GI 1 main points

What glands is the oral cavity composed of?

Saliva glands → help to moisten and start the metabolism of food

1) Parotid gland: located near the ear and cheek area.

2) Submandibular gland: located beneath the mandible (like jaw area)

3) Sublingual gland: located under the tongue.

What is the route of the GI tract from mouth to anus?

Oral cavity → pharynx → esophagus → stomach → duodenum → jejunum → ileum → cecum → ascending colon → transverse colon → descending colon → sigmoid colon → rectum → anal canal → anus

What is located in each quadrant of the digestive tract?

• RUQ

  • Liver

  • Gallbladder

• LUQ

  • Stomach

• RLQ

  • Ileum

  • Cecum

  • Appendix

• LLQ

  • Sigmoid colon

What organs are contained in the foregut? What are their individual peritoneal categorizations?

• Esophagus

• Stomach (intraperitoneal)

• Duodenum (sectors 1 and 2)

  • 1 - intraperitoneal

  • 2 - retroperitoneal (receiving point)

• Liver (intraperitoneal)

• Gall bladder (intraperitoneal)

• Pancreas (retroperitoneal)

What is the peritoneal specialization of the foregut (holistically)?

• Greater omentum

  • Hangs from the greater curvature of the stomach and over the intestines (curtain-like)

• Lesser omentum

  • Connects the liver to the lesser curvature of the stomach

Describe the blood supply of the foregut (arterial and venous).

• Arterials

  • Celiac trunk (arterial supply) splits into:

    • Left gastric artery

      • Supplies the lesser curvature of the stomach and lower esophagus

    • Common hepatic artery

      • Supplies liver, stomach, proximal duodenum

    • Splenic artery

      • Supplies the spleen, pancreas, and part of the stomach

• Venous

  • Blood drains into the spleen vein -> hepatic portal vein -> hepatic veins -> inferior vena cava

What organs are embodied in the midgut? What are their individual peritoneal categorizations?

• Duodenum (sectors 3 and 4)

  • 3 - retroperitoneal

  • 4 - retroperitoneal

• Jejunum (intraperitoneal)

• Ileum (intraperitoneal)

• Cecum (intraperitoneal)

• Appendix (intraperitoneal)

• Ascending colon (retroperitoneal)

• First ⅔ of the transverse colon (intraperitoneal)

  • Teniae coli -> smooth muscle bands along the large intestines -> peristalsis

What is the peritoneal specialization of the midgut (holistically)?

• The mesentery -> suspends the jejunum and ileum

  • Jejunum

    • More semi-circular folds within the tube of the jejunum (more SA for absorption of AA, fatty acids, and carbs)

    • Thicker artery circulation 

    • Thinners mesentery (can see through)

  • Ileum

    • Fewer semi-circular folds

    • Thinner, more spiderweb-like blood supply

    • Fattier mesentery (can't see through)

Describe the blood supply of the midgut (arterial and venous).

• Arterial

  • Superior mesenteric artery → branches into:

    • Intestinal arteries

      • Jejunum and ileum

    • Middle colic artery

      • Transverse colon

    • Right colic artery

      • Ascending colon

    • Ileocolic artery

      • Cecum and appendix

• Venous

  • Blood drains into the superior mesenteric vein -> joins the splenic vein = hepatic portal vein -> liver

What organs are embodied in the hindgut? What are their individual peritoneal categorizations?

• Last ⅓ of the transverse colon -> has a different blood supply than the first ⅔ (intraperitoneal)

• Descending colon (retroperitoneal)

• Sigmoid colon (intraperitoneal)

• Rectum (retroperitoneal)

• Proximal anal canal

Describe the blood supply of the hindgut (arterial and venous).

• Arterial

  • Inferior mesenteric artery (IMA) branches into:

    • Left colic artery → descending colon

    • Sigmoidal arteries → sigmoid colon

    • Superior rectal artery → rectum

• Venous

  • Blood drains via the inferior mesenteric vein -> drains into the splenic vein → meets up with the superior mesenteric vein = hepatic portal vein

Define the following: Parietal peritoneum, Visceral peritoneum, Mesentery, Intraperitoneal, and Retroperitoneal

• Parietal peritoneum: lines the abdominal wall 

• Visceral peritoneum: covers organs 

• Mesentery: a double layer that suspends organs and carries blood vessels 

• Organs can be: 

  • Intraperitoneal (suspended in the peritoneum) 

    • Contains mesentery, unlike retroperitoneal → FLOPPY

  • Retroperitoneal (behind it, against the posterior wall)

Where do SANS vs PANS nerves originate for the GI tract?

• SANS: Thoracolumbar spinal cord (mid spinal cord)

• PANS: Brainstem + sacral spinal cord

What is the autonomic innervation of the foregut?

• SANS: Greater + lesser splanchnic nerves (T5–T9)

• PANS: Vagus nerve (CN X)

What is the autonomic innervation of the midgut?

• SANS: Greater + lesser splanchnic nerves (T10–T11)

• PANS: Vagus nerve (CN X)

What is the autonomic innervation of the hindgut?

• SANS: Lumbar splanchnic nerves (L1–L2/3)

• PANS: Pelvic splanchnic nerves (S2–S4)

Explain the mechanism of referred pain from visceral organs.

• Visceral irritation activates shared spinal nerves

• The brain cannot distinguish the source

  • GI organs have poor localization of pain → since sharing spinal pathways with other parts of the body

• Pain is perceived in a somatic region with the same innervation

What are the functions of the GI tract?

• Digestion 

  • Breaks down food mechanically and chemically (enzymes) into smaller molecules that can be absorbed

• Defense

  • Protects the body from harmful substances (pathogens, toxins, irritants) entering the GI lumen

• Regulation of fluid and electrolyte balance

  • Absorbs and secretes water and electrolytes to maintain homeostasis.

What are the general symptoms of the GI tract (how can they be organized)?

• Motor

  • Dysphagia (difficulty swallowing)

  • Constipation

• Sensory

  • Dyspepsia (heartburn)

  • Pain

• Sensorimotor

  • Nausea/Vomiting

• Diarrhea

• Bleeding

What are the main mechanisms that initiate GI pain?

• Mechanical stretch

  • Peristalsis problems (innervation)

  • Luminal obstruction (adhesions, tumor)

• Chemical irritation

• Inflammation

  • Immune, autoimmune, infectious, chemical

How is GI pain detected and initiated at the cellular level?

• Enterochromaffin (EC) cells detect chemical/inflammatory stimuli

• Release serotonin (5-HT)

• 5-HT activates sensory neurons in ENS

• Mechanoreceptors detect stretch → signal via ENS neurons

• Signal travels through ENS → visceral sensory nerves → spinal cord → brain → perception of pain

What is the role of the enteric nervous system (ENS) in GI?

• Sensory role: detects stretch, food, irritation

• Motor role: controls peristalsis and secretion

• Can function independently of the CNS

  • Modulated by SANS and PANS

How is visceral GI pain regionally perceived?

• Follows embryologic regions:

  • Foregut: upper middle abdomen (epigastric)

  • Midgut: around the belly button (periumbilical)

  • Hindgut: lower abdomen (often LLQ)

How do medications reduce GI pain?

• NSAIDs: ↓ inflammation → ↓ nociceptor activation

• Opioids: ↓ pain transmission

  • Act peripherally and in the spinal cord

What is the main mechanism of GI bleeding?

Damage/erosion of mucosa → exposure of blood vessels → bleeding

What are the main causes of GI bleeding?

• Infection

• Inflammation (IBD)

• Chemical injury (e.g., peptic ulcer disease)

• Neoplasia (cancer)

• Ischemia

  • ↓ perfusion → tissue damage

  • Reperfusion/collateral flow → bleeding

What is hematemesis, and what do different appearances indicate?

• Hematemesis = vomiting blood

• Bright red blood:

  • Active bleeding

  • Faster GI transit

  • Usually proximal (esophagus/stomach)

• Coffee-ground appearance:

  • Blood has been digested/oxidized

  • Slower or older bleed

What is melena, and what does it indicate?

• Melena = black, tarry, shiny stool

• Indicates digested blood

• Usually from upper GI bleeding

  • Esophagus → stomach → small intestine

What does bright red blood in stool suggest?

• Lower GI bleeding (colon or rectum)

• Blood is not digested

• Common causes:

  • Hemorrhoids

  • Distal colon/rectal pathology

What is occult GI bleeding, and why is it important?

• Occult blood = not visible to the eye

• Small, slow bleed

• May present as:

  • Iron deficiency anemia

• Can be an early sign of colon cancer

What are alarm symptoms in GI disease? Why are these considered alarm symtoms?

• Anorexia (loss of appetite)

• Unintentional weight loss

  • May indicate colon cancer (causes weight loss and obstruction)

• Dysphagia (difficulty swallowing)

• Prolonged vomiting

• Hematemesis (vomiting blood)

• Melena (black, tarry stools)

These suggest a serious condition or require immediate intervention → Do NOT self-treat

What are considered to be normal patterns of GI motility and their functions?

• Segmentation

  • Non-propulsive movement of luminal contents: mixing and churning that enhances digestion.

• Peristalsis

  • A coordinated wave of contractions that propels food through the GI tract.

• Tonic contraction (sustained)

  • Prevents backflow of contents across the sphincter, allowing the stomach and large intestine to act as reservoirs (holds).

How are GI motility patterns established? How do they lead to contraction?

• Controlled by interstitial cells of Cajal (ICC)

• ICC generates slow waves (rhythmic depolarizations)

• Slow waves:

  • Set the baseline electrical rhythm

  • Do NOT cause contraction alone

• Slow wave amplitude reaches threshold → work of activating hormones like ACh

• Action potentials fire

• Ca²⁺ channels open → Ca²⁺ influx → Ca²⁺ binds calmodulin → Activates MLCK

• Myosin phosphorylation → actin-myosin interaction → contraction

What is the ionic mechanism behind ICC slow waves?

• ↑ intracellular Ca²⁺ in ICC

• Activates Ca²⁺-activated Cl⁻ channels

  • Loss of channels → no slow waves → no peristalsis (lethal)

  • Gain of function → excessive activity → smooth muscle hypertrophy

• Cl⁻ movement → depolarization (slow waves)

How do nerves/hormones regulate GI motility?

• PANS (ACh):

  • ↑ slow wave amplitude → work of ACh

  • Reaches threshold → action potentials → contraction

• SANS (NE):

  • ↓ slow wave amplitude → work of NE

  • → relaxation / ↓ peristalsis

Key difference in GI smooth muscle regulation vs vascular smooth muscle?

• Contraction mechanism is the same (Ca²⁺–calmodulin–MLCK)

• BUT in GI:

  • Norepinephrine (SANS) decreases slow wave amplitude

  • → inhibits contraction (↓ peristalsis)

How does the ENS regulate GI motility after activation?

• Trigger: stretch of lumen or irritation

• EC cells (enterochromaffin) release serotonin (5-HT) → activates sensory neurons

• ENS releases ACh → activates motor neurons:

  • Excitatory neurons:

    • Release ACh + Substance P

    • → contraction

  • Inhibitory neurons:

    • Release NO + VIP

    • → relaxation

How is peristalsis coordinated around a bolus?

• Behind bolus (oral side): contraction

• Ahead of bolus (caudal side): relaxation

How do opioids affect GI motility and how are they used clinically?

• Activate μ(mu)-opioid receptors

• ↓ ACh release from enteric neurons → ↓ smooth muscle contraction and ↓ peristalsis

• Effect: constipation

  • Used as an antidiarrheal (large intestine)

How do calcium channel blockers (CCBs) affect GI motility?

• Ca²⁺ needed for:

  • ACh release (neurons)

  • Muscle contraction

• Blocking Ca²⁺ → ↓ ACh + ↓ contraction

• Result: decreased motility → constipation

How do anticholinergic/antimuscarinic drugs affect the GI tract?

• Block muscarinic (M3) receptors

• ↓ ACh-mediated smooth muscle contraction

• → ↓ motility

• Used for: IBS symptom relief (pain, cramping) + antidiarrheal (drying effect → ANTIsludge)

How can other anticonvulsants, antidepressants, and statins contribute to decreased GI motility?

↓ neural signaling + altered smooth muscle function = slowed motility → constipation

What are the general criteria for adult/pediatric patients to be categorized with constipation? Why is it generalized?

• Adult

  • < 3 bowel movements per week

  • Hard, dry, or lumpy stools

  • Difficulty or pain with passing stool

  • Sensation of incomplete evacuation

• Pediatric

  • Delay or difficulty in BM ≥ 2 weeks

Bowel habits differ among individuals, and it is possible that some of the above are ok with some patients!

What are spasms in GI motility, and what causes them? What are some clinical signs?

• Spasms: continuous, uncoordinated maximal contraction

• Causes:

  • ↑ excitatory signaling (↑ ACh)

  • Dysregulated ENS activity

  • Loss of coordination between contraction and relaxation

• Clinical signs:

  • Crampy abdominal pain

  • Intermittent, severe discomfort

What is ileus, and what are its clinical features? What are some clinical signs?

• Ileus: ↓ or absent GI motility (especially small intestine)

• Causes:

  • ↓ ENS activity / impaired neural signaling

  • ↑ sympathetic tone

  • Medications (e.g., opioids)

• Effects: no peristalsis → buildup of contents

• Clinical signs:

  • Abdominal distension

  • Absent bowel sounds

  • Constipation, inability to pass gas

What is dysphagia, and what are its causes and symptoms? What are some clinical signs?

• Dysphagia: difficulty swallowing (± odynophagia = pain)

• Causes:

  • Impaired/uncoordinated esophageal peristalsis

  • Sphincter dysfunction

• Clinical signs:

  • Trouble swallowing solids or liquids

  • Sensation of food “sticking.”

What is gastroparesis and what are its clinical features? What are some clinical signs?

• Gastroparesis: delayed gastric emptying

• Causes:

  • Impaired gastric motility (often nerve dysfunction, e.g., diabetes)

• Mechanism: ↓ contractility → poor emptying

• Clinical signs:

  • Nausea, vomiting

  • Early satiety

  • Bloating

What is constipation, and what are its pathophysiologic mechanisms and causes? What are some clinical signs?

• Constipation: ↓ bowel movements or difficulty passing stool

• Mechanisms:

  • ↓ peristalsis

    • Causes:

      • ↓ ENS activity

      • ↑ sympathetic tone

      • Impaired neural signaling

  • ↑ water reabsorption

    • Slower transit → more water absorbed in colon

• Causes:

  • Medications (opioids, anticholinergics, diuretics)

  • Lifestyle factors

    • Exercise → increased gut transit time

    • Caffeine intake → diuretic effect

    • Alcohol → diuretic effect

    • Diet → lack of fiber (goal shouuld be 30g/day: men)

      • Increased salt → increase water weight → may need for furosemide (diuretic use)

  • Neurologic/metabolic conditions

• Clinical signs:

  • <3 bowel movements/week

  • Hard, dry stools

  • Straining, incomplete evacuation

How does PEG-ES differ from PEG?

• PEG-ES (PEG with electrolytes)

  • Onset: Fast bowel prep

    • Produces rapid, large-volume diarrhea (catharsis)

    • High dose + electrolytes → prevents major fluid shifts while enabling aggressive cleansing

• Standard PEG (Miralax, PEG 3350) 

  • Onset: Slow (12-72hrs -> up to 96 hours)

    • PO 17g 

    • Used for routine constipation, not full bowel prep -> helps create softer stools rather than rapid evacuation

What is the first-line treatment for mild acute constipation? What are pros and cons? Avoid when?

Bulk-forming laxatives

• Best for:

  • Mild constipation

  • First presentation

  • Low fiber intake

• Pros: physiologic, safe

• Cons: slow onset (up to ~72 hours)

• Avoid if:

  • Swallowing difficulty

  • Fluid restriction

When should PEG 3350 (osmotic laxative) be used? What are pros and cons of use?

First-line if fiber is ineffective or inappropriate

Use when:

• Mild–moderate symptoms

• Already adequate fiber intake

• Need more reliable effect

• Cannot tolerate fiber (bloating, swallowing issues)

Pros: effective, well tolerated

Cons: delayed onset (up to ~96 hours)

When are stimulant laxatives (senna, bisacodyl) appropriate?

Second-line (add-on)

Use when:

• PEG ineffective → Faster effect than bulk/PEG

• Moderate symptoms

• No BM for several days

• Persistent discomfort

When should a patient with constipation be referred?

• No improvement after ~7 days of self-treatment

• Chronic constipation

• Severe or persistent symptoms

• Presence of alarm symptoms

How is constipation classified as acute vs chronic?

• Acute: < 2 weeks

• Chronic: ≥ 3 months with ≥ 2 symptoms

  • Straining >25% of defecations

  • Hard/lumpy stools (Bristol 1–2) >25%

  • Sensation of incomplete evacuation >25%

  • Sensation of anorectal blockage >25%

  • Manual maneuvers needed >25%

  • <3 spontaneous BMs/week

What are general risk factors and lifestyle factors that can contribute to developing constipation?

• Risk factors

  • Female

  • Older age >65

  • Late pregnancy or post-partum

  • Medications

  • Obesity

  • Comorbid conditions 

  • Non-white ancestry

• Lifestyle factors

  • Low fiber diet → slowly increase to 25-35 Grams/day

  • Dehydration

    • Alcohol/caffeine → diuretics

  • Lack of physical activity

  • Ignoring the urge to defecate

  • High stress level

  • Not up to date with vaccinations

Which medications commonly cause constipation and how? (ACROYM)

• Opioids: Activate μ-receptors in gut → ↓ motility, ↓ secretion, ↑ water absorption

• Anticholinergics: Block muscarinic receptors → ↓ parasympathetic activity → ↓ peristalsis + ↓ secretion

• Iron: GI irritation → altered motility, harder stool

• Calcium antacids: ↓ smooth muscle contraction = decreased motility

• Aluminum antacids: smooth muscle relaxation

• Diuretics: systemic dehydration → less water in stool

• Verapamil (CCB): ↓ Ca²⁺ → ↓ contraction

• Antidepressants/muscle relaxants: CNS depression → ↓ motility

• NSAIDs (naproxen): ↓ prostaglandins → ↓ mucus + slight ↓ motility

Oh, am I crazy and dumb viewing anyone’s nudes?

What medical conditions are associated with constipation?

• Endocrine: hypothyroidism, diabetes (affects microvasculature → decreases gut peristalsis)

• Neurologic: Parkinson’s, MS, stroke

• GI: IBS-C

• Psychiatric: depression (can affect activity level, diet, motivation), eating disorders

What structural or mechanical causes can lead to constipation?

• Tumors

• Strictures

• Hernias

• Pelvic floor dysfunction

• Post-surgical changes

What symptoms suggest a serious structural cause of constipation?

• Pencil-thin stools

• Severe abdominal pain

• Unintentional weight loss

What are common signs and symptoms of constipation?

• Decreased frequency of bowel movements (<3/week)

• Hard, dry, or small stools

• Straining during bowel movements

• Feeling of incomplete evacuation

• Excessive time spent on the toilet

• Abdominal discomfort or cramping

• Bloating

• Decreased appetite (anorexia)

• Low energy/fatigue

• Lower back pain

• Psychosocial distress

Does hairy sex feel exactly alike? because donatello lwk likes pigs.

What symptoms suggest constipation should NOT be self-treated (red flags)?

• Symptoms

  • Severe abdominal pain (≥5/10)

  • Nausea/vomiting

  • Significant abdominal distention

  • Fever

  • Unintentional weight loss or anorexia

  • Blood in stool, rectal bleeding, or melena

  • Pencil-thin stools (change in stool caliber)

• Clinical situations

  • Symptoms >7 days despite treatment

  • Sudden change in bowel habits >2 weeks

  • Chronic/recurrent symptoms (≥3 months)

  • New or worsening symptoms during self-treatment

• Patient factors

  • Age <2 years

  • Daily laxative use (except fiber)

  • Chronic conditions (e.g., IBS, colostomy, paraplegia)

  • Unexplained or excessive flatulence

What key questions should you ask to determine if constipation is appropriate for self-care?

• Symptoms: severity, red flags

• Duration/recurrence: acute vs chronic

• Medication use: opioids, anticholinergics, etc.

• Medical history: underlying conditions

• Current management: what has been tried

• Lifestyle: diet, hydration, activity

• Special populations: age, pregnancy

What are non pharmacologic measures for treating and preventing constipation?

• Increase fiber intake (gradually) 

  • Daily recommended fiber intake for adults: 

    • Women: 25 grams/day 

    • Men: 38 grams/day 

• Eating foods with insoluble fiber: 

  • Whole grains 

  • Wheat bran 

  • Fruit 

  • Vegetables

• Drink adequate fluids each day (6-8, eight-ounce glasses multiple times per day) 

• Develop and maintain a physical activity routine 

• Respond to the urge to use the toilet 

• Maintain general well-being and avoid stressful situations

What are common causes of diarrhea? What increases risk for these?

• Traveler’s diarrhea (TD):

  • Contaminated food/water

  • High-risk regions: Africa, Asia, Latin America

• C. difficile infection:

  • Antibiotic exposure

  • PPI use

  • Recent GI surgery

  • Hospitalization

  • Immunocompromised state

  • Age ≥65

What drug classes are used to treat diarrhea?

• Salicylate antidiarrheals (e.g., bismuth)

• Opioid receptor agonists (e.g., loperamide)

  • NOT for self-treatment

• Mixed opioid agents

• Antimuscarinics

• 5-HT3 antagonists

• Antibiotics (for infectious causes)

What is the role of regulatory T cells (Tregs) in immune tolerance?

• Maintain immune tolerance → Inhibit effector T cell activation and function

• Allow response to pathogens while preventing damage to self tissues

• Suppress overactive immune responses
  → Prevent autoimmunity and tissue damage

What are the mechanisms of action of Tregs?

• Secrete anti-inflammatory cytokines:

  • TGF-β

  • IL-10

  • IL-35

• Sequester IL-2 → ↓ T cell proliferation

• Direct cell–cell inhibition of other T cells

Why are Tregs especially important in the gut?

• Gut is constantly exposed to:

  • Food antigens

  • Microbiota

• Tregs prevent unnecessary immune responses
  → Maintain mucosal tolerance

What are the main immune mechanisms that protect the gut mucosal barrier?

• Physical/epithelial barrier → create defensins (antimicrobial peptides)

• Mucus layer (“weep and sweep”) → ciliated

• Antimicrobial peptides (defensins)

• Secretory IgA → Bind and neutralize pathogens/microbes and toxins preventing infection and inflammation

• Peyer’s patches (lymphoid tissue)

• Targeted immune cell trafficking

• Microbiome

How do the epithelial barrier and mucus layer protect the gut?

• Epithelial cells: tight junctions prevent microbial entry

• Mucus layer:

  • Traps pathogens/toxins

  • “Weep and sweep” removes them via fluid movement

What are antimicrobial peptides and how do they function?

• Defensins produced by epithelial + immune cells

• Act like natural antibiotics:

  • Disrupt microbial membranes

  • Recruit immune cells

What is the role of secretory IgA in the gut?

• Dimeric IgA = main mucosal antibody

• Functions:

  • Binds pathogens/toxins

  • Neutralizes without strong inflammation

  • Exports microbes back to the lumen

  • Works with mucus to strengthen the barrier

How do Peyer’s patches initiate immune responses?

• Specialized lymphoid structures (e.g., Peyer’s patches)

  • Sites where immune responses are initiated in the gut

    • M cells: transport antigens across the epithelium

    • Dendritic cells: activate T cells

    • B cells: class switch → produce IgA

      • Dominate the lymph-node structurs in the gut

What is targeted immune cell trafficking in the gut?

• Activated T cells express homing receptors

• Return specifically to mucosal tissues
  → Focused immune response where needed

What role does the microbiome play in gut immunity?

• Competes with pathogens for space/nutrients

• Helps train and regulate the immune system

• Supports immune tolerance

What are the key steps in the pathogenesis of inflammatory bowel disease (IBD)?

1) Barrier breakdown

2) Abnormal immune response

3) Failed immune regulation

4) Genetic susceptibility

5) Environmental triggers

→ Leads to chronic inflammation

How does epithelial barrier dysfunction contribute to IBD?

• Damage to the epithelial lining → ↑ permeability

• Microbes/products cross into tissue → Triggers immune activation

What happens after microbes cross the epithelial barrier in IBD?

• Innate immune cells (macrophages, dendritic cells) are activated

• Release pro-inflammatory cytokines → activate adaptive immunity (T cells) → amplified and sustained inflammation

What role does immune dysregulation play in IBD?

• Failure of T regulatory cells (Tregs)

• Unchecked effector T cell activation
  → Persistent inflammation and tissue damage

How do genetics and environment contribute to IBD?

• Genetics:

  • Defects in microbial recognition

  • ↑ susceptibility

• Environmental factors:

  • Diet

  • Antibiotics (alter microbiome)

  • Smoking

  • Stress

  • NSAIDs

What is the final outcome of IBD pathogenesis? What are the characterizations of IBD?

• Chronic immune activation

• Continuous cytokine production

• Tissue injury:

  • Ulceration

  • Fibrosis

  • Complications

What are the key differences in location between ulcerative colitis (UC) and Crohn’s disease (CD)?

• UC:

  • Limited to colon

  • Starts at rectum → continuous spread proximally

• CD:

  • Can affect any part (mouth → anus)

  • Often terminal ileum ± colon

How does the pattern of inflammation differ in UC vs CD?

• UC: continuous, diffuse (no skip lesions)

• CD: patchy with skip lesions (normal areas between disease)

How does the depth of inflammation differ in UC vs CD?

• UC: superficial (mucosa + submucosa)

• CD: transmural (full thickness)

What complications distinguish UC from Crohn’s disease?

• UC:

  • No penetrating disease

  • Fistulas/abscesses/strictures rare

  • Perianal disease rare

• CD:

  • Penetrating disease common

  • Fistulas, abscesses, strictures

  • Perianal disease common

What are the histologic differences between UC and Crohn’s?

• UC: no granulomas

• CD: may have granulomas (suggestive, not always present)

What is the difference between induction therapy and maintenance therapy?

• Induction therapy → used to get symptoms under control quickly (treat a flare, achieve remission)

• Maintenance therapy → used to keep the patient in remission long-term and prevent relapse

What factors are used to classify high risk for IBD progression?

1) Age at diagnosis

• UC: ≤40

• CD: ≤30

2) Anatomic extent

• UC: Pancolitits

• CD: Extensive

3) Endoscopic severity (mod-severe)

4) History of hospitalization (yes)

5) (CD only): surgery, penetrating disease, perianal involvement

What age at diagnosis indicates high risk for IBD progression?

• UC: ≤40 years

• CD: ≤30 years

What disease extent indicates high risk in UC vs Crohn’s?

• UC: pancolitis

• CD: extensive involvement

What clinical history features indicate high risk in both UC and CD?

• Moderate to severe endoscopic disease

• History of hospitalization

What features indicate high risk specifically in Crohn’s disease?

• Prior bowel resection

• Penetrating disease (fistulas, abscesses, strictures)

• Perianal involvement

What administration should you avoid in immunocompromised patients? why?

Rectal delivery - risk of small tears and infection with gut bacteria

When should constipation raise concern for colon cancer?

Age >45 + new-onset constipation
→ Requires colon cancer screening/evaluation

What do you expect will happen to GFR if the amounts of salicylates are absorbed?

Decrease of GFR

What class of medications should not be used for maintenance for IBD? what about induction?

Maintenance: Corticosteroids

Induction: Immunomodulators

Which IBD biologic medications do NOT have box warnings?

Vedolizumab, risankizumab

HW is a 46 year old stay-at-home mom with a 4 year history of mild left-sided UC. She has never required hospitalization. HW has been taking oral mesalamine since diagnosis. Her usual stool pattern has been 1-2 soft, formed, nonbloody BMs daily without urgency. She is adherent to her medication. She recently caught the stomach flu and has had persistent diarrhea (4-6 episodes daily) without blood for two weeks. This is the first time her symptoms have recurred since diagnosis. The GI doctor believes she is experiencing a flare triggered by the virus. Her inflammatory markers are in range. (relapsing)

1) Has HW’s maintenance regimen effective? List one reason why or why not.

2) What would you recommend for HW’s current symptoms?

1) Yes; she has had only one flare in 4 years which reflects effectiveness ‒ Enema is preferred over oral for left sided UC, but oral is an option if the patient prefers it and it’s working.

2) Recommend a 7-day pulse with budesonide to calm the flare. She is not bleeding and ESR is in range, so budesonide may work.

KG is a 27 year old with a 15 year history of CD of the terminal ileum and proximal colon (ascending and transverse colon) (dx: age 12). He was hospitalized at diagnosis and had a resection 3 years later. • He was initially treated with infliximab and methotrexate, but symptoms recurred about 5 years ago. • He started daily azathioprine and vedolizumab every 7 weeks around that time. • He has been experiencing diarrhea and crampy pain for the past 5 days. No blood can be seen. His vedolizumab infusion is due in 10 days. KG reports that sometimes he experiences some pain and discomfort 1-2 weeks before vedolizumab is due

1) What was KG’s risk at diagnosis?

2) What tests would you recommend to help evaluate current symptoms?

3) Assess the efficacy and risks of KG’s current regimen

1) High risk due to age < 30 at diagnosis. Although he didn’t have a resection at diagnosis, he had one three years later which further keeps him in the high risk category.

2)

• Stool tests to rule out infection

• Stool calprotectin to assess intestinal inflammation

• vedolizumab level

• thiopurine metabolites to assess if azathioprine is therapeutic

• CBC to see if hemoglobin reflects blood loss

3)

• No apparent triggers for a flare

• Experiencing end-of-interval symptoms

• Vedolizumab level is low without antibodies

• Consider shortening the interval if insurance permits

• Vedolizumab has set dosing, so the dose cannot be increased

• Could consider switching biologics, but the patient is young and is already on his second biologic; would attempt to use vedolizumab as long as possible

• Azathioprine level is therapeutic, with low levels of metabolite associated with hepatotoxicity

• Vedolizumab + azathioprine does not carry the risk of fatal lymphoma, but does carry a risk of lymphoma from the azathioprine

Smoking is a risk factor for which disease state (relavant to this block)?

Crohn’s