Clase 49 Fisiología Gastrointestinal - Secreción Gástrica (IG:@doctor.paiva)

49th Class of Gastrointestinal Physiology

Overview of Gastric Secretion

• Introduction to the 49th class on gastrointestinal physiology by Eduardo Paiva, focusing on gastric secretion.

• Discussion on the anatomy of the stomach, including its divisions: fundus, body, antrum, cardia, pylorus, and greater/lesser curvature.

Gastric Glands and Their Functions

• Explanation of two main types of gastric glands:

• Gastric glands (80%): Located in the body and fundus; secrete hydrochloric acid (HCl), pepsinogen, intrinsic factor, and mucus.

• Pyloric glands (20%): Found in the antrum; secrete mucus and hormones like somatostatin.

Cellular Composition of Gastric Glands

• Description of parietal cells (also known as oxyntic cells), which secrete HCl and intrinsic factor.

• Identification of chief cells that produce pepsinogen and mucous neck cells that secrete mucus. Enterochromaffin-like cells release histamine.

Mechanism of Hydrochloric Acid Formation

• Detailed analysis of how HCl is secreted from parietal cells through various cellular processes involving ion exchange.

• The role of carbonic anhydrase in converting CO2 into bicarbonate within parietal cells.

Ion Transport Mechanisms

• Active transport mechanisms for hydrogen ions via the hydrogen-potassium ATPase pump (proton pump).

• Sodium-potassium ATPase pump's function in maintaining sodium gradients essential for ion exchange during gastric secretion.

Role of Chloride Ions in Acid Formation

• Chloride ions enter cytoplasm through chloride channels and are exchanged for bicarbonate at the basolateral membrane.

• The combination of hydrogen ions with chloride ions forms hydrochloric acid in the canaliculus.

Clinical Relevance: Proton Pump Inhibitors

• Mention that proton pump inhibitors like omeprazole reduce HCl concentration by inhibiting proton pumps.

Importance of Intrinsic Factor

• Parietal cells also secrete intrinsic factor crucial for vitamin B12 absorption; deficiency leads to pernicious anemia.

Summary on Vitamin B12 Absorption Process

Understanding Gastric Enzymes and Mucosal Protection

The Role of Pepsinogen and Pepsin

• Pepsinogen is an inactive enzyme with a molecular weight of 42,500. It becomes active as pepsin upon contact with hydrochloric acid in the stomach.

• Pepsin has a molecular weight of 35,000 and functions optimally in highly acidic environments (pH 1.8 to 3.5), losing activity rapidly at pH levels above 5.

Gastric Glands and Hormonal Regulation

• Gastric glands contain enterochromaffin-like cells that synthesize, store, and release histamine, stimulating parietal cells to secrete hydrochloric acid.

• Gastrin is a hormone released into the bloodstream that promotes hydrochloric acid secretion and stimulates mucosal growth in both gastric and intestinal tissues.

Mucous Cells and Their Functions

• There are two types of mucous cells: superficial mucous cells producing thick mucus rich in bicarbonate for gastric barrier protection, and neck mucous cells secreting fluid mucus located mainly in gastric glands.

Importance of the Gastric Mucosal Barrier

• The gastric mucosal barrier protects against hydrochloric acid (pH around 1 to 2). This barrier consists of a viscous layer of mucus containing bicarbonate that neutralizes acidity.

• Superficial mucous cells produce approximately one millimeter thick mucus that traps bicarbonate, raising local pH to about 7, counteracting harmful stomach acids.

Factors Affecting Mucosal Integrity

• Adequate microcirculation is crucial for nutrient supply to mucous cells for proper mucus production; prostaglandins play a significant role in maintaining this function.

• Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, inhibit prostaglandin synthesis leading to reduced mucus secretion and potential damage to the gastric lining.

Stimulation of Gastric Secretion

• Parietal (oxyntic) cells are stimulated by gastrin, histamine, and acetylcholine from parasympathetic stimulation via the vagus nerve.

• Distension or protein-rich food entering the stomach triggers gastrin release from G-cells located in the antrum which directly stimulates parietal cell activity.

Mechanisms Behind Acid Secretion

• Acetylcholine activates muscarinic receptors on parietal cells while gastrin binds directly to its receptors; histamine enhances this process through H2 receptors on parietal membranes.

• Both direct (via gastrin/histamine/acetycholine pathways) and indirect mechanisms contribute synergistically to stimulate hydrochloric acid secretion.

Pharmacological Interventions

• Antihistamines like cimetidine block H2 receptors on parietal cells reducing acid secretion; proton pump inhibitors like omeprazole effectively decrease overall gastric acidity by inhibiting proton pumps.

Regulation of Pepsinogen Secretion

Understanding Gastric Secretion Phases

Cefalic Phase of Gastric Secretion

• The cefalic phase occurs before food enters the stomach, triggered by sensory stimuli such as sight, smell, touch, or taste of food. These signals activate appetite centers in the central nervous system.

• This phase is critical for hydrochloric acid secretion even without food present in the stomach and accounts for approximately 30% of gastric secretion.

Gastric Phase of Gastric Secretion

• The gastric phase begins when food enters the stomach and causes gastric distension, activating local reflexes in the enteric nervous system and vagovagal reflexes that release acetylcholine.

• Presence of proteins and gastric distension stimulate G cells to release gastrin, which directly enhances gastric secretion.

• Histamine release from enterochromaffin-like cells is also stimulated by gastrin and acetylcholine, further promoting gastric secretion. This phase contributes about 60% to total gastric secretion.

Intestinal Phase of Gastric Secretion

• The intestinal phase is initiated by partially digested proteins entering the duodenum, stimulating G cells to secrete gastrin and increase hydrochloric acid production.

• However, this phase only represents about 10% of total gastric secretion.

Inhibition Mechanisms of Gastric Secretion

Nervous Factors

• Inhibition can occur through nervous factors via the enterogastric reflex triggered by food presence in the upper small intestine. It involves sympathetic nerves and vagal parasympathetic pathways.

Hormonal Factors

• Hormonal inhibition includes responses to fat degradation products and protein breakdown products that irritate intestinal mucosa or alter osmolarity.

• Somatostatin is a key inhibitory hormone released from D cells in response to low pH (less than 3), inhibiting gastrin-producing G cells.

Additional Inhibitory Hormones

• Secretin is released when acidic chyme enters the intestine; it inhibits gastric secretion while promoting pancreatic secretions.

• Other hormones like vasoactive intestinal peptide (VIP), cholecystokinin (CCK), and gastric inhibitory peptide (GIP) are also involved in inhibiting gastric secretion upon detection of fatty or protein-rich foods.

Summary of Key Cells Involved in Gastric Secretion

Cellular Interactions

• Various cell types play crucial roles: parietal cells have receptors for acetylcholine that stimulate histamine release; G cells produce gastrin; D cells secrete somatostatin which inhibits other secretory processes.

Understanding Gastric Secretion and Regulation

Mechanisms of Somatostatin and Gastric Cells

• Somatostatin inhibits the production of gastric cells, showcasing a complex feedback mechanism in gastric secretion.

• The release of somatostatin is part of a negative feedback loop that regulates acid secretion to maintain pH balance in the stomach.

• There is an intricate relationship where gastric cells stimulate somatostatin release while also promoting acid secretion, highlighting the body's effort to maintain equilibrium.

Body's Response to Acid Balance

• The body actively protects against hyperacidity to prevent mucosal damage, indicating a sophisticated regulatory system for acid-base balance.

• Disruptions in this balance can lead to conditions like peptic ulcers, emphasizing the importance of maintaining homeostasis.

Phases of Gastric Secretion

• Gastric secretion occurs in three phases:

• Cephalic Phase: Triggered by sensory stimuli (e.g., sight or smell), leading to acetylcholine release.

• Gastric Phase: Involves local nerve reflexes due to stomach distension and histamine stimulation from enterochromaffin-like cells.

• Intestinal Phase: Regulated by enterogastric reflexes and various hormones.

Inter-Digestive Period Secretion

• During the inter-digestive period, there is minimal gastric secretion characterized by mucus production with low acidity levels.