7.2 GI Physiology & Pathophysiology: Colon Motility, Defecation, Appetite Hormones, GERD & Intro to PUD

Large Intestine (Colon)

  • Primary functions

    • Drying & storage of residual chyme → feces

    • Absorption largely limited to Na+\text{Na}^+; water follows osmotically

  • Anatomical segments (in proximal → distal order)

    • Cecum / Ileocecal valve

    • Ascending → Transverse → Descending → Sigmoid colon

    • Rectum → Anal canal / Anus

  • Surface features

    • Haustra = sac-like pouches generated by longitudinal muscle (teniae coli)

Motility Patterns

  • Haustral contractions

    • Analogous to small-intestinal segmentation but much slower (≈ 1/30 min vs 9–12/min)

    • Mix & expose contents for salt/water reabsorption

  • Mass movements (MMC of colon)

    • Powerful peristaltic sweeps that propel a “mass” long distances toward sigmoid/rectum

    • Triggered chiefly by gastro-colic reflex (food in stomach → colon contracts)

    • Neuro-humoral mediators: vagal ACh\text{ACh} & hormone Gastrin\text{Gastrin} (“go-go-go”)

Defecation Reflex

  • Feces enter rectum → stretch receptors fire

  • Reflex arc (intrinsic + parasympathetic pelvic nerves)

    • Internal anal sphincter (IAS, smooth m.) relaxes automatically

    • Rectum + sigmoid contract strongly

  • Voluntary control

    • External anal sphincter (EAS, skeletal m.) can contract to delay

    • If EAS contraction maintained → rectal wall slowly relaxes → urge subsides until next mass movement

  • Clinical tie-ins

    • Diarrhea: continuous reflex activation; EAS fatigue → incontinence

    • Chronic postponement → prolonged water reabsorption → constipation

Constipation & Fiber Q&A

  • Prolonged colonic transit = excessive Na+\text{Na}^+/H$_2$O removal → hard stool

  • Dietary fiber retains luminal water; improves bulk & softness; water intake alone helps but many patients under-hydrate

Appetite & Energy-Balance Hormones (Overview)

  • Regulation integrates GI peptides, adipose signals, pancreatic hormones, CNS neurotransmitters, environment, emotion

  • Representative gut peptides (PYY, CCK, GLP-1, OXM, obestatin, PP, etc.)

  • Peripheral hormones: Leptin (adipose), Insulin (β-cell)

Focus Hormones

  • Leptin

    • Source: white adipocytes

    • CNS target: hypothalamic receptors → anorexigenic (↓ food intake, ↑ energy output)

  • Ghrelin

    • Source: stomach (fundus), peaks pre-meal

    • Hypothalamic action → orexigenic (↑ hunger)

  • Pathophysiology

    • Chronic over-nutrition → hyperleptinemia + receptor down-regulation (“leptin resistance”) → persistent hunger despite fat stores

GLP-1 & Drugs

  • GLP-1 (glucagon-like peptide-1)

    • Secreted by ileal/colonic L-cells post-meal

    • Actions: ↑ insulin (incretin), ↓ hepatic gluconeogenesis, ↓ gastric emptying, ↓ appetite

  • GLP-1 receptor agonists (e.g., semaglutide/Wegovy®, liraglutide, etc.)

    • Initially for Type 2 DM; now FDA-approved for obesity

    • Benefits: weight loss, improved glycemic control; side-effects: GI upset, pancreatitis risk, gallbladder issues

General GI Disorder Manifestations

  • Anorexia (loss of appetite)

    • Hypothalamic-mediated; triggered by smell, emotion, GI irritation, heat

  • Nausea (subjective queasiness)

    • Medulla vomiting center activation + autonomic signs (salivation, pallor, diaphoresis)

    • Often duodenal chemoreceptor input; may precede or accompany emesis

  • Vomiting (emesis)

    • Reverse peristalsis + diaphragm/abdominal muscle contraction; protective

  • GI bleeding terminology

    • Hematemesis = bright-red vomit (fresh upper GI bleed)

    • “Coffee-ground” emesis = dark granular vomit (older, digested blood)

    • Melena = black, tarry stool (digested blood from upper GI)

    • Occult blood = hidden; detected by guaiac/FIT chemical tests

Quiz example

  • Fresh stomach hemorrhage symptom? → Hematemesis

Esophageal Disorders Snapshot

  • Dysphagia = difficult swallow (neuromuscular or obstructive)

  • Diverticula = mucosal out-pouching through muscle wall

  • Mallory-Weiss tears = longitudinal mucosal lacerations at gastro-esophageal junction (often after forceful retching, alcohol)

  • Esophageal varices = portal HTN-induced dilated veins; high bleed risk

Gastro-Esophageal Reflux Disease (GERD)

Epidemiology

  • Prevalence ≈ 20%20\% adults report weekly reflux; > 99 million U.S. ambulatory visits / year; low mortality but high morbidity

Risk Factors

  • ↓ LES tone (primary mechanism)

  • Hiatal hernia (fundus above diaphragm)

  • Delayed gastric emptying

  • Transient LES relaxations

  • Decreased saliva buffering (xerostomia)

  • Lifestyle: obesity, pregnancy, alcohol, tobacco, caffeine, chocolate, peppermint, fatty or tomato-rich foods, large/night meals, tight garments

Pathophysiology Recap

  • LES should maintain tonic pressure > gastric pressure; failure → acidic gastric juice bathes distal esophagus

  • Esophageal mucosa lacks:

    • Thick alkaline mucus layer

    • Tight junction barrier comparable to stomach

  • Acid production logic: parietal cell H+/K+\text{H}^+/\text{K}^+-ATPase up-regulated by histamine (H$_2$-R), gastrin, vagal ACh\text{ACh}

Clinical Presentation

  • Typical (>75 %)

    • Heartburn (post-prandial retrosternal burn, worse supine/bending)

    • Water brash (acidic/sour regurgitation)

  • Less common

    • Food regurgitation, epigastric pain (dyspepsia), chest pain, dysphagia, odynophagia, chronic cough/asthma, laryngitis

  • Alarm features → endoscopy: GI bleed, anemia, weight loss, progressive dysphagia, chest pain, age >   50\;50 with new symptoms

Complications

  • Reflux esophagitis (inflammation)

  • Strictures (fibrotic narrowing)

  • Ulceration/bleeding or perforation

  • Barrett’s esophagus (metaplasia from stratified squamous → intestinal-type columnar)

    • Occurs in 5!–!10%5!\text{–}!10\% of GERD pts; increases adenocarcinoma risk (~10%10\% of Barrett’s develop CA)

Diagnosis

  • Clinical trial of PPI (4–6 wk) often sufficient

  • Upper endoscopy (EGD) if alarm sx, refractory, or screening Barrett’s

  • 24-h pH monitoring (wireless Bravo® capsule or catheter) = gold standard physiologic test

  • Barium swallow reserved for structural questions (diverticula, rings)

Management Goals

  1. Symptom relief

  2. Heal esophagitis

  3. Prevent recurrence/complications

  4. Cost-effective, safe plan

Lifestyle Modifications (variable evidence)

  • Elevate head of bed (≈ 15–20 cm15–20\,\text{cm})

  • Avoid recumbency ≤ 2–3 h post-meal

  • Smaller, more frequent meals; weight loss if obese

  • Limit triggers (alcohol, caffeine, chocolate, mint, fatty/spicy, tomato)

  • Stop smoking; loosen belts/clothing

Pharmacologic Therapy

  • Antacids (Mg/Al hydroxide, CaCO$_3$) → neutralize secreted acid

  • H$_2$-receptor blockers (ranitidine, famotidine, etc.)

    • Antagonize ECL-histamine → ↓ cAMP → ↓ H$^+$/K$^+$-ATPase numbers

  • Proton-pump inhibitors (PPI: omeprazole, pantoprazole, etc.)

    • Irreversible H+/K+\text{H}^+/\text{K}^+-ATPase blockade → most potent

  • Pro-kinetics (metoclopramide, bethanechol) to ↑ gastric emptying, ↑ LES tone

Surgical / Endoscopic Options

  • Nissen fundoplication (360° fundus wrap) or partial wraps

  • LINX® magnetic sphincter augmentation, radio-frequency Stretta®, endoscopic TIF

Peptic Ulcer Disease (PUD) & Stress Ulcers (intro only)

  • Definition: Mucosal break ≥ 5 mm5\,\text{mm} penetrating muscularis mucosa in stomach or duodenum

  • Epidemiology: Duodenal > Gastric; lifetime risk ≈ 10%10\%

Etiology

  1. 70!–!90%70!\text{–}!90\% Helicobacter pylori infection (spiral Gram-negative, urease +, acid-tolerant)

    • Transmission: fecal–oral / oral–oral; humans sole reservoir; contaminated water/produce possible

  2. NSAID / ASA / other salicylate use (chronic)

    • Responsible for 10!–!20%10!\text{–}!20\% gastric, 2!–!5%2!\text{–}!5\% duodenal ulcers

  3. Stress ulcers (critical illness, burns, brain injury; path: mucosal ischemia + acid hyper-secretion)

  4. Less common: Zollinger–Ellison (gastrinoma ↑↑ gastrin), Crohn disease, viral (CMV), drugs (bisphosphonates, KCl), radiation

[Signs/symptoms & full management to be continued in next lecture]

Study/Review Suggestions (Instructor’s Tips)

  • Create flowcharts: GI anatomy → key hormones → motility patterns → digestion/absorption steps

  • Summarize each nutrient:

    • Carbs: salivary amylase → pancreatic amylase → brush border; absorbed as Glu/Gal/Fru\text{Glu}/\text{Gal}/\text{Fru} via SGLT1\text{SGLT1}/GLUT

    • Protein: pepsin (stomach) → pancreatic trypsin, chymotrypsin, carboxypeptidase → brush border peptidases; absorbed as aa/di-tri via PEPT1\text{PEPT1}

    • Lipid: lingual/gastric lipase → bile emulsification, pancreatic lipase/colipase → micelle → diffusion + chylomicron assembly

  • Map hormone origins/effects: Gastrin (G cells, antrum) → parietal & ECL; CCK (I cells) → gallbladder, pancreas; Secretin (S cells) → bicarb, etc.

Upcoming Assessment Reminders

  • Blackboard quiz opens tomorrow; due Wed (one week); covers GI + female pathophys (from endometriosis onward)

  • In-person Examplify quiz next Thu; includes GI material through Tuesday’s lecture; 2 extra-credit \$\$\text{\"Money is\"} concept questions: gametogenesis, female hormonal feedback

Happy studying — and enjoy the holiday fireworks (but avoid lying down after the barbecue)!