Lab Investigation of Liver & GI Tract Disease Flashcards
Describe the size of the liver
The liver is the largest organ in the body, 1.5 kg in an average 70 kg male situated in upper right quadrant
How many lobes is the liver comprised of?
Comprised of large right lobe and smaller left lobe composed of lobules
What are lobules?
Lobules - sheets of hepatocytes
Describe the blood supply to the liver
Has dual blood supply
2/3 from gut via portal vein (nutrient rich)
1/3 from hepatic artery (oxygen rich)
How does blood drain from the liver?
Blood leaves the liver through the hepatic veins
Where are liver excretions removed from?
Substances for excretion from the liver are secreted from hepatocytes into canaliculi
Describe how the liver connects to the bile duct
The bile canaliculi merge and form bile ductules
They subsequently merge to become a bile duct; eventually common hepatic duct.
What are the major functions of the liver?
- Carbohydrate metabolism (gluconeogenesis)
- Fat metabolism
- Protein metabolism of plasma proteins
- Hormone metabolism (peptide and steroid hormones)
- Metabolism + excretion of drugs / foreign compounds
- Storage: glycogen, vitamin A, B12, iron and copper
- Metabolism and excretion of bilirubin
What is hepatitis?
Damage to hepatocytes
What is cholestasis?
Blockage; Intra or extrahepatic (e.g. bile ducts)
Outline the damage caused to the liver in cirrhosis
- Increased fibrosis
- Liver shrinkage
- Decreased hepatocellular function
- Obstruction of bile flow
What are the different tumours of the liver?
Primary cancer
Frequently secondary: colon, stomach, bronchus
How do we assess liver function?
Liver Function Test (LFT) provides a biochemical assessment of liver function
What markers are measured in a standard LFT?
- Bilirubin
- Albumin
- Alanine aminotransferase (ALT)
- Aspartate aminotransferase (AST)
- Alkaline phosphatase
- Gamma glutamyltransferase (gamma GT)
What does an LFT show us?
Insensitive indicators of liver ‘function’
Look for patterns of results - a single result rarely provides a diagnosis on its own
What is a LFT used for?
Not diagnostic but used for:
- Screening for liver disease
- Assessing prognosis
- Differential diagnosis; hepatic / cholestatic?
- monitoring disease progression
- Treatment efficacy measurement
- Severity assessments esp. cirrhosis
When would we expect to see a decrease in albumin levels?
Albumin concentrations only tend to decrease in chronic liver disease
What is bilirubin?
Yellow-orange pigment derived from haem from Hb breakdown
What are the 2 forms of bilirubin?
- Conjugated (direct-reacting bilirubin)
- Unconjugated (indirect-reacting bilirubin) - v. hydrophobic
What is the normal range of bilirubin?
Total bilirubin – SWLP Reference range <21 μmol/L
Conjugated (direct) bilirubin <10 μmol/L
How is bilirubin found in the body?
Binds tightly but reversibly to albumin
Where does conjugation of bilirubin occur?
Conjugation occurs in the liver → excreted in bile
Where are RBCs broken down?
Old RBCs undergo haemolysis in the spleen
What happens to the breakdown products of old RBCs in the spleen?
Fe is reutilised, Globin from Hb is transferred into bilirubin
Where is bilirubin conjugated?
Bilirubin transported to liver; albumin bound where its conjugated
Outline how conjugation occurs in the liver
Bilirubin is conjugated to diglucuronide via UDP-glucuronyl transferase enzyme
What is the product of bilirubin conjugation?
Leads to conjugation of mono / diglucuronides which are more water soluble, excreted via bile ducts into small intestine
How is bilirubin excreted?
Bilirubin converted to urobilinogen in small intestine
Re enters liver via extrahepatic circulation or enters systemic circulation to be excreted via kidneys
How is bilirubin excreted in faeces?
Some urobilinogen remains and reaches large intestine where it is converted into stercobilin by colon bacteria (gives stool brown colour)
What is jaundice?
Jaundice describes the yellow discolouration of tissue due to bilirubin deposition.
Mainly in skin and visualised in sclera
When does jaundice become noticeable?
Clinical jaundice may not be evident until the serum/plasma bilirubin concentration is 2x the upper reference of normal, >50 μmol/L
What causes jaundice to occur?
Increased serum/plasma [bilirubin] occur in imbalance between production & excretion
What is the first step in treating jaundice?
Important to determine if ↑bilirubin is conjugated or unconjugated (allows identification of liver function)
What does conjugated bilirubn elevation tell us?
Conjugated bilirubin elevation – obstruction of bilirubin flow
What does excess unconjugated bilirubin jaundice mean?
Unconjugated elevation - production is increased which is beyond capacity of liver conjugation
What are the prehepatic causes of jaundice?
Excess bilirubin production due to excessive RBC breakdown e.g.
- Haemolysis
- Haemolytic anaemia
- Genetic disorders
- Crigler-najjar
- Gilberts
What is gilberts syndrome?
Benign liver disorder, diagnosed on exclusion
Congenital disorder of UDP-glucuronyl transferase
What are the main causes of intrahepatic jaundice?
Damaged hepatic cells leading to cholestasis (both conjugated and unconjugated bilirubin present)
What factors leads to dysfunction of hepatic cells?
- Viral hepatitis
- Drugs
- Alcohol hepatitis
- Cirrhosis
- Pregnancy
- Infiltration
- Congenital disorder
What is the cause of extrahepatic jaundice?
Blockage of canaliculi due to conjugated bilirubin - impaired excretion
What may cause obstruction of the biliary drainage system?
- common duct stone
- carcinoma
- biliary structure
- sclerosing cholangitis
- pancreatitis
What causes neonatal jaundice?
Due to the immaturity of bilirubin conjugation enzymes
Common & transient (resolves in the first 10 days)
What are the consequences of neonatal jaundice?
High levels of unconjugated bilirubin - toxic to newborn → due to its hydrophobicity , can cross the blood-brain-barrier & cause kernicterus
What are the effects of kernicterus?
Kernicterus causes drowsiness and hypotenosity and seizures (can cause severe brain damage)
How is neonatal jaundice resolved?
Phototherapy with UV light – converts bilirubin to water soluble, non-toxic form
What causes pathological neonatal jaundice?
Pathological jaundice if high levels of conjugated bilirubin
Can be due to inborn errors of metabolism (galactosemia / tyrosinemia affecting liver)
E.g. Pale stools in babies with biliary atresia. Urgent surgical treatment is essential.
What is the frequency of gilberts syndrome?
Frequency : 10% of population
Males more frequently affected than females
Occurs when fasting or under physiological stress
What are the characteristics of gilberts syndrome?
Characterized by mild, fluctuating increases in unconjugated bilirubin
What are the causes of gilberts syndrome?
→ caused by ↓ ability of the liver to conjugate bilirubin
- genetic defect in promoter gene for UDP glucuronyl transferase
What are the most commonly measured markers of hepatocyte injury?
Liver Transaminases ALT and AST
What is the role of liver transaminases?
Catalyse transfer of amino group into acids
α -amino acid → α-oxo acid
What is ALT?
ALT Alanine Aminotransferase (ALT): predominantly localised to liver
What is AST?
AST Aspartate Aminotransferase (AST) has wide tissue distribution: heart, skeletal muscle, kidney, brain, erythrocytes, lung & liver
Where in hepatocytes are liver transaminases found?
Both are cytosolic but AST is also present in mitochondria
What is ALT used for?
ALT is used to identify liver damage arising from hepatocyte inflammation or necrosis
What do increases in ALT levels tell us?
Values >20x the upper limit of normal (ULN) may occur with severe liver damage
Small increases (<5x ULN) may occur in cholestasis due to secondary damage to hepatocytes.
When do AST and ALT levels increase?
Values increased in almost all liver disease
Which conditions are responsible for modest elevations in ALT and AST levels?
(5 x ULN):
- Fatty liver
- Chronic viral hepatitis
- Prolonged Cholestatic liver disease
- Cirrhosis