Manual of Medical Therapeutics PK Dash, UN Panda
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Gastrointestinal Diseases1

 
VOMITING
Vomiting is one of the commonest manifestations of gastrointestinal diseases. It is forceful expulsion of gastric contents through the mouth. Sometimes in oesophageal diseases, food may be expelled out of oesophagus without reaching the stomach. Besides local factors involving stomach and duodenum, medullary causes and reflex causes play an important role.
 
Treatment
Treatment is by antiemetics, antacids, fluid, electrolytes and maintenance of acid base balance. The drugs used are:
  1. Pyridoxine hydrochloride (Vitamin B6) is an effective antiemetic used in morning sickness of pregnancy, hyperemesis gravidarum and radiation sickness.
  2. Antihistaminics: Some antihistaminics have antiemetic property which is utilised for controlling or preventing vomiting, e.g. promethazine theoclate (Avomine), Promethazine hydrochloride (Phenergan), cyclizine (Marzine).
  3. Tranquillizers (Phenothiazine group) having antiemetic effect are prochlorperazine (Stemetil), chlorpromazine (Largactil), triflupromazine (Siquil).
  4. Metoclopramide acts by increasing the resting tone of the gastro-oesophageal sphincter and stimulating co-ordinated gastric movements and increasing the emptying time of stomach. It also acts on the vomiting centre by blocking the dopaminergic receptors. It is given in the dose of 1–2 tablets three times a day before meals. In severe vomiting 10–20 mg IV may be used. Side effects include skin rash, lassitude diarrhoea, dystonia, drowsiness, gynaecomastia. Concurrent use with phenothiazine may precipitate extrapyramidal symptoms. It should not be used in patients with breast cancer.
  5. Ondansetron, 32 mg IV infused over 15 minutes, beginning 30 minutes before chemotherapy or 1.5 mg/kg IV 4 hourly for 3 doses, is effective in preventing vomiting during chemotherapy, e.g. Cisplatin.2
  6. Domperidone (Domstal): This is also a dopamine receptor antagonist and used as antiemetic. It does not cross blood brain barrier and does not cause dystonia. Recommended dose 0.3 to 0.6 mg/kg 3 to 4 times a day.
  7. Antacids: Liquid antacids like Aluminium hydroxide gel (Alludrox MH gel, Digene gel) may be useful if there is heart burn following vomiting, due to hyperacidity or in case of gastritis.
  8. Cisapride 10–20 mg PO morning and at bed time is an important prokinetic agent, but may cause diarrhoea.
  9. Doxylamine succinate 10 mg takes care of vomiting of pregnancy.
 
DIARRHOEA
The term diarrhoea generally means frequent or loose stools. Physiologically diarrhoea may be defined as a faecal output exceeding 200 gm/day when dietary fibre content is low. If the patient presents with a history of frequent small volume stools, associated with urgency and tenesmus, the site of underlying disorder is most likely the distal colon. If the patient presents with a history of stools of large volume, the underlying disease is usually in small intestine (especially if the stools are greasy or show other signs of malabsorption). Acute diarrhoea is of abrupt onset and short duration and usually related to an infection process. Chronic diarrhoea is more gradual in onset and of longer duration, i.e. weeks or months, may be constant or intermittent, may be a functional symptom or manifestation of a serious illness.
 
Aetiology
  1. Drugs causing diarrhoea include laxatives, magnessium hydroxide antacid, antibiotics (See pseudomembranous colitis), digitalis, quinidine, ganglionic blocking agents, colchicine.
  2. Viruses and bacteria causing diarrhoea are Escherichia coli, shigella, salmonella, compylobacter, Yersinia, rotavirus, Norwalk virus.
  3. Parasites causing diarrhoea: Entamoeba histolytica, giardia,
  4. Other like cryptosporidium, Mycobacterium aviumintracellular (MAI). Watery diarrhoea is commonly caused by giardia, cryptosporidiosis or MAI.
 
Treatment
  1. Treatment of cause: Examples include metronidazole for amoebiasis and giardiasis, neomercazole 3for thyrotoxicosis, withdrawing laxatives and withdrawing milk in case of lactase deficiency.
  2. Symptomatic treatment.
    1. Electrolyte solutions replace fluid and salts that are lost in acute diarrhoea. Adults and older children should drink sufficient quantity of ORS (Oral rehydration salt) dissolved in boiled and cooled water. In infants ORS should be used as substitute for fluids in feeds. Quantity of electrolyte solutions given are as per degree of dehydration (e.g. mild, moderate, severe). Glucose saline solutions can be given as intravenous infusions in moderate to severe dehydration.
    2. Antibiotics are not routinely advised unless the patient is severely ill, there is blood or pus in stools. Use of antibiotics is justifiable in shigellosis while waiting for stool culture report. Antibiotics may induce pseudomembranous colitis further aggravating diarrhoea which confuses the clinical picture.
    3. Adsorbents are claimed to adsorb toxic substance that induce diarrhoea in infective cases. They remain popular if rather unpalatable remedy and form part of many anti-diarrhoeal suspension (e.g. Furapac suspension) Dose 60 to 90 ml PO 6 hourly.
    4. Bismuth subsalicylate prevents infection with enterotoxin producing. E. coli and gives symptomatic relief in infectious diarrhoea. It is used along with kaolin and pectin. However it stains stool black.
    5. Opioid agents should be used cautiously in patients with asthma, chronic lung disease, benign prostatic hypertrophy and acute angle-closure glaucoma (e.g. camphorated tincture of opium 4–8 ml PO qid or 4–8 ml PO after each liquid stool, Deodorized tr. of opium 0.5 ml PO tid of qid). Codein is used in acute diarrhoea. Side effects include nausea, vomiting, constipation and respiratory depression.
    6. Diphenoxylate (lomotil) is a meperidine congener. It effectively inhibits excessive gastro-intestinal motility. It has low analgesic activity and is free of parasympatholytic actions and addiction potential when used in the correct dosage range. Dosage is 5 mg tid or qid until initial control of diarrhoea is achieved, followed by maintenance 2.5 mg.4
      Table 1.1   Classification of diarrhoea
      Type
      Mechanism
      Stool Characteristics
      Examples
      Secretory
      Decreased absorption of electrolytes, increased secretion of electrolytes
      Clear
      Na+ + K+ = 2 × osmolality
      No polymorphs
      1. Cholera
      2. Entero toxigenic E. coli enteritis
      3. Islet cell tumors of pancreas causing diarrhoea
      4. Bilesalt enteropathy
      Osmotic
      Nonabsorbable intraluminal molecules
      Clear
      Na+ + K+ = 2 × osmolality
      No polymorphs
      1. Lactase deficiency
      2. Mg++ containing cathartics
      3. Carbohydrate malabsorption states
      Exudative
      Impaired colonic absorption, outpouring of cells and colloids, mucosal sloughing.
      Purulent polymorphs present Gross or occult blood
      1. Ulcerative colitis
      2. Shigellosis
      3. Amoebiasis
      4. Pseudomembranous colitis.
      Anatomical derangement
      Decreased absorption surface
      Variable
      1. Subtotal colectomy
      2. Major small bowel resection
      3. Inadvertent gastro ileostomy.
      Deranged intestinal motility
      —
      Variable
      Irritable bowel syndrome
      5Side effects with overdosage include nausea, vomiting, dizziness, pruritus, skin rash, respiratory depression. It is contraindicated in patients with advanced liver disease and children under 6 years of age.
    7. Loperamide hydrochloride is a non specific antidiarrhoeal agent available as 2 mg capsules/tablets and suspensions alone or in combination with other antidiarrhoeals or antibiotics (e.g. Diarlop, Diarlop Plus, Lopamide, Imosec-S). Dose is 4 mg start then 2 mg after each loose stool maximum 8 caps/tablets (16 mg) in 24 hours for 5 days. Children 2 mg start then 2 mg after each stool, maximum 6 caps/tablets (12 mg) per day.
    8. Specific drugs which may relieve the diarrhoea include prednisolone for inflammatory bowel disease, cholestyramine for bile acid enteropathy, phenothiazines for cholera and E. coli enterotoxins.
    9. Perianal discomfort is relieved by (a) sitz bath for 10 minutes bid or tid, (b) gentle washing of anal region by warm water after each bowel movement, (c) avoiding use of toilet paper, wash clothes, towels and soaps.
 
CONSTIPATION
Constipation may be defined as reduction in frequency of defecation or a constant sensation of rectal fullness with incomplete evacuation of stools, and sometimes painful defecation with passage of hard stools.
 
Aetiology
Aetiology includes insufficient dietary roughage, lack of exercise, suppression of defecatoy urges arising at inconvenient moment, inadequate allotment of time for full defecation, underlying depression, decreased colonic motility, diseases of anal canal, rectum and descending colon, metabolic causes (e.g. hypothyroidisism, porphyria, lead poisoning, etc.) and neurologic disorders (e.g. spinal cord injury, multiple sclerosis, cerebral palsy), prolonged immobilisation.
 
When to Avoid Constipation
(1) Patients with myocardial infarction, (2) Patients with recent abdominal surgery, (3) Patients with haemorrhoids, fissure and other anorectal pathology.6
 
Treatment
Treatment must be preceded by investigations to exclude organic causes such as obstructive pathology (carcinoma, stricture) or a painful condition in perianal region (fissure, fistula, haemorrhoids) by rectal examination, proctosigmoidoscopy and bariumenema.
  1. Bulking agents consist of plant fibres (e.g. bran, ispaghula, sterculie) or synthetic alternatives (e.g. methyl cellulose). They increase the volume of stool by absorbing water and softening of faeces, their onset of action is slow. They are safe except in patients with strictures when obstruction may be precipitated. They may be of value in treating irritable bowel syndrome and diverticular disease if dietary manipulation has failed. Adequate hydration should be maintained. Sodium containing agents should be avoided in cardiac and renal patients (e.g. Isogel, I gol, Ispaghula).
  2. Faecal softners ease straining and are useful in patients with painful anal, ano-rectal conditions. Paraffin lubricates the faecal passage. It is hardly absorbed and is relatively safe, rarely being aspirated and causing lipoid pneumonia, it may leak through the anus and may spoil undergarments. Docusate sodium has a detergent action which reduces surface tension. It may enhance absorption of drugs especially paraffin. It acts as a wetting agent softening the stools. Dioctyl sodium sulfosuccinate is given as 1 caps tid.
  3. Stimulant laxatives increase colonic motility. They may cause colicky pain and in the long run hypokalemia or cathartic colon. They should only be used in specific occasions and avoided in pregnancy and in children. In some preparations, they are combined with stool softeners. These are:
    1. Casteroil acts on large intestine, producing prompt evacuation. Ordinarily it is used only in bowel preparation for a special examination. Dosage is 15–30 ml PO.
    2. Bisacodyl. It stimulates peristalsis in the colon. It may be administered orally or as a suppository. Oral dose 2–3 tablets at bed time.
    3. Senna has the most gentle action, it stimulates the colon and usually produces a single bowel evacuation 6–10 hours after administration (e.g. Evacuol).
    4. Danthron is absorbed in small intestine and is therefore less potent.7
    5. Sodium picosulphate is very powerful, and the liquid preparation allows fine dose adjustment.
  4. Diet An increase in the roughage or fibre is beneficial. The high fibre containing foods include green vegetables, salads (raddish, lettuce), fruits (apples, figs) whole-meal bread, porridge. Adequate fluid should be taken in summer.
  5. Faecal impaction may be treated by senna (e.g. Evacuol, Senokot) 6 tablets bid, failing which, digital evacuation/breakage followed by bowel wash with enema fluid containing dioctyl sodium sulphosuccinate (2% solutions) or with 150 ml olive oil as retention enema may be tried.
 
HICCUP
It is a characteristic sound produced due to violent indrawing of air through approximated vocal cords. The cause is myoclonic contraction of the diaphragm. Afferent impulses for hiccup pass from various sites and structures through vagus and phrenic nerves to the respiratory centre in medulla oblongata of brain and hence the efferent impulses passing through the phrenic nerves to diaphragm.
 
Aetiology
Aetiology includes gastric irritation, indigestion, gastric distension, excess alcohol intake, hepatic encephalopathy, uremia, excessive laughter, tickling.
 
Treatment
  1. Nasogastric suction or icecold saline or sodabicarb gastric lavage is the primary step in managing hiccup.
  2. Local anaesthesia with Lidocaine (e.g. 4% xylocaine viscus) introduced through a ryles tube is a common method to terminate hiccup.
  3. Antacid preparations also help to relieve gastric irritation.
  4. Chlorpromazine, prochloperazine, neoctinum and sometimes amylnitrite capsule inhalation terminates hiccup.
  5. Carbon dioxide inhalation: rebreathing in a paper or plastic bag for 3 to 5 minutes may help.
  6. Phrenic nerve crushing or general anaethesia may be tried in intractable cases.
  7. Treatment of underlying cause is also essential.
8
 
REFLUX OESOPHAGITIS
Reflux oesophagitis may be defined as inflamation and damage to lower oesophageal mucosa caused by regurgitation or reflux of gastric/duodenal contents into the oesophagus secondary to decreased lower oesophageal sphincter (LES) pressure. This process results in bleeding or stricture formation. Hiatus hernia may be seen on radiograph of patients with reflux oesophagitis. However, it is the competency of this sphincter and not the presence of hernia will determine whether acid or gastric juice will enter oesophagus. Symptoms include heartburn, regurgitation, dysphagia, haematemesis and/or malena and pulmonary complaints (wheezing, cough, bronchitis), night awakening.
 
Diagnosis
Diagnosis is by barium meal studies, 24 hour oesophageal pH monitoring, radio isotope technique, upper GI endoscopy with or without biopsy, Bernstein test (reproduction of symptoms with 0.1 N/HCl infused by Ryle's tube into oesophagus).
 
Treatment
The goals of therapy are to reduce the quantity and acidity of stomach contents available for reflux and to elevate lower oesophageal sphincter (LES) pressure.
 
First Line Therapy
  1. Bed blocks raising the head end of bed at night by 4 to 6 inch with bed blocks under it.
  2. Diet discouraging eating or drinking before retiring. Alcohol, chocolate, coffee, aspirin should be avoided.
  3. Body weight the obese patients may achieve a reduction in reflux symptoms by losing weight.
  4. Smoking should be stopped as it lowers LES pressure.
  5. Antacids neutralise the acid contents of the stomach.
    1. For mild and intermittent symptoms, 2 table spoon full of antacid gel at bed time or with heartburn.
    2. For more severe reflux, antacids in same dosages and schedule as in peptic ulcer disease (See Peptic ulcer disease).
  6. Anti cholinergics should not be used as they decrease LES pressure and increase reflux.
 
Second Line Therapy
  1. H2 receptor antagonists Cimetidine (Tagamed) 200 mg tid PO with meals and 400 mg at bed time 9reduces nocturnal acid secretion by 80 per cent and reduces food stimulated acid secretion by 60 per cent. It has no direct effect on LES pressure. Ranitidine (Aciloc, Zinetac) 150 mg bid, Roxatidine 150 mg daily and famotidine 40 mg daily (Topcid) are alternative drugs.
  2. Omeprazole 20–40 mg PO in morning is very effective and given upto 8 weeks; Lansoprazole 30 mg once daily, PO Pantoprazole 40 mg PO daily are the alternatives.
  3. Metoclopramida (Reglan, Maxeran) increases LES pressure and improves gastric emptying at a dose of 10 mg PO 30 minutes before meals and at bedtime. It is supposed to act by antagonizing dopaminergic mechanism facilitating the action of acetylcholine or by a direct effect on the LES circular muscle fibers. The side effects include drowsiness, tiredness and rarely extrapyramidal symptoms.
  4. Bethanecol 25 mg PO given 30 minutes before meals and at bed time also increases LES pressure. But this cholinergic agent should not be used in patients with asthma, bladder outlet obstruction or ischaemic heart disease (IHD).
  5. Cisapride (CIZA) 1 tab 3 to 4 times daily increases LES pressure and is effective in erosive and nonerosive oesophagitis.
 
Third Line Therapy
Third line therapy is surgery which should be considered when all the above forms of therapy have failed and there are significant complications like:
  • Pulmonary aspiration
  • Bleeding
  • Stricture not readily managed by dilatation with bougienage.
 
INFECTIOUS OESOPHAGITIS
It presents as dysphagia and is commonly associated with AIDS, malignancy, diabetes or other immunocompromised states. The common infecting organisms are Candida albicans, HSV, and CMV. The presence of typical oral lesions (thrush, herpetic vesicles) may suggest an etiologic agent. Endoscopy with biopsy and brush cytology helps in diagnosis.
  1. General measure Symptomatic relief by xylocain viscus (2%) wash and swallow 15 ml 3 to 4 hourly.
  2. Candida oesophagitis Mild disease is treated by nystatin oral suspension 4 to 6 lakh units PO qid, or clotrimazole lozenges qid for 2 weeks, or ketoconazole 200 mg bid or 400 mg daily in severe cases. 10In resistant cases, short course of Amphotercin-β (Fungizone) infusion (0.3–0.5 mg/kg/d) or fluconazole 100 mg PO daily for 7 days may be tried.
  3. HSV oesophagitis Acyclovir 5 mg/kg IV 8 hourly for 7 days or 800 mg PO 5 times/d is helpful.
  4. CMV oesophagitis gancyclovir (DHPG) 5 mg/kg IV 12 hourly) may be effective. Oral dose of gancyclovir is 1g tid.
 
CARCINOMA OESOPHAGUS
This malignant condition of oesophagus manifests as progressive dysphagia, rapid weight loss, chestpain, pulmonary aspiration, hoarseness, bleeding and hypercalcemia. This is commonly of two types: squamous cell carcinoma and adenocarcinoma. Diagnosis is made by barium swallow, endoscopy with biopsy and CT scan.
 
Treatment
  1. Squamous cell carcinoma (upper and middle third). High voltage radiotherapy.
  2. Squamous carcinoma (lower third) (i) surgery (oesophagos gastrectomy) (ii) pre-operative radiotherapy plus surgery.
  3. Adenocarcinoma Surgery plus post operative radiotherapy; some physicians also prefer chemotherapy first (e.g. 5-FU, cisplatin), followed by surgery in squamous cell carcinoma. Post operative dilatation is required in all cases.
Other palliative measures Laser ablation, luminal prosthesis to bypass tumor, and bypass surgery. Gastrostomy or jejuno ileum nutritional support is essential.
 
UPPER GI HAEMORRHAGE
Upper gastrointestinal (GI) bleeding manifests as haematemesis and malena. Exsanguinating GI haemorrhage will rarely occur without the appearance of altered or gross blood passed by mouth or rectum. Haematemesis usually indicates bleeding proximal to the ligament of Treitz and malena usually denotes bleeding from the oesophagus, stomach or duodenum, but lesions in jejunum, ileum and even ascending colon may cause malena provided the GI transit time is sufficiently prolonged. Approximately 60 ml of blood is required to produce a single black stool.
 
Aetiology
The common causes of uppder GI bleeding are:
  1. Peptic ulceration
  2. Erosive gastritis11
  3. Variceal bleeding, which collectively account upto 90 per cent of upper GI haemorrhage. Other causes include
    • Mallory Weis tear in gastro-oesophageal junction due to retching
    • Oesophagitis
    • Carcinoma oesophagus
    • Gastric carcinoma
    • Arteriosclerotic aortic aneurysms
    • Primary blood dyscrasias
    • Amyloidosis
    • Osler-Weber-Rendu disease
    • Pseudoxanthoma elasticum
    • Intestinal haemangiomas
    • Peutz-Jeghers syndrome
    • Uraemia
    • Vascular ectasia
 
Evaluation
 
Assessment of blood loss (actual severity) from
  1. Evidence of shock (hypotension, tachycardia, sweating, oliguria, metabolic acidosis).
  2. Establishing postural (supine to upright) drop of systolic BP more than 10 mm Hg or postural rise in pulse rate greater than 20 per min.
  3. Measurement of all blood losses.
  4. Oliguria (urine output 20–30 ml/hour in absence of renal disease).
  5. Skin pallor or sweating.
  6. Gastric aspiration by nasogastric tube showing significant fresh blood although a negative gastric aspirate does not rule out upper GI bleeding.
 
Investigations
  1. Endoscopy is the primary method of investigation which is done: (a) to identify site of bleeding (b) to identify visible vessel. Identification of bleeding site is made in 60–90 per cent cases if endoscopy done within 12 hours and in 32–79 per cent cases if endoscopy done 48 hrs after bleeding (Horler foster). However early endoscopy has not been shown to increase survival nor it changes mortality in patients who stopped bleeding. Endoscopy has a higher diagnostic accuracy than Barium radiography, the latter localising bleeding site in only 22 per cent cases. With the advent of therapeutic endoscopy (electrocautery) or endoscopic sclerotherapy it is hoped that early endoscopy will 12improve survival. Endoscopy is also capable of predicting risk of rebleeding if: (a) a visible vessel is seen in relation to ulcer, (b) fresh bleeding from ulcer, (c) there is adherent clot in base of an ulcer.
  2. Barium radiography often identifies a potential source of haemorrhage but it cannot detect erosive gastritis or Mallory Weiss tear. Normally radiography is avoided in active bleeding patient as retained contrast material may make endoscopy difficult and arteriography impossible in case of rebleeding. After the patient stops bleeding and endoscopy is completed an air contrast barium radiography before elective surgery may be helpful.
  3. Arteriography When endoscopy cannot visualise the bleeding site in stomach or duodenum due to brisk haemorrhage, selective abdominal angiography may localise the site of bleeding. The procedure is successful when rate of bleeding is more than 0.5 ml/minute. The procedure is both diagnostic and therapeutic.
 
Treatment
 
General Treatment
  1. Gastric lavage by icecold saline is done repeatedly through nasogastric tube till bile stained material appears. With appearance of red blood or coffee grounds material, the lavage is again initiated. Normally lavage should be done in left lateral or prone position with the head lowered. It is not necessary to leave nasogastric tube in place as it may interfere with endoscopy.
  2. Replacement and Maintenance of Blood Volume: It is done by intravenous infusion of volume expanders and blood. Central venous pressure (CVP) monitoring is essential for patients with uncertain cardiovascular status. Whole blood is recommended in acute GI bleeding with shock. Packed red cells are recommended for subacute or chronic blood loss or in presence of congestive heart failure. Haematocrit should be maintained at 30–35 per cent and CVP at 8–15 cm H2O. While blood being arranged 3–4 units of normal saline are rapidly transfused. If blood is not available in sufficient quantities colloids such as plasma, dextran should be started.
 
Specific Treatment
  1. Peptic ulcer Upper GI bleeding due to peptic ulcer is treated by:13
    1. H2 antagonists: Intravenous cimetidine or ranitidine offers no advantage over placebo in stopping active upper GI bleeding but its role in healing duodenal ulcer and stopping bleeding due to erosive gastritis in fulminant hepatic failure and in stopping/preventing bleeding of curling's ulcer of burn patient is established.
    2. IV somatostatin may control peptic ulcer bleeding more effectively than either cimetidine or ranitidine.
    3. Laser Endoscopic argon laser photocoagulation is successful as a treatment of bleeding peptic ulcer (therapeutic endoscopy).
    4. Intra-arterial vasopressin stops bleeding in 50–84 per cent of gastric lesions and 12–60 per cent of duodenal ulcer. It is contraindicated in coronary artery disease and in patients with ECG abnormalities.
    5. Botropase A haemocoagulant isolated from the snake venoms used 1 ml IM/IV at 6–8 hours interval stops bleeding by transforming fibrinogen into fibrin. IV injection should be pushed rapidly as blood clot may form inside the syringe if injection is delayed.
    6. Arterial vasopressin 0.5- unit/minute controls bleeding in some patients with stress ulcers, gastritis and peptic ulcers. This therapy requires selective catheterisation of the bleeding artery by a skilled interventional radiologist and continuous infusion of vasopressin.
    7. Arterial embolization with absorbable gelatin sponge (Gelfoam) particles or metal coil springs is also beneficial. Bleeding is controlled (for 24 hours) with embolization in 72 per cent patients. Specific treatable lesions are GI malignancy, duodenal ulcer, bleeding, gastritis, gastric ulcer, stress ulcers, Malory Weiss tear. This method is an alternative to arterial vasopressin and also requires skilled radiologist.
  2. Variceal bleeding is managed by
    1. IV Vasopressin (Pitressin) lowers the portal pressure and stops bleeding by constriction of the splanchnic vessels. It is contraindicated in coronary artery disease. 20 units of vasopressin in 100 ml 5 per cent doxtrose is administered over 20 minutes. It controls bleeding in majority of patients but frequency 14of rebleeding is high. It is given before Sangastaken tube is introduced. Triglycyl lysine vasopressin (t-GLVP) is recent drug which is a depot preparation releasing vasopressin slowly so that effects can last for 10 hours and can be given safely in presence of cardiac diseases.
    2. Somatostatin in variceal bleeding is under evaluation; octreotide is more effective given in a dose of 1 μg/kg bolus followed by 25–50 μg/hour infusion.
    3. Cimetidine or ranitidine given IV 50 mg/h for 48–72 hours prevents erosive gastritis in fulminant hepatic failure.
    4. Balloon tamponade (by Sangstaken-Black More tube) has shown a 78 per cent over all efficacy rate, 14 per cent major complication rate and 3 per cent mortality rate. It has triple lumen, one for gastric balloon, one for oesophageal balloon and 3rd for stomach aspiration. It is introduced through the nose; gastric balloon is inflated, the tube is pulled out until the gastric balloon compreses the gastro-oesophageal junction. Then oesophageal balloon is inflated with 30 mm Hg pressure. The balloons are kept inflated for 24 hours, then deflated but the tube is kept inside for another 24 hours, as it can be re-inflated if bleeding recurs. The complications of balloon tamponade include ischaemic necrosis, perforation of oesophagus, respiratory infection or asphyxia (if tube slips into larynx). A single balloon tube (linton) gives better results in gastric varices. The position of Sangstaken tube and gastric balloon should be checked by X-ray before inflating.
    5. Endoscopic Sclerotherapy by sclerosing agents is found to be 71–96 per cent effective in controlling primary variceal haemorrhage but rebleeding is not unusual and complications like perforation and stricture oesophagus may occur in 5–10 per cent cases. Pulmonary complications like abnormal chest X-ray, pleural effusion and adult respiratory distress syndrome are also common. Intravariceal or paravariceal injection of a sclerosing agent (ethanolamine oleate, sodium tetradecyl sulphate, absolute alcohol) is given once a week for 4 or more injections, or until the varices are completely obliterated. Endoscopy is done there after every 2 or 3 months to detect fresh 15varices which are also injected. Indications of sclerotherapy are:
      • Actively bleeding patients as primary therapy or as a stabilising measure before shunt or transplant surgery.
      • Poor surgical risk and continuous bleeding.
      • Severe liver disease (Child's class C) and as a temporary measure till surgery is arranged.
      • Patients in whom others forms of therapy has failed.
      TIPSS (Transjugular portosystemic stent) can diminish variceal bleed as well as ascites of portal hypertension.
    6. Band ligation Band ligation of varices through endoscope is simple and effective.
    7. Surgery includes the oesophageal variceal ligation procedure and oesophageal transections or a shunt operation. The shunt procedure could be either a total shunt that diverts portal flow completely away from the liver (e.g. portacaval shunt) or a selective shunt that decompresses the coronary veins but does not completely divert portal flow to the lung (e.g. distal splenorenal shunt or DSRS). Either shunt controls variceal bleeding in 95 per cent cases, the over all mortality is 12 per cent; encephalopathy occurs in 16 per cent in portacaval and 6 per cent in DSRS. Emergency shunt surgery is associated with a high mortality. Operative mortality and long term survival may be predicted by the degree of liver decompensation as per childs criteria outlined in Table 1.2.
      Table 1.2   Child's criteria for classification of cirrhotics
      Distinguishing features
      Class A
      Class B
      Class C
      Serum bilirubin
      < 2.0 mg
      2–3 mg
      > 3 mg
      Serum Albumin
      > 3.5 gm/dl
      3-3.5 gm/dl
      < 3 gm/dl
      Ascites
      Nil
      Easily controlled
      Poorly controlled
      Encephalopathy
      Nil
      Mild
      Advanced (coma)
      Nutrition
      Excellent
      Good
      Poor
      16
      Child's class A patients are best suited for shunt surgery with lowest mortality. Though rebleeding is prevented after shunt surgery, shunt induced encephalopathy keeps the mortality rate high. Long-term survival in nonalcoholics with cirrhosis after DSRS is 89 per cent compared to 37 per cent in alcoholics, thereby making DSRS most suitable for non alcoholic cirrhosis.
    8. Propranolol and nadolol have been found beneficial in preventing variceal rebleed in cirrhosis of liver by reducing portal pressure perhaps by decreasing splanchnic blood flow. Oral propranolol is given in a bid dose necessary to reduce heart rate by 25 per cent. But is not yet found effective in non cirrhotic portal fibrosis (NCPF) a disease endemic in Northern and Eastern India. Parenteral propranolol 4–10 mg slow IV followed by 0.04 mg/kg/hour infusion is also tried.
  3. Malory Weiss tear Bleeding in Malory Weiss tear stops spontaneously. However, intra-arterial infusion of vasopressin into left gastric artery or ligation of bleeders by surgery may be needed, if bleeding continues. Nasogastric tube must be removed once diagnosis is established.
  4. Aortoenteric Fistula Any patient with an abdominal aortic graft who has a GI bleeding should be assumed to have a fistula until unless proved other wise. Quick surgical correction is advised to prevent exsanguinous haemorrhage in future.
  5. Prevention of stress ulcer bleeding is by IV cimetidine 300 mg qid or IV ranitidine 50–100 mg qid or hourly antacids till gastric pH is more than 3.5, or sucralfate. Patients at risk include those with head injuries, burns, major trauma, shock, sepsis, respiratory distress, coagulopathy, CNS disease.
  6. Angiodysplasia of stomach and small intestines are now another important cause of occult or recurrent GI bleeding and can be diagnosed by endoscopy. Actively bleeding lesions can be treated by therapeutic endoscopy followed by combined estrogen and progestrone therapy to decrease bleeding episodes.
 
LOWER GI BLEEDING
 
Diagnosis
  1. PR examination, proctoscopy, sigmoidoscopy are must for all cases of lower GI bleeding.17
  2. Radioisotopic detection by
    1. Technetium 99m labelled red blood cell scan can localise bleeding which occurs at a rate of 0.1 ml/min and may be used to investigate less severe and slow bleeding. It can detect as little as 5–70 ml of blood loss occurring within 24 hours after a single isotope injection.
    2. Technetium 99m sulphur colloid scintigraphy can detect bleeding at rates above 0.5 ml/minute. Visualisation takes place within the first 5 minutes after IV injection. But it is less sensitive than radio labelled red blood cell scan.
  3. Arteriography If brisk bleeding continues, arteriography may serve to localise the bleeding site and allow infusion of arterial vasopressin to control bleeding as primary therapy or in preparation for surgery. It may also demonstrate vascular anomalies and tumour.
  4. Colonoscopy is not a very effective diagnostic method as there is inadequate visualisation in presence of active lower GI bleeding. However, after the cessation of active bleeding, it is an useful diagnostic method.
  5. Air contrast barium enema is not suitable in active bleeding as it will interfere with other techniques like angiography and radio isotope scan. It should be performed in stabilised patient.
 
TREATMENT
  1. General treatment (See upper GI haemorrhage).
  2. Specific treatment
    1. Diverticulosis This is the cause of bleeding in 70 per cent cases of lower GI bleeding (although only 3–5 per cent patients of diverticulosis bleed). Selective arterial vasopressin stops bleeding in 90 per cent cases. Surgery is indicated if (a) patient fails to respond to vasopressin, (b) with past h/o bleeding diverticulosis, (c) rebleeding during same hospitalisation.
    2. Angiodysplasia (AV malformation) are usually found in cecum and right colon. Endoscopic electrocoagulation or heater probe application usually controls bleeding.
 
PEPTIC ULCER DISEASE (PUD)
The term peptic ulcer refers to an ulcer in the lower oesophagus, stomach or duodenum, in the jejunum after surgical anastomosis to stomach or rarely in the ileum adjacent to a Meckel's diverticulum. 5–10 per cent of 18general population will have a peptic ulcer during life time. It is a recurrent disease and atleast half of the patients will have a relapse within 5 years. Duodenal ulcers are not malignant, but about 5 per cent gastric ulcers are cancerous. The recent discovery of Helicobacter pylori (H.pylori), a spiral, gram negative urease producing bacteria has changed diagnosis and therapy of PUD. This organism is cultured from stomach in approximately 90 per cent of duodenal ulcer patients and 70–80 per cent gastric ulcer patients.
 
I. Evaluation
  1. Endoscopic biopsy of all gastric ulcers is generally recommended to determine whether the ulcer is benign or malignant. The combination of endoscopy with barium radiography gives 95 per cent success rate in diagnosis. After 4 weeks of the therapy, if the ulcer is unchanged or larger and is not at least 90 per cent healed at 8 weeks, malignancy should be suspected and surgery be considered.
  2. Barium radiograph is also routinely done for both gastric and duodenal ulcer.
  3. H.pylori is detected by serologic testing, carbon labelled urea breath tests, rapid urease assay (clotest), and culture or histologic analysis of endoscopic biopsies.
 
II. Treatment
The goals of ulcer treatment include: (1) relief of symptoms (2) ulcer healing (3) prevention of recurrences and complications.
The therapeutic efficacy of the anti ulcer drugs are compared by their ulcer healing effect. The therapies that have been shown to enhance ulcer healing are: (A) antacids, (B) H2 receptor antagonists, (C) sulphated polysaccharides, (D) several prostaglandin analogues.
Antacids, H2 receptor antagonists and sucralfate are each associated with a 70–85 per cent ulcer healing in 4–6 weeks and treatment with any of the groups is appropriate and effective for peptic ulcer. There is no reason for combination thereby. However, some physicians add either H2 blocker or sucralfate with antacids for relief of ulcer pain.
  1. Antacids: Reduction of gastric acidity is the corner stone of therapy in peptic ulcer disease. Gastric acidity can be effectively reduced with either antacids or H2 blockers. Antacids provide symptomatic relief from pain of peptic ulcer and in large 19doses given for 4–6 weeks they will induce healing, but side effects usually preclude their long-term use. The dose is 30 ml liquid gel taken 1 hour and 3 hour after meals and at bed time, total seven doses. Reports from India have suggested good effect even with half the above dose. Initially this dose is given for 4–6 weeks, if the ulcer fails to heal, another course of 4–6 weeks is required. Gastric ulcer patients may require longer duration of treatment (usually 8–12 weeks).
    Choice of antacid (a) Sodium bicarbonate is the quickest acting and widely used but its use is discouraged as it causes alkalosis. (b) Magnesium hydroxide is a potent antacid, but is contraindicated in renal diseases. It causes osmotic diarrhoea. (c) Aluminium hydroxide is present in most popular preparations but has only moderate buffering capacity. It is mainly used to balance the laxative effect (osmotic diarrhoea) of magnesium hydroxide. It binds phosphate in the lumen and may cause phosphate depletion, an effect which is used in management of renal failure. It binds a number of drugs in intestinal lumen including tetracycline, thyroxin, chloropromazine and this effect may result in decreased absorption of these drugs. (d) Calcium carbonate is an effective and well tolerated antacid but in high doses causes hyper calcemia and hypercalciuria.
    Antiflatulents like simethicone, methyl polysiloxane are commonly added to antacid formulation for adsorbing gas in stomach.
  2. H2 Receptor Antagonists include cimetidine, ranitidine, famotidine, roxatidine and nizatidine, all reduce the gastric acid secretion by blocking H2 receptor of parietal cells. All these drugs make almost all peptic ulcer patients asymptomatic within 7 days and most patients within 48 hours.
    Ulcer healing is seen in over 80 per cent of duodenal ulcers and 70 per cent of gastric ulcers at 6 weeks. A recurrence rate of 55 per cent within 6 months after successful therapy with cimetidine has been reported. After a relapse, healing can be achieved with a further course of weeks with cimetidine/ranitidine/famotidine. The healing rate with cimetidine and ranitidine is lower in gastric ulcer than in duodenal ulcer. It is important to follow gastric ulcers to complete healing to be sure that they are not malignant.20
    1. Uses of H2 receptor antagonists are in:
      • Acute duodenal ulcer and gastric ulcer.
      • Prevention of recurrence of duodenal ulcer.
      • Prophylaxis for GI bleeding.
    2. Dosage: Cimetidine 200 mg tid after meals and 400 mg bed time for 4 to 6 weeks. Patients with gastric ulcer may require treatment for 8–12 weeks or longer like antacids.
      • Ranitidine 150 mg bid after meals for 4 to 6 weeks; 300 mg at bed time is also found to be equally effective.
      • Nizatidine 300 mg bed time or 150 mg bid.
      • Famotidine 20 mg bid or 40 mg at bed time.
      • Roxatidine (e.g. Rotane) 75 mg bid or 150 mg bed time.
    3. Adverse reactions with cimetidine include gynaecomastia, mental confusion in elderly, diarrhoea, impotence, leucopenia, thrombocytopenia, and increases in serum creatinine. Gynaecomastia is commonly seen in patients of Zollinger-Ellison syndrome taking large doses of cimetidine for long periods. Impotency, gynaecomastia and confusion have been reported less frequently with ranitidine, famotidine, roxatidine and nizatidine. Reversible drug induced hepatitis has been reported in all types of H2 blockers and more frequently with ranitidine.
    4. Drug interactions: Cimetidine interferes with metabolism of warfarin, phenytoin, diazepam, chlorodiazepoxide, lidocaine, propranolol, theophylline.
  3. Omeprazole A porton pump inhibitor blocks parietal cell hydrogenpotassium ATPase and profoundly decreases gastric acid secretion. It heals duodenal ulcer in 2–4 weeks. Uncommon side effects include diarrhoea, nausea, dizziness and headaches. The risk of carcinoma after long term use of omeprazole is yet to be confirmed. Dose is 20 mg PO in morning and for Zollinger-Ellison syndrome 3 cap daily. Lansoprazole 30 mg daily and pantoprazole 40 mg daily are equally effective.
  4. Sucralfate (Ulcerfate, Sucrase). It is an aluminium salt of maximally sulphated sucrose. It is as effective as H2 antagonist and high dose antacids in the healing of duodenal ulcers. It appears to act locally at the mucosal surface and protects the ulcer by binding to the necrotic tissue. Dose is 1 gm PO qid, 1 hour before meals and at bed time. Side effect 21is constipation. It interferes with absorption of cimetidine, phenytoin, tetracycline, digoxin and fluoroquinolones.
  5. Carbenoxolone Sodium (e.g. Gastrilcer 50 mg cap) is found to accelerate the healing of both gastric and duodenal ulcer. It is a disodium salt of glycerhizinic acid, a glycoside extracted from liquorice. It is believed to act locally by increasing mucus secretion. It does not neutralise gastric acid nor inhibits gastric acid secretion. However because of its tendency to cause salt and water retention, it should not be prescribed in elderly patients or when there is history of heart failure. Dosage for gastric ulcer is 100 mg (2 caps) tid after meals first week followed by 50 mg (1 cap) tid for 4–6 weeks; for duodenal ulcer, dosage is 50 mg (1 cap) qid, 30 minutes before meals for 6–12 weeks. Side effects include oedema, hypokalemia, hypertension, exacerbation of heart failure.
  6. Deglycerhizinized Liquorice (Caved-S) It is also a preparation of liquorice; however, sodium retaining effect of liquorice is minimal in caved-S. It is as effective as H2 blocker in healing of both gastric and duodenal ulcer. Dosage is 2 tablets 6 times a day between meals for 6 weeks. It has no side effects.
  7. Colloidal Bismuth (De-Nol) It is as effective as H2 antagonists in healing of gastric and duodenal ulcer, though the symptomatic response may not be so rapid. It perhaps interacts with proteins present at the ulcer base to form a coagulum which protects it from acid peptic digestion. It has no side effects.
  8. Anticholinergics are often used for symptomatic pain relief in peptic ulcer. These drugs reduce basal acid by 50 per cent, but used alone in the treatment of duodenal ulcer are much less effective than H2 antagonists. They may have some role as adjuvants to H2 antagonists, in the therapy of Zollinger-Ellison syndrome, and other gastric hypersecretory states. Preparations include Probanthine, Antrenyle duplex, Stellabid.
  9. Sedatives Have no effect on ulcer healing.
  10. Other Drugs Imipramine, Pirenzepine (a tricyclic non depressant), prostaglandin E2 (misoprostol) and gefarnate have been used with varying degrees of success in healing of peptic ulcer and are currently under evaluation.
  11. Diet There is no evidence that bland diet effects the natural history of peptic ulcer. However patients 22should avoid foods that cause epigastric discomfort. Protein and calcium content of milk promote acid secretion, and also excess milk consumption leads to milk alkali syndrome.
  12. Drugs, tobacco, alcohol, aspirin should be avoided in peptic ulcer, or be used in enteric coated form with antacids. Similarly nonsteroidal anti-inflammatory drugs (NSAID) also lead to mucosal ulceration and be avoided. Corticosteroids are also avoided as they may precipitate GI bleeding and aggravate the ulcer. Alcohol in high concentrations damages the gastric mucosal barrier and is associated with gastritis. But patients with history of duodenal ulceration may take alcohol in moderation as the harmful effects of limited alcohol consumption is not established. Smoking is definitely harmful and should be stopped as it: (i) increases the risk of gastric and duodenal ulcer, (ii) delays ulcer healing, (iii) decreases incidence of ulcer healing, (iv) increases rate of ulcer recurrence.
  13. Triple drug regime consisting of amoxycillin 1000 μg bid/clarithromycin 250 μg bid plus tinidazole 500 μg bid plus omeprazole 20 μg bid for 7–10 days is 90 per cent effective in irradicating H. pylori. Cheaper regimes employ tetracycline, ranitidine, metronidazole and sucralfate for upto 2 weeks but a lower cure rate.
 
III. Prevention of Relapse
For repeated relapses or to prevent a relapse, the patient can be placed on a maintenance therapy of cimetidine 400 mg at bed time for several years or even life long. The long-term treatment is safe and has almost no side effect. Ranitidine due to its inhibitory effect on basal acid secretion leads to achlorhydria and not suitable for long-term maintenance therapy. The current practise is to treat each relapse as a fresh case and not to resort to long-term maintenance therapy. Famotidine 40 mg bed time or ranitidine 300 mg bed time for 1 year are used as maintenance.
Stoppage of smoking, avoidance of aspirin, NSAID and corticosteroid should be ensured.
 
IV. Treatment of Complications
  1. Upper GI Bleeding: See Upper GI haemorrhage See B (1)
  2. Gastric Outlet Obstruction: Surgery is the treatment of choice in these conditions.
  3. Perforation
  4. Penetration posteriorly to pancreas
  5. Intractable ulcer not responding to medical therapy.
23
 
V. Morbidity
Even after surgery (Gastrectomy and vagotomy), there may be further complications which need to be treated. They are:
  1. Dumping syndrome manifests as discomfort, pain, vomiting, palpitation, sweating, dizziness. This is treated by altering patient's diet i.e. eating 6 small meals/day of high protein, and low refined carbohydrate. Liquid with meals should be avoided. Anticholinergics may relieve symptoms.
  2. Malabsorption: Mild steatorrhoea, calcium and vitamin D deficiency may occur due to chronic malabsorption of fat, calcium and vitamin D respectively. Fat should be reduced in diet. Calcium (1–2 gm/day), vitamin-D (50,000 units 2–3 times weekly) supplements should be given after surgery as a regular therapy along with other vitamins.
  3. Anaemia due to deficiencies of folate, vit B12 and iron also develops. It should be corrected by supplements of Folic acid (1–5 mg/day orally for 4–5 weeks), Vit B12 (100–1000 microgram/day IM for 2 weeks, then monthly) and ferrous sulphate/gluconate 325 mg tablet qid).
 
VI. Zollinger-Ellison Syndrome
Zollinger-Ellison Syndrome is caused by a gastrin secreting, non-beta islet cell tumour of the pancreas or duodenum resulting in marked gastric acid hypersecretion. Approximately two-thirds of Zollinger-Ellison syndrome are malignant and multiple endocrine neoplasia type. One is associated with 25 per cent of cases of Zollinger-Ellison syndrome. The disease presents commonly as multiple duodenal or jejunal ulcers, or ulcer relapse after surgery of peptic ulcer. Diarrhoea is a common symptom and the syndrome requires heavy dose of omeprazole (initial dose 60 mg/d) or H2-receptor antagonist (famotidine 20 mg qid, upto 160 mg daily) Anti cancer drugs (streptozocin or 5FU) and, surgery (parietal cell vagotomy) may be required.
Non ulcer dyspepsia is a syndrome in which the patient gets persistent ulcer like symptoms in the absence of any evidence of peptic ulcer in barium radiography or endoscopy. Aetiology could be motor abnormalities, microscopic inflammation, H. pylori associated gastritis and associated psychiatric abnormalities. Treatment includes H2-receptor antagonists, psychoactive agents such as alprazolam 0.25–0.50 mg PO bid or tricyclic anti-depressants such as amitriptyline 25–50 mg PO bed time.24
 
GASTROPARESIS OR DELAYED GASTRIC EMPTYING
  1. Causes are a variety of acute and chronic disorders and metabolic derangements (hypokalemia, hyper or hypocalcemia, acute hyperglycemia) or drug induced (e.g.tricyclic antidepressants, narcotics, and anticholinergic agents). Chronic gastric retention is frequently associated with diabetes mellitus, sclerodema, and previous gastric surgery; may be idiopathic or due to many metabolic, endocrine and collagen vascular diseases. Mechanical obstruction could also be a cause.
  2. Diagnosis is made from symptoms (e.g. nausea, bloating, early satiety, and vomiting) or by radio-labelled solid meal to patient followed by scintigraphic analysis.
  3. Treatment includes avoiding high fat, high-fibre meals. Prokinetic agents often helpful include metoclopramide, 10 mg PO qid, or cisapride 10–20 mg PO after breakfast and at bed time. Short-term erythromycin may be helpful.
 
CARCINOMA OF STOMACH
Gastric carcinomas are almost always adenocarcinomas (95%) and the remaining are squamous cell carcinoma, adeno acanthoma, and carcinoid tumour. They originate with equal frequency in the antrum and body of stomach, where it involves the lesser curvature more often than greater curvature; 10–20 per cent occur at cardia. Diagnosis is by barium radiography and endoscopy with biopsy.
 
1. Treatment
Three modalities of treatment be offered to the patient: (A) Surgery (B) Chemotherapy (C) Radiotherapy.
  1. Surgery Surgical removal of tumour offers the only chance of cure and is advised in early resectable cancer without metastasis. It is not advisable in old age and chronic degenerative diseases.
    Operative mortality is as high as 10 per cent and 5-year survival rate after surgery is only 10–15 per cent. If the tumour is restricted to stomach at the time of surgery, 5-year survival in good centres reaches 50–60 per cent.
  2. Chemotherapy Various drugs used are 5-flurouracil (5FU), mitomycin, adriamycin, nitrosoureas (BCNU and methyl CCNU).
    Combination chemotherapy (5 FU + doxorubicin or adriamycin + mitomycin-C) induces a response 25in a higher percentage of cases, but the median survival is still less than 1 year.
  3. Radiotherapy Paliative radiotherapy may be useful to control bleeding and to alleviate pain from bone metastasis. A total dose of 3750 rads when given over 1 month with 5 FU 45 mg/kg by rapid injection in 4 divided doses has shown considerable improvement vis-a-vis either therapy used alone.
 
2. Other Palliative Measures
  1. Diet: Patient is advised to take small frequent meals.
  2. Nausea: Phenothiazines or metoclopramide are useful either orally or parenterally.
  3. Pain may be relieved by pentazocin (fortwin) either orally or parenterally.
  4. Replacement of iron and vitamin B12 is essential to prevent anaemia.
  5. Treatment of postgastrectomy problems may also be required.
  6. Dilatation of obstructing cardia tumours with or without placement of plastic tubular stents.
 
MALABSORPTION SYNDROME
A variety of illnesses can cause malabsorption of nutrients (especially fat). Malabsorption should be considered in patients with unexplained weight loss, steatorrhoea or chemical abnormalities concerned with malabsorption. Once malabsorption of one nutrient is established, investigations must be done to find out malabsorption of any other nutrient.
 
1. Diagnosis
(A) Stool fat excretion of above 6 gm/day, (B) Oral xylose absorption test, (C) Monitoring serum calcium, magnesium, serum carotenes, (D) Prothrombin time estimation for vit-K malabsorption, (E) Barium meal follow through radiography to diagnose Crohn's disease, celiac sprue, jejunal diverticula, etc. (F) Small intestine (Jejunum) biopsy to detect diffuse small intestine disease, giardiasis, Whipple's disease, etc.
 
2. General Treatment
General treatment is aimed at delivering common nutrients, (A) Calcium is given 1–2 gm/day. (B) Magnesium is given as magnesium gluconate 500 mg qid. (C) Iron is given as ferrous sulphate 325 mg tablet qid. (D) Vitamins.
  1. Vit A (25,000 units tablets) 25,000-100,000 units/day for severe deficiency, maintenance is 3000–5000 units/day. (2) Vit D: Initial dose 50,000 units 262–3 times weekly. (3) Vit K: 10 mg IM/orally or vitamine K3 (Menadione) 10 mg orally daily. (4) Folic acid 25 mg IM for 10 days followed by tablets of 5 mg tid for 3 months. (5) Vit B12: 500 microgram IM twice a week for 1 month, then 100–1000 microgram every month.
  2. Vit B Complex Any preparation that contains daily requirements (thiamine 1.6 mg, riboflavin 1.8 mg, niacin is 20 mg) administered bid.
 
3. Specific Treatment
  1. Celiac sprue (Gluten enteropathy). These patients are sensitive to gluten, a protein present in wheat, barley, rye, oat. Small intestine biopsy reveals complete absence of villi. Such patients are advised to avoid ice cream, salad dressing, canned vegetable, istant coffe, mustard, beer, candybars, hotdogs. Severely symptomatic or refractory patients may respond to prednisolone 10–20 mg PO daily. Worsening symptoms warrant barium study or CT abdomen.
  2. Lactase deficiency Patients having deficiency of enzyme lactase should avoid dairy products. Yogurt is tolerated. Lactaid liquid or tablets or lactase capsules (2–4 tablets or capsules with each lactose meal) is available.
  3. Bacterial over growth This is treated by tetracycline 250 mg qid for 3 weeks, then tid for 4 weeks and bid for 4 months. Amoxicillin/clavulanate (augmentin) 250–500 mg PO tid is also helpful. For long-term therapy antibiotics should be given for 2 weeks each month.
  4. Ileal resection Patients often have diarrhoea due to loss of bile salts into colon leading to fat malabsorption. A low fat diet is recommended.
  5. Giardiasis is treated with metronidazole 200 mg tid for 7 days or tinidazole 300 mg tid for 5 days.
 
TROPICAL SPRUE
It is a disease of unknown aetiology occurring in the residents or visitors to tropical countries. The clinical features include chronic diarrhoea, anaemia, nutritional deficiency (of at least two of the 4 nutrients: fat, d-xylose, vitamin B12 and folic acid). Mild to moderate abnormalities of jejunal mucosa on histology is demonstrated.
 
1. Diagnosis
See malabsorption syndrome (Sec I).27
 
2. Treatment
  1. General treatment See malabsorption syndrome Sec II.
  2. Antibiotics In tropical sprue there is bacterial colonisation of small intestine by coliform organisms, Klebsiella and anaerobic bacteria. It is treated by tetracycline (See malabsorption syndrome Sec IIIC).
  3. Diet Lactase deficiency is present in about 60–70 per cent of the Indian population and lactase levels are further lowered in tropical sprue.
Tropical sprue patients should avoid milk, but curd is well tolerated. Chana dal and spices are also to be avoided.
 
ULCERATIVE COLITIS (UC)
This is a chronic inflammatory disease of colon in young adults (of either sex), due to some unknown cause, characterised by exacerbations and remissions and manifested as bloody diarrhoea. Diagnosis is by barium enema, colonoscopy and biopsy.
 
1. Grading of Ulcerative Colitis
From therapeutic point of view ulcerative colitis is graded into 3 types.
  1. Mild disease (60%) The patient has less than 4 bowel actions/day with small amounts of blood, absence of systemic symptoms and has good health.
  2. Moderate disease (25%) Patient has 10–12 bowel actions/day with blood loss, abdominal pain, and no systemic symptoms.
  3. Severe disease (15%) The patient has severe diarrhoea, persistent rectal bleeding and tenesmus, systemic symptoms (anorexia, nausea, vomiting, tachycardia, fever, dehydration). Patient develops hypokalemia and hypoalbuminemia.
 
2. Drugs Used in Ulcerative Colitis
  1. Sulphasalazine is useful in maintenance therapy of ulcerative colitis to prevent relapse and to prolong the length of remissions and in combination with corticosteroids to treat mild acute attacks. It is split by bacteria in colon into sulpha-pyridine and 5 amino salicylic acid. The latter is probably the component responsible for reducing the chance of relapse of the disease, when corticosteroid has controlled the disease. The starting dose is 0.5 gm PO bid, slowly increasing to 0.5–1 gm qid and maintain 1 gm PO bid with food for 1 to 2 years. Side effects include nausea, vomiting, rashes, 28reversible sterility, diarrhoea, headache, agranulocytosis, aplastic anaemia. On occurence of side effects the drug is discontinued for 1–2 weeks, then restarted with smaller dose, 0.125 to 0.25 gm/day. Patients with allergic reaction or G6PD deficiency cannot be maintained on sulphasalazine.
  2. 5-Aminosalicylate (5-ASA) devoid of sulphamoiety of sulphasalazine is a better drug with fewer side effects, common side effect being diarrhoea. It is available as Mesachol used in slow release form or as enema; 4 g enema in distal and left sided colitis. Olsalazine, alternative drug may be used 500 mg PO bid in ulcerative colitis in remission and not recommended in acute stage.
  3. Corticosteroid Prednisolone 40–60 mg/day should be given in acute exacerbations and continued for 3–6 weeks, then gradually tappered; potassium supplementation is to be given. Hospitalised patients can be given hydrocortisone 50–100 mg IV 6 hourly or corticosteroid enema (hydrocortisone 100 mg dissolved in 100 ml water and instilled rectally by means of an infusion set over an hour). Alternate day oral corticosteroid therapy is also found to be effective.
  4. Azathioprine can be used in patients who are unresponsive to conventional medical therapy and are not fit for surgery. Initial dose is 50 mg tid, and tappered over 2–3 months after patient becomes asymptomatic, to 50 mg/day and continued as maintenance dose for a year or more. Side effects include bone marrow depression and teratogenicity. 6-mercaptopurine 50 mg PO daily upto 1.5 mg/kg daily is also used.
  5. Anticholinergics and antidiarrhoeal drugs are often beneficial but be best avoided.
  6. Disodium cromoglycate both oral and rectal suppositories have not yet shown any promising result and still are under evaluation.
  7. IV cyclosporine benefits over 75 per cent of patients, not responding to steroid and is alternative to colectomy.
 
3. Treatment of Acute Attack
  1. Mild disease is usually treated at home. Patient should be trained to receive hydrocortisone enema (See II B above) OD or bid, then reduced to alternate day, subsequently to twice a week and then completely stopped. Prednisolone orally 20 mg/day is given for 1 month, then tappered over next few 29weeks. Sulphasalazine 1 gm bid or tds may also be combined with corticosteroids.
  2. Moderate disease can be managed at home but a fresh case is best treated in hospital and managed as a severe disease or fulminant attack (See C below). Oral and rectal steroids and sulphasalazine are administered as (A) above. Patients with moderate severe disease, who have shown some improvement can be administered azathioprine (See II C above) and disodium cromoglycate (See I E above).
  3. Severe disease or fulminant attack requires treatment in an intensive care unit. Oral food and drinks are stopped. Fluid and electrolyte imbalance is corrected. A broad spectrum antibiotic (e.g. cefoxitin + gentamycin) should be started parenterally (See anti-infective agents). Blood transfusion may be needed to correct severe anaemia. Parenteral hydrocortisone 6 hourly and hydrocortisone enema bid are started (as per I B above). IV hydrocortisone is continued for 5–7 days, then oral corticosteroids (prednisolone 10 mg) started. IV metronidazole 500 mg bid is started to counter anaerobic infection. Plain X-ray abdomen is taken after 2–3 days in erect posture to rule out perforation or toxic megacolon. If no improvement is seen by 5th day, surgery should be contemplated. No anticholinergic or opioid drugs are given in fulminant attack as they precipitate toxic megacolon.
 
4. Surgery in Ulcerative Colitis
The indications for surgery in ulcerative colitis include: (a) Acute ulcerative colitis which fails to respond to medical treatment. (B) Acute ulcerative colitis with relapse in spite of adequate treatment. (C) Chronic disease which leaves a permanently damaged bowel, with stricture formation, fistulas, abscesses, perforation, and bleeding. (D) Long standing disease, with childhood onset and having a risk of carcinoma.
The types of surgery undertaken are: (1) Pancolectomy with ileostomy (bag required) if patient in good condition, (2) Colectomy with ileostomy, (3) Continent ileostomy, (4) Ileorectal anastomosis, (5) Ileoanal anastomosis with ileal reservoir. Where rectum is not grossly involved it may be preserved and ileorectal anastomosis is prefered. Patients after surgery should join an ileostomy association or be enrolled in a stoma therapy clinic.
 
5. Response to Medical Therapy
Poor resonse to therapy is predicted if: (1) Temperature more than 38°C, (2) Maximum pulse rate more than 30100/minute, (3) Bowel frequency more than 12/day, (4) Serum albumin <3 gm/dl during initial 4 days of treatment, (5) Presence of mucosal islands in plain X-ray.
 
6. Prevention of Relapse
Patient with ulcerative colitis will have relapse within 6 months in about 50 per cent cases. Prevention of relapse is by maintenance dose of sulphasalazine (2 gm/day) or azathioprine.
 
7. Cancer in Ulcerative Colitis
There is a tenfold greater incidence of adenocarcinoma of the colon due to ulcerative colitis. The incidence of cancer increases with the duration of disease. At 15 years, the cumulative risk is 5–8 per cent and at 25 years it is 25 per cent. Risk of carcinoma is more if onset is in childhood and after pancolectomy. Regular proctoscopic, colonoscopic examinations with multiple biopsies should be done as a part of follow up in long standing cases.
 
8. Ulcerative Colitis and Pregnancy
An acute exacerbation is managed in the same line as sec III with oral steroids, hydrocortisone enema and maintenance therapy with sulphasalazine. There is no proved injurious effect of corticosteroids or sulphasalazine on foetus.
 
CROHN'S DISEASE (CD)
Crohn's disease is characterised pathologically by localised areas of non specific granulomatous inflammation of any part of GI tract, usually terminal ileum and/or colon, transmural inflammation, bowel wall thickening, linear ulceration, discontinuous involvement (skip areas), fissures, and fistulas. Clinical features include, intermittent colicy pain in abdomen mostly in right lower quadrant, local tenderness and guarding, palpable mass per abdomen and PR, nonbloody diarrhoea, weight loss, fever and clubbing of fingers.
Diagnosis is made by: (a) Sigmoidoscopy/colonoscopy showing nodularity, rigidity, deep and longitudinal ulcers, cobble stoning, skip areas, strictures, fistulas (b) Biopsy, (c) Barium meal follow through showing marked narrowing of a segment of affected bowel (Kanter's strings), alteration of mucosal patterns, deep ulcers, (D) CT showing thickened, matted bowel loops (e) Stool test showing pus cells and RBC.
 
Treatment
  1. Supportive as per ulcerative colitis above31
  2. Drugs:
    1. Prednisolone is useful in active disease and ileal or ileocolonic CD, start 40 mg PO qid, then tapper to 10 to 20 mg daily for 4–6 weeks. In more fulminant disease glucocorticoid should be given parenterally, (methyl prednisolone 20–40 mg IV 6 hourly or the equivalent dose of another glucocorticoid. CD in remission is not usually benefited by glucocorticoids. Like UC, extra intestinal manifestations (eye, skin a joint disease) often respond to glucocorticoids.
    2. Salazopyrin 1 g PO bid in active disease, sometimes used 1 g PO qd for CD in remission, though efficacy not proved. Olsalazine 500 mg PO bid is limited to use by patients with colonic disease.
    3. Immunosuppressive agents (a) Azathioprine 50 mg tid and tappered over 2–3 months to 50 PO qd continued for a year or more, (b) Mercaptopurine 50 mg PO qid upto 1.5 mg/kg/d, have a controversial role in the management of active CD. They may be used when glucocorticoids have failed or when steroid dose is to be reduced. Major side effects include bone marrow suppression and pancreatitis. These drugs should be used by physician with expertise in handling complicated CD patients and experience in monitoring toxicity of such drugs. Cyclosporin may be helpful in acute exacerbation.
    4. Metronidazole 250 mg PO tid is as effective as sulfasalazine in active disease and used in 250 mg bid dose in remission phase. It is contraindicated in pregnancy.
    5. Maintenance of adequate nutrition. Patients with ileitis frequently need parenteral vitamin B12 therapy. Calcium, folic acid, iron, magnesium, vitamin D be given. To prevent oxalate stones in kidney in extensive small bowel CD or with ileal resection, low-fat, low-oxalate, high calcium diet is prescribed. Parenteral nutrition may be necessary in some patients.
    6. Total parenteral nutrition (TPN) and bowel rest with oral medication are advised prior to surgery.
  3. Surgery Resection for fixed obstruction (or stricturoplasty) drainage of abscesses (e.g. perianal), surgery for persistent symptomatic fistulas, intractability.32
    1. Perianal disease drainage of obvious abscess collection with metronidazole 250 mg PO or IV tid.
    2. Fistulas surgical consultation in conjunction with TPN, bowel rest, metronidazole or 6-MP.
    3. Intestinal obstruction due to stricture formation Nasogastric suction, parenteral hydration, glucocorticoids. Patients with intermittent obstructive symptoms should avoid nuts, popcorn, hard skinned fruits.
 
IRRITABLE BOWEL SYNDROME (IBS)
It is the most common gastro-intestinal problem faced by a physician. It is a functional disorder of the GI system that may affect any part of the bowel, but clinical symptoms are largely due to colonic dysfunction i.e. increased colonic motor activity.
 
1. Clinical Features
Include abdominal pain (steady or cramping), in any quadrant of abdomen, may radiate to back or chest; pain is accompanied by constipation or diarrhoea or alternating constipation with diarrhoea, some may have diarrhoea without abdominal pain. Lactase deficiency may mimic IBS. There is commonly an underlying psychiatric disorder i.e. hysteria or depression.
Diagnosis is always by exclusion of other disease; stool RE, sigmoidoscopy and barium enema are minimum investigations.
 
2. Treatment
  1. Diet: The common offending agents are spices, chillies, nuts, pulses (dals), chocolate and milk; role of a high fibre diet (e.g. brown bread, green vegetables, fruits) are not yet established.
  2. Bulk laxatives like wheat bran, isogel, isabgol are advised.
  3. Anticholinergics: like propanthelin (probanthin) 15–30 mg PO qid or belladona 10–15 drops PO tid are recommended for pain relief, though the side effects are common.
  4. Direct acting drugs such as mebaverine (colospa) relax the smooth muscles and do not have any systemic toxic effect. Dose is 100 mg tid or qid.
  5. Psychotropic drugs: often combining an anticholinergic with a tranquilizer (e.g. diazepam, chlorodiazepoxide) or sedatives (e.g. phenobarbitone) may be helpful. Antidepressants (e.g. amitryptiline) are more useful, depressions being very often an under 33lying disorder. A combination of tranquilizer/sedative with antidepressant is more beneficial and may be tried in selected cases.
 
PSEUDOMEBRANOUS COLITIS
This disease is nowadays commonly encountered due to some antibiotics e.g. lincomycin, tetracycline, ampicillin, chloramphenicol. It is also called antibiotic associated colitis. The manifestations include non bloody diarrhoea, fever, cramps etc. Causative organism is “Clostridium difficile”, a gram positive spore bearing anaerobe, which releases an enterotoxin that interferes with the net flux of sodium and water from the mucosa.
 
1. Treatment
  1. General measures The offending antibiotics be discontinued and fluid and electrolyte imbalance be corrected.
  2. Specific antibiotics
    1. Vancomycin in the dose of 125–500 mg PO qid for 10, days. Its disadvantages are high cost, bad taste and a relapse rate of 14–20 per cent after its use.
    2. Metronidazole 2 gm/day for 10–14 days is a more suitable drug in India.
    3. Bacitracin 25,000 units qid is also helpful.
  3. Anion exchange resins like cholestyramine and colestipol are also helpful by reversibly binding with the C difficile toxin. They are mostly beneficial in relapse cases. Colestipol is more palatable and is four times more potent than cholestyramine.
  4. Loperamide and diphenoxylate are potentially dangerous and not recommended in diarrhoea due to pseudomembranous colitis. Corticosteroids have no role.
 
2. Treatment of Relapse
Treatment of relapse is by a reduced dose of vancomycin 125 mg tid for 10–14 days. In a second relapse, anion exchange resins (See I C above) 4 gm bid may be added to vancomycin. Two drugs are delivered at different times. Vancomycin is tappered off but the resin is continued for another 2 weeks after remission of symptoms.
 
ACUTE PANCREATITIS
This disease manifests as severe agonizing pain in epigastrium or right hypochondrium. It is frequently precipitated within 12 to 24 hours of excessive alcohol 34consumption or a large meal. The other causes include gall stones, hyperparathyroidism, hyper lipoproteinemias and a number of drugs including thiazides, oral contraceptives, isoniazid, furosemide and azathioprine.
 
1. Diagnosis
Diagnosis is established by serum amylase > 200 Somogyi units, leucocytosis 15–20,000/cmm, raised serum bilirubin > 4 mg/dl, raised triglycerides, hypoxaemia (PO2 60 < mmHg), decreased serum calcium, plain radiography of abdomen, CT scan and ultrasonography.
 
2. Treatment
Treatment includes removal of causative factors and the following measures
  1. Pain relief is achieved by pethidine and pentazocin. Morphine is avoided as it causes contraction of sphincter of Oddi.
  2. Diet Patient is kept nil orally and on nasogastric suction which is continued till the patient is free of nausea, vomiting and abdominal pain. Once nasogastric suction stopped, patient should be given liquid diet followed by gradual introduction of solid food.
  3. Fluid and electrolyte balance Fluid loss should be replaced after careful monitoring of intake and output. Hypocalcemia should be corrected with IV calcium gluconate. Hypomagnesemia is also corrected. Blood glucose should be monitored as there is tendency for hyperglycemia.
  4. Drugs Aprotinin (Trasylol) has not been found beneficial and is not now recommended. Similarly glucagon, calcitonin, somatostatin, cimetidine or anticholinergics are not found useful.
  5. Antibiotics Prophylactice antibiotics have no role. However when presence of infection is suspected due to raised temperature (greater than 2°C above normal), broad spectrum antibiotics, i.e. combination such as ampicillin plus gentamycin, is started.
  6. Hypovolemia and Circulatory Collapse may be treated by increasing the circulatory volume by blood or plasma transfusion.
  7. Hypoxaemia is managed by doing arterial blood gas analysis and supplemental humidified oxygen therapy. Controlled ventilation may be necessary. IV furosemide is indicated in pulmonary oedema.35
  8. Renal failure is prevented by prompt correction of fluid and electrolyte deficit. In case of oliguria (Urine volume less than 30 ml/hr) circulating plasma volume is increased rapidly. After correction of hypovolemia, diuresis by IV laxis or mannitol may be tried or patient is managed by Peritoneal dialysis (PD).
  9. Myocardial ischaemia and infarction if occurs should be managed. Dopamine improves myocardial function.
  10. Disseminated intravascular coagulation (DIC) may occur which is managed by heparin therapy, platelets and plasma transfusion.
  11. Peritoneal lavage to remove proteolytic enzyme, vasoactive polypeptides and other toxic substances is not found to be beneficial.
 
2. Surgery in Acute Pancreatitis
Surgery in acute pancreatitis may be required in patients with (i) Common bile duct obstruction and cholangitis, (ii) Pancreatic abscess, (iii) Life threatening hemorrhagic pancreatitis.
Early cholecystectomy is recommended in patients having gall bladder disease. Similarly pancreatic abscess has to be drained but pseudopancreatic cyst is initially observed for some time before surgery.
 
CHRONIC PANCREATITIS
Chronic pancreatitis is usually associated with chronic alcoholism. Gallstones are not usually associated with chronic pancreatitis.
 
1. Treatment
Treatment includes abstinence from alcohol and following measures.
  1. Pain relief is achieved by pethidine or pentazocine (Fortwin, Pentawin). Pancreatic extracts given regularly have been found as good as pain relievers (e.g. Festal). Coeliac axis ganglion block is also advocated. The main possibility of narcotic addiction must be kept in mind. Octreotide 200 μg 3 times daily SC may relieve pain.
  2. Malabsorption due to exocrine pancreatic insufficiency can be managed with oral enzyme supplements (e.g. Alvizyme, Festal etc) and a diet high in protein, carbohydrate and low in fat (less that 50 gm/d). As steatorrhoea is diminished with enzyme supplementation, fat content of food is gradually increased. Since gastric acid inactivates the 36enzymes, antacids or cimetidine (ranitidine, omeprazole) is administered alongwith enzymes to maintain gastric pH above 4.0; cimetidine 200 mg is given 1 hour before every meals. Large amounts of Lipase (30,000 units or more) alongwith cimetidine is also found beneficial. Refined sugars are avoided in the presence of diabetes.
  3. Diabetes present in association with chronic pancreatitis usually responds to insulin, and large doses of soluble insulin (100 to 200 units) may be required.
  4. Surgery is indicated in recurrent, persistent or intractable pain. The various surgical procedures adopted are partial or subtotal pancreactomy, pancreaticojejunostomy, sphincteroplasty, sympathectomy; puestow drainage procedure (pancreatic duct is anastomosed to the side of a jejunal loop if duct is dilated).
 
GALLSTONES
Gallstones occur in patients who produce a lithogenic bile. Subsequently as a result of secondary infection, the gall bladder becomes fibrosed and deformed. The majority (over 75%) of patients manifest as a vague discomfort in right hypochondrium, fat intolerance, flatulent dyspepsia and nausea. There may be episodes of biliary colic. Diagnosis is by plain radiography, oral cholecystography and ultrasonography.
 
1. Treatment
Cholocystectomy is the appropriate therapy for majority of patients with symptomatic gall stones, but a minority group may benefit by medical therapy as under:
  1. Diet A low fat diet is usually advised.
  2. Anticholinergics and analgesics are frequently advised for relief of pain.
  3. Medical Dissolution of Gallstones is tried in a group of patients with
    1. Cholesterol gallstone.
    2. Severe cardiac or pulmonary disease that increases the risk of surgical intervention. However, only radioluscent gallstones in a functional gallbladder (well opacified in OCG) qualify for medical dissolution. The two drugs used are chemodeoxycholicacid (CDCA) and Ursodeoxycholicacid (UDCA). CDCA is given in a dose of 13–15 mg/kg/day and side effect of high dose (20–25 mg/kg) CDCA are diarrhoea and hepatotoxicity. As dissolution takes 6–12 37months, periodic USG and serum transaminase estimation are done to see dissolution and exclude side effects. The drug is contraindicated in pregnancy and in liver disease. However complete dissolution of stones occurs in only 30 per cent cases and partial dissolution in another 25 per cent cases. If partial dissolution is not seen in 9–12 months, drugs may be discontinued. Gallstone recurence can occur even after total dissolution by CDCA. UDCA is effective in a lower doses (5–10 mg/kg) and has less side effect compared to CDCA. It is the favoured drug now a days.
  4. Extra Corporeal Shock Wave Lithotripsy (ECSWL) is being utilised for disolution of single radioluscent (only 10% gall stones are radio opaque) gall stones in a functioning gall bladder. When less than 2 cm in diameter the recurrence rate is 3 per cent at 5 years.
  5. Laparoscopic cholecystectomy is the treatment of choice for symptomatic gallbladder disease, whether acute or chronic. Persistence of symptoms after cholecystectomy implies wrong diagnosis, functional bowel disease, or shincter of Oddi spasm.