GI

Advanced Physiology and Pathophysiology: Essentials for Clinical Practice

Chapter 13: Gastrointestinal Tract, Part 1

Editors

  • Nancy C. Tkacs, PhD, RN

  • Linda L. Herrmann, PhD, RN, AGACNP-BC, GNP-BC, ACHPN, FAANP
    © Springer Publishing Company, LLC.

Key Concepts

Anatomy

  • The Gastrointestinal (GI) tract: A continuous tube extending from the mouth to the anus.

  • Layered Structure:

    • Composed of four primary layers:

    • Mucosa (inner layer for absorption)

    • Submucosa (gland-rich)

    • Muscularis (two muscle layers)

    • Serosa (outer layer)

    • Influenced by:

    • Enteric nervous system

    • Autonomic nervous systems

    • Hormones and local mediators

    • Immune cells

Physiology

  • Motor Activity (Motility): Ensures propulsion and mixing of ingested food from the mouth to the rectum.

  • Secretion:

    • Various secretions from the GI tract and accessory organs (salivary glands, pancreas, liver).

  • Digestion and Absorption:

    • Various segments process ingested food and drink:

    • Mouth: Chewing

    • Stomach: Pulverizing and mixing

    • Small intestine: Mixing for digestion and increasing surface area for absorption

    • Large intestine: Water reabsorption and stool formation

    • Rectum and Anus: Excretion

Gastrointestinal Disorders

(1) Esophagus

  • Common Disorders:

    • Obstruction

    • Varices

    • Esophagitis

    • Gastroesophageal reflux disease (GERD)

    • Barrett esophagus

    • Esophageal cancer

Stomach

  • Common Disorders:

    • Peptic ulcers

    • Zollinger-Ellison syndrome

    • Helicobacter pylori infection

    • Gastroparesis

    • Vomiting

Pancreas

  • Common Disorders:

    • Acute pancreatitis

(2) Intestine

  • Common Disorders:

    • Diarrhea

    • Celiac disease

    • Inflammatory bowel disease

    • Crohn disease

    • Ulcerative colitis

    • Abdominal pain

    • Irritable bowel syndrome

    • Hemorrhoids

    • Intestinal failure

    • Short bowel syndrome

    • Malnutrition

    • Obesity

    • Colorectal cancer

    • Lynch syndrome

Gastrointestinal Disorders—Life-Span Considerations

Pediatric Considerations

  • Common Disorders:

    • Gastroenteritis:

    • Viral

    • Bacterial

    • Parasitic

    • Hypertrophic pyloric stenosis

    • Intussusception

    • Hirschsprung disease

Gerontologic Considerations

  • Common Disorders:

    • Dysphagia

    • Zenker diverticulum

    • Esophageal dysphagia

    • Constipation

    • Diverticular disease

Gastrointestinal Tract Accessory Organs

  • Salivary Glands: Produce saliva to lubricate food and contain enzymes for starch and fat digestion.

  • Liver (Detailed in Chapter 14):

    • Produces bile, essential for fat digestion.

  • Pancreas:

    • Produces bicarbonate-rich fluid to neutralize stomach acid.

    • Secretes digestive proenzymes activated in the small intestine.

The Layered Structure of the GI Tract

  • Outer Serosa: Protects and supports the GI tract.

  • Muscle Layers:

    • Two muscle layers that facilitate motility.

  • Nerve Plexuses: Two primary nerve plexuses involved in control of motility and secretion.

  • Submucosa: Rich in glands and supports the mucosa.

  • Inner Absorptive Region (Mucosa): Site of absorption and secretion.

Motility of the GI Tract

  • Functions:

    • Mixes ingested food and liquids with GI secretions.

    • Propels GI contents from the mouth to the anus (aboral direction).

  • Muscle Dependency:

    • Dependent on GI smooth muscle layers.

    • Influenced by enteric nervous system, autonomic nervous system, hormones, and mediators.

  • Types of Motility:

    • Peristalsis: Sequential movement of GI contents.

    • Segmentation: Mixing of GI contents.

  • Related Pathophysiological Mechanisms: Implicated in conditions like vomiting, diarrhea, and constipation.

GI Tract Innervation

  • Enteric Nervous System:

    • Operates independently for controlling motility and secretions.

  • Parasympathetic Innervation:

    • Stimulates motility and secretion from brainstem (via vagus nerves) and sacral cord.

  • Sympathetic Innervation:

    • Generally inhibitory and arises from thoracic spinal cord.

Hormonal GI Control

  • Mechanism:

    • Hormones secreted by endocrine cells in gut walls allow coordination of activity across GI segments via medium- and long-distance signaling.

  • Examples:

    • Gastrin: Released by G cells in the stomach, stimulates gastric acid secretion in parietal cells.

    • Cholecystokinin (CCK): Secreted by I cells in small intestine, promotes gallbladder contraction and pancreatic enzyme secretion while inhibiting gastric emptying.

    • Glucagon-like peptide 1 (GLP-1): Secreted by L cells in the small intestine, stimulates insulin secretion and inhibits gastric emptying.

GI Control by Peptides and Amines

  • Enteric Nervous System: Rich in opioid peptides that reduce motility—used therapeutically for diarrhea and constipation.

  • Gut Enterochromaffin (EC) Cells:

    • Secrete amines that influence digestion:

    • Histamine: Released in the stomach, stimulates gastric acid secretion.

    • Serotonin: Secreted in the small intestine, increases gastric motility.

Small Intestine Immune Components

  • Immune Function:

    • The small intestine has substantial immune protections against ingested pathogens.

    • Peyer’s Patches: Sites for immune activity in the gut.

Colon Immune Components

  • Gut Microbiota:

    • The colon contains the majority of gut microbiota, aiding in digestion, immune function, and immune tolerance.

  • Immune Cells: Lymphocytes and macrophages support immune protection in the colon.

The Gut Microbiome

  • Bacterial Composition: Gut bacteria outnumber total human cells.

  • Functions of Normal Flora:

    • Protects host from pathogens.

    • Produces metabolites (e.g., Vitamin K).

    • Aids in fiber digestion and short-chain fatty acid production.

    • Deconjugates bile acids for lipid digestion and absorption.

  • Dysfunction Implications: Alterations linked to conditions like:

    • Clostridioides difficile infection

    • Irritable bowel syndrome and functional GI disorders

    • Neural and mental health disorders via the microbiota-gut-brain axis.

Structure and Dysfunction of the Pharynx and Esophagus

  • Swallowing: (Deglutition)

    • Reflex initiated voluntarily in the mouth when the tongue pushes bolus back to the pharynx.

    • The swallowing center in the medulla controls involuntary phases.

  • Pharyngeal Phase: Soft palate elevation prevents food entry to nasal passages.

  • Esophagus Function:

    • Receives bolus from mouth, conveys it to stomach via peristaltic motility and mucus lubrication.

    • Sphincters: Lower esophageal sphincter (LES) tone managed by neural control (vagal nerve).

    • ACh causes sphincter contraction; nitric oxide and VIP cause relaxation.

  • Disorders:

    • Esophageal Obstruction: Stenosis from inflammation or achalasia from LES failure to relax.

    • Esophagitis: Commonly due to GERD; chronic cases can lead to Barrett esophagus and adenocarcinoma, associated with alcohol and tobacco use.

GERD Pathogenesis

  • GERD: Common cause of esophagitis.

  • LES Function:

    • Normally prevents stomach contents from refluxing into the esophagus.

    • Reflux occurs due to LES dilation or factors altering pressure gradients (e.g., obesity, Valsalva maneuver).

Structure and Function of the Stomach

  • Composition: Strong, muscular organ with a ridged lining for food pulverization.

  • Secretions: Emanate from gastric pits into the lumen.

  • Motility:

    • Includes contractions that mix food with secretions and propel contents into the duodenum.

    • pH: Acid secretion from parietal cells lowers stomach pH to around 2, activating pepsin and killing bacteria.

  • Other Secretions: Include pepsinogen, mucus, and gastrin.

Stomach Motility and Gastroparesis

  • Normal Stomach Motility: Involves receptive relaxation, strong contractions for mixing, and content movement to the duodenum.

  • Gastroparesis:

    • Characterized by reduced motility from altered neural modulation (e.g., diabetic autonomic neuropathy).

Neural Pathways Influencing Vomiting

  • Stimuli Convergence: Various stimuli trigger the vomiting center.

  • Nausea Recognition: Cortical regions recognize nausea.

  • Vomiting Reflex: Involves GI smooth muscle for reverse peristalsis and abdominal contraction, coordinated with breath holding.

Stomach Secretions: Gastric Glands and Gastric Pits

  • Cell Types Present:

    • Parietal Cells: Secrete hydrochloric acid and intrinsic factor.

    • Peptic Cells: Secrete pepsinogen.

    • Mucous Cells: Secrete bicarbonate-rich mucus for lining.

Parietal Cell Acid Secretion

  • Mechanism:

    • Hydrogen/Potassium ATPase: Also known as the proton pump, facilitates active countertransport of H+ and K+ ions.

    • Chloride enters the lumen via ion channels.

  • Stimulation: Enhanced by calcium and cAMP levels.

    • ACh and gastrin stimulate secretion via Gq pathway.

    • Histamine stimulates via Gs pathway.

    • Prostaglandins inhibit via Gi pathway.

Phases of Gastric Acid Secretion

  • Cephalic Phase: Initiated by thoughts and senses related to food; vagal acetylcholine release is prominent.

  • Gastric Phase: Food presence in the stomach stimulates gastrin and local histamine secretion, enhancing acid secretion.

  • Intestinal Phase: Signals that stimulate acid secretion decrease; inhibitory signals increase, slowing acid secretion.

Stomach Protection from Gastric Acid

  • Mucous Neck Cells: Secrete bicarbonate-rich mucus, protecting the stomach lining.

  • Mucus Layer: Lined closely; gastric acid secreted remains away from epithelial cells.

  • Prostaglandins: Provide protective effects by reducing acid secretion, increasing mucus secretion, and enhancing mucosal blood flow.

    • Implications: Blocking prostaglandins with NSAIDs increases the risk of acid damage.

Stomach Disorders

  • Peptic Ulcers: Most common in the duodenum and stomach.

    • Risk Factors: Hyperacidity, smoking (reduces gastric blood flow), small intestine reflux, NSAIDs, and Helicobacter pylori infection, which can lead to chronic conditions and stomach cancer.

    • Management: Focuses on acid secretion reduction through:

    • Histamine H2-blockers

    • Proton pump inhibitors

    • Antacids for short-term acid neutralization.

Advanced Physiology and Pathophysiology: Essentials for Clinical Practice

Chapter 13: Gastrointestinal Tract, Part 2

Editors

  • Nancy C. Tkacs, PhD, RN

  • Linda L. Herrmann, PhD, RN, AGACNP-BC, GNP-BC, ACHPN, FAANP
    © Springer Publishing Company, LLC.

Small Intestine—Structure Facilitates Absorption

  • Structural Features:

    • Crypts and villi increase absorptive area.

    • Intestinal epithelial cells (IECs) have microvilli, enhancing absorption.

    • Tight junctions link cells, blocking pathogen entry into circulation.

Digestion Requires Pancreatic Enzymes

  • Pancreatic Exocrine Function:

    • Produces proenzymes (zymogens) and zymogen granules, preventing autodigestion.

    • Secretes enzymes into the gut lumen activated by intestinal enterokinase.

    • Fluid secretions are rich in bicarbonate to neutralize acidic chyme from the stomach.

Acute Pancreatitis—Key Cellular Events

  • Pathophysiology:

    • Features activation of inflammation and oxidative stress.

    • Local cytokine elevations exacerbate cell stress and calcium accumulation.

    • Destabilization of lysosomes and zymogen granules leads to cell damage.

Clinical Aspects of Acute Pancreatitis

  • Causes:

    • Gallstones, alcohol, and drug reactions.

    • Can lead to systemic inflammatory response syndrome and multi-organ dysfunction.

    • Repeated acute episodes may predispose to chronic pancreatitis.

Lipid Digestion and Absorption Requires Bile

  • Bile Production:

    • Made in the liver, stored in the gallbladder, secreted into small intestine via common bile duct.

  • Function of Bile Acids:

    • Emulsify large fat droplets, forming micelles for lipid digestion absorption.

    • Excretes waste products (e.g., bilirubin) in feces.

  • Gallstones:

    • Common disorder, can cause obstruction, pain, infection, and altered liver function tests.

Small Intestine Structure, Motility, and Secretions

  • Segmentation Contractions: Mix ingested food particles with pancreatic digestive enzymes.

  • Peristaltic Movements: Propel intestinal contents toward the large intestine.

  • Secretions: Include mucus for protection and watery fluid important for digestion dilution.

Small Intestine Disorders

  • Common Disorders:

    • Celiac Disease:

    1. Ingestion of gluten leads to gliadin peptide production.

    2. Gluten peptides undergo deamidation, becoming antigenic.

    3. Antibodies against gluten, peptides, and transglutaminase increase.

    4. Local inflammation causes villi loss, leading to malabsorption and diarrhea.

Large Intestine Structure, Motility, and Secretions

  • Segments: Cecum, appendix, colon, rectum.

  • Contractions: Slow haustral contractions for mixing; mass movements to propel contents to the rectum.

  • Defecation Mechanism:

    • Involves relaxation of internal (smooth muscle) and external (skeletal muscle) anal sphincters.

  • Water Absorption: If disrupted, can cause watery diarrhea.

  • Secretions: Bicarbonate-rich, alkaline mucus.

Small and Large Intestine Disorders - Diarrhea

  • Types:

    • Secretory: Excessive secretions, e.g., cholera.

    • Malabsorptive: Loss of gut surface area as in celiac disease.

    • Osmotic: Lactose intolerance and resultant osmotic pull.

    • Inflammatory: Seen in inflammatory bowel diseases.

Inflammatory Bowel Disease (IBD)

  • Characteristics: Family history and previous autoimmune diseases are common in IBD patients.

Major Presentations:

  • Crohn Disease:

    • Relapsing abdominal pain with diarrhea.

    • Transmural and discontinuous lesions, primarily affecting the ileum.

    • High risk of fistulas and lesions from mouth to rectum.

  • Ulcerative Colitis:

    • Affects a large area of mucosa and submucosa in the colon.

    • Greater blood loss than Crohn's.

    • Managed with immunosuppressive drugs (steroids, biologics).

Irritable Bowel Syndrome (IBS)

  • Clinical Presentation: Pain/discomfort with constipation or diarrhea, lacking endoscopic pathology.

    • Most common Functional GI Disorder (FGID), affecting over 10% of global population.

  • Pathophysiology: Poorly understood, involving:

    • CNS and gut-brain axis

    • Genetic/environmental factors

    • Altered gut motility and microbiome

    • Immune mediators.

Lynch Syndrome

  • Colorectal Cancer (CRC): 4th most common cancer in the US, ~3% linked to Lynch Syndrome.

    • Known as hereditary nonpolyposis colon cancer, carries increased risk for several cancers.

    • Autosomal dominant inheritance of DNA mismatch repair gene mutation elevates cancer risk, especially for endometrial and ovarian cancers.

    • Enhanced screening protocols (e.g., colonoscopy) are recommended.

Basic Principles of Gut Digestion and Absorption

  • Nutrient Absorption: Mostly occurs in proximal small intestine (duodenum and jejunum).

    • Highly vascularized structure supports nutrient transport to liver through the portal vein.

  • End Products of Digestion:

    • Starch: Glucose, galactose, fructose

    • Proteins: Amino acids

    • Triglycerides: Free fatty acids and glycerol

    • Phospholipids: Free fatty acids and lysophospholipids

    • Cholesterol Esters: Cholesterol and free fatty acids.

Small Intestine—Intestinal Epithelial Cell (IEC) Absorption Mechanisms

  • Sodium/Potassium Pump: Drives secondary active transport for glucose and amino acids.

  • Oral Drug Absorption: May undergo:

    1. Absorption across apical/basal membranes unchanged.

    2. Reverse transport back to gut lumen.

    3. Absorption and metabolism, transport of metabolites to circulation.

Carbohydrate and Protein Digestion and Absorption

  • Dietary Starch: Hydrolyzed by salivary and pancreatic amylase; disaccharides broken down by brush border enzymes.

  • Dietary Proteins:

    • Enzymatic hydrolysis via pepsin, trypsin, chymotrypsin, carboxypeptidase, with subsequent absorption of amino acids and peptides via transporters.

Lipid Digestion

  • Process Overview:

    • Requires bile salts and pancreatic enzymes; enters the duodenum via the bile duct.

    • Bile emulsifies fats, creating smaller droplets.

    • Fat digestion products form micelles aiding in absorption.

    • IECs reesterify fats, forming chylomicrons for circulation via lymph.

Vitamin Absorption

  • Water-Soluble Vitamins: Absorbed by membrane transporters.

  • Vitamin B12: Binds to intrinsic factor for absorption in the ileum.

  • Iron: Absorption dependent on specific membrane transporters; body regulates iron loss through cellular turnover.

Water Secretion Follows Chloride Movements

  • Mechanism:

    • Water is secreted into the gut during digestion for optimal enzyme activity.

    • CFTR on the apical membrane, activated by cAMP, secretes Cl−, followed by Na+ and water.

    • Cholera toxin prevents G protein inactivation, leading to massive fluid loss and diarrhea.

Malnutrition and Obesity

  • Malnutrition: Global health issue, affects children's growth; characterized by low BMI, muscle mass, and poor food intake.

  • Obesity: Increasing worldwide, linked to excess caloric intake vs. expenditure; a chronic inflammatory state associated with various diseases.

  • Management: Evolving approaches include bariatric surgery and pharmacological agents like GLP-1 agonists.

Pediatric Considerations: GI Development

  • Embryological Development: GI organs develop in an oral-anal progression by week 11 gestation.

  • Functional Development: All GI functions present at birth but can be impaired (e.g., gastroparesis in preterm infants).

  • Common Congenital Malformations:

    • Hypertrophic Pyloric Stenosis: Diagnosed via history of vomiting and dehydration.

    • Hirschsprung Disease: Failure of enteric neurons to innervate the large intestine, leading to motility issues.

Pediatric Gastroenteritis

  • Acute Gastroenteritis: Common in children, notably in daycare settings; managed to prevent dehydration.

  • Viral Gastroenteritis: Most common causes include rotavirus and norovirus.

  • Bacterial Gastroenteritis: Accounts for less than 10% of cases in the U.S.

  • Parasitic Gastroenteritis: Mostly due to Giardia or Cryptosporidium.

Early Childhood GI Disorders

  • Common Disorders:

    • Infant GER: Painless vomiting of large meals, often resolves spontaneously.

    • GERD: Often presents with pain, vomiting, dysphagia, and food refusal.

    • Intussusception: Common cause of bowel obstruction in infants, may require surgical intervention in severe cases.

Gerontological Considerations

  • Age-Related Changes:

    • Oral issues (e.g., decay, reduced saliva)

    • Decreased motility and slower gastric emptying

    • Slower colonic transit

    • Higher rates of GI symptoms (indigestion, dysphagia, constipation).

    • Anatomical changes, such as increased prevalence of diverticular disease with aging.