Liver Biochemistry and Jaundice Flashcards
What is the liver enclosed in?
Capsule covered by visceral peritoneum
What does the falciform ligament do?
Divides the left lobe and the larger right lobe
What is a hepatic lobule?
A smaller hexagonal division of lobes
What does a hepatic lobule consist of?
Portal triad
Hepatocytes in linear cords
Capillary network and central vein
Lymphatics and vagus nerve
What is the functional unit of the hepatic lobule?
Liver acinus
What are sinusoids?
Capillaries with fenestrated epithelium that carry blood towards to central vein
What is the space of Disse?
The part of the liver between a hepatocyte and a sinusoid
What carbohydrate metabolism does the liver do?
Anabolism and catabolic of sugars
What fat metabolism does the liver do?
Break down and synthesis
Processing chylomicron remnants
Lipoprotein and cholesterol synthesis
What protein metabolism does the liver do?
Synthesis of proteins like albumin
Transamination and deamination of amino acids
Conversion of ammonia to urea
What hormones does the liver deactivate?
Insulin
Glucagon
ADH
Steroid hormones
What molecules does the liver store?
Vit B12 Vit A, D, E, K (fat-soluble) Iron Copper Glycogen
What is drug metabolism?
The breakdown of drugs to facilitate excretion
What happens in phase 1 of drug metabolism?
The polarity of the drug is increased by oxidation, reduction or hydrolysis in order to permit conjugation
What molecule plays a big role in phase 1 of drug metabolism?
Cytochrome P450
What happens in phase 2 of drug metabolism?
Polarity is further increased by adding a reactive group to the drug to result in an inactive product which can be excreted
Which blood tests are included in LFTs?
AST ALT ALP GGT Bilirubin Albumin Prothrombin time
Which are the ‘true’ LFTs and what does that mean?
Bilirubin
Albumin
PT
Ones involved in the synthesis of proteins that give a measure of whether the liver is making stuff
Which structures is ALT present in?
Liver
What increases the levels of ALT?
Hepatocellular injury
Which structures is AST present in?
Liver Heart Skeletal muscle Kidneys Brain RBC
What increases the levels of AST?
Liver injury MI Pancreatitis Haemolytic anaemia Renal or MSK disease
What does a higher level of AST than ALT indicate?
Muscle injury
What is AST a marker of?
How acute hepatocellular damage is
What is ALT a marker of?
Hepatocellular injury
Which structures is ALP present in?
Liver
Bile duct
Bone
Placenta
What alters the level of ALP?
Biliary obstruction Liver disease Bone pathology Thyroid abnormality Pregnancy
What is ALP a marker of?
Cholestasis
Which structures is GGT present in?
Liver Bile ducts Kidney Pancreas Gallbladder Spleen Heart Brain
What alters the level of GGT?
Biliary obstruction
Liver and pancreas disease
CV disease
Alcohol abuse
What does an increase in ALT and AST indicate?
Hepatocellular injury
What does an increase in ALP and GGT indicate?
Cholestasis
What does a more than 10 fold increase in ALT and a less than 3 fold increase in ALP indicate?
Predominately hepatocellular injury
What does a less than 10 fold increase in ALT and a more than 3 fold increase in ALP indicate?
Cholestasis
What is the primary marker of cholestasis?
ALP
How are GGT and ALP used to narrow down a cause?
If ALP is increased, look at GGT
If GGT is also increased this suggests biliary epithelial damage and bile flow obstruction, therefore indicating choletasis
If only ALP is increased the cause is likely to not be the liver
What is highly suggestive of cholestasis?
Marked increase in ALP and GGT
What is the relationship between GGT and alcohol?
GGT is elevated by large alcohol abuse, especially if disproportionate increase compared to ALT and others
What is AST < ALT suggestive of?
Chronic liver disease
What is AST > ALT suggestive of?
Acute alcoholic hepatitis
What is the normal ratio of AST:ALT?
0.8
What ratio of AST:ALT is suggestive of alcohol abuse?
> 2
What is the diagnosis likely to be if AST and ALT are both very high, >1000 U/L?
Almost certainly hepatitis
What will AST levels never surpass in chronic alcoholic disease?
> 1000
What conditions are indicated when AST levels are elevated to more than 20 times normal?
Viral hepatitis
Muscle trauma
Surgery
Drug induced hepatic trauma
What conditions are indicated when AST levels are elevated to 10-20 times normal?
Alcoholic cirrhosis
MI
What conditions are indicated when AST levels are elevated to 5-10 times normal?
Chronic cirrhosis
What conditions are indicated when AST levels are mildly elevated?
Steatosis
Liver metastases
PE
When is albumin synthesised?
In a functioning liver
What is the function of albumin?
Intravascular osmotic pressure
What may cause albumin levels to fall?
Cirrhosis
Inflammation in the acute phase decreases albumin temporarily
Protein-losing enteropathy, nephrotic syndrome
What is prothrombin time?
The time taken for blood to clot
What conditions can raise PT?
Liver disease in the absence of secondary causes
Reduced production of clotting factors
What is bilirubin?
A breakdown product of haemoglobin
When is bilirubin conjugated?
When it has been taken up in the liver
When is jaundice visible?
Bilirubin >60mmol/L
Does conjugated or unconjugated bilirubin have an effect on the colour of urine, and what is that effect?
Conjugated bilirubin causes darker urine
What causes pale and bulky stools (steatorrhoea)?
Bile (containing bilirubin) and lipase cannot reach the bowel due to blockage, fat is therefore not absorbed and cause this appearance of stools
What is pre-hepatic jaundice?
Excessive red cell breakdown overwhelms the liver
Decrease in conjugated and increase in unconjugated bilirubin
What is hepatocellular jaundice?
Liver loses conjugating ability and cirrhosis compresses the biliary tree
What is post-hepatic jaundice?
Obstruction to biliary drainage but bilirubin is stilll conjugated in the liver
What does dark urine and pale stools indicate?
Post-hepatic cause
What does normal urine and normal stools indicate?
Pre-hepatic cause
What does dark urine and normal stools indicate?
Hepatic cause
What are ALT, AST, ALP and GGT like in acute hepatocellular damage?
ALT - very elevated
AST - very elevated
ALP - normal or elevated
GGT - normal or elevated
What are ALT, AST, ALP and GGT like in chronic hepatocellular damage?
Everything is normal or elevated
What are ALT, AST, ALP and GGT like in cholestasis?
ALT - normal or elevated
AST - normal or elevated
ALT - very elevated
GGT - very elevated
What could be the cause if the patient is jaundiced but ALP and ALT are normal?
Gilbert’s syndrome
Haemolytic anaemia
What is Gilbert’s syndrome?
Disorder of bilirubin processing in the liver where there is increased unconjugated bilirubin in the blood with normal LFTs which can produce jaundice during illness, alcohol or stress
What is haemolytic anaemia?
Abnormal breakdown of red blood cells
Fatigue, SOB, jaundice
What are causes of acute hepatocellular jaundice?
Poisoning
Infection
Liver ischaemia
What are the causes of chronic hepatocellular jaundice?
Chronic liver diseases PBC, PSC Pregnancy Autoimmune hepatitis Haemochromatosis Wilson's disease
What are the causes of obstructive jaundice?
Gallstones
Strictures
Tumours
Congenital biliary atresia
