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2.2 Clinical Chemistry > Liver Function Tests > Flashcards

Liver Function Tests Flashcards

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1
Q

Write a note on the anatomy of the liver
(4)

A

A right and a left lobe

Sheets of hepatocytes embedded in capillary network

The liver has a dual blood supply - the portal vein and the hepatic artery

The liver has a huge regenerative capacity

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2
Q

What does the portal vein do?

A

It brings blood to the liver from GIT (low oxygen: high nutrients)

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3
Q

What does the hepatic artery do?

A

It supplies the liver with oxygen

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4
Q

List the functions of the liver
(4)

A

Synthesis

Storage

Detoxification and excretion

Metabolism

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5
Q

What does the liver synthesise
(8)

A

Carbohydrates
Proteins
Bile acids
Fatty acids
Cholesterol
Lipoproteins
Active vitamin D (calcitriol)
Clotting factors

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6
Q

The liver synthesises carbohydrates, write a note on this function
(5)

A

The liver uses glucose for its own cellular energy

The liver circulates glucose to peripheral tissue

The liver stores glucose as glycogen

The liver is a major player in maintaining stable glucose concentration due to glycogenesis, glycogenolysis and gluconeogenesis

Thus the liver is responsible for the synthesis, storage and release of glucose

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7
Q

The liver synthesises lipids, write a note on this function
(5)

A

The liver gathers free fatty acids from diet and breaks them down to Acetyl-CoA to form triglycerides, phospholipids or cholesterol

It converts insoluble lipids to soluble forms

The liver produces 70% pf cholesterol

It synthesises HDL, LDL and VLDL

Thus both degradation and synthesis of fats takes place in the liver

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8
Q

What does the liver do to free fatty acids

A

It breaks them down to Acetyl-CoA

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9
Q

What forms of cholesterol are formed by the liver?
(3)

A

HDL
LDL
VLDL

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10
Q

What does the liver do to insoluble lipids?

A

It converts insoluble forms to soluble forms

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11
Q

What % of cholesterol is produced by the liver?

A

70%

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12
Q

The liver produces proteins, write a note on this function.
(2)

A

The liver produces nearly all proteins bar immunoglobulins and haemoglobin

The liver synthesises enzymes and clotting factors

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13
Q

Write a note on the detoxification function of the liver
(3)

A

The liver has an immune function, Kupffer cells which serve as a gatekeeper between the circulation and absorbed substances

The liver detoxifies drugs and poisons and metabolic products like ammonia, alcohol and bilirubin

The liver can inactivate hormones such as cortisol, aldosterone, insulin, glucagon and testosterone

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14
Q

What are the immune cells of the liver?

A

Kuppfer cells

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15
Q

What can the liver detoxify?
(5)

A

Drugs
Poisons
Ammonia
Alcohol
Bilirubin

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16
Q

What hormones can the liver inactivate?
(5)

A

Cortisol
Aldosterone
Insulin
Glucagon
Testosterone

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17
Q

How does the liver detoxify chemicals?
(3)

A

By binding to material to reversibly inactive them

By chemically modifying compounds for excretion

Drug metaboliser for detoxification of drugs and poisons

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18
Q

The liver is responsible for ammonia metabolism and excretion, write a note on this
(3)

A

Ammonia must be carefully controlled because its toxic to the CNS and is freely permeable across the blood brain barrier

The liver is the only organ in which the complete Krebs cycle is expressed

In this ammonia is converted to urea which is much less toxic, water soluble and easily excreted in urine

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19
Q

What is ammonia converted to which is less toxic?

A

Urea

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20
Q

What does the liver store

A

Glycogen
Proteins
Vitamins A, B12 and C
Iron

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21
Q

The liver synthesises bile, write a note on this function
(5)

A

Bile is important for fat digestion and is also a route of excretion from the body

Bile consists of water, bile salts, cholesterol, phospholipids, electrolytes and bile pigments which give its typical yellowy-green colour

Bile is made up of bile salts, bile pigments and other substances dissolved in alkaline electrolyte solution

Metabolic wastes and drug products may form part of the bile which can be excreted from the body through the digestive tract in the faeces

e.g. bilirubin, the toxic end product of haemoglobin breakdown is excreted from the body in this way

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22
Q

What does bile consist of

A

Bile consists of water, bile salts, cholesterol, phospholipids, electrolytes and bile pigments which give its typical yellowy-green colour

Bile is made up of bile salts, bile pigments and other substances dissolved in alkaline electrolyte solution

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23
Q

How does bile act as a method of excretion and give an example of this method of excretion
(2)

A

Metabolic wastes and drug products may form part of the bile which can be excreted from the body through the digestive tract in the faeces

e.g. bilirubin, the toxic end product of haemoglobin breakdown is excreted from the body in this way

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24
Q

List some of the manifestations of liver disease
(6)

A

Jaundice

Portal hypertension

Bleeding oesophageal varices

Ascites

Altered drug metabolism

Liver failure

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25
Q

What is portal hypertension?

A

High pressure in the portal vein

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26
Q

What is bleeding oesophageal varices

A

Enlarged veins in the walls of the lower part of the oesophagus

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27
Q

What is ascites

A

Accumulation of fluid in the abdominal cavity

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28
Q

What is liver failure

A

Hepatic encephalopathy

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29
Q

What are the four applications of testing liver function

i.e. what are the four reasons for testing liver function

A
  1. Establish if an individual has liver disease (screening)
  2. Aid in making a specific diagnosis
  3. Establish the severity of liver damage once a diagnosis has been made
  4. Monitor the progression of liver disease and response to therapy
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30
Q

Write a note on the basis of testing liver function
(4)

A

Liver damage must be considerable to affect liver function

Liver function can only be assessed by means of functional assays

Liver function is assessed by looking at the ability of the liver to perform a task

True liver function tests are infrequently used

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31
Q

Explain why liver function is assessed by looking at the ability of the liver to perform a task

i.e. how do we measure liver function markers

A

We use clearance measurements of marker substances known to be metabolised by the liver

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32
Q

Why are true liver function tests infrequently used
(3)

A

They are time consuming

They are dependant on hepatic blood flow

There is huge variability

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33
Q

What are the two ways of non-biochemically investigating liver function

A

Imaging
Biopsy

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34
Q

What are some examples of imaging for liver function
(4)

A

Ultrasound scan

Endoscopic retrograde cholangiopancreatography (ERCP)

Computerised tomography (CT)

Magnetic resonance imaging (MRI)

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35
Q

What is endoscopic retrograde cholangiopancreatography (ERCP)

A

Imaging to examine the bile ducts and pancreatic ducts

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36
Q

What tests are used in a liver panel?
(7)

A

Albumin

Prothrombin Time

Bilirubin

Alanine aminotransferase (ALT)

Aspartate aminotransferase (AST)

Alkaline phosphatase (ALP)

Gamma glutamyl transferase (GGT)

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37
Q

Write a note on albumin
(4)

A

Synthesised mainly in the liver

Half life of 14-20 days

Long term marker of liver health

Poor marker in acute states

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38
Q

Write a note on prothrombin time to asses liver function
(2)

A

PTT measures measures the rate of conversion of prothrombin to thrombin in the presence of coagulation factors

It measures how long it takes a clot to form

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39
Q

Write a note on the formation of bilirubin

A

RBCs are destroyed in the liver, spleen and bone marrow

Haemoglobin is converted into haem and globin

Haem is converted into biliverdin through haem oxygenase

Biliverdin is converted into bilirubin through biliverdin oxidase

The bilirubin produced is hydrophobic and insoluble and transported to the liver in a complex with albumin (unconjugated bilirubin)

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40
Q

Where are rbcs destroyed

A

RBCs are destroyed in the liver, spleen and bone marrow

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41
Q

How is haemoglobin converted into bilirubin
(3)

A

Haemoglobin is converted into haem and globin

Haem is converted into biliverdin through haem oxygenase

Biliverdin is converted into bilirubin through biliverdin oxidase

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42
Q

What is unconjugated bilirubin?

A

The bilirubin produced from the breakdown of haemoglobin is hydrophobic and insoluble and transported to the liver in a complex with albumin (unconjugated bilirubin)

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43
Q

How is unconjugated bilirubin converted to conjugated bilirubin?
(4)

A

The hepatocytes conjugate bilirubin i.e. hepatocytes take up conjugated bilirubin

Water soluble conjugated bilirubin is taken up by the liver this is brought to the small intestine

Bacteria in the intestine deconjugate the bilirubin

Some unconjugated bilirubin is reabsorbed, the remainder is excreted

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44
Q

What is the equation for total bilirubin?

A

Unconjugated and conjugated bilirubin

45
Q

What are gallstones

A

Deposition of cholesterol or bilirubin in the gallbladder or in the common biliary duct

46
Q

How are gallstones treated

A

Treatment is cholecystectomy (gall bladder removal) or sometimes endoscopic approaches to remove stones from common biliary duct or sphincter of Oddi

47
Q

What are the consequences of gall bladder removal?

A

Inability to concentrate bile, which affects fat absorption, and fatty meals may need to be avoided

48
Q

What method is used to determine bilirubin concentration?

A

The Diazo Method

49
Q

What is the Diazo method?

A

A chemical method to determine bilirubin concentration

50
Q

What is the principle behind the Diazo method?
(4)

A

Diazotised sulfanilic acid + bilirubin -> two azodipyrroles

This produces a reddish-purple at neutral pH and blue at low/high pH

This measures the conjugated bilirubin (direct bilirubin)

An accelerant can be added to the reaction to measure total bilirubin

51
Q

How can you determine unconjugated bilirubin (indirect)?

A

Total bilirubin - conjugated bilirubin

52
Q

What should you do if total bilirubin is elevated

A

You can do a differential measurement to determine if conjugated or unconjugated bilirubin is elevated

53
Q

What are the main characteristics of unconjugated bilirubin

A

Indirect bilirubin
Fat soluble
Can cross the blood brain barrier when in excess

54
Q

What are the main characteristics of conjugated bilirubin?

A

Direct bilirubin
Water soluble

55
Q

What is the basis of liver function tests
(2)

A

We measure an analyte produced by hepatocytes, which is known to change in response to hepatocyte damage

Common LFTs include markers of liver damage rather than function

56
Q

List the first line LFTs
(7)

A

Total protein
Albumin
Bilirubin
ALT
AST
ALP
GGT

57
Q

What are the benefits of running LFTs?
(5)

A

Cheap
Reliable
Non-invasive
Direct the use of other more expensive/invasive tests (scans, biopsy)
Useful in detecting liver problems and following progression

58
Q

What are the two types of liver damage?

A

Hepatocyte damage pattern

Obstructive pattern (cholestasis)

59
Q

What LFTs indicate hepatocyte damage pattern?

A

Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)

60
Q

What LFTs indicate obstructive pattern (cholestasis)

A

Gamma glutamyl transferase
Alkaline phosphatase
Bilirubin

61
Q

Some LFTs measure liver enzyme levels, these are markers of hepatocellular damage, how does measuring theses markers work?
(4)

A

Enzymes are inside the hepatocytes

Damage to hepatocytes results in leakage into blood

Serum levels of enzymes increase

These markers are surrogate markers of liver damage

62
Q

Why is it important to carry out a panel of LFTs and not just a single test?

A

We need to be able to look at multiple LFTs and recognise patterns which are associated with different pathological pictures

63
Q

Write a note on ALT and AST
(3)

A

These are sensitive biomarkers of hepatocyte damage but they’re not very specific

Useful for monitoring, indicates worsening or improvement

Assays share common indicator reaction -> decrease in NADH is detected at 340nm

64
Q

Liver function enzyme assays are sensitive, what does this mean?
(2)

A

They increase plasma activity with relatively very few damaged cells

i.e. very little damage needs to have occurred for an elevated liver enzyme test

65
Q

Liver enzyme tests are not very specific, what does this mean
(3)

A

Both enzymes have wide tissue distribution i.e. they are found in liver, heart, muscle and rbcs

ALT has less activity in extra-hepatic tissues than AST so it is considered more specific for liver damage

Elevation in enzyme activity need to be considered in light of other tests, signs and symptoms

66
Q

Where is ALP expressed
(5)

A

Liver
Bone
Placenta

In adults, most circulating ALP is derived from liver
In liver cholestasis induces synthesis
In children, most circulating ALP is derived from bone

67
Q

What is the principle behind measuring ALP

A

ALP activity liberates paranitrophenol (yellow product) from the artificial substrate paranitrophenol phosphate (substrate)

68
Q

Write a note on gamma glutamyl transferase
(6)

A

Located in cell membranes

Expressed in liver, kidneys, pancreas, intestine

Can be elevated in all forms of liver disease

Elevated in cholestasis

Elevated GGT is a classic marker of alcohol use

Useful to measure alongside ALP when the origin of ALP is uncertain

69
Q

What is cholestasis?

A

Any condition in which the flow of bile from the liver is slowed or blocked

70
Q

Why is elevated GGT a classic marker of alcohol use?

A

Alcohol can induce expression of GGT without damage

71
Q

How is GGT measured?

A

Direct assay based on production of p-nitroanilide (yellow) from artificial substrate

72
Q

Why is bilirubin measured

A

To diagnose jaundice

73
Q

Why is bilirubin fractionation measured

A

To distinguish conjugated from unconjugated hyperbilirubinaemia

74
Q

Why is ALP measured?

A

Diagnosing cholestasis

75
Q

Why is AST measured

A

Diagnosing hepatocellular damage
AST>ALT in alcoholic disease, cirrhosis

76
Q

Why is ALT measured

A

Diagnosing hepatocellular disease

77
Q

Why is albumin measured

A

Indication of how chronic or severe

78
Q

Why is prothrombin time measured

A

Indication of severity

79
Q

What are the tell tale signs of liver damage
(3)

A

Jaundice
Hepatomegaly
Upper right quadrant pain

80
Q

What are six different types of liver disease?

A

Acute hepatitis

Chronic hepatitis

Liver failure (acute versus chronic)

Cholestasis

Non-alcoholic fatty liver disease

Cirrhosis

81
Q

What does hepatitis do to the liver
(3)

A

Irritation/inflammation of the liver

Acute or chronic forms recognised

Chronic can be persistent or active

82
Q

What may cause hepatitis - inflammation of the liver?
(5)

A

Viral and non-viral infections

Drugs and toxins (e.g. paracetamol overdose, alcohol)

Ischemia (lack of oxygen; hypoxia)

Autoimmune

Genetic disorders

83
Q

What are the timeline of events in hepatitis?
(4)

A

Injury to liver cell
Cell damage or death
Release of cytosolic enzymes to plasma
Increased activity of AST and ALT in plasma

84
Q

Write a note on how viral infections cause acute hepatitis
(4)

A

Hepatitis A, B, C, Epstein-Barr Virus, Cytomegalovirus cause hepatitis

Generally very mild and self-limiting

80% remain undiagnosed

Flu-like symptoms; fatigue, malaise, myalgia and loss of appetite

85
Q

Write a note on how toxic damage cause acute hepatitis

A

Alcohol, drugs e.g. paracetamol or chemicals cause hepatitis

86
Q

How does hepatitis lead to acute liver failure?

A

This happens when the rate of damage is greater than the capacity to regenerate

87
Q

What causes jaundice?

A

Hyperbilirubinaemia

88
Q

What is hyperbilirubinaemia?
(3)

A

Increased level of bilirubin in plasma

Yellowing of the skin and eyes due to bilirubin deposition

Need to measure if elevated conjugated or unconjugated bilirubin

89
Q

What indicates conjugated bilirubin?

A

Dark urine

90
Q

What causes an excess production of total bilirubin?

A

Pre-hepatic damage e.g. problem with bilirubin synthesis

91
Q

What indicates hepatocyte damage?

A

Failure of conjugation/excretion

92
Q

What indicates obstruction?

A

Blockage

Post-hepatic or cholestatic bilirubin

93
Q

What indicates obstruction?

A

Blockage

Post-hepatic or cholestatic bilirubin

94
Q

What are the three classifications of causes of hyperbilirubinaemia?

A

Pre-hapatic
Hepatic
Post-hepatic

95
Q

What indicates a pre-hepatic cause for hyperbilirubinaemia?

A

Raised unconjugated bilirubin

96
Q

What indicates a hepatic cause for hyperbilirubinaemia?

A

Raised unconjugated bilirubin

Raised conjugated bilirubin

97
Q

What indicates post-hepatic cause of hyperbilirubinaemia

A

Raised conjugated bilirubin

98
Q

What are the symptoms of pre-hepatic hyperbilirubinaemia

A

Haemolysis
Low plasma albumin

99
Q

What are the symptoms of hepatic hyperbilirubinaemia

A

Hepatitis
Malignancy
Drug interactions
Excretion defect

100
Q

What are the symptoms of post-hepatic hyperbilirubinaemia
(3)

A

Obstruction in the bile ducts e.g. gallstones, pancreatic carcinoma

ALP may also be up

Scans may be used to identify anatomical block

101
Q

What are the diagnostic criteria for Non-Alcoholic Fatty Liver Disease?
(5)

A

Ultrasound scan of a fatty liver
Alcohol intake is within the recommended limits
Need at least one of the following: obesity, diabetes, high blood pressure, abnormal lipids
Gold standard method is a liver biopsy
ALT is elevated in NAFLD

102
Q

What is the progression from obesity to carcinoma?

A

Obesity
NAFL
NASH
Cirrhosis
Hepatocellular carcinoma

103
Q

What is steatosis?

A

The progression of fatty liver

104
Q

How does steatosis progress
(4)

A

Normal numerous small fat vesicles -> nuclei are not displaced

Liver cells become engorged with fat nuclei displaced

NASH = inflammatory cells infiltrate tissue with or without fibrosis

Cirrhosis = disturbed architecture/fibrosis

105
Q

What is NASH?

A

Non-alcoholic steatohepatitis

106
Q

Write a note on cirrhosis
(4)

A

End-stage for many types of chronic liver disease

Hepatocytes become replaced by fibrous tissue

Architecture of liver becomes disrupted, this disrupts blood flow

Clinical signs due to vascular and hepatocellular effects

107
Q

What are the three phases of cirrhosis?
(3)

A

Quiescent/compensated: no progression of disease

Active: ongoing cell death

Decompensation: severe damage; functional reserve exhausted, plasma albumin drops -> bad sign

108
Q

Why is AST:ALT ratio important in Cirrhosis

A

The AST:ALT ratio is important to gauge the disease

As damage proceeds the capacity to synthesise and release ALT decrease

Ratio increases to above 1

109
Q

What is unconjugated bilirubin converted to?

A

The conjugated form = glucaronic acid

2.2 Clinical Chemistry (28 decks)

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