Liver + Biliary system Flashcards
What are the functions of the liver?
-Protein synthesis: albumin, clotting factors -Glucose and fat metabolism -Immune defense: reticukoendothelial system -Detoxification and excretions: drugs and hormones, ammonia, billirubin
What happens when ammonia detoxification of the liver is impaired?
Hepatic encephalopathy due to ammonia build up (can cross the BBB):
- Converted into glutamien –> osmotic imbalance in brain –> cerebral oedema
What happens when metabolism of carbs goes wrong?
Hypoglycaemia
What happens when albumin production goes wrong?
- Oedema
- Ascites
- Leukonychia (whitening on the nail bed due to low protein)
What happens when clotting factor production fails ?
Easy bleeding and bruising
What happens when bilirubin regulation is impaired?
Jaundice, stool and urine changes, pruritis
What happens when the immune function of the liver goes wrong?
Spontaneous bacterial infections can occur - bacterial peritonitis (usually following ascites)
What zone of the liver is most prone to injury?
Zone 3-rea around the central vein is most prone to ischaemic damage
What are the 2 broad types of kidney injury?
Acute and Chronic
Aetiology of acute liver disease
- Viral: HepA,B,EBV
- Drugs
- Alcohol
- Vascular
- Obstruction
- Congestion
Aetiology of Chronic liver disease
- Alcohol
- Viral-HepB,HepC
- Autoimmune
- Metabolic: iron, copper
Presentation of acute liver disease?
- Malaise
- Nausea
- Anorexia
- Jaundice
rare: Confusion, bleeding, pain, hypoglycaemia
Presentation of Chronic Liver disease?
- Ascites
- Oedema
- Malaise
- Anorexia
- Pruritis
- Clubbing
- Palmar erythema
- Xanthelasma
- Spider Naevia
- Dupuytren’s contracture
- Hepatmegaly
- Bleeding: haematemesis, easy bruising
rare: jaundice, confusion
Describe the possible outcomes in acute and chronic liver injury
What are LFTs and what do they tell you?
- Serum bilirubin
- Serum Albumin
- Prothrombin time -INR
Liver function - synthetic function of the liver - gage severity of liver disease
What is liver biochemistry (hepatic enzymes) and what do they tell you?
- Aminotransferases: AST, ALT
- ALP (alkaline phosphatase)
- GGT (gamma glutamyl transpeptidase)
Dont give an index of liver function but can indicate inflammation or damage
Non liver causes of hypoalbuminaemia?
- Malnutrition
- Urinary protein loss
- Sepsis
What are aminotransferases?
- Aspartate aminotransferase (AST)
- Alanine aminotransferase (ALT
Transaminases that are contained in hepatocytes and leak into the blood with liver cell damage
What is AST?
- Aspartate aminotransferase (AST)
- Mitochondrial enzyme (80%), 20% in cytoplasm
- Also present in the heart, muscle, kidney and brain
- High levels seen in: hepatic necrosis, MI, muscle injury and congestive heart failure
What non hepatic conditions cause a raised AST?
- MI
- Kidney disease - hepatic necrosis
- Muscle injury
- Congestive heart failure
Is AST or ALT more specific to liver disease?
ALT: rise is only seen in liver disease
Where is ALP present?
Alkaline phosphatase is present in
- Hepatic canalicular and sinusoidal membranes
- bone
- intestine
- placenta
When is serum ALP raised?
- Intra/extra hepatic cholestatic disease of any cause (due to increased synthesis): Cholestatic jaundice, Hepatic infiltrations, Cirrhosis
- Bone disease: osteomalacia, hypoparathyroidism, pagets disease
What non hepatic causes can cause a raised ALP
Bone disease:
- osteomalacia
- Hypoparathyroidism
- Pagets disease
How can the origin of ALP be determined (raised ALP)?
- Electrophoretic separation of isoenzymes or bone specific monoclonal antibodies
- Clinical practice: if the gamma-GT is also abnormal ,ALP is presumed to come from the liver
What is GGT?
Gamma-glutamyl transpeptidase
Microsomal enzyme present in the liver and many other tissues. Acitivity can be induced by numerous drugs (phenytoin, warfarin, rifampicin and alcohol)
What can induce GGT activity?
- Alcohol
- Phenytoin
- Warfarin
- Rifampicin
many drugs
What is GGT a sensitive indicator of?
Alcoholic liver disease
When is GGT raised?
- Mild elevations common – even with minimal alcohol consumption
- Fatty liver disease
- Cholestasis: rises in parallel with ALP
- Alcohol intake/ AFLD
If ALP is normal but there is raised gamma glutamyl transpeptidase, what could this indicate?
Useful guide to alcohol intake
In the absence of other LFT abnormalities but a slight raised gamma-glutamyl transpeptidase, what should be done?
Can be safely ignored
What is PT?
Measures extrinsic pathway- clotting cascade
When is the globulin fraction raised?A
Autoimmune hepatitis. If the globulin fraction falls –> succseful therapy
What is jaundice?
Yellowing of the skin and slcera due to hyperbilirubinaemia
What is the classification of jaundice?
Unconjugated or conjugated
What is the cause of unconjugated jaundice?
Pre-hepatic causes:
- Haemolytic jaundice (haemolysis of red cells)
- Congenital: Gilberts
What are the causes conjugated jaundice?
- Intrahepatic (due to failure of bile secretion)
- extrahepatic (due to a large duct obstruction of bile flow)
What are the causes of extrahepatic cholestasis?
- Common duct stones
- Carcinoma: bile duct, head of pancreas, ampulla
- Biliary stricture
- Sclerosing cholangitis
- Pancreatic pseudocyst
What are the causes of intrahepatic cholestasis?
- Viral hepatitis
- Drugs
- Alcoholic disease
- Cirrhosis
- Autoimmune cholangitis
- Pregnancy
- Recurrent idiopathic cholestasis
- Some congenital disorders
- Infiltrations
Difference in clinical presentation between pre-hepatic and cholestatic jaundice
- Cholestatic: pale stools and dark urine, serum bilirubin is conjugated, maybe itching, LFTS abnormal
- Pre-hepatic: Normal urine and stools, not itching and normal LFTs
Jaundice presentation - what questions should you ask?
- Dark urine? Pale stools? Itching? –> Cholestatic cause
- What are your symptoms? (biliary pain, rigorsm abdomen swelling, weight loss)
- PMHx: biliary disease/ intervention/ malignancy/HF/blood products/autoimmune disease
- Drug history: drugs/herbal meds started recently
- social history: Alcohol, foreign travel, sex, IVDU, certain foods
- FHx/ system review - not that helpful
Jaundice presentation: What investigations?
- Viral Markers: HepA,B,C
- Ultrasound examination
- Liver biochemistry
