PMP-201 Module: Human Biology and GI System Disorders

Human Biology and GI System Disorders

PMP-201 Module Overview

PMP-201 Module Human Biology Disorders of the GI system Dr Melanie Healy m.a.healy@swansea.ac.uk Swansea University - Prifysgol Abertawe Medical School ysgol FeddygaethPatient Centred Integration PMP201 Human Biology Clinical Pharmacy J Cellular & Molecular Bioscience Pharmacy Practice ? Pharmacology & Therapeutics Pharmaceutics Pharmaceutical Chemistry Integration within PMP-201 Module Come together in ICSGI conditions (of concern here) 20

Common GI Conditions

PMP201 · Heartburn is a burning feeling in the chest caused by stomach acid travelling up towards the throat (acid reflux). If it keeps happening, it's called gastro- oesophageal reflux disease (GORD). · Dyspepsia/Indigestion · Gastritis is when the lining of your stomach becomes irritated (inflamed). It can cause pain, indigestion and feeling sick. · Nausea and Vomiting · Peptic Ulcer Disease · Constipation and Defecation Problems · Diarrhoea . Gastroparesis chronic condition where the stomach cannot empty in the normal way. Food passes through the stomach slower than usual. It's thought to be the result of a problem with the nerves and muscles that control how the stomach empties.RECAP

Alimentary Canal and Food Processing

1. The layout: . Alimentary Canal: Mouth to anus · Accessory organs - liver/pancreas
2. The 6-stages of dealing with food:
   1. Ingestion
   2. Mechanical Breakdown
   3. Propulsion
   4. Digestion
   5. Absorption
   6. Defecation
3. All parts of the alimentary canal have 4 layers:

PMP201 · Mucosa (epithelium, lamina propria, muscularis mucosa) · Submucosa · Muscularis Externis · Serosa

Nerves of the Digestive System

1. Nerves of the digestive system: · Short axis (submucosal plexus) & myenteric plexus · Long axis (From the brain) - ParasympatheticRECAP

Saliva and Swallowing

1. Saliva can be secreted by intrinsic or extrinsic glands
2. Saliva is made of: · Amylase · Mucin · Water · Protective elements (Defensin, IgA, Lysozyme)
3. Stages of swallowing

PMP201 · Buccal phase · Pharyngo-oesophageal phase (blocking off nasopharynx) · Pharyngo-oesophageal phase (blocking off trachea) · Peristalsis · Sphincter opening

Stomach Cell Types

1. Types of cell in stomach · Mucus cells · Parietal cells · Chief cells · Enteroendocrine cellsRECAP

Regulation of Gastric Secretion and Vitamin Absorption

1. Regulation of gastric secretion
   1. Cephalic
   2. Gastric
   3. Intestinal

1. Food is broken down into small particles in the mouth by chewing Salivary glands 2. Digestion of food in the stomach releases vitamins. 4. The Pancreas releases digestive enzymes that help to release vitamins from food. Stomach Liver 3. The gallbladder releases bile, which emulsifies fat and helps in the absorption of fat-soluble vitamins Small Intestine Gallbladder 7. In the large intestine, your gut bacteria synthesize a small amount of vitamins, some of which are absorbed. Large Intestine 6. Water-soluble vitamins are absorbed into the mucosal cells dependent on energy-requiring transport or binding of other molecules. These vitamins then directly enter the blood. Micelles Bile acids Lumen of the Small Intestine Digested lipids and fat-soluble vitamins 5. Fat-soluble vitamins are integrated into micelles and absorbed by simple diffusion. Inside mucosal cells, they are packaged into chylomicrons and enter the lymphatic system. Water-soluble vitamins Fat-soluble vitamins Fatty Acid Microvilli Mucosal Cell Chylomicron Lymph vessel Blood vessel Pancreas

Stomach Wall Structure and Acid Regulation

Parietal cell Surface epithelium PMP201 Gastric pit Mucosa Gastric gland Lamina propria Chief cell Muscularis mucosae Submucosa Oblique layer Circular layer Muscularis externa Enteroendocrine cell Longitudinal layer Serosa The H+/K+ proton pump regulates acid secretion This Photo by Unknown Author is licensed under CC BY

Digestion: Squeeze, Churn, Mix

Digestion: Squeeze, Churn, Mix Gastric pits Epithelium: Simple columnar epithelium (goblet cells- thick alkaline mucus to protect cells.) Gastric pit 1 Surface epithelium Mucous nelk cells Gastn\gland- Pari al cell Gastric glands Chief cell Enteroendocrine (b) cell Thin acid Mucous producing cells Pepsinogen Pepsin HCI - Gastric gland secretes gastric juice Mitochondria in parietal cell Parietal cell Chief cell Enteroendocrine cell (c)

Gastric Glands and Secretions

Gastric pits of to Gastric pit Surface epithelium PMP201 Mucous neck cells Parietal cell Gastric gland Gastric glands Chief cell Enteroendocrine (b) cell Pepsin HCI Mitochondria in parietal cell Parietal cell Chief cell Enteroendocrine cell (c) Gastric glands secrete gastric juices · Mucous neck cells: in the duct portion · Parietal cells: mid portion secrete HCl & intrinsic factor for B12 absorption

Gastric Gland Cell Functions

Gastric glands secrete gastric juices · Mucous neck cells: in the duct portion · Parietal cells: mid portion of glands secrete HCI & intrinsic factor . Chief cells: base of gland; secretes pepsinogen a precursor molecule to pepsin (an enzyme that digests protein) Gastric pits of Lo to Gastric pit 1 Surface epithelium - Mucous neck cells Gastric gland Parietal cell Gastric glands Chief cell (b) Enteroendocrine cell Pepsinogen Pepsin 1 HCI Mitochondria in parietal cell Parietal cell Chief cell Enteroendocrine cell (c) PMP201 Enteroendocrine cells: secrete multiple hormonal products; · Gastrin (G cells) PYLORIC ATRUM, histamine, endorphins, serotonin, cholecystokinin, & somatostatin, which influence several digestive system organs

Therapeutic Targets in the Gut

https://theromefoundation.org/wp-content/uploads/pharmacologic- pharmacokinetic-and-pharmacogenomic-aspects-of-functional- 1324 Camilleri et al Gastroenterology Vol. 150, No. 6 Therapeutic Targets - Visceral sensitivity Smooth muscle Enteric neurons Motility Secretion Immune activation Barrier function Enterocytes Enterochromaffin cell Goblet cells Mast cell -> Microbiome Figure 3. Potential local therapeutic targets for drug action in the gut include visceral sensitivity, microbiome, motility, secretion, immune activa- tion, and barrier function. of rPMP-201 Module Human Biology

Antacids, H2 Antagonists & Proton Pump Inhibitors

Dr Melanie Healy m.a.healy@swansea.ac.uk Swansea University - Prifysgol Abertawe Medical School ysgol Feddygaeth

Stomach Acid Function

Why do we have stomach acid? r PMP201 Parietal cell Surface epithelium Gastric pit Mucosa - Gastric gland Lamina propria Chief cell Muscularis mucosae Submucosa Oblique layer Circular layer Muscularis externa Enteroendocrine cell Longitudinal layer Serosa This Photo by Unknown Author is licensed under CCBY

Digestive Processes in the Stomach

r PMP201 Digestive Processes (Stomach) · Acts as a holding vessel for ingested food · Participates in mechanical & chemical digestion · Propulsion: Delivers its product (chyme) to the small intestine · Protein digestion: · HCI denatures protein · HCI activates pepsinogen to pepsin · Pepsin breaks peptide bonds of proteins · Rennin: an enzyme that breaks down casein (milk protein) secreted in infants · Intrinsic factor: required for Vit. B12 absorption (needed to mature RBC) · Mucosal barrier: protects the stomach from its own secretions . Thin viscous mucus overlies a thick coating of HCO3- rich mucus · Tight junctions between epithelial cell PM of glandular cells are impermeable to HCI · Epithelium is replaced every 3-6 days

Dyspepsia Definition and Aetiology

Dyspepsia r PMP201 The British Society of Gastroenterology (BSG) defines dyspepsia as a group of symptoms that alert doctors to consider disease of the upper GI tract, and states that dyspepsia itself is not a diagnosis. 1. upper abdominal pain or discomfort, 2. heartburn, 3. gastric reflux, 4. nausea, or vomiting. The aetiology of dyspepsia symptoms includes gastric and duodenal ulcers, gastro- oesophageal reflux disease (GORD), oesophagitis, and oesophageal or gastric cancers

Acid Secretion and Alkaline Tide

In Figure 23.20. wnen parietal cells are appropriately stimu- lated, H+ is actively pumped into the stomach lumen by H+-K+ ATPases (proton pumps). As acid is pumped into the stomach base (HCO3 ) is exported into the blood. This flow of base is called the alkaline tide. Lo to PMP201 See Dr Mckeever's lecture Gastric gland Blood capillary Chief cell Stomach lumen 1 H+ and HCO3 (bicarbonate ions) are generated from the dissociation of carbonic acid (H2CO3) produced from CO2 and H2O by carbonic anhydrase. CO2 + CO2 + H2O Carbonic anhydrase H2CO3 > K+ H+-K+ ATPase 1 K+ 2 HCO3 + H+ >H+ Alkaline tide HCI HCO3 3 4 J CI CI > CI 3 | in the interstitial fluid is exchanged for intracellular HCO37. Parietal cell Interstitial fluid 4 Cl- diffuses through membrane channels into the lumen.

H+-K+ ATPase and Acid Regulation

2 H+-K+ ATPase pumps H+ into the lumen and K+ into the cell. K+ returns to the lumen through membrane channels.in Figure 23.20. wnen parietal cells are appropriatery stimu- lated, H+ is actively pumped into the stomach lumen by H+-K+ ATPases (proton pumps). As acid is pumped into the stomach base (HCO,") is exported into the blood. This flow of base i! called the alkaline tide. Gastric gland Chief cell Stomach lumen CO - CO2 + H2O Carbonic inhydrase 1.00. H *- K+ ATPase 0 K 2 HCO,- + H+ Alkaline tide HC HCO3 3 Interstitial 4 cl- diffuses through membrane channels into the lumen. Regulation of acid secretions of Lo to PMP201 Basal surface Apical surface Potassium channel (KCNQ1) Histamine H2 CAMP1 Acetylcholine M1 Ca++ +K+ Gastrin CCK IP3 Cholecystokinin K+ Somatostatin CAMPI Proton pump I H+ Prostaglandins CAMPI HCI CI Chloride channel This Photo by Unknown Author is licensed under CCBY Blood capMary H+ and HCO3- (bicarbonate ions) are generated from the dissociation of carbonic acid (H,CO2) produced from CO2 and H2O by carbionic anhydrase. 2 H+-K+ ATPase pumps H+ into the lumen and K+ into the cell. K+ returns to the lumen through membrane channels. 3 CI- in the interstitial fluid is exchanged for intracellular HCO.". Parietal cew

Pharmacological Treatments for GI Disorders

Pharmacological treatments · Antacids · Mucosal strengtheners: · Misoprostol · Reduction of acid secretion: · Proton pump inhibitors e.g. omeprazole . Histamine H2 receptor antagonists e.g. ranitidine · Muscarinc antagonists e.g. pirenzapine · H pylori eradication regimes · Dual therapy PPI and antibiotics Basal surface Apical surface Potassium channel (KCNQ1) Histamine H2 CAMP1 Acetylcholine M, Ca++ +K+ Gastrin CCK IP3 Cholecystokinin K+ Somatostatin CAMPI Proton pump D H+ Prostaglandins CAMPĮ HCI CI Chloride channel This Photo by Unknown Author is licensed under CC BY-SA V AUST A 156041 FAST . SOOTHING . LONG LASTING GAVISCON PEPPERMINT FLAVOUR NEW! ASTER TO CHE Effective Relief . Heartburn & Indigestion . D2004 GSM 12M Cooling Sensation 12HR MAXIMUM STR 24 CHEWABLE Zanta 15 MAXIMUM STRENGTH Zantac 150 antad 75 FAST RELIEF RELIEF HEARTBURN ACID INDIGESTION FAST RELIEF RTBURN NIGESTION OME 20 OME 20 BELIEVES & PREVENTS HEARTBURN A ACIO INIMGESTION Each tablet contains 250mg sodium alginate, 133.5mg sodium bicarbonate and 80mg calcium carbonate PMP201