What is it all about?The gastrointestinal (GI) system encompasses anatomy, embryology, physiology, pharmacology,biochemistry, immunology and pathology. We learn about what goes into the gut, how it is movedalong the gut, how it is broken down, what it gets turned into, where the products go and how weget rid of the unwanted stuff. Understanding the basic science of normal gut behavior makeslearning about the diseases a lot easier.Where does it happen?We all know that the gut begins at the mouth and ends at the anus. But the GI system isn’t justthe esophagus, stomach and intestines; it also includes the liver, biliary tract, pancreas andgallbladder.At the cellular level, a vast array of different cell types and functions interrelate to produce thepuzzle that is the working GI system. From hydrochloric acid (HCl) secretion by the oxyntic cellsin the stomach to phagocytic Kupffer cells in the liver, the GI system does a lot more than justbreak down food for us.It is important to learn some specifics about motility, and also about the mucosal surfaces, if weare going to understand disorders such as achalasia or ulcerative colitis. Things going wrong inthe gut can have a knock-on effect throughout the body. For example, liver damage leading toreduced drug metabolism can result in toxic metabolites entering the systemic circulation.100 high-return facts to get you startedGeneral principles• The gut is composed of a basic structure throughout its length: mucosa, submucosa,muscular layer and adventitia (or serosa).• It is innervated through intrinsic submucosal and mucosal nerve plexuses (Meissner’sand Auerbach’s plexuses). This activity is moderated by extrinsic innervation.• Food is moved through the tract by gravity and peristalsis, which is a wavelike movementinvolving coordinated contraction of muscle in one area and relaxation of muscle in thenext.• The major functions of the gut are: ingestion, breakdown and digestion of food; storage ofwaste; secretion of exocrine, endocrine and paracrine substances; and excretion ofwaste products.• The gut defense mechanisms include: sight, smell and taste; the vomit reflex; stomachacid; a natural flora; IgA secretions and Peyer’s patches in the gut wall.• Dietary fat is mostly composed of triglycerides (esters of free fatty acids and glycerols).The essential fatty acids are linoleic acid and α-linoleic acid. Dietary fat provides 37 kJ (9kcal) of energy per gram.• Vitamins are either fat soluble or water soluble. The fat-soluble vitamins are A, D, E andK. These are stored in fatty tissue and are more abundant than stores of water-solublevitamins.• The GI tract is derived from the endodermal germ layer. It forms passively and dependson the cephalocaudal and lateral folding of the embryo.• Between weeks 7 and 11 of gestation, the gut herniates and continues developingoutside the abdominal cavity.• The gut is divided into foregut, midgut and hindgut, which all have separate bloodsupplies: the celiac artery, superior mesenteric artery and inferior mesenteric artery,respectively.The mouth• The oral cavity extends from the lips to the pillars of the fauces, which is the opening tothe pharynx. The oral cavity is divided into the vestibule (anterior to the teeth) and theoral cavity proper (posterior to the incisors).
• The tongue comprises four pairs of intrinsic muscles: the superior and inferior longitudinaland the transverse and vertical muscles. The extrinsic muscles of the tongue are calledgenioglossus, hyoglossus, styloglossus and palatoglossus.• The functional unit of a salivary gland is called a salivon and consists of an acinus and aduct. Acini contain serous or mucous cells and their secretions are modified as they travelthrough the duct.• Swallowing involves a sequential swallowing motor program, which is generated in themedullary centers and consists of three phases: buccal, pharyngeal and esophageal.• Cleft lip and palate are common defects (1/100 and 1/2500 births, respectively). A cleft lipis more common in girls because the palatine shelves in the female fetus fuse about 1week later than in the male fetus.• Herpes simplex virus 1 (HSV-1) infection usually affects the body above the waist but cansometimes affect other parts of the body, including the genitalia. The virus can remainlatent in the trigeminal ganglia and can be reactivated to present as cold sores.• Sialadenitis is inflammation of the salivary glands; it can be caused by mumps (infectiousparotitis). Individuals with reduced amounts of saliva (e.g. Sjögren’s syndrome) are atincreased risk of sialadenitis.• The term ‘leukoplakia’ (hyperkeratosis and hyperplasia of squamous epithelium) is takenfrom the Greek words meaning ‘white patches’. It is a premalignant condition associatedwith excess alcohol, poor dental hygiene and smoking.• Oral candidiasis is caused by a yeast infection (Candida albicans) and looks similar toleukoplakia, but it can be scraped off. It responds well to nystatin, oral amphotericin ormiconazole.• Sublingual or buccal absorption allows diffusion of substances directly into the systemiccirculation, bypassing the liver and avoiding first-pass metabolism. Glyceryl trinitrate isgiven this way for angina.The esophagus• The esophagus is a fibromuscular tube that is about 25 cm in length and whichconnects the pharynx to the stomach. It enters the abdomen through the diaphragm atthe level of T10.• The upper third of the esophagus contains striated muscle and the lower third containssmooth muscle. The middle third is made up of both types of muscle.• The esophageal mucosa is lined by non-keratinized, stratified squamous epithelium.• Esophageal atresia and fistula occur together in 90% of cases. The most common forminvolves a blind ending in the upper part of the esophagus and a fistulous opening intothe trachea at the lower end.• In gastroesophageal reflux disease (GORD), reflux causes injury to and desquamationof the squamous esophageal cells. Increased loss of the cells is compensated by basalcell proliferation (hyperplasia).• Barrett’s esophagus is a premalignant disorder in which the normal squamousepithelium is subjected to prolonged injury and undergoes a metaplastic change to bereplaced by columnar epithelium. People with Barrett’s esophagus are 30–40 timesmore likely to develop adenocarcinoma than normal.• Achalasia involves the loss of coordinated peristalsis of the lower esophageal sphincter.This prevents the passage of food and liquid into the stomach. It can be caused bydamage to the esophageal innervation, as in Chagas’ disease.• A hiatus hernia is the herniation of part of the stomach through the diaphragm. They canbe described as sliding or rolling hernias.• Esophageal varices are dilated veins at the gastroesophageal junction. They are seenmost commonly in patients with liver cirrhosis and portal hypertension. The enlargedveins are at risk of tearing, resulting in hematemesis – a medical emergency.• Mallory–Weiss syndrome is hematemesis as a result of a tear at the gastroesophagealjunction. It is caused by prolonged retching or coughing, which causes asudden increase in intra-abdominal pressure.The stomach• The stomach is a mobile, muscular organ that acts as a reservoir for food. It can hold 2–3L of food. It mixes food and digestive juices to form chyme.
• The stomach is divided anatomically into three parts: the fundus (the superior part of thestomach), the body (which lies between the fundus and antrum) and the antrum (theinferior part of the stomach).• The gastric mucosa is lined with simple columnar epithelium and forms numerous gastricpits, which are the openings for the gastric glands.• Various cell types are found in the gastric glands: the mucus neck cells, parietal (oxyntic)cells, chief (zymogen) cells, enteroendocrine (amine precursor uptake anddecarboxylation or APUD) cells and undifferentiated stem cells.• The average adult produces 2–3 L of gastric juices every 24 h. Gastric juices containmucus, HCl, intrinsic factor and digestive enzymes (pepsinogen and lipase).• Fatty acids in the duodenum cause the release of gastric inhibitory polypeptide (GIP) andcholecystokinin (CCK), which both inhibit acid secretion. Together with secretin, GIP andCCK are called enterogastrones.• During gastric motility, large peristaltic contractions originate in the pacemaker zone ofthe distal body (on the greater curvature). They sweep down into the antrum and occur ata rate of three per minute, lasting between 2-20 seconds.• Chronic gastritis can be classified as type A (autoimmune), type B (bacterial infection)and type C (reflux). The bacterium Helicobacter pylori is present in about 90% of cases oftype B gastritis.• Gastric ulcers are caused by hyperacidity, H. pylori infection, reflux of duodenal contents,non-steroidal anti-inflammatory drugs (NSAIDs) and smoking; genetic factors are alsoinvolved. Peptic ulceration is more common in individuals with blood group O.• Pyloric stenosis is caused by hypertrophy of the circular muscles of the pylorus andobstructs flow of chyme into the duodenum. It typically presents in infants 4–6 weeksafter birth, with projectile vomiting within 30 minutes of a feed.The liver• The liver is situated in the right upper quadrant, under the diaphragm, and weighs about1.5 kg. It is surrounded by strong connective tissue, called Glisson’s capsule.• The blood supply to the liver comes from the hepatic artery (a branch of the celiacartery) and the portal vein, which carries venous blood, full of digestion products, from thegut.• Liver cells – hepatocytes – are arranged in cords, which radiate out in a spoke-likefashion around a central vein. A network of capillaries (or sinusoids), which are lined withdiscontinuous fenestrated epithelium and phagocytic Kupffer cells, is present betweenthe hepatocytes.• The main functions of the liver are: to metabolize protein, fat and carbohydrate; toproduce bile; to store vitamins, minerals and glycogen; to biotransform unwantedsubstances; and to detoxify and protect (by filtration of portal blood).• Drug or hormone metabolism occurs via biotransformation in three stages:- phase I: oxidation- phase II: conjugation- phase III: eliminationIn acetaminophen (paracetamol) overdose, there is saturation of liver enzymes and depletion ofglutathione, a conjugation group. This leads to liver necrosis and kidney damage by toxic metabolites.• Cirrhosis is a diffuse and irreversible condition that results from hepatocyte necrosis,followed by the formation of regeneration nodules with fibrosis. It can lead to portalhypertension, liver failure or hepatocellular carcinoma.• Jaundice is a clinical sign resulting from serum bilirubin levels exceeding 45 µmol/L.Hepatic causes include congenital or hepatocellular abnormalities; extrahepatic causesare the result of hemolytic and obstructive (or cholestatic) disorders.• Hepatitis A virus is spread by the fecal–oral route. Hepatitis B virus is transmittedthrough blood, body fluids, sexual contact, transplacentally and in breast milk. Hepatitis Cvirus is spread parentally (contaminated blood products or IV drug abuse).• Hemochromatosis is an autosomal recessive disorder with a mutation in the HFE gene,where too much iron accumulates in the liver, heart, pancreas and other endocrineorgans. Diabetes occurs in two-thirds of all cases.• Alcohol damage in the liver can cause a number of diseases, including hepatic steatosis(fatty liver), alcoholic hepatitis and alcoholic cirrhosis.
The pancreas and gall bladder• The gall bladder is a pear-shaped sac that concentrates and stores bile secreted from theliver. It can hold up to 60 ml of bile.• Cholecystokinin causes strong contractions of the smooth muscle is the wall of the gallbladder and relaxation of the sphincter of Oddi. This allows for release of bile into theduodenum.• Around 80% of gallstones are made up of cholesterol, although they can also becomposed of bile pigment or calcium. Asymptomatic gallstones remain in the gall bladderbut those that impact in the cystic duct cause biliary pain and acute cholecystitis.• The pancreas has an exocrine function involving secretion of digestive enzymes (e.g.lipase, amylase and trypsin). These are secreted as proenzymes (zymogens), to preventautodigestion of pancreatic tissue.• The pancreas also has an endocrine function involving the secretion of the hormonesinsulin, glucagon and somatostatin. These are secreted from β, α and δ cells, respectively.• The main pancreatic duct travels across the gland from left to right and, with the bile duct,opens into the second part of the duodenum at the ampulla of Vater.• Pancreatic juice is rich in bicarbonate, which acts to neutralize the stomach acid.• Annular pancreas is a congenital abnormality in which there is incomplete migration ofthe embryonic ventral bud, or the left portion migrates in the opposite direction to the rightportion, resulting in a ring of pancreatic tissue surrounding the duodenum.• Bruises on the flanks (Grey Turner’s sign) or around the umbilicus (Cullen’s sign) arefound in acute pancreatitis.• Chronic pancreatitis normally presents with a history of prolonged ill health, steatorrhea,weight loss, abdominal pain and diabetes mellitus.The small intestine• The small intestine is 6–7 m long and consists of the duodenum, jejunum and ileum. Theileum makes up two-fifths of the length.• The mucosa of the small intestine has a huge surface area for absorption of digestionproducts. This is facilitated by plicae circulares, numerous villi and a striated border ofmircovilli, which increase the absorptive area 600-fold.• Peyer’s patches are found in the mucosa of the ileum and extend into the submucosa.They consist of aggregations of lymphoid nodules.• Brunner’s glands are present only in the duodenum. They secrete mucus, bicarbonate,growth factors and urogastrone, an inhibitor of acid secretion.• The migrating motor complex occurs every 90–120 min during fasting in the smallintestine. It involves high frequency bursts of powerful contractions.• Meckel’s diverticulum is a remnant of the vitelline duct that is present in embryonic life. Itis present in 2% of the population, is about 2 inches long and is found about 2 feet fromthe cecum (rule of 2s).• Celiac disease occurs due to an abnormal reaction to gluten, which damages theenterocytes of the small intestine, causing villous atrophy and malabsorption.• Atresia and stenosis occur most often in the duodenum. The incidence is 1 in 500 births.• Exomphalos (umbilical hernia) occurs when the gut fails to return to the abdominal cavityafter physiological herniation and development during weeks 7–11 of gestation.• Cholera produces a potentially fatal secretory diarrhea. The bacterium Vibrio choleraeproduces an enterotoxin that binds to receptors on immature cells, causing an increase inadenylate cyclase, elevating cAMP and increasing the secretion of Na+ ions, Cl− ions andwater into the lumen.The large intestine• The outer, longitudinal muscle of the large intestine forms three bands called the taeniacoli. They gather the cecum and colon into a series of pouch-like folds calledhaustrations or sacculations.• The outer surface of the large intestine has appendices epiploicae, which are sacs ofomentum distended with fat.• The main function of the colon is water absorption. It absorbs over 90% of the water fromthe contents passing through it.
• ‘Mass movement’ describes the intense contraction beginning halfway along thetransverse colon. It pushes the contents towards the rectum and is responsible forcolonic evacuation.• Hirschsprung’s disease is due to an absence of ganglion cells in Auerbach’s andMeissner’s plexuses in the distal bowel. The colon can become distended with feces,leading to megacolon and acute enterocolitis, which can be fatal.• Crohn’s disease is an inflammatory bowel (IBD) disease characterized by skip lesions(patches of normal bowel in between areas of diseased bowel), granulomas and rosethornulcers. It involves both small and large bowel.• Ulcerative colitis is another inflammatory bowel disease but does not present with skiplesions. The mucosa is granular and hemorrhagic, but does not involve the muscle layerlike Crohn’s disease, and is confined to the colon.• Irritable bowel syndrome (IBS) is diagnosed by the exclusion of structural or metabolicabnormalities and the presence of symptoms. It is described as constipation or diarrheapredominant.• Inguinal hernias can be direct (protruding through the posterior wall of the inguinal canal)or indirect (passing through the inguinal canal).• ‘Diverticulitis’ describes outpouchings in the wall of the gut that have become inflamed.GI malignancy• Most esophageal carcinoma is squamous in origin, although adenocarcinoma can arisefrom Barrett’s esophagus, where there are areas of the distal esophagus lined withcolumnar epithelium.• Gastric carcinoma is associated with blood group A, atrophic gastritis, H. pylori, smoking,adenomatous polyps and low social class. It is especially common in Japan.• Chronic hepatitis B or hepatitis C infections, alcoholic cirrhosis and hemochromatosiscan all cause hepatocellular carcinoma.• Liver metastases may arise from the stomach, lung, colon, breast, uterus and rarely thepancreas. Leukemias and lymphomas also affect the liver.• Most carcinomas of the pancreas are ductal adenocarcinomas. Neither acute nor chronicpancreatitis is a risk factor for this malignancy.• Familial adenomatous polyposis is a rare autosomal dominant disorder that leads tointestinal cancer in more than 90% of cases. It involves the APC gene and ischaracterized by development of hundreds of adenomatous polyps throughout the intestines.• Colorectal cancer is closely related to diet. The dietary risk factors are low fiber, highcarbohydrate and high fat.• Staging of colorectal cancer is by Duke’s classification: -stage A: confined to bowel wall -stage B: extension through the bowel wall -stage C: involvement of regional lymph nodes -stage D: metastatic spread to other organs is sometimes used.• Gastrointestinal lymphoma is rare and can be of B cell or T cell lineage. T celllymphomas are associated with celiac disease.• Mesotheliomas arise from the mesothelium of the peritoneum. Secondary mesotheliomasare often caused by transcoelomic metastases from the ovaries and pancreas.Drugs• Antacids (e.g. salts of magnesium and aluminium) act by neutralizing stomach acid. Theyare useful in symptom relief for gastroesophageal reflux disease.• H2-receptor antagonists (e.g. ranitidine) act on the H2-receptors on oxyntic cells in thestomach and inhibit acid production.• Proton pump inhibitors (e.g. lansoprazole) also act on the acid-secreting cells in thestomach to inhibit acid production.• Misoprostol is a synthetic prostaglandin analogue and helps protect against peptic ulcerformation.• NSAIDs stop the stomach’s protective mechanisms and can lead to peptic ulceration.Therefore, NSAID treatment should be used concurrently with a proton pump inhibitor, Hreceptorantagonist or misoprostol, to suppress acid production.• H. pylori eradication therapy consists of a 2-week course of omeprazole and