Liver and GI Tract Disease Flashcards
1
Q
- What is the largest organ in the body?
A
The Liver
1.5 kg in 70kh male
2
Q
- How many lobes does the lung consist of-which one is bigger?
A
•Comprised of large right lobe and smaller left lobe (consisting of lobules- sheets of hepatocytes).
3
Q
- The Liver has a dual blood supply-what are its two supplies?
A
2/3 comes from the gut via the portal vein (nutrient rich) and 1/3 from the hepatic artery (oxygen rich).
4
Q
- What does blood leave the liver through?
A
Hepatic Veins
5
Q
- Where are substances for excretion from the hepatocytes of the liver secreted?
A
The Canaliculi
6
Q
- How is the common hepatic duct formed?
A
The canaliculi merge to form bile ductules, which subsequently merge to become left/right bile duct and eventually become the common hepatic duct.
7
Q
- What are some major functions of the liver?
A
- Carbohydrate metabolism, Fat metabolism, Protein metabolism, Hormone metabolism.
- Synthesis of plasma proteins.
- Metabolism and excretion of drugs/foreign compounds.
- Storage – glycogen, vitamin A and B12, plus iron and copper.
- Metabolism and excretion of bilirubin.
8
Q
- What are the 4 types of liver disease?
A
- Hepatitis (inflammation–> damage to hepatocytes)
- Cholestasis
- Cirrhosis
- Tumours: primary or frequently secondary (colon, stomach, bronchus).
9
Q
- What is Cholestasis?
A
•Cholestasis (decreased bile flow): blockage (extrahepatic) or impaired secretion by hepatocytes (intrahepatic).
10
Q
- What is Cirrhosis?
A
Development of scar tissue:
o Increased fibrosis leads to scarring.
o Liver shrinkage results in decreased hepatocellular function
o Obstruction of bile flow
11
Q
- What are two advantages of the Liver Function Test (LFT)
A
cheap and rapid
12
Q
- What is the standard LFT profile-what does it measure?
A
Bilirubin, Albumin, Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST), Alkaline phosphatase and Gamma glutamyltransferase
13
Q
- Does a LFT look at the results all together or each individual substance for a diagnosis?
A
It measures insensitive indicators of liver ‘function’ on their own so we look for pattern of results - a single result rarely provides a diagnosis on its own.
14
Q
- LFT is not diagnostic, but what else can it be used for?
A
Screening for the presence of liver disease
Assessing prognosis
Measuring the efficacy of treatments for liver disease
Differential diagnosis: predominantly hepatic or cholestatic
Monitoring disease progression
Assessing severity, especially in patients with cirrhosis
15
Q
- What levels of Bilirubin,ALT,ALP and Albumin would you expect in an inflammatory pattern –> hepatocyte damage?
A
Bilirubin = Normal to high
ALT = Very high
ALP = Normal to high
Albumin = Normal
16
Q
- What levels of Bilirubin,ALT,ALP and Albumin would you expect in a Cholestatic pattern –> Blockage of the liver)
A
Bilirubin = High to Very high
ALT = Normal to high
ALP = High to very high
Albumin = Normal
17
Q
- When does albumin levels decrease?
A
tend to only decrease in chronic level disease
18
Q
- What is bilirubin?
A
•Yellow-orange pigment derived from haem (RBC breakdown) that is conjugated in the liver and excreted in bile.
19
Q
- What two forms does bilirubin occur in?
A
Conjugated (direct-reacting bilirubin) or Unconjugated (indirect-reacting bilirubin).
20
Q
- What is the reference range for total and conjugated bilirubin?
A
Total bilirubin – SWLP Reference range <21 umol/L
oConjugated (direct) bilirubin <10 umol/L
21
Q
- What does bilirubin bind tightly too and why?
A
Binds tightly but reversibly to albumin because it’s very hydrophobic
22
Q
- Explain the process of bilirubin metabolism?
A
- RBC breakdown by spleen produces bilirubin, this is transferred to the liver with albumin.
- It is conjugated by the liver enzyme UDP-glucuronosyltransferase.
- Soluble conjugated bilirubin is converted into urobilinogen in the small intestine.
- Most of the bilirubin re-enters the enterohepatic circulation while some goes to the large intestine and is excreted by the large intestine.
23
Q
- When does clinical jaundice become evident?
A
•Clinical jaundice may not be evident until the serum/plasma bilirubin concentration is 2x the upper reference of normal, >50 μmol/L.
24
Q
- What is jaundice?
A
yellow discolouration due to bilirubin deposition
25
25. When there is an elevation of bilirubin, why is it important to determine whether it is conjugated or unconjugated?
o Unconjugated elevation - production is increased which is beyond capacity of liver conjugation.
o Conjugated bilirubin elevation – obstruction of bilirubin flow.
26
26. What are some prehepatic (Hb--> Bilirubin) causes of jaundice?
Excessive RBC breakdown (excessive production)
Haemolysis, Haemolytic anaemia
Crigler-Najjar (improper metabolism), Gilbert’s (improper processing).
27
27. What are some cholestatic-intrahepatic causes of jaundice?
Dysfunction of hepatic cells
| Viral hepatitis, Drugs, Alcoholic hepatitis, Cirrhosis, Pregnancy, Infiltration, Congenital (genetic) disorder.
28
28. What are some cholestatic-extrahepatic causes of jaundice?
```
Obstruction of biliary drainage
Common duct stone, Carcinoma,
Biliary structure
Sclerosing cholangitis
Pancreatitis
```
29
29. Is neonatal jaundice common?
•Normally common & transient (resolves in the first 10 days)
30
30. When is neonatal jaundice pathological- symptoms?
but pathological if high levels of conjugated bilirubin e.g. pale stools in babies with biliary atresia (blocked biliary flow).
31
31. What are some treatments for neonatal jaundice?
Urgent surgical treatment is required
| •Phototherapy with UV light – converts bilirubin to water soluble, non-toxic form
32
32. Why is neonatal jaundice so dangerous is very high levels?
* Immaturity of bilirubin conjugation enzymes causes high levels of unconjugated bilirubin which can cross the blood-brain-barrier (due to its hydrophobicity).
* Unconjugated bilirubin is neurotoxic and so causes kerkernicterus (seizures, tiredness etc.).
33
33. What is Gilbert's syndrome
| what % of the population does it affect?
Benign liver disorder which affects around 10% of population
34
34. What is Gilbert's syndrome characterised by?
•Characterised by mild, fluctuating increases in unconjugated bilirubin as the liver has decreased ability
35
35. Who is the most affected by Gilbert's syndrome?
•Males more frequently affected then females and young are more frequently affected.
36
36. What do the liver transaminases ALT and AST do?
•They catalyse the transfer of amino group: alpha -amino acid --> alpha-oxo acid.
37
37. Where are ALT and AST localised?
AST has wide tissue distribution (heart, skeletal muscle, kidney, brain, erythrocytes, lung & liver).
38
38. Out of ALT or AST, which one is used used to identify liver damage arising from hepatocyte inflammation or necrosis.
ALT
39
39. Both ALT and AST are cystolic, but one is also present in the mitochondria- which one
AST
40
40. What are increases of 20x the upper limit of normal of ALT and AST indications of?
May occur with severe damage
| oAcute viral hepatitis, Hepatic necrosis induced by drugs or toxins or Ischaemic hepatitis induced by circulatory shock.
41
41. What are small increases of 5x the upper limit of normal ALT and AST indications of?
oFatty liver, Chronic viral hepatitis, Prolonged Cholestatic liver disease, Cirrhosis-due to secondary damage to hepatocytes (values may be normal in compensated).
42
42. Are values of ALT and AST increased , decreased or the same in ALL liver diseases?
INCREASED
43
43. Where are enzyme isoforms of alkaline phosphatase (ALP) produced?
•Enzyme isoforms mainly produced in liver and bone (but also placenta and intestinal.
44
44. What increases the synthesis of ALP?
•Bile duct obstruction increases ALP synthesis (by bile duct epithelial cells and osteoblasts) and thus increase in measured activity.
45
45. What kind of obstruction can occur to bile ducts?
extrahepatic (stones, tumour or stricture) or intrahepatic (infiltration or space occupying lesion).
46
46. What do very high increases in osteoblastic activity result in?
Healing fractures, Vitamin D deficiency, Paget’s disease (fragile bones, dont get replaced by new bones)
47
47. What are ALP values >3x ULN (upper limit normal) found in?
Intra and extra hepatic cholestasis
48
48. What are ALP values <3x ULN (upper limit normal) found in?
Hepatocellular disease
49
49. What are the reference ranges for ALP and AST based on?
Age and sex related - as they relate to bones
50
50. If a patient has elevated levels of ALP, how can we determine the source of this?
```
Gel electrophoresis
Separates ALP isoenzymes into :
-liver
-bone
-intestinal fractions
```
51
51. What is unique about placental isoenzyme of ALP that makes it easily identifiable?
- Heat stable at 65 degrees celsius for 10 mins
| - Others are not
52
52. What two types of disease show elevated levels of ALP?
Liver and Bone disease
53
53. What is gamma glutamyl transferase (GGT)?
A membrane bound enzyme that transfers the gamma glutamyl group from peptides eg glutathione to other peptides and to L-amino acids
54
54. Where is GGT distributed?
•GGT has a wide tissue distribution, but liver isoenzyme activity predominates in serum.
55
55. What can the value of GGT tell us?
•Results are used in combination with ALP, Increase value confirms ALP of hepatic origin.
Increased levels: enzyme induction by alcohol or drugs e.g. anticonvulsants, cholestasis and hepatocellular disease, non-hepatic disorders, e.g. pancreatitis, myocardial infarction and diabetes mellitus.
56
56. What does INCREASED ALP and INCREASED GGT suggest?
suggestive of hepatic cause (cholestasis).
57
57. What does INCREASED ALP and NORMAL GGT suggest?
suggestive of bone source of ALP.
58
58.What does NORMAL ALP and NORMAL GGT suggest?
suggestive of excess alcohol intake
59
59. How many g's of Albumin is synthesised exclusively in the liver each day?
12g
60
60. What is the concentration of Albumin a good indication for?
•Concentration widely regarded as an index of hepatic synthetic function.
61
61. What kind of issues can there be with normal albumin levels?
early acute hepatitis due to its long half-life (21 days) or in a well-compensated disease.
62
62. What can decreased albumin levels indicate?
acute or chronic destructive liver diseases of moderate severity, Haemodilution, Impaired synthesis e.g. malnutrition, Increased loss e.g. nephrotic syndrome, Inflammatory leak
63
63. What is more prevalent:
- Non-alcoholic fatty liver disease (NAFLD)
OR
-Alcoholic liver disease
????
Alcoholic liver disease
64
64. What % of the population approx. have NAFLD and what % of type 2 diabetes patients?
20% of general population
70% in type 2 diabetes
65
65. What are the stages leading up to NAFLD?
o Hepatic steatosis (fat >5% liver volume)
| o Greater risk of progressing to fibrosis, cirrhosis, hepatic cell carcinoma.
66
66. What are some major risk factors of NAFLD?
Obesity,
| Diabetes/insulin resistance, Hypertension.
67
```
67. What are the following characteristics :
Body weight
Fasting plasma glucose or HbA1c
Reported daily alcohol intake
ALT
AST
AST:ALT ratio
GGT
Triglycerides
HDL cholesterol
Mean corpuscular volume
```
For NAFLD??
Body weight=Increased
Fasting plasma glucose or HbA1c = Increased
Reported daily alcohol intake =<20 g for women, <30 g for men
ALT =Increased or normal
AST = Normal
AST:ALT ratio=<0.8 (>0.8 with more advanced disease)
GGT = Increased or normal
Triglycerides= Increased
HDL cholesterol= Low
Mean corpuscular volume= Normal
68
```
68. What are the following characteristics :
Body weight
Fasting plasma glucose or HbA1c
Reported daily alcohol intake
ALT
AST
AST:ALT ratio
GGT
Triglycerides
HDL cholesterol
Mean corpuscular volume
```
FOR ALCHOLIC LIVER DISEASE?
Body weight = Variable
Fasting plasma glucose or HbA1c = Normal
Reported daily alcohol intake= >20g for women, >30g for men
ALT= Increased or normal
AST= Increased
AST:ALT ratio = >1.5
GGT = Considerably increased
Triglycerides= Variable , may be considerably increased
HDL cholesterol= Increased
Mean corpuscular volume = increased
69
69. If we think a patient has NAFLD because it is suggested by ultrasound or a negative liver screen, what are the next steps for that patient?
1. Determine the risk of liver fibrosis by calculating FIB4 or NAFLD fibrosis scores.
o Values <1.3 and ≤1.455 show low risk (higher cut off points are used for older patients).
2. ELF serum marker tests or elastography/FibroScan (modified for children).
o Cut off points for ARFI vary according to manufacturer.
3. The results of the tests determine if the patient is managed in primary care or referred to the hepatology clinic.
70
70. What does Effective digestion and absorption require?
continuous modification of gut contents.
71
71. Where does digestion occur?
stomach and duodenum release enzymes for digestion
72
72. Where does absorption occur?
Most of the small intestine and the large intestine.
73
73. Give a brief overview of how the GI tract works please mamacita x
First you start with ingestion (in the oesophagus) , enzymes are released and then moves onto digestion (in the stomach and duodenum) in which first the pH is lower and we continous releasing enzymes and then we increase the pH and add pancreatic enzymes , then we move onto absorption (occurs in the jejunum , ileum and colon) . we stabilise the pH and signal to the brain and body to handle the incoming nutrients and therefore modify hunger
74
74. What are gastric ulcers?
open sores that develop on the lining of the stomach
75
75. What are some signs and symptoms of gastric ulcers?
o Pain in the abdomen that may come and go (may be eased with antacid).
o Waking up with a feeling of pain in the abdomen.
o Bloating, retching and feeling sick.
o Feeling particularly ‘full’ after a normal size meal.
76
76. What are some common causes of gastric ulcers?
oHelicobacter pylori infection (80% of cases) and the use of medication such as aspirin and NSAIDs- non-steroidal anti-inflammatory drugs (20% of cases).
77
77. What is Helicobacter Pylori?
•H. pylori - helix-shaped gram-negative bacteria
78
78. How does H.Pylori survive in the gastric acid?
survives in gastric acid by secreting urease (breaks down urea into ammonia which neutralises stomach acid) and releasing toxins that cause epithelial cell damage.
79
79. How do we detect H.Pylori?
- Urea breath test: rapid and non-invasive procedure.
• Patient drinks a solution containing urea labelled with an uncommon isotope (non-radioactive carbon-13). This is broken down into isotope-labelled carbon dioxide which is exhaled.
• CO2 in exhaled breath indicates that the urea was split by urease -secreting H. pylori, present in the stomach and so shows the presence of urea.
80
80. What is Vit B12/Cobalamin, what is its function?
•Vitamin B12 (cobalamin) is a water soluble vitamin- role in the nervous system and the formation of red blood cells as a co-factor for DNA synthesis.
81
81. How is VItB12 absorbed?
* Vitamin B12 can’t be produced by the body and must be obtained from diet.
* When dietary B12 enters the stomach, it binds to intrinsic factor (IF), a 45 kDa glycoprotein by the parietal cells of the stomach.
* B12-IF complex enters the intestine where it binds to receptors on the mucosal cells of the ileum and is absorbed into the blood stream.
82
82. Are the effects of B12 deficiency seen immediately?
• It takes a long time period for Vit B12 deficiency to present itself because the liver contains large store of vitamin B12.
83
83. What is the cause of B12 deficiency?
Pernicious anaemia (autoimmune attack on the gastric mucosa) leads to atrophy of the stomach wall and the IF secretion is absent or severely depleted.
84
84. What are some signs and symptoms of B12 deficiency?
oMacrocytic anaemia (increased MCV, decreased haemoglobin)
oWeakness and tiredness
oPale skin
oGlossitis – inflammation of the tongue.
oNerve problems such as numbness or tingling (severe deficiency).
85
85. What value of serum Vit B12 classifies as a deficiency?
<150 pmol/L
86
86. What is more elevated in someone with a B12 deficiency ?
* Elevated Methylmalonic acid: B12 deficiency (or renal disease)
* Elevated Homocysteine in B12 deficiency because it’s not converted to methionine:
87
87. Is it better to test for MMA or Homocysteine for B12 deficiency?
Homocysteine test is less specific than MMA as it is also elevated in folate deficiency and hypothyroidism, but test is more readily available
88
88. What is Holotranscobalamin?
Holotranscobalamin (active B12): measurement of B12 bound to transcobalamin and may be the first detectable marker of B12 deficiency
89
89. What two things would be tested positively for in a patient with pernicious anaemia?
Intrinsic factor and antiparietal cell antibodies
90
90. What is Coeliac disease?
autoimmune disorder, primarily affecting the small intestine):
•Immunological hypersensitivity to ingested gliadin (gluten protein) that is found in wheat and other grains e.g. barley and rye.
91
91. What would happen if a patient with coeliac disease was exposed to gluten?
Inflammatory reaction leading to the shortening of the villi lining and villous atrophy.
92
92. Who does coeliac disease affect?
•Affects up to 1% of the general population and may present at any age.
93
93. What are some typical symptoms of coeliac disease?
anaemia, weight loss, and GI problems e.g. diarrhoea, abdominal distention, malabsorption and loss of appetite.
94
94. One way of testing for coeliac disease is through tissue transglutaminase (TTG) antibodies- how does this work?
* TGG is an enzyme that deaminates glutamine residues to glutamic acid on the gliadin fragment.
* TGG can be a target autoantigen in the immune response- leads to intestinal epithelial cell destruction and the production of anti-TTG antibodies.
* Anti-TTG antibodies belong to the IgA subclass of immunoglobulins.
95
95. Why might a false negative occur in a TTG test ?
As approximately 1 in 700 in the UK are deficient in IgA- false negative result in IgA deficient patients with coeliac disease.
Use igG deaminated gliadin peptide (DGP) antibodies instead
96
96. Other than the TTG test, what other tests are available?
* Endomysial antibodies (EMA): these become elevated as part of ongoing damage to the intestine.
* A duodenal biopsy is the gold standard diagnosis of coeliac disease.
* Gluten challenge: patients already on a gluten-free diet cannot be diagnosed as serology and histology tests will be normal until gluten is ingested.
97
97. What is inflammatory bowel disease (IBD)
umbrella term used to describe disorders that involve chronic inflammation of your digestive tract. Types of IBD include: Ulcerative colitis and Crohn's disease
98
98. What is ulcerative colitis?
diffuse inflammation affecting the mucosa of the colon only.
99
99. What is Crohn's disease?
patchy ulceration affecting any part of the GI tract and may extend through the full thickness of the bowel.
100
100. What are some complications of IBD?
fistulae (abnormal connection between two hollow spaces eg intestines)
abscess formation stricturing (narrowing in the intestine that makes it difficult for food to pass through)
101
101. What is the definitive test for the diagnosis of IBD?
Colonoscopy
102
102. What are some common signs and symptoms of IBD?
oAbdominal pain, Prolonged diarrhoea with bowel urgency, Blood and/or mucus in stools
oFatigue, Weight loss and malnutrition
103
103. What additional symptoms would Crohn's disease present with as well as typical IBD symptoms?
o Perianal lesions
| o Bowel obstruction i.e. abdominal bloating, distension, vomiting or constipation
104
104. What are some symptoms that are common to both IBD and IBS?
abdominal pain or discomfort with diarrhoea or constipation.
105
105. What is one major disadvantage to IBS patients in the sense that they have similar symptoms to IBD patients?
•Many people with IBS have unnecessary expensive and invasive hospital investigations for IBD such as a colonoscopy.
106
106. What do we need to have a differential diagnosis between IBD and IBS?
Biochemical markers
107
107. how many get IBD compared to IBS?
IBD: ~200 per 100,000 people
IBS: 10-20% of the adult population
108
108. What is Caprotectin?
•Zinc and calcium binding protein in neutrophils that leak out into the bowel and can be seen in faeces when there is damage to the mucosal surface e.g. in inflammation.
109
109. How do we measure Caprotectin levels in stool?
•Stable in stool- extracted and measured using a fluorescence enzyme immunoassay
110
110. What is the measurement of Calprotectin useful for?
•Useful for differentiating IBS and IBD in younger age group (i.e. patients <40 y).
111
111. What is the faecal calprotectin Algorithm (NICE DG11)??
o If cancer is suspected from symptoms: 2 week cancer referral.
o If cancer not suspected: primary diagnostics e.g. FBC or bone profile.
o If primary diagnostics negative: secondary diagnostics e.g. faecal calprotectin testing.
112
112. What is the third most common malignancy in the western world?
Colorectal Cancer
113
113. What does colorectal cancer arise from?
•It arises predominantly from adenomatous polyps (noncancerous growths)
114
114. Is colorectal cancer asymptomatic ?
is often asymptomatic until late-stage disease by which time, the prognosis is poor.
• Early detection greatly improves prognosis, and the condition is now routinely screened for in individuals > 60y
115
115. What are the tests for colorectal cancer?
Tests detect the small amounts of blood in faeces - may be present in asymptomatic individuals with bowel lesions.
o Guaic faecal occult blood (FOB) method widely used in screening.
116
116. What is a faecal immunochemical test (FIT)
* ‘Dipstick’ test for blood in stool that has a higher sensitivity than Guaic FOB method
* Recommended in NICE guidance DG30 (July 2017)- guide referral for suspected colorectal cancer patients who do not meet criteria for a suspected cancer pathway referral.
117
117. What is the criteria required for a FIT test?
- Over 50y with unexplained abdominal pain or weight loss
- 50 to 60y with changes in bowel habit or iron-deficiency anaemia
- 60y or over with anaemia without iron deficiency
118
118. What does FIT measure?
* Quantitative measurement of Hb in faeces
* OC-Sensor FIT kit (made by MAST) - immunoassay test which can be used with an automatic analyser.
* June 2019 – Bowel Cancer Screening Programme moved from the guaic FOB test to FIT. Threshold for positive screen is 120 ug Hb/g faeces.
* NICE DG30 Symptomatic threshold of 10 ug Hb/g faeces
* For FIT ≥10 µg Hb/g faeces: Further investigations are required in line with local guidelines.
