GI lecture 5 Large Bowel Disorders pt 1

Irritable bowel syndrome (IBS)

idiopathic chronic functional disorder characterized by abdominal pain or discomfort with alterations in bowel habits

Rome IV criteria

Recurrent abdominal pain on average for at least 1 day/week in the last 3 months associated with 2 of the following:

1. related to defecation

2. onset associated with change in stool freq

3. onset associated with change in stool form

other symptoms of IBS

gas, bloating, feeling of abdominal distention

straining or urgency

feeling of incomplete emptying with defecation

may have other somatic or psychological complaints

Bristol stool chart

IBS symptoms are exacerbated by

stress and irritants in the intestinal lumen

3 types of IBS

IBS-C: constipation predominant, type 1 and 2

IBS-D: diarrhea predominant, type 6 and 7

mixed IBS: characterized by intermittent periods of constipation and diarrhea

factors that play a role in IBS

GI motility dysfunction

visceral hypersensitivity

intestinal inflammation

fecal microflora differences

food sensitivities

genetics

early life stressors

female > male

GI motility dysfunction

increased freq and irregularity of bowel contractions, increased or decreased transit time, exaggerated response to cholecystokinin

visceral hypersensitivity

hypersensitivity of receptors triggered by bowel distention and bloating

intestinal inflammation

increased lymphocyte infiltration and release of mediators causing contraction, increased mast cell infiltration, elevated levels of pro-inflammatory cytokines

increased after enteritis

IBS diagnosis

positive diagnostic strategy w thorough H&P coupled with Rome IV criteria and selective lab eval

IBS labs

serologic testing to r/o celiac disease (anti-tissue transglutaminase and IgA levels) in pts w IBS/diarrhea symptoms

fecal calprotectin, CRP in pts w/o alarm features to r/u IBD

IBS diagnostic testing is based on

age, alarm symptoms, profession

symptoms that don't suggest IBS

nocturnal symptoms, progressive symptoms, weight loss, GI bleed hx, refractory symptoms, anemia

IBS-C treatment

laxatives (1st line)- soluble fiber, polyethylene glycol

secretory stimulators - linaclotide, plecanaide (2nd line), lubiprostone (3rd line)

laxatives improves constipation in IBS-C but not

abdominal pain

IBS-D treatment

Loperamide (1st line)

Cholestyramine (2nd line)

Rifaximin- avoid as 1st line due to effect on microbiome

Alosetron- females only and no GI tract abnormality

FODMAP diet

decrease these foods in IBS

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

constipation

fewer than 3 bowel movements per week

hard/lumpy

difficulty during defecation (straining, sensation of obstruction or incomplete evacuation, need to perform manual manipulations)

constipation causes

neuromuscular disease

endocrine disorders

electrolyte anormalities

IBS-C

Hirschsprung's disease

medications

strictures

functional (low fiber diet, dehydration)

medications that can cause constipation

opioids, SSRIs, anticholinergics, diuretics, cholestyramine, CCBs

Hirschsprung disease

absent ganglion cells in large intestinal causing decreased contractions and innervation for normal peristalsis

failure to pass meconium

constipation treatment

education- increase fiber, water, activity level

fiber supplements

osmotic laxatives

may add bisacodyl if not responding

lubiprostone, linaclotide (newer treatments)

linaclotide should be taken at least

30 min before 1st meal each day

treatment for opioid constipation

lubiprostone (female only)

naloxegol, methylnaltrecxone bromide, naldemedine

inflammatory bowel disease (IBD)

characterized by diffuse mucosal inflammation

Ulcerative colitis (UC) and Crohn's disease

nicotine worsens prognosis in ____ but improves symptoms with ____

Crohn's; UC

IBD has _____ age distribution

bimodal- early in life and 7th decade

IBD diet factors

poss due to high fat, processed foods

medication that is associated w exacerbation of disease

NSAIDs

IBD 3 major pathways

genetic predisposition

immune dysregulation

environmental antigen

IBD can be induced after intro of

commensal bacteria

Crohn's inflammation can be relieved by

diverting fecal material away from active mucosal inflammation (ileostomy)

extra-intestinal findings in IBD

oral ulcers, oligoarticular or polyarticular non-deforming peripheral arthritis, spondylitis or sacroilitis, uveitis, erythema nodosum, pyoderma gangrenosum, non-infectious hepatitis, sclerosing cholangitis, thromboembolic events

MC derm manifestation in IBD

erythema nodosum

generally on extensor aspects of lower legs

parallels disease activity

pyoderma gangrenosum

uncommon

often preceded by trauma to the skin; painful, ulcerative cutaneous lesions that develop from single or multiple erythematous papules or pustules

does not parallel disease

MC extra-intestinal manifestation of IBD

arthritis/arthropathy

nondestructive peripheral arthritis primarily involving large joints, anklosing spondylitis, osteoporosis, osteopenia, osteonecrosis

MC ocular manifestation of IBD

episcleritis

irritation, itching, or burning

doesn't cause significant ocular complications or impaired vision

managed w topical therapy and treatment of IBD

scleritis

severe, constant, boring pain that worsens at night and in the early morning that radiates to face and periorbital region

can impair vision

does not parallel disease

treat w NSAIDs, corticosteroids, and immunosuppressive agents

Ulcerative colitis (UC)

inflammation limited to the mucosal layer of the colon

ulcers + mucosal edema

usual onset of UC

20-40s w another smaller peak in 7th decade

UC symptoms

recurrent diarrhea mixed w blood/mucus (main symptom)

bowel movements small and frequent, gradual onset, tenesmus, abdominal pain

more extensive disease- fever, weight loss, fatigue d/t anemia, malabsorption

UC signs

PE normal esp in mild disease

abdominal tendernesss on palpation (LLQ), fever, hypotension, tachycardia, pallor

rectal exams may reveal blood

hallmark of UC

continuous ulceration starting in rectum and limited to colon

can see inflammation of the ileum due to backwash from colon

mild UC

4 or fewer bowel movements per day w or w/o blood, no signs of systemic toxicity, and normal ESR

moderate UC

>4 loose, bloody stools per day w mild anemia not req transfusion and abdominal pain that is not severe.

May have minimal signs of toxicity including low-grade fever

severe UC

>/= 6 loose, bloody stools w severe cramps and evidence of systemic toxicity including fever, tachycardia, anemia, and elevated ESR

UC diagnosis

best made w colonoscopy - uniform inflammation, abnormal erythematous mucosa w or w/o ulcerations

supportive testing- perinuclear antibeutrophil cytoplasmic antibodies (pANCA)

CT scan- good for abscess location and symptoms od colitits

double contrast barium enema- fine mucosal detail

stool eval for blood, leukocytes, ova, parasites, culture, toxins

UC labs

CBC - anemia

CMP- low albumin, K, mag. elevated alk phos

ESR correlates w disease activity

type and cross if significant bleeding

treatment to induce remission in mild-moderate UC

mesalamine (5-ASA agent)- start w high dose. suppository or edema daily, acts as topical antiinflammatory. enema reaches prox sigmoid colon and splenic flexure

hydrocortisone suppository or foam preparation (

prednisone- 1 week then taper for 4-8 weeks

recommended treatment for pts w left-sided or extensive UC

start w oral 5-ASA plus rectal mesalamine

mild-moderate UC maintenance therapy

pts that respond to topical 5-ASA: daily mesalamine suppository or enema

pts that require oral 5-ASA: saily admin

treatment to induce remission in moderate-severe UC

anti-TNF therapy w or w/o immunomodulator (1st line)- expected response in days-8weeks. Infliximab, adalimumab, golimumab

cyclosporine can be used short term and effective to avoid surgery

thiopurine immunomodulators- azathiprine, 6-mercaptopurine. reduce T and B proliferation, decrease cytotoxic T cells and plasma cells

screening before starting anti-TNFs

hep B and C, TB, varicella, EBV, and CMV

anti-TNF contraindications

active, untreated infection, latent TB, demyelinating disease, uncontrolled HF, active malignancy

side effects of thiopurine immunomodulators

dose dependent- leukopenia, abnormal liver chemistries

dose independent- nausea, pancreatitis, infection, malignancy

goal of UC management once remission is achieved

maintain glucocorticoid-free remission and prevent clinical and endoscopic relapse

moderate-severe UC maintenance therapy

methotrexate

thiopurine analogues- may take up to 12 weeks

S1P receptor modulators- estrasimod, ozanimod

JAK inhibitors- tofacitinib, upadacitinib. reserved for nonresponders to initial therapy

JAK inhibitors side effects

cytopenias, dyslipidemias, liver energy, reactivation of TB, hep B and C

UC maintenance therapy for flare-ups

nicotine patches

abx to consider for UC maintenance therapy

cipro, bactrim, flagyl

other maintenance therapy meds

antidiarrheals

pain relievers

replacement of electrolytes, minerals, and vitamins lost to malabsorption

when to treat UC w surgery

massive hemorrhage

perforation

toxic megacolon

dysplasia/cancer

colectomy (can be curative)

toxic megacolon

non-obstructive dilation of colon >6cm, fever, tachycardia, leukocytosis, postural hypotension, decreased bowel sounds

anemia, severe pain, abdominal distention

can lead to total sepsis and cardiopulmonary collapse

toxic megacolon treatment

reduce distention to prevent perforation - bowel rest w NG tube

correct fluid/electrolyte imbalance

treat toemia and precipitating factors

meds- IV steroids, broad spectrum abx (ampicillin, gentamycin, metronidazole), cyclosporine

early surgical consult

Crohn's disease

chronic inflammation that can occur from pharynx to rectum. can have transmural ulceration, strictures, fistulae, and fissures

peak incidence occurs btwn 15-30yo and 2nd peak in 7th decade

Crohn's disease s&s

depends on location

cardinal- crampy abdominal pain, chronic intermittent diarrhea w or w/o gross bleeding, fatigue, weight loss

tenesmus, fecal urgency, malabsorption, dehydration and electrolyte abnormalities, leukocytosis

transmural bowel wall inflammation is associated w

perianal fistulas or abscesses

Crohn's disease physical findings

RLQ tenderness (different from UC which has LLQ), tender mass

sequelae of Crohn's disease

intestinal obstruction- postprandial bloating, cramping, pains, loud borborygmi

penetrating disease and fistulae

perianal disease assoc w Crohn's

large painful skin tags

anal fissures

perianal abscesses

extraintestinal manifestations of Crohn's

arthralgias, arthritis, iritis or uveitits, pyoderma gangrenosum, erythema nodosum, oral ophthous lesions, gallstones, nephrolithiasis

Crohn's diagnosis-imaging

ileocolonoscopy (1st) - ulcers, strictures, skip lesion

CT/MR enterography- bowel wall thickening, vascularity, mucosal enhancement, fat stranding

capsule imaging for small bowel

barium upper GI w/ small bowel follow-through

Crohn's diagnosis- labs

anti-saccharomyces cerevisae IgA and IgG antibodies (ASCA)

CBC, serum albumin, sed rate, CRP

stool cultures- pathogens, ova, parasites, leukocytes, fat, c diff

serum iron, ferritin, vit d, b12

mild Crohn's treatment

step up approach

-step 1: aminosalicylates +/- abx (flagyl, cipro-for fistula or abscess)

-step 2: corticosteroids

-step 3: immune modifying agents (thiopurine agents, methotrexate)

-step 4: biologic agents and/or surgery

mod-severe Crohn's treatment

top-down approach

-anti-TNF for induction and maintenance

-humanized monoclonal antibody (natalizumab- prevents accumulation of lymphocytes)

-interleukin inhibitors (ustekinumab) key role in inflammatory and immune responses

-methotrexate

natalizumab reserved for

patients who are intolerant or have lost response to biologic/immunosuppresive therapy

interleukin inhibitors indications

patients who failed or were intolerant to immunomodulators or corticosteroids, but never failed a TNF

or

patients who failed or were intoleerant to 1 or more TNF blockers

indications for sx in Crohn's

intractability to medical therapy

intra-abdominal abscess

massive bleeding

symtomatic refractory internal or perianal fistula

intestinal obstruction

Crohn's prognosis

symptoms are chronic and intermittent but disease course varies

higher risk for hematologic malignancy