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Nutrition and Drug Monitoring > Gastro-Intestinal Function Testing and GI Disease > Flashcards

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
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2
Q

What are signs of Specific Nutritional Deficiencies?

A
  • Anaemia: Fe/B12/Folate
  • Osteomalacia/Rickets: Vit D
  • Easy bruising/bleeding: Vit K
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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
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4
Q

What are features of Ulcerative Colitis?

A
  • 1-2/1000 UK
  • Confined to colon
  • Extends proximally from rectum
  • Disease confined to mucosa
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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
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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)
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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
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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

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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)
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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
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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
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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
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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
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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%

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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
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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
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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
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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
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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
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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
Q

What are biochemical tests for Pancreatitis

A
  • Amylase
  • Lipase
  • Faecal Elastase
26
Q

What are features of Amylase measurement in Panceatitis?

A
  • 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
Q

What can lead to false positives in Amylase measurements of Pancreatitis?

A
  • Peptic ulcer disease
  • Cholecystitis
  • Intestinal obstruction
  • Salivary gland disease
  • Pneumonia
  • Head injury
  • Renal failure
  • Diabetic ketoacidosis (DKA)
  • Anorexia nervosa
28
Q

What is Macroamylase?

A

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
Q

What are features of Lipase measurements for Pancreatitis?

A
  • 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
Q

What other diseases can lead to elevated Lipase?

A
  • Peptic ulcer disease
  • Mesenteric ischaemia
  • Renal failure
  • Bone fractures
31
Q

What are features of Faecal Elastase?

A

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
Q

What are features of Cystic Fibrosis?

A
  • 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
Q

What are signs and symptoms of CF?

A
  • 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
Q

how is Newborn Screening for CF conducted?

A
  • 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
Q

How can blood quality for CF screening be preserved?

A
  • No overlaying
  • Must fill collection circle
  • Minimise ‘milking’
36
Q

What is the gold standard for CF diagnosis?

A

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
Q

How Sweat Test analysis conducted?

A

Sweat collection = Pilocarpine Iontophoresis

  • Measure sweat Cl- concentration on ISE, also measure Na+ concentration to ensure no discrepancy
38
Q

What are the cutoffs used for Sweat Tests?

A

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
Q

What are GI disorders leading to Chronic Diarrhoea?

A
  • GI malignancy
  • GI inflammation
  • Small bowel malabsorption
  • Pancreatic insufficiency
  • Motility disorders
40
Q

What is the definition of Chronic Diarrhoea?

A
  • Passage of ≥3 loose or liquid stools per day for >4 weeks, and/or daily stool weight >200 g/day
41
Q

What is the Clinical History for Chronic Diarrhoea?

A

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
Q

What are causes of Chronic Diarrhoea?

A
  • 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
Q

What are tests for the causes of Chronic Diarrhoea?

A
  • 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
Q

What is the Biochemical Tests for Liver Fibrosis?

A
  • Enhanced Liver Fibrosis (ELF) Test
  • Used a screening test in primary care population to reduce patients referred for needle biopsy of liver
45
Q

What are Biochemical Markers measured in the Enhanced Liver Fibrosis?

A
  • Hyaluronic acid (HA)
  • Procollagen III amino terminal peptide (PIIINP)
  • Tissue inhibitor of metalloproteinase 1 (TIMP-1)
46
Q

What are disadvanatges of Liver Biopsy?

A
  • Morbidity & mortality
  • Samples very small portion of liver
  • Costly & time consuming
  • Operator variability / error rate
  • Cannot perform repeat biopsy at short intervals
47
Q

What are advanatages of ELF test?

A
  • 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
Q

What are Disadvantages of ELF test?

A
  • Screening test, therefore, not 100% sensitive or specific
  • False positives and false negatives
  • Currently only available on Siemens analysers
49
Q

What are other GI disease investigations?

A
  • Radiology: Ultrasound, CT, MRI
  • Microbiology/Virology
  • Immunology: PBC/PSC
  • Histology
  • Breath test: Bacterial overgrowth

Nutrition and Drug Monitoring (17 decks)

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