Secretory Functions of the Alimentary Tract Study Guide

Fundamental Secretory Functions and Alimentary Gland Types

• Secretory glands throughout the gastrointestinal tract subserve two primary functions:
  • Digestive enzymes: These are secreted in most areas of the alimentary tract, extending from the mouth to the distal end of the ileum.
  • Mucous glands: Located from the mouth to the anus, these provide mucus for the lubrication and protection of all parts of the alimentary tract.
• Digestive secretions are typically formed in response to the presence of food, with the quantity secreted in each segment usually matching the amount needed for proper digestion.
• Types of specialized glands include:
  • Single-cell mucous glands (Mucous cells or Goblet cells): Billions of these cells are present on the surface of the epithelium in most parts of the gastrointestinal tract. They function mainly in response to local irritation, extruding mucus to protect and lubricate surfaces from excoriation and digestion.
  • Pits (Invaginations of epithelium): In the small intestine, these represent deep pits called Crypts of Lieberkühn which contain specialized secretory cells.
  • Tubular glands: Found in the stomach and upper duodenum, these are deep tubular structures. An example is the oxyntic gland (acid- and pepsinogen-secreting) in the stomach.
  • Complex glands: These include the salivary glands, pancreas, and liver. They lie outside the walls of the alimentary tract and contain millions of acini lined with secretory cells. These acini feed into a system of ducts that eventually empty into the alimentary tract.

Basic Mechanisms of Alimentary Tract Glandular Stimulation

• Contact of food with gut epithelium activates the enteric nervous system (ENS). Local effects result from direct tactile stimulation, chemical irritation, and distention of the gut wall.
• Nervous reflexes resulting from these stimuli increase the secretion of mucous cells and deep glands.
• Autonomic Regulation:
  • Parasympathetic Stimulation: Almost invariably increases the rates of glandular secretion. This is especially true for the salivary glands, esophageal glands, gastric glands, pancreas, and Brunner's glands (innervated by glossopharyngeal and vagus nerves) and distal large intestine glands (innervated by pelvic parasympathetic nerves).
  • Sympathetic Stimulation: Has a dual effect. Alone, it causes a slight to moderate increase in secretion. However, if parasympathetic or hormonal stimulation is already causing copious secretion, sympathetic stimulation reduces it by constricting blood vessels that supply the glands.
• Hormonal Regulation: Polypeptides or polypeptide derivatives are liberated from the gastrointestinal mucosa in response to food. These are absorbed into the blood and carried to the glands to stimulate secretion, which is particularly vital for gastric and pancreatic juice output.

Cellular Mechanisms of Organic and Inorganic Secretion

• Secretion of Organic Substances follows specific principles:
  1. Nutrients diffuse or are actively transported from capillaries into the base of the glandular cell.
  2. Mitochondria near the cell base provide oxidative energy to form adenosine triphosphate ($ATP$).
  3. Energy from $ATP$ and substrates are used to synthesize substances in the endoplasmic reticulum ($ER$) and Golgi complex. Ribosomes on the $ER$ form proteins.
  4. Materials pass through $ER$ tubules to the Golgi complex in approximately $20\,minutes$.
  5. The Golgi complex modifies, concentrates, and discharges materials into the cytoplasm as secretory vesicles stored at the apical ends.
  6. Extrusion occurs via exocytosis. A hormone or nerve signal increases cell membrane permeability to calcium ($Ca^{2+}$), causing vesicles to fuse with the apical membrane and break open.
• Water and Electrolyte Secretion: Nervous or hormonal stimulation causes a profusion of water and salts to pass through glandular cells, washing organic substances through the secretory border.

Characteristics and Protective Properties of Mucus

• Mucus is a thick secretion composed of water, electrolytes, and several glycoproteins (large polysaccharides bound with smaller quantities of protein).
• Essential characteristics include:
  1. Adherent qualities to food and surfaces.
  2. Sufficient body to coat the wall and prevent contact with mucosa.
  3. Low resistance for slippage (lubrication).
  4. Ability to cause fecal particles to adhere to one another.
  5. Resistance to digestion by gastrointestinal enzymes.
  6. Amphoteric properties (buffering acids/alkalies) and content of $HCO_3^-$ to neutralize acids.

Physiology and Ionic Mechanisms of Saliva

• The principal salivary glands are the parotid, submandibular, and sublingual glands, along with small buccal glands.
• Daily secretion volume: $800-1500\,ml$ (average $1000\,ml$).
• Types of protein secretion:
  • Serous: Contains ptyalin (an alpha-amylase) for starch digestion.
  • Mucus: Contains mucin for lubrication.
• Gland specificities: Parotid (mostly serous), Submandibular/Sublingual (both), Buccal (only mucus).
• Saliva $pH$: $6.0-7.0$.
• Ionic Composition (Two-Stage Operation):
  1. Acini stage: Secretion of a primary solution containing ptyalin/mucin in a solution with ion concentrations similar to extracellular fluid ($ECF$).
  2. Ductal stage: Active reabsorption of $Na^+$ and active secretion of $K^+$ (exchange). Excess $Na^+$ reabsorption creates an electrical negativity of $-70\,mV$, causing passive $Cl^-$ reabsorption. $HCO_3^-$ is secreted by ductal epithelium into the lumen (passive exchange for $Cl^-$ or active process).
• Net Resting Concentrations: $Na^+$ and $Cl^-$ are $15\,mEq/L$ (1/7th to 1/10th of plasma); $K^+$ is $30\,mEq/L$ (7 times plasma); $HCO_3^-$ is $50-70\,mEq/L$ (2-3 times plasma).
• Copious Secretion: During maximal salivation, acinar formation increases $20$-fold. Ductal reconditioning reduces, resulting in $NaCl$ concentrations being 1/2 to 2/3 of plasma and $K^+$ being 4 times plasma.

Nervous Regulation and Oral Hygiene of Saliva

• Hygiene Functions:
  1. Washing away pathogenic bacteria and food particles.
  2. Bactericidal factors: Thiocyanate ions and proteolytic enzymes such as lysozyme (attacks bacteria and digests food).
  3. Antibodies to destroy oral bacteria.
• Nervous Pathways:
  • Controlled by parasympathetic signals from superior and inferior salivatory nuclei (at the juncture of the medulla and pons).
  • Excited by taste (sour/acids elicit $8-20$ times basal rate) and tactile stimuli (smooth objects increase; rough objects may inhibit).
  • Appetite area (anterior hypothalamus) responds to cortex/amygdala smell and taste signals.
  • Stomach/small intestine reflexes (irritation/nausea) evoke saliva to dilute irritants.
  • Sympathetic stimulation: Increases salivation slightly, producing thicker saliva. Originates from superior cervical ganglia.
  • Vasodilation: Parasympathetic signals dilate blood vessels. Salivation also releases kallikrein, which splits alpha-globulin to form bradykinin (vasodilator).

Gastric Secretory Systems

• The stomach mucosa contains two major tubular glands:
  • Oxyntic (Gastric) Glands: Located in the proximal $80\%$ (body and fundus). They secrete $HCl$, pepsinogen, intrinsic factor, and mucus.
  • Pyloric Glands: Located in the distal $20\%$ (antrum). They secrete mucus and the hormone gastrin.
• Oxyntic Gland Cell Types:
  1. Mucous neck cells: Secrete mucus.
  2. Peptic (chief) cells: Secrete pepsinogen.
  3. Parietal (oxyntic) cells: Secrete $HCl$ and intrinsic factor.
  4. Enterochromaffin-like ($ECL$) cells: Secrete histamine.

The Mechanism and Stimulation of Hydrochloric Acid Secretion

• Parietal cells secrete acid with a concentration of $160\,mmol/L$ ($pH \approx 0.8$). The $H^+$ concentration is $3\,million$ times that of arterial blood.
• Energy requirement: More than $1500\,calories/L$ of gastric juice.
• Secretory Process:
  1. $H_2O$ dissociates into $H^+$ and $OH^-$ in the cytoplasm.
  2. $H^+-K^+$ $ATPase$ (hydrogen-potassium pump) actively secretes $H^+$ into the canaliculus in exchange for $K^+$.
  3. $OH^-$ combines with $CO_2$ (catalyzed by carbonic anhydrase) to form $HCO_3^-$.
  4. $HCO_3^-$ is exchanged across the basolateral membrane for $Cl^-$; $Cl^-$ is then secreted through channels into the canaliculus.
  5. Lumenal contents: Water (osmotic entry), $HCl$ ($150-160\,mEq/L$), $KCl$ ($15\,mEq/L$), and minor $NaCl$.
• Stimulants: Acetylcholine ($ACh$) stimulates all cells. Gastrin and Histamine strongly stimulate parietal acid secretion specifically.
• Pepsinogen Activation: Secreted by peptic cells (MW $42,500$). Contact with $HCl$ splits it into active pepsin (MW $35,000$). Optimum $pH$ is $1.8-3.5$. Above $pH = 5$, it is inactivated.
• Intrinsic Factor: Essential for vitamin $B_{12}$ absorption in the ileum. Absence leads to achlorhydria and pernicious anemia.

Phases and Inhibition of Gastric Secretion

• Phases of Secretion:
  1. Cephalic Phase ($30\%$): Occurs before food enters the stomach (sight, smell, thought, taste). Mediated by the vagis nerves.
  2. Gastric Phase ($60\%$): Food enters the stomach; involves vagal reflexes, local enteric reflexes, and the gastrin-histamine mechanism.
  3. Intestinal Phase ($10\%$): Food in the upper small intestine causes small amounts of gastrin release from duodenal mucosa.
• Inhibition:
  • Reverse enterogastric reflex: Initiated by distention, protein breakdown products, or irritation in the small bowel.
  • Hormones: Secretin (opposes stomach secretion), glucose-dependent insulinotropic peptide ($GIP$), vasoactive intestinal polypeptide ($VIP$), and somatostatin.
• Interdigestive period: Secretion is usually nonoxyntic (mostly mucus). Emotional stimuli can increase this to $50\,ml/hr$ or more.

Pancreatic Secretion: Enzymes and Bicarbonate

• Anatomy: Large compound gland beneath the stomach. Enzymes are secreted by acini; $Na^+-HCO_3^-$ and water are secreted by ductules/ducts.
• Digestive Enzymes:
  • Proteolytic: Trypsin (most abundant), Chymotrypsin, Carboxypolypeptidase. Trypsin and chymotrypsin split proteins into peptides; carboxypolypeptidase splits peptides into individual amino acids.
  • Carbohydrate: Pancreatic amylase (hydrolyzes starches, glycogen to disaccharides/trisaccharides).
  • Fat: Pancreatic lipase (neutral fat to fatty acids/monoglycerides), cholesterol esterase, and phospholipase.
• Zymogen Activation: Proteolytic enzymes are secreted as inactive forms (trypsinogen, chymotrypsinogen, procarboxypolypeptidase). Trypsinogen is activated by enterokinase (secreted by intestinal mucosa) or autocatalytically by trypsin.
• Trypsin Inhibitor: Prevents activation of enzymes inside the pancreas to avoid autodigestion. Pancreatic damage/blockage can lead to acute pancreatitis.
• Bicarbonate Secretion Mechanism:
  1. $CO_2 + H_2O \xrightarrow{CA} H_2CO_3 \rightarrow H^+ + HCO_3^-$.
  2. $HCO_3^-$ is exchanged for $Cl^-$ at the luminal border. $H^+$ is exchanged for $Na^+$ at the basolateral border via secondary active transport.
  3. Movement of $Na^+$ and $HCO_3^-$ into the duct creates an osmotic gradient for water entry.
  4. Concentration can reach $145\,mEq/L$ ($5$ times plasma).

Regulation of Pancreatic Secretion and Bile Synthesis

• Pancreatic Stimuli: Acetylcholine ($vagus$), Cholecystokinin ($CCK$ - from $I$ cells in response to proteoses, peptones, and fatty acids), and Secretin ($S$ cells in response to $pH < 4.5-5.0$). These stimuli potentiate each other.
• Bile serves two roles: Fat digestion/absorption (via bile acids) and excretion of waste ($bilirubin$ and excess $cholesterol$).
• Bilirubin Secretion Stages:
  1. Hepatocytes secrete primary bile (bile acids, cholesterol, organic constituents) into canaliculi.
  2. Bile flows to terminal ducts; ductal cells add a watery solution of $Na^+$ and $HCO_3^-$ (stimulated by secretin, doubling bile volume).
• Gallbladder Dynamics: Stores and concentrates bile up to $20$-fold (typical $5$-fold). Water, $Na^+$, and $Cl^-$ are absorbed. Volume capacity: $30-60\,ml$ (can store $12\,hours$ of secretion, approx. $450\,ml$).
• Bile Salts: Liver synthesizes $6\,g/day$. Precursor is cholesterol; converted to cholic or chenodeoxycholic acid, then conjugated with glycine or taurine.

Function and Enterohepatic Circulation of Bile Salts

• Actions of Bile Salts:
  1. Emulsification (Detergent function): Decreases surface tension to break fat globules.
  2. Micelle formation: Complexes with fatty acids, monoglycerides, and cholesterol to make them semisoluble for absorption.
• Enterohepatic Circulation: $94\%$ of bile salts are reabsorbed (diffused in early small intestine, active transport in distal ileum). They return via portal blood to liver. The average salt makes the circuit $17\,times$ before excretion.
• Daily secretion is dependent on salt availability. If reabsorption is blocked, liver production increases $10$-fold.
• Gallstones: Caused by excess water/bile salt absorption, excess cholesterol, or epithelial inflammation. Obesity and high-fat diets are risk factors.

Secretions of the Small and Large Intestines

• Brunner's Glands (Duodenum): Secrete alkaline mucus for protection and neutralization. Stimulated by tactile/irritating stimuli, vagal signals, and secretin. Inhibited by sympathetic stimulation.
• Crypts of Lieberkühn: Located between villi. Contain goblet cells (mucus) and enterocytes. Enterocytes in crypts secrete extracellular fluid ($1800\,ml/day$, $pH = 7.5-8.0$). Villi reabsorb this fluid.
• Small Intestine Enzymes: Peptidases, sucrase, maltase, isomaltase, lactase, and lipase. These remain in the enterocytes during absorption rather than being secreted into the lumen.
• Large Intestine: Contains crypts of Lieberkühn but no villi. Secretes only mucus (containing $HCO_3^-$). Regulated by direct tactile stimulation and pelvic parasympathetic nerves.
• Large Intestine Functions: Protection from excoriation/bacteria, holding feces together, and providing an alkaline barrier ($pH = 8.0$). Extreme irritation/bacterial infection results in diarrhea (hypersecretion of water and electrolytes to dilute and wash away irritants).