GI Tract Flashcards
Peptic ulcer disease
Peptic ulcer disease is caused by the Helicobacter pylori bacterium, which can live in the digestive tract for long periods, often leading to ulcers in the stomach or upper small intestine.
This infection is widespread, affecting about two-thirds of the global population.
The bacteria damage the stomach lining, which normally protects against digestive acids, causing tissue damage and ulcers.
In severe cases, this can result in bleeding and infections.
Diagnosing H. pylori involves invasive procedures like biopsy followed by histology, which gives a visual result & has 98% sensitivity.
A urease (CLO) test (90-95% sensitivity) on biopsy detects the bacteria’s urease enzyme, which breaks down into alkaline ammonia, causing a colour change.
Non-invasive methods include serology, which detects IgG antibodies produced in response to H. pylori infection. This has a good sensitivity but poor specificity, as antibodies can remain in body even after infection has cleared.
Breath test involves inhaling radioactive urea and tracking it’s clearance.
The urea is broken down by the urease enzyme produced by the bacteria into ammonia and carbon dioxide.
The radioactive carbon dioxide travels to the alveoli and is exhaled, where it can be measured to indicate a H. pylori infection.
However, there are concerns about the test due to the use of radioactivity, which carries potential risks associated with ionization.
This is used to confirm eradication after treatment.
Gastrin
Fasting plasma gastrin is a measure of the hormone gastrin, which is released by G cells in the gastric antrum in response to food intake.
Gastrin stimulates acid secretion in the stomach by parietal cells, aiding gastric motility and digestion by triggering histamine release, which stimulates HCl production.
This acid helps break down proteins, kill certain bacteria, and activate pepsinogen into pepsin for further protein digestion.
Fasting plasma gastrin levels are commonly measured to diagnose gastrin-secreting tumours (gastrinomas), as these tumours lead to high basal fasting acid secretion and peptic ulcer disease.
The test is conducted using an immunoassay.
Acute Pancreatitis
Acute pancreatitis is characterized by severe abdominal pain and acute inflammation of the pancreas, which has both exocrine and endocrine functions involved in digestion.
The condition is commonly caused by excessive alcohol consumption, gallstones, or may be idiopathic (without a known cause).
A serum amylase level more than 10 times the upper limit of normal strongly suggests pancreatitis.
Amylase rises quickly within 12 hours of symptom onset and returns to normal within 3-5 days.
It is produced by the pancreas’ alpha cells and leaks into the bloodstream when the pancreas is damaged.
While high amylase levels are indicative of pancreatitis, lower elevations may also occur due to conditions like perforated duodenal ulcers, intestinal obstruction, or renal failure, as amylase is small and excreted in urine.
Chronic pancreatitis
Chronic pancreatitis is persistent inflammation of the pancreas that worsens over time, leading to permanent damage and loss of pancreatic function.
It is often caused by chronic alcohol use, autoimmune disorders (where the immune system attacks the pancreas), or cystic fibrosis.
In contrast to acute pancreatitis, serum amylase levels are typically normal or low in chronic pancreatitis.
To diagnose type 1 autoimmune pancreatitis, an elevated serum IgG4 level (>135 mg/dl) is often used, as IgG4 autoantibodies can damage the pancreas.
Two biochemical tests are used: non-invasive tests, such as measuring IgG4 levels in blood and invasive tests, such as organ biopsy (though less commonly used now).
There is also a strong link between chronic pancreatitis and gastrinomas, as their uncontrolled proliferation causes widespread inflammation and damage to the pancreas.
Noninvasive test for chronic pancreatitis
Pancreatic elastase 1 in stool is a non-invasive biomarker for diagnosing exocrine pancreatic insufficiency.
This enzyme, exclusively produced by the pancreas, remains undigested and can be measured in stool, making it a patient-friendly approach.
Low levels in stool indicate pancreatic dysfunction, with normal levels being above 200 µg/g.
The test, performed using ELISA, has a sensitivity and specificity of over 90% and correlates strongly with invasive gold-standard tests.
A key advantage is that results are not affected by enzyme replacement therapy (pancreatin), allowing patients to continue treatment while undergoing testing.
Secretin/CCK test
The invasive Secretin/CCK test evaluates pancreatic function by measuring secretions stimulated by the hormones secretin and cholecystokinin (CCK).
Secretin regulates water homeostasis and duodenal secretions, while CCK stimulates fat and protein digestion.
The procedure involves fasting, inserting a double-lumen tube to aspirate gastric and pancreatic secretions, and collecting samples before and after intravenous administration of secretin and CCK.
Healthy individuals typically exhibit a fluid secretion rate of 2.0 ml/kg and bicarbonate levels >75 mM, with trypsin and amylase activities analyzed.
Though considered the “gold standard” for research and validating new tests, it is costly, requires specialized equipment and staff, carries infection risks, and is uncomfortable for patients, limiting its routine use.
Non-biochemical test for chronic pancreatitis
Endoscopic ultrasonography is an invasive procedure used in rare cases of chronic pancreatitis.
It provides excellent imaging and allows fine needle aspiration for cytology by inserting a small tube with a needle into the stomach.
While useful for detailed assessments, it is expensive, invasive, and carries risks of infection or damage, limiting its routine use.
Coeliac disease
Coeliac disease is a common small bowel enteropathy in the Western world (affecting 1 in 200 people in Europe) caused by an immune reaction to gluten, a protein found in wheat, rye, and barley.
Consuming gluten triggers an immune response that damages the small intestine’s lining, leading to nutrient malabsorption.
Symptoms include diarrhoea, weight loss, stunted growth, and secondary anaemia.
Coeliac disease diagnosis
Coeliac disease diagnosis involves testing for anti-tissue transglutaminase (tTG) IgA antibodies, which have high sensitivity (85%) and specificity (97%).
tTG plays two roles in coeliac disease: enhancing the immunostimulatory effect of gluten (as a deamidating enzyme) and acting as the target autoantigen, triggering inflammation.
Total IgA should be measured since 1 in 50 patients are IgA deficient, which can lead to false negatives.
In IgA deficiency, IgG antibodies to tTG are tested, though they are less specific.
Diagnosis is confirmed by biopsy, often after a gluten challenge, where gluten consumption reveals shortened or absent intestinal villi, reducing nutrient absorption.
Malabsorption
Malabsorption is the inability to absorb nutrients, leading to deficiencies.
Key deficiencies include iron, folate, and vitamin B12, which can cause anaemia.
Symptoms such as weight loss and oedema occur due to unabsorbed proteins drawing water into the extracellular fluid.
Testing involves measuring mean red cell volume, mean corpuscular haemoglobin, serum ferritin, vitamin B12, and folate to assess anaemia, as well as serum albumin, calcium, and phosphate to evaluate protein and nutrient levels.
Malabsorption
Malabsorption is the inability to absorb nutrients, leading to deficiencies.
Key deficiencies include iron, folate, and vitamin B12, which can cause anaemia.
Symptoms such as weight loss and oedema occur due to unabsorbed proteins drawing water into the extracellular fluid.
Testing involves measuring mean red cell volume, mean corpuscular haemoglobin, serum ferritin, vitamin B12, and folate to assess anaemia, as well as serum albumin, calcium, and phosphate to evaluate protein and nutrient levels.
Lactase deficiency
Lactase deficiency occurs when the body lacks lactase, leading to symptoms such as abdominal cramps and diarrhoea after consuming lactose-containing products.
This is due to undigested lactose being fermented by gut bacteria, producing gas, and its high osmotic pressure drawing water into the gut, causing diarrhoea.
These symptoms reduce nutrient absorption.
Lactase persistence is linked to a mutation in a cis-acting enhancer upstream of the lactase gene.
Diagnostic tests include measuring blood glucose response after ingesting 50g of lactose (a rise <1.1 mmol/L above baseline indicates deficiency), breath hydrogen testing, and lactase activity assays from a biopsy.
Fat Metabolism
Dietary fat is crucial as an energy source, a key membrane component, a part of the myelin sheath in neurons, and a precursor for hormone production.
Fat malabsorption can be assessed using the 14C-triolein test, though it is rarely used due to the involvement of radioisotopes.
The test involves fasting overnight, collecting a baseline CO2 sample, and consuming a fat meal with radioactive 14C-triolein.
Hourly CO2 samples are collected for 6–7 hours, and their radioactivity is measured.
If fat metabolism is impaired, there will be little to no radioactive CO2 produced, indicating malabsorption.
While effective, the use of radioactive meals limits its application.
Positive test for fat malabsorption
Fat malabsorption can result from various conditions, including cholestatic liver disease (lack of bile salts), pancreatic disease (absence of triglyceride lipase), and intestinal issues such as coeliac disease, Crohn’s disease, or bacterial overgrowth (causing bile salt deconjugation and diarrhoea).
Diagnosis is clarified through a combination of biopsy and tests assessing liver and pancreatic function.
Bile salt malabsorption
Bile salt malabsorption occurs when bile salts, normally reabsorbed in the ileum and recycled to the liver, aren’t adequately reabsorbed.
This leads to excess bile salts in the large bowel, drawing water into the bowel and causing watery stools.
The condition can be detected using tests such as selenium-labelled homotaurocholic acid retention, which uses a gamma camera to record retention after 30 min & 7 days.
<10% retention after seven days is considered abnormal. This test is expensive and time-consuming.
More practical detection involves measuring serum 7α-hydroxycholestenone, an intermediate in bile acid synthesis.
Elevated levels of this intermediate suggest bile salt malabsorption, and it can be measured non-invasively using High-Pressure Liquid Chromatography (HPLC), where higher concentrations produce larger peaks.
