Gastrointestinal tract

Question 1

Biochemical function tests often need to be used together with other investigative procedures:

Answer 1

• Biopsy/histology, endoscopy, CAT scans etc.
• Particularly true of most of the G.I. tract where access is relatively easy.

Question 2

Endoscopes

Answer 2

Question 3

Peptic ulcer disease caused by Helicobacter pylori.

Invasive procedures and non-invasive

Answer 3

• Biopsy followed by:
• Histology (98% sensitivity).
• Urease (CLO) test on biopsy (90-95% sensitivity).
• Colour change due to alkaline ammonia.
• Non-invasive procedures:
• Serology (IgG against H. pylori) – good sensitivity but poor specificity (false positives).
• ELISA for stool antigens.
• Breath test using [¹⁴C] or [¹³C] urea – eradication check.
• Antibodies persist.

Question 4

Urea breadth test for H. pylori

Answer 4

Question 5

Fasting plasma gastrin

Answer 5

• Gastrin is released from the G cells in the gastric antrum in response to food intake and stimulates acid secretion.
• Measured by immunoassay.
• The most common reason for measuring fasting plasma gastrin is a gastrin secreting tumour (gastrinoma).
• Patients with gastrinoma will have a high basal fasting acid secretion and as a consequence peptic ulcer disease.

Question 6

Acute pancreatitis

Answer 6

• Severe abdominal pain with acute inflammation of pancreas.
• Caused by excessive alcohol, gall stones but many cases idiopathic (no cause identifiable).
• Serum amylase > 10 times upper limit of normal is very strong evidence.
• Amylase is a pancreatic enzyme which has leaked into the blood stream.
• Lower elevations may be due to other causes:
• perforated duodenal ulcer, intestinal obstruction, renal failure (amylase is quite small and is excreted in urine).

Question 7

Chronic pancreatitis

Answer 7

• Loss of pancreatic function, often due to chronic alcohol intake. Also autoimmune forms and in cystic fibrosis.
• Serum amylase is normal or low.
• Serum IgG4 level (>135 mg/dl) has a fairly high sensitivity to diagnose type 1 autoimmune pancreatitis.
• Two types of biochemical test:
• Non-invasive.
• Invasive (not used any more).

Question 8

Chronic pancreatitis- non-inasive

Answer 8

• Pancreatic elastase 1 in stool (not degraded).
• Non-invasive marker - low levels in faeces indicate exocrine pancreatic insufficiency.
• Specificity and sensitivity of >90%
• Determined by ELISA. Above 200 µg /g stool is considered normal
• Note the test is not influenced by patients on the enzyme substitution therapy pancreatic.

Question 9

Secretin/CCK (cholecystokinin) test.

Answer 9

• Patient fasts and double lumen radio-opaque tube positioned to aspirate gastric and pancreatic secretions.
• Basal collection 2 x 10 min.
• Intravenous secretin: 6 x 10 min collections. Healthy subjects show fluid secretion rate of 2.0 ml/kg body weight and bicarbonate concentration normally > 75 mM
• Intravenous cholecystokinin: 2 x 10 min collections. Trypsin and amylase activities compared to local standards.
• Research use only and as a ‘Gold standard’ to evaluate new tests

Question 10

Non-biochemical complement these.

Answer 10

Endoscopic ultrasonography provides excellent imaging and has the option of fine needle aspiration for cytology.

Question 11

Coeliac disease

Answer 11

• Malabsorption of nutrients.
• Most common small bowel enteropathy in Western world (1 in 200 in Europe).
• Intolerance to ingested gluten (storage protein) found in wheat, rye and barley.
• Symptoms such as diarrhoea, weight loss, retarded growth and secondary anaemia.

Question 12

Untreated patients have anti-tissue transglutaminase IgA antibodies which show high sensitivity (85%) and high specificity (97%).

Answer 12

• Total IgA should be measured where Coeliac disease is suspected as 1 in 50 patients are IgA deficient.
• If IgA deficient, measure IgG antibodies to tissue transglutaminase although this is less specific.
• Confirm by biopsy.
• Done with gluten challenge.
• Short villi.

Question 13

Malabsorption

Answer 13

Anaemia.

• Iron, folate and vitamin B12 deficiency.
• Measure mean red cell volume, mean corpuscular haemoglobin, serum ferritin, vitamin B12 and folate.
• Weight loss, oedema.
• Reduced absorption of protein and nutrients.
• Measure serum albumin, calcium and phosphate

Question 14

Lactose deficiency

Answer 14

Question 15

Lactase persistence is due to

Answer 15

A single nucleotide change in a cis-acting enhancer upstream of the lactase gene.

Question 16

Lactose deficiency

Affected individuals have abdominal cramps and

Answer 16

diarrhoea.

Question 17

What are the tests for lactose deficiency?

Answer 17

Tests:

• Blood glucose response after 50g oral lactose is low < 1.1 mmol/l above baseline.
• Breath hydrogen in response to lactose ingestion.
• Assay biopsy for lactase activity.

Question 18

Fat malabsoption

Answer 18

• ¹⁴C-triolein test.
• Fast patient overnight.
• Collect basal sample of expired CO₂.
• Give 10 µCi of ¹⁴C-triolein in 60 g fat meal.
• Collect 1 mmol sample of expired CO₂ hourly for 6-7 h.
• Measure radioactivity of CO₂ samples.
• Involvement of radioisotopes limits use!!

Question 19

Specific activity of expired CO₂

Answer 19

Question 20

Fat malabsorption

Positive test could be due to:

Answer 20

• Cholestatic liver disease - no bile salts.
• Pancreatic disease - no triglyceride lipase.
• Intestinal origin (coeliac disease, Crohn’s disease, bacterial overgrowth with bacterial deconjugation of bile salts which are not absorbed and which in the colon cause diarrhoea).

Situation resolved by biopsy coupled with tests of hepatic and pancreatic function.

Question 21

What is bile salt malabsorption?

Answer 21

Normally actively absorbed in the ileum and travel back to the liver for reuse – enterohepatic circulation.

Question 22

What is bile salt malabsorption detected by?

Answer 22

• Whole body retention of selenium labelled homotaurocholic acid.
• Retention after 30 min and 7 days is recorded by a gamma camera or whole body scanner.
• < 10 % retention after seven days is considered abnormal.
• Expensive and time consuming test.

Question 23

How is bile salt malabsorption also detected?

Answer 23

• Serum 7 a-hydroxycholestenone is an intermediate in the synthesis of bile acids from cholesterol.
• If there is elevated bile acid synthesis, such as occurs in bile acid malabsorption, its concentration in serum increases.
• Non invasive test performed by HPLC.

Question 24

Breath H₂ tests

Answer 24

• Used to detect bacterial overgrowth.
• Drink lactose loaded drink (10 g).
• Breath analysed for hydrogen.
• Normally very little hydrogen produced.
• Undigested lactose produces H₂.
• Takes 2-3 h.NB: 50 g glucose may be used to detect bacterial overgrowth

Question 25

Inflammatory bowl disease

Answer 25

• Many possible causes e.g.
• Malabsorption, laxatives, irritable bowel syndrome and inflammatory bowel disease.
• Biochemical investigations must be conducted along with microbiological tests e.g. for C. difficile.§Laxative abuse is quite common - test urine sample for stimulant laxatives such as bisacodyl and senna.
• Faecal osmotic gap (mosmol/kg) = 290 – 2 x ([faecal sodium] + [faecal potassium])