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• Role of the Gastrointestinal (GI) System: Mechanically and chemically breaks down food into absorbable components, with absorption depending on the sequential exposure to different secretions.

GIT Glands

• Secretion from Secretory Glands: Enzymes for digestion, mucous secretions for lubrication and protection.
• Types of GI Glands: Single cell mucous glands (e.g., Goblet cells, Mucous cells), pits (e.g., Crypts of Lieberkuhn), deep tubular glands (e.g., Gastric Oxyntic Glands), and complex glands (e.g., Salivary glands, Pancreas, Liver).
• Basic Stimulation of GIT Glands: Local Epithelial, Enteric Nervous System (ENS), Tactile, Chemical, Distension, and Autonomic Nervous System (ANS).
• Parasympathetic stimulation increases the activity of GIT glands
• Sympathetic stimulation either increases or decreases the activity of GIT glands
• Hormone stimulation of GIT Glands.

Gastrointestinal Tract (GIT) Secretions

• The pH of the secretions is fine-tuned to the optimal pH where the secretion is released.
• Example: Gastric secretions require an acidic environment for pepsinogen to be cleaved into pepsin.
• Glands associated with the GIT release water and substances into the gastrointestinal tract lumen
• Glandular secretions must be coordinated with motility, otherwise, mixing and digestion will not happen.

Salivary Secretion - General Information

• Salivary secretions are the first secretions in the GIT.
• 3 pairs of major salivary glands: Parotid, Submandibular, and Sublingual.
• Minor salivary gland: Buccal glands
• Production: 1,000-1,500 cc of saliva per day.

The Salivon

• Salivon: Functional unit of the salivary duct system.
• Acinar cells: Release primary secretion.
• Ductal cells: Modify secretions.
• Myoepithelial cells surround acinar and ductal cells.

Salivary Glands

• Parotid: Serous or watery secretion.
• Submandibular: Mixed secretion.
• Sublingual: Mucous secretion.

Salivary Secretion

• Primary Secretion: Secreted by Acinar cells, nearly isotonic salivary solution similar to plasma (Amylase mucous ECF).
• Tubular Modification: Duct cells modify the isotonic solution.
• Na+ and Cl- undergo active absorption (removal) while K+undergoes active absorption (addition), and HCO3 secretion (addition).
• End product: hypotonic, alkaline secretion.
• Function: Alkaline secretion is needed to inhibit bacterial growth and neutralize the reflux of gastric acid.
• Farther from the initial composition of the primary secretion, saliva has a high K+ and low Na+, Cl, HCO3.

Regulation of Salivary Secretion

• Almost exclusively nervous: Sympathetic and Parasympathetic.
• Sympathetic stimulation leads to Scanty, thick, viscous saliva
• Parasympathetic stimulation leads to a large volume of watery saliva with decreased enzymes
• Unconditioned and conditioned reflex
• e.g. Pavlov's dog experiment
• Increased salivary secretion is associated with chewing,thinking of food or spicy food
• Decreased Salivary Secretion is associated with sleep, dehydration, fear or anxiety

Esophageal Secretion

• Glands: Mainly mucous cells.
• Secretion: Mucus.
• Control: Local Reflexes.
• Function: To lubricate the bolus as it passes through the esophagus.

Gastric Secretion - General Information

• Production: ~1.5 Liters a day.
• pH: Fasting 1.0 - 2.0.
• Acid secretion initiates protein breakdown and provides the optimal pH for pepsin and possess Antibacterial properties
• Intrinsic Factor is used for DNA synthesis and Vitamin B12 absorption in the terminal ileum of the small intestines
• Absence of Intrinsic Factor causes pernicious anemia, requiring parenteral vitamin B12 administration.
• Mucus aids Lubrication and protection, Pepsinogen is a Precursor of pepsin.

Secretions of the Stomach

• Different parts of the stomach have different secretions.
• Cardia and Pylorus secrete mucus via Mucus-secreting glands.
• Body secretes mucus, pepsinogen and HCl.
• Antrum secretes mucus, pepsinogen, and gastrin released as an endocrine hormone.

Fundic Gastric Glands

• Fundic or Oxyntic Gland (Fundus and Body).
• Parietal Cells produce acid that sterilizes and begins hydrolysis of proteins, and Intrinsic factors for Vitamin B12 production.
• Chief Cells secrete pepsinogen for protein digestion and gastric lipase for Fat digestion.
• Enterochromaffin Cells secrete histamine.
• Surface Mucous Cells secrete mucus and bicarbonate to Protects stomach from digesting itself, and trefoil peptid to Stabilize mucus bicarbonate layer.

Mechanism of Gastric Secretion

• Stimulates all key players in the stomach
• All the cells are stimulated by acetylcholine (ACh), EXCEPT gastrin-releasing cells (G Cells) that are stimulated by gastrin-releasing peptide (GRP).

Gastric Secretion Proton Pump

• Mechanism of H+ and Cl secretion by an activated parietal cell in the gastric mucosa
• Takes place in the parietal cells of the stomach, involving carbonic anhydrase.
• Proton Pump/H+-K+ ATPase pump: Secretes H+ ions across the luminal membrane, inhibited by proton pump inhibitor drugs.
• CI/HCO₃ Exchanger: Transports bicarbonate in exchange for chloride ions, maintaining intracellular pH
• Alkaline Tide: Temporary increase in blood pH after a meal due to the release of bicarbonate (HCO3¯) in the bloodstream

Gastric Parietal Cells

• Contain the proton pumps, intracellular canaliculi, tubulovesicular structures, and Golgi Apparatus (For packaging of protein production)

Stimulation of Gastrict Secretion

• Receptors on the basolateral membrane for Gastrin and Acetylcholine to increase cytosolic free Ca2+, and Histamine to Increase intracellular cyclic adenosine monophosphate (cAMP).
• Proton pumps from tubulovesicular structures (TV) to canaliculi are under the influence of Gastrin, Histamine, and Acetylcholine.
• Histamine is the strongest agonist, exhibiting synergistic action with the other regulators.
• Prostaglandin Synthesis: Inhibits gastric secretion, stimulates mucus and HC03 secretion.
• Alkaline Mucus Layer

Gastric Acid Negative Feedback

• Acid can be damaging without control.
• When antral pH < 3 , somatostatin is released from D cells in the antral mucosa.
• Somatostatin inhibits gastrin release, thus limiting HCI release

Mucous Neck Cells

• Produce alkaline mucus layer with lubricant properties, protecting against abrasion and acids/enzymes
• Secrete bicarbonate ions (HCO3¯).

Phases of Gastric Secretion

• Cephalic phase (30%): HCl an Intrinsic factor, Sight and scent of food stimulate vagal and muscarinic cholinergic receptors.
• Gastric phase (60%): Most important and Local nervous secretory reflexes triggered by Gastric distention
• Vagal reflexes and Gastrin-histamine stimulation by the presence of food in the stomach would further increase gastric secretion.
• Intestinal phase (10%): Duodenal gastrin
• Nervous and hormonal mechanisms increase gastric secretion.

Cells of Gastric Secretion

• Parietal cells: HCl and Intrinsic factor (essential), stimulated by Acetylcholine or Histamine
• Chief cells: Pepsinogen (converted to pepsin at low pH), stimulated by Vagal stimulation (ACh)

Pancreatic Secretion - Composition

• Clear, colorless, alkaline, isotonic secretions.
• Osmolality constant with flow rate.
• Composition: Organic:Includes digestive enzymes (usually inactive except amylase, lipase, DNAse, and RNAse), trypsin inhibitor and colipase. Inorganic: Include cations of Na+, K+, Ca2+and Mg2+, and anions of HCO3, Cland SO4 Aqueous or HCC₃ component Neutralize pH and Prevent damage Sets enzyme pH and Solubilizes bile

Pancreatic Duct Morphology

• Main pancreatic duct → lobules →interlobular ducts → intralobular ducts → pancreatic acinar and ductal cells.

Pancreatic Secretions

• Enzymes in the pancreas undergo exocytosis into pancreatic ductumen then Pancreatic duct of Wirsung, joining the common bile duct, then Ampulla of Vater.

Pancreas as an Acinus and Draining Duct

Pancreatic cells: Acinar, centroacinar and ductal. Acinar cells: synthesizes, stores and secretes digestive enzymes. Centroacinar and Ductal cells: secrete bicarbonate.

Concentrations in Pancreatic Secretions Compared with Plasma

Sodium and potassium concentrations are equal to the plasma. Bicarbonate concentration is greater than the plasma HCO₃. Chloride concentration is less than the plasma.

Sodium Bicarbonate Secretion

• Carbon dioxide (CO2) from metabolism joins water to form carbonic acid (H₂CO₃) in the pancreatic duct cell.
• H+ inside the cell is exchanged for Nat, and Sodium ions also enter the cell by cotransport with bicarbonate across the basolateral membrane.
• Sodium ions are then transported across the luminal border into the pancreatic duct lumen.

Phases of Pancreatic Secretion- Proportions of Secretions

• Cephalic phase (20%):Sight and scent of food; vagus and muscarinic cholinergic receptors
• Gastric phase (5-10%): Food in the stomach; vagovagal and gastrin release
• Intestinal phase (80%): Food is in the intestines; most important for pancreatic secretions

Cholecystokinin VS Secretin

• Cholecystokinin (CCK): secreted by I cells, causes Low output pancreatic secretion, High Protein secretion and Low HCO3
• Secretin: secreted by S cells, High volume H₂O, Weak protein secretion High HCO3

Pancreatic Duct Cells

• Secretin
• Stimulated by acid
• Opens CFTR Chloride drives bicarbonate
• The overall result is high concentration HCO2 in the lumen

Intestinal Secretion -Small intestine

Secretion of the Brunner's Gland:

• Submucosal mucous glands in the duodenal bulb (alkaline)
• Protects duodenal wall from digestion by gastric acid
• Secretes enterokinase: trypsinogen into trypsin
• Stores enzymes as proenzymes
• Proenzymes must be exposed to enterokinase in the small intestine

Secretion of the Crypts of Lieberkuhn

Succus entericus (intestinal juice): water, mucus, electrolytes, enzymes, produced by epithelial cells, secreted: 1L per day, rapidly absorbed in the villi.

• Crypt cells are for secretion
• Villar cells are for absorption

Secretion Regulation

• Stimulated by: Vagal stimulation, tactile or irritating stimuli or local Stimuli, Hormonal regulation through chyme,CCK for acid
• Inhibited by: Sympathetic stimulation

Large Intestine Secretion

• Mucus secretion through stimuli,Presence of food protects against excoriation and Holds fecal matter together
• Water and electrolytes, protects against bacterial activity and acid formed e.g. enterocolitis

Biliary Secretion - Hepatic Blood Flow

• Steps for hepatic blood flow: Oxygenated blood, liver sinusoids, central vein, hepatic Vein, inferior Vena Cava, right Atrium of the Heart

Difference between Zone 1 vs 3

• Zone 1: Receives O2 quicker, active in detoxification & is periportal
• Zone 3:More sensitive to toxins & is pericentral

Liver Function Categories and Actions

• Phagocytosis by Kupffer cells
• Chemical alteration of biologically active molecules (hormones and drugs).

Liver Parenchyma Architecture

The Anatomic Unit of the Liver and Functional Unit (Related to the portal triad), the liver lobule is divided into three zones. The location of the zones would impact how they respond to stimuli

Biliary Secretion

Hepatocytes synthesize bile to aid Fat digestion and absorption through bile acids

• Hepatocytes synthesize
• Extracted
• Eventually store in gallbladder

Bile Acid Production - Important

• Cholesterol Diffuses into hepatocytes and is acted upon by 7α hydroxylase
• Acted by 7α hydroxylase
• Conjugated with Glycine or Taurine (Hepatocyte) to form bile salt with conjugated bile acids
• The negative charge by glycine and taurine will increase the solubility Locked into the bile
• Have to be uptaken at the terminal ileum

Biliary Secretion - Regulations

• It occurs if we have a lot of bile acid causing secretin
• Inc the H20 HCO3
• Gallbladder bile contains
• Bile acids
• Bilirubin
• Fatty acids
• Lecithin ( bile )

Process of Bilirubin Flow

• Products are Metabolised
• Recycled
• Stored in tissues
• Used or dispersed

Functions of the Gallbladder

• storage between meals

Biliary Secretion Control - Composition of Bile

• water reabsorbed
• osmosis sodium

Enterohepatic Circulation

Bile Salts and Acids:

• Difficult to produce recycle them
• Bile salts being produced by the liver make (from the gallbladder), are concentrated ,and secreted into the 2nd part of the duodenum where they create ,micelle , and they reach this point, and have to be taken up by hepatic enzymes

Control biliary Secretion

Canalicular Bile secretion is acid dependent Ductural Bile Secretion

Bilirubin Metabolsim

• Products are Metabolised from old fragile cells or from the Reticuoendothelial system converted by bilirubin with albumin with the liver where it comes bile action