SALIVARY ION AND FLUID SECRETION Christopher Nosrat Room: 3218 Phone: 5 - 4388 E-Mail: nosrat@umich.edu

SALIVARY ION AND FLUID SECRETION References Bradley, R.M. 1995. Salivary secretion. Chapter 9 In Essentials of Oral Physiology, pp.161-184, Mosby, St Louis. Garrett, J.R. and Proctor, G.B. 1998. Control of Salivation. In Linden, R.W.A. (ed.) The Scientific Basis of Eating. Front. Oral Biol., Basel, Karger pp. 135-155. Petersen, O.H. 1994. Electrophysiology of salivary and Pancreatic Acinar Cells. Chapter 25 In Johnson, L.R. (Ed.) Physiology of the Gastrointestinal Tract, pp. 1025 -1059, Raven, NY. Petersen, O.H. 1994. Secretion by the major salivary glands. Chapter 26 In Johnson, L.R. (Ed.) Physiology of the Gastrointestinal Tract, pp. 1061 -1117, Raven, NY.

SALIVARY ION AND FLUID SECRETION SALIVARY GLAND DIVERSITY STRUCTURE OF SALIVARY GLANDS GLANDULAR MECHANISMS OF SECRETION FACTORS AFFECTING FLOW SECRETION OF WATER AND ELECTROLYTES

MAJOR FUNCTIONS OF SALIVA Solvent Anti-bacterial Anti-fungal Buffering Lubrication Remineralization Temperature regulation Production of growth factors and other regulatory peptides Digestion based on Essentials of Oral Physiology by R. M. Bradley

A CONSIDERABLE VOLUME OF SALIVA IS PRODUCED OVER A DAY 0.5 to 0.75 liter of fluid is secreted in a day This represents about 1/5 of the total plasma volume This fluid is not lost as most of it is swallowed and reabsorbed by the gut

NO TWO SALIVARY GLANDS ARE THE SAME! Much of the information on salivary secretion has been derived from the rat parotid gland. Parotid glands in other species have different morphologies and physiology.

GENERAL RULES COMMON TO ALL SALIVARY GLANDS 1. Secretomotor autonomic nerves invariably control flow. 2. The osmotic pressure (tonicity) exerted by saliva is usually lower than plasma - saliva is usually hypotonic to plasma. 3. Tonicity increases as flow rate increases. 4. Saliva contains potassium ions at 2-10 times the concentration of serum potassium. 5. Saliva in many animals contains a high level of the digestive enzyme amylase.

SALIVARY GLAND STRUCTURE Salivary glands are made up of thousands of identical units

Saliva formed in acini flows down DUCTS to empty into the THE SECRETORY UNIT The basic building block of all salivary glands Saliva formed in acini flows down DUCTS to empty into the oral cavity. ACINI - water and ions derived from plasma enter here.

Components of a salivary gland Autonomic nerve fibers Myoepithelial cell Ducts Acini Blood vessels

(Submandibular gland) Serous salivary gland (Parotid gland) Mucous salivary gland (Submandibular gland)

Mixed sero-mucous secretory unit Striated ducts Mixed sero-mucous secretory unit

Actions of nerves on salivary gland cells Hydrokinetic - water mobilization Protokinetic - protein secreting Synthetic - inducing synthesis Trophic - maintaining normal functional state and size

Neural stimulation of myoepithelial cells 1. Speeds up the initial outflow of saliva 2. Reduces luminal volume 3. Contributes to secretory pressure 4. Supports underlying parenchyma 5. Helps the flow overcome increased peripheral resistance

GLANDULAR MECHANISMS OF SECRETION FACTORS AFFECTING FLOW RATE Time of day Feeding Stimulus frequency

CIRCAIDIAN RHYTHM OF SALIVA FLOW No sleep sleep 12 am 6 am 12 pm 6 pm 30 20 10 Time of day

Effect of feeding on salivary secretion Meal during this period 10 min collection periods

observed during feeding Range of flow rates observed during feeding Classic experiment in which the nerve supply to the submandibular gland of a dog was stimulated electrically at different frequencies to initiate salivary flow. Note the relationship between the frequency of stimulation and the salivary flow rate (Emmelin and Holmberg, 1967)

GLANDULAR MECHANISMS OF SECRETION FACTORS AFFECTING COMPOSITION FLOW PARASYMPATHETIC STIMULATION SYMPATHETIC STIMULATION

ELECTROLYTE COMPOSITION OF HUMAN PAROTID SALIVA COMPARED WITH PLASMA

PROTEIN COMPOSITION OF HUMAN PAROTID SALIVA

Concentration (mM) FLOW RATE ml/min

Parasympathetic Sympathetic

Parasympathetic nervous system

TECHNIQUES TO STIMULATE EITHER THE PARASYMPATHETIC OR SYMPATHETIC NERVOUS SYSTEM Stimulate different branches of the autonomic nervous system - not practical in human experiments. Use drugs that act at either the parasympathetic ( ) or sympathetic ( ) synapses with the salivary gland. carbachol isoproterenol

NOTE different values on X and Y axes. High flow rates with parasympathetic stimulation when compared to sympathetic stimulation and no increases in flow rate after about 15 Hz for sympathetic stimulation. Flow rate plateaus out after 150 Hz for parasympathetic. 120 100 Parasympathetic stimulation 80 Flow rate (µl/min) 60 40 20 50 100 150 200 14 12 10 Sympathetic stimulation Flow rate (µl/min) 8 6 4 2 5 10 15 20 Stimulus frequency (Hz)

Area of secretory granules (µm2) Control 3 mg/kg 30 mg/kg 50 100 150 Area of secretory granules (µm2) Dose of isoproterenol

TWO STAGE HYPOTHESIS OF SALIVA FORMATION Most proteins Na+ Cl- resorbed Hypotonic final saliva into mouth Water & electrolytes Some proteins electrolytes K+ secreted Isotonic primary saliva

Concentration (mEq/l) 100 Na 80 HCO3 60 Concentration (mEq/l) Cl 40 20 K 10 20 30 40 Flow of saliva (ml/min) Classic experiment in which the concentration of ions in human parotid saliva was measured at different flow rates produced by parasympathetic stimulation (Thaysen et al., 1954)

IONIC COMPOSITION OF PRIMARY SALIVA

QUESTIONS YOU SHOULD BE ABLE TO ANSWER 1. Where do salivary components come from? 2. How is saliva formed? 3. What makes saliva flow? 4. What controls salivary flow rate? 5. What are the underlying mechanisms of salivary reflexes? 6. What good is saliva? 7. What do salivary glands and saliva have in common? 8. What differences are there between salivary glands and saliva? 9. What is the current hypothesis of the mechanism of salivary secretion? 10. What factors contribute to changes in salivary composition and flow rate?