11: LFTs and Cases Flashcards
6 major functions of the liver
- Intermediary metabolism
- Xenobiotic metabolism
- Bile synthesis
- Protein synthesis
- Hormone metabolism
- Reticulo-endothelial
Intermediary metabolism: functions
enzyme-catalysed processes within cells that extract energy from nutrient molecules and use that energy to construct cellular components:
Functions:
- glycolysis, glucose synthesis, FA synthesis, glycogen storage, AA synthesis, liporprotein metabolism
Consequences of acute liver failure (3)
Hypoglycaemia (due to lack of glycogen)
Lactic acidosis (as can no longer metabolise lactic acid)
Increase in ammonia (cannot process AAs)
Xenobiotic metabolism (chemical modification)
Xenobiotic metabolism (chemical modification)
Hormone metabolism
vit D hydroxylation (25-hydroxylase)
steroid hormones (conjugated and excreted)
peptide hormones (catabolism)
Bile synthesis: constituents, functions
Constituents
- water, phospholipids, drugs and metabolites, bile salts/acids, cholesterol, BR, proteins
Functions
- excretion
- micelle formation
- digestion
BR metabolism and transport
BR metabolism and transport
- Red cells are broken down releasing heme, iron and globin
- The heme then goes on to form bilirubin → bound to albumin in the plasma
- This uBR goes to the liver and becomes glucuronidated (conjugated)
- The conjugated bilirubin is released into the bile
Reticulo-endothelial
Kupffer cells:
- clearance of infection and LPS
- antigen presentation
- immune modulation (i.e. cytokines, etc.)
Erythropoiesis
markers of liver damage
markers of synthetic function
tumour marker
markers of liver damage
markers of synthetic function
tumour marker
Liver architecture
- blood comes up portal vein
- goes throughs sinusoids
- into central vein
- bile canaliculi run in other direction
liver damage and zones
liver damage and zones
ALT and AST
Location
- liver = hepatocytes
- other = muscle, kidney, bone + pancreas but in small amounts
Catalyse transfer of alanine and aspartate to alpha-keto group of alpha-ketoglutarate → pyruvate and oxaloacetate formation
AST rises more in alcohol and cirrhosis
- AST:ALT ratio >2 = alcoholic liver disease (S = SHOTS)
- In absence of alcohol, AST:ALT >0.8 = advanced fibrosis or cirrhosis
GGT
Catalyses transfer of the gamma-glutamyl group from gamma-glutamyl peptides such as glutathione to other peptides and to L-amino acids
Locations:
- liver = hepatocytes, bile duct (epithelium)
- other = kidney, pancreas, spleen, heart, brain and seminal vesicles
Elevated in chronic alcohol use, in bile duct disease, and hepatic metastases
- can also rise in response to medications
ALP
Catalyse hydrolysis of large number of organic phosphate esters at alkaline pH (precise function is UNKNOWN)
Locations:
- liver (isoenzyme) = bile ducts (sinusoidal and canalicular membranes)
- other = BONE, PLACENTA, small intestine, kidney, WBCs
Markedly elevated in…
- obstructive jaundice
- bile duct damage
- pregnancy
- bone disease
Albumin: (amount synthesised and half-life), function, when is it low/raised, relation to clotting cascade
8-14g/day, 20 days (long half-life)
main contributor to ONCOTIC PRESSURE and BINDS to steroids/drugs/BR/calcium
low in:
- low production states (CLD, malnutrition) - chronic course (not acute)
- increased loss (nephrotic syndrome)
- sepsis (3rd spacing - when endothelium leaky, to albumin leaks into tissues)
Raised in = causes of acute abdomen (i.e. acute pancreatitis)
clotting cascade:
- PT (or INR) is a marker of ACUTE liver function (as BR half-life is 20 days)
AFP: what is it, role, raised in?
Glycoprotein of the albumin superfamily
Involved in foetal transport, immune regulation/tolerance
In the FOETUS it is made by:
- Yolk sac
- GI epithelium
- Liver
In ADULTS, the concentration is low, and it has no apparent function
Raised in:
- Hepatocellular carcinoma (may rise late or not at all)
- Hepatic damage/regeneration
- Pregnancy
- Testicular cancer
BR
interpret in contact of other liver enzymes
also, image the biliary tree:
- dilated ducts = gallstones, cancer, etc.
- non-dilated ducts → other tests → ?biopsy
Causes of jaundice
Causes of jaundice
Urine dipstick tests
BR = should be NONE in urine (only cBR can be found in urine when bile duct blocked or cBR spills back into circulation → dark urine)
Urobilinogen = breakdown of BR in intestines by bacteria. Soluble so enters enterohepatic circulation, some excreted in small amounts in urine
- Urobilinogen in urine ABSENT in obstructive jaundice
- Urobilinogen in urine PRESENT normally
- Urobilinogen in urine INCREASED in haemolysis, hepatitis, sepsis (more BR -→ more uroBR)
Pale stools/dark urine = feature of obstructive jaundice
- high cBR and no stercobilinogen
What is in a liver panel?
What is in a liver panel?
ALT raised in isolation → fatty liver disease
ALT raised in isolation → fatty liver disease
3 ways of measuring liver function
Dye tests = indocyanine green/bromsulphalein
Breath tests = aminopyrine/galactose (carbon 14)
Serum bile acids = elevated esp. in cholestasis (10-100x in cholestasis of pregnancy, 25x in PBC/PSC)
Causes of low urea
Severe liver disease, (synthesised in liver), malnutrition, pregnancy
Causes of raised urea (x10 ULN)
Upper GI bleed (or large protein meal)
Dehydration/AKI (urea excreted renally)
When is ALP normal in a bone condition?
Plasma cells suppress osteoblasts, hence ALP is normal in myeloma
summary of liver enzymes
summary of liver enzymes
Gilbert’s syndrome
- Drug-induced cholestasis from Augmentin
pancreatic adenocarcinoma (head)
acute hepatitis A
3 things that make ALT go over 1000
- Toxins (paracetamol)
- Viruses (i.e. hepatitis viruses)
- Ischaemia (e.g. post-resuscitation)
liver function test results in cirrhosis, acute liver failure, cholestasis, alcohol abuse
Albumin and clotting factors summary (synthetic hepatocellular dysfunction)
BR processing
pre-hepatic, hepatic, post-he[atioc
