GIT Internal Medicine PDF

Introduction  The gastrointestinal tract has many functions such as digestion, absorption and excretion as well as the synthesis of many hormones.  The enteric nervous system is present in the gut to control its function and communicate with the central and peripheral nervous systems.  The ga...

Introduction  The gastrointestinal tract has many functions such as digestion, absorption and excretion as well as the synthesis of many hormones.  The enteric nervous system is present in the gut to control its function and communicate with the central and peripheral nervous systems.  The gastrointestinal tract by the large foreign antigens that contains share in the expression of the immune response. Gastrointestinal symptoms and signs: - Many of the gastrointestinal consultations are for non-organic symptoms (functional). - As 20% of all cancers occur in the gastrointestinal tract, therefore the clinician‘s main task is to recognize an organic disease among the symptoms, signs and investigations. - In developing countries, malnutrition, viral and bacterial infections and parasitic infestations further add to the picture. - The physician must sought for 'Alarm' symptoms- Red flag symptoms:  Dysphagia.  Weight loss.  persistent vomiting.  Anorexia.  Hematemesis or melena. - Patients with these features have a higher possibility of significant gastrointestinal pathology and should be investigated properly. Stomatitis: - It is an inflammation in the mouth from any cause (e,g: ill-fitting dentures). - Angular stomatitis is inflammation of the corners of the mouth. Dysphagia: Difficulty of swallowing. Odynophagia: Painful swallowing. Dyspepsia: It is an inexact term used to describe a number of upper abdominal symptoms such as heartburn, acidity, pain or discomfort, nausea, wind, fullness or belching. 1 Vomiting: Vomiting centers are located in the reticular formation in the medulla and are stimulated by the chemoreceptor trigger zone (CTZ), and by the vagus. Direct stimulation of these zones also occurs by drugs, motion sickness and metabolic causes. Two phases will be experienced by the patient before the actual vomiting : Nausea: associated with autonomic symptoms such as salivation , pallor , sweating. Retching: strong , involuntary , unproductive effort of vomiting associated with contraction of abdominal muscles. The amount and character of vomiting may suggest the pathology: - large in amount and projectile may suggest gastric outlet obstruction or upper intestinal obstruction. - Feculent vomiting may suggest lower intestinal obstruction. Causes of vomiting: -Any Gastrointestinal disease -Infections ( viral and bacterial) -CNS diseases - Increase Intracranial pressure - Vestibular disease - Migraine -Metabolic causes : Chronic renal failure , diabetic Ketoacidosis. -Drugs : e.g Digoxin. -Reflex : e.g. Myocardial infarction. -Psychogenic -Pregnancy -Alcohol Flatulence This term describes excessive wind. It is used to indicate belching, abdominal distension, gurgling and the passage of flatus per rectum. Among causes of increase gas production are colonic bacterial breakdown of non- absorbed carbohydrate, high fiber diet , carbonated drinks. 2 Diarrhea and constipation: - Common complaint in the community and not necessarily due to organic disease. Diarrhea: It can be defined as change of normal bowel habits in the form of - Increase in frequency. - Increase in amount. - Decrease in consistency. Feces exceeding 200g per day when dietary fiber content is low is considered diarrhea - The presence of large volume of watery stool is usually due to organic cause. - Bloody diarrhea is usually due to a colonic cause. - The presence of fever and acute diarrhea for several days is usually due to an infective cause. - A single episode of diarrhea is usually due to dietary changes or may be psychogenic. Constipation: The diagnosis of constipation is difficult as some individuals thought that they must open there bowel on daily basis , the presence of hard stool can be considered also a constipation Constipation can be defined as the presence of 2 or more of the following: - Infrequent Stools 1/4 times of defecation. - Incomplete evacuation >1/4 times of defecation. - Straining in >1/4 times of defecation. - Manual maneuvers as digital evacuation and support of pelvic floor >1/4 times of defecation. 3 Abdominal pain: Pain is stimulated mainly by the stretching of smooth muscle or organ capsules. Severe acute abdominal pain can be due to a large number of gastrointestinal conditions, and normally presents as an emergency. An apparent 'acute abdomen' can occasionally be due to referred pain from the chest, as in pneumonia or to metabolic causes, such as diabetic ketoacidosis or porphyria. Check: - Intensity, character, duration and frequency of the pain - Aggravating and relieving factors - Associated symptoms, including non-gastrointestinal symptoms. Upper abdominal pain: Epigastric pain is very common and is often related to food intake. Although functional dyspepsia is the commonest diagnosis, the symptoms of peptic ulcer disease can be identical. Heartburn (a burning pain behind the sternum) is a common symptom of gastro- esophageal reflux. Right hypochondrial pain: may originate from the gall bladder or biliary tract. Biliary pain can also be epigastric. Biliary pain is typically intermittent and severe, lasts a few hours and remits spontaneously to recur weeks or months later. Hepatic congestion (e.g. in hepatitis or cardiac failure) and sometimes peptic ulcer disease can present with pain in the right hypochondrium. Chronic, persistent or constant pain in the right (or left) hypochondrium in a well- looking patient is a frequent functional symptom. Lower abdominal pain: Pain in the left iliac fossa may be colonic in origin (e.g. acute diverticulitis) but chronic pain is most commonly associated with functional bowel disorders. Lower abdominal pain in women occurs in a number of gynaecological disorders and the differentiation from GI disease is important , but may be difficult. Pain in the right iliac fossa may be due to acute appendicitis or ilececal disease, but may also be functional Abdominal wall pain: Persistent abdominal pain with localized tenderness, which is not relieved by tensing the abdominal muscles. 4 Anorexia and weight loss Anorexia describes reduced appetite. It is common in systemic disease and may be seen in psychiatric disorders. Anorexia often accompanies cancer but is usually a late symptom and not of diagnostic help. Weight loss is almost always due to reduced food intake and is a frequent accompaniment of gastrointestinal diseases. Weight loss in malabsorption disorders is primarily due to anorexia. Weight loss with a normal or increased dietary intake may occur with hyperthyroidism and other catabolic states. Weight loss should always be assessed objectively as patients' impressions are unreliable. Gastrointestinal (GIT) bleeding: It presents with one of the followings: Hematemesis (the vomiting of blood) Melena (the passage of black tarry stools)  It can occur with bleeding from any lesion proximal to the right colon.  It needs more than 50 ml blood.  The black color due to blood altered by passage through the gut.  Following a bleed from the upper G I tract, unaltered blood can appear per rectum, but the bleeding must be massive and is almost always accompanied by shock.  The passage of dark blood and clots without shock is always due to lower GI bleeding. Hematochezia : It is bright red or maroon rectal bleeding. It usually occurs with lesion distal to the ligament of Treitz ( at junction between duodenum and jejunum) but it can occur with massive upper GIT bleeding with rapid transit time. 5  Investigations Routine haematology and biochemistry. followed by endoscopy and radiology, are the principal investigations. Laboratory Stool examination is useful to confirm a patient's complaint (e.g. passing of blood or Steatorrhea). Fecal occult blood test: Can detect blood in stool that is not visibly apparent The new Fecal Immunochemical test (FIT) is more accurate and have fewer false positive tests Fecal calprotectin: when elevated in stool , it indicates intestinal inflammation , calprotectin increase is seen with inflammatory bowel disease Tumour markers of the gastrointestinal tract include CEA for colon cancer, CA 19-9 for pancreatic cancer, also AFP for hepatocellular cancer The Endoscopy Esophagogastroduodenoscopy (EGD) It is the investigation of choice for upper GI disorders with the possibility of therapy and mucosal biopsy. Findings include reflux esophagitis, gastritis, ulcers and cancer Therapeutic EGD is used to treat upper GI haemorrhage and both benign and malignant obstruction. Relative contraindications include severe chronic obstructive pulmonary disease, a recent myocardial infarction. Sigmoidoscopy : Can be considered as part of the routine hospital examination in cases of diarrhea and in patients with lower abdominal symptoms such as a change in bowel habit or rectal bleeding. The rigid sigmoidoscope allows inspection of a maximum of 20-25 cm of distal colon. Flexible sigmoidoscope can reach up to the splenic flexure Colonoscopy It allows good visualization of the whole colon and terminal ileum. Biopsies can be obtained and polyps removed. Benign strictures can be dilated and malignant strictures, stented Cancer, polyps and diverticular disease are the commonest significant findings. 6 Balloon enteroscopy Either double or single balloon, can examine the small bowel from the duodenum to the ileum using specialized enteroscopes in expert centers. Capsule endoscopy Used for the evaluation of obscure GI bleeding (after negative gastroscopy and colonoscopy) and for the detection of small bowel tumors and occult inflammatory bowel disease. It should be avoided if strictures are suspected. Endoscopic ultrasound (EUS) Performed with a gastroscope incorporating an ultrasound probe at the tip. It is used diagnostically for lesions in the esophageal or gastric wall, including the TNM staging of oesophageal/gastric cancer and for the detection and biopsy of pancreatic tumors and cysts. Imaging Full clinical information must be provided before the examination, and ideally, the images obtained should be reviewed with the radiologist to aid interpretation. The optimal technique to be used will depend on local expertise. 1. Plain X-rays of the chest and abdomen Are chiefly used in the investigation of an acute abdomen. Interpretation depends on analysis of gas shadows inside and outside the bowel. Plain films are particularly useful where obstruction or perforation is suspected, to exclude toxic megacolon in colitis and to assess fecal loading in constipation. Calcification may be seen with gall bladder stones and in chronic pancreatitis, though CT is more sensitive for both. 2. Ultrasound involves no radiation and is the first-line investigation for abdominal distension, e.g. ascites, mass or suspected inflammatory conditions. It can show dilated fluid-filled loops of bowel in obstruction and thickening of the bowel wall. It can be used to guide biopsies or percutaneous drainage. In an acute abdomen, ultrasound can diagnose cholecystsitis, appendicitis, enlarged mesenteric glands and other inflammatory conditions. 7 3. Computed tomography (CT) With intraluminal contrast injection ( e,g gastrografin) and intra-venous contrast injection enhance diagnostic capability ( kidney functions must be assessed before the IV injection of the contrast). CT is widely used as a first line investigation for the acute abdomen. CT is sensitive for small volumes of gas from a perforated viscus as well as leakage of contrast from the gut lumen. Inflammatory conditions such as abscesses, appendicitis, diverticulitis, Crohn's disease and its complications are well demonstrated. In high-grade bowel obstruction, CT is usually diagnostic of both the presence and the cause of the obstruction. CT is widely used in cancer staging and as guidance for biopsy of tumor or lymph nodes. CT colonography (virtual colonoscopy) after CO2 insufflation into a previously cleansed colon provides an alternative to colonoscopy for diagnosis of colon mass lesions. 4. Magnetic Resonance Imaging MRI It has the advantage over CT that it uses no radiation and is useful in the evaluation of rectal cancers and abscesses and fistula in the perianal region. It is also useful in small bowel disease and in hepatobiliary and pancreatic disease. 5. Magnetic resonance enterography Is a magnetic resonance imaging technique used to evaluate bowel wall features of both upper and lower gastro-intestinal tract. Although it is usually used for small bowel evaluation. It is a less invasive technique with the advantages of no ionizing radiation exposure, multiplanarity and high contrast resolution for soft tissue. 6. Positron emission tomography (PET) relies on detection of the metabolism of fluorodeoxyglucose. It is used for staging esophageal, gastric and colorectal cancer and in the detection of metastatic and recurrent disease 8 7. Contrast studies Barium swallow: Examines the esophagus and proximal stomach. Its main use is for investigating dysphagia. Double-contrast barium meal: Examines the esophagus, stomach and duodenum, however Gastroscopy is a more sensitive test and enables biopsy of suspicious areas. Small bowel follow-through: Specifically examines the fold pattern and calibre of the small bowel. Specific views of the terminal ileum can be obtained and are used to identify early changes in patients with suspected Crohn's disease or TB Small bowel enema (enteroclysis): A tube is passed into the duodenum and a large volume of dilute barium is introduced. It is particularly used to demonstrate strictures or adhesions when there is suspicion of intermittent obstruction. Generally, this has been replaced by MR enteroclysis. Barium enema examines the colon and is used for altered bowel habit. Colonoscopy and CT colonography have largely replaced this examination for rectal bleeding, polyps and inflammatory bowel disease. Absorbable water-soluble (Gastrografin ) contrast agents should be used in preference to barium when perforation is suspected anywhere in the gut. 9  The esophagus Structure and physiology: - the esophagus is 20 cm long that connects the pharynx to the stomach. - the esophagus is lined by stratified squamous epithelium. - the esophagus is separated from the pharynx by the upper esophageal sphincter (UES). - The lower esophageal sphincter (LES) consists of a 2-4 cm in the distal end of the esophagus that responsible for the prevention of gastric reflux. Symptoms of esophageal disorders 1. Dysphagia: - Difficulty of swallowing. - The characteristics of the progression of dysphagia can be helpful progression over a few weeks suggests a malignant stricture. - The slow onset of dysphagia for solids and liquids at same time suggest motility disorder (e.g. Achalasia). Causes of dysphagia - Disease of mouth and tongue e.g. Tonsillitis. - Neuromuscular disorders e.g. Bulbar palsy , myasthenia gravis. - Esophageal motility disorders e.g. Achalasia ,scleroderma ,diffuse esophageal spasm, diabetes mellitus, chagas' disease. - Extrinsic pressure e.g. Mediastinal glands , goiter ,enlarged left atrium - Intrinsic lesion e.g. Foreign body, stricture: Benign or malignant - carcinoma, esophageal web ,pharyngeal pouch. 2. Odynophagia: Is pain during swallowing and is suggestive of esophagitis. 3. Substernal discomfort, heartburn: This is a common symptom of reflux of gastric contents into the esophagus. 4. Regurgitation: Is the effortless reflux of esophageal contents into the mouth and pharynx. 10 Signs of esophageal disorders The main sign of esophageal disease is weight loss due to reduced food intake. Investigations for esophageal disorders 1. Esophagoscopy. 2. Barium swallow and meal. 3. Manometry: It is used to assess esophageal motor activity. 4. PH monitoring: 24-hour ambulatory monitoring uses a PH-sensitive probe positioned in the lower esophagus 11  Gastroesophogeal reflux disease (GERD) Pathophysiology - The reflux occur when the anti-reflux mechanisms fail, allowing acidic gastric contents to make prolonged contact with the lower esophageal mucosa. - Decrease tone of lower esophageal sphincter (LES). Risk factors 1) Increase intra-abdominal pressure : Pregnancy or obesity 2) Diet: Fat, chocolate, coffee, alcohol and large meals. 3) Drugs: Antimuscarinic, calcium channel blockers, nitrates. 4) Cigarette smoking 5) Hiatus hernia ( described below ) Clinical features - Heartburn is the major feature. The burning is aggravated by lying down and relieved by oral antacids. - Regurgitation of food and acid into the mouth. - Aspiration pneumonia Diagnosis and investigations - The clinical diagnosis can usually be made without investigation. - If there is alarm signs e.g. Weight loss, no response to ppi the following Investigations: 1) 24-hour ph monitoring. 2) Upper endoscopy. 3) Manometry. Esophageal reflux and cardiac ischemia - Reflux pain: Burning, worse on lying down , don‘t radiates to the arms ,worse with hot drinks or alcohol and is relieved by antacids - Cardiac ischemic pain: Gripping or crushing radiates to neck or left arm ,worse with exercise accompanied by dyspnea 12 Treatment - Simple measures :  Simple antacids.  Loss of weight and raising the head of the bed at night.  Reduction in caffeine consumption.  Stop smoking and alcohol intake. - Drugs:  Proton pump inhibitors e.g. Omeprazole, reduce gastric acid secretion and are the drugs of choice for mild cases.  H2 blockers e.g. Ranitidine.  Antacids.  Dopamine antagonist as metoclopramide and domperidone are increase peristalsis and speed emptying. - Endoluminal gastroplication: This recent technique could be performed by endoscopy: endoscopic full-thickness plication (GERDX): A endoscopic device has been designed to inhibit gastroesophageal reflux by placing a transmural plication near the gastroesophageal junction under direct endoscopic visualization. Anti-reflux mucosal ablation (ARMA): Mucosal ablation around the gastroesophageal junction to cause a healing process to re-form the cardiac opening - Surgery: Management of sliding hiatus hernia (described below ) Complications - peptic stricture: since the introduction of PPIs, peptic strictures have become less common. 13  Barrett's esophagus - The normal esophageal squamous epithelium is replaced by metaplastic columnar mucosa. - Premalignant: Esophageal adenocarcinoma. - Barrett's is commonest in middle-aged obese men. - Diagnosis: Endoscopy, chromo-endoscopy. - Treatment : Radiofrequency ablation (RFA). Benign esophageal stricture - Peptic stricture secondary to reflux is the most common cause of benign strictures - They also occur after the ingestion of corrosives, after radiotherapy, after sclerosis of varices. - Dysphagia is usually managed by endoscopic dilatation. - Surgery is sometimes required. Esophageal infections - Infection is a cause of painful swallowing and is seen in immunosuppressed (e.g. On Chemotherapy) and aids. - Infection can occur with: candida - herpes simplex - cytomegalovirus - tuberculosis. - In candidiasis, the characterize by white plaques. - Most patients on large doses of immunosuppressive agents are treated prophylactically for candida with nystatin or amphotericin. 14  Hiatus hernia - A hiatus hernia describes the protrusion of an organ from the abdominal cavity into the chest through the esophageal hiatus. - This is typically the stomach that herniates. - Extremely common disease. Classification Sliding hiatus hernia (85 %): The gastro-oesophageal Junction (GOJ), the abdominal part of the oesophagus, and the cardia of the stomach ‘’slide‟ upwards through the diaphragmatic hiatus into the thorax. ( fig. A ) Rolling or paraesophageal hernia (10%): An upward movement of the gastric fundus through esophageal hiatus occurs to lie alongside a normally placed GOJ. This is a true hernia with a peritoneal sac. ( fig. B ) A mixed type hiatus hernia: which has both a rolling and sliding components Risk factors Age: Is an important risk factor, due to: A combination of age- related loss of diaphragmatic tone, increasing intra-abdominal pressures (e.g. Repetitive coughing), and widening of diaphragmatic hiatus. Increased intra-abdominal pressure: Pregnancy, obesity, and ascites due to upwards displacement of the abdominal viscera. Clinical features of sliding h.h The majority of hiatus hernias are asymptomatic. Gastro-esophageal reflux symptoms: 1) Marked burning epigastric pain: made worse by lying flat and on leaning forwards, patient experiences relief on raising head of bed. 2) Vomiting – Regurgitation. 3) Bleeding and anemia secondary to esophageal ulceration leading either melena, occult blood in stool or hematemesis in severe cases. 4) Dysphagia (esophageal stricture on long-standing cases) 5) Sometimes weight loss in case of long duration vomiting and dyspepsia. Epigastric tenderness in case of associated gastritis 15 Investigations 1.upper endoscopy: It is the standard investigation for esophageal disorders showing upward displacement of the gastro-esophageal junction also (z-line). During inspiration the GOJ is opened and closed in expiration It shows evidence of reflux as hyperemia, fissuring, ulceration or stricture of the lower esophagus Biopsy may be taken from suspicious areas (areas of barrett's) 2. Plain x-ray chest: Fundic air may be evident in the chest Detects chest complications as aspiration pneumonia. CXR: stomach in the chest 3. Barium swallow: Evidence of complication as stricture esophagus. 4. Barium meal in trendlenberg‘s position: Reflux of the barium to the esophagus in GERD Stomach above the diaphragm in big hiatus hernia. 5. Ct abdomen and chest Barium meal: sliding H.H 6. Ph test: Shows increased acid level in the esophagus.(diagnostic for reflux) Treatment: Life-style changes as:  Losing weight.  Decreasing the size of meals.  Avoiding certain acidic foods, such as tomato sauce and citrus  Limiting fried and fatty foods, foods containing caffeine (including chocolate),  Eating meals at least three to four hours before lying down, and avoiding bedtime snacks  Keeping head higher than the rest of body when lying on the back.  Stop smoking  Avoid a tight belt or tight clothing. 16 Medications: I. Antacids that neutralize stomach acid. Ii. H2 blockers. Iii. Proton pump inhibitors. NB: ppi stronger acid blockers than h2 blockers and allow for damaged esophageal tissue to heal. Surgery:  To correct gastro-esophageal reflux by creating a competent valve mechanism at the lower end of the esophagus.  To repair the widened esophageal hiatus Indications:  severe symptoms of reflux with failure of medical treatment  patient has large h.h.  presence of complications: (ulceration, severe inflammation, bleeding, stricture, Barrett‘s) Fundoplication:  Surgery involves pulling the hiatal hernia (fundus) back into the abdomen  Wrapping the fundus of the stomach around the lower portion of the esophagus.  This creates a permanently competent sphincter so that stomach contents will not reflux back into the esophagus  Repair the wide esophageal hiatus of the diaphragm.  The fundic wrap is 360° (in nissen‘s technique) and 270° in (toupet technique)  The procedure can be done laparoscopically better than laparotomy. Complications of fundoplication: O Dysphagia O Inability to belch O Slipped nissen and recurrence of herniation 17  Achalasia of esophagus - It is a primary esophageal motility disorder characterized by failure of LES relaxation and loss of peristalsis in the distal esophagus. Pathophysiology Vagal degeneration: LES contraction and relaxation are regulated through vagus nerve Degeneration of ganglion cells in mesenteric plexus concerned with the inhibitory neurons → increased tone in LES → severe spasm. Causes of achalasia I- primary achalasia: Etiology unknown,hereditary, degenerative, autoimmune Ii-secondary achalasia: (e.g. Secondary to chaga‘s disease) Clinical presentations - Dysphagia for liquids more than solids most significant symptom. (effect of weight). - Difficulty belching. - Regurgitation (especially when lying flat at night) - Heartburn and chest pain in case of esophagitis - Weight loss is minimal and late - Hiccups Complications associated with achalasia Pneumonic aspiration Esophageal cancer 18 Investigations I- Radiographic evaluation II- Manometric evaluation III- endoscopic evaluation I- radiographic evaluation 1- chest x-ray: Markedly dilated esophagus with widening of mediastinum Absent gastric air bubble: Swallowed air does not reach the fundus 2- barium swallows: Diagnostic tool Smooth narrowing of the distal esophagus at the level of the lower esophageal sphincter with the characteristic “bird beak” appearance. The proximal esophagus is markedly dilated Absent gastric air bubble II-esophageal manometry: Confirm the diagnosis Elevated resting LES pressure (spasm). Incomplete LES relaxation. Weak peristalsis of esophageal wall (aperistalsis). III- endoscopic evaluation: To exclude cancer of the gastro-esophageal junction. Detects spasm of the LES. 19 Management Pharmacological agents: Patients who are unable to tolerate more invasive treatment modalities. 1- Calcium channel blockers and nitrates decrease LES pressure. 2- Endoscopic intra-sphincteric injection of botulinum toxin: Blocks release of Acetylcholine at the level of the LES → relaxation of the sphincter Endoscopic techniques: A- pneumatic dilatation: It is the most effective non-surgical treatment option for patients with achalasia. The balloon is inflated at the level of the gastro-esophageal junction to dilate the muscle fibers while leaving the mucosa intact. B- The per-oral endoscopic myotomy, or Poem: It is a minimally invasive endoscopic procedure for the treatment of achalasia Where in the inner circular muscle layer of the lower esophageal sphincter is divided through a submucosal tunnel. Surgical: Laparoscopic heller’s cardio-myotomy Weakens LES by cutting muscle fibers through performing an anterior myotomy across the LES. 20  The Stomach and duodenum Anatomy The stomach consists of: Cardia: adjacent to the gastroesophageal junction. Fundus: dome-shaped and extends above and to the left of the cardia, toward the left hemidiaphragm. Body: extends from the fundus to the lower end of the lesser curve, known as the incisura angularis. Antrum: extends from the incisura to the pyloric canal. Pylorus: area between antrum and duodenum. -There are two sphincters, the gastro-oesophageal sphincter and the pyloric sphincter. - The mucosa of the upper two-thirds of the stomach contains parietal cells that secrete hydrochloric acid, and chief cells that secrete pepsinogen (which initiates proteolysis). - The antral mucosa secretes bicarbonate and contains mucus-secreting cells and G cells, which secrete gastrin, stimulating acid production. - Somatostatin, a suppressant of acid secretion, is also produced by specialized antral cells (D cells). - Mucus-secreting cells are present throughout the stomach and secrete mucus and bicarbonate. - The mucus is made of glycoproteins called mucins. - The 'mucosal barrier', made up of the plasma membranes of mucosal cells and the mucus layer, protects the gastric epithelium from damage by acid , aspirin, NSAIDs alcohol and bile salts. - Prostaglandins stimulate secretion of mucus, and their synthesis is inhibited by aspirin and NSAIDs, which inhibit cyclo-oxygenase - The duodenal mucosa has villi like the rest of the small bowel, and also contains Brunner's glands that secrete alkaline mucus, This along with the pancreatic and biliary secretions, helps to neutralize the acid secretion from the stomach when it reaches the duodenum. 21 Physiology Acid secretion is central to the functionality of the stomach. Acid is not essential for digestion but does prevent some food-borne infections. It is under neural and hormonal control and both stimulate acid secretion through the direct action of histamine on the parietal cell. Acetylcholine and gastrin also release histamine via the enterochromaffin cells. Somatostatin inhibits both histamine and gastrin release and therefore acid secretion. Other major gastric functions are: - Reservoir for food. - Emulsification of fat and mixing of gastric contents. - Secretion of intrinsic factor. 22  Gastritis Gastritis is the inflammation of the gastric mucosa. Gastritis is classified based on the acuity of the condition (acute versus chronic), the histological features of inflammation, or the etiology. Gastropathy is a gastric mucosal disorder without inflammation, featuring epithelial injury and subsequent regeneration. Gastropathy is usually caused by:  Bile reflux.  Hypovolemia.  Chronic congestion as in portal hypertension (called portal hypertensive gastropathy) Gastritis and gastropathy are not mutually exclusive conditions and might sometimes coexist. In clinical practice, gastritis may be accompanied by signs of mucosal injury, whereas gastropathy may present with an inflammatory reaction in the gastric mucosa. Causes of Gastritis : 1-H.pylori gastritis (commonest cause). 2-Erosive and hemorrhagic gastritis (NSAIDs). 3-Autoimmune gastritis. 4-Viral infection (CMV & herpes simplex). 5-Crohn’s disease. Acute Gastritis Acute gastritis refers to a sudden onset of inflammation of the gastric mucosa. In contrast, chronic gastritis refers to long-lasting inflammation of the gastric mucosa. With acute gastritis, a disruption in the gastric mucosa triggers an inflammatory immune response that attracts white blood cells to the site of injury. If the mucosal damage is severe enough, acute gastritis can progress to erosive gastritis, which consists of shallow lesions of the mucosa (i.e. gastric erosions), ulcerations , and small areas of bleeding within the mucosa. 23 Causes of acute gastritis Acute gastritis occurs as a result of weakness or injury to the gastric mucosa, which can allow stomach acids to further damage and inflame the lining. Frequent or long-term use of non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen. ( Erosive and hemorrhagic gastritis ) NSAIDs work by blocking the enzyme cyclo-oxygenase, resulting in inhibition of production of prostaglandin E2 that normally increase the production of gastric mucus and decrease the production of gastric acid. Bacterial infection by Helicobacter pylori (H. pylori) is the commonest cause of gastritis, Although early infection by H. pylori does not cause many symptoms and usually goes unnoticed. However, long-lasting or chronic infection by H. pylori can lead to persistent inflammation of the gastric mucosa , gastric ulcer and duodenal ulcer. Acute gastritis can also occur as a result of extreme physiological stress, often due to major surgery, trauma, severe burns, or severe illnesses. Additional risk factors for developing acute gastritis include increased intake of alcohol and caffeine and exposure to cigarette smoke, all of which can irritate the gastric mucosa. Pathogenesis Acute gastritis usually lasts for a short period of time. In most cases, it resolves spontaneously within a few days or weeks once the inflammation has settled. In other cases, however, acute gastritis can lead to recurrent or long-term inflammation of the gastric mucosa and can lead to chronic gastritis. With time, chronic gastritis can increase the risk of developing other complications, such as stomach ulcers, upper gastrointestinal bleeding, and certain types of stomach neoplasm Signs and symptoms of acute gastritis Most individuals with acute gastritis are asymptomatic or experience mild symptoms, such as loss of appetite, upper abdominal discomfort, belching, nausea, and vomiting. In more severe cases, some individuals may experience upper gastrointestinal bleeding due to gastric erosions and ulcerations of the mucosa. 24 Diagnosis of acute gastritis Initially, an assessment of the individual‘s medical history is performed to identify possible causes of acute gastritis, such as long-term use of NSAIDs, excessive alcohol consumption, or H. pylori infection. Since acute gastritis is often self-resolving, if a clear cause of inflammation can be identified and treated successfully, no additional tests may be required. However, if the diagnosis is uncertain, or if bleeding occurs, an upper endoscopy may be performed to take a direct look at the gastric mucosa and obtain a biopsy sample to examine. Treatment of acute Gastritis Treatment of acute gastritis is aimed at relieving the underlying cause of inflammation. Some cases of acute gastritis resolve without any treatment, while others require treatment via lifestyle changes or medications. Proton-pump inhibitors, such as omeprazole or pantoprazole, may aid in relieving the symptoms of gastritis by helping decrease gastric acid production. Proton-pump inhibitors, along with a combination of various antibiotics, can also be used to treat H. pylori infection. Along with proton-pump inhibitors, medication may feature antacids, including H2 blockers (e.g., famotidine). It is also important, when possible, to remove or avoid any risk factors that may contribute to the inflammation. This may include ceasing use of NSAIDs, reducing caffeine intake, stopping alcohol intake and smoking. 25 Chronic Gastritis There are two types of chronic gastritis: chronic autoimmune gastritis and Helicobacter pylori-associated gastritis. Chronic autoimmune gastritis Affects the body and fundus of the stomach (pangastritis) ; and it represents an example of a type IV hypersensitivity. In chronic autoimmune gastritis, there are auto-antibodies against H+/K+ ATPase on parietal cells and intrinsic factor. leading to atrophic gastritis and loss of parietal cells with achlorhydria and intrinsic factor deficiency lead to decreased absorption of vitamin B12 causing the clinical syndrome of pernicious anemia. Autoantibodies against H+/K+ ATPase decrease gastric acid secretion, thereby causing hypochlorhydria, which is associated with impaired iron absorption and hyperplasia of gastrin cells. Metaplasia, usually of the intestinal type, is almost always in the context of atrophic gastritis As a result, there‘s an increased secretion of gastrin, hypergastrinemia, which is a hormone that has a trophic effect on enterochromaffin-like cells, or ECL cells; therefore, these individuals are at risk for developing neuroendocrine tumors. Finally, in chronic autoimmune gastritis chief cells are also lost and this results in decreased levels of serum pepsinogen. Diagnosis of chronic autoimmune gastritis includes endoscopic biopsy, but also detection of anti-parietal cell antibodies, anti-IF antibodies; and levels of serum gastrin and pepsinogen. 26 Helicobacter pylori Gastritis - H. pylori is a slow-growing spiral Gram-negative flagellate urease-producing bacterium which plays a major role in gastritis and peptic ulcer disease. - It colonizes the mucous layer in the gastric antrum, but is also found in the duodenum in areas of gastric metaplasia. - Antral gastritis is the usual effect of H. pylori infection. It is usually asymptomatic, although patients without ulcers do sometimes experience relief of dyspeptic symptoms after Helicobacter eradication. - Chronic antral gastritis causes hypergastrinaemia due to gastrin release from antral G cells. - The subsequent increase in acid output is usually asymptomatic, but can lead to duodenal ulceration H Pylori gastritis. Epidemiology The prevalence of H. pylori is high in developing countries (80-90% of the population), and much lower (20-50%) in developed countries. Infection rates are highest in lower income groups. Infection is usually acquired in childhood; although the exact route is uncertain, it may be fecal-oral or oral-oral. The incidence increases with age. 27 Pathogenesis -The pathogenetic mechanisms are not fully understood, with the majority of the colonized population remaining asymptomatic throughout their life. -H. pylori is highly adapted to the stomach environment, exclusively colonizing gastric epithelium and inhabiting the mucous layer, or just beneath. -The production of urease enables the conversion of urea to ammonium and chloride, which are directly cytotoxic. -Ulcers are commonest when the infecting strain expresses CagA (cytotoxic- associated protein) and VacA (vacuolating toxin) genes secondary to a more pronounced inflammatory and immune response -The precise mechanism of duodenal ulceration is unclear, as only 15% of patients infected with H. pylori (50-60% of the adult population worldwide) develop duodenal ulcers. - Factors that have been implicated include: increased gastrin secretion, smoking, bacterial virulence and genetic susceptibility. - Gastric ulcer (GU): Gastric ulcers are associated with a gastritis affecting the body as well as the antrum of the stomach (pangastritis) causing parietal cell loss and reduced acid production. - The ulcers are thought to occur because of reduction of gastric mucosal resistance due to cytokine production by the H pylori infection or perhaps to alterations in gastric mucus. Other H. pylori associated diseases : - Gastric adenocarcinoma.  The incidence of distal (but not proximal) gastric cancer parallels that of H. pylori infection in countries with a high incidence of gastric cancer.  Serological studies show that people infected with H. pylori have a higher incidence of distal gastric carcinoma (Gastric B cell lymphoma).  Over 70% of patients with gastric B cell lymphomas (mucosal-associated lymphoid tissue - MALT) have H. pylori. - H. pylori gastritis has been shown to contain the clonal B cell that eventually gives rise to the MALT lymphoma. 28 Diagnosis of Helicobacter pylori infection Diagnosis of H. pylori is necessary if the clinician plans to treat a positive result. This is usually in the context of active peptic ulcer disease, previous peptic ulcer disease or MALT lymphoma, or to 'test and treat' patients with dyspepsia under the age of 55 with no alarm symptoms (i.e. weight loss, anemia, dysphagia, vomiting, or family history of gastrointestinal cancer). Non-invasive methods  Stool antigen test. This is beginning to be the method of choice to determine the H. pylori status. A specific immunoassay using monoclonal antibodies for the qualitative detection of H. pylori antigen is now widely available. The overall sensitivity and specificity is over 95%. It is useful in the diagnosis of H. pylori infection and for monitoring efficacy of eradication therapy. Patients should be off PPIs for 2 weeks but can continue with H2 blockers.  13 C Urea breath test. This is a quick and reliable test for H. pylori and can be used as a screening test. The measurement of 13 CO 2 in the breath after ingestion of 13 C urea. The test requires a mass spectrometer. The test is sensitive (90%) and specific (96%), but the sensitivity can be improved by insuring the patient has not taken antibiotics in the 4 weeks prior and proton pump inhibitors in the 2 weeks before the test. Urea breath test for detection of  Serological tests detect IgG antibodies H pylori Are reasonably sensitive (90%) and specific (83%). They have been used in diagnosis and in epidemiological studies. IgG titres may take up to 1 year to fall by 50% after eradication therapy and therefore are not useful for confirming eradication or the presence of a current infection. 29 Invasive (endoscopy) Biopsy urease test Gastric biopsies, usually antral are added to a substrate containing urea and phenol red. If H. pylori are present, the urease enzyme that they produce splits the urea to release ammonia which raises the pH of the solution and causes a rapid colour change (yellow to red). This enables a patient's H. pylori status to be determined 28 before they leave the endoscopy unit. The test may be falsely negative if patients are taking PPIs or antibiotics. Histology H. pylori can be detected histologically on routine (Giemsa) stained sections of gastric mucosa obtained at endoscopy. Culture Biopsies obtained can be cultured on a special medium, and in vitro sensitivities to antibiotics can be tested. This technique is typically used for patients with refractory H. pylori infection to identify the appropriate antibiotic regimen and routine culture is rare. - Diagnosis of H. pylori is necessary if the clinician plans to treat a positive result. - This is usually in the context of active peptic ulcer disease, previous peptic ulcer disease or MALT lymphoma, or to 'test and treat' patients with dyspepsia under the age of 55y with no alarm symptoms i.e., weight loss, anemia, dysphagia, vomiting, or family history of gastrointestinal cancer. 30 Management Eradication therapy - One of the most commonly used regimen triple therapy for 14 days is : Omeprazole 20 mg twice / day + Amoxicillin 1g twice / day + clarithromycin 500 mg twice /day. Treatment should be given for 14 days. -Metronidazole, clarithromycin, amoxicillin, tetracycline are the most widely used agents. - Bismuth subcitrate (120–300 mg) can be used in a quadriple therapy -Quinolones such as ciprofloxacin are also used when standard regimens have failed (`rescue therapy'). -None of these drugs is effective alone; eradication regimens therefore usually comprise two antibiotics given with powerful acid suppression in the form of a PPI -There is a high incidence of resistance to metronidazole and clarithromycin, particularly in some populations -Oral metronidazole has frequent side-effects -Current recommendations are that all patients with duodenal and gastric ulcers should have H. pylori eradication therapy if the bacteria is present. -Eradication therapy is controversial if the patients have incidental H. pylori infection with no gastric or duodenal ulcer - In developing countries reinfection is common, compliance with treatment may be poor and metronidazole resistance is high (>50%) as it is frequently used for parasitic infections), so failure of eradication is common. 31 Erosive and hemorrhagic gastritis This form of gastritis is usually due to drugs as aspirin and NSAIDs. Aspirin inhibits the synthesis of the protective prostaglandin E2 and F2 α leading to increased acid secretion and decreased formation of the protective mucosal layer. The condition may be chronic due to recurrent use of these drugs as in patients with osteoarthritis. Alcohol may lead to damage of the mucosal protective layer and gastric erosions. Stress gastritis occur in stressful situations as in acute myocardial infarction and cerebrovascular strokes. Clinical picture  Epigastric pain  Dyspepsia  Gastrointestinal bleeding  In alcoholics and chronic NASID’s users, the gastritis become chronic and may be completely asymptomatic. Investigations Upper endoscopy confirms the diagnosis and is mandatory in any patient having hematemesis. Treatment - H2 receptor blockers. - Proton pump inhibitors. - Sucralfate. - When aspirin and NSAIDs should be prescribed additional gastric protective treatment may be added. 32  Peptic ulcer disease - A peptic ulcer consists of a break in the superficial epithelial cells penetrating down to the muscularis mucosa of either the stomach or the duodenum; there is a fibrous base and an increase in inflammatory cells. - Erosions, by contrast, are superficial breaks in the mucosa alone. - Most DUs are found in the duodenal cap; the surrounding mucosa appears inflamed, hemorrhagic or friable (duodenitis). - GUs are most commonly seen on the lesser curve near the incisura, but can be found in any part of the stomach. Epidemiology of peptic ulcer disease: - Duodenal ulcers affect approximately 10% of the adult population and are two to three times more common than gastric ulcers. - Ulcer rates are declining rapidly for younger men and increasing for older individuals, particularly women. - Both DUs and GUs are common in the elderly. - There is considerable geographical variation, with peptic ulcer disease being more prevalent in developing countries related to the high H. pylori infection. - In the developed world the percentage of NSAID-induced peptic ulcers is increasing, as the prevalence of H. pylori declines. Zollinger Ellison syndrome is a rare cause of peptic ulcer disease which is due to a tumor called a gastrinoma. A gastrinoma is a neuroendocrine tumor that is typically located in the duodenal wall or pancreas, and secretes abnormal amounts of gastrin. Excess gastrin stimulates parietal cells to release excess hydrochloric acid, overwhelming normal defense mechanisms and allowing ulcers to develop in the first portion of the duodenum or even in the distal duodenum or jejunum. 33 Clinical features of peptic ulcer disease -The characteristic feature of peptic ulcer is recurrent, burning epigastric pain. - It has been shown that if a patient points with a single finger to the epigastriurm as the site of the pain this is strongly suggestive of peptic ulcer disease. - The relationship of the pain to food is variable and on the whole not helpful in diagnosis. - The pain of a DU classically occurs at night (as well as during the day) and is worse when the patient is hungry, but this is not reliable. - The pain of both gastric and duodenal ulcers may be relieved by antacids. - Nausea may accompany the pain; vomiting is infrequent but can relieve the pain. - Anorexia and weight loss may occur, particularly with GUs. - Persistent and severe pain suggests complications such as penetration into other organs. - Back pain suggests a penetrating posterior ulcer. - Severe ulceration can occasionally be symptomless, as many who present with acute ulcer bleeding or perforation have no preceding ulcer symptoms. - Untreated, the symptoms of a DU relapse and remit spontaneously. - The natural history is for the disease to remit over many years due to the onset of atrophic gastritis and a decrease in acid secretion. -Examination is usually unhelpful ; epigastric tenderness is common in non-ulcer dyspepsia. Investigation of suspected peptic ulcer disease  Patients under 55 years of age with typical symptoms of peptic ulcer disease who test positive for H. pylori can start eradication therapy without further investigation.  Endoscopic diagnosis and exclusion of cancer is required in older patients.  All gastric ulcers must be biopsied to exclude an underlying malignancy and should be followed up endoscopically until healing has taken place.  Endoscopy is required in all patients with alarm symptoms.  Patients with a risk of bleeding or those with complications, i.e. haemorrhage or perforation, should always have a stool test for H. pylori or a 13 C urea breath test 6 weeks after the end of treatment to be sure eradication is successful. 34  FORREST I FORREST II FORREST III NSAIDs and ulcers - Aspirin and other NSAIDs deplete mucosal prostaglandins by inhibiting the cyclo- oxygenase (COX) pathway, which leads to mucosal damage. - Cyclo-oxygenase occurs in two main forms: COX-1, the constitutive enzyme, and COX-2, inducible by cytokine stimulation in areas of inflammation. - COX-2 specific inhibitors have less effect on the COX-1 enzyme in the gastric mucosa. It still produce gastric mucosal damage but less than with other conventional NSAIDs. - Only a small proportion of patients have symptoms (about 5%) and only 1-2% have a major problem, i.e. GI bleed. - Because of the large number of patients on NSAIDs including low-dose aspirin for vascular prophylaxis, this is a significant problem, particularly in the elderly. Figure 14 ; Mechanism of action of traditional NSAID and anti COX -2 inhibitors 35 Treatment - Stop the ingestion of NSAIDs. - A PPI should be given. - H. pylori eradication therapy if H. pylori positive. - In many people with severe arthritis, stopping NSAIDs may not be possible, therefore - Use: -A NSAID with low GI side-effects at lowest dose possible or if there is no cardiovascular risk, a COX-2 NSAID can be used. - Prophylactic cytoprotective therapy, e.g. PPI or misoprostol (a synthetic analogue of prostaglandin for all high-risk patients, i.e. over 65 years; those with a peptic ulcer history, particularly with complications, and patients on therapy with corticosteroids or anticoagulants. - PPIs reduce the risk of endoscopic duodenal and gastric ulcers and are better tolerated than misoprostol, which causes diarrhoea. 36  Gastrointestinal bleeding Acute upper gastrointestinal bleeding - The cardinal features are hematemesis (the vomiting of blood) and melena (the passage of black tarry stools; the black color due to blood altered by passage through the gut). - Melena can occur with bleeding from any lesion proximal to the right colon (the ligament of Teriz). - Following a bleed from the upper G tract, unaltered blood can appear per rectum, but the bleeding must be massive and usually accompanied by shock. - The passage of dark blood and clots without shock is always due to lower GI bleeding. Etiology Peptic ulceration is one of the commonest causes of serious and life-threatening gastrointestinal bleeding. The relative incidence of causes depends on the patient population. Drugs:  Aspirin (even 75 mg/day) and other NSAIDs can produce ulcers and erosions. These agents are also responsible for GI hemorrhage from both duodenal and gastric ulcers, particularly in the elderly.  Corticosteroids in the usual therapeutic doses have no influence on GI hemorrhage.  Ant-coagulants do not cause acute GI hemorrhage but bleeding from any cause is greater if the patient is anti-coagulated. Clinical approach to the patient All cases with a recent (within 48 hours) significant GI bleed should be seen in hospital. An ABCDE assessment is mandatory to determine whether the patient is unstable or stable. 37 The ABCDE approach : Airway (A) Airway obstruction is an emergency. Untreated, airway obstruction causes hypoxia to the vital organs, cardiac arrest, and death. Breathing (B) During the immediate assessment of breathing, it is vital to diagnose and treat immediately life-threatening conditions (e.g. acute severe asthma, pulmonary oedema, tension pneumothorax, and massive haemothorax). Circulation (C) In almost all medical and surgical emergencies, consider hypovolemia to be the primary cause of shock, until proven otherwise. Unless there are obvious signs of a cardiac cause, give intravenous fluid to any patient with cool peripheries and a fast heart rate. Disability (D) Common causes of unconsciousness include profound hypoxia, hypercapnia, cerebral hypoperfusion, or the recent administration of sedatives or analgesic drugs. Exposure (E) To examine the patient properly full exposure of the body may be necessary. The patient‘s dignity must be respected , also care to minimize heat loss. In many, no immediate treatment is required as there has been only a small amount of blood loss. Approximately 85% of patients stop bleeding spontaneously within 48 hours. Emergency management of unstable patient with acute GI bleeding  History and examination. Note co-morbidity  History suggestive of acid – peptic disease  Alcoholic liver diseases / chronic hepatitis / Cirrhosis  History of anticoagulant / anti platelets / NSAIDS / Alcohol binge intake / steroids  History of Coagulation disorder / Blood Dyscrasias  History of Epistaxis or Hemoptysis to rule out the GI source of bleeding  Patients of BURN, Sepsis, Head Trauma may have stress ulcers 38  Monitor the pulse and blood pressure half-hourly  Take blood for hemoglobin, urea, electrolytes, liver biochemistry, coagulation screen, group and cross-matching (2 units initially)  Establish intravenous access - 2 large bore i.v. cannulae Plasma expanders or 0.9% saline are given until the blood becomes available  Give blood transfusion/colloid if necessary. Blood volume: The major principle is to rapidly restore the blood volume to normal. This can be best achieved by transfusion of red cell concentrates via one or more large bore intravenous cannulae; plasma expanders or 0.9% saline are given until the blood becomes available. The pulse rate and venous pressure are the best guides to adequacy of transfusion. A central venous pressure line is inserted for patients with organ failure who require blood transfusion, and in those most at risk of developing heart failure. Indications for blood transfusion are: a. SHOCK (pallor, cold nose, systolic BP below 100 mmHg, pulse >100 b.p.m.) b. Low Hb in patients with recent or active bleeding Hemoglobin levels are generally a poor indicator of the need to transfuse because anemia does not develop immediately as hemodilution has not taken place. However, if the Hb is 1 L per day). 2) Stools are watery in consistency. 3) Stools do not contain pus or blood. 4) Diarrhea typically continues while the patient fasts for 24 to 48 hours. Causes Of Secretory Diarrhea 53 Exudative diarrhea There is mucus, blood, and protein from sites of active inflammation into the bowel lumen If the intestinal mucosa is inflamed and ulcerated, mucus, blood, and pus leak into the lumen and are discharged as stool. This may also create a 1) increased osmotic load and If a large surface area of the bowel lumen is involved, 2) absorption of ions, solutes, and water will also be impaired, and patients may have largevolume diarrhea Inflammation may 3) generate prostaglandins, which stimulate secretion and may increase bowel motility, thus compounding the diarrhea. The severity of the diarrhea and the systemic signs and symptoms depends on the extent of bowel involvement. Causes Of Exudative Diarrhea Altered motility There is increased or decreased contact between luminal contents and mucosal surface. Increased motility of the small intestine Results in decreased contact time of chyme with absorptive surfaces. Large amounts of fluid delivered to the colon may overwhelm its absorptive capacity and result in diarrhea. The reduced contact time in the small intestine may interfere with absorption of fatty acids and bile salts, allowing them to reach the colon where they induce a secretory diarrhea. decreased motility of the small intestine May allow colonization of the small intestine with colonic-type bacteria. 54 Clinical classification of diarrhea Acute diarrhea Approximately 80% of acute diarrheas are due to infections with viruses, bacteria, helminthes, and protozoa. The remainder are secondary to the ingestion of medications, poorly absorbed sugars (fructose polymers or sorbitol). Most infectious diarrheas are acquired through fecal-oral transmission from water, food, or person-to-person contact. Patients with infectious diarrhea often complain of nausea, vomiting, and abdominal pain and have watery, malabsorptive, or bloody diarrhea and fever (dysentery). Food poisoning: is produced by a preformed bacterial toxin that contaminates the food. Bacterial replication in the host is not necessary for the development of disease. Diarrhea resulting from multiplication of organisms in the intestine may be divided into inflammatory-invasive versus noninflammatory-noninvasive categories. Epidemiology Of Acute Infectious Diarrhea 55 Causes of Acute Diarrhea According to the mechanism Remarks about treatment of acute diarrhea Acute diarrhea with fluid and electrolyte depletion is a major cause of mortality, especially in children in developing countries of the world. Fluid repletion by intravenous or oral routes can prevent death. Oral rehydration therapy can be accomplished with a simply prepared oral rehydration solution. The use of Opiate derivatives include paregoric (tincture of opium), diphenoxylate with atropine (Lomotil), and loperamide (Imodium) may help in certain selected cases. They should not be used in patients with fever, systemic toxicity, or bloody diarrhea. Antimicrobials should be only used when there is evidence of mucosal invasion. 56 Refractory diarrhea Refractory chronic diarrhea unresponsive to specific antimicrobial therapy or standard unspecific medication may present a challenging and serious clinical problem. Causes Protracted diarrhea in infants and children Tropical sprue Persistent diarrhea in travelers Post-infectious diarrhea induced irritable bowel syndrome Protracted infectious diarrhea in adults In the United States, some organisms typically cause a prolonged course of diarrhea. Organisms that are difficult to diagnose and are known to cause protracted or prolonged diarrheas include enteropathogenic (enteroadherent) E. coli , Giardia , amoeba , Cryptosporidium , Aeromonas , Yersinia enterocolitica , Clostridium difficile infection is often difficult to clear, and five or more relapses have been observed. Clostridium difficile colitis Originally known as pseudomembranous colitis, was first described as an etiology of diarrhea from antibiotic use. Clostridium difficile infection is triggered by toxin production from the bacteria. Normal bacterial flora is disrupted, the colon is colonized with the Clostridium difficile bacteria, and toxins are released that cause mucosal damage and inflammation Diagnosis requires the presence of 1) diarrhea (at least 3 unformed stools in 24 h) or 2) radiographic evidence of ileus or toxic megacolon, in addition to 3) positive stool testing for Clostridium difficile toxin or 4) colonoscope or pathologic findings showing pseudo membranes. Treatment of Clostridium difficile infection involves discontinuation of the offending antibiotic. Metronidazole is the drug of choice for mild infection. Vancomycin should be used for more severe episodes. Fidaxomicin is a macrocyclic antibiotic which is more active than vancomycin. The role of probiotics in prevention and treatment of Clostridium difficile infection is promising. Fecal microbiota transplantation has typically been reserved for patients who have refractory Clostridium difficile colitis. 57  Pseudomembranous Colitis Post-infectious diarrhea induced irritable bowel syndrome (Brainerd's syndrome) After documented infectious diarrhea, 25% of patients experience pain, bloating, urgency, a sense of incomplete evacuation, and loose stools for 6 months or longer. This syndrome of infectious diarrhea–induced irritable bowel syndrome, also called Brainerd's diarrhea if it is particularly prolonged and accompanied by severe diarrhea. The pathophysiology is thought to be unresolved, mild intestinal inflammation. In some patients, the syndrome may be the result of bacterial overgrowth and may be responsive to non-absorbable antibiotics In others, it may be the result of acquired bile acid malabsorption. Celiac disease also may manifest after intestinal infections, so patients should be screened for it in this setting 58 Chronic Diarrhea Diarrhea lasting >4 weeks warrants evaluation to exclude serious underlying pathology. In contrast to acute diarrhea, most of the causes of chronic diarrhea are noninfectious. Causes Infections Giardia lamblia. Entamoeba histolytica. Tubercle bacillus. Clostridium difficile. Inflammatory bowel disease Ulcerative colitis and Crohn's disease may result in diarrhea of varying severity, depending on the extent and degree of bowel involvement. Diarrhea in Crohn's disease of the small bowel may be compounded by concomitant bile salt and fat malabsorption. Endocrine disorders Zollinger-Ellison syndrome. Hyperthyroidism. Carcinoid. Non-β- cell pancreatic tumor. Malabsorption syndromes Neoplasms Drugs and laxatives Irritable bowel syndrome 59  Malabsorption In the past, it was believed that most malabsorptive diseases manifested with diarrhea, steatorrhea, or both. It is now recognized that many malabsorptive disorders, such as celiac disease, might have subtle clinical presentations or mainly extraintestinal manifestations. Classically, maldigestion is defined as defective intraluminal hydrolysis of nutrients, and malabsorption is defined as defective mucosal absorption. The clinical presentation and complications of maldigestion and malabsorption are similar. Malabsorption can be caused by many diseases of the small intestine as well as by diseases of the pancreas, liver, biliary tract, and stomach. In some of these diseases, malabsorption may be the presenting feature; in others, malabsorption may be only a minor clinical problem or detected only as a laboratory abnormality. Malabsorption is caused by many different diseases. Dietary fat is the nutrient most difficult to absorb. Fat is predominantly insoluble in the aqueous milieu of the intestine and critically depends on all phases of digestion, absorption, and delivery for its assimilation. Steatorrhea (excess fat in the stool) is the hallmark of malabsorption. Malabsorption Syndromes Malabsorption is characterized by suboptimal absorption of fats, fat-soluble and other vitamins, proteins, carbohydrates, electrolytes and minerals, and water. At the most basic level, it is the result of disturbance of at least one of these normal digestive functions: 1) Intraluminal digestion: The process begins in the mouth with saliva, receives a major boost from gastric peptic digestion, and continues in the small intestine, assisted by pancreatic enzyme secretion and the emulsive action of bile. 2) Terminal digestion: which involves the hydrolysis of carbohydrates and peptides by disaccharidases and peptidases, respectively, in the brush border of the small intestinal mucosa. 3) Transepithelial transport: in which nutrients, fluid, and electrolytes are transported across the epithelium of the small intestine for delivery to the intestinal vasculature or to the intestinal lymphatic system. 60  Overall digestive and absorptive process in small intestine The Major Malabsorption Syndromes Disorders of absorption constitute a broad spectrum of conditions with multiple etiologies and varied clinical manifestations. Most, but not all, malabsorption syndromes are associated with steatorrhea, an increase in stool fat excretion of >6% of dietary fat intake. Some malabsorption disorders are not associated with steatorrhea. Disorders of absorption (malabsorption) must be included in the differential diagnosis of chronic diarrhea. Most patients will indicate that they have diarrhea, not that they have fat malabsorption. Mechanism of malabsorption according to the condition 61 Clinical Consequences Of Malabsorption Of Nutrients, Water, And Electrolytes 62 Specific disease examples Lactase Deficiency ( lactose intolerance) Acquired lactase deficiency is the most common cause of selective carbohydrate malabsorption. The prevalence of lactase deficiency is highest (85 to 100%) in persons of Asian, African, and Native-American descent. Adults with lactase deficiency typically complain of gas, bloating, and diarrhea after the ingestion of milk or dairy products but do not lose weight. Unabsorbed lactose is osmotically active, drawing water followed by ions into the intestinal lumen. On reaching the colon, bacteria metabolize lactose to short-chain fatty acids, carbon dioxide, and hydrogen gas. Short-chain fatty acids are transported with sodium into colonic epithelial cells, facilitating the reabsorption of fluid in the colon. If the colonic capacity for the reabsorption of short-chain fatty acids is exceeded, an osmotic diarrhea results. The diagnosis of acquired lactase deficiency can be made by 1) empirical treatment with a lactose-free diet, which results in resolution of symptoms;2) by the hydrogen breath test after oral administration of lactose. Many intestinal diseases cause secondary reversible lactase deficiency, including viral gastroenteritis, celiac disease, giardiasis, and bacterial overgrowth. 63 Intestinal Bacterial Overgrowth In health, only small numbers of lactobacilli, enterococci, gram-positive aerobes, or facultative anaerobes can be cultured from the upper small bowel lumen. Motility And Acid are the most important factors in keeping the number of bacteria in the upper small bowel low. Any condition that produces local stasis or re-circulation of colonic luminal contents allows development of a predominantly colonic flora (coliforms and anaerobes, such as Bacteroides and Clostridium) in the small intestine. This will cause impaired micelle formation by releasing cholylamidases, which deconjugate bile salts. As a result, the concentration of bile salts decreases in the intestinal lumen causing malabsorption of fats and fat-soluble vitamins. Vitamin B12 deficiency and carbohydrate malabsorption also can occur with generalized bacterial overgrowth. Anaerobic bacteria ingest vitamin B12 and release proteases that degrade brush- border disaccharidases. Individuals with bacterial overgrowth usually have low serum vitamin B12 levels but normal or high folate levels. This helps distinguish bacterial overgrowth from tropical sprue. Some Causes Of Bacterial Overgrowth 64 Celiac Disease Celiac disease, also called celiac sprue, nontropical sprue, and gluten-sensitive enteropathy, is an inflammatory condition of the small intestine precipitated by the ingestion of wheat, rye, and barley in individuals with certain genetic predispositions. It is the prototype of a noninfectious cause of malabsorption resulting from a reduction in small intestinal absorptive surface area The basic disorder in celiac disease is sensitivity to gluten, the component of wheat and related grains (oat, barley, and rye) that contains the water insoluble protein gliadin. The small intestinal mucosa, when exposed to gluten, accumulates large numbers of B cells and plasma cells sensitized to gliadin; accumulation of lymphocytes in gastric and colonic mucosa also may occur. Total flattening of mucosal villi (and hence loss of surface area) is the outcome, affecting the proximal more than the distal small intestine. Patients with celiac disease have increased levels of serum antibodies to a variety of antigens, including IgA antiendomysial , anti gliadin and anti tissue transglutaminase antibodies ( TTG Ab). The age of presentation with symptomatic diarrhea and malnutrition varies from infancy to mid-adulthood. About half of adults with celiac disease in the present with anemia or osteoporosis without diarrhea or other gastrointestinal symptoms. These individuals most likely have proximal disease that impairs iron, folate, and calcium absorption but an adequate surface area in the remaining intestine for absorption of other nutrients. Other Extraintestinal Manifestations Of Celiac Disease include  Rash (dermatitis herpetiformis)  Reproductive disorders (infertility, spontaneous abortion)  Neurologic disorders (peripheral neuropathy, ataxia, epilepsy)  Short stature  Psychiatric disorders (depression,  Dental enamel hypoplasia paranoia)  Chronic hepatitis 65  Cardiomyopathy. Disease association with ciliac disease Individuals with significant mucosal involvement present with watery diarrhea, weight loss or growth retardation, and the clinical manifestations of vitamin and mineral deficiencies. Diarrhea is caused by many mechanisms, including 1) Decreased surface area for water and electrolyte absorption. 2) The osmotic effect of unabsorbed luminal nutrients 3) Increased surface area for chloride secretion (crypt hyperplasia) 4) Stimulation of intestinal fluid secretion by inflammatory mediators and unabsorbed fatty acids. Recently The perception that gluten causes gastrointestinal and extra gastrointestinal symptoms in patients who do not have coeliac disease (CD), and are not allergic to wheat, is an increasing clinical problem. This has been called Non-coeliac Gluten Sensitivity (NCGS). It is purely a clinical diagnosis as, in contrast to CD, it has no biomarker or characteristic intestinal biopsy findings. 66 Tropical Sprue And Whipple Disease Are two disorders that exemplify malabsorption syndromes arising from intestinal infection. Tropical sprue resembles celiac disease in symptomatology but occurs almost exclusively in persons living in or visiting the tropics. Small intestinal changes vary from near normal to a severe diffuse enteritis with villus flattening. In contrast to celiac disease, injury is seen at all levels of the small intestine. It is caused by overgrowth of predominantly coliform bacteria. Individuals with tropical sprue classically present with diarrhea and megaloblastic anemia secondary to vitamin B12 and folate deficiency, but some have anemia only. Intestinal biopsy characteristically shows subtotal and patchy villous atrophy in the proximal and distal small intestine. Treatment is a prolonged course of tetracycline (250 mg PO four times daily) or doxycycline (100 mg PO two times daily), folic acid (5 mg/day PO), and, with coexistent deficiency, vitamin B12 injections (1000 μg weekly). Whipple disease is a rare, systemic infection that may involve any organ of the body but principally affects the Intestine, Central Nervous System, And Joints. The hallmark of Whipple disease is a small intestinal mucosa laden with distended periodic acid-Schiff (PAS)-positive macrophages in the lamina propria. The organism responsible for causing Whipple disease is a gram-positive actinomycete, Tropheryma whippelii. Approximately one third of patients have cardiac involvement, most commonly culture negative endocarditis. Occasionally, individuals present with ocular or neurologic disease without gastrointestinal symptoms. Men are affected more commonly than women, particularly white men. Treatment is with a prolonged course of broad-spectrum antibiotics (e.g., ceftriaxone, 2 g/day intravenously (IV) or meropenem 1 g IV three times daily; then trimethoprim 160 mg and sulfamethoxazole 800 mg PO two times daily for 1 year. 67 Diagnostic tests for malabsorption 1) General tests of absorption Quantitative stool fat test Gold standard test of fat malabsorption. Requires ingestion of a high-fat diet (70- 100 g) for 2 days before and during the collection. Stool is collected for 2-3 days. Normally, 90% 68 4) Tests for Mucosal Disease Small-bowel biopsy: Distal duodenal biopsy specimens are usually adequate for diagnosis. Permeability studies: These tests of mucosal integrity are gaining favor as screening tests for small intestinal disease and for monitoring response to treatment 5) Test of Ileal Function SeHCAT test This is a test of bile acid absorption. Seven days after ingestion of radiolabeled synthetic selenium–homocholic acid conjugated with taurine (SeHCAT), whole body retention is measured by a gamma- counting device. The result is expressed as a fraction of baseline ingestion Schilling test: No longer used 69 Algorithm To Chronic Diarrhea And Malabsorption 70  Constipation Constipation is a common gastrointestinal condition characterized by infrequent bowel movements and difficulty passing stool. It happens when the intestines don't move waste to the rectum properly, and pelvic muscles and anal sphincter don't coordinate well to expel stool. Bases on the cause, constipation can be classified as - Primary, also known as idiopathic or functional constipation. - Secondary, which occurs as a side effect of some medications or due to another medical condition, such as malignancy. A focused history and physical examination including digital rectal examinations are mandatory. The patient will report a history of infrequent bowel movements, usually fewer than three stools per week, as well as straining, hard stools, and a feeling of incomplete evacuation. Additionally, history might reveal abdominal discomfort or bloating, and sometimes the patient might report the use of manual maneuvers to defecate. Next, in patients with acute onset constipation, always ask about the ability to pass gas, as failure to pass gas can signal bowel obstruction. Other symptoms that point to obstruction include obstipation, which refers to severe or complete constipation with practically no stool passage and absence of flatus, and can be accompanied by abdominal pain, nausea, and vomiting. By physical examination findings, which typically include fecal impaction and a palpable stool ball. Additionally, some patients may have anal fissures, hemorrhoids, or functional problems like pelvic floor Dys-synergia, this is when the anal sphincter fails to relax or the perineum does not descend when the patient bears down during evacuation. Based on these history and physical exam findings, it's important to look for red flag features that could indicate underlying serious conditions like malignancy. Red flag features: - Hematochezia - Unintentional weight loss - A family history of colorectal cancer - Acute onset of constipation in an older adult - Change in stool caliber - Anemia - The presence of a rectal mass. 71 If any of these red flag features are present, we should consider colorectal cancer and proceed with an endoscopy, such as colonoscopy, with a biopsy to look for obstructive lesions. For patients with no red flag features, to assess for secondary causes of constipation. Secondary causes: - Medication side effects, commonly seen in patients taking opioid medications or iron supplements. - Endocrine or metabolic disorders like hypothyroidism, hypokalemia, or hypercalcemia. - Neurogenic conditions, such as spinal cord injury or multiple sclerosis. In primary constipation a trial of empiric therapy, which includes increasing dietary fiber or starting a fiber supplement, advising sedentary patients to increase their physical activity, and starting an over-the-counter laxative, such as an osmotic agent or a stimulant laxative. If there is an adequate response to empiric therapy no further workup is needed. On the other hand, if they have an inadequate response to empiric therapy, additional testing will be mandatory as anorectal manometry and a balloon expulsion test or defecography. These tests measure pressures inside the rectum and anus and the ability of the pelvic muscles to expel stool from the rectum. These test are abnormal in defecatory disorder. In this condition constipation arises from difficulty in evacuating stool from the rectum. MRI Defecography 72 However, if the anorectal manometry and balloon expulsion test are normal, a colonic transit study will be recommended. During colonic transit studies, patients swallow radioopaque markers, which are then tracked through the gastrointestinal tract using X-rays. If the markers are not passed within the expected time frame, then the test is abnormal, so you can diagnose slow transit constipation. On other side, if the colonic transit study results are normal, diagnose normal transit constipation, which is also referred to as a disorder of the gut-brain axis. There are different types of normal transit constipation. One type is irritable bowel syndrome, which might be marked by alternating episodes of diarrhea and constipation, or dominated by either symptom. Functional Bowel disorders and Irritable Bowel Syndrome Irritable bowel syndrome Functional dyspepsia Functional chest pain of presumed esophageal origin Functional heartburn characterized by chronic, recurrent symptoms of pain and discomfort referred to the lower abdomen, the epigastrium and upper abdomen, and the retrosternum, respectively. They belong to the family of functional gastrointestinal (GI) disorders (also referred to as disorders of brain-gut interactions) that comprise a wide spectrum of often overlapping chronic GI disorders that are common in both the adult and pediatric populations. 73 Irritable bowel syndrome or IBS It is a chronic bowel condition characterized by recurrent abdominal pain associated with abnormal bowel movements. The cause is unknown but could be related to changes in the normal gut microbiota, autonomic dysfunction, altered motility of the gastrointestinal tract, and psychological factors. Based on the clinical manifestations, IBS can be classified as subtypes: - IBS-D ( Diarrhea predominant type ) - IBS-C (constipation-predominant type ) - IBS-M, that includes features of both IBS-D and C. History findings typically include bowel habit changes for at least 6 months, which are usually related to diarrhea or constipation. The patient will also report abdominal pain or discomfort that‘s typically relieved with defecation. In some cases, bloating, or history of depression, anxiety, fibromyalgia, trauma, or recent infectious gastroenteritis. On the physical exam, abdominal tenderness and distention could be elicited. Before diagnosis of IBS , we should exclude the presence of red flag features , these includes:  Hematochezia  Unintentional weight loss  A family history of colon cancer  Acute onset of constipation in an older adult  Change in stool caliber  Anemia  The presence of a rectal mass. 74 If the red flag features are present , we should consider alternative diagnosis. The next step is to order labs to rule out other non-malignant gastrointestinal conditions with similar clinical manifestations , so the requested investigation will be:  CBC to assess for anemia or infection  Inflammatory markers like ESR and CRP to look for inflammation  TSH to assess for thyroid dysregulation  Tissue transglutaminase IgA for patient presenting with diarrhea to evaluate for possible Celiac disease.  Fecal calprotectin to rule out colonic inflammation which may indicate uncontrolled inflammatory bowel disease. Diagnosis of IBS: we should assess for Rome IV Criteria. Which define IBS as recurrent abdominal pain that occurs at least 1 day per week in the last 3 months, with at least two of the following criteria: the pain is related to defecation, a change in stool frequency, or a change in stool form. Management of IBS: Diet modification, which includes consuming soluble fiber, and a trial of a diet low in a specific set of carbohydrates, which is also known as the low FODMAP diet. Some examples of foods that the patient should limit include potatoes, brown rice, oats, and almonds. The use of peppermint oil, has been shown to relax smooth muscle and target spasming of the GI tract. As well as tricyclic antidepressants, like amitriptyline or nortriptyline, which are beneficial in relieving IBS associated abdominal pain. Finally, gut-directed psychotherapy can be beneficial since IBS has a strong association with mental health. Probiotics are not prescribed as there is a lack of evidence supporting their efficacy. For patients with the diarrhea-predominant type, the goal is to increase stool firmness or decrease bowel movement frequency. Treatment can be achieved by the non-absorbed antibiotic rifaximin, which works by addressing bacterial growth associated with diarrhea. On the other hand, there‘s the constipation-predominant type. Treatment for these individuals is geared towards stool softening and increasing bowel movement frequency. There are two options available for treatment. The first one includes chloride channel activators, like lubiprostone. While the second one covers guanylate cyclase activators, like linaclotide which help soften the stool and stimulate bowel movement. 75  Inflammatory bowel disease (IBD) Definition Chronic inflammatory diseases of the gastrointestinal tract. They are diagnosed by a set of clinical, endoscopic, and histologic characteristics, but no single finding is absolutely diagnostic for one disease or the other. Moreover, some patients have a clinical picture that falls between the two diseases and are said to have indeterminate colitis. Epidemiology The highest rates occur in white populations in northern Europe and North America, where the incidence for each disease is about 5 per 100,000 and the prevalence is approximately 50 per 100,000. The peak age at onset is between 15 and 25 years of age, with a second, lesser peak between 55 and 65 years. Pathology 76 Clinical features Ulcerative Colitis The dominant symptom in ulcerative colitis is diarrhea, which is usually associated with blood in the stool. Other symptoms include fever and pain, which may be in either lower quadrant or in the rectum. The initial attack of ulcerative colitis may be Fulminant with bloody diarrhea, but more commonly the disease begins indolently, with non-bloody diarrhea progressing to bloody diarrhea. Crohn's Disease Crohn's disease is marked by one of three major patterns: (1) disease in the ileum and cecum (40% of patients). (2) disease confined to the small intestine (30%). (3) disease confined to the colon (25%). The predominant symptoms are diarrhea, abdominal pain, and weight loss. In patients with colonic disease, especially with rectal involvement, diarrhea is of small volume and associated with urgency and tenesmus. Prolonged inflammation and scarring in the rectum can leave it so rigid and nondistensible that the patient is incontinent. In disease confined to the small intestine, stools are of larger volume and not associated with urgency or tenesmus. Patients with severe involvement of the terminal ileum and those who have undergone surgical resection of the terminal ileum may have bile salt diarrhea or steatorrhea. 77 Extra-intestinal Manifestations Diagnosis Laboratory Studies A complete blood count (CBC), urinalysis, stool analysis and culture and serum chemistry tests are appropriate during the initial evaluation. Serologic examination of blood for specific antibodies , perinuclear antineutrophil cytoplasmic antibodies (pANCA)[frequent in UC], antibodies to Saccharomyces cerevisiae (ASCA) [frequent in CD]. A newly recognized and clinically useful inflammatory marker for UC disease activity is fecal calprotectin, which is a protein secreted by neutrophils in the feces and is therefore a marker of intestinal inflammation. Barium enema and barium follow through Endoscopy Colonoscope of ulcerative colitis Friable mucosa, extensive ulceration, and exudates were detected. Colonoscope of Crohn’s disease A single aphthous ulcer, the Multiple edematous earliest endoscopic finding in inflammatory polyps give a Crohn's disease “cobblestone” appearance to the 78 mucosa. Differential diagnosis Treatment Diet and nutrition Patients with mild symptomatic IBD usually are able to take food orally. The diet should be nutritious. Patients with Crohn's disease who have terminal ileal involvement and steatorrhea may require supplemental fat-soluble vitamins, medium-chain triglycerides, and parenteral vitamin B12. Replacement iron may be indicated in patients who are iron-deficient. 79 Drugs  Sulfasalazine and amino  Immunomodulators  salicylates  Biologic therapy  Corticosteroids.  Probiotics and prebiotics  Antibiotics Corticosteroids Historically, corticosteroids have been used in patients with severe UC or Crohn's disease to induce a remission. Intravenous (IV) steroids (i.e., hydrocortisone 100 mg IV q6h or methyl prednisolone 10-30 mg IV q6-8h) are usually used in such patients. When patients can take oral medications, prednisone at doses of 40 to 60 mg per day is usually given. Antibiotics Bacteria is known to play an important role in the pathogenesis of Crohn's disease and it may play a role in UC. In Crohn's diseases, the indications for the use of antibiotics include perianal disease, localized peritonitis due to microperforation, bacterial overgrowth secondary to a chronic stricture, and as an adjunct to drainage therapy for abscesses and fistulas. Metronidazole ,Ciprofloxacin and Rifaximin can be used. Immunomodulators and biologic therapy Immunomodulator drugs act by blocking lymphocyte proliferation, activation, or effector mechanisms. Azathioprine Methotrexate Cyclosporin can be used. 80 Anti–Tumor Necrosis Factor Antibody (biologic therapy) TNF is a key inflammatory cytokine and mediator of intestinal inflammation. The expression of TNF is increased in IBD. Infliximab is a chimeric mouse-human monoclonal antibody against TNF that is effective in CD. Novel Therapies Anti-Adhesion Molecules Adhesion molecules are important in cellular trafficking in IBD and other diseases, in which immune and inflammatory cells from the periphery are recruited into sites of inflammation. Gut-selective anti-adhesion molecule, vedolizumab shows promising results. Kinase Inhibitors The Janus kinase (JAK) family of kinases, which include JAK1 and JAK3 which are critical for lymphocyte proliferation, function, and activation. Tofacitinib, a novel oral inhibitor of JAK1 and JAK3, was recently shown to be safe and effective for the treatment of moderate to severe active UC. Indications for surgical intervention 81 Complications Ulcerative Crohn’s Colitis Disease Toxic Abscesses megacolon and Fistulas Malignancy Obstruction Perianal Disease Toxic megacolon Toxic megacolon is a condition in which the colon becomes atonic and dilated because of transmural inflammation. It is characteristically associated with severe ulcerative colitis, but it may complicate any severe inflammatory condition of the bowel, including Crohn's disease, bacterial colitis, amoebiasis, pseudomembranous colitis, and ischemic colitis. Worsening of the patient's clinical condition and the development of fever, tachycardia, and leukocytosis. Medical therapy is designed to reduce the likelihood of perforation. If the patient does not begin to show signs of clinical improvement during the first 24 to 48 hours of medical therapy, the risk for perforation increases markedly, and surgical intervention is indicated. Follow up for Malignancy Patients with extensive ulcerative colitis have a markedly increased risk for colon cancer in comparison to the general population beginning 8 to 10 years after diagnosis and increasing with time. There should be surveillance colonoscopy with random biopsies in patients with long standing ulcerative colitis beginning 8 to 10 years after the onset of disease and repeated every 1 to 2 years. If the specimens show dysplasia the patient is sent for colectomy. 82