GI function and dysfunction

From Iusmphysiology

  • started here on 02/10/11 at 11AM.


Contents

Gastric function and dysfunction

Objectives

Chewing and swallowing

  • Helps break up food.
  • Mixes food with saliva.
  • Saliva fx:
    • lubrication
    • protects oral cavity (and teeth from decay)
    • amylase (breaks down starch)

Salivary glands

  • Parotid (25%), submandibular, sublingual
  • Parotid
    • 25% of saliva
    • serous
    • low in glycoprotein
    • high in amylase
  • Submandibular
    • Two pops of cells: mucus and serous
    • Mucus secreting gives off high glycoprotein
    • 70%
  • Sublingual
    • Mixed like
    • 5%

Histo of glands

  • zymogen granules have amylase.

Salivary secretions

  • alpha-amylase
    • starts to digest starches
  • proline-rich prots
    • Protect epithelial cells and enamel
  • Mucin glycoproteins
    • impt for lubrication
  • lipase
    • digestion of fat begins
  • Lactoperoxidase, lysozyem, IgA receptors
    • Important for oral hygeine and immunology


  • Dry mouth:
    • Loss of taste and smell
    • Can be caused by meds and radiation
    • Enamel becomes week
    • Bacteria increases
    • Tooth decay
    • Sjorgen syndrome, too

Ducts

  • Isotonic granules pass water, Na, bicarb, etc.
  • Ductal cells modify the solution as it moves along
    • Na and Cl is reabsorbed.
    • The slower the solution goes, the more hypotonic it goes.
  • Parasym stimulate secretion (via ach)
  • Symp can stimulate secretion, too, via adrenergics.

Swallowing and the esophagus

  • Swallowing is initiated consciously but finished unconscioiusly.
  • Bolos reaches back of the mouth, soft palate moves to block nose, constrictors are triggered to constrict (Moves food to back of mouth), larynx muscle contrct to close airway, parystalsis triggered, pushes food down esoph.

Esophagus

  • Two sphincters: upper and lower.
    • Regulate passage of food into and out of esoph.
  • Bolus in back of throat, upper sphincter relaxes.
  • Peristalsis moves it down.
  • Then lower sphincter relaxes.

Swallowing reflex

  • Vagal reflexes cover both upper and lower, but autonomic and (the other side) have to coordinate to get skeletal and smooth muscle to work together.
  • When stuck, we can detuct.
    • Generates secondary wave of peristalsis.
    • Through short or long reflexes.
    • Long through swallowing center of the brain.

Gastroesophageal reflux disease

  • GERD
  • REflux of axis from stomach into esophagus.
  • Normally sphincter is closed tightly to stop acid reflux.
    • Impt because esophagus tissue is not protected from acid; hence burning.
  • Some foods make it work by generating more acid.
    • Chocolate, pepermint, alcohol, coffee and nicotine.
    • The help weaken the lower esophageal sphincter.
  • Tx:
    • Lifestyle changes:
      • Don't eat before bed, b/c of horizontal position.
      • Stop smoking
      • Smaller portions so stomach isn't as full
      • Loose clothes
      • Elevate bed
      • Lose weight
    • Decrease acid:
      • Malox
      • Histamine receptor blockers
      • Proton pump blockers
    • Tighten lower sphincter
      • Raglan (D2 antagonist, 5-HT agonist)
      • Laproscopic fundoplication

Esophagela achalasia

  • Lower sphincter is closed too much
  • Two causes:
    • Food isn't moved correctly so it doesn't get pushed through
    • Sphincter won't relax
      • Can be from a lack of inhibitory signal.
  • Tx:
    • Botox injection
    • Nitrates and calcium channel blockers; forcibly relax the smooth muscle layer
    • Balloon dilations, surgery

The stomach

  • Three parts: fundus, corpus (body), antrum
  • Sphincter restricts chyme from duod
  • Wall looks like rest of the tract:
    • Mucosal layer of the stomach has gastric pits.
  • Pits:
    • Special cells for fxn.
    • Stem cells
    • Mucous cells
    • Parietal cells (oxyncic) make acids and intrinsic factor
    • Chief cells make proenzymes (pepsinogen) for protein digestion
    • Endocrine cells
      • Make hormones: gastrin, somatistatin, histamine

Motility in the stomach

  • Storage is important.
    • Can get a large expanstion to 1.5 liters
  • Mixing of food with gastric joices
  • Grinding
  • Regulated expulsion
    • We try to pass just a little to the duod at a time.
  • Rate of movement through depends on what's in there:
    • Saline would exit fast
    • Then carbs
    • Then lipids
    • Diff solutions cause diff hormones, thus the difference in timing.
  • Propulsion:
    • Simply peristalsis, pushes food out to duodenum.
    • This doesn't happen much because the pylorus is closed so it goes through retropulsion which mixes it nicely.

Regulation of gastric motility

  • Excitation
    • Mostly from stomach entering stomach, causing distension.
    • Long and short reflexes activated: increase gastric distensibility.
    • Long through vagal, CNS, and back.
    • Presence of food in stomach stimulates release of hormeones from G cells: gastrin
      • Released by by stomach and pancreas (to blood), acts on stomach.
    • Thought and stress and higher order thought can affect motility.

Gastrin

  • Peptide hormnone
  • Made by duod (big gastric) and stomach (little gastrin).
  • Can be released by distension or neural stim.
  • Inhibited by somatostatin; which generally turns off motility and secretion.
  • GAstrin causes: motility, secretion, and growth of ?

Inhibition of motility

  • Mostly by inhibition from duod.
    • makes sense
  • Both hormonal:
    • Hyperosmotic / distension act on endocrine in duod mucosa to release ? which then act on stomach by endocrine pathways
  • And neuronal:
    • Sensors in the duod (chemo, osmo, mechano) detect acids /distension, trigger short and long reflexes
  • This is basically negative feedback to hinhibit overwhelming of the duod.

Gastroparesis

  • When stomach muscles don't work weell: poor motility.
  • Causes:
    • Damage to vagus
    • Damage to muscles
    • Diabetes: poor blood supply to vagus
    • Surgery can ingjur vagal
    • Rx: antidepressants can inhbiit vagal
  • Tx:
    • Lower fat in diet (slow to move through)
    • Low fiber (same)
    • Puree the food
    • Use dietary supplements (predigested)
    • Use antiemetics to control vomitting
    • Use prokinetics:
      • Metoclopramide to lower threshold for short wave activation.
    • Pacemaker

Acid secretion

  • Parietal cells when resting has vesicles.
  • When secreting the vescicles fuse and increase plasma membrane and have hydorgen pump transporters to make acid.
  • The pump moves H+ out of the cell into the lumen.
    • uses ATP hydrolysis
    • Makes very high concentration gradient.
    • Inhibited by proton pump inhibitors: nexium, prilosec, and omeprazole.
  • H+ comes from H20 which means we have Oh sitting around which is toxic.
  • CA is used to take OH and CO2 to from bicarbonate, a neutral product.
  • Bicarb is then put in the blood.
  • Net effect is that hydrogen is put in lumen and bicarb is put in the blood.
    • Causes alkaline tide (increased pH of the blood as it passes the stomach).

Acid regulation

  • Agonists to increase parietal cell production:
    • Gastrin:
      • Binds to receptors on paerieta clels
    • Ach
      • Released by muscarinic nerves that act on parietal cells
    • Histamine
      • Binds on receptors of parietal cells
  • Indirect ways:
    • ECL cells are on the wall of the stomach
    • Can be activated by gastrin or neurons to release histamine
    • Histamine then acts on parietal cells
    • Anti-histamine: pepcid, tagamet, zantec
      • Not as effective as the proton pumps b/c only blocking one agonist of the pump

REgulation of acid secretion

  • Four phases
  • Basal
    • during digestive, follows circadian
  • Cephalic:
    • Thinking about food can stimulate receptors in the head to stimulate acid secretion
  • Gastric
    • REgulated by stimuli within the stomach (mechano receptors, chemo receptors).
  • Intestinal
    • Chemo receptors of the duod and intestin detect metabolites and cause secretion in the stomach
Cephalic phase
  • Sight, thought, smell, etc.
  • Neurons act on parietal and ECL cells
    • ECL then act on parietal via hormones.
  • So this is neuronal and neurona-hormonal
  • Can also act on G cells:
    • GAstrin then acts via paracrine or endocrine to act on parietal cells
  • Vagus will also be turning of the inhibitory pathway:
    • Inhibit D cells, lowers somatostatin,
GAstric phase
  • Stimuli within the stomach start this.
  • Vagal-vagal reflex
    • G cells, ecl cells, pareital cells activated
  • Enteric system
  • As acidity rises:
    • D cells are stimulated to release somatostatin; then endocrinly goes to inhibit G cells.
Intestinal phase
  • Two aspects: stimulatino and inhibition
  • Protein digestion products act on intestinal G cells to increase acid.
  • aa presence will also increase G cells to increase acid.
  • Once acid is high, secretin inhibits gastrin.
  • GIP ?

Regulation over time

  • Between meals, the gastric pH is about 2, such that somatostatin is stimulated and gastrin secretion is decreased.
  • During meals, the pH goes up (because of the food), so D cell stop making somatostatin, so G cells generate acid.
  • Low acid is important betwene meals to help kill bacteria.

The organic constituents

  • Pepsinogen made by chief cells.
    • Low pH is required for pepsionogen activation to pepsin.
    • Pepsin auto activates, also; positive feedback.
    • Starts digestion of protein.
  • Intrinsic factor:
    • Made by parietal cells
    • Deficiency causes pernicious anemia because B12 isn't absorbed
  • Mucins
    • Lubrication
  • Gastric lipase
    • Starts digestion of fats

Protein digestion

  • Chief cells make the pepsinogen.
  • In new borns, there is also chymosin which helps with milk digestion.
    • Not in older kids.

GAstric diffusion barrier

  • Fights low pH damage.
  • Apical membranes of epithelial cells ahve tight jxns that keep acid from getting through.
  • Protective mucus layer helps line the epithelial cells.
    • Rich in bicarb, which neutralizes acid that gets through.
  • Low pH stimulates somatostatin so the pH doesn't just keep going down and down.
  • Prostaglandins stimulate the generation of the diffusion barrier.
    • Stoping prostalgandins means no mucin barrier!

Neutralization of acid in the duod

  • Lots of acid gets dumped in
  • Secrete lots of things to neut
  • Secretin
    • STimulates fluid and bicarb release by pancreas, dudo, and biliary system

Peptid ulcer

  • When diffusion barrier doesn't work; erosion in the wall of the stomach to the epithelial cells.
  • Cause:
    • The careful balance of factors that protect and increase acid is tipped.
    • Pepsin is a protease that can digest the diffusion barrier.
    • Mucins could be low
    • Bicarbs could be low
    • Nicotine, gastring, NSAIDS, and H. pylori all increase acid secretion
    • NSAIDS h. pylori and bile acids decrease the barrier.

Helicopacter pylori and peptic ulcuers

  • Most peple have this bacteria but not all have ulcers.
    • Depends on strain and host immune response
  • Causes inflammatory response
    • Increases sensitivity to histamine
    • More acid
  • Less barrier
  • Junctions break down; leaks between epithelial cells.

NSAIDS and peptic ulcuers

  • Inhibit COxs (inhibit inflammatory response).
  • Also decrease bicarb, lose protective layer.

Tx of peptic ulcers

  • Decrease acid in stomach:
    • Antacids: Maalox, etc.
    • Histamine receptor blockers: Tagament, Zantec, Pepcid
    • Proton pump blockers: prilosec, protonix, nexium
  • Also want to decrease the h pylori:
    • Give antibiotics along with acid-decreasing rx.


  • Prazole = proton pump inhibitors

Summary

  • Salive glands important for watery and protien release for starting digestion.
  • Swallowing is a reflext that moves food
  • Stomach mobility good for expansion, mixing, and emptying into duod
  • Filling is facilitated by relaxation of smooth muscle cells; can be with or without food.
  • Churing has three phases: propulsion, grinding next to antrum, retroflow to start over.
  • Material int he stomach helps produce acid and negative feedback helps reduce acid.
  • Parietal cells produce acid vai proton pumps
    • Fuseing occurs to regulate
    • REgulators: histamine, ach, and gastrine
  • Somatostatin is made by D cells to control parietal cells.
  • Four phases of stomach motility: cephalic (can think and control acid produciton via lots of cell regulation), gastric (stimuli is from stomach itself: stretch or hormone), intestinal phase (activation and inhibition: activation from G cells, inhibition from ?)


  • stopped here on 02/10/11 at 12PM.
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