Gastrointestinal Disease Lecture Flashcards

Anatomy and Physiology of the Gastrointestinal Tract

• General Anatomy of the GI Tract

  • Mucus Secretion: Mucus is secreted to protect the stomach lining from acids, enzymes, and abrasive materials.

  • Epithelium: The stomach is lined by an epithelium composed primarily of mucous cells.

• Layers of the Digestive Tract: The digestive tract consists of four distinct layers:

  1. Mucosa: This layer produces digestive enzymes and mucus, which provides essential lubrication.

  2. Submucosa: This layer is involved in producing digestive enzymes, facilitating lubrication, and acid neutralization.

  3. Muscularis Externa: This layer facilitates the movement of contents along the gastrointestinal (GI) tract through muscular contraction.

  4. Serosa: This layer produces serous fluid, creating a moist and slippery surface that reduces surface tension.

• Types of Gastric Cells:

  • G cells: These cells secrete gastrin.

    • Stimulated by: Epinephrine, amino acids (AA), $Ca^{2+}$ containing food, and alcohol.

    • Functions: Increases gastric acid and pepsinogen secretion; increases gastric blood flow; stimulates gastric smooth muscle (SM) contraction; stimulates the growth of gastric and intestinal mucosa cells.

  • Parietal Cells: These cells secrete intrinsic factor and hydrochloric acid ($HCl$).

    • Stimulated by: Histamine ($H_2$) receptors, parasympathetic activity (acetylcholine), and gastrin.

  • Chief Cells: These cells secrete Pepsinogen and lipase.

    • Pepsin Conversion: Pepsinogen is converted into the active enzyme Pepsin by hydrochloric acid ($HCl$).

  • ECL cells (Enterochromaffin-like cells): These cells synthesize and secrete histamine.

    • Stimulated by: The hormones gastrin and pituitary hormones.

Mechanism of Gastric Acid Secretion

• Receptor Activation on Parietal Cells: Acid secretion depends on the activation of three specific receptors:

  • Gastrin receptors.

  • Histamine ($H_2$) receptors.

  • Muscarinic ($M_3$) receptors.

  • Inhibition: Prostaglandins inhibit proton secretion and stimulate mucus production for protection.

• Pathways of Secretion:

  • G Cells produce Gastrin, which acts on Parietal cells and ECL cells.

  • ECL Cells release Histamine, which acts on Parietal cells.

  • Neurons release Acetylcholine ($ACh$), which acts on both G cells, ECL cells, and Parietal cells.

  • Specific ECL Mechanism:

    • Release of histamine activates Adenyl Cyclase.

    • This leads to an increase in intracellular cyclic adenosine monophosphate ($[cAMP]$).

    • Activation of protein kinase A occurs.

    • This causes the translocation of the proton pump to the membrane for acid secretion.

• Chemical and Enzymatic Process in Parietal Cells:

  • Activation occurs via Gastrin, Histamine ($H_2$), and Acetylcholine ($ACh$) at the basolateral membrane.

  • Carbonic Anhydrase Reaction: Carbon dioxide ($CO_2$) from aerobic metabolism reacts with water ($H_2O$) to form carbonic acid ($H_2CO_3$).

  • Dissociation: $H_2CO_3 \rightarrow H^+ + HCO_3^-$.

  • Proton Pump: The involvement of the $H^+/K^+$ ATPase transporter (proton pump) and chloride ($Cl^-$) channels on the luminal membrane facilitates acid secretion.

  • Alkaline Tide: Bicarbonate ($HCO_3^-$) moves out of the cell into the blood from the basolateral membrane, which is responsible for the "alkaline tide" observed after a meal.

Dyspepsia and Gastritis

• Dyspepsia: A common discomfort described as indigestion, gaseousness, fullness, or pain that is gnawing or burning in quality. It is usually localized to the upper abdomen or chest.

  • Causes of Dyspepsia: Stomach ulcers, duodenal ulcers, stomach cancer, gastritis (stomach inflammation), Helicobacter pylori bacteria, gallstones, and certain drugs such as Aspirin and Non-Steroidal Anti-Inflammatory Drugs (NSAIDs).

• Gastritis: A group of disorders involving inflammatory changes in the gastric mucosa, which can lead to gastric mucosal atrophy.

  • Types of Gastritis:

    • Erosive gastritis: Caused by noxious irritants.

    • Reflux gastritis: Caused by exposure to bile and pancreatic fluids.

    • Hemorrhagic gastritis.

    • Infectious gastritis.

• Classifications of Gastritis:

  • Acute Gastritis: Mucosal inflammation that is transient in nature. Often caused by local irritants like NSAIDs, alcohol, or bacterial toxins. Symptoms include heartburn, sour stomach, vomiting, and may be accompanied by hemorrhage.

  • Chronic Gastritis: Characterized by progressive inflammatory changes leading to the atrophy of the glandular epithelium of the stomach. There may be no visible changes initially. Helicobacter pylori gastritis is the most common form of chronic gastritis.

Peptic Ulcer Disease (PUD)

• Definition: A group of ulcerative disorders in the upper GI tract exposed to acid-pepsin secretion. It involves a discrete mucosal defect.

  • Gastric Ulcer: Located in the stomach.

  • Duodenal Ulcer: Located in the duodenum.

  • Nature: Spontaneous remission and exacerbation (flare-ups) are common.

• Pathophysiology (The Balance Model):

  • PUD and gastritis are thought to result from an imbalance between aggressive factors and defensive factors.

  • Aggressive Factors: Acid production and pepsin.

  • Defensive Factors: Mucus production, bicarbonate secretion, and adequate blood flow.

  • Injury Mechanism: Damage from irritants leads to increased intracellular pH, impaired enzyme function, disrupted cellular structures, ischemia, vascular stasis, and tissue death.

• Risk Factors for Peptic Ulcer:

  • Major Factors: Infection with H. pylori and use of Aspirin or NSAIDs (which inhibit cyclooxygenase, reducing mucosal prostaglandins and making the mucus layer vulnerable).

  • Minor/Aggravating Factors: Increasing age, concurrent use of Warfarin or Corticosteroids. (Lower mucosa production)

  • Diet: There is no evidence that diet contributes to the formation of ulcers.

  • Zollinger-Ellison Syndrome: A Gastrinoma (gastrin-secreting tumor) results in massive gastric acid secretion and ulceration.

  • Stress and Reflux: Severe stress (trauma, burns), alcohol, bile reflux, and pancreatic enzyme reflux can disrupt the gastric mucosal barrier.

• Complications of Peptic Ulcer:

  1. Hemorrhage: The most common complication. Evidence includes hematemesis (vomiting blood) or melena (black, tarry feces).

  2. Perforation: GI contents enter the peritoneum, leading to peritonitis.

  3. Penetration: The ulcer erodes through the wall into adjacent organs such as the liver or pancreas.

Diagnosis and Symptoms of PUD

• Diagnosis:

  • Imaging: Endoscopy (to visualize the ulcer and obtain a biopsy) or contrast radiography.

  • H. pylori Testing: Gastric mucosal biopsy culture, the $^{13}C$-urea breath test, and Enzyme-linked immunosorbent assay (ELISA) for H. pylori immunoglobulins.

  • H. pylori: 1. urease → convert urea → ammonia → buffer acidity → multiple flagella → colonize deep layer mucosa.

2. Cause PUD: Disrupt mucosa’s protective properties

• cyclooxygenase → lower mucosa production by lowering prostaglandins

• elicit high immune response against mucosa layer

• Symptoms:

  • Primary Symptom: Pain or discomfort in the upper central portion of the abdomen, usually occurring when the stomach is empty (between meals).

  • Pain Descriptions: Burning, aching, gnawing, sore, sharp, stabbing, or cutting.

  • Differential Pain: Gastric ulcer pain often occurs soon after eating; duodenal ulcer pain is typically relieved by eating or drinking milk.

  • General Symptoms: Belching, nausea, bloating, and vomiting (clear, green, yellow, blood-streaked, or bloody).

  • Severe Symptoms: Internal bleeding leading to anemia, rapid heart beat, pallor, sweating, feeling faint, weight loss, and dark, sticky, foul-smelling bowel movements.

• General Treatment:

  • Neutralizing acid via antacids.

  • Decreasing acid production using $H_2$ receptor antagonists or Proton Pump Inhibitors (PPIs).

Gastroesophageal Reflux Disease (GERD)

• Definition: The backward movement of gastric contents into the esophagus. Reflux that is persistent is referred to as GERD.

• Pathophysiology:

  1. Weakening of the lower esophageal sphincter (LES).

  2. Impaired defensive factors (decreased salivation and salivary buffering capacity).

  3. Impaired esophageal clearance (weak peristalsis delaying acid clearance).

  4. Compromised mucosal defense (dilated intercellular spaces allowing acid to reach nerve endings).

  5. Delayed gastric emptying.

• Symptoms and Risk Factors:

  • Symptoms: Heartburn (most frequent), belching, chest pain, chronic cough, and hoarseness. Symptoms worsen when bending at the waist or lying down.

  • Common in: Patients with obesity, pregnancy, or diets high in fat, caffeine, or alcohol, and those who smoke.

• Complications: Barrett esophagus, where squamous mucosa is replaced by columnar epithelium. This condition increases the risk of esophageal cancer.

• Non-Pharmacologic Therapy:

  • Avoid tight clothing.

  • Do not bend at the waist or lie down immediately after eating.

  • Avoid overeating; avoid high-fat meals, caffeine, and alcohol.

  • Stop smoking.

  • Sleep with the head elevated and lose weight.

Constipation

• Clinical Definition:

  • Bowel frequency of less than (<) 3 motions per week.

  • Straining during defecation more than (>) 25% of the time.

  • Lumpy or hard stools more than (>) 25% of the time.

  • Sensation of incomplete evacuation more than (>) 25% of the time.

• Causes of Constipation:

  • Disease-induced: Colorectal cancer, Diabetes mellitus, Hypothyroidism, Parkinson’s Disease.

  • DM: Diabetic necropathy (nerve change) → GI → lower GI mobility (peristalsis)

  • Lower Thyroid Hormone → Lower GI mobility

  • Parkinson’s Disease: Nerve change of GI

  • Depression/Eating disorder: Lower food/fluid intake → Lower bulk stool formation

  • Drug-induced: Antacids, Anticholinergics, Antihistamines (e.g., diphenhydramine), Verapamil, Iron supplements, Hypotensives (ACE inhibitors, Beta blockers), Opiates.

  • Psychogenic: Depression, Eating disorders.

  • Lifestyle: Low calorie/carb/fiber diets, inadequate fluid intake, ignoring the urge to defecate.

  • Age-related: Higher prevalence in those > 60 years old due to physiologic transit time prolongation, immobility, or comorbid conditions like dementia.

  • Hormonal: Pregnancy and childbirth.

  • Children: Emotional distress, febrile illness, or dietary changes.

• Management:

  • Non-pharmacologic: Increase dietary fiber (insoluble like whole grain/prunes; soluble like beans/oat bran) and increase fluid intake. Note: Fiber is not recommended for patients with fecal impaction (hardening of stool at rectum) → soften/remove → complete bowel → Life-threatening obstruction

  • Pharmacologic: Used if immediate relief is needed or in conjunction with lifestyle changes.

• Barrette esophagus: - Squamous Epithelial cells replaced with columnal cell (gastric). - Higher risk of esophagus cancer

Diarrhea

• Definition: Abnormal increase in stool frequency or liquidity caused by a fluid and electrolyte imbalance in the GI tract.

  • Acute Diarrhea: Short duration.

  • Chronic Diarrhea: Lasts for more than 4 weeks; associated with IBD, IBS, malabsorption, or endocrine disorders.

• Causes of Acute Diarrhea:

  • Food-induced: Allergies, fatty/spicy foods, high roughage/seeds, or lactose intolerance.

  • Viral Gastroenteritis: Most common pathogen is norovirus; sudden onset with vomiting, fever, and abdominal cramps.

  • Protozoal: Giardia lamblia, Entamoeba.

  • Bacterial: Salmonella sp, E. coli, Staphylococcus sp, Clostridium sp. Infection of the small intestine leads to large volume watery stools; the large intestine involves frequent small-volume stools with blood or mucus.

  • Drug-induced: Antibiotics and cytotoxic chemotherapy agents.

  • AIDS-associated: Increased susceptibility to intestinal infections.

Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD)

• Irritable Bowel Syndrome (IBS):

  • Characterized by persistent symptoms (at least 12 weeks) of abdominal pain, altered bowel function, flatulence, bloating, and constipation/diarrhea.

  • Key Distinction: Symptoms are relieved with defecation.

  • Causes: Increased gut sensitivity, abnormal contractions, inappropriate gas pooling, low-grade inflammation, stress, and diet.

• Inflammatory Bowel Disease (IBD):

  • An umbrella term for two specific diseases of unknown cause leading to profuse bloody diarrhea and pain.

  1. Crohn's Disease: Involves granulomatous lesions and "skip lesions" (normal tissue between affected areas). All bowel layers are involved, primarily the submucosal layer. Affects any area of the GI tract. Nutritional deficiencies are common.

  2. Ulcerative Colitis: Inflammatory response is continuous and affects mainly the mucosal layer. Commonly affects the rectum and colon. Cancer of the colon is a potential complication.

• Management and Therapy:

  • Goals: Correct fluid/electrolyte loss, relieve symptoms, and treat the cause.

  • Dietary Management: Consume complex carbohydrates (rice, potatoes), fruits, and vegetables; avoid fatty foods, spicy foods, and caffeine.

Hemorrhoids

• Definition: Swollen or enlarged veins in the superior or inferior hemorrhoidal plexus caused by persistent increase in venous pressure. They appear as grayish-blue painful swellings around the anus.

• Types of Hemorrhoids:

  • Internal: Originate above the dentate line. Lie inside the rectum and are generally not painful (few pain nerves). If they prolapse, they appear as pink pads and may hurt.

  • External: Develop below the dentate line. They have sensory fibers and are painful. If they prolapse, blood clots may form (thrombosis), turning them purple or blue.

• Symptoms and Management:

  • Symptoms: Itching, irritation, burning, pain, swelling, and small stains of fresh blood on toilet paper.

  • Non-Pharmacologic Therapy:

    • Diet: High fiber and fluid intake.

    • Toilet Habits: Avoid sitting on the toilet for > 5 minutes to reduce pressure; do not ignore the urge to defecate.

    • Anal Hygiene: Use mild, unscented soap; avoid excessive scrubbing.

    • Sitz Baths: Sit in warm water ($40-46^{\circ}C$) for 15 minutes, 2-3 times daily.

    • Lifestyle: Increase exercise and avoid heavy lifting.