Unit VI- Salivation and Gastric Function Flashcards
1
Q
Hormones
A
- peptides released from endocrine cells of the GI tract
- they are secreted into the portal circulation, pass through the liver and enter the systemic circulation
- the circulation delivers the hormones to their target cells (e.g parietal cells in the stomach in the case of gastrin)
2
Q
Paracrines
A
- secreted by endocrine cells of the GI tract
- they act locally in the same tissue that secretes them
- somatostatin is a paracrine peptide; histamine is not a peptide
3
Q
Paracrine control in GI system
A
1) Serotonin: produced by enterochromaffic cells (EC) in intestine in response to distension ; indirectly excites the ENS to increase motility and secretions
2) Somatostatin: produced by D cells and is a potent inhibitor of several processes (pancreatic and gastric secretions, motility); cam act in an endocrine as well as paracrine manner
3) Histamine: released by EC-like cells in stomach; potently stimulates HCl secretion ( H2 receptors)
4
Q
Neurocrines
A
- synthesized in neurons in the GI tract and released following an action potential
- after release, they diffuse across the synaptic cleft and act on the target cell
- examples include ACh, Norepi, VIP, gastrin-releasing peptide (GRP) and substance P
5
Q
GI hormones
A
- peptides released from cells scattered throughout the GI tract
- with the ANS and paracrine factors, they participate in an integrated response that promotes the digestion and absorption of food
6
Q
Gastrin
A
- secreted by antral mucosa cells ( G cells in stomach) in response to food, distension, vagus
- acts to increase acid secretion by parietal cells
- stimulates growth of gastric mucosa
7
Q
Cholecystokinin/CCK
A
- secreted by mucosa of intestine (I-cells in duodenum and jejunum) in response to fats and proteins/peptides/amino acids
- acts to increase gall bladder contraction, and increase pancreatic enzyme and bicarbonate secretion (e.g. trypsin, chymotrypsin, lipases, amylases)
- inhibits gastric emptying
8
Q
Secretin
A
- secreted by mucosa of small intestine (S-cells in duodenum) in response to the arrival of acidic chyme from the stomach
- acts to increase bicarbonate (HCO3-) and fluid secretion by pancrease
- decreases gastric acid secretion in stomach by decreasing gastrin
- inhibits gastric emptying
9
Q
Motilin
A
- secreted by mucosa of small intestine ( M cells in duodenum and jejunum) during the fasting period
- promotes contractions in distal stomach and intestines to clear the tract of indigestible materials
10
Q
Glucose-dependent insulinomic peptide (GIP)
A
- secreted by mucosa of small intestine (K cells in duodenum and jejunum) in response to fat and carbohydrates
- acts on pancreas to stimulate insulin secretion, inhibits HCl secretion by parietal cells
11
Q
Digestive Enzymes
A
- ingested food and liquid must be converted to a form that can be absorbed by the small intestine. The process of digestion requires the action of multiple enzymes
- for carbs and lipids digestion in mouth by salivary and lingual enzymes: amylase for carbs and some lipase for lipids
- for proteins, digestion initiated in stomach by gastric proteases called pepsin. Additional lipid digestion with swalloed lingual lipase, and some gastric lipase is also secreted.
- small intestine pancreatic enzymes such as lipase (lipids), chymotrypsin (protein), amylase (carbs)
- enzymes on luminal surface of small intestine (brush border disaccharidases and dipeptidases complete digestion of carbs and proteins (membrane digestion)
12
Q
Salivon
A
- physiological secretory unit,similar in structure to the pancrease
- 1.5L saliva is secreted per day
- acinar cells of the parotid glands secrete a serous substance rich in alpha mylase, 25% of saliva
- acinar cells of the sublingual (5%) and submandibular (70%( secrete a seromucous product rich in mucin glycoproteins
13
Q
Lubrication functions of saliva
A
- moistening the mouth to prevent dehydration or the oral mucosa
- lubricating the food to aid in swallowing. It depends on the presence of mucous in saliva
14
Q
Protective functions of saliva
A
- saliva flow across the teeth helps to clear bacteria
- saliva contains substances that reduce bacterial growth (lysozyme, IgA-binding protein)
15
Q
Digestive functions of saliva
A
- relatively minor
- salivary amylase (ptyalin) is identical to pancreatic amylase
- ptyalin converts starch to sugar at pH optimum of 7; denatured below pH 4 in stomach
- lingual lipase hydrolyzes triglycerides and is secreted by small salivary glands on the tongue surface
16
Q
Sjogren syndrome
A
-chronic and progressive autoimmune disease that destroys the salivary and lacrimal glands
17
Q
Xerostomia
A
- dry mouth
- results from inadequate saliva production and typically leads to difficulty speaking due to poor lubrication and dental caries and halitosis due to bacterial overgrowth
18
Q
Transport of saliva
A
- at low (basal) flow rates, Na+ and Cl- are absorbed and K+ is secreted by the duct cells of most salivary glands= K+-rich, hypotonic salivary secretion at rest
- the tightness of the ductal epithelium inhibits paracellular water movement contributing to the hypotonic product
- at high flow rates, saliva is more like plasma (because the ductular transport processes have limited capacity to handle the increased load)
- High HCO3 makes saliva more alkaline, neutralize gastric acid
- aldosterone is only humoral agent to affect salivation, stimulating Na+ reabsorption and K+ secretion by the salivary glands
19
Q
Salivary Acinar Cells
A
- during salivary secretion, blood flow to the acini is increased by PNS stimulation and ultrafiltrate from plasma (mostly serous fluid) enters the acini
- filtrate from the cells enters the lumen of the acinar cells mixing with secreted mucus and alpha amylase creating primary secretion
- the secretion is modified as it passes through the ducts into the mouth
- lingual lipase (secreted from the Von Ebner’s glands of the tongue) is added to the saliva in the mouth
-mouth K+ stays pretty constant with flow of saliva, Na and Cl increase a lot, HCO3-
20
Q
ANS and Salivary
A
- salivary secretion is unaffected by gastrointestinal hormones and is controlled by autonomic innervation
- PNS- increased and sustained salivary secretion in which flow is increased 10x over the basal rate
- SNS- causes a lesser and more transient stimulation, sympathetic nerves originate from the superior cervical ganglia and travel along the surfaces of the blood vessel walls to the salivary glands
- activation of salivary glands causes release of kallikrein, resulting in the production of the potent vasodilator bradykinin from its precursors; vasodilation increases capillary hydrostatic pressure and capillary filtration, thereby supplying the fluid for secretion
- salivation reflex can be conditioned (Pavlov)
21
Q
Salivary nuclei
A
- located near the junction of the medulla and pons and are excited by taste and tactile stimuli from the tongue and other areas of the mouth and pharynx
- many taste stimuli, especially sour taste (caused by acids) elicit copious secretion of saliva- often 8-20 times the basal rate
- certain tactile stimuli, such as smooth objects in the mouth (pebble) caused marked salivation, whereas rough objects cause less salivation and may inhibit salivation
22
Q
Salivation and nervous signals
A
- can be stimulation or inhibited by nervous signals arriving in the salivatory nuclei from the higher centers of the CNS (smells or eating fav foods stimulates salivation compared to unappetizing foods)
- appetite area of the brain, which partially regulates these effects, is located in proximity to the parasympathetic centers of the anterior hypothalamus and it responds to signals from the taste and smell area, and it responds to signals from the taste and smell areas of the cerebral cortex or amygdala
23
Q
Salivation and reflexes
A
- reflexes originating in the stomach and upper small intestines- particularly when irritating foods are swallowed or when a person is nauseated because of some gastrointestinal abnormality
- saliva, when swallowed, helps to remove the irritating factor in the gastrointestinal tract by diluting or neutralizing the irritant substances
24
Q
Gastric juice
A
- the body of the stomach contains oxyntic glands that empty their secretory products via ducts into the lumen.
- duct opens are pits that contain parietal cells and chief cells
- the antrum of the stomach contains pyloric glands, oxynic glands but with deeper pits, contain G cells and mucus cells
25
Oxyntic glands
- tubular glands on stomach mucosa
- acid forming glands located on the inside surfaces of the body and fundus of the stomach in the proximal 80% of the stomach
- mucous neck cells secrete mainly mucus, peptic (or chief) cells secrete pepsinogen and gastric lipase, parietal (or oxyntic) cells secrete hydrochloric acid and intrinsic factor (essential for absorption of vitamin B12 in the ileum)
- when parietal cells are destroyed (chronic gastritis) the individual develops achlorhydria (lack of stomach acid secretion) and often pernicious anemia due to failure of maturation of the RBCs in the absence of the vitamin B12 stimulation of the bone marrow
26
Pyloric glands
- secrete mucus for protection of the pyloric mucosa from the stomach acid
- they also secrete the hormone gastrin (G cells) and the endocrine and paracrine factor somatostatin (D cells)
- the pyloric glands are located in the antral portion of the stomach (the distal 20%)
- the pyloric glands are structurally similar to the oxyntic glands but contain few peptic cells and almost no parietal cells
- have mostly mucus cells = mucous neck cells of oxyntic glands
- mucus-secreting cardiac glands in a limited area near the esophageal orifice
27
Pepsin
- pepsins are proteolytic enzymes that attack the internal peptide bond in proteins
- pepsinogens secreted from oxyntic (and some from pyloric glands) is stimulated by the vagus and ENS
- pepsins digest the protein collagen present in connective tissue in meats. Thus, individual who lack pepsin in stomach juices digest meats poorly
28
Activation of the pepsinogens to pepsins
- at pH values from 5 to 3, pepsinogens spontaneously activate to pepsins by the removal of an N terminal (activation peptide)
- this spontaneous activation is even faster at pH values that are below 3
- the newly formed pepsins themselves which are active only at pH values below 3.5 can catalyze the activation of pepsinogens
29
Digestion of proteins in the stomach
- initiated in the stomach to produce proteoses, peptones and some polypeptides
- primarily in intestines through pancreatic proteolytic enzyme secretion
- HCl is secreted by parietal cells at pH of 0.8 but mix with stomach contents to 2-3 (favorable for pepsin)
30
Alkaline mucus layer
- mucus secreted by surface cells as diffusion barrier for H+ and pepsins
- mucus layer also traps HCo3-, titrates H+
- inactivates pepsin
- if H+ penetrates gastric epithelium it damages mast cells -> increase blood flow promote production of mucus and HCO3-
- if insult too big decrease blood flow and there is cell injury
31
Erosive gastritis
- result from chronic use of NSAIDS, inhibit prostaglandin synthesis in the stomach
- prostaglandin is supposed to be the physiochemical barrier by stimulating the secretion of mucus and HCO3-
32
HCl secretion
- H+-K+ ATPase in luminal membrane
- CO2 -> H2CO3 -> H+ and HCO3- -> H+ is secreted with Cl- in the lumen of the stomach
- HCO3- across basolateral membrane into extracellular fluid for Cl- which enter cell and secreted through Cl channels into the canaliculus (lots HCl)
- apical membrane: H+ secreted into lumen in exchange for K+ via H+-K+ ATPase, Cl- follows by diffusing through Cl- channels
- at basolateral membrane, HCO3- absorbed from cell into the blood via a Cl- -HCO3- exchanger
33
Parietal Cell HCl Production
- the apical H+/K+ ATPase (proton pump) causes the active secretion of H+ into the lumen of the gastric pits
- the H+/K+ ATPase is the target for proton pump inhibitors to decrease gastric acid release in patients with GERD or ulcers
34
Vomiting center
- in medulla oblongata
- stimuli for vomiting also induces salivation and retching
- reverse peristalsis occurs from the mid-small intestine to the pylorus which relaxes to allow chyme to enter the stomach
- stomach fills and strong abdominal contractions force gastric contents to esophagus, causing retching
- further stimulation leads to relaxation of UES and expulsion of contents through the mouth
35
Stimuli that initiate the vomiting
- irritants in stomach or small intestine, enteric virus or bacteria
- systemic irritant sensed by chemoreceptor trigger zone in 4th ventricle of brain
- head injury (concussion) a central effect
- abnormal stimulation of vestibular organs (central effect via ANS to chemoreceptor trigger zone, then to vomiting center)
36
Effects of vomiting
- leads to a disproportionate loss of H+, Cl-, and K+ as well as loss of fluid from the extracellular space
- prolonged vomiting results in dehydration, alkalosis, and hypokalemia (low plasma K+)
- impaired renal function can also lead to azotemia (elevated urea and creatinine in the blood)
37
Stimulators of acid secretion
- Histamine- from ECL cells, diffuses through the mucosa to act on adjacent parietal cells
- the vagus- via direct and indirect effects
- gastrin- carried through the blood, acts directly on parietal cells + stimulates histamine release
- insulin- carried through the blood acts directly on parietal cells and promotes HCl secretion
- Caffeine- phosphodiesterase inhibitor) increases cAMP in the parietal cells, increasing proton pump activity
- stress- increases acid secretion and cofactor in ulcer formation
38
Inhibitors of acid secretion
- somatostatin- released from endocrine cells in the gastric pits, acts in a paracrine manner on the parietal cells, as well as on G-cells to inhibit gastrin
- glucose insulinotropic peptide or gastric inhibitory peptide (GIP), released from the duodenum and jejunum, acts directly on the parietal cells
- secretin- releases from the duodenum and jejunum, acts at the G cells to suppress gastrin
39
Vomiting center
- in medulla oblongata
- stimuli for vomiting also induces salivation and retching
- reverse peristalsis occurs from the mid-small intestine to the pylorus which relaxes to allow chyme to enter the stomach
- stomach fills and strong abdominal contractions force gastric contents to esophagus, causing retching
- further stimulation leads to relaxation of UES and expulsion of contents through the mouth
40
Stimuli that initiate the vomiting
- irritants in stomach or small intestine, enteric virus or bacteria
- systemic irritant sensed by chemoreceptor trigger zone in 4th ventricle of brain
- head injury (concussion) a central effect
- abnormal stimulation of vestibular organs (central effect via ANS to chemoreceptor trigger zone, then to vomiting center)
41
Effects of vomiting
- leads to a disproportionate loss of H+, Cl-, and K+ as well as loss of fluid from the extracellular space
- prolonged vomiting results in dehydration, alkalosis, and hypokalemia (low plasma K+)
- impaired renal function can also lead to azotemia (elevated urea and creatinine in the blood)
42
Cephalic phase
- stimuli for HCl secretion in the cephalic phase are smelling, tasting, and conditioned reflexes
- HCl is secreted by direct stimulation of the vagus nerve (Ach receptor on parietal cell) and also indirect stimulation fo the parietal cell by gastrin
- vagus releases Gastrin Releasing Peptide (GRP) onto G cells, releasing gastrin
- gastrin enters the circulation (hormone) and stimulates the parietal cells to produce HCl
- 30%
43
Inhibitors of acid secretion
- somatostatin- released from endocrine cells in the gastric pits, acts in a paracrine manner on the parietal cells, as well as on G-cells to inhibit gastrin
- glucose insulinotropic peptide or gastric inhibitory peptide (GIP), released from the duodenum and jejunum, acts directly on the parietal cells
- secretin- releases from the duodenum and jejunum, acts at the G cells to suppress gastrin
44
Receptors and signal transduction pathways in the parietal cell
- has separate receptors
- ACh and gastrin bind M3 and CCKB that are coupled to the G protein G-alpga-q -> activate protein kinase C (PKC) and release of Ca2+
- histamine binds H2 receptor coupled to G alpha S to adenylyl cyclase -> production of cAMP and activation of PKA
- somatostatin and prostaglandins bind to separate receptors that are linked to G-alpha-I (oppose histamine)
45
H2 receptor antagonists
- cimetidine
- effective as OTC antacid agents because of strong cooperativity of ACh, gastrin, and histamine in stimulating HCl production
46
Proton pump inhibitor
-omeprazole/prilosec- are even more effective than histamine receptor antagonists because they block the final common pathway
47
Cephalic phase
- stimuli for HCl secretion in the cephalic phase are smelling, tasting, and conditioned reflexes
- HCl is secreted by direct stimulation of the vagus nerve (Ach receptor on parietal cell)
48
Gastric phase
- stimuli distension of the stomach and the presence of breakdown products or proteins (amino acids, small peptides)
- direct and indirect vagal effects plus distension of antrum activates local reflexes to enhance gastrin release plus amino acids and small peptides stimulate G cells to release gastrin
- 60%
49
Intestinal phase
- 10% of acid secretion
- mediated by products of protein digestion
- HCl secretion inhibited when no longer needed for activation of pepsinogen, or through somatostatin
50
Overview of gastric secretions
- corpus of stomach- vagus directly stimulates parietal cells via ACh and also stimulates ECL cells(increased histamine release) and D cells (decreased somatostatin release)
- antrum- vagus stimulates both G cells and D cells
- vagus stimulates the G cells via GRP (gastrin releasing peptide), promoting gastrin release -> directly via parietal cell and indirectly via the ECL cell which releases histamine
- vagal stimulation of D cells via ACh inhibits release of somatostatin which would inhibit release of gastrin from G cells and by endocrine mechanism acid secretion by parietal cells
- luminal H+ directly stimulates the D cells to release somatostatin- neg feedback
- products of protein digestion directly stimulate G cells to release gastrin which stimulates gastric acid secretion (pos feedback)
