Bilirubin Practical

Question 1

What is the normal range for bilirubin

Answer 1

2-20 umol/L

Question 2

What causes the faeces to be brown

Answer 2

Normally bilirubin is conjugated in the liver to give bilirubin diglucuronide and then secreted in the intestine. Bacteria in the gut oxidise to uncoloured urobilinogens (sterobilinogen) which are then oxidised to urobilins (stercobilin) which are coloured and cause faeces to be brown

Question 3

What are the two possible causes of pale stools

Answer 3

Bilirubin metabolism is abnormal or the ducts leading from the liver to the duodenum are blocked so that although conjugated bilirubin is formed it cannot be excreted

Question 4

What makes stools pale

Answer 4

No urobilinogens are formed as no conjugated bilirubin is excreted. There is an absence of urobilins (stercobilin) causing the stool to be pale

Question 5

What is the cause of dark urine

Answer 5

Liver is still functioning so that conjugated bilirubin is produced but the ducts are blocked

Question 6

What makes urine dark

Answer 6

The ducts are blocked resulting in conjugated bilirubin leaking from the hepatocytes and entering the blood stream. There are increased amounts of conjugated bilirubin in the blood leading to increased excretion of the bilirubin pigment in the urine which gives the urine a dark orange colour

Question 7

Why is skin discoloured (yellow)

Answer 7

Due to a buildup of bilirubin in the skin. Bilirubin has a high affinity for the elastic fibers in the skin’s connective tissue, it binds to the fibers resulting in the yellow colouration

Question 8

Why is the sclera affected early with discolouration

Answer 8

The sclera has a high content of elastin which has a high affinity for bilirubin

Question 9

Why is skin itchy

Answer 9

Due to bile salts.

Question 10

What causes itchiness

Answer 10

2/3 of organic material in bile is bile salts formed by the conjugation of bile acids with taurine or glycine. As teh hepatocytes swell some may apoptose. Due to the back flow from the obstructed bile ducts, bile salts will enter the blood stream

Question 11

What is a normal Gamma GT value

Answer 11

5-45 IU/L

Question 12

What does a high Gamma GT value indicate

Answer 12

There is a problem with the hepatocytes or bile ducts, which is where this enzyme is normally situated

Question 13

What does both a raised GGT and ALP indicate

Answer 13

Liver or bile ducts damage, the fact that both are high suggests cholestatic jaundice

Question 14

What would only high ALP suggest

Answer 14

The ALP was of bone or placental origin

Question 15

What would only high GGT suggest

Answer 15

The hepatocellular damage was drug-induced e.g. alcohol

Question 16

What does a normal AST result indicate

Answer 16

The problem is not related to the liver cells (hepatocytes)

Question 17

What does a high GGT, high ALP and normal AST say about this type of jaundice

Answer 17

The results indicate cholestatic jaundice which is a pathological condition of impaired bile formation and bile flow. It can be caused by extrahepatic or intrahepatic obstruction or by defects in hepatocyte secretion.

Question 18

What is the suggested caused of abdominal pain with high GGT, high ALP and normal AST

Answer 18

Due to a biliary obstruction by the tumour so post-hepatic cholestatic jaundice

Question 19

What would be the expected liver function test results in cholestatic jaundice

Answer 19

High GGT, high ALP and normal AST

Question 20

What does the presence of bilirubin and urobilinogen in the urine imply

Answer 20

It is most in keeping with hepato-cellular jaundice

Question 21

What do the high AST, high GGT, prolonged prothrombin time and low levels of normal of albumin concentration suggest in terms of liver damage

Answer 21

The albumin levels are at the low level of normal, as this is acute a normal albumin is to be expected. The prothrombin time is prolonged as this is a more sensitive marker of acute liver damage. AST and GGT (which are indicative of liver damage) are high indicating hepatocellular damage

Question 22

How does only minimally elevated ALP with high AST and high GGT help with differential diagnosis

Answer 22

ALP is only minimally elevated suggesting primary hetapocellular damage rather than bile duct damage. As the bile canaliculi are in very close proximity to the hepatocytes it is not unusual to get a slight rise in ALP when hepatocellular damage occurs

Question 23

What do you conclude about this particular type of jaundice with high AST, high GGT, minimally elevated ALP, prolonged prothrombin time and low levels of normal of albumin concentration. Also history of drug abuse

Answer 23

Most likely hepatic conjugated hyperbilirubinaemia. The high AST and GGT signify damage to hepatocytes probably due to acute hepatitis. In this case with history of drug abuse viral hepatitis should be high on the list of causes

Question 24

What liver function test results would you expect in hepatic conjugated hyperbilirubinaemia

Answer 24

High AST, high GGT and minimally elevated ALP

Question 25

What causes for hepatic conjugated hyperbilirubinaemia and drug abuse would you consider as possibilities

Answer 25

The acute nature suggests hepatitis. With high risk levels for blood borne viruses hepatitis B or C, probably associated with use of an infected needle, should be tested for. Acute hepatitis may also be caused by drug overdoses e.g. paracetamol, alcohol and other viruses e.g. Epstein-Barr virus (glandular fever) and hepatitis E and A.

Question 26

In the case of a paracetamol overdose why are LFTs performed on a blood sample taken 4 hours after the overdose

Answer 26

Because absorption, metabolism and distribution are still taking place

Question 27

Until when may biochemical evidence of maximal damage be attained

Answer 27

72-96 hours after ingestion

Question 28

Severe liver damage in the context of paracetamol poisoning has been defined as the peak ALT activity exceeding what

Answer 28

1000 IU/L

Question 29

What are the the clinical features of the toxic effects of high dose paracetamol

Answer 29

If any -> anorexia, nausea and vomiting

Question 30

What are the the clinical features of the toxic effects of high dose paracetamol 24-48 hrs

Answer 30

Abdominal pain, hepatic tenderness, increased PTT (best marker of severity), increased AST/ ALT, increased bilirubin, metabolic acidosis

Question 31

What are the the clinical features of the toxic effects of high dose paracetamol > 48 hours

Answer 31

Jaundice, encephalopathy, renal (creatinine not urea) and hepatic failure

Question 32

Comment on the significance of the time course for the changes in liver function tests with normal values at 4 hours but rapid rises 2-3 days later

Answer 32

Delayed onset after an overdose therefore normal values initially but then deteriorates. Liver damage occurs after one day with signs appearing after 2-3 days. High AST suggests necrosis of the liver and the decreasing AST suggests widespread hepatocyte death

Question 33

What is the significance of prothrombin clotting time and what does it indicate about the liver

Answer 33

Prothrombin clotting time is a marker of synthetic function. Because of it’s short half-life it is a sensitive indicator of both acute and chronic liver disease. Increased prothrombin clotting time demonstrates that there is a reduction on the “clotting proteins” and hence shows an impairment of protein synthetic function by the liver. Some of the clotting factors have very short half lives (4-6 hours) hence are good indicators of liver function not liver damage

Question 34

What is the toxicity of a paracetamol overdose due to

Answer 34

The production of N-acetyl-q-benzoquinone-imine (a reactive metabolite) which interact with glutathione to form mercapturic acid meaning that glutathione becomes depleted eventually and NABQI becomes in excess and causes hepatic and renal damage

Question 35

What is the biochemical basis of the treatment with N-acetylcysteine

Answer 35

N-acetylcysteine acts as a precursor for glutathione helping the body regenerate enough to prevent liver damage. It may also repair oxidation damage caused by NAPQI.

Question 36

Why is N-acetylcysteine administered intravenously

Answer 36

Oral NAC induces vomiting

Question 37

What do 5% of patients treated with intravenous N-acetylcysteine develop

Answer 37

Rash, angio-oedema, hypotension and bronchospasm.

Question 38

What effect does alcohol in the body have on a paracetamol overdose

Answer 38

GHS (gluathione) levels are also reduced due to the presence of other drugs (e.g. alcohol, phenytoin) making them more susceptible to paracetamol overdose.

Question 39

Does data with all normal liver enzymes support a diagnosis of acute infectious hepatitis

Answer 39

No because all liver enzymes are within normal range and there is no sign of jaundice

Question 40

What alternative diagnosis would you make (raised amylase, high levels of alcohol)

Answer 40

Acute pancreatitis. Amylase is secreted by salivary glands and the pancreas. Acute pancreatitis could be induces by alcohol abuse and often leads to hypertriglyceridaemia. Hypertriglyceridaemia can also lead to acute pancreatitis. There are other causes of acute pancreatitis, the most common of which is due to gallstones causing an element of obstruction in the biliary/ pancreatic tree

Question 41

What does a high white blood count and pneumococci in the sputum suggest

Answer 41

The presence of an infection. Increased white blood cells to phagocytose the bacteria (pneumococci found in sputum sample)

Question 42

What do low levels of RBCs with low Hb suggest

Answer 42

Low levels of haemoglobin= increase in rate of breakdown of red blood cells and/or fewer rbcs being synthesised. RBC numbers are low and with low Hb and increased AST suggests haemolysis

Question 43

What do elevalated conjugated bilirubin levels and slightly elevated AST, normal PTT and albumin levels and normal urine colour suggest

Answer 43

Haemolysis (AST is released in small amounts when red cells are broken down. The PTT and albumin levels are normal. This suggests that the liver therefore is functioning normally. The normal urine suggests no conjugated bilirubin in the urine

Question 44

What does the low value for G6PDH (glucose 6-phosphate dehydrogenase) suggest

Answer 44

There is a deficiency of this enzyme

Question 45

What does G6PDH deficiency present with

Answer 45

Haemolytic anaemia

Question 46

What are the clinical syndromes of G6PDH

Answer 46

Acute drug-induced haemolysis (usually dose related), favism (ingestion of fava beans), chronic haemolytic anaemia, neonatal jaundice, infections and acute illness will also precipitate haemolysis in patients with G6PD deficiency

Question 47

How does low G6PDH value relate to low RBC count

Answer 47

NADPH is essential for RBCs as it is required to recycle reduced glutathione from oxidised glutathione. Glutathione is essential to protect these cells from a range of oxidative and chemical insults. NADPH is produced in the pentose phosphate pathway on the oxidation of glucose-6-phosphate to 6-phospoglucono-gamma-lactone catalysed by G6PDH during which NADp is reduced to NADPH. Hence producing the NADPH is essential for RBCs. If G9PDH is low then NADPH is not produced and therefore reduced glutathione cannoted be recycled or is impaired. Any drug-induced oxidative stress leads to excessive damage and excessive lysis of RBCs (haemolysis) resulting in haemolytic anaemia

Question 48

Why does low G6PDH activity lead to jaundice

Answer 48

Jaundice results because the lysis of RBCs releases haemoglobulin which is in excess of that which can be coped with by the hepatic detoxification pathways. Therefore unconjugated bilirubin accumulates in plasma and in the tissues such as sclera and skin