Bilirubin Practical Flashcards
What is the normal range for bilirubin
2-20 umol/L
What causes the faeces to be brown
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
What are the two possible causes of pale stools
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
What makes stools pale
No urobilinogens are formed as no conjugated bilirubin is excreted. There is an absence of urobilins (stercobilin) causing the stool to be pale
What is the cause of dark urine
Liver is still functioning so that conjugated bilirubin is produced but the ducts are blocked
What makes urine dark
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
Why is skin discoloured (yellow)
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
Why is the sclera affected early with discolouration
The sclera has a high content of elastin which has a high affinity for bilirubin
Why is skin itchy
Due to bile salts.
What causes itchiness
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
What is a normal Gamma GT value
5-45 IU/L
What does a high Gamma GT value indicate
There is a problem with the hepatocytes or bile ducts, which is where this enzyme is normally situated
What does both a raised GGT and ALP indicate
Liver or bile ducts damage, the fact that both are high suggests cholestatic jaundice
What would only high ALP suggest
The ALP was of bone or placental origin
What would only high GGT suggest
The hepatocellular damage was drug-induced e.g. alcohol
What does a normal AST result indicate
The problem is not related to the liver cells (hepatocytes)
What does a high GGT, high ALP and normal AST say about this type of jaundice
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.
What is the suggested caused of abdominal pain with high GGT, high ALP and normal AST
Due to a biliary obstruction by the tumour so post-hepatic cholestatic jaundice
What would be the expected liver function test results in cholestatic jaundice
High GGT, high ALP and normal AST
What does the presence of bilirubin and urobilinogen in the urine imply
It is most in keeping with hepato-cellular jaundice
What do the high AST, high GGT, prolonged prothrombin time and low levels of normal of albumin concentration suggest in terms of liver damage
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
How does only minimally elevated ALP with high AST and high GGT help with differential diagnosis
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
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
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
What liver function test results would you expect in hepatic conjugated hyperbilirubinaemia
High AST, high GGT and minimally elevated ALP
What causes for hepatic conjugated hyperbilirubinaemia and drug abuse would you consider as possibilities
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.
In the case of a paracetamol overdose why are LFTs performed on a blood sample taken 4 hours after the overdose
Because absorption, metabolism and distribution are still taking place
Until when may biochemical evidence of maximal damage be attained
72-96 hours after ingestion
Severe liver damage in the context of paracetamol poisoning has been defined as the peak ALT activity exceeding what
1000 IU/L
What are the the clinical features of the toxic effects of high dose paracetamol
If any -> anorexia, nausea and vomiting
What are the the clinical features of the toxic effects of high dose paracetamol 24-48 hrs
Abdominal pain, hepatic tenderness, increased PTT (best marker of severity), increased AST/ ALT, increased bilirubin, metabolic acidosis
What are the the clinical features of the toxic effects of high dose paracetamol > 48 hours
Jaundice, encephalopathy, renal (creatinine not urea) and hepatic failure
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
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
What is the significance of prothrombin clotting time and what does it indicate about the liver
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
What is the toxicity of a paracetamol overdose due to
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
What is the biochemical basis of the treatment with N-acetylcysteine
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.
Why is N-acetylcysteine administered intravenously
Oral NAC induces vomiting
What do 5% of patients treated with intravenous N-acetylcysteine develop
Rash, angio-oedema, hypotension and bronchospasm.
What effect does alcohol in the body have on a paracetamol overdose
GHS (gluathione) levels are also reduced due to the presence of other drugs (e.g. alcohol, phenytoin) making them more susceptible to paracetamol overdose.
Does data with all normal liver enzymes support a diagnosis of acute infectious hepatitis
No because all liver enzymes are within normal range and there is no sign of jaundice
What alternative diagnosis would you make (raised amylase, high levels of alcohol)
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
What does a high white blood count and pneumococci in the sputum suggest
The presence of an infection. Increased white blood cells to phagocytose the bacteria (pneumococci found in sputum sample)
What do low levels of RBCs with low Hb suggest
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
What do elevalated conjugated bilirubin levels and slightly elevated AST, normal PTT and albumin levels and normal urine colour suggest
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
What does the low value for G6PDH (glucose 6-phosphate dehydrogenase) suggest
There is a deficiency of this enzyme
What does G6PDH deficiency present with
Haemolytic anaemia
What are the clinical syndromes of G6PDH
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
How does low G6PDH value relate to low RBC count
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
Why does low G6PDH activity lead to jaundice
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
