Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands,...

86
Salivary Glands Esophagus Stomach

Transcript of Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands,...

Page 1: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Salivary GlandsEsophagusStomach

Page 2: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach.

2. An understanding of the physiologic defects in esophageal reflux and dysmotility.

3. An understanding of how our knowledge of gastric physiology is exploited in the therapy of gastric disorders.

4. An understanding of the mechanisms underlying the treatment of peptic diseases.

Salivary gland; esophagus; stomach; antacids

Page 3: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Grant’s Atlas, 1972

Page 4: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 5: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 6: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 7: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 8: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Salivary GlandsGross anatomy◦parotid◦submandibular◦sublingual

Histology◦serous◦mucus◦mixed

Page 9: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Salivary Gland FunctionsLubrication◦Swallowing◦Speech◦Prevention of dental caries

Digestion

Page 10: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Secretory Products (1,500 mls/day)◦Amylase◦ Lipase◦Mucin◦Growth factors

Nerve growth factor EGF

◦ Fluid and electrolytes

Page 11: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Berne & Levy, Principles of Physiology, 1996

Page 12: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Adapted from Am J Physiol 178:155 (1954)

Page 13: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Regulation of Secretion

Regulation is via both the sympathetic and parasympathetic nervous systems

Page 14: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Grant’s Atlas, 1972

Page 15: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

N Engl J Med (1997) 336:924-932

Page 16: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 17: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 18: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Feldman: Sleisenger & Fordtran’s Gastrointestinal and Liver Disease, 7th ed.

Page 19: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Achalasia

- Loss of primary peristalsis

- Elevated lower esophageal sphincter pressures

Page 20: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Feldman: Sleisenger & Fordtran’s Gastrointestinal and Liver Disease, 7th ed.

Page 21: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Spastic Esophagus

Page 22: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

N Engl J Med (1997) 336:924-932

Page 23: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 24: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

N Engl J Med (1997) 336:924-932

Page 25: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 26: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Spechler, S. J. N Engl J Med 2002;346:836-842

Endoscopic Photograph Showing Traditional, or Long-Segment, Barrett's Esophagus

Page 27: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 28: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 29: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Grant’s Atlas of Anatomy, 1972

Page 30: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Enteroendocrine cells - Ghrelin

Page 31: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 32: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Stomach Anatomy Cardia

◦ mucus cells Fundus and Body

◦ mucus cells◦ parietal cells

acid secretion and intrinsic factor

◦ chief cells Pepsiniogen

◦ enteroendocrine cells ghrelin

Antrum◦ mucus◦ enteroendocrine cells

gastrin,somatostatin

Page 33: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 34: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 35: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Gastric Functions Storage Mechanical breakdown of food Exocrine secretion (~2,500 mls/day)

◦ Acid◦ Pepsinogen◦ Intrinsic Factor

Endocrine secretion◦ Gastrin◦ Ghrelin

Page 36: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 37: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Grant’s Atlas of Anatomy, 1972

Page 38: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Receptive RelaxationStomach exhibits high compliance◦1.5 L of air results in an increase of 10 mm Hg in

intraluminal pressureDependent upon the vagus nerve◦Non-adrenergic, non-cholinergic control◦Dependent on nitric oxide

Page 39: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Gastric Functions Storage Mechanical breakdown of food Exocrine secretion (~2,500 mls/day)

◦ Acid◦ Pepsinogen◦ Intrinsic Factor

Endocrine secretion◦ Gastrin◦ Ghrelin

Page 40: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 41: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Grant’s Atlas of Anatomy, 1972

Page 42: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

300 ml starting volume

Page 43: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Gastric Functions Storage Mechanical breakdown of food Exocrine secretion (~2,500 mls/day)

◦ Acid◦ Pepsinogen◦ Intrinsic Factor

Endocrine secretion◦ Gastrin◦ Ghrelin

Page 44: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

No acid, no ulcersPeptic ulcer disease affects up to 10% of

the population

Acid Secretion

Page 45: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

H+-K+:ATPaseExpressed by parietal cellsIntraluminal pH = 0.8Cytosolic pH = 7.3Proton gradient = 2,400,000

Page 46: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 47: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

H+-K+:ATPaseEnzyme requirements◦ATP

1 ATP > 2 H+

◦Potassium Required on the luminal side

◦Hydrogen Produced via carbonic anhydrase

Page 48: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 49: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 50: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 51: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Sawaguchi, A. et al. J. Histochem. Cytochem. 2004;52:77-86

Light (A,B) and electron (C-E) micrographs of isolated rabbit gastric glands stimulated with histamine for 30 min

Page 52: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Fundus

Body

Antrum

Parietal cells

Chief cells

G cells gastrin

pepsinogen

Intrinsic factor

HCl +

Page 53: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Regulation of Acid SecretionAcetylcholine - vagal inputGastrin - G cells◦pH > 3, amino acids Phe, Trp

HistamineInhibition of any one pathway will also

significantly affect stimulation by other agents.

Page 54: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Ach Histamine Gastrin

Muscarinic Receptor H2 receptor

IP3, Ca2+ cAMP IP3, Ca2+

H+ secretion

Atropine Cimetidine

Omeprazole

(inhibits H+/K+ ATPase)

Page 55: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 56: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Nature (1992) 360:458-461

Page 57: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Nature (1992) 360:458-461

Page 58: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 59: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Aspirin/NSAID ulcersIncrease risk of ulcers with aspirin or NSAID

(non-steroidal antiinflammatory drugs)◦Mechanism of action may include the inhibition of

prostaglandin synthesis, which normally promotes mucus production.

◦Analogs of prostaglandin E (misoprostil) are used to reduce the incidence of NSAID ulcers. Acid inhibition is more commonly used now.

Page 60: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Gastric Exocrine Protein SecretionMucus - lubrication and mucosal protectionIntrinsic factor - binding and absorption of

vitamin B12. Produced by the same cells (parietal cells) that secrete acid.

Pepsinogen - activated by acid to pepsin, an endoprotease. Produced by the chief cells.

Page 61: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Vitamin B12

• Methylation-facilitates 1-carbon transfers– conversion of homocysteine to methionine

• Intramolecular rearrangement– isomerization of methylmalonyl coenzyme A to succinyl CoA

Page 62: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Feldman: Sleisenger & Fordtran’s Gastrointestinal and Liver Disease, 7th ed.

Page 63: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Intrinsic Factor represents the only major essential factor produced by the stomach◦ Intrinsic Factor is essential for vitamin B12 absorption.◦Patients who undergo a gastrectomy must have vitamin

B12 replaced. Deficiency results in CNS and peripheral neuropathic

problems, megaloblastic anemia, etc.

Page 64: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

PepsinogenSecreted by the chief cells as an in active

proprotein.Activated by cleavage in an acid environment.Cleaves at aromatic amino acids.

Page 65: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Gastric Endocrine Protein Secretion

GastrinGhrelin

Page 66: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 67: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 68: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Ulcer Disease Therapy

Ulcers occur only in the presence of acid

Page 69: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Oral AntiacidsAdvantages of the oral antacids

include their low cost, rapid onset of action and absence of systemic adverse reactions. Disadvantages include that short duration of beneficial effects

Page 70: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

Oral AntacidsSodium bicarbonate (baking soda,

Alka Seltzer)Calcium carbonate (Tums, Os-Cal)Magnesium hydroxide (Mylanta)◦side effects: diarrhea

Aluminum Hydroxide◦side effects: constipation

Page 71: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

AnticholinergicsInhibit neural stimulation of acid secretionHigh incidence of side effects

Page 72: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 73: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 74: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 75: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 76: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 77: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

H2 receptor antagonistimidazole ring - related to histamineCompetitive antagonists for histamineRapidly absorbed with peak levels in 90min. Not

protein bound.T1/2 = 4-12 hours depending on formulationExcreted largely in the urine, which requires

dosage adjustments in renal failure

Page 78: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

CimetidineAdverse reactions◦Anti-androgenic effects: gynecomastia◦Diarrhea, headache, dizziness◦ inhibits the hepatic cytochrome P450 such that the

half-life of warfarin-containing anticoagulants, phenytoin, propranolol, nifedipine, and others may be longer

Page 79: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 80: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 81: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

PPI - OmeprazoleCovalently binds to the pump in low pH First pass effect in the liver after intestinal

absorption◦Excreted in the urine (70%) and feces

Few significant adverse reactions◦Elevated risk of osteoporosis with chronic use.

Page 82: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 83: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 84: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.

H. pylori

Page 85: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.
Page 86: Salivary Glands Esophagus Stomach. 1. An understanding of the physiologic role of salivary glands, the esophagus, and the stomach. 2. An understanding.