SALIVA

Functions and Components of the Gastrointestinal Tract (GIT)

• Primary Functions: The central role of the GIT is the transfer of digested organic nutrients, minerals, and water from the external environment into the internal environment of the body. This involves two distinct processes:

  • Digestion: The conversion of food into absorbable molecules. This is achieved through GIT motility, modifications in $pH$, and the action of "biologic detergents" and enzymes. Enzymes are predominantly produced by the pancreas.

  • Absorption: The movement of digested food products from the intestinal lumen into either the blood or the lymphatic system.

• Secondary Functions:

  • Excretion: The removal of non-absorbable food components, bacteria, sloughed intestinal cells, and hydrophobic molecules such as certain drugs, cholesterol, and steroids.

  • Host Defense: The GIT lumen is technically continuous with the exterior of the body. The tract serves as a protective barrier and houses a highly developed immune system designed to inactivate harmful bacteria and microorganisms.

• Anatomical Components: The GIT is a long muscular tube comprising the mouth, pharynx, esophagus, stomach, small intestine (duodenum, jejunum, ileum), and large intestine.

• Accessory Organs: There are three major accessory organs: the pancreas, liver, and gallbladder.

Histological Organization of the GIT Wall

• General Structure: The GIT stretches from the mouth to the anus. While the top third of the human esophagus is composed of skeletal muscle, the remainder of the tract is composed of smooth muscle.

• The Lumen: The interior of the tube. It features numerous folds and processes to maximize surface area for absorption.

  • Circular Folds: Large-scale folding of the inner surface.

  • Villi (singular: Villus): Finger-like projections that extend into the lumen.

  • Crypts: Invaginations or pits located below the surface between villi.

• Major Layers (from Lumen Outward):

  1. Mucosa: Divided into three subsections: the Epithelium, the Lamina Propria, and the Muscularis Mucosa.

  2. Submucosa: Contains blood and lymphatic vessels, connective tissue, and a nerve network.

  3. Muscularis Externa: The primary outer muscular layer.

  4. Serosa: The outermost layer of connective tissue.

The Intestinal Epithelium: Structure, Turnover, and Transport

• Epithelial Polarization: Epithelial cells are polarized, meaning they have two distinct surfaces:

  • Apical Surface: Faces the lumen (inside of the tube).

  • Basolateral Surface: Faces the blood supply (away from the tube), consisting of both the basal and lateral surfaces.

• Transport Proteins: Selective transport is enabled by different proteins located at the apical vs. basolateral surfaces. These proteins are kept in their respective domains by the presence of tight junctions.

• Function of the Epithelial Layer: Acts as a single-cell layer responsible for the selective uptake of nutrients, electrolytes, and water while preventing the entry of harmful substances. Surface area is further amplified by microvilli found on the epithelial cells of the villi.

• Cell Turnover: Stem cells located within the crypts divide and produce daughter cells. These cells migrate up the villus, differentiate, and eventually reach the tip where they slough off. In the small intestine, the entire layer is replaced every $5\,\text{days}$. Because these cells divide rapidly, they are often collateral targets for anticancer drugs.

• Pathways of Transport:

  • Paracellular Pathway: Molecules move between cells through tight junctions. In a healthy intestine, this is highly limited; only water and small ions can diffuse this way.

  • Transcellular Pathway: Molecules must cross the cell membrane, which requires specific transport proteins.

Submucosa, Muscularis Externa, and Serosa

• Lamina Propria: Found within the mucosa; consists of connective tissue, blood vessels, nerve fibers, lymphatic vessels (including lacteals), and immune/inflammatory cells.

• Muscularis Mucosa: A very thin layer of smooth muscle. It is not involved in major GIT contractions but may help move the villi.

• Submucosa: Contains the Submucosal Nerve Plexus, which relays sensory and motor information to and from the mucosa.

• Muscularis Externa: Composed of two distinct layers:

  • Circular Muscle: Fibers oriented in a ring; contraction closes the tube.

  • Longitudinal Muscle: Controls the length of the tube; contraction shortens the tube without changing diameter.

  • Myenteric Nerve Plexus: Located between the circular and longitudinal muscle layers; primarily regulates muscle function.

• Serosa: A connective tissue layer that encases the intestine and connects it to the abdominal wall.

Blood Supply and Portal Circulation

• Nutrient Transport: Blood carries water-soluble nutrients, while lacteals (lymphatics) in the lamina propria are essential for fat absorption.

• The Portal System: Blood does not return directly to the heart from the GIT. Instead, blood from the stomach, pancreas, small intestine, and large intestine travels via the portal vein to the liver.

• Liver Perfusion: Unlike most organs that receive only arterial blood, the liver receives a mix of oxygenated and deoxygenated blood:

  • Hepatic Artery: Supplies fully oxygenated blood.

  • Hepatic Portal Vein: Supplies nutrient-rich, oxygen-poor blood from the GIT.

• Series vs. Parallel Circulation: Most organs are in parallel within the systemic circulation. The liver is in "series" because it is predominantly perfused by blood that has already passed through the digestive organs.

• Blood Source Ratios: In a fasting state, roughly $30\%$ of liver blood is arterial. After eating, the arterial contribution drops to $10\%$. The liver acts as a filter, removing harmful substances and processing nutrients.

Regulation of GI Processes: Reflexes and Neuronal Control

• Initiating Stimuli: GIT processes (secretion and motility) are regulated by the volume and composition of the contents within the lumen. Specific triggers include:

  1. Distension of the GIT wall (volume).

  2. Osmolarity of the contents.

  3. $pH$ of the contents.

  4. Concentrations of digestion products (monosaccharides, fatty acids, peptides, and amino acids).

• Receptors: These stimuli act on mechanoreceptors (pressure/stretch), osmoreceptors (osmolarity shifts), and chemoreceptors (chemical signals).

• Intrinsic Regulation (Enteric Nervous System): Often called the "Brain of the Gut," the ENS is contained entirely within the GIT walls. It consists of a large number of neurons and can function independently of the Central Nervous System (CNS).

  • Myenteric Plexus: Influences smooth muscle (motility).

  • Submucosal Plexus: Influences secretion.

• Extrinsic Regulation (Autonomic Nervous System):

  • Parasympathetic Division: The "rest and digest" response. Stimulates watery saliva, peristalsis, secretion, and bile release.

  • Sympathetic Division: The "fight of flight" response. Stimulates thick, low-volume saliva; inhibits peristalsis and secretion.

• Short vs. Long Reflexes:

  • Short Reflex: Pathway stays within the ENS (receptors to nerve plexus to effector).

  • Long Reflex: Pathway involves the CNS (receptors to CNS to ENS/effectors via autonomic nerves).

Chemical Messenger Regulation and Hormonal Control

• Classification of Messengers:

  • Endocrine: Hormone released into the blood to act on distant target cells.

  • Neurocrine: Neurotransmitter released by a nerve cell across a synapse.

  • Paracrine: Substance diffuses through interstitial fluid to act on neighboring cells.

  • Autocrine: Substance acts on the identical cell that released it.

• Enteroendocrine Cells: Located in the epithelium of the stomach and small intestine. They release hormones across the basolateral surface into the blood vessels of the lamina propria.

• Major GI Hormones:

  • Gastrin, Secretin, and Cholecystokinin (CCK): All are peptide hormones involved in feedback control.

• CCK Case Study: The presence of fatty acids and amino acids in the small intestine stimulates CCK release into the blood. CCK then stimulates the pancreas (enzyme secretion) and the gallbladder (contraction to release bile). Once fats and amino acids are absorbed, CCK release stops (negative feedback).

Intestinal Motility: Peristalsis, Segmentation, and Electrical Rhythm

• Peristalsis: The primary force for propulsion. Circular muscle contracts on the oral side of a bolus while the longitudinal muscle relaxes. The wave moves toward the anus as the distal circular muscle relaxes to allow passage.

• Segmentation: Primarily occurs in the small intestine. It involves localized contraction and relaxation to mix food with enzymes and slow transit time for better absorption.

• Pacemaker Cells and Slow Waves: Pacemaker cells within the smooth muscle undergo spontaneous depolarization-repolarization cycles called slow waves, creating the Basic Electrical Rhythm (BER).

  • Slow waves spread via gap junctions.

  • Without external stimuli, slow waves do not reach threshold.

  • When excitatory neurons or hormones are present, they further depolarize the membrane until threshold is reached, causing action potentials and muscle contraction.

  • The number of action potentials corresponds to the force of contraction, while the BER dictates frequency.

Phases of Gastrointestinal Control

Control is categorized by the site where the stimulus originates, not the site of effector activity:

1. Cephalic Phase: Initiated in the head (sight, smell, taste, chewing). Regulated by parasympathetic fibers.

2. Gastric Phase: Initiated in the stomach (distension, acidity, amino acids, peptides). Mediated by short and long reflexes; involves the hormone Gastrin and the neurotransmitter Acetylcholine.

3. Intestinal Phase: Initiated in the intestine (distension, acidity, osmolarity, digestive products). Mediated by short and long reflexes and hormones (Secretin, CCK, GIP).

Regulation of Food and Water Intake

• Hypothalamus Control Centers:

  • Feeding Center (Lateral Region): Activation increases hunger. Lesions cause anorexia.

  • Satiety Center (Ventromedial Region): Activation causes fullness. Lesions cause obesity.

• Orexigenic Factors (Increase Intake):

  • Neuropeptide Y: Hypothalamic neurotransmitter.

  • Ghrelin: Released by the stomach during fasting; stimulates Neuropeptide Y.

• Anorexigenic Factors (Decrease Intake):

  • Leptin: Produced by adipose tissue. High levels inhibit Neuropeptide Y and increase metabolic rate.

  • Insulin: Produced by the pancreas.

  • Peptide YY: Released from the intestine.

  • Melanocortin: Released within the hypothalamus.

• Thirst Regulation: Controlled by the thirst center in the hypothalamus.

  • Stimuli: Increased plasma osmolarity (via osmoreceptors), decreased plasma volume (via baroreceptors), and dry mouth/throat.

  • Renin-Angiotensin System: Decreased renal blood pressure activates the production of Angiotensin II, which acts on the hypothalamus to increase thirst.

  • Vasopressin (Antidiuretic Hormone): Released in response to high osmolarity to conserve water at the kidney.

Anatomy and Composition of Saliva

• Major Gland Pairs: Parotid, submandibular, and sublingual glands.

• Saliva Properties: Hypotonic and slightly alkaline.

• Chemical Components:

  • Water and Electrolytes: Rich in $K^+$ and $HCO_3^-$; poor in $Na^+$ and $Cl^-$.

  • Digestive Enzymes: Amylase (starch breakdown) and Lingual Lipase (fat breakdown).

  • Glycoproteins: Mucin (forms mucus when mixed with water).

  • Antimicrobials: Lysozyme (breaks bacterial cell walls) and Lactoferrin (chelates iron to prevent bacterial growth).

Formation, Modification, and Regulation of Saliva

• Cellular Structure:

  • Acinar Cells: Secrete initial "primary" saliva which is isotonic (similar to plasma). They have leaky tight junctions allowing paracellular movement of $Na^+$ and $H_2O$.

  • Ductal Cells: Modify saliva into a hypotonic, alkaline state. They have tight junctions impermeable to water. They actively reabsorb $Na^+$ and $Cl^-$ and secrete $K^+$ and $HCO_3^-$.

  • Myoepithelial Cells: Contractile cells that expel saliva from the acinus into the duct.

• Regulation: Regulated entirely by the nervous system; there is no hormonal regulation.

  • Parasympathetic: Dominant pathway. Increases blood flow and protein secretion; stimulates myoepithelial contraction. Inhibited by sleep, fear, and fatigue.

  • Sympathetic: Minor stimulatory effect; increases flow and protein secretion.

Role of Saliva in Digestion and Pathophysiology

• Amylase (Ptyalin): Cleaves internal $\alpha-1,4$ linkages in starch.

  • Amylose (straight chain): Broken into maltose and maltotriose.

  • Amylopectin (branched): Broken into maltose, maltotriose, and $\alpha$-limit dextrins (retaining $\alpha-1,6$ linkages).

  • Amylase is inactivated by low gastric $pH$. Pancreatic amylase performs over $95\%$ of carbohydrate digestion.

• Lingual Lipase: Acid-stable; remains active in the stomach. Important in neonates and pancreatic insufficiency.

• Xerostomia (Dry Mouth): Caused by Sjögren’s syndrome (autoimmune destruction of glands), radiation, or drugs (antidepressants, psychotropics, etc.).

  • Consequences: Decreased oral $pH$, tooth decay, esophageal erosions, and difficulty swallowing.

  • Treatment: Sips of water and fluoride treatments.