GIT pdf - غير معروف

Medicine

د. رﺑﺎح

Lec. 66

inflammatory bowel diseases

Ulcerative colitis and Crohn's disease

An immune-mediated chronic inflammatory bowel diseases with relapsing
and remitting course

· Ulcerative colitis only involves the colon

· Crohn's disease can involve any part of the gastrointestinal tract from

mouth to anus.

Epidemiology

· In developing world

o Crohn's disease appears to be rare
o Ulcerative colitis, more common.

· In the West

o Ulcerative colitis prevalence of 100-200 per 100 000
o Crohn's disease prevalence of 50-100 per 100 000.

· Young adults (between 15 and 30 years), second smaller incidence

peak in the seventh decade (between 60 and 80 years)

· The male to female ratio for UC is 1:1 and for CD is 1.1–1.8:1.

· UC and CD have two- to fourfold increased frequency in Jewish.

Etiology

o Abnormal host response

to an environmental

trigger in genetically

susceptible individuals

o This causes inflammation

of the intestine and
release of inflammatory

mediators, such as TNF,

IL-12 and IL-23, which
cause tissue damage.

Inf

ses

Lecture 66

Medicine

Dr. Rabah

Factors associated with the development of IBD
Genetic

o  More common in Ashkenazi Jews
o  10% have a first-degree relative or at least one close relative with IBD
o  High concordance between identical twins
o  Crohn's  disease  is  associated  with  the  NOD2,  ATG16L1  and  IRGM

genes

o  Ulcerative colitis is associated with the ECM-1 gene
o  Associated with autoimmune thyroiditis and SLE
o  HLA-DR103 associated with severe ulcerative colitis
o  Ulcerative  colitis  and  Crohn's  patients  with  HLA-B27  commonly

develop ankylosing spondylitis

Environmental

o  Ulcerative colitis is more common in non-smokers
o  Most Crohn's patients are smokers
o  Associated with low-residue, high refined sugar diet
o  Appendicectomy protects against ulcerative colitis

Pathology

Ulcerative Colitis

Macroscopic Features

o  Extends proximally to involve all or part of the colon.
o  40–50% of patients involve the rectum, rectosigmoid
o  30–40% beyond the sigmoid
o  20% have a total colitis
o  Inflammation is diffused

Mild:

o The mucosa is erythematous and fine granular surface

More severe

o The mucosa is hemorrhagic, edematous, and ulcerated (superficial

diffused)

o Fulminant disease can develop a toxic megacolon where the bowel

wall thins and the mucosa is severely ulcerated; this may lead to
perforation.

In long-standing disease

o Inflammatory polyps (pseudopolyps) may be present as a result of

epithelial regeneration.

o Many years of disease it appears atrophic and featureless and the

Inf

ses

Lecture 66

Medicine

Dr. Rabah

entire colon becomes narrowed and shortened

Inf

ses

Lecture 66

Medicine

Dr. Rabah

Microscopic Features

o Mucosal vascular congestion, edema and focal hemorrhage
o Inflammatory cell infiltrate of neutrophils, lymphocytes, plasma cells,

and macrophages may be present.

o The neutrophils invade the epithelium, usually in the crypts, giving

rise to cryptitis and, to crypt abscesses

Histological features of chronicity

o First, the crypt architecture of the colon is distorted
o Second, some patients have basal plasma cells and multiple basal

lymphoid aggregates

Crohn's Disease:

Macroscopic Features

o  30–40% of patients have small-bowel alone
o  40–55% have disease involving both the small and large intestines
o  15–25% have colitis alone.
o  30 % have anal involvement
o  The rectum is often spared in CD.

Inf

ses

Lecture 66

Medicine

Dr. Rabah

 Segmental inflammation (skip areas of inflammation)

 Aphthous ulcerations

 Stellate ulcerations fuse longitudinally and transversely to demarcate

islands of mucosa that frequently are histologically normal.

"Cobblestone" appearance

 Ulcers may penetrate bowel wall to initiate abscesses or fistulas

o  The bowel
o  Bladder
o  Uterus

o Vagina
o Skin of the perineum

 Bowel narrowed and fibrotic, with chronic, recurrent bowel

obstructions

 Mesenteric lymph nodes are enlarged and the mesentery is

thickened.

Microscopic

· Transmural inflammation

· Fissures penetrate deeply into the bowel wall

· Bowel wall thickened

· Chronic inflammatory infiltrate all layers.

· Focal crypt abscesses

· Noncaseating granulomas

· Microscopic skip areas

· Other histological features submucosal or subserosal lymphoid

aggregates.

Inf

ses

Lecture 66

Medicine

Dr. Rabah

Crohn’s ulcer

Crohn’s cobblestone

Crohn’s stricture

Crohn’s disease

Inf

ses

Lecture 66

Medicine

Dr. Rabah

Clinical features

Ulcerative colitis

Bloody diarrhea relapses and remissions

· Emotional stress

· Intercurrent infection

· Gastroenteritis

· Antibiotics

· NSAID therapy may all

provoke a relapse

Proctitis

· Rectal bleeding

· Mucus discharge

· Tenesmus.

· Frequent, small-volume fluid stools

Proctosigmoiditis

· Bloody diarrhoea with mucus.

Extensive colitis

· Bloody diarrhea

· Passage of mucus.

· Severe cramping

· Abdominal pain can occur with severe attacks of the disease.

· Constitutional symptoms do not occur only in moderate to severe

disease

Severe colitis

· Bleeding

· Severe diarrhea

· Severe pain

· Fever

· Tachycardia

· Abdominal tenderness

Mild

· <4 stool/day no or small

blood amount

· No fever

· No tachycardia

· Mild anemia

· ESR<30

Moderate

· Intermediate between mild and moderate

Severe

· 6 stool /day with blood

· Fever > 37.5c

· Heart rate > 90

· Anemia < 75% of the normal

· ESR > 30

Crohn's Disease

· The major symptoms are:

Inf

ses

Lecture 66

Medicine

Dr. Rabah

o  Pain is often associated with diarrhea
o  Diarrhea usually watery not contain blood or mucus.
o  Weight loss
o  Intestinal obstruction sub-acute or even acute
o  Malabsorption

Mechanism of the diarrhea

(1) Bacterial overgrowth in obstructive stasis or fistulization,

(2) Bile-acid malabsorption due to a diseased or resected terminal ileum
(3) Intestinal inflammation with decreased water absorption and

increased secretion of electrolytes

Crohn's colitis

· As ulcerative colitis

· Rectal sparing

· Stricturing can occur in the colon in 4–16% of patients

Perianal disease

· Affects about one-third of

· Large hemorrhoidal tags

· Anal strictures

· Anorectal fistulae

· Perirectal abscesses.

· Incontinence

Ileocolitis

· Recurrent right lower quadrant pain

· Diarrhea.

· Palpable mass

· Fever, leukocytosis.

· Weight loss is common

· Fistula formation

· Abscess cavity in the mesentery

Small intestinal Crohn’s

· Malabsorption and steatorrhea.

· Nutritional deficiencies.

· Vomiting from jejunal strictures or severe oral ulceration.

Differential diagnosis

· Colitis

· Infective

o Bacterial

Salmonella

Shigella

Inf

ses

Lecture 66

Medicine

Dr. Rabah

Campylobacter jejuni

E. coli

Gonococcal proctitis

Pseudomembranous colitis

Chlamydia proctitis

o Viral

Herpes simplex proctitis

Cytomegalovirus

o Protozoal

Amoebiasis

· Non-infective

o Vascular

Ischaemic colitis

Radiation proctitis

o Idiopathic

Collagenous colitis

Behçet's disease

o Drugs

NSAIDs

o Neoplastic

Colonic carcinoma

o Other

Diverticulitis

Small bowel Crohn's disease

· Right iliac fossa mass

Caecal carcinoma
Appendix abscess

· Infection

Tuberculosis

Yersinia
Actinomycosis

· Intestinal Lymphoma

· Mesenteric adenitis

· Pelvic inflammatory disease

Complications

Toxic megacolon

· Acute colonic dilatation due severe flare of the colitis

· More with extensive colitis

Inf

ses

Lecture 66

Medicine

Dr. Rabah

· 5% incidence

· Precipitating factors as hypokalemia, antimotility, colonoscopy

Clinical features

· Features of severe colitis with

· Diffused abdominal distension

· Diffused tenderness

· Decease bowel sound

· Lab sings of systemic

inflammation

Treatment

· Conservative

Indication for surgery

· No response within 72 hr

· Sings of peritonitis or perforation

Hemorrhage

· Hemorrhage major artery is rare

· Can occur in both conditions.

Fistulas

Enteroenteric

diarrhoea
Malabsorption.

Enterovesical

recurrent UTI

pneumaturia.

Enterovaginal

a feculent vaginal discharge.

Bowel fistulation

perianal ischiorectal

Abscesses

Fissures

Fistulas.

Inf

ses

Lecture 66

Medicine

Dr. Rabah

Cancer

· Active colitis of more than 10 years'.

· The cumulative risk 10%

· Lower for Crohn's colitis.

· Tumors develop in areas of dysplasia

· Surveillance programmes beginning 8-10 years after diagnosis by

colonoscopy 1-2-yearly.

· Mild to moderate dysplastic changes are the frequency of screening

is increased

· High-grade dysplasia panproctocolectomy

Strictures

In Crohn's disease
Extra intestinal complications

· Common in IBD

· May dominate the clinical picture.

· Some of these occur during relapse of intestinal disease

· Others unrelated to intestinal disease activity

Inf

ses

Lecture 66

Medicine

Dr. Rabah

Investigations

· Confirm the diagnosis

· Define disease distribution

· Define activity

· Identify complications.

· Full blood count may show anaemia

· Serum albumin.

· The ESR and CRP

Elevated in exacerbations and in response to abscess formation

Bacteriology

· Stool microscopy

· Culture and examination

Ova

Cysts

Clostridium difficile toxin

· Blood cultures

· Serological tests p ANCA, ASCA

Endoscopy with Biopsies

· Confirm the DX

· Define disease extent

· Detect dysplasia in long-standing colitis.

In ulcerative colitis

· Loss of vascular pattern

· Granularity

· Friability

· Ulceration.

· Pseudopolyps

· Stricture formation does not occur

In Crohn's disease

· Patchy inflammation

· Discrete, deep ulcers

· Perianal disease (fissures, fistulas and skin tags)

· Rectal sparing

Capsule endoscopy

· The identification of small bowel inflammation, but should be

avoided in the presence of strictures.

Inf

ses

Lecture 66

Medicine

Dr. Rabah

Radiology
Barium enema

· Less sensitive investigation than colonoscopy

· Crohn's disease; affected areas are narrowed and ulcerated, and

multiple strictures are common

CT and MRI scans

· Bowel thickining and extrahepatic disease

· Pelvic or perineal involvement.

A plain abdominal X-ray

· With severe active disease.

o  Dilatation of the colon
o  Perforation may be found.
o  In  small  bowel  Crohn's  disease  there  may  be  evidence  of

intestinal obstruction or displacement of bowel loops by a

mass.

Ultrasound

· Thickened small bowel loops

· Abscess development in Crohn's disease.

Management

· Treat acute attacks

· Prevent relapses

· Select patients for surgery

· Detect carcinoma at an early stage

Inf

ses

Lecture 66

Medicine

Dr. Rabah

Treat acute attacks
Aminosalicylates

Mode of action: modulate cytokine release
Oral or topical (enema/suppository)

Mesalamine

· Pentasa (time dependent release)

· Ascol (PH dependent release)

With carrier

· Sulfasalazine, balsalazide, olsalazine

Side-effects 10-45%

· Headache

· Nausea

· Diarrhea

· Blood dyscrasia

Corticosteroids

· Anti-inflammatory

· Topical and oral and I.V

· Prednisolone

· Hydrocortisone

· Budesonide

Cyclosporine

· Suppresses T-cell expansion

· Rescue' therapy to prevent surgery in ulcerative colitis responding

poorly to corticosteroids.

· No value in Crohn's disease

· Major side-effects in 0-17% nephrotoxicity, infections, neurotoxicity

· Minor complications in up to 50%: tremor, paraesthesiae, abnormal

liver function tests, hirsutism

Anti-TNF antibodies

(Infliximab and adalimumab)

· Suppress inflammation and induce apoptosis of inflammatory cells

· Moderately to severely active Crohn's disease, especially fistulating

· Severe active ulcerative colitis

· Anaphylactic reactions after multiple infusions

· Contraindicated in the presence of infections; reactivation of

tuberculosis

Antibiotics

· Useful in perianal Crohn's disease

Antidiarrhoeal agents (codeine phosphate, loperamide, lomotil)

· Reduce gut motility and small bowel secretion

Inf

ses

Lecture 66

Medicine

Dr. Rabah

· Avoided in acute flare-ups of disease

· May precipitate colonic dilatation

Prevent relapses

Thiopurines

(Azathioprine, 6-mercaptopurine)

· Immunomodulation by inducing T-cell cytotoxic effect

· Effective after 12 weeks of starting therapy

Complications in 20%.

· Flu-like syndrome with myalgia

Leucopenia in 3%

· Safe during pregnancy

Methotrexate

· Anti-inflammatory (folic acid antagonist)

· In 10-18%. Nausea, stomatitis, diarrhoea, hepatotoxicity and

pneumonitis

Ciclosporin
Anti-TNF antibodies

Ulcerative colitis

Active proctitis and proctosigmoiditis

· In mild to moderate disease mesalamine enemas or suppositories

combined with oral mesalazine are effective first-line therapy.

· Topical corticosteroids are less effective and are reserved for patients

who are intolerant of topical mesalazine.

· Patients who fail to respond are treated with oral prednisolone.

Active left-sided or extensive colitis

· In mildly active cases, high-dose aminosalicylates combined with

topical aminosalicylate

· Oral prednisolone 40 mg daily is indicated for more active disease or

when initial aminosalicylate therapy is ineffective

Severe ulcerative colitis

· Hospital admission

· Monitored clinically: for the presence of abdominal pain,

temperature, pulse rate, stool blood and frequency

· Laboratory; haemoglobin, white cell count, albumin, electrolytes,

ESR and CRP

· Radiologically: for colonic dilatation on plain abdominal X-rays.

Inf

ses

Lecture 66

Medicine

Dr. Rabah

· Intravenous fluids

· Transfusion blood if Hb < 10 g/L

· Nutritional support
§

IV corticosteroids (hydrocortisone 400 mg/day)

Avoidance of opiates and antidiarrhoeal agents

Topical and oral aminosalicylates.

Patients who do not promptly respond to corticosteroids are
considered for intravenous ciclosporin or infliximab

· Those who do not respond after ' maximal medical treatment usually

require urgent colectomy.

· Which, in approximately 30% of cases, 7-10 days overcomes the need

for urgent colectomy.

Maintenance of remission

· Life-long therapy recommended

· Extensive disease

· Distal disease who relapse more than once a year.

· Oral aminosalicylates first line

· Patients who frequently relapse despite aminosalicylate drugs are

treated with thiopurines.

Crohn's disease
Active colitis or ileocolitis

· Aminosalicylates

· Corticosteroids

· In severe disease intravenous steroids

Isolated ileal disease

· Corticosteroids.

· Aminosalicylates have little added value

· Poorly responding patients should, at an early stage, be considered

for surgical resection since this is associated with prolonged remission
in most cases.

Fistulas and perianal disease.

· Surgical intervention required for abscess

· For simple perianal disease metronidazole and/or ciprofloxacin are

first-line therapies.

· Treatment of underlying active disease with corticosteroids and

nutritional support usually by TPN.

Inf

ses

Lecture 66

Medicine

Dr. Rabah

· Infliximab and adalimumab heal enterocutaneous fistulas and

perianal disease in many patients.

Maintenance of remission

· Aminosalicylates have minimal efficacy.

· Thiopurines for relapse more than once a year or severe disease.

· Patients who are intolerant of or resistant to thiopurines should be

treated with once-weekly methotrexate combined with folic acid.

· Patients with aggressive disease are managed using a combination of

immunosuppressives and anti-TNF therapy.

Indications for surgery in ulcerative colitis

Impaired quality of life

· Loss of occupation or education

· Disruption of family life

Failure of medical therapy

· Dependence upon oral corticosteroids

· Complications of drug therapy

Fulminant (severe) colitis no response

Disease complications unresponsive to medical therapy

· Arthritis

· Pyoderma gangrenosum

Colon cancer or severe dysplasia

Indications for surgery in Crohn's disease

· The indications for surgery are similar to those for ulcerative colitis.

· Unresponsive fulminant disease

· Operations are often necessary to deal with abscesses

· Relieve small or large bowel obstruction.

· Chronic fistulating small bowel disease may require resection if no

reponse

The end of this lecture

Sabeeh & CHW

Inf

ses

Lecture 66

Medicine

Dr. Rabah

اﻟﺳﻼم ﻋﻠﯾﻛم

ﻣﺣﺎﺿرة

Hyperlipidaemia

د. ﺳﺎﻟم اﻟرﺑﯾﻌﻲ ﻧزﻟت ﺑﺎرت

واﺣد و ﻻ ﯾوﺟد ﺑﺎرت آﺧر ﻷن ھذا ﻛل ﻣﺎ ﺷرﺣﮫ اﻟدﻛﺗور و ﺳﺄﻗوم

ً ﺑرﻓﻊ اﻟﺑورﺑوﯾﻧت ﻟﻣن ﯾﺣب اﻹطﻼع ﻋﻠﻰ ﺑﺎﻗﻲ اﻟﺳﻼﯾدات )ﺷﻛرا

ﺑﺔ آﻻء ﺗرةَ ﻛرﺑ و ءﻻآ و لﯾﺑﻧ ﻰﻔطﺻﻣﻟ

(

ﺑﮭذه اﻟﻣﺣﺎﺿرة ﻧﺧﺗﺗم ﻣﺣﺎﺿرات اﻟﺑﺎطﻧﯾﺔ ﻟﮭذا اﻟﻌﺎم

أﺣب أن أوﺟﮫ ﺷﻛري ﻟﻛل ﻣن

ﺳﺎﻋد ﻓﻲ اﻟﻣﺣﺎﺿرات ﺑﺄي ﺷﻛل

ﻟﻛم ﺟﻣﯾﻌﻛمً ارﻛﺷ اذﻟ ةرﯾﺛﻛ ءﺎﻣﺳﻷا

My last Medicine lecture ever!!

THE END OF ALL LECTURES J

ﻣﻊ

اﻟﺗﻣﻧﯾﺎت ﺑﺎﻟﻣوﻓﻘﯾﺔ و اﻟﻧﺟﺎح ﺑﺎﻟﻔﺎﯾﻧل

Yours

Sabeeh & CHW

JJJJJJJJJJ