salivary and gastric secretion

Learning Objectives:

Learning Objectives:

• Describe the mechanisms controlling intake of food

• Name and describe the role of acinar and ductal cells in salivary secretion

• Describe the composition of salivary secretion

• Describe the mechanisms involved in generating a hypotonic saliva

• Describe neural regulation of salivary secretion

• Describe the mechanisms involved in the swallowing reflex

saliva function

• Saliva lubricates food for swallowing and glycoproteins secreted from submandibular, sublingual glands, buccal glands aid in starch digestion

• release analyse and lypase

• speech

• Maximum rate of saliva flow in humans ~1 ml/min.g.

• Vasculature is highly fenestrated and a 5-10-fold increase in blood flow during neural activation of salivary secretion guarantees sufficient supply of water, electrolytes and nutrients to sustain epithelial cells and active salivary secretion

• digestive and protective function (cleaning/ antimicrobial actions)

The salivary glandular epithelium is comprised of ( micrvascular arrangement)

• specialised groups of cells called acinar cells, arranged as endpieces surrounding small central lumen, opening into ductule-striated or intercalated duct, which in turn converge into large ducts and open into main excretory ducts draining into mouth (e.g. sublingual-cheek, submandibular-below tongue)

acinar and ductal cells function

In salivary glands, both acinar cells and ductal cells play crucial roles in the production and modification of saliva. Here's a breakdown of their roles:

Acinar Cells

- Function:

- Acinar cells are responsible for the initial production of saliva. They secrete a primary fluid that is rich in water, electrolytes, enzymes, and mucus.

- There are two main types of acinar cells: serous cells and mucous cells.

- Serous acinar cells secrete a watery fluid rich in digestive enzymes, particularly amylase, which begins the process of starch digestion in the mouth.

- Mucous acinar cells produce a more viscous, mucin-rich fluid that helps lubricate the oral cavity and form the bolus of food for easier swallowing.

- This primary saliva produced by acinar cells is isotonic, meaning it has a similar ion concentration as blood plasma.

2. Ductal Cells

- Function:

- Ductal cells modify the primary saliva as it passes through the ducts.

- Striated duct cells are particularly important for this modification. They reabsorb sodium (Na⁺) and chloride (Cl⁻) ions from the saliva and secrete potassium (K⁺) and bicarbonate (HCO₃⁻) ions into it.

- This ion exchange process makes the final saliva hypotonic (having a lower ion concentration compared to blood plasma), which is essential for maintaining the ionic balance in the body.

- Ductal cells also play a role in adjusting the pH of the saliva, making it more alkaline due to the secretion of bicarbonate. This helps neutralize acids in the mouth and protects teeth from decay.

Together,they ensure that the saliva is properly composed to perform its functions, including lubrication, digestion, protection against pathogens, and maintaining oral hygiene.

• Describe the composition of salivary secretion

it includes a mixture of water, electrolytes, enzymes, mucus, antimicrobial agents, and other organic and inorganic substances. Here’s a breakdown of its components:

### 1. Water (99%)

- Function: Water is the primary component of saliva, making up about 99% of its volume. It provides the medium for dissolving food particles, which aids in taste perception and the formation of the food bolus, facilitating swallowing.

### 2. Electrolytes

- Sodium (Na⁺): Present in saliva in lower concentrations than in blood plasma, sodium is involved in maintaining osmolarity and pH balance.

- Potassium (K⁺): Found in higher concentrations in saliva compared to plasma, potassium helps regulate the electrical charge and osmotic balance in cells.

- Chloride (Cl⁻): Chloride ions are essential for maintaining electrical neutrality and osmotic balance, and they help in the transport of bicarbonate.

- Bicarbonate (HCO₃⁻): Bicarbonate is crucial for buffering acids in the mouth, maintaining an optimal pH level (around 6.2 to 7.6), which helps prevent dental erosion and supports enzyme activity.

- Calcium (Ca²⁺): Calcium is important for the remineralization of teeth and helps in maintaining tooth enamel strength.

- Phosphate (PO₄³⁻): Phosphate, like calcium, is essential for tooth remineralization and helps buffer acids in the mouth.

### 3. Enzymes

- Amylase: The most abundant enzyme in saliva, amylase (specifically alpha-amylase) begins the digestion of starches by breaking down complex carbohydrates into simpler sugars like maltose.

- Lingual Lipase: Secreted by glands in the tongue, this enzyme starts the digestion of lipids (fats) in the mouth, although its activity is more significant in the stomach.

- Lysozyme: An antimicrobial enzyme that breaks down bacterial cell walls, helping to control the growth of bacteria in the mouth.

Describe neural regulation of salivary secretion

• Parasympathetic stimulation mediated via chorda lingual nerve, evoking a marked fluid secretion accompanied by increased blood flow and oxygen consumption.

• Secretion of saliva, but not blood flow, blocked by atropine (co-release of VIP or substance P from cholinergic fibres mediates atropine-resistant increase in blood flow).

• Although blood flow increases 5-10-fold, salivary secretion is not due to increased hydrostatic pressure gradient from blood to saliva.

• Sympathetic activation generally causes vasoconstriction and scanty viscous secretion rich in proteins. b-adrenergic stimulation leads to a secondary reactive hyperaemia.

Salivary secretory mechanism:

1. reflex response controlled by parasympathetic and sympathetic nerves.

2. Stimuli for salivary secretion include taste, touch and smell of food.

3. Saliva formed by 2 stage process in which isotonic primary fluid (plasma-like electrolyte composition) formed by acinar cells is modified in the striated duct system by reabsorption of Na+ & Cl- and secretion of K+ and HCO3-.

4. Micropuncture techniques confirm isotonic primary fluid.

5. Recent patch-clamp evidence confirms neurotransmitters and hormones act on basolateral membrane of acinar epithelial cells to elevate intracellular Ca2+, which leads to activation of K+ channels in basolateral membrane and possibly Cl- channels in luminal membrane.

6. Stimulus evoked loss of KCl and reuptake via basolateral Na+-K+-2Cl- co-transporter and Na+-K+ pump. Rate of Cl- uptake directly linked to cycle of K+ release and reuptake.

7. In steady state, three basolateral transport proteins are operative: K+ channel, Na+-K+ pump and the Na+-K+-2Cl- co-transporter operating as an electrogenic Cl- pump.

8. Cl- exits into lumen (negative charge) and Na+ follows through paracellular space drawing water through and between cells by osmotic force.

9. Cl- & K+ conductance increases when stimulation stops and the Na+-K+ pump and co-transporter restore intracellular KCl concentrations.

lecture

1. reflex résponse set off by taste, smell, touch receptors in mouth by chewing

2. production of watery saliva is elicited by choligernic, adregernic and peptidregic stimulation

3. increase blood flowr- delivery of nutrients, electrolytes and water

4. reflex response controlled by parasympathetic and sympathetic nerves.

role of acing and ductal cells in salivary secretion:

1. salivary glands compound organs that secrete electrolytes and proteins as a fluid in the oral cavity

2. saliva lubricates food for swallowing, glycoproteins and amylase for starch digestion

3. increase In blood flow= guarantees sufficient nutrient and water supply to sustain active secretion

4. sodium diffuses out, potassium in= hypertonic saliva= less electrolytes than in plasma

aging = hyposalvation

• normal function reduced in ageing= sensory stimuli, reflexes, impulse transmission, hormones, blood flow

• salivary gland hypofunction

• salivary secretion decreases

take home- saliva

• several salivary glands in the mouth

• activated by sympathetic and parasympathetic nerve fibres

• transmitter for sympathetic = noradrenaline

• parasympathetic= acetylcholine

• if you block parasympathetic with a drug called atropine= should stop salivation

• gland had other nerve fibres ( not sympathetic/ parasympathetic) = can stop salivation but not blood flow

• ageing has consequence for health of the mouth and ability to swallow and digestion

Swallowing reflex:

1. Voluntary phase of swallowing is initiated following separation of bolus of food in mouth from the mass in the mouth with tip of tongue.

2. Bolus is moved upwards and backward by pressure of tongue against hard palate, forcing bolus into esophagus, activating tactile receptors that initiate the swallowing reflex.

3. Pharyngeal phase of swallowing involves pulling of soft palate upwards, inward movement of palatopharyngeal fold toward one another, preventing reflux into the nasopharynx.

4. Vocal cords pulled together, epiglottis covers the opening to larynx – both prevent entry of food into trachea.

5. Upper esophageal sphincter relaxes to receive food, pharynx contracts strongly to force bolus deep into pharynx.

6. Persistaltic waves now force food bolus through relaxed esophageal sphincter.

function of stomach

Stomach is an exocrine organ, secreting a large acid volume after meal. Secretion also contains pepsin which initiates protein digestion, a process continued in the intestine by pancreatic enzyme

Stomach layers

• muscularis mucosa - thin layer smooth muscle arranged as 2 or 3 sublayers, separates mucosa from serosa.

• Submucosa - dense connective tissue, larger blood vessels, lymphatics, nerves. Secretion accompanied by increased mucosal blood flow.

• Muscularis - 3 primary layers: inner oblique, middle circular, outer longitudinal; myenteric nerve plexus of Auerbach occurs in thin connective tissue layer separating circular & longitudinal muscle, co-ordinates contractions for churning food.

• Serosa - outermost layer thin connective tissue plus mesothelium is continuous via the omenta with peritoneum.

Divisions of gastric mucosa

• cardiac glands: mucous secretion, near esophageal end, tubular, highly-branched & coiled glands with few or no

  peptic or oxyntic cells. These glands secrete some electrolytes

• pyloric glands: constitute 15-20% of total gastric mucosal area. Resemble mucous cells in neck and base regions

  of oxyntic glands; secrete alkaline mucous juice and some electrolytes as Ca phosphate, bicarbonates, NaCl & KCl; characteristic deep gastric pits; at junction with duodenum a thickened circular muscle layer is found at the pyloric sphincter. 5 x 105 cells/sq. mm, predominant cell type in antrum of stomach; release by exocytosis into basal and lateral cell surfaces, involvement of contractile filaments and microtubules.

• oxyntic glands: occupy fundus and body of stomach, 75-80% of total gastric mucosa; numerous invaginations called gastric pits, 100 per sq.mm, 3-7 empty - into each pit, ca. 35 million in total. Oxyntic gland is the key site of gastric HCl secretion. 3 regions: isthmus - parietal & surface mucous cells, neck - parietal & mucous cells, base - chief cells (secrete pepsinogen), some endocrine cells. Gastrin producing cells (G-cells) have been localised by immunofluorescence in middle third of mucosa. In man parietal cells more abundant pylorus than cardiac region, chief cell distribution reverse.

Surface mucous cells are made up of

• simple columnar epithelium, secrete neutral carbohydrate-rich glycoproteins. The mechanism of granule release is poorly understood but aspirin, ethanol, stress & food are stimulants.

• Mucous neck cells mucous granules larger than surface granules, stem cells for epithelial replacement, usually 1 week renewal period, secrete acidic glycoproteins.

• Note these mucus cells secrete both HCO3- and viscous mucus to protect against HCl.

• There is general acceptance that this mucus gel layer is relatively impermeable to the diffusion of H+ from the stomach lumen to the surface cells.

0. Parietal or oxyntic cells

secrete 0.1 N HCl, located predominantly in middle and upper part of gastric gland, 25 μM diameter with base bulging into lamina propria, numerous mitochondria, specialised intracellular canaliculi extending from lumen to basal cytoplasm, microvilli on lumen & canaliculi walls providing a greatly increased surface area. HCl secretion occurs along this internalised structure following activation of basolateral membrane receptors by ACh, histamine and gastrin

0. Chief or peptic cells

secrete protein in manner similar to salivary/pancreatic acinar cells. Chief cells synthesise & secrete pepsinogen, which is converted to pepsin in acid milieu.

• Chief/Peptic Cells Functions:

  1. Secretion of Pepsinogen: Inactive precursor of pepsin, crucial for protein digestion.

  2. Secretion of Gastric Lipase: Enzyme involved in the digestion of fats, especially in infants.

  3. Coordination with Parietal Cells: Chief cells work in tandem with parietal cells to create the acidic environment necessary for the activation of digestive enzymes.

Overall, chief cells play a vital role in the initial stages of digestion by secreting enzymes that break down proteins and fats, which are essential processes in nutrient absorption and overall digestive health

Parietal Cell Receptors and Regulation of Acid Secretion

1. Acid secreting parietal cells regulated by chemical messengers: acetylcholine, histamine & gastrin (Soll's three receptor hypothesis).

2. ACh released at or near basolateral surface of cells from postganglionic neurons (neurocrine mechanism).

3. Gastrin released by G cells of antral mucosa and first part of duodenum into bloodstream which carries this hormone to the parietal cells (endocrine mechanism).

4. Histamine released from mast-like cells of lamina propria of oxyntic (acid secreting) mucosa into extracellular fluid and subsequently diffuses to the parietal cells (paracrine mechanism).

5. Most current textbooks refer to potentiation of acid secretion when 2 of these 3 agonists bind to their receptors simultaneously.

6. Recent evidence from Prof Rod Dimaline (Univ Liverpool) suggests the key final mediator of HCl secretion is mediated by gastrin acting on CCK2 receptors on enterochromaffin-like cells, which in turn release histamine, which then binds to H2 receptors on parietal cells (see powerpoint presentation).

7. Gastric juice is a complex solution of acidic component (HCl) from parietal cells and alkaline component containing pepsinogen from peptic cells & electrolytes such as Cl, Na, K from several cell types.

8. Parietal cells postulated to secrete hydrogen ions at constant concentration of ca. 150 mEq/L, variation of acid in juice depends on rate of non-parietal cell secretion of alkaline component.

9. Mechanism of H+ secretion against enormous gradient (high in canaliculi) requires energy (luminal H+-K+-ATPase), generated in oxyntic glands by aerobic metabolism.

10. ATPase theory suggests energy available from ATP hydrolysis transferred to protein carrier, moves proton against electrochemical gradient. In patients with peptic ulcers or acid reflux, inhibitors of the proton pump (omeprazole) or H2 receptors (cimetidine) provide valuable clinical therapy.

Phases of Gastric Acid Secretion

Acid secretion divided into basal (fasting) and stimulated (post-prandial) phases. 5 - 10% of maximal rate in man.

• Cephalic: activated by sight, smell, taste & chewing of food; mediated by efferent impulses through vagus fibres to stomach and abolished by vagotomy. Pavlov: "conditioned reflex can be established by appropriate pairing of an unconditioned stimulus, such as food, with a conditioned stimulus as a bell".

• Gastric: food enters stomach, distension and chemical composition of food factors evoking gastric phase of secretion. Distension of stomach stimulates reflex acid secretion without release gastrin: intramural and longer vago-vagal pathways.

• Intestinal: food entering intestine. Liver extract, peptone, amino acid mixtures effective stimulants of acid secretion. Acid secretion occurs after all extrinsic nerves between intestine and stomach severed but blood supply left intact. Intestinal acid, fat and hyperosmolar solutions inhibit acid secretion.

phases of gastric acid secretion

Gastric acid secretion occurs in three distinct phases: the cephalic phase, the gastric phase, and the intestinal phase. Each phase is triggered by different stimuli and involves various neural and hormonal mechanisms that regulate the secretion of hydrochloric acid (HCl) from the parietal cells in the stomach. Here's an overview of each phase:

### 1. Cephalic Phase

- Trigger: This phase is initiated by the sight, smell, taste, or even thought of food before it enters the stomach.

- Mechanism:

- Neural Control: The cephalic phase is primarily controlled by the central nervous system, specifically the vagus nerve. When food-related stimuli are perceived, the brain sends signals via the vagus nerve to the stomach.

- Release of Acetylcholine (ACh): The vagus nerve stimulates the release of acetylcholine (ACh), which binds to M₃ muscarinic receptors on parietal cells, leading to the secretion of HCl.

- Stimulation of Gastrin and Histamine: The vagus nerve also stimulates G cells in the stomach to release gastrin, which further stimulates acid secretion both directly and by inducing histamine release from enterochromaffin-like (ECL) cells. Histamine then binds to H₂ receptors on parietal cells, increasing acid secretion.

- Contribution: The cephalic phase accounts for approximately 30-40% of the total gastric acid secretion.

### 2. Gastric Phase

- Trigger: This phase begins when food enters the stomach, causing distension (stretching of the stomach walls) and chemical stimulation from food components, particularly proteins.

- Mechanism:

- Gastric Distension: The stretching of the stomach walls due to the presence of food activates stretch receptors, which send signals to the brainstem via the vagus nerve, leading to further stimulation of acid secretion through the same mechanisms as in the cephalic phase (release of ACh, gastrin, and histamine).

- Chemical Stimulation: Proteins and amino acids in the stomach stimulate G cells to release more gastrin. Gastrin is a potent stimulator of acid secretion, both by directly acting on parietal cells and indirectly by promoting histamine release from ECL cells.

- Local Reflexes: The presence of food in the stomach also activates local enteric reflexes that further stimulate the release of gastrin and enhance acid secretion.

- Contribution: The gastric phase accounts for 50-60% of the total gastric acid secretion.

### 3. Intestinal Phase

- Trigger: This phase is initiated as partially digested food (chyme) begins to enter the small intestine, particularly the duodenum.

- Mechanism:

- Stimulation: Early in this phase, the presence of peptides and amino acids in the duodenum can cause a small, brief increase in gastrin release, which slightly stimulates acid secretion.

- Inhibition: The primary role of the intestinal phase is inhibitory, serving as a feedback mechanism to slow down acid secretion as the chyme leaves the stomach.

- Enterogastric Reflex: Distension of the duodenum, along with the presence of acidic chyme, triggers the enterogastric reflex, which inhibits vagal stimulation and reduces acid secretion.

- Hormonal Inhibition: The duodenum releases hormones such as secretin, cholecystokinin (CCK), and gastric inhibitory peptide (GIP) in response to the presence of acidic chyme, fatty acids, and hyperosmolar content. These hormones inhibit gastric acid secretion by directly acting on the stomach or by reducing gastrin release.

- Contribution: The intestinal phase accounts for only a small percentage of acid secretion and is more focused on reducing acid output as digestion proceeds into the intestines.

### Summary of Phases

- Cephalic Phase: Initiated by sensory input (sight, smell, taste) before food enters the stomach; controlled by the vagus nerve; accounts for 30-40% of acid secretion.

- Gastric Phase: Triggered by the presence of food in the stomach, causing distension and chemical stimulation; involves neural reflexes and gastrin release; accounts for 50-60% of acid secretion.

- Intestinal Phase: Begins when chyme enters the duodenum; initially provides a small stimulatory effect but primarily inhibits further acid secretion to regulate digestion; accounts for a minor portion of acid secretion.

These phases ensure that gastric acid is secreted in a controlled manner, optimized for the digestion of food while protecting the stomach lining and regulating the digestive process as it moves into the intestines.