BMS150 Stomach Physiology and Pathology PDF

Physiology 5.04 Pathology 5.0X Stomach physiology and pathology Dr. Hurnik BMS 150 Week 11 Outline PHL5.04: Stomach anatomy and physiology Stomach anatomy Regions, sphincters, curvatures Arterial and vascular supply Innervation Stomach histology Mucosa Gastric glands, cell types Submucosa, musculari...

Physiology 5.04 Pathology 5.0X Stomach physiology and pathology Dr. Hurnik BMS 150 Week 11 Outline PHL5.04: Stomach anatomy and physiology Stomach anatomy Regions, sphincters, curvatures Arterial and vascular supply Innervation Stomach histology Mucosa Gastric glands, cell types Submucosa, muscularis externa, serosa Stomach physiology Motility Secretion PAT 5.02 - Stomach pathology Acute and chronic gastritis Peptic ulcer disease Learning outcomes Coming soon… Stomach - intro Stomach is a J-shaped enlargement of GI tract directly inferior to diaphragm in abdomen Most distensible part of GI tract: can accommodate a large quantity of food Functions: § Serves as reservoir for food before release into SI § Mixes saliva, food and gastric juice to form chyme Stomach: Anatomy 4 main regions § § § § Cardia Fundus Body Pyloric 2 sphincters: § lower esophageal § Pyloric 2 main curvatures: § Lesser § Greater Anatomy and Physiology (Betts et al). Figure 23.15 Moore et al et. al., Moore’s Clinically Oriented Anatomy (7th ed). Fig 2.37, p. 233 Stomach: Anatomy 4 main regions § § § § Cardia Fundus Body Pylorus 2 sphincters: § lower esophageal § Pyloric 2 main curvatures: § Lesser § Greater Anatomy and Physiology (Betts et al). Figure 23.15 Stomach: Anatomy 4 main regions § § § § Cardia Fundus Body Pylorus 2 sphincters: § lower esophageal § Pyloric 2 main curvatures: § Lesser § Greater Anatomy and Physiology (Betts et al). Figure 23.15 Stomach – Vasculature: arteries Main arterial supply comes from celiac trunk of aorta 4 main arteries supply stomach: § à Hepatic artery à Right gastric à Right gastro-omental § à Celiac trunk à Left gastric § à Splenic artery à Left gastroomental Moore et al et. al., Moore’s Clinically Oriented Anatomy (7th ed). Fig 2.40, p. 236 Stomach – Vasculature: Veins Veins run parallel with arteries Drain into hepatic portal vein or superior mesenteric vein § Left gastric vein à Hepatic Portal Vein § Right gastric à Hepatic Portal Vein § Left gastro-omental vein à Superior Mesenteric Vein § Right gastro-omental à Superior Mesenteric Vein Moore et al et. al., Moore’s Clinically Oriented Anatomy (7th ed). Fig 2.41, p. 237 Stomach - Innervation Parasympathetic Supply: § Anterior and posterior vagal trunks from vagus nerve Sympathetic Supply: § From T5-T9 segments of sympathetic trunk § Passes to celiac plexus via greater splanchnic nerve Moore et al et. al., Moore’s Clinically Oriented Anatomy (7th ed). Fig 2.35, p. 231 Stomach - Innervation Parasympathetic Supply: § Anterior and posterior vagal trunks from vagus nerve Sympathetic Supply: § From T5-T9 segments of sympathetic trunk § Passes to celiac plexus via greater splanchnic nerve Moore et al et. al., Moore’s Clinically Oriented Anatomy (7th ed). Fig 2.35, p. 231 Stomach - Histology Mucosa § Epithelium § Lamina propria Loose CT, smooth muscle, lymphoid cells § Muscularis mucosae Arranged in 3 layers: inner circular, outer longitudinal and outermost circular Anatomy and Physiology (Betts et al). Figure 23.16 Stomach - Histology Epithelium and lamina propria are arranged into glands § Glands have three regions: Pit Neck (Isthmus) Base § Different cells types are found in different regions of the glands § Different regions of the stomach have different glands Neck Base Anatomy and Physiology (Betts et al). Figure 23.16 Stomach - Histology Cells types: § Surface epithelium and gastric pits: Surface mucus cells: § Simple columnar epithelium lining surface of stomach and gastric pits Lots of mucin granules in apical surface Mucin is a large glycoprotein Short microvilli Medical Physiology (Boron and Boulpaepl). 3rd ed. Figure 42.1 Stomach - Histology Cells types: § Neck/Ismuth Mucus neck cells Simple columnar epithelium found within neck of gastric glands usually interspersed between parietal cells Shorter and contain less mucin granules in apical surface Medical Physiology (Boron and Boulpaepl). 3rd ed. Figure 42.1 Stomach - Histology Cells types: § Neck & base Parietal cells (Oxyntic) § Found mainly in upper half of gastric gland § Rounded/ pyramidal shape § Tubuloversicular structures Medical Physiology (Boron and Boulpaepl). 3rd ed. Figure 42.1 in apical region Re-arrange to form lumen canaliculi when active § Function: produce HCl and IF Medical Physiology (Boron and Boulpaepl). 3rd ed. Figure 42.3 Stomach - Histology Cells types: § Base Chief cells (aka zymogenic) § Found in lower regions of gastric glands § Abundant RER for synthesizing proteins § Contain granules containing pepsinogen § Function Pepsinogen secretion Medical Physiology (Boron and Boulpaepl). 3rd ed. Figure 42.1 Stomach - Histology Cells types: § Glands Enteroendocrine cells § Found deep within gastric pits § Types Enterochromaffin-like cells Secrete histamine G-cells Secreted gastrin D cells Secrete somatostatin Medical Physiology (Boron and Boulpaepl). 3rd ed. Figure 42.1 Stomach - Histology Submucosa § Dense, irregular collagenous CT § Rich vascular and lymphatic network draining lamina propria Anatomy and Physiology (Betts et al). Figure 23.16 Anatomy and Physiology (Betts et al). Figure 23.15 Stomach - Histology Muscularis externa § 3 layers Inner oblique Middle circular Outermost longitudinal Serosa Anatomy and Physiology (Betts et al). Figure 23.16 Stomach Physiology - Motility There are 4 different stages: § 1. Food entry into stomach § 2. Storage in Fundus § 3. Mixing (aka churning) § 4. Emptying into small intestine Stomach Physiology – Motility - 1 1. Food entry into stomach § Lower esophageal sphincter Function § Controls movement of food into the stomach § Also prevent reflux of gastric contents into the esophagus Resting tone is maintained via intrinsic myogenic properties of sphincter muscles & cholinergic regulation § Relaxation is required to facilitate entry of food into the stomach Stomach Physiology – Motility - 1 1. Food entry into stomach § To allow food to enter the stomach a wave of relaxation moves along esophagus, lower esophageal sphincter, and into stomach and small intestine Initiated by a vasovagal reflex called receptive relaxation § Triggers by swallowing and esophageal distension § Then, a wave of peristalsis from esophagus approaches stomach and pushes food into the stomach Stomach Physiology – Motility - 2 2. Storage in fundus § Food can be stored in the fundus until it is ready to be processed. § Presence of food stretches the stomach walls Reduces the tone in muscular wall of body of the stomach (aka active dilation) § This is known as gastric accommodation § Stomach wall bulges progressively outward to accommodate larger and larger quantities of food FYI - Completely relaxed stomach can hold ~0.8-1.5L Stomach Physiology – Motility - 3 3. Mixing (aka churning) § Presence of food triggers mixing waves Initiated by gastric pacemakers § Waves start in mid- to upper portion and move toward pyloric antrum This is called propulsion § Magnitude of contraction increases on approach to pyloric antrum Contractions in pyloric antrum “grinds” the food bolus § Aka Grinding § Contents are forced into pylorus under high pressure Pylorus opening is very small (few milliliters) so antral contents are pushed back upstream toward body of stomach This is called retropulsion Medical Physiology (Boron and Boulpaepl). 3rd ed. Figure 42.15 Stomach Physiology – Motility - 3 3. Mixing (aka churning) § Only liquid can leave the stomach through the pyloric sphincter If particles are > 2mm in size, mixing continues § Eventually anything remaining in the stomach will eventually be emptied into the duodenum by the migrating motor complex Occurs during the inter-digestive period ~2 hours after eating Stomach Physiology - Motility 4. Gastric emptying § Movement of liquid chyme from the stomach into the small intestine § The rate of gastric emptying is governed signals from the stomach and duodenum This ensures pH inside the duodenum therefore does not become too acidic § Why is this important? Ensure travel time is slow enough for nutrient absorption Physiology – Secretions: Gastric Acid Gastric acid § Released from _______ cells § pH of 1-2 § Composed of: Hydrochloric acid Large amounts of KCl & small amounts of NaCl Small amounts of NaCl § Functions Digestion of _______ § How does it contribute? Bacteriostatic Needed for conversion of pepsinogen to pepsin Physiology – Secretions: Gastric Acid Gastric acid – secretion mechanism § Water dissociates into H+ and OH- in cell cytoplasm § CO2 combines with OHto form bicarbonate ions Enzyme? § H+ is pumped into lumen of canaliculus H+ / K+ ATPase § Cl- transported passively from cytoplasm of parietal cell into lumen of canaliculus Guyton and Hall Textbook of Medical Physiology (Hall). 13th ed. Figure 65-5, page 822 Physiology – Secretions: Gastric Acid Gastric acid – secretion mechanism § H+/K+ ATPase is blocked by the class of drugs called “proton pump inhibitors” Guyton and Hall Textbook of Medical Physiology (Hall). 13th ed. Figure 65-5, page 822 Physiology – Secretions: Gastric Acid Parietal cells can be stimulated by several sources: § Acetylcholine acting on Muscarinic receptors Parasympathetic stimulation § Gastrin acting on CCK2 receptors § Histamine acting on H2 receptors What cell secretes gastrin? Medical Physiology (Boron and Boulpaepl). 3rd ed. Figure 42.5 Physiology – Secretions: Histamine Histamine § Histamine is stored and released from enterochromaffin-like cells (ECL) of the stomach Type of enteroendocrine cell § Function: Histamine acts on _______ receptors on ________ cells Stimulates release of gastric acid Stimulates vasodilation Physiology – Secretions: Gastric Acid Parietal cells can be stimulated by several sources: § Another commonly used class of drug in GERD are “H2 receptor antagonists”, they work by blocking the H2 receptor Medical Physiology (Boron and Boulpaepl). 3rd ed. Figure 42.5 Physiology – Secretions: Gastrin Gastrin § Secreted by _______ cells Type of enteroendocrine cell § Secreted in response to: Stomach distension Vagal stimulation Presence of partially digestion proteins (peptides and amino acids) § Function: Acts on ECL cells to stimulate release of histamine § What does histamine do? Directly stimulates parietal cells by binding to _____ receptor Physiology – Secretions: Gastric Acid Parietal cells can be inhibited by: § Somatostatin § Prostaglandins FYI - The drug misoprostol used in GERD acts on the prostaglandin receptor § Prostaglandin analogue Medical Physiology (Boron and Boulpaepl). 3rd ed. Figure 42.6 Physiology – Secretions: somatostatin Somatostatin aka growth hormone inhibiting hormone (GHIH) § Released from D cells in the stomach and intestine (also delta cells in the pancreas) § Function Acts on parietal cells to reduce secretion of gastric acid Also reduce release of gastrin, secretin, and histamine Suppresses released of pancreatic hormones § Secreted in response to: Luminal H+ § What kind of feedback is this? Stomach Physiology – Secretions: Gastric acid Gastric acid secretion is substantially higher after meals and low between meals Phases of gastric acid secretion after meals can be divided into three phases: § Cephalic § Gastric § Intestinal Secretions: Gastric acid – putting it all together Phases of gastric acid secretion after meals can be divided into three phases: § Cephalic Triggered by smell, sight, taste, thought and swallowing food Primarily mediated by the vagus nerve § Vagus nerve releases Ach Ach acts directly on ______ cells to release H+ Ach acts on ______ cells to release histamine Ach acts on D cells, inhibiting release of ______ § Vagus nerve releases GRP to induce _____ release from G cells Accounts for 30% of total acid secretion Secretions: Gastric acid – putting it all together Phases of gastric acid secretion after meals can be divided into three phases: § Gastric Food enters the stomach, distending the gastric mucosa and activating: § Vagovagal reflex & local ENS reflex Initiates same 4 mechanisms of gastric acid secretion seen in the cephalic phase Partially digested proteins stimulate G cells to produce ______. § FYI – carbohydrates nor lipids participate in gastric acid secretion, but components of wine, beer, and coffee can promote gastric acid secretion by stimulating G cells Negative feedback § Low luminal pH stimulates D cells to secrete ________, which inhibits gastrin production Accounts of 50-60% of gastric acid secretion Medical Physiology (Boron and Boulpaepl). 3rd ed. Figure 42.10 Secretions: Gastric acid – putting it all together Phases of gastric acid secretion after meals can be divided into three phases: § Intestinal Presence of amino acids and partially digested peptides in proximal intestine § Stimulates G cells in duodenum to secrete gastrin Accounts for 5-10% of total gastric acid secretion Physiology - Secretions: Intrinsic Factor Intrinsic Factor § Glycoprotein § Also secreted by parietal cells § Function Required for the absorption of vitamin B12 in the ileum § Details covered in B vitamin biochemistry in year 2 Physiology - Secretions: Intrinsic Factor Pepsinogen § Secreted from Chief cells via exocytosis Pepsinogen is spontaneously cleaved to active pepsin in the presence of HCl Pepsin function § _______ digestion How does it contribute? § Function of pepsin is dependent on low pH (optimal 1.83.5) § Secretion is stimulated by: Ach release from vagus nerve or ENS § Ach bind to M receptors on chief cells § *Most important stimulus Presence of acid in the duodenum triggers secretin from S cells § Secretin also stimulates chief cells to release more pepsinogen Protecting the gastric mucosa How is the stomach able to withstand the low pH and high pepsin levels? § Gastric diffusion barrier – maintained by: Mucus gel layer on surface epithelium Bicarbonate microclimate adjacent to surface epithelial Tight junctions in gastric glands Protecting the gastric mucosa How is the stomach able to withstand the low pH and high pepsin levels? § Gastric diffusion barrier – maintained by: Mucus gel layer on surface epithelium § Gastric mucin is secreted by which cell types? § Mucus combines with phospholipids, electrolytes, and water to form a gel layer Protects against: acid, pepsin, bile acid, & ethanol Also lubricates gastric mucosa to minimize abrasions from food § Mucin secretion is induced by: Vagal stimulation Chemical irritation Medical Physiology (Boron and Boulpaepl). 3rd ed. Figure 42.13 Protecting the gastric mucosa How is the stomach able to withstand the low pH and high pepsin levels? § Gastric diffusion barrier – maintained by: Bicarbonate microclimate § Surface epithelial cells secrete HCO3-, which remains trapped into the mucus gel layer § HCO3- can neutralize most acid that diffuses through the mucosal layer and inactivate any pepsin that penetrates the mucus § HCO3- secretion is induced by: Vagal stimulation PGE2 Intraluminal pH Medical Physiology (Boron and Boulpaepl). 3rd ed. Figure 42.13 Gastric pathologies We will discuss two main pathologies: § Gastritis Acute & chronic § Peptic ulcer disease § Gastric neoplasms will be covered later in the term with other GI neoplasms Gastric pathologies - definitions Gastritis – inflammation of stomach mucosa Gastric erosion § Damage is limited to the gastric mucosa (ie. does not penetrate beyond the lamina propria) Peptic Ulcer § Damage extends beyond lamina propria Gastric Atrophy § Loss of gastric glandular cells Acute Gastritis - Intro Gastric mucosal inflammation caused by an imbalance between protective factors and secretion of acid and pepsin § Ranges in severity - can be asymptomatic and discovered incidentally or can cause catastrophic blood loss, anemia, or peritonitis Etiology: § NSAID toxicity, alcohol, bile, shock/sepsis, intracranial lesions, H. pylori H. pylori more closely linked to chronic gastritis Acute Gastritis – Etiology & pathogenesis NSAIDs § Inhibit prostaglandins Review - What was the effect of prostaglandins on gastric acid secretion and the gastric diffusion barrier? Effect is most significant for nonselective inhibitors (aspirin, ibuprofen, and naproxen) it can also occur with selective COX-1 inhibitors (celecoxib) Alcohol consumption § Causes direct cellular damage Intracranial lesions § Thought to stimulate the parasympathetic nervous system Acute gastritis - pathophysiology Notes Kumar et. al., Robbins and Cotran Pathologic Basis of Disease 9th ed. Fig 17.12, p. 765 Acute gastritis - pathology Initially mild inflammation § Lamina propria shows moderate edema and slight vascular congestion § Surface epithelium intact with scattered neutrophils Progression to active inflammation § Lots of neutrophils found above the basement membrane, in direct contact with epithelial cells In severe cases, mucosal damage progressed to erosions and bleeding with pronounced neutrophilic infiltrate & fibrincontaining purulent exudate can be found in stomach lumen § Erosion = loss of superficial epithelium (damage does not penetrate beyond ________) § Bleeding may occur § Erosion + bleeding = acute erosive hemorrhagic gastritis Acute gastritis – Clinical features Clinical features § May be asymptomatic but often includes: Dyspepsia Nausea, vomiting, loss of appetite, belching, and bloating Acute abdominal pain Complications § Perforation leading to peritonitis – medical emergency § Bleeding § Chronic gastritis Chronic gastritis One of the most common GI disorders Etiology: § Most common: H. pylori Gram negative motile curved rod that lives in the mucous layer Most commonly infected site is stomach antrum § Can progress to gastric body or fundus Common § Prevalence of Canadian population is 20-30% § Other causes: pernicious anemia, Crohn’s disease, radiation toxicity, amyloidosis Retrieved from: https://upload.wikimedia.org/wikipe dia/commons/d/d6/EMpylori.jpg Chronic gastritis Types: § Non-atrophic Inflammation without loss of gastric glandular cells Caused by H.pylori § Atrophic Loss of gastric glandular cells Replaced by intestinal epithelium, pyloric-type glands, fibrous tissue Change of one differentiated cell type to another is called _____? § Associated with development of gastric carcinoma § Caused by H. pylori and autoimmunity § FYI - Other (uncommon) Eosinophilic Lymphocytic Granulomatous Chronic H. pylori gastritis – pathogenesis Pathogenic mechanisms are poorly understood: § Virulence factors allow for survival of bacteria in the stomach Flagella allow them to be motile within viscous mucus Produce ammonia via an enzyme called urease, § Also toxic to epithelial cells Produce adhesins that allow bacterial to adhere to surface epithelial cells Release toxins that may be linked to development of malignancy § Elicit a robust inflammatory response – intraepithelial neutrophils, plasma cells, lymphocytes § Bacteria seem to cause reduced mucous and bicarbonate secretion Kumar et. al., Robbins and Cotran Pathologic Basis of Disease 9th ed. Fig 17.13, p. 768 Chronic H. pylori gastritis – pathogenesis H. pylori infections most often occur predominantly in the stomach antrum § Increase local gastric production and increased acid secretion is seen § This leads to a greater risk of PUD Long-standing H. pylori can progress to involve gastric body and fundus § Associated with gastric atrophy Moore et al et. al., Moore’s Clinically Oriented Anatomy (7th ed). Fig 2.37, p. 233 Chronic H. pylori gastritis – pathology Pathology: § Erythematous antral mucosa with large amounts of plasma cells and increased levels of lymphocytes, macrophages, and neutrophils in the lamina propria § Neutrophils can infiltrate the basement membrane and accumulate in lumen of gastric glands to form pit accesses. § With progression, gastric epithelium can become atrophic Atrophic gastric is associated with what? § Increases the risk of gastric adenocarcinoma § Overgrowth of MALT associated with H. pylori may also be associated with gastric lymphoma Chronic H. pylori gastritis – Clinical features & diagnosis Clinical features § May be asymptomatic but can cause: Epigastric pain Nausea, vomiting, anorexia, early satiety Weight loss Diagnosis includes: § Presence of antibodies to H. pylori in serum § Fecal bacteria detection § Urea breath test Chronic H. pylori gastritis – Treatment and complications Complications: § PUD § Gastric adenocarcinoma § MALT lymphoma Treatment: § Triple therapy: two antibiotics + PPI § Eradication of bacteria tends to cure the disease Comparison of acute & chronic gastritis Acute gastritis Chronic gastritis Inflammation of gastric mucosa with presence of lots of neutrophils among epithelial cells, glands, and within the stomach lumen in advanced cases. (minimal lymphocytes and plasma cells) Erythematous mucosa with plasma cells, lymphocytes, macrophages, and neutrophils in lamina propria. Neutrophils can infiltrate the basement membrane to form pit abbesses. Can progress to erosion and bleeding Can progress to atrophy of gastric epithelium and promote overgrowth of MALT Symptoms: Symptoms: Complications: Complications: Peptic ulcer disease Major complication of chronic gastritis Two main types: § Duodenal 4x more common Lower likelihood of perforation and malignancy § Gastric 4% are malignant, higher likelihood of perforation Tend to occur in the antrum, along the lesser curvature Etiology § H. pylori infection, NSAIDs, or cigarette smoking Most common- induce by H. pylori infection Peptic ulcer disease - pathogenesis Pathogenesis § Ultimately occurs due to imbalance between defense mechanisms and damaging factors causing chronic gastritis. Typically develops as a result of chronic gastritis § Duodenal ulcers & antral gastric ulcers Not well understood, linked to H. pylori despite H. pylori not colonizing duodenum Colonization may be linked to: § Decreased bicarbonate secretion in the duodenum § Increased gastric acid secretion in the stomach § Gastric ulcers in fundus or body Caused by mucosal atrophy Slightly higher acid secretion and greatly decreased production of mucin and other protective factors Peptic ulcer disease - Pathology Pathology: § Round to oval shaped, sharply punched-out defect § Mucosal margin usually level with surrounding mucosa but may overhand the base Base is usually smooth & clean with granulation tissue below and fibrous/collagenous scar § Larger vessels within scarred area can thickened and thrombosed Retrieved from: https://commons.wikimedia.org/wiki/File:Ga stric_Ulcer_Antrum.jpg Peptic ulcer disease – Clinical features Clinical Features: § Vague, though sometimes intense, pain with a variable relationship with meals More intense pain can be associated with perforation, bleeding, and peritonitis Duodenal ulcers § Are relieved by food, worsened 2-3 hours after eating § Duodenal ulcers commonly awaken a patient at night Gastric ulcers § Poorly relieved by eating – pain re-occurs shortly after a meal § Weight loss is common § Can also present with iron-deficiency anemia, bleeding, nausea/vomiting, bloating, belching Peptic ulcer disease - treatment and prognosis Treatment: § Withdraw offending agent § Eradicate H. pylori infection Complications § Perforation leading to peritonitis – medical emergency § Bleeding § Gastric adenocarcinoma & MALT lymphoma References Moore et al. Moore’s Clinically Oriented Anatomy (7th ed). Kumar et. al., Robbins and Cotran. Pathologic Basis of Disease (9th ed). Boron and Boulpeap. Medical Physiology (3rd ed). Guyton and Hall. Textbook of Medical Physiology (13th ed). Betts et al. Anatomy and Physiology. OpenStax Images: § https://commons.wikimedia.org/wiki/File:Gastric_Ulcer_Antrum.jp g § https://upload.wikimedia.org/wikipedia/commons/d/d6/EMpylori.j pg