Module 4 - the Digestive System C: Saliva, Gastric Secretion (3/30 and 4/1 lectures)

• avg body produces 6700mL of intestinal secretions per day

  • saliva, gastric secretions, pancreatic secretions, bile, small intestine secretions, Brunner’s gland secretions, and large intestine secretions

  • pH varies 6-8

salivary glands

• 3 of them: parotid, submandibular, and sublingual glands

• produce saliva, release it to oral cavity through ducts

  • e.g. Stensen’s (parotid) duct

• parasym. innerv. from superior and inferior salivary nuclei, through CN VII and IX (facial and glossopharyngeal)

  • reminder: branches of facial n. can be found w/ five fingers: temporal, zygomatic, buccal, mandibular, superior cervical

saliva

• functions:

  • initial digestion of starch by alpha-amylase (ptyalin) and of triglycerides by lingual lipase

  • lubrication of digested food by mucus

  • protection of mouth and esophagus by dilution

  • buffering of ingested foods

• characteristics:

  • high V (relative to small size of salivary glands)

  • high [K+] and [HCO3-]

  • low [Na+] and [Cl-]

  • hypotonic

  • a-amylase, lingual lipase, and kallikrein are present

• composition varies with flow rate

  • at lowest flow rate: lowest osmolarity, lowest [Na+, Cl-, HCO3-], highest [K+]

  • at highest flow rate (up to 4ml/min): composition is closest to comp. of plasma

• formed by 3 glands

  • glands are structured like gunches of grapes

  • acinus: blind end of each duct

    • lined w/ acinar cells

    • secretes initial saliva, similar comp. to plasma

      • initial saliva is isotonic, same [Na+, K+, Cl-, HCO3-] as plasma

      • initial saliva is modified by a branching duct system lined w/ columnar epith. cells

    • contraction of myoepithelial cells (lining acinus and ducts) → ejects saliva into mouth

• regulation of production is controlled by parasym. and sym. NS, not GI hormones

  • unique: increased by BOTH parasym. and sym. NS

  • parasym. stimulation: CN VII and IX

    • cause vasodilation → increased transport processes in acinar and ductal cells → increased saliva production

    • cholinergic receptors on acinar and ductal cells are muscarinic

    • 2nd messenger is IP3 and increased cellular [Ca2+]

  • sym. stimulation

    • growth of salivary glands → increased production of saliva

      • but effects are smaller than effects of parasym. stimulation

    • 2nd messenger is cAMP

• production is increased (parasympathetic) by food in the mouth, smell of food, and conditioned reflexes/nausea

• production is decreased by sleep, dehydration, fear, anticholinergics

  • inhibition of parasympathetic

phases of gastric secretion

• cephalic phase: starts in the head (sight, smell, thought, taste, appetite)

  • neurogenic signals from appetite centers in cerebrum (amygdala, hypothalamus) travel via parasym. (dorsal motor nuclei) vagi to ENS

    • causes ~20% of acid secretion assoc. with a meal

• gastric phase: chemical presence/distention in stomach → vasovagal and enteric reflexes

  • activate gastrin mechanism

  • causes ~65% of acid secretion assoc. with a meal

• intestinal phase: chemical presence/distention in duodenum → causes stomach to enhance gastric fluid secretion

  • enhanced fluid secretion is another type of enterogastric reflex

  • duodenum also secretes some gastrin

inhibition of gastric H+ secretion

• (-) feedback inhibit secretion by parietal cells

  • low pH (<3) in stomach inhibits gastrin secretion → inhibits H+ secretion

    • after digestion of a meal, H+ secretion is stimulated

    • more is secreted after digestion and stomach emptying → further decrease pH

    • low pH is (-) feedback mech.

  • chyme in duodenum inhibits H+ secretion directly and by hormonal mediators

    • hormonal mediators: GIP (released by fatty A.s in duodenum) and secretin (released by H+ in duodenum)

pathophysiology of gastric H+ secretion

• gastric ulcers

  • normal protective barrier of stomach is damaged → presence of H+ and pepsin may damage mucosa

  • H. pylori infection is a big causative factor

    • high urease activity: converts urea → NH4+ → damages mucosa

  • H+ secretion is decreased

  • gastrin levels are increased by (-) feedback

    • due to lower-than-normal H+ secretion

  • “no acid, no ulcer” because acid is what irritates the defective/damaged mucosa

  • treatment:

    • peptic ulcer + H. pylori infection: treatment is 2 antibiotics and a proton pump inhibitor for 5-14 days

    • without H. pylori infection, or ulcer caused by taking aspirin/NSAIDs: proton inhibitor for 8 weeks

    • surgery: hemigastrectomy

      • billroth I and II, vagotomy, antrectomy

• duodenal ulcers

  • more common than gastric ulcers

  • H+ secretion is higher than normal

    • with pepsin, responsible for mucosal damage

  • gastrin levels in response to a meal are higher than normal

  • tropic effect of gastrin → increased parietal cell mass

• gastritis: inflammation, irritation, or erosion of stomach lining

  • can be acute or chronic

  • causes:

    • irritation due to xs alcohol use, chronic vomiting, stress

    • medications, e.g. aspirin, anti-inflammatories, H. pylori infection, pernicious anemia, bile reflux, infection by bacteria or viruses

  • if left untreated, can lead to severe blood loss

  • symptoms:

    • nausea, recurrent upset stomach, abdominal bloating or pain, vomiting, indigestion, burning feeling in stomach btwn meals or at night, hiccups, loss of appetite, vomiting blood or coffee ground-like material, black/tarry stool

  • treatment:

    • antacids: neutralize stomach A, provide fast pain

      • e.g. maalox

    • acid blockers: reduce amount of acid if antacids aren’t enough

      • e.g. Cimetidine

    • proton pump inhibitors: block action of pumps within acid-secreting cells of stomach

      • e.g. omeprazole

    • for H. pylori infection: 2 antibiotics and a proton pump inhibitor

• hypertrophic gastritis: aka Menetrier’s disease

  • giant rugal folds simulate cancer

  • mucosa is atrophic w/ associated protein loss

clinical points

• tapping on buccal branch of CN VII → abnormal lip movement: means hypocalcemia (<10mg/dl)

• gastritis and gastric ulcers have similar symptoms, but ulcers are more severe

  • severe abdominal pain (especially after eating), vomiting, pain from GI irritation, etc.

• mumps: inflammation of parotid gland caused by myxovirus (Mumps virus)

• anticholinergic drugs (e.g. atropin) inhibit production of saliva → cause dry mouth

• H+ secretion blockers:

  • atropine: inhibits cholinergic muscarinic receptors on parietal cells → inhibits ACh stimulation of H+ secretion

  • cimetidine: blocks H2 receptors → inhibits histamine stimulation of H+ secretion

    • very effective: blocks histamine stimulation AND blocks histamine’s potentiation of ACh effects

  • omeprazole: directly inhibits H+/K+-ATPase and H+ secretion

• H. pylori can also cause stomach cancer sometimes w/o treatment

• pernicious anemia: stomach lacks intrinsic factor → cannot properly absorb and digest vit B12

clinical cases

• Pt has cancer. Surgeon removes pt’s fundus and body of stomach because of tumor location. What are side symptoms post-op?

  • lack of intrinsic factor, less acid, reduced HCl, reduced pepsinogen, pernicious anemia, protein deficiency, deficiency of paracrine hormones, lack of gastrin

• Pt has severe abdominal pain immediately after eating because food is accumulating about stomach and lower part of esophagus. What is diagnosis?

  • aperistalsis, achalasia because LEs cannot open completely → food can’t get into stomach

  • enteric NS has problem

• A newborn, 1 day old, has difficulty during breastfeeding. Symptoms: coughing and vomiting immediately after breastfeeding. What are your thoughts?

  • atresia and fistula

    • congenital esophageal atresia: middle part of esophagus did not develop

      • causes vomiting

    • tracheoesophageal fistula: abnormal opening btwn esophagus and trachea

      • causes coughing