Liver: Chemical Pathology. Flashcards
Name 5 main functions of the liver:
Protein metabolism - Urea synthesis - Plasma protein synthesis and coagulation factors - NOT Immunoglobulins Carbohydrates metabolism - Glycogen synthesis and breakdown - Gluconeogenesis Fat metabolism - Bile salt synthesis - lipoprotein synthesis - Fatty acid synthesis - Cholesterol synthesis and excretion Metabolism and excretion - Billirubin - Steroid hormone - Detox and Excretion of drugs and toxins Storage - Glycogen, Vitamin B12, Iron, Vitamin A
Name 7 Biochemical features of impaired liver function:
Increase in Bilirubin Increase in creatine and metabolic acidosis Increase in cholesterol and LDL Decrease in Albumin Hypokalaemia Hypoglycaemia Hyponatraemia
What kind of tests are best for detecting liver disease?
Tests that reflect active hepatocyte damage are best for detecting liver disease:
AST, ALT, GGT, ALP
What is the purpose of a standard liver function test?
Reflect basic underlying diseases
Does not give a specific diagnosis
How is a specific diagnosis of liver impairment made?
A standard liver function test must be done
Alongside other findings like
- Imaging
- Tests for specific liver disease.
Name 3 basic Liver function tests:
- Total and direct Bilirubin
- Liver enzymes (ALP, GGT, AST, ALT)
- Plasma proteins (Total protein, Albumin)
Name 4 disease of the liver:
Hepatitis - Damage of hepatocytes Cholestasis - Decrease of the bile flow Cirrhosis - End stage fibrosis with hepatocyte damage - Causing impaired function and portal hypertension Tumors
Explain the first part of the metabolism of bilirubin:
Within the spleen: reticuloendothelial cells
Hemoglobin is catabolized into haem and globin.
Haem is them catabolized into iron and bilirubin.
Once Bilirubin released into the plasma, it is transported throughout the body bound to albumin. (Prevents it’s precipitation and deposition in tissue)
The albumin-bilirubin complex reaches the liver and permeates to the sinusoid surface of all hepatocytes allowing the pigment to dissociate from albumin and enter the liver. In the hepatocyte, bilirubin is bound to ligandin (a cytosolic protein, that facilitates transfer to the endoplasmic reticulum, the site of bilirubin conjugation)
Explain the second part of the metabolism of bilirubin:
Conjugation is mandatory to render bilirubin an aqueous soluble facilitating its secretion across canalicular membranes and its secretion into bile without a protein carrier
Bilirubin is conjugated within the hepatocyte into bilirubin diglucuronide.
The conjugated bilirubin is excreted into the bile and then transported Into the small intestine.
Here, the conjugated bilirubin is rapidly reduced and deconjugated by colonic flora to a series of molecules termed urobilinogen and stercobilinogen.
Thereafter it is excreted.
Explain the third part of the metabolism of bilirubin:
Enterohepatic circulation also occurs.
Intestinal beta-glucuronidase hydrolyzes the conjugated bilirubin.
Free bilirubin is then released
It is then reabsorbed and transported by the portal circulation to the liver
Name 2 pre-hepatic major causes of jaundice:
Ineffective erythropoiesis
Haemolysis
Name 4 post-hepatic major causes of jaundice:
Gallstones
Cholangitis
Biliary strictures
Carcinoma of the pancreas and biliary tree
Name a few major hepatic causes of jaundice:
Pre- Microsomal
- Drugs that interfere with bilirubin uptake e.g rifampicin
Microsomal
- Prematurity
- Hepatitis
- Gilbert syndrome
- Crigler-Najjar syndrome
Post- Microsomal
- Impaired excretions
- Hepatitis
- Rotor syndrome
- Dublin-Johnson syndrome
Intra-hepatic obstruction.
- Hepatitis
- Cirrhosis
- Bilary atresia
- Tumors
- Extrahepatic sepsis
At what point is Jaundice clinically visible?
When bilirubin exceeds 50 umol/L
An increase in Serum bilirubin is also associated with bilirubinurinia (dark urine)
What is the enzyme used in bilirubin conjugation?
UDP- Glucuronyltransferase
