Updated: 10/29/2018

Gastric Secretion

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Overview
  • Gastric secretion
    • cells of gastric mucosa secrete gastric juice
      • composed of hydrochloric acid (HCl), pepsinogen, intrinsic factor (IF), and mucus
        • HCl and pepsinogen initiate protein digestion
        • IF is required for vitamin B12 absorption in ileum
        • mucus protects gastric mucosa from corrosive action of HCl and lubricates gastric contents
Gastric Glands
  • Oxyntic glands
    • body of stomach contains oxyntic glands
      • oxyntic glands empty secretory products via ducts into lumen of stomach
        • opening of ducts are called gastric pits
      • oxyntic glands contain parietal cells and chief cells
        • parietal cells secrete HCl and IF into oxyntic ducts
        • chief cells secrete pepsinogen into oxyntic ducts
  • Pyloric glands
    • antrum of stomach contains pyloric glands
      • pyloric glands empty secretory products via ducts into lumen of stomach
        • opening of ducts are called gastric pits
      • pyloric glands contain G cells and mucosal neck cells
        • G cells secrete gastrin into systemic circulation, not into pyloric ducts
        • mucosal neck cells secrete mucus and HCO3- into pyloric ducts
          • mucus forms a gel-like protective barrier between gastric mucosal cells and gastric lumen
            • protects gastric mucosal cells against acid (HCl) and digestive enzymes (pepsin)
          • HCO3- embeds in mucosal gel-like protective barrier
            • neutralizes any HCl that may penetrate mucosal layer
            • inactivates any pepsin that may penetrate mucosal layer
Gastric Parietal Cell
  • Parietal cell polarity 
    • apical membrane
      • contains H+-K+ ATPase and Cl- channels
    • basolateral membrane
      • contains Na+-K+ ATPase and Cl-/HCO3- exchanger
  • Parietal cell secretion 
    • parietal cells secrete HCl and IF into oxyntic ducts that empty into lumen of stomach
    • HCl acidifies gastric contents
      • 1 ≤ pH ≤ 2
        • low pH converts inactive pepsinogen zymogen to active pepsin enzyme
          • pepsin is a protease that initiates protein digestion
  • Mechanism of HCl secretion
    • aerobic metabolism of gastric parietal cell produces CO2
    • intracellularly, CO2 combines with H2O to form H2CO3, which dissociates into H+ and HCO3-
      • CO2 + H2O → H2CO3 → H+ + HCO3-
      • carbonic anhydrase catalyzes hydration of CO2
    • at apical membrane, H+ is secreted into lumen of stomach via H+-K+ ATPase
      • H+ secretion inhibited by omeprazole, a proton pump inhibitor and an antacid
    • at apical membrane, Cl- "follows" H+ and is secreted into lumen of stomach via Cl- channels
    • at basolateral membrane, HCO3- is absorbed from cell into bloodstream via Cl-/HCO3-exchanger
      • HCO3- moves out of cell and into bloodstream
        • HCO3- is responsible for "alkaline tide" (high pH) that is observed in gastric venous blood following a meal
        • eventually, HCO3- is secreted back into gastrointestinal tract in pancreatic secretions
      • Cl- moves out of bloodstream and into cell
  • Activation of HCl secretion
    • stimuli
      • smellingtasting, and conditioned reflexes in anticipation of food
        • via vagal stimulation
          • direct and indirect pathways of stimulation
      • distension of stomach
        • via vagal stimulation
          • direct and indirect pathways of stimulation
      • presence of breakdown products of protein (small peptides and amino acids)
        • via stimulation of gastric G cells to secrete gastrin
        • phenylalanine and tryptophan are most potent stimuli for gastric secretion
    • vagal stimulation
      • direct pathway
        • vagus nerve innervates gastric parietal cells
        • at synapse, ACh is released and binds muscarinic M3 receptors coupled to Gq proteins
        • ↑ ACh → (+) M3 receptors → (+) Gq proteins → (+) PLC → ↑ DAG and IP3
        • IP3 releases Ca2+ from intracellular stores
        • DAG and Ca2+ → (+) PKC → (+) H+-K+ ATPase → ↑ HCl secretion via gastric parietal cells
      • indirect pathway
        • vagus nerve innervates gastric G cells
        • at synapse, gastrin-releasing peptide (GRP) is released
        • GRP → ↑ gastrin secretion via gastric G cells
      • atropine
        • atropine inhibits HCl secretion via gastric parietal cells
          • atropine is a cholinergic muscarinic antagonist
          • atropine blocks muscarinic M3 receptors on gastric parietal cells
            • blocks ACh-mediated, direct pathway of HCl secretion
        • atropine does not inhibit HCl secretion via gastric parietal cells completely
          • atropine does not block GRP-mediated, indirect pathway of HCl secretion
    • histamine
      • histamine is released from enterochromaffin-like (ECL) cells in gastric mucosa
      • histamine diffuses to nearby gastric parietal cells
        • paracrine mechanism of delivery
      • histamine binds H2 receptors coupled to Gs proteins on gastric parietal cells
        • histamine → (+) H2 receptors → (+) Gs proteins → (+) adenylyl cyclase → ↑ cAMP
        • ↑ cAMP → (+) PKA → (+) H+-K+ ATPase → ↑ HCl secretion via gastric parietal cells
          • HCl secretion inhibited by cimetidine, a H2 receptor inhibitor and an antacid
    • gastrin 
      • gastrin is released from G cells of antrum of stomach into systemic circulation
        • gastrin is not released into pyloric ducts that empty into lumen of stomach
      • gastrin is delivered back to stomach via systemic circulation
        • endocrine mechanism of delivery
      • gastrin stimulates HCl secretion via gastric parietal cells by 2 mechanisms
        • gastrin binds CCKB receptors coupled to Gq proteins on gastric parietal cells
          • gastrin → (+) CCKB receptors → (+) Gq proteins → (+) PLC → ↑ DAG and IP3
          • IP3 releases Ca2+ from intracellular stores
          • DAG and Ca2+ → (+) PKC → (+) H+-K+ ATPase → ↑ HCl secretion via gastric parietal cells
        • gastrin binds CCKB receptors on ECL cells
          • gastrin → (+) CCKB receptors → ↑ histamine secretion → ↑ HCl secretion via gastric parietal cells
        • gastrin stimulates HCl secretion primarily by acting on ECL cells
      • Zollinger-Ellison syndrome 
        • increased HCl secretion via gastric parietal cells caused by a gastrin-secreting tumor (gastroma)
          • increased HCl (H+) secretion may cause duodenal ulcers
          • increased acidification inactivates pancreatic lipase, an enzyme necessary for lipid digestion
            • lipids are not adequately digested nor absorbed
            • lipid excretion in feces (steatorrhea)
  • Inhibition of HCl secretion
    • occurs when chyme is propelled along gastrointestinal tract from stomach to duodenum of small intestine
      • HCl is no longer required to activate pepsinogen zymogen to active pepsin enzyme
    • ↓ pH
      • gastric contents acidify (pH lowers) when chyme is propelled along gastrointestinal tract from stomach to duodenum of small intestine
        • food acts as a buffer for H+ in stomach
        • food in stomach
          • as gastric parietal cells secrete HCl, food buffers H+ and gastric contents acidify only slightly
        • food in duodenum
          • buffering capacity in stomach is reduced
          • as gastric parietal cells secrete HCl, gastric contents further acidify
            • pH < 1.5 initiates a negative feedback mechanism by inhibiting gastrin secretion via G cells
    • somatostatin
      • somatostatin is secreted by D cells of gastric mucosa
      • somatostatin binds receptors coupled to Gi proteins on gastric parietal cells
        • somatostatin → (+) receptors → (+) Gi proteins → (-) adenylyl cyclase → cAMP
        •  cAMP → (-) PKA → (-) H+-K+ ATPase →  HCl secretion via gastric parietal cells
      • somatostatin antagonizes stimulatory effect of histamine on HCl secretion
    • prostaglandins
      • prostaglandins bind receptors coupled to Gi proteins on gastric parietal cells
        • prostaglandins → (+) receptors → (+) Gi proteins → (-) adenylyl cyclase → cAMP
        •  cAMP → (-) PKA → (-) H+-K+ ATPase →  HCl secretion via gastric parietal cells
      • prostaglandins antagonizes stimulatory effect of histamine on HCl secretion
  • IF secretion
    • IF is required for vitamin B12 absorption in ileum
    • IF is only essential secretion of stomach
    • IF deficiency causes pernicious anemia
Gastric Chief Cell
  • Chief cell function
    • chief cells secrete pepsinogen into oxyntic ducts that empty into lumen of stomach
    • pepsinogen is a zymogen (inactive enzyme) that must be activated through cleavage
      • increased concentration of H+ in gastric contents provides the low pH signal
      • low pH converts inactive pepsinogen zymogen to active pepsin enzyme
        • pepsin is a protease that initiates protein digestion
  • activation of pepsinogen secretion
    • stimuli
      • vagal stimulation → ↑ pepsinogen secretion via chief cells
      • ↑ H+ → ↑ pepsinogen secretion via chief cells
 

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Questions (2)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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