Secretion I Flashcards

1
Q

Major flow in unstimulated
state comes from:

A

submandibular

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Major flow in unstimulated
state comes from:

A

parotid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

parotid VS sublingual VS submandibular VS minor salivary (% + type of secretion)

A

table slide 5!!!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

salivary gland anatomy:

A
  • Grape-like clusters of acini
  • Serous acinar cells largely supply
    proteinaceous components
    (enzymes), whereas mucous
    acinar cells secrete watery
    mucus.
  • Saliva makes its way through the
    acini, via intercalated and
    intralobular ducts.
    o Intercalated ducts are linked
    directly to the acini
    o Help to expel saliva and
    prevent backflow
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

secretory products of acinar cells:

A

o Proteinaceous components
* Digestive enzymes
* Lysozymes, antibacterial peptides
* Lactoferrin sequesters iron
* Secretory IgA
* Growth factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

secretory products of mucous acinar cells:

A

o Mucin (glycoproteins, viscoelastic)
o Water (1ml/min/g of gland tissue)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

secretory products of inorganic solutes:

A

Ca, Phosphates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q
  • ioni composition = similar to:
  • composition = modified by active transport:
A
  • plasma (electrolytes + salt)
  • because there is some additional reabsorption or secretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Constituents of saliva and their functions:

A

table slide 8

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Regulation of salivary secretion:

A
  • Almost entirely mediated by neural pathways.
  • Salivary glands are positively regulated by both the parasympathetic and
    sympathetic branches (this contrast with the reciprocal roles of these
    branches in other functions).
  • Parasympathetic has the predominant role on secretion and
    composition of saliva (quantitatively important).
  • Sympathetic modifies composition but has little effect on volume
  • GI hormones - not a major role on salivary secretion, but can influence
    composition of saliva. Eg. aldosterone increases the ability of the salivary
    ducts to absorb sodium ions.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

parasympathetic VS sympathetic roles in secretory glands:

A

table slide 10

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

muscarinic receptor def:

A

Muscarinic receptors mediate parasympathetic nervous system responses, which are typically rest-and-digest activities (slowing heart rate, increasing digestion, constricting pupils, etc.).
They respond to the neurotransmitter acetylcholine, which is released by nerve endings to influence organ functions.
Receptor Types:

There are five subtypes of muscarinic receptors, labeled M1 to M5. Each subtype has different functions and locations in the body:
M1: Found mainly in the brain and some glands, involved in memory and cognitive functions.
M2: Primarily in the heart, slows down the heart rate.
M3: In smooth muscles and glands, involved in contracting smooth muscles and stimulating gland secretion.
M4 and M5: Mostly in the brain, involved in regulating various neural activities.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

beta-adrenergic vs alpha def:

A

Beta-adrenergic receptors are a type of adrenergic receptor that respond to the neurotransmitters epinephrine (adrenaline) and norepinephrine (noradrenaline). These receptors are found in various tissues throughout the body and play a crucial role in the sympathetic nervous system (the “fight-or-flight” response).
- Alpha-adrenergic receptors:
Primarily found in smooth muscles of blood vessels, especially those in the skin, gastrointestinal system, kidneys, and brain.
Present in other tissues like the eye (influencing pupil dilation), and internal organs such as the bladder and prostate.
- Beta-adrenergic receptors:
Located primarily in the heart, lungs, blood vessels, skeletal muscles, and fat cells.
Different subtypes are found in specific locations: β1 in the heart, β2 in smooth muscles of the airways and blood vessels, and β3 in adipose (fat) tissue.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Control of Salivary Secretion-Neural:

A

slide 11
- the superior cervical ganglion = used during sympathetic to control (The SCG provides sympathetic innervation to many structures in the head and neck. Sympathetic innervation is responsible for the “fight-or-flight” responses, such as increasing heart rate, constricting blood vessels, and dilating pupils)
NE = norepinephrine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

VIP, IP3, cAMP roles:

A
  • VIP: (neurotrasnmitter/hormone) Vasodilation, smooth muscle relaxation, inhibits gastric acid secretion, stimulates intestinal secretion.
  • IP3: (messenger) Triggers calcium release from the endoplasmic reticulum, regulates smooth muscle contraction, and secretion.
  • cAMP: (messenger) Activates PKA, regulates metabolism, smooth muscle relaxation, heart rate increase, and gene expression.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Characteristics of saliva:

A
  • Concentrations of
    electrolytes vary with the
    rate of secretion, but it is
    always hypotonic.
  • Is always lower in sodium
    and chloride than plasma.
  • Is always higher in
    potassium than plasma.
  • Is rich in bicarbonate most
    of the time .
  • At very high rates of
    secretion its concentration
    resembles plasma’s.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Two-Stage Mechanism of Saliva Secretion:

A

Primary Secretion:

Produced by acinar cells.
Composition similar to plasma (isotonic), rich in Na⁺, Cl⁻, K⁺, and HCO₃⁻.
Contains water, enzymes (like amylase), mucins, and electrolytes.
Modification:

Occurs in the ducts, mainly in the striated ducts.
Sodium (Na⁺) and chloride (Cl⁻) are reabsorbed.
Potassium (K⁺) and bicarbonate (HCO₃⁻) are secreted.
No water reabsorption, resulting in hypotonic saliva.
- summary:
(* Composition changes from acini to ducts
* In acini same as plasma
* Na+ and Cl- are extracted
* K and bicarbonate added
* Loss of NaCl renders saliva hypotonic
* When secretion rate increases, tonicity rises)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Digestion and absorption in the oral cavity:

A
  • The salivary enzymes merely
    serve to begin the process,
    neither is essential to the
    digestion of food.
  • Amylase: begins catalysis of
    complex carbohydrates to
    oligosaccharides
  • Lipase: begins the biochemical
    breakdown of fat (important in
    infants)
  • No absorption of food occurs in
    the mouth.
    o Therapeutic agents such as
    nitroglycerin, etc. directly absorbed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Salivary pathophysiology:

A
  • Xerostomia (absence of saliva, dry mouth)
  • Sjogren’s syndrome (autoimmune - atrophy of the
    glands). Primary (drug use) or secondary
    development (radiation)
  • Tumors of the mouth and esophagus – excessive
    salivation
  • Cysts, mucocele
  • Parkinson’s disease – excessive salivation
  • Impaired salivation decreases oral
    pH
  • Tooth decay, esophageal erosions,
    difficulty lubricating and
    swallowing, poor nutrition,
    infections
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

stomach functional regions (cardia, fundus, antrum roles):

A

o Cardia is 5% of the gastric
surface, with transitional cell zone
o Fundus and body contains approx
75% of the gastric glands- so-
called oxyntic glands.
o Antrum contains glands that
secrete gastrin. Fulfills motility
functions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

secretion in stomach - functions:

A
  • Critical for absorption of Vit. B12 and
    non-heme iron.
  • The most characteristic secretory
    product of the stomach is hydrochloric
    acid.
  • Acidity begins digestion via simple
    hydrolysis.
  • The acid sterilizes the meal; maintains
    sterility of intestine.
  • Protects mucosa
  • Motility
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

gastric cell types:

A

slide 20
- pepsinogen = pepsin (enzyme for digestion) precursor
- EE cells ( secretes CCK) = digestion + motility + appetite
- ECL cells (secrete Histamine, stimulate acid secretion from parietal cells)
- G cells (gastrin) stimulates acid secretion + motility (après goes into blood stream)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Gastric cells, products & functions:

A

table slide 21

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Mucosal protection:

A
  • Throughout the stomach, the surface cells are covered with a layer of mucus.
  • The stability of the layer is additionally enhanced by the activity of small peptides, known as trefoil factors.
  • Bicarbonate ions are secreted into the base of the mucus layer that protects it from excessively low and potentially injurious pH.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Innervation:
* Vagal afferent conveys information from the dorsal vagal complex * It integrates with info coming from hypothalamus, to set the level of secretory function * Visceral inputs also contribute to gastric regulation via vagus  Output of taste receptors to the brain region (NTS) regulate secretion and other gastric functions  Activation of sympathetic nerves tends to oppose the parasympathetic limb  ENS coordinates local reflexes and conveys to CNS  DVC integrates gastric secretory function inputs  Gastric sensory nerves containing neurotransmitter calcitonin gene – related peptide (CGRP) participate in down regulation of acid secretion
25
ENS !!!! (little brain)!!!!!
The ENS consists of over 100 million neurons, organized into two main plexuses: Myenteric Plexus (Auerbach's Plexus): Located between the longitudinal and circular muscle layers of the gut wall, it primarily regulates motility (movement) of the intestines. Submucosal Plexus (Meissner's Plexus): Found in the submucosa, this plexus regulates glandular secretions and blood flow within the GI tract.
26
DVC:
The DVC is involved in regulating parasympathetic outflow to various organs, particularly those in the gastrointestinal tract, heart, and lungs. It helps maintain homeostasis by balancing the body’s stress responses with relaxation and restorative functions. (pr GI tract: functions of secretion and motility)
27
Regulation of gastric secretion:
 Neuronal reflexes contribute to both stimulation and inhibition of secretion.  Two type of reflexes control secretion: short reflexes (entirely within the ENS), and long reflexes (vago-vagal).  Acetylcholine mediates both short and long reflexes. Stimulates parietal, chief and ECL cells.  Gastrin releasing peptide (GRP) released by enteric nerves in vicinity of gastrin-containing G cells in the gastric antrum. (slide 25)
28
vagal activation stimulation:
slide 26!!!
29
neural regulation: gastric distention:
Stretch of the stomach wall increases acid secretion via both intrinsic reflexes and vago-vagal reflexes.
30
what is HCI?
HCl (hydrochloric acid) is an essential component of gastric juice in the stomach, playing a key role in digestion, protecting against pathogens, and facilitating nutrient absorption. Its secretion is regulated by hormones and neurotransmitters to ensure proper digestive function. - Parietal Cells Secrete HCl
31
Humoral regulation:
* Gastrin from antral G cells acts on ECL and parietal cells. * Gastrin is negatively regulated by somatostatin (antral D cells) (l'amoindrit) * Gastrin and Ach act on ECL cell to release Histamine (slide 28!!!)
32
humoral control:
parietal cell responses: *The tubulovesicular membrane is a storage site for the H+/K+ ATPase. Fusion of tubulovesicles to the apical membrane increases availability of the H+/K+ ATPase for H+ secretion. - Amplification of the apical surface area is accompanied by an increased density of H+, K+ ATPase molecules at this site. - Note that ACh and gastrin signal via calcium, whereas histamine signals via cAMP. The additive effects of Ach, Hist and gastrin potentiate acid secretion.
33
when intracellular canniculi fuse to the apical membrane, and the tubulovesicles fuse to the canniculi (des parois de l'estomac), what happens:
 Upon stimulation, the intracellular canniculi fuse to the apical membrane, and the tubulovesicles fuse to the canniculi, increasing the apical (luminal) membrane surface area 5-10 times.  Parietal cells also provide signals that controls proliferation and differentiation of other cell types, especially chief cells.  Increase in mitochondria mass (30-40% of cell’s volume)
34
gastrin, histamine, AcH secretion origin schémas (just as a reminder) + places of each cell:
slide 31 !!!
35
Direct and indirect actions of secretagogues on parietal cells (AcH, gastrin and histamin pr H+ secretion):
- direct pathway = gastrin + AcH + histamine = release of H+ in lumen - indirect pathway: gastrin + AcH stimulate ECL which stimulates H+ (slide 32)
36
ECL schéma to acid secretion (y a cAMP involved)
slide 33
37
Acetylcholine and Acid Secretion schema:
slide 34
38
Gastrin & Acid Secretion schema:
slide 35
39
HCI production:
* Parietal cells secrete H+ into gastric lumen by primary active transport, through H+/ K+ ATPase pump. * Parietal cell’s basolateral membrane takes in Cl- against its electrochemical gradient, by coupling its transport with HC03-. (slide 36)
40
Inhibition of Acid Secretion by Histamine Type 2 Receptor Antagonists (schema):
slide 37
41
inhibition of acid secretion (schema)
slide 38
42
prostaglandins, what they stimulate and what they inhibit: (+ example)
Prostaglandins Stimulate Blood Flow, Bicarbonate and Mucous Secretion, But Inhibit Acid Secretion MISOPROSTOL IS A PROSTAGLANDIN
43
what do NSAIDs block and what do they reduce
NSAIDs Block Cycloogenases And Reduce Prostaglandin Synthesis
44
Interaction of Neural and Chemical Regulatory Mechanism:
* Parietal cells have receptors for histamine, Ach (M3 and gastrin (CCK-2) * The neural and humoral mechanisms potentiate each other (synergism) * Histamine is released under combined effect of gastrin and Ach * The result: increased acid secretion
45
Control of HCl Secretion at the Parietal Cell Level: (how is HCI secretion controlled?)
* Ach, histamine and gastrin act as agonists of HCl secretion by distinct mechanisms. * Somatostatin, prostaglandins (PGE), epidermal growth factors (EGF) and transforming growth factors (TGF) act as endogenous antagonists of HCL secretion by inhibiting adenylyl cylase
46
Regulation of Secretion in the Interdigestive Phase:
* Between meals, stomach secretory products are low. * The basal secretion rate is under combined influences of histamine and Ach, released from ECL cells and nerve endings, respectively, tempered by the influence of somatostatin from fundic D cells. * Gastrin production is low (suppressed by a minimal pH 3 or bellow)
47
Regulation of Postprandial Secretion: (cephalic - gastric - intestinal phases)
Cephalic phase (10-30%) * mediated by vagus (DVC) & CNS * triggered by sight, smell, taste or even thought * Involves ENS>GRP&Ach>gastrin>parietal&chief cells Gastric phase (70-90%) * triggered by stomach stretch * chemical and mechanical sensing are involved. Intestinal phase (5-10%). * Triggered by presence of chyme, probably amino acids * Gastrin is suppressed (by somatostatin from D cells)
48
cephalic phase:
slide 47!!!
49
- Short and long reflexes further enhance secretory response by release of Ach either directly by parietal cells, or indirectly, by activating ECL cells, or GRP that activates G cells to release gastrin - The vago-vagal reflexes transmit info downstream to ready more distal segments of the intestine - Histamine from ECL cells influences both neurocrine and endocrine signals further amplifying secretion (slide 48) - Both Vago-vagal Reflexes and Gastrin Increase HCl and Pepsinogen Release.(slide 49!!!) - !! The ENS is also stimulated by distension!!
50
Intestinal phase:
* Out of stomach into duodenum. pH begins to fall * At pH 3, CGRP triggers somatostatin release from D cells in the gastric antrum, which acts on G cells to suppress gastrin release. * Somatostatin released form D cells in the oxyntic mucosa, or from nerve ending acts directly to inhibit secretory function.
51
Gastric digestion/absorption:
* Digestion: * Carbohydrates: the process of catabolizing carbohydrates continues in the body of the stomach (limited chemical, more mechanical) * Lipids: gastric lipase (acidic; fundic chief cells; limited digestion; important in infants) * Protein: digestion occurs in the antrum where it mixes with HCl and pepsin * Absorption: * Water (dehydration) * ETOH diffuses across the mucosa * Medication: aspirin weak acid, lipid soluble * Aminoacids * Vitamins (production of IF for B12) * Caffeine
52
Diffusion Barrier in the Gastric Mucosa
Protects Against Mucosal Damage (Ulcers) (slide 56)
53
Helicobacter pylori:
* Gram- bacillus colonizes antral mucosa & induces inflammation- inhibited release of somatostatin by D-cells; somatostatin inhibits gastric release * Damaged mucosa with H+ penetration into the gastric epithelium - a type of bacteria that is commonly found in the stomach. It is a gram-negative, spiral-shaped organism that is well-adapted to survive in the harsh acidic environment of the stomach. H. pylori is significant due to its association with various gastrointestinal diseases. - Gram negative bacteria – uses high urease activity to metabolize urea into NH4+ and is believed to be major cytotoxin
54
Atrophic gastritis:
* Chronic inflammation of the gastric mucosa, with injury and destruction of epithelial cell lineage, is seen in a number of GI infection (H.Pylori), or in absence of infection (Pernicious anemia). * Pernicious anemia is an autoimmune condition; patients develop antibodies to parietal cells and/or intrinsic factor. * Pernicious anemia is relatively rare; associated with other autoimmune disease such as Graves disease or thyroiditis.
55
Gastrinoma:
* Also known as Zollinger-Ellison (Z-E syndrome) * A rare disease affecting gastric secretory function. * An endocrine tumor- secrete large amounts of gastrin in an unregulated fashion. * The tumor cells are unaffected by the normal negative feedback mechanisms that reduce gastric release from G cells as the luminal pH falls, serum gastrin levels increase yet further.
56
succus entericus (intestine secretory products):
* An aqueous salt and mucus solution secreted by enterocytes in the crypts on Lieberkühn and mucous cells along the villi * Triggered by chyme * It provides lubrication and mucosal protection * Necessary for enzymatic hydrolysis
57
Small Intestine: Digestion/Absorption of Major Nutrients
slide 63 !!!
58
Absorption of other nutrients: (water-soluble vitamins, lipid, bile salts, minerals):
slide 64!!!
59
Intestinal Secretion: Standing Gradient Osmosis:
* Active Na+ pumping (Na/K ATPase) into lateral intercellular space * Passive entry of Cl- into lateral intercellular space * Establish osmotic gradient in lateral space * Entry of water by osmosis into lateral space * Hydrostatic flow of water
59
Absorption and Secretion in GIT (fluids)
o Total fluid in GI lumen ~2 L/day ingested and ~7L/day secreted o Small intestines absorb ~7 L/day and colon absorbs ~1.9 L/day o Balance of 100 ml/day lost in feces (slide 66)
59
Intestinal tight junctions:
 Transcellular vs. Paracellular transport ◦ Tight junctions connect epithelial cells of the GI tract. Tight junctions are leaky (the most in the duodenum) for water and ions. ◦ Transmucosal transport of water and ions can occur through tight junctions and lateral intercellular space (paracellular transport = 2) or through epithelial cells (transcellular transport = 1)
60
Intestinal absorption of Na+:
 Highest in jejunum (more than half). ◦ Enhanced with glucose, galactose, and neutral amino acids. ◦ Na+-nutrient symporter (SGLT1), Na+-H+ antiporter and Cl—HCO3- antiporter ◦ Basolateral membrane GLUT2 facilitates diffusion into blood  less Na+ absorption in ileum  Colon Na+ absorption enhanced by short chain fatty acids (SCFA)
61
Intestinal absorption of Cl- and HCO-3:
 Chloride uptake occurs via NKCC1 and exit via CFTR  In duodenum, HCO3- is secreted by antiporter; taken up by NBC1  In jejunum, both Cl- and HCO3- are absorbed in large amounts  In ileum and colon, Cl- reabsorption but HCO3- is secreted (antiporter)
62
Intestinal absorption of K+:
Active absorption and secretion only in colon * In jejunum and ileum, net absorption of K+ * With diarrhea, life threatening hypokalemia resulting in arrhythmias
63
Ion movement in the small intestine:
slide 72
64
regulation of water and electrolyte transport:
* General considerations: o Postprandial: passive absorption o Absorption of Na+ and Cl-, independent of nutrient uptake o Primary regulators: neurocrine, paracrine, immune * Neural: o Epithelial transport mediated by ENS nerve endings neurotransmitters o Ach, VIP-stimulatory, secrete Cl- o CNS control on secretomotor neurons o Vago-vagal reflexes: luminal contents, stretch receptor activation o Local stimulation by nutrients-release 5HT, cholinergic activation, Cl- release * Humoral-limited short term o PGE stimulate Cl- and bicarbonate o Histamine transient Cl- release * Luminal regulators: o Acute: Various apical receptors (e.g guanylin-regulates epithelial Cl- secretion in EEC; 5’-AMP, bile acids o Chronic: aldosterone increases transporters for Na absorption in colon; Ca, Fe transporters
65
Crypt Cells Secrete Electrolytes Leading to Water Secretion:
* Cl- enters the crypt epithelial cell by cotransport with Na+ and K+; Na+ is pumped back out via Na pumps, and K is exported * Activation of adenylyl cyclase by a secretagogues leads to generation of cyclic AMP. * Elevated intracellular cAMP activate CFTR, and secretion of Cl- into the lumen. * Accumulation of Cl- in the crypt attracts Na, pulling it into the lumen, across tight junctions - the net result is secretion of NaCl. * Secretion of NaCl into the crypt creates an osmotic gradient across the tight junction and water is drawn into the lumen.
66
Secretion and Absorption of Water and Ions: (normal VS infection):
slide 77
67
Large intestine secretion: (mucus & intestinal gas):
* Mucus: Secrete an alkaline, HCO3--rich mucus solution. o Lubricating the lumen, provides protection against mechanical and chemical injury. o HCO3- neutralize acids produced by the metabolism of resident bacteria. * Intestinal gas (flatus): o Methane and hydrogen sulfide produced from certain bacteria residing in the large intestine. o These gaseous secretion, plus ingested air during swallowing cause borborygmi. o Flatus is then expelled through the anus with voluntary contraction through the external anal sphincter
68
pathophysiology:
* Problems resulting from altered colonic absorption o Diarrhea: many problems arise in the small intestine o Constipation: prolonged retention of fecal matters that allows for the additional absorption of H2O (infrequent passing of stool) * Symptoms due to prolonged distention of rectum, and are removed following its evacuation * Causes: voluntary, decreased colonic motility, obstruction, impairment of the defecation reflex
69