11. Jaundice and Liver Failure Flashcards
1
Q
What does jaundice/icterus describe?
A
- Yellow discolouration of sclerae and skin
- Raised bilirubin
- Detectable clinically - serum bilirubin >50µmol/litre
2
Q
Outline bilirubin metabolism
A
- Free bilirubin enters hepatocyte, binds to cytoplasmic proteins
- Unconjugated bilirubin => bilirubin glucuronide [glucuronyl transferase]
- => diglucoronide BR
- Conjugation makes bile water soluble
- Transported across concentration gradient into bile canaliculi
- Bilirubin glucuronide => mixture of compounds/urobilinogen/stercobilinogen (in the gut)
- Most of the stercobilinogen is oxidised to stercobilin (brown colour of faeces)
- 10% of sterconbilinogen is reabsorbed and returned to the liver
3
Q
What is haemolytic jaundice?
A
- Pre-hepatic (spleen)
- Haemolytic anaemias e.g. SCD
- Higher breakdown of erythrocytes, higher production of bilirubin
- Unconjugated bilirubin - insoluble, doesn’t pass into urine
- Increase serum urobilinogen
- Normal liver biochemistry
- Hb drop without overt bleeding
4
Q
Describe bile flow/formation through hepatocytes/cholangiocytes
A
• Excretion of bile salts and toxins by transporters on the apical surface • Transporters govern the rate of flow • Dysfunction - cholestasis • Main transporters: - Bile Salt Excretory Pump (BSEP) - MDR related proteins (MRP1 & MRP3)
5
Q
How does BESP work?
A
- Active transport of bile acids
- Across hepatocyte canalicular membranes
- Determines bile flow
6
Q
How does MDR 1 and 3 work?
A
- MDR1 - mediates canalicular excretion of xenobiotics, cytotoxins
- MDR 3 - encodes a phospholipids transporter protein that translocates phosphatidylcholine from inner to outer part of canalicular membrane
7
Q
What effect does terminal ileal resection/disease have on bile?
A
- Less reabsorption
- More bile in stool
- More fat in stool - liver can’t increase rate of bile production enough
- Malabsorption of fat soluble vitamins (ADEK)
8
Q
What is a cholecystectomy and what are the effects of this?
A
- Removal of gall bladder
- Normal health and nutrition
- Slow bile discharge into duodenum
- Avoid food with high fat content
9
Q
Where does bilirubin come from?
A
- Haemoglobin breakdown
- Catabolism of other haem proteins
- Ineffective bone marrow erythropoeisis
10
Q
What form of metabolised bilirubin can be reabsorbed by the GIT mucosa?
A
• Unconjugated bilirubin
• Urobilinogens
(- urine excretion)
11
Q
What is hepatic jaundice?
A
- Defective uptake => high unconjugated
- Defective conjugation => high unconjugated
- Defective excretion => high conjugated
- Liver failure => high conjugated
- Intrahepatic cholestasis
12
Q
What is post-hepatic jaundice?
A
- Defective transport by biliary duct system
- bile duct stones, HepPancBil malignancy, lymphadenopathy
- Build up of serum bilirubin
- Could cause cholangitis - sepsis
13
Q
What is the most common hereditary cause of increased bilirubin?
A
- Gilbert’s Syndrome
- Up to 5% of the population
- Autosomal recessive
- Reduction in glucurodination activity of UDPGT-1A1 (uridine-diphosphate-glucuronosyltansferase isoform 1A1)
- Elevated unconjugated bilirubin
- Mild jaundice may appear under: infections, stress, exertion, fasting
- Usually asymptomatic
14
Q
What are the most common causes of liver disease?
A
- Developed world - alcohol and non-alcoholic fatty liver disease (genetic predisposition, immunological mechanisms, 10-20% of heavy drinkers => cirrhosis)
- Developing world - chronic viral hepatitis B or C
15
Q
What is Cirrhosis?
A
- Final common pathway for liver disease
- Response to chronic liver injury
- Necrosis of liver cells
- Progressive fibrosis and nodule formation
- Impairment of liver cell function
- Distortion of architecture
- Portal hypertension
