Gastrointestinal Disorders Lecture 8 PDF

Biochemistry Department Clinical Biochemistry (PB416/PBC416) Nora Aborehab, PhD, FHEA, PGCHE Assoc. Prof. of Biochemistry & Molecular Biology Head of Biochemistry Department Faculty of Pharmacy Ahram Canadian University  Lecture 8 Gastrointe...

Biochemistry Department Clinical Biochemistry (PB416/PBC416) Nora Aborehab, PhD, FHEA, PGCHE Assoc. Prof. of Biochemistry & Molecular Biology Head of Biochemistry Department Faculty of Pharmacy Ahram Canadian University  Lecture 8 Gastrointestinal Disorders  References 1. Clinical chemistry : principles, techniques, and correlations/Michael L. Bishop, Edward P. Fody, Larry E. Schoeff.-7th ed. 2. Lecture notes: Clinical biochemistry/Simon Walker, Geoffrey Beckett, Peter Rae, Peter Ashby- 9th ed. Interactive teaching methods & activities 1- E-learning asynchronous 2- Case-based learning Learning outcomes of the lecture: By the end of this lecture the students will be able to: 1. Discuss the causes and symptoms of peptic ulcer and Zollinger–Ellison syndrome 2. Differentiate between acute and chronic pancreatitis. 3. Explain Bacterial colonisation of the small intestine. 4. Demonstrate Coeliac disease Stomach  Stomach The stomach mucosa’s epithelial lining consists only of surface mucus cells, which secrete a protective coat of alkaline mucus. A vast number of gastric pits dot the surface of the epithelium, mark the entry to each gastric gland, which secretes a complex digestive fluid referred to as gastric juice. The gastric glands are made up of a variety of secretory cells: ✓ Parietal cells ✓ Chief cells ✓ Mucous neck cells, and ✓ Enteroendocrine cells.  Stomach: Gastric gland Parietal cells: produce both hydrochloric acid (HCl) responsible for the high acidity (pH 1.5 to 3.5) of the stomach contents and is needed to activate pepsin enzyme, and intrinsic factor is a glycoprotein necessary for the absorption of vitamin B12 in the small intestine. Chief cells: which secrete pepsinogen, the inactive proenzyme form of pepsin. HCl is necessary for the conversion of pepsinogen to pepsin. Mucous neck cells: secrete alkaline mucus. Enteroendocrine cells: secrete various hormones include gastrin, which is released mainly by enteroendocrine G cells. Stomach: Peptic Ulcer Disease (PUD) It is a painful lesion in the lining (mucosa) of stomach (gastric ulcer) or duodenum (duodenal ulcer). Symptoms include: ✓ A burning pain in the middle or upper stomach or at night. ✓ Bloating. ✓ Heartburn. ✓ Nausea or vomiting. ✓ Dark or black stool due to bleeding. ✓ Vomiting blood; (that can look like "coffee-‐ grounds") ✓ Weight loss. ✓ Severe pain in the mid to upper abdomen. Stomach: Peptic Ulcer Disease (PUD) Causes: Most of cases are caused by Helicobacter pylori (H. pylori) infection. Other causes of PU include: ✓ Excessive use of NSAIDS ✓ Alcoholism ✓ Radiation treatment ✓ Zollinger-‐Ellison syndrome  Stomach: H. pylori Virulence factors: ✓ Flagella ▪ Provide motility. ▪ Play an important role in the colonization of the gastrointestinal mucosa ✓ large amounts of urease ▪ Breakdown of Urea into ammonia and carbon dioxide. ▪ NH3 neutralizes the stomach HCl thus protecting the bacteria ✓ Multiple Adhesins ▪ These help in the attachment/penetration of the gastric mucosa  Stomach: PUD diagnosis Endoscopy-based Laboratory testing (Invasive) (non-Invasive) ✓ Urea breath test ✓ Serological tests ✓ Faecal antigen testing  PUD: Urea breath test ▪ Principle: ✓ Relies on the urease activity of H. pylori to detect active infection. ▪ Procedure: ✓ The patient ingests either 13C‐ or 14C‐labelled urea, and urease, if present, hydrolyses urea into ammonia and isotopically labelled carbon dioxide. ✓ Carbon dioxide is absorbed from the gut and subsequently expired in the breath where it can be trapped and quantified.  PUD: Urea breath test ▪ Used for both: ✓ The identification of patients with active infection. ✓ Establishing the effectiveness of treatment. ▪ Highly sensitive and specific.  PUD: Serological test Patients infected with H. pylori develop antibodies to the organism that can be detected by serological testing. It is useful to identify patients who have been infected with the organism BUT are less helpful in confirming its eradication because of the slow reduction in antibody titres.  PUD: Faecal antigen testing Enzyme immunoassays can be used to detect the presence of H. pylori in stool specimens Excellent for pre-‐ and post--treatment Stomach: Zollinger-‐Ellison Syndrome Causes: Gastrinoma: neoplasia of gastrin-producing cells. Increased gastrin production leads to chronic hypersecretion of gastric acid, which in turn causes: ✓ Peptic ulceration ✓ Diarrhea ✓ Fat malabsorption leading to steatorrhea; due to high H+ in the intestinal lumen, which inhibits the action of pancreatic lipase. Diagnosis: is based on the detection of elevated fasting plasma gastrin in the presence of gastric acid hypersecretion. Patients should not be receiving proton pump inhibitors or H2 receptor blockers at the time of measurement. Pancreas  Pancreas It is a complex gland with important endocrine and exocrine functions. ✓ Its endocrine role through the secretion of insulin and glucagon from the islets of Langerhans to regulate glucose metabolism. ✓ Pancreatic juice (alkaline solution) is produced by the exocrine tissue and released into the duodenum where it is mixed with partially digested food. Pancreas Nutrient Enzyme CHO Amylase Fats Lipase and Colipase Proteins Trypsinogen and Chymotrypsinogen  Pancreas: Acute Pancreatitis Causes: Gall stones: ✓ Obstruction of the major papilla by the stone causes reflux of bile into the pancreatic duct. ✓ The presence of bile in the pancreatic duct appears to initiate a complex cascade effect that results in acute pancreatitis. Alcohol: ✓ Metabolites increases oxidative stress inside the pancreas. Hypertriglyceridemia  Acute Pancreatitis: Diagnosis Endoscopic retrograde Laboratory testing (non- cholangiopancreatogra Invasive) phy (ERCP) (Invasive) ✓ Amylase ✓ Lipase  Acute Pancreatitis: Diagnosis Amylase (>10x) Lipase (>5x) Highly sensitive and specific diagnostic marker for acute pancreatitis Salivary Pancreatic Symptoms 5-8 hours 12-72 hours 3-5 days Symptoms 4-8 hours 24 hours 8-14 days onset onset  Serum Amylase Moderate and more transient increase may occur in ✓ Any acute abdominal condition (e.g. perforated peptic ulcer, ruptured ectopic pregnancy), or ✓ After injection of morphine and other drugs that cause spasm of the sphincter of Oddi. ✓ Diabetic ketoacidosis (DKA). Pancreas: Chronic Pancreatitis Usually occurs after acute pancreatitis. Symptoms: ✓ Constant, dull, unremitting abdominal pain ✓ Epigastric tenderness ✓ Weight loss Complications include: ✓ Malabsorption with consequent steatorrhea. ✓ The elevated random plasma glucose which is consistent with clinical diabetes that tends to occur relatively late in the course of chronic pancreatitis.  Chronic Pancreatitis: Diagnosis Pancreatic imaging technique Laboratory testing Fecal Elastase ▪ Elastase is a pancreas‐specific enzyme that is not degraded during intestinal transport. ▪ Fecal concentrations are 5–6 times higher than those of duodenal fluid ▪ low levels are associated with pancreatic insufficiency. ▪ False‐positive results may be observed in some patients with watery diarrhea.  Small intestine & Colon 1. Bacterial colonisation of the small intestine Also known as small intestinal bacterial overgrowth syndrome (SIBO) When immune mechanisms are impaired, anaerobic bacteria colonize the intestine. This often causes fat malabsorption, due to excessive deconjugation of bile acid conjugates by the bacteria and the premature passive reabsorption of the resulting unconjugated bile acids. This leads to a relative deficiency of bile salts in the intestinal lumen and decreased micelle formation. Vitamin B12 deficiency may also develop due to its consumption by the bacteria. Diagnosis: – Culture of small bowel aspirate – Glucose hydrogen breath test  Small intestine & Colon 1. Bacterial colonisation of the small intestine Glucose hydrogen breath test  Small intestine & Colon 1. Bacterial colonisation of the small intestine Glucose hydrogen breath test This is based on the ability of some bacteria to ferment carbohydrates with an end‐product of hydrogen, which is not produced by mammalian cells. The hydrogen produced in the gut by bacterial action following an oral glucose load is absorbed from the intestine and transported to the lungs where it is excreted in expired air and can be measured.  Small intestine & Colon 2. Coeliac disease (Celiac sprue) It is an inflammatory autoimmune disorder Triggered by sensitivity to gliadin (an alcohol-soluble fraction of gluten, storage protein in wheat, barley, and rye) The most common small bowel enteropathy in the Western world. It causes malabsorption and eventually cancer if untreated Diagnosis: ✓ The presence of antibodies to tissue transglutaminase anti‐tTG IgA (high sensitivity & specificity) and is useful both in screening and in monitoring the response to treatment. ✓ The test also might be done if a child has a condition that makes celiac disease more likely (such as type 1 diabetes), thyroid disease, or a family member with celiac disease. ✓ A small intestinal biopsy remains the gold standard in making the final diagnosis.  Small intestine & Colon 2. Coeliac disease (Celiac sprue) IgA deficiency ✓ It occurs in 1:500 of the general population and in approximately 2–3% of patients with coeliac disease. ✓ To avoid false‐negative serum IgA antibody tests, total IgA levels should be measured in all patients undergoing initial screening. ✓ In IgA‐deficient patients, anti‐tTG IgG should be measured.