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2.2 Clinical Chemistry > Liver Function Tests > Flashcards

Liver Function Tests Flashcards

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
What is portal hypertension?
High pressure in the portal vein
26
What is bleeding oesophageal varices
Enlarged veins in the walls of the lower part of the oesophagus
27
What is ascites
Accumulation of fluid in the abdominal cavity
28
What is liver failure
Hepatic encephalopathy
29
What are the four applications of testing liver function i.e. what are the four reasons for testing liver function
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
30
Write a note on the basis of testing liver function (4)
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
31
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
We use clearance measurements of marker substances known to be metabolised by the liver
32
Why are true liver function tests infrequently used (3)
They are time consuming They are dependant on hepatic blood flow There is huge variability
33
What are the two ways of non-biochemically investigating liver function
Imaging Biopsy
34
What are some examples of imaging for liver function (4)
Ultrasound scan Endoscopic retrograde cholangiopancreatography (ERCP) Computerised tomography (CT) Magnetic resonance imaging (MRI)
35
What is endoscopic retrograde cholangiopancreatography (ERCP)
Imaging to examine the bile ducts and pancreatic ducts
36
What tests are used in a liver panel? (7)
Albumin Prothrombin Time Bilirubin Alanine aminotransferase (ALT) Aspartate aminotransferase (AST) Alkaline phosphatase (ALP) Gamma glutamyl transferase (GGT)
37
Write a note on albumin (4)
Synthesised mainly in the liver Half life of 14-20 days Long term marker of liver health Poor marker in acute states
38
Write a note on prothrombin time to asses liver function (2)
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
39
Write a note on the formation of bilirubin
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)
40
Where are rbcs destroyed
RBCs are destroyed in the liver, spleen and bone marrow
41
How is haemoglobin converted into bilirubin (3)
Haemoglobin is converted into haem and globin Haem is converted into biliverdin through haem oxygenase Biliverdin is converted into bilirubin through biliverdin oxidase
42
What is unconjugated bilirubin?
The bilirubin produced from the breakdown of haemoglobin is hydrophobic and insoluble and transported to the liver in a complex with albumin (unconjugated bilirubin)
43
How is unconjugated bilirubin converted to conjugated bilirubin? (4)
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
44
What is the equation for total bilirubin?
Unconjugated and conjugated bilirubin
45
What are gallstones
Deposition of cholesterol or bilirubin in the gallbladder or in the common biliary duct
46
How are gallstones treated
Treatment is cholecystectomy (gall bladder removal) or sometimes endoscopic approaches to remove stones from common biliary duct or sphincter of Oddi
47
What are the consequences of gall bladder removal?
Inability to concentrate bile, which affects fat absorption, and fatty meals may need to be avoided
48
What method is used to determine bilirubin concentration?
The Diazo Method
49
What is the Diazo method?
A chemical method to determine bilirubin concentration
50
What is the principle behind the Diazo method? (4)
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
How can you determine unconjugated bilirubin (indirect)?
Total bilirubin - conjugated bilirubin
52
What should you do if total bilirubin is elevated
You can do a differential measurement to determine if conjugated or unconjugated bilirubin is elevated
53
What are the main characteristics of unconjugated bilirubin
Indirect bilirubin Fat soluble Can cross the blood brain barrier when in excess
54
What are the main characteristics of conjugated bilirubin?
Direct bilirubin Water soluble
55
What is the basis of liver function tests (2)
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
List the first line LFTs (7)
Total protein Albumin Bilirubin ALT AST ALP GGT
57
What are the benefits of running LFTs? (5)
Cheap Reliable Non-invasive Direct the use of other more expensive/invasive tests (scans, biopsy) Useful in detecting liver problems and following progression
58
What are the two types of liver damage?
Hepatocyte damage pattern Obstructive pattern (cholestasis)
59
What LFTs indicate hepatocyte damage pattern?
Alanine aminotransferase (ALT) Aspartate aminotransferase (AST)
60
What LFTs indicate obstructive pattern (cholestasis)
Gamma glutamyl transferase Alkaline phosphatase Bilirubin
61
Some LFTs measure liver enzyme levels, these are markers of hepatocellular damage, how does measuring theses markers work? (4)
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
Why is it important to carry out a panel of LFTs and not just a single test?
We need to be able to look at multiple LFTs and recognise patterns which are associated with different pathological pictures
63
Write a note on ALT and AST (3)
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
Liver function enzyme assays are sensitive, what does this mean? (2)
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
Liver enzyme tests are not very specific, what does this mean (3)
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
Where is ALP expressed (5)
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
What is the principle behind measuring ALP
ALP activity liberates paranitrophenol (yellow product) from the artificial substrate paranitrophenol phosphate (substrate)
68
Write a note on gamma glutamyl transferase (6)
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
What is cholestasis?
Any condition in which the flow of bile from the liver is slowed or blocked
70
Why is elevated GGT a classic marker of alcohol use?
Alcohol can induce expression of GGT without damage
71
How is GGT measured?
Direct assay based on production of p-nitroanilide (yellow) from artificial substrate
72
Why is bilirubin measured
To diagnose jaundice
73
Why is bilirubin fractionation measured
To distinguish conjugated from unconjugated hyperbilirubinaemia
74
Why is ALP measured?
Diagnosing cholestasis
75
Why is AST measured
Diagnosing hepatocellular damage AST>ALT in alcoholic disease, cirrhosis
76
Why is ALT measured
Diagnosing hepatocellular disease
77
Why is albumin measured
Indication of how chronic or severe
78
Why is prothrombin time measured
Indication of severity
79
What are the tell tale signs of liver damage (3)
Jaundice Hepatomegaly Upper right quadrant pain
80
What are six different types of liver disease?
Acute hepatitis Chronic hepatitis Liver failure (acute versus chronic) Cholestasis Non-alcoholic fatty liver disease Cirrhosis
81
What does hepatitis do to the liver (3)
Irritation/inflammation of the liver Acute or chronic forms recognised Chronic can be persistent or active
82
What may cause hepatitis - inflammation of the liver? (5)
Viral and non-viral infections Drugs and toxins (e.g. paracetamol overdose, alcohol) Ischemia (lack of oxygen; hypoxia) Autoimmune Genetic disorders
83
What are the timeline of events in hepatitis? (4)
Injury to liver cell Cell damage or death Release of cytosolic enzymes to plasma Increased activity of AST and ALT in plasma
84
Write a note on how viral infections cause acute hepatitis (4)
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
Write a note on how toxic damage cause acute hepatitis
Alcohol, drugs e.g. paracetamol or chemicals cause hepatitis
86
How does hepatitis lead to acute liver failure?
This happens when the rate of damage is greater than the capacity to regenerate
87
What causes jaundice?
Hyperbilirubinaemia
88
What is hyperbilirubinaemia? (3)
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
What indicates conjugated bilirubin?
Dark urine
90
What causes an excess production of total bilirubin?
Pre-hepatic damage e.g. problem with bilirubin synthesis
91
What indicates hepatocyte damage?
Failure of conjugation/excretion
92
What indicates obstruction?
Blockage Post-hepatic or cholestatic bilirubin
93
What indicates obstruction?
Blockage Post-hepatic or cholestatic bilirubin
94
What are the three classifications of causes of hyperbilirubinaemia?
Pre-hapatic Hepatic Post-hepatic
95
What indicates a pre-hepatic cause for hyperbilirubinaemia?
Raised unconjugated bilirubin
96
What indicates a hepatic cause for hyperbilirubinaemia?
Raised unconjugated bilirubin Raised conjugated bilirubin
97
What indicates post-hepatic cause of hyperbilirubinaemia
Raised conjugated bilirubin
98
What are the symptoms of pre-hepatic hyperbilirubinaemia
Haemolysis Low plasma albumin
99
What are the symptoms of hepatic hyperbilirubinaemia
Hepatitis Malignancy Drug interactions Excretion defect
100
What are the symptoms of post-hepatic hyperbilirubinaemia (3)
Obstruction in the bile ducts e.g. gallstones, pancreatic carcinoma ALP may also be up Scans may be used to identify anatomical block
101
What are the diagnostic criteria for Non-Alcoholic Fatty Liver Disease? (5)
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
What is the progression from obesity to carcinoma?
Obesity NAFL NASH Cirrhosis Hepatocellular carcinoma
103
What is steatosis?
The progression of fatty liver
104
How does steatosis progress (4)
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
What is NASH?
Non-alcoholic steatohepatitis
106
Write a note on cirrhosis (4)
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
What are the three phases of cirrhosis? (3)
Quiescent/compensated: no progression of disease Active: ongoing cell death Decompensation: severe damage; functional reserve exhausted, plasma albumin drops -> bad sign
108
Why is AST:ALT ratio important in Cirrhosis
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
What is unconjugated bilirubin converted to?
The conjugated form = glucaronic acid

2.2 Clinical Chemistry (28 decks)

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