Liver Functions & Investigations Flashcards
1
Q
What is the Liver?
A
- Located in the upper right quadrant of the abdomen
- Largest Organ in the Body
- Vital role in metabolism
- Large capacity for regeneration
- Large functional reserve capacity
2
Q
What is the structure of the Liver?
A
Dual blood supply:
- 2/3 from portal vein which drains from the gut
- Everything from the gut comes straight to the liver
- Remainder from the hepatic artery
Substances for excretion are secreted from hepatocytes into canaliculi
- These lead to intrahepatic ducts
- Finally reach the duodenum via the common bile duct
- Bile canaliculus is a thin tube that collects bile secreted by hepatocytes. The bile canaliculi merge and form bile ductules, which eventually become the common hepatic duct.
Hepatocytes constitute 60% liver mass
- Each hepatocyte is in contact with: Sinusoid, Bile canaliculus, Neighbouring hepatocyte
3
Q
What are liver functions?
A
- Carbohydrate metabolism: Gluconeogenesis, Glycogen synthesis and metabolism
- Fat Metabolism: Fatty acid synthesis, Cholesterol synthesis and excretion, Lipoprotein synthesis, Bile Acid synthesis, Ketogenesis
- Protein Metabolism: Synthesis of plasma proteins (not Igs), Urea synthesis and nitrogen removal
- Hormone Metabolism: Metabolism of steroid hormones, 25-hydroxylation of vitamin D, Metabolism of polypeptide hormones
- Storage: Glycogen, Vitamins A, Vitamin B12, Iron
- Toxin/Drug: Metabolism and Excretion
- Bilirubin: Metabolism and Excretion
4
Q
What is the use of Liver Function Tests?
A
- Screening for the presence of liver disease
- Assessing prognosis
- Measuring the efficacy of treatments for liver disease
- Differential diagnosis: predominantly hepatic or cholestatic
- Assessing severity, especially in patients with cirrhosis
- Monitoring disease progression
5
Q
What are clinical manisfestations of Liver Disease?
A
- Ascites
- Hepatic Encephalopathy
- Hepatorenal syndrome
- Jaundice
- Disordered Haemostasis
- Enzyme Release
- Portal Hypertension
- Palmar Erythema
- Gynaecomastia
- GI Varices
- Spider Naevi
6
Q
What is included in the Liver Profile test?
A
Usually includes:
- Serum bilirubin
- AST or ALT: Indicate hepatocellular damage
- ALP: Indicate a cholestatic picture
- Serum albumin: Determines synthetic function and Determines chronicity of disease
May also include:
- PT or INR: Determines synthetic function and Helps identify severity of disease
7
Q
What is hepatic and cholestasis?
A
Hepatocellular injury
- Injury to hepatocytes causes intracellular contents to be released
Cholestasis
- Reduction or absence of bile flow in the duodenum
- Impairment of bile secretion at the level of bile ductules
- Functional defect in bile formation at hepatocyte level
8
Q
How Haem broken down?
A
- Heme is converted to Bilverdin by Heme Oxygenase
- Bilverdin is converted to Unconjugated Bilirubin by Bilverdin Reductase
- Unconjugated Bilirubin is converted to Conjugated Bilirubin through addition of glucoronic acid by UDP-glucuronyltransferase (UGT) which can be readily excred in urine and faeces
9
Q
How is Bilirubin transported?
A
- Reversible addition of albumin allows unconjugated bilirubin to be transported in the blood yet kept in the vascular space
- Free bilirubin can cause cerebral toxicity
10
Q
How is Bilirubin metabolised?
A
- In the intestinal tract bilirubin glucuronides are hydrolysed and reduced by bacteria to form colourless urobilinogens
- These undergo enterohepatic circulation
11
Q
What are bile acids and how are they produced?
A
- Cholesterol homeostasis is largely maintained by the conversion of cholesterol to bile acids and their subsequent metabolism
- Requires the terminal ileum to absorb bile acids for recirculation
- Essential to normal digestion especially the absorption and metabolism of fats
12
Q
What are characterisitics of Alanine Aminotransferase?
A
- In terms of tissue distribution, most specific marker for liver injury (with GGT)
- Also found in Muscle and kidney
- Half life is ~47 hours
- Cytosolic enzyme and therefore released upon cellular injury
13
Q
What are characterisitics of Aspartate Aminotransferase?
A
- AST is found in the liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas, lungs, leukocytes, and erythrocytes
- Less specific than ALT for liver disease
- Half life is ~17 hours
- Found in the cytosol and mitochondria
- Immunologically distinct isoenzymes
14
Q
What are characteristics of γ Glutamyl Transferase (GGT)?
A
- Enzyme catalyses transfer of the gamma-glutamyl group from peptides such as glutathione to other peptides and to L-amino acids
- Relatively specific marker for liver injury but also found in cell membrane of kidneys, pancreas, gall bladder, spleen, heart and brain
- Membrane-bound glycoprotein enzyme
- Found on canalicular membrane of hepatocytes
- In neonates, serum GGT activity is 6 - 7 times that of adults
- Levels decline to adult levels by 5 to 7 months
- Enzyme induction by drugs such as barbiturates and phenytoin
15
Q
What are characteristics of Alkaline Phosphatase (ALP)?
A
- Found in a number of tissues, primarily reflects bone and liver
- Also intestinal and placental ALP
- Membrane-bound glycoprotein enzyme
- Found on canalicular membrane of hepatocytes
- Major value in diagnosis of cholestatic disease
- ALP is elevated in children which correlates well with rate of bone growth and appears to be accounted for by the influx of enzymes from osteoid tissue
