Lecture 5 - Secretions I Flashcards
10 hormones secreted by the GIT?
- Gastrin
- Secretin
- CCK
- Gastric inhibitory peptide
- Motilin
- Glucagon-Like Peptide (GLP)-1
- Peptide YY
- Ghrelin
- Histamine
- Somatostatin
Site of secretion of gastrin?
G-cells of antrum and duodenum
6 general actions of gastrin?
- Stimulates gastric H+ secretion by parietal cells
- Stimulates antral motility
- Stimulates effective gastric emptying
- Inhibits gastric emptying by maintaining the tone of the pyloric sphincter
- Stimulates gastric mixing
- Stimulates lower GIT motility
4 primary stimuli of gastrin? Which ones are duodenal?
- Stretch
- Peptides**
- AAs**
- Vagus nerve release of gastrin release peptide (GRP)
Site of secretion of secretin?
S-cells of duodenum
3 general actions of secretin?
- Stimulates pancreatic, biliary, and intestinal secretions of buffers, electrolytes, and enzymes
- Inhibits gastric H+ secretion by inhibiting gastrin secretion
- Inhibits gastric emptying by maintaining the tone of the pyloric sphincter
2 primary stimuli of secretin?
- Acidic chyme**
2. Long chain FAs**
Site of secretion of CCK?
I-cells of the duodenum and jejunum
7 general actions of CCK?
- Stimulates pancreatic enzyme secretion
- Contracts gallbladder
- Relaxes sphincter of Oddi
- Inhibits gastric emptying by maintaining the tone of the pyloric sphincter
- Stimulates bile production by liver
- Lower GI motility
- Stimulates chief cells
3 primary stimuli of CCK? Which ones are duodenal?
- Small peptides**
- AAs**
- Fats**
Site of secretion of GIP?
Duodenum and jejunum
Other name for gastric inhibitory peptide?
Glucose insulinotropic peptide
4 general actions of GIP?
- Stimulate pancreatic insulin secretion
- Inhibit gastric H+ secretion and gastrin secretions at HIGH physiologic levels
- Inhibit gastric mixing
- Inhibit gastric emptying by maintaining the tone of the pyloric sphincter
3 primary stimuli of GIP? Which ones are duodenal?
- FAs**
- Glucose**
- AAs**
Site of secretion of motilin?
M-cells of duodenum
General action of motilin?
Stimulates phase III of MMC
Primary stimulus of motilin?
Fasting
Site of secretion of GLP-1?
L-cells of mainly jejunum, and lower small intestine
Site of secretion of peptide YY?
Jejunum and ileum
General action of both GLP-1 and peptide YY?
Inhibit hypothalamic secretion of NPY => satiety
Primary stimulus of GLP-1 and peptide YY?
Chyme
Site of secretion of ghrelin?
Oxyntic cells of stomach = parietal
General action of ghrelin?
Stimulate hypothalamic secretion of NPY => hunger
Primary stimulus of ghrelin?
Fasting
What regulates both thirst and feeding?
Hypo
Describe the 4 steps of thirst.
- Failure to ingest/absorb enough fluid OR excessive fluid loss
- Decreased extracellular volume = hypovolemia => plasma hypertonicity (~2% increase)
- Decreased firing of baroreceptors and increased hormones (angiotensin II, ADH, aldosterone) stimulate thirst center => thirst response of cerebral cortex
- Ingestion of fluids => increased blood volume and decreased plasma osmolarity
What nucleus of hypo secretes NPY?
Arcuate nucleus
Other than GIT hormones, what other hormone regulates hunger and satiety?
Lepin produced by adipose and other tissues inhibits hypo secretion of NPY => satiety
What does NPY stand for?
Neuropeptide Y
What do we call hormones that stimulate hunger?
Orexigenic hormones
3 paired glands that secrete saliva? List in order of % saliva secretion. What kid of fluid does each secrete?
- Submandibular glands: mixed serous/mucous fluid
- Parotid glands: serous fluid with amylase
- Sublingual glands: mucous fluid
Describe the tonicity of saliva compared to plasma and the ion concentrations.
Saliva is ALWAYS hypotonic to plasma, at ANY flow rate through the salivary duct:
- Na+, Cl-, HCO3- all higher in plasma
- K+ higher in saliva (20 mEq vs 5)
Effect of parasympathetic innervation of salivary glands?
Increase blood flow to the glands
2 types of glands? What differentiates them?
- Endocrine glands secrete in blood
2. Exocrine glands secrete in ducts
2 types of exocrine glands of the GIT?
- Salivary glands
2. Pancreatic exocrine glands
Describe the secretion of saliva by salivary glands.
- Fluid passes from blood to cells of the gland = serous solution with electrolytes and small peptides or AAs = isotonic ultrafiltrate
- Acinar cells (aka serous cells) can produce mucous and/or enzymes and add them to the saliva = primary secretion
- Transcobalamin I, a protein carrier that binds vitamin B12 (essential vitamin) is added to the saliva
- As saliva passes through the salivary striated ducts, modifications to its ionic content are made depending on the rate of flow (reabsorption of Na+, Cl-, and HCO3-)
- Myoepithelial cells contract
Role of amylase?
Starch digestion
Role of lingual lipase?
Lipid digestion
What is vitamin B12 important for?
Maturation of RBC
Consequence of lack of vitamin B12? 2 names
Pernicious anemia = megaloblastic anemia
Why is transcobalamin I necessary?
Because VB12 will be absorbed later in the GIT so needs to be protected along the way
2 other names for transcobalamin I?
R proteins = R-binders
What is the rule of thumb about absorption?
Faster flow => decreased absorption
What happens if the chyme is hypertonic in the small intestine?
Gastric emptying will be slowed while tonicity is decreased with water
Which parasympathetic nerves control salivary flow?
- Facial nerve to submandibular and sublingual glands
2. Glossopharyngeal nerve to parotid glands
What happens to the salivary glands if we severe the facial and glossopharyngeal nerves?
They will atrophy
7 factors that increase salivary flow?
- Parasympathetic innervation with ACh and VIP release
- Cephalic phase by CNS
- Nausea
- Esophageal distention
- Chewy and flavorful foods
- Dry acidic and alkaline foods
- Meats, sweets, and bitter foods
6 factors that decrease salivary flow?
- Sympathetic innervation with NE release
- Hormones: ADH and aldosterone
- Sleep
- Dehydration
- Drugs
- Aging
3 drug examples that decrease salivary flow?
- Barbituates
- Chemotherapies
- Amphetamines
7 roles of saliva? Describe each.
- Increases the taste of food because breaks it down and moistens it so it interacts more with taste buds
- Digestion of starch and lipids
- Lubrication of food with mucin and water
- Coagulation action with factors and platelet-activating factor (PAF)
- Antimicrobial action: physical removal, WBCs, opsonins, dimeric IgA, lactoferrins
- Protection: reduces food temperature, buffers, protects stomach
- Oral hygiene: buffers, cleansing
10 gastric secretions?
- Hydrochloric acid, HCl
- Intrinsic factor
- Pepsins
- Gastric lipase
- Mucus
- Histamine
- Somatostatin
- Gastrin
- Serotonin
- Ghrelin
3 roles of HCl secreted by stomach?
- Gross breakup of food
- Kills bacteria
- Converts pepsinogens to pepsins
What gastric cells secrete HCl?
Parietal cells
What gastric cells secrete intrinsic factor?
Parietal cells
Role of intrinsic factor secreted by stomach?
Protects vitamin B12 from pancreatic and gastric proteases by binding on another site of B12 than the one where transcobalamin 1 from saliva is bound
What gastric cells secrete pepsins? How?
Chief cells secrete them as pepsinogens, which are then activated by the low pH of the stomach
Where does carb digestion start?
Mouth
Where does protein digestion start?
Stomach
Where does lipid digestion start?
Mouth
What gastric cells secrete gastric lipase?
Chief cells
What kind of molecules do chief cells secrete?
Enzymes
Purpose of mucus secreted by the stomach?
- Protect the gastric epithelium from low pH = cytoprotection
- Lubricates food
- Buffering with HCO3- content
Role of histamine secreted by stomach?
Potent acid that stimulates HCl secretion by the parietal cells
What gastric cells secrete histamine?
Enterochromaffin-like cell
3 roles of somatostatin secreted by stomach? Overall?
LOCAL action
- Inhibits HCl secretion by the parietal cells
- Inhibits gastrin secretion by G-cells
- Inhibits histamine and serotonin secretion by ELC
Where do most of the secretions of the stomach occur?
Body of stomach
Describe the process of HCl production by the parietal cells of the stomach. What is the rate-limiting step?
- Stimulation of parietal cell causes tubular vesicles to open to increase surface area for secretion
- ***H+-K+ ATPase proton pumps insert on the tubular vesicles
- Pumps push H+ out (generated by CO2 metabolism) until concentration is 10^6 x more on the outside of the parietal cell and takes K+ in
- Basolateral HCO3-/Cl- exchanger with capillary takes in Cl- into parietal cell to be pumped out of the cell on the lumenal side through electrogenic channels => HCl production AND releases HCO3- generated by carbonic anhydrase in the parietal cells into the capillary
- Excess K+ leaks out the cell down its concentration gradient => KCl production also contributes to acid of the stomach
What is special about the parietal cells of the stomach? How long does this take?
Their morphology changes between their stimulated and non-stimulated state (10 min)
Which is a weaker acid: HCl or KCl?
KCl
Describe the pH of the blood draining from an actively secreting stomach? What do we call this?
Alkaline pH => alkaline tide from stomach
What do the drugs regulating gastric acid target? Examples?
- Block the proton pumps on the lumen of the parietal cells of the stomach: omeprazole
- Block the action of histamine at the histamine H2 receptors of the parietal cells in the stomach: H2 receptor antagonist: cimetidine or rantidine
How does chronic vomiting affect electrolyte levels in the body?
The following will be lost:
- HCl mainly, leading to alkalemia
- Some K+, potentially leading to hypokalemia
What is the hormone ghrelin considered the counterpart to?
Leptin
Other name for amylase?
Ptyalin
Is HCO3- only absorbed in the salivary ducts?
NOPE, also some secretion
Effect of ADH on salivary glands?
Increases water absorption by salivary ducts => concentrates saliva
Effect of aldosterone on salivary glands?
Increases K+ secretion and Na+ resorption in/out of saliva
Where are WBCs found in the GIT?
WBCs traverse the entire GI tract (mouth to rectum): they extravasate from capillaries through tissue epithelium into the lumen and also seep out through the gingival crevices!
Why does sympathetic stimulation of salivary glands causes an initial small and brief secretion?
Because it constricts the myoepithelial cells, which spits out their contents, but then don’t secrete much more
3 unique properties of saliva?
- Large volume relative to gland size
- Low osmolality
- Relatively high K+ concentration (compared to plasma)
Describe esophageal secretions.
Minor serous and mucous glands primarily in lower segment to lubricate the bolus
What’s the difference between mucous, mucus, and mucin?
Mucous glands secrete mucus which is bicarbonate-rich to buffer and lubricate the GI tract; mucins are glycoproteins which help to form the viscosity of the mucus
What is the only INDISPENSABLE gastric secretion?
Intrinsic factor
Where does intrinsic factor bind B12 mainly?
Duodenum
When is transcobalamin I cleaved from B12? By what?
By trypsin in duodenum
What are the main secretory cell types in the gastric pit and their products?
- Surface mucous cells: mucus secretion for protection, replace cells in the lumen after desquamation
- Mucous neck cells: mucus secretion for protection, progenitors of other cells lower in pit
- Parietal cells: HCl, intrinsic factor, and ghrelin
- Chief cells: pepsinogens, gastric lipase
- Endocrine cells: gastrin (G-cells), somatostatin (D-cells)
- Enterochromaffin-like cells (ECL): secretions act locally! histamine, serotonin
What are the 3 types of regulation of gastric secretions? Describe each.
- Endocrine: gastrin (HCl), secretin (gastrin), GIP (HCl), CCK (pepsinogens)
- Paracrine: somatostatin (HCl), histamine (HCl)
- Neural: vagal ACh and GRP
Is parietal cell production of HCl under intrinsic or extrinsic control?
Intrinsic
What % of body serotonin is secreted by gut ECL cells?
90%
Role of serotonin in GIT?
Vasoactive neuropeptide that has vasoconstrictor actions in the intestines that are associated with peristalsis
Other than ECL cells, what other cells secrete histamine in GIT?
Mast cells
What is an antiemetic? Example?
Drug that is effective against vomiting and nausea
5HT antagonists are useful as anti-emetics
What bacteria is HCl not antibactericidal against? Effect? What to note?
Helicobacter pylori: gram negative bacteria that can be present in the gastric mucosa
- It secretes urease that produces ammonia, which neutralizes the H+ (making NH4+) around the bacteria, and allows it to live adjacent to the gastric mucosa
- It produces a mucinase which disrupts the mucus/bicarbonate barrier so acid and inflammation then causes ulcerations as the acid can access the epithelial cells causing erosion
A critical amount of H. pylori is needed to have the damaging effects, and that is why not everyone with H. Pylori has ulcers…however it is clear that this bacteria accounts for 90% of non-NSAID associated gastric ulcers and 100% of non-NSAID duodenal ulcers
What is Chief cell pepsinogen production stimulated by?
- Vagus
- Gastrin
- Histamine
- Secretin
- CCK
How is the helicobacter pylori transmitted?
Fecal-oral
Treatment for helicobacter pylori infection?
- Long-term antibiotic treatment
2. Proton pump inhibitor or H2 antagonist
3 types of regulation of HCl secretion in stomach? Describe each.
- Endocrine: gastrin (stimulates), GIP (inhibits) act directly on parietal cells; secretin, peptide YY act indirectly by suppressing gastrin secretion by G-cells
- Paracrine: histamine (stimulates), somatostatin (inhibits), and prostaglandins (inhibit)
- Neural: vagal ACh inhibits D cells (somatostatin), stimulates parietal cells (HCl), mast/ECL cells (histamine to stimulate), and GRP on G cells (stimulate)
How do different compounds stimulate HCl gastric secretion?
Increase number of proton pumps on the parietal cell membrane
How can NSAIDs cause ulcers?
They suppress prostaglandin production, which are cytoprotectors of the stomach as they inhibit HCl secretion by parietal cells
Site of secretion of somatostatin?
D-cells in the antrum, the duodenum and the pancreatic islets
Is the action of gastrin local or systemic?
Systemic
Other than satiety promotion, what is peptide YY’s other roles?
Suppression of gastrin and pancreatic secretion
5 effects of vagal stimulation on gastric secretions?
- Stimulates HCl secretions of parietal cells
- Stimulates gastrin release by G-cells
- Stimulates histamine release by ELCs
- Inhibits somatostatin release by D-cells
- Stimulates chief cells to secrete pepsinogens
Purpose of gastric HCl breaking down food?
Increase surface area for digestive enzymes to access the food
What other enzyme can be added to saliva and does not come from the salivary glands?
Tongue Von Ebner’s glands can produce lingual lipase and add it to the saliva
What kind of molecule is transcobalamin?
Glycoprotein
In what form does VB12 enter the duodenum?
TC1-VB12-IF
What happens to VB12 absorption if gastric parietal cells do not work?
It is not absorbed because pancreatic proteases will chew it up in the duodenum
How to treat intrinsic factor deficiency?
VB12 shot every 1-2 months
How long will it take to deplete liver VB12 stores if ingestion is ceased?
1-2 months, which will then be stored by the liver
What causes vomiting?
Irritation of the upper GIT => reverse peristalsis
Does the vagus nerve stimulate ALL gastric secretions?
YUP
Why do we say that histamine is a paracrine secretagogue of HCl?
ECL cells are near G-cells and histamine diffuses in the interstitium to stimulate them
Does secretin stimulate buffer secretions all along the intestine?
YUP
Is HCl secretion by parietal cells mainly under extrinsic or intrinsic control?
Mainly intrinsic
Are the myoepithelial cells of the salivary glands also stimulated by parasympathetic innervation to contract or only adrenergic sympathetic fibers?
Only sympathetic
