INFLAMMATORY BOWEL DISEASE :INFLAMMATORY BOWEL DISEASE Scope of presentation: Shivali Dr.Sandhya Satyanarayana Satish Dr.Sandeep H.L


INFLAMMATORY BOWEL DISEASE :INFLAMMATORY BOWEL DISEASE IBD is a group of inflammatory conditions of large intestine ,in some cases small intestine.


FORMS OF IBD :FORMS OF IBD Crohn's disease Ulcerative colitis Collagenous colitis Lymphocyte colitis Ischemic colitis Bechet's syndrome Infective colitis Indeterminate colitis


ULCERATIVE COLITIS :ULCERATIVE COLITIS Ulcerative colitis (Colitis ulcerosa, UC) is a form of inflammatory bowel disease (IBD). Ulcerative colitis is a form of colitis, a disease of the intestine, specifically the large intestine or colon, that includes characteristic ulcers, or open sores, in the colon. The main symptom of active disease is usually diarrhea mixed with blood, of gradual onset. Ulcerative colitis is, however, a systemic disease that affects many parts of the body outside the intestine


AETILOGY :AETILOGY Exact cause is unknown. Several causes have been suggested .it includes GENETIC FACTORS ENVIRONMENTAL FACTORS AUTO IMMUNE DISEASE SEVERAL OTHER THEORIES


Genetic factors :Genetic factors A genetic component to the etiology of ulcerative colitis can be hypothesized based on the following Aggregation of ulcerative colitis in families. Identical twin concordance rate of 10% and dizygotic twin concordance rate of 3% Ethnic differences in incidence


ENVIRONMENTAL FACTORS :ENVIRONMENTAL FACTORS Diet: as the colon is exposed to many different dietary substances which may encourage inflammation, dietary factors have been hypothesized to play a role in the pathogenesis Breastfeeding: There have been conflicting reports of the protection of breastfeeding in the development of inflammatory bowel disease. One Italian study showed a potential protective effect. 3. Other childhood exposures, or infections


Autoimmune disease :Autoimmune disease Some sources list ulcerative colitis as an autoimmune disease Disease in which immune system malfunctions,attacking some parts of body. But it is seen that surgical removal of large intestine cures disease,including manifestations outside digestive system. This suggests cause of disease is in colon itself,not in immune system.


Alternative theories :Alternative theories Levels of sulfate-reducing bacteria tend to be higher in persons with ulcerative colitis. This could mean that there are higher levels of hydrogen sulfide in the intestine. An alternative theory suggests that the symptoms of the disease may be caused by toxic effects of the hydrogen sulfide on the cells lining the intestine.


Epidemiology :Epidemiology The incidence of ulcerative colitis in North America is 10-12 cases per 100000 Peak incidence at age 15-25 There is bimodal distribution.second peak in incidence occuring in 6th decade of life Disease affects females more than males.


Clinical presentation :Clinical presentation Diarrhoea mixed with blood and mucus. Gradual onset. Signs of weight loss. Different degrees of abdominal pain ranging from mild discomfort to severely painful cramps.


CLASSIFICATION :CLASSIFICATION Extent of involvement The disease is classified by the extent of involvement, depending on how far up the colon the disease extends 1.Distal colitis a.Proctitis: Involvement limited to the rectum. b.Proctosigmoiditis: Involvement of the rectosigmoid colon, the portion of the colon adjacent to the rectum. c.Left-sided colitis: Involvement of the descending colon, which runs along the patient's left side, up to the splenic flexure and the beginning of the transverse colon. 2.Extensive colitis, inflammation extending beyond the reach of enemas: Pancolitis: Involvement of the entire colon


Slide 15:Severity of disease: Mild disease : fewer than 4 stools daily,no signs of systemic toxicity,normal ESR,mild abdominal pain. Moderate disease :more than 4 stools daily,minimal signs of toxicity,anaemia,moderate abdominal pain,low grade fever. Severe disease :more than 6 bloody stools,evidence of toxicity with fever,tachycardia,elevated ESR Fulminant disease :more than 10 stools,bleeding,toxicity,abdominal tenderness,blood transfusion requirement.unless treated will lead to death.


Extraintestinal features :Extraintestinal features Iritis Episcleritis Aphthous ulcers involving tongue,lips,palate,pharynx. Arthritis Ankylosing spondylitis Erythema nodusum Deep venous thrombosis Pulmonary embolism Auto immune hemolytic anaemia Clubbing of fingers


Diagnosis :Diagnosis Complete blood count-anaemia,thrombocytosis,high platelet count. Electrolyte studies-hypokalemia,hypomagnesia Renal function tests Liver function tests X-ray Stool culture ESR C-reactive protein


H&E stain of a colonic biopsy showing a crypt abscess:a classic finding in ulcerative colitis :H&E stain of a colonic biopsy showing a crypt abscess:a classic finding in ulcerative colitis [edit] General


Crohn's Disease :Crohn's Disease


Contents :Contents Introduction and definition of Crohn’s Disease Classification Cause Pathology Complications Clinical features Diagnosis Investigations Disease at glance


Introduction to Crohn’s disease: :Introduction to Crohn’s disease: This is a chronic inflammatory disease which causes stomach pains, diarrhoea, and weight loss. The disease is characterised by periods of activity and remissions. It typically affects the lower part of the small intestine (ileum) or the large intestine (colon), but it can affect any part of the digestive system.


Slide 22:The affected areas become red and swollen and ulceration may occur. As the ulcers heal, the formation of scar tissue makes the intestine increasingly narrow, leading to obstruction. There is no cure for Crohn's disease, but the symptoms can be treated and the periods of remission can be made to last several years.


Definition: :Definition: Crohn's disease (also known as regional enteritis) is a chronic, episodic, inflammatory condition of the gastrointestinal tract characterized by transmural inflammation (affecting the entire wall of the involved bowel) and skip lesions (areas of inflammation with areas of normal lining between). Crohn's disease is a type of inflammatory bowel disease (IBD) and can affect any part of the gastrointestinal tract from mouth to anus; as a result, the symptoms of Crohn's disease vary between affected individuals.


Classification: :Classification: Based on location.


Classification contd.. :Classification contd..


Classification :Classification Based on behaviour of disease Stricturing disease. Penetrating disease. Inflammatory disease.


Cause: :Cause: The exact cause of Crohn's disease is unknown. However, genetic and environmental factors have been invoked in the pathogenesis of the disease. Mutations in the CARD15 gene (also known as the NOD2 gene) are associated with Crohn's disease and with susceptibility to certain phenotypes of disease location and activity. Recently, research has indicated that Crohn's disease has a strong genetic link.


Cause contd.. :Cause contd.. Abnormalities in the immune system Many environmental factors. Diets Smoking Methods of hormonal contraception Some bacteria: Eg Mycobacterium avium subsp. Paratuberculosis, mannose, anti saccharomyces cerevisiae antibodies and E. coli


Pathology: :Pathology: Odeomatous and thickened bowel wall Cobblestone Patchy inlammation Skip lessions Transmural inflammation H and E section of colectomy showing transmural inflammation.


Clinical Features :Clinical Features Ileal Crohn’s Disease Abdominal pain Diarrhea Weight loss Crohn’s colitis Bloody diarrohea Passage of mucus Lethargy Malaise Anorexia Weight loss


Complications: :Complications: Intestinal:- Severe, life-threatening inflammation of colon. Perforation of the small intestine or colon. Life-threatening acute haemorrhage. Fistulae and perianal disease. Cancer. Extraintestinal.


Differential Diagnosis :Differential Diagnosis Indium- or technetium- labelled white scanning.


Investigations: :Investigations: Endoscopic image of Crohn's colitis showing deep ulceration.


Contd….. :Contd….. Bacteriology Barium studies Other investigations X-ray Radio labelled white cell scan Ultrasound MRI scans


Contd.. :Contd.. CT scan showing Crohn's disease in the fundus of the stomach.


Crohn’s Disease at Glance: :Crohn’s Disease at Glance: Crohn's disease is a chronic inflammatory disease of the intestines. The cause of Crohn's disease is unknown. Crohn's disease can cause ulcers in the small intestine, colon, or both. Abdominal pain, diarrhea, vomiting, fever, and weight loss are symptoms of Crohn's disease. Crohn's disease of the small intestine may cause obstruction of the intestine.


Contd.. :Contd.. Crohn's disease can be associated with reddish, tender skin nodules, and inflammation of the joints, spine, eyes, and liver. The diagnosis of Crohn's disease is made by barium enema, barium x–ray of the small bowel, and colonoscopy. The choice of treatment for Crohn's disease depends on the location and severity of the disease. Treatment of Crohn's disease includes drugs for suppressing inflammation or the immune system, antibiotics, and surgery.


Comparison of UC and CD :Comparison of UC and CD


Treatment of Inflammatory Bowel Disease :Treatment of Inflammatory Bowel Disease


Goals of Treatment :Goals of Treatment Remission Maintenance


TREATMENT :TREATMENT Treatment for IBD may include: DIETARY CHANGES LIFESTYLE CHANGES DRUG THERAPY SURGERY


DIETARY CHANGES :DIETARY CHANGES Taking specific nutritional supplements, Limiting dairy products, Eating low-fat foods, Avoiding foods high in undigestible fiber Following doctor-recommended diets and Eating smaller, more frequent meals.


LIFESTYLE CHANGES :LIFESTYLE CHANGES . Taking rest nonsmoking Stress reduction Doing exercise


Drug Therapies :Drug Therapies 5-Aminosalicylates (5-ASA) Glucocorticoids (steroids) Antibiotics Immunosuppressants Biological Therapy


Aminosalicylates :Aminosalicylates Sulfasalazine (5-aminosalicylic acid and sulfapyridine as carrier substance) Mesalazine (5-ASA), e.g. Asacol, Pentasa Balsalazide (prodrug of 5-ASA) Olsalazine (5-ASA dimer cleaves in colon) Oral, rectal preparation


Slide 46:Use Maintaining remission May reduce risk of colorectal cancer Adverse effects Nausea, headache, epigastric pain, diarrhoea, hypersensitivity, pancreatitis Caution in renal impairment, pregnancy, breast feeding


Glucocorticoids :Glucocorticoids Antiinflammatory agents for moderate to severe relapses Inhibition of inflammatory pathways (?IL transcription, suppression of arachidonic acid metabolism, lymphocyte apoptosis) Budesonide Prednisolone


Steroid Side Effects :Steroid Side Effects -Acne -“Moon” face -Hair growth -“Buffalo” hump -Obesity -Purple / red streaks (striae) -Bone thinning -Bruising -Depression -Anxiety -Muscle weakness


Antibiotics :Antibiotics Metronidazole, ciprofloxacin Precise role in management is unclear Treatment of complications such as abscesses and skin infections Side effects Diarrhoea,nausea Metallic taste Thrombophlebitis Hypersensitivity reaction


Immunosupressants :Immunosupressants Drugs include: Thiopurines Azathioprine 6-mercaptopurine Methotrexate Cyclosporin Interfere with inflammatory pathway Need close monitoring for toxicity Safety Methotrexate not to be used in pregnancy


Thiopurines :Thiopurines Azathioprine, mercaptopurine Inhibit ribonucleotide synthesis Inducing T cell apoptosis Azathioprine metabolised to mercaptopurine and 6-thioguanine nucleotides


Slide 52:Use Active and chronic disease Steroid sparing Side effects Leucopaenia Sore throat Flu like symptoms after 2 to 3 weeks, liver, pancreas toxicity


Methotrexate :Methotrexate Inhibits dihydrofolate reductase Probably inhibition of cytokine and eicosanoid synthesis Use Relapsing or active CD refractory or intolerant to AZA or Mercaptopurine Side effects GI irritation Hepatotoxicity, pneumonitis


Cyclosporin :Cyclosporin Preventing clonal expansion of T cell subsets Use Steroid sparing Active and chronic disease Side effects Tremor, paraesthesiae, malaise, headache Gingival hyperplasia, hirsutism Major: renal impairment, infections, neurotoxicity


Biological Therapy :Biological Therapy Infliximab Anti TNF-a monoclonal antibody Infliximab binds to TNF- a trimers with high affinity,preventing cytokine from binding to its receptors It also binds to membrane-bound TNF- a and neutralizes its activity & also reduces serum TNF- a levels


REMICADETM (infliximab)Mechanisms of Action :van Deventer SJH. Gut 1997: 40; 443–8. Scallon BJ et al. Cytokine 1995: 7; 251–9. Feldmann M et al. Adv Immunol 1997; 64: 283–350. REMICADETM (infliximab)Mechanisms of Action Infliximab Neutralisation of soluble TNF? TNF? producing macrophages of activated T cells Neutralisation of transmembrane TNF?


: Use Fistulizing CD Severe active CD refractory/intolerant of steroids or immunosuppression Side effects Infusion reactions Sepsis Reactivation of Tb, increased risk of Tb


Endoscopic Improvement With REMICADETM (infliximab) :Reprinted with permission of van Dullemen HM et al. Gastroenterology 1995; 109: 129–35. Endoscopic Improvement With REMICADETM (infliximab) Pre-treatment 4 weeks post-treatment


Other medications :Other medications Anti- diarrhoeals. Loperamide (Imodium) Laxatives ..senna, bisacodyl Pain relievers. acetaminophen (Tylenol). Iron supplements Nutrition


Surgery for Crohn's Disease :Surgery for Crohn's Disease Types of surgery for CD include: Stricturoplasty Small bowel resection . Colectomy .


Surgery for Ulcerative Colitis :Surgery for Ulcerative Colitis Types of surgery for UC include: Proctocolectomy Ileal pouch anal anastomosis (IPAA


IRRITABLE BOWEL SYNDROME :IRRITABLE BOWEL SYNDROME


INTRODUCTION :INTRODUCTION First described in 1771. 50% of patients present <35 years old. 70% of sufferers are symptom free after 5 years. The cause of IBS is unknown. Affects up to ~20 % adults in the industrialized world The condition is more frequent in women.


What is IBS ?!. :What is IBS ?!. IBS is a functional GI disorder characterised by abdominal pain & altered bowel habits ( C & D ) in the absence of specific & unique organic pathology synonyms for ibs spastic colon spastic colitis mucous colitis nervous diarrhoea.!!.


Pathophysiology :Pathophysiology 3 theories: 1. Altered G.I motility : 5HT pathway, glutamate activation of NMDA receptors, 2. Visceral hyperalgesia : activation of neurokinin receptors 3. Psychopathology Factors : psychological, social & neuro-humeral factors


Factors affecting IBS :Factors affecting IBS


Epidemiology :Epidemiology Incidence : 10-20% in INDIA 15-25% in UK Ref : prevalence studies in Birmingham & Edinburgh, BJGP’04 Sex : F:M = 2-3:1 Age : 20 – 30 yrs


Aetiology :Aetiology Psychological morbidity Role of stress Consulting behaviour Abnormal illness behaviour Gut motility Visceral hypersensitivity Post-infective bowel dysfunction Diet


Supportive symptoms of IBS :Supportive symptoms of IBS Diarrhea-predominant IBS (IBS-D) More than 3 bowel movements a day Loose or watery stools Feeling of incomplete bowel movement Constipation-predominant IBS (IBS-C) Fewer than 3 bowel movements a week Hard or lumpy stools Urgency Passing mucus during a bowel movement Abdominal cramps


G. I. Symptoms :G. I. Symptoms


Non – G.I Symptoms :Non – G.I Symptoms Lethargy Poor sleep Fibromyalgia Backache Dyspareunia Anxiety Depression Somatisation


Urgent Referral :Urgent Referral Constant abdominal pain. Constant diarrhoea. Constant distension. Rectal bleeding.


Diagnosis :Diagnosis Working diagnosis : 1. Typical symptoms 2. physical examination 3. No red flags Diagnosis should be confirmed in G.P by observation over time Supportive features : Female Age 2 yrs Frequent attendance with non-G.I symptoms


Differential Diagnosis :Differential Diagnosis Coeliac disease Infectious colitis IBD Endocrine disorder : thyroid, carcinoid, calcium Pancreatitis Lactose intolerance Peptic ulcer disease Diverticulitis Bowel cancer


Diagnostic Criteria :Diagnostic Criteria Rome 11 Diagnostic criteria. Manning’s Criteria


Rome 11 Diagnostic Criteria :Rome 11 Diagnostic Criteria Supportive symptoms. Constipation predominant: one or more of: BO less than 3 times a week. Hard or lumpy stools. Straining during a bowel movement. Diarrhoea predominant: one or more of: More than 3 bowel movements per day. Loose [mushy] or watery stools. Urgency.


Rome 11 Diagnostic Criteria :Rome 11 Diagnostic Criteria General: Feeling of incomplete evacuation. Passing mucus per rectum. Abdominal fullness, bloating or swelling.


Manning’s Criteria. :Manning’s Criteria. Three or more features should have been present for at least 6 months: Pain relieved by defecation. Pain onset associated with more frequent stools. Looser stools with pain onset. Abdominal distension. Mucus in the stool. A feeling of incomplete evacuation after defecation.


Investigations :Investigations Bloods : FBC, ESR, TFT Stool : microscopy Urine: screen for laxatives Lactose tolerance testing Sigmoidoscopy Colonoscopy


Sigmoidoscopy Colonoscopy :Sigmoidoscopy Colonoscopy


Slide 82:TREATMENT OF IRRITABLE BOWEL SYNDROME


TREATMENT :TREATMENT PSYCOTHERAPY ANTISPASMODIC AGENTS ANTI-MOTILITY DRUGS TRICYCLIC ANTIDEPRESSANTS SELECTIVE SEROTONIN REUPTAKE INHIBITORS(SSRI) 5-HT3 RECEPTOR antagonists 5-HT4 receptor agonists Other agents


PSYCOTHERAPY :PSYCOTHERAPY Cognitive behavioral therapy Hypnosis Stress management or relaxation therapy Psychotherapy should be confined to the patients who are motivated and have severe or disabling symptoms


ANTISPASMODIC AGENTS :ANTISPASMODIC AGENTS Antispasmodic agents relax smooth muscle in the gut and reduce contractions. Inhibit intestinal smooth-muscle depolarization at the muscarinic receptor. Dicyclomine and hyoscyamine are the commonly used drugs. Dicyclomine: 10-40mg QID (4 times in a day). Hyoscyamine: (levsin) 0.125-0.250mg every 4 hours.


ANTI-MOTILITY DRUGS :ANTI-MOTILITY DRUGS The opioid drugs which increase small bowel tone and segmental activity reduce propulsive movement and diminish intestinal secretion while enhancing absorption. Its action is mediated through µ-opioid receptors located on enteric neuronal network. Codiene Lopramide: 60mg TDS(thrice times a day) (4-8mg per day) Diphenoxylate:2.5mg+atropine(0.025mg) 2.5-5mg 6 hourly


TRICYCLIC ANTIDEPRESSANTS :TRICYCLIC ANTIDEPRESSANTS They have shown to relieve pain with low doses. Tricyclic antidepressants facilitate endogenous endorphin release and block norepinephrine reuptake, which leads to enhancement of descending inhibitory pathways blockage of the pain.


CONCLUSION :CONCLUSION


TRICYCLIC ANTIDEPRESSANTS… :Amytriptyline: 50-200mg QID Clomipramine: 50-150mg TID Desipramine: 50-200mg Trimipramine: 50-150mg TID Doxepine: 50-150mg TID TRICYCLIC ANTIDEPRESSANTS…


Selective serotonin reuptake inhibitors(SSRI) :Selective serotonin reuptake inhibitors(SSRI) These drugs inhibit the uptake of serotonin only. The exact mechanism of action is yet to be known. Probable mode of action is, it acts through central and peripheral. It is used in constipation predominant IBS. Its not used as first line of drugs and also for routine use. Paroxetine (Paxil) 10 to 40 mg of per day.


5-HT3 RECEPTOR ANTAGONISTS :These drugs Antagonizes the serotonin receptor subtype 5-hydroxytryptamine-3. They reduces noxious stimuli perception, increases colonic compliance, and decreases gastro colonic reflexes. Alosetron: (Lotronex): 1 mg per day for four weeks1 mg once or twice per day. 5-HT3 RECEPTOR ANTAGONISTS


5-HT4 AGONIST :5-HT4 AGONIST Stimulation of the serotonin receptor subtype 5-hydroxytryptamine-4 (5-HT4). Increases colonic transit time and inhibits visceral sensitivity. Tegaserod (Zelnorm), a partial 5-HT4 receptor agonist. Renzapride.


OTHER AGENTS :OTHER AGENTS There are a variety of other agents with reported advantages in treating IBS symptoms. ANTIBIOTICS: may be recommended for the treatment of refractory diarrhea if bacterial infection is suspected. However, antibiotics should not be used routinely for treatment of IBS. Antibiotics are not indicated for long-term use because they may increase diarrhea through changes in the bowel flora.


OTHER AGENTS…. :OTHER AGENTS…. PROBIOTICS: consist of a preparation containing a single or mixed-culture of live microbes that exert beneficial health effects by altering the gastrointestinal flora. Probiotics are presumed to restore normal bowel flora. Cisapride (Propulsid).


Bibliography :Bibliography Davidson,s principles&practice of Medicine Basic and clinical pharmacology-KATZUNG