GastroIntestinal Transport of Electrolyes and Water
PHY423 Dr. Linda N. Peterson Linda.peterson@ubc.ca Remember to view notes page
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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
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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)
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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
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Intake and Output
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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
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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
• •
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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
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• •
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Gastric Secretions
Fundus
Body
• Gastric Pits/Glands
•
are located in fundus and body Pyloric Glands are located in the Antrum
Antrum
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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
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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
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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
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D cells Somatostatin Paracrine and endocrine
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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
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Histamine
ECL cell
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G-cell
ECL
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Histamine, Ach and Gastrin
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PPIs block final common pathway of HCl Secretion
ECL
CCK/B
Proton Pump
Inhibitor
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Read note- check all slides
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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
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Pancreatic Secretions
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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
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Pancreatic Secretions
• CFTR
RequiredCystic Fibrosis Leads to Pancreatic Destruction
pH pH
CFTR= Cystic Fibrosis Transmembrane conductance Regulator April 5, 2008 31
Pancreatic Enzymes Are Packaged for Secretion
• Acinar Cell
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What Stimulates Pancreatic Secretion During the Intestinal Phase?
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Biliary Secretions Enter Via Bile Duct-
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Small Intestine
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Secretion and Reabsorption Occur in Different Cells
• Villous Cells reabsorb
predominantly
– Some pathogens/toxins seem to target villous cells more
• Crypt Cells secrete
predominantly
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NaCl +/- nutrients
Na Na Cl Cl
Na-Nutrient Reabsorption-note Cl is Reabsorbed Too
Lumen
Read Note
Blood Side
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TEPD becomes Negative due to
K
2 SGLUT1 GLUT2
No Na binding site
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NaCl +glucose are transported 44 water follows
Na Glucose Reabsorption
Read note
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Kellett and Laroche, Diabetes 54:3056, 2005
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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.
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NaCl Secretion Normally Supports Nutrient Reabsorption
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NaCl is transported
Na enters into cell but is pumped back out
Water follows
Na gets to the other side this way
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Role of CFTR In Intestinal NaCl Secretion in Crypt Cells
Lumen
Blood Side
Cholera Toxin Stimulation of Intestinal NaCl Secretion
Lumen
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Fig. 10.
Kunzelmann, K. et al. Physiol. Rev. 82: 245-289 2002
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Copyright ©2002 American Physiological Society
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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.
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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
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WHO Oral Rehydration Solution Concentrations mmol/l
Molecule Glucose Na K Cl HCO3
ORS
111
90
20
80
30
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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
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Colon
• Usually
reabsorbs Chloride in exchange for bicarbonate • Rich in K • Fluid is alkaline
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Colon – Na reabsorption and K Secretion
K+
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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
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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)
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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
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Differentiating The Type/Cause of Diarrhea
OSMOTIC SECRETORY
Lactose Intolerance
Magnesium containing antacids Sorbitol
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Vibrio cholerae toxin
Other enterotoxins Hormones – VIPoma, gastrinoma, carcinoid tumour Bile Salt Malabsorption
VIP = Vasoactive Intestinal Peptide
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