Gastro-Intestinal Function Testing and GI Disease Flashcards
1
Q
What are Signs and Symptoms of GI disease?
A
- Altered bowel habits: Frequency, Watery/Diarrhoea, Blood, Mucous, Steatorrhea
- Abdominal/chest pain exacerbated by food intake
- Weight loss
- Nausea, Vomiting, Dysphagia
2
Q
What are signs of Specific Nutritional Deficiencies?
A
- Anaemia: Fe/B12/Folate
- Osteomalacia/Rickets: Vit D
- Easy bruising/bleeding: Vit K
3
Q
What are Inflammatory Bowel Disease?
A
- A chronic inflammatory condition of unknown aetiology affecting any part of the intestine.
- Split into Ulcerative Colitis and Crohns Disease
4
Q
What are features of Ulcerative Colitis?
A
- 1-2/1000 UK
- Confined to colon
- Extends proximally from rectum
- Disease confined to mucosa
5
Q
What are features of Crohns Disease?
A
- 0.5-1.0/1000 UK
- Affects any part of GI tract
- Inflammation through full thickness of bowel wall
- Fistulation, abscess formation, stricturing
6
Q
How is IBD diagnosed?
A
- History & examination
- Bloods: Raised platelets/white cells, Raised CRP/ESR
- Colonoscopy or Sigmoidoscopy
- Histology
- Faecal calprotectin (36 kDa)
7
Q
What is Faecal Calprotectin?
A
Calcium and zinc binding protein that present in cytosol in neutrophilic granulocytes. Faecal levels correlate well with neutrophilic infiltration of intestinal mucosa
- >2000 µg/g = Severe inflammation
- >1000 µg/g = Severe inflammation
- >100 µg/g = Active Inflammation
- 51-100 µg/g = Equivocal
- 0-50 µg/g = Normal
8
Q
What is the Use of Faecal Calprotectin?
A
Differentiate IBD from IBS
- Primary Care
- Reduce number of patients referred for endoscopy
Assessment of disease activity in patients with known IBD
Monitoring response to treatment
9
Q
What are the Faecal Protectin Assays?
A
- Semi quatitative POCT: Buhlmann Quantum Blue
- ELISA: Buhlman, CALPRO, Immunodiagnostik
- Stand-Alone Analyser: Thermo ELIA (Phadia)
10
Q
What are features of Colorectal Cancer?
A
- Most common malignancy in Western world
- 2nd most common cause of cancer death. Improved prognosis if detected early
- Gold standard diagnosis and detection carcinoma and early adenomas/polyps = colonoscopy/sigmoidoscopy
11
Q
What are tumour markers of Colorectal Cancer?
A
CEA
- Non-specific marker of colon cancer.
- Also elevated in other malignancies such as Pancreatic, Peritoneal, Ovarian
- Also elevated in benign conditions such as Ascites, Pancreatitis, Liver disease
CA19-9
- Non-specific marker of pancreatic cancer
- Also elevated in other malignancies such as Colon, Biliary tract
- Also elevated in benign conditions such as Pancreatitis, Hepatitis
12
Q
Which tests are used for screening Colorectal Cancer?
A
- Guaiac faecal occult blood (FOB) test
- Faecal Immunochemical Test for Hb
- Tumour M2-PK
- Faecal tumour DNA
13
Q
How is Guaiac faecal occult blood (FOB) test conducted?
A
- Patient collects and smear faeces on the card. Peroxide added to card.
- Peroxidase activity of Hb oxidises guaiac in presence of H2O2 inducing blue colour formation
14
Q
What are Pitfalls of Guaiac faecal occult blood (FOB) test?
A
Dietary restriction required 3 days prior
- False +ve = Red meat, Turnips, Horseradish, Broccoli, Cauliflower
- False –ve = Vitamin C (counter the oxidation)
Non/intermittent bleeding lesions
Multiple sample collections
Poor sensitivity for detection of adenoma/carcinoma 15-50%
15
Q
What are features of Faecal Immunochemical Test for Hb in Colorectal Cancer?
A
- Qualitative or quantitative assays available
- Recommended faecal test - European guidelines colorectal cancer screening & diagnosis
16
Q
What are Advantages of FIT over Guaic FOB?
A
- Higher sensitivity to presence of blood
- Higher specificity – reduced false positives
- Fewer medication interferences
- Fewer dietary interferences
- Quantitative
- Dedicated automated analysers
17
Q
What are disadvantages of FIT over Guaic FOB?
A
- More expensive
- Can still miss bleeding if intermittent bleeding or very low-level bleeding
18
Q
What is Tumour M2-PK?
A
- M2 isoform of pyruvate kinase (PK) predominant isoform in rapidly proliferating cells eg fibroblasts, lung, bladder, kidney etc. M2-PK can exist in two forms
- Almost all PK in tumour cells is of dimeric form hence cell metabolism favours tumour growth = Tumour M2-PK
- Available as quantitative ELISA or rapid test for stool samples
19
Q
What are the forms of Tumour M2-PK?
A
Tetrameric form
- Highly active
- Favours glycolytic flux, converting phospoenolpyruvate to pyruvate
Dimeric form
- Virtually inactive
- Favours build up and channelling of early glycolytic pathway intermediates into synthetic processes eg nucleic acid, amino acid and fatty acid synthesis
- Dimerisation induced by oncoproteins
20
Q
What are appplications of Tumour M2-PK?
A
CRC Stool Screening
- Improved sensitivity and specificity compared to gFOBT
- Single stool sample
- No dietary interferences
- No false positives due to other causes of GI bleeding
- Detection not dependent on tumour/adenoma bleeding
- Quantitative ELISA or qualitative POCT available
Serum tumour marker
- GI, pancreatic, breast, melanoma, thyroid, lung, renal, oesophageal, ovarian, cervical
- Early detection of relapse
- Monitoring / Response to therapy
- Staging
21
Q
What is the Pathophysiology of Pancreatitis & Pancreatic Insufficiency?
A
- Pancreatic over stimulation / injury
- Co-localisation of lysosomal enzymes with pancreatic exocrine enzymes
- Accumulation of activated intracellular trypsin
- Pancreatic tissue destruction and release of further enzymes from damaged cells
- Profound acute inflammatory response, pancreatic tissue necrosis and ischaemia
22
Q
What is the Aetiology of Acute Pancreatitis?
A
- G = Gallstones
- E = Ethanol
- T = Trauma
- S = Steroids
- M = Mumps
- A = Autoimmune (SLE, Sjogrens)
- S = Scorpion Sting
- H = Hypertriglyceridemia, Hypercalcaemia
- E = Endoscopic retrograde cholangiopancreatography (ERCP)
- D = Drugs (steroids, opiates, estrogens, azathioprine)
23
Q
What is the aetiology of Chronic Pancreatitis?
A
All causes of acute pancreatitis if prolonged, plus:
- Cystic fibrosis
- Hereditary haemochromatosis
- Schwachman-Diamond syndrome
- SBDS gene
- 2nd most common cause pancreatic insufficiency in children
24
Q
What are Historical Tests for Pancreatitis?
A
Faecal fat
- 72 hr faeces collection and measurement of fat content
- No longer used other than situations where malabsorption is strongly suspected and standard investigations proven negative
Direct pancreatic exocrine tests
- Intubation of duodenum or pancreatic duct
- Collection of secretions for analysis of bicarbonate and pancreatic enzyme activity following stimulation with a test meal or hormones
Indirect pancreatic exocrine test
- Administration of test substance from which a measurable marker is released following pancreatic enzymatic cleavage. Marker subsequently excreted and measured in the urine
- NT-PABA
- Fluorescein dilaurate
25
What are biochemical tests for Pancreatitis
* Amylase
* Lipase
* Faecal Elastase
26
What are features of Amylase measurement in Panceatitis?
* Serum amylase \>3x upper limit of normal (ULN) strongly suggestive of pancreatitis, cut-off most often used in biochemistry labs
* Concentrations begin to rise within hrs onset of pancreatic injury, and falls after 3-5 days
* Urine amylase remains elevated several days after serum concentrations fall to normal, hence good test for late presentation
* Serum amylase within ref range in up to 30% cases acute pancreatitis
27
What can lead to false positives in Amylase measurements of Pancreatitis?
* Peptic ulcer disease
* Cholecystitis
* Intestinal obstruction
* Salivary gland disease
* Pneumonia
* Head injury
* Renal failure
* Diabetic ketoacidosis (DKA)
* Anorexia nervosa
28
What is Macroamylase?
Benign cause of elevated serum amylase. Low urine amylase as large macro complex not filtered at glomerulus
**Amylase-creatinine clearance:**
* \<1% consistent with macroamylasaemia
* \>5% consistent with AP
29
What are features of Lipase measurements for Pancreatitis?
* Longer half life than amylase and higher activity hence better than amylase for late presentation patients
* Similar sensitivity and specificity to amylase, but slightly more expensive
* If elevated serum amylase but ?acute pancreatitis, can measure concurrent lipase
30
What other diseases can lead to elevated Lipase?
* Peptic ulcer disease
* Mesenteric ischaemia
* Renal failure
* Bone fractures
31
What are features of Faecal Elastase?
Pancreatic Elastase-1
* Pancreas specific protease that passes unchanged through the intestine
* Excellent test of severe pancreatic insufficiency but less sensitive in mild and moderate disease
* Potential for false positives in watery stool samples
* Also useful for monitoring CF patients
* Non-invasive
32
What are features of Cystic Fibrosis?
* Autosomal recessive ~1/2500 N.European
* Mutation in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. CFTR protein regulates movement of Cl- and Na+/H2O across epithelial membranes – present in cells lining entire GI tract
* Leads to multi organ dysfunction affecting Lungs, Pancreas, Liver, GI Tract
* Most common mutation = ∆F508, ~1/30 heterozygous carriers
33
What are signs and symptoms of CF?
* **Pancreas:** Pancreatitis, Steatorrhea, Diabetes, Fat soluble vitamin deficiencies
* **Lungs:** Bronchiectesis, Pneumonia , Respiratory failure, Hemoptypsis
* **GI:** Meconium Ileus, Volvulus, Steatosis, Splenomegaly, Biliary cirrhosis
* **Other:** Growth failure, Infertility, Delayed puberty, Osteoporosis
34
how is Newborn Screening for CF conducted?
* Day 5-8 heelprick bloodspot
* CF screening test = Immunoreactive Trypsinogen (IRT)
* Screening test only, not 100% sensitive or specific hence will be false positives and false negatives
* Confirmation by repeat IRT and DNA analysis of common CFTR mutation panel. Quality of bloodspot important
35
How can blood quality for CF screening be preserved?
* No overlaying
* Must fill collection circle
* Minimise ‘milking’
36
What is the gold standard for CF diagnosis?
Sweat Test is the gold standard. It is performed after 2 weeks of age and has requirements such as:
* \>3Kg
* Normally hydrated
* No systemic illness
* No eczema at sweat collection site
* Not on corticosteroids
37
How Sweat Test analysis conducted?
Sweat collection = Pilocarpine Iontophoresis
* Measure sweat Cl- concentration on ISE, also measure Na+ concentration to ensure no discrepancy
38
What are the cutoffs used for Sweat Tests?
Guidelines, sweat Cl- concentration cut-offs:
* **\>60 mmol/L =** supports diagnosis of CF
* **40-60 mmol/L =** equivocal, requires repeat (or 20-60 mmol/L if \<6 months age)
* **\<40 mmol/L =** low probability for CF (or \<30 mmol/L if \<6 months age)
2 positive results on 2 separate days essentially diagnostic for CF, should be confirmed with DNA analysis
39
What are GI disorders leading to Chronic Diarrhoea?
* GI malignancy
* GI inflammation
* Small bowel malabsorption
* Pancreatic insufficiency
* Motility disorders
40
What is the definition of Chronic Diarrhoea?
* Passage of ≥3 loose or liquid stools per day for \>4 weeks, and/or daily stool weight \>200 g/day
41
What is the Clinical History for Chronic Diarrhoea?
**Organic vs Functional disease**
* History \<3 months, Nocturnal/Continuous, Weight loss
**Signs of Malabsorption**
* Steatorrhea, Signs and symptoms of specific nutritional deficiencies
**Signs of Inflammatory Disease**
* Liquid stools, Blood/mucous, Abdominal pain
42
What are causes of Chronic Diarrhoea?
* **GI Inflammation:** Crohn’s, Ulcerative Colitis, Coeliac Disease, Malignancy
* **Pancreatic Disease:** Pancreatitis, Malignancy, Cystic Fibrosis
* **Endocrine:** Hyperthyroidism, Hypoparathyroidism, Diabetes Mellitus, Addison’s, VIPoma, Gastrinoma, Carcinoid
* **Others:** Lactose Intolerance, Drugs, Alcohol, Laxative Abuse
43
What are tests for the causes of Chronic Diarrhoea?
* **GI Inflammation:** Test with Faecal Calprotectin, Anti-tTG/Endomysial Ab, Tumour Marks FOB/FIT
* **Pancreatic Disease:** Test with Amylase, Lipase, Faecal Elastase, Tumour Markers IRT/Sweat Test
* **Endocrine:** Test with TFTs, Bone/PTH, OGTT/HbA1c, Cortisol/SST, Gut hormones, 5HIAA
* **Others:** Test with Faecal Reducing Substances, Urine Laxative Screen, GGT/CDT
44
What is the Biochemical Tests for Liver Fibrosis?
* Enhanced Liver Fibrosis (ELF) Test
* Used a screening test in primary care population to reduce patients referred for needle biopsy of liver
45
What are Biochemical Markers measured in the Enhanced Liver Fibrosis?
* Hyaluronic acid (HA)
* Procollagen III amino terminal peptide (PIIINP)
* Tissue inhibitor of metalloproteinase 1 (TIMP-1)
46
What are disadvanatges of Liver Biopsy?
* Morbidity & mortality
* Samples very small portion of liver
* Costly & time consuming
* Operator variability / error rate
* Cannot perform repeat biopsy at short intervals
47
What are advanatages of ELF test?
* Identify patients at early stages liver fibrosis before progressing to cirrhosis
* Cost effective and safer compared to biopsy
* Single blood test no patient preparation required
* As good as Fibroscan
48
What are Disadvantages of ELF test?
* Screening test, therefore, not 100% sensitive or specific
* False positives and false negatives
* Currently only available on Siemens analysers
49
What are other GI disease investigations?
* **Radiology:** Ultrasound, CT, MRI
* **Microbiology/Virology**
* **Immunology:** PBC/PSC
* **Histology**
* **Breath test:** Bacterial overgrowth
