INFLAMMATORY BOWEL DISEASE:

CROHN’S DISEASE &

ULCERATIVE COLITIS
Michelle Gaxiola Gastélum - A01741321 Lorraine Suaste Arroyo - A01704737
Marianna Lozano Guardado - A01352009 Anagaby Litz Cantú - A01411906
Andrea Arellano Cervantes- A01641671 Arlet Esparza López - A01635573
 INFLAMMATORY BOWEL DISEASE (IBD)
A group of disorders that develop a chronic (long- term) inflammation of the gastrointestinal
tract tissues. This prolonged inflammation = damaged tissue

Crohn Disease Ulcerative Colitis

Epidemiology:

Incidence: 1-1.5 of 100,000 people

in Latin America
Most common:

Affects women and men, more

often between 18 - 25 yo and
between 60-75 yo

(Secretaria de Salud, 2022)

 CROHN’S DISEASE
An IBD that can affect any part of the GI tract, usually the
end of the small bowel (ileum) and the beginning of the
colon. It can affect the thickness of the bowel wall.
It isn´t a continuous area = patches all around
the bowel
Classification

Ileocolitis
Epidemiology: Ileitis
Gastroduodenal
Incidence: 2% in Mexico = 20 of 1,000 Mexicans Jejunoileitis
Typical Age Onset: 15 - 35 yo and 55-75 yo Colitis
Same in women and men
Prevalence:
Individuals of Northern European descent
Individuals of Ashkenazi Jewish descent

(John Hopkins Medicine, 2022)

PATHOPHYSIOLOGY
Crohn´s Disease
PATHOPHYSIOLOGY
Crohn´s Disease

NOD2
NOD2

NFKB
PATHOPHYSIOLOGY
Crohn´s Disease

Immune response against luminal bacteria in the gut

CD4 T-Cells, CD8 T-Cells, B-Cells, CD14 monocytes and natural

killers

interaction of these cells with integrins, adhesion molecules

and multiple chemokines.

MAcCAM-1 receptor in leukocytes for the α4β4 integrin

Hyperactivity of T cells with excessive production of cytokines,

between which IL-12 and IFN-γ, promoting a TH1 lymphocytic
phenotype
Petagna L. et al 2020 Pathophysiology of Crohn’s disease inflammation and recurrence
.
PATHOPHYSIOLOGY
Crohn´s Disease

Immune response against luminal bacteria in the gut

IL-21 converts naive B-Cells into B-Cells expressing granzyme-B: it possesses a

cytotoxic activity on the intestinal mucosa and perpetuates the epithelial
damage

Microbial-associated molecular pattern (MAMP) sensed by toll-like receptors on

immune cells, contributes to the activation of immune response in the context of
chronic inflammation

Petagna L. et al 2020 Pathophysiology of Crohn’s disease inflammation and recurrence

.
PATHOPHYSIOLOGY
Crohn´s Disease

Petagna L. et al 2020
Pathophysiology of
Crohn’s disease
inflammation and
recurrence
.
RISK FACTORS:
Familial aggregation

Genetic predisposition (e.g., mutation of the NOD2 gene, HLA-B27 association)

Tobacco smoke

Developed cities and countries

Northern climate places

CLINICAL FEATURES:
Low-grade fever
Weight loss
Fatigue

Gastrointestinas Symptoms:

Chronic Diarrhea Malabsortion (anemia)

Decreased appetite Enterocutaneous perianal fistulas
Abdominal pain, RLQ Abscess
Palpable adbominal mass
Lower GI bleeding (uncommon)
COMPLICATIONS Fistulizing CD
Colorectal cancer

Short bowel syndrome and associated issues after surgery

Stenosis/strictures → bowel obstruction

Intestinal perforation
Systemic
Primary sclerosing cholangitis

Impaired bile acid reabsorption inflammation

Bile acid diarrhea

Bile acid malabsorption → steatorrhea and deficiencies in fat-soluble vitamins

Abscess formation/phlegmons
 DIAGNOSIS
The order of clinical tests will depend on the patients
status

1 2 3
Ileocolonoscopy MRI, CT and stool CBC, CPR, Clostridium
Used in every patient antigen. difficile toxin, fecal
calprotectin and or fecal
along with biopsy,
lactoferrin, albumin and
high sensibility
total proteins
 ILEOCOLONOSCOPY

Linear or spirginous Spirginous ulcerations aphtous ulcerations

ulcerations cobble stone sign
Strictures erytema

Skip pattern
MRI AND CT

String sign
Thickening of the
intestinal wall
Creeping fat
 LABORATORY STUDIES
Lactoferrin
Neutrophil activation

Calprotectin

Anti-
Saccharomyces Fungical infection
cerevisiae
antibodies (ASCA)

CPR, ESR, Platelets Inflammation evolution

Thrombocytes
Coagulation process
increases

Vitamin B12 and

Anemia caused by deficiency
Iron levels
 Treatment

Biologic +/- MP/ AZA/ MTX

Prednisone oral (induction of remission only)

Sulfasalazine (colon)

Budesonide (ileal an right colon)

Mild to Moderate Crohn´s Disease

 Treatment

Total parenteral nutrition and

bowel rest
Total parenteral nutrition and
bowel rest
Biologic +/- MP/ AZA/ MTX
Biologic +/- MP/ AZA/ MTX
Hydrocortisone or Solumedrol IV (induction
of remission only)
Abscess drainage and antibiotics
Prednisone oral (induction of remission only)

Mild to Severe Crohn´s Disease Fistulizing Crohn´s Disease

 PROGNOSIS
It doesn´t have a cure.
The life expectancy is slightly reduced due to the development of
malignancies, genitourinary disease, and liver, and biliary tract
complications.
The majority of Px who develop complications need surgery and as
the disease progresses, some need multiple procedures.
Px with the proximal disease have higher mortality than those with
the distal disease.
 Ulcerative Colitis
CIUC: Chronic idiopathic ulcerative colitis
 Chronic inflammatory disorder that affects the colon, rectum and cecum
Inflammation starts in the rectum, is continuous, and superficial
Only affecting the epithelial layer of the mucosa
Bloody diarrhea
Major form of IBD

Genetic and environmental factors predispose

IBD
Nucleotide oligomerization domain (NOD):
chromosome 16 gene NOD2
Altered expression of claudins and occludins
Diet: packaged food, fast food, increased fat
(monounsaturated and polyunsaturated fatty
acids) consumption and sugar intake, and less
dietary fiber
 Risk factors for UC
Incidence (North America) per person-years: 0.19.2 per 100,000

Genetic predisposition: HLA-B27 association

Ethnicity
Greatest incidence among white & Ashkenazi Jewish descent
Incidence among Hispanics and Asian people is increasing
Family history of UBD (approximately 20% of cases)
Episodes of previous intestinal infection
Increased fat intake (saturated fat and animal fat)
Oral contraceptives
NSAIDs may exacerbate UC
Age
most people get diagnosed between 15 and 30 years old or
when they are older than 60. Feldman, M., Friedman, L.S. and Lawrence, B.J. (2010)
 Pathophysiology

IL-6 IL-12
TNF-α
Cytotoxic
Disregulation
Intestinal epithelium Immune system

activation of
permeability macrophages and CD4
dendritic cells
Intestinal epithelial cells are the first line of defense
The mucus layer in UC appears to be thinner than normal TH2
Colonocytes express class II MHC antigens and can function as APCs IL-4

Expression of adhesion molecules is critical to amplify the immune response.

1 selectins 2 chemokines (IL-8) 3 integrins

B
Plasma
cell

“Structural similarity” Autoantibodies (p-ANCA)

gut bacteria
 Pancolitis
Distal Colitis

Proctosigmoiditis

Pattern:
Ascending inflammation. ---- begins in the rectum
Proctitis
Mucosa and submucosa
Intestinal Sx Clinical Features
Major Sx
Diarrhea* (Intermittent and mild that patient does not seek medical attention)
Rectal bleeding*
Tenesmus
Passage of mucus
Crampy abdominal pain
The severity of the symptoms correlates with the extent of the disease
Symptoms usually have been present for weeks to months
Sx in moderate to severe disease
patients pass a liquid stool containing blood, pus, and fecal matter
cramping
abdominal pain
anorexia
nausea
vomiting
fever
weight loss
→
Patients with Toxic colitis have severe pain & bleeding
Sx in extensive disease →
Patients with Megacolon have hepatic tympany
tenderness to palpation directly over the colon *Both may have signs of peritonitis if a perforation has occurred.

Harrison's principles of internal medicine. (2011). New York :McGraw-Hill, Health Professions Division,
Extraintestinal Sx Clinical Features
General:
fatigue*
fever

Skeletal (most common extraintestinal manifestation of UC)

osteoarthritis
ankylosing spondylitis (> 90% of patients are positive for the HLA-B27 genotype)
sacroiliitis

Ocular
uveitis
episcleritis

Biliary
primary sclerosing cholangitis (associated with autoimmune diseases: IBD)
only 4% of patients with IBD will develop PSC

Cutaneous
erythema nodosum
pyoderma gangrenosum
aphthous stomatitis

(Levine JS, Burakoff ,2011)

Diagnostic
No single symptom, sign, or diagnostic test establishes the diagnosis of IBD
Complete assessment of the clinical presentation, radiologic, endoscopic, and pathologic findings.

WBC count may be normal or elevated

CBC ---> Anemia
Fecal calprotectin or lactoferrin
Elevated GGT and ALP
Stool studies should include culture, examination for ova and parasites, and testing for C. difficile infection
(performed before endoscopy)
Serology for Entamoeba histolytica should be considered in travelers to endemic areas like developing parts of
Central and South America, Africa, and Asia.
Serologic testing (ASCA and P-ANCA) may be used as an adjunct to diagnosis (can not effectively differentiate)
New biomarkers ---> fecal volatile organic metabolites [VOMs]) can be analyzed by gas chromatography mass
spectrometry and help differentiate CD from UC

(Kaplan, 2020)
 (Kaplan, 2020)

Diagnostic
Sigmoidoscopy with biopsies usually is
sufficient to confirm the diagnosis
Endoscopy
Avoid excessive distention (perforation)
during colonoscopy (extent)

C= Histopathology showing a severe acute and chronic

Symmetric and continuous inflammation:
Begins from the anorectal junction
Decrease or loss of the normal vascular pattern, with
mucosal erythema and edema and patchy subepithelial
hemorrhage (earliest sign)
inflammatory process, with multiple crypt abscesses
D= distortion of the colonic architecture with a loss of crypts
and abnormal branching of the crypts
With more severe inflammation, mucosa may be covered by yellow-
brown mucopurulent exudates associated with mucosal ulcerations.
 Diagnostic
Endoscopy
Pseudopolyps typically are small, soft, pale, fleshy, and glistening
They may be large, sessile, or pedunculated and may have surface ulcerations
Rarely obstruct the lumen of the colon.
Epithelial regeneration with recurrent attacks

(Kaplan, 2020)
 Diagnostic
lead-pipe (barium enema)

Loss of normal colonic architecture

Muscular hypertrophy
Loss of the normal haustral fold pattern
Decreased lumenal diameter
Shortening of the colon

(Kaplan, 2020)
 Diagnostic
Radiology (CT and MRI)
The lumenal margin of the colon (the interface between
the colonic mucosa and the lumenal gas) becomes
edematous and irregular
Thickening of the colonic wall
Islands of residual mucosa surrounded by extensive deep
ulcerations
Distention of the small bowel
Dilatation of the colon can be detected
The presence of intraperitoneal air may be missed on plain
abdominal films ---> CT has demonstrated a better
diagnostic yield than plain abdominal radiology for
detecting disease complications and extent.

Plain abdominal film, severe UC. (Kaplan, 2020)

 (Kaplan, 2020)

Combination of clinical findings and laboratory parameters

Assessment of disease
activity

(extensive colitis)

Complete colonoscopic examination should be avoided (perforation)

Fulminant colitis: severe colitis who appear toxic, >38.3°C (101°F),
tachycardia, abdominal distention, signs of localized or generalized
peritonitis, and leukocytosis. Clinical and endoscopic assessments
Toxic megacolon: radiologic of transverse colon dilatation >6 cm In remission <2
(abdominal x-ray) Severe disease if the score is >10.
5-ASA Agent
Are effective at inducing and
maintaining remission in UC.
Peroxisome proliferator–activated
receptor γ (PPAR-γ) may mediate 5-
ASA therapeutic action by
decreasing nuclear localization of
NF-κB.

Side effects of the 5-ASA medications

Headaches, nausea, hair loss, and

abdominal pain.
Renal impairment, hematuria,
pancreatitis, and paradoxical
worsening of colitis. (rare)

Lialda is a once-a-day formulation of mesalamine [MMX] designed to release mesalamine in the colon. (resistant to degradation, Ph<7)
 Treatment
Tofacitinib

Cyclosporine IV
Biologic +/-
MP/AZA/MTX

Prednisone oral (induction Tofacitinib

of remission only)

Biologic +/- MP/AZA/MTX

Hydrocortisone rectal

Hydrocortisone or Solumedrol IV
Budesonide rectal and/or oral (induction of remission only)

5-ASA oral and/or rectal Prednisone oral (induction of remission only)

Mild to Moderate Ulcerative Colitis Moderate to Severe Ulcerative Colitis

 Pharmacology
5-aminosalicylic acid preparations (eg, mesalamine), 6-mercaptopurine, infliximab, colectomy.

DRUG In UC Mechanism Adverse effects

A combination of sulfapyridine
Malaise, nausea, sulfonamide toxicity,
(antibacterial) and 5-aminosalicylic acid
Sulfasalazine mild to moderate UC reversible oligospermia.
(anti-inflammatory). Activated by colonic
bacteria.

Lialda y Apriso Se administran una vez al día

 Treatment
Urgent or emergent surgical intervention
for toxic or fulminant colitis is best
managed by abdominal colectomy

Colectomy
Proctocolectomy
Proctectomy (rectum)
 Complications & Prognosis for UC
Only 15% of patients with UC present with catastrophic illness
Toxic megacolon -->
↑ Risk of cancer: risk increases with duration of disease
UC patients have six times greater risk of developing colorectal cancer than those of average risk
In patients with extensive disease (pancolitis) the cancer risk is approx 5-10% after 20 years.

Massive hemorrhage (1%)

Occurs with severe attacks of disease
Treatment for the disease stops the bleeding
If a patient requires 6-8 units of blood within 24-48 hours, colectomy is indicated

Perforation
Most dangerous of local complications
The physical signs of peritonitis may not be obvious, especially if the patient is receiving glucocorticoids
Although perforation is rare the mortality rate for perforation complicating a toxic megacolon is about
(15%)

Colonic strictures (5-10%)

Always a concern because of the possibility of underlying neoplasia.
Strictures that are impassable with the colonoscopy should be presumed malignant
Strictures that prevents passage of the colonoscope is indication for surgery

Anal fissures, perianal abscesses, hemorrhoids (occasionally)

the occurrence of extensive perianal lesions should suggest CD Feldman, M., Friedman, L.S. and Lawrence, B.J. (2010)
 Toxic Megacolon
Defined as: acute colonic dilatation with transverse colon diameter of
more than 6 cm and loss of haustration in a patient with severe attack
of colitis.

Occurs in approximately 5% of severe flares of UC

Results from extension of colonic inflammation beyond the mucosa to

the underlying tissues; including the muscularis propria

Loss of contractility from the inflammatory reaction leads to the

accumulation of gas & fluid within the lumen

Precipitating factors
Electrolyte imbalance: hypokalemia
Antimotility drugs including anticholinergic agents
Narcotics

Medical management is directed at:

a. Treating the inflammation
b. Restoring colonic motility
c.Preventing free colonic perforation

Harrison's principles of internal medicine. (2011). New York :McGraw-Hill, Health Professions Division,
 References
Feldman, M., Friedman, L.S. and Lawrence, B.J. (2010). Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. 10th Edition,
Saunders, Elsevier Science, 1554 p.

Harrison's principles of internal medicine. (2011). New York :McGraw-Hill, Health Professions Division,

Levine JS, Burakoff R. Extraintestinal manifestations of inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2011
Apr;7(4):235-41. PMID: 21857821; PMCID: PMC3127025.

Mayo Clinic. (2022, 3 septiembre).Inflammatory bowel disease (IBD) - Symptoms and causes - Mayo Clinic.
https://www.mayoclinic.org/diseases-conditions/inflammatory-bowel-disease/symptoms-causes/syc-20353315

Secretaria De Salud. (s. f.). 240. Enfermedad inflamatoria intestinal, padecimiento autoinmune. gob.mx.
https://www.gob.mx/salud/prensa/240-enfermedad-inflamatoria-intestinal-padecimiento-
autoinmune#:~:text=La%20enfermedad%20inflamatoria%20intestinal%20es,M%C3%A9xico%2C%20Emir%20Israel%20Ju%C3%A1re
z%20Vald%C3%A9s.

Amboss. (2024). Crohn’s Disease. AMBOSS. https://next.amboss.com/us/article/VS0GA2?q=crohns%20disease

Crohn’s Disease. (2022, 19 abril). Johns Hopkins Medicine. https://www.hopkinsmedicine.org/health/conditions-and-

diseases/crohns-disease

Kaplan, G., Ng, S. (2020). Epidemiology, Pathogenesis, and Diagnosis of Inflammatory Bowel Diseases. Sleisenger and Fordtran’s
Gastrointestinal and Liver Disease. Cap. 115
 References
Petagna, L., Antonelli, A., Ganini, C., Bellato, V., Campanelli, M., Divizia, A., Efrati, C., Franceschilli, M., Guida, A. M., Ingallinella, S.,
Montagnese, F., Sensi, B., Siragusa, L., & Sica, G. S. (2020). Pathophysiology of Crohn's disease inflammation and recurrence.
Biology direct, 15(1), 23. https://doi.org/10.1186/s13062-020-00280-5