Clinical Medicine Disease of Large Bowel

large intestine diseases

diverticular disease & ibd
diverticulosis: formation of many small pouches (diverticula) along muscular mucosal lining. diverticulitis caused by pockets becoming infected diverticulosis caused by progressive increase in pressure within the bowel affects about 10% of americans over the age of 40. the condition becomes more common as people age. about half of all people over the age of 60 have diverticulosis.chronic diverticular disease is managed with increased dietary fiber. dominant theory is that a low-fiber diet is the main cause of diverticular disease.
what foods should be avoided with diverticular disease?
fiber keeps stool soft and lowers pressure inside the colon so that bowel contents can move through easily.
ibd inflammation and ulceration of the lining of the intestine 2 types
ulcerative colitis – begins in the rectum and extends upward with remission and exaberations
crohn’s disease or regional enteritis – can effect any area but usually the terminal ilium. may involve regional lymph nodes and fistulas to the bladder, vagina, and perianal area.
treatment for both is similar, except for surgical approach
cause is unknown / present in both genders . 2nd – 4th decades
crohn’s disease
pathology throughout gi tract
often skip lesions with intervening normal gut
transmural inflammation and fistulous disease
ulcerative colitis
localised to the colon and rectum .mucosal inflammation characteristic usually contiguous disease .occasionally difficult to distinguish the two
indeterminate colitis
epidemiology
incidence in western countries up to14/100,000
prevalence in west up to 240/100,000
ibd aetiology
1 . probable polygenic disease(5-10 % of affected persons have +ve family history.ibd 2 locus(12q13) may be associated with uc.chromosome 6 ibd3 associated with mhc class ii genes.
2 . environmental (gut infection)
3 . immunological
symptoms can be varied depending on site .often: diarrhea, abdominal pain, pr bleeding, pr mucous .nutritional disorders .iron deficiency, vitamin b12 deficiency, folate deficiency etc
extraintestinal manifestations:
arthritis, uveitis, skin changes, primary sclerosing cholangitis
pathogenesis of ibd: leading theories
inappropriate activation of the mucosal immune system
driven by the normal luminal flora .facilitated by defects in the barrier function of the intestinal epithelium and the mucosal immune system
genetics are non-mendelian (multiple genes thought to contribute) and likely more important in cd than uc
7% risk in first-degree relatives of dz
endothelial defect with microthromboembolic dz also thought to play a role (hence possible tx w/ viagra)
nod2 on chromosome 16/card 15 is the most promising cd candidate gene located on chromosome 16 in the ibd1 locus
uc epidemiology:
incidence of u.c 2.2-14.3 / 100000 ,the highest incidence is in northern europe, u.k, n.america, but now increasing in africa and asia.more in whites than in blacks
occur in 3 peaks of age :early adulthood , 40-60 years and the 3rd after 70 years. 1-2 / 100,000 in children are affected

complications of ulcerative colitis:
perforation and peritonitis with fistula formation
toxic megacolon
hemorrhage
risk of colon cancer 18%
nutritional problems
extra intestinal manifestations
pathology
macroscopic :
it is called(pancolitis ) when the entire colon is involved.
sometimes terminal ileum is affected it is called (backwash ileitis).largely limited to mucosa & submucosa of the colorectum.
the rectum is always involved.the disease is present in continuous fashion. shows confluence of numerous ulcers with area of regenerating mucosa called pseudo polyps.it lacks thickening and fibrosis.
microscopic appearance:
-acute inflammatory cells-neutrophils infiltrating into crypts of lieberkuhn at the base of the mucosa to form crypt abscess.
-superficial desquamation of the overlying epithelium leads to ulcers formation.
-in sever inflammation , the muscularis propria may undergo myocytolysis resulting in hyperemia & wall thinning.
colitis severity :mild < 6 bm/day. sever > 6 bm/day with abd.pain , anemia , fever ,wt loss .toxic megacolon sever .diarrhea,fever , shock
the manifestations of proctitis include :
1- urgency
2-tenesmus
3-frequency
4-blood mucoid diarrhea
can be diagnosed by anoproctoscopy, it will demonstrate
inflamed mucosa & mucous on the gloved finger. also presentation of anemia ,malaise ,anorexia ,fatigue& weight loss

extra-intestinal manifestations of ibd :
dermatological:
1- erythema nodosum (9 %)rash , tender,symmetric raised erythematus papules.on the external surface of arms & legs.skin disease parallel the activity but not severity.it is rare to precede the dx.
2-pyoderma gangrenosum (50 %)starts as erythematous plaques, papules or blebs in the pretibial region.can progress to ulcerated,necrotizing,tender wound with ill defined purple-red margin
ocular:
1-episcleritis pain & tender eye is red w/out visual dst.
2-iritis & uveitis ( blindness, painful eye blurred vision headache) with joint & skin manif. also involvement includes iris , ciliary body , vitreous or retina

musculoskeletal:
1-acute synovitis 20%
2-ankylosing spondylitis 3-5% - risk w/pt hla b27
l/o truncal motion- chest expansion
tender sacroiliac joint.
hepatic:

diagnosis
history ,lab workup ,imaging ,endoscopy
cbc:leucocytosis anemia low hct. platelets.
liver enzymes
stool analysis for fecal leucocytes
stool culture for campylobacter ,salmonella ,shigella ,pathogenic e.coli clost.difficile giardia cytomegalo virus
calprotectin:
is an abundant neutrophil protein found in both plasma and stool . 130 mg/kg stool were 68% sensitive and 67% specific in predicting relapse risk. allow for serial monitoring of the disease as well as success or failure of treatment. it is stable in faeces for several days.it allows for differentiation between organic diarrhoea and functional diarrhoea
serological tests:
p-anca (perinucliar anti- neutrophil cytoplasmic antibody) diagnostic for u.c in 60-80%.indicates earlier need for surgery. no relation to post-op. complications.specific 94%- sensitive 57%
asca (anti–saccharomyces cerevisiae antibodies ) +ve in 12% of u.c patients








the ibd comparison
cd uc features
f, d, abd pain, wt loss, malnutrition, perianal dz, abd mass, growth failure kids, associated with psc, smoking makes worse
f, d, wt loss, malnutrition, smoking improves, extraintestinal manifestations more common (jsem)
clinical
colon, ileum, infrequently other sites
colon site
stricture, fistula, & cancer, toxic megacolon absent, perforation uncommon
cancer
no fistulae complications
submucosal, mucosal, transmural inflammation granulomas, serosal erythema and creeping fat
mucosal, crypt abscesses
pathology
friability, apththous and linear ulcers, “cobble stone,” pesuopolyps and rectal dz
friability, pseudopolyps, rectal dz
endoscopy
discontinuous, segmented, deep submucosal ulceration, fissures, strictures or fistulae, narrow and nodular ileal dz, “string sign” on sibft
continuous distribution, superficial ulceration, dilated ileal disease (“backwash ileitis”)
radiology
> 50% asca +
70% p-anca+
serology

management:
1 . supportive
2 . medical( corticosteroids, 5asa, immunomodulators , biologic agents )
3 . surgical ( emergency , elective )
medical :
1) 5-asa
mechanism :colonic bacteria contain azo-reductase enzyme that split sulfasalazine to liberate 5-asa, which acts topically.
drug forms
1-sulfasalazine = 5 asa + sulfapyridine
2-mesalamine (asacol) released at ph > 7 (pentasa).
controlled release in duodenum.
rowasa = ph> 6 for distal ileum and colonic exposure .
2 ) steroids
mechanism: used to control symptoms not to maintain long term remission.has immunologic & anti-inflammatory effect through 1-cytokine cascade
2- prostaglandin production
3-leucocyte reaction
used for moderate to sever u.c.&failed asa treatment
dosage: in sever cases prednisone 40-60 mg/day ,in hospital 300 mg hydrocortisone or 60 mg methylprednisone
recent drug : budesonide ,less side effects great potency to glucocorticoid receptors ,1st pass hepatic metabolism
3 . immunomodulators
cyclosporin therapy dosage: 4mg/kg
mechanism:
1-it is a lipophilic peptide w/inhibitory effect on cellular & immune system.
2-it blocks production of il2 produced by t-helper lymphocytes.
3-it binds cyclophilin and inhibit calcineurin which is cytoplasmic phosphatase enzyme, and involved in the action of t-cells and inhibit b-cell function.
indication: for refractory colitis
side effects: renal insufficiency ,htn seizures ,paraesthesias
long term follow/up failed to demonstrate decreased incidence of colectomy with 60-80% of patients required operation within one year.
4 . biological agents
anti tnf( infliximab)
inhibits production of interferon,il2,il 12.
of benefit in 88% of steroid refractory patients. in sever colitis 5mg/kg i.v at 0,2,6 weeks.
anti il2r ( daclizumab )
recobinent humanized ig monoclonal ab to il2r . produces clinical response in 2 weeks.
anti cd3 ( visilizumab )induces remission for several months.growth factor ,epidermal growth factor.

treatment of mild u.c : symptomatic therapy diet changes: incr iron, decr. lactose, low-roughage diet.
anti diarrheal agents: not if moderate to sever: diphenoxylate 2.5-5 mg loperamide2-4 mg
deoderized tincture of opium 10-15 dropings or
codeine 15-30 mg tid.
bulk formers: psyllium. rectal installations:( limited proctosigmoiditis or tenesmus):
hydrocortisone enema (100 mg in 60 ml)
hydrocortisone foam 10 % or suppository
25 mg in daytime
5 asa 4 gm in 60 ml if refractory
sulfasalazine for mild – moderate colitis: 0.5-1.5 gm, 2-4 times/day.nicotine may improve symptoms in approx. 40 % (transdermal 11-22 mg/day)
treatment of moderate colitis:prednisone 30-40 mg qd, tapering after remission. antimetabolites: azathioprine 2mg/kg/day or 6 mercaptopurine 1.5 mg/kg/day
treatment of sever u.c , hospitalize
i.v hydrocortisone (300 mg qd,cont.iv infusion q 6 hr
i.v adrenocort. acth 120 u/ day.
electrolytes: supplement kcl in ivf 20-40 meq/l
prognostic factors in sever ulcerative colitis:
bowel motion > 8 stools/day .
ph > 7.5, crp > 45 mg/l, albumin < 3 gm/100 ml
pulse > 120/min
fever > 38 c
intestinal sound < 5/ min
ca++ < 4.0 meq/l
cl < 95
k+ < 2.5
hco3 > 32
altered consciousness

toxic megacolon
pathophysiology toxic fulminant colitis due to deep transmural dissection of ulcerating inflammatory process.generalized paralysis of bowel wall with systemic toxicity
? diagnosis: by plain x-ray
1. bowel sounds
2. painful ,distended ,tender abdomen
3. systemic: fever, tachycardia , leukocytosis

treatment
1-npo, ng to intermittent suction
2-discontinue antidiarrheal drugs.
3-ivf , frequent electrolytes, transfuse as necessary
4- iv hydrocortisone or iv acth.
5- b/s abx : triple therapy
metronidazole (500mg q8hr)
gentamicin (5 mg/kg 1st dose)
clindamycin (900 mg iv q8h)
6- rotate patient to prone position every few hours to redistribute colonic gas.
7-frequent abd.exam. for fear of peritonitis or perforation.
8- kub upright/supine bid for colonic dilatation or free air.
indications for surgery in uc:absolute:
1.fulminant colitis
2.local complications:
- toxic megacolon
- massive haemorrhage
- frank perforation
- peritonitis
3.carcinoma
4.growth retardation in pediatric patients
relative indications :
progressive course of dis.
intractebilitydespite maximal medical therapy
flat displasia ??-??? gr.
pseudopolyposis, extracolonic manifestations
operative
terminal ileostomy

j pouch rectal anastomosis
j or s pouch anal anastomosis



cd management
medical
nutritional replacement ,oral 5-aminosalicylates sulphasalazine, mesalazine ,antibiotics corticosteroids (oral/iv) ,immunomodulators azathioprine, methotrexate
anti-tnf antibodies infliximab, adalumimab experimental therapies
surgical
resection of bowel, abscess drainage , fistula repair strictureoplasty management by multidisciplinary gastroenterologist surgeon dietician nurse psychologist radiologist