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Clinical biochemistry > Investigation of Liver and GI tract disease > Flashcards

Investigation of Liver and GI tract disease Flashcards

1
Q

What is the largest organ in the body?

A

The liver

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2
Q

Where is the liver located?

A

Located in the upper right quadrant of the abdomen

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3
Q

How much does the liver weigh ?

A

Weighs approximately 22 g/kg of body weight

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4
Q

What’s the blood supply of the liver?

A

Has dual blood supply

  • 2/3 comes from the gut via the portal vein
  • 1/3 from the hepatic artery (rich in oxygen)
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5
Q

Where does the blood leave the liver through?

A

Blood leaves through the hepatic vein

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6
Q

How many loves does the liver have and which one is bigger?

A

The liver has two lobes

Right lobe is slightly larger than left

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7
Q

What are these lobes composed of?

A

Composed of multiple liver lobules

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8
Q

What do the lobes consist of and what do they do?

A

These consist of plates of hepatocytes radiating from a central vein

Which carries blood from the liver

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9
Q

What is the liver acini?

A

the smallest functional unit of the liver

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10
Q

What do the bile canaliculi merge and form?

A

The bile canaliculi merge and form bile ductules

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11
Q

What are the major functions of the liver?

A 
Carbohydrate metabolism 
Fat metabolism 
-Cholesterol and fatty acid synthesis  
Protein metabolism 
Synthesis of plasma proteins 
Hormone metabolism 
-Peptide and steroid hormones  
Metabolism and excretion of drugs and foreign compounds 
Storage – glycogen, vitamin A and B12, plus iron and copper 
Metabolism and excretion of bilirubin
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12
Q

What does hepatitis do to the liver?

A

Causes damage to hepatocyte

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13
Q

What does cirrhosis do to the liver?

A
  • Increased fibrosis
  • Liver shrinkage
  • Decreased hepatocellular function
  • Obstruction of bile flow
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14
Q

Why does it take a while for liver function to decrease?

A

Liver has a big functional reserve so takes a while for liver function to decrease

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15
Q

What are LFT’s indicators of?

A

Insensitive indicators of liver function

Sensitive indicators of liver damage

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16
Q

What do LFT’s look for?

A

Look for pattern of results - a single result rarely provides a diagnosis on its own

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17
Q

What context must LFT’s be interpreted within?

A

Interpretation must be performed within the context of the patient’s risk factors, symptoms, medications, current condition/illness and physical findings

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18
Q

What can LFT’s be used for?

A
  • Screening the presence of liver disease
  • Assessing prognosis
  • Differential diagnosis: predominantly hepatic or cholestatic
    - i.e. destruction of liver cells or blockage
  • Monitoring disease progression
  • Measuring efficacy of treatments for liver disease
  • Assessing severity
    - Especially in patients with cirrhosis as this is a chronic disease
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19
Q

What results do standard LFT’s provide?

A
  • Total bilirubin
  • Alanine aminotransferase (ALT)
  • Alkaline phosphatase (ALP)
  • Albumin
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20
Q

When do albumin concentrations tend to decrease in?

A

Albumin concentrations only tend to decrease in chronic liver disease

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21
Q

What is bilirubin?

A

Bilirubin is the breakdown of the haem of haemoglobin

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22
Q

What is bilirubin broken down by?

A

Broken down by spleen

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23
Q

What state is bilirubin produced in and what’s it bound to when its transported?

A

Bilirubin produced is unconjugated

-Has to be transported bound to protein – albumin

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24
Q

Where does unconjugated bilirubin get transported to and enters what cells?

A

Unconjugated bilirubin gets transported to liver, enters hepatocytes

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25
Q

Why does bilirubin become conjugated and for what?

A

Becomes conjugated to make it more soluble for excretion

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26
Q

What causes bilirubin to become conjugated?

A

UDP-glucoronyl transferase

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27
Q

Where does conjugated bilirubin get excreted to and what’s it broken down to in the gut?

A

Conjugated bilirubin gets excreted to gut where it is broken down to urobilinogen and stercobilin

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28
Q

What causes the brown colour of faeces?

A

stercobilin

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29
Q

What can urobilinogen escape to and where can it be seen then?

A

Urobilinogen can sometimes escape to extra-hepatic circulation so some may be seen in kidneys

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30
Q

What does jaundice describe?

A

Jaundice describes the yellow discolouration of tissue due to bilirubin deposition

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31
Q

What is hyperbilirubinemia?

A

An increase in total bilirubin

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32
Q

When is clinical jaundice evident?

A

When the serum/plasma bilirubin concentration is 2x the upper reference of normal

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33
Q

What are the causes of jaundice?

A
  • Haemolysis
  • Hepatocellular damage
  • Cholestasis
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34
Q

What effect does haemolysis have on bilirubin?

A

Increased bilirubin production

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35
Q

What effect does hepatocellular damage have on bilirubin?

A

Impaired bilirubin metabolism

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36
Q

What effect does cholestasis have on bilirubin?

A

Decreased bilirubin excretion

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37
Q

What is bilirubin measured in samples as?

A

Bilirubin is measured in serum/plasma samples as:

  • Total bilirubin - Unconjugated and conjugated bilirubin (& delta bilirubin)
  • Direct – Conjugated bilirubin (& delta bilirubin)
  • Indirect – Unconjugated bilirubin (calculated)
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38
Q

What is delta bilirubin formed by and what does it occur in the presence in?

A

Delta bilirubin is formed by the irreversible covalent addition of bilirubin to albumin
-Occurs in the presence of prolonged conjugated hyperbilirubinemia

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39
Q

How can bilirubin be measured in urine?

A

Bilirubin can be measured in urine using a simple dipstick

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40
Q

Why is unconjugated bilirubin not normally found in urine?

A

As unconjugated bilirubin is protein bound it is not normally found in urine
-It is insoluble

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41
Q

What does bilirubin in urine indicate presence of?

A

Presence of bilirubin in the urine therefore indicates the presence of conjugated hyperbilirubinaemia

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42
Q

What darkens the urine and what cases is this seen in?

A

Excess conjugated bilirubin will darken the urine

-This is seen in cases of hepatitis or impaired flow of bile in patients with biliary obstruction

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43
Q

What does the presence of urobilinogen demonstrate and what can this be detected by?

A

If urobilinogen is present in the urine it demonstrates that bilirubin is reaching the gut
-It can be detected by a urine dipstick

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44
Q

What does excess urobilinogen in the urine indicate?

A

Excess urobilinogen in the urine may indicate liver disease such as viral hepatitis and cirrhosis or haemolytic conditions associated with increased red cell destruction.

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45
Q

What happens to our stool if bilirubin doesn’t reach the gut?

A

When bilirubin does not reach the gut, stercobilin is not produced and stools appear pale in colour

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46
Q

What is the alanine aminotransferase enzyme(ALT) and what is it a key enzyme in?

A

ALT is a intracellular cytoplasmic enzyme that catalyses the transfer of an amino group from alanine to α-ketoglutarate
-Key enzyme in gluconeogenesis

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47
Q

What is ALT the most specific marker for and what is it expressed by other than the liver

A

ALT is the most specific marker for liver injury although it is also expressed by the kidneys and cardiac and skeletal muscle

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48
Q

What is ALT used to identify and arising from what?

A

ALT is used to identify liver damage arising from hepatocyte inflammation or necrosis

49
Q

What can happen to the levels of ALT with severe liver damage?

A

Values >20x the upper limit of normal (ULN) may occur with severe liver damage

50
Q

What happens to levels of ALT in cholestasis and due to what?

A

Small increases (<5x ULN) may occur in cholestasis due to secondary damage to hepatocytes.

51
Q

What is asparate aminotransferase enzyme(AST)?

A

AST is a intracellular cytoplasmic and mitochondrial enzyme that catalyses the transfer of an amino group from aspartate to α-ketoglutarate

52
Q

What is the only indication for measuring ALT and AST and to suggest what disease?

A

The only indication for measuring ALT and AST is to determine the AST:ALT ratio:
-<0.8 – suggestive of non-alcoholic fatty liver disease (NAFLD); >1.5 – alcoholic liver disease (ALD)

53
Q

Where are AST and ALT released from?

A

AST and ALT are released from the cytosol (AST is also being released by mitochondria)

54
Q

What is alkaline phosphatase(ALP)?

A

ALP is a membrane bound glycoprotein enzyme that removes phosphate groups from proteins and nucleic acids

55
Q

When does ALP have a maximum catalytic activity?

A

It has maximum catalytic activity at pH 9-10.5

56
Q

Where are ALP isoenzymes found?

A

ALP isoenzymes are found in a number of tissues

57
Q

What is ALP a major value in the diagnosis of?

A

ALP is of major value in the diagnosis of cholestatic disease along with GGT as cholestasis stimulates enhanced synthesis of liver ALP

58
Q

When is ALP elevated other than diseases?

A

ALP is elevated in children and correlates well with the rate of bone growth (child-specific reference ranges). Also increased during pregnancy due to an increase in placental ALP

59
Q

What can the source of elevated ALP be determined by?

A

The source of an elevated ALP can be determined by gel electrophoresis

60
Q

What is it possible to separate ALP isoenzymes into?

A

It is possible to separate ALP isoenzymes into liver, bone, and intestinal fractions

61
Q

How can placental isoenzyme of ALP be identified?

A

The placental isoenzyme of ALP can be identified as it is heat stable at 65C for 10 minutes, unlike the other isoenzymes

62
Q

What is Gamma glutamyl transferase(GGT)?

A

GGT is a membrane bound enzyme that transfers the gamma glutamyl group from peptides

63
Q

What is GGT a marker for?

A

A relatively specific marker for liver injury found on the canalicular membrane of hepatocytes, but also found on the cell membranes of other tissues

64
Q

What is elevated plasma GGT in response to?

A

Plasma GGT is elevated in response to consumption of alcohol and other drugs

65
Q

What does an increased ALP and GGT suggest?

A

↑ ALP and ↑ GGT – suggestive of hepatic cause

66
Q

What does an increased ALP and normal GGT suggest?

A

↑ ALP and N GGT – suggestive of bone source of ALP

67
Q

What does normal ALP and increased GGT suggest?

A

N ALP and ↑ GGT – suggestive of excess alcohol intake

68
Q

What is the half life of albumin?

A

Half life around 20 days

69
Q

How many grams of albumin does the liver synthesis around a day?

A

liver synthesises around 12g every day

70
Q

What happens to the levels of albumin in chronic liver disease?

A

Decreases in chronic liver disease

71
Q

What is albumin and what is its roles?

A

Albumin is an essential plasma protein and has many roles including maintaining the plasma oncotic pressure and binding several hormones, drugs, anions and fatty acids

72
Q

What is the GI tract?

A

The GI tract is a 7-10 m continuous tube that runs from the mouth to anus

73
Q

What is the GI tract partitioned into?

A

Partitioned into many sections with distinct structure, anatomy and function

74
Q

Different parts of the GI tract

A

LOOK AT DIAGRAM ON PPT SLIDE

75
Q

What is the GI tract encased in?

A

The GI tract is encased in layers of voluntary and involuntary muscle (contraction in waves)

76
Q

What does the GI tract have a large sysem of?

A

Has a large arterial system linking the different sections to the circulation

77
Q

What percentage of the cardiac output innervates the GI tract?

A

30%

78
Q

What is the enteric endocrine system?

A

Hormone signalling allows different parts of the GI tract to ’switch on’ and ‘switch off’

79
Q

What are gastric ulcers caused by?

A

Gastric (or peptic) ulcers are caused by a break in the protective mucosal lining of the stomach

80
Q

What are signs and symptoms of gastric ulcers?

A
  • Pain in the abdomen that may come and go (may be eased with antacid)
  • Waking up with a feeling of pain in the abdomen
  • Bloating, retching and feeling sick
  • Feeling particularly ‘full’ after a normal size meal
81
Q

What are the causes of gastric ulcers?

A

Causes of gastric ulcers are infection with helicobacter pylori (80% of cases) or the use of NSAIDs(20% of cases)

82
Q

What is H.Pylori?

A

H. pylori is a helix-shaped gram-negative bacteria

83
Q

Dimensions of H.pylori

A

Diameter of 0.5 μm and length of 3 μm

84
Q

What does H.pylori cause damage to?

A

Causes damage to the mucosal layer of gut

85
Q

What does H.pylori cause in the duodenum?

A

In the duodenum, it causes hypersecretion of acid

86
Q

What is the urea breath test used to identify?

A

The urea breath test is rapid and non-invasive procedure used to identify infections by H. pylori

87
Q

Steps involved in urea breath test

A

First take a basal breath test

Then patient drinks a solution containing urea labelled with an uncommon isotope (radioactive carbon-14 or non-radioactive carbon-13)

Take second breath test

If H.pylori is present, it will split the urea and release the uncommon isotope

The detection of isotope-labelled carbon dioxide in exhaled breath indicates that the urea was split and that that urease, and therefore H. pylori, is present in the stomach

88
Q

Why must Vitamin B12 be obtained from diet?

A

Vitamin B12 cannot be produced by the human body and so must be obtained from the diet

89
Q

What does vitamin B12 play a role in?

A

Essential role in the nervous system and the formation of red blood cells as a co-factor for DNA synthesis

90
Q

What do we need for the absorption of vitamin B12 by the small intestine?

A

Needs intrinsic factor for its absorption by the small intestine

91
Q

What is the intrinsic factor?

A

a 45 kDa glycoprotein made by the parietal cells of the stomach

92
Q

What does the B12-IF complex do when it enters the intestine?

A

The B12-IF complex enters the intestine where it binds to receptors on the musocal cells of the ileum and is absorbed into the blood stream

93
Q

Why would it take a long time for B12 deficiency to present itself?

A

The liver can store 3-5 years worth of vitamin B12, meaning that it can take a long time for vitamin B12 deficiency to present itself

94
Q

What are signs and symptoms of B12 deficiency?

A

Macrocytic anaemia (increased MCV, decreased haemoglobin)

Weakness and tiredness

Pale skin

Glossitis – inflammation of the tongue

Nerve problems such as numbness or tingling (severe deficiency)

95
Q

What is severe deficiency of vitamin B12 caused by?

A

Severe deficiency of vitamin B12 is usually caused by pernicious anaemia, an autoimmune attack on the gastric mucosa

96
Q

What is there a loss of in pernicious anaemia?

A

Loss of intrinsic factor as there is loss of parietal cells

97
Q

What is coeliac disease?

A

Coeliac disease is an autoimmune disorder, primarily affecting the small intestine

98
Q

What does coeliac disease result from?

A

The disease results from immunological hypersensitivity to ingested to gliadin

99
Q

What does coeliac disease do to the villi in the small intestine?

A

Flattens the villi in small intestine

100
Q

What do classic symptoms of coeliac disease include?

A

GI problems such as diarrhoea, abdominal distention, malabsorption and loss of appetite

101
Q

What is used for the diagnosis of coeliac disease?

A

A duodenal biopsy is the gold standard diagnosis of coeliac disease

102
Q

What are tissue transglutaminase antibodies?

A

Enzyme that deaminates glutamine residues to glutamic acid on the gliadin fragment

103
Q

what antibodies to TTG are found in approx. 96% of patients with coeliac disease?

A

IgA antibodies to TTG are found in approximately 96% of patients with coeliac diseas

104
Q

What other antibody to TTG do we test for in coeliac disease?

A

Also test for IgG antibodies to TTG

105
Q

When do we test for endomysial antibodies?

A

Do this test if patient does not have IgA

106
Q

What is the endomysium?

A

The endomysium is the supporting structure that surrounds the middle third of the oesophagus

107
Q

What are endomysial antibodies indicative of?

A

Endomysial antibodies are indicative of coeliac disease

108
Q

What test is more sensitive for coeliac disease?

A

Endomysial antibody test is not as sensitive as the TTG antibody test

109
Q

What are the signs and symptoms of IBS and IBD?

A

abdominal pain or discomfort with diarrhoea or constipation

110
Q

How can IBD be treated and why?

A

can be treated with anti-inflammatory drugs because IBD is autoimmune

111
Q

What is calprotectin, where’s it found and what’s it released upon?

A

Calprotectin is a small zinc and calcium containing protein found in neutrophils and released upon inflammation

112
Q

What happens to neutrophils in the presence of active intestinal inflammation neutrophils?

A

In the presence of active intestinal inflammation neutrophils migrate to the intestinal mucosa from the circulation

113
Q

What does disturbance In mucosa architecture due to inflammatory processes result in?

A

Any disturbance in the mucosa architecture due to the inflammatory process results in leakage of neutrophils and hence calprotectin is excreted in feces

114
Q

What is the faecal immunochemical test(FIT)?

A

‘Dipstick’ test for blood in stool

115
Q

What does FIT allow an early detection of?

A

Colon cancer

116
Q

Why may we get erroneous test results in FIT?

A

Erroneous test results due to improper specimen collection, failure to follow the recommended sample collection procedure, handling or storage, or an insufficient concentration of starting material

117
Q

What does FIT measure?

A

Quantitative measurement of Hb in faeces

118
Q

FIT result <9.5 µg Hb/g faeces

A

These patients have a low risk of colorectal cancer.

119
Q

FIT ≥10 µg Hb/g faeces

A

Further investigations are required in line with local guidelines.

Clinical biochemistry (6 decks)

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