen and released in glycogenolysis
gluconeogenesis - synthesis of glucose from other sources eg lactate, pyruvate, glycerol, alanine
glucose as an energy substrate - glycolysis, citric acid cycle, synthesis of FA and TG
conversion of fructose and galactose to glucose phosphates
lipid metabolism in the liver
mitochondrial beta oxidation of short chain fatty acids
synthesis of FA, TG, CHOL, phospholipids and lipoproteins
cartnitine acyl transferase allows FAs to enter mitochondria
protein metabolism in the liver
most circulating proteins are synthesised wholly or largely by liver
albumin, glycoproteins
glycation of protein
breakdown of RBCs
hb broken down into
haeme - converted to bilirubin
globins - broken into amino acids and recycled
iron - bound by transferrin and returned to iron stores in the liver or bone marrow
inherited metabolism disease presenting with acute onset liver failure
neonatal to 3 years
episodic vomitting since neonatal period, possible failure to thrive, possible family history
abnormal stress such as infection, fasting, exercise
progressive encephalopathy and anicteric multisystem failure and acidosis
what can be measured in a LFT
bilirubin albumin alanine aminotransferase (ALT) aspartate aminotransferase (AST) alkaline phosphatase gamma glutamyl transferase (y-GT) total protein
role of AST and ALT in gluconeogenesis
they catalyse the transfer of amino groups from aspartic acid or alanine to ketoglutaric acid to produce oxaloacetic acid and pyruvic acid respectively
function of (y-GT)
responsible for the transfer of glutamyl groups from gamma-glutamyl peptides to other peptides or amino acids
LFTs in hepatocellular disease v cholestatic disease
hepatocellular - AST >3x url, ALP<2x url
cholestatic disease - AST <3x url, ALP >2x url
gilberts syndrome
genetic defect on chromosome 2 for the locus coding for the UGT-1A1 protein
this protein is involved in converting UB to CB
5 Fs for gall stones
female fair fertile forty fat
3 main types of gallstones
cholesterol stone - usually solitary, oval and large
bile pigment stone - multiple, irregular, hard and associated with chronic haemolysis
mixed stones - most common, multiple, multi-faced, laminated structure with layers of cholesterol, bile pigment and calcium salts
pathology of gallstones
cholesterol supersaturation
biliary stasis - occurs during periods of fasting or starvation
increased bilirubin secretion - can be due to increased RBC breakdown in disease or failure of hepatic conjugation
acute cholecystitis
impacted stone in gallbladder leading to GB oedema/inflamation and bacterial infection
raised inflammatory markers, sometimes normal LFT, can have jaundice
murphy’s sign - extreme tenderness over GB fundus
