Human Digestive System

Components of the Digestive System

• Gastrointestinal tract (GI tract): The continuous muscular tube through which food and waste pass.

• Accessory organs: These structures assist with the digestive process through mechanical or chemical means:     * Teeth: Responsible for mechanical breakdown (mastication).     * Tongue: Assists in manipulating food and swallowing.     * Salivary glands: Initiate chemical digestion.     * Liver and gallbladder: Produce and store bile for fat emulsification.     * Pancreas: Secretes digestive enzymes and buffers.

Overview of Digestive Processes

• Nutrient Fulfillment: All living organisms obtain nutrients for two primary metabolic purposes:     1. Anabolism: The building of new molecules and the creation of new macromolecules.     2. Catabolism: The breaking apart of existing molecules to release energy for use elsewhere.

• Core Functions of the Digestive System:     1. Ingestion: The selective intake of solid and liquid nutrients.     2. Motility: Voluntary and involuntary movements required to mix and move materials through the length of the GI tract.     3. Secretion: The release of water, acids, enzymes, hormones, salts, and buffers.     4. Digestion: The physical (mechanical) and chemical breakdown of food.     5. Absorption: The uptake of nutrients into epithelial cells, followed by movement into the blood or lymph.     6. Defecation: The elimination of undigested residues and metabolic wastes.

Histological Organization and Peritoneum

• Peritoneum:     * The peritoneal cavity is lined by a serous membrane known as the Serosa peritoneum.     * This membrane provides a low-friction environment for the sliding and movement of GI structures.     * Ascites: A clinical condition where fluid accumulates within the peritoneal cavity.

• Layers of the Digestive System Wall:     1. Mucosa: The innermost layer consisting of epithelium, the lamina propria, and the muscularis mucosae.     2. Submucosa: A layer of loose connective tissue (CT) containing the Submucosal plexus (Meissner plexus).     3. Muscularis externa: The primary muscle layer containing the Myenteric plexus (Auerbach plexus).     4. Serosa or Adventitia: The outermost protective layer; adventitia is found in areas like the esophagus within the mediastinum.

The Enteric Nervous System (ENS)

• General Characteristics: A semiautonomous neural network embedded in the walls of the GI tract that coordinates digestion. It can operate independently of the Central Nervous System (CNS) but is modified by CNS activity.

• Submucosal nerve plexus (Meissner plexus):     * Comprised of axons and ganglia located in the submucosal layer.     * Innervates smooth muscle and glands within the submucosa and mucosa.

• Myenteric nerve plexus (Auerbach’s plexus):     * Located between the circular and longitudinal layers of smooth muscle in the muscularis externa.

• Sensory Neurons of the ENS:     * Mechanoreceptors: Detect the stretch of the GI wall.     * Chemoreceptors: Detect the chemical composition of the contents within the lumen.

• Reflex Pathways:     * Short reflexes: Mediated entirely by the enteric system in response to local stimuli; these control patterns of segmentation and peristalsis independent of the CNS.     * Long reflexes: Involve the Autonomic Nervous System (ANS), allowing for extrinsic influence on GI activity.

Protective Role of the GI Lining

• The lining protects surrounding tissues against:     1. Auto-digestion: The corrosive effects of internal digestive enzymes and acids on the body's own tissues.     2. Mechanical stresses: Such as abrasion from food particles.     3. Bacteria: Both bacteria swallowed with food and those residing naturally in the tract.

The Oral Cavity and Salivation

• Mouth/Oral Cavity: Site of ingestion and the initiation of physical and chemical digestion.

• Mastication: Physical breakdown involving $20$ deciduous teeth and $32$ permanent teeth.

• Chemical Digestion: Initiated by Salivary amylase (carbohydrates) and Lingual lipase (lipids).

• Histology: Lined by stratified squamous epithelium to resist abrasion. Most is non-keratinized, with the exception of the lips and hard palate. The mucosa inferior to the tongue is thin and vascular, permitting the absorption of lipid-soluble substances like nitroglycerin.

• Tongue Muscles:     * Intrinsic muscles: Contained within the tongue; change its shape.     * Extrinsic muscles: Originate on bones; change the tongue's position.

• Extrinsic Salivary Glands:     1. Parotid: The largest glands; produce enzyme-rich saliva.     2. Submandibular: Secrete the majority ($70 \%$) of total saliva.     3. Sublingual: Produce mucus-rich saliva.

• Saliva Properties:     * Production: $1$ to $1.5\,L/day$.     * Composition: Mostly water; $pH$ range of $6.8$ to $7.0$.     * Functions: Lubrication, moistening food into a bolus, dissolving taste chemicals, and inhibiting bacteria via IgA antibodies and lysozymes.     * Control: Secretions are triggered by the Parasympathetic Nervous System.

The Esophagus and Swallowing

• Histology of the Esophagus:     * Mucosa is non-keratinized stratified squamous epithelium.     * Submucosa contains scattered esophageal glands for mucus production.     * Muscularis externa transition: Upper $1/3$ is skeletal muscle; Middle $1/3$ is mixed; Lower $1/3$ is smooth muscle.     * Lacks a serosa; it has an adventitia due to its location in the mediastinum.

• Deglutition (Swallowing):     * Involves $22$ different muscles.     * Occurs approximately $2400\,times/day$.     * Coordinated by the swallowing center of the medulla.     * Phases:         1. Voluntary phase.         2. Pharyngeal phase (involuntary).         3. Esophageal phase (involuntary).

Anatomy and Histology of the Stomach

• Epithelium: Simple columnar epithelium that produces a layer of alkaline mucus.

• Surface Features: Features large folds called rugae (gastric folds) and depressions called gastric pits.

• Muscle Layers: Unlike the rest of the GI tract, it has three layers of smooth muscle: inner oblique, middle circular, and outer longitudinal.

• Secretory Cells of the Gastric Gland:     1. Surface mucous cells: Line the stomach; secrete alkaline mucus.     2. Mucous neck cells: Located at the base of the gastric pit; secrete acidic mucus.     3. Parietal cells: Located in the proximal portion of the gland; produce intrinsic factor and Hydrochloric acid (HCl). Feature microvilli to increase surface area.     4. Chief cells: Deep in the gland; secrete pepsinogen (a zymogen) and gastric lipase.     5. Enteroendocrine (G cells): Secrete gastrin (hormone) and histamine (paracrine).

Gastric Juice and the Mucosal Barrier

• Gastric Juice Production: $2$ to $3\,L/day$.

• Properties: Primarily water, HCl, and pepsin; $pH$ can be as low as $0.8$. The concentration of $H^+$ is $100,000\,times$ that of blood.

• Protective Mucosal Barrier:     * Bicarbonate-rich mucus neutralizes acid near the lining.     * Tight junctions prevent acid leakage between columnar cells.     * Epithelial replacement occurs every $3$ to $6$ days.

• Ulcers: $90 \%$ of recurring ulcers are caused by Helicobacter pylori (H. pylori), which burrows via negative chemotaxis and creates toxic ammonia. Other factors include aspirin, NSAIDs, alcohol, and smoking.

• Intrinsic Factor: A glycoprotein necessary for Vitamin $B_{12}$ absorption in the ileum. $B_{12}$ is vital for hemoglobin synthesis. Loss of this factor (e.g., via gastrectomy or geriatric atrophy) leads to pernicious anemia.

Physiology of HCl Production

• Mechanism in Parietal Cells:     * Parietal cells contain carbonic anhydrase for the reaction: $CO_2 + H_2O \rightleftharpoons H_2CO_3 \rightleftharpoons H^+ + HCO_3^-$.     * $H^+$ is pumped into the lumen by the $H^+-K^+$ ATPase pump (proton pump).     * Chloride Shift: $HCO_3^-$ is exchanged for $Cl^-$ into the blood.     * Alkaline Tide: Blood leaving the stomach during digestion has a higher $pH$ due to the influx of bicarbonate.     * $Cl^-$ diffuses into the lumen to join $H^+$ and form $HCl$.

• Functions of Stomach Acid:     * Activates pepsin and lingual lipase.     * Breaks down animal connective tissue and plant cell walls.     * Denatures proteins to facilitate digestion.     * Converts $Fe^{3+}$ to $Fe^{2+}$ for absorption.     * Pathogen resistance.

Pepsin Activation and Regulation

• Pepsin: Chief cells secrete pepsinogen; HCl removes amino acids to convert it to active pepsin at low $pH$.

• Autocatalytic Effect: Pepsin itself can activate more pepsinogen.

• Three Phases of Gastric Regulation:     1. Cephalic Phase: Brain-controlled. Activated by sight, smell, or taste. Medulla signals via the Vagus nerve to increase secretion.     2. Gastric Phase: Stomach-controlled. Triggered by food arrival, stretch (mechanoreceptors), and increased $pH$ (chemoreceptors). $2/3$ of secretion occurs here. Stimulated by ACh, Histamine, and Gastrin.     3. Intestinal Phase: Small intestine-controlled. Arrival of chyme in the duodenum triggers the Enterogastric reflex to inhibit the stomach.

Feedback and Enterogastrones

• Positive Feedback: Oligopeptides from protein digestion buffer acid and raise $pH$, which stimulates more gastrin.

• Negative Feedback: When pH < 2, parietal and G cells are inhibited as the stomach empties.

• Hormonal Responses (Enterogastrones): Released by the duodenum to suppress the stomach and coordinate emptying:     * Secretin: Secreted in response to low $pH$ ($chyme$); stimulates pancreatic bicarbonate secretion.     * Cholecystokinin (CCK): Secreted in response to fats; causes gallbladder contraction, pancreatic enzyme secretion, and relaxation of the hepatopancreatic sphincter.     * Glucose Insulinotropic Peptide (GIP): Stimulates insulin release in response to glucose and amino acids.     * Vasoactive Intestinal Peptide (VIP): Secreted by enteric neurons; causes vasodilation to enhance absorption.

The Pancreas and Liver

• Pancreatic Secretion:     * ACh and CCK stimulate the release of pancreatic enzymes from acini.     * Secretin stimulates the release of bicarbonate from duct cells.     * Neutralization: The alkaline tide from the stomach is neutralized by acidic blood from the pancreas, stabilizing venous blood $pH$.

• The Liver:     * Hepatocytes: Form bile ($900\,ml/daily$), synthesize cholesterol, store glucose as glycogen, produce plasma proteins, and detoxify (convert ammonia to urea).     * Hepatic Macrophages (Stellate cells): Remove worn-out RBCs and bacteria.

• Bile:     * Daily production: $500$ to $1000\,ml$.     * Bile Salts: Synthesized from cholesterol; amphiphilic agents that work with lecithin to emulsify fats. $80 \%$ are recycled via enterohepatic circulation.     * Bilirubin: Waste product of heme catabolism.

Pathologies of the Liver and Gallbladder

• Gallstones: Caused by crystallized cholesterol when bile salts are insufficient or cholesterol is excessive. Treatments include lithotripsy or surgical removal.

• Non-Alcoholic Fatty Liver Disease (NAFLD): Now the most common liver disease in North America; linked to obesity/insulin resistance. Doctors recommend a gradual $7 \%$ weight reduction over $1$ year.

• Cirrhosis: The final stage of chronic inflammation marked by fibrosis.     * Complications: Reduced plasma proteins (ascites), jaundice (bile issues), portal hypertension, and hepatocellular carcinoma.

The Small Intestine

• Regional Anatomy:     1. Duodenum: Proximal $10\,inches$. Retroperitoneal. Receives accessory organ secretions.     2. Jejunum: Middle $7.5\,feet$. Primary site of chemical digestion and absorption. Has numerous circular folds.     3. Ileum: Distal $11\,feet$. Ends at the ileocecal valve. Contains fewer folds; site of $B_{12}$ absorption.

• Intestinal Motility:     * Segmentation: Most common movement; ringlike constrictions for kneading and churning contents.     * Peristalsis: Occurs after absorption; travels in waves ($10$ to $70\,cm$) from the duodenum.     * Gastroileal reflex: Triggered by food in the stomach to relax the ileocecal valve.

• Cell Types:     * Enterocytes: Absorptive cells with microvilli.     * Paneth cells: Secrete defensins and lysozymes.     * Duodenal glands: Secrete bicarbonate-rich mucus.

Chemical Digestion and Absorption

• Carbohydrates:     * Starch breakdown starts with salivary amylase ($pH\,6.8-7.0$), stops in the stomach, and continues with pancreatic amylase in the small intestine.     * Brush Border Enzymes: Dextrinase, glucoamylase, maltase, sucrase, and lactase.     * Absorption: $80 \%$ is glucose; uses the Sodium-glucose transport protein (SGLT) for cotransport.

• Proteins:     * Hydrolysis starts with Pepsin ($15 \%$, optimal $pH\,1.5-3.5$).     * Pancreatic enzymes: Trypsin and Chymotrypsin decompose polypeptides into oligopeptides.     * Brush border enzymes: Carboxypeptidase, aminopeptidase, and dipeptidase.     * Absorption uses sodium-dependent cotransporters. Infants can absorb intact proteins via pinocytosis (linked to IgA transfer and food allergies).

• Lipids:     * Digestion requires emulsification by bile.     * Micelles: Small droplets containing fatty acids, monoglycerides, and fat-soluble vitamins; diffuse into enterocytes.     * Chylomicrons: Reassembled lipids packaged with protein; transported via lacteals (lymph) as chyle to the subclavian veins.

• Water and Minerals:     * The GI tract receives $9\,L\,H_2O/day$; $8.8\,L$ is reabsorbed via osmosis.     * Iron and calcium are unique because they are absorbed in proportion to the body’s specific needs.

• Large Intestine: Processes residue into feces over $12$ to $24$ hours; harvests bacterial vitamins and absorbs remaining water and electrolytes.