Interpreting Liver Biochemistry Flashcards
1
Q
Lecture summary points:
Bilirubin in urine?
AST/ALT compared to ALP/GGT?
Low albumin?
High PT/INR?
Isolated increase in GGT?
Isolated increase in ALP?
A
Positive Bilirubin in Urine—always pathological-
Conjugated hyperbilirubinaemia.
AST/ALT> ALP/GGT—- Hepatocellular injury
ALP/GGT> AST/ALT—-Cholestasis
Low Albumin—- Indicator of chronicity and severity
High PT/INR—–Indicator of severity of cholestasis
Isolated increase in GGT—Enzyme induction-
Ethanol/drugs
Isolated increase in ALP— Bone origin
2
Q
List the major functions of the liver
A
1 Metabolism and Excretion - Bilirubin and bile acids - Steroid Hormones - Drugs and foreign compounds 2 Carbohydrate Metabolism - Gluconeogenesis - Glycogen Synthesis and breakdown 3 Protein Metabolism - Most proteins are produced by the liver except immunoglobulins - Synthesis of Urea from Ammonia (Urea cycle) 4 Fat Metabolism - Cholesterol synthesis and excretion - Fatty acid synthesis - Lipoprotein synthesis - Ketogenesis - Bile acid synthesis 5 Catabolic site for many of the hormones - 25-Hydoxylation of Vitamin D - Insulin, glucagon, oestrogens, GH, glucocorticoids and PTH, 6 Contribution to the immune response (Kupffer cells, cytokines, TGF-B)
3
Q
List the major symptoms of liver disease
A
Jaundice Abdo distention and pain Ankle swelling Haematemesis Pruritus Pale stools and dark urine Nausea or vomiting Fatigue Dark urine
4
Q
List the major liver function tests
A
Liver damage:
Hepatocellular enzymes / aminotransferases (ALT and AST) Hepatobiliary enzymes (ALP, GGT)
Liver function:
Bilirubin
Albumin
Total protein
PT/INR
5
Q
Summarise ALT and AST.
A
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are found in hepatocytes and are released in large amounts when there is hepatic parenchymal damage—that is, hepatitis.
- They are also found in substantial amounts in the heart, skeletal muscles, and red blood cells, and can increase after myocardial infarction, rhabdomyolysis, and haemolysis.
6
Q
Summarise GGT.
A
- γ-Glutamyltransferase is present in the liver, renal tubules, pancreas, and intestine. However, it is largely the liver that is responsible for the presence of γ-glutamyltransferase in the blood.
- It is increased by biliary disease / cholestasis and thus can be a good marker for whether alkaline phosphatase rises occur because of bony or biliary causes.
- It is also raised by “enzyme induction”—for example, prolonged exposure to excessive alcohol or to certain drugs, such as rifampicin, phenobarbital, and griseofulvin.
7
Q
Summarise albumin.
A
Albumin is the main blood protein and is largely made by the liver.
- Low levels in a medically stable outpatient could indicate poor underlying liver synthetic function.
- Albumin levels are extremely variable in acute illness, however, and in many acute illnesses can fall, particularly if associated with sepsis. They can also be low in extreme malnutrition or where protein loss occurs from the kidneys (nephrotic syndrome) or bowels (protein losing enteropathy).
8
Q
Summarise bilirubin.
A
- Bilirubin is a waste product produced by the catabolism of haemoglobin. The liver is responsible for much of this breakdown process, conjugating bilirubin to make it water soluble and allowing excretion in the bile.
- Raised bilirubin levels might reflect increased red cell breakdown (pre-hepatic jaundice), reduced liver function (hepatic jaundice), or biliary obstruction (post-hepatic jaundice).
- Five per cent of the population have low levels of conjugating enzymes (Gilbert’s syndrome) that cause raised unconjugated bilirubin levels in the presence of otherwise normal LFTs.
- Chronic liver disease, especially cirrhosis, where the causative agents have been treated (for example, abstinent alcoholic cirrhosis or treated viral hepatitis) is often characterised by only minimal abnormalities of LFTs. Many patients with cirrhosis will have normal LFTs. In these patients, serial measurements of bilirubin and albumin over prolonged periods provide good markers of the progression of hepatic synthetic dysfunction and thus the severity of the liver disease.
9
Q
Summarise ALP.
A
- Alkaline phosphatase is found in large amounts in the liver (where it is contained in biliary cells), bone, and placenta.
- Raised blood levels can reflect biliary obstruction or bony disease such as Paget’s disease, fractures, or metastatic disease. Osteoporosis and myeloma typically do not raise alkaline phosphatase levels unless they are associated with fractures
- Bony and biliary causes of raised alkaline phosphatase levels can usually be distinguished on clinical grounds. When clinically unclear, it can be useful to examine γ-glutamyltransferase levels, which rise with biliary but not bony disease.
- Occasionally, it may be necessary to request analysis of the individual types of alkaline phosphatase (known as isoenzymes) to identify the tissue type of the source.
10
Q
List 6 patterns of LFTs and their most common corresponding cause.
A
1 - ALT raised to less than 5 times upper limit of normal—“mild hepatitic”
- Alcoholic hepatitis, chronic viral hepatitis (B and C), Acute glandular fever (Epstein-Barr virus or cytomegalovirus), autoimmune hepatitis, fatty liver disease
2 - ALT 10 to 15 times upper limit of normal—“severe hepatitic”
- Acute viral hepatitis (A, B, or E), ischaemic hepatitis, paracetamol overdose
3 - Raised bilirubin—all other LFTs normal
- Gilbert’s syndrome
4 - Raised ALP and GGP (+/- raised bilirubin)
- Common bile duct stones, cancer of the head of pancreas, cholangiocarcinoma, chronic pancreatitis
5 - Raised alkaline phosphatase alone
- Consider non-hepatic causes: physiological (adolescence (due to rapid bone turnover) and pregnancy (from the placenta)), Paget’s disease, fractures
6 - Raised GGP alone
- Chronic hazardous alcohol consumption,
drugs including some anticonvulsants, rifampicin, griseofulvin
11
Q
List the components of a liver screen for investigation of abnormal LFTs.
A
1 - Abdominal US
- Metastases, biliary obstruction, gallstones, liver fibrosis / cirrhosis
2 - Serum ferritin
- Haemochromatosis
3 - Autoantibodies (smooth muscle, nuclear and mitochondrial)
- Autoimmune hepatitis, PBC and PSC
4 - Hepatitis serology
- Hepatitis A, B and C
5 - Cytomegalovirus and EBV serology
6 - Copper and caeruloplasmin
- Wilson’s disease
7 - A1-antitrypsin
12
Q
Summarise bilirubin metabolism.
A
- Unconjugated bilirubin is produced by haemolysis.
- Unconjugated bilirubin is water insoluble so is bound by albumin.
- Unconjugated bilirubin enters hepatocytes and is conjugated to glucuronic acid.
- Glucuronic acid is converted into conjugated bilirubin.
- Conjugated bilirubin is secreted into the biliary system.
- Conjugated bilirubin in the small intestine is converted by bacterial proteases into urobilinogen.
- 90% of urobilinogen is excreted in the faeces (first converted to stercobilinogen then excreted as stercobilin).
- 10% of urobilinogen enters the portal vein to re-enter the liver, where it is secreted back into the blood to be removed by the kidney in urine (just as urobilinogen).
13
Q
List the causes of hyperbilirubinaemia.
A
Pre-hepatic:
- Haemolytic conditions, decreased delivery of unconjugated bilirubin (e.g. cardiac failure and portocaval shunt) and decreased uptake of unconjugated bilirubin (e.g. drugs and Gilbert’s) cause UNCONJUGATED hyperbilirubinaemia WITHOUT bilirubinuria.
Hepatic:
- Hepatobiliary disease (eg. hepatitis) causes CONJUGATED AND UNCONJUGATED hyperbilirubinaemia WITH bilirubinuria.
Post-hepatic:
- Bile outflow obstruction (stones, carcinoma of head of pancreas, PSC) causes CONJUGATED hyperbilirubinaemia WITH bilirubinuria.
- Only conjugated bilirubin can enter the urine - presence in urine must be pathological because conjugated bilirubin should be converted to urobilinogen in the small intestine.
