The clinician’s first task is to determine the likely origin of the patient’s digestive symptoms and this relies on an accurate history.
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After a history has been taken, the next task is to investigate the area of interest (oesophagus, stomach, small or large intestine) to determine whether the symptoms arise from the mucosal surface or, more commonly, from the muscles, nerves and connection with the brain.
Video Capsule:
Light transmission through fibre-optic bundles was a defining technology of the 20th Century. This enabled the development of the endoscope, a device that magically illuminated the pitch blackness of the digestive tract, allowing direct visualisation of normal or abnormal mucosa. The endoscope has to be manually pushed through the organ and the physical constraints of the instrument limits the depth to which the instrument can be passed. Current endoscopes are designed to examine the oesophagus, stomach and duodenum and large intestine. This instrument cannot inspect the lining of the 5 metres of small intestine.
The 21st Century has witnessed the remarkable impact of miniaturisation and wireless video transmission. The video capsule is a scouting device propelled by a natural bowel movement from the mouth to rectum. During its 7 metre journey, an LED light source illuminates the bowel wall and a tiny chip camera transmits a wireless signal to a video recorder, capturing the entire journey.
Painless video capsule changes the clinical pathway, allowing a preliminary step for the gastroenterologist to determine whether or not an interventional fibre-optic endoscopy is required to biopsy, removed a polyp or stop bleeding or whether a more physiological approach is indicated. Video capsule powers the pathway.
Breath Tests:
Long-standing diabetes can cause impaired gastric emptying resulting in unpredictable delivery of carbohydrate to the small intestine and poor diabetic control. In addition, pancreatic exocrine function might be impaired in chronic pancreatic disorders. Diabetes is complicated by fatty liver and progressive liver disease. Stable isotope breath testing provides a convenient method for assessing and following up gastric, exocrine and functional liver capacity.
The MIGe Diagnostics Unit offers the following non-radioactive stable isotope breath tests:
• 13C isotope-labelled urea (Diabact UBT) for Helicobacter pylori – a 10 minute breath test
• 13C-Sodium-Acetate test of gastric emptying
• 13C-Mixed Triglyceride test of pancreatic function
• 13C-Methacetin breath test of functional liver mass
Test for presence of Helicobacter pylori
Test principle
Isotopically labelled urea is metabolised into carbon dioxide and ammonia by the enzyme urease, which is produced by the bacteria Helicobacter pylori. The available non-radioactive 13C isotope, now in the form of 13CO2, diffuses into the blood to be transported to the lungs, where it is exhaled in the breath to be capture during sampling. An increased ratio of 13C is conclusive proof of the presence of Helicobacter pylori in the patient’s stomach.
Diabact UBT – 13C Urea Breath Test
Diabact UBT is a proprietary formulation from Kibion, with several advantages in a clinical setting:
• no need for a test meal
• only 10 minutes wait
• high specificity (100%)
• high sensitivity (99%)
• result immediately available
Patient preparation
The patient should have fasted for 6 hours prior to the test and not have taken PPI for 2 weeks before the test is performed. Antibiotic treatment should have been discontinued one month before testing.
Liquid gastric emptying test 13C-Sodium-Acetate
Metabolic principle
13C-Sodium-Acetate is administered together with a liquid or semi-solid test meal. After passing through the stomach, where it is not absorbable, absorption occurs in the small intestine and metabolised in the liver. About 50% enters the body´s bicarbonate pool and is exhaled. As the rate-limiting step in this process is the stomach-emptying rate, this test is a reliable application to assess liquid gastric emptying.
Applications of 13C-Sodium-Acetate Breath Test
The 13C-Sodium-Acetate breath test is very useful for the investigation of functional dyspepsia and autonomic diabetic neuropathy and gastroparesis.
Patient preparation
The patient should have fasted for 10 hours prior to the test and should not drink carbonated water or soft drinks prior to the test since, these can interfere with the results.
Pancreatic function test using 13C-Mixed Triglyceride
Metabolic principle
1,3-distearyl-2-{carboxyl-13C}octanoylglycerol, otherwise known as 13C-Mixed Triglyceride passes through the stomach and is digested by lipase activity in the duodenum. The two distearyl groups have to be hydrolysed by pancreatic lipase before absorption and metabolism of the 13C-octanoyl monoglyceride. Thus, the oxidation to 13CO2 is dependent on the rate-limiting step of hydrolysis of the fatty acids.
Applications of 13C -Mixed Triglyceride Breath Test
The 13C-Mixed Triglyceride breath test assesses duodenal pancreatic lipase activity. It is therefore useful for the investigation of severe exocrine pancreatic insufficiency. If applied under strict conditions even mild to moderate forms can be assessed with high sensitivity and specificity.
Patient preparation
The patient should have fasted for 10 hours prior to the test. The patient must not drink carbonated water or soft drinks prior to the test since these might interfere with the results. Thirteen consecutive breath samples are exhaled at designated time points and the lipase activity can be extrapolated from the exhalation profile.
Liver function – 13C-Methacetin Breath Test
Metabolic principle
Methacetin is metabolised rapidly in normal subjects, due to high liver extraction. This implies that methacetin metabolism is mainly dependent on liver blood flow which is decreased in cirrhotic patients. Methacetin undergoes dealkylation by hepatic CYP1A2 to acetaminophen with the methoxy group being eliminated as 13CO2. The Methacetin breath test is a rapid and precise quantitative liver function test without any evidence of toxicities.
Applications of 13C -Methacetin Breath Test
The liver status of patients diagnosed with liver disease can be assessed or monitored non-invasively using the 13C-Methacetin breath test.
Patient preparation
The patient should be fasted for 8 hours prior to the test. Smoking should also be avoided for at least one hour prior to the test. Prior to the test, the patient should not drink carbonated water or soft drinks as these might interfere with the results.
HRV:
A further test may help to complete the picture. Heart rate variability (HRV) monitoring can be useful to investigate the brain-gut axis.
The autonomic nervous system plays an important role in regulating digestion. In general, the parasympathetic vagus nerve stimulates digestion, growth and recovery whilst the sympathetic (“fight or flight”) autonomic nerves are inhibitory. The vagus acts as a brake on the fight and flight reaction, only allowing the sympathetic response to emerge in the face of danger, stress and anxiety.
There is considerable evidence that autonomic nervous balance is disturbed in disorders such as irritable bowel syndrome and functional dyspepsia, where stress and anxiety are thought to play an important role.
Our heart rate varies between inspiration and expiration and this phenomenon, known has “heart rate variability”, is a healthy physiological response that is altered in the face of physical and emotional stress.
Measuring the variability, with FirstBeat Bodyguard2, provides a physiological measure of stress and its relationship to daily activities, which opens a window to measuring autonomic balance (see video).
By providing patients with an illustrated print out and by illustrating the relationship between HRV and the patient’s diary of daily activity, meals, mood and sleep, it is possible to identify triggers that might be contributing to the perception of gastrointestinal symptoms, and then work towards reversing these factors.
Further, the assessment of autonomic tone by measuring three day HRV may provide insights into a range of patients presenting with medically unexplained symptoms.