PHYS Investigation of Jaundice - Week 5

Question 1

Jaundice

Answer 1

Yellow appearance of skin, sclera, mucous membranes caused by excess bilirubin in blood.

Question 2

When is jaundice detectable clinically?

Answer 2

Detectable clinically when serum bilirubin > 50umol or 3mg/dl (normal range < 17umol/L or 1 mg/dL).

Question 3

Biliverdin colour

Answer 3

Green-yellow.

Question 4

Unconjugated bilirubin colour & solubility.

Answer 4

Orange-yellow. Fat soluble.

Question 5

Sources of bilirubin production and breakdown.

Answer 5

• 80% daily bilirubin production (250-400mg in adult) – derived from haemoglobin.
• 20% daily bilirubin production – derived from rapidly turning-over small pool of free haem.

Question 6

Pathway of bilirubin production & circulation & excretion.

Answer 6

Haem -> unconjugated bilirubin [fat soluble] @ reticulo-endothelial system (RES) of the spleen -> bilirubin bound to albumin @ transported via blood to liver -> taken up by hepatocytes -> conjugated w sugar residues (glucoronic acid) -> conjugated bilirubin [water soluble] -> enters biliary system @ mid-duodenum.
-> 95% secreted bilirubin -> reabsorbed in the terminal ileum -> travels to the liver via portal circulation -> bile is re-secreted via liver into the small intestine… (enterohepatic circulation).
&
-> 5% secrete bilirubin -> hydrolysed by the intestinal flora -> reduced to form urobilinogen [water soluble]
-> oxidised by gut bacteria -> stercobilin [brown/stool colour].
OR -> reabsorbed via portal system -> recycled by the liver.
OR -> reabsorbed via portal system -> excreted in urine.

Question 7

Urobilinogen colour

Answer 7

Colourless.

Question 8

Causes of unconjugated hyperbilirubinaemia.

Answer 8

Haemolysis (faster than normal breakdown of RBCs), congenital defects in the liver’s uptake or transport system, physiological jaundice - babies develop in the first week of life (neonatal jaundice).

Question 9

Biochemistry/tests for unconjugated hyperbilirubinaemia.

Answer 9

• For blood -> Total blood Br – conjugated Br = unconjugated Br increased
• For urine -> urinalysis urobilinogen increased (no increase w bilirubin)

Question 10

Causes of conjugated hyperbilirubinaemia

Answer 10

Anything that causes obstruction in the excretion of bilirubin post-conjugation. E.g., gall stones, tumours (usually at the head of the pancreas), multiple small blockages within the liver itself (intrahepatic cholestasis), primary & secondary liver tumours causing intrahepatic cholestasis.

Question 11

Signs/results of conjugated hyperbilirubinaemia - bloods, urine & stool samples

Answer 11

• For blood -> raised alk.phos & yGT
• For urine -> dark urine.
• For stools -> pale stools.

Question 12

Causes of hepatocellular jaundice

Answer 12

Damage to the hepatocytes themselves. E.g., viral hepatitis, alcohol, non-alcoholic steotosis hepatitis (NASH).

Question 13

HPC recurrent pain in RUQ may indicate

Answer 13

Gall stones

Question 14

HPC painless, progressive jaundice & weight loss may indicate

Answer 14

Carcinoma of the head of the pancreas.

Question 15

PMHx previous cancer, weight loss may indicate

Answer 15

Hepatic metastases.

Question 16

PMHx acute onset jaundice, fever, travel, prodromal anorexia, shellfish ingestion may indicate

Answer 16

Viral Hep A

Question 17

PMHx of blood transfusions may indicate

Answer 17

Viral hep B & C

Question 18

SHx of recreational drugs, IVDU, tattoos, sexual promiscuity/unprotected sex may indicate

Answer 18

Viral hep B & C

Question 19

MHx OTC paracetomol, alternative medicines (e.g., Chinese herbal medicines), ecstasy/amphetamines may indicate

Answer 19

Liver failure.

Question 20

FHx jaundice may indicate

Answer 20

Wilson’s disease, haemochromatosis.

Question 21

Investigations of jaundice

Answer 21

• Urinalysis
  o Urobilinogen
  o Bilirubin
• LFT
  o Alkaline phosphatase (alk.phos .) – produced by epithelial cells lining the bile canaliculi
  o Gamma-glutamyl transferase (yGT ) – produced by epithelial cells lining the bile canaliculi
  o ALT, AST – contained within the hepatocytes
• Ab Ultrasound
• Ab CT
• Viral screen: hepatitis, leptospirosis, etc.
• Immunology: auto-antibodies

Question 22

Increased presence/concentration of urobilinogen may indicate

Answer 22

Prehaptic or hepatic impairment.

Question 23

Absence of urinary urobilinogen may indicate

Answer 23

Cholestasis.

Question 24

Absence of bilirubin may indicate

Answer 24

Pre-hepatic jaundice.

Question 25

Presence of bilirubin in the urine may indicate

Answer 25

Obstructive jaundice (due to leakage of conjugated bilirubin out of the hepatocytes).

Question 26

Increased alk phos may indicate

Answer 26

Intrahepatic or extrahepatic obstruction.

Question 27

Increased yGT may indicate

Answer 27

Intrahepatic obstruction, mixed enzyme induction by alcohol or drugs.

Question 28

Raised ALT & AST may indicate

Answer 28

Hepatitis.

Question 29

Alk. phos is produced by

Answer 29

Epithelial cells lining the bile canaliculi.

Question 30

yGT is produced by

Answer 30

Epithelial cells lining the bile canaliculi.

Question 31

ALT, AST is produced by

Answer 31

Contained within the hepatocytes.

Question 32

Explain how conjugated hyperbilirubinaemia causes dark urine & pale stools

Answer 32

Conjugated bilirubin from the liver cannot enter gut.
Thus, spills into bloodstream. As water soluble, will pass via glomerulus -> urine (making urine dark).
Reduced Br in gut -> reduced urobilinogen -> no urobilinogen in the urine & little stercobilin.

Question 33

In normal circumstances, how much urobilinogen is found in urine…

Answer 33

Only a trace.

Question 34

If the skin appears yellow, but the sclera is not, can this be classified as jaundice?

Answer 34

No. Not jaundice.

Question 35

Pathology of which part of the pancreas can cause jaundice?

Answer 35

Head.

Question 36

What does a decrease in prothrombin time suggest?

Answer 36

Pathology of the liver - as liver is responsible for synthesis of coagulation factors (which incl. prothrombin).