GastroIntestinal Transport of Electrolyes and Water

GastroIntestinal Transport of Electrolyes and Water PHY423 Dr. Linda N. Peterson Linda.peterson@ubc.ca Remember to view notes page March 31, 2008 1 Objectives • See detailed objectives provided for this topic • Read the objectives first before reviewing the slides and notes • Work on the objectives as you view the presentation March 31, 2008 2 GI function is not constant throughout the day • Activity is related to food intake and thinking about food intake plus+ other • Three phases have classically been described – Cephalic Phase(thinking about food-hunger) – Gastric Phase (food is in the stomach) – Intestinal Phase (gastric contents have entered the intestinal tract) March 31, 2008 3 Intake and Output • • • • • • • Diet Saliva Gastric Pancreas Bile Intestine Output 1.5 1.5 2.5 1.5 0.5 1.0 0.1 L L L L L L L March 31, 2008 4 Intake and Output March 31, 2008 5 Fluid Balance • Normally the volume moving from blood to lumen (secreted) is less than the volume moving from lumen to blood (reabsorbed) i.e state of net absorption • This can be reversed if there is inhibition of reabsorption or stimulation of secretion and can lead to serious Effective Circulating Volume Depletion March 31, 2008 6 Salivary Secretion • Impressive rates of secretion per gram of tissue • The solution produced by the parotid gland is serous (watery), hypotonic, alkaline and contains an amylase and a lipase enzyme. The sublingual produces mucin which becomes a mucous secretion. The submandibular gland produces a mixture of both types of fluids. Very important for swallowing Contains secretory IgA • • March 31, 2008 7 Decreased Salivary Secretion • Absence of saliva (xerostomia - dry mouth) occurs in few conditions (Sjogren's disease, systemic amyloidosis and following radiation to head and neck) Patients will complain of dysphagia, of being unable to taste their food, and being more prone to dental caries and heartburn Reduced salivary production with anti-cholinergic medications 8 • • March 31, 2008 Gastric Secretions Fundus Body • Gastric Pits/Glands • are located in fundus and body Pyloric Glands are located in the Antrum Antrum March 31, 2008 9 Gastric Glands Gastric Pit • Parietal Cells secrete • HCl and Intrinsic Factor*** Peptic Cells-aka Chief cells secrete Pepsinogen *** = only indispensable substance secreted by the stomach March 31, 2008 10 Gastric Glands • Mucus + HCO3- afford protection for the glands the surface of the stomach • Histamine secreting cells are adjacent to the parietal cells in the gastric pits ECLenterochromaffin-like cells March 31, 2008 11 Parietal Cell HCl Secretion Venous Blood NaHCO3 + H2 O C.A. HCl NaCl NaCl Arterial Blood SEE NOTE Mechanism of HCl Secretion Stomach HCl K+ H+ ClHCO3ClNaCl Lumen K+ Blood NaHCO3 SEE NOTE Mechanism of HCl Secretion Stomach HCl Lumen K+ H+ ClHCO3ClNaCl Blood NaHCO3 Gastric Secretions Fundus Body • Pyloric Glands are • • located in the Antrum G cells secrete Gastrin D cells secrete somatostatin Antrum March 31, 2008 19 D cells Somatostatin Paracrine and endocrine March 31, 2008 20 How is HCl Secretion Controlled? These control stimulation- remember neutralization and inhibition.. • Ach -Neurocrine- Neurotransmitter • Gastrin-Endocrine- Circulating Hormone • Histamine-Paracrine-acts locally ECL Cells- Enterochromaffin-like Cells near the Parietal Cells March 31, 2008 21 Histamine ECL cell March 31, 2008 23 G-cell ECL March 31, 2008 Histamine, Ach and Gastrin 24 PPIs block final common pathway of HCl Secretion ECL CCK/B Proton Pump Inhibitor March 31, 2008 Read note- check all slides 26 Condition Normal Gastric Ulcer Pernicious Anemia Duodenal Ulcer Zollinger-Ellison Syndrome Gastrinoma-usually from pancreas Basal rate mEq/hr 1-5 0-3 0 2-10 10-30 Stimulated mEq/hr 6-40 1-20 0-10 15-60 30-80 What Inhibits HCl Secretion? FYI only • Somatostatin released by Gastric D cells is the central inhibitory mechanism on acid production. – SS acts both by paracrine and endocrine mechanisms. – Directly inhibits parietal cell acid production, inhibits ECL histamine release, and inhibits release of gastrin from G cells. – SS release is stimulated by Gastrin and neural inputs in D cells in the fundus, and by low pH in D cells in the antrum • Secretin from duodenal S cells plays the main role in inhibiting acid secretion after the entry of fat and acid into the duodenum • Cholecystokinin CCK, GIP and VIP can all inhibit acid secretion but are less important than secretin. Also background levels of PGE2 inhibit parietal cells and contribute to the control of acid production. • Demonstrates the redundancy that is built into the system to regulate acid secretion March 31, 2008 28 Pancreatic Secretions March 31, 2008 29 Pancreatic Secretions • Highest rates of protein synthesis and secretion of any organ in the body! • Bicarbonate rich- pH close to 8.0 • Mechanism of NaHCO3 secretion is similar for intestinal cells March 31, 2008 30 Pancreatic Secretions • CFTR RequiredCystic Fibrosis Leads to Pancreatic Destruction pH pH CFTR= Cystic Fibrosis Transmembrane conductance Regulator March 31, 2008 31 Pancreatic Enzymes Are Packaged for Secretion • Acinar Cell March 31, 2008 32 What Stimulates Pancreatic Secretion During the Intestinal Phase? March 31, 2008 34 Biliary Secretions Enter Via Bile Duct- March 31, 2008 35 Small Intestine March 31, 2008 36 March 31, 2008 37 Secretion and Reabsorption Occur in Different Cells • Villous Cells reabsorb predominantly – Some pathogens/toxins seem to target villous cells more • Crypt Cells secrete predominantly March 31, 2008 41 NaCl +/- nutrients Na Na Cl Cl Na-Nutrient Reabsorption-note Cl is Reabsorbed Too Lumen Read Note Blood Side 43 March 31, 2008 2 TEPD becomes Negative due to K 2 SGLUT1 GLUT2 No Na binding site March 31, 2008 NaCl +glucose are transported 44 water follows Na Glucose Reabsorption Read note March 31, 2008 Kellett and Laroche, Diabetes 54:3056, 2005 45 Na-Glucose reabsorption remains intact in Cholera and other Infectious Disease (ID) induced diarrheas There are other co-transport systems that reabsorb NaCl in the jejenum and the illeum which are not coupled to nutrient reabsorption. These transportors are inhibited by cholera toxin and other enterotoxins but the Na-glucose cotransporter is not affected by these enterotoxins. This can be used to the benefit of people suffering with ID induced diarrhea by providing oral rehydration of lost NaCl and water from the body by the addition of glucose to the solution. March 31, 2008 46 NaCl Secretion Normally Supports Nutrient Reabsorption March 31, 2008 47 NaCl is transported Na enters into cell but is pumped back out Water follows Na gets to the other side this way March 31, 2008 49 Role of CFTR In Intestinal NaCl Secretion in Crypt Cells Lumen Blood Side Cholera Toxin Stimulation of Intestinal NaCl Secretion Lumen March 31, 2008 51 Fig. 10. Kunzelmann, K. et al. Physiol. Rev. 82: 245-289 2002 March 31, 2008 Copyright ©2002 American Physiological Society 52 Question? • What do you think about the occurrence of • severe cholera toxin induced diarrhea in individuals with cystic fibrosis? Answer: CF patients do not develop cholera induced diarrhea, but carriers have same degree of severity as people without the CF gene. There may be other reasons to explain the high prevalence of the mutant gene in the population. 53 March 31, 2008 WHO Formula for ORT Oral Rehydration Therapy • UNICEF/WHO O.R.S • Sodium Chloride 3.5 grams Sodium Bicarbonate 2.5 grams Potassium Chloride 1.5 grams Glucose 20 grams • to be dissolved in one litre of clean drinking water March 31, 2008 54 WHO Oral Rehydration Solution Concentrations mmol/l Molecule Glucose Na K Cl HCO3 ORS 111 90 20 80 30 March 31, 2008 55 http://www.aafp.org/afp/20030301/979.html Colon • Receives less than 1 Liter/day • Reabsorbs Na and Secretes K • Aldosteronesensitive • Fluid is nearly Isotonic March 31, 2008 58 Colon • Usually reabsorbs Chloride in exchange for bicarbonate • Rich in K • Fluid is alkaline March 31, 2008 59 Colon – Na reabsorption and K Secretion K+ March 31, 2008 60 K Secretion Increases With Increasing Colon Flow Rate • The greater the rate of fluid delivery to the colon • • the greater the amount of K secreted- just as we saw in the CCD in the kidney! Large K deficits can develop with severe diarrhea Since the fluid loss is also rich in bicarbonate, K deficiency and (hypokalemic- see slide note) metabolic acidosis develops March 31, 2008 61 Diarrhea • Malabsorption in the Small Intestine or Increased Secretion can easily overwhelm the capacity of the Colon to reabsorb the electrolytes and water (maximum reabsorption is 4-5 Liters/day) March 31, 2008 62 Osmotic vs Secretory Diarrhea • It is important to determine the cause of a chronic diarrhea to chose the right treatment • In general: • Fasting in patients with Osmotic Diarrhea will reduce severity • Fasting in patients with Secretory Diarrhea will not reduce severity March 31, 2008 64 Differentiating The Type/Cause of Diarrhea OSMOTIC SECRETORY Lactose Intolerance Magnesium containing antacids Sorbitol March 31, 2008 Vibrio cholerae toxin Other enterotoxins Hormones – VIPoma, gastrinoma, carcinoid tumour Bile Salt Malabsorption VIP = Vasoactive Intestinal Peptide 65