Gastrointestinal Functions & Digestive Disease PDF

GASTROINTESTINAL FUNCTIONS & DIGESTIVE DISEASE 5-6/11/2024 Prof. Dr. Halil Resmi INTRODUCTION The gastrointestinal tract is mainly located in the abdomen, GI tarct is a muscular tube lined with epithelial cells , It extends 10 meters from mouth to the anus, A...

GASTROINTESTINAL FUNCTIONS & DIGESTIVE DISEASE 5-6/11/2024 Prof. Dr. Halil Resmi INTRODUCTION The gastrointestinal tract is mainly located in the abdomen, GI tarct is a muscular tube lined with epithelial cells , It extends 10 meters from mouth to the anus, Along its lenght, it structure is modified to special sections according to the requirement of the digestion and absorprion of the foods. 2  GI tract is controlled by an elaborate hormonal and neural network, It produces a number of hormon such as; gastrin and secretin. These hormones largely act locally to affect the function of the intestine and other organs (pancreas and gallbledder) involved in digestive process. 3  The lower digestive tract contains large number of microorganisms that coexist with the body without causing a disease. They provide nutrients (such as vitamin K) to the body, Change in the microbial flora or introduction of unusual microorganisms can lead disease of intestinal tract. 4 6 Gastric mucosa cells The gastric mucosa contains a number of cells with specific function: Mucous cells found throughout the stomach, secret mucus (to protect the organ from acid and enzymes), Parietal cells produce HCl and intrinsic factor, Chief cells produce a proenzyme, pepsinogen, G-cells in the antrum produce the hormon, gastrin. 11  The sight and smell of food trigger messages from the brain through the vagus nerve to stimulate of production of HCl and gastrin, gastrin further stimulates HCl production. Chief cells contains some receptor that sensitive to acidic environment and secret pepsinogen. Pepsinogen is rapidly converted to its active form, pepsin at pH 3. These actions convert food into chyme. 12 Duedonum Chyme enters the duodenum in which the bile and pancreatic exocrine enzymes are secreted, Further enzymatic degradation takes place in the duodenum, Food material enters to the rest of small intestine, Through this procces, complex macromolecules in the food are broken down to amino acids, simple sugars, fatty acids and glycerol. 13  The small intestine is 4 meters long tube, apart from the duodenum the small intestine consist of two additional segments; jejunum and ileum. Its microvillous structure increases the absorption surface. The undegredable residual matter enters the large intestine, where a process of selective water and electrolyte absorption occurs, The digestive process terminates with the formation of feces. 14 EM 15  Portal vein Portal vein collects all absorbed substances and carry them to the liver 16  Brain-gut axis The intestinal tract also contains many endocrine cells, The peptide hormones produced by these cells are involved in the regulation of GI functions, Central nervous system has a significant number of receptor for these hormones, while neural impulses control the secretion of many intestinal hormones; these relationships are often termed as brain-gut axis. 17  Digestion & Absorption of Carbohydrates Most carbohydrates are ingested as starch, a long chain polysaccharide of glucose consisting of long-staright chains with some branchings. Starch digestion begins in mouth with the action of salivary amylase. 18 Starch digestion by the action of pancreatic amylase in the duodenum 21 Brush border enzymes Three intermediate products of starch are hydrolyzed bu brush border enzymes located on microvilli of the epithelial cells of the small intestine. These enzymes (sucrase and lactase) also hydrolize dietary sucrose and lactose into their component monosaccharides. 22 Monosaccharide transporters of the epithelium Digestion & Absorption of Proteins Protein digestion begins in stomach with action pepsin, a proteolytic enzyme, A small amount of amino acids are liberted in stomach, Major products of pepsin digestion are short- chain polypeptides, Most protein digestion occurs in duodenum and jejunum. 27 Endopeptidase & Exopeptidase The pancreatic enzymes trypsin, chymotrypsin and elastase cleave peptide bonds in the interior of polypeptide chains (endopeptidases). Enzyme that remove amino acids from ends of polypeptide chains (by contrast!) are exopeptidases. Exopeptidases include pancreatic enzyme carboxypeptidase and brush border enzyme aminopeptidase. 28 31  Newborn babies have an ability of absorbing a substantial amount of undigested protein, hence they can absorb some antibodies from their mother’s milk. 32 Digestion & Absorption of Lipids The salivary glands of newborns and stomach produce lipase, In adult, very little lipid digestion occurs in the mouth. The arrival of lipids in the duodenum serves a stimulus for the secretion of bile, In a process called emulsification, bile salt micelles are secreted into the duodenum, and break up the fat droplets into tiny droplets of triglycerides. 33  The emulsification is not a chemical digestion, the bonds between fatty acids and glycerol are not hydrolyzed by this process. 34  Through hydrolysis, lipase removes two of the three fatty acids from each triglycerides, and liberates fatty acids and monoglycerides. 36 39  Triglicerides, phospholipids and cholesterol are then combined with special protein in the epithelial cells to form small particles called chylomicrons This lipid-protein particle (a lipoprotein) are secreted into the lacteals (lymphatic capillaries) of the intestinal microvilli Absorbed lipids then pass through the lymphatic system, eventually entering the venous blood by the way of thoracic duct 40 41 Water & Sodium Absorption Sodium is absorbed by an active transport mechanism that is linked to the absorption of amino acids, glucose and bicarbonate in small intestine. Water is also absorbed by large intestine. Aldosterone, glucocorticoids and somatostatin increases the absorption of water and electrolytes. 42  GASTROINTESTINAL HORMONES Gastrin The hormone is secreted by gastric G-cells, The main function of gastrin is to stimulte acid secretion and gastric motility, Gastrin is primarily released in response to vagal signals and gastrin releasing-peptide and secondary to the ingestion of peptide, gastric distantion and an elevated stomach pH. A number of hormones, including secretin and glucagon inhibits gastrin secretion. 45 Cholecystokinin (CCK) It is produced by mucosa of upper small intestine, CCK has a role in regulation of gallbladder and intestinal motility, CCK stimulates pancreas to release of pancreatic enzymes, Amino acids and fatty acids stimulates CCK secretion. 46 Secretin Secretin is released by S-cells of mucosa of the duodenum and jejunum, Secretin inhibits smooth muscle cell contraction and decrease gastric acid secretion, It also stimulates water and bicarbonate secretion from pancreas, It works together with CCK to stimulate gallbladder contraction and pancreatic enzyme secretion. 47  PATHOLOGICAL CONDITIONS Stomach Disease Ulcers An ulcer result from loss of normal internal and external surface of the body, In the intestinal track, mucosal ulcers occurs most commonly in the stomach and duodenum surface. Excess acid action (peptic ulcers) is responsible for most cases, H. Pylori is the direct cause of most chronic gastritis and peptic ulsers. 49 Zollinger-Ellison Syndrome The Zollinger-Ellison Syndrome is an extreme form of peptic ulser disease that it results from most commonly by a gastrin-secreting tumor of pancreas and duodenum. The excessive secretion of gastrin causes excessive HCl secretion by the stomach. 50 Pernicious Anemia Vitamin B12 bind to a protein called intrensic factor in stomach, IF is produced by gastric parietal cells, IF-Vitamin B12 complex is absorbed in terminal ileum, An antibody that binds and blocks intrensic factor result in intrensic factor deficiency and thus vitamin B12 deficiency. 51  Small Intestine Disease Malabsorption Disease Malabsorption results from disease of GI truct that affects digestion and absorption of nutrients, and causes malnutrition. In true malabsorption, there is a damage to the intestinal mucosa, One of the most common types of intestinal injury is Celiac Disease. In Celiac disease, an autoimmun response to the wheat proteins in gluten, result in an inflammatory condition in small intestine. 52 Lactose Intolerance The most common isolated carbohydrate malabsorption disorder is lactose intolerance, All infants have the intestinal enzyme lactase to split milk sugar lactose to glucose and galactose. In about 70% of world’s population, lactase activity in intestine reduces markedly after first few years, The undigested and unabsorbed lactose causes cramps, bloating sensetion and diarrhea. Bacterial digestion of lactose causes excessive gas production in large bowel and thus worsen the complaints. 53 GASTROINTESTINAL FUNCTION TESTS 54 Helicobacter pylori diagnostic tests A number of tests are available for determination of infection by H. Pylori, The most widely used is the urea breath test, The test bases on the presence of urease activity of H. pylori. The person ingest a test meal that contains carbon-13-labeled urea, urea is converted to carbon-13-labeled CO2 by urease, The amount of CO2 is directly related urease activity. 55 Fat Absorption Test The definitive test of fat absorption is the quantitative measurement of fat in timed collections of feces obtained while the patients is maintained on a diet that contains known amount of fat. Because collection is extermely difficult for the patient …. The method is rarely used. 56 Fat Screening Test Fat screening is carried out first by evaluation of the weight and appearance of the stool. A pale, frothy appearance is virtual diagnostic of excessive fat, The microscopic evaluation of fecal material stained with a fat-specific dye is more reliable. 57 Lactose Tolerance Test In the test, 50 g of lactose dissolved in water and is given to orally to the patient, The standart protocol includes the collection of a baseline ( zero time) specimen and 5-,10-, 30-, 60-, 90- and 120-minute specimens for plasma glucose measurement, Glucose levels will increase if lactose can be cleaved successfully and then absorbed. 59 Lactose Tolerance Test Healthy person will demonstrate a glucose rise to greather than 200 mg/dL (11.1 mmole/L) over a baseline sample. The person with lactase deficiency will have a peak plasma glucose less than 100 mg/dL (5.5 mmole/L). 60  CHANGE OF ANALYTE IN DISEASE Malabsorption Testing-Screening Approach Screening for malabsorption symptoms is best done by using clinical signs associated with malabsorption and by investigating population on risk, For example, elderly people are at risk for occult malabsorption. 61  Laboratory screening for malabsorption is not very sensitive, however measurement of serum; – Albumin – Calcium – Vitamin B12 – Iron – Peripheral smear (to look for evidence of microcytosis and iron deficiency) These tests are reasonable laboratory tests to screen for malabsorption. 62  For a suspected fat malabsorption; the feces should be examined first, and then a microscopic evaluation should be carried out, The biochemical assessment of protein malabsorption is difficult, Only when a amino acid absorption is serious albumin production will be depressed. 63 Evaluation of Diarrhea In person with acute onset diarrhea, laboratory tests (other than culture and stain for fecal leukocyte) usually are not required, This field belongs mostly to microbiology laboratory. 64 Occult Blood in Stool The presence of hemoglobin (blood) in feces the strongest evidence of a bleeding in GI tract, A number of methods are available to detect trace amount of hemoglobin in feces, Most of them base on the ability of Hb and its derivatives to act as peroxidase and catalyze the reaction of H2O2 and chromogenic organic acid (such as benzidine and guaic acid). 65 Carcinoembriyonic Antigen CEA is a glycoprotein that is abudant in fetal endodermally derived tissue (GI mucosa, pancreas and lung). CEA is produced by a variety of tumors, including most tumors of the GI tract, but especially in colon cancers. Serum CEA levels are related to tumor mass, CEA is elevated in less than one fourth of localized tumors, this prevents its use in screening for colon cancers, CEA is most useful in monitoring the course of disease in persons who have been treated for cancer. 66